title: Sigma-1 Receptor Modulates Neuroinflammation After Traumatic Brain Injury.
abstract: Traumatic brain injury (TBI) remains a significant clinical problem and contributes to one-third of all injury-related deaths. Activated microglia-mediated inflammatory response is a distinct characteristic underlying pathophysiology of TBI. Here, we evaluated the effect and possible mechanisms of the selective Sigma-1 receptor agonist 2-(4-morpholinethyl)-1-phenylcyclohexanecarboxylate (PRE-084) in mice TBI model. A single intraperitoneal injection 10 μg/g PRE-084, given 15 min after TBI significantly reduced lesion volume, lessened brain edema, attenuated modified neurological severity score, increased the latency time in wire hang test, and accelerated body weight recovery. Moreover, immunohistochemical analysis with Iba1 staining showed that PRE-084 lessened microglia activation. Meanwhile, PRE-084 reduced nitrosative and oxidative stress to proteins. Thus, Sigma-1 receptors play a major role in inflammatory response after TBI and may serve as useful target for TBI treatment in the future.
authors.affiliation: Department of the Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, People's Republic of China.|Department of the Pediatric Neurosurgery, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Dong
authors.affiliation: Department of the Pediatric Neurosurgery, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, People's Republic of China.
authors.forename: Yunfu
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of the Neurosurgery, Pingdingshan Second People's Hospital, Pingdingshan, 467000, Henan, People's Republic of China.
authors.forename: Zengxi
authors.initials: Z
authors.lastname: Ren
authors.affiliation: Department of the Neurosurgery, Shanxi Dayi Hospital, Taiyuan, 030000, Shanxi, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.affiliation: Department of the Pediatric Neurosurgery, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, People's Republic of China.
authors.forename: Yunhe
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of the Pediatric Neurosurgery, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of the Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, People's Republic of China. dr_yangbo@126.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
mesh_terms: D000818:Animals; D001929:Brain Edema / Q000378:metabolism / Q000473:pathology; D000070642:Brain Injuries, Traumatic / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D007249:Inflammation / Q000378:metabolism*; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000378:metabolism; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D017480:Receptors, sigma / Q000378:metabolism*; D000097605:Sigma-1 Receptor
chemical_list: D009025:Morpholines; D018696:Neuroprotective Agents; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor; C071738:2-(4-morpholino)ethyl-1-phenylcyclohexane-1-carboxylate
keywords: Nitrosative stress; Oxidative stress; Sigma-1 receptor; Traumatic brain injury