CYCLOSPORINE-A RETARDS THE WALLERIAN DEGENERATION OF PERIPHERAL MAMMALIAN AXONS

The distal (anucleate) segments of mammalian peripheral axons typicall y undergo complete WaIlerian degeneration within 1-3 days after severa nce from their cell bodies, unlike invertebrates and lower vertebrates , where anucleate axons do not degenerate for weeks to months. This ra pid Wallerian degeneration in mammals could be due to a more efficient immune system and/or to differences in calcium-dependent pathways rel ative to invertebrates and lower vertebrates. To suppress the immune s ystem and to inhibit calcium-dependent pathways in axons, we gave dail y 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-treat ed rats. Our data showed that the number of surviving anucleate myelin ated axons at 5 postoperative days in CsA-treated rats was significant ly 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 wit h the hypothesis that the immune response and/or calcium-dependent pat hways play important roles in the rapid Wallerian degeneration of anuc leate mammalian axons. (C) 1997 Academic Press.