Abstract TP119: Upregulation of MicroRNA-128 in the Peripheral Blood of Acute Ischemic Stroke Patients is Correlated With Stroke Severity Partially Through Inhibition of Neuronal Cell Cycle Reentry and Apoptosis

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Aim: MiR-128, one of the most enriched miRNAs in the human brain, has been reported to protect MCAO mice via inhibiting P38α MAPK. Whether it is involved in pathogenesis in acute ischemic stroke patients remains to be determined. The present study focused on the clinical importance of miR-128 and its underlying mechanisms. Methods: MiR-128 levels in the circulating lymphocytes, neutrophils, and plasma of acute ischemic stroke patients were detected by using RT-PCR. Meanwhile, we collected infarction volume, NIHSS and mRS scores, and compare their correlations with miR-128 levels. Bioinformatics analysis was applied to predict inflammation related pathways targeted by miR-128. Then cerebral ischemia was induced by middle cerebral artery occlusion in C57/BL6 mice, and miR-128 levels in the brain tissues were assessed by using RT-PCR. Apoptosis related protein caspase-3 and-12, cell cycle related proteins and pathway molecules were detected in Neuro-2a cells upon H 2 O 2 plus miR-128 stimulation by flow cytometry, and western blot, respectively. Results: MiR-128 levels were significantly elevated in the circulating lymphocytes, neutrophils, and plasma of patients with acute ischemic stroke. In addition, the miR-128 levels in circulating lymphocytes positively correlated with the infarction volume, NIHSS scores at 7 days and mRS at 90 days after ischemic stroke onset. Subsequent KEGG pathway analysis showed that the MAPK signaling pathway and cell cycle were among the pathways targeted by miR-128. Although no correlation was found between miR-128 in plasma and peripheral inflammatory cell numbers, miR-128 decreased in the penumbra and increased in the infarction core of ipsilateral brain tissues in MCAO mice. Moreover, the in vitro study demonstrated that miR-128 inhibited neuronal apoptosis and reversed cell cycle reactivation induced by H 2 O 2 stimulation; the underlying mechanism involved decreasing cyclin A2 expression and inhibiting phosphorylation of PTEN and ERK. Conlusion: The upregulation of miR-128 in circulating lymphocytes of acute ischemic stroke patients was correlated with stroke severity and protected against oxidative stress via inhibiting neuronal apoptosis and cell cycle reentry.