The SINTN seminar series proudly presents

Brian MacVicar

Astrocyte regulation of cerebral blood flow

Brian MacVicar PhD
Professor
Canada Research Chair in Neuroscience
Psychiatry
Brain Research Centre

Website: MacVicar lab Web Site

Abstract:

Calcium signalling in astrocytes couples changes in neural activity to alterations in cerebral blood flow by eliciting vasoconstriction or vasodilation of arterioles. We have investigated the mechanism for how opposite astrocyte influences provide appropriate changes in vessel tone within an environment that has dynamic metabolic requirements. We found that the ability of astrocytes to induce vasodilations over vasoconstrictions relies on the metabolic state of the tissue. When oxygen availability is lowered and astrocyte calcium is elevated, astrocyte glycolysis and lactate release are maximized. External lactate attenuates transporter-mediated uptake from the extracellular space of prostaglandin E2, leading to accumulation and subsequent vasodilation. In low oxygen extracellular adenosine also increases, which blocks astrocyte-mediated constriction, facilitating dilation. These data reveal the role of metabolic substrates in regulating brain blood flow and provide a mechanism for differential astrocyte control over cerebrovascular diameter during different states of brain activation.

Recent Papers:

[1] Grant R. J. Gordon, Hyun Beom Choi, Ravi Rungta, Graham C. R. Ellis-Davies, Brian A. MacVicar (2008) Brain metabolism dictates the polarity of astrocyte control over arterioles. Nature 456(7223):745-9

[2] Roger J. Thompson, Michael F. Jackson, Michelle Olah, Ravi Rungta, Dustin J. Hines, Michael A. Beazely, John F. MacDonald and Brian A. MacVicar (2008) Activation of Pannexin-1 Hemichannels Augments Aberrant Bursting in the Hippocampus. Science 322(5907):1555-9.

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