Astrocyte control of blood flow

Abstract

Astrocytes have recently been shown to be essential participants in the control of cerebral blood flow (CBF) through their prominent control of cerebral vessel diameter. Although the unique close relationship of astrocytes with cerebral blood vessels has long been recognized it is only within the last few years that evidence has shown how astrocytes might translate information to the vasculature on the activity level and energy demands of neurons. These findings suggest that astrocytes are key players in the system for the delivery and clearance of molecules important to brain function. Astrocytes possess the necessary signaling capability to induce both vasoconstriction as well as vasodilation in response to elevations in astrocyte end-feet Ca2+. Both types of vasomotor responses are initiated by the generation of arachidonic acid (AA) in astrocytes by Ca2+ sensitive phospholipase A2 (PLA2). Subsequent to AA formation, vasoconstriction occurs as a result of the generation of 20-hydroxyeicosatetraenoic acid (20-HETE), while vasodilation ensues from the production of epoxyeicosatrienoic acid (EET) or prostaglandin E2 (PGE2). Notably, the level of nitric oxide (NO) seems to control which of these two routes is utilized, either by the inhibition of critical enzymes by NO or by an indirect effect on vessel tone. In addition to the Ca2+-activated PLA2 pathway, the activation of large conductance Ca2+ - activated K+ channels in astrocyte end-feet has been proposed to induce vasodilation by hyperpolarizing smooth muscle cells (SMCs) through the effect of increased external [K+ ] on SMC Kir channels. This large array of possibilities highlights the importance of astrocytes as well as the need for additional experimentation to fully delineate their contributions to vascular dynamics.