INHIBITION OF NITRIC-OXIDE SYNTHASE ENHANCES PERIPHERAL-NERVE REGENERATION IN MICE

We tested the hypothesis that inhibition of nitric oxide synthase (NOS ) following transection of the sciatic nerve in the mouse would advers ely influence regeneration of myelinated fibers from the proximal stum p. NOS was inhibited by N-omega-nitro-L-arginine-methyl ester (L-NAME; 10 mg/kg i.p.), a broad spectrum NOS inhibitor given twice daily for the first 10 days following nerve transection in Swiss mice. Controls received the inactive enantiomer N-omega-nitro-D-arginine methyl ester (D-NAME). Regeneration was assessed by serial recordings of the M pot ential from interosseous muscles of the foot innervated by sciatic-tib ial motor fibers and morphometric analysis of myelinated fibers distal to the injury site. Contrary to expectation, M potentials reappeared earlier in the mice treated with L-NAME and were higher in amplitude ( reflecting the number of reinnervating motor fibers) at 10 weeks after the injury. In the L-NAME treated mice, the mean axonal diameter of r egenerating tibial myelinated fibers was larger and the fiber size his togram was shifted to larger fibers. Inhibition of NOS in a transected peripheral nerve is associated with enhanced regeneration of myelinat ed fibers. Local elaboration of NO may be toxic to regenerating axons. (C) 1997 Elsevier Science Ireland Ltd.