@article{a4ed66e255494fc0afe5d2c661a743a8,
title = "Loss of Orai2-Mediated Capacitative Ca2+ Entry Is Neuroprotective in Acute Ischemic Stroke",
abstract = "Background and Purpose- Ischemic stroke is one of the leading causes of disability and death. The principal goal of acute stroke treatment is the recanalization of the occluded cerebral arteries, which is, however, only effective in a very narrow time window. Therefore, neuroprotective treatments that can be combined with recanalization strategies are needed. Calcium overload is one of the major triggers of neuronal cell death. We have previously shown that capacitative Ca2+ entry, which is triggered by the depletion of intracellular calcium stores, contributes to ischemia-induced calcium influx in neurons, but the responsible Ca2+ channel is not known. Methods- Here, we have generated mice lacking the calcium channel subunit Orai2 and analyzed them in experimental stroke. Results- Orai2-deficient mice were protected from ischemic neuronal death both during acute ischemia under vessel occlusion and during ischemia/reperfusion upon successful recanalization. Calcium signals induced by calcium store depletion or oxygen/glucose deprivation were significantly diminished in Orai2-deficient neurons demonstrating that Orai2 is a central mediator of neuronal capacitative Ca2+ entry and is involved in calcium overload during ischemia. Conclusions- Our experimental data identify Orai2 as an attractive target for pharmaceutical intervention in acute stroke.",
keywords = "calcium, cell death, neurons, neuroprotection, reperfusion, RETICULUM CALCIUM SENSORS, MAST-CELL ACTIVATION, ENDOVASCULAR THROMBECTOMY, MOLECULAR-MECHANISMS, GLUCOSE DEPRIVATION, STORE, RELEASE, STIM2, CHANNELS, ORAI1",
author = "David Stegner and Sebastian Hofmann and Schuhmann, {Michael K.} and Peter Kraft and Herrmann, {Alexander M.} and Sandy Popp and Marlen Hoehn and Michael Popp and Vanessa Klaus and Antonia Post and Christoph Kleinschnitz and Attila Braun and Meuth, {Sven G.} and Klaus-Peter Lesch and Guido Stoll and Robert Kraft and Bernhard Nieswandt",
note = "Funding Information: This work was supported by the Deutsche Forschungsgemeinschaft (project-number 374031971—TRR240; project B06 to Dr Schuhmann and Dr Stegner, B01 to Dr Stoll; grant KR3408/2-1 to Dr R. Kraft; NI556/10-3 to Dr Nieswandt, For2289, ME3283/6-1 to Dr Meuth). Funding Information: Dr Meuth receives honoraria for lecturing, and travel expenses for attending meetings from Almirall, Amicus Therapeutics Germany, Bayer Health Care, Biogen, Celgene, Diamed, Genzyme, MedDay Pharmaceuticals, Merck Serono, Novartis, Novo Nordisk, ONO Pharma, Roche, Sanofi-Aventis, Chugai Pharma, QuintilesIMS and Teva. His research is funded by the German Ministry for Education and Research (BMBF), Deutsche Forschungsgemeinschaft (DFG), Else Kr{\"o}ner Fresenius Foundation, German Academic Exchange Service, Hertie Foundation, Interdisciplinary Center for Clinical Studies (IZKF) Muenster, German Foundation Neurology and Almirall, Amicus Therapeutics Germany, Biogen, Diamed, Fresenius Medical Care, Genzyme, HERZ Burgdorf, Merck Serono, Novartis, ONO Pharma, Roche, and Teva. None of these had any influence on the design of this study. The other authors report no conflicts. Publisher Copyright: {\textcopyright} 2019 American Heart Association, Inc.",
year = "2019",
month = nov,
doi = "10.1161/strokeaha.119.025357",
language = "English",
volume = "50",
pages = "3238--3245",
journal = "Stroke",
issn = "0039-2499",
publisher = "Wolters Kluwer Health",
number = "11",
}