RESEARCH CENTER FOR CEREBRAL VASCULAR DISEASE

脑血管疾病研究中心

• 批准号: 3107458
• 负责人: MYRON DAVID GINSBERG
• 金额: $ 88.73万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1976
• 资助国家: 美国
• 起止时间: 1976-08-01 至 1990-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3107458
• 关键词: bioenergetics; brain circulation; brain metabolism; cerebral ischemia /hypoxia

The interaction of intra-ischemic and postischemic events in the pathogenesis of ischemic brain injury will be studied in a model of diffuse, high-grade, reversible cerebral hemispheral ischemia in the awake rat. Ischemia will be produced in rats with prior occlusions of the vertebral arteries by bilateral common carotid artery occlusions. This insult produces coma and an isoelectric electroencephalogram in most animals. Removal of the carotid ligatures permits cerebral recirculation. Autoradiographic methods of local cerebral blood flow (14C-iodoantipyrine) and local cerebral glucose utilization (14C-2-deoxyglucose) will be employed. These data will be correlated with regional patterns of ATP and pH alterations and with regional NADH fluorescence, using topographic, pictorial methods. Regional assessments of glycolytic and energy metabolites, indices of free radical reactions, brain water and ion homeostasis, blood-brain barrier function, and histopathological alterations will be performed. The effects of preischemic glucose administration and of postischemic hypertension and hyperoxygenation on the severity of ischemic injury will be assessed. These studies will define regionally heterogeneous patterns of ischemic brain injury and will serve to clarify the contributions of events during ischemia and of postischemic factors in producing these lesions. The results will provide data on the basis of which future studies of the efficacy of therapeutic agents in ameliorating brain ischemia may be carried out.

缺血与缺血后事件的相互作用在脑缺血发病机制中的作用 缺血性脑损伤的研究将在弥漫性，高级别， 清醒大鼠可逆性脑半球缺血。缺血将会是 大鼠双侧椎动脉闭塞模型 颈总动脉闭塞。这种侮辱会导致昏迷和等电 大多数动物的脑电。颈动脉结扎的移除允许 大脑再循环。局部脑血流的放射自显影方法 ~(14)C-安替比林)和局部脑葡萄糖利用(~(14)C-2-脱氧葡萄糖) 将会被雇佣。这些数据将与ATP的区域模式相关联 和pH变化以及区域NADH荧光，利用地形， 图画法。糖酵解和能量代谢物的区域评估， 自由基反应、脑水和离子动态平衡、血脑指标 屏障功能，并进行组织病理学改变。这个 缺血前给予葡萄糖对缺血后高血压的影响 并将评估高氧血症对缺血损伤的严重程度。这些 研究将确定局部不同类型的缺血性脑损伤 并将有助于澄清缺血期间事件的贡献和 造成这些损害的缺血后因素。结果将提供数据 在此基础上，未来对治疗药物疗效的研究 改善脑缺血可能是可行的。