PATHOPHYSIOLOGY OF BRAIN PH REGULATION

大脑 PH 调节的病理生理学

• 批准号: 2038175
• 负责人: MITCHELL CHESLER
• 金额: $ 22.17万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-03-01 至 2001-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2038175
• 关键词: acidity /alkalinity; astrocytes; bicarbonates; brain metabolism; carbon dioxide; cerebral cortex; cerebral ischemia /hypoxia; homeostasis; hypercapnia; interstitial; laboratory rat; microspectrophotometry; tissue /cell culture; voltage /patch clamp

DESCRIPTION: (Adapted from Applicant's Abstract): The acid-base status of the brain has been shown to play a critical role in the manifestation of ischemic brain injury. Although modest reductions in the interstitial pH can mitigate insults, severe acidosis is associated with a significantly worse outcome. Astrocytes are thought to play an active role in the regulation of brain pH, and therefore the survival of these cells may be a determinant factor in the development of ischemic injuries. However, the role of astrocytes in ischemic acid-base disturbances is not understood. Under normal conditions, the intracellular pH of these cells undergoes rapid shifts in response to neuronal activity. This unique behavior has been attributed to a voltage-sensitive transport system that imports sodium and bicarbonate ions when the cells are depolarized. As a result, the pH of astrocyte cytoplasm rapidly increases while the interstitial compartment is acidified. In view of the voltage dependence of this transporter, it is likely to be an important contributor to the acid base status of cerebral ischemia, where membrane depolarization is extreme. This proposal will address the role of astrocyte Ph regulatory mechanisms in the context of cerebral ischemia. Studies will begin with the first complete description of interstitial acid base status in ischemic cortex, using recently developed methods for the simultaneous measurement of pH, carbon dioxide, bicarbonate and carbonate. These data will aid in the design of subsequent mechanistic studies, where factors faced by astrocytes in cerebral ischemia will be examined separately. Here, microspectrofluorometric and ion-selective microelectrode techniques will be combined in an in vitro investigation of astrocyte pathophysiology. Conclusions derived from in vitro studies will be compared against direct intracellular measurements obtained in vivo from ischemic rat cortex. These studies will elucidate the factors that govern brain Ph in cerebral ischemia. The results will therefore contribute to the understanding of the mechanisms of ischemic brain injury and the development of management strategies in the context of cardiac arrest and stroke.

描述：（改编自申请人的摘要）： 大脑已被证明在表现中起着关键作用 缺血性脑损伤。 虽然间隙pH的适度减少 可以减轻侮辱，严重的酸中毒与 结果更糟。 星形胶质细胞被认为在 调节脑pH，因此这些细胞的存活可能是 缺血性损伤发展的决定因素。 但是， 星形胶质细胞在缺血性酸碱障碍中的作用尚不清楚。 在正常条件下，这些细胞的细胞内pH迅速经历 响应神经元活性的转移。 这种独特的行为一直是 归因于对钠和进口钠和 当细胞去极化时，碳酸氢离子。 结果， 星形胶质细胞细胞质迅速增加，而间质室是 酸化。 鉴于该转运蛋白的电压依赖性，它是 可能是大脑酸碱状态的重要贡献者 缺血，其中膜去极化是极端的。 该提案将解决星形胶质细胞pH调节机制的作用 脑缺血的背景。 研究将从第一个开始 缺血性皮质中的间质酸碱状态的完整描述， 使用最近开发的方法来同时测量pH， 二氧化碳，碳酸氢盐和碳酸盐。 这些数据将有助于 随后的机械研究的设计，星形胶质细胞面临的因素 在脑缺血中将分别检查。 这里， 微光谱和离子选择性微电极技术将是 在体外研究星形胶质细胞病理生理学中结合在一起。 从体外研究得出的结论将与直接进行比较 从缺血大鼠皮质中在体内获得的细胞内测量。 这些 研究将阐明脑pH的因素 缺血。 因此，结果将有助于理解 缺血性脑损伤的机制和管理的发展 心脏骤停和中风的策略。