Cyclosporin A affects axons and macrophages during Wallerian degeneration.

Abstract

A traumatic injury of a peripheral nerve leads to Wallerian degeneration. It includes the recruitment of macrophages and the phagocytosis of myelin and the remnants of axons. We have previously studied the recruitment of macrophages and now wished to determine if the immunosuppressant cyclosporin A (CsA) affects the number of macrophages at the site of nerve injury. The primary target of CsA is T-cells, but it may also have an effect on mononuclear phagocytes which exert a key role during Wallerian degeneration. Rats were divided into two groups: CsA-treated animals and control animals. Following transection of the sciatic nerve in the treatment group, the animals received 5 mg/kg CsA subcutaneously. The groups were further subdivided into a freely regenerating nerve group and a sutured nerve group. The number of macrophages and MHC class II positive cells were counted 3 days, 7 days, 2 weeks, 4 weeks, and 8 weeks posttransection; also CD4, CD8, IL-2 receptor positive cells, B cells, and the axonal sprouting were studied. In the CsA-treated group, there were more macrophages in the distal areas under 8 weeks than in the controls (p < 0.05); thus, the clearance of macrophages is delayed in the CsA-treated rats compared to the control rats. In the proximal area, the difference in macrophage number did not gain statistical significance. Additionally, CsA retarded axonal degeneration. CsA affects number of macrophages during Wallerian degeneration, while retarding axonal degeneration and subsequent reinnervation. Its mechanism of action appears to involve either direct or indirect via T-cells-mediated responses.