title: Neuroprotective effects of ebselen in traumatic brain injury model: involvement of nitric oxide and p38 mitogen-activated protein kinase signalling pathway.
abstract: Previous investigations have found that ebselen is able to treat neurodegenerative diseases caused by radical and acute total cerebral ischaemia. The aim of the present study was to investigate the neuroprotective effects of ebselen in a traumatic brain injury (TBI) model. Ninety Sprague-Dawley rats were randomly divided into five groups (n = 18 in each): (i) sham operation; (ii) an injury model group; (iii) low-dose (3 mg/kg) ebselen-treated group; (iv) a moderate-dose (10 mg/kg) ebselen-treated group; and (v) a high-dose (30 mg/kg) ebselen-treated group. The TBI model was created according using a modified weight-drop model. Neurological severity score (NSS), brain water content and histopathological deficits were assessed as parameters of injury severity. Expression of nitric oxide (NO), inducible NO synthase (iNOS) mRNA, Toll-like receptor (TLR) and phosphorylated (p-) p38 mitogen-activated protein kinase (MAPK) were examined by chemical colorimetry, quantitative polymerase chain reaction and western blotting 24 h after intragastric ebselen administration. Rats in the TBI model group exhibited markedly more severe neurological injury (higher NSS, more brain water content and more histopathological deficits) than those in the sham-operated group. Ebselen treatment significantly ameliorated the neurological injury of TBI rats in a dose-dependent manner. Moreover, ebselen significantly reduced the NO and iNOS mRNA levels and inhibited TLR4 and p-p38 MAPK expression, indicating the involvement of NO and p38 MAPK signalling pathways in the neuroprotection afforded by ebselen. In conclusion, ebselen ameliorated neurological injury, possibly by reducing NO levels and modulating the TLR4-mediated p38 MAPK signalling pathway. Therefore, ebselen may have potential to treat secondary injuries of TBI.
authors.affiliation: Department of Neurosurgery, East Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Wei
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Zhang
authors.forename: Cheng
authors.initials: C
authors.lastname: Yang
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.forename: Zhongwei
authors.initials: Z
authors.lastname: Zhuang
authors.forename: Zhiyang
authors.initials: Z
authors.lastname: Sun
mesh_terms: D000818:Animals; D001393:Azoles / Q000008:administration & dosage / Q000627:therapeutic use*; D015153:Blotting, Western; D001930:Brain Injuries / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015601:Injury Severity Score; D054833:Isoindoles; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000096:biosynthesis*; D016566:Organoselenium Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D001393:Azoles; D054833:Isoindoles; D018696:Neuroprotective Agents; D016566:Organoselenium Compounds; D009569:Nitric Oxide; C042986:ebselen
keywords: ebselen; inflammation; neuroprotection; traumatic brain injury