Administration of low-dose FK 506 accelerates histomorphometric regeneration and functional outcomes after allograft nerve repair in a rat model

Abstract

A substantial loss of peripheral nerves requires grafts for repair. In animal experiments, the use of allografts is successful only when rejection of the transplant is prevented and nerve regeneration is improved by the administration of the immunosuppressant FK 506 used in high doses. In this study, we examined the functional and morphometric outcome after allograft transplantation of the sciatic nerve in rats at low doses of FK 506. Functional recovery and quantitative assessment of myelination were investigated in un-operated controls, in rats receiving isograft transplants without FK 506 treatment and in rats receiving allograft transplants with FK 506 treatment (0.1mg/kg and 0.2mg/kg per day). Walking-track analysis at 4, 8, 12 and 16 weeks post-operation revealed significant functional recovery in allograft with FK 506 (0.1mg/kg) compared with other groups, although levels of the un-operated controls were not reached. At 16 weeks, myelination of nerve sections from FK 506 (0.1mg/kg)-treated and un-operated animals did not differ significantly. There was significantly less effect of the 0.2mg/kg dose than of the 0.1mg/kg dose, both in the histomorphological outcome and in the functional outcome. These findings indicate that higher doses of FK 506 are not necessary for nerve regeneration, and low-dose administration could be acceptable for clinical settings in future.