Endothelial
sphingosine-1-phosphate receptors are emerging as relevant therapeutic targets during
acute ischemic stroke (AIS). Physiologically, the cerebrovascular endothelium plays a vital role in maintaining barrier integrity and cerebrovascular homeostasis. During a cerebral ischemic event, products from parenchymal cell death are released and trigger vascular endothelial dysfunction and vascular
inflammation leading to barrier integrity disruption. Endothelial dysfunction,
inflammation, and a breach in barrier property play a significant role in contributing to a vicious cycle which promotes
brain edema formation and exacerbates neuronal injury post
stroke. Data from experimental
stroke models and clinical trials suggest that selective
sphingosine-1-phosphate receptor type 1 (S1PR1) modulation improves endothelial health and function and, as a result, contributes to improved neurological outcome post ischemic injury. This review highlights the impact of
sphingosine-1-phosphate (S1P)/S1PR1 signaling involved in blood brain barrier (BBB) integrity and cerebrovascular
inflammation following AIS. We focus on the beneficial actions of S1PR1 signaling during ischemic injury including barrier protection to lessen
brain edema formation and reduction in the development and progression of vascular
inflammation by attenuating endothelial cell activation resulting in reduced neurovascular
inflammation. Potential gaps and future directions related to the role of S1PR during AIS are also discussed.