CELLULAR BIOLOGY OF BRAIN MICROVESSELS

脑微血管的细胞生物学

• 批准号: 3349639
• 负责人: SAMI I HARIK
• 金额: $ 17.66万
• 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/3349639
• 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 构成大脑复杂功能的机制 循环，以及如何控制这种循环以满足 对大脑的变化和挑剔的要求。这个 脑微血管内皮细胞站在界面上 体循环和神经组织之间的关系 病毒在维持神经元稳定环境中的作用 功能和防止有毒物质进入 大脑。为了做到这一点，大脑的毛细血管内皮细胞 具有独特的特征的，如紧密的细胞间 连接，运输必要的水溶性分子，如 作为葡萄糖和氨基酸，以及可以 有效防止某些脂溶毒素进入人体。 血到脑。计划中的员工实验 免费赠送生化、药理和超微结构 活体研究大脑微循环的技术，以及在 在体外用分离的微血管富含的制剂。 实验将针对以下主题：(1) 多肽神经递质和神经调节剂的受体将 在脑宏血管和微血管中被评估，以及机制 通过这些代理人调解他们的影响将被调查。 (2)血脑屏障生化方面的研究 与全身性1-甲基-4-苯基-1，2，3，6- 四氢吡啶(MPTP)神经毒性。(3)诱导酶 在能够代谢MPTP的脑微血管中，其类似物和 其他可能的神经毒素。(4)18F标记MPTP的合成 用于MPTP毒性神经生物学研究的类似物 通过正电子发射断层扫描。(5)超微结构 葡萄糖分布的不均一性研究 不同脑区的转运蛋白和Na~+，K~+-ATPase 在微血管单位内，通过免疫细胞化学方法。 (6)生物化学细胞和亚细胞分离研究 脑微血管。 更好地了解大脑循环的功能可能会 是了解本病病理生理学的前提 发行量。建议的研究可能为研究提供科学依据。 合理治疗脑血管疾病，代谢 脑病和神经退行性疾病，如 帕金森氏症。