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  • 1
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Prostaglandins (PGs) are critical mediators of physiologic processes and inflammation. They are produced by two different isoforms of the cyclooxygenase (COX) enzyme, namely COX-1 and COX-2. In particular COX-2 was demonstrated to be crucial for PG-synthesis in inflammation. Recently, inhibition of COX-2 was shown to prevent the loss of motor neurons in a model of amyotrophic lateral sclerosis (ALS). Furthermore, spinal COX-2 expression was shown to be increased in transgenic mice that produce an ALS–like syndrome. Therefore, we investigated the expression of COX-1 and COX-2 in the spinal cord of seven human sporadic ALS patients by means of immunohistochemistry. Specimens from seven patients without any neurological disease served as controls. COX-2 expression was dramatically increased in the spinal cord of patients with ALS. Its protein was found in motor neurons, interneurons and glial cells. Statistical analysis showed a significantly higher expression of COX-2 in ALS for both neurons and glia. In contrast, COX-1 expression was predominantly confined to microglia and no apparent difference was detected between controls and ALS. In addition, we studied the concentration of prostaglandin E2 (PG E2) as a marker for COX activity in the cerebrospinal fluid of nine patients diagnosed for ALS and compared the results with those from nine patients without motor neuron disease. PG E2 levels were markedly increased in ALS cases (45.8 ± 35.1 pg/mL) compared to the non-ALS specimens (15.8 ± 3.7 pg/mL). The results of our study corroborate a potential role for COX-2 in the pathogenesis of motor neuron death in ALS. Selective COX-2 inhibition might therefore offer a new possibility in the treatment of human ALS. However, to determine the exact role of COX-2 in human ALS will require further research.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 200 (1999), S. 125-135 
    ISSN: 1432-0568
    Keywords: Key words Enteric nervous system ; Morphology ; Innervation ; Intestine ; Neuron
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The first differentiation of enteric neurons into three morphological types was done by the russian histologist A. S. Dogiel on the basis of the different shapes and lengths of their dendrites. Although a number of authors considered his results during the following decades, only a division into two types withstood time: type I neurons had one long and several short processes, whereas type II neurons were characterized by several long processes. Some further structural features were discussed but substantial progress was not made until the late 1970s. This stagnation was due to some inaccuracies in Dogiel´s descriptions, to the fact that most histologists in this field followed the reticular concept of the nervous system, to the idea that enteric neurons represent no more than a vegetative, postganglionic relay station between the central nervous system and the periphery, and to methodological difficulties. With the application of modern neuroanatomical techniques it was realized that the enteric nervous system contains a considerable number of neuronal subpopulations. The search for morphological correlates of the chemical diversity of enteric neurons was done mainly in the pig and the guinea-pig. In the pig, additional structural features such as axonal projection, distribution of neurons within ganglia, within different plexuses and along the length of the gut, blood supply etc. were included as criteria for further refining neuronal classification. Most of our knowledge about functional features of enteric neurons, e.g. chemical coding, neuronal connectivity, electrophysiological behaviour, was derived from studies in the guinea-pig small intestine. In light of interspecies differences, comparison of findings from different species is mandatory. The search for morphological and functional peculiarities of human enteric neuronal circuitry has to consider all methodological and conceptual advances made within the past 100 years since the pioneering work of Dogiel.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 158 (1980), S. 349-360 
    ISSN: 1432-0568
    Keywords: Afferent neurons ; Hypoglossal nerve ; Rat ; HRP-tracing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Cell bodies of sensory neurons of the rat's hypoglossal nerve were demonstrated by the somatopetal horseradish peroxidase (HRP) transport technique. Labelled perikarya were found within the second and third cervical spinal ganglia and in the vagal sensory ganglia. After application of HRP to the cut peripheral trunk of the hypoglossal nerve about 200 labelled cell bodies were counted in each animal. The vast majority of the axons from cervical spinal ganglion cells reach the hypoglossal nerve via the descending ramus (N. descendens hypoglossi). However, there may exist an additional pathway, probably via the cervical sympathetic trunk. Application of HRP to the medial and lateral end branches led to a labelling of much fewer spinal ganglion cells while the number of labelled vagal sensory neurons remained unchanged. Thus, it is suggested that the majority of the cervical afferents of the hypoglossal nerve originates within the extrinsic tongue musculature and the geniohyoid muscle, whereas the vagal afferents may perhaps derive exclusively from the intrinsic muscles. Histograms of the mean diameters of labelled cell bodies show a predominance of very small perikarya. This contrasts with the diameter distribution of sensory perikarya labelled after HRP application to nerves supplying other skeletal muscles. It is therefore assumed that the afferent component of the hypoglossal nerve is composed mainly of small-calibre axons.
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  • 4
    ISSN: 1432-0568
    Keywords: Visceral afferents ; Hypogastric nerve ; Preganglionic sympathetic neurons ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The central projections of visceral primary afferents of the inferior mesenteric plexus and hypogastric nerve of the rat were investigated using the transganglionic transport of horseradish peroxidase (HRP). In addition, the location of the corresponding spinal ganglion cells as well as the preganglionic sympathetic neurons is demonstrated. Labelled afferent axons were found in dorsal roots, dorsal root entry zone (preferentially in its lateral part), in all parts of the tract of Lissauer, and in the dorsolateral funiculus. Preterminal axons and/or terminals were distributed mainly to laminae I, IIa and the nucleus of the dorsolateral funiculus. Fewer afferents reached laminae IIb, III–V and X. Afferent projections are densest at L1 and 2 and the caudal T13, but extend up to T10 rostrally, and at least down to L4 caudally. A few visceral afferents ascend to the nucleus gracilis. The great majority of sensory and preganglionic sympathetic cell bodies is located at levels L1 and 2 bilaterally. A few cells are found in decreasing numbers rostrally up to T11. Preganglionic sympathetic neurons (PSN) are located in nucleus intermediolateralis (IML), n. intercalatus (IC) and n. commissuralis dorsalis (DCN). Axons of DCN and IC neurons run laterally, joining those of IML neurons on their way to the ventral roots. Dendrites of IML neurons ramify in all directions but preferentially to the dorsal horn and dorsolateral funiculus. Dendrites of IC and DCN neurons are distributed mainly mediolaterally, the latter also ventrally around the canalis centralis.
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  • 5
    ISSN: 1432-0568
    Keywords: Hepatic branch of vagus ; Vagal paraganglia ; Dil ; WGA-HRP ; Laser scanning confocal microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In order to investigate the distribution and structure of the vagal liver innervation, abdominal vagal afferents and efferents were selectively labeled by injecting WGA-HRP or Dil into the nodose ganglia, and DiA into the dorsal motor nucleus, respectively. Vagal afferent fibers produced characteristic terminal-like structures at three locations in the liver hilus: 1. Fine varicose endings preferentially surrounding, but not entering, the numerous peribiliary glands in the larger intra and extrahepatic bile ducts 2. Large, cup-shaped terminals in almost all paraganglia 3. Fine varicose endings in the portal vein adventitia. No fibers and terminals were found in the hepatic parenchyma. While about two thirds of the vagal afferent fibers that originate in the left nodose ganglion, and are contained in the hepatic branch, bypass the liver hilus area on their way to the gastroduodenal artery, a significant number (approx. 10% of the total) of vagal afferents that do innervate the area, originates from the right nodose ganglion, and projects to the periarterial plexus of the common hepatic artery and liver pedicle most likely through the dorsal celiac branch. Varicose vagal efferent fibers were present within the fascicles of the vagal hepatic branch and fine terminal-like structures in a small fraction of the paraganglia. No efferents were found to terminate in the hepatic parenchyma or on the few neurons embedded in nerves or paraganglia. In contrast to the paucity of vagal terminals in the hepatic parenchyma, an abundance of vagal efferent and afferent fibers and terminals with distinctive distribution patterns and structural characteristics was present in esophagus and gastrointestinal tract. It is concluded that vagal intralobular hepatic innervation is largely absent in rats, and that the putative hepatic vagal nutrient, osmo-, and pressure receptors are located either in the portal vein, bile ducts, and/or the hepatic paraganglia.
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  • 6
    ISSN: 1432-0568
    Keywords: Visceral afferents ; Spinal ganglion cells ; Stomach ; HRP ; Somatopetal transport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Spinal ganglion cells innervating the stomach of the rat were demonstrated using the somatopetal horseradish peroxidase (HRP) transport technique. After injection of the tracer into the anterior wall of the stomach, labelled neurons were observed bilaterally within spinal ganglia T4-L1. They were most numerous in ganglia T8-T10. No clear evidence of somatotopic organization of the labelled cells was found. Most of the cells measured 35–40 μm in diameter. There was a striking paucity of cells smaller than 30 μm. The predominance of medium-sized spinal ganglion cells may indicate that the stomach is innervated mainly by small myelinated rather than unmyelinated splanchnic afferent fibers.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 193 (1996), S. 239-248 
    ISSN: 1432-0568
    Keywords: Autonomic nervous system ; Blood flow regulation ; NADPH diaphorase ; Nitric oxide ; Visual system
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Immunohistochemistry for neuronal nitric oxide synthase (nNOS) and vasoactive intestinal peptide (VIP), and NADPH diaphorase histochemistry, were applied to investigate neurons in the choroid and the ciliary ganglion of the muscovy duck Anis carina. Up to 1000 neurons in the choroid stained for NADPH diaphorase and showed virtually complete colocalization for nNOS immunoreactivity. Almost all of them co-stained for VIP, while about 90% of VIP immunoreactive cell bodies showed colocalization for nNOS. Two-thirds of the neurons were located, mostly singly, at nodes of a widemeshed nerve plexus in the suprachoroid and were only rarely grouped in ganglia of up to 3 neurons. Numerous varicose nNOS/NADPH-diaphorase-positive nerve fibers were seen around large arterial blood vessels. These fibers derived mainly from paravascular cell bodies that represented about one-third of all choroidal neurons and also displayed costaining for nitrergic markers and VIP. Colocalization of nNOS/NADPH-d and VIP could be demonstrated in most of the perivascular fibers, while slightly more VIP-positive axons in the suprachoroid plexus did not costain for nNOS/NADPH-d. Small-caliber blood vessels and those localized in the choriocapillaris were not endowed with VIP/nNOS/NADPH-diaphorase-positive fibers. A few reactive neuronal cell bodies were also found in ciliary nerves, while most ciliary axons were unstained. In the ciliary ganglion a small subpopulation of neurons showed VIP/nNOS/NADPH-diaphorase colocalization. There were also nNOS/ NADPH-d-positive cap-like terminals on ciliary ganglion cells. The presence of VIP/nNOS/NADPH-diaphorase positive neurons and nerve fibers in both the choroid and ciliary ganglion, and in the choroidal perivascular plexus, indicates peripheral nitrergic and VIPergic control of blood flow in the choroid of the duck.
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  • 8
    ISSN: 1432-0568
    Keywords: Key words Vagal afferents ; Visceral afferents ; Visceral sensation ; Myenteric plexus ; Enteric nervous system
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Intraganglionic laminar endings (IGLEs) are special terminal structures of vagal afferent fibers and have been demonstrated in the myenteric plexus of esophagus and stomach. In order to quantitatively map their presence and distribution over the entire gastrointestinal tract, including the small and large intestines, vagal afferents were anterogradely labeled in vivo by microinjections of the fluorescent carbocyanine dye DiI into the left or right nodose ganglion of adult male rats. In the most successfully labeled cases the highest density of IGLEs was found in the stomach, with about half to one-third of the myenteric ganglia receiving at least one IGLE. The proportion of myenteric ganglia innervated by IGLEs decreased in the small intestine; however, because of its large surface area this gut segment was estimated to contain the highest total number of IGLEs. Both the cecum and colon also contained significant numbers of IGLEs. In the stomach, this vagal afferent innervation by IGLEs was more or less lateralized, with less than 20% of labeled IGLEs found on the contralateral side with respect to the injection. The left/ventral vagus contributed a larger proportion of IGLEs to the proximal duodenum, while the right/dorsal vagus contributed a larger proportion of IGLEs to the distal duodenum and jejunum. Laser scanning confocal microscopy on select specimens revealed further structural details. The parent axon typically formed two or more branches that flanked the ganglia laterally, and in turn produced numerous highly arborizing laminar terminal branches that covered one or both flat sides of the ganglion in a dome-like fashion. The similar distribution patterns and structural details suggest a uniform function for the IGLEs throughout the gastrointestinal tract, but there is as yet no clear proof for any of the hypothesized roles as specialized mechanosensors or local effector terminals.
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  • 9
    ISSN: 1432-0568
    Keywords: Key words Enteric nervous system ; Innervation ; Intestine ; Mucosa ; Pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The aim of this study was to determine locations and morphologies of enteric neurons innervating the small intestinal mucosa of the pig after application of the carbocyanine tracer DiI onto a single villus. The tissue was processed in two ways: incubation (1) of fixed material (postmortem tracing) for several months and (2) of living specimens within organotypic culture in vitro for several days (supravital tracing). In both procedures DiI-labelled neurons were found in the three ganglionated plexuses, the internal and external submucous plexus as well as the myenteric plexus. Postmortem tracing revealed different neuronal morphologies. Adendritic type II neurons were present in all three plexuses, type IV neurons with short, scarcely branched, polarly emerging dendrites were mainly found in the myenteric plexus and small dendritic neurons were mainly present in the internal submucous plexus. The latter may correspond to minineurons hitherto described only immunohistochemically. Tracing within tissue culture showed somata of neurons and, partly, proximal segments of processes to be labelled. Subsequent immunohistochemistry using general neuronal markers revealed some neurons to be adendritic type II neurons. Visualization of dendrites was less clear, hampering an accurate morphological classification of dendritic neurons. Our results suggest that neurons of all ganglionated enteric nerve plexuses of the pig participate in the innervation of the mucosa, and that postmortem tracing revealed enteric neuronal morphology more clearly than supravital tracing. Since the former method cannot be applied for deciphering the chemical coding of enteric neurons, combination of both methods will extend our knowledge of the morphological substrate for the intrinsic neuronal microcircuits in the gastrointestinal tract.
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  • 10
    ISSN: 1432-0568
    Keywords: Vagus nerve ; Vagal afferents ; Nodose ganglion ; Confocal microscopy ; Small intestine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Results from functional studies point to the importance of chemoreceptive endings in the duodenum innervated by vagal afferents in the regulation of gastrointestinal functions such as gastric emptying and acid secretion, as well as in the process of satiation. In order to visualize the vagal sensory innervation of this gut segment, vagal afferents were selectively labeled in vivo by injecting the lipophilic carbocyanine dye DiI into either the left or the right nodose ganglion of young adult rats. Thick cryostat sections or whole-mounted peels of muscularis externa or submucosa of formalinfixed tissue were analyzed with conventional and/or confocal microscopy. In the mucosa, many DiI-labeled vagal afferent fibers were found with terminal arborizations mainly between the crypts and the villous lamina propria. In both areas, vagal terminal branches came in close contact with the basal lamina, but did not appear to penetrate it so as to make direct contact with epithelial cells. Labeled vagal afferent fibers in the villous and cryptic lamina propria were found to be in intimate anatomical contact with fibrocyte-like cells that may belong to the class of interstitial cells of Cajal, and with small granular cells that might be granulocytes or histiocytes. Although our analysis was not quantitative, and considering that labeling was unilateral and not complete, it appears that the overall density of vagal afferent mucosal innervation was variable; many villi showed no evidence for innervation while other areas had quite dense networks of arborizing terminal fibers in several neighboring villi. Analysis of separate whole-mounted muscularis externa and submucosa peels revealed the presence of large bundles of labeled afferent fibers running within the myenteric plexus along the mesenteric attachment primarily in an aboral direction, with individual fibers turning towards the antimesenteric pole, and either penetrating into the submucosa or forming the characteristic intraganglionic laminar endings (IGLEs). Although the possibility of individual fibers issuing collaterals to myenteric IGLEs and at the same time to mucosal terminals was not demonstrated, it cannot be ruled out. These anatomical findings are discussed in the context of absorptive mechanisms for the different macronutrients and the implication of enteroendocrine cells such as CCK-containing cells that may function as intestinal “taste cells”.
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