Long nerve allografts in sheep with Cyclosporin A immunosuppression

Rodent studies of nerve allografts are limited by a relatively short length of graft segment. The authors attempted to establish an outbred sheep model that would allow the study of longer, more clinically relevant nerve gaps. Using outbred ewes, two 8-cm long radial sensory nerves were grafted into gaps (5 cm) in the median nerve. Sheep received an autograft and an allograft. Four sheep were immunosuppressed with Cyclosporin A (CsA) and four were controls. Blood CsA levels greater than 1000 microg/L were obtained. Systemic immunosuppression resulted in severe opportunistic infections, and the sheep were sacrificed between 35 and 47 days following surgery. Histologically, in the autografts and CsA-treated allografts, evidence of nerve regeneration was seen. Non-immunosuppressed allografts were clearly rejected. While clear differences in the histology of experimental and control grafted nerve tissues were seen, the sheep allograft model presents considerable challenges due to immunosuppression-related infectious complications.