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Transcriptional mRNA of bone morphogenetic proteins 2, 3, 4, and 5 in trigeminal nerve, benign and malignant peripheral nerve sheath tumors.

Bone morphogenetic proteins (BMPs) have been shown to play an important role in cell growth and differentiation. BMPs, a rapidly expanding family closely related to transforming growth factor-beta (TGF-beta) superfamily, have been proven recently to possess a regulatory role and neurotrophic capacity in neurogenesis. The aim of the present study is to reveal the relationship among BMPs, peripheral nerve and neoplastic lesions of nerve sheath tumors. The mRNA transcriptions of BMP 2, 3, 4 and 5 in 12 cases of schwannoma, four cases of malignant schwannoma and three cases of trigeminal neuralgia were detected using an in situ hybridization technique. Our results demonstrated that the myelin sheaths of schwann cell from the peripheral neuroectomy of trigeminal neuralgia were positively expressing mRNA of BMP-2, 3, 4 and 5. However, the nerve fibers of trigeminal nerve showed only BMP-2 positive staining. All of the neoplastic lesions of nerve sheath showed a consistent but variant expression of BMP-2, 3, 4, and 5. Except for the BMP-4 mRNA, the expression signals of BMP-2, 3 and 5 mRNA in malignant schwannoma were relatively lower than in benign lesions. On the basis of the findings, we concluded that selected members of BMPs existed in the peripheral nerves and might contribute to the health maintenance, proliferation, regeneration and neoplastic transformation of the peripheral nerve system. Moreover, the effects of BMP-2, 3, 4 and 5 on peripheral nerve system and its neoplastic transformation might be widespread, diverse and antagonistic.

Adult↗

[Mechanisms which control the peripheral nerve excitability].

Peripheral nerve excitability is currently tested via the strength/duration curves, and by measuring the minimal intensity level (rheobase) of an efficient stimulation, and the minimal duration (chronaxy) for a stimulus equal to two times the minimal threshold. New "threshold tracking techniques" were recently described (Bostock et al., 1991), which afford an automatic evaluation of nerve excitabilty. These methods investigate the mechanisms responsible for the membrane potential: passive ionic currents, activity of ionic pumps like the Na-K-ATPase; and the dynamic behaviour of large conductance sodium, potassium, and calcium channels, responsible for the generation and conduction of action potentials. Results obtained must however be evaluated taking into account the following items: stimulation is delivered through the skin and subcutaneous tissue; a nerve trunk is explored, and not a single fiber; most often the response is recorded over a muscle, hence through neuromuscular synapses.

Axons↗

Upper extremity peripheral nerve assessment.

Peripheral nerve injuries are an unfortunate and serious complication of trauma and medical interventions. By anticipating which patients are more likely to experience such problems, emergency care personnel can carefully assess and document a person's nerve function. This should be done on contact with the patient, preceding and after any interventions that may aggravate the problem. This allows the nurse to provide a baseline of information that can be used to initiate immediate care if necessary or to document the onset of problems.

Arm Injuries↗

Peripheral nerve elongation by laser Doppler flowmetry-monitored expansion: an experimental basis for future application in the management of peripheral nerve defects.

Nerve grafting often fails to achieve optimal functional results and is always associated with donor-site morbidity. Peripheral nerve elongation by the use of a tissue expander may provide a useful adjunct in the management of segmental nerve loss. In the present study, rabbit sciatic nerve (n = 40) was elongated by expansion while nerve blood flow was monitored by laser Doppler flowmetry. Elongation was possible up to 40 percent with preservation of clinical nerve function. Nerve conduction velocity of the expanded nerves decreased in a linear relation to elongation. The reduction in nerve conduction velocity may be secondary to the observed widening of the nodes of Ranvier and altered membrane properties after remyelination. Demyelination and remyelination of whole internodes and axonal degeneration occurred only sporadically. Thus laser Doppler flowmetry-monitored expansion provides a safe method for elongation of intact rabbit sciatic nerve while nerve function and axonal continuity are preserved. Further studies are needed before clinical use is considered. This technique may represent a favorable alternative to nerve grafting for the treatment of peripheral nerve defects.

Action Potentials↗

The extent of axonal exposure and axo-axonal apposition in the non-myelinated nerve fibres of peripheral nerve trunks and their dependence on buffer molarity.

Nineteen rats were perfused intracardially with a 2% glutaraldehyde solution in cacodylate buffers adjusted in molarity from 0 to 0 . 4 m. Ultrathin sections of the inferior alveolar nerve were photographed in the electron microscopy. From prints of unmyelinated nerve fibres, the following measurements were made: axon circumference, the proportion of axons which were incompletely covered by the Schwann cell and the extent of this 'exposure', the proportion of axons which were apparently in contact with each other and the extent of this contact and the axon-Schwann cell gap. Axonal size and the spacing between the axon and Schwann cell were not related to buffer molarity. Very few (0-3 . 4%) of the axons were in contact and the degree of contact was unrelated to buffer concentration. Of the axons, 10-34% were partially unsheathed, the proportion being linearly related to the molarity of the buffer vehicle. It is concluded that axo-axonal apposition is an insignificant feature in this nerve trunk, but that axonal exposure is a constant finding although its extent is dependent on the conditions of fixation.

Animals↗

High performance liquid chromatography of integral glycoproteins of peripheral nerve myelin.

Peripheral nerve myelin contains a large quantity of integral glycoproteins, such as PO and PASII protein. The present paper reports a fast and sensitive method for separation of these glycoproteins. High performance liquid chromatography (HPLC) with TSK-GEL 3000 SW column in the presence of sodium dodecyl sulfate (SDS) or lithium dodecyl sulfate (LDS) was used. Whereas the separation of PO and PASII was inadequate with low concentrations of the detergent, better separation profiles were obtained with high concentrations (1-2%) of the detergent in 0.1 M phosphate buffer. The two glycoproteins were able to be purified by rechromatography. High concentration of the detergent presumably diminished interaction between these glycoproteins. LSD-phosphate, SDS-lithium citrate or SDS-Tris buffer as an eluent was also compared with SDS-phosphate system. This method will be applicable to the detection and purification of proteins from myelin or other organelles.

Animals↗

A tissue-engineered conduit for peripheral nerve repair.

BACKGROUND: Peripheral nerve repair using autograft material has several shortcomings, including donor site morbidity, inadequate return of function, and aberrant regeneration. Recently, peripheral nerve research has focused on the generation of synthetic nerve guidance conduits that might overcome these phenomena to improve regeneration. In our laboratory, we use the unique chemical and physical properties of synthetic polymers in conjunction with the biological properties of Schwann cells to create a superior prosthesis for the repair of multiply branched peripheral nerves, such as the facial nerve. OBJECTIVES: To create a polymeric facial nerve analog approximating the fascicular architecture of the extratemporal facial nerve, to introduce a population of Schwann cells into the analog, and to implant the prosthesis into an animal model for assessment of regeneration. RESULTS: Tubes of poly-L-lactic acid (molecular weight, 100000) or polylactic-co-glycolic acid copolymer were formed using a dip-molding technique. They were created containing 1, 2, 4, or 5 sublumina, or "fascicular analogs." Populations of Schwann cells were isolated, expanded in culture, and plated onto these polymer films, where they demonstrated excellent adherence to the polymer surfaces. Regeneration was demonstrated through several constructs. CONCLUSIONS: A tubular nerve guidance conduit possessing the macroarchitecture of a polyfascicular peripheral nerve was created. The establishment of resident Schwann cells onto poly-L-lactic acid and polylactic-co-glycolic acid surfaces was demonstrated, and the feasibility of in vivo regeneration through the conduit was shown. It is hypothesized that these tissue-engineered devices, composed of widely used biocompatible, biodegradable polymer materials and adherent Schwann cells, will be useful in promoting both more robust and more precisely directed peripheral nerve regeneration.

Animals↗

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↗

Transcriptional mRNA of BMP-2, 3, 4 and 5 in trigeminal nerve, benign and malignant peripheral nerve sheath tumors.

The aim of our study was to document whether relationships existed among bone morphogenetic proteins (BMPs), peripheral nerve and neoplastic lesions of nerve sheath tumors. The mRNA transcriptions of BMP-2, 3, 4 and 5 in 10 cases of schwannoma, three cases of malignant schwannoma and two cases of trigeminal neuralgia were detected using an in situ hybridization technique. Our results demonstrated that the myelin sheaths of Schwann cell from the peripheral neuroectomy of trigeminal neuralgia positively expressed mRNA of BMP-2, 3, 4, and 5. The most interesting finding was that the nerve fibers of trigeminal nerve showed only BMP-2 positive staining. All of the neoplastic lesions of nerve sheath showed a consistent but variant expression of BMP-2, 3, 4, and 5. The expression signals of BMP-2, 3, 5 mRNA in malignant schwannoma were relatively lower than in benign lesions except for the expression of BMP-4 mRNA. Our results indicated that selected members of BMPs were expressed in the peripheral nerves that might contribute to the health maintenance, proliferation, regeneration and neoplastic transformation of the peripheral nerve system. Furthermore, the effects of BMP-2, 3, 4 and 5 on peripheral nervous system during neoplastic transformation might be widespread, diverse and antagonistic.

Adult↗

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↗

Cytokines and peripheral nerve disorders.

Peripheral nerve production of cytokines originates from resident and recruited macrophages, lymphocytes, mastocytes, Schwann cells, and probably neurons. Cytokines are involved in nerve lesions and repair. Tumor necrosis factor-alpha (TNF-alpha) injected into nerve induces Wallerian degeneration, whereas, interleukin-1 (IL-1) production promotes detersion by scavenger macrophages, and synthesis of neurotrophic factors (nerve growth factor-NGF- and leukemia inhibitory factor-LIF). After experimental axotomy, other neurotrophic factors, including IL-6, LIF and transforming growth factor-beta 1 (TGF-beta 1), are overexpressed in nerve and promote axonal growth until axon/Schwann cell contact. Proinflammatory cytokines are instrumental in the course of inflammatory demyelinating neuropathies. They increase vascular permeability and blood nerve barrier breakdown (TNF-alpha, vascular endothelial growth factor/ vascular permeability factor-VEGF/VPF), favor transmigration of leukocytes into nerve, induce activation and proliferation of lymphocytes (IL-1, IL-2) and macrophages (gamma-interferon-IFN-gamma), and have a direct myelinotoxic activity (TNF-alpha and TNF-beta). In addition, downregulation of the immunosuppressive cytokine TGF-beta 1 may favor the nerve inflammatory reactions.

Animals↗

Peripheral nerve (PNS) spinal cord anastomoses bridging spinal cord transection--enhancement of central neurons (CNS) axonal regeneration.

These studies involve 76 mature female dogs at 5.5 to 16 kg. The enhancement of axonal regeneration in the spinal cord transection is shown by implanting intercostal nerve with origin cephalic to spinal cord transection. The nerve is implanted in the distal isolated spinal cord near the transection site. The intercostal nerve peripheral portion is anchored in the distal spinal cord using a plasma clot suture. Regeneration of CNS axons and PNS axons in the spinal cord transection demands care, rehabilitation, and maintenance of normal body functions. After a period of two years repair and rehabilitation "reflex" standing and walking developed in 26 mature female dogs. Surgical section of the implanted nerve resulted in loss of standing and reflex walking and return to a paraplegic condition in 12 dogs. Stimulation of the motor cortex and implanted intercostal nerve resulted in movements of the hind limbs of the standing and reflex walking dogs all having cord transection and intercostal nerve anastomoses.

Anastomosis, Surgical↗