MODELS FOR BRAIN ANGIOGENESIS

这项工作涉及软脑膜血管重塑在 大脑及其内部血管的生长和分化。 神经活动、腺苷和血流速度将被测试为 决定萌芽、扩大或 血管退行性变。 在透明非洲爪哇蝌蚪的视顶盖中 直径、流速和剪切率将在 用视频显微镜和荧光显微镜观察单个毛细血管和小静脉 活体内的示踪剂。视顶盖的神经活动将发生改变 在眼内TTX或眼球摘除的变态过程中。 新生小鼠须桶皮质软脑膜的消退 毛细血管、小动脉侧支的修剪和血管的扩张 供应内部毛细血管的特定小动脉和小静脉将 有记录在案。对一排排胡须的选择性操作将用于 测试神经活动对血管发育的影响。 腺苷激动剂将长期鞘内给药 测试血管生长情况。将使用腺苷拮抗剂 对体温过高的蝌蚪和选择性地去传入的 小鼠测试对增加的血管生成的抑制反应 更高水平的新陈代谢和神经活动。

This work addresses the remodeling of pial blood vessels during the growth and differentiation of the brain and its internal vessels. Neural activity, adenosine, and rates of blood flow will be tested as interrelated factors that determine sprouting, enlargement, or regression of vessels. In the optic tectum of transparent Xenopus laevis tadpoles the diameters, velocities of flow,and shear rates will be followed in individual capillaries and venules with videomicroscopy and fluordscent tracers in vivo. Neural activity in the optic tectum will be altered during metamorphosis by intraocular TTX or enucleation. In the whisker barrel cortex of neonatal mice the regression of pial capillaries, pruning of arteriolar collaterals, and enlargement of specific arterioles and venules that supply internal capillaries will be documented. Selective manipulations to rows of whiskers will be used to test the effects of neural activity on vascular development. Adenosine agonists will be administered chronically intrathecally to test vascular growth. Adenosine antagonists will be administered chronically to hyperthernlic tadpoles and to selectively deafferented mice to test for inhibition of increased vascularization in response to higher levels of metabolism and neural activity.