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Aim: Sphingosine kinase 2 (SPK2) and autophagy are both involved in cerebral preconditioning, but whether preconditioning-induced SPK2 upregulation and autophagy activation are linked mechanistically remains to be elucidated.In this study, we used in vitro and in vivo models to explore the role of SPK2-mediated autophagy in isoflurane (ISO) and hypoxic preconditioning (HP).