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DYNAMICS OF PH REGULATION IN NORMAL AND ISCHEMIC BRAIN

DYNAMICS OF PH REGULATION IN NORMAL AND ISCHEMIC BRAIN
正常和缺血大脑中 PH 调节的动态
批准号:
2270104
负责人:
MITCHELL CHESLER
金额:
$21.71万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1993
资助国家:
美国
项目状态:
已结题
起止时间:
1993-09-01 至 1997-08-31

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中文摘要
翻译
pH值的调节对大脑的正常运作至关重要, 因为许多通道和酶对细胞内的微小变化敏感, 氢离子浓度 酸碱状态可能特别 在脑损伤中很重要,它可以在脑损伤中发挥决定性作用。 脑损伤的表现和功能的恢复。 正常和 病理性电活动已经显示出引起大的变化 在pH值,足以影响大脑生理。 这些 细胞外和细胞内的pH值的变化, 在神经元和神经胶质细胞的机制,因此显示显着 区域异质性和刻板的发展模式。期间 脑缺血时,这些酸碱通量会变得非常大, 可能因此影响导致次生组织形成的过程 损伤 本研究的目的是阐明 控制成熟和发育中大脑的pH动态行为, 确定正常情况下酸碱变化的功能相关性 和缺血性疾病。 通过研究pH值, 系统、区域和细胞层面的动态。 因此,委员会认为, 实验将使用麻醉大鼠、脑切片和 分离的单细胞。 对整个动物的病理生理学研究将 在局部缺血期间进行,重点是梗死边缘, 已知该区域经历严重的电生理紊乱。 前所未有的解决酸碱状态将提供新的 微电极技术,允许第一次实时测定 pH值,碳酸氢盐和二氧化碳在细胞外空间的 个脑袋 这些研究将提供新的见解的功能和 发展作用pH值,并将增加关键细节,我们的理解 氢离子如何影响中风后的结果和恢复, 围产期缺氧和心脏骤停
英文摘要
The regulation of pH is critical for the normal operation of the brain, as numerous channels and enzymes are sensitive to small shifts in hydrogen ion concentration. Acid base status can be particularly important in brain injury, where it can play a determinant role in the manifestation of brain damage and the recovery of function. Normal and pathological electrical activity have been shown to cause large changes in pH, of sufficient magnitude to influence brain physiology. These extracellular and intracellular pH shifts arise from specialized mechanisms in both neurons and glia, and therefore display marked regional heterogeneity, and stereotyped developmental patterns. During brain ischemia, these acid base fluxes can become extremely large, and may therefore influence the processes which lead to secondary tissue injury. The objective of this study is to elucidate the mechanisms which govern the dynamic behavior of pH in mature and developing brain, and to determine the functional relevance of the acid-base shifts under normal and ischemic conditions. The broad aim will be addressed by studying pH dynamics at the systems, regional and cellular levels. Accordingly, experiments will be conducted using anesthetized rats, brain slices, and isolated single cells. Pathophysiological studies on whole animals will be performed during focal ischemia, with emphasis on the infarct rim, a region known to undergo severe electrophysiological disturbances. Unprecedented resolution of acid base status will be provided by new microelectrode techniques, allowing the first real-time determination of pH, bicarbonate, and carbon dioxide in the extracellular space of the brain. These studies will provide new insights into the functional and developmental role pH, and will add critical detail to our understanding of how hydrogen ions affect outcome and recovery, following, stroke, perinatal hypoxia, and cardiac arrest.
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