Ceramide accumulation has been associated with ischemic stroke. Myriocin is an effective SPT inhibitor, which reduces the levels of ceramides by inhibiting de novo synthesis pathway. However, the role of myriocin in cerebral ischemia/reperfusion (I/R) injury and its underlying mechanism remains unknown. The present study established an experimental rat model of middle cerebral artery occlusion (MCAO). We employed UPLC-Q-TOF/MS-based lipidomic analysis to identify the disordered lipid metabolites and the effects of myriocin in cerebral cortical tissues of rats. In this study, we found 15 characterized lipid metabolites involved in sphingolipid and glycerophospholipid metabolism in cerebral I/R-injured rats, which were significantly reversed by myriocin. Specifically, the mRNA expression of metabolism-related enzyme genes was detected by real-time quantitative polymerase chain reaction (RT-qPCR).We demonstrated that myriocin could regulate the mRNA expression of ASMase, NSMase, SGMS1, SGMS2, ASAH1, ACER2, ACER3 involved in sphingolipid metabolism and PLA2 involved in glycerophospholipid metabolism. Moreover, TUNEL and western blot assay showed that myriocin played a key role in regulating neuronal cell apoptosis. In summary, the present work provides a new perspective for a systematic study of metabolic changes in ischemia stroke and the therapeutic applications of myriocin.

Ceramide accumulation has been associated with ischemic stroke. Myriocin is an effective SPT inhibitor, which reduces the levels of ceramides by inhibiting de novo synthesis pathway. However, the role of myriocin in cerebral ischemia/reperfusion (I/R) injury and its underlying mechanism remains unknown.The present study established an experimental rat model of middle cerebral artery occlusion (MCAO). We employed UPLC-Q-TOF/MS-based lipidomic analysis to identify the disordered lipid metabolites and the effects of myriocin in cerebral cortical tissues of rats. In this study, we found 15 characterized lipid metabolites involved in sphingolipid and glycerophospholipid metabolism in cerebral I/R-injured rats, which were signi cantly reversed by myriocin. Speci cally, the mRNA expression of metabolism-related enzyme genes was detected by real-time quantitative polymerase chain reaction (RT-qPCR).We demonstrated that myriocin could regulate the mRNA expression of ASMase, NSMase, SGMS1, SGMS2, ASAH1, ACER2, ACER3 involved in sphingolipid metabolism and PLA2 involved in glycerophospholipid metabolism. Moreover, TUNEL and western blot assay showed that myriocin played a key role in regulating neuronal cell apoptosis. In summary, the present work provides a new perspective for a systematic study of metabolic changes in ischemia stroke and the therapeutic applications of myriocin.