MicroRNA-323-5p Involved in Dexmedetomidine Preconditioning Impart Neuroprotection

Abstract

Background and Objectives: Cerebral ischemia is one of the major preoperative complications. Dexmedetomidine is a well-known sedative–hypnotic agent that has potential organ-protective effects. We examine the miRNAs associated with preconditioning effects of dexmedetomidine in cerebral ischemia. Materials and Methods: Transient infarcts were induced in mice via reperfusion after temporary occlusion of one side of the middle cerebral artery. A subset of these mice was exposed to dexmedetomidine prior to cerebral infarction and miRNA profiling of the whole brain was performed. We administered dexmedetomidine and miRNA-323-5p mimic/inhibitor to oxygen–glucose deprivation/reoxygenation astrocytes. Additionally, we administered miR-323-5p mimic and inhibitor to mice via intracerebroventricular injection 2 h prior to induction of middle cerebral artery occlusion. Results: The infarct volume was significantly lower in the dexmedetomidine-preconditioned mice. Analysis of brain samples revealed an increased expression of five miRNAs and decreased expression of three miRNAs in the dexmedetomidine-pretreated group. The viability of cells significantly increased and expression of miR-323-5p was attenuated in the dexmedetomidine-treated oxygen–glucose deprivation/reoxygenation groups. Transfection with anti-miR-323-5p contributed to increased astrocyte viability. When miRNA-323-5p was injected intraventricularly, infarct volume was significantly reduced when preconditioned with the miR-323-5p inhibitor compared with mimic and negative control. Conclusions: Dexmedetomidine has a protective effect against transient neuronal ischemia–reperfusion injury and eight specific miRNAs were profiled. Also, miRNA-323-5p downregulation has a cell protective effect under ischemic conditions both in vivo and in vitro. Our findings suggest the potential of the miR-323-5p inhibitor as a therapeutic agent against cerebral infarction.

Keywords

• dexmedetomidine
• hypoxia–ischemia
• brain
• ischemic preconditioning
• miRNAs
• neuroprotection