Soluble epoxide hydrolase inhibition Promotes White Matter Integrity and Long-Term Functional Recovery after chronic hypoperfusion in mice

Abstract Chronic cerebral hypoperfusion induced cerebrovascular white matter lesions (WMLs) are closely associated with cognitive impairment and other neurological deficits. The mechanism of demyelination in response to hypoperfusion has not yet been fully clarified. Soluble epoxide hydrolase (sEH)...

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Autores principales:	Yuxue Chen, Hao Tian, Ensheng Yao, Yeye Tian, Huaqiu Zhang, Li Xu, Zhiyuan Yu, Yongkang Fang, Wei Wang, Peng Du, Minjie Xie
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/dde769c088264e80ba3b5f7bd1ec25f5
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spelling	oai:doaj.org-article:dde769c088264e80ba3b5f7bd1ec25f52021-12-02T16:06:22ZSoluble epoxide hydrolase inhibition Promotes White Matter Integrity and Long-Term Functional Recovery after chronic hypoperfusion in mice10.1038/s41598-017-08227-z2045-2322https://doaj.org/article/dde769c088264e80ba3b5f7bd1ec25f52017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08227-zhttps://doaj.org/toc/2045-2322Abstract Chronic cerebral hypoperfusion induced cerebrovascular white matter lesions (WMLs) are closely associated with cognitive impairment and other neurological deficits. The mechanism of demyelination in response to hypoperfusion has not yet been fully clarified. Soluble epoxide hydrolase (sEH) is an endogenous key enzyme in the metabolic conversion and degradation of P450 eicosanoids called epoxyeicosatrienoic acids. Inhibition of sEH has been suggested to represent a prototype “combination therapy” targeting multiple mechanisms of stroke injury with a single agent. However, its role in the pathological process after WMLs has not been clarified. The present study was to investigate the role of a potent sEH inhibitor, 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), on multiple elements in white matter of mice brain after chronic hypoperfusion. Adult male C57BL/6 mice were subjected to bilateral carotid artery stenosis (BCAS) to induce WMLs. Administration of TPPU significantly inhibited microglia activation and inflammatory response, increased M2 polarization of microglial cells, enhanced oligodendrogenesis and differentiation of oligodendrocytes, promoted white matter integrity and remyelination following chronic hypoperfusion. Moreover, these cellular changes were translated into a remarkable functional restoration. The results suggest that sEH inhibition could exert multi-target protective effects and alleviate cognitive impairment after chronic hypoperfusion induced WMLs in mice.Yuxue ChenHao TianEnsheng YaoYeye TianHuaqiu ZhangLi XuZhiyuan YuYongkang FangWei WangPeng DuMinjie XieNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yuxue Chen Hao Tian Ensheng Yao Yeye Tian Huaqiu Zhang Li Xu Zhiyuan Yu Yongkang Fang Wei Wang Peng Du Minjie Xie Soluble epoxide hydrolase inhibition Promotes White Matter Integrity and Long-Term Functional Recovery after chronic hypoperfusion in mice
description	Abstract Chronic cerebral hypoperfusion induced cerebrovascular white matter lesions (WMLs) are closely associated with cognitive impairment and other neurological deficits. The mechanism of demyelination in response to hypoperfusion has not yet been fully clarified. Soluble epoxide hydrolase (sEH) is an endogenous key enzyme in the metabolic conversion and degradation of P450 eicosanoids called epoxyeicosatrienoic acids. Inhibition of sEH has been suggested to represent a prototype “combination therapy” targeting multiple mechanisms of stroke injury with a single agent. However, its role in the pathological process after WMLs has not been clarified. The present study was to investigate the role of a potent sEH inhibitor, 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), on multiple elements in white matter of mice brain after chronic hypoperfusion. Adult male C57BL/6 mice were subjected to bilateral carotid artery stenosis (BCAS) to induce WMLs. Administration of TPPU significantly inhibited microglia activation and inflammatory response, increased M2 polarization of microglial cells, enhanced oligodendrogenesis and differentiation of oligodendrocytes, promoted white matter integrity and remyelination following chronic hypoperfusion. Moreover, these cellular changes were translated into a remarkable functional restoration. The results suggest that sEH inhibition could exert multi-target protective effects and alleviate cognitive impairment after chronic hypoperfusion induced WMLs in mice.
format	article
author	Yuxue Chen Hao Tian Ensheng Yao Yeye Tian Huaqiu Zhang Li Xu Zhiyuan Yu Yongkang Fang Wei Wang Peng Du Minjie Xie
author_facet	Yuxue Chen Hao Tian Ensheng Yao Yeye Tian Huaqiu Zhang Li Xu Zhiyuan Yu Yongkang Fang Wei Wang Peng Du Minjie Xie
author_sort	Yuxue Chen
title	Soluble epoxide hydrolase inhibition Promotes White Matter Integrity and Long-Term Functional Recovery after chronic hypoperfusion in mice
title_short	Soluble epoxide hydrolase inhibition Promotes White Matter Integrity and Long-Term Functional Recovery after chronic hypoperfusion in mice
title_full	Soluble epoxide hydrolase inhibition Promotes White Matter Integrity and Long-Term Functional Recovery after chronic hypoperfusion in mice
title_fullStr	Soluble epoxide hydrolase inhibition Promotes White Matter Integrity and Long-Term Functional Recovery after chronic hypoperfusion in mice
title_full_unstemmed	Soluble epoxide hydrolase inhibition Promotes White Matter Integrity and Long-Term Functional Recovery after chronic hypoperfusion in mice
title_sort	soluble epoxide hydrolase inhibition promotes white matter integrity and long-term functional recovery after chronic hypoperfusion in mice
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/dde769c088264e80ba3b5f7bd1ec25f5
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Soluble epoxide hydrolase inhibition Promotes White Matter Integrity and Long-Term Functional Recovery after chronic hypoperfusion in mice

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