The Treatment of Peripheral Nerve Injuries Using Irradiated Allografts and Temporary Host Immunosuppression (in a Rat Model)

ABSTRACT

Irradiation of allografts prior to transplantation and host immunosuppression with cyclosporin-A were studied separately and in combination as means of lessening the rejection of transplanted peripheral nerve tissue. Lewis and Brown Norway rats were used in the animal model, as they differ at both major and minor histocompatibility loci. Sciatic nerve grafts (2.5 cm) were used and the animals were followed for 16 weeks after nerve grafting. The outcome was studied by functional measurements (sensory testing, gait analysis, joint flexion contracture, and muscle weight), as well as by measurements of biochemical and histologic parameters (hydroxyproline concentration and axon counts, respectively). Sensory testing was not reliable because of crossover innervation by the saphenous nerve. Evaluation by standard gait-testing techniques was found to be unsatisfactory. However, the allografted animals receiving cyclosporin-A had significantly smaller flexion contractures, compared to the allografted animals without immunosuppression (17° ± 12° vs. 44° ± 13° and 51° ± 13°, p < 0.005). Allografted animals receiving short-term cyclosporin-A had contractures that were not significantly different from those seen in isografted control animals (17° ± 12° vs. 22° ± 15°, NS). Muscle hydroxyproline concentration analysis revealed a lower hydroxyproline concentration among the allografted groups that received irradiated allografts, compared to groups receiving nonirradiated allo-geneic grafts. The studies of muscle hydroxyproline concentration and muscle weight both showed substantial reinnervation, even in allografted animals without pretreatment of the grafts or immunosuppression of the recipient animal. Histologic examination revealed significant axonal ingrowth into grafts in all groups, without any correlation to graft irradiation or host immunosuppression.

Nerve transplantation in the rat model provides evidence that autogenous nerve grafts can be replaced by allogeneic nerve grafts, when combined with short-term immunosuppression, in order to obtain comparable results. Even without immunosuppression, substantial reinnervation can occur with transplanted tissue to bridge segmental defects in peripheral nerves.