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Bone marrow-derived elements in the peripheral nervous system. An immunohistochemical and ultrastructural investigation in chimeric rats.

BACKGROUND: Currently available studies on the peripheral nervous system (PNS) give little information on the presence, distribution, turnover and function of bone marrow-derived cells such as monocytes, macrophages, and dendritic cells. To address such issues, the present investigation of PNS tissues from bone marrow transplanted chimeras was performed. EXPERIMENTAL DESIGN: Inbred DA rats were lethally irradiated and transplanted with (Lewis x DA)F1 bone marrow carrying the non-DA major histocompatibility antigens from Lewis rats. The anti-RT-1A antibody (anti-Lewis MHC class I), I1-69, and the macrophage markers, Ed2 and Ox42 were used to visualize immunohistochemically donor bone marrow-derived cells and resident macrophages of sensory and autonomic ganglia as well as in peripheral nerves. RESULTS: In the ganglia, up to 80% and within peripheral nerves, up to 60% of macrophages were replaced by donor cells within 3 months of established chimerism. Ultrastructurally these cells were located: (a) between the perineurial sheaths, (b) in a perivascular position, or (c) freely dispersed within the endoneurium but outside the basal lamina of Schwann cells and ganglion cells. On the rare occasions where myelin and axonal pathology was noted, or during central chromatolysis of ganglion cells, donor marrow-derived cells became positioned under the basal lamina and incorporated tissue debris. CONCLUSIONS: These data suggest a rapid and significant turnover of bone marrow-derived cells within the PNS. Our observations are relevant to the understanding of the pathogenesis of reactive, immunologic, and HIV-associated processes within the PNS.

Animals↗

[The characteristics of peripheral nervous system involvement in Lyme borreliosis in an endemic region of Russia].

Clinical and laboratory data are available on affection of the peripheral nervous system (PNS) in 27 patients with Lyme-borreliosis (LB) in the endemic region of Russia. PNS disorders arose early, 88.9% of the patients had them within one month of the disease. 9 (37.5%) patients had meningoradiculoneuropathy (MRN) which emerged in the acute period in 77.8% of the patients. Inflammation in the cerebrospinal fluid was registered only in patients with clinical signs of meningitis. MRN developed more frequently in facial nerve neuritis (FNN) than in radiculopathy (RP)-80.0% and 14.3%, respectively, p = 0.01. Intrathecal synthesis of antibodies to B. burgdorferi in combination with pleocytosis was found only in FNN patients (16.7%). In 6 (37.5%) of 16 patients with neuroborreliosis concentrations of C-reactive protein were elevated. Its high level occurred significantly more frequently in RP (83%) than in FNN (17%) (p = 0.05). 5 out of 14 LB patients exhibited high level of Willebrand factor antigen. No clear clinical relations between this value and PNS lesions in LB were found.

Adult↗

Immunochemical characterization of peripheral nervous system myelin 170,000-Mr glycoprotein.

A recently described 170,000-Mr glycoprotein, specific to peripheral nervous system (PNS) myelin, was purified from rat PNS myelin by preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis and used to immunize guinea pigs and rabbits. The resultant antisera proved specific for 170,000-Mr glycoprotein by enzyme-linked immunosorbent assay, by immunoprecipitation of the appropriate peptide from solubilized PNS myelin, and by immunoblot analysis of rat PNS myelin. The anti-rat 170,000-Mr glycoprotein antisera cross-reacted with proteins of similar molecular weight in human and bovine PNS myelin, but such proteins were not detected in human or rat CNS myelin or other rat tissues. The 170,000-Mr glycoprotein was also detected by this immunoblot procedure in recently isolated rat Schwann cells but not in those kept in culture for greater than or equal to 3 days. By indirect immunofluorescent microscopy, anti-rat 170,000-Mr glycoprotein antibody bound to rat PNS myelin sheaths but not to other rat tissues. Together, these studies indicate the 170,000-Mr glycoprotein is specific to PNS myelin of several species and that a neuronal influence may be required for its expression by Schwann cells.

Animals↗

Cardiac sympathetic afferent cell bodies are located in the peripheral nervous system of the cat.

Studies of the stellate ganglion and middle cervical ganglion indicate that sympathetic efferent nerve activity can be modified by peripheral excitatory inputs and that these neural connections may function as pathways for a peripheral reflex at the level of the thoracic sympathetic ganglia. This excitatory synaptic input could have a soma in either the central or the peripheral nervous system. A study was designed to determine whether chronic decentralization (3 weeks) of the stellate ganglion in cats would 1) abolish sympathetic cardiac afferent nerve activity recorded at the stellate cardiac nerve and 2) abolish local thoracic reflexes that are generated by stimulation of peripheral nerves. The ansae subclaviae, T3 and T4 rami, and stellate ganglion were also examined by electron microscopy for the extent of Wallerian degeneration. Afferent cardiac activation of the axon collaterals arising from cell bodies located in the dorsal root ganglia was abolished due to degeneration. However, sympathetic afferent nerve activity from the left ventricular receptors was still present and was recorded from the stellate cardiac nerve in all cats. Cardiac receptors were sensitive to mechanical distortion, increases in the left ventricular pressure, and epicardial application of veratrine hydrochloride. These data imply that 1) cardiovascular afferent input to the stellate ganglion persists following chronic decentralization and 2) the sensory neurons are located in the peripheral sympathetic nervous system. Thus, we find that regulation of the heart occurs in part via thoracic ganglia, independently of the central nervous system.

Afferent Pathways↗

Distribution of GABA immunoreactivity in the central and peripheral nervous system of amphioxus (Branchiostoma lanceolatum Pallas).

On the basis of labeling with an anti-gamma-aminobutyric acid (GABA) antibody, we report for the first time the presence and distribution of GABA-immunoreactive cells in the central and peripheral nervous system of amphioxus. In the nerve cord, there is a large dorsorostral group of cerebrospinal-fluid-contacting (CSFc) cells at the caudal end of the brain vesicle that gives rise to a large ventral commissure and neuropilar region. In the middle and caudal region of the brain, numerous commissural and CSFc neurons are situated below the region of large dorsal cells. In the spinal cord, several types of GABA-immunoreactive neurons of different size, appearance, and distribution were observed. In the dorsalmost region, very small commissural cells are scattered regularly along the cord. More ventrally in the cord, GABAergic neurons, both of commissural and CSFc cell types, form segmental groups, but scattered cells are observed throughout. These cells give rise to dense longitudinal fascicles of GABAergic fibers and to scattered commissural fibers. The caudal ampulla lacks GABAergic cells and fibers. Some of the fibers of the most rostral and caudal peripheral (sensory) nerves, as well as some sensory cells of the rostral and caudal epidermis, are GABA immunoreactive. The significance of these results for the understanding of the evolution of GABAergic systems of vertebrates is discussed.

Animals↗

Mutations affecting the development of the peripheral nervous system in Drosophila: a molecular screen for novel proteins.

In our quest for novel genes required for the development of the embryonic peripheral nervous system (PNS), we have performed three genetic screens using MAb 22C10 as a marker of terminally differentiated neurons. A total of 66 essential genes required for normal PNS development were identified, including 49 novel genes. To obtain information about the molecular nature of these genes, we decided to complement our genetic screens with a molecular screen. From transposon-tagged mutations identified on the basis of their phenotype in the PNS we selected 31 P-element strains representing 26 complementation groups on the second and third chromosomes to clone and sequence the corresponding genes. We used plasmid rescue to isolate and sequence 51 genomic fragments flanking the sites of these P-element insertions. Database searches using sequences derived from the ends of plasmid rescues allowed us to assign genes to one of four classes: (1) previously characterized genes (11), (2) first mutations in cloned genes (1), (3) P-element insertions in genes that were identified, but not characterized molecularly (1), and (4) novel genes (13). Here, we report the cloning, sequence, Northern analysis, and the embryonic expression pattern of candidate cDNAs for 10 genes: astray, chrowded, dalmatian, gluon, hoi-polloi, melted, pebble, skittles, sticky ch1, and vegetable. This study allows us to draw conclusions about the identity of proteins required for the development of the nervous system in Drosophila and provides an example of a molecular approach to characterize en masse transposon-tagged mutations identified in genetic screens.

Animals↗

Peripheral nervous system complications of coronary artery bypass graft surgery.

Among 421 patients undergoing coronary artery bypass graft surgery, 55 (13%) developed 63 new peripheral nervous system (PNS) complications postoperatively. Most common was a brachial radiculoplexopathy, which occurred in 23 patients. Of these, 21 involved lower trunk or medial cord fibers. In 17 there was a correlation between the site of jugular vein cannulation and the side affected, suggesting that needle trauma played a role. Stretching from chest wall retraction may have caused some cases. Other deficits included 13 saphenous, 8 common peroneal, and 5 ulnar mononeuropathies. Six patients had persistent singultus, suggesting phrenic nerve involvement. Unilateral vocal cord paralysis was found in 5. An isolated partial Horner syndrome and a facial neuropathy were also identified. Males were more likely to develop PNS complications. Hypothermia during surgery was associated with increased risk. Most PNS deficits were transient, and lasting disability was rare.

Adult↗

[Operations on the peripheral nervous system in the treatment of spasmodic torticollis].

The aetiopathogenesis of spasmodic torticollis has not yet been explained. The problem of surgical treatment selection is also at issue. The authors present own observations in 5 cases treated by operations on the peripheral nervous system. In 3 cases a very good therapeutic results was obtained, in 2 cases the results was not satisfactory. A characteristic fact was appearance of ultimate improvement only several months after the operation, similarly as it is observed after stereotactic operations. In the light of own observations and a survey of the literature the authors reach the conclusion that operations on the peripheral nervous system as the first stage of surgical treatment give good results in most cases.

Accessory Nerve↗

Differential protooncogene expression characterizes histopathologically indistinguishable tumors of the peripheral nervous system.

We have found highly predictable patterns of protooncogene expression in cell lines and tumor tissue of neuroblastoma (NB), a tumor of the peripheral nervous system (PNS). These patterns make it possible to recognize two different genetically definable subgroups among histopathologically indistinguishable tumors. Additionally, we have identified a difference in neurotransmitter biosynthetic enzyme activity in these two subgroups of NB. The patterns of protooncogene expression and neurotransmitter biosynthetic enzymes suggests that these tumors arise in different cells of the PNS.

Cell Line↗

Ultrastructural aspects of peptidergic modulation in the peripheral nervous system of Helix pomatia.

The ultrastructural characteristics of peptidergic peripheral contacts in the snail, Helix pomatia, were investigated, with special attention to the innervation of the heart, buccal mass, and salivary gland by Mytilus inhibitory peptide-immunoreactive neurons. Following the application of correlative light- and electron-microscopic pre-embedding immunocytochemistry, the peripheral tissues reveal a rich innervation by Mytilus inhibitory peptide-immunoreactive elements. These neurons establish three types of neuromuscular contacts in the heart and buccal mass: (1) close (16-20 nm) unspecialized membrane contacts; (2) contacts with a relative wide (40-100 nm) intersynaptic cleft; and (3) labeled varicosties located freely in the extracellular space, far (0. 5-several microm) from the muscle cells. In the salivary gland, the immunoractive profiles contact both the muscular and glandular elements with close (type 1) and wider (type 2) membrane attachments. The great majority of Mytilus inhibitory peptide-immunoreactive profiles contain an ultrastructurally uniform population of large (120-150 nm) electron dense granules. The ultrastructural features of the innervation by Mytilus inhibitory peptide-immunoreactive elements are compared with those established by immunogold labelled FMRFamide-containing profiles in the heart and salivary gland. These latter display similarities in forming the different kinds of intercellular contacts, and differences in the morphological variability of the content of granules in the immunolabeled profiles. The results suggest diverse, non-synaptic modulatory roles of neuropeptides in the peripheral nervous system of Helix pomatia, including localized membrane effects and neurohormonal-like remote global controls, that may also be of significance in orchestrating the effects of neuropeptides released at the same time on different targets.

Animals↗

Advances in understanding and treatment of immune-mediated disorders of the peripheral nervous system.

During recent years, novel insights in basic immunology and advances in biotechnology have contributed to an increased understanding of the pathogenetic mechanisms of immune-mediated disorders of the peripheral nervous system. This increased knowledge has an impact on the management of patients with this class of disorders. Current advances are outlined and their implication for therapeutic approaches addressed. As a prototypic immune-mediated neuropathy, special emphasis is placed on the pathogenesis and treatment of the Guillain-Barré syndrome and its variants. Moreover, neuropathies of the chronic inflammatory demyelinating, multifocal motor, and nonsystemic vasculitic types are discussed. This review summarizes recent progress with currently available therapies and--on the basis of present immunopathogenetic concepts--outlines future treatment strategies.

Animals↗

[The treatment of organic pain of the peripheral nervous system using clomipramine. 30 cases (author's transl)].

Clomipramine used alone is an affective analgesic against organic pain due to a lesion of the peripheral nervous system, in particular post-herpetic pain. The quality of the result is related to the dose, and hence to tolerance. Fluohydrocortisone is the most powerful drug against orthostatic hypotension, the chief cause of limitation of treatment. No complications were seen, even in very elderly patients.

Adult↗

Peripheral nervous system involvement in experimental tuberculosis.

Following intravenous injection of mycobacteria in the mouse the bacilli are regularly found in the peripheral nervous system after the 5th day. The peripheral nerves and autonomic ganglia are involved at the level of the perineural cells and the sheath of Schwann. When the organisms are of low virulence (BCG, Mycobacterium intracellulare) the development of the nodules is limited. In the case of a virulent strain (Ravenel) extensive granulomas are found but epitheloid cells, always found in other organs, are constantly absent. In animals previously immunized, the bacilli seem to implant themselves as in the controls, but multiply more slowly; the nodules are more infrequent and the lymphoid infiltration appears earlier with the multiplication of interstitial cells.

Animals↗

Fast optical signals in the peripheral nervous system.

We present a study of the near-infrared optical response to electrical stimulation of peripheral nerves. The sural nerve of six healthy subjects between the ages of 22 and 41 was stimulated with transcutaneous electrical pulses in a region located approximately 10 cm above the ankle. A two-wavelength (690 and 830 nm) tissue spectrometer was used to probe the same sural nerve below the ankle. We measured optical changes that peaked 60 to 160 ms after the electrical stimulus. On the basis of the strong wavelength dependence of these fast optical signals, we argue that their origin is mostly from absorption rather than scattering. From these absorption changes, we obtain oxy- and deoxy-hemoglobin concentration changes that describe a rapid hemodynamic response to electrical nerve activation. In five out of six subjects, this hemodynamic response is an increase in total (oxy+deoxy) hemoglobin concentration, consistent with a fast vasodilation. Our findings support the hypothesis that the peripheral nervous system undergoes neurovascular coupling, even though more data is needed to prove such hypothesis.

Adult↗

Immunocytochemical demonstration of neuropeptides in the peripheral nervous system of the roundworm Ascaris suum (Nematoda, Ascaroidea).

The localisation and distribution of neuropeptides in the peripheral nervous system of the pig roundworm Ascaris suum have been determined by an indirect immunofluorescence technique in conjunction with confocal microscopy. Of the 31 antisera tested, immunostaining was obtained only with antisera to peptide YY (PYY), pancreatic polypeptide (PP) and FMRFamide. Immunostaining for PYY and FMRFamide was evident in the amphidial and papillary ganglia associated with the anterior nerve ring and in the nerves from these ganglia that terminated in sensory receptors within the buccal lips of the parasite. The only peptide immunoreactivity (IR) observed in the reproductive system of either sex was that evident in the nerve supply to the distal region of the vagina in the female worm. It took the form of a well-developed plexus of parallel nerve fibres, cross-connectives and looped commissures. The nerve net diminished in the more proximal region of the vagina. PP-IR was less intense than that for PYY and FMRFamide and was more restricted in distribution, being confined to a small number of nerve fibres in the nerve supply to the vagina; it did not occur in the nerves supplying the anterior sensory receptors. The possible roles of neuropeptides in the sensory and reproductive biology of nematodes are discussed.

Animals↗

Autonomic neuropathy in transgenic mice caused by immunotoxin targeting of the peripheral nervous system.

Autonomic neuropathy in several neurodegenerative disorders results from disturbance in physiological functions of different cell types in the central and peripheral nervous systems. For a clearer understanding of the etiology and pathogenesis of the autonomic disorders it is necessary to create animal models in which degeneration of the causative neuronal types can be induced. Immunotoxin-mediated cell targeting (IMCT) is a novel transgenic mouse technology for eliminating selective cell types with the cytotoxic activity of a recombinant immunotoxin anti-Tac(Fv)-PE40. In this study we conditionally disrupted peripheral catecholaminergic cells with IMCT to generate a mouse model developing autonomic failure based on primary defects of the sympathetic nervous system. Transgenic mice expressing human interleukin-2 receptor alpha subunit under the control of the dopamine beta-hydroxylase gene promoter were intravenously treated with a proper dose of anti-Tac(Fv)-PE40. The immunotoxin induced a selective loss of the target cells in peripheral tissues of the transgenic mice and an impairment of catecholamine metabolism in the tissues. Targeting of the peripheral catecholaminergic cells resulted in severe and progressive phenotypic abnormalities mainly characterized by cardiac dysfunction, hypoactivity, and hypothermia, which explain development of autonomic neuropathy. Our IMCT strategy is useful for elucidating the involvement of different neuronal types and their interactions in the development and symptom of autonomic disorders.

Animals↗

Structure and expression of proteolipid protein in the peripheral nervous system.

Proteolipid protein (PLP), the major myelin protein in the central nervous system (CNS), is also made by Schwann cells (SC) in the peripheral nervous system (PNS) but is not incorporated into the SC myelin sheath. We analyzed several PLP cDNA clones isolated from a rat sciatic nerve cDNA library and found that their coding sequences were identical to PLP cDNAs previously isolated from the CNS. In addition, we have discovered an unusual form of PLP message, present in both brain and sciatic nerve RNA, that is likely formed by alternative splicing within the 3' untranslated region of the primary PLP transcript. The absence of PLP from the SC myelin sheath thus cannot be explained by an alteration in its amino acid sequence. Steady-state levels of PLP mRNA in SC cultures treated with the cAMP analogue dibutyryl cAMP (dBcAMP) were not increased, whereas dBcAMP increased steady-state levels of mRNA encoding the major myelin protein, P0. We have also shown that expression of PLP, unlike that of P0, is regulated in SC in vitro at a posttranscriptional level. Finally, the steady-state levels of P0 mRNA are much more dramatically reduced than those of PLP mRNA during Wallerian degeneration of the peripheral nerve. Thus PLP expression in the PNS is probably controlled by different molecular mechanisms from P0, and may not be part of the coordinate program of myelin gene expression. In contrast to its expression in the PNS, transcription of PLP in the CNS is coordinately regulated along with the other myelin protein genes, suggesting there may be differences in the cis-acting elements and transacting factors involved in the regulation of PLP transcription in SC and oligodendrocytes (OC). Consistent with this notion, we have found that most PLP transcripts are initiated at the more proximal of two start sites in the PNS, while in the CNS proportionally more PLP transcripts are initiated from the distal start site. We propose that the proximal site, utilized predominantly in SC, is responsible for maintenance expression of PLP and is not inducible, while the distal site is responsible for the rapid, inducible increase of PLP message during brain development.

Animals↗

Sequence of morphological alterations in the nervous system of metachromatic leucodystrophy. Light- and electronmicroscopic observations in the central and peripheral nervous system in a prenatally diagnosed foetus of 22 weeks.

Light and electronmicroscopic findings are reported in a case of metachromatic leukodystrophy diagnosed prenatally who died after iatrogenic abortion during the 23th week of gestation. The brain of this foetus was not yet myelinated while the spinal cord showed early, and the peripheral nerves advanced myelination. The onset and the degree of myelination were similar as in a normal foetus of the same age. Ultrastructurally there was evidence of sulphatide storage before the beginning of myelination. During myelination lysosomal storage material, staining metachromatically in acid cresyl violet preparations, appeared in oligodendrocytes and Schwann cells. Besides sulphatide storage material, prominent amounts of neutral lipids were found in oligodendrocytes. Myelin breakdown was encountered very seldom.

Central Nervous System↗