title: Soluble epoxide hydrolase inhibition provides multi-target therapeutic effects in rats after spinal cord injury.
abstract: 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.
authors: Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China.|Department of Neurology, Nanyang City Center Hospital, Nanyang, 473000, People's Republic of China.
authors: Xiaojing
authors: X
authors: Chen
authors: Department of Neurology, Xinhua Hospital of Hubei Province, Wuhan, 430015, People's Republic of China.
authors: Xiaoqi
authors: X
authors: Chen
authors: Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China.
authors: Xiaojiang
authors: X
authors: Huang
authors: Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China.
authors: Chuan
authors: C
authors: Qin
authors: Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China.
authors: Yongkang
authors: Y
authors: Fang
authors: Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China.
authors: Yang
authors: Y
authors: Liu
authors: Department of neurology, Xiangyang hospital affiliated to Hubei University of Medicine, Xiangyang, People's Republic of China.
authors: Guibing
authors: G
authors: Zhang
authors: Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China.
authors: Dengji
authors: D
authors: Pan
authors: Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China.
authors: Wei
authors: W
authors: Wang
authors: Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China. xie_minjie@126.com.
authors: Minjie
authors: M
authors: Xie
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors*; D005106:Exploratory Behavior / Q000187:drug effects; D019922:GAP-43 Protein / Q000096:biosynthesis / Q000235:genetics; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000235:genetics; D007850:Lauric Acids; D008297:Male; D017628:Microglia / Q000187:drug effects; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors*; D020556:Neutrophil Infiltration / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000098:blood supply / Q000201:enzymology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000201:enzymology
chemical_list: C504897:12-(3-adamantan-1-ylureido)dodecanoic acid; D019922:GAP-43 Protein; D053583:Interleukin-1beta; D007850:Lauric Acids; D009419:Nerve Tissue Proteins; D004851:Epoxide Hydrolases; C529022:EPHX2 protein, rat; D000218:Adamantane
keywords: Glial scar; Inflammation; Myelin loss; Neuronal apoptosis; Spinal cord injury; sEH