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  • 1990-1994  (193)
  • 1980-1984
  • 1992  (193)
  • Rat  (193)
  • Nuclear reactions
  • 1
    ISSN: 1432-0428
    Keywords: Rat ; basal hyperglycaemia ; insulin action ; Type 2 (non-insulin-dependent) diabetes mellitus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We aimed to assess prandial responses, basal glucose turnover and insulin action (euglycaemic clamp) in a very low-dose neonatal streptozotocin model of Type 2 (noninsulin-dependent) diabetes mellitus. Male Wistar rats were injected at 2 days of age with 45 mg/kg streptozotocin or vehicle (control). At 8 weeks, the groups were subdivided and fed either a high-fat or high-starch diet for 3 weeks. Both the fat diet and streptozotocin treatments had independent hyperglycaemic effects (streptozotocin/fat 9.3±0.3 mmol/l; streptozotocin/starch 7.5±0.3 mmol/l; control/fat 7.4±0.1 mmol/l; all p〈0.01 vs control/starch 6.4±0.1 mmol/l). The fat diet effect was associated with both a reduction in basal glucose clearance (p〈0.001) and in basal hepatic glucose output (p〈0.05). Streptozotocin increased basal hepatic glucose output. Significantly higher prandial glycaemia in the streptozotocin/starch group occurred despite similar insulin levels and appeared to be related to an impaired early insulin response. Whole-body and tissue-specific insulin sensitivity were significantly depressed in fat-fed animals compared to starch-fed animals, however there were no significant effects of streptozotocin treatment. We conclude that fasting hyperglycaemia associated with abnormalities in both glucose production and clearance can exist in the presence of a basal hepatic glucose output which is reduced compared to control animals. Furthermore, dietary-fat-induced insulin resistance is not exacerbated by the relative insulin deficiency and/or mild hyper glycaemia observed when dietary fat and neonatal streptozotocin-treatments are combined.
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  • 2
    ISSN: 1432-0428
    Keywords: Rat ; diabetes mellitus ; insulin ; blastocyst ; pre-implantation development
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Pre-implantation embryos were recovered from control, diabetic and insulin-treated diabetic rats on day 5 of pregnancy. Compared to control animals, diabetic rats had a 20 % reduction in the number of embryos per rat and blastocysts recovered from diabetic rats showed a 19 % decrease in total cell number. The cellular decrease observed in blastocysts was mainly at the expense of the inner cell mass. Insulin replacement therapy was started on day 1 of pregnancy and normalized the glycaemia of diabetic rats but failed to raise the number of embryos per rat toward the control value. Insulin treatment, however, fully restored the normal cell number in both the inner cell mass and trophectoderm of blastocysts. The dead cell index, which was significantly elevated in the inner cell mass of blastocysts from diabetic rats, also returned to the control value following insulin treatment. Our data suggest that diabetes-induced impairment of pre-implantation development can be partly prevented by insulin treatment started shortly after conception.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 35 (1992), S. 517-521 
    ISSN: 1432-0428
    Keywords: Rat ; teratology ; diabetic pregnancy ; mandible ; congenital malformation ; proteoglycans ; proteoglycan synthesis ; chondroitin sulphate ; costal cartilage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Fetuses from normal and manifestly diabetic rats were obtained on pregnancy day 20. The fetuses from the diabetic rats were of normal or malformed morphology. Three tissue groups were dissected free; costal cartilage, the hard tissue of the rear, and of the frontal portion of the mandible. These tissues were maintained in vitro for 24 h during which time they were labelled with [35S]sulphate. After the culture period the tissues were extracted with guanidine HCl and the resulting residues were further extracted with alkali. The culture medium was saved and its macromolecular content was compared to that of the extracts. The proteoglycans recovered in all extracts eluted at two distinct positions after chromatography on a Sepharose CL-2B column (peak I: Kav ∼0.4, and peak II: Kav ∼0.8), but the elution patterns were markedly different in extracts from various tissues. Thus, in rib cartilage, the majority of the labelled proteoglycans were located in peak I (∼90%) with no difference between extracts of fetuses from normal and diabetic pregnancies. In extracts of mandibular cartilaginous tissue from normal rat off-spring the peak I percentage (60–80 %) was lower than in the rib cartilage extracts. In the extracts from the frontal portion of malformed mandibles of fetuses of diabetic rats, the peak I percentage (35±21%) was the lowest of all recorded and the only one to significantly differ from the other percentages in its (the frontal mandible) group. The results show an association between a congenital malformation, micrognathia, and a disturbance in the production of chondroitin sulphate proteoglycans in the malformed region.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 185 (1992), S. 217-223 
    ISSN: 1432-0568
    Keywords: Rat ; Embryo culture ; Cephalic neurulation ; 5-Azacytidine ; Methylation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Head-fold stage rat embryos (9.5 days of gestation) were cultured for 48 h in rat serum with or without 0.8 μM 5-azacytidine. Incomplete closure of the cephalic neural tube was observed in 5-azacytidine-treated embryos cultured for 48 h (25-somite stage). Control embryos showed complete fusion of cephalic neural folds at 33 h (16-somite stage) in culture. Drug administration or removal experiments revealed that embryos were sensitive to 5-azacytidine during 6–12 h of culture (three to five somite stages). Electron microscopical studies indicated that the arrangement and fine structure of cephalic neuroepithelial cells were almost the same in control and treated embryos. There was no significant difference in DNA and protein contents between control and treated embryos cultured for 36 h. Immunocytochemical observations using 5-methylcytosine-specific antibody revealed that the staining of neuroepithelial cells in the median part of the transversely sectioned cephalic neural plate, and of mesenchymal cells near the apices of the plate, was suppressed by 5-azacytidine. These results suggest that DNA methylation of these cells plays an important role in closure of the cephalic neural tube.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 185 (1992), S. 559-569 
    ISSN: 1432-0568
    Keywords: Cochlea ; Organ of Corti ; Development ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The development of the rat organ of Corti was studied during the first postnatal weeks. The temporal and the spatial patterns of cochlear development were investigated between 4 and 24 days after birth by means of semi-thin sections at approx. ten equidistant positions along the entire cochlear duct. At all examined positions width, thickness and cross sectional area of basilar membrane, cross-sectional area of tectorial membrane, of cells of Hensen, Claudius and Boettcher and of the organ of Corti were quantitatively analyzed. The most conspicuous maturational changes occur between 8 and 12 days after birth. These are the detachment of the tectorial membrane, the first appearance of filaments within the basilar membrane, the formation of the tunnel of Corti and the opening of the inner spiral sulcus. Quantitative analysis revealed that structures of a given position along the cochlear duct do not develop synchronously. Width of the basilar membrane and cross-sectional area of the tectorial membrane are already mature at the onset of hearing (10–12 days after birth). Length, thickness and cross-sectional area of the basilar membrane as well as cross-sectional area of the organ of Corti and of the cells of Hensen, Claudius and Boettcher still develop after the onset of hearing (up to 20–24 days after birth). We suggest that basic cochlear function is established by structures which are mature before the onset of hearing. Cochlear structures which develop after the onset of hearing might be involved in this improvement during this period.
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 185 (1992), S. 571-581 
    ISSN: 1432-0568
    Keywords: Cochlea ; Development ; Rat ; Hair cells ; Stereocilia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The development of cochlear receptor cells and their supporting elements was studied by means of semi-thin and ultra-thin sections during the first postnatal weeks in the rat. The temporal and spatial patterns of the receptor cell development were investigated between the 4th and 24th days after birth. At approx. ten equidistant positions along the entire cochlear duct length of inner and outer hair cells, width of outer hair cell triad and stereocilia-length of the outer hair cells were quantitatively analyzed. Striking maturational changes take place before the 12th day after birth, that is, when the onset of hearing occurs. These changes are the formation of the tunnel of Corti, of the Nuel spaces, the appearance of filaments within the supporting elements and the change in cell shape of the hair cells. Between 4 days and 20 days after birth the maturation of outer hair cells is characterized by a decrease of organelles in the cytoplasm and establishment of the subsurface cistern. The quantitative analysis revealed a unique developmental pattern of the length of the outer hair cells, the width of the outer hair cell triad and the stereocilia length of the outer hair cells. Shortly after birth these structures have an almost constant size along the whole cochlear duct, but with increasing age the structures shorten at the cochlear base and enlarge at the apex. This pattern results in the establishment of a basoapical gradient of the above mentioned structures. We assume that this baso-apical gradient is of central importance for the frequency representation.
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  • 7
    ISSN: 1432-0568
    Keywords: Training ; Motor nerve terminals ; Neuromuscular junction ; Extensor digitorum longus muscle ; Soleus muscle ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The morphology of nerve terminals in the rat extensor digitorum longus and soleus muscles was studied with light microscopy in 13-week-old male animals after 6 weeks of treadmill running and compared with data from untrained controls. The terminals were stained with methylene blue. Physical training tended to increase the area and length of the nerve terminals in relation to the corresponding muscle fiber diameter, and to reduce the density of nerve terminal varicosities, but significant differences between the trained group and the control group were obtained only in the extensor digitorum longus muscle. The different degrees of effect on the nerve terminals in the two muscles may be due to different abilities to respond to the training, but may also be due to differences in work load caused by the training. The effect of training on extensor digitorum longus junctions may reflect some transformation from fast to slow morphological characteristics.
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  • 8
    ISSN: 1432-0568
    Keywords: Superior colliculus ; Periaqueductal gray ; NADPH-diaphorase ; Golgi method ; Neuronal types ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have studied the laminar distribution of reduced nicotinamide dinucleotide phosphate diaphorase (NADPH-d) activity and the morphology of positive neurons in the superior colliculus (SC) and the underlying periaqueductal gray (PAG) of the rat. The morphology of NADPH-d-positive neurons has been compared to that of Golgi-impregnated cells. The highest activity occurs in the stratum zonale and stratum griseum superficiale, contrasting with the pale neuropil in the stratum opticum, where only a few positive neurons are found. In the stratum griseum intermedium positive neurons are grouped in patches separated by narrow, NADPH-d-negative bands. In the deeper layers, the neuropil is NADPH-d-negative, and few neurons show enzymatic activity. In contrast, numerous neurons in the dorsolateral part of the PAG are intensely positive. They are continuous with the positive neurons in the stratum album profundum, with no clear border between the two centers. In both SC and PAG, only small and medium sized neurons are NADPH-d-positive. In comparison with Golgi material, all types of small neurons in the superficial layers show NADPH-d activity; NADPH-d histochemistry, however, does not visualize the characteristic dendritic appendages of these neurons. The large neurons of the SC and PAG, probably representing the long-projecting neurons of these centers, do not contain the enzyme.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 185 (1992), S. 69-76 
    ISSN: 1432-0568
    Keywords: Human-tumor-associated antigens ; Rat ; Colon
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The patterns of expression of the human-tumor-associated antigens, CO17-1A, GA73-3, BR55-2, GICA19-9, CA50 and carcino-embryonic antigen (CEA) were studied in the normal colonic mucosa (the last three also in the serum) of Sprague-Dawley rats. Four immunohistochemically different segments were identified: caecum, ascending colon, transverse colon and descending colon. The immunohistochemical reactions of the cells at the lower part of the crypt were essential for the distinction of the four segments. In the caecum, the MAbs 17-1A, 73-3 and 19-9 stained the glycocalyx of the cells of the lower part of the crypts and the Golgi apparatus of the intercalated cells (IC). MAb55-2 stained very weakly the goblet-like cells (GLC) of the lower part of the crypt of transverse colon, in addition to a nearly complete lack of reaction in the upper part of the crypts. In the ascending colon, the lower part of the crypts showed a characteristic diffuse staining of the intercalated cells with MAb55-2. The perinuclear and mucosal staining observed in the GLC of the transverse colon with MAbs 17-1A, 73-3 and 19-9 as against the supranuclear and Golgi zone staining observed in the GLC/goblet cells (GC)/columnar cells (CC) of the lower part of crypts of the descending colon with the same MAbs, distinguished the former segment from the latter. The IC demonstrated by immunohistochemistry in the lower parts of the crypts of caecum and ascending colon appear to correspond to the replicating cells of the colonic crypts.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 186 (1992), S. 497-503 
    ISSN: 1432-0568
    Keywords: Skeletal muscle ; Regeneration ; Morphometry ; Histology ; Rat ; Laser
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of low-energy laser (He-Ne) irradiation on the rate of skeletal muscle regeneration after partial excision of the rat gastrocnemius muscle was studied using quantitative histological morphometric methods. The injured zones of the experimental rats were subjected to direct He-Ne laser (632.8 nm wavelength) irradiation (6.0 mW for 2.3 min) immediately following injury and once daily thereafter for 5 days. Muscles that were injured as above and subjected to red or room light irradiation served as a control group. The volume fraction (percent of total volume of injured zone) of the mononucleated cells in the injured zone decreased gradually with time after injury, but more rapidly in the laser irradiated muscles than in the control. At 3 days post-injury the myotubes in the laser-irradiated muscles populated a significantly higher percentage (13.9 ± 1.1%) of the injured area than in the control muscles (7.8 ± 1.0%). The volume fraction of the young myofibers in the laser irradiated muscles exceeded 30.6 ± 2.2% and 49.6 ± 5.6% at 8 and 11 days post-injury, respectively, while in control muscles these structures comprised only 9.6 ± 1.0% and 27.2 ± 3.8% of the injured zone at 8 and 11 days after injury, respectively. It is concluded that He-Ne laser irradiation during the regeneration process promotes muscle maturation in the injured zone following partial excision of the rat gastro-cnemius muscle.
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  • 11
    ISSN: 1432-0568
    Keywords: Vestibular nuclei ; Spinal cord ; Dorsal horn ; Tracing study ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Phaseolus vulgaris leucoagglutinin and wheat germ agglutinin-horseradish peroxidase were iontophoretically injected into different parts of the vestibular nuclear complex (VNC) of the rat. Injections centered into the caudal part of the medial vestibular nucleus revealed a vestibulospinal projection predominantly to the dorsal horn of the cervical spinal cord, besides the expected projection to the intermediate zone (IZ) and ventral horn (VH). While most of the anterogradely labelled fibres could be localized in laminae III to V, some scattered fibres were also seen in laminae I and VI. Lamina II remained free of labelling. The dorsal horn (DH) area with detectable anterograde labelling showed a rostrocaudal extension from C1-C6. Injections into other parts of the VNC labelled fibres and terminals in the IZ and VH while the DH remained almost free of labelling. Additionally, fluorogold and wheat germ agglutininhorseradish peroxidase were pressure- or iontophoretically injected at different levels into the spinal cord to confirm the projection to the dorsal horn by means of retrograde tracing. Labelled neurons in the area of the medial vestibular nucleus (MVN), from which anterograde labelling in the DH was obtained, were only detectable after fluorogold and wheat germ agglutinin-horseradish peroxidase injections into the cervical spinal cord, in particular its DH. This projection from the caudal medial vestibular nucleus to the dorsal horn of the cervical spinal cord probably enables the VNC to influence sensory processing in the DH, in addition to its well-established influence on posture and locomotion via projections to the intermediate zone and ventral horn.
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  • 12
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 83 (1992), S. 379-385 
    ISSN: 1432-0533
    Keywords: Hypoglycemia ; Hypothermia ; Neuronal damage ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of hypothermia on hypoglycemic brain damage were studied in rats after a 30-min period of hypoglycemic coma, defined as cessation of spontaneous EEG activity. The rats were either normothermic (37°C) or moderately hypothermic (33°C). Morphological brain damage was evaluated after various periods of recovery. Hypothermic animals with halothane anesthesia never resumed spontaneous respiration, thus requiring artificial ventilation during recovery (maximally 8h). In contrast, when isoflurane was used as the anesthetic agent, all animals survived and were examined after 1 week of recovery. There was a tendency towards gradually higher arterial plasma glucose levels during hypoglycemia with lower body temperature. The time period from insulin injection until isoelectric EEG appeared was gradually prolonged by hypothermia, and was shorter when isoflurane was used for anesthesia. Brain damage was examined within the neocortex, caudoputamen and hippocampus (CA1, subiculum and the tip of the dentate gyrus). Damage to neurons was found to be of two types, namely condensed dark purple neurons (pre-acidophilic) and shrunken bright red-staining neurons (acidophilic). In the neocortex, no clear influence of temperature on the degree of injury was seen. In the caudoputamen, the number of injured neurons clearly decreased at lower temperature (33°C,P〈0.001) when halothane was used, while no such difference was seen when isoflurane was used as the anesthetic agent. Likewise, a protective effect of hypothermia was seen in subiculum (P〈0.01) when halothane, but not isoflurane was used. Damage to CA1 neurons was mild in both groups with halothane, but slightly less frequent (P〈 0.05) in the hypothermic group, in which the majority of animals showed no damage. No protection of hypothermia was seen in the animals with isoflurane anesthesia. Furthermore, with isoflurane, more damaged CA1 cells were seen in the normothermic situation as compared to when halothane was used (P〈0.01). In contrast, damage to the tip of the dentate gyrus was remarkedely resistant to hypothermia, with the majority of animals showing the same degree of damage as the normothermic ones irrespective of the anesthetic agent used. In summary, hypothermia seemed to have only a partial protective effect on the development of hypoglycemic brain damage, the effects differing between regions previously described to be selectively vulnerable to hypoglycemia, and also differing when halothane or isoflurane were used as anesthetic agents. While long-term survival was achieved with the use of isoflurane, the protective effect of hypothermia seemed to be lost.
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  • 13
    ISSN: 1432-0533
    Keywords: Cisplatin ; Spinal ganglia ; Peripheral neuropathy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We performed a morphological, morphometric and toxicological study on the spinal ganglia and peripheral nerves of the rat after chronic administration of cisplatin (cis-dichlorodiammineplatinum II; DDP) with two different schedules. Severe damage of the spinal ganglia neurons was demonstrated with predominant involvement of the nucleus and nucleolus associated with a decrease in the cell size. Morphological and morphometric changes also occurred in the sciatic and peroneal nerves with the features of axonopathy. All these changes were more marked in the group of rats which underwent the most intense DDP treatment and the tissue platinum concentrations were also higher in this group. This experimental model is the first available for chronic DDP administration in which concomitant spinal ganglia and peripheral nerve damage has been confirmed pathologically. Our study supports the hypothesis that DDP-induced peripheral nerve fiber degeneration may result from nuclear and nucleolar changes in the sensory ganglion cell perikaryon.
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  • 14
    ISSN: 1432-0533
    Keywords: Microglia ; Hippocampus ; Ischemia ; Rat ; Major histocompatibility complex antigens
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We show a differential up-regulation of immunomolecules in the rat dorsal hippocampus accompanying neuronal cell death as a consequence of transient forebrain ischemia (four-vessel occlusion model). Using a panel of monoclonal antibodies (mAbs), we have examined the time course of expression of major histocompatibility complex (MHC) antigens class I (OX-18) and class II (OX-6), leukocyte common antigen (OX-1), CD4 (W3/25) and CD8 (OX-8) antigens, CR3 complement receptor (OX-42), as well as brain macrophage antigen (ED2). The study was performed at time intervals ranging from 1 to 28 days after reperfusion. Throughout all post-ischemic time periods, strongly enhanced immunoreactivity on microglial cells in the CA1 region and dentate hilus and, to a lesser extent, in CA3 was demonstrated with mAb OX-42. MHC class I-positive cells (OX-18) appeared on day 2, whereas cells immunoreactive with OX-1 and W3/25 became evident in the CA1 and hilar regions on post-ischemic day 6. In contrast, MHC class II (Ia) antigen was first detected on indigenous microglia by day 13. In some animals, the OX-8 antibody resulted in the labelling of scattered CD8-positive lymphocytes, but perivascular inflammatory infiltrates were absent. No changes in the expression of ED2 immunoreactivity on perivascular cells could be observed. The results show that following ischemic injury, microglial cells demonstrate a timedependent up-regulation and de novo expression of certain immunomolecules, indicative of their immunocompetence. The findings are compared with those obtained in other models of brain injury.
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  • 15
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 85 (1992), S. 55-70 
    ISSN: 1432-0533
    Keywords: Excitotoxin ; Substantia nigra ; Neuronal degeneration ; Calcification ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The excitotoxin ibotenic acid (IBO) induces local calcium deposits upon injection into rat substantia nigra. Their formation has been investigated at the ultrastructural level in a time course study from 2 days to 8 weeks survival. Potassium bichromate stain was used to visualize pathological calcium accumulation. Two days after IBO application, reaction product for calcium was observed in mitochondria of degenerating perikarya and dendrites, but not in axons, boutons or glia. Four days after the lesion, calcium stain was found, in addition, in a seemingly free form in a few dendrites, especially those still contacted by intact boutons and not sequestrated by invading glia. Two days later, most of these calcium-accumulating dendrites were separated by astroglia from their synaptic partners. At the border between glia and dendrite a fibrillar matrix was formed which further accumulated calcium. During the following weeks this matrix enlarged stepwise and was infiltrated with calcium, thus giving a picture resembling the annual growth rings of trees. The evolving bodies incorporated smaller deposits in their vicinity, finally representing the large concretions seen at the light microscopic level from the 4th postoperative week onward. Similarities and dissimilarities of these observations with the results from other ultrastructural studies on excitotoxin lesions are detailed. It is suggested that the different outfit of neuronal subpopulations and of glia with ligand-gated and metabotropic glutamate receptors in the single brain region, as well as the local response repertoire of glial cells towards the excitotoxic injury with the subsequent formation of a calcium-accumulating matrix provide the molecular basis for the formation of calcium deposits.
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  • 16
    ISSN: 1432-0533
    Keywords: Traumatic brain injury ; Hypothermia ; Blood-brain barrier ; Hypertension ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of moderate hypothermia on blood-brain barrier (BBB) permeability and the acute hypertensive response after moderate traumatic brain injury (TBI) in rats were examined. TBI produced increased vascular permeability to endogenous serum albumin (IgG) in normothermic rats (37.5°C) throughout the dorsal cortical gray and white matter as well as in the underlying hippocampi as visualized by immunocytochemical techniques. Vascular permeability was greatly reduced in hypothermic rats cooled to 30°C (brain temperature) prior to injury. In hypothermic rats, albumin immunoreactivity was confined to the gray-white interface between cortex and hippocampi with no involvement of the overlying cortices and greatly reduced involvement of the underlying hippocampi. The acute hypertensive response in normothermic rats peaked at 10 s after TBI (187.3 mm Hg) and returned to baseline within 50 s. In contrast, the peak acute hypertensive response was significantly (P〈0.05) reduced in hypothermic rats (154.8 mm Hg, 10 s after TBI) and returned to baseline at 30 s after injury. These results demonstrate that moderate hypothermia greatly reduces endogenous vascular protein-tracer passage into and perhaps through the brain. This reduction may, in part, be related to hypothermia-induced modulation of the systemic blood pressure response to TBI.
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  • 17
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 89 (1992), S. 133-139 
    ISSN: 1432-1106
    Keywords: Defence response ; Ventrolateral periaqueductal grey matter ; Rostral ventrolateral medulla ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In rats anaesthetised with alphaxalone/alphadolone, electrical stimulation in the dorsal periaqueductal grey matter (PAG) evoked a presser response with tachycardia, vasodilatation in the hindlimb and hyperpnoea: a pattern of response known as the defence reaction. Microinjection of the synaptic excitant, D,L-homocysteic acid (DLH), but not saline, into the ventrolateral PAG at the level of the decussation of the superior cerebellar peduncle (approximately 7.3–8.3 mm caudal to bregma) produced a reduction in the size of the cardiovascular components of the defence reaction evoked by electrical stimulation in the dorsal PAG. Injections of DLH made outside this region had no effect on the defence response. Injection of DLH into the “defence inhibition area” had no effect on the presser response evoked distally in the efferent pathway for the defence reaction, by electrical stimulation in the rostral ventrolateral medulla (RVLM). Activation of neurones in a restricted portion of the caudal ventrolateral PAG appears to modulate activity in the descending pathway for the defence response evoked from the dorsal PAG. It is argued that the inhibitory interaction probably occurs at the level of synapses in the RVLM.
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  • 18
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 90 (1992), S. 275-290 
    ISSN: 1432-1106
    Keywords: Movement ; Sequence ; Basal ganglia ; Frontal cortex ; Cerebellum ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Rats emit grooming actions in sequences that follow characteristic patterns of serial order. One of these patterns, a syntactic chain, has a particularly stereotyped order that recurs spontaneously during grooming thousands of times more often than could occur by chance. Previous studies have shown that performance of this sequence is impaired by excitotoxin lesions of the corpus striatum. In this study we examined whether the striatum is unique in its importance to this behavioral sequence or whether control of the sequence instead depends equally upon the cortex and cerebellum. In two experiments, a fine-grained behavioral analysis compared the effects of striatal ablation to the effects of motor cortex ablation, ablation of the entire neocortex, or ablation of the cerebellum. Cortical and cerebellar aspiration produced mere temporary deficits in grooming sequences, which appeared to reflect a general factor that was nonsequential in nature. Only striatal damage produced a permanent sequential deficit in the coordination of this syntactic grooming chain. We conclude that the striatum has a unique role in the control of behavioral serial order. This striatal role may be related to a number of sequential disorders observed in human diseases involving the striatum.
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  • 19
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 90 (1992), S. 271-274 
    ISSN: 1432-1106
    Keywords: Area postrema ; Lesion ; Supraoptic nucleus ; Oxytocin ; Osmotic stimulation ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Experiments were performed to examine whether or not the area postrema (AP) is involved in the osmotic control of neurohypophysial hormone release. In control rats and in rats bearing extensive lesions of AP, extracellular action potentials were recorded from neurosecretory cells in the supraoptic nucleus (SON) and firing rates determined before and after the intraperitoneal (i.p.) injection of 1.5 M-NaCl solution. Lesion of the AP significantly (p≦0.05, Mann-Whitney's U-test) lowered firing rate of putative vasopressin (phasic) cells but not that of oxytocin (non-phasic) cells. In lesioned animals, i.p. injection of hypertonic saline, however, caused similar changes in plasma osmotic pressure, plasma oxytocin concentration and mean firing rates of both putative oxytocin and vasopressin cells to those in control rats. The results suggest that the osmotic control of SON neurosecretory cell activity in the rat can take place in the absence of the AP.
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  • 20
    Electronic Resource
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    Springer
    Experimental brain research 90 (1992), S. 291-296 
    ISSN: 1432-1106
    Keywords: Cholinergic systems ; Acetylcholinesterase ; Choline acetyltransferase ; Superior colliculus ; Guinea pig ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We studied the distribution of acetylcholinesterase activity and choline acetyltransferase immunoreactivity in the superior colliculus of the guinea pig and the albino rat, using enzyme histochemical and immunohistochemical methods. Choline acetyltransferase-like immunoreactivity was localized in the neuropil throughout the colliculi, but the density of the immunoreactive neuropil varied among layers as well as between species. In the intermediate collicular layers the pattern of choline acetyltransferase immunoreactivity was closely matched by the distribution of acetylcholinesterase activity in guinea pig and rat, confirming our previous findings in the cat. Furthermore, in the guinea pig, but not in the rat, choline acetyltransferase-like immunoreactivity was localized in a prominent population of perikarya of the superficial gray layer.
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  • 21
    ISSN: 1432-1106
    Keywords: Retina ; Transplant ; Parvalbumin ; Immunocytochemistry ; Development ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Retinas from embryonic day 14 Sprague-Dawley rats were transplanted to the midbrain or cerebral cortex of newborn (P0) rats of which the right eye was enucleated at the time of transplantation. Parvalbumin immunoreactive (PV-I) neurons were studied in the developing retinal transplants, and in the remaining retina of the host, as well as in normal retinas. PV-I neurons were identifiable in retinas of normal and host rats from postnatal day 5 (P5) onward, with the PV-I somata primarily in the inner half of the inner nuclear layer and in the ganglion cell layer. An adult-like distribution of PV-I neurons was attained at P35, as judged by cell packing density, intensity of immunostaining, laminar distribution and soma size of subpopulations of PV-I cells. A similar time course of development and distribution of PV-I somata was observed in the retinal transplants, except for some minor differences such as a slight delay in PV-I cells achieving their final distribution. These findings provide evidence that PV-I neurons can survive, differentiate and mature according to pre-determined programmes intrinsic to the retinal tissue following transplantation to a new and foreign environment.
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  • 22
    ISSN: 1432-1106
    Keywords: Somatosensory cortex ; Pain-related behaviour ; Mononeuropathy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Single-unit recordings were made under moderate gaseous anaesthesia in the hindpaw representation area of the two primary somatosensory motor cortices (SmI) of rats (n = 58) rendered mononeuropathic by four loose ligatures placed around one common sciatic nerve 2–3 weeks beforehand. The rats exhibited clear hyperalgesia and allodynia from the paw with the ligated sciatic nerve, to both mechanical and thermal stimuli. From the tested neuronal population (n = 640), about the same proportion could be activated by somatic stimuli in each cortex: 165/362 (45%) in the cortex contralateral to the ligated sciatic nerve (Cc), 105/278 (37%) in the cortex ipsilateral to the ligated sciatic nerve (Ci). Neurones driven by light touch, exhibited RFs strictly contralateral to the recording sites. Their proportion and response characteristics were similar regardless of recording side. However, the number of neurones with RFs in the sciatic nerve territory was above 95% in the Ci, and was dramatically reduced to 43 % in the Cc. By contrast, the number of neurones with RFs supplied by the saphenous nerve reached 57% on this side. Although the RF size of all the neurones appeared roughly normal, there were fewer Cc than Ci neurones with RFs located on the paw itself and with RFs of extremely small size in the sciatic nerve territory. The proportion of neurones responding to a joint stimulus was significantly higher in the Cc than in the Ci. The neuronal responses to joint stimuli of the paw with the ligated sciatic nerve were significantly more sustained than those recorded in the Ci and elicited from the normal paw. The proportion of neurones driven by mechanical stimulation which gave rise to nociceptive reactions in freely moving animals, i.e. “nociceptive” neurones, was comparable in each cortex. However, half of the Cc neurones exhibited paroxysmal discharges occuring without intentional stimulation and of long duration (l min to several minutes). Only 66% of Cc but 93% of Ci “nociceptive” neurones were exclusively activated by pinch. The remaining Cc neurones were also activated by applying moderate pressure to the paw with the ligated nerve. Pinch responses from the paw with the ligated nerve were often more intense and of longer duration than responses elicited from the intact paw. The “nociceptive” Cc neurones were especially sensitive to thermal stimuli of 39–44° C when the stimuli were applied to the paw with the ligated nerve. They also responded vigorously to a 10° C stimulus applied to this paw. They were therefore, sensitive to thermal stimuli usually considered to be in the non-noxious range. In the SmI cortex opposite to the ligated sciatic nerve, there was no change in the proportion of somatosensory neurones, but a rearrangement of the various somatic inputs. Although reduced, there were consistent light tactile inputs from the damaged sciatic nerve giving rise to roughly normal neuronal responses, and simultaneously a noticeable increase in tactile signals from the saphenous nerve territory. There was also a significant increase in joint inputs from the paw with the ligated sciatic nerve. The possible functional role of such input rearrangement is discussed. The dramatic changes in the responses of “nociceptive” neurones to stimuli applied to the paw with the ligated sciatic nerve and the clear decrease in their activation threshold to mechanical and thermal stimuli could account for some of the abnormal pain-related behaviours that were exhibited. These data emphasize, again, that the primary sensory cortex is involved in nociceptive processing.
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  • 23
    ISSN: 1432-1106
    Keywords: Anterograde axonal tracing ; Brain repair ; Neocortical projections, injury, and transplants ; Phaseolus vulgaris-leucoagglutinin ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Fetal rat neocortex grafted into lesion cavities made in the newborn rat neocortex can exchange multiple axonal connections with the host brain. Most previous studies demonstrating efferent transplant-tohost brain connections have used fluorescent retrograde tracers injected into the host brain (Castro et al. 1985, 1987; Floeter and Jones 1984; O'Leary and Stanfield 1989). Other studies have used anterograde axonal tracing with either tritium-labelled amino acids impregnating the transplant and its efferents (Floeter and Jones 1985) or horseradish peroxidase injected into the transplants (Chang et al. 1984, 1986). In the present study we used the anterograde axonal tracer Phaseolus vulgaris — leucoagglutinin (PHA-L) to examine in detail the course and termination of the efferent neocortical graft fibers. Twenty-six newborn rats had the right frontal cortex forepaw area removed by vacuum aspiration, while anesthetized by hypothermia. A piece of fetal frontal cortex 14–16 embryonic days old (E14–16) was immediately thereafter placed in the lesion, and the recipient rats allowed to survive for 5–7 months. At this time the rats were reoperated under sodium pentobarbital (Nembutal) anesthesia and the transplants iontophoretically injected with PHA-L. Two weeks later the animals were again anesthetized, perfused, and processed for PHA-L immunocytochemistry and routine histology. Analysis of acetylcholinesterase- (AChE) and Nissl-stained sections showed graft survival in 19 of the 26 animals used in this study. When these 19 brains were processed for PHA-L immunocytochemistry, 5 of them were found with certainty to have the PHA-L injection confined to the transplant. Based on these cases PHA-L-reactive fibers arising from labelled transplant neurons were traced into the ipsilateral host neocortex adjacent to the transplant and found to project through the subcortical white matter to the ipsilateral parietal neocortical area 1, and claustrum. Callosal fibers were traced to the contralateral frontal neocortical forelimb and parietal areas. Transplant fibers were also observed to descend through the caudate putamen in the dispersed fiber bundles of the internal capsule to distribute as terminal branches and varicose fibers within the mesencephalic periaqueductal gray, red nucleus, deep mesencephalic nucleus, and intermediate gray of the superior colliculus, as well as in the pontine gray. Similar fibers and terminations were present in the caudate putamen, the reticular, ventrobasal, centrolateral, posterior, and parafascicular thalamic nuclei. On the side contralateral to the transplant, fewer fibers were observed in the caudate putamen, the ventrobasal, centrolateral, and posterior thalamic nuclei, as well as more caudally in the deep mesencephalic nucleus and the intermediate gray of the superior colliculus. Our findings demonstrate that homotopic grafts of fetal rat frontal neocortex can project to the developing host brain in a manner which for most projections corresponds to the normal rat neocortical parietal area 1–2 and forelimb area. The density of these transplant-to-host projections is, however, less than in the normal rat corticofugal pathways.
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  • 24
    ISSN: 1432-0738
    Keywords: Ethoxyquin(6-ethoxy-1,2-dihydro-2,2,4-trimethylquinoline) ; Nephrotoxicity ; Rat ; Proteinuria
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The toxicity of ethoxyquin (EQ) to rat kidney was examined in males which were either weanling or adult at the beginning of the experiment, and also in adult females. Female rats were much less susceptible to the toxic effects of EQ than males of the same age. In males damage to the cortex, mainly as an acceleration of the normal ageing process, was similar in both age groups, but rats exposed to EQ as weanlings also suffered from extensive papillary necrosis. Male rats were more prone than females to proteinuria, which was greatly exacerbated by EQ in both age groups. Thus there is very little evidence of nephrotoxicity in adult female rats on exposure to EQ at 0.5% in the diet for 26 weeks. In males, the initial age of the animal, as well as the length of treatment, influences the extent of damage.
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  • 25
    ISSN: 1432-0738
    Keywords: Toxicology ; Poisoning ; Toluene ; Brain regional distribution ; Rat ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Toluene concentrations in 9 brain regions of acutely exposed rats and that in 11 brain regions of a human case who inhaled toluene prior to death are described. After exposure to toluene by inhalation (2000 or 10000 ppm) for 0.5 h or by oral dosing (400 mg/kg), rats were killed by decapitation 0.5 and 4 h after onset of inhalation and 2 and 10 h after oral ingestion. After each experimental condition the highest range of brain region/blood toluene concentration ratio (BBCR) was in the brain stem regions (2.85–3.22) such as the pons and medulla oblongata, the middle range (1.77–2.12) in the midbrain, thalamus, caudate-putamen, hypothalamus and cerebellum, and the lowest range (1.22–1.64) in the hippocampus and cerebral cortex. These distribution patterns were quite constant. Toluene concentration in various brain regions were unevenly distributed and directly related blood levels. In a human case who had inhaled toluene vapor, the distribution among brain regions was relatively similar to that in rats, the highest concentration ratios being in the corpus callosum (BBCR: 2.66) and the lowest in the hippocampus (BBCR: 1.47)
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  • 26
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 66 (1992), S. 279-285 
    ISSN: 1432-0738
    Keywords: Acetaminophen ; Aminophenazone ; Ammonium metavanadate ; Brain ; Buthionine sulfoximine ; Cobalt ; Diethylmaleate ; Glutathione ; Lomustine ; Morphine ; Mouse ; Nitrofurantoin ; Phenytoin ; Propyphenazone ; Rat ; Starvation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Since glutathione is thought to be involved in cerebral functions, changes in the glutathione level imply modulations of the neurotransmission in addition to all the known effects of GSH. It was investigated whether alterations of the cerebral glutathione can be induced by consumption of GSH, by inhibition or stimulation of the synthesis of GSH, or by an inhibition of the re-reduction of the oxidized glutathione. Aminophenazone, propyphenazone, acetaminophen, phenytoin, morphine and nitrofurantoin, known to deplete hepatic GSH, had no effects on cerebral GSH. Diethyl maleate (0.6 ml/kg) decreased the cerebral content of GSH and GSSG in adult rats as well as in fetuses. The depletion of the cerebral GSH caused by diethyl maleate treatment for 4 days was followed by an increase up to 125% and a subsequent return to the normal level after 1 week. In rats starved up to 71 h deficiency of exogenous amino acids caused only a minimal or no decrease in cerebral GSH. The specific inhibitor of the gamma-glutamylcysteine synthetase BSO only depleted GSH in the brain of young mice following the repeated s. c. administration of a high dose (890 mg/kg). After cobaltous chloride (20 mg/kg; twice a day for 2 or 4 days) the GSH level in the brain was unchanged. In vivo inhibition of the cerebral glutathione reductase was caused by ammonium metavanadate (12.5 mg/kg; three times a week for 6 weeks). Nitrofurantoin (150 mg/kg) had no effect. After lomustine (10 mg/kg) a minimal increase in glutathione reductase was found, but simultaneously also an increase in GSSG and of the ratio GSSG/total glutathione.
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  • 27
    ISSN: 1432-0738
    Keywords: Kidney ; Liver ; Cell proliferation ; Rat ; Mouse ; p-Dichlorobenzene
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cell proliferation in the kidneys and livers of rats and mice exposed short-term to p-dichlorobenzene (p-DCB) was evaluated by immunohistochemical measurement of bromodeoxyuridine (BrdU) incorporation into nuclei of DNA-synthesizing cells. p-DCB was given by gavage at two doses up to 600 mg/kg body weight for 4 days. The cumulative fraction of proliferating cells was increased in the proximal tubule epithelial cells of male rats at the high dose, but not at the low dose nor in females at either dose using gamma-glutamyl transferase reaction to identify tubular cells. Also, no increase in cell proliferation was found in mouse kidneys. The fractions of proliferating cells in the livers of rats and mice of both sexes were also increased. The increased cell proliferation in only male rat kidney and in the livers of mice of both sexes correlates with the reported carcinogenic effects of p-DCB in those tissues. However, the finding that p-DCB also induced cell proliferation in the livers of rats of both sexes, which were not a site of p-DCB-induced tumors in bioassays, and in female mice at the low dose, which was not affected by an increase in tumors, reveals a lack of concordance and indicates that acute induction of cell proliferation is not sufficient to lead to carcinogenesis.
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  • 28
    ISSN: 1432-0738
    Keywords: Pyridoxine ; Vitamin B6 ; Testis ; Reproductive system ; Spermatogenesis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Although it has been indicated that many neurotoxicants also cause reproductive toxicity, the reproductive toxicity of megadoses of pyridoxine, which is a neurotoxicant, has not been studied. In this paper, we studied the effects of megadoses of pyridoxine on male reproductive organs. Pyridoxine hydrochloride, 125 mg/kg, 250 mg/kg, 500 mg/kg or 1000 mg/kg, daily, was intraperitoneally injected into Wistar male rats 5 days a week for 2 or 6 weeks, and its effects on the male reproductive organs were investigated. After 2 weeks of administration, absolute weights of the testis in the 500 and 1000 mg/kg epididymis in all the exposed groups and prostate gland in the 1000 mg/kg group decreased, and mature spermatid counts in the testis decreased in the 1000 mg/kg group. After 6 weeks administration, the absolute and relative weights of the testis, epididymis, prostate gland and seminal vesicle decreased in the 500 mg/kg and 1000 mg/kg groups, and mature spermatid counts in the testis and sperm counts in the epididymis decreased in these groups. Among the marker enzymes of the testicular cells, LDH-X activity decreased, and β-glucuronidase activity, cytochrome P-450 content and cytochrome b5 content increased in the 1000 mg/kg group. Plasma testosterone concentration did not significantly alter in all the exposed groups. From these results, it was concluded that megadoses of pyridoxine affected the spermatogenesis and decreased reproductive organ weights in the rat.
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  • 29
    ISSN: 1432-0738
    Keywords: Inhalation ; Mouse ; Pharmacokinetic model ; physiologically-based, two-compartment ; Rat ; Acetone ; 1,3-Butadiene ; 2-Butanone ; 1,1-Dichloroethylene ; 1,1-Difluoroethylene ; 1,2-Epoxybutene-3 ; Ethylbenzene ; Ethylene oxide ; n-Hexane ; Isobutene ; Isoprene ; 2-Nitropropane ; Toluene ; 1,1,1-Trichloroethane ; 1,1,2-Trichloroethane ; Styrene ; m-Xylene
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Experimental data obtained in vivo with the closed-chamber gas uptake technique have been reported for a series of volatile chemicals. Pharmacokinetic analyses of these data have been performed either by using a two-compartment model or physiological models. In the former the transfer rate of chemical from ambient air to body is defined by the clearance of uptake. In the latter models the transfer rate depends on alveolar ventilation, cardiac output, and blood: air partition coefficient. In this communication we describe the quantitative relationship between clearance of uptake and alveolar ventilation, cardiac output, and blood: air partition coefficient. Theoretical values of clearance of uptake were calculated for a variety of volatile chemicals using literature data on alveolar ventilation, cardiac output, and blood: air partition coefficient. For most chemicals the experimentally determined values in rats and mice were about 60% of the theoretical values. This suggests that the inhalatory uptake rate of chemical may be overestimated if literature values of alveolar ventilation are used in physiological pharmacokinetic models for rodents.
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  • 30
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 66 (1992), S. 315-320 
    ISSN: 1432-0738
    Keywords: Cadmium ; Rat ; Bone ; Long-term administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A decrease in mechanical strength of bones was observed both in young and old rats for long periods of administration of cadmium. Young (3-week-old) female rats were given 0 (control), 5 and 10 ppm cadmium in drinking water, respectively, for 20 weeks. Old (18-month old) female rats were given 0 (control) and 40 ppm cadmium in drinking water, respectively, for 7 months. The compression strengths of bones of young rats which were given 10 ppm cadmium, and those of old rats which were given 40 ppm cadmium, significantly decreased at the distal end portion of femur. Cadmium contents in bones in the 10 ppm and 40 ppm groups were about 110 and 210 ng/g dry weight, respectively. The present result confirmed that cadmium has a lesional effect on the mechanical strength of bone at the concentration of 100–200 ng/g in dry weight of bone, for both young and old rats.
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  • 31
    ISSN: 1432-0738
    Keywords: Bezafibrate ; Rat ; Strain differences ; Lipids ; Marker enzymes ; Peroxisomes ; Mitochondria ; Micro-somes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of bezafibrate administered at 10 and 50 mg/kg/day for 7 days to male Sprague-Dawley (SD) and Lewis rats were investigated in order to determine the interrelation between the changes in serum and hepatic lipid contents and activities of selected peroxisomal, microsomal and mitochondrial enzymes in the two rat strains. In both strains, bezafibrate effectively reduced serum and hepatic lipids, increased the liver weight, induced a proliferation of peroxisomes, and selectively elevated the activities of carnitine acetyltransferase and of the enzymes of the peroxisomal Β-oxidation system. Moreover, immunoblotting revealed that the drug specifically enhanced the concentration of only those peroxisomal enzymes involved in fatty acid Β-oxidation. The data obtained demonstrate that although the responses initiated by bezafibrate are qualitatively similar in both strains, they differ in their magnitude in a dose-dependent manner, with the Lewis strain exhibiting a more pronounced response than the SD rats. These results show that dose-dependent strain differences as well as the generally known species differences should be taken into account in pharmacological and toxicological evaluations of fibrates in rodents. Furthermore, generalization and extrapolation from rodent studies should be treated with great caution.
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  • 32
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 66 (1992), S. 496-502 
    ISSN: 1432-0738
    Keywords: Spontaneous ; Tumor ; Neoplasm ; Rodent ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Incidence of neoplastic lesions in untreated Sprague-Dawley rats (1340 males and 1329 females) used as controls in 17 carcinogenicity studies are tabulated and evaluated. In male rats, the most common neoplasms were benign pheochromocytomas and keratoacanthomas (4.0% in each case) followed by pancreatic islet cell adenomas (3.7%), thyroid parafollicular cell adenomas (3.6%), fibromas and squamous cell papillomas of the skin and hepatocellular adenomas (2.0% in each), malignant lymphoma lymphocytic (1.9%), histiocytic sarcomas (1.4%), and adrenal cortical adenomas (1.2%). In female rats, the most common neoplasms were of mammary gland origin (31.3%: fibroadenoma 19.0%, adenocarcinomas 8.8%, and adenomas 3.5%) followed by thyroid parafollicular cell adenomas (2.9%), uterine endometrial stromal polyps (2.6%), adrenal cortical adenomas (1.9%), malignant lymphoma lymphocytic (1.6%), fibromas in the skin (1.3%), and pancreatic islet cell adenoma (1.1%). Metastases were observed from pheochromocytomas, hepatocellular carcinomas, nephroblastomas, renal pelvis transitional cell carcinoma, interstitial cell tumor and seminoma of the testes, Zymbal's gland adenocarcinomas, and mammary adenocarcinomas.
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  • 33
    ISSN: 1432-0738
    Keywords: Neurotransmitter ; Haloperidol ; Rat ; Brain -HPLC
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We investigated the influence of the dopamine antagonist haloperidol on the neurotransmitter content in the developing rat brain. Dopamine (DA), serotonin (5-HT) and the corresponding metabolites dopac, HVA and HIAA were determined in the corpus striatum of the rat between day 1 and day 21 pn by HPLC with electrochemical detection. A consistent increase in the content of dopamine was found during postnatal development. The concentrations (ng/g wet tissue; mean ±standard deviation) increased from 793±237 on day 1 pn to 4584±581 on day 21 pn, but remained still lower than in adult animals (9763±494). Similar results were found for the metabolites dopac and HVA. The content of dopac increased from 59±22 (day 1 pn) to 551±59 (day 21 pn) and the content of HVA from 53±18 (day 1 pn) to 419±41 (day 21 pn). Both metabolites were also about two times lower than in adult animals (dopac 1090± 282, HVA 744± 206). In contrast to dopamine and its metabolites we found no age-dependent changes in the content of 5-HT from day 1 pn (99± 11) to day 14 pn(121±21). A remarkable increase in the content of 5-HT was seen from day 14 pn to day 21 pn (438±56), reaching almost adult levels (570±92). The metabolite HIAA was nearly three times higher on day 21 pn (610±123) than on day 14 pn (223±28) and two times higher than in adults (321±58). One hour after application of haloperidol to the pups (1 mg/kg body wt i.p.) a significant increase (i.e. day 21 pn) of dopac (1755±496) and HVA (966±279), but not of 5-HT (382±72) or HIAA (614±130) was detected.
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  • 34
    ISSN: 1432-0827
    Keywords: Cortisol ; Cortical bone ; Bone biomechanics ; Rat ; Femur
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Doses of 8, 16 (low), 32, 48, 64 (medium), and 150 (high) mg/kg/day of cortisol were administered to groups of 8 growing rats each during 16 days, and their femurs were then submitted to 3-point bending tests at low strain rate. Low doses had no effect. Medium doses, previously shown to improve calcium (Ca) balance and weight gain in the species, augmented diaphyseal elastic and ultimate strength, stiffness, and plastic-to-elastic deformation ratio with respect to untreated controls. This effect was achieved either by enhancing bone mass (volume, sectional moment of inertia, wall/lumen ratio) without changes in material quality parameters (32 mg/kg/day) or, conversely, by increasing bone tissue mechanical properties (stress, modulus of elasticity) not affecting bone geometry (48 and 64 mg/kg/day). The highest dose, known to depress Ca balance and weight gain, impaired diaphyseal mechanical performance in controls by substantially reducing bone mass without major variation in bone material properties, that is, developing a true osteopenic state in mechanical terms. The energy elastically absorbed per unit volume (proportional to the risk of comminute fractures) was greater with the highest dose because of enhanced deformability and diminished bone mass. The biphasic dose-response curves obtained, grossly parallel to those previously demonstrated for metabolic actions of cortisol in the same species, showed that biomechanical repercussion of this treatment on bone depends on different, dose-dependent effects which vary independently in temporal course, intensity, and sign.
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  • 35
    ISSN: 1432-0827
    Keywords: Rat ; Osteoblast-like culture ; Ovariectomy ; Estrogens ; Bone blood supply
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Ovariectomy in the rat induces a rapid osteopenia associated with an elevated bone turnover. One hundred and twenty-day-old rats were ovariectomized (OVX) or sham-operated (n=6–8 per group and per time period studied). 45Ca accretion rate and bone blood flow (microspheres trapping technique) in the femurs were determined at 28, 42, 84, and 119 days after ovariectomy. Both parameters were markedly increased by 84 days and subsided thereafter. At the 42nd day, when bone turnover was maximal, bone marrow and trabecular bone cultures were obtained from shamoperated and ovariectomized animals (n=10/group). Proliferation rate of bone marrow cells and trabecular osteoblast-like cells estimated by fibroblast colony-forming units (FCFU) efficiency and cell counting was markedly increased in primary and secondary cultures in ovariectomy. These data fitted well with the enhanced number of osteoblasts observed in situ in the long bone metaphyses of estrogen-depleted animals. As estrogens were shown in the literature to inhibit proliferation of the red cell line and of other hemopoietic lines, it is possible that estrogens, through a general mechanism, inhibit hemopoietic and stromal lines and also the proliferation of bone marrow-derived trabecular bone cells.
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  • 36
    ISSN: 1432-0827
    Keywords: Bone alkaline phosphatase ; Rat ; Vitamin D ; Sorbitol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary In the femoral extremities of the adult rat containing the metaphysis, the epiphyseal cartilage, and the epiphysis, four alkaline phosphatase (AP) forms were distinguished on polyacrylamide gel electrophoresis. Two soluble forms were present in the 160,000 g supernatant: one of Mr 165 kDa and another of Mr 110–115 kDa, which exhibited a strong catalytical activity. Moreover, from the pellet, three membrane-bound forms of Mr 130, 110–115, and 100 kDa could be extacted with sodium deoxycholate. When denaturated AP was visualized by postelectrophoretic autoradiography of the phosphorylated intermediates, subunits always appeared as three monomers of Mr 75–80, 60–70, and 50–60 kDa. As four native forms but only three types of subunits were found to be present in the femur, it seems that, apart from homodimers, some heterodimers could also occur. Three types of diets were administered to three groups of rats for 5 weeks. Two are known to disturb bone mineralization: (1) a vitamin D3-deficient diet, and (2) the same as (1) but enriched with 12% sorbitol. The third was a normal diet containing vitamin D3. Concerning the effects on AP of dietary sorbitol and the vitamin D3-deficient diet, it was found that rats receiving the diet supplemented with sorbitol showed a substantial rise in the activity of the Mr 165 kDa form with the concomitant appearance of a new monomer of Mr 100 kDa. In contrast, rats fed the vitamin D3-deficient diet always displayed an increase in enzyme activity, principally of the Mr 100 and 110 kDa forms. In conclusion, the femur extracts of normal rats contained different forms of AP: either soluble 110–115 and 165 kDa forms or membrane-bound 130, 110–115, and 100 kDa forms. The administration of sorbitol-enriched diet induced a marked increase of the 165 kDa form whereas the administration of vitamin D3-deficient diet increased the 100 and 110 kDa forms.
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  • 37
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    Electronic Resource
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    Calcified tissue international 50 (1992), S. 524-526 
    ISSN: 1432-0827
    Keywords: Verapamil ; Bone ; Osteopenia ; Rat ; Female ; Intestinal calcium absorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Verapamil inhibits the intestinal absorption of calcium (Ca) and increases serum parathyroid hormone in rats. The effects of verapamil on bone tissue after long-term treatment is, however, not well described. Adult female and male Sprague-Dawley rats received verapamil in their drinking water at a dosage of 0.075 mg/ml (low dose) or 0.75 mg/ml (high dose) for 12 weeks; control rats received only drinking water. All rats were fed a diet containing 0.1% Ca and 0.5% P. In female rats, the amount of bone ash per volume was significantly reduced from 0.742 g/ml in controls to 0.713 g/ml after low-dose treatment of verapamil, and to 0.667 g/ml following high-dose treatment (P〈0.01). The tibial length was increased from 39.7 mm in controls to 40.3 mm or to 40.7 mm after low or high doses (P〈0.01). The tibial volume increased from 0.385 ml in controls to 0.397 ml after low doses and to 0.429 ml after high doses (P〈0.01). In contrast, in male rats the amount of bone ash per volume was significantly increased from 0.578 g/ml in controls to 0.580 g/ml after low doses and to 0.620 g/ml after high doses of verapamil (P〈0.01). The tibial bone volume in males as decreased from 0.633 ml in controls to 0.641 ml after low doses and to 0.583 ml after high doses (P〈0.05). The tibial length in the males was not changed by verapamil. The intestinal absorption of Ca was reduced in male rats from 5.28 in controls to 4.03 (serosa/mucosa) after low-dose treatment and to 2.46 after high-dose treatment with verapamil (P〈0.05). In female rats, the intestinal absorption of Ca did not change after verapamil treatment. Thus, chronic treatment with verapamil in female rats induced osteopenia whereas in male rats bone growth was inhibited.
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  • 38
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    Calcified tissue international 51 (1992), S. 30-34 
    ISSN: 1432-0827
    Keywords: PTHRP ; Anabolic ; Rat ; Bone ; Potency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Parathyroid hormone-related protein (PTHRP) has recently been purified from human tumors associated with the syndrome of humoral hypercalcemia of malignancy. The gene encoding PTHRP has been cloned, and based on predicted amino acid sequence, polypeptides comprising the first 36 [36Tyr(1–36) PTHRP amide] and 74 [(1–74)PTHRP] amino acids have been synthesized. Human (h) PTHRP (1–36) and (1–74) are potent bone-resorbing agents, and are catabolic for bone in vivo when given continuously at high doses. Bovine parathyroid hormone (bPTH) (1–34) is also catabolic for bone at high dose levels, but when given in low doses for weeks to months, it is anabolic. Although PTHRP possess several PTH-like properties in bone, hPTHRP (1–34) is reported to be only weakly anabolic in vivo. As polypeptide length influences PTHRP action, we evaluated hPTHRP(1–74) as an anabolic agent for bone in vivo. Twenty-four 4-week-old male Sprague-Dawley rats were given daily subcutaneous injections of hPTHRP(1–74) (1 and 2 nmol/100 g body weight, bw), bPTH(1–34) (4 nmol/100 g bw) or vehicle. Rats were sacrificed on day 12, and serum calcium, phosphorus, and 1,25 dihydroxyvitamin D and femoral bone dry weight, calcium content, and hydroxyproline content were measured. Serum calcium and phosphorus were equivalent in all groups. A significant increase in dry bone weight was observed in both PTHRP-treated groups compared with controls. PTHRP also caused a significant, dose-dependent increase in bone calcium and hydroxypro-line content. Results of these studies indicate that PTHRP (1–74) is anabolic for bone in vivo when administered at low-dosage levels for a prolonged period.
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  • 39
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    Calcified tissue international 51 (1992), S. 137-142 
    ISSN: 1432-0827
    Keywords: Swimming exercise ; Bone histomorphometry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary To specify the exercise-induced changes on different skeletal sites, the effect of a 5-week endurance swin training was studied in rats. Eighteen Lyon strain (Sprague-Dawley) 5-week old female rats were divided into nine sedentary and nine swimming rats. Each swim training session was increased by 15 minutes from 2–6 hours per day. A histomorphometric study was performed at the primary and secondary spongiosa of the distal femur and at the secondary spongiosa of lumbar and thoracic vertebral bodies. After training, bone loss was observed in the secondary spongiosa of lumbar vertebral bodies (24.7%) and in the primary spongiosa of distal femur (15.2%). A tendency to bone loss was also detected in the secondary spongiosa of distal femur (10.8%), whereas no change was detected in thoracic vertebral bodies. In secondary spongiosa, bone loss was accompanied with a thinning of trabeculae. Total eroded surfaces and osteoid surfaces were significantly decreased in the three studied skeletal sites, suggesting a decreased bone turnover. The decreased thickness of osteoid seams in both lumbar vertebrae and distal femur could mean that the osteoblastic activity has also been altered at the cell level, leading to thinning of trabeculae. Five-week swim training with such duration and intensity of exercise appears unable to increase bone volume in rats and, therefore, causes adverse effects. The three studied bones seemed to adapt differently to experimental conditions. The lack of ground reaction forces induced by water immersion might have contributed to the observed bone loss. “Normal” gravity would be an important cofactor in the osteogenic effects of exercise.
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  • 40
    ISSN: 1438-2199
    Keywords: Amino acids ; Aminooxyacetic acid ; Neostriatum ; Kynurenic acid ; N-Methyl-D-aspartic acid ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The endogenous tryptophan metabolite quinolinic acid elicits in rodent brain a pattern of neuronal degeneration which resembles that caused by L-glutamate. Its qualities as a neurotoxic agent raised the hypothesis that quinolinic acid might be involved in the pathogenesis of human neurodegenerative disorders. Kynurenic acid, another endogenous tryptophan metabolite and preferential N-methyl-D-aspartate (NMDA) antagonist, has been shown to block quinolinic acid neurotoxicity. Here we report that microinjections of aminooxyacetic acid (AOAA), an inhibitor of kynurenine transaminase and of other pyridoxal phosphate-dependent enzymes, into the rat striatum produce neuronal damage resembling that caused by quinolinic acid. AOAA-induced striatal lesions can be prevented by kynurenic acid and the selective NMDA antagonist 2-amino-7-phosphonoheptanoic acid. These results suggest that AOAA produces excitotoxic lesions by depleting brain concentrations of kynurenic acid (inhibition of synthetic enzyme) or due to impairment of intracellular energy metabolism (depletion of cell energy resources). The concept of deficient neuroprotection due to metabolic defects might help to clarify the pathogenesis of human neurodegenerative disorders and to develop strategies that may be useful in their treatment.
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  • 41
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    Amino acids 3 (1992), S. 131-138 
    ISSN: 1438-2199
    Keywords: Amino acids ; Osmolytes ; Dehydration ; Rat ; Taurine ; Myoinositol ; Sorbitol ; Betaine ; Glycerophosphorylcholine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary During antidiuresis cells in the renal inner medulla contain large amounts of sorbitol, myo-inositol, glycerophosphorylcholine and betaine to adjust the intracellular osmolality to the extracellular hyperosmolality. Although the accumulation of these four major organic osmolytes in the inner medulla of the dehydrated animal has been a consistent finding, the role of another class of organic osmolytes, amino acids, in osmoregulation in the kidney remains controversial. In the present study, renal responses of four major osmolytes and amino acids to dehydration were investigated using two HPLC systems. Taurine levels were significantly higher in the inner medulla of the dehydrated rats as compared with the control rats, and increased monotonically from the cortex to the inner medulla along the corticopapillary axis in the dehydrated rats. As for four major osmolytes, we confirm previously reported patterns in antidiuresis in greater detail. In conclusion, not only the four major osmolytes but taurine also plays a salient role in the osmoregulation in the kidney.
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  • 42
    ISSN: 1432-2307
    Keywords: Monoclonal antibody ; Digestive tract ; Colon cancer ; Rat ; Golgi apparatus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A monoclonal antibody, F11C, was raised against rat colon cancer cells. Its immunoreactivity on normal human and rat gut as well as human and rat colonic tumours was studied by the avidin-biotin-peroxidase complex technique. In both normal rat and human gastrointestinal tract, F11C stained surface epithelial cells from the fundus to distal colon, mainly as supranuclear vesicles. These vesicles appeared to be part of the Golgi apparatus on electron microscopy with immunogold labelling. Twenty primary rat colon tumours and 28 of 43 human colon tumours were also stained, with a heterogeneous pattern but much more strongly than the normal colonic mucosa. Biochemical purification suggested that in rat tumours F11C epitope was carried by a high molecular weight glycoprotein. Absorption experiments with synthetic oligosaccharides showed that F11C monoclonal antibody reacted with blood group A-related oligosaccharides. Nevertheless, F11C reactivity on human tissues was not related to the individual ABO or Lewis phenotype.
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  • 43
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    Archives of toxicology 66 (1992), S. 700-705 
    ISSN: 1432-0738
    Keywords: Aluminum ; Toxicokinetics ; Rat ; Parenterals
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The toxicokinetics of aluminum (Al) in male Wistar rats was studied after single intragastric (IG) doses of 1000 and 12000 μg Al/kg and intravenous (IV) doses of 10, 100, 1000, and 12000 μg Al/kg. Serial blood samples, daily samples of urine and feces as well as brain, liver, kidney, spleen, quadriceps muscle, and femur samples were collected. Al was measured by atomic absorption spectrometry. Al blood profiles after IV doses were adequately described by a two-compartment open model. Al toxicokinetics was dose dependent and appeared to plateau at 12000 μg/kg. At IV doses between 10 and 1000 μg/kg the terminal half-life of elimination from whole blood (t1/2β) increased from 29.9±7.8 to 209.3±32.6 min, and the total body clearance (CL) decreased from 2.45±0.64 to 0.28±0.03 ml min−1 kg−1. Following an IV bolus of 10 and 100 μg/kg the administered Al was recovered completely from urine (94.4%±9.9% and 98.5%±3.2%). Twenty-nine days after the IV dose of 1000 μg/kg daily renal excretion decreased to baseline values while only 55.1%±8.0% of the dose was excreted. Nineteen days after the single IV dose of 1000 μg/kg Al accumulated in liver (28.1±7.7 versus 1.7±0.5 μg/g of control rats) and spleen (72.5±21.1 versus 〈0.4 μg/g). After the single 1000 μg/kg IG dose no absorption of Al was detectable. The IG dose of 12000 μg/kg resulted in a maximum blood Al level of 47.9±12.4 μg/l after 50 min. The blood concentration time curve fitted a one-compartment open model with a half-life of absorption of 28.2±3.6 min and a t1/2β of 81.2±20.2 min. Cumulative renal Al excretion was 0.18%±0.10% of the dose and oral bioavailability was 0.02%. Seventeen days after the 12000 μg/kg IG dose the Al content in femur samples was increased (2.7±1.3 versus 0.6±0.4 μg/g). In no case was fecal elimination of incorporated Al observed.
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  • 44
    ISSN: 1432-0738
    Keywords: N-Nitrosamine ; Cytochrome P-450 ; Rat ; Phenobarbital ; β-Naphthoflavone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Five cytochrome P-450 forms were purified from livers of rats pretreated with phenobarbital (PB) or β-naphthoflavone (BNF), and the oxidative dealkylation of N-nitrosodialkylamines by the reconstituted cytochrome P-450 systems was measured. PB-II (P450IIB1) showed very high N-nitrosomethybutylamine (NMBA) debutylase activity, high NMBA demethylase activity and high N-nitrosomethyl-benzylamine (NMBeA) debenzylase activity, suggesting that the increase following PB treatment in hepatic microsomal NMBA debutylation and NMBeA debenzylation was due to the induction of PB-II. BNF-H (P450IA2) showed very high NMBA debutylase and high NMBeA debenzylase activities, and BNF-L (P450IA1) showed NMBA debutylase and high NMBeA debenzylase activities. These results suggested that the increase by BNF pretreatment in hepatic microsomal NMBA debutylation was due mainly to the induction of BNF-H and in some part to that of BNF-L. PB-II also showed very high dealkylation activity of lipophilic N-nitrosodialkylamines with long alkyl moieties. On the other hand, BNF-H dealkylated N-nitrosodipropylamine (NDPA), N-nitrosomethylbutylamine (NMBA) and N-nitrosoethylbutylamine (NEBA) at higher rates than N-nitrosodibutylamine (NDBA). BNF-L dealkylated NEBA at higher rates than NMBeA and NDBA. These results reveal that substrate specificity of each cytochrome P-450 form in N-nitrosodialkylamine metabolism is different from each other and several forms of cytochrome P-450 support each N-nitrosamine dealkylase activity in mammalians.
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  • 45
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    Journal of comparative physiology 171 (1992), S. 657-664 
    ISSN: 1432-1351
    Keywords: Inferior olivary complex ; Cerebellum ; 3-acetylpyridine ; Harmaline ; Learning ; Memory ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary DA/HAN-strained male rats (pigmented rats) were submitted to two experimental tasks consisting of spatial learning (water-escape) and a passive avoidance conditioning. Both these tasks were performed by different animals. In order to destroy the inferior olivary complex, the animals were injected with 3-acetylpyridine either 9 days prior to the initial learning session or 24 h after completion of the learning task. They were retested (retrieval test) 10 days after the initial learning was achieved. Learning and retention were compared to those noted in control rats. Administration of 3-acetylpyridine before the initial learning did not prevent the spatial learning but the scores were greatly altered and the number of trials needed to reach the fixed learning criterion was much greater than in controls. However, 10 days later the animals had memorized their initial experience. Injection of 3-acetylpyridine after the initial learning session impaired memory: the animals had completely forgotten their initial learning. It can therefore be concluded that lesion of the afferent climbing fibres to the cerebellar cortex alters learning and retention of a spatial task. Such a lesion does not interfere with learning and retention of a passive avoidance conditioning, since in this condition the experimental animals injected with 3-acetylpyridine either before or after the initial learning behave similarly to controls. The effects of the inferior olivary complex lesion are obviously different according to the task to be learnt, suggesting that these two tasks do not require the integrity of the same nervous structures.
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  • 46
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    Journal of comparative physiology 170 (1992), S. 645-650 
    ISSN: 1432-1351
    Keywords: Milk ejection reflex ; Positive pressure oscillations ; Motor activity of pups ; Tactile stimulation of nipples ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Changes of positive pressure exerted by pups on nipples during sucking were investigated using anesthetized, lactating dams. It was found that, every 50–60 s, individual pups performed bouts of pressure oscillations (3/s) of high amplitude which lasted about 10–12 s and coincided with periods of increased motor activity. During the intervals, when pups were quiet, series of low-amplitude oscillations (3/s) were also observed. Using a strain measuring method to record the activity of sucking pups, synchronization of activity of two or more pups was found to occur periodically every 25–30 s and, most frequently, 10–30 s before the reflex increase of milk pressure. In further experiments, artificial tactile stimulation was applied to the dam's nipples using the joint action of suction and positive pressure. Following a short-term (10–20 s) increase in frequency and amplitude of artificial nipple stimulation, 60%–80% of all reflexive peaks of milk pressure were elicited with a latency of 19 ± 5 s. This suggests that there are specific conditions under which the stimulation of nipples by pups may trigger the formation of the milk ejection reflex in the rat.
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  • 47
    ISSN: 1432-1106
    Keywords: GABA ; Iontophoresis ; Somatotopy ; SR95531 ; Ventrobasal thalamus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have recently described extensive inhibitory interactions between inputs to the ventroposterolateral (VPL) (Roberts and Wells 1990, 1991) and ventropos-teromedial (VPM) (Salt 1989) portions of the ventrobasal nucleus of the thalamus (VB). We wished to determine whether (i) the inhibition observed in the VPL was operating at the thalamic level, (ii) was dependant on GABA receptors, (iii) was demonstrable on neurons of the ventro-posteromedial nucleus of the thalamus (VPM) and (iv) was operant on test responses evoked by natural stimuli. Conditioning stimulation of sciatic nerve afferents caused inhibition of air jet evoked test responses of single VB neurons in urethane-anaesthetized rats. Both VPM and VPL neurons were subject to inhibition by conditioning stimulation of hindlimb afferents, indicating the widespread nature of the inhibitory process. This inhibition was reduced by the iontophoretic application of SR95531, a GABAA receptor antagonist. We conclude that there is a widely distributed inhibitory system operating in the somatic thalamus which involves both the medial and lateral portions of the nucleus and is, at least in part, mediated by GABAA receptors. The possible involvement of inhibitory processes and intrinsic membrane properties of thalamic neurones in the somatotopic plasticity of the sensory thalamus following deafferentation and in deaf-ferentation pain is discussed.
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  • 48
    ISSN: 1432-1106
    Keywords: Cerebellum ; Nucleus lateralis ; Rat ; Motor organization ; Microstimulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The motor organization of the nucleus lateralis (NL) of the rat's cerebellum was investigated by observing the motor effects of electrical microstimulations of the NL. The movements evoked by the NL mainly concerned forelimb and head segments. Only in a few cases were movements of hindlimb segments evoked. Motor effects were obtained according to a precise topographical pattern. This pattern delimited functional zones, or representations, within the NL, each zone being specifically related to a particular segment of the body. A few body segments were activated from single zones only (single representation) whereas some other body segments could be activated from different zones of the NL. Among them, the axio-proximal body segments were activated in a similar way from all sites (multiple representation) whereas the distal body segments were differently activated from the various representation zones (specific representation). The multiple and specific representations were distributed between the 3 cytoarchitectonic subregions of the NL (NLm, DLH and slp) in such a way that the body segments were usually represented only once in each individual NL subregion. Each NL subregion included sets of representations concerning body segments characterized by a topographical continuity (e.g. the different segments of the forelimb in both DLH and slp). Thus, the individual NL subregions may bring into play coordinate plurisegmental muscular activities of the limbs and/or of the head. The NLm controls movements of all the segments of the head and those of axio-proximal segments of both limbs. The DLH particularly controls movements of the head, including both the proximal (neck) and the oral regions. To a lesser degree, DLH controls movements of the various segments of the forelimb, including synchronous flexion of all the digits. The slp is specifically involved in the control of motor activities of: i) the proximal segment of the head (rotation of the neck) as well as its distal segments (displacement of individual vibrissae, rotation of the ear pinna) and ii) the various segments of the forelimb including individual digits. Functionally, the proximal segments would be concerned in the spatial displacement of the limbs or of the head whereas the distal segments would be involved in the realization of precise and discrete movements related to specific functions of the distal segments concerned. The 3 subregions of the NL may be concerned in different motor functions. The results suggest the involvement of: i) the NLm in the postural adjustments of the body, or of part of it; ii) the DLH in motor behaviours which integrate the oral and the forelimb motor activities; iii) the slp in exploratory activities (by moving individual vibrissae, the ear pinna and individual digits) and/or in discrete manipulative activities.
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  • 49
    ISSN: 1432-1106
    Keywords: Miniature EPSP ; Spinal cord cultures ; Motoneuron ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Miniature excitatory postsynaptic potentials (mEPSPs) were recorded in motoneurons grown in organotypic cocultures of embryonic rat spinal cord, dorsal root ganglia and muscle in the presence of TTX. The motoneurons were electrically compact with a mean electrotonic length of 0.6. Spontaneous EPSPs were found in most of these motoneurons. With TTX the large EPSPs disappeared, whereas in more than half of the experiments mEPSPs persisted with a range in size of 1 to 4 mV (mean: 2.1 mV), probabely originating from the spontaneous release of single vesicles. The net inward charge transfer at the soma ranged from 0.12 to 0.34 pC. The mEPSPs were heterogeneous in size even within pools of potentials that were homogeneous in shape. They had similar shapes and amplitudes as the smallest spontaneous unitary EPSPs mediated by presynaptic impulses, suggesting that for the smallest afferents not more than one vesicle was released per afferent impulse. Both the miniature and the TTX-sensitive EPSPs were readily blocked by the glutamate antagonist DNQX.
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  • 50
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    Experimental brain research 89 (1992), S. 459-464 
    ISSN: 1432-1106
    Keywords: Fetal breathing ; Respiratory centers ; Development ; Ontogeny ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A fetal rat brain stem-spinal cord in vitro preparation (15–20 days) which retains for several hours respiratory-like discharges on cervical and cranial ventral roots has been developed for analysing fetal central respiratory activity. Two different patterns of easily distinguishable rhythmic activity were recorded. The first, of spinal origin, appeared every 2–10 min as long bursts of potentials (3–30 s) on cervical, but not hypoglossal, roots. The second pattern corresponded to brief bursts (1 s) of potentials occurring on both cervical and hypoglossal roots at a frequency ranging from 3–4 cycles min-1. The second type of activity was likely to be respiratory since it originated from the medulla, and behaved similarly to the respiratory activity recorded in vitro from newborn rats. The fetal respiratory-like activity was never observed at day 15, appeared at day 16 in 30% of the preparations with fluctuating frequency and amplitude bursts, and stabilised at day 20 where it was usually present and resembled newborn rat respiratory activity: its frequency was stable but was reduced by withdrawal of CO2 and pH stimuli and modulated by a pontine noradrenergic influence. This fetal preparation offers many advantages for studying the ontogeny of the central respiratory activity because of the background knowledge available on the adult and newborn rat respiratory centers and the possibility of performing electrophysiological, morphological and pharmacological fetal studies directly at the central level without any feedback from the periphery.
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  • 51
    ISSN: 1432-1106
    Keywords: Colchicine ; Choline acetyltransferase ; Cholinergic degeneration ; Phosphoinositide hydrolysis ; Cytoskeletal proteins ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Colchicine, a microtubule disrupting toxin, was administered intracerebroventricularly to rats, followed by measurements of (i) the activity of choline acetyltransferase, a biochemical marker of cholinergic neurons, (ii) cytoskeletal protein concentrations, including tau, MAP-2, spectrin, and tubulin, and (iii) the activity of the second messenger-generating system, receptor-coupled phosphoinositide hydrolysis. One week after colchicine treatment there was a 60% decrease in choline acetyltransferase activity in the hippocampus, which was followed by a gradual increase to only a 29% deficit after 12 weeks. In the striatum and cerebral cortex, choline acetyltransferase activity was slightly reduced (by 13% and 19%, respectively) 1 week after colchicine treatment followed by increases to control values. The concentrations of tau and tubulin in the hippocampus were unaltered by colchicine treatment, and MAP-2 and spectrin were only slightly reduced 4 weeks after colchicine. Hippocampal phosphoinositide hydrolysis induced by norepinephrine was elevated approximately 28% 1 and 2 weeks after colchicine treatment and that induced by ibotenate was increased by 53% 2 weeks after colchicine. These results demonstrate that colchicine causes a severe depletion of choline acetyltransferase 1 week after administration. There was not a significant reduction of the concentration of any of the cytoskeletal proteins after 1 week, possibly due to the cell-selectivity of the toxic effect of colchicine, but there was a delayed, and temporary, decline of MAP-2 and spectrin concentrations. Associated with the decreased choline acetyltransferase activity after 1 week was an enhanced phosphoinositide hydrolysis in response to norepinephrine, and after 2 weeks there were enhanced responses to norepinephrine and to ibotenate. Thus, colchicine-induced toxicity results in neurotransmitter- and time-specific alterations in the activity of the phosphoinositide second messenger-generating system in the hippocampus.
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  • 52
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    Experimental brain research 91 (1992), S. 94-104 
    ISSN: 1432-1106
    Keywords: Frequency modulation ; Intracellular recordings ; Horseradish peroxidase ; Inferior colliculus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The response characteristics to linear frequency sweeps were studied in two groups of FM (frequency modulation) sensitive neurons in the rat inferior colliculus. ‘FM specialized’ cells responded to frequency sweeps but not to pure tones. ‘Mixed’ cells responded to both frequency sweeps and pure tones. FM specialized cells preferred faster and broader sweeps of higher intensity than did mixed cells and were more directionally selective. In addition, FM specialized cells were more sharply tuned to FM velocity and FM range and had longer response latencies. Physiologically identified FM cells stained intracellularly with horseradish peroxidase revealed differences in morphology correlating with the differences in their responses to tones. FM specialized cells had larger dendritic fields, more dendritic branching and more dendritic spines than did mixed cells. The findings are taken as evidence that the two groups of inferior colliculus neurons are both functionally and morphologically distinct.
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  • 53
    ISSN: 1432-1106
    Keywords: Basic fibroblast growth factor ; Forebrain ischemia ; Astrocyte ; Immunoreactivity ; mRNA level ; Hippocampus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We examined the time course of basic fibroblast growth factor (bFGF) immunoreactivity and its mRNA level mainly in the hippocampus after transient forebrain ischemia using immunohistochemistry, enzyme immunoassay (EIA), Western blot analysis and in situ hybridization. Neuronal death in the hippocampal CA1 subfield was observed 72 h after 20 min of ischemia. The number of bFGF-immunoreactive(IR) cells increased 48 h–5 days after ischemia in all hippocampal regions. At 10 and 30 days, the bFGF-IR cells in the CA1 subfield had further increased in numbers and altered their morphology, enlarging and turning into typical reactive astrocytes with the advancing neuronal death in that area. In contrast, the number of bFGF-IR cells in other hippocampal regions had decreased 30 days after ischemia. The EIA study showed a drastic increase in bFGF levels in the hippocampus 48 h after ischemia (150% of that in normal rat) which was followed by further increases. In Western blot analysis, three immunoreactive bands whose molecular weights correspond to 18, 22 and 24 kDa were observed in normal rat and ischemia increased all their immunoreactivities. In the in situ hybridization study of the hippocampus, bFGF mRNA positive cells were observed in the CA1 subfield in which many bFGF-IR cells existed after ischemia. These data demonstrate that transient forebrain ischemia leads to an early and strong induction of bFGF synthesis in astrocytes, suggesting that the role of bFGF is related to the function of the reactive astrocytes which appear following brain injury.
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  • 54
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    Experimental brain research 90 (1992), S. 47-53 
    ISSN: 1432-1106
    Keywords: Energy metabolism ; Free nucleotides ; Ischemia ; Brain ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Loss of cellular ion homeostasis during anoxia, with rapid downhill fluxes of K+, Ca2+, Na+ and Cl-, is preceded by a slow rise in extracellular K+ concentration (K e + ), probably reflecting early activation of a K+ conductance. It has been proposed that this conductance is activated by either a rise in intracellular calcium concentration (Ca i 2+ ), or by a fall in ATP concentration. In a previous study from this laboratory (Folbergrová et al. 1990) we explored whether the early activation of a K+ conductance could be triggered by a rise in Ca i 2+ . To that end, labile metabolites and phosphorylase a, a calcium sensitive enzyme, were measured after 15, 30, 60 and 120 s of complete ischemia (“anoxia”). In the present study, we investigated whether brief anoxia is accompanied by changes in ATP/ADP ratio, or in the phosphate potential, which could cause activation of a K+ conductance. To provide information on this issue, we added a group with 45 s of anoxia to the previously reported groups, and derived changes in intracellular pH (pHi). This allowed calculations of the free concentrations of ADP (ADPf) and AMP (AMPf) from the creatine kinase and adenylate kinase equilibria, and hence the derivation of ATP/ADPf ratios. In performing these calculations we initially assumed that the free intracellular Mg2+ concentration remained unchanged at 1 mM. However we also explored how a change in Mg i 2+ of the type described by Brooks and Bachelard (1989) influenced the calculation. The results showed that ADPf must have risen to 150–200% of control within 15 s, and to 330–350% of control within 45 s of anoxia. The concentration of AMPf should have increased 2–4 fold in 15 s and 10–20 fold in 45 s. Thus although tissue ATP concentration usually remains 〉90% of control within the first 30s of anoxia, and 〉80% of control within the first 45 s, the ATP/ADPf ratios change markedly at a time when alterations in ion homeostasis are dominated by a moderate rise in K e + , and long before massive ion fluxes occur and the cells depolarise (after about 60–70 s). Such early changes in ATP/ADPf ratio, or in phosphate potential, could well influence reactions which are coupled to ATP hydrolysis, and perhaps lead to activation of ATP-dependent K+ conductances.
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  • 55
    ISSN: 1432-1106
    Keywords: Basal forebrain ; Acetylcholine ; Attention ; Transplantation ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Degeneration of the cholinergic magnocellular neurons in the basal forebrain and their cortical projections is a major feature of the neuropathology of Alzheimer's disease. In the present study, two experiments examined the disruptive effects on visual attentional performance of two different manipulations that reduce central cholinergic function. In Expt. I, pharmacological manipulation of the cholinergic system was investigated using icv administration of hemicholinium (HC-3), a 9high affinity choline uptake blocker, administered either alone or in conjunction with the anticholinesterase, physostigmine. The results revealed impairments in the ability of the rats to localize brief visual targets in a serial reaction time task, as shown in particular by a reduction in choice accuracy and lengthening of the latency to respond correctly to the visual stimulus. Cholinergic specificity was supported by the reversal of these behavioural impairments by pre-treatment with the anticholinesterase, physostigmine. In Expt. II, quisqualateinduced lesions of the basal forebrain produced behavioural deficits at 3 weeks post-lesion surgery similar to those observed following icv infusion of HC-3. In an attempt to restore the extrinsic cortical cholinergic innervation by reinnervation of the deafferented cortex, embryonic basal forebrain cholinergic cells were transplanted into the cortex of lesioned animals. After three months recovery, impairments in performance on the baseline schedule of the task were no longer apparent in lesioned animals. However, behavioural deficits, observed predominantly as a lengthening of correct response latency, could be reinstated in the lesioned animals by interpolation of distracting bursts of white noise during each trial, and this deficit was ameliorated by the cholinergic grafts. Furthermore, a non-specific effect of both cholinergic and non-cholinergic grafts in controlling the increase in perseverative time-out responses which occurred as a result of the basal forebrain lesion was consistently observed. These results suggest that cholinergic dysfunction can produce deficits in visual attention which can be ameliorated by cholinergic treatments such as physostigmine or cholinergic-rich cortical grafts. These data provide support for a role for the basal forebrain-neocortical cholinergic projection in attentional function.
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  • 56
    ISSN: 1432-1106
    Keywords: Transplantation ; Developmental neurobiology ; Retrograde labelling ; Immunocytochemistry ; Acetylcholinesterase histochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Embryonic spinal cord grafts from 12-day-old rat embryos were placed into the lumbar spinal cord of adult rats depleted of sciatic motoneurones by a neonatal nerve injury. A soleus muscle was removed from the leg and implanted paravertebrally, the proximal end of its nerve connected to the graft site. Fluorescent retrograde tracers injected into the soleus implant, 37–64 days postoperatively, labelled neurones that had grown axons to the muscle. Approximately one-fifth of retrogradely labelled neurones were within the graft; however, the majority were found within the host spinal cord close to the graft. These included large neurones within the motoneurone-depleted dorsolateral ventral horn. In control experiments a muscle and nerve were implanted but no embryonic tissue grafted. Significantly fewer neurones were labelled. In some animals, one tracer was injected into the soleus muscle whilst another was applied to the cut sciatic nerve ipsilateral to the graft site. No neurones were found to project axons to both targets. In animals that received grafts prelabelled with bromodeoxyuridine (BrDU) some neurones were found to be both BrDU positive and retrogradely labelled from the soleus implant. These were most frequently within the motoneuronedepleted ventral horn ipsilateral to the graft. Thus, grafted neurones may migrate to an appropriate location within the host neuropil. Acetylcholinesterase (AChE) histochemistry showed the graft site contained immature but AChE-positive neurones. Some regions of host ventral horn contained unusually few AChE-positive nerve fibres and occasional large AChE-positive neurones, some of which were also retrogradely labelled from the implanted muscle. Studies of implanted soleus 21–90 days after transplantation showed that muscle fibres, after initial degeneration, regenerated displaying differing phenotypes, presumably under the influence of new motor innervation.
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  • 57
    ISSN: 1432-1106
    Keywords: Vibrissae ; Somatosensory system ; Cortical columns ; Receptive field ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A “barrel” is an interconnected network of layer IV neurons that is an important component of a functional cortical column in the whisker area of the rodent primary somatosensory cortex. The present study was undertaken in order to resolve apparently conflicting findings from single-unit studies of barrel neurons conducted in rats maintained under different anesthetic conditions. Multiunit responses to controlled deflections of mystacial vibrissae were recorded from the whisker/ barrel cortex of awake, undrugged rats, and responses at the same recording site were reexamined after the animal was anesthetized with urethane. In contrast to the awake condition, stimulus-evoked responses under urethane were characterized by a large late component. Such effects were more pronounced for deflections of noncolumnar or “adjacent” whiskers than for the the columnar whisker. Latencies to peak responses were virtually identical for the columnar whisker in awake and urethane states (11.9 vs 11.8 ms) but were considerably longer for adjacent whisker deflections in urethane-anesthetized animals (15.5 vs 29.0 ms). The magnitudes of adjacent whisker responses, relative to the response evoked by the columnar whisker, varied with the laminar location of the recording site in awake but not in urethane-anesthetized animals; in awake rats, receptive fields were clearly smallest in the layer IV barrels. Results in the awake condition confirm those of previous studies conducted in unanesthetized or lightly sedated animals, and data obtained with urethane are comparable to others' results in urethane-anesthetized rats. The former have important implications for how barrel cortex processes information in behaving animals.
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  • 58
    ISSN: 1432-1106
    Keywords: GAP-43 ; In situ hybridization ; Spinal cord ; Axotomy ; Rat ; Cat ; Monkey
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In situ hybridization histochemistry was used to detect cell bodies expressing mRNA encoding for the phosphoprotein GAP-43 in the lumbosacral spinal cord of the adult rat, cat and monkey under normal conditions and, in the cat and rat, also after different types of lesions. In the normal spinal cord, a large number of neurons throughout the spinal cord gray matter were found to express GAP-43 mRNA. All neurons, both large and small, in the motor nucleus (Rexed's lamina IX) appeared labeled, indicating that both alpha and gamma motoneurons express GAP-43 mRNA under normal conditions. After axotomy by an incision in the ventral funiculus or a transection of ventral roots or peripheral nerves, GAP-43 mRNA was clearly upregulated in axotomized motoneurons, including both alpha and gamma motoneurons. An increase in GAP-43 mRNA expression was already detectable 24 h postoperatively in lumbar motoneurons both after a transection of the sciatic nerve at knee level and after a transection of ventral roots. At this time, a stronger response was seen in the motoneurons which had been subjected to the distal sciatic nerve transection than was apparent for the more proximal ventral root lesion. An upregulation of GAP-43 mRNA could also be found in intact motoneurons located on the side contralateral to the lesion, but only after a peripheral nerve transection, indicating that the concomitant influence of dorsal root afferents may play a role in GAP-43 mRNA regulation. However, a dorsal root transection alone did not seem to have any detectable influence on the expression of GAP-43 mRNA in spinal motoneurons, while the neurons located in the superficial laminae of the dorsal horn responded with an upregulation of GAP-43 mRNA. The presence of high levels of GAP-43 in neurons has been correlated with periods of axonal growth during both development and regeneration. The role for GAP-43 in neurons under normal conditions is not clear, but it may be linked with events underlying remodelling of synaptic relationships or transmitter release. Our findings provide an anatomical substrate to support such a hypothesis in the normal spinal cord, and indicate a potential role for GAP-43 in axon regeneration of the motoneurons, since GAP-43 mRNA levels was strongly upregulated following both peripheral axotomy and axotomy within the spinal cord. The upregulation of GAP-43 mRNA found in contralateral, presumably uninjured motoneurons after peripheral nerve transection, as well as in dorsal horn neurons after a dorsal root transection, indicates that GAP-43 levels are altered not only as a direct consequence of a lesion, but also after changes in the synaptic input to the neurons.
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  • 59
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    Experimental brain research 92 (1992), S. 69-78 
    ISSN: 1432-1106
    Keywords: Kindling ; Reactive sprouting ; Dendritic spines ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A Golgi and electron microscopy study of the hippocampal CA3 region was performed on control and kindled Wistar rats. The observations provide evidence that, in epileptic rats, mossy fibres sprout and establish novel synapses with the basilar dendrites of CA3 pyramidal neurons. These newly-developed synapses showed the typical features of mossy synapses observed in the stratum lucidum, including the appearance of complex giant spines. The morphological changes reported here may represent a histopathological substrate for the epilepsy in the absence of overt signs of a hippocampal lesion.
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  • 60
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    Experimental brain research 92 (1992), S. 46-58 
    ISSN: 1432-1106
    Keywords: Medullary reticular formation ; Gigantocellular reticular nucleus ; Reticulospinal ; Lateral and medial longissimus ; Lumbar and cervical spinal cord ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary These experiments tested hypotheses about the logic of reticulospinal and reticuloreticular controls over deep back muscles by examining descending efferent and contralateral projections of the sites within the medullary reticular formation (MRF) that evoke EMG responses in lumbar axial muscles upon electrical stimulation. In the first series of experiments, retrograde tracers were deposited at gigantocellular reticular nucleus (Gi) sites that excited the back muscles and in the contralateral lumbar spinal cord. The medullary reticular formation contralateral to the Gi stimulation/deposition site was examined for the presence of single- and double-labeled cells from these injections. Tracer depositions into Gi produced labeled cells in the contralateral Gi and Parvocellular reticular nucleus (PCRt) whereas the lumbar injections retrogradely labeled cells only in the ventral MRF, indicating that separate populations of medullary reticular cells project to the opposite MRF and the lumbar cord. In the second series of experiments the precise relationships between the location of neurons retrogradely labeled from lumbar spinal cord depositions of the retrograde tracer, Fluoro-Gold (FG) and effective stimulation tracks through the MRF were examined. The results indicate that the Gi sites that are most effective for activation of the back muscles are dorsal to the location of retrogradely labeled lumbar reticulospinal cells. To verify that cell bodies and not fibers of passage were stimulated, crystals of the excitatory amino acid agonist, N-methyl-d-asparate (NMDA) were deposited at effective stimulation sites in the Gi. NMDA decreased the ability of electrical stimulation to activate back muscles at 5 min postdeposition, indicating a local interaction of NMDA with cell bodies at the stimulation site. In the third series of experiments, electrical thresholds for EMG activation along a track through the MRF were compared to cells retrogradely labeled from FG deposited into the cervical spinal cord. In some experiments, Fast Blue was also deposited into the contralateral lumbar cord. Neurons at low threshold points on the electrode track were labeled following cervical depositions, indicating a direct projection to the cervical spinal cord. The lumbar depositions, again, labeled cells in MRF areas that were ventral to the locations of effective stimulation sites, primarily on the opposite side of the medulla. In addition, the lumbar depositions back-filled cells in the same cervical segments to which the Gi neurons project. These results suggest that one efferent projection from effective stimulation sites for back muscle activation is onto propriospinal neurons in the cervical cord, which in turn project to lumbar cord levels. In a final series of experiments, a stimulating electrode track through the MRF again identified low threshold and ineffective sites for activating lumbar epaxial EMG. Fluoro-Gold was deposited in the contralateral MRF (MRFc) at a low threshold stimulation site for activating back muscles on that side. Retrogradely labeled cells surrounded effective, but not ineffective, stimulation sites along the electrode track in the MRF. Thus, another projection from effective stimulation sites is to effective stimulation sites in the opposite MRF. These results suggest that neurons in Gi whose stimulation most effectively activates back muscle EMG do not project directly to the lumbar cord, but relay to cervical cord neurons, which in turn project onto lumbar neurons. The MRF commissural connections presumably amplify this descending MRF control of axial back muscles.
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  • 61
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    Experimental brain research 91 (1992), S. 12-20 
    ISSN: 1432-1106
    Keywords: Choleragenoid ; Horseradish peroxidase ; Lumbar spinal ganglia ; Brainstem nuclei ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Brain stem projections from each of the L1–L6 lumbar dorsal root ganglia (DRGs) were investigated in adult rats following DRG injections of choleragenoid-horseradish peroxidase. All these DRGs projected throughout the rostrocaudal extent of the gracile nucleus (Gr). Labeling from L1–L6 DRGs was transported to successively more dorsomedial areas of Gr. Investigation of the Gr projections from the DRGs revealed a somatotopic organization which was most prominent in the middle part of Gr. The cuneate nucleus showed smaller projections from all investigated DRGs. Minor projections to the internal basilar nucleus, external cuneate nucleus, medial vestibular nucleus, ventral cochlear nucleus and trigeminal sensory nuclei were also found from some of the DRGs.
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  • 62
    ISSN: 1432-1106
    Keywords: Peripheral nerve injury ; Glabrous skin ; Sensory nerve endings ; Neuropeptide ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Immunohistochemistry has been used to study, the capacity of different types of sensory axons in the saphenous nerve to extend into denervated glabrous skin territory after a chronic sciatic nerve lesion. In this study, the extension of the intact or regenerating thin peptidergic and coarse saphenous nerve fibres in adult and neonatal rats was determined. Substance P (SP) and calcitonin gene-related peptide (CGRP) antibodies were used as markers for thin axons and neurofilament (NF) antibodies for coarse axons. In addition, S-100 protein (S-100) antibodies, which primarily stain Schwann cells associated with myelinated axons, as well as innervated lamellated cells of Meissner corpuscles, were used. After a chronic sciatic nerve lesion in adult rats, thin dermal and epidermal SP-immunoreactive (IR) and CGRP-IR saphenous nerve fibres were present in an area lateral to that normally innervated by the saphenous nerve in the foot sole. In neonatally lesioned animals, thin dermal and epidermal SP-IR and CGRP-IR, as well as coarse dermal NF-IR fibres and S-100-IR cells, all of which derived from the saphenous nerve, were found in the sciatic nerve territory. In addition, some dermal SP-IR and CGRP-IR fibres were transiently present in the lateral part of the foot sole. After chronic sciatic nerve lesion and a concomitant crush injury of the saphenous nerve in adults or neonatals, thin dermal and epidermal SP-IR and CGRP-IR fibres, as well as coarse dermal NF-IR fibres and S-100-IR cells, were found in the innervation area normally occupied by the sciatic nerve. After a sciatic nerve cut and a concomitant crush injury of the saphenous nerve in adult rats, the SP-IR and CGRP-IR fibres, as well as the NF-IR fibres and S-100-IR cells were restricted to the medial part of this area. After a sciatic nerve cut and a concomitant crush injury of the saphenous nerve in neonatal rats, a few thin dermal SP-IR and CGRP-IR fibres were found in the lateral part of the foot sole as well. The findings of the present study together with those of previous morphological studies indicate that intact thin axons from the saphenous nerve, including those exhibiting peptide immunoreactivity, but not coarse saphenous axons, are capable of extending into “foreign” denervated glabrous skin after chronic sciatic nerve injuries. In neonatally sciatic-nerve-injured animals, both groups of axons spread from the intact saphenous nerve into the sciatic nerve territory. This was also the case when the saphenous nerve had been crushed and allowed to regenerate in rats injured neonatally, or as adults. However, judging from previous physiological data, the regenerating axons do not develop into functional low-threshold mechanoreceptors.
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  • 63
    ISSN: 1432-1106
    Keywords: Autoradiography ; Cerebral blood flow ; Cerebral ischemia ; Iodoantipyrine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Cerebral blood flow and histopathological changes after bilateral carotid artery ligation (BCAL) in Wistar rats were studied. Eight of the 38 rats (21%) died within one week. In the 30 survivors, the incidence of histopathological change was 90% in the caudate nucleus, 23% in the cortex, 30% in the hippocampus, and 0% in the other structures. Local cerebral blood flow (LCBF) was measured using the quantitative autoradiographic 14C-iodoantipyrine technique in 24 anatomically discrete regions of the brain. BCAL induced ischemia in the entire forebrain. The percent reduction of LCBF was between 25–94% of the control at 2.5 h after BCAL. LCBF tended to recover 1 week after BCAL except for the regions of neuronal damage. These results suggest that neuronal damage does not correlate with the flow rate. In the present study, selective neuronal damage was also observed in rats with chronic cerebral ischemia.
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  • 64
    ISSN: 1432-1106
    Keywords: Basal ganglia ; Pedunculopontine nucleus ; Substantia nigra pars compacta ; Excitatory amino acids ; Acetylcholine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Extracellular single-neuron recordings were obtained from electrophysiologically identified nigrostriatal neurons in chloral hydrate anesthetized rats, in order to test the hypothesis that excitatory amino acid receptors are involved in responses of these neurons to electrical stimulation of the pontine region where the pedunculopontine nucleus (PPN) is located. The effects of iontophoretic application of excitatory amino acids and their antagonists as well as of cholinergic antagonists were tested on the fast orthodromic excitation of nigrostriatal neurons evoked by stimulation of the PPN region. The N-methyl-D-aspartate (NMDA) receptor antagonist D-a-aminoadipic acid as well as the cholinergic receptor antagonists mecamylamine and atropine failed to suppress the synaptic excitation of nigral neurons. The NMDA receptor antagonist DL-2-amino-5-phosphonovalerate exerted a weak depressant action on the synaptic response in a few neurons only. On the contrary, the broad spectrum antagonists of excitatory amino acid receptors kynurenic acid and gamma-Dglutamyl-amino-methyl-sulphonate were found to block simultaneously both the synaptic excitation and the neuronal responses to iontophoretic pulses of glutamate while leaving unaffected the neuronal responses to local application of acetylcholine or carbachol. The competitive antagonist of non-NMDA receptors 6-cyano-2,3-dihy-droxy-7-nitro-quinoxaline suppressed the synaptic excitation at ejection currents which antagonized neuronal responses to quisqualate and kainate. These results suggest that PPN excitatory fibers synapsing onto pars compacta nigrostriatal neurons utilize an excitatory amino acid as a synaptic transmitter acting preferentially on non-NMDA receptors.
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  • 65
    ISSN: 1432-1106
    Keywords: Synaptic-Plasticity ; Cerebellum ; Metabotropic-glutamate-receptor ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Using an in vitro slice preparation, we studied the effects, on parallel fiber (PF)-mediated EPSPs, of coactivation of metabotropic-glutamate receptors and of voltage-gated calcium (Ca) channels of Purkinje cells (PCs) by bath application of 50 μM trans-1-aminocyclopentyl-1,3-dicarboxylate (trans-ACPD) and by direct depolarization of the cells, respectively. These effects were compared with changes in synaptic efficacy obtained when α-amino-3hydroxy-5-methylisoxalone-4-propionate (AMPA) receptors of PCs were also activated through stimulation of PFs during the pairing protocol, as well as when similar experiments were performed without trans-ACPD in the bath. In a control medium, pairing for 1 min of PF-mediated EPSPs evoked at 1 Hz with Ca spikes evoked by steady depolarization of PCs (n = 13) led to LTD of synaptic transmission in 9 cases whereas for the others EPSPs were not affected. No LTD occurred in 9 out of 10 other cells tested when PF stimulation was omitted during the 1 min period of Ca spike firing of PCs. Bath application of 50 μM trans-ACPD, in conjunction with the same pairing protocol as before (n = 8), led to a significantly larger LTD of PF-mediated EPSPs after washing out of this drug. Moreover, a clearcut LTD of PF-mediated EPSPs was also observed in 5 of the 8 other cells, when PF stimulation was omitted during Ca spike firing in the presence of trans-ACPD. As trans-ACPD alone induced fully reversible depressions of EPSPs, coactivation of metabotropic-glutamate receptors and of voltage-gated Ca channels is therefore likely to be sufficient to induce LTD of PF-mediated EPSPs.
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  • 66
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    Experimental brain research 90 (1992), S. 343-345 
    ISSN: 1432-1106
    Keywords: Motoneuron ; Motor axon ; Nerve conduction ; Development ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Axon conduction distance, conduction velocity, and conduction time were measured for individual triceps surae motoneurons in Sprague-Dawley rats weighing 230–630 g (i.e., age range 6–16 weeks). Both conduction distance (nerve length) and velocity were closely correlated with weight (r=0.95 and r=0.82, respectively). In contrast, conduction time did not change as weight increased nearly threefold. This striking constancy is probably due to a corresponding increase in axon diameter. It could contribute to maintenance of stable motor performance during rapid growth.
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  • 67
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    Experimental brain research 92 (1992), S. 259-266 
    ISSN: 1432-1106
    Keywords: Hypoglycemia ; Neuronal death ; N-methyl-D-aspartate ; AMPA ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Excitatory amino acids are implicated in the development of neuronal cell damage following periods of reversible cerebral ischemia or insulin-induced hypoglycemic coma. To explore the importance of glutamate receptor activation in the posthypoglycemic phase, we exposed rats to 20 min of insulin-induced severe hypoglycemia. The rats were treated immediately after the hypoglycemic insult with four regimes of glutamate receptor antagonists: (1) the AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propriate)-receptor antagonist NBQX [2.3-dihydroxy-6-nitro-7-sulfamoyl-benzo (F) quinoxaline] given as a bolus dose of 30 mg · kg-1 i.p., followed by an i.v. infusion of 225 μg · kg-1 · min-1 for 6 h; (2) the non-competitive NMDA-receptor antagonist, dizocilpine (MK-801) 1 mg · kg-1 given i.v.; (3) a combined NBQX treatment, (a bolus dose of 10 mg · kg-1 i.p., followed by an i.v. infusion of 225 μg · kg-1 · min-1 for 6 h), with dizocilpine 0.33 mg · kg-1 given twice i.p. at 0 and 15 min after recovery and (4) the competitive NMDA-receptor blocker CGP 40116 [D-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid] 10 mg · kg-1 given i.p.. In the striatum, all glutamate receptor blockers significantly decreased neuronal damage by approximately 30%. An approximately 50% decrease in neuronal damage was demonstrated in neocortex and hippocampus following the combined treatment with NBQX and dizocilpine, while protection was variable following the treatment with a single glutamate-receptor antagonist. We conclude that neuronal damage continues to develop in the striatum and in cortical brain regions in the posthypoglycemic period and that both NMDA- and AMPA-receptors contribute to this process, possibly by a change in the cellular response to both AMPA- and NMDA-receptor stimulation.
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  • 68
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    Experimental brain research 89 (1992), S. 581-587 
    ISSN: 1432-1106
    Keywords: Norepinephrine ; Hippocampus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Glutamate pressure ejections in the vicinity of locus coeruleus (LC) neurons have been shown to produce both short and long-lasting potentiation of perforant path (PP) evoked population spike amplitude in the dentate gyrus (DG). These effects of LC-glutamate activation resemble those produced by direct application of NE in vitro or in vivo. The present study monitored the cellular response of LC neurons to local glutamate ejections concomitant with stimulation of the PP evoked potential. Double barrel micropipettes or 33 ga cannulaelectrode assemblies permitted LC unit recording and glutamate ejection at or near the same site in urethane anesthetized rats. Glutamate ejections produced a burst of LC activity lasting 250–400 ms and followed by a depression of unit activity lasting 4.6 min. The maximal spike potentiation produced by LC activation was 158%. The first spike to exceed the control range occurred 34 s after the LC burst. Comparable silent intervals in LC unit activity induced by systemic clonidine were not accompanied by population spike amplitude potentiation. The mean duration of potentiation was 4.4 min except in four cases where responses remained potentiated for the duration of the experiment. The duration of potentiation was not correlated with the termination of LC depression. LC units recovered to baseline rates following glutamate induced depression of activity. The occurrence of potentiation appeared to require that glutamate activation reach a critical number of LC neurons since small glutamate ejections could produce a local burst without eliciting potentiation. Long-lasting changes were also related to larger glutamate volumes (100 nl). EPSP slope increases were briefer and occurred less frequently than spike amplitude changes suggesting EPSP-spike dissociation. The delay between the burst of LC activity and amplitude increases in the DG supports a model of NE action in which there are both rapid and slowly developing effects of NE release in the DG. In summary, brief, but intense, activation of LC neurons produces a delayed potentiation of DG responses lasting minutes to hours following the LC burst.
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  • 69
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    Experimental brain research 90 (1992), S. 11-20 
    ISSN: 1432-1106
    Keywords: Homocysteic acid ; Cerebellum ; Taurine ; Glial cells ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An antiserum to homocysteic acid was raised in rabbits. Immunogens were prepared by coupling this amino acid to bovine serum albumin by means of glutaraldehyde and paraformaldehyde. When applied to semithin or ultrathin sections of rat cerebellum, the antiserum produced selective labelling of glial cells and processes, including the Bergmann fibers. No enrichment of immunoreactivity was detected in nerve terminals of the major excitatory fiber systems. The distribution of homocysteic acid-like immunoreactivity was very different from that of taurine (another sulphur-containing amino acid), as judged from consecutive semithin sections labelled with a postembedding immunoperoxidase procedure and from ultrathin sections labelled with a postembedding double immunogold procedure. Taurine-like immunoreactivity was concentrated in Purkinje cells and was low in glial elements. Our data suggest that the cerebellum contains a glial pool of homocysteic acid (and/or precursors that may undergo spontaneous oxidation to homocysteic acid) and that this amino acid is unlikely to act as a cerebellar transmitter.
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  • 70
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    Experimental brain research 90 (1992), S. 29-39 
    ISSN: 1432-1106
    Keywords: Direct Cortical Response ; Sensory Evoked ; Response ; Current Source Density ; Somatosensory Cortex ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A current-flow and current-source-density analysis of the sensory evoked response (SER) and the direct cortical response (DCR) in the somatosensory cortex of rats was performed to determine the origin of these potentials. The SER was found to originate in layers II and III, as in cats, with a single excitatory neuronal circuit component. The DCR, on the other hand, has five components, three inhibitory and two excitatory. The activation and magnitude of these components vary with stimulus strength and frequency. During the second and fourth ms of the response, two inhibitory currents flow in layers V and VI; 2 ms later, excitatory current flows in layers II and III. This excitatory current appears to be the same one involved in the SER. Five ms later, the superficial excitatory current is replaced by an inhibitory one in the neighborhood of the DCR's negative peak. At strong stimulus strengths, this is followed by an excitatory current in layer V. The early inhibitory and excitatory components step up through layers upper-VI, V and III over time, implying that inhibition followed by excitation moves upward through cortex. The currents associated with the DCR in somatosensory cortex are compared with those for the DCR in motor and association cortex.
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  • 71
    ISSN: 1432-1106
    Keywords: Neural grafting ; Neural transplantation ; Parkinson's disease ; Cryopreservation ; Fetal mesencephalon ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the present study we quantitatively assessed to what extent freeze-storage at liquid nitrogen temperature influences the survival and function of fetal mesencephalic grafts in the dopamine-depleted rat striatum. Ventral mesencephalic (VM) tissue was dissected from rat fetuses and stored overnight in a preservative medium at 4 °C (hibernation). It was grafted intrastriatally either as a fresh cell suspension or was frozen as tissue fragments or as a cell suspension after stepwise incubation in ascending concentrations of dimethyl-sulphoxide. Following a cryopreservation interval of 80 days in liquid nitrogen, the frozen samples were rapidly thawed, rinsed, and grafted. Cellular viabilities of graft cell suspensions, as assessed by ethidium bromide/acridine orange staining, were decreased from 90% in fresh tissue to 38-35% in frozen and thawed tissue. Amphetamine-induced turning behavior at 6 weeks post-grafting was significantly attenuated in hosts that had received fresh grafts or grafts that were frozen as tissue fragments. Tyrosine hydroxylase-(TH-) immunocytochemistry of recipient brains revealed significant decreases in TH-positive graft cell numbers in rats grafted with cryopreserved tissue (38–42% of fresh tissue). Moreover, the dye exclusion viability of thawed VM tissue was found to accurately predict the subsequent graft survival. There was no difference with respect to graft cell numbers between the two freezing methods employed, though block storage seems to be more simple from a practical point of view. The present study indicates that freezing in liquid nitrogen may be a feasible method for long-term storage of fetal neural tissue for grafting, although a marked decrease in graft survival and function of cryopreserved tissue must be taken into account.
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  • 72
    ISSN: 1432-1106
    Keywords: X-ray irradiation ; GABA ; Catecholamine ; Calcium binding proteins ; Olfactory bulb ; Development ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the rat olfactory bulb, the majority of interneurons in the glomerular layer (GL) are supposed to be generated during first postnatal week. Low and repeated doses of X-rays (200 rad x 4 and 200 rad x 6) were used during this period to impair the development of interneurons. The resulting effects on olfactory bulb neurons were examined stereologically and immunocytochemically in animals of 4 and 12 weeks of age. Quantitative analysis showed that, 1) the volume of the GL decreased to 55% (1200 rad) – 70% (800 rad) of control, 2) numerical cell densities in GL decreased to 40% (1200 rad) – 60% (800 rad) of control, thus resulting in 3) a decrease of the total cell number in GL to 20% (1200 rad) – 40% (800 rad) of control in irradiated olfactory bulbs of animals 4 weeks old. In comparison, mitral cells, which are generated prenatally, were much less affected (total cell number: 70–80% of control), indicating a selective loss of cells generated during the first postnatal week in GL. Effects on somata and processes immunoreactive for GABA, tyrosine hydroxylase (TH), calbindin D-28K and parvalbumin (PV) were examined in irradiated bulbs of both 4 and 12 week-old rats. All of these immunoreactive elements showed a drastic decrease in all layers. Semiquantitative analysis showed that in the GL, calbindin D-28K immunoreactive (calbindin D-28K(+)) neurons decreased more extensively than TH immunoreactive (TH(+)) and GABA-like immunoreactive (GABA(+)) neurons; that is, TH(+) and GABA(+) neurons decreased to 20% (1200 rad) – 40% (800 rad) of control, whereas calbindin D-28K(+) neurons decreased to 10% (1200 rad) – 30% (800 rad) of control in the GL of irradiated bulbs. These findings indicated that larger proportions of calbindin D-28K(+) neurons might be generated during the first postnatal week than those of GABA(+) and TH(+) neurons. Furthermore, in irradiated bulbs the proportion of GABA(-)TH(+) cells in TH(+) cells increased to about twice of control, and the estimated total numbers of GABA(-)TH(+) cells in irradiated rats were 95% (800 rad) and 40% (1200 rad) of control. These observations suggest that the majority of GABA(-)TH(+) neurons were less affected by X-ray irradiation during the first postnatal week and thus that they might be generated in the prenatal period. Since during the first 2 postnatal weeks, neurons showing GABA(-)TH(+) were not seen in GL (Kosaka et al. 1987a), the majority of GABA(-)TH(+) neurons in adult olfactory bulb were assumed to change their phenotype at some postnatal developmental period.
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  • 73
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    Experimental brain research 91 (1992), S. 408-414 
    ISSN: 1432-1106
    Keywords: Taste ; Cortex ; Receptive fields ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Receptive fields (RFs) of 59 cortical taste neurons (35 in the granular insular area, area GI, 21 in the dysgranular insular area, area DI, and 3 in the agranular insular area, area AI) were identified in the oral cavity of the rat. The fraction of the neurons with RFs in the anterior oral cavity only was significantly larger in area GI (74.3%) than in area DI (42.9%). On the other hand, the fraction of neurons with RFs in both the anterior and posterior oral cavity was larger in area DI (42.9%) than in area GI (11.4%). On the whole, it is suggested that area GI is involved in discrimination of several taste stimuli in the oral cavity, whereas in area DI taste information originating from various regions of the oral cavity is integrated. When neurons were classified according to the best stimulus which most excited the neuron among the four basic tastes, different categories of taste neurons had RFs in different parts of the oral cavity. It is suggested that, in either taste area, different categories of taste neurons are involved in different sorts of taste coding. The majority of neurons in both areas had bilateral RFs. In area GI, neurons with RFs on single subpopulations of taste buds were significantly more numerous at the rostral region of the cortex than at the caudal region. There was no such relation between RF types and cortical localization in area DI. Otherwise, topographic representation of the oral cavity by taste neurons on the cortical surface was not obvious. RF features of taste neurons did not differ across layers in either cortical area.
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  • 74
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    Experimental brain research 91 (1992), S. 415-424 
    ISSN: 1432-1106
    Keywords: Taste ; Insular cortex ; Response profile ; Inhibitory response ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The responses of 84 taste neurons to stimulation of the oral cavity in rats were examined; most taste neurons were found in either a granular insular area (area GI; n = 55) or dysgranular insular area (DI; n = 25), and the others (n = 4) were in an agranular insular area (area AI). The fraction of neurons responding to only one of the four basic stimuli was significantly larger in area GI than in area DI. When neurons were classified by the stimulus which most excited the neuron among the four basic stimuli, every “best-stimulus category” of neurons was found in both GI and DI areas. Quinine-best and “multistimulus-type” neurons, whose responses to some non-best stimulus exceeded 90% of the maximum, were more numerous in the cortex than in the thalamocortical relay neurons. When responses were plotted against taste stimuli arranged in the order of sucrose, NaCl, HCl, and quinine along the abscissa (taste coordinate), response profiles of taste neurons often showed two peaks. The double-peaked type of response profiles were found in every best-stimulus category of neurons in both areas; though, a significantly large fraction of quinine-best neurons in area GI were of the double-peaked type. Some taste neurons in area GI (n = 21) and in area DI (n = 7) were inhibited by one to two taste stimuli, particularly by the stimuli present next to the best one along the taste coordinate. In correlation profiles — correlation coefficients between sucrose and NaCl and between HCl and quinine — pairs of stimuli which were located next to each other on the taste coordinate were significantly smaller in area GI than in area DI. It is thus highly probable that area GI plays an important role in fine taste discrimination and area DI in integration of taste information.
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  • 75
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    Experimental brain research 91 (1992), S. 477-483 
    ISSN: 1432-1106
    Keywords: Transplantation ; Neocortex ; Parvalbumin and calbindin immunocytochemistry ; Numerical density ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Numerical density and morphology of the two main GABAergic neuronal classes, the parvalbumin (PV) and calbindin- (CaBP)-containing nerve cells were investigated in long-term neocortical transplants in rats. It was observed that 4 months after the transplantation both CaBP- and PV-immunoreactive neurons survive and grow in neocortical grafts. However, the numerical density of PV cells decreased to about half of the control value (host cortex), while the density of CaBP-positive cells was 25–60% of that seen in the host cortex, depending on the degree of integration of the graft. The mean diameter of PV neurons rose to double of the control value, while the size of CaBP-positive perikarya did not change. This indicates that GABAergic neurons with hypertrophic perikarya (Bragin et al. 1991a) are identical to PV neurons. On the basis of these qualitative and quantitative morphological data it is concluded that PV- and CaBP-containing GABA cells in the transplant exhibit different sensitivities to transplantation-related structural and functional alterations.
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  • 76
    ISSN: 1432-1106
    Keywords: Nociceptor ; Bradykinin ; Serotonin ; Substance P ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A broad mixture of inflammatory mediators (“inflammatory soup”) was used to investigate the responsiveness of primary afferents from rat hairy skin in an in vitro skin-saphenous nerve preparation. In addition, a conditioning effect of the tachykinin substance P on chemosensitivity of nociceptors was examined. Inflammatory soup (IS) was made up in synthetic interstitial fluid from bradykinin, serotonin, histamin and prostaglandin E2 (all 10-5 M). In addition, the potassium and the hydrogen ion concentration (7 mM, pH 7.0) and the temperature (39.5°C) were elevated. The latter agents, in a control solution, did not excite nociceptors (n = 5). IS was repeatedly superfused over the receptive fields for 5 min at 10 min intervals; substance P (SP 10-6 and 10-5 M) was applied during the last 5 min of the interval and during the subsequent IS stimulation. IS excited more than 80% of the mechano-heat sensitive (“polymodal”) afferents with slowly conducting nerve fibres (n = 72), but none of the low-threshold mechanoreceptive slow and fast conducting units (n = 17). Slow conducting afferents with high mechanical threshold (n = 35) were weakly, and less frequently (〈20%), driven by IS. A majority, but not all, of the responsive units showed tachyphylaxis upon repeated IS application. None, however, lost its responsiveness completely. Conditioning heat stimulation (32–46.5°C in 20 s) did not enhance the subsequent IS response, which may indicate that sensitizing substances normally released by a noxious heat stimulus were already contained in IS. No sensitization to mechanical (von Frey) or heat stimulation could be established in the period after the IS response had subsided and after the washout was completed, respectively. A short-lived sensitization may have been overlooked under these temporal restrictions. Conditioning SP in 10-5 M but not in 10-6 M concentration significantly increased the IS response of polymodal C fibres, by 58% on average (n = 14). SP did not excite the units. Comparing with previous data, we conclude that there is a significant synergism between inflammatory mediators, acting to induce more intense and more sustained discharge via many nociceptors than single mediators alone could achieve. Conditioning substance P can further enhance this algogenic action. Mechanisms of interaction and relative contributions of single substances remain to be elucidated.
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  • 77
    ISSN: 1432-1106
    Keywords: Medial vestibular nuclei ; Potentiation ; Depression ; AP5 ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of high frequency stimulation (HFS) of the primary vestibular afferents on field potentials recorded in the ipsilateral Medial Vestibular Nuclei (MVN) was studied. Our results show that potentiation and depression can be induced in different portions of MVN, which are distinguishable by their anatomical organization. HFS induces potentiation of the monosynaptic component in the ventral portion of the MVN, whereas it provokes depression of the polysynaptic component in the dorsal portion of the same nucleus. The induction of both potentiation and depression was blocked under AP5 perfusion, thus demonstrating that NMDA receptor activation mediates both phenomena. Furthermore, the finding that the field potentials were not modified during perfusion with DL-AP5, as previously reported, supports the hypothesis that NMDA receptors are not involved in the normal synaptic transmission from the primary vestibular afferent fibres, but are only activated following hyperstimulation of this afferent system. Our results suggest that the mechanisms of long term modification of synaptic efficacy observed in MVN may underlie the plasticity phenomena occurring in vestibular nuclei.
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  • 78
    ISSN: 1432-1106
    Keywords: Opioid peptides ; Neurohypophysis ; Nerve endings ; Vasopressin ; Oxytocin ; Calcium ; Release ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Rat neural lobes and isolated nerve terminals from the neurohypophysis were stimulated in the presence of different opioid agonists and antagonists. The secretion of arginine vasopressin and oxytocin and rise in cytoplasmic calcium induced by depolarization were analyzed by radioimmunoassay and the fluorescent probe fura-2, respectively. The kappa-agonists dynorphin A1 -13 and dynorphin A1 -8 did not affect electrically evoked release of vasopressin, although oxytocin release was slightly reduced. U-50 488, a relatively specific kappa-receptor agonist, had no effect on the amount of vasopressin or oxytocin secreted, although it significantly reduced K+-evoked changes in [Ca2+]i in isolated nerve endings. Two kappa-receptor antagonists, MR 2266 and diprenorphin, alone had no effect on vasopressin and oxytocin secretion from isolated nerve endings depolarized with potassium. Opioid agonists less selective for the kappa receptors, etorphin and ethylketocyclazocin, were found to inhibit the release of both vasopressin and oxytocin significantly. Naloxone, a nonselective opiate receptor antagonist, alone had no effect on vasopressin release but potentiated the electrically evoked release of oxytocin. Naloxone also could overcome the inhibitory effect of etorphin on oxytocin and vasopressin release observed after electrical stimulation of the neural lobe. A number of inconsistencies therefore exist between the effects of opioid agonists and antagonists on neuropeptide release and on the evoked changes in [Ca2+]i. In view of these inconsistencies and the high concentrations of opioid agonists and antagonists necessary to modify release, we conclude that it is doubtful that opioid molecules have a physiological role in controlling neurohypophysial secretion.
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  • 79
    ISSN: 1432-1106
    Keywords: Brain ischemia ; Idazoxan ; Metabolism ; Noradrenaline ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The brain noradrenaline (NA) system is known to modulate ischemic neuronal damage, and the turnover of NA has been suggested to increase in the early recovery period following cerebral ischemia. Using HPLC and gas chromatography-mass spectrometry we analyzed the tissue levels of NA and its metabolites, 3,4-dihydroxyphenylethyleneglycol (DHPG) and 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG), in rat brain cortex after 10 min of forebrain ischemia followed by 1 h of recirculation. The effect of idazoxan, given in cerebro-pbrotective doses, as a bolus of 0.1 mg·kg-1 immediately after ischemia followed by 10 μg·kg-1·min-1 for 1 h, was also investigated. Ischemia decreased basal NA cortical levels from 384 ng/g tissue in control animals to 214 ng/g, while DHPG increased from 74 to 103 ng/g (+39%) and MHPG from 82 to 154 ng/g (+88%). Conjugated but not free DHPG increased, while both free and conjugated MHPG increased equally. The findings indicate an enhanced postischemic NA turnover with a major proportion of uptake and metabolism occurring extraneuronally, possibly secondary to a saturation of neuronal NA uptake in the postischemic phase. Idazoxan further increased NA turnover, as evidenced by higher postischemic levels of free MHPG and a higher MHPG/NA ratio. A correlation may exist between the protective action of idazoxan and its effect on NA turnover.
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  • 80
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    Experimental brain research 90 (1992), S. 567-571 
    ISSN: 1432-1106
    Keywords: Mesencephalic trigeminal neurons ; Peripheral nerve transection ; Cell loss ; Transganglionic degeneration ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of peripheral nerve transection on mesencephalic trigeminal (MeV) neurons have been studied qualitatively and quantitatively in the rat. In the qualitative part of the study the brain stem was studied in Fink-Heimer stained sections 3–30 days after a masseteric nerve transection. Degeneration argyrophilia was observed both in the MeV tract and in the supratrigeminal and trigeminal motor nuclei, as well as in the lateral part of the brain stem reticular formation. The first signs of transganglionic degeneration (TGD) were seen 7 days postoperatively, and the amount of degeneration increased considerably with longer survival times. A quantitative analysis of the MeV nucleus was made 60 days after transection of the left masseteric nerve. This analysis showed a 10.5–22.7% reduction of cells on the side that had undergone masseteric nerve transection. The mean difference (left vs right side) was -2.4% in animals that had not been operated on. These findings show that mesencephalic trigeminal neurons with proprioceptive functions are very sensitive to peripheral nerve injury with a substantial cell loss and TGD as the result.
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  • 81
    ISSN: 1432-1106
    Keywords: Cervical ; Cuneate ; Trigeminal ; Primary afferents ; Somatosensory ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Experiments were performed on rats to determine whether primary afferents from the upper cervical region terminate directly on Spinothalamic and propriospinal neurones. The central terminations of primary afferents from the upper cervical region were identified by diffusely filling their axons with horseradish peroxidase. Spinothalamic neurones or propriospinal neurones were identified in the same experimental animals by using retrograde transport of wheat germ agglutinin conjugated to horseradish peroxidase. Approximately 3–11 % of Spinothalamic cells in laminae 4–6 of spinal segments C2–4 received apparent synaptic contacts from primary afferents on the soma or primary dendrites. Approximately 18–36% of propriospinal neurones with axons descending to lower thoracic or lumbar levels received apparent synaptic contacts on the soma or primary dendrites. These data provide anatomical evidence that Spinothalamic and long propriospinal neurones in the upper cervical cord are excited directly by primary afferents. The data also help to clarify the neural circuitry underlying somatic sensation and reflex movements evoked by neck receptors.
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  • 82
    ISSN: 1432-1106
    Keywords: Tectogeniculate projections ; SP ; VIP ; CCK ; WGA-HRP ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Substance P (SP)-, vasoactive intestinal polypeptide (VIP)-, and cholecystokinin (CCK)-like immunoreactive (LI) neurons were found in the superior colliculus (SC) of the rat, and examined to ascertain whether they sent projection fibers to the dorsal lateral geniculate nucleus (LGNd). Immunocytochemical staining with antisera against SP, VIP, and CCK showed that many immunoreactive neuronal cell bodies were located in the superficial layers of the SC, especially in the stratum griseum superficiale. The pattern of distribution of these immunoreactive neuronal cell bodies in the SC was similar to that of neuronal cell bodies which were retrogradely labeled with WGA-HRP (wheat germ agglutinin-horseradish peroxidase conjugate) injected ipsilaterally into the LGNd. On the other hand, SP-, VIP- and CCK-LI axons were seen most densely in the lateral part of the LGNd, especially in the small-celled LGNd zone adjacent to the optic tract, where anterograde labeling was also observed after injection of WGA-HRP ipsilaterally into the superficial layers of the SC. When a lesion was produced by kainic acid injection into the superficial layers of the SC, axons showing SP-, VIP-, or CCK-LI in the LGNd ipsilateral to the lesion were markedly depleted. The results indicate that SC-LGNd projection neurons contain SP, VIP, and/or CCK in the rat.
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  • 83
    ISSN: 1432-1106
    Keywords: Vision ; Excitatory amino acids ; Thalamocortical connections ; Intrinsic connections ; Visual cortex ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To examine the organization of axon collaterals of neurons that selectively take up and transport excitatory amino acids, we have used retrograde tracing with D-[3H]Aspartate after injections into different layers of rat primary visual cortex. The results show cells in the lateral geniculate nucleus retrogradely labeled from the cortex. Additional topographically precise input to the thalamic recipient layer 4 originates from neurons in the visual cortex lying in layers 2/3, 5 and 6. These inputs are reciprocated by point-to-point projections from layer 4. Layer 2/3 cells project to layers 5 and 6 in columnar fashion. Putative excitatory input to layer 2/3 originates from a vertical column of cells in layer 5 and the middle of layer 6. In addition layer 2/3 receives input via horizontal collaterals of topographically distant upper layer neurons, from more widespread projections in lower layer 6, and from very widespread projections of cells at the layer 5/6 border. Cells in the depth of layer 5 also distribute collaterals within layers 5 and 6. Our findings provide anatomical evidence that the geniculo-cortical pathway in the mammalian visual system may use excitatory amino acid transmitters. In addition, the results support the notion that most long range connections that link distant points of the topographic map are excitatory.
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  • 84
    ISSN: 1432-1106
    Keywords: Noradrenergic hyperactivity ; NE ; ACh ; Fornix section ; DSP4 ; Spatial memory ; Alzheimer's disease ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Rats with unilateral or bilateral partial section of the fornix were impaired on an eight arm radial maze task. Neurochemical analysis of hippocampal tissue four weeks after the lesions revealed a 50% reduction of choline acetyltransferase (ChAT) activity. The cholinergic marker was correlated negatively with the number of errors in the maze; the lower the ChAT activity, the higher the error score. The fornix lesion also induced a 50% reduction in norepinephrine (NE), but no change in the noradrenergic metabolite methylhydroxyphenylglycol (MHPG), suggesting a net increase in turnover of NE in these animals. Additional lesion of the noradrenergic system with the neurotoxin DSP4 reduced both MHPG and NE levels by more than 90%, compared to nonlesioned controls, and reversed the behavioral deficit. This treatment had no further effect on cholinergic markers. There was a significant negative correlation between ChAT activity and the index of NE turnover, suggesting that hyperactivity in the noradrenergic system after fornix section inhibits the spared cholinergic function and thus exacerbates the cognitive deficit. The pattern of neurochemical results bear a striking resemblance to those seen in some Alzheimer's patients and suggest that an equilibrium among neurotransmitters is important to cognitive function.
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  • 85
    ISSN: 1432-1106
    Keywords: Visual system ; Superior colliculus ; Transplantation ; Retinotectal specificity ; Development ; Neuronal phenotype ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Tectal tissue from E15 or E16 Wistar rat embryos was dissociated and reaggregated (DR) prior to transplantation on to the midbrain of newborn host rats. We wished to determine how complete disruption of the donor tissue (i) affected the subsequent morphological development of the grafts in the host brain, and (ii) whether this procedure affected the selectivity with which host retinal axons innervated target regions in the tectal transplants. Forty-three to 135 days after transplantation, host rats received binocular injections of wheatgerm agglutinin-conjugated horseradish peroxidase. After perfusion, frozen sections of the grafts and underlying host brainstem were cut and reacted with tetramethylbenzidine to identify retinal projections, or stained for either acetylcholinesterase (AChE), Nissl or neurofibrils. All host brains contained identifiable DR grafts. Each brain contained at least one large transplant and numerous smaller pieces of graft tissue. The fragmentation of DR grafts was greater than that seen in direct, undissociated tectal transplants; however the morphology of individual DR grafts was markedly similar to direct grafts. Of particular interest was the presence in DR grafts of localized, often oval or circular regions, that possessed high AChE activity and contained mostly small (5 to 10 μm) close-packed neurons. AChE-dense patches were found both superficially and deep within DR grafts and appeared identical to those seen in direct transplants. These regions are thought to be homologous to the superficial, retinorecipient layers of normal superior colliculus (SC) and it is likely that the formation of these localized areas resulted from the selective association of presumptive SGS neurons within the reaggregating neuropil. In almost all cases, host retinal input to DR grafts was confined to the localized AChE-dense patches, suggesting that despite the dissociation procedure, specific retinal innervation of regions containing at least some of the appropriate target cells was maintained in DR tectal grafts.
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  • 86
    ISSN: 1432-1106
    Keywords: Dopamine-rich transplants ; Fos protein ; Nigrostriatal system ; Immunohistochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The aim of the present experiment was to characterize the effect of intrastriatal grafts of embryonic dopaminergic neurones on the expression of Fos protein in the striatum when challenged with amphetamine. Unilateral 6-hydroxydopamine lesions of the nigrostriatal pathway were made in adult rats and grafting was performed 3 weeks later. The numbers of Fos-positive nuclei in the ipsi- and contralateral striata were counted on coronal sections following immunohistochemical staining 5 months after grafting. Administration of d-amphetamine induced an increase in the density of Fospositive nuclei in the intact striatum. This stimulatory effect of amphetamine on c-fos expression was blocked by 6-hydroxydopamine hydrobromide lesions and was restored in the striata bearing transplants. However, an overshoot was observed as the density of Fos-positive cells within the grafted striatum was larger than that observed within the intact striatum. This hyperexpression of Fos-positive nuclei was correlated with the exaggerated compensation of amphetamine-induced rotation in the same animals.
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  • 87
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    Experimental brain research 90 (1992), S. 141-146 
    ISSN: 1432-1106
    Keywords: Spike train ; Pattern recognition ; Hippocampal neurons ; Spontaneous activity ; Cell culture ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Spontaneous activity and rhythmical oscillations are common features of large neuronal networks in mammals. Detection of repetitive spike patterns or pacemaker activity during electrophysiological recording of spontaneous action potentials from single neurons can be difficult if a “noisy” background is present. This paper describes an improved method for an online spike train analysis based on joint interval histograms (JIH, Rodiek et al. 1962). By means of higher ordered JIH the discrimination of spike patterns with repetitive bursting activity or oscillations is possible even when randomly distributed action potentials appear. Examples of simulated spike trains and those recorded from cultured hippocampal neurons are presented.
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  • 88
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    Experimental brain research 90 (1992), S. 147-152 
    ISSN: 1432-1106
    Keywords: Periaqueductal grey matter ; Rostral ventrolateral medulla ; Cardiovascular control ; Medullo-spinal neurones ; Defence reaction ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A study has been carried out to investigate the influence of the periaqueductal grey matter (PAG) on spinally-projecting neurones in the rostral ventrolateral medulla (RVLM) in rats anaesthetised with urethane. Microinjection of D,L-homocysteic acid was used to selectively activate nerve cell bodies in the PAG. Stimulation throughout the rostral half of the PAG and in the caudal PAG on a level with and dorsolateral to the level of the aqueduct evoked excitatory responses in 21 medullospinal cells in the RVLM. The neuronal excitation was associated with a rise in blood pressure. In contrast, stimulation within a restricted area of the ventrolateral PAG at the level of the dorsal raphe nucleus inhibited 10 medullo-spinal neurones in the RVLM, and produced variable changes in blood pressure. Convergence of excitatory and inhibitory influences from dorsolateral and ventrolateral stimulating sites in the PAG on to individual cells was also demonstrated. The results are discussed with respect to the role of the ventrolateral PAG in modulating the cardiovascular components of the “defence” response which is integrated by the dorsal PAG.
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  • 89
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    Experimental brain research 90 (1992), S. 175-179 
    ISSN: 1432-1106
    Keywords: Inferior colliculus ; Spinal cord ; Retrograde transport ; Tyrosine hydroxylase ; Glutamate decarboxylase ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The localization and the transmitter phenotype of subparafascicular thalamic nucleus (Spf) neurons projecting to the inferior colliculus (IC) and to the spinal cord (Sp) were studied by using a retrograde fluorescent double labeling technique, and a combined technique of retrograde tracing and immunohistochemistry for tyrosine hydroxylase (TH) and glutamate decarboxylase (GAD). The cell population of Spf-IC neurons was totally differentiated from that of Spf-Sp neurons which have been reported to be dopaminergic. The former were densely distributed, small to medium sized cells and localized in the central portion of the Spf, while the latter were sparsely distributed, large cells and localized in the marginal portion of the Spf. Spf-IC neurons were completely devoid of TH immunoreactivity and, instead, approximately half of them showed GAD immunoreactivity. From these findings, it is concluded that the Spf is distinctly compartmentalized by the presence at least two separate neuronal subpopulations, which are distinguishable in terms of their cell size, distribution patterns, transmitter phenotypes and trajectories.
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  • 90
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    Experimental brain research 90 (1992), S. 469-478 
    ISSN: 1432-1106
    Keywords: Pain ; Nociception ; Spinal cord ; Withdrawal reflexes ; Spinal cord injury ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The spatial organization of the cutaneous input to hindlimb withdrawal reflexes was studied in spinalized, decerebrated, unanesthetized rats. Reflex activity in plantar flexors of the digits, pronators of the foot, dorsiflexors of the digits, and/or the ankle and flexors of the knee was recorded with electromyographic techniques for up to 12 h after spinalization. Graded mechanical (pinch) and thermal stimulation (CO2 laser) of the skin were used. Reflexes were absent (“spinal shock”) during approximately 10–20 min after spinalization. The reflex thresholds for pinch and CO2 laser stimulation then decreased considerably during the following 5–8 h. After this time, even mild pressure (less than 0.1 N/mm2) on the skin was sufficient to evoke a reflex in most muscles. During the period from about 0.5–3 h after spinalization, the nociceptive receptive field of each muscle usually corresponded to the area of the skin withdrawn by the muscle. Maximal responses were evoked from the area of the receptive field maximally withdrawn. During this period, responses to innocuous pinch were evoked mainly from the most sensitive area of the receptive fields. Concomitant with the decrease in reflex thresholds, the nociceptive receptive fields expanded for all muscles, often to include areas of the skin not withdrawn by the muscles. For most muscles, reflexes on tactile stimuli were eventually elicited from the entire receptive fields. The receptive fields for thermonociceptive and mechanonociceptive inputs were similar in most muscles. The interossei muscles were exceptional in that they responded very weakly to thermal stimulation. It is concluded that there are neuronal networks in the spinal cord that translate cutaneous nociceptive and tactile input into a withdrawal. However, the control exerted by descending pathways is necessary to maintain a functionally adequate excitability in these reflex pathways and an appropriate size for their receptive fields.
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  • 91
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    Experimental brain research 90 (1992), S. 508-518 
    ISSN: 1432-1106
    Keywords: Subparafascicular nucleus ; Inferior colliculus ; Superior olivary complex ; Cochlear nuclei ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the course of our study on the neuronal connections of the subparafascicular nucleus (SPF) in the rat, descending projections from the SPF to the lower brain stem were examined by using the anterograde tracer PHA-L (Phaseolus vulgaris leukoagglutinin) and retrograde tracer WGA-HRP (horseradish peroxidase conjugated to wheat germ agglutinin). When PHA-L was injected into the magnocellular and/or parvicellular division of the SPF (SPFm and/or SPFp), presumed terminal labeling was seen, bilaterally with an ipsilateral dominance, in the mesencephalic and pontine central gray matter, peripheral shell regions of the inferior colliculus, cuneiform nucleus, and superior olivary complex (mainly in the superior paraolivary nucleus, and additionally in the nuclei of the trapezoid body). A few labeled axon terminals were also seen in the cochlear nuclei bilaterally with a contralateral dominance. In the second set of experiments, WGA-HRP was injected into the inferior colliculus, superior olivary complex, or cochlear nuclei. When WGA-HRP was injected into the peripheral shell regions of the inferior colliculus or the superior olivary complex, many labeled neuronal cell bodies were seen in the SPFm bilaterally with an ipsilateral dominance, and a moderate number of labeled neuronal cell bodies were observed in the SPFp (lateral SPF) bilaterally with an ipsilateral dominance. When WGA-HRP was injected into the cochlear nuclei, a moderate number of labeled neuronal cell bodies were observed in the SPFm and SPFp bilaterally with a contralateral dominance. The results indicate that the SPFm and SPFp (lateral SPF) of the rat send a considerable number of projection fibers to the lower brain stem. The target regions of these projection fibers include the auditory relay nuclei, such as the inferior colliculus, superior olivary complex, and cochlear nuclei.
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  • 92
    ISSN: 1432-1106
    Keywords: Interneuron ; Axo-axonic cell ; Pyramidal cell ; Inhibition ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary During the course of an in vivo intracellular labeling study, a chandelier (axo-axonic) cell was completely filled with biocytin in the CA1 region of the hippocampus. Chandelier cells are known to provide GABAergic terminals exclusively to the axon initial segment of pyramidal cells. The lateral extent and laminar distribution of the dendritic arborization of the chandelier cell was very similar to that of pyramidal cells; the numerous basal and apical dendrites reached the ventricular surface and the hippocampal fissure, respectively. The dendrites, however, had very few spines. The neuron had an asymmetric axonal arbor occupying an elliptical area of 600 by 850 μm in the pyramidal cell layer and stratum oriens, with over three-quarters of the axon projecting to the fimbrial side of the neuron. Counting all clusters of terminals, representing individually innervated axon initial segments, the chandelier cell was estimated to contact 1214 pyramidal cells, a number that exceeds previous estimations, based on Golgi studies, by several-fold. The findings support the view that chandelier cells may control the threshold and/or synchronize large populations of principal cells.
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  • 93
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    Experimental brain research 91 (1992), S. 489-495 
    ISSN: 1432-1106
    Keywords: Regulation ; Synthesis ; Release ; Dopamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the urethane-anesthetized rat, electrical stimulation (10 Hz, 30 s, 250 μA) of the medial forebrain bundle (MFB), at 20-min intervals over an 8-h period, combined with intracerebral microdialysis in the striatum caused: an undiminished increase in the release of dopamine (DA) with each stimulation episode; a decreased efflux of 3,4-dihydroxyphenylacetic acid (DO-PAC) and 4-hydroxy-3-methoxyphenylacetic acid (HVA) after the first stimulation only; a delayed increased efflux of DOPAC with no change in HVA; and a poststimulation depression of firing of dopaminergic neurons in the substantia nigra (before, 3.1±0.7 Hz; after, 1.9±1.0 Hz; P〈0.05). After the last stimulation episode, the release of DA declined to prestimulation values, while the increased efflux of DOPAC persisted for three more hours. After the infusion of tetrodotoxin (4.0×10-7 M, 1.5 μl, 1.0 μl/min) into the MFB, the basal release of DA was reduced (P〈0.05), while the efflux of DOPAC and HVA was increased (P〈0.05). A model is proposed suggesting that: (1) during increased release of DA in the striatum, the metabolism of DA is decreased; (2) inhibition of nigrostriatal dopaminergic neurons is the usual cause of increased synthesis and metabolism of DA in the striatum; and (3) increased release of DA, and increased synthesis and metabolism of DA in the striatum are not causally linked and are noncoupled processes.
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  • 94
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    Experimental brain research 90 (1992), S. 639-642 
    ISSN: 1432-1106
    Keywords: Vibrissae ; Barrels ; Somatosensory cortex ; 2-deoxyglucose ; Neuronal plasticity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Effects of sensory deprivation upon ability of a vibrissa to activate a functional column in the barrel field of somatosensory cortex were examined with 2 deoxyglucose (2DG) autoradiography in the rat. After six weeks of whisker plucking started at birth, and one week of recovery, the cortical column activated by the deprived whisker and labeled with 2DG had a reduced diameter but higher labeling density than the normal vibrissal column. Loss of a peri-barrel labeling zone, possibly due to loss of intracortical activation, is suggested.
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  • 95
    ISSN: 1432-1106
    Keywords: Intermediolateral cell column ; Degeneration ; Serotonergic projections ; Thyrotropin-releasing hormone ; Immunocytochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In this study, we investigated the effects of the neonatal removal of the right superior cervical ganglion on the serotonin-like and thyrotropin-releasing-hormone-like immunoreactivities (5-HT-LI and TRH-LI) in the intermediolateral cell column (IML) of the spinal cord by quantitative image analysis. Two weeks after the lesion, we observed a 60% reduction in 5-HT-LI, while TRH-LI was not significantly reduced, in the right IML (lesioned side) at T1-2 levels. One month after the lesion, 5-HT-LI and TRH-LI were significantly reduced by 60% in the right IML at T1-2 levels. After 3 months, this decrease persisted at this level. In addition, we observed a 30% loss of the 5-HT-LI in the right IML at T3-4 levels, whereas TRH-LI did not decrease significantly at T3-4 levels. These findings are discussed and compared with those of other experimental studies on serotonergic reorganization in the rat spinal cord.
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  • 96
    ISSN: 1432-1106
    Keywords: Glutamate ; Glutamine ; Cochlea ; Neurotransmitter ; Immunocytochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The light- and electron microscopic localization of glutamate and glutamine in the rat organ of Corti was studied by means of antisera raised against the respective amino acids coupled to carrier proteins. The light microscopic analysis was performed in semithin sections treated according to the peroxidase-antiperoxidase procedure. The two amino acids were visualized in the same ultrathin sections by use of postembedding immunocytochemistry with two different gold particle sizes. The distribution of aspartate-like immunoreactivity was also recorded, but only at the light microscopic level. In the hair cells, the level of glutamate-like immunoreactivity was higher than that in supporting cells but lower than that in the presumed glutamatergic terminals of cerebellar parallel and mossy fibres. The latter types of terminal were sampled from ultrathin sections that had been incubated under the same conditions as the cochlear sections. Within the hair cells, gold particles signalling glutamate were enriched on mitochondria but not on clusters of synaptic vesicles. Glutamine-like immunoreactivity was present in hair cells as well as supporting cells. The glutamate/glutamine ratio, expressed as the ratio between the respective gold particle densities, was considerably lower for hair cells compared with the cerebellar excitatory terminals. No consistent difference was found between outer and inner hair cells in relation to the levels and subcellular distribution of glutamate and glutamine immunoreactivities. Aspartate-like immunoreactivity was accumulated in outer hair cells, with some labelling also of border cells and Böttcher cells. While the present study confirmed the presence of glutamate in hair cells and demonstrated that these cells are also endowed with the important glutamate precursor glutamine, it revealed notable differences between hair cells and presumed glutamatergic terminals in the CNS. These could reflect differences in the synthesis and compartmentation of transmitter glutamate. Methodological factors could also contribute. Alternatively, the differences could be interpreted to suggest that the hair cell transmitter is not glutamate, but a similar compound. Aspartate could be a candidate in the case of the outer hair cells.
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  • 97
    ISSN: 1432-1106
    Keywords: Hyperalgesia ; Peripheral neuropathy ; Nerve histopathology ; Neuropathic pain ; Unmyelinated fibre ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A mononeuropathy, produced by ligation of the sciatic nerve in rats, has recently been proposed as an animal model of experimental pain and pain-related disorders (hyperalgesia and allodynia). We investigated quantitatively the morphological changes in myelinated and unmyelinated fibres of the sciatic nerves 2 weeks after ligation in rats exhibiting allodynia to thermal stimulation. There was a marked reduction in the number of large myelinated fibres distal to the ligature (711 ± 34 compared with 5315 ± 230 in normal nerves). We also found a significant loss of small myelinated fibres (2429 ± 109 compared with 3197 ± 308 in normal nerves), the remaining fibres of this type showing pathological properties. Finally, ultrastructural evidence of damage to unmyelinated fibres was found. The typical pattern of large clusters of normal unmyelinated axons was no longer present within most regions of the nerve. There was a significant reduction in the size of the unmyelinated fibres (0.41 μm ± 0.15 compared with 0.71 μm ± 0.08 in normal nerves), together with a twofold increase in their number per cluster. Hypotheses about the mechanism of thermal allodynia in this pain model therefore must take into account the fact that all fibre classes show pathological changes.
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  • 98
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    Experimental brain research 88 (1992), S. 67-77 
    ISSN: 1432-1106
    Keywords: Retina ; Ganglion cells ; Alpha cells ; Lucifer yellow ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The somato-dendritic morphologies of large ganglion cells were studied by intracellular injections of Lucifer yellow in perfusedin vitro preparations of the albino rat retina. The ganglion cells were prelabeled with retrogradely transported granular blue or labeled with acridine orange dropped into the perfusate ofin vitro preparations. After the dye injection, somato-dendritic morphologies were successfully studied for 210 cells, the majority of which had a large soma more than 20 µm in diameter and were identified as alpha cells. According to the level of dendritic extensions within the inner plexiform layer (IPL) these alpha cells were further classified into inner ramifying (inner) and outer ramifying (outer) cells. Both qualitative and quantitative observations led us to conclude the following:1) The outer cells have a spherical soma with relatively few primary dendrites, while inner cells have a large polygonal soma with more primary dendrites.2) The dendritic field of inner cells was always larger than that of outer cells at every retinal location. The dendritic field diameter tended to increase as a function of retinal eccentricity from the optic disk, the tendency being more clear among inner cells.3) The dendrites of outer cells branch more frequently in the proximal part of the dendritic field while those of inner cells branch more distally.4) Total dendritic length of outer cells increases linearly with eccentricity whereas that of the inner cells does not change much irrespective of retinal location.
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  • 99
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    Experimental brain research 88 (1992), S. 33-40 
    ISSN: 1432-1106
    Keywords: Corpus callosum ; Frontal agranular cortex ; GABA receptor ; NMDA receptor ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A slice preparation of rat frontal agranular cortex preserving commissural inputs has been used for intracellular recording from layer V pyramidal cells, in order to characterize the synaptic potentials induced by stimulation of the corpus callosum and to reveal the subtypes of amino acid receptors involved. Stimulation of the corpus callosum induced EPSPs followed by early IPSPs with a peak latency of 30 ± 2 ms and late IPSPs with a peak latency of 185 ± 18 ms. Reversal potentials for early and late IPSPs were −75 ± 5 mV (early) and −96 ± 5 mV (late). Late IPSPs were more dependent on extracellular K+ concentration. The early IPSPs were blocked by GABAA antagonists, bicuculline and picrotoxin, whereas the late IPSPs were reduced by the GABAB antagonist, phaclofen. CNQX (6-cyano-7-nitroquinoxaline-2,3-dione), an antagonist of non-NMDA (N-methyl-D-aspartate) receptors, suppressed both EPSPs and late IPSPs at 5 µM. Early IPSPs remained at this concentration but were suppressed by 20 µM CNQX. In Mg2+-free solution, EPSPs were larger and more prolonged than in control solution. These enhanced EPSPs persisted after 5 to 20 µM CNQX, but were reduced in amplitude, and their onset was delayed by 3.6 ± 0.8 ms. The remaining EPSPs were suppressed by 50 µM APV (DL-2-amino-5-phosphono-valeric acid), an antagonist of NMDA receptors. In Mg2+-free solution containing 5 to 20 µM CNQX, the late IPSPs were not diminished. The remaining late IPSPs were suppressed by APV or by phaclofen. By contrast, the amplitude of early IPSPs was not affected by APV in Mg2+-free solution containing 5 µM CNQX. These results show that stimulation of the corpus callosum can induce GABAA and GABAB dependent IPSPs and NMDA and non-NMDA dependent excitation. It is suggested that these four types of amino acid-based transmission are conveyed by intracortical pathways with different characteristics.
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  • 100
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    Experimental brain research 89 (1992), S. 67-78 
    ISSN: 1432-1106
    Keywords: Cerebral ischemia ; Experimental stroke ; Recirculation ; Cerebral blood flow ; Brain damage ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary It has become increasingly clear that a stroke lesion usually consists of a densely ischemic focus and of perifocal areas with better upheld flow rates. At least in rats and cats, some of these perifocal (“penumbral”) areas subsequently become recruited in the infarction process. The mechanisms may involve an aberrant cellular calcium metabolism and enhanced production of free radicals. In general, though, the metabolic perturbation in the penumbra requires better characterization. The objective of this article was to define flow distribution in a rat model of reversible middle cerebral artery (MCA) occlusion, so as to allow delineation of the metabolic aberrations responsible for the subsequent infarction. We modified the intraluminal filament occlusion model recently developed by Koizumi et al. (1986), and described in more detail by Nagasawa and Kogure (1989), adopting it for use in both spontaneously breathing and artificially ventilated rats. Successful occlusion of the MCA (achieved in about 9/10 rats) was judged by unilateral EEG depression in ventilated rats, and neurological deficits, such as circling, in spontaneously breathing ones. CBF in the ipsilateral hemisphere was reduced to nearly constant values after 20, 60, and 120 min of occlusion, flow rates in the focus being about 10% and in the perifocal ipsilateral areas about 15–20% of control (contralateral side). When the filament was left in place (permanent occlusion) 2,3,5-triphenyl tetrazolium chloride (TTC) staining and histopathology after 24 h showed a massive infarct on the occluded side, extending from caudoputamen and overlaying cortex to the occipital striate cortex. Animals recirculated after 60 min of MCA occlusion, and allowed to survive 7 days for histopathology, showed infarction of the caudoputamen (lateral part or whole nucleus) in 5/6 animals and selective neuronal necrosis in one animal. The neocortex showed either infarcts, selective neuronal necrosis, or no damage. There was some overlap between neocortical areas which were infarcted and those which were salvaged by reperfusion. In general, though, both the CBF data and the recovery studies with a histopathological endpoint define large parts of the neocortex as perifocal (penumbral) areas which lend themselves to studies of metabolic events leading to infarction.
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