Effects of Excitatory Amino Acid Antagonists and Calcium Channel Blockers in the Treatment of Ischemic Brain Injury

兴奋性氨基酸拮抗剂和钙通道阻滞剂治疗缺血性脑损伤的作用

基本信息

批准号：
03670729
负责人：
ARAI Tatsuru
金额：
$ 1.22万
依托单位：
Ehime University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

项目摘要

Increase in the levels of excitatory amino acid (EAA) in extracellular fluid and Ca^<2+> in neuronal cell may be playing an important role in the occurrence of neuronal cell injury after transient brain ischemia. This study was carried out to deter-mine the effects of EAA receptor antagonist, Ca^<2+> channel blocker and barbiturate on the process of brain cell injury after ischemia.Materials and Methods: Fifty-three Mongolian gerbils were divided into 3 groups, sham, control and experimental. In experimental group one of following drugs was administered intraperitoneally 15 min before 3 min of forebrain ischemia by carotid occlusion; Pentobarbital 30 mg/kg, Ketamine 10 mg/kg, Benidipine 10, 30 and 50 micg/kg and MK801 4 mg/kg. NBQX 60 mg/kg was given immediately after ischemia in one group. In Pentobarbital group influences of 5 min ischemia was studied as well. During the ischemia brain temperature was kept at 37ﾟC strictly monitoring brain and rectal temperatures continuously. The brains were excised 1 week later and the grade of injury of hippocampal CA1 cells were examined microscopically. Results: In the control group CA1 cell injury as severe as in 5 min ischemia with ordinary ischemia method was observed. The groups in which Pentobarbital was given before ischemia and NBQX after ischemia were the only ones in the drug groups, which had significantly better results than control group. Discussion: That pretreatment with barbiturate is beneficial for ischemic cell injury has been well known and is confirmed in our study. Beneficial effect of NBQX, the AMPA receptor antagonist, was demonstrated as well but Benidipine, the voltage sensitive Ca^<2+> channel blocker, and MK801, the NMDA receptor antagonist, were not beneficial for the preservation of brain cells during ischemia. This indicates the importance of AMPA receptor in the process of ischemic brain cell injury.

神经元细胞中细胞外液和CA^<2+>中兴奋性氨基酸（EAA）水平的增加可能在短暂性脑缺血后神经元细胞损伤的发生中起重要作用。进行这项研究是为了确定EAA受体拮抗剂，Ca^<2+>通道阻滞剂的影响，并在缺血后对脑细胞损伤过程进行巴比妥酸盐。材料和方法：五十三个蒙古语的蒙古语被分为3组，Sham，Sham，对照和实验。在实验组中，以下药物在前脑缺血3分钟之前通过颈动脉闭塞在腹膜内进行15分钟。戊巴比妥30 mg/kg，氯胺酮10 mg/kg，贝尼迪平10、30和50 micg/kg和mk801 4 mg/kg。一组缺血后立即给予NBQX 60 mg/kg。在五骨组的影响中，还研究了5分钟的缺血。在缺血期间，将大脑温度保持在37℃下严格监测大脑和直肠温度。大脑在1周后表现出色，并在显微镜下检查海马CA1细胞的损伤等级。结果：在对照组的CA1细胞损伤中，与普通缺血法的5分钟缺血中一样严重。缺血之前和NBQX在缺血之前给出的五仅的组是药物组中唯一的五核病患者，其结果明显好于对照组。讨论：巴比妥酸盐预处理对缺血性细胞损伤是有益的，在我们的研究中得到了证实。也证明了NBQX（AMPA受体拮抗剂）的有益作用，但贝尼迪平（Benidipine），电压敏感的Ca^<2+>通道阻滞剂和NMDA受体拮抗剂MK801对缺血期间的脑细胞保存无益。这表明AMPA受体在缺血性脑细胞损伤过程中的重要性。