MODELS FOR BRAIN ANGIOGENESIS

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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.