MECHANISMS OF CEREBRAL MICROVASCULAR CONTROL

脑微血管控制机制

• 批准号: 2225478
• 负责人: KEVIN Scott LEE
• 金额: $ 18.96万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-12-01 至 1997-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2225478
• 关键词: Mammalia; brain circulation; brain electrical activity; cell cell interaction; cell communication molecule; electron microscopy; electrophysiology; excitatory aminoacid; hippocampus; histology; horseradish peroxidase; microcirculation; neural transmission; nitric oxide; paracrine; transmission electron microscopy; vascular smooth muscle nervous control; vasomotion; video microscopy

DESCRIPTION (Investigator's abstract): The regulation of blood flow within the brain is characterized by extraordinary precision and speed. The high energy demands of active neurons and the restricted patterns of neuronal activity necessitate accurate temporal and spatial control over the cerebral microvasculature. This highly specIfic control suggests the existence of neurovascular mechanisms which couple blood flow and neuronal activity. The central goal of this proposal will be to; identify cellular substrates and mechanisms of local neurovascular communication. Studies of local neurovascular communication within the brain have historically been hampered by the complexity of the neuropil; parenchymal vessels are quite small and are deeply embedded in a meshwork of neural and glial elements. We present here a newly-developed model system that permits the simultaneous analysis of neuronal and microvascular elements in deep brain structures. This system will be utilized to examine several fundamental issues of local neurovascular signalling. The studies proposed herein will: I) characterize the effects of various forms of local neuronal activity on regional microvessels, II) identify the structural substrates for local neurovascular communication, and III) evaluate the role of neuronally-derived signal molecules as synaptic and/or paracrine messengers in local neurovascular communication. The manner in which cerebral microvessels respond to changes in local neuronal activity is, at best poorly understood. The present proposal will provide important insights into local neurovascular communication and the mechanisms underlying this form of intercellular signalling. The results of the proposed studies will have significant clinical as well as theoretical implications. In addition to enhancing our comprehension of a fundamental CNS function, the findings will contribute to a basic understanding of how microvessels might participate in cerebral pathology. Disturbances in microvascular function are thought to participate in the pathophysiology of ischemia and head injury. In order to optimize the restoration of blood flow under these conditions, it will be necessary to identify strategies for manipulatIng parenchymal vessels. The hopes for achieving this goal will ultimately depend on a clear understanding of how local neurovascular control is achieved. The current proposal will provide a critical foundation for this effort.

描述(研究人员摘要)：血流的调节 大脑内部的特征是非凡的精确度和速度。 激活神经元的高能量需求和限制性模式 神经元的活动需要精确的时间和空间控制 通过脑微血管系统。这种高度特定的控制 暗示了神经血管机制的存在 流量和神经元活动。这项提案的中心目标将是 确定局部神经血管的细胞底物和机制 沟通。 对大脑内局部神经血管通讯的研究已经 在历史上被神经纤维的复杂性所阻碍的；实质的 血管很小，深深地嵌入在神经网络中 和神经胶质成分。我们在这里介绍一个新开发的模型系统，它 允许同时分析神经元和微血管成分 在大脑的深层结构中。该系统将被用来检查 局部神经血管信号的几个基本问题。这个 这里提出的研究将：i)表征各种不同的 局部微血管上局部神经元活动的形式，II)识别 局部神经血管通讯的结构底物，以及 三)评估神经来源的信号分子的作用 局部神经血管中的突触和/或旁分泌信使 沟通。 脑微血管对局部血管改变的反应方式 充其量，人们对神经元的活动知之甚少。目前的建议 将为局部神经血管沟通提供重要的见解 以及这种形式的细胞间信号传递背后的机制。这个 拟议的研究结果也将具有重要的临床意义。 作为理论上的暗示。除了提高我们的理解 对于中枢神经系统的基本功能，这一发现将有助于 对微血管如何参与大脑的理解 病理学。微血管功能障碍被认为是 参与脑缺血和脑损伤的病理生理学研究。按顺序 为了在这种情况下优化血流的恢复，它 将有必要确定操纵实质的策略 船只。实现这一目标的希望最终将取决于 清楚地了解局部神经血管控制是如何实现的。这个 目前的提案将为这一努力提供重要的基础。