The role of amino acid neurotransmitters in focal cerebral ischemia

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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