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Hypoxia pp 209–219Cite as

Bidirectional Control of Blood Flow by Astrocytes: A Role for Tissue Oxygen and Other Metabolic Factors

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 903))

Abstract

Altering cerebral blood flow through the control of cerebral vessel diameter is critical so that the delivery of molecules important for proper brain functioning is matched to the activity level of neurons. Although the close relationship of brain glia known as astrocytes with cerebral blood vessels has long been recognized, it is only recently that these cells have been demonstrated to translate information on the activity level and energy demands of neurons to the vasculature. In particular, astrocytes respond to elevations in extracellular glutamate as a consequence of synaptic transmission through the activation of group 1 metabotropic glutamate receptors. These Gq-protein coupled receptors elevate intracellular calcium via IP3 signaling. A close examination of astrocyte endfeet calcium signals has been shown to cause either vasoconstriction or vasodilation. Common to both vasomotor responses is the generation of arachidonic acid in astrocytes by calcium sensitive phospholipase A2. Vasoconstriction ensues from the conversion of arachidonic acid to 20-hydroxyeicosatetraenoic acid, while vasodilation ensues from the production of epoxyeicosatrienoic acids or prostaglandins. Factors that determine whether constrictor or dilatory pathways predominate include brain oxygen, lactate, adenosine as well as nitric oxide. Changing the oxygen level itself leads to many downstream changes that facilitate the switch from vasoconstriction at high oxygen to vasodilation at low oxygen. These findings highlight the importance of astrocytes as sensors of neural activity and metabolism to coordinate the delivery of essential nutrients via the blood to the working cells.

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Acknowledgments

The research was funded by Canadian Institutes for HealthResearch (CIHR) and the Fondation Leducq. GRJG is a CIHR Bisby Postdoctoral Fellow, CH was a Sir Henry Wellcome Post Doctoral Fellow and BAM is a Canada Research Chair in Neuroscience.

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Authors and Affiliations

  1. Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada

    Grant R. J. Gordon, Clare Howarth & Brian A. MacVicar

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  1. Grant R. J. Gordon
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  2. Clare Howarth
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  3. Brian A. MacVicar
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Correspondence to Grant R. J. Gordon .

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Editors and Affiliations

  1. Altitude Research Center, University of Colorado Anschutz Medical, AURORA, Colorado, USA

    Robert C. Roach

  2. Institute for Altitude Medicine, Telluride, Colorado, USA

    Peter H. Hackett

  3. Division of Physiology 0623A, University of California - San Diego, La Jolla, California, USA

    Peter D. Wagner

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Gordon, G.R.J., Howarth, C., MacVicar, B.A. (2016). Bidirectional Control of Blood Flow by Astrocytes: A Role for Tissue Oxygen and Other Metabolic Factors. In: Roach, R., Hackett, P., Wagner, P. (eds) Hypoxia. Advances in Experimental Medicine and Biology, vol 903. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-7678-9_15

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