CELLULAR BIOLOGY OF BRAIN MICROVESSELS

脑微血管的细胞生物学

• 批准号: 3349641
• 负责人: SAMI I HARIK
• 金额: $ 20.67万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-09-30 至 1993-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3349641
• 关键词: Cercopithecidae; adenosine; adenosinetriphosphatase; angiotensin II; arginine vasopressin; basement membrane; blood brain barrier; brain circulation; carbonate dehydratase; cardiovascular pharmacology; cell membrane; electron microscopy; endoplasmic reticulum; enzyme mechanism; gel electrophoresis; glucose; glucose receptor; histochemistry /cytochemistry; homeostasis; immunochemistry; innervation; ionophores; laboratory rabbit; laboratory rat; methylphenyltetrahydropyridine; microcirculation; neurochemistry; neuropeptides; neurotoxins; neurotransmitter receptor; positron emission tomography; radioassay; radiotracer; sodium potassium exchanging ATPase; swine; transport proteins; vasoactive intestinal peptide

The goals of this proposal are to continue studies of the cellular mechanisms that underlie the complex functions of the brain circulation, and how this circulation is controlled to meet the changing and fastidious requirements of the brain. The endothelial cells of brain microvessels stand at the interface between the systemic circulation and nervous tissue and have a viral role in maintaining a stable environment for neuronal function and in preventing the entry of toxic substances into the brain. To accomplish this, the brain capillary endothelium is endowed with unique features, such as tight intercellular junctions, transporters for essential water-soluble molecules such as glucose and amino acids, and enzyme system that can effectively prevent the entry of some lipid-soluble toxins from blood to brain. The proposed experiments with employ complimentary biochemical, pharmacological, and ultrastructural techniques to study the brain microcirculation in vivo, and in preparations enriched with isolated microvessels, in vitro. The experiments will address the following subjects: (1) Receptors for peptide neurotransmitters and neuromodulators will be assessed in brain macro- and microvessels, and the mechanisms by which these agents mediate their effects will be investiagated. (2) Studies of the biochemical aspects of the blood-brain barrier that related to systemic 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) neurotoxicity. (3) To induce enzymes in brain microvessels that can metabolize MPTP, its analogs and other putative neurotoxins. (4) Synthesis of 18F-labeled MPTP analogs for use in investigating the neurobiology of MPTP toxicity by positron emission tomography. (5) Ultrastructural investigation of heterogenieties in the distribution of the glucose transporter and Na+,K+-ATPase in different brain regions and within the microvascular unit, by immunocytochemical methods. (6) Biochemical cellular and subcellular fractionation studies of brain microvessels. Better understanding of how the brain circulation functions may be prerequisite for appreciating the pathophysiology of this circulation. The proposed research may provide scientific bases for rational therapy of cerebrovascular disorders, metabolic encephalopathies and neurodegenerative disorders such as Parkinson's Disease.

这项建议的目标是继续研究细胞的 大脑复杂功能的基础机制 循环，以及如何控制这种循环，以满足 不断变化和挑剔的大脑需求。 的 脑微血管内皮细胞位于界面处 在体循环和神经组织之间， 病毒在维持神经细胞稳定环境中的作用 功能和防止有毒物质进入 个脑袋 为了实现这一点，脑毛细血管内皮细胞是 具有独特的功能，如细胞间紧密的 连接点，重要水溶性分子的转运体， 如葡萄糖和氨基酸，以及可以 有效地防止一些脂溶性毒素进入， 血液流向大脑 建议的实验采用 免费的生化、药理学和超微结构 技术来研究大脑微循环在体内， 用分离的微血管富集的制剂，在体外。 本实验将针对以下主题：（1） 肽神经递质和神经调质的受体将 在大脑的大血管和微血管中进行评估， 这些药物通过什么途径介导其作用将被研究。 (2)血脑屏障的生物化学研究 1-甲基-4-苯基-1，2，3，6- 四氢吡啶（MPTP）神经毒性。 (3)来诱导酶 在脑微血管中，可以代谢MPTP，其类似物， 其他神经毒素 (4)18F标记的MPTP的合成 用于研究MPTP毒性的神经生物学的类似物 正电子发射断层扫描 (5)超微结构 葡萄糖分布的异质性研究 不同脑区的转运蛋白和Na+，K+-ATP酶， 在微血管单位，通过免疫细胞化学方法。 (6)生化细胞和亚细胞分级研究 脑微血管 更好地了解大脑循环功能可能会 这是理解这一疾病的病理生理学的先决条件。 流通 这项研究可能为我们提供科学依据 脑血管疾病的合理治疗，代谢 脑病和神经退行性疾病， 帕金森氏症