Regulation of the Cerebral Circulation During Development

The cerebral microcirculation undergoes dynamic changes in parallel with the development of neurons, glia, and their energy metabolism throughout gestation and postnatally. Cerebral blood flow (CBF), oxygen consumption, and glucose consumption are as low as 20% of adult levels in humans born prematurely but eventually exceed adult levels at ages 3 to 11 years, which coincide with the period of continued brain growth, synapse formation, synapse pruning, and myelination. Neurovascular coupling to sensory activation is present but attenuated at birth. By 2 postnatal months, the increase in CBF often is disproportionately smaller than the increase in oxygen consumption, in contrast to the relative hyperemia seen in adults. Vascular smooth muscle myogenic tone increases in parallel with developmental increases in arterial pressure. CBF autoregulatory response to increased arterial pressure is intact at birth but has a more limited range with arterial hypotension. Hypoxia-induced vasodilation in preterm fetal sheep with low oxygen consumption does not sustain cerebral oxygen transport, but the response becomes better developed for sustaining oxygen transport by term. Nitric oxide tonically inhibits vasomotor tone, and glutamate receptor activation can evoke its release in lambs and piglets. In piglets, astrocyte-derived carbon monoxide plays a central role in vasodilation evoked by glutamate, ADP, and seizures, and prostanoids play a large role in endothelial-dependent and hypercapnic vasodilation. Overall, homeostatic mechanisms of CBF regulation in response to arterial pressure, neuronal activity, carbon dioxide, and oxygenation are present at birth but continue to develop postnatally as neurovascular signaling pathways are dynamically altered and integrated. © 2021 American Physiological Society. Compr Physiol 11:1-62, 2021.