Abstract WMP43: Microrna-210 Improves Long-term Outcome in the Ischemic Mice via La Regulation of BDNF

Abstract

Objective: MicroRNAs played an important role in the ischemia brain injury and repair. However, the key microRNA and its function in the stroke patients remain unclear. Methods: The blood miRNAs profile was analyzed by quantitative Polymerase Chain Reaction (PCR) methods in ischemic stroke patients in the acute phase (48 hours) and subacute phase (10 days), compared to healthy controls with vascular risk factors. The predicted network of differences in the expression of miRNAs was further explored by Ingenuity Pathway Analysis (IPA). The key miRNA was selected and its function and mechanism were explored in ischemic mice subjected to lentivirus vector mediated overexpression. The predicted target was confirmed by the dual luciferase reporter assay system. Results: After cerebral ischemia, 24 microRNAs were high or low differently expressed in the peripheral blood of stroke patients. The bioinformatics analysis showed a regulated network of stroke cascade, which was consisted of 10 miRNAs including mir-210 and their predicted targets. The lentivirus vector mediated miR-210 overexpression increased microvessel density and the number of neural progenitor cells via regulating brain-derived neurotrophic factor (BDNF) expression in normal and ischemia mice brain. MiR-210 overexpression could ameliorate neurobehavioral outcomes in ischemic mice. The dual luciferase reporter assay system identified that BDNF was the direct target of miR-210. Conclusions: MiR-210 is a key stroke related miRNA. Overexpression of miR-210 promotes focal angiogenesis and neurogenesis via directely regulating BDNF expression. Furthermore, miR-210 improves long-term outcomes in ischemic mice and proved to be a potential novel therapeutic target for stroke.