title: Flumazenil administration attenuates cognitive impairment in immature rats after controlled cortical impact.
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.
authors.affiliation: Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA. ochalskipg@upmc.edu
authors.forename: Pawel G
authors.initials: PG
authors.lastname: Ochalski
authors.forename: Wendy
authors.initials: W
authors.lastname: Fellows-Mayle
authors.forename: Lily B
authors.initials: LB
authors.lastname: Hsieh
authors.forename: Ravi
authors.initials: R
authors.lastname: Srinivas
authors.forename: David O
authors.initials: DO
authors.lastname: Okonkwo
authors.forename: C Edward
authors.initials: CE
authors.lastname: Dixon
authors.forename: P David
authors.initials: PD
authors.lastname: Adelson
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D001923:Brain Chemistry / Q000187:drug effects* / Q000502:physiology; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005442:Flumazenil / Q000494:pharmacology* / Q000627:therapeutic use; D018757:GABA Modulators / Q000494:pharmacology / Q000627:therapeutic use; D007274:Injections, Intraperitoneal; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D018697:Nootropic Agents / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D016896:Treatment Outcome; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018757:GABA Modulators; D018697:Nootropic Agents; D011963:Receptors, GABA-A; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid