The treatment of peripheral nerve injuries using irradiated allografts and temporary host immunosuppression (in a rat model).
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 degrees +/- 12 degrees vs. 44 degrees +/- 13 degrees and 51 degrees +/- 13 degrees, p less than 0.005). Allografted animals receiving short-term cyclosporin-A had contractures that were not significantly different from those seen in isografted control animals (17 degrees +/- 12 degrees vs. 22 degrees +/- 15 degrees, NS). Muscle hydroxyproline concentration analysis revealed a lower hydroxyproline concentration among the allografted groups that received irradiated allografts, compared to groups receiving nonirradiated allogeneic 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Easterling
K J
KJ
Department of Orthopaedics and Rehabilitation, Yale University School of Medicine, New Haven, CT 06510.
Trumble
T E
TE
D000818:Animals; D001369:Axons / Q000648:ultrastructure; D003286:Contracture / Q000503:physiopathology; D003524:Cyclosporins / Q000097:blood / Q000627:therapeutic use*; D005684:Gait / Q000502:physiology; D006614:Hindlimb / Q000503:physiopathology; D006909:Hydroxyproline / Q000032:analysis; D007165:Immunosuppression Therapy; D008297:Male; D009132:Muscles / Q000737:chemistry / Q000473:pathology; D009929:Organ Size; D051381:Rats; D011917:Rats, Inbred Lew; D012584:Sciatic Nerve / Q000473:pathology / Q000503:physiopathology / Q000528:radiation effects / Q000637:transplantation*; D014110:Touch / Q000502:physiology
D003524:Cyclosporins; D006909:Hydroxyproline