Functional assessment of the sciatic nerve after repair with local delivery of FK 506 in rats

Abstract

Difficulties with nerve repair are addressed principally in two ways – one is a meticulous apposition of nerve fibres by microsurgical techniques and the other is the facilitation of the regeneration of proximal axons by neurotrophic factors. The latter concept essentially involves optimizing the microenvironment at the site of injury by biochemical influences. FK 506 (tacrolimus), an immunosuppressive agent, has been recently found to have nerve regenerative potential in experimental animals; however, the various toxic effects of the drug, when used systemically (which has been the case in all of these experiments), limit its clinical use. To prevent such toxic effects of FK 506 in a nerve injury model, a local drug delivery method was developed by suspending a known concentration of FK 506 in fibrin glue (fibrin sealant) to release slowly 1 mg of the drug at the local site. Materials and Methods The sciatic nerve was transected in 18 rats and primary microsurgical repair was performed. Rats in group 1, the control group, had transection and primary repair, those in group 2 had transection and primary repair reinforced with fibrin sealant, and those in group 3 had primary repair that was reinforced with fibrin sealant and FK 506 (1 mg). A walking track analysis was performed, beginning in the second week, to evaluate functional recovery of the sciatic nerve. Results Overall, the animals that received FK 506 showed earlier recovery than those in the control group. Further, mean footprint length factors of the rats in group 3 showed significant early improvement between four and five weeks after surgery, whereas the improvements in groups 1 and 2 started toward normalization a week later, between five and six weeks after surgery. The experimental goal of the study was to determine whether locally delivered FK 506 is beneficial to nerve regeneration.