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:
  • 金额:
    $ 1.22万
  • 依托单位:
  • 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.
短暂性脑缺血后细胞外液兴奋性氨基酸(EAA)和神经细胞内Ca^2+水平升高可能在神经细胞损伤的发生中起重要作用。本研究旨在探讨兴奋性氨基酸(EAA)受体拮抗剂、Ca^<2+>通道阻滞剂和巴比妥类药物对缺血性脑细胞损伤的影响。实验组于颈动脉阻断前15 min腹腔注射戊巴比妥钠30 mg/kg,氯胺酮10 mg/kg,贝尼地平10、30、50 mg/kg,MK 801 4 mg/kg。一组缺血后立即给予NBQX 60 mg/kg。戊巴比妥钠组观察缺血5 min对心肌细胞的影响。在缺血期间,将脑温保持在37 ℃,连续严格监测脑温和直肠温。1周后取脑,光镜下观察海马CA 1区细胞损伤程度。结果:对照组CA 1细胞损伤程度与常规缺血方法缺血5 min时相当。药物组中仅缺血前给予戊巴比妥钠、缺血后给予NBQX组效果明显优于对照组。讨论:巴比妥酸盐预处理对缺血性细胞损伤有益,这一点已被熟知,并在我们的研究中得到证实。AMPA受体拮抗剂NBQX也有保护作用,但电压敏感性Ca^2+通道阻断剂贝尼地平和NMDA受体拮抗剂MK 801对缺血时脑细胞的保护不利。这表明AMPA受体在缺血性脑细胞损伤过程中的重要性。

项目成果

期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Yasushi Andou: "Re-evaluation of ischemia-induced neuronal damage in hippocampal regions in the normothermic gerbil" Acta Neuropathologica. 85. 10-14 (1992)
安藤靖 (Yasushi Andou):“重新评估常温沙鼠海马区缺血引起的神经元损伤”《神经病理学报》。
  • DOI:
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    0
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  • 通讯作者:
Yasushi Andou: "Re-evaluation of ischemia-induced neuronal damage in hippocampal regions in the normothermic gerbil" Acta Neuropathologica. Vol.85. 10-14 (1992)
安藤靖 (Yasushi Andou):“重新评估常温沙鼠海马区缺血引起的神经元损伤”《神经病理学报》。
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ARAI Tatsuru其他文献

ARAI Tatsuru的其他文献

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{{ truncateString('ARAI Tatsuru', 18)}}的其他基金

The pathophysiology and treatment of postischemic hypoperfusion after complete cerebral ischemia
完全性脑缺血后缺血后低灌注的病理生理学及治疗
  • 批准号:
    63570728
  • 财政年份:
    1988
  • 资助金额:
    $ 1.22万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)
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