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Inhibition of soluble epoxide hydrolase regulates monocyte/macrophage polarization and improves neurological outcome in a rat model of ischemic stroke

Yeh, Chien-Fua,b,e,*; Chuang, Tung-Yuehf,*; Hung, Yu-Wenh; Lan, Ming-Yingb,e; Tsai, Ching-Hanf; Huang, Hao-Xiangf; Lin, Yung-Yanga,c,d,f,g

doi: 10.1097/WNR.0000000000001248

It is generally understood that continuing neuroinflammation after ischemic stroke can exacerbate the brain damage. During the inflammatory hematogenous recruitment process, the monocytes and macrophages are activated into proinflammatory M1 and anti-inflammatory M2 cell types. Inhibition of soluble epoxide hydrolase (sEH) activity has been reported to regulate monocytes/macrophages, and attenuates neuroinflammation. This study aimed to evaluate whether a selective sEH inhibitor, 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), can regulate monocyte/macrophage polarization and improve motor function in the rats with ischemic stroke induced by middle cerebral artery occlusion. We measured the infarct volume with 2,3,5-triphenyltetrazolium chloride staining and used the rotarod test to assess motor performance in rats. The monocyte/macrophage activation and mRNA expression of proinflammatory mediators were measured by flow cytometry and reverse-transcription quantitative PCR, respectively. Our results showed better neurological function and less infarct volume in the rats treated with AUDA. Compared with the vehicle group, the AUDA-treated group showed a reduction in M1 monocyte/macrophage activation and proinflammatory mRNA expressions in the infarct cortex of rats. Our data suggest that the sEH inhibition may regulate monocyte/macrophage polarization and improve neurological outcome after ischemic stroke.

aInstitute of Brain Science

bDepartment of Otorhinolaryngology

cInstitute of Physiology

dInstitute of Clinical Medicine, National Yang-Ming University

Departments of eOtolaryngology-Head and Neck Surgery

fCritical Care Medicine

gDepartment of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei

hInstitute of Cellular and System Medicine, National Health Research Institutes, Miaoli County, Taiwan (Republic of China)

* Chien-Fu Yeh and Tung-Yueh Chuang contributed equally to the writing of this article.

Correspondence to Yung-Yang Lin, MD, PhD, Department of Critical Care Medicine, Taipei Veterans General Hospital, No. 201, ShiPai Road, Taipei 112, Taiwan (Republic of China) Tel: +886 228 757 398; fax: +886 228 757 579; e-mail:

Received February 3, 2019

Accepted March 20, 2019

© 2019 Wolters Kluwer Health | Lippincott Williams & Wilkins