Influence of Tacrolimus (FK506) on Nerve Regeneration Using Allografts: A Rat Sciatic Nerve Model

Abstract

FK506 is an immunosuppressant agent used to prevent rejection after organ transplantation. The aim of the present study was to assess effects of tacrolimus (FK506) on peripheral nerve regeneration using allografts in a rat sciatic nerve model. Thirty male white Wistar rats were divided randomly into a normal control (NC) group (n = 10), an allograft (ALLO) group (n = 10), and an FK506-treated (ALLO/FK506) group (n = 10). In the NC group, the left sciatic nerve was exposed through a gluteal muscle incision and, after homeostasis, the muscle was sutured. In the ALLO group, the left sciatic nerve was exposed through a gluteal muscle incision and transected proximal to the tibioperoneal bifurcation, where a 10-mm segment was excised. The same procedure was performed in the ALLO/FK506 group. The harvested nerves of the ALLO group served as allografts for the ALLO/FK506 group and vice versa. The NC and ALLO groups received sterile olive oil 300 μL intraperitoneally once a day for 1 week and the ALLO/FK506 group received FK506 300 μL (1 mg/kg) intraperitoneally once a day for 1 week. Behavioral, functional, and biomechanical recovery and gastrocnemius muscle mass showed earlier regeneration of axons in the ALLO/FK506 than in the ALLO group (P < .05). Histomorphometric and immunohistochemical studies also showed earlier regeneration of axons in the ALLO/FK506 than in the ALLO group (P < .05). Administration of FK506 could accelerate functional recovery of the sciatic nerve after nerve allografting. It could have clinical implications for the surgical management of patients after facial nerve transection.