Soluble epoxide hydrolase inhibition provides multi-target therapeutic effects in rats after spinal cord injury

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• 作者：Xiaojing Chen ; Xiaoqi Chen ; Xiaojiang Huang ; Chuan Qin…
• 关键词：sEH ; Spinal cord injury ; Glial scar ; Inflammation ; Neuronal apoptosis ; Myelin loss
• 刊名：Molecular Neurobiology
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：53
• 期：3
• 页码：1565-1578
• 全文大小：11,420 KB
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• 作者单位：Xiaojing Chen (1) (4)
  Xiaoqi Chen (2)
  Xiaojiang Huang (1)
  Chuan Qin (1)
  Yongkang Fang (1)
  Yang Liu (1)
  Guibing Zhang (3)
  Dengji Pan (1)
  Wei Wang (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
  4. Department of Neurology, Nanyang City Center Hospital, Nanyang, 473000, People’s Republic of China
  2. Department of Neurology, Xinhua Hospital of Hubei Province, Wuhan, 430015, People’s Republic of China
  3. Department of neurology, Xiangyang hospital affiliated to Hubei University of Medicine, Xiangyang, People’s Republic of China
  
• 刊物主题：Neurosciences; Neurobiology; Cell Biology; Neurology;
• 出版者：Springer US
• ISSN：1559-1182

文摘

Multiple players are involved in motor and sensory dysfunctions after spinal cord injury (SCI). Therefore, therapeutic approaches targeting these various players in the damage cascade hold considerable promise for the treatment of traumatic spinal cord injury. Soluble epoxide hydrolase (sEH) is an endogenous key enzyme in the metabolic conversion and degradation of P450 eicosanoids called epoxyeicosatrienoic acids (EETs). sEH inhibition has been shown to provide neuroprotective effects upon multiple elements of neurovascular unit under cerebral ischemia. However, its role in the pathological process after SCI remains unclear. In this study, we tested the hypothesis that sEH inhibition may have therapeutic effects in preventing secondary damage in rats after traumatic SCI. sEH was widely expressed in spinal cord tissue, mainly confined to astrocytes, and neurons. Administration of sEH inhibitor AUDA significantly suppressed local inflammatory responses as indicated by the reduced microglia activation and IL-1 β expression, as well as the decreased infiltration of neutrophils and T lymphocytes. Meanwhile, reactive astrogliosis was remarkably attenuated. Furthermore, treatment of AUDA improved angiogenesis, inhibited neuron cells apoptosis, alleviated demyelination and formation of cavity and improved motor recovery. Together, these results provide the first in vivo evidence that sEH inhibition could exert multiple targets protective effects after SCI in rats. sEH may thereby serve as a promising multi-mechanism therapeutic target for the treatment of SCI.