Effects of long-term FK506 administration on functional and histopathological outcome after spinal cord injury in adult rat.

Abstract

FK506 (tacrolimus), a potent immunosuppressive drug primarily used for reduction of allograft rejection in organ transplantation, also offers neuroprotection after central nervous system injury. FK506-mediated immunosuppression and neuroprotection may occur through different mechanisms that could affect neurological recovery and the severity of spinal lesions where cells transplantation therapy is combined with FK506 application. We assessed effects of long-term FK506 administration using the same dose regiment (1 mg/kg/day for 6 weeks) as is used in spinal cord transplantation studies following a balloon-compression induced spinal cord injury (SCI). Body weight and locomotor recovery quantified by the BBB (Basso-Beattie-Bresnehan) locomotor rating scale were evaluated for up to 42 days post-injury. The area of the preserved spinal cord tissue within a 13 mm segment of the spinal cord (lesion epicenter and 6 mm rostral-caudal) was examined histologically. The results showed no significant effects of FK506 on spinal cord tissue sparing or improvement of locomotor recovery. However, body weight fell significantly (P < 0.05) with FK506 treatment when compared with placebo from day 7 until sacrifice. In our experimental design, long-term FK506 treatment did not affect the parameters of outcome following balloon-compression SCI in the rat; however, multiple effects of FK506 should be taken into account when evaluating the outcomes in transplantation studies.