Effect of FK506 and basic fibroblast growth factor on nerve regeneration using a polytetrafluoroethylene chamber for nerve repair.

Peripheral nerve repair can be accomplished by using a polytetrafluoroethylene tubular chamber to guide nerve healing and regeneration. In this study, we delivered basic fibroblast growth factor (bFGF) into the chamber for sciatic nerve repair in rats. In addition, the animals were given systemically 1 mg/kg/day FK506 (tacrolimus), a potent immunosuppressant with neurotrophic properties. Nerve regeneration was evaluated by means of a nociceptive test and a grasping test starting 2 weeks postoperatively. Animals that received bFGF and FK506 showed a significantly faster recovery from injury than did the control group. Morphometric analysis at 3 months showed no difference between the two groups in total number of axonal fibers, fiber diameter, fiber density, and myelin:axon ratio. We conclude that the combination of bFGF and low dose FK506 enhances nerve healing in this animal model by accelerating early regrowth but has no effect on the final outcome.

Low dose discontinued FK506 treatment enhances peripheral nerve regeneration.

FK506 has been reported to enhance nerve regeneration in various rodent models. However, both the immunosuppressive properties and potential side effects may preclude the broad clinical use of FK506 to speed nerve regeneration. In this study, we examined the nerve regenerative property of a low, nonimmunosuppressive dose (0.5 mg/kg/day) of FK506. Two treatment schedules (continuous versus discontinuous) were compared. Evaluations were perforrmed at 1, 2, and 3 months. The gastrocnemius muscle mass was significantly higher in treated groups compared with the untreated group at 3 months, and the total number of fibers, percentage of neural tissue, fiber density, and fiber diameter were greater in treated groups than in the untreated group. However, at 3 months there was no difference in these parameters between groups in which FK506 was administered continuously and those in which the drug was stopped at 2 months. This study confirms that daily administration of low dose FK506 enhances peripheral nerve recovery after transection injury.