FK506 promotes functional recovery in crushed rat sciatic nerve.

In this study we examine whether the systemic administration of FK506 or Cyclosporin A (CsA) expedited functional recovery following an axonotmetic nerve injury, and compared their effects in a rat model. Seventy-five adult Buffalo rats received a crush injury to the right posterior tibial nerve and subsequently underwent either no treatment (group I), daily injections of FK506 (group II), or daily injections of CsA (group III). Walking track analysis demonstrated return of hindlimb function by 20 days postoperatively in group I, 14 days in group II, and 18 days in group III. The blood-nerve barrier (BNB) was reconstituted by postoperative day (POD) 7 in both FK506- and CsA-treated animals and by POD 13 in control animals. These results suggest that recovery of function is more rapid with daily administration of FK506 than with CsA or no treatment, perhaps because of earlier restoration of the blood-nerve barrier. Agents that facilitate nerve regeneration have the potential to limit the extent of motor endplate loss and muscle atrophy seen with prolonged denervation, thereby limiting permanent functional loss.