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Biomedical subjects

W L Neuhuber

Publications and source records attributed to W L Neuhuber.

At least 19 recordsLinked to original sources
PubMed2002

Tissue engineering of a differentiated cardiac muscle construct.

Cardiac tissue engineering is an emerging field. The suitability of engineered heart tissue (EHT) for both in vitro and in vivo applications will depend on the degree of syncytoid tissue formation and cardiac myocyte differentiation in vitro, contractile function, and electrophysiological properties. Here, we demonstrate that cardiac myocytes from neonatal rats, when mixed with collagen I and matrix factors, cast in circular molds, and subjected to phasic mechanical stretch, reconstitute ring-shaped EHTs that display important hallmarks of differentiated myocardium. Comparative histological analysis of EHTs with native heart tissue from newborn, 6-day-old, and adult rats revealed that cardiac cells in EHTs reconstitute intensively interconnected, longitudinally oriented, cardiac muscle bundles with morphological features resembling adult rather than immature native tissue. Confocal and electron microscopy demonstrated characteristic features of native differentiated myocardium; some of these features are absent in myocytes from newborn rats: (1) highly organized sarcomeres in registry; (2) adherens junctions, gap junctions, and desmosomes; (3) a well-developed T-tubular system and dyad formation with the sarcoplasmic reticulum; and (4) a basement membrane surrounding cardiac myocytes. Accordingly, EHTs displayed contractile characteristics of native myocardium with a high ratio of twitch (0.4 to 0.8 mN) to resting tension (0.1 to 0.3 mN) and a strong beta-adrenergic inotropic response. Action potential recordings demonstrated stable resting membrane potentials of -66 to -78 mV, fast upstroke kinetics, and a prominent plateau phase. The data indicate that EHTs represent highly differentiated cardiac tissue constructs, making EHTs a promising material for in vitro studies of cardiac function and tissue replacement therapy.

Action Potentials↗
PubMed2001

Characterization of vagal input to the rat esophageal muscle.

There is recent morphological evidence for an interaction of autonomic nerve fibers and extrinsic motor nerves of the rat esophagus. The aim of the present study was to investigate a possible functional role of this autonomic innervation of vagal motor fibers on rat esophageal smooth and striated muscle function in vitro. The entire esophagus with both Nn vagi, including the Nn recurrentes, was dissected and placed in an organ bath with oxygenated Krebs-Ringer buffer. Contractile activity was measured in longitudinal direction with a force transducer. Both Nn vagi were placed on a bipolar platinum electrode 2 cm apart from the esophagus. Vagal stimulation, applied for 1 s (40 V, 0.5 ms, 20 Hz) resulted in a biphasic contractile response, which was completely blocked by tetrodotoxin (10(-6) M). The first part consisted of a tetanic striated muscle contraction, which was abolished by tubocurarin (10(-5) M) but unaffected by atropine (10(-6) M) or hexamethonium (10(-4) M). In contrast, the second part was completely abolished by hexamethonium (10(-4) M) and atropine (10(-6) M), whereas tubocurarine (10(-5) M) showed no influence, suggesting a stimulation of preganglionic nerve fibers supplying esophageal smooth muscle (muscularis mucosae). In order to characterize possible autonomic transmitters of the ENS of the esophagus, the following experiments were carried out. The magnitude of the striated muscle response was unaffected by VIP (10(-7) M), 5-HT (10(-6) M) and galanin (10(-8) - 10(-7) M), whereas they caused an inhibition of the smooth muscle response (VIP: -53.8 +/- 4.2%; galanin 10(-8) M: - 18.5 +/- 2.2%; 10(-7) M: -40.4 +/- 2.9%; 5-HT: -78.2 +/- 2.1%). The inhibitory effects of VIP and galanin on smooth muscle were reversible by the antagonists VIP 10-28 and galanin 1-15. In the presence of the nitric oxide synthase (NOS) inhibitor L-NNA (10(-4) M), the smooth and striated muscle contraction were not significantly influenced. Exogenous application of the NO-donor DEA-NO (10(-4) M) reduced the smooth muscle contraction by -81.6 +/- 7.4%, but had no significant effect on the striated muscle contraction. Though immunohistochemical findings are highly suggestive of an nitrergic autonomic modulation of striated muscle contraction by enteric neurons, we could not demonstrate a NO-mediated action on striated muscle activity. Therefore, the physiological relevance of the immunohistochemical findings remain unclear.

Animals↗
PubMed2001

Local differences in vagal afferent innervation of the rat esophagus are reflected by neurochemical differences at the level of the sensory ganglia and by different brainstem projections.

The objective of the present study was to characterize further the vagal afferent fibers in the rat esophagus, particularly those in its uppermost part, their cell bodies in vagal sensory ganglia, and their central projections. We applied immunohistochemistry for calretinin, calbindin, and calcitonin gene-related peptide (CGRP); retrograde tracing with FluoroGold; and transganglionic tracing with wheat germ agglutinin-horseradish peroxidase in combination with neurectomies. Vagal terminal structures in the muscularis propria of the whole esophagus consisted of calretinin-immunoreactive intraganglionic laminar endings that were linked to cervical vagal and recurrent laryngeal nerve pathways. The mucosa of the uppermost esophagus was innervated by a very dense net of longitudinally arranged, calretinin-positive fibers that were depleted by section of the superior laryngeal nerve. Distal to this area, the mucosa was virtually devoid of calretinin-immunoreactive vagal afferents. Calretinin-positive mucosal fibers in the upper cervical esophagus were classified into four types. One type, the finger-like endings, was sometimes immunoreactive also for CGRP. About one-third of cell bodies in vagal sensory ganglia retrogradely labeled from the upper cervical esophagus expressed CGRP, whereas two-thirds coexpressed calretinin and calbindin but not CGRP. In addition to the central subnucleus of the nucleus of the solitary tract, vagal afferents from the upper cervical esophagus also projected heavily to the interstitial subnucleus. This additional projection was attributed to mucosal afferents traveling through the superior laryngeal nerve. The present study provides a possible morphological basis for bronchopulmonary and aversive reflexes elicited upon stimulation of the esophagus.

Animals↗
PubMed2001

Enteric co-innervation of striated muscle fibers in the esophagus: just a "hangover"?

Striated muscle of the esophagus was until recently considered to consist of "classical" skeletal muscle fibers innervated by cholinergic vagal motoneurons. The recently described co-innervation originating from enteric neurons expressing nNOS, VIP, NPY, and galanin added a new dimension of complexity. The aim of this study was to summarize current knowledge about, and to get further hints as to the possible function of enteric co-innervation of striated esophageal muscle fibers. Aldehyde fixed rat esophagi were processed for immunocytochemistry for CGRP or VAChT (to demonstrate vagal motor terminals), nNOS/NADPH-d, VIP, NPY, and galanin (to demonstrate enteric terminals), met-enkephalin, mu opiate receptor, muscarinic receptors m1-3, soluble guanylyl cyclase, and cGMP dependent kinase type I and II. Motor endplates were visualized using fluorochrome tagged alpha-bungarotoxin to label nicotinic receptors, or with AChE histochemistry. Besides light and confocal laser scanning microscopy, immuno electron microscopy was also employed. Up to 80% of motor endplates were co-innervated. In addition to nNOS, VIP, NPY, and galanin, many enteric terminals in esophageal motor endplates expressed met-enkephalin. Some appeared to stain for the muscarinic m(2) receptor. There was prominent immunostaining for the micro opioid receptor in the sarcolemma at both junctional and extrajunctional sites. Immunostaining for soluble guanylyl cyclase was prominent immediately beneath the clusters of nicotinic receptors. Enteric varicosities and vagal terminals intermingled in motor endplates often without intervening teloglial processes. During ontogeny, initially high co-innervation rates were reduced to adult levels in a cranio-caudally progressing manner. We conclude that, in addition to a possible nitrergic, VIP-, NPY-, and galaninergic modulation of neuromuscular transmission by enteric neurons, opioidergic mechanisms could play a role. On the other hand, cholinergic influence on enteric neurons may be exerted also by the nucleus ambiguus via motor endplates, in addition to the input from the dorsal motor nucleus. The observations that enteric nerve fibers contact striated muscle fibers at specialized sites, i.e., motor endplates, and that these contacts appear in an ordered cranio-caudal sequence after cholinergic motor endplates have been established point to a specific function in neuronal control of esophageal muscle rather than to be an unspecific "hangover" from the smooth muscle past of this organ.

Animals↗
PubMed2001

Intrinsic neurons in the duck choroid are contacted by CGRP-immunoreactive nerve fibres: evidence for a local pre-central reflex arc in the eye.

Intrinsic choroidal neurons represent peripherally displaced autonomic nerve cells supposed to work as a local integrative network similar to the enteric nervous system, to control choroidal vasculature and stromal smooth muscle. A typical feature of such intramural neuronal networks is the innervation by primary afferent collaterals expressing peptides, e.g. CGRP. The present study was aimed at determining primary afferent contacts on nitrergic intrinsic choroidal neurons (ICN) in the duck eye. In addition, a sympathetic innervation of ICN was assessed. Choroids were immunohistochemically processed for the following markers: neuronal nitric oxide synthase (nNOS), galanin (GAL), calcitonin gene-related peptide (CGRP), and tyrosine hydroxylase (TH). For evaluation, fluorescence as well as confocal laser scanning microscopy were used. For electron microscopy, immunoperoxidase staining for CGRP in combination with NADPH-diaphorase histochemistry was applied. ICN immunoreactive for nNOS or GAL spread over the entire choroid, although they were concentrated in an equatorial zone passing obliquely from naso-cranial to temporo-caudal. About 40% of ICN showed close relationships with CGRP-immunoreactive nerve fibres, originating most likely in the trigeminal ganglion, as seen in the fluorescence and confocal laserscanning microscope. These appositions could be ultrastructurally defined as both synapses and close contacts without synaptic specialization. Some ICN endowed with CGRP-positive fibres also received TH-immunoreactive boutons. CGRP-immunoreactive profiles were also detected in close relationship to choroidal non-vascular smooth muscle cells and collagen fibres connected to them. In many instances, they were intercalated between smooth muscle cells and processes of ICN forming triads. These results suggest that ICN, similar to other intramural autonomic systems integrate signals from trigeminal primary afferent collaterals. The 'sensory' terminals of these primary afferents may be located in the anterior eye segment but also within the smooth muscle stroma of the choroid itself. Thus, ocular homeostasis may be regulated via intraocular pre-central reflexes which are probably subject to sympathetic modulation.

Afferent Pathways↗
PubMed2001

Intrinsic choroidal neurons in the duck eye receive sympathetic input: anatomical evidence for adrenergic modulation of nitrergic functions in the choroid.

Intrinsic choroidal neurons (ICN) in the duck eye form an intramural ganglionic plexus that may subserve complex integrative functions. A key feature of such ganglia is an innervation by sympathetic postganglionic neurons. The present study was thus aimed at determining the sympathetic postganglionic innervation of ICN. Choroids were processed for double immunofluorescence labelling with the following markers: tyrosine-hydroxylase (TH)/nitric oxide synthase (nNOS), TH/galanin (GAL), dopamine-beta-hydroxylase (DBH)/vasoactive intestinal polypeptide (VIP), TH/DBH and DBH/alpha-smooth-muscle actin (alphaSMA), and for triple immunofluorescence labelling with VIP/DBH/TH. Epifluorescence and confocal laser scanning microscopy were used for evaluation. Immunoperoxidase staining for TH or DBH in combination with NADPH-diaphorase histochemistry was applied for electron microscopy. ICN spread over the entire choroid but were concentrated in an equatorial zone passing obliquely from naso-cranial to temporocaudal. More than 80% of nNOS-positive ICN showed close appositions of TH/DBH-immunoreactive varicose nerve fibres at the light-microscopic level, as could be confirmed by confocal laser scanning microscopy. Ultrastructurally, these appositions could be defined as both synapses or close contacts without synaptic specialisation. Vascular and non-vascular smooth muscle fibres also received TH/DBH-immunopositive innervation. Our findings suggest that most ICN receive a sympathetic input that might modulate their nitrergic effects upon vascular and non-vascular smooth muscle fibres in the choroid and that they may have more complex functions than merely being a simple parasympathetic relay.

Actins↗
PubMed2001

Pivotal role of the interstitial cells of Cajal in the nitric oxide signaling pathway of rat small intestine. Morphological evidence.

The nitric oxide (NO) signaling pathway is a major nonadrenergic-noncholinergic transmitter mechanism in the enteric nervous system. Our aim was to localize the enzymes in question, i.e., neuronal nitric oxide synthase (nNOS), soluble guanylate cyclase (sGC), and cGMP-dependent kinase type I (cGK-I) in rat small intestine by indirect immunofluorescence. nNOS staining was found in neurons of the myenteric plexus and in varicose nerve fibers mainly in the circular muscle layer. The cells positive for neurokinin-1 (NK-1) receptor and c-kit (interstitial cells of Cajal, ICC) in the deep muscular plexus (DMP) did not show nNOS reactivity, but nNOS-positive nerve fibers were directly adjacent to them. sGC was found in flattened cells surrounding myenteric ganglia (periganglionic cells, PGC), in ICC of the DMP, faintly in smooth muscle cells (SMC), and in cells perivascularly scattered throughout the circular muscle layer. cGK-I immunoreactivity was found abundantly in PGC (which presumably are ICC), in ICC of DMP, in SMC of the innermost circular and longitudinal muscle layers, but less intensively in the outer circular layer. Weak cGK-I staining occurred in nerve cells within the myenteric and submucosal plexus. Conclusively the key enzymes of the NO signaling pathway are differentially distributed: Occurrence of nNOS exclusively in neurons and the presence of sGC and cGK-I predominantly in ICC suggest a sequence of neuronal NO release, activation of ICC, and consecutive smooth muscle relaxation. ICC of the DMP seem to be the primary targets for neurally released NO.

Animals↗
PubMed2000

Functional and chemical anatomy of the afferent vagal system.

The results of neural tracing studies suggest that vagal afferent fibers in cervical and thoracic branches innervate the esophagus, lower airways, heart, aorta, and possibly the thymus, and via abdominal branches the entire gastrointestinal tract, liver, portal vein, billiary system, pancreas, but not the spleen. In addition, vagal afferents innervate numerous thoracic and abdominal paraganglia associated with the vagus nerves. Specific terminal structures such as flower basket terminals, intraganglionic laminar endings and intramuscular arrays have been identified in the various organs and organ compartments, suggesting functional specializations. Electrophysiological recording studies have identified mechano- and chemo-receptors, as well as temperature- and osmo-sensors. In the rat and several other species, mostly polymodal units, while in the cat more specialized units have been reported. Few details of the peripheral transduction cascades and the transmitters for signal propagation in the CNS are known. Glutamate and its various receptors are likely to play an important role at the level of primary afferent signaling to the solitary nucleus. The vagal afferent system is thus in an excellent position to detect immune-related events in the periphery and generate appropriate autonomic, endocrine, and behavioral responses via central reflex pathways. There is also good evidence for a role of vagal afferents in nociception, as manifested by affective-emotional responses such as increased blood pressure and tachycardia, typically associated with the perception of pain, and mediated via central reflex pathways involving the amygdala and other parts of the limbic system. The massive central projections are likely to be responsible for the antiepileptic properties of afferent vagal stimulation in humans. Furthermore, these functions are in line with a general defensive character ascribed to the vagal afferent, paraventricular system in lower vertebrates.

Animals↗
PubMed2000

Intrinsic choroidal neurons in the duck eye express galanin.

Recently, it has been shown that the choroid of the duck eye harbours approximately 1,000 intrinsic choroidal neurons positive for vasoactive intestinal polypeptide and neuronal nitric oxide synthase. Their connections and functional significance are largely unknown. This study was performed to establish a typical chemical code for these neurons and to define their targets by using immunocytochemistry and confocal laser scanning microscopy. Almost all intrinsic choroidal neurons coexpressed galanin (GAL), vasoactive intestinal polypeptide (VIP), and neuronal nitric oxide synthase (nNOS)/NADPH-diaphorase. A few stained for GAL and/or nNOS only. Among extrinsic ganglia, GAL/VIP/nNOS coexpressing neurons were only found in the pterygopalatine ganglion where they accounted for approximately 30% of the neuronal population. Thus, GAL/VIP/nNOS-positive nerve fibres around branches of the ciliary artery and within the nonvascular smooth muscle stroma of the choroid may originate mainly from intrinsic neurons and to some extent in a subpopulation of pterygopalatine ganglionic neurons exhibiting the same chemical coding. Close contacts of GAL-positive fibres upon intrinsic choroidal neurons may indicate reciprocal connections between them. Thus, intrinsic choroidal neurons may represent peripherally displaced pterygopalatine ganglion neurons forming a local network for regulation of vascular and nonvascular smooth muscle tone in the duck choroid. They may be integrated in the neuronal circuitry controlling intraocular pressure, choroidal thickness, accommodation, and axial bulbus length.

Actins↗
PubMed2000

Cysteine-rich protein 2, a novel substrate for cGMP kinase I in enteric neurons and intestinal smooth muscle.

Nitric oxide/cGMP/cGMP kinase I (cGKI) signaling causes relaxation of intestinal smooth muscle. In the gastrointestinal tract substrates of cGKI have not been identified yet. In the present study a protein interacting with cGKIbeta has been isolated from a rat intestinal cDNA library using the yeast two-hybrid system. The protein was identified as cysteine-rich protein 2 (CRP2), recently cloned from rat brain (Okano, I., Yamamoto, T., Kaji, A., Kimura, T., Mizuno, K., and Nakamura, T. (1993) FEBS Lett. 333, 51-55). Recombinant CRP2 is specifically phosphorylated by cGKs but not by cAMP kinase in vitro. Co-transfection of CRP2 and cGKIbeta into COS cells confirmed the phosphorylation of CRP2 in vivo. Cyclic GMP kinase I phosphorylated CRP2 at Ser-104, because the mutation to Ala completely prevented the in vivo phosphorylation. Immunohistochemical analysis using confocal laser scan microscopy showed a co-localization of CRP2 and cGKI in the inner part of the circular muscle layer, in the muscularis mucosae, and in specific neurons of the myenteric and submucosal plexus. The co-localization together with the specific phosphorylation of CRP2 by cGKI in vitro and in vivo suggests that CRP2 is a novel substrate of cGKI in neurons and smooth muscle of the small intestine.

Amino Acid Sequence↗
PubMed2000

Spatial and temporal organization of TrkB expression in the developing musculature of the mouse esophagus.

TrkB expression was investigated immunocytochemically in the developing musculature of mouse esophagus using conventional and confocal laser scanning microscopy. To demonstrate spatial relationships of TrkB immunoreactive cells to striated and smooth muscle fibers we combined TrkB immunocytochemistry with fluorochrome-tagged alpha-bungarotoxin for labeling of nicotinic acetylcholine receptors, and alpha-smooth muscle actin for labeling of smooth muscle cells. At developmental stages E15 to P7, TrkB immunoreactive cells transiently occurred in a transformation zone where striated intermingled with smooth muscle fibers. This transformation zone started in the rostral esophagus at E15, moved caudally, and disappeared between P7 and P10 in the caudal esophagus. The first TrkB-immunoreactive cells appeared in the outer muscle layer at E15. No TrkB-positive cells exhibited acetylcholine receptor clusters or were positive for alpha-smooth muscle actin. A few showed slight alpha-bungarotoxin staining over their entire surface. Taken together, the appearance of TrkB-expressing cells in the transformation zone suggest a role in muscle transdifferentiation. Alternatively, these results, together with recent in vitro data, suggest that TrkB is expressed in a subpopulation of myoblasts in which acetylcholine receptor clustering may be inhibited through a TrkB-mediated pathway.

Aging↗
PubMed2000

Calcium-dependent inactivation of neuronal calcium channel currents is independent of calcineurin.

Dephosphorylation by the Ca2+/calmodulin-dependent phosphatase calcineurin has been suggested as an important mechanism of Ca2+-dependent inactivation of voltage-gated Ca2+ channels. We have tested whether calcineurin plays a role in the inactivation process of two types of high-voltage-activated Ca2+ channels (L and N type) widely expressed in the central nervous system, using the immunosuppressive drug FK506 (tacrolimus), which inhibits calcineurin after binding to intracellular FK506 binding proteins. Inactivation of L- and N-type Ca2+ channels was studied in a rat pituitary tumor cell line (GH3) and chicken dorsal root ganglion neurons, respectively. With the use of antisera directed against the calcineurin subunit B and the 12,000 mol. wt binding protein, we show that both proteins are present in the cytoplasm of GH3 cells and chicken dorsal root ganglion neurons. Ionic currents through voltage-gated Ca2+ channels were investigated in the perforated-patch and whole-cell configurations of the patch-clamp technique. The inactivation of L- as well as N-type Ca2+ currents could be well fitted with a bi-exponential function. Inactivation was largely reduced when Ba2+ substituted for extracellular Ca2+ or when the Ca2+ chelator EGTA was present intracellularly, indicating that both types of Ca2+ currents exhibited Ca2+-dependent inactivation. Extracellular (perforated-patch configuration) or intracellular (whole-cell configuration) application of FK506 to inactivate calcineurin had no effect on the amplitude and time-course of Ca2+ channel current inactivation of either L- or N-type Ca2+ channels. In addition, we found that recovery from inactivation and rundown of N-type Ca2+ channel currents were not affected by FK506. Our results provide direct evidence that the calcium-dependent enzyme calcineurin is not involved in the inactivation process of the two Ca2+ channel types which are important for neuronal functioning, such as gene expression and transmitter release.

Animals↗
PubMed2000

Endomorphin-1 and -2, endogenous ligands for the mu-opioid receptor, inhibit striated and smooth muscle contraction in the rat oesophagus.

Recently, morphological evidence for an interaction of autonomic nerve fibres and extrinsic motor innervation of the rat oesophagus has emerged. The aim of the present study was to investigate the possible influence of endogenous and exogenous opioids on rat oesophageal smooth and striated muscle function in vitro. The entire oesophagus (excluding the lower oesophageal sphincter) with both Nervi (Nn) vagi, including the Nn recurrentes, was dissected and placed in an organ bath (100 mL, 37 degrees) with oxygenated Krebs-Ringer buffer. Contractile activity was measured in a longitudinal direction with a force transducer. Both Nn vagi were placed on a bipolar platinum electrode 2 cm distant from the oesophagus. Vagal stimulation (VS), applied for 1 s (40 V, 0.5 ms, 20 Hz) resulted in a biphasic contractile response that was completely blocked by 10(-6) M tetrodotoxin. The first part consisted of a tetanic striated muscle contraction, as it was abolished by tubocurarine (10(-5) M, n=5) but unaffected by atropine (10(-6) M, n=3) or hexamethonium (10(-4) M, n=4). In contrast, the second part was completely inhibited by hexamethonium (10(-4) M) and atropine (10(-6)M), whereas tubocurarine (10(-5) M) showed no influence, indicating a stimulation of preganglionic nerve fibres supplying oesophageal smooth muscle (muscularis mucosae) via relays in myenteric ganglia. In order to characterize opioid influence on the oesophageal striated and smooth muscle contractility, the following experiments were carried out. 10(-6) M endomorphin-1 and -2, endogenous mu-opioid-receptor agonists, reduced the contractile response of the striated (EM-2, -25.1+/-5.3%; n=16), and the smooth muscle (EM-2, -81.9+/-3.3%; n=11). Both effects were reversible by the opioid receptor antagonist naloxone (10(-6) M) and therefore, mediated via opioid receptors. Neither SNC-80, an agonist on the delta-opioid-receptor, U-69593, an agonist on the kappa-opioid-receptor, nor nociceptin, an agonist at the ORL1 (opioid receptor-like) receptor, had a significant effect on the striated muscle contraction. In contrast to SNC-80, U-69593 and nociceptin inhibited smooth muscle contraction but this relaxation could not be antagonized by naloxone. None of the opioid receptor antagonists used had an effect on basal tonus or muscle contraction following VS. Our data provide evidence for an autonomic modulation of vagal motor innervation of the striated and smooth oesophageal muscle. Endomorphin-1 and -2, both selective mu-opioid receptor agonists, cause an inhibition of striated and smooth muscle response which is reversible by naloxone, an opioid receptor antagonist. The location of the mu-opioid receptor still has to be established.

Animals↗
PubMed1999

Requirement of peptidergic sensory innervation for disease activity in murine models of immune hepatitis and protection by beta-adrenergic stimulation.

To investigate the interaction between the peripheral nervous and the immune system in vivo, we used two mouse models of T cell and TNF-alpha dependent liver injury inducible by either concanavalin A or a combination of D-galactosamine and staphylococcal enterotoxin B. Mice depleted of peptidergic sensory nerve fibres by capsaicin were protected from liver injury. Moreover, TNF-alpha production was significantly reduced. Examination of the effect of catecholamines on liver injury showed that the beta2-adrenergic agonist salbutamol prevented, whereas chemical sympathectomy by 6-hydroxydopamine, deteriorated the disease. Hence, strategies reducing the activity of peptidergic sensory nerve fibres or stimulating beta2-adrenoreceptors, may be of benefit in immune-mediated liver disease.

Adrenergic beta-Agonists↗
PubMed1998

Vagal and spinal afferent innervation of the rat esophagus: a combined retrograde tracing and immunocytochemical study with special emphasis on calcium-binding proteins.

Vagal afferent neurons contain a variety of neurochemical markers and neuroactive substances, most of which are present also in dorsal root ganglion cells. To test for the suitability of the calcium-binding protein calretinin as a specific marker for vagal afferent fibers in the periphery, immunocytochemistry for this protein was combined with retrograde tracing. Nerve fibers in the rat esophagus, as well as vagal and spinal sensory neurons innervating the esophagus, were investigated for co-localization of calretinin with calbindin, calcitonin gene-related peptide, and NADPH diaphorase. The results indicated that calretinin immunocytochemistry demonstrates neuronal structures known as vagal afferent from other studies, in particular intraganglionic laminar endings. A few enteric neurons whose distribution was unrelated to intraganglionic laminar endings also stained for calretinin. Strikingly, calretinin immunoreactivity was absent from spinal afferent neurons innervating the rat esophagus. In intraganglionic laminar endings and nodose ganglion cells calretinin was highly co-localized with calbindin but not with calcitonin gene-related peptide. On the other hand, calbindin was also found in spinal afferents to the esophagus where it was co-localized with calcitonin gene-related peptide. Vagal afferent neurons innervating the esophagus were never positive for NADPH diaphorase. Thus, calretinin appears to be a more specific marker for vagal afferent structures in the esophagus than calbindin, which is expressed by both vagal and spinal sensory neurons. Calretinin immunocytochemistry may be utilized as a valuable tool for investigations of subpopulations of vagal afferents in certain viscera.

Animals↗
PubMed1998

Vagal efferent and afferent innervation of the rat esophagus as demonstrated by anterograde DiI and DiA tracing: focus on myenteric ganglia.

Anterograde tracing with the carbocyanine tracer DiI and the aminostyrol derivative DiA was used to selectively label fibers from the nucleus ambiguus, dorsal motor nucleus and nodose ganglion, respectively, terminating in the rat esophagus, and to compare them with the innervation of the gastric fundus in the same animals. Ambiguus neurons terminated on motor endplates distributed mainly to the ipsilateral half of the esophagus. There was no evidence of preganglionic innervation of myenteric ganglia from ambiguus neurons. Neurons of the dorsal motor nucleus supplied sparse fibers to only about 10% of enteric ganglia in the esophagus while they innervated up to 100% of myenteric ganglia in the stomach. Neurons of the nodose ganglion terminated profusely on more than 90% of myenteric ganglia of the esophagus and on about 50% of ganglia in the stomach. Afferent vagal fibers were also frequently found in smooth muscle layers starting at the esophago-gastric junction. In contrast, they were extremely rare in the striated muscle part of the esophagus. These morphological data suggest a minor influence of neurons of the dorsal motor nucleus and a prominent influence of vagal afferent terminals onto myenteric neurons in the rat esophagus.

Animals↗
PubMed1998

[Characteristics of the innervation of the head and neck].

Innervation of the head and neck differs from other regions of the body in certain respects. In particular, besides the external cuneate nucleus, thick-calibre neck muscle afferents project directly, to the vestibular nuclear complex. This projection is most prominent in segments C2 and 3 and is sparse or absent in more caudal segments. Thus, proprioceptive neck muscle afferents gain direct access to vestibulospinal, vestibulooculomotor and other secondary or even higher order vestibular neurons that receive labyrinthine input. Proprioceptive input via indirect spinovestibular pathways is also most prominent from C2 and 3 compared to more caudal levels. Likewise, thin calibre, mainly nociceptive afferents from cervical segments are channelled via the parabrachial nuclei in the rostral pons to limbic structures different from the targets of thoracolumbar afferents. It is tempting to consider these neuroantomical peculiarities relevant for the pathogenesis of the puzzling symptoms after whiplash injury.

Brain Stem↗