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Journal of Molecular Neuroscience

, Volume 65, Issue 1, pp 43–53 | Cite as

microRNA-21 Confers Neuroprotection Against Cerebral Ischemia-Reperfusion Injury and Alleviates Blood-Brain Barrier Disruption in Rats via the MAPK Signaling Pathway

  • Xiaofeng Yao
  • Yahui Wang
  • Dongya ZhangEmail author
Article

Abstract

The mechanism contributing to blood-brain barrier (BBB) disruption, involved in poststroke edema and hemorrhagic transformation, is important but elusive. We investigated microRNA-21 (miR-21)-mediated mechanism in the disruption of BBB following cerebral ischemia-reperfusion (I/R) injury. Rats with cerebral I/R injury were prepared after middle cerebral artery occlusion and subsequent reperfusion. The underlying regulatory mechanisms of miR-382 were investigated with treatment of miR-382 mimics, miR-382 inhibitors, or SB203580 (an inhibitor of the MAPK signaling pathway) prior to I/R modeling. Compared with sham-operated rats, rats following I/R showed increased Longa’s scores, ischemic hemisphere volume, cerebral infarct volume, EB content in brain tissues, enhanced levels of p38, iNOS, and MMP-9. The ectopic expression of miR-21 by mimics and MAPK signaling inhibition by SB203580 reduced Longa’s scores, ischemic hemisphere volume, cerebral infarct volume, EB content in brain tissues, decreased levels of p38, MAP2K3, iNOS, and MMP-9. The luciferase activity determination showed miR-21 bound to MAP2K3 in its 3′UTR. miR-21 downregulation mediated by inhibitors appeared to yield an opposed trend. We also found that MAPK signaling inhibition by SB203580 could rescue rats with treatment of miR-382 inhibitors. The study highlights the neuroprotective role of MiR-21 during cerebral I/R injury and its preventive effect against BBB disruption by blocking the MAPK signaling pathway via targeted inhibition of MAP2K3, potentially opening a novel therapeutic avenue for the treatment of cerebral ischemia.

Keywords

microRNA-21 MAPK signaling pathway Cerebral ischemia-reperfusion injury Blood-brain barrier Neuronal remodeling 

Notes

Acknowledgments

The authors thank the reviewers for their helpful comments.

Compliance with Ethical Standards

The experimental protocols of the present study were approved by the Animal Care Committee at Xianyang hospital, Yan’an University.

Conflict of Interest

The authors declare that they have no conflicts of interest.

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Neurosurgery, Xianyang HospitalYan’an UniversityXianyangPeople’s Republic of China
  2. 2.Department of GerontologyBaoJi Central HospitalBaoJiPeople’s Republic of China
  3. 3.Department of Neurology, Xianyang hospitalYan’an UniversityXianyangPeople’s Republic of China

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