title: Neuroprotective effects of exogenous methane in a rat model of acute carbon monoxide poisoning.
abstract: OBJECTIVE
  Delayed neuropsychological sequelae (DNS) are the most common and serious effects of severe carbon monoxide (CO) poisoning, occurring in approximately half of all CO poisoning cases. Growing evidence suggests that oxidative stress and secondary reactions in delayed brain injury are crucial to CO toxicity, similar to ischaemia-reperfusion injury. Exogenous methane plays a protective role in ischaemia-reperfusion injury by affecting key events through anti-oxidant, anti-inflammatory, and anti-apoptosis actions. Our study aimed to explore the potential of exogenous methane to relieve the severity of DNS.
  
  
  METHODS
  Thirty-six male Sprague-Dawley (SD) rats were divided into three groups of normal-, CO- and CO plus methane-treated rats. The rats in the latter two groups were exposed to 1000 ppm CO for 40 min and then to 3000 ppm CO for another 20 min. Following CO exposure, saline or methane saline (10 ml/kg) was intraperitoneally administered to rats in the CO group or the CO plus methane group, respectively. On the ninth day after CO exposure, Morris water maze testing, histological analysis, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) and immunohistochemical labelling were performed on 6 rats in each group. The remaining 6 rats in each group were used to detect oxidative damage markers, inflammatory cytokines and apoptosis proteins.
  
  
  RESULTS
  Methane significantly improved CO-impaired pathological characteristics as well as learning and memory performance. In addition, methane significantly increased the superoxide dismutase (SOD) activity, lowered the CO-increased level of malondialdehyde (MDA) 3-nitrotyrosine (3-NT) and 8-hydroxy-2-deoxyguanosine (8-OHdG), inhibited levels of tumour necrosis factor-α (TNF-α), interleukin 1-β (IL1-β) and caspase-3 in the rat cerebral cortex and hippocampus but had no effect on IL-6 levels.
  
  
  CONCLUSIONS
  The hippocampus was the main target of CO-induced alterations in the rat brain compared to the cerebral cortex. Methane treatment protected the rat brain from the harmful effects induced by CO exposure and improved the outcome of DNS through anti-oxidant, anti-inflammatory and anti-apoptosis activities.
authors.affiliation: Department of Naval Aeromedicine, Faculty of Naval Medicine, Second Military Medical University, No. 800, Xiangyin Road, Shanghai 200433, PR China; Department of Hyperbaric Oxygen, Navy General Hospital, No. 6, Fucheng Road, Beijing 100048, PR China.
authors.forename: Dan-Feng
authors.initials: DF
authors.lastname: Fan
authors.affiliation: Department of Naval Aeromedicine, Faculty of Naval Medicine, Second Military Medical University, No. 800, Xiangyin Road, Shanghai 200433, PR China; Department of Hyperbaric Oxygen, Navy General Hospital, No. 6, Fucheng Road, Beijing 100048, PR China.
authors.forename: Hui-Jun
authors.initials: HJ
authors.lastname: Hu
authors.affiliation: Department of Hyperbaric Oxygen, Navy General Hospital, No. 6, Fucheng Road, Beijing 100048, PR China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Department of Hyperbaric Oxygen, Navy General Hospital, No. 6, Fucheng Road, Beijing 100048, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lv
authors.affiliation: Department of Naval Aeromedicine, Faculty of Naval Medicine, Second Military Medical University, No. 800, Xiangyin Road, Shanghai 200433, PR China.
authors.forename: Zhou-Heng
authors.initials: ZH
authors.lastname: Ye
authors.affiliation: Department of Naval Aeromedicine, Faculty of Naval Medicine, Second Military Medical University, No. 800, Xiangyin Road, Shanghai 200433, PR China. Electronic address: sunxjk@hotmail.com.
authors.forename: Xue-Jun
authors.initials: XJ
authors.lastname: Sun
authors.affiliation: Department of Hyperbaric Oxygen, Navy General Hospital, No. 6, Fucheng Road, Beijing 100048, PR China. Electronic address: hbofandf@163.com.
authors.forename: Shu-Yi
authors.initials: SY
authors.lastname: Pan
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002249:Carbon Monoxide Poisoning / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008697:Methane / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D018696:Neuroprotective Agents; D008697:Methane
keywords: Apoptosis; Carbon monoxide poisoning; Methane; Neuroprotection; Oxidative stress