Effects of chronic, post-injury Cyclosporin A administration on motor and sensorimotor function following severe, experimental traumatic brain injury

Purpose: Cyclosporin A (CsA) is widely used in clinical situations to atten uate graft rejection following organ and central nervous system transplanta tion. Previous studies demonstrated that CsA administration is neuroprotect ive in models of traumatic brain injury (TBI). However, no studies, to date , have evaluated the influence of post-injury CsA administration on behavio ral recovery after TBI. Methods: Rats (n = 33) were anesthetized and subjected to severe, lateral f luid percussion brain injury. Fifteen minutes thereafter, animals were rand omized to receive the first of 28 daily injections of either CsA (10 mg/kg, ip) or saline. Sham-operated animals (n = 14) were anesthetized and surgic ally prepared without injury and treated daily either with CsA or saline. M otor and sensorimotor functions were assessed at one day before and two day s after injury, and weekly thereafter up to 4 wks post-injury. Cognition wa s assessed at 1 and 4 wks post-injury using a Morris Water Maze test. Results: Injured animals showed significant impairments in motor, sensorimo tor and cognitive function over the 4-week post-injury period. Injured anim als treated with CsA showed a significant improvement in motor function ass essed using a composite neuroscore (at day 28) and in sensorimotor function assessed using a sticky paper test (at days 2, 14, and 28) (p < 0.05, when compared to vehicle treated, injured animals). No beneficial effects on co gnitive function were observed following CsA administration. Conclusion: These data suggest that daily post-injury treatment with CsA im proves certain aspects of motor and sensorimotor function following experim ental TBI.