Ohno M, Yamamoto T, Ueki S, Watanabe S
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Neurosci Lett. 1992 Apr 13;138(1):1-4. doi: 10.1016/0304-3940(92)90458-j.
A 5-min period of cerebral ischemia increased the number of errors (attempts to pass through two incorrect panels of the three panel-gates at four choice points) assessed by the working memory procedure applied in a three-panel runway task. The selective and competitive N-methyl-D-aspartate (NMDA) receptor antagonist CGS 19755 (3.2 and 10 mg/kg), administered i.p. immediately after blood flow reperfusion, significantly reduced the increase in errors expected to occur 24 h after 5 min of ischemia. CGS 19755 10 mg/kg had no effect on the increase in errors when injected 6 h after ischemia. The i.p. administration of the non-competitive NMDA antagonists dextrorphan 10 and 32 mg/kg and MK-801 1.0 mg/kg immediately after reperfusion decreased the increase of errors in the ischemic rats. The protective effects of NMDA antagonists suggest that the mechanism mediated by NMDA receptors during the early reperfusion phase plays a pivotal role in the postischemic impairment of working memory.
5分钟的脑缺血增加了通过在三板跑道任务中应用的工作记忆程序评估的错误数量（在四个选择点尝试通过三个板门中的两个不正确板门）。选择性和竞争性N-甲基-D-天冬氨酸（NMDA）受体拮抗剂CGS 19755（3.2和10mg/kg），在血流再灌注后立即腹腔注射，显著减少了预计在5分钟缺血后24小时出现的错误增加。缺血6小时后注射CGS 19755 10mg/kg对错误增加没有影响。再灌注后立即腹腔注射非竞争性NMDA拮抗剂右啡烷10和32mg/kg以及MK-801 1.0mg/kg可减少缺血大鼠的错误增加。NMDA拮抗剂的保护作用表明，早期再灌注阶段由NMDA受体介导的机制在缺血后工作记忆损伤中起关键作用。
