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 peripheral nerve allograft: an assessment of regeneration across nerve allografts in rats immunosuppressed with cyclosporin A.

Lewis rats (RT1(1] were the recipients of 3-cm nerve grafts from syngeneic Lewis donors or allogeneic ACI (RT1a) donors. Microneurosurgical repair of the nerve graft to the transected sciatic nerve of the recipient animal was performed with 10-0 epineurial sutures. Recipients were randomly allocated to cyclosporin A (CsA) immunosuppressed or untreated groups. Cyclosporin A was administered in the minimal effective dosage to prevent nerve allograft rejection across this major histocompatibility disparity (5 mg/kg per day). Nerve regeneration across the nerve grafts was assessed by sciatic function index (SFI) and toe spread index (TSI) determinations serially and by electrophysiologic, histologic, and morphologic assessments 14 weeks after engraftment. Sciatic nerve regeneration across allogeneic nerve grafts in cyclosporin A immunosuppressed recipients was significantly superior compared to the untreated controls (p less than 0.008) and not significantly different from that across the syngeneic control animals.

An assessment of the effects of internal neurolysis on a chronically compressed rat sciatic nerve.

Chronically compressed nerves were treated with three surgical modalities. Simple decompression was compared to internal neurolysis with and without the addition of extrafascicular steroid. Electrophysiologic, histologic, and morphometric assessments were performed. Compressed control nerves demonstrated changes compatible with severe nerve compression (Wallerian degeneration). With simple decompression, improvement in histologic and electrophysiologic parameters occurred. When internal neurolysis was added to the decompression, further improvement in histologic and electrophysiologic parameters was noted. There was no added improvement with the addition of steroids.

The peripheral nerve allograft: an assessment of regeneration in the immunosuppressed host.

Regeneration across the nerve allograft in the immunosuppressed host was assessed using electrical and histologic parameters. The Lewis rat (RTIl) served as the recipient animal, and ACI rats (RTIa) provided the donor nerve allografts. Hydrocortisone and azathioprine were used in various dose schedules as the immunosuppressive agents. Animals were immunosuppressed for either 30 or 100 days. Histologic and electrophysiologic measurements of nerve regeneration were assessed at 30, 100, and 180 days. The degree of nerve regeneration was similar in all experimental groups. Short-term, low-dose immunosuppression was as successful as longer-term, higher-dose immunosuppression therapy. The degree of nerve regeneration in all experimental groups was significantly better than that in the fresh, untreated nerve allograft control group (Lewis/ACI) but was not as good as that seen in the autograft control group (Lewis/Lewis).

Chronic human nerve compression--a histological assessment.

While compression neuropathy is a common clinical problem, the opportunity to study human nerve material is rare. A histological assessment of the superficial radial nerve of four human cases with entrapment syndrome is reported. Changes in the perineurium and the endoneurial microvessels as well as the presence of Renaut bodies were the earliest histological abnormalities noted. Connective tissue changes included epineurial and perineurial fibrosis. Nerve fibre pathology varied from fascicle to fascicle. The myelinated and unmyelinated fibre populations responded differently to this compression. In the myelinated fibre population, marked thinning of the myelin was noted. In the unmyelinated fibre population, a shift in the fibre histogram due to a new population of very small fibres was observed suggesting degeneration with subsequent regeneration of this fibre population.

Histologic assessment of nerve regeneration in the rat.

This study reports the degree of spontaneous regeneration that will occur in the sciatic nerve of a rat 5 months after complete resection of the nerve. In 30 animals, the sciatic nerve was excised. Histological assessment at 5 months revealed evidence of regeneration for a variable distance (mean 23.7 mm +/- 6.4 mm). Histological sections were studied at 1-cm intervals along the length of the nerve. Evidence of compartmentation with "minifascicle" formation was noted. The orientation of the nerve fibers was parallel to the long axis of the nerve. This study assessing spontaneous regeneration is meant to serve as a control for other studies evaluating the effect of factors that may influence nerve regeneration in the rat model.

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.

Peripheral nerve allograft: an immunological assessment of pretreatment methods.

An in vivo immunological assay was used to determine quantitatively the nerve allograft response in a rat model. The nerve allograft was then pretreated with a number of pretreatment methods that have been used clinically and experimentally. Using the same immunological assay to determine quantitatively the nerve allograft response, we found that lyophilization and high doses of irradiation could modify the nerve allograft in such a way as to make it less immunogenetic to the host animal. The other methods of pretreatment did not alter the antigenicity of the allograft.