tacrolimus and Trauma--Nervous-System

FK-506 is used in organ transplantation because it promotes neurite outgrowth in vitro and enhances neuroregeneration in peripheral nerve injury transection models. Immunosuppressive mechanisms of FK-506 are well defined, with demonstration of decreased neuroregenerative effects with delayed administration. The purpose of this study was to describe the effects of preinjury administration of FK-506 in rats with tibial nerve transection injury.. Eight inbred male Lewis rats per group in three separate groups underwent tibial nerve transection with primary repair. Group I received placebo, group II received FK-506 treatment at 1 day before surgery, and group III received FK-506 preloading 3 days before surgery.. Histologic and histomorphometric results demonstrated the preload FK-506 group had superior results compared with the immediate FK-506 group. Both FK-506 groups were superior to the placebo group. The preload FK-506 demonstrated superior regeneration in mean total nerve fiber counts (p < 0.05), greater percentage neural tissue (p < 0.05), greater mean nerve fiber density (p < 0.05), and lower percentage of debris (p > 0.05). Mean nerve fiber widths were similar in the preload and immediate FK-506 groups but superior to the placebo group.. These data suggest that enhancement of FK-506's neuroregenerative effect is enhanced when administered before nerve injury such as when performing elective surgery.

Topics: Animals; Disease Models, Animal; Male; Nerve Regeneration; Neurosurgical Procedures; Peripheral Nervous System Agents; Preoperative Care; Rats; Rats, Inbred Lew; Tacrolimus; Tibial Nerve; Trauma, Nervous System

The authors hypothesized that FK506 improves maximal muscle force (P (0)) recovery during early muscle reinnervation. Rat peroneal nerve was unilaterally cut and repaired. Rats received subcutaneous injections of vehicle (controls) or FK506 at 1 mg/kg (FK506-1MG) or 5 mg/kg (FK506-5MG) for 3 weeks. Extensor digitorum longus (EDL) isometric muscle P (0) was measured bilaterally 4 weeks postoperatively. FK506 treatment adversely affected body mass. With body mass as a covariate, the P (0) for denervated-reinnervated muscle in the FK506-5MG group was statistically significantly higher by 34 percent and 32 percent, compared with controls and FK506-1MG groups. There was no group difference for the contralateral, nerve-intact EDL muscle P (0), when loss of body mass was considered. NCAM immunohistologic data showed significantly better reinnervation of the denervated muscle in a dose-dependent fashion. Thus, FK506 treatment at high dose improves early recovery of force in denervated-reinnervated muscle, following nerve repair, when loss of body mass is considered.

Topics: Animals; Immunosuppressive Agents; Injections, Subcutaneous; Male; Models, Animal; Muscle, Skeletal; Muscular Diseases; Neurosurgical Procedures; Peroneal Nerve; Rats; Rats, Inbred F344; Recovery of Function; Tacrolimus; Trauma, Nervous System