SPHK1 and ischemia: Mice lacking eNOS expression have previously been shown to exhibit a larger infarcted area in the brain following ischemia relative to wild‐type controls,43 with eNOS also being known to be essential as a regulator of cell proliferation and apoptosis.44, 45 In this study, we found that endothelial cells rapidly induced eNOS following cerebral IRI (Figure 2), with Sphk1/S1P being essential mediators of NO generation and angiogenesis in an eNOS‐dependent manner in an HBMEC model of OGDR (Figures 5, 6, 7).