Electrochemical tools to measure local cerebral blood flow and metabolism

测量局部脑血流量和代谢的电化学工具

• 批准号: 8217549
• 负责人: Robert Mark Wightman
• 金额: $ 36.33万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-03-01 至 2017-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8217549
• 关键词: Acetylcholine; Adenosine; Astrocytes; Behavior; Behavioral Paradigm; Biogenic Amine Neurotransmitters; Biogenic Amines; Blood Pressure; Blood Vessels; Blood capillaries; Blood flow; Body Weight; Brain; Brain region; Caliber; Cerebrovascular Circulation; Chemicals; Coupled; Coupling; Dendrites; Dopamine; Dorsal; Electrodes; Ensure; Functional Magnetic Resonance Imaging; Glucose; Glutamates; Homeostasis; Human; Hydrogen; Hyperemia; Knowledge; Laboratories; Measurement; Measures; Metabolic; Metabolism; Methods; Microelectrodes; Migraine; Monitor; Motor Activity; Nerve; Neuroglia; Neurons; Neurotransmitters; Nitric Oxide; Nucleus Accumbens; Nutrient; Optics; Oxygen; Physiological; Play; Process; Rattus; Regulation; Research; Resolution; Rewards; Role; Self Stimulation; Serotonin; Signal Transduction; Site; Smooth Muscle; Spectrum Analysis; Substantia nigra structure; Sudden infant death syndrome; Surface; Synapses; Techniques; Testing; Time; Vasoconstrictor Agents; Vasodilation; Work; arteriole; base; brain tissue; capillary; dopaminergic neuron; extracellular; in vivo; meetings; millisecond; neuronal cell body; neurotransmission; relating to nervous system; sensor; tool

DESCRIPTION (provided by applicant): Electrochemical tools to measure local cerebral blood flow and metabolism The human brain comprises 2% of body weight and yet consumes 20% of the total energy to support the electrical activity in the brain. To meet this demand, cerebral blood flow (CBF) is coupled to changes in energy use. There are two primary control points. Blood vessels near the brain surface maintain blood pressure in a relatively constant range according to the physiological requirements. CBF is also locally regulated within brain tissue at the level of the intraparenchymal microvessels, the subject of the proposed research. Microvessels spaced approximately 50 5m apart within brain tissue, are associated with smooth muscles that allow them to constrict and dilate, a process termed functional hyperemia. The chemical signaling that controls the capillaries' diameter primarily originates from astrocytes, glial cells that surround the blood vessels and also surround synapses. Neural activity activates astrocytes, which, in turn, secrete substances that trigger local vasodilation of capillaries. Here, we propose to test the role of serotonin (5-HT) on CBF in brain regions where it is present in high amounts. 5-HT is a potent vasoconstrictor, and its terminals are adjacent to arterioles and capillaries suggesting it can exert action directly on blood vessels or indirectly by activation of astrocytes. These actions are of importance because they have been suggested to be involved in migraine headaches and sudden infant death syndrome, and also to contribute to the signals observed in functional magnetic resonance imaging. My laboratory has developed several electrochemically based techniques for in vivo measurements of neurotransmitters as well as species governed by CBF such as O2 and pH. This proposal has 4 specific aims. 1. We will microfabricate an electrochemical probe of CBF based on the hydrogen clearance technique. This is necessary because the concentration of extracellular O2 is equal to the amount delivered by CBF less the amount consumed by ongoing metabolism. While extracellular O2 is readily measured with microelectrodes, to fully characterize functional hyperemia, a method to measure CBF is required. 2. We will test the hypothesis that 5-HT plays a unique role in the control of blood flow in select brain regions. Our primary target will be the substantia nigra, pars reticulata, a brain region with high 5-HT. 3. We will test the hypothesis that extracellular O2 in the nucleus accumbens core (NAc) fluctuates during reward based activity. Measurements will be made in the freely moving rats during intracranial self-stimulation while monitoring oxygen and biogenic amine neurotransmitters. 4. We will test the hypothesis that extracellular O2 changes in the substantia nigra during ICSS. This region contains the dendrites of dopamine neurons and is involved in the regulation of locomotor activity. We will make chemical measurements of O2 and 5-HT and electrophysiological measurements of GABAergic neurons in this region with the same electrode during ICSS. PUBLIC HEALTH RELEVANCE: Project Narrative: New devices employing electrochemical principles will be devised to measure blood flow in the brain as well as extracellular oxygen levels. These tools will be used to monitor oxygen regulation during reward based behaviors.

描述（由申请人提供）：测量局部脑血流和代谢的电化学工具人脑占体重的2%，但消耗总能量的20%来支持脑中的电活动。 为了满足这一需求，脑血流量（CBF）与能量使用的变化相结合。 有两个主要控制点。 脑表面附近的血管根据生理需要将血压维持在相对恒定的范围内。 CBF也在脑组织内的实质内微血管水平上局部调节，这是拟议研究的主题。 脑组织内的微血管间隔约50 - 5 m，与平滑肌相关，允许它们收缩和扩张，这一过程称为功能性充血。 控制毛细血管直径的化学信号主要来自星形胶质细胞，即围绕血管和突触的神经胶质细胞。 神经活动激活星形胶质细胞，星形胶质细胞反过来分泌触发毛细血管局部血管舒张的物质。 在这里，我们建议测试的作用，5-羟色胺（5-HT）对CBF在大脑区域，它是目前在高金额。 5-HT是一种强有力的血管收缩剂，其终末与小动脉和毛细血管相邻，表明它可以直接或间接地通过激活星形胶质细胞对血管施加作用。 这些作用很重要，因为它们被认为与偏头痛和婴儿猝死综合征有关，也有助于功能性磁共振成像中观察到的信号。 我的实验室已经开发了几种基于电化学的技术，用于在体内测量神经递质以及由CBF控制的物种，如O2和pH。 1. 我们将以氢清除技术为基础，微制作一个脑血流的电化学探针。 这是必要的，因为细胞外O2的浓度等于CBF输送的量减去正在进行的代谢消耗的量。 虽然细胞外O2很容易用微电极测量，但为了充分表征功能性充血，需要测量CBF的方法。 2. 我们将测试的假设，即5-羟色胺发挥了独特的作用，在控制血液流动的选择大脑区域。 我们的主要目标是黑质网状部，一个5-HT含量高的大脑区域。 3. 我们将测试的假设，即细胞外O2在神经核的核心（NAc）波动在奖励为基础的活动。 将在颅内自我刺激期间对自由活动大鼠进行测量，同时监测氧和生物胺神经递质。 4. 我们将测试的假设，细胞外O2的变化在黑质ICSS。 该区域包含多巴胺神经元的树突，并参与运动活动的调节。 在ICSS过程中，我们将用同一电极对该区域的O2和5-HT进行化学测量，并对GABA能神经元进行电生理测量。 公共卫生相关性： 项目叙述：采用电化学原理的新装置将被设计来测量大脑中的血流量以及细胞外的氧气水平。 这些工具将用于在基于奖励的行为期间监测氧气调节。