PATHOPHYSIOLOGY OF BRAIN PH REGULATION

描述：(改编自申请人摘要)：酸碱状态 大脑已被证明在脑部疾病的表现中起关键作用 缺血性脑损伤。尽管间质pH值略有下降 可以减轻侮辱，严重的酸中毒与显著相关 更糟糕的结果。星形胶质细胞被认为在 调节大脑的pH值，因此这些细胞的存活可能是一种 缺血性损伤发展中的决定性因素。然而， 星形胶质细胞在缺血性酸碱失衡中的作用尚不清楚。 在正常情况下，这些细胞的细胞内pH会迅速下降。 对神经元活动作出反应的变化。这一独特的行为一直是 归因于一个电压敏感的运输系统，它进口了钠和 当细胞去极化时，重碳酸盐离子。因此，水的酸碱度 星形胶质细胞胞浆迅速增加，而间质 酸化了。鉴于这种传送器的电压依赖性，它是 可能是导致脑组织酸碱状态的重要因素 缺血，膜去极化是极端的。 这项建议将解决星形胶质细胞Ph调节机制在 脑缺血的背景。研究将从第一个开始 缺血皮质间质酸碱状态的完整描述， 使用最近开发的同时测量pH的方法， 二氧化碳、碳酸氢盐和碳酸盐。这些数据将有助于 后续机制研究的设计，其中星形胶质细胞面临的因素 在脑缺血时将另行检查。这里, 显微荧光光谱和离子选择微电极技术将是 结合星形胶质细胞的体外病理生理学研究。 从体外研究得出的结论将与直接 缺血大鼠大脑皮质活体细胞内测量。这些 研究将阐明大脑中控制大脑Ph的因素 缺血症。因此，研究结果将有助于理解 缺血性脑损伤的机制及治疗进展 在心脏骤停和中风的背景下的战略。

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.