Flumazenil Administration Attenuates Cognitive Impairment in Immature Rats after Controlled Cortical Impact

Evidence suggests that the gamma-aminobutyric acid (GABA) ergic system may be involved in cognitive dysfunction following traumatic brain injury (TBI). We investigated the effect of flumazenil treatment, a benzodiazepine antagonist approved by the U.S. Food and Drug Administration, on learning and memory in the immature rat following experimental brain injury. Post-natal day 17 rats were injured using controlled cortical impact. Systemic treatment with flumazenil at 1, 5, and 10 mg/kg was initiated on post-injury day 1 and administered for 13 days via daily intraperitoneal injections. Morris water maze (MWM) testing was used to measure latency to find a submerged platform and the results from experimental and control animals were compared. We demonstrated a significant dose-dependent improvement in MWM performance in drug-treated animals. This is the first study demonstrating the efficacy of flumazenil in reducing post-TBI cognitive deficits and we propose that these effects may be related to modulation of the GABA(A) receptor.