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Published on: January 3, 2025
An analytical overview of the ceramide-sphingosine-sphingosine-1-phosphate axis in ischemic stroke: synthesis,
Mingda Xie1, Xiaoyu Shang2, Tongyu Zhou1
1Institute of Translational Medicine, School of Medicine, Yangzhou University, Yangzhou 225009, China; Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou University, Yangzhou 225009, China.
Abstract:
Ischemic stroke rapidly remodels sphingolipid metabolism across the neurovascular unit. Ceramide (Cer), sphingosine (Sph), and sphingosine-1-phosphate (S1P) form an interconvertible axis that connects membrane metabolism with mitochondrial dysfunction, endoplasmic reticulum stress, inflammatory signaling, blood-brain barrier integrity, and immune-cell trafficking. Cer accumulation is generally associated with cellular stress and inflammatory injury, whereas the effects of S1P depend on receptor subtype, cell type, and timing. This review briefly outlines sphingolipid classification according to LIPID MAPS structure database and investigates how the Cer-Sph-S1P axis changes during ischemia and reperfusion. The review focuses on the biology of chain-length-specific ceramides, temporal remodeling, astrocyte and microglial responses, the limitations of current lipidomic methods, and the translational constraints of S1P receptor modulators. Defining these context-dependent changes more precisely may improve biomarker interpretation and facilitate the identification of appropriate therapeutic windows.
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