Signals and targets underlying mechanisms for neurovascular coupling in the brain

大脑神经血管耦合的信号和目标潜在机制

• 批准号: 8059688
• 负责人: JESSICA A FILOSA
• 金额: $ 29.4万
• 依托单位: AUGUSTA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8059688
• 关键词: Acids; Address; Affect; Astrocytes; Blood Vessels; Brain; Calcium; Calcium-Activated Potassium Channel; Cells; Cerebral cortex; Cerebrovascular Circulation; Cerebrum; Chronic; Communication; Coupling; Disease; Event; Glucose; Glutamates; Health; Hyperemia; Hypertension; Ions; Learning; Light; Link; Mediating; Mediator of activation protein; Metabolic; Microcirculation; Migraine; Muscle Cells; Nature; Neuroglia; Neurons; Neurotransmitters; Oxygen; Pathology; Pattern; Physiological; Potassium; Potassium Channel; Preparation; Process; Production; Property; Rattus; Research Personnel; Signal Pathway; Signal Transduction; Slice; Smooth Muscle Myocytes; Stroke; Synapses; Vasodilation; Vasodilator Agents; Work; arteriole; cell type; extracellular; gamma-Aminobutyric Acid; innovation; insight; intercellular communication; large-conductance calcium-activated potassium channels; multidisciplinary; neurovascular unit; programs; relating to nervous system; response; spreading depression; vasoconstriction

The main focus of this study is to characterize the cellular mechanisms underlying functional hyperemia in the cerebral cortex. Functional hyperemia occus as a function of the communication between neurons, astrocytes and the cerebral microcirculation. Disturbances in the signaling pathways leading to the proper hyperemic response have been linked to a number of pathologies including hypertension, stroke, migraine, and spreading depression, to mention a few. Although functional hyperemia occurs within seconds, the underlying mechanisms mediating such rapid signaling response are still to be defined. This project will address three major aims: First, to determine if astrocytes are intermediaries in neurovascular coupling (Aim 1). Second, to determine if the mechanism by which astrocytes communicate with parenchymal arterioles, to induce vasodilation, results from the rapid activation of Ca2+-activated K+ (BK) channels and the release of K+ into the narrow space between the astrocytic endfoot and vascular cells. Also to determine if epoxyeicosatrienoic acids contribute to the activation of BK channels in the astrocytic endfeet amplifying the signaling communication between astrocytes and blood vessels (Aim 2). Third, to determine if both functional and structural alterations occur in the neurovascular unit during hypertension (Aim 3). We hypothesize that following neuronal stimulation, the rise in intracellular Ca2+ in the astrocytes activated BK channels in astrocytic endfeet resulting in the rapid release of K+ (a strong vasodilator) in the space between the endfoot and the vascular cells. The rise in Ca2+ also increases the production of epoxyeicosatrienoic acids which act on BK channels in the astrocytic endfeet further activating these channels. Because functional and anatomical changes in neurons, asttrocytes and parenchymal arterioles are linked to one another, an understanding of the modes of communication within the neural-glial-vascular network under physiological conditions will provide insights on pathologies, such as hypertension, which affect one or more of these three cellular components constituting the neurovascular unit.

本研究的主要重点是表征功能性充血的细胞机制