DYNAMICS OF PH REGULATION IN NORMAL AND ISCHEMIC BRAIN

PH的调节对大脑的正常运作至关重要， 因为许多通道和酶对微小的变化很敏感 氢离子浓度。酸碱状态可能会特别 在脑损伤中很重要，在脑损伤中它可以起决定性作用 脑损伤和功能恢复的表现。正常和 病理性电活动已被证明会引起大的变化。 在pH值中，其大小足以影响大脑生理。这些 细胞外和细胞内的pH变化是由特殊的 在神经元和胶质细胞中的机制，因此显示出明显的 区域异质性，发展模式千篇一律。在.期间 脑缺血，这些酸碱通量可以变得非常大，并且 因此可能会影响导致次级组织的过程 受伤。这项研究的目的是阐明 控制成熟和发育中大脑的pH动态行为，并 确定正常情况下酸碱移位的功能相关性 和缺血状态。这一广泛的目标将通过研究pH来实现 系统、区域和细胞层面的动力学。因此， 实验将使用麻醉的大鼠、脑片和 分离的单个细胞。整个动物的病理生理学研究将 在局灶性缺血期间进行，重点是梗塞边缘，a 已知遭受严重电生理干扰的区域。 史无前例的酸碱状态解决方案将由新的 微电极技术，允许第一次实时检测 PH、碳酸氢盐和二氧化碳在细胞外空间的作用 大脑。这些研究将提供对功能和功能的新见解 发展的作用，并将增加关键细节，我们的理解 氢离子如何影响预后和康复，继而，中风， 围产期缺氧和心脏骤停。

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.