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: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=572708
• 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.

当一个人在阅读、听音乐或做任何其他活动时，大脑的一个区域是活跃的。大脑的这一激活区域需要来自血液的更多营养和氧气。为了调节这种与神经元活动相关的血液供应增加，这种现象被称为神经血管耦合，大脑使用复杂的机制。神经血管偶联的这些机制已经被研究了一个多世纪，许多来自神经元和星形胶质细胞的血管活性因子被认为与神经血管偶联有关。星形胶质细胞是一种特殊类型的脑细胞，它约占大脑的一半，但被认为在大脑过程中没有作用。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的神经元与血管联系起来，参与神经血管耦合。在目前的建议中，我们认为一氧化氮(NO)是神经元和星形胶质细胞在神经元刺激过程中产生的一种气体，通过作用于星形胶质细胞而诱导血管扩张。这个概念是非常创新的，因为它通常被认为是NO扩散到血管系统直接诱导血管扩张。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增加了星形胶质细胞中的钙，这是一种诱导血管扩张的机制。我们将利用分离的细胞和组织以及活体动物来研究NO对神经血管偶联的影响。分离的细胞和组织将允许在分子水平上了解机制，活的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。这一方法将使我们从分子相互作用到整个动物对神经血管调节有一个完整的理解。本提议的长期目标是加强我们对神经活动与血液流动的关系的理解。