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Differential expression of interleukin-10 mRNA in Wallerian degeneration and immune-mediated inflammation of the rat peripheral nervous system.

Interleukin-10 (IL-10) is a potent immunosuppressant cytokine which downregulates MHC class II antigen expression and inflammatory cytokine production. In this study we localized mRNA for IL-10 in the rat peripheral nervous system (PNS) by nonradioactive in situ hybridization using a digoxygenin-labeled riboprobe specific for rat IL-10. IL-10 mRNA was expressed by some Schwann cells (SCs) in the normal sciatic nerve. During Wallerian degeneration, SCs strongly expressed IL-10 mRNA between days 2 and 4 after transection. By day 14 only occasional cells were positive for IL-10 mRNA. The vast majority of ED1-positive macrophages were IL-10 negative after axotomy. Contrastingly, infiltrating macrophages expressed IL-10 mRNA conincident with beginning clinical recovery in experimental autoimmune neuritis (EAN), the rat model of human Guillain-Barré syndrome. Our data suggest that SCs provide a constitutive immunosuppressant system in the PNS. In EAN additional macrophage-derived IL-10 may be important for the resolution of the T cell-mediated immune response.

Animals↗

Immunolocalization of laminin in neoplasms of the central and peripheral nervous systems.

Laminin is a basement membrane glycoprotein that is expressed in vitro by immature and neoplastic astrocytes. The expression of laminin in vivo was examined immunohistochemically in normal adult brain and 90 neoplasms of the central and peripheral nervous systems. In normal adult brain, laminin was detected in the vasculature, arachnoid, pial-glial membrane, and choroid plexus. The vasculature in all 90 tumors demonstrated intense laminin immunoreactivity. Deposits of laminin were observed at the glioma-mesenchymal junction in several neoplasms, but never between or within neuroepithelial cells. The glial basement membrane often remained intact although surrounded on both sides by invasive glioma or medulloblastoma. However, there was always fragmentation and disruption of the glial membrane in adjacent fields. Laminin expression by tumor cells was observed in 10/10 schwannomas, 9/10 fibroblastic meningiomas, 3/19 nonfibroblastic meningiomas, and 3/6 mixed glioma-sarcomas. Laminin expression in the normal nervous system and in neuroepithelial neoplasms corresponds to regions of recognized basal lamina formation, including the junction between glial and mesenchymal elements. Although invasive gliomas are able to break down the pial-glial basement membrane and gain access to the perivascular or subarachnoid space, this membrane often remains intact late in the invasive process and may represent a partial barrier to tumor invasion. Laminin may be a useful marker for schwannomas, fibroblastic meningiomas, and vascular neoplasms of the nervous system.

Basement Membrane↗

Effects of lithium administration on central and peripheral nervous system in rats. Biochemical and morphological findings.

The effect of 4 weeks' treatment with lithium chloride on the central and peripheral nervous system of Wistar albino rats was studied. Normal activity values of some brain enzymes related to energy transduction (LDH, MDH, COX, NADH-ccRT) and neuro-transmission (ACHe), evaluated both in the homogenate in toto and in the crude mitochondrial fraction, were obtained. Fine changes in mitochondrial organelles and nerve processes of neurocytes were ultrastructurally observed. The peripheral nerve studies revealed in some treated rats a slight motor nerve conduction velocity impairment by electro-physiological methods, but no significant alterations in the sciatic nerve specimens examined by electron microscopy.

Animals↗

Neurotensin. Immunohistochemical localization in central and peripheral nervous system and in endocrine cells and its functional role as neurotransmitter and endocrine hormone.

The present study attempts to compile information on the possible physiologic role of the endogenous peptide neurotensin (NT) as a hormone and/or neurotransmitter. The methodological approach is immunohistochemical localization of NT in the entero-endocrine system as well as in the central and peripheral nervous systems. The results found in the three systems are first related to the pharmalogical and physiological findings in the literature. Subsequently their significance is discussed for each organ separately before attempting a final overall interpretation. Briefly, the present study reveals the following essential findings: The occurrence and distribution of NT-IR entero-endocrine cells (N-cells) in different mammals including man, as well as in representative members of all classes of vertebrates and higher invertebrates, are analyzed and evaluated morphometrically. The NT-IR cells in all investigated species are demonstrated to be of the open type. The innervation of paravertebral and prevertebral ganglia by NT-IR fibers is described; at least a portion of these fibers is thought to originate in NT-IR perikarya of the substantia intermedia of the spinal cord. The involvement of these NT-IR fibers in the regulation of systemic blood flow (hypertension) is suggested. The existence of NT-IR innervation of the gastro-intestinal tract is considered to be a general phenomenon. This notion is reaffirmed by phylogenetic investigation of the NT-IR enteric nerves. The pharmacological effects of NT in different portions of the gastro-intestinal tract, reported in the literature are related to the immunohistochemical localization of NT. In light of the present results, some of the effects of NT which were previously considered to be of an endocrine or paracrine nature - such as contraction of the guinea-pig ileum - are interpreted as effects of NT of neuronal origin. The specific NT-IR innervation of target cells in the exocrine pancreas (vascular smooth muscle, acinar cells) is demonstrated, and participation of NT-IR nerve fibers in regulation of the secretion of pancreatic juice is postulated. The innervation of the heart (coronary vasculature, myocardium, conduction system) by NT-IR fibers is demonstrated in various mammals and for the first time also in man. The cardiac NT-IR nerve fibers are thought to be the cytological substrate for different NT effects on heart action (coronary vasoconstriction, positive inotropy and chronotropy) reported in the literature.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

[Significance of modifying factors in the development of peripheral nervous system tumors in rabbits].

The experiments conducted on 170 rabbits have indicated that the development of neurogenic tumors under the exposure to methylnitrosourea procedes more rapidly in immunization with the tissue homogenate from the rabbit sciatic nerve (using a complete Freund's adjuvant) in chronic irritation of the peripheral trunk and in hypothyroidism and estrogenization of the organism of animals under test. Castration and thyroidin administration would reduce the number of experimental tumors of the peripheral nervous system and lengthen the latent period of their development.

Animals↗

Alternative cell fate choice induced by low-level expression of a regulator of protein phosphatase 2A in the Drosophila peripheral nervous system.

The Drosophila gene twins encodes the regulatory B subunit of type 2A protein phosphatase. Here we report that its partial loss-of-function mutations caused abnormal morphogenesis in the adult peripheral nervous system. In wild-type flies, the mechanoreceptor, one major class of sensory organs, is composed of four specialized cells (one neuron and three accessory cells) that are derived from a single precursor cell. The hypomorphic twins mutations did not block division of this precursor, but most likely altered cell fate in this lineage to produce only accessory cells that form sensory structures. Stepwise reductions of twins protein enhanced this transformation. In these mutants, another regulatory subunit, A, and the catalytic subunit, C, of the phosphatase were expressed at normal levels. Therefore, the modulation of the phosphatase activity by the B subunit appears to be crucial for specification of neural cell identity.

Alleles↗

[Affection of the central and peripheral nervous systems in systemic lupus erythematosus].

Using the complex methods of morphological, neurohistological and histochemical methods in the study of the central and peripheral nervous system in systemic lupus erythematosus, the authors observed 20 patients who died at the age of 12-56. The studies detected phenomena of disorganization of the connective tissue and vascular walls which are accompanied by a significant accumulation of muccopolysaccharides, thrombovasculites, endovasculites, lymphoid-plasmocellular infiltration and degenerative changes in the nervous elements.

Adolescent↗

Metabolism of phosphate and sulfate groups modifying the P0 protein of peripheral nervous system myelin.

We have examined the metabolism of phosphate and sulfate groups modifying the P0 protein, the major protein of peripheral nervous system myelin, using an in vitro incubation system. Incorporation of [3H]leucine into the P0 peptide backbone decreased approximately 25-fold between 10 and 90 days of age, a finding reflecting a decreased rate of myelin synthesis in the older animals. In contrast, incorporation of [32P]phosphate into P0 decreased only four- to fivefold, a result indicating that phosphate groups are metabolized independently of the peptide backbone. Developmental decreases in the incorporation of sulfate groups into P0 were similar to those seen for leucine, an observation suggesting that this modifying group is metabolized together with the peptide backbone as a single metabolic entity. The time course of labeling of P0 isolated from the starting homogenate and from myelin was also compared. Results are consistent with sulfation of P0 protein taking place before insertion of newly synthesized P0 into myelin. In contrast, incorporation of phosphate into P0 appears to involve both the newly synthesized pool and the preexisting pool of P0 in myelin. Presumably, entry of phosphate into P0 in myelin involves turnover of preexisting phosphate groups and rephosphorylation by myelin protein kinases. Developmental decreases in the specific activity of P0 phosphate groups in myelin are consistent with the presence of a small, rapidly turning-over pool of phosphorylated P0 (perhaps associated with the axon-myelin interface), which does not increase to the same extent as the marked increase in bulk myelin that occurs during development.

Aging↗

Stimulation of the central and peripheral nervous system for the control of pain.

After suffering some setbacks since its introduction in 1967, stimulation of the spinal and peripheral nervous systems has undergone rapid development in the last ten years. Based on principles enunciated in the Gate Control Hypothesis that was published in 1968, stimulation-produced analgesia [SPA] has been subjected to intensive laboratory and clinical investigation. Historically, most new clinical ideas in medicine have tended to follow a three-tiered course. Initial enthusiasm gives way to a reappraisal of the treatment or modality as side-effects or unanticipated problems arise. The last and third phase proceeds at a more measured pace as the treatment is refined by experience. This review is divided into three parts as it traces the progress of spinal cord stimulation [SCS] and peripheral nerve stimulation [PNS]. The review commences with a discussion of the theory of SCS and PNS, and is followed by early reports during which it became apparent that the modality is essentially only effective in the treatment of neuropathic pain. The last section describes the modern experience including efficacy in specific types of pain and concludes with recent accomplishments that dramatize the relief of pain which can be achieved in nonoperable peripheral vascular disease or myocardial ischemia. Over the years, a search for those transmitters that might be influenced by spinal cord stimulation focused on somatostatin, cholecystokinin (CCK), vasoactive intestinal polypeptide (VIP), neurotensin and other amines, although only substance "P" was implicated. More recently, in animal studies, evidence that GABA-ergic systems are affected may explain the frequent successful suppression of allodynia that follows spinal cord stimulation. During the past eight years, much attention has been directed to studies that use a chronic neuropathic pain model. While PNS held significant promise as a pain relieving modality, early electrode systems and their surgical implantation yielded variable results due to evolving technical and surgical skills. These results dramatically reduced the continued development of PNS, which then gave way to a preoccupation with SCS. Modern development of SCS with outcome studies, particularly in relation to failed back surgery syndrome [FBSS] and the outcome of peripheral nerve surgery for chronic regional pain syndromes, has earned both modalities a place in the ongoing management of patients with intractable neuropathic pain. The last section, dealing with pain of peripheral vascular and myocardial ischemia, is perhaps one of the more exciting developments in stimulation produced analgesia and as the papers discussed demonstrate, can provide a level of analgesia and efficacy that is unattainable by other treatment modalities. SCS and PNS has an important role to play in the management of conditions that are otherwise refractory to conservative or other conventional management.

Analgesia↗

[Pulmonary and pulmonary-related reflexes mediated by serotonin receptors in the peripheral nervous system].

It is known that serotonin is widely distributed in the body; its receptors are located in various tissues and organs. It has been reported that serotonin receptors without apparent synaptic structure exist in the peripheral nervous system. These serotonin receptors might be the target of circulatory serotonin. In particular, serotonin has a potent depolarizing action on vagal afferent nerves. This stimulation causes various autonomic reflexes, so-called von Bezold-Jarisch reflex, that consist of bradycardia, hypotension and apnea. The peripheral 5-HT3-receptor subtype seems to be responsible for the initiation of these reflexes. The physiological and pathophysiological significance of these serotonin-induced modulations have not, however, been established. The present study was designed to examine the effects of exogenous serotonin on the chemosensitive afferent nerves including carotid sinus nerves, cervical vagus nerve, and efferent motor nerves, such as phrenic nerves and pharyngeal nerves. Because little is known about the involvement of the serotonergic system in the pulmonary reflex and pulmonary-related reflexes (swallowing or vomiting), the distribution of the motor component of these nerves within the brain stem of the rat was also determined.

Animals↗

Retinoid X receptor-gamma gene expression is developmentally regulated in the embryonic rodent peripheral nervous system.

The retinoid X receptor-gamma (RXRgamma) is a transcription factor that belongs to the thyroid hormone/retinoid family of nuclear receptors. Previous studies have shown that RXRgamma is expressed in the developing peripheral nervous system (PNS) of chick embryos, but such expression has not been reported previously in rodent embryos. Indeed, the pattern of RXRgamma expression appears to be different between avian and rodent species. Using in situ hybridisation and northern blot experiments we show that RXRgamma is expressed in elements of the PNS in rat and mouse embryos and in postnatal rats. However, unlike the chick, where RXRgamma is expressed from the onset of neural crest migration, rat RXRgamma expression in the dorsal root ganglia and trigeminal ganglia was detectable at 14.5 days post coitum (dpc), but not at 13, 12, or 11 dpc. These data suggest that RXRgamma may have a role in the dorsal root ganglia and trigeminal ganglia of late embryos, and that this could be evolutionarily conserved between chick and rodent. On the other hand, rat RXRgamma transcripts in the facio-acoustic (VII-VIII) ganglion were detectable at 11 dpc in neural crest cells condensing to form this ganglion. We discuss the possible significance of the timing of RXRgamma expression in the developing PNS and suggest that closer examination of the structure and function of the PNS of RXRgamma null mutant mice would be of interest.

Animals↗

[Diseases of the lumbosacral portion of the peripheral nervous system (treatment and prevention)].

A critical analysis of modern literature and personal experience permits the author in a discussional aspect to speak on diagnosis formulation in patients with lesions of the sacrolumbar area of the peripheral nervous system. The paper contains detailed recommendations in relation to different forms of medicative therapy and prevention in this group of patients. The subsequent perspectives and further studies, as well as organizational questions are being discussed.

Back Pain↗

Formation of the peripheral nervous system during tail regeneration in urodele amphibians: ultrastructural and immunohistochemical studies of the origin of the cells.

In the regenerating newt tail, epimorphic regeneration--which recapitulates morphologically normal embryonic development--proceeds along a rostrocaudal differentiation gradient. Innervation of the new myomeres results from the spinal roots of segments rostral to the amputation plane and from ventral roots emerging from the lateroventral region of the regenerating spinal cord, in which motor neurons are differentiating. Electron microscopy and an indirect immunofluorescence study with anti-glial fibrillary acid protein (GFAP) confirm that the ventrolateral part of the regenerated ependymal tube gives rise to cells of the ventral root sheath and the spinal ganglia. Anti-GFAP and anti-neurofilament antibodies showed that ependymoglial cells and Schwann cells may play a role in neuronal pathfinding by helping guide and stabilize pioneering axons as they extend toward the myomeres. The carbohydrate epitope NC-1 is expressed in the spinal cord, in sheath cells of the spinal ganglia and in the non-myelin-forming Schwann cells of the peripheral nervous system. L1, a Ca++ independent neural cell adhesion molecule, was detected in the axonal compartments of the regenerating spinal cord, on immature and/or non-myelin-forming Schwann cells within the peripheral nervous system (PNS), and on nerve fibers within the regenerate. These immunohistochemical observations collectively support the hypothesis that Schwann cells already present in the blastema could be involved in organizing neural pathways.

Animals↗

Pentachlorophenol and the peripheral nervous system: a longitudinal study in exposed workers.

A longitudinal study was performed to examine whether chronic occupational exposure to pentachlorophenol (PCP) or its compounds causes measurable alterations in the conduction velocity in peripheral nerves as an "adverse effect." In total, the results of nerve conduction velocity (NCV) determinations in 1980 and 1984 in 10 subjects (7 men, 3 women) who had been exposed for an average of 16 years (range 4-24) were available. The concentrations of PCP in the air at the workplace varied between 0.3 and 180 micrograms/m3 and were thus below the maximum allowed concentration (MAK value) of 500 micrograms/m3. The biological monitoring carried out showed the following results: PCP in the serum: 38-1270 micrograms/l; PCP in the urine: 8-1224 micrograms/l. Compared with the upper normal limits (PCP in the serum 150 micrograms/l, PCP in the urine 60 micrograms/l), distinct internal exposure to PCP has resulted in some of the employees. Determinations of the NCV of motor and sensory nerve fibres (ulnar, median, peroneal, and sural nerve) were always in the normal range. A significant difference in the NCV for the period 1980-4 could not be detected. In addition, the correlation analyses did not show any hints of "dose-effect relations." It is concluded that occupational exposure to PCP over several years in the concentrations observed probably do not lead to any adverse effects on the peripheral nervous system.

Adult↗