Alan R. Hudson

Chronic nerve compression - an experimental model in the rat

This study reports a rat model of chronic nerve compression. The sciatic nerves of adult male Sprague Dawley rats were banded with 1-cm lengths of tubing with varying internal diameters. Histological and electrical studies as well as studies to assess the blood-nerve barrier function were carried out at one through six months. With marked compression of the sciatic nerve, profound electrical changes were noted as early as one month, and histological findings were those of degeneration and regeneration. In the rats with minimal compression, nerve conduction studies remained normal. The earliest findings were alterations in the bloodnerve barrier, followed by histological changes in the large myelinated fibers at the periphery of the fascicles and changes about the nodes of Ranvier. This model appears to be a valid one with which to study other aspects of both the pathophysiology and treatment of chronic nerve compression.

Clinical application of peripheral nerve transplantation.

Surgical reconstruction of extensive peripheral nerve injuries frequently exhausts the patients own source of expendable autogenous nerve grafts. Nerve allografts would offer a limitless supply of graft material. A 23-cm, 10-cable sciatic nerve allograft was performed in an 8-year-old boy in September of 1988. The patient was managed with Cyclosporin A for 2 years. Forty-four months after the transplant surgery and 19 months after the cessation of Cyclosporin A therapy, the patient has evidence of nerve regeneration across the allograft with recovery of functional sensibility in his foot. In the selected patient with an otherwise irreparable nerve injury, consideration can be given to the use of a nerve allograft.

Nerve regeneration through a pseudosynovial sheath in a primate model.

This study investigated nerve regeneration through a pseudosynovial sheath in a primate. After resecting a 3-cm segment of the ulnar nerve at the elbow, the two ends of the divided nerve were placed at either end of the pseudosynovial tube, positioning the nerve ends such that they were separated by a 3-cm gap. Histologic evaluation at 3, 5, 7, and 9 months demonstrated evidence of nerve regeneration across this gap. Nerve fiber diameter and density assessment demonstrated a maturation of the fiber pattern with time. The overall morphologic pattern of the regenerating nerve within the pseudosheath was that of multiple small fascicles, each within its own perineurial compartment. This pattern resembled neither the proximal nor distal nerve fascicular pattern.

Nerve injection injury with local anesthetic agents: a light and electron microscopic, fluorescent microscopic, and horseradish peroxidase study.

Although regional anesthesia is generally considered to have no neurotoxic properties, significant nerve injury has been reported after its use. The present study was undertaken to examine possible toxic effects on peripheral nerve tissue of local anesthetic agents. We injected the sciatic nerve of

A model of chronic nerve compression in the rat.

This article describes a model of chronic nerve compression in the rat. The sciatic nerve of adult male Sprague Dawley rats was banded with a 1-cm Silastic tube for varying periods of time. Morphometric analysis, electrodiagnostic studies, and histological evaluation were carried out 3, 5, 8, and 12 months after banding.Histological evaluation at 3 months was normal. At 5 months perineurial thickening was demonstrated. In the periphery of the fascicles, segmental demyelination was noted; central fibers appeared normal. At 8 months there was further epineurial and perineurial thickening. Marked thinning of the myelin was noted in all fibers and evidence of Wallerian degeneration was apparent. Progressive connective tissue and nerve fiber changes were noted at 12 months.Nerve conduction studies after 3 months of compression demonstrated an increase in conduction velocity compared to the normal unbanded control nerves. Progressive slowing of conduction velocity was noted from 5 through 12 months.

Peripheral nerve allograft: an assessment of regeneration across pretreated nerve allografts.

Regeneration across lyophilized and irradiated peripheral nerve allografts was assessed using electrical and histological parameters. Regeneration did occur across these pretreated nerve allografts and was intermediate between that regeneration which occurred across a fresh, untreated nerve allograft and that which occurred across the control autograft.

Clinical and experimental aspects of injection injuries of peripheral nerves.

Injury to peripheral nerves complicating deep intramuscular injections of antibiotic and other agents is well recognized and can result in significant permanent neurological deficit. The purpose of this paper is to review the subject of nerve injection injuries, and report on a series of recent experimental studies carried out in this laboratory designed to improve our understanding of the pathophysiology of this condition and help provide a rational basis for its treatment. A wide variety of chemotherapeutic, prophylactic, and local anaesthetic agents in common use were injected into the sciatic nerve of the adult Wistar rat. Both intrafascicular and extrafascicular injections were examined. Results revealed that the site of injection was the most crucial factor in determining the degree of nerve fiber injury. Following intrafascicular injection, the degree of injury varied significantly, depending upon the specific agent injected. The most severe injuries were associated with wide-spread axonal and myelin degeneration. Pathological alterations in the nerve were evident as early as 30 minutes following injection injury. Regeneration was a constant finding in nerve damage by injection of the various agents. The mechanism of injury appeared to be a direct toxic effect of the injected compound on neural tissue, with an associated break down of the blood-nerve barrier.

Peripheral nerve injection injury: an experimental study.

In an attempt to answer questions regarding nerve injection injuries, we injected 11 agents in current use and commonly administered by intramuscular injection into the sciatic nerves of adult Wistar rats. Equal volumes of normal saline were used as control. We harvested the sciatic nerves at various times after injection and examined them by both light and electron microscopy. We performed myelinated nerve fiber counts and constructed histograms. Any impairment of motor function was also noted. We gave injections to 79 animals a total of 158 times; 116 injections were directly into the nerve fascicle (intrafascicular) and 42 were into the epineural tissue (extrafascicular). The results revealed considerable variation in the degree of nerve fiber injury according to the agent injected. Minimal damage resulted from the injection of iron-dextran, meperidine, and cephalothin, and maximal nerve injury followed the injection of penicillin, diazepam, and chlorpromazine. The site of injection was crucial. Intrafascicular injection was invariably associated with severe nerve injury, but, with few exceptions, extrafascicular injection resulted in minimal damage. The quantity of drug injected was also important in determining the degree of injury. Large, heavily myelinated fibers were more susceptible to injection injury than smaller, thinly myelinated nerve fibers. The effect of the injected drug seemed to be related to injury of the nerve fiber unit--both the axon and the Schwann cell with its myelin sheath. Regeneration in damaged nerves was a constant finding; even the most severely injured nerves, with total axonal degeneration, underwent subsequent regeneration.

The peripheral nerve allograft in the primate immunosuppressed with cyclosporin A. I: Histologic and electrophysiologic assessment

Nerve regeneration across peripheral nerve allografts and control autografts in primates immunosuppressed with Cyclosporin A was quantitatively evaluated by electrophysiologic and histologic methods. Twelve cynomolgus monkeys received 3-cm autografts and allografts in contralateral ulnar nerves. They were immunosuppressed with Cyclosporin A at 25 mg/kg per day or placebo vehicle. Morphometric analysis of nerve graft and distal nerve segments was assessed at 1 year after engraftment. Quantitative electrophysiologic studies were performed percutaneously at 6 and 12 months, and compound action potentials were measured directly across the nerve grafts at 1 year. Excellent regeneration was seen across autografts and allografts in Cyclosporin A-treated and placebo-treated recipients.

The nerve allograft response--an experimental model in the rat.

The nerve allograft response in a rat model is presented. The Lewis rat (RTII) served as the recipient animal while Fischer rats (RTII) and ACI rats (RTIa) provided the donor nerve allografts. A Lewis/Lewis autograft group was used as the control group. Histological and electrophysiological measurements of nerve regeneration were assessed at five months. While good regeneration was noted in the autograft and matched allograft groups, regeneration across the unmatched allograft was poor. The degree of nerve regeneration (as measured with histological and electrophysiological values) correlated well with previous immunological studies and would support the use of this model for future investigation of the nerve allograft response in the rat.