CELLULAR BIOLOGY OF BRAIN MICROVESSELS

这项提议的目标是研究基本的细胞机制。 这是大脑微循环复杂功能的基础，以及如何 这种循环受到控制，以满足 大脑。脑微血管内皮细胞站在界面上。 在体循环和神经组织之间，起着至关重要的作用 维持一个稳定的神经功能环境。要完成 这，大脑毛细血管内皮细胞被赋予了独特的功能，如 作为紧密的细胞间连接，以及各种转运蛋白 必需的脂类不溶分子，如葡萄糖和氨基酸。许多 我们对潜在的基本细胞机制的了解仍然存在差距 大脑血管的复杂功能。建议数 实验将采用互补的生化、药理学和 用超微结构技术研究完全性脑微循环 组织和富含分离微血管的制剂中。 这些实验将解决：(1)腺苷通过哪些细胞机制 它的类似物对大脑循环产生影响。 腺苷受体和腺苷转运体将在 用配基结合技术分离脑微血管。(2) 推定的多肽神经递质受体的存在可能 调节脑循环：血管紧张素II、加压素、 胆囊素和血管活性肠多肽。(3)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钠，钾-三磷酸腺苷酶，以及 在微血管单位内，通过免疫细胞化学方法。(4) 脑基底板的分离及其生化特性 微血管。(5)生化测定和可能的超微结构 碳酸酐酶在脑微血管中的定位。 更好地了解大脑微循环的功能可能是 了解大脑病理生理学的前提条件 发行量。这一研究可为理性的 治疗脑血管疾病、代谢性脑病和 血脑屏障功能障碍。

The goals of this proposal are to investigate the basic cellular mechanisms that underlie the complex functions of the brain microcirculation, and how this circulation is controlled to meet the 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 vital role in maintaining a stable environment for neuronal function. To accomplish this, the brain capillary endothelium is endowed with unique features, such as tight intercellular junctions, and a variety of transporters for essential lipid-insoluble molecules like glucose and amino acids. Many gaps remain in our knowledge of the basic cellular mechanisms underlying the complex functions of the brain's blood vessels. The proposed experiments will employ complementary biochemical, pharmacological, and ultrastructural techniques to study the brain microcirculation in intact tissue, and in preparations enriched with isolated microvessels. The experiments will address: (1) Cellular mechanisms by which adenosine and its analogues exert their affects on the cerebral circulation. Adenosine receptors and the adenosine transporter will be investigated in isolated cerebral microvessels by ligand binding techniques. (2) The presence of receptors for putative peptide neurotransmitters which may regulate the cerebral circulation: angiotensin II, vasopressin, cholecystokin, and vasoactive intestinal polypeptide. (3) Ultrastructural investigation of heterogeneities in the distribution of the glucose transporter and sodium, potassium-ATPase in different brain regions, and within the microvascular unit, by immunocytochemical methods. (4) Isolation and biochemical characterization of the basal lamina of brain microvessels. (5) Biochemical determination and possible ultrastructural localization of carbonic anhydrase in cerebral microvessels. A better understanding of how the brain microcirculation functions may be a prerequisite for appreciating the pathophysiology of the cerebral circulation. This research may provide scientific bases for rational therapy of cerebral vascular disorders, metabolic encephalopathies and blood-brain barrier dysfunction.