Physiologic angiodynamics in the brain.

Hypoxic acclimatization includes increased brain capillary density. Adaptive angiogenesis, which occurs over a 3-week period, is mediated by upregulation of vascular endothelial growth factor induced by hypoxia-inducible factor-1 in concert with the capillary remodeling molecule angiopoietin-2, which is upregulated through cyclooxygenase-2 production of prostaglandin E2. The process is apparently orchestrated by pericytes, which regulate the microvascular milieu and coordinate the interactions within the neurovascular unit. The return to normoxia is accompanied by microvascular regression and decreasing numbers of capillaries to prehypoxic densities. Regression is the result of endothelial cell apoptosis, suggesting the existence of physiologic mechanisms for adjusting capillary density to balance oxygen availability and oxygen consumption. The capacity for adaptation is diminished in older rats because of the attenuation of the hypoxia-inducible factor-1 response.