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

Muscle Nerve. 2001 Jul;24(7):905-15. doi: 10.1002/mus.1088.

Abstract

We compared the effects of FK506 administration on regeneration and reinnervation after sciatic nerve resection and repair with an autologous graft or with a silicone tube leaving a 6-mm gap in the mouse. Functional reinnervation was assessed by noninvasive methods to determine recovery of motor, sensory, and sweating functions in the hindpaw over 4 months after operation. Morphometric analysis of the regenerated nerves was performed at the end of follow-up. The nerve graft allowed for faster and higher levels of reinnervation in the four functions tested than silicone tube repair. Treatment with FK506 (for the first 9 weeks only) resulted in a slight, although not significant, improvement of the onset of reinnervation and of the maximal degree of recovery achieved after autografting. The recovery of pain sensibility and of the compound nerve action potentials in the digital nerves, which directly depend on axonal regeneration, showed better progression with FK506 than reinnervation of muscles and sweat glands, which require reestablishment of synaptic contacts with target cells. The myelinated fibers in the regenerated nerve showed a more mature appearance in the FK506-treated rats. However, FK506 showed a marginal effect in situations in which regeneration was limited, as in a silicone tube bridging a 6-mm gap in the mouse sciatic nerve. In conclusion, treatment with FK506 improved the rate of functional recovery after nerve resection and autograft repair.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology
  • Animals
  • Female
  • Immunosuppressive Agents / pharmacology*
  • Mice
  • Mice, Inbred Strains
  • Nerve Fibers, Myelinated / physiology
  • Nerve Regeneration / drug effects*
  • Nerve Regeneration / physiology
  • Neural Conduction / physiology
  • Pain Threshold / physiology
  • Recovery of Function / drug effects
  • Recovery of Function / physiology
  • Sciatic Nerve / physiology*
  • Sciatic Nerve / surgery
  • Sciatic Nerve / transplantation*
  • Silicones
  • Tacrolimus / pharmacology*
  • Transplantation, Autologous

Substances

  • Immunosuppressive Agents
  • Silicones
  • Tacrolimus