The role of amino acid neurotransmitters in focal cerebral ischemia

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的作用，如谷氨酸和天冬氨酸，吸引了人们的注意。本研究观察了大鼠局灶性脑损伤后慢性期神经元的变化，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，以及大鼠局灶性脑缺血后的行为变化。在神经病理学研究中，我们特别关注同侧丘脑和同侧黑质的延迟性改变。在大鼠大脑中动脉闭塞模型中，大脑中动脉闭塞后6个月，同侧丘脑和黑质均出现明显的萎缩。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迟发性神经元丢失。最初在大鼠大脑中动脉闭塞模型中发现的同侧丘脑和黑质的这些神经病理改变在大脑中动脉区域的脑梗塞临床病例中类似地发生。其次，我们考察了MK-801对局灶性脑缺血模型的影响。结果，治疗组的大脑皮层梗塞面积显著减少。结果表明，兴奋性毒性机制可能与大脑皮层神经元的缺血性损伤有关。第三，我们研究了大鼠局灶性脑缺血后的行为变化。在一次性被动回避反应和主动回避反应中，大脑中动脉闭塞动物较假手术动物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这种相关性。较少

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