MODELS FOR BRAIN ANGIOGENESIS

脑血管生成模型

• 批准号: 3358539
• 负责人: CARL M ROVAINEN
• 金额: $ 12.15万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-07-01 至 1991-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3358539
• 关键词: Xenopus; angiogenesis; biological models; blindness; blood brain barrier; cerebrovascular system; histochemistry /cytochemistry; hormone regulation /control mechanism; immunochemistry; macrophage; monoclonal antibody; retinopathy of prematurity; superior colliculus; vascular endothelium

The long term goal of this research is to understand how the growth of blood vessels in the brain is controlled. Endothelium is a vital cellular component of the nervous system, is the conduit for circulation and exchange of metabolites, is the major interface of the blood-brain barrier, and has important chemical and regulatory functions. The cellular and molecular mechanisms which regulate the growth of brain endothelium during normal angiogenesis are uncertain. These mechanisms relate to congenital arteriovenous malformations, which arise from errors during brain angiogenesis, and to brain hemangioblastomas, in which proliferation of endothelial-like cells is uncontrolled. In addition, insufficient capillary growth in the retina of premature infants may initiate retrolental fibroplasia and blindness. Finally, brain tumors depend upon angiogenesis from brain endothelium for their growth and survival and might be controlled by inhibiting these mechanisms. The model selected for brain angiogenesis is the transparent albino Xenopus laevis tadpole. The structure of individual capillaries on the surface of the optic tectum can be resolved by light microscopy in vivo. The first specific aim is to chart the growth of the network of blood vessels in individual tadpoles from stage 43 with only a few capillaries through the major 4-6 week period of angiogenesis as the optic tectum grows about 10-fold in surface area. Second, quantitative determinations will be made for density of capillary sprouts, intratectal vascular branches, and capillary lengths per surface area. Third, angiogenic growth factors and inhibitors will be injected into the blood, ventricular fluid, and pial spaces with micropipettes to alter the growth of tectal blood vessels. Fourth, antisera and monoclonal antibodies will be produced against Xenopus endothelium as developmental markers. A fifth aim is to culture capillary endothelium, macrophages, and pericytes from the same albino strain of Xenopus and to test angiogenic responses in vitro and interactions of marked cells with brain angiogenesis in vivo.

这项研究的长期目标是了解 控制大脑血管的生长。 内皮是 神经系统的重要细胞成分是导管 为了循环和交换代谢物，是主要的 血脑屏障的界面，具有重要的化学物质 和监管功能。 调节生长的细胞和分子机制 正常血管生成期间脑内皮的脑部内皮尚不确定。 这些机制与先天性动脉静脉化有关 畸形是由脑血管生成期间错误引起的， 以及脑血管母细胞瘤，其中 内皮样细胞不受控制。 另外，不足 早产婴儿视网膜的毛细血管生长可能会引发 后纤维状和失明。 最后，脑肿瘤取决于 从脑内皮的血管生成来生长和 生存，可以通过抑制这些机制来控制。 选择用于脑血管生成的模型是透明的 白化Xenopus laevis t。 个体的结构 视神经底面表面上的毛细血管可以通过 体内光显微镜。 第一个具体目的是图表 从 第43阶段，只有几个毛细血管到主要的4-6周 血管生成的时期随着视神经膜的增长约10倍 表面积。 其次，将做出定量确定 用于毛细血管芽的密度，直肠内血管分支和 每个表面积的毛细管长度。 第三，血管生长 因素和抑制剂将被注入血液，心室 流体和带有微夹的沿沿岸，以改变 直肠血管。 第四，抗血清和单克隆抗体 将针对爪蟾内皮产生作为发育 标记。 第五个目标是培养毛细管内皮， 巨噬细胞和来自同一白化菌株的周细胞 爪蟾并在体外测试血管生成反应和相互作用 在体内具有脑血管生成的明显细胞。