RNA IN POSTISCHEMIC BRAIN

缺血后大脑中的 RNA

• 批准号: 2265952
• 负责人: KUSUM KUMAR
• 金额: $ 9.96万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-08-01 至 1996-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2265952
• 关键词: actins; antioxidants; autoradiography; carotid artery; caudate nucleus; cell death; cerebral cortex; cerebral ischemia /hypoxia; cerebrovascular occlusions; deferoxamine; free radical oxygen; gene expression; gerbil /jird; hippocampus; in situ hybridization; messenger RNA; nervous system disorder diagnosis; neuroprotectants; northern blottings; nucleic acid probes; polyadenylate; protein biosynthesis; reperfusion; statistics /biometry; stress proteins; thalamus; tubulin; actins; antioxidants; autoradiography; carotid artery; caudate nucleus; cell death; cerebral cortex; cerebral ischemia /hypoxia; cerebrovascular occlusions; deferoxamine; free radical oxygen; gene expression; gerbil /jird; hippocampus; in situ hybridization; messenger RNA; nervous system disorder diagnosis; neuroprotectants; northern blottings; nucleic acid probes; polyadenylate; protein biosynthesis; reperfusion; statistics /biometry; stress proteins; thalamus; tubulin

Neurological outcome remains a major limiting factor in the quality of life following an ischemic insult to the brain; e.g., in stroke or after cardiac arrest and resuscitation. The differing susceptibility of various regions of the brain to ischemia is well known but the precise mechanisms are not clear. A critical factor leading to delayed irreversible neuronal death in selectively vulnerable regions of the brain is considered to be the prolonged inhibition of total protein synthesis. While the total protein synthesis is reduced, the expression of a family of heat shock proteins. (HSP) is actually enhanced in the postischemic brain during reperfusion. The mechanisms of these changes are not clear. Specifically, it is not understood whether there are regional differences in the expression of inducible heat shock proteins in the postischemic brain following reperfusion, and whether their induction helps to explain the resistance of certain neuronal populations to postischemic injury. The specific aims of this project are to characterize the time course of changes in mRNA expression of HSP-70 in comparison with that of alphatubulin, beta-actin, and poly A+ in various regions of differing susceptibility in the postischemic brain at various reperfusion periods. Ischemia will be produced in gerbils by bilateral common carotid artery occlusion for 10 min and will be followed by reperfusion for 0 min, 15 min, 1 h, 6 h, 1, 2, and 7 days. The expression of mRNA for HSP-70, alpha-tubulin, beta-actin, and Poly A+ will be localized & quantitated in specific cell types in hippocampus, cortex, caudate & thalamus of the brains of nonischemic controls and of postischemic gerbils with and without reperfusion, by in situ hybridization. Quantitation of the message will be performed by utilizing an image analyzer. The changes in mRNA will also be studied by Northern blot hybridization. Quantitative morphologic neuronal damage scores will also be obtained in selected regions of the brains and correlated with the changes in mRNA. Results obtained in the first 4 yrs of this study will provide a better understanding of the basic molecular changes in the neurons and will serve as a baseline for evaluating the efficacy of selected therapeutic agents in the 5th yr. Long term goal is to develop specific therapy for amelioration of ostischemic neurologic damage.

神经系统结果仍然是质量的主要限制因素 对大脑的缺血性侮辱之后的生活；例如，中风或 心脏骤停和复苏后。 不同的易感性 大脑到缺血的各个区域是众所周知的，但精确 机制尚不清楚。 导致延迟的关键因素 在有选择性的脆弱区域的不可逆神经元死亡 大脑被认为是对总蛋白的延长抑制 合成。 虽然总蛋白质合成降低，但表达 热休克蛋白家族。 （HSP）实际上在 再灌注过程中缺血后的大脑。 这些变化的机制 不清楚。 具体来说，尚不理解是否有 诱导热激蛋白表达的区域差异 在再灌注后的缺血后大脑中，他们是否是否 诱导有助于解释某些神经元种群的抵抗力 治疗后损伤。 该项目的具体目的是 表征HSP-70 mRNA表达的时间过程 与α-蛋白，β-肌动蛋白和poly A+的α-蛋白的比较 各种易感性不同的区域 再灌注期。 缺血将通过双侧共同颈动脉在沙鼠中产生 动脉阻塞10分钟，然后再灌注0 最小，15分钟，1 H，6 H，1、2和7天。 mRNA的表达 HSP-70，α-微管蛋白，β-肌动蛋白和Poly A+将被定位; 在海马，皮质，尾状＆的特定细胞类型中进行定量 非缺血对照和缺血后大脑的丘脑 通过原位杂交带有和没有再灌注的沙鼠。 消息的定量将通过使用图像来执行 分析仪。 北印迹还将研究mRNA的变化 杂交。 定量的形态神经元损伤评分也将 可以在大脑的选定区域获得 mRNA的变化。 在本研究的前4年中获得的结果将 更好地了解 神经元，将作为评估功效的基线 在第五年中选定的治疗剂。 长期目标是发展 改善骨质神经系统损害的特定疗法。