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-org an reinnervation may influence the response of the axon, with survival of axons for appropriate innervation vs degeneration for inappropriat e innervation. The rat femoral nerve model was chosen, as it has appro ximately equal sensory (S) and motor (M) divisions. Four ACI rat peron eal nerve allografts were sutured in straight (right leg; MM and SS) o r switched (left leg; MS and SM) orientation in each femoral nerve tra nsection gap in each Lewis rat recipient. Rats received CsA for 8 week s to allow endorgan reinnervation, after which immunosuppression was d iscontinued. Rats were killed at various times thereafter, and underwe nt histologic and morphometric analysis of the graft segment axons. Th e 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 mo tor. After CsA withdrawal, there was a marked decrease of host axons a s part of an ensuing rejection episode. The overall proportional decre ase of axons was similar across all nerve orientation groups and, ther efore, did not appear to be influenced by the nerve of origin or by th e end-organ. However, the sensory proximal groups (SS and SM) containe d more mature, noninjured fibers, while the motor proximal groups (MM and MS) contained significantly more degeneration and newly regenerati ng axons. We conclude that the motor or sensory nerve origin of the ho st axon, rather than the end-organ, influences axon survival after imm unosuppression cessation. It is hypothesized that sensory axons may be more resilient while motor axons are selectively vulnerable to this s econd injury.