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Motor nerve conduction velocity and nerve fibre diameter in experimental protein deprivation. Studies on rat peripheral nerve during development.

Motor nerve conduction velocity (MCV) and nerve fibre calibre spectra of peripheral nerves were determined at different ages, during development in normal and protein-deprived rats. The protein deprivation was achieved by feeding female rats a protein deficient diet. Compared to control rats which were given a balanced diet, given ad lib from 2 weeks before conception and onwards. After weaning, the offspring were fed the same protein-deficient diet, the protein-deprived rats showed considerably reduced body weights but moderately reduced values of albumin and total protein in serum at 6 and 15 weeks of age. Although essentially the same, the mean nerve fibre diameter of the studied dorsal tail nerve was slightly larger in the protein-deprived rats at 6 weeks of age than in controls, while the inverse relationship was found at 15 weeks of age. The increase of MCV in normal and protein-deprived rats followed essentially the same curve during the period from 5-30 weeks of age. The results indicate that the MCV and nerve fibre diameter during development are correlated to chronological age and not to body size, although protein deprivation may, to a minor extent, influence nerve fibre calibre growth.

Animals↗

A contemporary overview of peripheral nerve research from the Cleveland Clinic microsurgery laboratory.

Despite our better understanding of the pathophysiology of peripheral nervous system and advancements in microsurgical repair techniques, peripheral nerve injuries are still considered as a reconstructive challenge for all surgeons. For achieving a better nerve regeneration and better end organ reinnervation, advanced microsurgical manipulations are parallel with molecular biological discoveries. The field of peripheral nerve research is still developing and includes more sophisticated approach at the basic science level. In our Microsurgery Research Laboratory we have been working on different nerve repair techniques, including sleeve neurorrhaphy, sleeve grafts, single and polyfascicular nerve grafting techniques and studies on nerves in diabetic rats, in addition to the roles of different growth factors and pharmacological agents on peripheral nerve regeneration. New approaches for filling nerve gaps with nerve allografts and tolerance inducing strategies with their effect on nerve regeneration are included into our research armamentarium. In this overview we will summarize our 15-year experience in peripheral nerve research.

Animals↗

Paradoxical clinical consequences of peripheral nerve injury: conduction of nerve impulses does not occur across the site of injury immediately following nerve division and repair.

The occasional apparent clinical phenomenon of the immediate although transient return of peripheral nerve function after nerve division and primary repair has been previously reported. Electrophysiological findings from the sciatic nerve of the rabbit have been previously presented in support of the concept of the transmission of nerve impulses across a freshly divided and repaired peripheral nerve for a short period until the onset of Wallerian degeneration. This paper presents experimental evidence to show that these findings were misinterpreted and that a compound action potential cannot be transmitted across a surgically repaired division in a peripheral nerve. Observations from previous experimental research in neurophysiology are discussed which confirm these conclusions. The claim that failure to diagnose a peripheral nerve injury at presentation can be explained in some circumstances by "jump transmission" is not based on sound evidence and the concept of "jump transmission" cannot be accepted as a defence for clinicians who fail to diagnose a peripheral nerve injury.

Action Potentials↗

Surface mapping of peripheral nerves in children with a nerve stimulator.

Defining anatomical landmarks may be difficult in the growing child. With the aid of a peripheral nerve stimulator, the path of many superficial peripheral nerves can be 'mapped' prior to skin penetration by stimulating the motor component of the peripheral nerve percutaneously with a 2-3.5 mA output. The required current will vary and is dependent upon the depth of the nerve and the moistness of the overlying skin. This 'nerve mapping technique' has proved particularly useful for brachial plexus, axillary, ulna and median nerve blocks in the upper limb and femoral and popliteal nerve blocks in the lower limb. It is a useful teaching tool and improves the success rate of peripheral nerve blocks in children of all ages.

Child↗

Novel technique for peripheral nerve reconstruction in the absence of an artificial conduit.

The purpose of this study is to promote nerve regeneration across a peripheral nerve gap, using a biologic, tissue-engineered nerve (TEN), containing a high density of viable Schwann cells (SCs) in the absence of supportive foreign materials and a tubular system. Isolated SCs from adult rat sciatic nerve were seeded onto biodegradable constructs and implanted into the backs of nude mice to create TENs. Six weeks later, the constructs were harvested, implanted into surgically created sciatic nerve gaps in rats without supportive artificial conduits and compared with both an autograft group and a silicone conduit group using SCs. Two months later, functional assessment was evaluated by walking track analysis and the implanted lesions were imaged by transmission electron microscopy. The axonal number and sciatic function index of the TEN were significantly higher than those of the silicone group and achieved a comparable level to the autograft group. The results indicate that the large number of SCs within their own extracellular matrix appeared sufficient to enable neuronal growth across a nerve gap in the absence of an artificial conduit and that these circumstances may have a positive effect on the supplement of growth factors from the surrounding tissues of implanted TEN.

Absorbable Implants↗

The anatomy and physiology of the peripheral nerve.

The anatomy and physiology of nerve tissue and the peripheral nerve are reviewed. The importance of the anatomical and physiological understanding of nerve tissue in the surgical repair of nerve injuries is discussed. This includes an outline of the light and electron microscopic histology of nerve and a short review of axoplasmic flow. In addition, the nerve coverings, endoneurium, perineurium, and epineurium, are described. The relationship of these coverings to the surgical therapy of nerve injuries is outlined. By maintaining, where possible, nerve fascicle continuity and by restoring, where practical, the normal physiology of distorted but not disrupted fascicles, with the use of careful internal neurolysis, optimal clinical return of function should be achieved.

Animals↗

Peripheral nerve catheterization in the management of terminal cancer pain.

BACKGROUND AND OBJECTIVES: Peripheral nerve catheterization techniques were used in two patients with severe pain associated with the terminal stages of metastatic cancer. The first patient had severe upper limb pain and lymphedema secondary to breast carcinoma, and the second patient had an acutely ischemic leg secondary to pelvic obstruction from an ovarian tumor. The goal of treatment was to relieve the pain, which was resistant to opioid drugs, and to optimize the quality of life that remained, estimated to be only a few weeks. METHODS: The first patient received a continuous brachial plexus block via an epidural catheter, introduced by means of a Tuohy needle and a peripheral nerve stimulator to locate the plexus accurately. The second patient required catheterization of both the sciatic and femoral nerves, again with a peripheral nerve stimulator used to locate the nerves prior to inserting the catheters. RESULTS: Analgesia was established with a bolus of local anesthetic and maintained with a continuous infusion of local anesthetic in the first patient. For the second patient, fentanyl was added to the local anesthetic, as it had been shown to improve analgesia in the lower limb in previous work. In the first patient, the analgesia allowed active treatment of the lymphedema and mobilization of the limb, and she remained pain free until her death 2 weeks later. In the second patient, the infusions controlled the pain both before and after surgical amputation of the limb, until the stump was well healed. CONCLUSIONS: Peripheral nerve catheterization proved beneficial in two patients who presented with difficult pain management problems and should be more widely considered for the relief of severe cancer-related pain in both the upper and lower limbs.

Aged↗

The neuropathy of plasma cell dyscrasia: binding of IgM M-proteins to peripheral nerve glycolipids.

In some patients with neuropathy and plasma cell dyscrasia, the M-proteins bind to peripheral nerves. Binding of M-proteins to peripheral nerve glycolipids was examined by immunostaining after thin-layer chromatography. The IgM from 16 patients with anti-MAG M-proteins bound to the same two glycolipid bands in peripheral nerve. The IgM that bound to the glycolipids had the same idiotype as the anti-MAG M-protein, indicating that it was the M-protein that bound to both glycolipids. The reactive glycolipids did not contain sialic acid and were not gangliosides. No immunostaining of peripheral nerve glycolipids was observed with IgM from patients with neuropathy and IgM M-proteins that did not bind to MAG, and the anti-MAG antibodies did not bind to brain glycolipids. Anti-MAG M-proteins probably bind to the same or closely related carbohydrate determinants that are shared by a number of glycoproteins and glycolipids of peripheral nerve.

Antibodies↗

The influence of dose of microspheres on nerve blood flow, electrophysiology, and fiber degeneration of rat peripheral nerve.

Microsphere embolization of peripheral nerve results in a variable degree of ischemic fiber degeneration. To enhance the utility of the model, we evaluated the relationship between dose of microspheres to the supplying arteries of the sciatic-tibial nerve to nerve blood flow (NBF), electrophysiology, morphology, and behavioral changes. There was considerable variability in the effect of embolization on nerve pathology in individual nerves. However, the dose of microspheres regressed with the degree of hindlimb paresis, reduction in NBF, degree of fiber pathology, and ischemic conduction failure of the tibial nerve, evaluated at day 7. All nerves with severe (grade 4) fiber degeneration had flows of < 3 mL x 100 g-1 x min-1. We conclude that it is possible to predict with a high degree of accuracy the severity of fiber degeneration by the degree of NBF reduction and by the electrophysiologic abnormalities.

Action Potentials↗

[Pathological study of malignant peripheral nerve sheath tumor in rat].

Sequential morphological studies of rat malignant peripheral nerve sheath tumors induced with ethylnitrosourea were performed by light microscopy, transmission electron microscopy, scanning electron microscopy, immunohistochemistry and nude mice transplantation. The result indicated that rat malignant peripheral nerve sheath tumor was actually a sarcoma arising from Schwann cell within the peripheral nerve, which possesses some basic morphological characteristics as those of human malignant peripheral nerve sheath tumor, and is considered worthy to be used as a model for further studies.

Animals↗

[Modeling for activating peripheral nerves by transverse electric field].

The classical cable function has been used to represent the response of peripheral nerves stimulated by external parallel electric field. It can not describe the excitation of peripheral nerves stimulated by perpendicular electric field. In this paper, responses of the nodes of Ranvier to transverse-field are deeply investigated by mathematic simulation and in-vitro experiments. The paper demonstrates that, under perpendicular electric field stimulation, the responses evoke a two-stage process including an initial polarization and the actual change of the transmembrane potential. It is the net inward current along a radial direction of the node of Ranvier that causes the peripheral nerve excitation. Based on the two-stage process, a novel model is introduced to describe peripheral nerves stimulated by transverse-field, and the classical cable function is modified. The new model and the improved cable function are verified by several in-vitro experiments. They can be used to represent peripheral nerves responses by arbitrary electric field stimulation.

Animals↗

Spinal cord interneuron degenerative atrophy caused by peripheral nerve lesions is prevented by serotonin depletion.

Peripheral nerve section causes a degenerative atrophy of substance P sensory input and of met-enkephalin interneurons in the dorsal horn of the spinal cord. Radioimmunoassay of both peptides indicates that the decrease in peptide levels ranges from 30 to 50%, that it occurs several days after lesioning, and that it is simultaneous for the two peptides. Quantitative immunocytochemistry performed by computer-assisted analysis of met-enkephalin-positive boutons shows that following sciatic nerve lesions there is a decreased density of immunoreactive boutons per unit area in the substantia gelatinosa of the dorsal horn in the lumbar cord ipsilateral to the lesion. Within 24 h of nerve injury there is a significant and transient enhancement of serotonin turnover, as indicated by the increased levels of 5-hydroxyindolacetic acid in the lumbar cord, without any change in serotonin concentrations. The restoration of normal serotonin metabolism at d 10 postlesioning coincides with the peptidergic loss. However, if, prior to nerve resection, serotonin stores are depleted by p-chlorophenylalanine treatment, the damage to met-enkephalin interneurons is fully prevented, while substance P loss does still occur. These results suggest that signals caused by the section of a peripheral nerve are directly responsible for substance P loss in the spinal cord and are, presumably, rapidly transported into the CNS, causing an activation of the serotoninergic raphe neurons projecting to spinal cord. The activation of this system is likely responsible for the degenerative atrophy of the met-enkephalin interneurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Peripheral nerve regeneration by autografts in rats. II. Electrophysiological assessment].

Peripheral nerves repairing using freeze-thawed skeletal muscle autografts were compared to conventional nerve grafts with respect to their electrical properties. It was found that the amplitude and distal latency of action potentials in both groups were not significantly different 3 and 6 months after the operation. These observations support the thesis that peripheral nerve repair by freeze-thawed autogenous muscle grafts may have a significant role in the reconstruction of injured nerves.

Animals↗

Descending facilitatory control of mechanically evoked responses is enhanced in deep dorsal horn neurones following peripheral nerve injury.

Pain resulting from peripheral nerve injury, characterised by ongoing pain, hyperalgesia and allodynia arises from peripheral and central processes. Here, we studied the potential role of central facilitations in nerve injury by investigating the effect of blocking the excitatory 5HT3 receptor with ondansetron. 5HT3 receptors play a pronociceptive role in the spinal cord and ondansetron has previously been shown to produce antinociception in behavioural studies. We investigated the effects of spinally administered ondansetron (10, 50 and 100 microg) on the responses of deep dorsal horn neurones, evoked by peripheral electrical stimuli and a range of natural (mechanical punctate and heat) stimuli, 2 weeks after nerve injury induced through tight ligation of L5/6 spinal nerves (SNL). Comparisons were made between SNL rats and a sham-operated group. Ondansetron produced little effect on the electrically evoked responses (Abeta-, Adelta- and C-fibre-evoked responses, postdischarge); however, responses to mechanical punctate stimuli (von Frey filaments 1-75 g) were markedly reduced in both SNL and control groups. Furthermore, the drug effect was significantly enhanced after SNL (p<0.05). In particular, the lowest dose (10 microg) now became effective after SNL. Ondansetron produced less marked effects on thermal responses. Our results demonstrate that neuropathic pain states are associated with an enhanced descending facilitatory control of mechanical responses of spinal neurones, mediated through the activation of spinal 5HT3 receptors. These excitatory influences are likely to contribute to the development and maintenance of central sensitisation in the spinal cord, and furthermore, to the behavioural manifestation of tactile allodynia.

Action Potentials↗

Microsurgical management of old injuries of the peripheral nerve and brachial plexus.

A prospective study was carried out in patients suffering from old peripheral nerve and brachial plexus injuries to attempt to validate that functional improvement was possible after microsurgical management. Fifty patients underwent operative procedures, of whom 35 were peripheral-nerve injury cases, from 1.2 to 50 years after injury, and 15 were brachial-plexus injury cases, from 1.2 to 12 years after injury. The patients were treated by external and interfascicular neurolysis and/or autogenous nerve grafts. In cases of preganglionic nerve injury, neurotization from C3, C4 roots was done for reinnervation of trunks or cords. During external and interfascicular neurolysis in 19 of the 35 peripheral-nerve injuries, significant improvement was found in amplitude (p = 0.0001) and latency (p = 0.01) of compound muscle action potentials (CMAPs) at the end of the surgery, compared to the onset of surgery. Twenty (57 percent) of the 35 showed functional motor improvement up to M4-or M4. Electrophysiologic analysis of amplitude of CMAPs 1 year after surgery showed statistically significant improvement (p = 0.0003). Five (33 percent) of the 15 patients with upper brachial-plexus injuries showed functional motor improvement up to M4-(active movements against gravity and slight resistance) or M4 (active movements against gravity and moderate resistance) after surgery and of these, 11 also had lower brachial-plexus injuries, with four (36 percent) showing antigravity function M3 (active movement against gravity). Statistical analysis of recruitment 1 year after surgery demonstrated the appearance of or significant voluntary muscle activity in 45 percent of the muscles. Intraoperative electrophysiologic findings after external and interfascicular neurolysis confirmed that the viability of nerve tissue is of longer duration than previously considered. This study suggests that the use of microsurgical techniques results in the functional improvement of patients suffering from old injuries of the peripheral nerve and brachial plexus.

Action Potentials↗

Use of a static magnetic field to promote recovery after peripheral nerve injury.

OBJECT: While pulsed electromagnetic stimulation has been shown to enhance peripheral nerve regeneration, the effect of a static magnetic field on nerve repair is less clear. The aim of this study was to establish what effect an imposed exogenous static magnetic field has on peripheral nerve regeneration after transection and repair. METHODS: Three groups of six adult sheep were used. The first group acted as normal controls. In the second group, the median nerve was divided and immediately repaired by entubulation within a "controlled-release" biodegradable glass tube. In the third group, small magnets were applied to the sides of the biodegradable glass tubes before the median nerve was repaired using these magnetic tubes. The sheep were allowed to recover and were reexamined 10 months later. The animals underwent comprehensive morphometric (cross-sectional morphometry and measurement of internodal lengths), electrophysiological (determinations of stimulated jitter, maximum conduction velocity, refractory period, and F waves), and isometric tension (isometric twitch and tetanic tension) assessments. CONCLUSIONS: Exogenously applied static electromagnetic fields do not enhance peripheral nerve regeneration.

Anastomosis, Surgical↗

Peripheral nerve elongation with tissue expansion techniques.

Elongation of peripheral nerves would facilitate the repair of peripheral nerve injuries. The purpose of this study was to determine the efficacy of nerve expansion and the effect of different levels of intraluminal expander pressure upon nerve conduction. A 2-mL Silastic expander was placed under one sciatic nerve of adult male rats. The other nerve served as a control. Electroneuromyography (ENMG) was done at the time of initial expansion in seven animals. At 40 mm Hg expansion pressure a significant change in latency was found with an increase of 17% +/- 5%. Expansion was carried out for 14 days in two groups of seven rats, group I at 20 mm Hg and group II at 40 mm Hg. Length gain on the expanded side was 30% in group I and 40% in group II. No significant changes in latency or velocity were found after expansion. We conclude that nerves can be expanded at low pressures with no significant conduction changes but long-term recovery of histologic changes needs to be evaluated.

Animals↗

Pathobiological reactions of C-fibre primary sensory neurones to peripheral nerve injury.

Mammalian primary sensory neurones display profound anatomical and chemical changes in response to injury of their peripheral processes. Peripheral nerve damage results in transganglionic degeneration of central terminals of A-fibre primary afferent neurones terminating in the deeper layers of the medullary or spinal dorsal horn. The depletion of neuropeptides and other neurone-specific macromolecules from neurones in sensory ganglia and from the superficial dorsal horn, the known central projection area of C-fibre primary afferents, is a salient phenomenon commencing after peripheral nerve lesions. A recently devised new experimental procedure, termed the capsaicin-gap method, permitted evaluation of the transganglionic degenerative phenomena which develop in C-fibre primary sensory neurones after a lesion is inflicted upon their peripheral branches. The experimental findings indicated that C-fibre primary afferent terminals underwent transganglionic degeneration following a perineural treatment with capsaicin, and that this was associated with, and probably resulted from, ganglionic cell degeneration. Studies on the effects of peripheral nerve section yielded similar results. It has therefore been suggested that the observed depletion of specific macromolecules, including sensory peptides, specific glycoconjugates and sensory neurone specific acid phosphatase, may be accounted for, at least in part, by an irreversible loss of sensory ganglion neurones. In contrast, many injured neurones express peptides, including vasoactive intestinal polypeptide, peptide histidine-isoleucine and galanin, which can be demonstrated in only a few neurones under normal conditions. These seem to be involved in dorsal horn regenerative and/or compensatory processes following peripheral nerve damage. There is suggestive evidence that the partial deafferentation caused by the transganglionic degeneration of C-fibre primary afferents creates favourable circumstances for an anatomical rearrangement of neuronal connections within the spinal cord dorsal horn. These changes may provide a morphological substrate of some of the functional alterations demonstrated after peripheral nerve lesions.

Animals↗