Loss of Orai2-Mediated Capacitative Ca2+ Entry Is Neuroprotective in Acute Ischemic Stroke
Stegner D., Hofmann S., Schuhmann M. K., Kraft P., Herrmann A. M., Popp S., Höhn M., Popp M., Klaus V., Post A., Kleinschnitz C., Braun A., Meuth S. G., Lesh K. Yu., Stoll G., Kraft R., Nieswandt B.
Stroke: a Journal of Cerebral Circulation
Vol.50, Issue11, P. 3238-3245
Опубликовано: 2019
Тип ресурса: Статья
DOI:10.1161/STROKEAHA.119.025357
Аннотация:
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 c
Ключевые слова:
calcium; cell death; neurons; neuroprotection; reperfusion
calcium; calcium release activated calcium channel 2; Orai2 protein, mouse; acute disease; animal; brain ischemia; calcium signaling; cell death; cerebrovascular accident; genetics; knockout mouse; metabolism; mouse; nerve cell; neuroprotection; pathology; Acute Disease; Animals; Brain Ischemia; Calcium; Calcium Signaling; Cell Death; Mice; Mice, Knockout; Neurons; Neuroprotection; ORAI2 Protein; Stroke
Язык текста: Английский
ISSN: 1524-4628
Stegner D.
Hofmann S.
Schuhmann M. K.
Kraft P.
Herrmann A. M.
Popp S.
Höhn M.
Popp M.
Klaus V.
Post A.
Kleinschnitz C.
Braun A.
Meuth S. G.
Lesh K. Yu. Klaus-Peter Yulius 1957-
Stoll G.
Kraft R.
Nieswandt B.
Стегнер Д.
Хофманн С.
Счухманн М. К.
Крафт П.
Херрманн А. М.
Попп С.
Хöхн М.
Попп М.
Клаус В.
Пост А.
Клеинсчнитз C.
Браун А.
Меутх С. Г.
Леш К. Ю. Клаус-Петер Юлиус 1957-
Столл Г.
Крафт Р.
Ниесwандт Б.
Loss of Orai2-Mediated Capacitative Ca2+ Entry Is Neuroprotective in Acute Ischemic Stroke
Текст визуальный непосредственный
Stroke: a Journal of Cerebral Circulation
Lippincott Williams & Wilkins
Vol.50, Issue11 P. 3238-3245
2019
Статья
calcium cell death neurons neuroprotection reperfusion
calcium calcium release activated calcium channel 2 Orai2 protein, mouse acute disease animal brain ischemia calcium signaling cell death cerebrovascular accident genetics knockout mouse metabolism mouse nerve cell neuroprotection pathology Acute Disease Animals Brain Ischemia Calcium Calcium Signaling Cell Death Mice Mice, Knockout Neurons Neuroprotection ORAI2 Protein Stroke
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 c