Optimal cerebral blood flow is coordinated by functional hyperemia and cerebral autoregulation. These processes ensure that the metabolic demands of the brain are met at all times. Both in vivo and in vitro studies support a role for astrocytes in the regulation of cerebral blood flow. In this we review the cellular mechanisms contributing to astrocyte-mediated vasodilation and vasoconstriction of parenchymal arterioles. Primarily, we discuss how activity-dependent changes in astrocytic Ca2+
contribute to the release of vasoactive signals involved in neurovascular coupling. Following the rise in astrocytic Ca2+
and phospholipase A2
activation, arachidonic acid is released and metabolized into multiple vasoactive signals (e.g., prostaglandins, epoxyeicosatrienoic acids, and 20-HETE). The level of arteriole tone along with the metabolic conditions of the tissue can alter the action of these signals leading to either vasodilation or vasoconstriction. Moreover, increased Ca2+
also activates large conductance Ca2+
-activated K+ channels expressed in astrocytic endfeet processes. Depending on the K+ efflux concentration released, this pathway can also elicit vasodilation or vasoconstriction of parenchymal arterioles. Finally, we conclude by discussing recent divergent in vivo findings which question a role for astrocyte in functional hyperemia.
Table of Contents
Constituents of the Neurovascular Unit
Astrocyte Regulation of Vascular Tone
Pericytes and Neurovascular Coupling
Overall Considerations when Studying NVC-Mediated Responses
Titles of Related Interest
About the Author(s)Jessica A. Filosa
, Georgia Regents University
Dr. Jessica A. Filosa was born in Buenos Aires, Argentina. In 1991 she moved to the United States to conduct her studies and stayed thereafter. She received her Ph.D. in Biomedical Sciences from Wright State University in Dayton, Ohio. Her Ph.D. work, under the mentorship of Dr. Robert Putnam, focused on the cellular mechanisms involved in the chemosensitive response of locus coeruleus neurons. During this time, Dr. Filosa received training in electrophysiology and fluorescent imaging microscopy. However, following her passion for the physiology of blood vessels, in 2005 she completed her postdoctoral training in the laboratory of Dr. Mark Nelson at the University of Vermont where she concentrated on the signaling events underlying communication between cerebral blood vessels and neighboring cells, particularly astrocytes. In 2008, Dr. Filosa started working in the Department of Physiology at Georgia Regents University, Augusta, GA; she holds the rank of Associate Professor. Dr. Filosa's current research interests focus on the characterization of the cellular mechanisms underlying bidirectional communication at the neurovascular unit in health and disease, with a particular emphasis on hypertension and stroke. Over the years Dr. Filosa has received funding from the American Heart Association and the NIH. She is a co-author of 31 peer reviewed research articles and reviews.