Mechanisms underlying neurovascular coupling

神经血管耦合的机制

• 批准号: 355990-2013
• 负责人: Girouard, Hélène
• 金额: $ 1.82万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=595768
• 关键词: Mechanisms; underlying; neurovascular; coupling

A sector of the brain is active when a person is reading, listening to music, or doing any other activity. This activated region of the brain needs more nutrients and oxygen that come from the blood. To regulate this increase in blood supply associated with neuronal activity, a phenomenon called NEUROVASCULAR COUPLING, the brain uses complex mechanisms. These mechanisms underlying neurovascular coupling have been the subject of enquiry for more than a century, and numerous vasoactive factors derived from neurons and ASTROCYTES have been implicated in neurovascular coupling. Astrocytes are a specific type of brain cells which comprises about half the brain but were thought to play no role in brain processes. Recent important discoveries showed that astrocytes are involved in neurovascular coupling by linking, anatomically and functionally, the brain's neurons to blood vessels. In the present proposal, we HYPOTHETIZE that nitric oxide (NO), a gas derived from neurons and astrocytes during neuronal stimulation induces vasodilation by acting on astrocytes. This concept is very innovative because it is generally assumed that NO diffuses to the vasculature to directly induce a vasodilation. However, astrocytes are anatomically closer to the sites of NO release and our very exciting preliminary results showed that NO increases calcium in astrocytes, a mechanism that induces vasodilation. We will study the effect of NO on neurovascular coupling using isolated cells and tissues as well as living animals. The isolated cells and tissues will allow the understanding of mechanisms at the molecular level and the living animals will permit to verify the functional significance of the results we get from isolated cells or tissues. This approach will give an integrated understanding of neurovascular regulation from molecular interactions to the whole animal.The LONG-TERM GOAL of the present proposal is to enhance our understanding of how neural activity is related to blood flow.

当一个人阅读、听音乐或进行任何其他活动时，大脑的某个区域会处于活跃状态。大脑的这个激活区域需要更多来自血液的营养和氧气。为了调节与神经元活动相关的血液供应增加（一种称为神经血管耦合的现象），大脑使用复杂的机制。一个多世纪以来，神经血管耦合的这些机制一直是研究的主题，并且来自神经元和星形细胞的许多血管活性因子与神经血管耦合有关。星形胶质细胞是一种特殊类型的脑细胞，约占大脑的一半，但被认为在大脑过程中不起任何作用。最近的重要发现表明，星形胶质细胞通过在解剖学和功能上将大脑神经元与血管连接起来，参与神经血管耦合。在本提案中，我们假设一氧化氮（NO），一种在神经元刺激过程中源自神经元和星形胶质细胞的气体，通过作用于星形胶质细胞诱导血管舒张。这个概念非常创新，因为通常认为NO扩散到脉管系统直接引起血管舒张。然而，星形胶质细胞在解剖学上更接近 NO 释放的部位，我们非常令人兴奋的初步结果表明，NO 会增加星形胶质细胞中的钙，这是一种诱导血管舒张的机制。我们将使用分离的细胞和组织以及活体动物来研究 NO 对神经血管耦合的影响。分离的细胞和组织将允许我们在分子水平上理解机制，活体动物将允许验证我们从分离的细胞或组织获得的结果的功能意义。这种方法将提供对从分子相互作用到整个动物的神经血管调节的综合理解。本提案的长期目标是增强我们对神经活动如何与血流相关的理解。