Experimental studies at the organ and single vessel level suggest that hemodynamic factors play a role in angiogenesis; however, the proposed factors have not been proven to work in microvascular networks. This proposal focuses on the hypothesis that the development of mature microvascular network from the primitive neonatal vascular plexus (the process of network remodeling) is the result of gradual adaptation of vessels to local mechanical forces, such as, shear stress exerted by blood flow on the vessel wall and intravascular pressure. To test the hypothesis in cerebral tissue, experiments will be performed to study changes in intracortical and pial microvascular architecture and vascular dimensions in two to five week old rats, and to correlate some of these changes with wall shear stress, intravascular pressure and other hemodynamic variables. Subsequently, a mathematical model will be developed to test whether the architecture of intracortical microvascular networks can be predicted from the microvascular architecture of the neonate and certain properties of vascular adaptation learned from the experiments. These studies will provide important new information on the role of hemodynamic factors in the development of the cerebral microvascular bed which may influence growth and repair of cerebral tissue.
