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

AMPA/KA 受体对体外缺氧神经元损伤的作用

• 批准号: 6243801
• 负责人: Dennis W Choi
• 金额: $ 12.96万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-02-01 至 1998-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6243801
• 关键词: NMDA receptors; calcium channel; cell death; cerebral ischemia /hypoxia; cobalt; excitatory aminoacid; glutamate receptor; in situ hybridization; inhibitor /antagonist; kainate; laboratory mouse; neurotoxins; polymerase chain reaction; receptor expression; single cell analysis; tissue /cell culture; voltage /patch clamp

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.

最近的证据表明，α-氨基-3-羟基-5-甲基-4-- 异恶唑署/海藻酸盐（AMPA/KA）型谷氨酸受体可能 在缺氧缺血性损伤后对脑损伤重要重要 体内。 提出的实验将利用简化的模型 暴露于氧气葡萄糖剥夺的皮质细胞培养系统 解决此贡献的三个方面：1） AMPA/KA受体介导的整体缺氧神经元死亡的损伤， 此AMPA/KA受体介导的损伤与 低氧NMDA受体介导的损伤； 2）AMPA/KA受体的作用 在介导缺氧引起的死亡时，特别是发现了 皮质神经元亚群，可能表达大量 AMPA/KA受体门控Ca2+通道，因此尤其是 容易受到AMPA/KA受体介导的损伤； 3） 在随后的神经元上缺乏氧气葡萄糖 GLUR-2 mRNA和功能性AMPA/KA受体门控Ca2+的表达 频道。 这些研究应产生有关AMPA/KA方式的新信息 受体可能介导缺氧神经元死亡，这可能证明是有价值的 指导制定旨在的有效治疗策略 在中风或 心脏停搏。