Soluble Epoxide Hydrolase Inhibitor Ameliorates Olfactory Dysfunction, Modulates Microglia Polarization, and Attenuates Neuroinflammation after Ischemic Brain Injury.

IF 6.2
Chien-Fu Yeh, Tung-Yueh Chuang, Ming-Ying Lan, Yung-Yang Lin, Wei-Hao Huang, Yu-Wen Hung
{"title":"Soluble Epoxide Hydrolase Inhibitor Ameliorates Olfactory Dysfunction, Modulates Microglia Polarization, and Attenuates Neuroinflammation after Ischemic Brain Injury.","authors":"Chien-Fu Yeh, Tung-Yueh Chuang, Ming-Ying Lan, Yung-Yang Lin, Wei-Hao Huang, Yu-Wen Hung","doi":"10.1007/s11481-024-10155-5","DOIUrl":null,"url":null,"abstract":"<p><p>Olfactory bulb (OB) microglia activation and inflammation can lead to olfactory dysfunction, which often occurs after an ischemic stroke. Inhibition of soluble epoxide hydrolase (sEH) attenuates neuroinflammation in brain injuries by reducing the degradation of anti-inflammatory epoxyeicosatrienoic acids. However, whether sEH inhibitors can ameliorate olfactory dysfunction after an ischemic stroke remains unknown. Ischemic brain injury and olfactory dysfunction were induced by middle cerebral artery occlusion (MCAO) in Wistar Kyoto rats. The rats were administered 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), a selective sEH inhibitor. Olfactory function, cerebral infarct volume, and the degree of degeneration, microglial polarization and neuroinflammation in OB were evaluated. Following treatment with AUDA, rats subjected to MCAO displayed mild cerebral infarction and OB degeneration, as well as better olfactory performance. In OB, AUDA triggered a modulation of microglial polarization toward the M2 anti-inflammatory type, reduction in proinflammatory mediators, and enhancement of the antioxidant process. The effectiveness of AUDA in terms of anti-inflammatory, neuroprotection and anti-oxidative properties suggests that it may have clinical therapeutic implication for ischemic stroke related olfactory dysfunction.</p>","PeriodicalId":73858,"journal":{"name":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","volume":null,"pages":null},"PeriodicalIF":6.2000,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1007/s11481-024-10155-5","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

Abstract

Olfactory bulb (OB) microglia activation and inflammation can lead to olfactory dysfunction, which often occurs after an ischemic stroke. Inhibition of soluble epoxide hydrolase (sEH) attenuates neuroinflammation in brain injuries by reducing the degradation of anti-inflammatory epoxyeicosatrienoic acids. However, whether sEH inhibitors can ameliorate olfactory dysfunction after an ischemic stroke remains unknown. Ischemic brain injury and olfactory dysfunction were induced by middle cerebral artery occlusion (MCAO) in Wistar Kyoto rats. The rats were administered 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), a selective sEH inhibitor. Olfactory function, cerebral infarct volume, and the degree of degeneration, microglial polarization and neuroinflammation in OB were evaluated. Following treatment with AUDA, rats subjected to MCAO displayed mild cerebral infarction and OB degeneration, as well as better olfactory performance. In OB, AUDA triggered a modulation of microglial polarization toward the M2 anti-inflammatory type, reduction in proinflammatory mediators, and enhancement of the antioxidant process. The effectiveness of AUDA in terms of anti-inflammatory, neuroprotection and anti-oxidative properties suggests that it may have clinical therapeutic implication for ischemic stroke related olfactory dysfunction.

可溶性环氧化物水解酶抑制剂能改善缺血性脑损伤后的嗅觉功能障碍、调节小胶质细胞极化并减轻神经炎症。
嗅球(OB)小胶质细胞的活化和炎症可导致嗅觉功能障碍,这种情况通常发生在缺血性中风之后。抑制可溶性环氧化物水解酶(sEH)可减少抗炎性环二十碳三烯酸的降解,从而减轻脑损伤中的神经炎症。然而,sEH 抑制剂能否改善缺血性中风后的嗅觉功能障碍仍是未知数。通过大脑中动脉闭塞(MCAO)诱导 Wistar Kyoto 大鼠出现缺血性脑损伤和嗅觉功能障碍。给大鼠注射选择性sEH抑制剂12-(3-金刚烷-1-基-脲基)-十二烷酸(AUDA)。对大鼠的嗅觉功能、脑梗塞体积、OB变性程度、小胶质细胞极化和神经炎症进行了评估。经 AUDA 治疗后,MCAO 大鼠表现出轻度脑梗塞和 OB 退化,嗅觉功能也有所改善。在OB中,AUDA引发了小胶质细胞向M2抗炎型极化的调节、促炎介质的减少以及抗氧化过程的增强。AUDA在抗炎、神经保护和抗氧化方面的功效表明,它可能对缺血性中风相关的嗅觉功能障碍具有临床治疗意义。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
自引率
0.00%
发文量
0
期刊介绍:
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信