MODELS FOR BRAIN ANGIOGENESIS

这项研究的长期目标是了解 大脑中血管的生长受到控制。 内皮是 是神经系统的重要细胞组成部分， 对于代谢物的循环和交换， 血脑屏障的界面，并具有重要的化学物质 和监管职能。 调节生长的细胞和分子机制 脑内皮细胞在正常血管生成过程中的变化是不确定的。 这些机制与先天性动静脉 脑血管生成过程中的错误引起的畸形， 以及脑血管母细胞瘤，其中 内皮样细胞不受控制。 此外，不足 早产儿视网膜中的毛细血管生长可能开始 晶状体后纤维增生和失明。 最后，脑肿瘤依赖于 在脑内皮血管生成后， 生存，并可能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 白化病非洲爪蟾蝌蚪。 个体结构 视顶盖表面的毛细血管可以通过 体内光学显微镜检查。 第一个具体目标是绘制 蝌蚪个体血管网络的生长 第43期，只有少数毛细血管通过主要的4-6周 血管生成期视顶盖生长约10倍 表面积 第二，将进行定量测定 毛细血管芽、顶盖内血管分支的密度， 毛细管长度/表面积。 第三，血管生成性生长 因子和抑制剂将被注射到血液中，心室 液体和软脑膜空间与微量移液器，以改变生长的 顶盖血管 第四，抗血清和单克隆抗体 将针对非洲爪蟾内皮细胞产生， 标记。 第五个目的是培养毛细血管内皮， 巨噬细胞和周细胞来自相同的白化病菌株， 非洲爪蟾和测试血管生成反应在体外和相互作用 标记细胞与脑血管生成的关系。

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.