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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 183 (1991), S. 129-134 
    ISSN: 1432-0568
    Keywords: Vasopressin ; Endothelium ; Pulmonary artery ; Immunocytochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The localization of arginine-vasopressin in the endothelial cells of rat pulmonary artery was investigated by immunocytochemistry at the light and electron microscopic levels. The immunogold silver staining method was used for light microscopy of sheets of endothelium, removed from the artery, and the pre-embedding peroxidase-antiperoxidase technique was used for electron microscopy of cross sections of the artery. With both of the methods used, numerous vasopressin-positive endothelial cells were observed. None of the subendothelial elements showed labelling for vasopressin. The results are discussed in terms of the involvement of the endothelium in local control of the pulmonary circulation.
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  • 2
    ISSN: 1432-0568
    Keywords: Glutamine ; Glutamate ; Cerebellum ; Immunocytochemistry ; Glia ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The cellular and subcellular localization of glutamine, a major glutamate precursor, was studied by means of an antiserum raised against glutaraldehydefixed glutamine. Ultrathin sections from the cerebellar cortex of rat and baboon (Papio anubis) were incubated sequentially in the primary antiserum and in a secondary antibody coupled to colloidal gold particles. The labelling intensity was quantified by computer-aided calculation of gold particle densities. High levels of immunoreactivity occurred in glial cells (Bergmann fibres, astrocytes, and oligodendrocytes), intermediate levels in cell bodies and processes of granule cells, and low levels in terminals of presumed GABAergic or glutamatergic fibres (terminals of basket and Golgi cells, and of parallel, mossy, and climbing fibres). The labelling intensity of Purkinje cells showed some variation, but never exceeded that in glial cells. Within the nerve fibre terminals, the glutamine-like immunoreactivity showed some preference for mitochondria, but was otherwise evenly distributed. The predominant glial localization of glutamine was also obvious in light microscopic preparations processed according to the postembedding peroxidase-antiperoxidase procedure. Gold particle densities over different types of profile in glutamine immunolabelled sections were compared with particle densities over the corresponding types of profiles in neighbouring sections labelled with an antiserum to glutaraldehyde-fixed glutamate. The glutamate/glutamine ratio, expressed arbitrarily by the ratio between the respective gold particle densities, varied by a factor of about 6, with the highest ratio in the putative glutamatergic mossy and parallel fibre terminals, and the lowest ratio in glial elements. The remaining tissue components displayed intermediate ratios. The present study provides direct morphological evidence for the existence in the brain of distinct compartments with differing glutamate/glutamine ratios.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 184 (1991), S. 269-273 
    ISSN: 1432-0568
    Keywords: Rat ; Skeletal muscle ; Muscle fibre types ; Histochemistry ; Cluster analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Different histochemical identification methods for muscle fibre types have been introduced over the years. Most of them have been based on myosin ATPase activity after different kinds of preincubations, alone or in combination with oxidative enzymes. Comparative studies have shown, however, that the different methods result in nonidentical subgroups of type II fibres. Optical density values of individual fibres after incubation of serial sections for alkali- or copper-preincubated ATPase, NADH-TR, and fibre diameter, combined in two-dimensional plots, have for a long time been used in our laboratory to separate three subgroups of type II fibres. A cluster analysis, based on the data mentioned above, results in three subgroups of type II fibres in rat plantaris muscle. In comparison, earlier studies comparing different histochemical methods and reporting lack of correspondence between them have been based on two subgroups of type II fibres only. It is suggested that part of the lack of correspondence is due to unequal and incomplete separation by the methods used in the comparative studies, and that the three subgroups of type II fibres identified in the cluster analysis are type IIA, IIX and IIB, respectively. The need for a consensus on a common basis for histochemical identification of muscle fibre types is emphasized.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 183 (1991), S. 483-489 
    ISSN: 1432-0568
    Keywords: ChAT ; Cochlea ; Olivocochlear system ; Development ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Several studies present a great deal of information about putative efferent neurotransmitters and their distribution in the adult and developing cochlea. Anatomical mapping of outer hair cell efferent fibres during ontogeny is still not available. Using quantitative electron microscopy in combination with immunocytochemistry, the distribution of ChAT-like immunoreactivity in the developing rat was investigated. Adult-like immunoreactivity in the whole cochlea is first observed in 30-day-old rats. We localized the adult-like immunoreactivity in all efferent fibres and synapses of the outer hair cells along the entire cochlear duct. An adult-like reaction in the whole cochlea could be observed on the 25th day after birth in two out of three cases. On the 20th postnatal day, no adult-like ChAT immunoreactivity was found, with the exception of one case where labelling was seen in the basal region only. The adult-like ChAT immunoreactivity on the 30th day, 2–3 weeks after the onset of hearing, is the latest maturation of all features of the organ of Corti so far investigated. Synaptogenesis of the outer hair cell efferents reaches an adult-like appearance already on the 16th day after birth.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 183 (1991), S. 81-87 
    ISSN: 1432-0568
    Keywords: Trachea ; Airways ; Smooth muscle ; Sensory receptors ; Vagus nerve ; Guinea-pig ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The trachea of guinea-pigs was stained as a whole-mount preparation with the zinc iodide-osmium technique. A distinct class of nerve endings was observed associated with the tracheal muscle. The endings, issued from myelinated fibres of the vagus nerve via the recurrent laryngeal nerve, are distributed on either side of the midline and ventral to the tips of cartilages. They are interpreted as afferent nerve endings that may correspond to slow adapting stretch receptors identified by physiological studies. Each nerve contributes predominantly, but not exclusively, to the receptors of the ipsilateral side. There are 120–180 receptors along the full length of the guinea-pig trachea, their density being higher at the cranial end. The receptors are variable in size and structural complexity, and, to some extent, also in spatial orientation, but distinct subtypes are not recognizable. Receptors of similar morphology and distribution are found also in the rat trachea. The receptors can also be visualized with a cytochrome oxidase method for nerve endings, but they do not stain with immunohistochemistry for the neuropeptides substance P, calcitonin gene-related peptide, vasointestinal polypeptide and neurotensin.
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  • 6
    ISSN: 1432-0568
    Keywords: Ontogeny ; Cerebrovascular innervation ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The development of cerebrovascular nerves containing noradrenalin (NA), acetylcholinesterase (AChE), neuropeptide Y (NPY), and vasoactive intestinal polypeptide (VIP) was studied in rats from before birth to adulthood. All these nerves entered the cranial cavity along the cerebral carotid, internal ethmoidal, and vertebral arteries during the early stages of development, but the subsequent growth and distribution of NA-containing and NPY-immunoreactive (IR) nerves differed greatly from that of AChE-positive and VIP-IR nerves. NA-containing and NPY-IR nerves extended rapidly from the cerebral carotid artery and spread over all the major arteries of the internal carotid system by postnatal day 3, as well as descending the posterior ramus of the cerebral carotid to mingle with nerves from the vertebral artery around the mid-basilar artery by day 5. AChE-positive and VIP-IR nerves from the internal ethomoidal artery covered the whole internal carotid system during the first postnatal week, and projected to the upper basilar artery after the second week, while those from the cerebral carotid artery remained limited to the middle cerebral artery throughout development. By day 21, all major arteries of the internal carotid system had dense plexuses of the four nerve types that were similar to those observed in adult rats. The vertebrobasilar system also had a well-organized network of NA-containing and NPY-IR nerves, but only a poor supply of AChE-positive and VIP-IR nerves. Even on day 30, the latter two nerve types were sometimes absent from the middle to caudal basilar artery, owing to a lack of interdigitation by nerves from the internal ethomoidal and vertebral arteries.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 184 (1991), S. 65-70 
    ISSN: 1432-0568
    Keywords: Stereology ; Development ; Coronaries ; Corrosion casts ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To study myocardial vascular development, stereological parameters were estimated in 24 Wistar rat hearts of six different age groups, from newborn to adult. The vascular surface density showed a sharp increase in the first 2 weeks, a peak around the age of 2 weeks, and then a steady decrease until it flattened in adulthood. In contrast, the vascular volume percentage, when plotted against age, decreased continuously with the greatest change in the first week, after which the curve flattened. These findings are compatible with an increase in the number of capillaries with a concomitant decrease of their diameters. Qualitative scrutiny of the histology did indeed support the idea that vessels become thinner. Reconstructions of the histological sections showed the same change three dimensionally. The reconstructions also demonstrated very small holes that seemed to go through the capillaries in the younger stages. Corrosion casts of the blood vessels were made using a casting resin. This was injected into the umbilical artery of rat embryos from 15 days gestation to birth. In postnatal rats of six age groups methacrylate was injected directly into the left ventricle. These casts supported the stereological data by showing an increase in number and decrease in diameter of capillaries, while during pre- and postnatal development, the intervascular spaces lengthened from small, irregular spaces to long, rectangular ones. Small holes, the probable precursors of such spaces, were clearly visible in the wider vessels of the youngest stages. All data point to an interesting mode of capillary growth, i.e. growth by division of existing vessels.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 81 (1991), S. 546-551 
    ISSN: 1432-0533
    Keywords: Rat ; Sciatic nerve ; Mineralization ; Aging ; X-ray microanalysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A spontaneous mineralization of the sciatic nerve of senescent specific pathogen-free-bred rats (aged 42 months) is reported. Deposits were found in the endoneurium of different branches of the nerve at mid-thigh level. They appeared as small discrete deposits or as large tubular-shaped concretions, probably formed by the growth and merger of the smaller deposits. Some of the concretions were found in close proximity to blood vessels. Deposits consisted of dense aggregations of randomly entangled spicules spreading within bundles of collagen fibrils. Calcium was detected by histochemistry and X-ray dispersion microanalysis. Phosphorus was also found, possibly associated with calcium to form hydroxyapatite.
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  • 9
    ISSN: 1432-0533
    Keywords: 72-kDa heat-shock protein ; Neuronal necrosis ; Forebrain ischemia ; Immunohistochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We evaluated the relationship between the induction of the 72-kDa heat-shock protein (hsp 72) and the presence of necrotic neurons in the rat hippocampus, 48 h after an 8-min episode of forebrain ischemia in eight rates. Hsp 72 was detected using the monoclonal antibody C92 on vibratome brain tissue sections. Hematoxylin and eosin (H&E) staining on adjacent paraffinembedded sections was used to determine histopathological features. All morphologically intact CA1/2 neurons, 70% of which are destined to become necrotic 7 days after ischemia, exhibited intense hsp 72 staining, while necrotic or damaged neurons were devoid or low in hsp 72. Hsp 72 was also detected in CA3 neurons destined to survive 7 days after ischemia. Blood vessels positive for hsp 72 were detected in focal brain regions, in which severely damaged neurons were either devoid or low in hsp 72 staining. Occasional glial cells expressed hsp 72 in both normal and damaged brain regions. Hsp 72 response to a transient forebrain ischemia seemingly reflects differences in the selective ischemic vulnerability of CA1/2 and CA3 neurons. Further, the presence of hsp 72 within a neuron is likely only a marker of stress and is not necessarily indicative of eventual neuronal survival.
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  • 10
    ISSN: 1432-0533
    Keywords: Blood-brain barrier ; Ischemic edema ; Lanthanum ; Cerebral endothelium ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The distribution patterns of ionic Lanthanum (La3+; mol.wt. 139) were evaluated after 15, 30 and 60 min of middle cerebral artery occlusion in perfused-fixed rats. Blood-brain barrier (BBB) permeability to Evans blue (EB) and horseradish peroxidase (HRP; mol. wt. 40,000) in vivo was also evaluated. Brain tissue specific gravity was measured. An increase in brain water content was found as early as 30 min following occlusion. HRP and EB extravasation was not observed. La3+ crossed the interendothelial clefts of venoles and capillaries at 30 and 60 min and was seen in both extracellular and intracellular brain compartments at 60 min. La3+ extravasation was seen in nonedematous areas bordering the regions of water accumulation. Our findings suggest that the early phase of incomplete continuous ischemia is accompanied by changes in BBB permeability and the interendothelial clefts of venoles and capillaries seem to represent one of the early sites of ischemic damage.
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  • 11
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 82 (1991), S. 217-224 
    ISSN: 1432-0533
    Keywords: Hydrocephalus ; Rat ; Cerebral cortex ; Cortical cell density ; Capillary density
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Hydrocephalus in the H-Tx rat first develops in late gestation and causes death at 4–7 weeks. The effect of hydrocephalus on overall cortical dimensions and on five specific regions (frontal, sensory-motor, parietal, auditory and visual) has been studied by quantitative light microscopy at 10 and 30 days after birth. The lateral ventricle volumes in hydrocephalic rats were about 40x larger than controls and increased fourfold between 10 and 30 days. Cortical volume was reduced by a small amount at 10 days but was larger in hydrocephalics at 30 days. Thinning of the cortical mantle was severe with disruption of the laminar structure, particularly in the auditory and visual regions, where it was already present at 10 days. The density of cortical cells (neurones and glia) was not altered in hydrocephalics at 10 days but was reduced in all regions at 30 days. Estimates of total cell number suggest that the lower density was not associated with an overall loss of cells. Capillary numerical density was not affected by the hydrocephalus at 10 days after birth but by 30 days it was significantly lower, particularly in the worst-affected posterior regions. The results show that the cerebral cortex is severely distorted and that in advanced hydrocephalus, although overall cell number is not affected, both cell density and capillary density are lower by up to 30%.
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  • 12
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular evolution 33 (1991), S. 442-449 
    ISSN: 1432-1432
    Keywords: Humans ; Mouse ; Rat ; Codon usage ; Mutation bias ; Selection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary A new statistical test has been developed to detect selection on silent sites. This test compares the codon usage within a gene and thus does not require knowledge of which genes are under the greatest selection, that there exist common trends in codon usage across genes, or that genes have the same mutation pattern. It also controls for mutational biases that might be introduced by the adjacent bases. The test was applied to 62 mammalian sequences, the significant codon usage biases were detected in all three species examined (humans, rats, and mice). However, these biases appear not to be the consequence of selection, but of the first base pair in the codon influencing the mutation pattern at the third position.
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  • 13
    ISSN: 1432-1106
    Keywords: Substantia nigra ; Apamin ; Ca2+-activated K++ channel ; Afterhyperpolarization ; Intracellular recording ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Intracellular recording techniques were used to study the effects of apamin (APA), a selective inhibitor of one type of Ca2+-activated K+ channel, on the electroresponsive properties of dopamine (DA)-containing neurons within the zona compacta of the substantia nigra (SNc) in rat. Bath application of APA (1 μM) blocked the slow component of a complex post-spike afterhyperpolarization (AHPs) without affecting other characteristics of the action potential. Blockade of AHPs was accompanied by an increase in the number and frequency of action potentials evoked by depolarizing current pulses. However, APA failed to affect the cellular mechanisms underlying spike frequency adaptation or poststimulus inhibitory period. These data indicate that AHPs can exert a strong influence on the interspike interval but is probably not involved in regulating slower adaptive neuronal responses.
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  • 14
    ISSN: 1432-0738
    Keywords: Ciprofibrate ; Cytochrome P450IVA1 ; Peroxisomes ; Rat ; Marmoset
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Chronic ciprofibrate administration resulted in distinct differences in hepatic responses between the two species examined. In the rat, hepatomegaly was observed with the coordinate induction of carnitine acetyltransferase, peroxisomal β-oxidation and cytochrome P450IVA1 activities. The latter induction of cytochrome P450IVA1-dependent fatty acid hydroxylase activity was specific to this cytochrome P450 sub family, as ciprofibrate pretreatment resulted in an inhibition of the enzyme activities associated with the cytochrome P450 IIB and IA sub-families. Induction of mitochondrial enzymes were also noted in the rat, but at a substantially lower level than the microsomal and peroxisomal enzyme changes noted above. The majority of these enzyme changes were reversible in the rat after a 4-week, inducer-free period. In contrast, the marmoset displayed a different pattern of enzyme changes in response to ciprofibrate and at the high dose level, inhibition of microsomal fatty acid hydroxylase activity was observed in addition to no change in carnitine acetyltransferase activitiy. Although peroxisomal β-oxidation activity was induced in the marmoset, the specific activity was 10-fold lower than in the rat, concomitant with only minimum changes in the liver: body weight ratio. Taken collectively, our data have demonstrated that the marmoset is relatively refractory to ciprofibrate-induced liver enzyme changes with the implication that the extrapolation of the associated hepatotoxicity clearly documented in rodents must be viewed with extreme caution in non-human primates.
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  • 15
    ISSN: 1432-0738
    Keywords: Hydrogen cyanamide ; Rat ; Human ; Metabolism ; Urinary excretion ; Acetylcyanamide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The main urinary metabolite of hydrogen cyanamide (syn.: cyanamide) in rat and man is acetylcyanamide (syn.: N-acetylcyanamide). An analytical method was developed to determine acetylcyanamide in the urine with a limit of quantification of 〈10 μg/l (mean recovery 96.1 % using spikes of 20 μg/l; relative standard deviation 〈4%). This methodology is based upon ion chromatography using column-switch techniques and UV detection. It could be demonstrated that in rats an average of 45.6% of oral applied cyanamide (10 mg/kg) was excreted in the urine as acetylcyanamide. In male human volunteers a mean of 40% of oral administered cyanamide (mean dose 0.25 mg/kg body weight) was excreted via the urine as acetylcyanamide. The same group of volunteers participated in a skin absorption study with dermal application of the above cyanamide dose onto a skin surface area of 32 cm2. Within an application period of 6 h an average cyanamide quantity of 2.3 mg was available for skin absorption. A mean portion of 7.7% of this quantity was found as acetylcyanamide in the urine of the participants. Findings from literature state that cyanamide is metabolized in vitro to cyanide. According to examinations performed in vivo, however, such a metabolic pathway seems to be irrelevant for man. In comparison with the control values there was no significant increase of both the cyanide concentrations in the blood and the thiocyanate concentrations in the urine of the above volunteers after the described oral cyanamide administration.
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  • 16
    ISSN: 1432-0738
    Keywords: Polychlorinated biphenyls ; 2,2′,3,3′,6,6′-hexachlorobiphenyl ; 2,2′,4,4′,5,5′-hexachlorobiphenyl ; Cytochrome P450 isoenzymes ; Enzyme induction ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Tissue distribution and effects induced by 2,2′,4,4′,5,5′-hexachlorobiphenyl (245-HCB) on cytochrome P450 isozymes were compared with those of 2,2′,3,3′,6,6′-hexachlorobiphenyl (236-HCB). Male Wistar rats were given a single intragastric dose (23 mg/kg body wt) of either isomer, and killed after 72 h. At termination the tissue concentrations of 245-HCB were considerably higher than those of 236-HCB, suggesting a more effective metabolism of the latter. The binding affinity of 236-HCB to cytochrome P450 was higher and the magnitude of binding greater than of 245-HCB. 245-HCB-treatment elevated the hepatic concentration of cytochrome P450 and also the activities of 7-pentoxyresorufin O-depentylase (50-fold), aniline p-hydroxylase (2-fold) and 7-ethoxycoumarin O-deethylase (2-fold), a response typical of phenobarbital-type inducers. In the Western immunoblot of liver microsomes from 245-HCB treated rats, an increased amount of P450IIB1/2 was detected by a monoclonal antibody 2-66-3, which specifically detects phenobarbital inducible isoenzymes. The minimum molecular mass of the P450 isozyme induced was 52 kDa. After 236-HCB administration, a weak inducing effect was observed.
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  • 17
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 65 (1991), S. 678-680 
    ISSN: 1432-0738
    Keywords: Acetaldehyde ; Collagen ; Intoxication ; Ethanol ; Liver ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract It was found that chronic intoxication of rats with acetaldehyde results in a distinct, progressive increase of 53H-proline incorporation into collagen synthesized by liver. At the same time, biosynthesis of other proline-containing (noncollagenous) proteins does not change significantly. The effects are similar to those induced by chronic intoxication of rats with ethanol. Since acetaldehyde is an intermediary metabolite formed during ethanol oxidation in liver, it may be concluded that acetaldehyde is a factor responsible for alcohol-induced liver fibrosis.
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  • 18
    ISSN: 1432-0738
    Keywords: Polyvinylchloride (PVC) dust ; Intratracheal instillation ; Tracheobronchial lymph nodes (TBLN) ; Pathobiochemical response ; Long-term toxicity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PVC dust, following a single intratracheal instillation (25 mg/rat), was substantially cleared through the lymphatic circulation and progressively accumulated in the tracheobronchial lymph nodes (TBLN) in a time-dependent manner for up to 1 year. The tissue response in TBLN during 60–270 days post-instillation of PVC dust was characterized by progressive increase in total organ fresh weight, dry weight, DNA, RNA and protein contents, concurrent with the proliferation of macrophages and hyperplasia of reticular cells. Active phagocytosis and enhanced hydrolytic activity in TBLN was evident around 270 days post-instillation by the appearance of PVC-laden macrophages near and within the dust foci, and increased activity of acid phosphatase, DNAse, RNAse and β-glucuronidase. PVC dust caused degeneration of macrophages, and consequent release of hydrolytic enzymes resulted in limited cytotoxicity without inducing reticulination and fibrosis in the TBLN. The histology and clinical biochemistry of liver, kidney, spleen and serum were not altered and there were no detectable PVC particles in these tissues at up to 365 days. It is therefore concluded that lymphatic clearance of intratracheally instilled PVC dust results in its accumulation and mild foreign body reaction in TBLN which is non-fibrogenic at up to 365 days post-instillation.
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  • 19
    ISSN: 1432-0738
    Keywords: Carbon tetrachloride ; Taurine ; Liver damage ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Carbon tetrachloride (CCl4) caused a dose-dependent increase in urinary taurine which correlated with both the histological and biochemical assessment of liver damage. The peak elevation in urinary taurine occurred within the first 48 h after dosing but there was still significant taurinuria 72 and 96 h after the intermediate dose (1 ml.kg−1) and highest dose (2 ml.kg−1), respectively. Levels of taurine in serum were also elevated over the 24 h period following a hepatotoxic dose (2 ml.kg−1) of CCl4. In contrast, although initially elevated, levels of taurine in the liver declined over the 24 h period following dosing and were significantly lower 96 h after a hepatotoxic dose of CCl4 (2 ml.kg−1). Male rats showed a different urinary profile for taurine than female rats after dosing with CCl4. A reduction in food intake seemed to lower urinary taurine levels although these changes were not statistically significant. There was a significant correlation between the level of urinary taurine and the level of serum AST for individual animals given a hepatotoxic dose of CCl4 (2 ml.kg−1). The data presented suggest that: i) taurine is produced by the liver in response to a toxic insult and subsequent leakage from damaged cells leads to increased levels in the urine; ii) the urinary taurine level may be a useful non-invasive marker of liver damage.
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  • 20
    Electronic Resource
    Electronic Resource
    Springer
    Amino acids 1 (1991), S. 225-237 
    ISSN: 1438-2199
    Keywords: Amino acids ; Catalepsy ; Movement initiation ; NMDA antagonists ; Glycine ; Parkinson's disease ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The anticataleptic effects of non-competitive and competitive NMDA antagonists as well as those of an agonist at the allosteric glycine binding site of the NMDA receptor were tested in the catalepsy model. Some of these drugs were further tested in a reaction time task demanding rapid locomotor initiation. The results show that the non-competitive NMDA antagonists dizocilpine and memantine as well as the competitive antagonists CGP 39551, CGP 37849 and CPPene antagonized dopamine D2 receptor mediated catalepsy induced by haloperidol. D-cycloserine, a partial glycine agonist per se had no effects, but it enhanced the anticataleptic effects of dizocilpine when coadministered. However, the effects of CGP 37849 were abolished. Dopamine D1 receptor mediated catalepsy induced by SCH 23390 was antagonized by dizocilpine, memantine, CPPene, but not by CGP 37849. In the reaction time task dizocilpine, memantine and CGP 37849 were tested for their anti-akinetic and anti-bradykinetic potencies. All these compounds improved haloperidolinduced slowing of reaction time. However, they acted differentially on haloperidol-induced slowing of movement execution and decreased initial acceleration. Thus, antagonists at the NMDA receptor may have a therapeutic potential in the treatment of Parkinson's disease. Their potency can be manipulated specifically at the glycine binding site.
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  • 21
    Electronic Resource
    Electronic Resource
    Springer
    Child's nervous system 7 (1991), S. 121-128 
    ISSN: 1433-0350
    Keywords: Congenital hydrocephalus ; Rat ; Synaptogenesis ; Golgi study ; Ventriculoperitoneal shunt ; Learning disability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Using HTX-rats with congenital hereditary hydrocephalus, we used neuropathological methods, including quantitative Golgi study and neurobehavioral evaluation, to investigate the following problems. (1) What kind of damage does congenital hydrocephalus cause to developing brain tissue? (2) How much can the damage be repaired by ventriculoperitoneal shunting if performed at 4 weeks of age, enabling 4-week-old hydrocephalic rats to survive beyond sexual maturation? (3) What is the status of learning ability of long-term surviving rats with arrested shunt-dependent hydrocephalus? The findings of our study suggest that congenital hydrocephalus impairs the development and formation of the dendrites and spines of the cerebrocortical neurons. Following ventriculoperitoneal shunting, we confirmed that rats with arrested shunt-dependent hydrocephalus demonstrated learning disability in a light-darkness discrimination test using a Y-maze. The development of the dendrites and spines of the cerebrocortical neurons seemed to take place to some degree after shunting, but normal spine density could not be restored. Also suggested was a possible relationship between learning disability and a decrease in spine density, i.e., impairment of synaptogenesis.
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  • 22
    Electronic Resource
    Electronic Resource
    Springer
    Cancer immunology immunotherapy 33 (1991), S. 50-53 
    ISSN: 1432-0851
    Keywords: Brain neoplasm ; Immunotherapy ; Interleukin-2 ; Lymphokine-activated killer cells ; Rat ; Splenocyte ; Thymocyte
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We studied the lymphokine-activated killer (LAK) activity in splenocytes and thymocytes of rats with brain tumors chronologically from the early stage to the late stage, in order to clarify how much LAK activity would be developed at each stage. Simultaneously the natural killer (NK) activity in splenocytes, as one aspect of the host immunocompetence, was also determined. The splenic NK activity was significantly depressed in rats with brain tumors during the 2nd and 3rd weeks after tumor transplantation, as compared with normal controls. On the other hand, the splenocytes incubated with interleukin-2 showed the same killer activity in rats with brain tumors as in normal rats at all times. The LAK activity in thymocytes from rats with brain tumors was significantly higher than that of controls in the 1st and 2nd weeks and became equal to that of the controls during the 3rd week. The killer activity after incubation with interleukin-2 in thymocytes was superior to that in splenocytes throughout the experiment in both tumor-bearing rats and controls, which suggested that the precursor of LAK cells was not NK cells.
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  • 23
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    Archives of toxicology 65 (1991), S. 52-58 
    ISSN: 1432-0738
    Keywords: p-Chloronitrobenzene ; Urinary metabolites ; Rat ; Gas chromatography-mass spectrometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Urinary metabolites in rats treated withp-chloronitrobenzene were identified by gas chromatography-mass spectrometry. A single dose of 100 mg/kg body wtp-chloronitrobenzene was administered intraperitoneally to male Sprague-Dawley rats and urine samples were collected from the 8th to 24th hour after the administration. Urinary metabolites were extracted with diethylether at pH 1.0 and pH 10.0 from urine samples hydrolyzed with acid and base and from intact urine samples. Aliquots of the ethereal extracts were injected into a gas chromatograph-mass spectrometer. Nine substances were identified:p-chloroaniline, 2,4-dichloroaniline,p-nitrothiophenol, 2-chloro-5-nitrophenol, 2-amino-5-chlorophenol,p-chloroformanilide, 4-chloro-2-hydroxyacetanilide, a small amount ofp-chloroacetanilide and traces of unchangedp-chloronitrobenzene.
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  • 24
    ISSN: 1432-0738
    Keywords: 1,2-Epoxybutene-3 ; Butadiene monoxide ; Microsomes ; Cytosol ; Pharmacokinetics ; Mouse ; Rat ; Man ; Epoxide hydrolase ; Glutathione S-transferase ; Cytochrome P-450-dependent monooxygenase ; In vivo extrapolation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Kinetics of the metabolism of 1,2-epoxybutene-3 (butadiene monoxide) were investigated in liver fractions of mouse, rat, and man. In these species similar enzyme characteristics were found. In microsomes, no NADPH-dependent metabolism of butadiene monoxide was detectable. Epoxide hydrolase activity was found only in microsomes. The Vmax [nmol butadiene monoxide/(mg protein x min)] was 19 in mouse, 17 in rat, and 14 in man and the apparent Km (mmol butadiene monoxide/l incubate) was 1.5 in mouse, 0.7 in rat, and 0.5 in man. Glutathione S-transferase activity was found in cytosol only, revealing first order kinetics in the measured range. The ratio Vmax/Km [(nmol butadiene monoxide x l)/(mg protein × min × mmol of butadiene monoxide)] was 15 in mouse, 11 in rat, and 8 in man. The data obtained were used to extrapolate on the total rate of butadiene monoxide metabolism for each species in vivo: it was calculated to be 1.3 times higher in mice and 2.3 times lower in man compared to rats, when corrected for body weight.
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  • 25
    ISSN: 1432-0738
    Keywords: TCDD ; Serotonin ; Appetite suppression ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The major cause of TCDD-induced death in rats is a progressive voluntary feed refusal which has been correlated with reduced gluconeogenesis. Since centrally administered TCDD does not cause death or decreased feed intake in rats, the ability of TCDD to suppress appetite via peripheral mechanisms acting on the central nervous system was examined in two experimental models. First, it was found that the feed intake of rats on scheduled feeding cycles was not decreased by blood transfused from rats with TCDD-induced appetite suppression (8 days after a lethal dose of TCDD, i.p.). In contrast, a similar transfusion from normal, satiated rats did reduce feed intake of recipient rats by approximately 40%, suggesting that TCDD-treated rats are not satiated but rather that they are not hungry. In the second study tryptophan (the amino acid precursor of the neurotransmitter serotonin) was measured in the plasma and tryptophan, serotonin, norepinephrine and dopamine in the hypothalamus as well as dopamine and its metabolites in the striatum 4, 8, and 16 days after TCDD dosage (125 μg/kg, i.p.). Progressive time-dependent increases in tryptophan levels in plasma and brain were paralleled by increases in brain serotonin and 5-hydroxyindoleacetic acid (the primary metabolite of serotonin) in TCDD-treated rats. No changes were observed regarding the other biogenic amines. It is suggested based on these data and on substantial evidence from the published literature that a serotonergic mechanism may be involved in TCDD-induced feed intake reduction.
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  • 26
    ISSN: 1432-0738
    Keywords: Deltamethrin ; In vivo oxidative drug metabolizing activity ; Urinary antipyrine metabolites ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of deltamethrin pretreatment on the pharmacokinetics and metabolism of antipyrine was studied in male rats. The total plasma clearance of antipyrine was significantly decreased by deltamethrin pretreatment (20 mg/kg and 40 mg/kg daily for 6 days prior to antipyrine administration), while the elimination half-life at β phase, the area under the concentration-time curve and the mean residence time of antipyrine were significantly increased. The magnitude of the observed changes was dose dependent. The urinary excretion of norantipyrine, 4-hydroxyantipyrine and 3-hydroxymethylantipyrine was decreased by 39%, 32% and 26%, respectively (p〈0.001) in the presence of deltamethrin. In addition, the rate constants for formation of each of these metabolites were significantly decreased by an average of approximately 71%. These results suggest that deltamethrin is capable of inhibiting oxidative metabolism, a finding which could be of clinical and toxicological significance.
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  • 27
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    Archives of toxicology 65 (1991), S. 169-176 
    ISSN: 1432-0738
    Keywords: 1,2-Dichloroethane ; Carcinogens ; DNA binding ; Rat ; Inhalation ; Dose response
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 1,2-Dichloroethane (DCE) was reported to be carcinogenic in rats in a long-term bioassay using gavage in corn oil (24 and 48 mg/kg/day), but not by inhalation (up to 150–250 ppm, 7 h/day, 5 days/week). The daily dose metabolized was similar in the two experiments. In order to address this discrepancy, the genotoxicity of DCE was investigated in vivo under different exposure conditions. Female F-344 rats (183–188 g) were exposed to [1,2-14C]- DCE in a closed inhalation chamber to either a low, constant concentration (0.3 mg/l=80 ppm for 4 h) or to a peak concentration (up to 18 mg/l=4400 ppm) for a few minutes. After 12 h in the chamber, the dose metabolized under the two conditions was 34 mg/kg and 140 mg/kg. DNA was isolated from liver and lung and was purified to constant specific radioactivity. DNA was enzymatically hydrolyzed to the 3′-nucleotides which were separated by reverse phase HPLC. Most radioactivity eluted without detectable or with little optical density, indicating that the major part of the DNA radioactivity was due to covalent binding of the test compound. The level of DNA adducts was expressed in the dose-normalized units of the Covalent Binding Index, CBI = (μmol adduct per mol DNA nucleotide/mmol DCE per kg body wt. In liver DNA, the different exposure regimens resulted in markedly different CBI values of 1.8 and 69, for “constant-low” and “peak” DCE exposure levels. In the lung, the respective values were 0.9 and 31. It is concluded that the DNA damage by DCE depends upon the concentration-time profile and that the carcinogenic potency determined in the gavage study should not be used for low-level inhalation exposure.
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  • 28
    ISSN: 1432-0738
    Keywords: Thioacetamide ; Rat ; Hepatocyte ; Flow-cytometry ; Polyploidization ; Binuclearization ; Non-genotoxic carcinogens ; Oxygen tension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rat hepatocytes were cultured at 4% O2 and 13% O2 and exposed to the nongenotoxic rodent carcinogen thioacetamide (TA) from 24 to 72 h after isolation at exposure levels between 0.01 and 0.33 mM. Hepatocytes and isolated nuclei were analyzed by DNA-protein flow cytometry. An aggregate correction procedure was applied and the proportion of S-phase, diploid, tetraploid or octoploid hepatocytes as well as binucleated cells, were measured or calculated. The proportion of S-phase cells within the diploid hepatocytes increased with increasing concentration of TA up to 3.9-fold, whereas the corresponding increase in S-phase mononucleated tetraploid cells was only 1.8-fold. S-phase binucleate tetraploid cells showed no increase. In the tetraploid hepatocytes, the mitogenic stimuli was detectable only in cultures maintained at 4% O2. The relative contribution of binuclear cells was increased 1.5-fold in the octoploid cells. It is concluded that the mitogenic activity of TA initiates DNA synthesis in diploid hepatocytes in the G1 and in the following G2 cell-cycle phase, omitting karyogenesis. The cellular protein content is not affected which indicates that the mitogenic activity of the chemical is not necessarily associated with an increase in cellular protein content. The results obtained correspond well with data of in vivo studies. The method applied therefore allows the mitogenic activity of nongenotoxic carcinogens to be detected in vitro within 48 h and their mode of action to be elucidated.
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  • 29
    ISSN: 1432-0738
    Keywords: Butylated hydroxytoluene ; Chlorpromazine ; 8-Methoxypsoralen ; Photobinding ; PUVA ; Rat ; Alpha-tocopherol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The possible formation of singlet oxygen via photoexcited psoralens has been associated with the occurrence of, amongst others, erythema. Therefore it has been suggested to combine PUVA with the topical or systemic administration of antioxidants. However, the effect of these antioxidants on the photobinding of psoralens to DNA, which is held responsible for the anti-proliferative effect, should be taken into account. In the present study the effect of two phenolic antioxidants, alpha-tocopherol (AT) and butylated hydroxytoluene (BHT), on the in vivo photobinding of 8-methoxypsoralen (8-MOP) to not only epidermal DNA, but also proteins and lipids was determined. After topical application of an ethanolic antioxidant solution onto the shaven skin of Wistar rats, labeled 8-MOP was applied using the same solvent. After this the rats were exposed to UV-A. By separating epidermal lipids, DNA/RNA and proteins by a selective extraction method, irreversible binding of 8-MOP to each of these biomacromolecules was determined. Both AT and BHT caused a decrease in the photobinding of 8-MOP to epidermal DNA and proteins. To investigate the underlying mechanism of this protection, the effect of AT was compared with that of AT-acetate. It also proved helpful to study the effects of the antiooxidants on the photobinding of another photosensitizer, namely chlorpromazine. From these experiments it was concluded that AT and BHT affect 8-MOP photobinding by quenching reactive 8-MOP intermediates, involving the phenolic hydroxyl group of the antioxidants. BHT offered protection against lipid binding of 8-MOP but AT, especially at high concentrations, enhanced the UV-A-induced binding of 8-MOP to lipids. This is noteworthy with respect to the current interest in the role of 8-MOP-lipid adducts in PUVA therapy.
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  • 30
    ISSN: 1432-0738
    Keywords: Isopropanol ; Protein synthesis ; Adaptation ; Brain ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Long-term treatment of rats with isopropanol in the drinking water results in a change or process of adaptation occurring in in vitro brain protein synthesis which increases the resistance of the ribosomal machinery to the acute effect of either ethanol or isopropanol. Such an increase was observed both in the system coded by endogenous messenger and in the system coded by polyuridylic acid. In both translation systems, the adaptation seems to affect the ribosomal step of polypeptide chain elongation. The increase in resistance to the alkanols apparently did not affect the inhibitory action of puromycin, fusidic acid and cycloheximide on the ribosome.
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  • 31
    ISSN: 1432-1084
    Keywords: Magnetic resonance imaging ; Middle cerebral occlusion ; Brain oedema ; Cerebral infarct ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The development of ischaemic brain oedema caused by middle cerebral artery (MCA) occlusion was studied by serial magnetic resonance imaging (MRI) in rats. Multiple spin echo sequences were used with TR = 1500 ms and TE = 30–240 ms (8 echos). Subtraction images were obtained by subtracting the last three echos from the first echo. Fourteen rats were studied 3, 6, and 12 h and 1, 1.5, 3, 4, 6, and 8 days after MCA occlusion, and 2 of them also 3 and 6 weeks later. Two T2 components could be separated, a fast one representing bound water and a slow one representing free bulk water. MR showed T2 prolongation even on the first examination, and the highest values were observed 24h after occlusion. The subsequent examinations showed a slow reduction in oedema. MR studies 3 and 6 weeks after occlusion revealed an area of very long T2, which correlated well with infarction shown by histology. The subtraction images demonstrated both the infarct location and the oedematous changes in the surrounding uninfarcted tissue. MRI imaging employing T2 components and subtraction images appears to be a valuable method for observing the time course of the development and resolution of oedema in cerebral infarction.
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  • 32
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    Experimental brain research 87 (1991), S. 223-226 
    ISSN: 1432-1106
    Keywords: Globus pallidus ; Inferior colliculus ; Retrograde fluorescent tracer ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary After injection of fluorescent tracer into the inferior colliculus (IC), retrogradely labeled cells were observed not only in the temporoauditory cortex (ACx) and the substantia nigra pars lateralis, but also in the globus pallidus (GP). These labeled GP cells were localized exclusively in the caudal portion of the GP, which has been known to project to the ACx. Employing a retrograde fluorescent double labeling technique, the GP-IC neurons were found to be distributed in a separate manner from the GP-ACx neurons within the caudal GP. The present study provides further anatomical evidence that the caudal GP has a functional role in auditory processing.
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  • 33
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    Experimental brain research 87 (1991), S. 245-253 
    ISSN: 1432-1106
    Keywords: Thalamus ; VL neurons ; Cerebellum ; Intracellular recording ; Biocytin ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Intracellular recordings from thalamic neurons receiving cerebellar inputs were performed under urethane anesthesia in the rat. A total of 64 neurons were recorded intracellularly with micropipettes filled with 4% biocytin solution (dissolved in 0.5 M K-acetate), and cerebellar-induced EPSPs (CN-EPSPs), the membrane resistance and firing properties were analyzed with intracellular current injections. The mean latency of CN-EPSPs was 1.9 ± 0.8 ms and the mean input resistance measured in 10 neurons was 17.6 ± 5.0 MΩ. Thirty-two out of 35 stained neurons were analysed morphologically; 28 of these neurons were located in the VL, and 26 received CN-EPSPs. Their somata were round or polygonal in shape and the mean size was 22.5 × 15.2 μm. They had radially extending spinous dendrites, and the mean radii of the dendritic fields were 214.7 μm in the frontal and 171.4 μm in the sagittal planes. These morphological features were similar to those observed in the sensory relay nucleus of the thalamus.
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  • 34
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    Experimental brain research 87 (1991), S. 363-370 
    ISSN: 1432-1106
    Keywords: Visceral neuropathy ; Acrylamide ; Neurofilaments ; Neurofilament proteins ; Autonomic nerves ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A variety of visceral nerves were studied by intermediate filament immunocytochemistry in rats intoxicated with acrylamide. In such animals, oesophageal and diaphragmatic motor end-plates were invaded and deformed by neurofilament protein-like material, while afferent fibres of diaphragmatic neuromuscular spindles and myelinated sensory fibres of the iris showed striking terminal accumulation of similar material. Conversely, the rich population of thin afferent fibres of the iris showed no obvious abnormality, while pre-terminal changes were seen along the extrinsic nerve fibres supplying the cornea and myenteric ganglia. Multiple lesions were demonstrated in gut nerves of acrylamide-treated rats, while scattered “enteric glial cells” showed abnormally coarse morphology and a striking increase in glial fibrillary acidic protein immunoreactivity. A distinct, delicately varicose appearence was revealed by neurofilament protein-immunostaining in bladder nerve fibres of normal rats, which was changed to one of coarse dilations by acrylamide. In conclusion, apparently selective changes were found along different types of axons, in dicating marked heterogeneity in cytoskeletal organisation among visceral nerves. Taken together with the proposed inhibition by acrylamide of neurofilament proteins degradation, the above findings may suggest a non-uniform distribution of neurofilament degradation sites along distal regions of different axons.
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  • 35
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    Experimental brain research 85 (1991), S. 324-334 
    ISSN: 1432-1106
    Keywords: HRP/WGA-HRP injections ; Retinotopically organized areas ; Thalamic afferents ; Laminar distribution of cortical afferent neurons ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Afferent connections of rat primary visual cortex (area 17 or V1 area) and the rostral and caudal parts of areas 18a and 18b were studied, by placing in each of the areas, small electrophoretic injections of enzyme horseradish peroxidase (HRP) or wheat germ agglutinated-HRP. The results indicate that: 1) each of the areas has a distinct pattern of distribution of afferent neurons in the ipsilateral visual thalamus — area 17 receives its principal thalamic input from the dorsal lateral geniculate nucleus, the caudal parts of areas 18a and 18b receive a major thalamic input from the lateral posterior nucleus and a minor input from the posterior nucleus, while the rostral parts of areas 18a and 18b receive a major input from the posterior nucleus, and a minor projection from the lateral posterior nucleus; 2) the rostral and caudal parts of areas 18a and 18b each receive an associational input from area 17; 3) the rostral parts of areas 18a and 18b each receive associational input from three different extrastriate regions, the caudal part of the same extrastriate area, and the rostral and caudal parts of the other extrastriate area, whereas the caudal parts of areas 18a and 18b receive associational inputs only from one or two extrastriate regions; 4) area 17, area 18b and rostral area 18a each receive a substantial associational input from lamina V of the caudal part of the frontal eye field (FEF) in the motor cortex; however the input from the FEF to caudal area 18a (if present) is very small; 5) The extrastriate areas studied receive associational input from the restrosplenial cingulate area 29d; however, the input from area 29d to area 17 appears to be very small. The distinct patterns of distribution of prosencephalic afferents suggest to us that multiple retinotopically organized areas described previously in the rat cortex (cf Montero 1981; Espinoza and Thomas 1983) represent functionally distinct areas.
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  • 36
    ISSN: 1432-1106
    Keywords: AP5 ; MK801 ; NMDA antagonists ; Memory ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Rats were trained to alternate responses on a discrete trial working memory task on a T-maze. In Experiment 1, the rats were then matched for choice accuracy and allocated to three treatment groups. These were: implantation of osmotic minipumps for intraventricular infusion of either (a) 15 mM D-2-amino-5-phosphonopentanoic acid (AP5) or (b) artificial cerebrospinal fluid (VEH); and an unoperated control group (UNOP). In Phase 1 we assessed alternation performance with a minimal delay between responses: the UNOP and VEH rats continued to choose accurately; the AP5 rats showed an impairment of choice accuracy, but recovered over days. In Phase 2 a 20-s delay between responses was enforced, and choice accuracy was assessed following injections either of saline or of Milacemide HC1 (10 mg/kg). There was now a severe and enduring impairment of choice accuracy in the AP5 group, but Milacemide injections did not affect performance in any of the treatment groups. In Experiment 2 rats were trained in a similar way, and then given intraperitoneal injections of MK801 or of physiological saline in a within-subjects design and tested for T-maze performance with a minimal or a 20-s delay between responses. In the first Phase, MK801 was given 10-min before behavioural testing commenced; in the second Phase, it was given 28–40 min before behavioural testing commenced. The outcome depended critically on the time between drug injection and testing. There was a significant drug-induced impairment of choice accuracy in both Phases; but in Phase 1 there was no impairment in testing with a minimal retention interval and an impairment with a 20-s retention interval. In Phase 2, the impairment was significant at both retention intervals. We conclude that AP5, but not MK801, interferes with temporary memory storage in a delay-dependent manner.
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  • 37
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    Experimental brain research 85 (1991), S. 359-363 
    ISSN: 1432-1106
    Keywords: Dorsal raphe ; Paraventricular nucleus ; Serotonin ; Magnocellular neurons ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In order to determine the responses of paraventricular nucleus magnocellular neurones following activation of central serotonergic pathways, single unit activity was recorded and responses following electrical stimulation of the midbrain dorsal raphe nucleus were examined. Approximately one third (32%) of the phasically active, vasopressin-secreting neurones were inhibited by the stimulation, the remaining such cells being nonresponsive. In contrast, only two of the non-phasic cells (13%) were inhibited by the stimulation whilst 53% were excited (p〈 0.005, chi2-test). The onset latency of both inhibitory and excitatory responses were similar, whilst offset of the inhibitory responses was about twice that of the excitatory responses (p 〈 0.005, t-test). Two of the nonphasic cells were antidromically identified as projecting to the dorsal raphe. The results obtained indicate a role for dorsal raphe projections to the paraventricular nucleus in the regulation of neurohypophysial hormone secretion. The observation that different sub-populations of the cells recorded showed different responses, suggests that several mechanisms may be involved in the control of neuronal activity in the region recorded, in response to activation of the central serotonergic pathway examined. The results obtained are intended to further clarify the neural mechanisms regulating the secretion of vasopressin and oxytocin from the neurohypophysis.
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  • 38
    ISSN: 1432-1106
    Keywords: Lordosis ; Proceptive ; Muscimol ; Progesterone ; Estrogen ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The inhibitory neurotransmitter, GABA, has been implicated in the control of lordosis behavior. Previous studies indicate that modulation of GABAA transmission can have dual effects on lordosis, being facilitative in the ventromedial hypothalamus and inhibitory in the preoptic area. The midbrain central gray (MCG) is also known to be an important neural site for regulating lordosis as well as defensive and escape behaviors, and plays an integral role in the control of nociception. Because of the multitude of behaviors regulated at the level of the MCG, we utilized a two-chamber testing apparatus that allowed simultaneous measurement of the females' proceptive (hopping and darting), receptive and rejection behaviors, as well as an index of nociception and general motor activity. We found that microinfusion of the GABAA antagonist, bicuculline, into the MCG of steroid-primed female rats resulted in a significant decrease in lordosis and proceptive behaviors at 5 min post-infusion. There was full recovery to pretest levels by 60 min. Furthermore, microinfusion of the GABAA agonist, muscimol, to estrogen-treated females that displayed low levels of receptivity and high levels of rejection behavior during a pretest, resulted in a significant increase in lordosis responding and a decrease in rejection behaviors. Neither drug significantly affected time spent in the vicinity of the male, motor activity or vocalizations. It is concluded that the decrease in lordosis resulting from blockade of GABA transmission is not solely due to the induction of antagonistic behaviors since there was no increase in rejections after bicuculline administration. The current findings are consistent with the interpretation that GABA facilitates lordosis in the MCG via disinhibition. When the retrograde tracer, Fluoro-gold, was infused into the same cannula sites in the MCG as the GABAA drugs it demonstrated the presence of strong projections from the ventromedial nucleus, zona incerta, medullary reticular formation and spinal cord. These projections to the MCG may be important for the integration of the diverse behaviors regulated at the level of the MCG and GABAergic transmission may play a role in this integration.
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  • 39
    ISSN: 1432-1106
    Keywords: Status epilepticus ; Pilocarpine ; Substantia nigra pars reticulata ; Astrocytes ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The substantia nigra has a gating function controlling the spread of epileptic seizure activity. Additionally, in models of prolonged status epilepticus the pars reticulata of substantia nigra (SNR) suffers from a massive lesion which may arise from a massive metabolic derangement and hyperexcitation developing in the activated SNR. In this study, status epilepticus was induced by systemic injection of pilocarpine in rats. The neuropathology of SNR was investigated using immunohistochemical techniques with the major emphasis on the time-course of changes in neurons and astrocytes. Animals surviving 20, 30, 40, 60 min, 2, 3, 6 hours, 1, 2, and 3 days after induction of status epilepticus were perfusion-fixed, and brains processed for immunohistochemical staining of SNR. Nissl-staining and antibodies against the neuron-specific calcium-binding protein, parvalbumin, served to detect neuronal damage in SNR. Antibodies against the astroglia-specific cytoskeletal protein, glial fibrillary acidic protein (GFAP), and against the glial calcium-binding protein, S-100 protein, were used to assess the status of astrocytes. Immunohistochemical staining for serum-albumin and immunoglobulins in brain tissue was taken as indicator of blood-brain barrier disturbances and vasogenic edema formation. Immunohistochemical staining indicated loss of GFAP-staining already at 30 min after induction of seizures in an oval focus situated in the center of SNR while sparing medial and lateral aspects. At 1 h there was additional vacuolation in S-100 protein staining. By 2 hours, parvalbumin-staining changed in the central SNR indicating neuronal damage, and Nissl-staining visualized some neuronal distortion. Staining for serum-proteins occurred in a patchy manner throughout the forebrain during the first hours. By 6 h, vasogenic edema covered the lesioned SNR. By 24 h, glial and neuronal markers indicated a massive lesion in the center of SNR. By 48–72 h, astrocytes surrounding the lesion increased in size, and polymorphic phagocytotic cells invaded the damaged area. In a further group of animals surviving 1 to 5 days, conventional paraffin-sections confirmed the neuronal and glial damage of SNR. Additional pathology of similar quality was found in the globus pallidus. Since astrocytes were always damaged in parallel with neurons in SNR it is proposed that the anatomical and functional interrelationship between neurons and astrocytes is particularly tight in SNR. Both cell elements may suffer in common from metabolic disturbance and neurotransmitter dysfunction as occur during massive status epilepticus.
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  • 40
    ISSN: 1432-1106
    Keywords: NMDA receptors ; Nucleus accumbens ; Quisqualate/kainate receptors ; Paired-pulse facilitation ; Postsynaptic potential ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The principal aim of this study was to characterize the transmitter mechanisms mediating fast postsynaptic potentials in identified neurons of the rat nucleus accumbens. Using the biocytin-avidin labeling technique, impaled neurons were identified as medium spiny neurons. The basic membrane characteristics of these neurons were determined. Local electrical stimulation or stimulation of the corpus callosum elicited a depolarizing postsynaptic potential consisting of an EPSP often followed by an IPSP. The quisqualate/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (4 μM) abolished most of the depolarizing postsynaptic potential. The N-methyl-D-aspartate receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid depressed a small part of the decay phase of the depolarizing postsynaptic potential. Paired-pulse facilitation of postsynaptic potentials was found using interstimulus-intervals between 10 and 150 ms. N-methyl-D-aspartate receptors were found to contribute only slightly to the facilitation of the decay phase of the depolarizing postsynaptic potential, but not to its rising phase. This contribution was particularly clear under conditions of reduced GABAA receptor mediated inhibition. The present study indicates that postsynaptic responses of medium spiny neurons in the nucleus accumbens to local stimulation or stimulation of neocortical afferents are primarily mediated by quisqualate/kainate receptors. The contribution of NMDA receptors is normally limited to a portion of the decay phase of these responses, but is enlarged in the absence of GABAergic inhibition and following paired-pulse stimulation.
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  • 41
    ISSN: 1432-1106
    Keywords: Sympathetic preganglionic neurons ; Monoaminergic terminals ; Dendritic organization ; Cholera toxin ; Immunohistochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A ladder-like pattern of distribution of sympathetic preganglionic neurons (SPNs) was compared with that of monoaminergic terminals in the upper thoracic spinal cord of the rat. SPNs were identified by a retrograde labeling with cholera toxin subunit B (CTb) injected into the superior cervical ganglia of both sides. Monoaminergic terminals were stained immunohistochemically by using antisera raised against 5-hydroxy-tryptamine (5-HT) or dopamine- β -hydroxylase (DBH). SPNs showing full dendritic arbors were found in all of the sympathetic preganglionic nuclei. They formed a ladder in the horizontal plane. The nucleus intermediolateralis was connected with the central autonomic nucleus by many transverse dendritic bundles. Photomontages of serial sections of material stained alternatively with antisera against CTb and 5-HT or DBH clearly showed a close correlation between SPNs and monoaminergic terminals. There is no transverse dendritic bundle of SPNs without the accompaniment of monoaminergic terminals.
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  • 42
    ISSN: 1432-1106
    Keywords: Cerebral ischemia ; Calbindin-D28K ; Parvalbumin ; retrograde axonal tracing ; CNS repair ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Cerebral ischemia can be caused by many diverse conditions such as cardiac arrest and severe hypotension and is often the cause of secondary brain damage following head injury or infantile birth trauma. The inadequate cerebral blood flow can result in permanent loss of essential brain circuitries and neurological deficits. The CA1 region of the hippocampal formation is the region of the brain that is most often lesioned following transient forebrain ischemia and is associated with impairments of learning and memory. Furthermore, the loss of such a large target area can lead to detrimental post-trauma synaptic reorganization. Since methods are not currently available for the prevention of neuronal loss following cerebral ischemia, a number of anatomical methodologies were utilized to investigate whether transplanted neurons had the potential to afford some measure of repair. The hippocampal CA1 region of the rat brain was lesioned by transient forebrain ischemia and subsequently repopulated with suspensions of fetal hippocampal tissue. The ability of the transplanted neurons to remain viable when placed into a degenerating environment was confirmed by the histological demonstration of 3H-thymidine labelled neurons in the lesioned region. Histological and immunohistochemical techniques showed that the transplanted neurons developed cytological features that were indistinguishable from their normal CA1 counterparts, often showed a remarkable degree of organization, and expressed some of the same neuron specific proteins; specifically calbindin-D28K and parvalbumin. Acetylcholinesterase histochemistry and retrograde axonal transport of Fluorogold demonstrated that some afferent and efferent fibre projections to and from the septal nucleus could be reinstated. The data have shown that the transplanted neurons can demonstrate many of the anatomical properties that are characteristic of the adult cells they have replaced and therefore have great potential for the reconstruction of severe focal lesions due to ischemia.
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  • 43
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    Experimental brain research 86 (1991), S. 248-256 
    ISSN: 1432-1106
    Keywords: Bicuculline ; Epilepsy ; Neocortex ; NMDA receptor ; Non-NMDA receptor ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Conventional intracellular recording techniques were used to investigate the N-methyl-D-aspartate (NMDA) and non-NMDA mediated synaptic mechanisms underlying the stimulus-induced paroxysmal depolarization shift (PDS) generated by cells in rat neocortical slices treated with bicuculline methiodide (BMI). The NMDA receptor antagonists CPP or MK-801 were ineffective in abolishing the PDS. However, both drugs were able to attenuate the late phase of the PDS and delay its time of onset. In contrast, the non-NMDA receptor blocker CNQX demonstrated potent anticonvulsant property by reducing the PDS into a depolarizing potential that was graded in nature. This CNQX-resistant depolarizing potential was readily blocked by CPP. Voltage-response analysis of the PDS indicated that the entire response (including its NMDA-mediated phase) displayed conventional voltage characteristics reminiscent of an excitatory postsynaptic potential that is mediated by non-NMDA receptors. We conclude that the activation of non-NMDA receptors is necessary and sufficient to induce epileptiform activity in the neocortex when the GABAergic inhibitory mechanism is compromised. The NMDA receptors contribute to the process of PDS amplification by prolonging the duration and reducing the latency of each epileptiform discharge. However, the participation of NMDA receptors is not essential for BMI-induced epileptogenesis, and their partial involvement in the PDS is dependent upon the integrity of the non-NMDA mediated input. The lack of NMDA-like voltage dependency observed in the PDS's late phase might reflect an uneven distribution of NMDA receptors along the cell and/or an association of this excitatory amino acid receptor subtype in the polysynaptic pathways within the neocortex.
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  • 44
    ISSN: 1432-1106
    Keywords: Sympathetic nerve ; Superior cervical ganglion ; Cerebral arteries ; Reinnervation ; WGA-HRP anterograde labeling ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In order to clarify the manner in which previously denervated cerebral arteries become reinnervated after unilateral excision of the superior cervical ganglion (SCG), we observed directly the reinnervating sympathetic nerve fibers originating in the contralateral SCG by using anterograde labeling with wheat germ aggulutinin-horseradish peroxidase in rats. The nerve fibers sprouted from the nerve fibers in the contralateral anterior cerebral artery and reinnervated the arterial wall of the anterior cerebral artery of the denervated side as early as one week after ganglionectomy. In addition to this sprouting route, three other reinnervating nerve fiber routes were observed in the circle of Willis of the denervated side two weeks after ganglionectomy: the proximal portion of the internal carotid artery, the route passing between bilateral ethmodial arteries, and the posterior communicating artery. Eight weeks after ganglionectomy, these reinnervating nerve fibers formed a fairly dense plexus in a circular pattern in the circle of Willis. However, the reinnervation could not be observed in the arterial branches derived from the circle of Willis (middle cerebral artery and posterior cerebral artery) even 16 weeks after ganglionectomy. The present results clearly demonstrated the time course, distribution pattern and limitation of the reinnervation from the contralateral SCG following unilateral ganglionectomy. The fact that reinnervation could be observed only in the main cerebral arteries of the circle of Willis, in which the nerve plexus appeared to have a circular pattern, suggests a difference between the qualities of sympathetic innervation controlling the cerebral circulation in these arteries and the other arterial branches related to these differences in reinnervation capacity.
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  • 45
    ISSN: 1432-1106
    Keywords: 5-Hydroxytryptophan ; Parachlorophenylalanine ; Benserazide ; Sleep ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the rat, the insomnia which follows the administration of parachlorophenylalanine (p-CPA), a serotonin synthesis inhibitor, is transiently reversed either by intra-cisternal injection of L-5-HTP or by an associated injection of 5-HTP and an L-aromatic-aciddecarboxylase inhibitor (benserazide). Histochemical, immunohistochemical and chemical investigations showed that 5-HTP administration does not lead to a detectable increase in cerebral 5-HT. These findings suggest that the restoration of sleep after p-CPA treatment could be mediated by the central action of 5-HTP.
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  • 46
    ISSN: 1432-1106
    Keywords: Dopamine ; Levodopa ; Parkinson's Disease ; Transplantation ; Rotational Behavior ; DA Receptors ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of chronic levodopa treatment on the function of embryonic mesencephalic tissue grafts was assessed in rats by monitoring rotational behavior elicited by dopamine (DA) agonists before and after neural grafting. Rats were given unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal pathway and baseline measures of rotational behavior induced by D1 receptor stimulation, D2 receptor stimulation, or amphetamine were determined. Subsequently, DA grafts were implanted into the lesioned striatum and chronic regimens of either saline or levodopa began one day after neural grafting and were continued for 7 weeks. Rotational behavior elicited by the D1 agonist, SKF 38393, was completely attenuated throughout the six week-period following the commencement of levodopa treatment, regardless of the absence or presence of a DA graft. Conversely, rotational behavior elicited by the D2 agonist, quinpirole, was significantly elevated in ungrafted animals receiving chronic levodopa. Grafted animals receiving chronic levodopa did not show a significant reduction in rotational behavior, whereas grafted animals receiving chronic saline showed a significant 67% reduction in quinpirole-induced rotational behavior. Amphetamine-induced rotational behavior was reduced in both levodopa and saline treated grafted animals, however grafted animals receiving chronic levodopa treatment showed a reduction of rotational behavior that was uncharacteristic and less compensatory than that observed in grafted animals receiving chronic saline treatment. Morphology of grafts indicate that there were areas of impaired neurite outgrowth of TH-positive fibers in animals treated with levodopa. The results of the present study suggest that the impaired recovery in quinpirole and amphetamine-induced rotational behavior in grafted animals receiving chronic levodopa treatment may be related to (1) impaired graft function, (2) an alteration in pre- and postsynaptic mechanisms in the host DAergic system, or (3) a combined effect of (1) and (2).
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  • 47
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    Experimental brain research 86 (1991), S. 182-189 
    ISSN: 1432-1106
    Keywords: Xenograft ; Development ; Trophism ; Retinal ganglion cell ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Fetal rabbit retinae can grow and differentiate when transplanted to the collicular region of neonatal rats. In addition, the observed survival of retinal ganglion cells within grafts is associated with the extension of axons into the superior colliculus of the host brain, suggesting that the factors influencing the guidance of axons and the survival of ganglion cells may be homologous across different mammalian orders.
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  • 48
    ISSN: 1615-2573
    Keywords: Bronchial artery ; Blood flow ; Microspheres ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The intrapulmonary bronchial blood flow of the left lung (systemic arterial blood flow to the left lung via the bronchial artery) was determined in 45 anesthetized and artificially ventilated male Wistar rats, weighting 263±5 g (mean ± SEM). The microsphere method was employed and designed so that recirculating microspheres across the peripheral arteriovenous anastomoses were prevented from lodging in the left lung, and disturbances of the isovolemic state of the animals became minimal. Under normal conditions with a mean arteiral pressure of 115±2 mmHg (n=40), the bronchial blood flow of the left lung was found to be 0.307±0.033 ml/min on average, and amounted to 0.52±0.06% of the cardiac output. The flow (ml/min) normalized per kg body weight, 100 g wet lung, or 100 g dry lung was 1.14±0.12, 76±8, or 368±39, respectively. The total intrapulmonary bronchial blood flow of the left and right lungs could be estimated by multiplying the intrapulmonary bronchial flow of the left lung by the weight ratio (total: left) of 2.9. The variability of the flow data was small, as confirmed in a study with simultaneous injection of two differently radiolabeled microspheres. The reproducibility of duplicate measurements was excellent.
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  • 49
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    Pflügers Archiv 419 (1991), S. 38-42 
    ISSN: 1432-2013
    Keywords: Growth and aging ; Rat ; Metabolic rate ; Ventilation ; Blood gas ; Regulation of Respiration ; Carbon dioxide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The long-term adjustment of ventilation and blood gases throughout life was studied in halothane anaesthetized male Wistar rats of various ages (1.5–20 months). Basal metabolic rate (O2 consumption, CO2 production), ventilation and ventilatory response to CO2 changed significantly during growth and aging, whereas arterial partial pressure of CO2 (P aCO2) and pH remained unchanged. Changes in the rate of CO2 production were associated with proportional changes in alveolar ventilation and in the sensitivity of the ventilatory control system to a CO2 stimulus at various ages. Ventilatory equivalent (ratio of alveolar ventilation to CO2 production) and the slope of the CO2/ventilation response line normalized for CO2 production were maintained constant throughout life, despite significant changes in the breathing pattern. These findings suggest that P aCO2 homeostasis is maintained by ventilatory regulation coupled tightly with CO2 production throughout life.
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  • 50
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    Journal of molecular medicine 69 (1991), S. 1095-1098 
    ISSN: 1432-1440
    Keywords: Liver ; Warm ischemia ; Reperfusion ; Oxygen radicals ; Allopurinol ; Deferoxamine ; Iron ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The generation of free oxygen radicals is presumed as a substantial pathogenetic principle in reperfusion injury. Although demonstrated in gut, muscle and kidneys its role in liver reperfusion injury is still under investigation. In an experimental rat model of warm liver ischemia of 60 min and 8 h reperfusion electron resonance spectroscopy assessed the increased generation of free radicals in early reperfusion period, leading to a decrease of polyunsaturated free fatty acids in liver tissue within 15 min of reperfusion. Histologically, single cell death, local and patchy necrosis of hepatic lobuli could be observed after 8 h reperfusion (n=6). These histologic signs of liver injury could be attenuated by administration of superoxid-dismutase in combination with catalase but not by allopurinol. Best results could be obtained by deferoxamine. This indicates that increased generation of free oxygen radicals in reperfusion is not caused by the known conversion of xanthine-dehygrogenase to -oxidase but is mediated by an increased generation of hydroxyl-radicals, which can be scavenged by deferoxamine.
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  • 51
    ISSN: 1432-1106
    Keywords: Cyproterone ; Hypothalamus ; Pituitary ; Morphology ; Function ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Fetal exposure to cyproterone acetate (CPA), while allowing, normal sexual morphogenesis, has previously been shown to lead to functional endocrine abnormalities in adult rats of both sexes. Because of this, we examined morphologically and morphometrically the hypothalamic nuclei involved in sexual dimorphism as well as the pituitary lactotropes of rats exposed in utero from day 15 to 20 of gestation to CPA. Male and female offspring was studied at the age of 70–80 days. In both sexes the brain weight was lower (p〈0.05) in CPA-treated than in control rats. Morphometrical investigations showed that the surface density (Sv) and the volume density (Vv) of the ventromedial nucleus were higher (p〈0.05) in CPA-treated male than in control rats. By comparing sexes the Sv and Vv of the ventromedial nucleus were higher (p〈0.01) in CPA-treated male than in corresponding female rats. Also the nuclear surface of the tyrosine hydroxylase-immunoreactive neurons of the arcuate nucleus was higher (p〈0.05) in CPA-treated male than in female rats. In lactotropes of the pituitary gland the immunoreactive prolactin (PRL) was densitometrically increased (p〈 0.05) in CPA-treated female compared with control rats. By electron microscopy, PRL granules and autophagocytosis appeared to be more abundant in CPA-treated rats of both sexes. These data show that fetal exposure to CPA results in long-term anatomical and physiological alterations of hypothalamic and preoptic nuclei as well as of the pituitary lactotropes. These permanent changes support the functional endocrine abnormalities observed in adult rats.
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  • 52
    ISSN: 1432-1106
    Keywords: Explants ; Basal ganglia ; Substantia nigra ; Dopamine ; Ventral mesencephalon ; Neural development ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Organotypic slice cultures of striatum and neocortex were prepared from newborn to seven day old rats and cultured for three to 60 days. When processed for tyrosine hydroxylase (TH) immunocytochemistry medium-sized, aspiny TH immunoreactive (TH-i) neurons with a similar morphology were revealed in the striatum and the neocortex. The neurons had a very similar morphology in both tissues and were present both when the two tissues were grown separately as single cultures and when grown together either en bloc as part of the same tissue slices or as co-cultures. In order to examine whether innervation by dopaminergic fibers would affect the expression of TH-i neurons in the striatal slice cultures, co-cultures of ventral mesencephalon (VM) and striatum were prepared, but the ingrowth of TH-i fibers from the VM did not alter the expression of TH immunoreactivity by a subpopulation of striatal neurons.
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  • 53
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    Experimental brain research 84 (1991), S. 487-494 
    ISSN: 1432-1106
    Keywords: Paraventricular nucleus ; Vagal afferents ; Gastric distension ; Vasopressin neuron ; Oxytocin neuron ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Extracellular recordings were made from vasopressin (AVP) and oxytocin (OXT)-secreting cells in the paraventricular nucleus (PVN) of the hypothalamus in rats anesthetized with urethane-chloralose to determine the effects of electrical stimulation of vagal gastric nerves and gastric distension on their activity. Electrical stimulation of gastric branches of the vagus nerves inhibited 5 and excited 10 of 32 phasically firing neurosecretory cells. Approximately one third of the phasically firing neuro-secretory cells (9 out of 29 cells) were transiently inhibited by gastric distension; an effect which was completely abolished by bilateral cervical vagotomy. In contrast, gastric nerve stimulation excited 45 of 72 non-phasically firing paraventricular cells. Thirteen of 77 non-phasically firing cells tested were excited by gastric distension. We conclude that there are some sensory afferent inputs originating from gastric receptors and transmitted by gastric vagal afferents which inhibit the activity of AVP- secreting neurons in the PVN although other inputs excite the cells. Similar inputs also excite some of the putative OXT-secreting neurons in the PVN.
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  • 54
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    Experimental brain research 84 (1991), S. 517-524 
    ISSN: 1432-1106
    Keywords: Temporal/entorhinal cortices ; Retroactive memory ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary It has previously been shown that the temporal and entorhinal cortices may be critically involved in memory. In Experiment 1, rats with either damage to the temporal cortex (TC), lateral entorhinal cortex (LEC), or the medial entorhinal cortex (MEC) were tested for retention of a preoperatively acquired simultaneous brightness discrimination task. TC and LEC lesions impaired retention, whereas MEC lesions were without mnemonic effect. In Experiment 2, rats with either disruptions of the anterior neural connections of TC (TC/Ant), posterior connections of TC (TC/Post), or conjoint disruptions (Ant/Post) were tested for retention of the visual discrimination task. TC/Ant and Post/Ant lesions resulted in relatively mild, but significant memory impairment, whereas a profound effect was seen after TC/Post lesions. The results are discussed in terms of a very important role for LEC and its connections with TC in mnemonic function.
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  • 55
    ISSN: 1432-1106
    Keywords: Ischemia ; GABA ; Autoradiography ; Microdialysis ; In vitro electrophysiology ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have investigated the GABAergic system in rat hippocampus at 1 hour and up to 21 days following 20 min of global cerebral ischemia. Distribution of 3H-GABA (in excess of unlabeled baclofen) and 3H-Ro-15-1788 (benzodiazepine antagonist) binding sites in hippocampus was studied utilizing quantitative autoradiography. The 3H-GABA binding was unchanged (p〉 0.01) after ischemia, whereas the 3H-Ro-15-1788 binding decreased significantly (p〈 0.01) in all hippocampal subfields 1–21 days after ischemia. Using microdialysis in CA1, we found that K+-stimulated GABA release at 1 hour and 1 day after ischemia was unchanged (p〉 0.01) in comparison to preischemic controls. Electrophysiological recordings were made from CA1 of hippocampal slices prepared from rats sacrificed 1 hour, 1 day and 2 days after ischemia. Field potentials evoked by stimulation of the Schaffer collaterals showed no differences (p 〉 0.01) from those taken from controls. Postischemic intracellular recordings from the CA1 pyramidal cells showed that fast and slow inhibitory postsynaptic potentials were readily evoked on orthodromic stimulation. Together with our previous morphological results, demonstrating survival of hippocampal interneurons following ischemia, we conclude that hippocampal GABAergic interneurons preserve their inhibitory potential in the period preceding delayed CA1 pyramidal cell death. This conclusion taken together with the observation that postischemic 3H-Ro-15-1788 binding in hippocampus declined, suggest that benzodiazepines (by increasing the receptor affinity), GABA analogs, and GABA uptake inhibitors may be usefull in the treatment of ischemic CA1 pyramidal cell death in the rat.
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  • 56
    ISSN: 1432-1106
    Keywords: Superior cervical ganglion ; Intraocular ; Transplants ; Tyrosine hydroxylase ; Neuropeptide Y ; Enkephalin ; Calcitonin gene-related peptide ; Neuro-peptide-‘like immunoreactivity’ ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The purpose of the present study was to investigate the viability, growth characteristics and neuropeptide expression of intraocular superior cervical ganglia (SCG) grafts from neonatal (1–3 d), mature (4–5 months) and aged (20–24 months) rats. In vivo measurements, Falck-Hillarp histochemistry using iris whole mounts to assess catecholamine fiber outgrowth and immuno-cytochemical localization of tyrosine hydroxylase (TH-), neuropeptide Y (NPY-), leu-enkephalin (ENK-) and calcitonin gene-related peptide (CGRP-) like immuno-reactivity (LI) were used. Measurements indicated a marked decrease in volume during the first week after grafting and a more gradual decrease thereafter. This was most evident in newborn SCG. With prolonged survival time, the newborn ganglia demonstrated more varicose nerve terminals and increased catecholamine fiber outgrowth and arborization. Extensive and complex outgrowth of catecholamine fibers with varicose nerve terminals occurred more rapidly with mature and aged ganglia. In situ, all ganglion cell bodies and fibers demonstrated TH-LI. Localization of TH-LI after grafting indicated an increase in fiber density and a decrease in cell body density of 65%, 40% and 40% in newborn, mature and aged ganglia respectively. NPY-LI in cell bodies had a perinuclear fluorescence pattern consistent with localization in the Golgi apparatus. Grafting of newborn, mature and aged SCG resulted in a 20%, 20% and 35% decrease respectively of cell bodies containing NPY-LI. A concommitant increase in fiber diameter, fluorescence intensity and extent of arborization was observed. The characteristic distribution of ENK-LI in cell bodies and axons in mature and aged ganglia was not affected by grafting. However, there was a greater than 50% reduction in the number of cell bodies expressing ENK-LI. CGRP-LI, localized in fibers and axon terminals in SCG in situ, was not identified after grafting. In summary, we have demonstrated that SCG from all age groups form extensive fiber networks and continue neuropeptide expression after intraocular grafting. This was seen best in mature and aged donors and may suggest a role for SCG transplants in the replacement of monoaminergic neurons in the CNS.
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  • 57
    ISSN: 1432-1106
    Keywords: Hypothalamic paraventricular nucleus ; PHA-L ; Spinal projection ; Sympathetic preganglionic neurons ; Dendritic organization ; Cholera toxin ; Immunohistochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The descending projection of the hypothalamic paraventricular nucleus (PVN) to the sympathetic preganglionic neurons (SPNs) in the upper thoracic cord of the rat was studied. PVN-fibers were labeled by anterograde transport of Phaseolus vulgaris leucoagglutinin (PHA-L), while SPNs were retrogradely labeled with cholera toxin subunit B (CTb) which was injected into the superior cervical ganglion. SPNs labeled with CTb were mainly observed in the nucleus intermediolateralis (IML) pars principalis and pars funicularis, and a small number of them were in the nucleus intercalatus (IC) and central autonomic nucleus (CA). SPNs found in the IML had dendrites that projected in various directions. Five types of dendritic projections were noted: medial, rostral, caudal, lateral (including dorsolateral) and ventral. Longitudinal dendritic bundles interconnected each cell cluster in the IML. Medial dendrites of the IML, together with dendrites of the IC and CA, formed transverse dendritic bundles extending from the IML to the central canal. The transverse dendritic bundles disentangled near the midline and formed a loose dendritic plexus in the region just dorsal to the central canal. PVN-fibers labeled with PHA-L were observed primarily in lamina I and intermediate gray (lamina VII). Although varicose PVN-fibers and SPNs coexisted in the IML, the tight packing of the dendritic bundles prevented any clear demonstration of direct contacts between them. On the other hand, PVN-fibers were occasionally found to appose and wind around the primary or secondary dendrites of some SPNs of the CA and IC. These dendrites were studded with varicosities of PVN-fibers for a short length, and terminal boutons of PVN-fibers were also seen to make contact directly with the dendrites. The results of this study substantiated a direct connection between the PVN and SPNs, using a combination of immunohistochemical techniques for PHA-L and CTb. The possible involvement of a direct pathway from the PVN to SPNs in cardiovascular regulation is discussed.
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  • 58
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    Experimental brain research 86 (1991), S. 459-466 
    ISSN: 1432-1106
    Keywords: Pedunculopontine nucleus ; Substantia nigra ; Intracellular recording ; IPSP ; Antidromic activation ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Responses of 43 pedunculopontine area (PPN area) neurons to electrical stimulation of the substantia nigra (SN) were studied in anesthetized rats. An intracellular recording technique was used to demonstrate that SN stimulation evoked hyperpolarizing potentials, which were identified by intracellular injections as inhibitory postsynaptic potentials (IPSPs). These IPSPs were often followed by a rebound depolarization that originates several spike potentials. These IPSPs were characterized as monosynaptic, with latencies varying from 1.0 to 8.5 ms. Similar results were observed in some animals with chronic unilateral coronal lesion just rostral to subthalamic nucleus (STH), which severed the rostral afferents. PPN area neurons were also antidromically activated by SN stimulation. Two PPN area projection neurons were clearly identified. Mean latency of one group was 0.71 ms; mean latency of the second group was 5.16 ms. The morphological analysis of a neuron inhibited by SN stimulation and labeled with horseradish peroxidase (HRP) demonstrated that the soma was fusiform in shape, with the axon originating in the soma and collaterals and a large dendritic field extending in the ventrodorsalis direction. The results indicate that the PPN area is reciprocally connected with the SN, which elicits an inhibitory effect on PPN area neurons.
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  • 59
    ISSN: 1432-1106
    Keywords: Dopamine ; Dopamine and cAMP regulated phosphoprotein ; DARPP-32 ; Ischemia ; Striatum ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To evaluate the development of striatal ischemic cell damage in relation to alterations in dopamine (DA) transmission, one year old male Wistar rats underwent a 15 min incomplete cerebral ischemia (ICI) induced by occlusion of the common carotid arteries and by hypovolemic hypotension. The animals were divided into the following experimental groups: sham operated rats, rats with ICI without reperfusion, and rats with ICI followed by 60 min, 24 h, 72 h and 144 h of recirculation. The ischemia induced striatal lesions were investigated in serial coronal brain sections, stained with cresylviolet or immunostained for dopamine and cAMP regulated phosphoprotein (DARPP-32), for tyrosine hydroxylase (TH) and for glial fibrillary acidic protein (GFAP) immunoreactivities (IR). Measurements of striatal dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels were made on analogous experimental groups using HPLC methods. Signs of degeneration in small to medium sized neurons were already seen after 60 min of postischemic reperfusion together with slight decreases of DARPP-32 IR and increases of GFAP IR. The damage continued to increase up to 144 h, and after 24 h of recirculation there were clearly defined areas of reduced DARPP-32 IR, overlapping with increased TH IR and increased GFAP IR. The levels of DA, DOPAC and HVA increased sharply after 60 min (151%, 462% and 201%, respectively) remained high after 24 h and normalized after 72 h of recirculation. The DA metabolism was high after 60 min and had already normalized after 24 h of recirculation. The increased DA metabolism in striatal nerve terminals in response to ischemic injury may reflect an early degenerative change in the DA terminals. The long-lasting increase in TH IR may to some extent represent an adaptive change in response to the disappearance of DA receptor-containing nerve cells. Based on the present findings it is possible that an increased D1 transmission in neostriatum immediately following the ischemic injury may contribute to striatal nerve cell degeneration in which an enhancement of NMDA receptor transduction may be implicated.
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  • 60
    ISSN: 1432-1106
    Keywords: Cortex ; Glutamic acid decarboxylase ; In situ hybridization ; mRNA ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In situ hybridization histochemistry (ISHH) was used to study the expression of glutamic acid decarboxylase (GAD) mRNA changes in the rat cerebral cortex following unilateral frontal and somatosensory cortical lesion by devascularisation. 4 days after the lesion, a significant transient increase in GAD mRNA level in the ipsilateral cortex was observed when compared with contralateral, ipsi-sham operated and ipsi-normal control cortices. The change occurred throughout the ipsilateral neocortex, with no significant difference between the magnitude of increase in frontal, parieto-occipital, parieto-temporal, cingulate or retrosplenial areas; no obvious change was seen in pyriform, entorhinal or hippocampal cortices. This unexpected GAD mRNA increase in neocortex may be part of a long term adaptive functional alteration and changes in the gene expression of the cerebral cortex following focal cortical injury.
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  • 61
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    Experimental brain research 85 (1991), S. 501-506 
    ISSN: 1432-1106
    Keywords: Neural grafts ; Striatum ; Cocaine ; Immediate-early gene ; c-fos ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Cocaine, a catecholamine agonist, has been shown to produce a transient induction of the immediate-early gene c-fos and its protein product Fos in the striatum of normal rats. In the present study we report that the expression of Fos can be induced by cocaine challenge in intrastriatal grafts derived from cell suspensions of embryonic striatal primordia. Fos-like immunoreactivity in the nuclei of grafted neurons was detected 2 hr after the injection of 50 mg/kg cocaine into the host rats. Neurons with Fos-immunoreactive nuclei tended to form clusters in the striatal grafts. The Fos-rich clusters were aligned with acetylcholinesterase (AChE)-rich and tyrosine hydroxylase (TH)-rich patches demonstrated in adjoining sections. Previous studies have shown that presynaptic and postsynaptic cellular markers of the dopaminergic system in the striatum, including immunostaining for TH and dopamine- and adenosine 3′:5′-monophosphate-regulated phosphoprotein (DARPP-32), and binding for high affinity dopamine uptake sites and for dopamine D1 and D2 receptor sites, are all concentrated in the AChE-rich patch regions (P regions) of such embryonic striatal grafts. The preferential expression of Fos in neurons of the P regions of the grafts thus implies that the induction of Fos was cell-type specific in being concentrated in the parts of the grafts that express striatal phenotype and that are innervated by catecholamine-containing fibers. This specificity strongly suggests that the activation of Fos expression in neurons of the P regions of the grafts reflects dopaminergic interactions between the grafts and host nigrostriatal fibers. We conclude that the cellular messenger systems and transcriptional activation mechanisms responsive to dopaminergic stimulation by the host can be activated in the embryonic striatal grafts, and that the grafts are thus functionally integrated into the host brain at the level of cellular signaling systems.
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  • 62
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    Experimental brain research 85 (1991), S. 543-551 
    ISSN: 1432-1106
    Keywords: Voltage-dependent Ca2+-currents (HVA or L-type) ; Inactivation ; Intraneuronal Ca2+ ; Buffering ; Dentate gyrus granule cells ; Kindling-induced epilepsy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Nerve cells that lack the cytoplasmic Ca2+ binding protein Calbindin-D28K (CaBP) appear to be selectively vulnerable to Ca2+-related injury consistent with a postulated intraneuronal Ca2+-buffering role of CaBP. We have confirmed the selective loss of CaBP from the dentate gyrus during kindling-induced epilepsy in acutely dissociated granule cells (GCs) from kindled rats. Immunohistochemically stained kindled neurons showed a significant loss of CaBP when compared to controls (p 〈 0.001; ANOVA). The Ca2+-buffering role of CaBP was assessed in acutely dissociated control and kindled GCs by examining a physiological process highly sensitive to intracellular Ca2+-buffering: the Ca2+ -dependent inactivation of high-voltage activated (HVA or L-type) Ca2+ currents in the absence (or presence) of exogenous Ca2+-chelators. Whole-cell patch clamp recordings in kindled GCs demonstrated a markedly enhanced Ca2+-dependent inactivation of Ca2+-currents. After brief conditioning Ca2+ currents, in the absence of an exogenous intraneuronal Ca2+-chelator, subsequent test Ca2+ currents were inactivated by 58.3% in kindled GCs, a significant increase from the 37.4% inactivation observed in control GCs (p〈 0.005; ANOVA). The differential Ca2+ current decay and Ca2+-dependent inactivation were prevented in both control and kindled GCs upon loading the neurons with the exogenous Ca2+-chelator BAPTA. These experiments demonstrate a high correlation between the loss of CaBP and changes in Ca2+ current inactivation and are consistent with the hypothesis that CaBP contributes to the physiological Ca2+-buffering in mammalian neurons.
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  • 63
    ISSN: 1432-1106
    Keywords: Preoptic area ; Opioid binding ; Diprenorphine ; Noradrenergic transmission ; Ventral noradrenergic tract lesion ; Autoradiography ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Experiments were undertaken to establish whether opioid receptors exert a direct presynaptic influence on noradrenergic (NA) terminals in the preoptic/ anterior hypothalamus (PO/AH) of the female rat. Thus, opioid binding studies were performed in rats with lesions of the ventral NA tract (VNAT; the main NA projection to the hypothalamus) to assess whether a loss of NA terminals may also result in a decrease in opioid binding in the PO/AH. In the first experiment, unilateral electrolytic lesions of the VNAT caused a significant reduction in both the NA content and specific [3H]-diprenorphine binding to membrane homogenates in the ipsilateral PO/AH. In the second experiment bilateral 6-hydroxydopamine (6-OHDA)-induced lesions of the VNAT caused a significant reduction in NA levels in the PO/AH as well as significant decreases in the density of [3H]-diprenorphine binding to tissue sections of the PO/AH when compared to control animals. These results strongly suggest that the NA input to the PO/AH is regulated by endogenous opioid peptides, and provide an anatomical substrate to explain opioid-NA interactions in the control of gonadotrophin releasing hormone (GnRH) and gonadotrophin secretion.
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  • 64
    ISSN: 1432-2013
    Keywords: Vitamin E (deficiency) ; Muscle damage ; Sex difference ; Muscle histology ; Exercise ; Rat ; Morphology ; Creatine kinase ; Isoenzymes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats, fed a vitamin-E-deficient diet for 6 weeks, performed treadmill exercise for 2 h. Muscle damage was assessed by measuring the creatine kinase (CK) activity in plasma before and after exercise, and by studying semithin longitudinal sections of the soleus muscle 48 h after running. Vitamin-E-deficient male and female rats showed an increased post-exercise CK activity when compared to matched controls, but male rats showed a larger CK response than females. This rise in plasma CK activity was caused mainly by an increased activity of the muscle-specific CK-isoenzyme, CK-MM (males + 1238%; females + 540%, P〈0.05). In a parallel histological study we observed in vitamin-E-deficient male rats a dramatic and significant disturbance of the normal cyto-architecture of the muscle fibres after exercise (focal necrosis, phagocytosis and cellular infiltrates), whereas in females only minor, non-significant, changes were seen. We conclude that vitamin E deficiency enhances the susceptibility to exercise-induced muscle damage in male rats more than in female rats. This difference between the sexes is attributed to the protective effect of oestradiol that remains operative in female rats when the vitamin E status is disturbed: male rats lack such hormonal protection.
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  • 65
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    Naunyn-Schmiedeberg's archives of pharmacology 343 (1991), S. 595-602 
    ISSN: 1432-1912
    Keywords: Periaqueductal gray slices ; [3H]Noradrenaline release ; [3H]Dopamine release ; [3H]5-Hydroxytryptamine release ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The periaqueductal gray is a brain region of considerable interest. It is innervated by monoamine-containing neurons as well as by a variety of peptidergic fiber systems, and it participates in the regulation of various functions. Virtually nothing is known about monoamine release in the periaqueductal gray and its receptor-mediated modulation. We therefore studied the release of radioactivity from periaqueductal gray slices preloaded with tritriated monoamines, using an in vitro superfusion method. The release of radioactivity from superfused periaqueductal gray slices after preloading of the tissue with [3H]noradrenaline increased upon electrical stimulation in a frequency-dependent manner. The stimulus-evoked release of radioactivity was Ca2+-dependent. Clonidine reduced and yohimbine enhanced the release. The inhibition curve for the effect of clonidine was shifted to the right in the presence of 10−6 M yohimbine. While phenylephrine, isoprenaline, SK&F 38393, quinpirole, carbachol, [Arg8]vasopressin, α-MSH and ACTH-(1-24), at a concentration of 10−6 M, did not influence the electrically evoked release of radioactivity, [Leu5]enkephalin reduced it. The selective μ-opioid receptor agonists [d-Ala2,NMePhe4,Gly-ol5]enkephalin and [d-Arg2,Lys4]-dermorphin-(1–4)-amide reduced the release of radioactivity, whereas the selective δ opioid receptor agonist [d-Pen2,d-Pen5]enkephalin and the selective K opioid receptor agonist U-69593 had no effect. In the presence of naloxone, which by itself had no effect on the release of radioactivity, the effect of [d-Arg2,Lys4]dermorphin-(1–4)-amide was abolished. These results show that the release of noradrenaline from periaqueductal gray slices is via a Ca2+-dependent. exocytotic process, and that it is modulated through α2-adrenoceptors as well as via μ-opioid receptors. Though the overflow of radioactivity from slices preloaded with [3H]dopamine in the presence of desipramine was measurable, there are reasons to assume that we are dealing here with the release of tritiated catecholamines from a population of nerve endings consisting of noradrenergic and dopaminergic terminals. The release of radioactivity from periaqueductal gray slices preloaded with [3H]5-hydroxytryptamine upon elevation of the K+ concentration in the superfusion medium was much more pronounced than that induced by electrical stimulation. The K+-evoked release of radioactivity was almost completely abolished in the absence of Cat2+; showing that the release is via a Ca2+-dependent process. 5-Hydrotryptamine reduced the K+-evoked release of radioactivity in a concentration-dependent manner.
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  • 66
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    Naunyn-Schmiedeberg's archives of pharmacology 343 (1991), S. 439-446 
    ISSN: 1432-1912
    Keywords: 5-HT4 ; Oesophagus ; Rat ; ICS 205–930 ; Benzamides
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The present study was designed to characterize an “atypical” 5-hydroxytryptamine (5-HT) receptor mediating relaxation of the rat oesophageal tunica muscularis mucosae. All experiments were performed under equilibrium conditions, using pargyline to inhibit the oxidative deamination of indoleamines, and cocaine and corticosterone to inhibit neuronal and extraneuronal uptake. Under these conditions 5-HT (0.3–1000 nmol/l) produced a concentration-dependent relaxation of carbachol-induced tension. The concentration-effect curve to 5-HT was unaffected by potent antagonists for 5-HT1, 5-HT2, 5-HT3 and so called 5-HT1P receptors (metergoline, methysergide, ketanserin, ondansetron, N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophan amide), but was antagonized competitively by ICS 205–930 (pA2 = 6.7). Responses to 5-HT were mimicked by other indoleamines and substituted benzamides with the following order of potency: 5-HT ≥ 5-methoxytryptamine 〉 cisapride = α-methyl-5-HT = (S)-zacopride = renzapride 〉 (RS)-zacopride 〉 5-carboxamido-tryptamine = metoclopramide = (R)-zacopride 〉 tryptamine 〉 2-methyl-5-HT. ICS 205–930 afforded similar pA2 values (6.0–6.7) against each agonist, indicating a common site of action. Concentration-effect curves to 5-HT were not affected by tetrodotoxin or indomethacin, sugesting that 5-HT-induced relaxation of the tunica muscularis mucosae was mediated via a postjunctional receptor, independent of endogenous prostanoids. The pharmacological profile of the 5-HT receptor in the rat oesophageal tunica muscularis mucosae correlates well with the 5-HT4 receptor characterized recently in both the CNS and gastro-intestinal tract.
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    Naunyn-Schmiedeberg's archives of pharmacology 343 (1991), S. 46-51 
    ISSN: 1432-1912
    Keywords: Aortic baroreceptor reflex ; Excitatory amino acid receptors ; Caudal ventrolateral medulla ; Kynurenate ; Muscimol ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The caudal ventrolateral medulla (CVLM) contains vasodepressor neurons which, when activated, decrease vasomotor tone. To investigate whether excitatory amino acid receptors in the CVLM of the rat are involved in mediation of the aortic baroreceptor reflex, we microinjected amino acid antagonists unilaterally into the CVLM and examined their effects on the depressor response to electrical stimulation of the aortic nerve which contains mainly baroreceptor afferent fibers in rats. Male Wistar rats were anaesthetized with urethane, paralyzed and artificially ventilated. To block reflex vagal effects, methylatropine (1 mg/kg) was given intravenously. Kynurenate (227 ng), an excitatory amino acid antagonist, injected ipsilaterally but not contralaterally into the CVLM markedly inhibited the depressor response to aortic nerve stimulation, while both injections produced a similar small increase in basal blood pressure. Muscimol (1 ng), a GABA receptor agonist, injected ipsilaterally into the CVLM partly inhibited the baroreflex response, while it produced a moderate increase in basal blood pressure. 2-Amino-5-phosphonovalerate (APV) (10 ng), a N-methyl-d-aspartate (NMDA) receptor antagonist, and MK-801 (30 ng), a NMDA receptor channel blocker, partly inhibited the baroreflex response. MK-801 (30 ng) injected into the CVLM reduced the depressor response to the NMDA receptor agonist NMDA (0.3 ng) but not to the quisqualate receptor agonist quisqualate (0.1 ng) and the kainate receptor agonist kainate (0.1 ng), while kynurenate (227 ng) inhibited the depressor response to all three excitatory amino acid receptor agonists. These findings provide further evidence for the presence of excitatory amino acid receptors involved in mediating the aortic baroreceptor reflex in the rat CVLM. It appears that neurons other than the vasodepressor neurons in the CVLM, at least in part, play a role in transmitting the aortic baroreceptor reflex. In addition, both NMDA and non-NMDA receptors may be responsible for the mediation of the reflex.
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  • 68
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    Naunyn-Schmiedeberg's archives of pharmacology 344 (1991), S. 79-83 
    ISSN: 1432-1912
    Keywords: Antidepressant drugs ; Hippocampus ; Long-term potentiation ; NMDA-receptor ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The actions of three clinically effective antidepressant drugs with different pharmacological profiles were investigated in the CAI area of rat hippocampal slices. Imipramine and (+) or (−)-oxaprotiline had negligible effects on population spikes evoked by stratum radiatum stimulation, but reduced postsynaptic excitability in low Ca high Mg medium after an exposure of more than 15 min. Imipramine and (+)-oxaprotiline at 10 μmol/l enhanced long-term potentiation (LTP) when a lower stimulation strength was applied while (+)-oxaprotiline reduced UP when a higher stimulus amplitude was used to evoke population spikes. (−)-oxaprotiline (levoprotiline) had a similar effect which was, however, not significant in either stimulation paradigm at the P〈0.05 level. Imipramine actions were also studied on epileptiform discharges in Mg2+-free medium: a facilitation-inhibition sequence with a slow time course was seen with 50 μmol/l but no effect with 10 μmol/l. An involvement of N-methyl-D-aspartate (NMDA)-receptors in acute actions of antidepressants is unlikely but long-term potentiation in the hippocampus is modulated by these drugs.
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  • 69
    ISSN: 1432-198X
    Keywords: Diet ; Protein ; Uraemia ; Rat ; Growth ; Amino-acids ; Keto-acids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The nutritional effects of low-protein diets are difficult to assess in humans. Normal and uraemic growing rats were therefore fed: a moderately low-protein (12%) reference diet (diet R), two 5% casein diets, one supplemented with essential amino acids (AA) (diet A) and the other with their keto acids (diet K), and a 7% casein diet isonitrogenous with diet K (diet L). Appetite and growth of both uraemic and control rats were identical on diets R and A and were reduced on diets K and L. Stunting was prominent in rats fed diet L and more severe than in those on diet K. Diet K induced marked anorexia in controls. This effect was smaller in uraemic rats, which were all anorectic, regardless of the diet. Plasma essential AA were similar in rats on diets R and A but low in control rats fed diets L and K. In particular, diet K did not improve the branchedchain AA levels although it produced better growth than diet L. Plasma and muscle threonine were surprisingly elevated in rats on the semi-synthetic diets A and K, despite identical or lower consumptions. Regardless of the diet, uraemia resulted in unchanged or increased plasma essential AA, despite reduced appetite and stunting. Uraemia caused a marked rise in some non-essential AA. Muscle essential AA, except for threonine, were essentially unaltered and did not correlate with growth or uraemia.
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  • 70
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    Pediatric nephrology 5 (1991), S. 501-504 
    ISSN: 1432-198X
    Keywords: Sodium-deficient ; Protein turnover ; Protein synthesis ; Salt-depletion ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study examines the consequences of sodium chloride supplementation to young rats previously made salt deficient by feeding them a sodium-deficient, chloride-replete diet. Salt-deficient rats received the test diet and distilled water for 10 days. As in our previous studies, rats cared for in this manner grew more slowly than rats fed the identical diet but allowed to drink 37 mM sodium chloride. On day 11, half of the salt-depleted animals received 37 mM sodium chloride in their drinking water. Sodium-deficient and supplemented rats were studied 1, 2, 5–6 and 11–12 days later. Urinary sodium rapidly rose from undetectable to 46 mEq/l urine within 1 day of supplementation and there was no further increase the next day, suggesting that extracellular fluid volumes were rapidly repleted. Food intake increased in the supplemented rats compared with the deficient animals but the difference in food intake equalled only 2.25 g/day for the first 2 days of supplementation. Over the last 12 days of the first 2 days of supplementation. Over the last 12 days of the study, the slopes of both weight and length gains were equal in both the supplemented and the control group and significantly higher than those in the deficient rats. Over the course of the study, full catchup was not obtained in either length or weight. In addition to total weight and length gains, liver and kidney weights increased proportionately and by 5–6 days of supplementation were equivalent to the weights seen in the control group. After 2 days of supplementation, the incorporation of14C-phenylalanine into epitrochlearis muscle preparations increased 21% (P=0.02) and by 5–12 days after supplementation, muscle protein synthesis rates increased 30%–40% (P=0.01). Net degradation, was not significantly altered by sodium repletion. Whether measured as total gastrocnemius (or liver) RNA or as the ratio of RNA/DNA, RNA levels rapidly increased after sodium chloride supplementation (P〈0.01). Thus, sodium supplementation rapidly restores weight gain and linear growth, muscle and liver RNA levels and muscle protein synthesis rates in young, salt-depleted rats. Since salt depletion may exist in a variety of clinical conditions often associated with poor growth, its presence must be considered in attempts to maximize growth in infants and children with chronic illness.
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  • 71
    ISSN: 1432-1106
    Keywords: Cutaneous nerve projections ; Dorsal horn ; Clarke's column ; Choleragenoid ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The aim of the present study has been to investigate the spinal projections of cutaneous hindlimb afferents particularly to the deep dorsal horn and to Clarke's column (CC), by using the B-subunit of cholera toxin conjugated to horseradish peroxidase. Injections into three different cutaneous hindlimb nerves in adult rats resulted in dense labeling in the dorsal horn laminae IIi-IV/V, moderate labeling in lamina I and modest labeling in dorsomedial parts of CC. Footpad injections gave similar results, except for a lack of labeling in CC and only weak labeling in laminae I and V. The results suggest that B-HRP should be a useful marker for studying cutaneous myelinated nerve fiber projections to the rat spinal cord.
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  • 72
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    Experimental brain research 84 (1991), S. 91-101 
    ISSN: 1432-1106
    Keywords: Ischemia ; Hyperglycemia ; Hypothermia ; Seizures ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Preischemic hyperglycemia aggravates brain damage following transient ischemia, and adds some special features to the damage incurred, notably a high frequency of postischemic seizures, cellular edema, and affectation of additional brain structures, such as the substanta nigra pars reticulata (SNPR). We raised the question whether mild intra-ischemic hypothermia (32–33° C), known to reduce selective neuronal vulnerability in normoglycemic subjects, also ameliorates the characteristic damage observed in hyperglycemic animals. To that end, two series of experiments were performed. In the first, normo- and hypothermic animals were subjected to 10 min of ischemia during hyperglycemic conditions (plasma glucose 20–25 mmol · 1-1), and allowed either 15 h or 1 week of recovery. In the second, both normo- and hyperglycemic animals were subjected to 15 min of ischemia (at normal or reduced temperature) and surviving animals were studied after 1 week of recovery. All normothermic, hyperglycemic animals developed postischemic seizures and died within the first 24 h. Mild hypothermia afforded substantial protection. Thus, 6/7 hypothermic animals subjected to 10 min of ischemia survived 1 week of recovery and none developed postischemic seizures. Of the hypothermic animals subjected to 15 min of ischemia 6/11 survived for 1 week, only one of which developed seizures. Protection by hypothermia was also shown by the histopathological analysis. Experiments with 10 min of ischemia and 15 h of recovery showed the expected damage in normothermic, hyperglycemic subjects. Hypothermia markedly reduced damage in all vulnerable structures, including the cingulate cortex and SNPR. The protection was most pronounced in the caudoputamen, where no affected neurons were seen in the hypothermic subjects. The experiments with 15 min of ischemia confirmed previous findings that mild hypothermia protects normoglycemic animals against the insult. The results also showed that hypothermia prevented most of the exaggeration of damage caused by hyperglycemia. However, under hypothermic conditions hyperglycemia still augmented damage in the cingulate cortex, medial and lateral venteroposterior thalamic nuclei, and SNPR, structures specifically damaged under hyperglycemic, normothermic conditions. This suggests that hypothermia has less of a protective effect on mechanisms causing such damage than on neuronal damage in the classic selectively vulnerable regions, particularly the caudoputamen.
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  • 73
    ISSN: 1432-1106
    Keywords: Monoclonal antibody (mabQ113) ; Zebrin I ; Purkinje cells ; Spinocerebellar projections ; Central cervical nucleus ; Cholera toxin ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have examined the topographic relationship between the sagittal bands of zebrin I immunoreactive Purkinje cells revealed by a monoclonal antibody, mabQ113, and the distribution of spinocerebellar fibers originating from the central cervical nucleus in the rat. The mossy fiber terminals were anterogradely labeled following injections of cholera toxin subunit B into the C1–C3 segments and visualized immunohistochemically. Zebrin I positive Purkinje cells appeared in seven sagittal bands (P1+ to P7+ bands). In lobules I–V of the anterior lobe, labeled mossy fiber terminals were distributed in the midline region, subjacent to the P1+ bands and at around 0.5 mm from the midline region, subjacent to the P2+ band in the lateral A1 to the medial A2 zones of Voogd et al. (1985). Labeled terminals were seen in the entire B zone and those distributed in its medial part were related to the P3+ band. In lobule VIII, labeled terminals were seen subjacent to the P1+, P2+ and P3+ bands, which were located in the lateral A1–A3 (or B) zones. In the copula pyramidis, labeled terminals appeared subjacent to the P4+, P5+ and the P6+ bands in the C1 and C2 zones (or the C1-C3 zones). Although the labeled terminals were seen beneath the zebrin I positive bands, the borders of terminal distribution were not well-delineated, and did not respect the borders of zebrin I positive bands.
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    Experimental brain research 84 (1991), S. 159-166 
    ISSN: 1432-1106
    Keywords: Plasticity ; Reactive synaptogenesis ; Inhibition ; Somatotopy ; Single units ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The present experiments were designed to determine the effects of removing the dorsal column nuclei on the evoked responses of the ventroposterolateral nucleus (VPL) neurons in the rat. Previously, we have observed inhibitory interactions between forelimb and hindlimb inputs to VPL (Roberts and Wells 1990), and have also observed a synaptic recovery process within VPL following dorsal column nuclei (DCN) lesions (Wells and Tripp 1987). In an attempt to describe any changes in VPL responses that correlate with the synaptic recovery in VPL following lesions to the DCN, we have studied the incidence of the inhibition process in VPL, the latency of activation of single unit VPL responses to peripheral nerve stimulation, the number of evoked unit responses observed per track studied and the somatotopy of responses in VPL. Dorsal column nuclei lesions did not alter the incidence or duration of the inhibitory interaction between forelimb and hindlimb inputs to VPL. Following DCN lesions, there was a significant increase in the latency to activation of VPL neurons by both forelimb and hindlimb inputs. This increase in latency returned to a non-significant difference from control over the same interval of time that is required for the structural recovery in VPL. There was a significant reduction in the number of evoked unit responses observed per track studied in the deafferented group at the twenty day post-lesion time course. This difference was no longer statistically significant in the sixty-four day post-lesion group. Finally, we have observed little change in the overall anatomic distribution of responses to forelimb or hindlimb stimulation in VPL following DCN lesions. This distribution is not discretely somatotopic when evoked by electrical stimulation of peripheral nerves either prior to or following DCN lesioning.
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  • 75
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    Experimental brain research 84 (1991), S. 142-158 
    ISSN: 1432-1106
    Keywords: Thalamic lesions ; Kainic acid ; HRP ; Callosal connections ; Laminar density ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The patterns of callosal interconnections between the visual cortices of rats display considerable plasticity in response to various neonatal manipulations. In the present study, many neurones in the principal visual thalamic relay nuclei, the dorsal lateral geniculate nucleus (DLG) and to a lesser extent those in the lateral posterior nucleus (LP) were destroyed by injections of the neurotoxin — kainic acid — on the first day of postnatal life. Four weeks later, as demonstrated with the anterograde and retrograde transport of the enzyme horseradish peroxidase (HRP) injected into the occipital lobe of one hemisphere, callosally projecting neurones and terminals were distributed more widely in the retinotopically organized areas 17, 18a and 18b of the visual cortex ipsilateral to the lesioned visual thalamus than in unoperated control animals of the same age. By contrast, in the visual cortex contralateral to the lesioned visual thalamus the areal distribution of callosally projecting neurones and terminals was similar to that of the controls, that is, largely but not exclusively restricted to the common border of areas 17 and 18a. Both in unoperated and operated animals, cells in lamina V of several cytoarchitectonically defined areas that are not retinotopically organized (area 8 in the frontal lobe, area 29d in the retrosplenial limbic cortex and perirhinal areas 35/13 in the temporal lobe) also project to contralateral visual cortices. In areas 8 and 29d, the total numbers, laminar distributions and densities of labelled callosal cells both ipsilateral and contralateral to the kainate-injected visual thalamus were similar to those in the controls. However, in the temporal lobe, the areal distribution of the labelled callosal neurones was more extensive than that in the controls and labelled cells in areas 35/13 of the cortex contralateral to the kainate-lesioned visual thalamus merged with those in the neighbouring areas 20 and 36. By contrast, the areal distribution of associational neurones in area 18a and in nonretinotopically organized areas projecting to area 17 were very similar in controls and in operated animals (neonatal kainate lesion of the visual thalamus, neonatal section of the corpus callosum or both procedures combined). However, in operated animals, the labelled associational neurones projecting from the supragranular laminae (II/III) of area 18a to area 17 constituted a higher proportion of all cells than did those in the unoperated control animals. Thus, overall the number of associational neurones projecting from area 18a to area 17 was slightly increased by the experimental manipulations performed. The implications of these results concerning the mechanism(s) underlying the developmental changes in the distribution of commissural and associational neurones projecting to the rat's visual cortex are discussed.
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    Experimental brain research 84 (1991), S. 224-228 
    ISSN: 1432-1106
    Keywords: Dihydropyridine ; Hippocampus ; Calcium channel ; Nootropic ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Intracellular recording in the in vitro hippocampal slice was utilized to examine the effects of nimodipine and nifedipine on CA1 pyramidal cell excitability. The excitatory postsynaptic potential (EPSP) elicited by a single stimulus in stratum radiatum was enhanced by nifedipine as evidenced by increases in EPSP amplitude, area and slope. Threshold for synaptically-evoked somatic action potentials was decreased following either nifedipine or nimodipine application, often resulting in spontaneous action potential activity. A secondary, late EPSP-like event appeared in the intracellular recordings during and following bath application of nimodipine, and was associated with burst-like activity in field potential recordings. In accordance with the hydrophobic nature of these compounds, extensive washout in normal Krebs' solution failed to reverse their effects, but nifedipine's actions were photolabile. These results indicate that dihydropyridines can enhance synaptic efficacy in the CA1 region of the hippocampus.
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  • 77
    ISSN: 1432-1106
    Keywords: Hippocampus ; Fluoride ; G-proteins ; Calcium ; Long-term potentiation ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Rat hippocampal slices were exposed briefly (12–15 min) to AlF4- (10 mmol/l NaF, 10 μmol/l AlCl3). The effect on synaptic transmission in area CAl was measured using extracellular electrodes placed in the stratum pyramidale and stratum radiatum. During fluoride exposure, both spike and EPSP amplitude fell to very low levels. Upon washout, spike amplitude recovered beyond control values, and in half of the preparations a prolonged enhancement of spike amplitude (〉 2 h) occurred. Similar modulation of EPSP slope indicated that these charges were primarily synpatic. If Al3+ was omitted from the F--containing saline, enhancement of spike amplitude, when observed, was brief (20–30 min) and no enhancement of EPSP slope was seen. Omission of Ca2+ from the AlF4--containing saline also abolished any long-lasting enhancement of synaptic transmission, though population spike amplitude in most slices showed a brief (20–30 min) stimulatory response. In preparations in which LTP had previously been saturated, synaptic transmission was not enhanced by exposure to AlF4-. It is concluded that NaF/ACl3 exposure induces an LTP-like process by G-protein activation, which involves recruitment of processes involved in LTP, possibly including an enhancement of Ca2+-influx.
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  • 78
    ISSN: 1432-1106
    Keywords: Degeneration ; Retina ; Electroretinogram ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A lesion to the optic nerve of adult mammals leads to the retrograde degeneration and finally to the death of injured retinal ganglion cells. In this study, we have evaluated the effects induced by different sites of axotomy on the functional changes occurring in the retinal ganglion cells after optic nerve section. We have investigated the functional properties of retinal ganglion cells of adult rats by recording the retinal responses to patterned stimuli (pattern electroretinogram) after unilateral section of the optic nerve at two different levels: intraorbital and intracranial. The results show that the site of lesion of the optic nerve affects the time of disappearance of the pattern electroretinogram. The pattern electroretinogram takes longer to be degraded after an intracranial section than an intraorbital section.
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  • 79
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    Experimental brain research 85 (1991), S. 559-564 
    ISSN: 1432-1106
    Keywords: Thyroid hormone ; Development ; Hippocampus ; Dentate gyrus ; LTP ; Learning ; Memory ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Excess thyroid hormone at an early stage of development produces marked neurochemical and morphological alterations in the rat hippocampal formation. In order to better understand the functional significance of these changes, we tested adult rats treated neonatally with triiodothyronine (T3), and their control litter mates, in a spatial learning task and for the induction of longterm potentiation (LTP) in the dentate gyrus (DG) of the hippocampal formation. The T3-treated rats were significantly impaired in their performance on the spatial task in comparison to their matched controls. Similarly, the efficacy of LTP induction was significantly attenuated in the T3-treated animals. Further, a significant correlation was obtained between LTP induction and performance on the spatial learning task. Thus, a brief neonatal excess of thyroid hormone produces impairments in spatial learning along with decreases in LTP, long held as a model of learning and memory. This relationship provides a unique opportunity to study associations between behavioral, physiological, pharmacological and morphological processes intimately associated with the hippocampal formation
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  • 80
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    Experimental brain research 85 (1991), S. 577-586 
    ISSN: 1432-1106
    Keywords: Acoustic thalamus ; Amygdala ; Emotional memories ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Projections from the acoustic thalamus to the lateral nucleus of the amygdala (AL) have been implicated in the formation of emotional memories. In order to begin elucidating the cellular basis of emotional learning in this pathway, the ultrastructure and synaptic associations of acoustic thalamus efferents terminating in AL were studied using wheat-germ agglutinated horse-radish peroxidase (WGA-HRP) and Phaseolus vulgaris Leucoagglutinin (Pha-L) as ultrastructural anterograde axonal markers. The tracers were injected into those areas of the thalamus (medial division of the medial geniculate body and posterior intralaminar nucleus, MGM/PIN) known both to project to AL and to receive afferents from the inferior colliculus. Terminals labeled with WGA-HRP or Pha-L in AL contained mitochrondria and many small, round clear vesicles and 0–3 large, dense-core vesicles. Most labeled terminals formed asymmetric synapses on unlabeled dendrites; of these the majority were on dendritic spines. These data demonstrate that projections from the acoustic thalamus form synapses in AL and provide the first characterization of the ultrastructure and synaptic associations of sensory afferent projections to the amygdala.
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  • 81
    ISSN: 1432-1106
    Keywords: Superior colliculus ; Immunocytochemistry ; Serotonin ; Hamster ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Immunocytochemistry for serotonin (5-HT) was carried out in both hamsters and rats in order to determine whether or not 5-HT-positive cells existed in the superior colliculus (SC) of either species. In both hamster and rat, the superficial and deep SC laminae contained dense networks of 5-HT-positive fibers. The rat's SC contained no 5-HT-positive neurons. In hamster, numerous 5-HT-immunoreactive cells were visible throughout the depth of the stratum griseum superficiale (SGS). These neurons had a variety of morphological characteristics and included marginal cells, horizontal cells, and neurons with vertically oriented dendritic trees. No 5-HT-positive neurons were found in any other portion of the hamster's SC. 5-HT-positive SC cells were observed with antisera from two different sources and they were not seen in animals that were pretreated with reserpine. Pretreatment with fluoxetine (an inhibitor of 5-HT uptake) also resulted in a disappearance of 5-HT-positive neurons in the hamster's SC. This result indicated that “serotonergic” cells in the colliculus of this species are capable of taking up, but probably not synthesizing, this indoleamine. The dorsal and ventral lateral geniculate nuclei (LGNd and LGNv, respectively) both contain numerous 5-HT-positive fibers and both of these structures receive input from the SGS. Combination of retrograde tracing with fluorogold and immunocytochemistry indicated that 5-HT-accumulating SC neurons were not the source of these fibers. Unilateral ablation of the superficial SC laminae also failed to reduce 5-HT immunoreactivity in either the LGNd or LGNv. These results are consistent with the possibility that 5-HT-accumulating cells in the hamster's SC may be interneurons that take up this transmitter after it is released by afferents to this nucleus.
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  • 82
    ISSN: 1432-1106
    Keywords: Glutamate receptor agonists ; Metabolic inhibitors ; Neurotoxicity ; Hippocampus ; Evoked field potentials ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The perforant path evoked field potentials in the dentate gyrus of the rat hippocampus are distinctive and thus were used as a marker for the accurate positioning of injection cannulae. The time course of the changes in these potentials caused by various toxins were determined and correlated with the extent of neuronal loss produced subsequently. Glutamate and the glutamate receptor agonists, kainate and N-methyl-D-aspartate (NMDA), caused an immediate loss of the evoked field potentials, suggesting a massive depolarization block. After the glutamate agonists there was only a small recovery in potentials over a period of 8 h, whereas after glutamate the potentials recovered within 5 h. Short-term decreases in evoked potential (up to 2 h) were also found after saline injections. Hippocampal evoked potentials were still reduced 8 h after NMDA, even in areas not showing subsequent neuronal loss. Sodium iodoacetate (10 nmol) caused a delayed loss of evoked potentials, reaching a minimum 15 min after injection and lasting for at least 8 h, whereas after sodium cyanide (10 nmol) the potentials decreased immediately to a similar extent to those found 15 min after iodoacetate, but recovery was reversible over 8 h. There was a significant correlation between the degree to which the evoked potentials were decreased and the extent of death of the granule cell neurons, examined histologically four days later.
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  • 83
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    Experimental brain research 85 (1991), S. 621-624 
    ISSN: 1432-1106
    Keywords: Long-term depression ; Long-term potentiation ; Excitatory postsynaptic potentials ; NMDA receptors ; Prefrontal cortex ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary All the experiments were carried out in slices of rat prefrontal cortex maintained in vitro. The effect of 2-amino-5-phosphonovalerate (APV) was tested on the postsynaptic potential (PSP) recorded in layer V pyramidal cells, in response to single or high frequency stimulation of the superficial layers I–II. Wash-out of Mg2+ increased the amplitude and duration of the PSPs. This effect resulted from activation of N-methyl-D-aspartate (NMDA) receptors since it was suppressed by bath application of APV. Furthermore, in every cell tested in Mg2+ containing medium (N=16), exposure to APV reversibly reduced both mono- and polysynaptic components of the PSPs, indicating that, even in the control solution, activation of NMDA-coupled channels contributed to these synaptic events. Finally, the anomalous voltage-dependence of the EPSP in the presence of Mg2+ and its sensitivity to APV suggests that at least a fraction of the NMDA receptors are postsynaptically located. Tetanization was applied to the afferents of cells bathed in control- or APV-medium. Long-term potentiation (LTP) or long-term depression (LTD) is defined as an increase or a decrease respectively, of the PSPs peak amplitude or initial slope, lasting 20 min. In the control medium, LTP in synaptic efficacy was observed in 34% of the cells and LTD in 48% (N=23). When exposed to APV, none of the cells tested (N=16) showed LTP of the response. In contrast, the tetanus induced a LTD of the PSP amplitude or slope in 14 out of these 16 cells. The percentage of cells showing LTD in synaptic efficacy (87%) when the NMDA receptors activation was blocked was significantly higher than that in control-medium.
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  • 84
    ISSN: 1432-1106
    Keywords: Thyrotropin-releasing hormone (TRH) ; Receptors ; Autoradiography ; Spinal cord ; Experimental transection ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The autoradiographic localization of thyrotropin-releasing hormone (TRH) receptors was investigated in the rat spinal cord after transection at the level of T8–T9. The discrete distribution of [3H]-MeTRH binding was measured with a computerized image analyzer at the cervical (C6–C7) and lumbar (L2–L3) level, one week and three weeks after injury. The TRH receptor density was expressed in fmol/mg protein. There was no significant change in the density of TRH receptors below the injury site. In the cervical region, TRH receptor concentration in the dorsal gray matter did not differ from normal controls; in contrast we found a time-dependent change in lamina 10 and in the ventral gray, with a significant decrease (25% and 19%, respectively) of TRH receptor binding sites one week after transection and a return to control levels by three weeks. From these data and the known increase of TRH immunoreactivity above a spinal injury, a down-regulation of spinal cord TRH receptors in response to elevated levels of TRH is suggested.
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  • 85
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    Experimental brain research 83 (1991), S. 411-418 
    ISSN: 1432-1106
    Keywords: In situ hybridization ; Messenger RNA ; Preprotachykinin A ; Substance P/neurokinin A ; Calcitonin gene-related peptide ; Somatostatin ; Neuropeptide Y ; Cholecystokinin ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In situ hybridization was used to determine whether genes for neuropeptides [substance P/neurokinin A (SP/NKA), calcitonin gene-related peptide (CGRP), somatostatin (SOM), neuropeptide tyrosine (NPY) and cholecystokinin (CCK)] are expressed in inferior ganglia of the vagus (nodose) and glossopharyngeal (petrosal) nerves. Synthetic oligodeoxyribonucleotides, complementary to the cognate, mRNAs were labeled with [32P] or [35S], and hybridized to 10 μm thick sections of unperfused tissue which were then processed for film and emulsion autoradiography. We found numerous, clustered neuronal perikarya throughout the nodose and petrosal ganglia that expressed preprotachykinin A (SP/NKA) and CGRP mRNAs to varying degrees. Neurons expressing preproSOM mRNA were less abundant and more scattered throughout both ganglia. Notably, we found mRNA for NPY in cells (usually 5–10 per section) in both ganglia. To our knowledge, this is first evidence for NPY in these sensory ganglia. In contrast to previous immunohistochemical findings, we found no evidence for expression of preproCCK in either the nodose or petrosal ganglia. The present findings demonstrate that cells of the nodose and petrosal ganglia express the genes for a number of neuropeptides that are presumably involved with transmission of visceral sensory afferent information to higher order neurons of the central nervous system.
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  • 86
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    Experimental brain research 83 (1991), S. 434-438 
    ISSN: 1432-1106
    Keywords: Nilvadipine ; Ca2+ entry blocker ; Focal cerebral ischemia ; Cerebral edema ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of nilvadipine, a Ca2+ entry blocker, on focal cerebral ischemia were investigated in rats having unilateral middle cerebral artery occlusion. All rats had 24 h ischemia, and were divided into threegroups (ten rats per group). Groups 1 and 2 received 1.0 and 3.2 mg/kg nilvadipine s.c. respectively, just after the occlusion. Control rats received an equal volume of the vehicle. Control animals had a % infarct volume of 28.2 ± 11.4%,and a left/right hemispheric volume ratio of 112 ± 12 %. Group-1 and -2 rats had % infarct volumes of 25.5 ±11.6% and 13.9 ±9.2% (p〈0.01) respectively, and left/right hemispheric volumeratios of 111 ± 9% and 103 ± 7% (p 〈 0.05), respectively. Thus, the drug reduced the infarct size and the brain edema in a dose-dependent manner. The significant decrease in the infarct volumewas observed in the periphery of the frontoparietal cortex. This study supports the hypothesis that nilvadipine may be a potential therapeutic agent for cerebral ischemia. Neuropathological findings suggest the possible therapeutic effects of the drug in the ischemic penumbra.
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  • 87
    ISSN: 1432-1106
    Keywords: 2-Aminophosphonopentanoate ; NMDA receptors ; Spatial learning ; Visual discrimination ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Chronic intraventricular infusion of the selective NMDA receptor antagonist AP5 appears to cause an impairment of spatial but not visual discrimination learning. However, Goddard (1986) has questioned whether this dissociation in task-selectivity reflects a difference in the underlying neural mechanisms or differential drug diffusion. Two experiments conducted to address this issue established (a) that chronic intraventricular infusion of AP5, at a dose sufficient to cause a spatial learning impairment, results in a relatively uniform distribution of the drug across the brain, and (b) that chronic bilateral intracortical infusion at sites very close to visual cortex also fails to impair visual discrimination learning. These findings argue against differential diffusion being a major cause of the sensitivity of spatial but not visual discrimination tasks to AP5, and raises the possibility that representational and procedural memory tasks may depend upon distinct cell-biological mechanisms of plasticity.
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  • 88
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    Experimental brain research 83 (1991), S. 549-554 
    ISSN: 1432-1106
    Keywords: Beta-endorphin ; Formalin test ; Pain ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The involvement of the beta-endorphin (B-EP) system during acute prolonged (tonic) pain was investigated by biochemical and behavioral approaches in freely-moving rats after subcutaneous injection of a small amount of a dilute formaldehyde solution (0.08 ml, 5%) in a forepaw. Beta-endorphin-like immunoreactivity levels were increased over the respective control groups in rats killed 30, 60 and 120 min after injection in discrete regions of the rat brain, namely ventro-medial hypothalamus, ventro-basal thalamus and periaqueductal gray matter, and at 30 and 60 min in postero-medial thalamus. In a separate group of experiments a small amount of anti-B-EP or normal rabbit serum was injected in the lateral ventricle; 6 h later rats received formalin injection as in previous groups and their behavior was scored over the following 2 h. A significant hyperalgesia (as expressed by an increase in the amount of time rats spent licking or chewing the injected paw) was observed 10–50 min and 70–80 min after formalin in the anti-B-EP icv-injected group. Other behavioral parameters such as general motor activity, grooming and limb flexion were not different in the two groups, nor was animal behavior prior to formalin injection. Altogether these data suggest that the central beta-endorphin system is triggered by prolonged noxious stimulation in freely-moving animals, and in turn plays a physiological role in the modulation of the reaction to, or perception of, tonic pain.
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  • 89
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    Experimental brain research 83 (1991), S. 598-606 
    ISSN: 1432-1106
    Keywords: Frequency modulation ; Inferior colliculus ; Click-sensitive units ; Receptive space ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The response of 835 click-sensitive neurons in the inferior colliculus (IC) to ramp frequency modulated (FM) tones was studied in the anaesthetized rat. More than 70% of the cells were sensitive to the FM sound, and over 25% were “FM specialized”. Systematic variations of the stimulus parameters showed that sweep velocity, sweep range, and intensity of the FM signal were the 3 basic determinants for the unit response. For an“FM specialized” cell, the response pattern to each of the parameters was either monotonic or bell-shaped. The population statistics of response patterns to the FM parameters, including the tuning factors, were generated. A stimulus domain was proposed to represent the“receptive space” of the FM cells.
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  • 90
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    Experimental brain research 83 (1991), S. 683-686 
    ISSN: 1432-1106
    Keywords: Experimental epilepsy ; Penicillin ; Interneurons ; Afterpotentials ; Paroxysmal depolarization shifts ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Interneurons of rat motor cortex in vivo and of rat hippocampal slices were studied during penicillin induced epileptic discharges. Synchronous with pyramidal cells, they showed transient depolarizations similar to paroxysmal depolarization shifts in pyramidal cells. The transient depolarizations were followed by hyperpolarizing or depolarizing afterpotentials lasting 600 to 1200 ms. During the transient depolarizations and the afterdepolarizations the interneurons discharged with increased frequency. This may contribute to the enlarged and prolonged synaptic inhibitions following interictal discharges in pyramidal cells.
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  • 91
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    Experimental brain research 83 (1991), S. 687-690 
    ISSN: 1432-1106
    Keywords: Tetrodotoxin ; Intracerebral injection of drugs ; Edinger ; Westphal nucleus ; Functional ablation ; Pupil ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Spatial extent and duration of the functional blockade elicited by intracerebral injection of tetrodotoxin (TTX) was examined in rats anesthetized with pentobarbital. Pupillary diameter was measured under dissecting microscope before and up to 24 h after injection of TTX (10 ng/l μl saline) into or 1.0, 1.5 and 2.0 mm lateral from the Edinger-Westphal nucleus. TTX administration elicited mydriasis the latency of which was directly and amplitude indirectly proportional to the target-injection distance. The maximum mydriasis attained 3.4 mm, lasted 2 h and slowly decayed over subsequent 20 h. Impulse transmission and conduction was blocked in a spherical volume of tissue about 3 mm in diameter the development of which could be approximated by diffusion from an instantaneous point source. Completeness and full reversibility make the TTX block a convenient research tool.
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  • 92
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    Experimental brain research 84 (1991), S. 57-74 
    ISSN: 1432-1106
    Keywords: Hippocampal formation ; Neural networks ; HRP ; Tracing techniques ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We used in vivo intracellular labeling with horseradish peroxidase in order to study the somadendritic morphology and axonal projections of rat entorhinal neurons. The cells responded to hippocampal stimulation with inhibitory postsynaptic potentials, and thus likely received direct or indirect hippocampal input. All cells (n = 24) showed extensive dendritic domains that extended in some cases for more than 1 mm. The dendrites of layer II neurons were largely restricted to layers I and II or layers I–III, while the dendrites of deeper cells could extend through all cortical layers. Computed 3D rotations showed that the basilar dendrites of deep pyramids extended roughly parallel to the cortical layering, and that they were mostly confined to the layer containing the soma and layers immediately adjacent. Total dendritic lengths averaged 9.8 mm ± 3.8 (SD), and ranged from 5 mm to more than 18 mm. Axonal processes could be visualized in 21 cells. Most of these showed axonal branching within the entorhinal cortex, sometimes extensive. Efferent axonal domains were reconstructed in detail in 3 layer II stellate cells. All 3 projected axons across the subicular complex to the dentate gyrus. One of these cells showed an extensive net-like axonal domain that also projected to several other structures, including the hippocampus proper, subicular complex, and the amygdalo-piriform transition area. The axons of layer III and IV cells projected to the angular bundle, where they continued in a rostral direction. In contrast to the layer II, III and IV cells, no efferent axonal branches leaving the entorhinal cortex could be visualized in 5 layer V neurons. The data indicate that entorhinal neurons can integrate input from a considerable volume of entorhinal cortex by virtue of their extensive dendritic domains, and provide a further basis for specifying the layers in which cells receive synaptic input. The extensive axonal branching pattern seen in most of the cells would support divergent propagation of their activity.
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  • 93
    ISSN: 1432-1106
    Keywords: Chronic inflammation ; Arthritic rat joints ; Joint capsule mechanoreceptors ; PGE2 ; Bradykinin ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The role of PGE2 in the sensitization of highthreshold tarsal joint mechanoreceptors (putative nociceptors) has been investigated in 11 arthritic and 16 normal rats. Injections of a low dose of Freund's complete adjuvant at multiple sites into the tissues surrounding the ankle joint induced a chronic unilateral monoarthritis in the injected limb. Measurements of both spontaneous activity and responses of tarsal joint mechanoreceptors to repeated graded mechanical stimuli were made. All of the mechanoreceptors examined had afferent fibres with conduction velocities in the C or A-δ range. Using this new model of joint inflammation we have shown that lysine acetylsalicylate reduces the mechanical sensitivity of these joint mechanoreceptors and reduces the spontaneous activity in afferent nerve fibres. Prostaglandin E2 is unable to restore either the spontaneous activity in the afferent axon or the mechanical sensitivity of tarsal joint mechanoreceptors after lysine acetylsalicylate in the arthritic rat. Similarly, PGE2 does not sensitize or excite tarsal joint mechanoreceptors in the normal rat. In the normal rat, however, PGE2 potentiates the excitatory action of bradykinin and enhances the sensitizing effect of bradykinin on the responses of joint mechanoreceptors to mechanical stimulation when both substances are injected simultaneously. These results indicate that PGE2 is not important in the sensitization of these joint mechanoreceptors in this model of chronic joint inflammation but that in other circumstances PGE2 may be able to contribute to a sensitization of joint mechanoreceptors by enhancing the action of bradykinin.
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  • 94
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    Experimental brain research 84 (1991), S. 620-630 
    ISSN: 1432-1106
    Keywords: Substantia nigra ; Serotonin ; Autoreceptor ; Dopamine release ; Nigrostriatal ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Extracellular single unit recordings were obtained from antidromically identified nigrostriatal dopaminergic neurons in anesthetized rats to determine the effects of dorsal raphé stimulation on the somatodendritic excitability of substantia nigra dopaminergic neurons. Stimulation of the dorsal raphé with a brief train of pulses delivered 7–2 ms prior to the neostriatal-evoked antidromic response significantly reduced the proportion of neostriatal-evoked antidromic responses that consisted of both initial segment and somatodendritic components without significantly altering the neostriatal-evoked post-stimulus inhibitory period. Raphé stimulation alone facilitated post-stimulus neuronal firing in almost half of the cells examined. The raphé-induced decrease in somatodendritic excitability was blocked by the serotonin antagonist, metergoline (0.5–2.0 mg/kg, i.v.), without significantly affecting the rate or pattern of spontaneous activity. The tryptophan hydroxylase inhibitor, parachlorophenylalanine (400 mg/kg, i.p. for three consecutive days), abolished the decrease in somatodendritic excitability following raphé stimulation which could be re-instated by intravenous administration of 5-HTP. The dopamine antagonists haloperidol (25–100 μg/kg, i.v.) and sulpiride (10–30 mg/kg, i.v.) also blocked the effects of dorsal raphé stimulation on somatodendritic invasion. These data suggest that in vivo, serotonin liberated from raphé-nigral terminals facilitates the release of dopamine from nigrostriatal dendrites resulting in a local, autoreceptor-mediated reduction in somatodendritic excitability without affecting the spontaneous firing rate and excitability of the neuron as a whole.
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  • 95
    ISSN: 1432-1106
    Keywords: Neocortex ; Transplantation ; Methods of grafting ; GABA-immunoreactive neurons ; GABA-negative neurons ; Numerical density ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Quantitative investigation of GABA-immunopositive and GABA-immunonegative neurons was performed in grafts of embryonic tissue of somatosensory cortex, (1) injected intraparenchymally into the barrel field of adult rats (n = 5); (2) placed in an acute cavity in the same area (n = 9); or (3) inplanted into the anterior eye chamber (n = 5). Analysis of initial embryonic tissue at the age of grafting (E17) demonstrated high numerical density of neurons both GABA-positive and other. Six months after grafting the total neuronal density was higher than in normal cortex in both groups of intracortical grafts, but was lower than normal in the intraocular grafts. The numerical density of GABA-positive somata, however, decreased in all types of the grafts, and their ratio to GABA-negative neurons was significantly lower than in normal neocortical tissue. The total numerical density of the neurons in the grafts had strong positive correlation to the degree of morphological graft/host integration, which was evaluated as a ratio of extent of area of direct graft/host neuropil confluence versus the total extent of the border. The mean diameters of nuclei of GABA-negative cells in both groups of intracortical grafts did not differ from those of the intact neocortex, but in the isolated grafts they were substantially larger. Nuclei and somata of the GABA-positive cells, however, were hypertrophic in all groups of grafts, and especially in the intraocular ones. Measurements of the diameters of host neocortical neurons adjacent to the grafts also exhibited a less marked but still significant hypertrophy. The possible role of various factors (synaptic, trophic, functional), determining the described alterations in neuronal populations within the grafts is discussed.
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  • 96
    ISSN: 1432-1106
    Keywords: Neural stimuli ; Paraventricular nucleus ; Corticotropin-releasing factor ; Serotonin ; 5,7-dihydroxytryptamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In view of the role of serotonin in adrenocortical regulation, the effects of depletion of hypothalamic serotonin, using localized injections of the neurotoxin 5,7-dihydroxytryptamine into the hypothalamic paraventricular nucleus, on the rise in plasma corticosterone following afferent neural stimulation, were studied. The neurotoxin caused a significant reduction (p〈0.001) in hypothalamic serotonin content of about 50% during the first month and about 30% up to two months later. Basal and ether stress-induced rises in plasma corticosterone levels were unaffected at all times after this treatment, but responses to stimulation of the sciatic nerve were reduced for up to four weeks (p〈0.01), recovering at later times. Responses to photic and acoustic stimuli were almost entirely prevented up to four weeks following the treatment (p〈0.001) but showed a gradual recovery to full, or almost full, adrenocortical responses at eight weeks, following acoustic and photic stimulation respectively. These results demonstrate a differential recovery of the adrenocortical responses, following the neurotoxin injection and indicate that different neural modalities require different 5-HT concentrations in the PVN for the expression of a full adrenocortical response.
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  • 97
    ISSN: 1432-1106
    Keywords: Sleep ; Stress ; Pain ; Serotonin (5-HT) ; 5-hydroxyindoleacetic acid (5-HIAA) ; Monoamine oxidase inhibitors (MAOI) ; Voltammetry ; High pressure liquid chromatography (HPLC) ; Raphe dorsalis (n.RD) ; Hypothalamus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the present work, voltammetric method combined with polygraphic recordings were used in animals under long-term chronic conditions; the extracellular concentrations of 5-hydroxyindole compounds (5-OHles) and in particular 5-hydroxyindoleacetic acid (5-HIAA) were measured in the hypothalamus and in the nucleus Raphe Dorsalis (n.RD). The hypothesis that extracellular detection of 5-HIAA, in animals under physiological conditions, might reflect serotonin (5-HT) release is suggested by the following observations: — serotoninergic neurons are reported to contain only monoamine oxidase type B (MAO-B); — an inhibitor of such an enzyme, MDL 72145 (1 mg/kg), fails to decrease the extracellular 5-HIAA peak 3 height; — MAO type A is contained in non-5-HT cells or neurons; — only the inhibitor of this last type of enzyme (Clorgyline 2.5 mg/kg) induces a complete disappearance of the voltammetric signal. The 5-HIAA measured in the extracellular space thus comes from the 5-HT released and metabolized outside the 5-HT neurons. Throughout the sleep-waking cycle, 5-OHles release occurs following two different modes: 1 — during sleep, in the vicinity of the 5-HT cellular bodies in the n.RD; this release might come from dendrites and be responsible for the 5-HT neuronal inhibition occurring during sleep; 2 — during waking, at the level of the axonal nerve endings impinging on the hypothalamus; this release might be related to the synthesis of “hypnogenic factors”. Finally, we have observed that in the hypothalamus, 30 min. of immobilization-stress (IS) induces a larger increase of the voltammetric signal (+ 80%) than a painful stimulation of the same duration (+ 30%); the possible link between the 5-OHles release occurring in this area during an IS and the subsequent paradoxical sleep rebound is discussed.
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  • 98
    ISSN: 1432-1106
    Keywords: Luteinizing hormone-releasing hormone ; Gamma-aminobutyric acid ; In situ hybridization ; Immunocytochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Gamma-aminobutyric acid (GABA) is thought to play an important role in the regulation of luteinizing hormone-releasing hormone (LHRH) release but its role in the regulation of LHRH gene expression and LHRH synthesis is not known. We hypothesized that since GABA appears to have primarily inhibitory effects on LHRH cells (at the level of the cell body), GABA may act to decrease LHRH gene expression and peptide synthesis. This hypothesis was tested by examining the effect of GABA receptor activation and GABA receptor blockade on LHRH mRNA and peptide levels employing in situ hybridization and immunocytochemistry. Cells in the preoptic area (POA) of ovariectomized (ovx) rats were selectively exposed in vivo to specific GABA-ergic receptor agonists or an antagonist for up to 24 h. THIP, a specific GABA a receptor agonist, did not have a significant effect on either the intensity of LHRH immunoreactivity, or the number of LHRH-ir cells, observed as compared to controls. Baclofen, a GABA b receptor agonist appeared to decrease the number of cells with the greatest intensity of LHRH immunoreactivity, compared to controls. In situ hybridization, with either a tritiated RNA probe or a 32P-labelled oligonucleotide, complementary to LHRH mRNA, revealed that THIP either had no effect on the labelling intensity (32P-labelled oligonucleotide) or (contrary to our hypothesis) a slight excitatory effect on the level of LHRH mRNA detected per cell (tritiated RNA probe). Bicuculline (a specific GABA a receptor antagonist) decreased both the number of labelled cells observed per section through the POA, and the intensity of labelling observed in sections hybridized with the 32P-labelled oligonucleotide. These results suggest that in the POA GABA a receptors do not exert an inhibitory effect on LHRH gene expresssion, but rather could affect LH perhaps by electrically inhibiting LHRH neurons. In contrast, baclofen appeared to exert an inhibitory effect on LHRH gene expression, since the number of grains per labelled cell in the POA of baclofen treated rats was lower than the grains per labelled cell of control rats. Also, similar to the results obtained with immunocytochemistry, in situ hybridization following baclofen treatment suggested that activation of GABA b receptors is able to reduce the number of neurons with the highest levels of LHRH mRNA. Thus, in the POA, GABA acting through GABA b receptors could be effective through changes in mRNA or peptide synthesis.
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  • 99
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 86 (1991), S. 568-578 
    ISSN: 1432-1106
    Keywords: Motor learning ; Flocculus ; Retinal image slip ; Climbing fibers ; Plasticity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The gain of the vestibulo-ocular reflex (VOR) of intact pigmented rats was adaptively modified by training protocols that created a visual-vestibular conflict. For training, head restrained animals were oscillated on a turntable in front of an optokinetic pattern projected onto a cylindrical wall. The optokinetic pattern either moved the same amplitude with the animal (“in-phase”: 0.05 Hz ± 20°/s) or opposite in direction (“out-of-phase”: turntable and pattern 0.05 Hz ± 10°/s each). VOR responses were tested in darkness before and after each 8 min training period for a duration of 40 min. During “out-of-phase” training the gain of compensatory eye movements measured in light was close to 2 from the beginning on and the VOR tested in darkness increased in gain progressively from 0.48 (±0.12) to 0.9 (±0.3; P 〈 0.05) in 5 out of 7 rats. Two rats did not adapt their VOR gain. Phase values decreased slightly by about 10°. During “in-phase” stimulation compensatory eye movements were almost completely suppressed (gain close to 0) from the beginning on and the VOR tested in darkness decreased gradually in gain from 0.62 (±0.17) to 0.13 (±0.1; P〈0.001) in all 6 trained rats. Phase values decreased in parallel from 151° to 119° (P〈 0.01). The effectiveness of the “in-phase” training paradigm in the absence of compensatory eye movements indicates that retinal image slip is the relevant signal for adaptation. In seven rats with histologically verified almost complete inferior olive (IO) lesions (chemically induced at least 45 days prior to training), “out-of-phase” and “in-phase” stimulation evoked compensatory eye movements with gains comparable to those in intact rats. VOR parameters measured in darkness were altered with respect to those of control rats. Gain differed extremely between individuals and phase lag re acceleration was in all IO-lesioned rats larger than in intact rats. The time constant of the VOR in response to table velocity steps was significantly longer (17 s ±4) than in intact rats (11 s ± 3). Training did not alter the gain of the VOR in 5 out of 7 IO-lesioned rats. One rat increased its gain during “out-of-phase” training in the first, but not during a second training session (and not during “in-phase” training) and another rat decreased its gain during “in-phase” training (but not during “out-of-phase” training). These changes in VOR gain might have occurred by chance rather than by learning. The absence of adaptation in IO-lesioned rats can be explained either by the absence of climbing fiber mediated slip signals in the cerebellar cortex or by lesion-induced secondary changes which result in a long-term reduction of the inhibitory efficacy of Purkinje-cells. In the absence of arousing stimuli VOR responses of intact rats exhibit a strong decrement during table oscillations in darkness. Between trials, with the rat at rest, response magnitude recovered spontaneously. Six out of 8 IO-lesioned rats expressed a very similar modification of their VOR gain. These results indicate that the neural mechanisms responsible for adaptive gain decrease during “in-phase” training and those responsible for a gain decrease during short-term habituation are different.
    Type of Medium: Electronic Resource
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  • 100
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 85 (1991), S. 537-542 
    ISSN: 1432-1106
    Keywords: Generators ; Brainstem auditory evoked potentials ; Stereotaxic radiofrequency coagulation ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The generators of brainstem auditory evoked potentials (BAEPs) in rats were investigated experimentally. Discrete lesions of the brainstem auditory pathway were made unilaterally using a stereotaxic radiofrequency coagulation method, and the BAEPs were recorded before and after the lesions to observe the alterations. The waves of the BAEPs were affected by the lesions as follows: (1) all of the BAEP waves were attenuated or eliminated by a lesion of the auditory nerve; (2) wave II was abolished or attenuated in amplitude following a lesion of the cochlear nucleus; (3) marked reduction or abolition of wave III occurred with some effect on waves IV and V following lesions of the superior olivary complex; (4) the following trough in the wave III was significantly attenuated by lesions of the lateral lemniscus that were associated with inconsistent changes in waves IV and V; (5) no waves were affected significantly by a lesion of the inferior colliculus. The method of radiofrequency lesion using stereotaxic localization proved to be a simpler and more rapid procedure for determining the generators of BAEPs in animals than other surgical lesion methods.
    Type of Medium: Electronic Resource
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