Orai1^−/− chimeras are protected from cerebral ischemia without displaying major bleeding. (A left panel) Representative images of 3 corresponding coronal sections from control and Orai1^−/− chimeras mice stained with TTC 24 hours after tMCAO. Infarct areas are marked with arrows. (Right panel) Brain infarct volumes in control (n = 7) and Orai1^−/− chimeras (n = 7); ***P < .001. (B,C) Neurologic Bederson score and grip test assessed at day 1 following tMACO of control (n = 7) and Orai1^−/− chimeras (n = 7); **P < .01. Error bars represent plus or minus SD. (D) The coronal T2-w MR brain image shows a large hyperintense ischemic lesion at day 1 after tMCAO in controls (left). Infarcts are smaller in Orai1^−/− chimeras (middle, white arrow), and T2 hyperintensity decreases by day 5 during infarct maturation (right). Importantly, hypointense areas indicating intracerebral hemorrhage were not seen in Orai1^−/− chimeras, demonstrating that Orai1 deficiency does not increase the risk of hemorrhagic transformation, even at advanced stages of infarct development. (E) Hematoxylin and eosin–stained sections of corresponding territories in the ischemic hemispheres of control and Orai1^−/− chimeras. Infarcts are restricted to the basal ganglia in Orai1^−/− chimeras but consistently include the cortex in controls. Magnification, 100×-fold and ×400 (10×/0.3 NA and 40×/0.75 NA objectives; Carl Zeiss, Heidelberg, Germany). Bars represent 300 μm (left) and 37.5 μm (right). (F) Bleeding time is only mildly prolonged in Orai1^−/− chimeras after amputating the tail tip of anesthetized mice. Each dot represents 1 individual.