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

• Published in: Experimental neurology Vol. 300; pp. 41 - 50
• Main Authors: Huang, Lei, Ma, Qingyi, Li, Yong, Li, Bo, Zhang, Lubo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2018
• Subjects: Animals; Brain Injuries - drug therapy; Brain Injuries - metabolism; Brain Ischemia - drug therapy; Brain Ischemia - metabolism; Infarction; Inflammation; Inflammation Mediators - antagonists & inhibitors; Inflammation Mediators - metabolism; Injections, Intraventricular; Ischemic stroke; Male; Mice; Mice, Inbred C57BL; microRNA; MicroRNAs - antagonists & inhibitors; MicroRNAs - metabolism; miR-210; MRI; RNA, Untranslated - administration & dosage; Stroke - drug therapy; Stroke - metabolism; microRNA; Infarction; Inflammation; Ischemic stroke; MRI; miR-210
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2017.10.024

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. •Inhibition of miR-210 reduced stroke-induced cerebral infarction and edema.•Inhibition of miR-210 ameliorated the behavioral deficits after stroke.•Inhibition of miR-210 suppressed post-stroke inflammatory reaction.•MiR-210 inhibitor posttreatment reduced infarction and behavioral deficits.•MiR-210 inhibitor posttreatment improved long-term behavioral recovery after stroke.