Soluble epoxide hydrolase inhibition enhances anti-inflammatory and antioxidative processes, modulates microglia polarization, and promotes recovery after ischemic stroke

Chien-Fu Yeh,1–3,* Tung‐Yueh Chuang,4,* Yu-Wen Hung,5 Ming-Ying Lan,2,3 Ching-Han Tsai,4 Hao-Xiang Huang,4 Yung-Yang Lin1,4,6–8 1Institute of Brain Science, National Yang-Ming University, Taipei 11221, Taiwan; 2Department of Otorhinolaryngology, National Yang-Ming University, Tai...

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Autores principales:	Yeh CF, Chuang TY, Hung YW, Lan MY, Tsai CH, Huang HX, Lin YY
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	ischemic stroke microglia polarization middle cerebral artery occlusion soluble epoxide hydrolase anti-inflammation antioxidant Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/318105bf8bc24512b946e3ffa8555386
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spelling	oai:doaj.org-article:318105bf8bc24512b946e3ffa85553862021-12-02T04:26:11ZSoluble epoxide hydrolase inhibition enhances anti-inflammatory and antioxidative processes, modulates microglia polarization, and promotes recovery after ischemic stroke1178-2021https://doaj.org/article/318105bf8bc24512b946e3ffa85553862019-10-01T00:00:00Zhttps://www.dovepress.com/soluble-epoxide-hydrolase-inhibition-enhances-anti-inflammatory-and-an-peer-reviewed-article-NDThttps://doaj.org/toc/1178-2021Chien-Fu Yeh,1–3,* Tung‐Yueh Chuang,4,* Yu-Wen Hung,5 Ming-Ying Lan,2,3 Ching-Han Tsai,4 Hao-Xiang Huang,4 Yung-Yang Lin1,4,6–8 1Institute of Brain Science, National Yang-Ming University, Taipei 11221, Taiwan; 2Department of Otorhinolaryngology, National Yang-Ming University, Taipei 11221, Taiwan; 3Department of Otolaryngology-Head and Neck Surgery, Taipei Veterans General Hospital, Taipei 11217, Taiwan; 4Department of Critical Care Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan; 5Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli County 35053, Taiwan; 6Institute of Physiology, National Yang-Ming University, Taipei 11221, Taiwan; 7Institute of Clinical Medicine, National Yang-Ming University, Taipei 11221, Taiwan; 8Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei 11217, Taiwan*These authors contributed equally to this workCorrespondence: Yung-Yang LinDepartment of Critical Care Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Rd., Taipei 11217, TaiwanTel +886-2-2871-2121Fax +886-2-2875-7890Email g2000kev@gmail.comBackground: Ischemic stroke triggers inflammatory responses and oxidative stress in the brain, and microglia polarization affects the degree of neuroinflammation. It has been reported that the inhibition of soluble epoxide hydrolase (sEH) activity protects brain tissue. However, the anti-inflammatory and antioxidative effects of sEH inhibition in the ischemic brain are not fully understood. This study aimed to investigate the effects of a selective sEH inhibitor, 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), after ischemic stroke.Methods: Adult male rats with middle cerebral artery occlusion (MCAO) were administered with AUDA or a vehicle. Behavioral outcome, infarct volume, microglia polarization, and gene expression were assessed.Results: Rats treated with AUDA showed better behavioral outcomes and smaller infarct volumes after MCAO. After AUDA treatment, a reduction of M1 microglia and an increase of M2 microglia occurred at the ischemic cortex of rats. Additionally, there was an increase in the mRNA expressions of antioxidant enzymes and anti-inflammatory interleukin-10, and pro-inflammatory mediators were decreased after AUDA administration. Heme oxygenase-1 was mainly expressed by neurons, and AUDA was found to improve the survival of neurons.Conclusion: The results of this study provided novel and significant insights into how AUDA can improve outcomes and modulate inflammation and oxidative stress after ischemic stroke.Keywords: ischemic stroke, microglia polarization, middle cerebral artery occlusion, soluble epoxide hydrolase, anti-inflammation, antioxidantYeh CFChuang TYHung YWLan MYTsai CHHuang HXLin YYDove Medical Pressarticleischemic strokemicroglia polarizationmiddle cerebral artery occlusionsoluble epoxide hydrolaseanti-inflammationantioxidantNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol Volume 15, Pp 2927-2941 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	ischemic stroke microglia polarization middle cerebral artery occlusion soluble epoxide hydrolase anti-inflammation antioxidant Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
spellingShingle	ischemic stroke microglia polarization middle cerebral artery occlusion soluble epoxide hydrolase anti-inflammation antioxidant Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Yeh CF Chuang TY Hung YW Lan MY Tsai CH Huang HX Lin YY Soluble epoxide hydrolase inhibition enhances anti-inflammatory and antioxidative processes, modulates microglia polarization, and promotes recovery after ischemic stroke
description	Chien-Fu Yeh,1–3,* Tung‐Yueh Chuang,4,* Yu-Wen Hung,5 Ming-Ying Lan,2,3 Ching-Han Tsai,4 Hao-Xiang Huang,4 Yung-Yang Lin1,4,6–8 1Institute of Brain Science, National Yang-Ming University, Taipei 11221, Taiwan; 2Department of Otorhinolaryngology, National Yang-Ming University, Taipei 11221, Taiwan; 3Department of Otolaryngology-Head and Neck Surgery, Taipei Veterans General Hospital, Taipei 11217, Taiwan; 4Department of Critical Care Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan; 5Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli County 35053, Taiwan; 6Institute of Physiology, National Yang-Ming University, Taipei 11221, Taiwan; 7Institute of Clinical Medicine, National Yang-Ming University, Taipei 11221, Taiwan; 8Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei 11217, Taiwan*These authors contributed equally to this workCorrespondence: Yung-Yang LinDepartment of Critical Care Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Rd., Taipei 11217, TaiwanTel +886-2-2871-2121Fax +886-2-2875-7890Email g2000kev@gmail.comBackground: Ischemic stroke triggers inflammatory responses and oxidative stress in the brain, and microglia polarization affects the degree of neuroinflammation. It has been reported that the inhibition of soluble epoxide hydrolase (sEH) activity protects brain tissue. However, the anti-inflammatory and antioxidative effects of sEH inhibition in the ischemic brain are not fully understood. This study aimed to investigate the effects of a selective sEH inhibitor, 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), after ischemic stroke.Methods: Adult male rats with middle cerebral artery occlusion (MCAO) were administered with AUDA or a vehicle. Behavioral outcome, infarct volume, microglia polarization, and gene expression were assessed.Results: Rats treated with AUDA showed better behavioral outcomes and smaller infarct volumes after MCAO. After AUDA treatment, a reduction of M1 microglia and an increase of M2 microglia occurred at the ischemic cortex of rats. Additionally, there was an increase in the mRNA expressions of antioxidant enzymes and anti-inflammatory interleukin-10, and pro-inflammatory mediators were decreased after AUDA administration. Heme oxygenase-1 was mainly expressed by neurons, and AUDA was found to improve the survival of neurons.Conclusion: The results of this study provided novel and significant insights into how AUDA can improve outcomes and modulate inflammation and oxidative stress after ischemic stroke.Keywords: ischemic stroke, microglia polarization, middle cerebral artery occlusion, soluble epoxide hydrolase, anti-inflammation, antioxidant
format	article
author	Yeh CF Chuang TY Hung YW Lan MY Tsai CH Huang HX Lin YY
author_facet	Yeh CF Chuang TY Hung YW Lan MY Tsai CH Huang HX Lin YY
author_sort	Yeh CF
title	Soluble epoxide hydrolase inhibition enhances anti-inflammatory and antioxidative processes, modulates microglia polarization, and promotes recovery after ischemic stroke
title_short	Soluble epoxide hydrolase inhibition enhances anti-inflammatory and antioxidative processes, modulates microglia polarization, and promotes recovery after ischemic stroke
title_full	Soluble epoxide hydrolase inhibition enhances anti-inflammatory and antioxidative processes, modulates microglia polarization, and promotes recovery after ischemic stroke
title_fullStr	Soluble epoxide hydrolase inhibition enhances anti-inflammatory and antioxidative processes, modulates microglia polarization, and promotes recovery after ischemic stroke
title_full_unstemmed	Soluble epoxide hydrolase inhibition enhances anti-inflammatory and antioxidative processes, modulates microglia polarization, and promotes recovery after ischemic stroke
title_sort	soluble epoxide hydrolase inhibition enhances anti-inflammatory and antioxidative processes, modulates microglia polarization, and promotes recovery after ischemic stroke
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/318105bf8bc24512b946e3ffa8555386
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Soluble epoxide hydrolase inhibition enhances anti-inflammatory and antioxidative processes, modulates microglia polarization, and promotes recovery after ischemic stroke

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