SPHK1 and ischemic stroke: Sphingosine kinase 1 enlarges the brain infarct volume and exacerbates neurological symptoms by upregulating the expression of pro-inflammatory cytokines.310 Intriguingly, the S1PR agonist fingolimod has been recently reported to switch microglia from a pro-inflammatory to an alternatively activated phenotype in a chronic hypo-perfused ischemic stroke model in mice.311 Thus, the pro-inflammatory mechanism of S1PRs in ischemic stroke requires further exploration.