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Glia. 2009 May;57(7):767-76. doi: 10.1002/glia.20804.

Photothrombosis ischemia stimulates a sustained astrocytic Ca2+ signaling in vivo.

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1
Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri 65211, USA. dings@missouri.edu

Abstract

Although there is significant information concerning the consequences of cerebral ischemia on neuronal function, relatively little is known about functional responses of astrocytes, the predominant glial-cell type in the central nervous system. In this study, we asked whether focal ischemia would impact astrocytic Ca(2+) signaling, a characteristic form of excitability in this cell type. In vivo Ca(2+) imaging of cortical astrocytes was performed using two-photon (2-P) microscopy during the acute phase of photothrombosis-induced ischemia initiated by green light illumination of circulating Rose Bengal. Although whisker evoked potentials were reduced by over 90% within minutes of photothrombosis, astrocytes in the ischemic core remained structurally intact for a few hours. In vivo Ca(2+) imaging showed that an increase in transient Ca(2+) signals in astrocytes within 20 min of ischemia. These Ca(2+) signals were synchronized and propagated as waves amongst the glial network. Pharmacological manipulations demonstrated that these Ca(2+) signals were dependent on activation of metabotropic glutamate receptor 5 (mGluR5) and metabotropic gamma-aminobutyric acid receptor (GABA(B)R) but not by P2 purinergic receptor or A1 adenosine receptor. Selective inhibition of Ca(2+) in astrocytes with BAPTA significantly reduced the infarct volume, demonstrating that the enhanced astrocytic Ca(2+) signal contributes to neuronal damage presumably through Ca(2+)-dependent release of glial glutamate. Because astrocytes offer multiple functions in close communication with neurons and vasculature, the ischemia-induced increase in astrocytic Ca(2+) signaling may represent an initial attempt for these cells to communicate with neurons or provide feed back regulation to the vasculature.

PMID:
18985731
PMCID:
PMC2697167
DOI:
10.1002/glia.20804
[Indexed for MEDLINE]
Free PMC Article
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