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

J Neurotrauma. 2010 Mar;27(3):647-51. doi: 10.1089/neu.2009.1142.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / drug effects*
  • Brain / pathology
  • Brain / physiopathology
  • Brain Chemistry / drug effects*
  • Brain Chemistry / physiology
  • Brain Injuries / complications
  • Brain Injuries / drug therapy*
  • Brain Injuries / physiopathology
  • Cognition Disorders / drug therapy*
  • Cognition Disorders / etiology
  • Cognition Disorders / physiopathology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Flumazenil / pharmacology*
  • Flumazenil / therapeutic use
  • GABA Modulators / pharmacology
  • GABA Modulators / therapeutic use
  • Injections, Intraperitoneal
  • Male
  • Maze Learning / drug effects
  • Maze Learning / physiology
  • Nootropic Agents / pharmacology
  • Nootropic Agents / therapeutic use
  • Rats
  • Rats, Sprague-Dawley
  • Reaction Time / drug effects
  • Reaction Time / physiology
  • Receptors, GABA-A / drug effects
  • Receptors, GABA-A / metabolism
  • Treatment Outcome
  • gamma-Aminobutyric Acid / metabolism*

Substances

  • GABA Modulators
  • Nootropic Agents
  • Receptors, GABA-A
  • Flumazenil
  • gamma-Aminobutyric Acid