Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA.
J Neurotrauma. 2010 Mar;27(3):647-51. doi: 10.1089/neu.2009.1142.
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.
有证据表明，γ-氨基丁酸（GABA）能系统可能参与创伤性脑损伤（TBI）后的认知功能障碍。我们研究了氟马西尼治疗的效果，氟马西尼是一种美国食品和药物管理局批准的苯二氮䓬拮抗剂，用于研究实验性脑损伤后未成熟大鼠的学习和记忆。在出生后第 17 天，使用皮质控制冲击对大鼠进行损伤。在损伤后第 1 天开始使用 1、5 和 10mg/kg 的氟马西尼进行全身治疗，并通过每日腹腔注射给药 13 天。使用 Morris 水迷宫（MWM）测试来测量找到水下平台的潜伏期，并比较实验组和对照组动物的结果。我们证明了在药物治疗的动物中，MWM 表现有显著的剂量依赖性改善。这是第一项研究表明氟马西尼在减少创伤性脑损伤后认知缺陷方面的有效性，我们提出这些作用可能与 GABA(A)受体的调节有关。
