Protein kinase inhibition by fasudil hydrochloride promotes neurological recovery after spinal cord injury in rats

Object. In Japan fasudil hydrochloride (HA1077), a protein kinase inhibitor , is widely administered to prevent vasospasm in patients after subarachnoi d hemorrhage. The effects of fasudil on experimental spinal cord injury (SC I) were investigated and compared with those obtained using methylprednisol one. Methods. Spinal cord contusion was induced in rats by applying an aneurysm clip extradurally to the spinal cord at T-3 for 1 minute. After injury thre e groups of rats were treated with intravenously administered saline (contr ol), intraperitoneally administered fasudil (10 mg/kg), or intravenously ad ministered methylprednisolone (four 30 mg/kg injections). Neurological reco very was evaluated periodically over 1 month by using a modified combined b ehavioral scale and histopathological examination. Leukocyte infiltration n ear the injury site was evaluated by measuring myeloperoxidase (MPO) activi ty at 24 hours. Spinal cord blood flow was measured at intervals up to 3 ho urs after injury by using laser Doppler flowmetry. In rats in the fasudil-treated group significant improvement in mollified c ombined behavioral score was demonstrated at each time point, whereas in th e methylprednisolone-treated rats no beneficial effects were shown. In the fasudil-treated group, reduction of traumatic spinal cord damage was eviden t histologically in the caudal portion of the injured areas, and tissue MPO activity in tissue samples was reduced. Spinal cord blood flow was not sig nificantly different between fasudil-treated and control group rats. Conclusions. Fasudil hydrochloride showed promise of effectiveness in promo ting neurological recovery after traumatic SCI. Possible mechanisms of this effect include protein kinase inhibition and decreased infiltration by neu trophils.