MECHANISMS OF CEREBRAL MICROVASCULAR CONTROL

描述(改编自申请者摘要)：血管内血流 大脑具有动态的空间和时间控制特征。这个 区域神经元活动的不断变化模式和高 活跃神经元的能量需求需要能够 快速、精确地调节血液流动。实质 微血管是最终的脑血管要素，负责 满足这些需求；然而，这些需求通过的地方机制 人们对船舶的监管知之甚少。这个项目的总体目标是 应用程序是为了提高我们对地方机制如何在 脑实质在生理和心理状态下调节微血管功能 病理生理环境。在最初的支持期间 这项工作，我们有：1)开发和测试新的方法来检查 正常细胞微环境中的实质微血管，2) 确定了参与大脑调节的关键局部机制 微血管张力，以及3)开始检查微血管功能如何 在新陈代谢挑战期间受到干扰，如中风后。这个 这项建议的具体目标是：1)确定地方政府的作用 神经元和胶质细胞在实质微血管调节中的作用，2) 阐明微血管形成的病理生理机制 功能障碍。拟议的研究将提供对一个基本的 细胞间信号传递的一种形式，参与连接局部血液 流向大脑中的局部神经元活动。清醒地认识到 微血管控制的生理学和病理生理学将有助于识别 限制继发性脑缺血损伤的新策略。

DESCRIPTION (Adapted from Applicant's Abstract): Blood flow within the brain is characterized by dynamic spatial and temporal control. The constantly shifting patterns of regional neuronal activity and the high energy demands of active neurons necessitate local mechanisms capable of regulating blood flow in a rapid and precise manner. Parenchymal microvessels are the final cerebrovascular elements responsible for supplying these needs; however, the local mechanisms through which these vessels are regulated are poorly understood. The overall goal of this application is to improve our understanding of how local mechanisms within the brain parenchyma regulate microvascular function under physiological and pathophysiological circumstances. During the initial period of support for this work, we have: 1) developed and tested novel approaches for examining parenchymal microvessels within their normal cellular microenvironment, 2) identified key local mechanisms involved in the regulation of cerebral microvascular tone, and 3) begun to examine how microvascular function is disturbed during metabolic challenge such as occurs after stroke. The Specific Aims of this proposal are to: 1) characterize the roles of local neurons and glia in the regulation of parenchymal microvessels, and 2) elucidate pathophysiological mechanisms contributing to microvascular dysfunction. The proposed studies will provide insights into a fundamental form of intercellular signalling that is involved in coupling local blood flow to local neuronal activity in the brain. A clear understanding of the physiology nd pathophysiology of microvascular control will help identify novel strategies for limiting secondary ischemic injury to the brain.