Correlation of local changes in cerebral blood flow, capillary density, and cytochrome oxidase during development

Although elevations in cerebral metabolic demand during development may induce angiogenesis, the correlation among ontogenic changes in local cerebral blood flow, cytochrome oxidase activity (an index of oxidative capacity) and capillary density have not been examined previously. We measured these parameters in selected regions of the brains of anesthetized rabbits of various ages. Increases in all three parameters occurred postnatally within the cerebral cortex and striatum, whereas in the medulla, values at birth were similar to those in adults. In newborns, the pattern of distribution of blood flow within the parietal cortex was such that levels were maximal in the outer layers and declined in deeper layers. This distribution correlated closely with that of capillary density, whereas cytochrome oxidase activity was maximal at levels deeper in the cortex. By postnatal day 17, the distribution for all three parameters was similar to that of cytochrome oxidase activity in young animals. A regression analysis of the regional values demonstrated a positive correlation between capillary density and blood flow in young (< or = postnatal day 8) and old (> or = postnatal day 17) animals. In contrast, cytochrome oxidase activity and capillary density were poorly correlated in young animals but positively correlated in older animals, with the slopes being markedly different (P < 0.005). The results suggest that early in postnatal development, the pattern of cytochrome oxidase activity is relatively mature compared with that of capillary density. By postnatal day 17, microvascular anatomy is closely associated to oxidative capacity, likely reflecting a steady state regulation of capillary density to metabolic requirements.