Hypoxia-Induced Brain Angiogenesis

Abstract

The energy requirements of the brain are large and immediate. The need to deliver adequate oxygen and glucose and to remove carbon dioxide specifies the vascular architecture. Taken as a whole, the metabolic demand of the brain is fairly constant during natural functions including wakefulness and sleep. Matched against this constant central demand is the varying cardiac output that serves the changing systemic needs that vary with physical activity. This major autoregulatory function occurs at the level of the larger brain vessels which act to keep brain blood flow constant despite wide systemic swings in cardiac output and blood pressure. Although overall brain blood flow is relatively constant, local and regional brain flow must be characterized as both spatially and temporally heterogeneous. An additional important constraint is that central nervous system neurons are vulnerable to oxidative damage from reactive oxygen species, and, therefore, lower exposure to oxygen is more compatible with long term continuance of function. Thus, normal brain function appears to occur with very low levels of tissue oxygen in brain regions that are not active. Once activated, however, blood flow to these regions becomes elevated while activity persists. The challenge for the cerebrovascular control mechanisms, then, is to maintain a low oxygen cellular milieu during quiescence, but rapidly provide a high oxygen supply during transient periods of neuronal activation. This latter task becomes more difficult in a low ambient oxygen environment.