Yeh_2019_Neuroreport_30_567

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.