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Critical Role of the Sphingolipid Pathway in Stroke: a Review of Current Utility and Potential Therapeutic Targets

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Abstract

Sphingolipids are a series of cell membrane-derived lipids which act as signaling molecules and play a critical role in cell death and survival, proliferation, recognition, and migration. Sphingosine-1-phosphate acts as a key signaling molecule and regulates lymphocyte trafficking, glial cell activation, vasoconstriction, endothelial barrier function, and neuronal death pathways which plays a critical role in numerous neurological conditions. Stroke is a second leading cause of death all over the world and effective therapies are still in great demand, including ischemic stroke and hemorrhagic stroke as well as poststroke repair. Significantly, sphingolipid activities change after stroke and correlate with stroke outcome, which has promoted efforts to testify whether the sphingolipid pathway could be a novel therapeutic target in stroke. The sphingolipid metabolic pathway, the connection between the pathway and stroke, as well as therapeutic interventions to manipulate the pathway to reduce stroke-induced brain injury are discussed in this review.

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Acknowledgments

This study was supported by grants NS-073595, NS-079157, NS-084049, NS-090925, NS-096917 and NS-091545 from the National Institutes of Health (NIH) and 973 Program-2014CB541600.

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Authors and Affiliations

  1. Department of Neurosurgery, University of Michigan, 5018 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI, 48109-2200, USA

    Na Sun, Richard F. Keep, Ya Hua & Guohua Xi

  2. Department of Neurology, Tianjin Medical University General Hospital, Tianjin, China

    Na Sun

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  1. Na Sun
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  2. Richard F. Keep
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  3. Ya Hua
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  4. Guohua Xi
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Corresponding author

Correspondence to Guohua Xi.

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All institutional and national guidelines for the care and use of laboratory animals were followed.

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The authors declare that they have no conflict of interest.

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Sun, N., Keep, R.F., Hua, Y. et al. Critical Role of the Sphingolipid Pathway in Stroke: a Review of Current Utility and Potential Therapeutic Targets. Transl. Stroke Res. 7, 420–438 (2016). https://doi.org/10.1007/s12975-016-0477-3

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  • DOI: https://doi.org/10.1007/s12975-016-0477-3

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