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PATHOPHYSIOLOGY OF BRAIN PH REGULATION

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
依托单位国家:
美国
项目类别:
财政年份:
1997
资助国家:
美国
项目状态:
已结题
起止时间:
1997-03-01 至 2001-02-28

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中文摘要
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英文摘要
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.
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ACID-BASE HOMEOSTASIS IN BRAIN INJURY
ACID-BASE HOMEOSTASIS IN BRAIN INJURY
ACID-BASE HOMEOSTASIS IN BRAIN INJURY
PATHOPHYSIOLOGY OF BRAIN PH REGULATION
国内基金
海外基金
Ascl1介导Wnt/beta-catenin通路在TLE海马硬化中反应性Astrocytes异常增生的作用及调控机制
  • 批准号:
    31760279
  • 项目类别:
    地区科学基金项目
  • 资助金额:
    35.0万元
  • 批准年份:
    2017
  • 负责人:
    丁银秀
  • 依托单位: