Epoxyeicosanoid Signaling Provides Multi-target Protective Effects on Neurovascular Unit in Rats After Focal Ischemia

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• 作者：Yang Liu ; Yue Wan ; Yongkang Fang ; Ensheng Yao…
• 关键词：sEH ; Epoxyeicosatrienoic acids ; Ischemia ; Neuroprotection ; Neurovascular unit
• 刊名：Journal of Molecular Neuroscience
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：58
• 期：2
• 页码：254-265
• 全文大小：3,997 KB
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• 作者单位：Yang Liu (1)
  Yue Wan (2)
  Yongkang Fang (1)
  Ensheng Yao (1)
  Shabei Xu (1)
  Qin Ning (3)
  Guibing Zhang (4)
  Wei Wang (1)
  Xiaojiang Huang (1)
  Minjie Xie (1)
  
  1. Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China
  2. Department of Neurology, The Third People’s Hospital of Hubei Province, Wuhan, 430030, China
  3. Department of Infectious Disease, Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
  4. Department of Neurology, Xiangyang Hospital Affiliated to Hubei University of Medicine, Xiangyang, 441000, China
  
• 刊物主题：Neurosciences; Neurochemistry; Cell Biology; Proteomics; Neurology;
• 出版者：Springer US
• ISSN：1559-1166

文摘

Multiple players are involved in the highly complex pathophysiologic responses after stroke. Therefore, therapeutic approaches that target multiple cellular elements of the neurovascular unit in the damage cascade hold considerable promise for the treatment of stroke. Cytochrome P450 (CYP) epoxygenases metabolize arachidonic acid to biologically active eicosanoids called epoxyeicosatrienoic acids (EETs), which are further converted by soluble epoxide hydrolase (sEH) to less bioactive diols. EETs have been shown to exert direct cytoprotective effects upon several individual components of the neurovascular unit under simulated ischemic conditions in vitro. However, the cellular mechanism underlying EET-mediated neuroprotective effects after ischemia remains to be clarified. In this study, we investigated the effects of 14,15-EET and 12-(3-adamantan-1-yl-ureido)dodecanoic acid (AUDA), a selective inhibitor of sEH, on multiple elements of neurovascular unit of the rat brain after middle cerebral artery occlusion-induced focal ischemia. The results showed that exogenous administration of 14,15-EET or AUDA could suppress astrogliosis and glial scar formation, inhibit microglia activation and inflammatory response, promote angiogenesis, attenuate neuronal apoptosis and infarct volume, and further promote the behavioral function recovery after focal ischemia. The results suggest that epoxyeicosanoid signaling is a promising multi-mechanism therapeutic target for the treatment of stroke. Keywords sEH Epoxyeicosatrienoic acids Ischemia Neuroprotection Neurovascular unit