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: 6112508
• 负责人: Dennis W Choi
• 金额: $ 14.01万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-02-01 至 2000-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6112508
• 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- 异恶唑丙酸/海人藻酸(AMPA/KA)型谷氨酸受体可能 对缺氧缺血性脑损伤有重要作用 在活体内。拟议的实验将使用简化的模型 缺氧缺糖条件下大脑皮层细胞培养体系 要解决这一贡献的三个方面：1) AMPA/KA受体介导的损伤导致整体缺氧性神经元死亡 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 在介导一种新发现的低氧诱导的死亡中 皮质神经元亚群，可能表达大量的 AMPA/KA受体门控的钙通道，因此可能是特别的 易受AMPA/KA受体介导的损伤；3) 亚致死性缺氧-葡萄糖剥夺对后续神经元的影响 Glur-2基因表达与功能性AMPA/KA受体门控钙离子 频道。 这些研究应该会产生关于AMPA/KA途径的新信息 受体可能介导缺氧性神经元死亡，这可能被证明是有价值的 指导制定有效的治疗策略，旨在 减少疾病环境中的这种形式的伤害，如中风或 心脏骤停。