Flumazenil administration attenuates cognitive impairment in immature rats after controlled cortical impact

Journal of Neurotrauma
Pawel G OchalskiP D Adelson

Abstract

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.

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Citations

Aug 10, 2011·Neural Plasticity·Stephen W Briggs, Aristea S Galanopoulou
Nov 7, 2012·British Journal of Clinical Pharmacology·Sean David HoodGary Kenneth Hulse
Aug 22, 2014·Journal of Neurosurgical Anesthesiology·Daniel N HertleOliver W Sakowitz

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Brain Injury & Trauma

brain injury after impact to the head is due to both immediate mechanical effects and delayed responses of neural tissues.

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