SPHK1 and ischemic stroke: S1PRs form a group of G protein-coupled receptors abundant in microglia and are thought to regulate inflammatory responses in ischemic stroke.308 In vitro studies have shown that the addition of S1P to microglia subjected to oxygen-glucose deprivation/reperfusion exacerbates hypoxia-induced neuronal apoptosis.309 In experimental ischemic stroke models, sphingosine kinase 1 phosphorylates sphingosine to S1P, which binds to S1PR3 and confers microglia a pro-inflammatory phenotype.