Motor and sensory specificity of host nerve axons influence nerve allograft rejection

Previous studies have shown both survival and loss of regenerated host axons within nerve allograft segments after withdrawal of Cyclosporin A (CsA) immunosuppression. We hypothesized that the nature of end-organ reinnervation may influence the response of the axon, with survival of axons for appropriate innervation vs degeneration for inappropriate innervation. The rat femoral nerve model was chosen, as it has approximately equal sensory (S) and motor (M) divisions. Four ACI rat peroneal nerve allografts were sutured in straight (right leg: MM and SS) or switched (left leg; MS and SM) orientation in each femoral nerve transection gap in each Lewis rat recipient. Rats received CsA for 8 weeks to allow end-organ reinnervation, after which immunosuppression was discontinued. Rats were killed at various times thereafter, and underwent histologic and morphometric analysis of the graft segment axons. The regenerated axon population in the allograft reflected the nerve of origin: significantly more but smaller fibers when the proximal nerve was sensory and fewer but larger fibers when the proximal nerve was motor. After CsA withdrawal, there was a marked decrease of host axons as part of an ensuing rejection episode. The overall proportional decrease of axons was similar across all nerve orientation groups and, therefore, did not appear to be influenced by the nerve of origin or by the end-organ. However, the sensory proximal groups (SS and SM) contained more mature, noninjured fibers, while the motor proximal groups (MM and MS) contained significantly more degeneration and newly regenerating axons. We conclude that the motor or sensory nerve origin of the host axon, rather than the end-organ, influences axon survival after immunosuppression cessation. It is hypothesized that sensory axons may be more resilient while motor axons are selectively vulnerable to this second injury.