CONTRIBUTION OF AMPA/KA RECEPTOR TO HYPOXIC NEURONAL INJURY IN VITRO

最近的证据表明，α-氨基-3-羟基-5-甲基-4- 异恶唑丙酸盐/红藻氨酸盐（AMPA/KA）型谷氨酸受体可 对缺氧缺血性损伤后的脑损伤有重要作用 in vivo. 拟议的实验将利用简化模型 皮质细胞培养体系暴露于氧-糖剥夺 讨论这一贡献的三个方面：1） AMPA/KA受体介导的对整体缺氧神经元死亡的损伤，以及 这种AMPA/KA受体介导的损伤与 缺氧NMDA受体介导的损伤; 2）AMPA/KA受体的作用 在介导缺氧诱导的死亡，特别是一个新发现的 皮质神经元亚群，可能表达大量的 AMPA/KA受体门控Ca 2+通道，因此可能特别是 易受AMPA/KA受体介导的损伤;以及3） 亚致死性氧糖剥夺对随后的神经元 GluR-2 mRNA的表达和功能性AMPA/KA受体门控Ca 2 + 渠道 这些研究应该产生关于AMPA/KA 受体可能介导缺氧性神经元死亡，这可能证明是有价值的， 指导制定有效的治疗策略， 减少这种形式的伤害，在疾病的设置，如中风或 心脏骤停

Recent evidence has suggested that alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionate/kainate (AMPA/KA) type glutamate receptors may contribute importantly to brain damage following hypoxic-ischemic insults in vivo. The proposed experiments will utilize the simplified model system of cortical cell cultures exposed to oxygen-glucose deprivation to address three aspects of this contribution: 1) the contribution of AMPA/KA receptor-mediated injury to overall hypoxic neuronal death, and the relationship between this AMPA/KA receptor-mediated injury and hypoxic NMDA receptor-mediated injury; 2) the role of AMPA/KA receptors in mediating the hypoxia-induced death specifically of a newly=discovered cortical neuronal subpopulation, that likely expresses large numbers of AMPA/KA receptor-gated Ca2+ channels, and hence may be especially vulnerable to AMPA/KA receptor-mediated injury; and 3) the effect of sublethal oxygen-glucose deprivation on the subsequent neuronal expression of GluR-2 mRNA and functional AMPA/KA receptor-gated Ca2+ channels. These studies should yield novel information about the way AMPA/KA receptors may mediate hypoxic neuronal death, which may prove valuable in guiding the developing of effective therapeutic strategies aimed at reducing this form of injury in disease settings such as stroke or cardiac arrest.