Photothrombosis Ischemia Stimulates a Sustained Astrocytic Ca2+ Signaling In Vivo

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 ghal-cell type in the central nervous system. In this study, we asked Whether focal ischemia would impact astrocytic Ca2+ signaling, a characteristic form of excitability in this cell type. In vivo Ca2+ 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 isehemic core remained structurally intact for a few hours. In vivo Ca2+ imaging showed that an increase in transient Ca2+ signals in astrocytes within 20 min of ischemia. These Ca2+ signals were synchronized and propagated as waves amongst the glial network. Pharmacological manipulations demonstrated that these Ca2+ 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 Ca2+ in astrocytes with BAPTA significantly reduced the infarct volume, demonstrating that the enhanced astrocytic Ca2+ signal contributes to neuronal damage presumably through Ca2+-dependent release of glial glutamate. Because astrocytes offer multiple functions in close communication with neurons and vasculature, the ischemia-induced increase in astrocytic Ca2+ signaling may represent an initial attempt for these cells to communicate with neurons or provide feed back regulation to the vasculature. (C) 2008 Wiley-Liss, Inc.