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 神经系统的一个重要细胞组件，就是管道 用于代谢产物的循环和交换，是主要的 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尚不确定。 这些机制与先天性动静脉有关。 由于脑血管生成过程中的错误而导致的畸形， 和脑血管母细胞瘤，在其中增殖 内皮样细胞不受控制。此外，还不够 早产儿视网膜毛细血管生长可能启动 晶状体后纤维增生症和失明。最后，脑瘤依赖于 脑内皮细胞血管生成对其生长的影响 存活，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 非洲爪哇小蝌蚪。个体的结构 视顶盖表面的毛细血管可以通过 活体光学显微镜。第一个具体目标是绘制 个体蝌蚪体内血管网络的生长 阶段43，在主要的4-6周内只有几条毛细血管 视顶盖增大约10倍时的血管生成期 表面积。第二，将做出定量的决定 对于毛细血管芽密度、肠管内血管分支密度和 单位表面积的毛细管长度。第三，血管新生生长 因子和抑制剂将被注入血液、脑室 液体和带有微吸管的软膜空间，以改变生长 顶盖血管。第四，抗血清和单抗 将产生针对非洲爪哇内皮细胞的发育 记号笔。第五个目标是培养毛细血管内皮细胞， 巨噬细胞和周细胞来自同一白化菌株 非洲爪哇和测试体外血管生成反应及其相互作用 体内有脑血管生成的标记细胞。

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.