Upregulation of miR-219a-5p Decreases Cerebral Ischemia/Reperfusion Injury In Vitro by Targeting Pde4d

Background: Ischemic stroke is the leading cause of disability and death globally. Micro-RNAs (miRNAs) have been reported to play important roles in the develop-ment and pathogenesis of the nervous system. However, the exact function and mechanism of miRNAs have not been fully elucidated about brain damage caused by cerebral ischemia/reperfusion (I/R). Methods: In this study, we explored the neu-roprotective effects of miR-219a-5p on brain using an in vitro ischemia model (mouse neuroblastoma N2a cells treated with oxyglucose deprivation and reperfu-sion), and in vivo cerebral I/R model in mice. Western blot assay and Reverse Tran-scription-Polymerase Chain Reaction were used to check the expression of molecules involved. Flow cytometry and cholecystokinin were used to examine cell apoptosis, respectively. Results: Our research shows that miR-219a-5p gradually decreases in cerebral I/R models in vivo and in vitro. In vitro I/R, we find that miR-219a-5p mimics provided evidently protection for cerebral I/R damage, as shown by increased cell viability and decreased the release of LDH and cell apopto-sis. Mechanically, our findings indicate that miR-219a-5p binds to cAMP specific 3', 5'-cyclic phosphodiesterase 4D (PDE4D) mRNA in the 3'-UTR region, which subse-quently leads to a decrease in Pde4d expression in I/R N2a cells. Conclusions: Our results provide new ideas for the study of the mechanism of cerebral ischemia/ reperfusion injury, and lay the foundation for further research on the treatment of brain I/R injury. Upregulation of miR-219a-5p decreases cerebral ischemia/reper-fusion injury by targeting Pde4d in vitro.