Resilient versus fragile aspects of blood flow in the mammalian brain

哺乳动物大脑血流的弹性与脆弱性

• 批准号: 10318944
• 负责人: David Kleinfeld
• 金额: $ 89.12万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-12-01 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10318944
• 关键词: Affect; Area; Beds; Behavior; Biophysics; Blood; Blood Vessels; Blood capillaries; Blood flow; Brain; Caliber; Cerebrovascular system; Contralateral; Distant; Frequencies; General Practitioners; Goals; Hippocampus (Brain); Image; Immunity; Impaired cognition; Individual; Ischemia; Magnetism; Measures; Nature; Neurons; Pathway interactions; Pattern; Phase; Physiology; Principal Investigator; Resistance; Sensory; Signal Transduction; Stimulus; Stroke; Surface; Technology; Testing; Training; Ursidae Family; Vascular blood supply; Vasodilation; Work; arteriole; awake; design; experimental study; neurotransmission; neurovascular; next generation; programs; relating to nervous system; response; vasoconstriction; vasomotion

Principal Investigator (Last, first, middle): KLEINFELD, DAVID We propose to advance our understanding of the key factors involved in the distribution of blood within the brain. Our focus begins with the relation of flow dynamics to the topology of the underlying angioachitecture. In cortex, a highly interconnected network of surface vessels and a network of subsurface vasculature were shown to be effective in distributing blood and in providing a robust immunity to occlusions. In contrast, the penetrating arterioles that shuttle blood from the cortical surface to the underlying microvessels were shown to be a bottleneck to the supply of blood within the brain and a locus for cognitive decline after a microstroke. We will determine if other brain areas follow the same vascular plan or rather have a different set of design rules. Our initial emphasis is on hippocampus, given the great sensitivity of hippocampal neurons to ischemia. While the topology of the vasculature is fixed, the diameter and thus the resistance to flow of individual can change. First, the diameter of brain blood vessels changes with vasomotion at a frequency of 0.1 Hz. It is not known if this slow signal phase-locks to vasomotion in a distant region or in the contralateral hemisphere that is also activated by a common stimulus. We will determine the effects of awake sensory stimulation on vasomotion along pathways over large regions of cortex. The finding of activity induced correlation of vasomotion should have implications as a basis for the functional connectivity derived by bold oxygenation level dependent (BOLD) functional magnetic resonant imaging (fMRI). A second aspect of neurovascular signaling concerns changes in diameter in arterioles and potentially microvascular capillaries in response to modulators released by stimulus-induced neural activity. The mechanism by which neural activity leads to both vasoconstriction and to vasodilation is a puzzle. We will determine the competitive nature of vasoactive signaling by concomitant measure of extrasynaptic modulator concentration and activation of specific neuronal subtypes in terms of their affects on changing blood flow through vasoconstriction or vasodilation. We note that all of the proposed experiments make use of a broad range of technologies, ranging from behavior to physiology to probes to imaging, and thus provide a fertile test bed for scientific discovery as well as a means to train the next generation of neuroscientists as generalists.

首席研究员（后、一、中）：大卫·克莱因菲尔德