Effects of FK506 on nerve regeneration and reinnervation after graft or tube repair of long nerve gaps

We compared the effects of FK506 administration on regeneration and reinner vation after sciatic nerve resection and repair with an autologous graft or with a silicone tube leaving a 6-mm gap in the mouse. Functional reinnerva tion was assessed by noninvasive methods to determine recovery of motor, se nsory, and sweating functions in the hindpaw over 4 months after operation. Morphometric analysis of the regenerated nerves was performed at the end o f follow-up. The nerve graft allowed for faster and higher levels of reinne rvation in the four functions tested than silicone tube repair. Treatment w ith FK506 (for the first 9 weeks only) resulted in a slight, although not s ignificant, improvement of the onset of reinnervation and of the maximal de gree of recovery achieved after autografting. The recovery of pain sensibil ity and of the compound nerve action potentials in the digital nerves, whic h directly depend on axonal regeneration, showed better progression with FK 506 than reinnervation of muscles and sweat glands, which require reestabli shment of synaptic contacts with target cells. The myelinated fibers in the regenerated nerve showed a more mature appearance in the FK506-treated rat s. However, FK506 showed a marginal effect in situations in which regenerat ion was limited, as in a silicone tube bridging a 6-mm gap in the mouse sci atic nerve. In conclusion, treatment with FK506 improved the rate of functi onal recovery after nerve resection and autograft repair. (C) 2001 John Wil ey & Sons, Inc.