CELLULAR BIOLOGY OF BRAIN MICROVESSELS

这项计划的目标是研究基本的细胞机制 大脑微循环复杂功能的基础， 控制这种循环以满足 个脑袋 脑微血管内皮细胞位于界面处 在体循环和神经组织之间， 维持神经元功能的稳定环境。 完成 这个，脑毛细血管内皮被赋予了独特的功能， 紧密的细胞间连接，以及多种转运蛋白， 必需的脂不溶性分子，如葡萄糖和氨基酸。 许多 我们对这些疾病的基本细胞机制的认识仍然存在空白， 大脑血管的复杂功能 拟议 实验将采用互补的生物化学，药理学， 超微结构技术研究脑微循环完整 组织以及富含分离微血管的制剂中。 实验将解决：（1）细胞机制，腺苷 及其类似物对脑循环发挥作用。 腺苷受体和腺苷转运蛋白将在 通过配体结合技术分离脑微血管。 (2)的 存在推定的肽类神经递质的受体， 调节脑循环：血管紧张素II、加压素， 胆囊收缩素和血管活性肠多肽。 (3)超微结构 葡萄糖分布不均匀性的研究 转运蛋白和钠，钾-ATP酶在不同的大脑区域， 在微血管单位，通过免疫细胞化学方法。 （四） 脑基底板层的分离和生化特性 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一个 了解脑血管病病理生理学的先决条件 流通 本研究可为临床合理用药提供科学依据 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.