BIOCHEMICAL EVOLUTION OF ISCHEMIC BRAIN DAMAGE

缺血性脑损伤的生化演变

• 批准号: 3396869
• 负责人: FRANK A WELSH
• 金额: $ 13.03万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1980
• 资助国家: 美国
• 起止时间: 1980-07-01 至 1989-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3396869
• 关键词: acidosis; biochemical evolution; bioenergetics; brain metabolism; cerebral ischemia /hypoxia; enzyme mechanism; glucose; histochemistry /cytochemistry; laboratory mouse; lactates; neurochemistry; nicotinamide adenine dinucleotide

The objective of this proposal is to identify biochemical alterations that play a critical role in ischemic brain damage. Our primary effort is directed at the role of lactacidosis in cellular damage. We hypothesize that there is a sharp threshold for brain pH (and/or lactate), at which restoration of high-energy phosphates is prevented even if the tissue is reperfused. Thus, the specific aims of this proposal are (i) to determine whether such a threshold exists by correlating tissue pH and lactate directly with energy state, (ii) to quantitate the critical levels of pH and lactate in various regions of brain, (iii) to determine the metabolic sites of inhibition using measurements of tissue metabolites and enzyme activities, and (iv) to modify the threshold level of lactacidosis by restricting lactate production and by increasing the buffer capacity of the tissue. Two models of focal ischemia in mouse brain will be employed: first, occlusion of the middle cerebral artery and second, occlusion of one carotid artery combined with systemic hypoxia. Both of these models have been developed and characterized in our laboratory and are suitable for the investigation of transient focal ischemia and extended recovery (1 week). Regional alterations of metabolite levels, pH (using the creatine kinase equilibrium), and tissue enzymes will be determined in microscopic samples (10-50 ng) using quantitative microchemical techniques in freeze-dried tissue. Further, the biochemical alterations will be correlated directly with histologic change in adjacent sections of frozen brain. Finally, exogenous agents, such as Tris buffer or dichloroacetate, will be used to modify the ischemic lactacidosis.

这项提议的目的是确定生化变化

项目成果

Effect of glucose on recovery of energy metabolism following hypoxia-oligemia in mouse brain: dose-dependence and carbohydrate specificity.

葡萄糖对小鼠脑缺氧低血症后能量代谢恢复的影响：剂量依赖性和碳水化合物特异性。

• DOI: 10.1038/jcbfm.1983.75
• 发表时间: 1983
• 期刊: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
• 作者: Welsh,FA;Sims,RE;McKee,AE
• 通讯作者: McKee,AE

Columnar alterations of NADH fluorescence during hypoxia-ischemia in immature rat brain.

未成熟大鼠脑缺氧缺血期间 NADH 荧光的柱状变化。

• DOI: 10.1038/jcbfm.1982.22
• 发表时间: 1982
• 期刊: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
• 作者: Welsh,FA;Vannucci,RC;Brierley,JB
• 通讯作者: Brierley,JB