Glutamate Neurotoxicity and Effect of Antagonists —In Vitro Study using Hippocampal Neurons Exposed to Hypoxia
Roles of glutamate in various pathological situations are suggested, though it is an physiological neurotransmitter. Studies using in vivo microdialysis technique showed rapid increase of extracellular glutamate concentration during the ischemic period in models of transient global ischemia, but it declined also rapidly after recirculation (Benveniste et al., 1984; Hagberg et al., 1985). Therefore slowly ongoing neuronal injury such as delayed neuronal loss is difficultly explained by elevated glutamate concentration during the ischemic period. We speculated that neurons might become more vulnerable to glutamate after exposure to ischemia and they might be thereafter injured by lower amount of glutamate. We intended to evaluate possible changes of glutamate neurotoxicity induced by subcritical hypoxia in vitro. We indeed confirmed increased sensitivity to glutamate after subcritical hypoxia(Kohmura et al., 1990). In this paper specific agonists and antagonists for the glutamate receptor subtypes were tested in order to evaluate the underlying mechanism.
KeywordsNMDA Receptor Neuronal Loss AMPA Receptor Neuronal Injury Hypoxic Stress
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