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 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.
Ding
Shinghua
S
Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri 65211, USA. dings@missouri.edu
Wang
Tiannan
T
Cui
Wenju
W
Haydon
Philip G
PG
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002545:Brain Ischemia / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005073:Evoked Potentials, Somatosensory; D008027:Light; D008297:Male; D051379:Mice; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D043682:Receptor, Adenosine A1 / Q000378:metabolism; D064529:Receptor, Metabotropic Glutamate 5; D018080:Receptors, GABA-B / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D012395:Rose Bengal; D014738:Vibrissae
D002614:Chelating Agents; C578936:Grm5 protein, mouse; D018696:Neuroprotective Agents; D043682:Receptor, Adenosine A1; D064529:Receptor, Metabotropic Glutamate 5; D018080:Receptors, GABA-B; D018094:Receptors, Metabotropic Glutamate; D018048:Receptors, Purinergic P2; D012395:Rose Bengal; D004533:Egtazic Acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium