Regeneration following rejection of peripheral nerve allografts of rats on withdrawal of cyclosporine.

Sequential changes in the sciatic nerve function and morphology were evaluated in transplanted nerve allografts from ACI-RT1a into Lewis RT1I rats after withdrawal of cyclosporine, which had been administered subcutaneously daily (5 mg/kg) for 12 weeks. Experimental groups were established as follows: (1) allograft with cyclosporine (evaluated and sacrificed at 12, 14, 16, 20, 24, and 36 weeks, 10 rats at each week), (2) allograft without cyclosporine (12 and 24 weeks, 10 rats at each week), (3) isograft with cyclosporine (12 and 24 weeks, 6 rats at each week), and (4) isograft without cyclosporine (12 and 24 weeks, 10 rats at each week). Regeneration was evaluated through walking track analysis, electrophysiologic studies, weight of the anterior tibial muscle, and axon counts, diameter, and myelin thickness. Regeneration was observed through 14 weeks after grafting; by 16 weeks, all rats had demonstrated a clear rejection phase, but regeneration indices then recovered quickly by 24 weeks. Electron microscopy of both the graft and distal nerve suggested that both Schwann cells and axons were affected by the rejection phenomenon. Allografts without cyclosporine showed inferior regeneration histologically at 24 weeks. Morphologically, allografts were equivalent to isografts treated with cyclosporine at 24 weeks. Although nerve allografts are rejected after cyclosporine withdrawal, they may still serve as effective nerve conduits.