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At least 19 recordsLinked to original sources

Characterization of the sprouting response of axon-like processes from retinal ganglion cells after axotomy in adult hamsters: a model using intravitreal implantation of a peripheral nerve.

Peripheral nerves provide a favourable environment for damaged CNS axons to sprout and regenerate. It has also been demonstrated that retinal ganglion cells respond to a peripheral nerve segment grafted to the retina by emitting axon-like processes from the somatodendritic compartment into the graft. The factors influencing the pattern of sprouting of axotomized retinal ganglion cells were explored in this study by implanting a short segment of peripheral nerve, which did not come into contact with the retina, into the vitreous body of an eye whose optic nerve was concurrently crushed. Silver staining was used to assess the morphology of the retinal ganglion cells which underwent sprouting. Some retinal ganglion cells were induced to sprout axon-like processes; these emerged primarily from dendrites and less frequently from the soma or intraretinal axon. Implantation of a nonviable graft (freeze-thawed) elicited only minimal sprouting. These results suggest that diffusible factors secreted by cells in the graft are a possible stimulus to sprouting in axotomized retinal ganglion cells. Examination of the pattern of dendritic sprouting indicates that sprouting was most intense (in terms of number of sprouts per cell) at early times post-axotomy. Moreover, a differential pattern of development of sprouts arising from individual primary dendrites of the same cell was observed; sprouts tend to arise from all primary dendrites initially but as the post-axotomy time increased, retraction of sprouts from some primary dendrites occurred. Concomitant with this retraction, however, there was an increase in the number of sprouts on those primary dendrites which were still in the active phase of sprouting. Selective stabilization of sprouts by extrinsic factors may account for this phenomenon. Changes in the area and outline (irregularity) of the somata of retinal ganglion cells with sprouts from two weeks to two months after optic nerve crush could be correlated temporally with the intensity of sprouting from the dendritic tree, suggesting that during sprouting, intrinsic mechanisms coordinate the responses of different cellular compartments. In contrast to extensive ectopic sprouting of axotomized retinal ganglion cells in the presence of an intravitreal graft, when a long peripheral nerve segment is grafted to the cut optic nerve, there is extensive axonal regeneration into the graft from retinal ganglion cells, most of which did not exhibit ectopic sprouting. Thus, a hierarchy of sprouting sites within a neuron seems to exist, with the damaged axonal tip being the most favoured site, followed by the dendrites, and then the intraretinal axon.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Lesion-induced changes in the production of newly synthesized and secreted apo-E and other molecules are independent of the concomitant recruitment of blood-borne macrophages into injured peripheral nerves.

Peripheral nerve injury produces Wallerian degeneration characterized by a change in the composition of resident nonneuronal cells: macrophages are recruited from the circulation to join Schwann, fibroblast, and endothelial cells. At the same time, the nonneuronal cell population exhibits, as a whole, alterations in synthesis and secretion of diffusible molecules, some of which are instrumental in nerve repair mechanisms. In this study, we determined whether changes in the production of secreted molecules depend on the concomitant modification in cell composition. Therefore, we studied the secretion of newly synthesized molecules by defined cell populations of intact nerves, intact nerve explants undergoing in vitro axonal degeneration, in vivo degenerating nerves, and recruited cells. Nerves were incubated in serum-free, [35S]methionine-containing media. Secreted, radioactively labeled proteins were precipitated from the medium and analyzed by gel electrophoresis. Reduced production of 43-, 46-, and 48-kDa proteins and increased production of 33-34-, 37-, 49-, 59-, and 67-kDa proteins were detected in in situ degenerating nerves. High-density ultracentrifugation and immunoblot analysis revealed that the 33-34-kDa protein is apolipoprotein-E (apo-E). Similar alterations in the production of these molecules were detected in intact nerve explants from which blood-borne cells were excluded. Apo-E, 37-, 49-, 59-, and 67-kDa proteins were also produced in frozen nerves that lacked the intact nerve nonneuronal cell population. Instead, these preparations contained blood-borne cells, primarily macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)

Ammonium Chloride

Infection of armadillos with Mycobacterium leprae. Ultrastructural studies of peripheral nerve.

Peripheral nerves of armadillos were studied 16 to 30 months after intradermal or intravenous inoculation with Mycobacterium leprae. Numerous bacilli were found within macrophages, Schwann cells, and perineurial cells; endothelial cells, pericytes and fibroblasts were involved as well. The bacilli were characteristically contained in membrane-limited vacuoles that were interpreted as being phagosomes. Some of the phagosomes contained granular, membranous, and vesicular debris considered to be bacillary degradation products, suggesting that lysosomal activity was present within the phagosomes. Multivesicular bodies, a few of which contained bacilli, were abundant in macrophages and perineurial cells. An unusual proliferation of irregular tubulovesicular profiles was noted, especially in Schwann and perineurial cell cytoplasm, surrounding and within phagosomes containing bacilli. The pattern of cellular involvement of neural structures with M leprae was similar to that observed in lepromatous leprous neuritis in humans.

Animals

Incorporation of glycoproteins into peripheral nerve myelin.

Peripheral nerve myelin contains a dominant low molecular weight glycoprotein called Po. To study the metabolism of this glycoprotein, tritiated fucose was injected into the peripheral nerves of adult mice and developing rats, and the temporal distribution of label was examined by autoradiography and gel electrophoresis. Mice and rat pups, injected with fucose, were sacrificed from 1 h to 98 days later. Series of autoradiographs were prepared. At the shortest labeling periods, newly formed product was confined to juxtanuclear Schwann cell cytoplasm, in association with regions rich in Golgi apparatus. After longer labeling periods, silver grain levels in Schwann cell cytoplasm decreased; concomitantly, there was an increase of silver grains associated with myelin. In adult animals, label associated with myelin was concentrated over outer layers of thickly myelinated fibers. Even at the longest time intervals examined (72 and 98 days), this distribution of label was largely retained. In contrast, in developing animals, label became associated with inner layers of the thicker sheaths. At no time was label observed over axons. Gel electrophoresis revealed that tritiated fucose was a suitable precursor for the faster migrating peripheral nerve glycoprotein(s). At all times examined, there was a single major peak of radioactivity that co-migrated on sodium dodecyl sulfate (SDS) acrylamide gels with the Po protein. Sometimes, a faster migrating shoulder of radioactivity was noted. With increased labeling periods, there was an enrichment of radioactivity associated with Po, indicative of a relatively slow turnover rate.

Animals

Recent developments in peripheral nerve surgery. Management of open traumatic peripheral nerve lesions.

The modern technique of operative repair of traumatic nerve interruption is discussed. The results of microsurgical repair have proved to be superior to those of conventional methods. Besides the anatomy and the operative technique, the indications and timing for surgical intervention are discussed. Reference to the literature and the authors' own experience show that delayed primary repair is the method of choice.

Humans

Postnatal change in lipid composition and nerve conduction of peripheral nerves of young rhesus monkeys.

Body weight, motor and sensory nerve conduction velocities of fore and hind limbs, and lipid composition were measured sequentially in peripheral nerves of 15 rhesus monkeys. Initially measurements were made with monkeys six to eight months of age. There were significant increases in body weight, motor, and sensory nerve conduction and myelin marker lipids over a five months period, but no change was observed in free fatty acids, triglycerides, and esterified cholesterol. These results indicate that myelination continues at least for 11 to 13 months of postnatal age in rhesus monkeys.

Aging

Subperineurial space of the sural nerve in various peripheral nerve diseases.

The size of the subperineurial space of the sural nerve has been evaluated quantitatively in 69 cases of various peripheral nerve diseases and in controls. A significant increase was found in beriberi neuropathy (6 cases) and idiopathic polyradiculoneuropathy (9 cases) as compared with the control (8 cases). On electron microscopy a few macrophages, fibroblast processes, collagen fibrils with a diameter of 50 nm, microfibrils with a diameter of 8 nm, and amorphous material were observed in both the enlarged subperineural space and the endoneurial intercellular space. They were less frequently observed in controls. No significant correlation was found between the size of subperineurial space and the density of myelinated fibers.

Adolescent

Nerve grafting in the repair of complicated peripheral nerve trauma.

Peripheral nerve trauma has been a challenge to surgeons, with significant advances in the surgery of repair occurring in major wars. The standard method of treatment involving wide mobilization and end-to-end suture to close traumatic gaps in peripheral nerves has not produced consistently acceptable results, particularly with large gaps. However, with the recent development of microsurgical techniques and instrumentation, the method of interfascicular nerve grafting has been applied to selected patients with trauma problems of the peripheral nerve, by resecting and autogenous nerve grafting at staggered levels to distribute scar formation, followed by plaster immobilization for 3 weeks. Ten patients are reported, with motor nerve recovery ranging from M2 to M4 and sensory recovery, S2-S4 (See Table I), based on Seddon's classification (11).

Adolescent

Effect of parathyroid hormone and uremia on peripheral nerve calcium and motor nerve conduction velocity.

Peripheral neuropathy is not an uncommon complication of chronic uremia. Because parathyroid hormone, by raising brain calcium, is partly responsible for central nervous system aberrations in uremia, we studied the relative role of uremia, per se, and(or) parathyroid hormone on peripheral nerve calcium and motor nerve conduction velocity (MNCV). Studies were made in six groups of six dogs each, as follows: (a) normal dogs, (b) thyroparathyroidectomized (T-PTX) animals, (c) dogs with 3 days of uremia produced by bilateral nephrectomy, (d) T-PTX before the induction of acute renal failure, (e) normal dogs receiving 100 U/day of parathyroid extract (PTE) for 3 days, and (f) normal animals receiving 3 days of PTE followed by 5 days without PTE. Calcium content in peripheral nerve (expressed as milligram per kilogram of dry weight) was 252+/-5 (SE) in normal animals and 262+/-4 in T-PTX dogs. It was significantly (P < 0.01) higher in dogs with acute renal failure and intact parathyroid glands (410+/-12) and in normal animals receiving PTE (362+/-7). T-PTX, before acute renal failure, prevented the rise in peripheral nerve calcium (262+/-4) and PTE withdrawal was followed by the return of peripheral nerve calcium to normal (261+/-3). The increments in peripheral nerve calcium were associated with slowing of MNCV. It decreased significantly from 70+/-4 to 43+/-1 m/s after 3 days of acute uremia in dogs with intact parathyroid glands and T-PTX before acute renal failure prevented the fall in MNCV. Administration of PTE to normal animals reduced MNCV from 63+/-3 to 35+/-3 m/s and the withdrawal of PTE restored MNCV to normal (73+/-2 m/s). The results show that (a) excess parathyroid hormone increases peripheral nerve calcium and slows MNCV, (b) T-PTX, previously performed, prevents these changes in acute uremia, and (c) the withdrawal of PTE administration is followed by a reversal of the abnormalities.

Animals

Saturable transport of manganese(II) across blood-nerve barrier of rat peripheral nerve.

To determine whether the blood-nerve barrier of the rat peripheral nerve transports manganese(II) (Mn) by a saturable mechanism similar to that found at the blood-brain barrier, we measured the uptake of 54Mn from blood into desheathed sciatic nerve and into cerebral cortex of awake rats at different plasma concentrations of unlabeled Mn using an intravenous infusion technique. The unidirectional influx (Jin) of Mn into sciatic nerve was facilitated and saturable, when steady-state plasma Mn ranged from 4 to 4,312 ng/ml (0.073-78.4 microM), as was the unidirectional influx of Mn into the cerebral cortex. Michaelis-Menten constants (Km and Vmax) and the passive diffusion constant (Kd), determined by nonlinear least squares, were as follows: for the blood-nerve barrier (sciatic nerve) Km = 4.7 microM, Vmax = 0.56 x 10(-3) nmol.s-1.g wet wt-1, and Kd = 6.3 x 10(-6) ml.s-1.g wet wt-1; for the blood-brain barrier (cerebral cortex) Km = 1.0 microM, Vmax = 0.40 x 10(-3) nmol.s-1.g wet wt-1, and Kd = 0.3 x 10(-6) ml.s-1.g wet wt-1. The results demonstrate facilitated concentration-dependent mechanisms of transport of Mn at the blood-nerve and blood-brain barriers.

Animals

Innervator NS 252, a new, constant current and programmable peripheral nerve stimulator.

A peripheral nerve stimulator should be able to deliver a constant current to provide supramaximal nerve stimulation even under conditions of increasing resistance. We tested a new programmable peripheral nerve stimulator, the Innervator NS 252. It was able to maintain a constant current of 80 mA up to a resistance of 3.9 kohm. The pulse appearance was correct and there were only small variations in stimulation time intervals. The different type of double burst stimulation and the lack of synchronization with the previously applied stimulus pattern may be regarded as slight disadvantages.

Electric Impedance

[Tumors of nerve sheaths of the peripheral nerves].

Objectives of this paper are the analysis of the confidence in the complementary investigation for the differential diagnostic between schwannoma and neurofibroma, and the retrospective evaluation of the therapy based on the consequent follow-up. The study has been conducted on 36 patients, most of them observed by University Clinic of Navarra (Pamplona), and the others by N. Picardi, all with preoperative diagnosis of schwannoma and neurofibroma, localized in 13 cases in peripheral nerves. Diagnostic iter, pathologic definition, therapy and evolution has been evaluated for all of them. In conclusion we feel that this pathology has to be suspected every time we find a tumor with neurologic symptomatology and that surgical indication of exeresis is the most correct in the majority of cases; moreover imaging investigations is rather useful, but if any doubt occurs we must proceed to biopsy or directly to exeresis of the tumor. Our experience shows that schwannoma, thanks to its anatomic patterns, can be treated less radically toward the nerve continuity than neurofibroma, and that the technique of nerve graft could be a useful alternative in this kind of surgery.

Adolescent

Laminin B1 and collagen type IV gene expression in transected peripheral nerve: reinnervation compared to denervation.

The expression of B1 laminin and type IV collagen was followed in the microsurgically isolated endoneurium of transected rat sciatic nerves from 3 days until 8 weeks. Northern hybridizations revealed that after nerve transection the proximal stumps of denervated, as well as freely regenerating, nerves showed a markedly increased expression of laminin and type IV collagen which lasted from 3 days up to 8 weeks. In the distal stumps, close to the site of transection (2-7 mm), the expression of laminin, and to a certain extent that of type IV collagen, seemed to be enhanced if free axonal reinnervation was allowed. Further distally (10-15 mm), the patterns of B1 laminin and type IV collagen expression were similar in both experimental groups, so that an increased expression was noticed during the first 2 weeks. The present results suggest that laminin and type IV collagen gene expression is markedly different in different parts of transected rat sciatic nerve. During peripheral nerve regeneration, there is a long-lasting basement membrane gene expression in the proximal stump. In the distal part of the transected nerve, the axonal reinnervation possibly up-regulates, but is not essential for, the expression of B1 laminin and type IV collagen.

Animals

Syngeneic Schwann cells derived from adult nerves seeded in semipermeable guidance channels enhance peripheral nerve regeneration.

At present, clinical strategies to repair injured peripheral nerve concentrate on efforts to attain primary suture of the cut nerve ends. If this is not possible, autografts are used to unite the separated nerve segments. Both strategies are based on the recognition that the Schwann cells resident in the peripheral nerve trunk play a crucial role in the regenerative process. Neither strategy may be feasible, however, in extensive or multiple injuries because the amount of autograft material is limited, and allografts are subject to immune rejection. Artificially produced nerve bridges constructed of autologous Schwann cells seeded in guidance channels could be used to overcome these limitations. In the present experiments, the potential of Schwann cells derived from adult nerves and seeded in permselective guidance channels to promote neurite regeneration across an 8 mm nerve gap was evaluated in transected rat sciatic nerves. Immunological sequalae were evaluated by comparing Schwann cells from syngeneic and heterologous rat strains. Schwann cells from either adult outbred (Sprague-Dawley, CD) rats or inbred (Fisher, F) rats were suspended in a Matrigel solution at a density of 80 x 10(6) cells/ml (CD) or 40, 80, or 120 x 10(6) cells/ml (F-40, F-80, and F-120 channels, respectively). Channels containing Schwann cells were compared to sciatic nerve autografts, empty channels, or channels filled with Matrigel alone. One day after seeding permselective synthetic guidance channels with a Schwann cell suspension, a central cable of Schwann cells oriented along the axis of the tube was formed due to syneresis of the hydrogel. By 3 weeks postimplantation, regenerating axons had grown into all channels and autografts. Sciatic nerve autografts supported extensive regeneration, containing 4-5 x 10(4) myelinated axons at the graft midpoint. The ability of channels containing syngeneic Schwann cells to foster regeneration was dependent on the Schwann cell seeding density. At the channel's midpoint, the myelinated axon population in F-120 tubes was intermediate between that in sciatic nerve autografts and F-80 channels, and was significantly higher than in F-40 or control channels. The nerve cable in Schwann cell-containing tubes consisted of larger, more organotypic fascicles than acellular control channels. In contrast, heterologous (CD) Schwann cells elicited a strong immune reaction that impeded nerve regeneration. The present study shows that cultured adult syngeneic Schwann cells seeded in permselective synthetic guidance channels support extensive peripheral nerve regeneration.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals