An analytical overview of the ceramide-sphingosine-sphingosine-1-phosphate axis in ischemic stroke: synthesis, metabolic dynamics, and functional conversion.

Abstract

Ischemic stroke rapidly remodels sphingolipid metabolism across the neurovascular unit. Ceramide, sphingosine, 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. Ceramide 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 nomenclature and examines how the Cer-Sph-S1P axis changes during ischemia and reperfusion. The review focuses on chain-length-specific ceramide biology, 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 help identify appropriate therapeutic windows.