RESEARCH CENTER FOR CEREBRAL VASCULAR DISEASE

脑血管疾病研究中心

• 批准号: 3099244
• 负责人: MYRON DAVID GINSBERG
• 金额: $ 101.69万
• 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/3099244
• 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.

缺血内和缺血后事件在脑缺血发病机制中的相互作用 缺血性脑损伤将在弥漫性，高级别， 可逆性大脑半球缺血清醒大鼠。 缺血将是 产生于双侧椎动脉闭塞的大鼠 颈总动脉闭塞 这种损伤产生昏迷和等电位 大多数动物的脑电图。 移除颈动脉结扎线 大脑再循环 局部脑血流的放射自显影方法 （14 C-碘安替比林）和局部脑葡萄糖利用（14 C-2-脱氧葡萄糖） 将被雇用。 这些数据将与ATP的区域模式相关联 和pH值的变化，并与区域NADH荧光，使用地形， 图像方法。 糖酵解和能量代谢物的区域评估， 自由基反应指数、脑水和离子稳态、血脑 屏障功能和组织病理学改变。 的 缺血前葡萄糖给药和缺血后高血压的影响 和过度氧合对缺血性损伤严重性的影响。 这些 研究将确定缺血性脑损伤的区域异质性模式 并将有助于阐明缺血期间事件的作用和 缺血后因素在产生这些病变。 结果将提供数据 在此基础上，未来对治疗剂在 可以改善脑缺血。