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The role of amino acid neurotransmitters in focal cerebral ischemia

氨基酸神经递质在局灶性脑缺血中的作用

基本信息

批准号：
63440054
负责人：
TAMURA Akira
金额：
$ 16.19万
依托单位：
Teikyo University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (A)
财政年份：
1988
资助国家：
日本
起止时间：
1988 至 1991
项目状态：
已结题

项目摘要

Recently, the potential role of neurotransmitters on ischemic neuronal injury has come to be widely realized. In particular, the role of excitatory amino acids neurotransmitters, such as glutamate and aspartate, atracts attention. In this study, we examined neuronal alterations in a chronic phase after focal cerebral damage, changes of neurotransmitters after ischemia, the effect of a non-competitive antagonist of excitatory amino acid receptor, MK-801, on focal cerebral ischemia model in rats, and behavioral changes after focal cerebral ischemia. In the neuropathological study, we particularly focused on the delayed changes in the ipsilateral thalamus and also those in the ipsilateral substantia nigra. In the rat MCA occlusion model, marked atrophic chenges were obserbed in the ipsilateral thalamus and also ipsilateral substantia nigra at 6 months following MCA occlusion. The degeneration and shrinkage of these areas on the ischemic side is most likely due to neurotransmitter-mediated … More cell death. These results show the delayed neuronal loss in the distant, non-ischemic areas after focal cerebral ischemia. These neuropatholocgical changes in the ipsilateral thalamus and substantia nigra initially found in the rat MCA occlusion model similarly occurred in clinical cases of cerebral infraction in the MCA territory. Secondary, we examined the effect of MK-801 on focal cerebral ischemia model. Consequently, the area of infraction in the cerebral cortex was significantly decreased in the treated group. The results show that the excitotoxic mechanism may be responsible for ischemic injury in the cortical neurons. Thirdly, we studied behavioral changes after focal cerebral ischemia in rats. The MCA-occluded animals showed a significant impairment of learning behavior compared to the sham-operated animals in the one trial passive avoidance response and also active avoidance response. In the active avoidance task, the the learning impairment closely correlated with tissue damage, although the correlation was not observed in the passive avoidance task. Less

近年来，神经递质在缺血性神经元损伤中的潜在作用已被广泛认识。特别是，兴奋性氨基酸神经递质，如谷氨酸和天冬氨酸的作用，引起了人们的注意。在本研究中，我们检测了局灶性脑损伤后慢性期神经元的改变，缺血后神经递质的变化，兴奋性氨基酸受体非竞争性拮抗剂MK-801对大鼠局灶性脑缺血模型的影响，以及局灶性脑缺血后的行为改变。在神经病理学研究中，我们特别关注了同侧丘脑和同侧黑质的延迟变化。在大鼠MCA闭塞模型中，在MCA闭塞6个月后，在同侧丘脑和同侧黑质中观察到明显的萎缩。缺血侧这些区域的退化和萎缩很可能是由于神经递质介导的…更多的细胞死亡。这些结果显示局灶性脑缺血后远端非缺血区域的延迟神经元损失。这些最初在大鼠MCA闭塞模型中发现的同侧丘脑和黑质的神经病理变化，同样出现在MCA区域脑梗死的临床病例中。其次，我们观察了MK-801对局灶性脑缺血模型的影响。因此，治疗组大脑皮层的梗死面积明显减少。结果表明，皮质神经元的缺血性损伤可能与兴奋毒性机制有关。第三，研究大鼠局灶性脑缺血后的行为变化。与假手术动物相比，mca闭塞动物在被动回避反应和主动回避反应中表现出明显的学习行为障碍。在主动回避任务中，学习障碍与组织损伤密切相关，而在被动回避任务中没有观察到相关。少