Cyclosporin A retards the wallerian degeneration of peripheral mammalian axons.

The distal (anucleate) segments of mammalian peripheral axons typically undergo complete Wallerian degeneration within 1-3 days after severance from their cell bodies, unlike invertebrates and lower vertebrates, where anucleate axons do not degenerate for weeks to months. This rapid Wallerian degeneration in mammals could be due to a more efficient immune system and/or to differences in calcium-dependent pathways relative to invertebrates and lower vertebrates. To suppress the immune system and to inhibit calcium-dependent pathways in axons, we gave daily subcutaneous injections of cyclosporin A (CsA: 10 mg/kg) to Sprague-Dawley rats for 7 days before, and 5 days after, severing their right ventral tail nerves. To confirm that CsA suppressed the immune system, white blood cell density was measured in CsA-treated and in non-treated rats. Our data showed that the number of surviving anucleate myelinated axons at 5 postoperative days in CsA-treated rats was significantly higher than the number in non-treated rats. Anucleate unmyelinated axons in the ventral tail nerve also exhibited better survival in CsA-treated rats than in nontreated rats. These results are consistent with the hypothesis that the immune response and/or calcium-dependent pathways play important roles in the rapid Wallerian degeneration of anucleate mammalian axons.