Delayed, Post-Injury Treatment with Aniracetam Improves Cognitive Performance after Traumatic Brain Injury in Rats

Abstract

Chronic cognitive impairment is an enduring aspect of traumatic brain injury (TBI) in both humans and animals. Treating cognitive impairment in the post-traumatic stages of injury often involves the delivery of pharmacologic agents aimed at specific neurotransmitter systems. The current investigation examined the effects of the nootropoic drug aniracetam on cognitive recovery following TBI in rats. Three experiments were performed to determine (1) the optimal dose of aniracetam for treating cognitive impairment, (2) the effect of delaying drug treatment for a period of days following TBI, and (3) the effect of terminating drug treatment before cognitive assessment. In experiment 1, rats were administered moderate fluid percussion injury and treated with vehicle, 25, or 50 mg/kg aniracetam for 15 days. Both doses of aniracetam effectively reduced injury-induced deficits in the Morris water maze (MWM) as measured on postinjury days 11-15. In experiment 2, injured rats were treated with 50 mg/kg aniracetam or vehicle beginning on day 11 postinjury and continuing for 15 days. MWM performance, assessed on days 26-30, indicates that aniracetam-treated animals performed as well as sham-injured controls. In experiment 3, animals were injured and treated with aniracetam for 15 days. Drug treatment was terminated during MWM testing on postinjury days 16-20. In this experiment, aniracetam-treated rats did not perform better than vehicle-treated rats. The results of these experiments indicate that aniracetam is an effective treatment for cognitive impairment induced by TBI, even when treatment is delayed for a period of days following injury.