Role of astrocytes in matching blood flow to neuronal activity

The brain is critically dependent on oxygen and glucose supply for normal function. Various neurovascular control mechanisms assure that the blood supply of the brain is adequate to meet the energy needs of its components. Emerging evidence shows that neuronal activity can control microcirculation using astrocytes as a mediator. Astrocytes can sense neuronal activity and are involved in signal transmission. Synaptic activity triggers an increase in the intracellular calcium concentration [Ca(2+)]i of adjacent astrocytes, stimulating the release of adenosine triphosphate (ATP) and glutamate. The released ATP mediates the propagation of Ca(2+) waves between neighboring astrocytes, thereby recruiting them to mediate adequate cerebrovascular response to neuronal activation. Simultaneously, sodium-dependent glutamate uptake in astrocytes generates Na(+) waves and subsequently increases glucose uptake and metabolism that leads to the formation of lactate, which is then delivered to neurons as an energy substrate. Further, astrocytic Ca(2+) elevations can lead to secretion of vasodilatory substances from perivascular endfeet, such as epoxyeicosatrienoic acid (EETs), adenosine, nitric oxide (NO), and cyclooxygenase-2 (COX-2) metabolites, resulting in increased local blood flow. Thus, astrocytes by releasing vasoactive molecules mediate the neuron-astrocyte-endothelial signaling pathway and play a profound role in coupling blood flow to neuronal activity.