Astrocytes and the Regulation of Cerebral Blood Flow

Moment-to-moment changes in local neuronal activity lead to dynamic changes in cerebral blood flow. Emerging evidence implicates astrocytes as one of the key players in coordinating this neurovascular coupling. Astrocytes are poised to sense glutamatergic synaptic activity over a large spatial domain via activation of metabotropic glutamate receptors and subsequent calcium signaling and via energy-dependent glutamate transport. Astrocyte foot processes can signal vascular smooth muscle by arachidonic acid pathways involving astrocytic cytochrome P450 epoxygenase, astrocytic cyclooxygenase-1 and smooth muscle cytochrome P450 omega-hydroxylase activities, and by astrocytic and smooth muscle potassium channels. Non-glutamatergic transmitters released from neurons, such as nitric oxide, cyclooxygenase-2 metabolites and vasoactive intestinal peptide, might modulate neurovascular signaling at the level of the astrocyte or smooth muscle. Thus, astrocytes have a pivotal role in dynamic signaling within the neurovascular unit. Important questions remain on how this signaling is integrated with other pathways in health and disease.