Inhibition of microRNA-210 suppresses pro-inflammatory response and reduces acute brain injury of ischemic stroke in mice

Authors

Lei Huang, The Lawrence D. Longo, MD Center for Perinatal Biology, Department of Basic Sciences, Loma Linda University, School of Medicine, Loma Linda, CA 92350, United States.Follow
Qingyi Ma, The Lawrence D. Longo, MD Center for Perinatal Biology, Department of Basic Sciences, Loma Linda University, School of Medicine, Loma Linda, CA 92350, United States.Follow
Yong Li, The Lawrence D. Longo, MD Center for Perinatal Biology, Department of Basic Sciences, Loma Linda University, School of Medicine, Loma Linda, CA 92350, United States.Follow
Bo Li, The Lawrence D. Longo, MD Center for Perinatal Biology, Department of Basic Sciences, Loma Linda University, School of Medicine, Loma Linda, CA 92350, United States.
Lubo Zhang, The Lawrence D. Longo, MD Center for Perinatal Biology, Department of Basic Sciences, Loma Linda University, School of Medicine, Loma Linda, CA 92350, United States.Follow

Document Type

Article

Publication Date

2-1-2018

Publication Title

Experimental neurology

E-ISSN

1090-2430

Abstract

Stroke is a leading cause of mortality and chronic neurologic disability. Yet, the successful treatment remains limited. In this study, we investigated the efficacy and the mechanism of a novel treatment, microRNA-210 (miR-210) inhibition, in protecting acute ischemic brain injury in adult mice. Focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) in adult male C57BL/6 mice. MiR-210-LNA (miR-210 inhibitor) or the negative control was administered via intracerebroventricular injection 24h prior or 4h after MCAO. Cerebral infarction volume and behavioral deficits were determined 48h after MCAO. The expression of inflammation-related genes and infiltration/activation of various immune cells in the brain were assessed by RT-qPCR, flow cytometry, and immunohistochemistry. Acute ischemic stroke significantly increased miR-210 levels in the brain, which was abolished by miR-210-LNA administered prior to MCAO. Pre- and post-MCAO treatments with miR-210-LNA significantly decreased cerebral infarction and ameliorated behavioral deficits induced by MCAO. Long-term behavioral recovery was also improved by miR-210-LNA post-treatment. At the same time, inhibition of miR-210 significantly reduced the expression of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) and chemokines (CCL2 and CCL3), but had no significant effect on anti-inflammatory factors (TGF-β and IL-10). In addition, MCAO-induced macrophage infiltration and microglial activation in the brain were inhibited by the miR-210-LNA treatment. In summary, inhibition of miR-210 suppresses pro-inflammatory response and reduces brain damage in the acute phase of ischemic stroke, providing new insight in molecular basis of a novel therapeutic strategy of miR-210 inhibition in the treatment of acute ischemic stroke.

Volume

300

First Page

41

Last Page

50

DOI

10.1016/j.expneurol.2017.10.024

PubMed ID

29111308

Recommended Citation

Huang, Lei; Ma, Qingyi; Li, Yong; Li, Bo; and Zhang, Lubo, "Inhibition of microRNA-210 suppresses pro-inflammatory response and reduces acute brain injury of ischemic stroke in mice" (2018). Loma Linda University Faculty Publications. 334.
https://scholarsrepository.llu.edu/fac_pubs/334