ORAI1/STIM1 Interaction Intervenes in Stroke and in Neuroprotection Induced by Ischemic Preconditioning Through Store-Operated Calcium Entry

Background and Purpose— Disturbance of endoplasmic reticulum (ER) Ca2+ homeostasis causes neuronal cell injury in stroke. By contrast, ischemic preconditioning (IPC)—a brief sublethal ischemic episode affording tolerance to a subsequent ischemic insult—restores ER Ca2+ homeostasis. Under physiological conditions, ER calcium content is continuously refilled by the interaction between the ER-located Ca2+ sensor STIM (stromal interacting molecule) 1 and the plasma membrane channel ORAI1 (a structural component of the CRAC calcium channel)—2 key mediators of the store-operated calcium entry (SOCE) mechanism. However, the role played by ORAI1 and STIM1 in stroke and in IPC-induced neuroprotection during stroke remains unknown. Therefore, we explored whether ORAI1 and STIM1 might be involved in stroke pathogenesis and in IPC-induced neuroprotection. Methods— Primary cortical neurons were subjected to oxygen and glucose deprivation+reoxygenation to reproduce in vitro brain ischemia. Focal brain ischemia and IPC ...