Protective effect of sphingosine 1‐phosphate (S1P) in the cerebral microvasculature

Abstract

Introduction: Sphingosine 1‐phosphate (S1P), an endogenous phospholipid, is involved in pre‐conditioning responses in the heart. The present study evaluated whether exogenous S1P could have a similar protective role in the cerebral microvasculature following hypoxic insult.Methods: Human brain microvessel endothelial cells (HBMECs) were exposed to oxygen‐glucose deprivation (OGD) for 0–6 hours. Cell viability was assessed using MTT assay immediately after OGD or following a 24‐hr re‐oxygenation period. The effects of S1P on OGD‐mediated cell toxicity was determined by pre‐treating the cells with various concentrations of S1P (0–10 μM) for 0, 1, or 24 hours.Results: Exposure of HBMECs to OGD resulted in a significant decrease (approximately 20%) in cell viability when assessed immediately after OGD. Pre‐treating HBMEC cells with S1P for 1 hr prior to OGD provided a dose dependent protection, with 1.0 and 10 μM S1P completely reversing the loss in cell viability associated with OGD at all time points examined. However, the protective effects of S1P were not apparent in the 24‐hour pre‐treatment protocol.Conclusion: Activation of S1P receptors within the brain microvasculature prior to hypoxic events may help prevent toxicity to the cerebral microvasculature.Funding support provided by Canadian Institutes of Health Research and Manitoba Health Research Council.