title: Protective effects of hydrogen sulfide in a rat model of traumatic brain injury via activation of mitochondrial adenosine triphosphate-sensitive potassium channels and reduction of oxidative stress.
abstract: BACKGROUND
  Hydrogen sulfide (H2S) is considered an important neuromodulator in the central nervous system. We designed the present study to investigate the effects of exogenous H2S in a rat model of traumatic brain injury (TBI) and the mechanism(s) that underlie this effect.
  
  
  METHODS
  We induced a TBI model by controlled cortical impact injury. We intraperitoneally administered sodium hydrosulfide (NaHS) (an H2S donor) (3 mg/kg) or vehicle alone at 5 min after a TBI operation. We then measured the H2S level, brain edema, blood-brain barrier integrity, neurologic dysfunction, and lesion volume in all animals. Moreover, we assessed the role of mitochondrial adenosine triphosphate-sensitive potassium (mitoKATP)channels by intraperitoneal injection of the selective blocker 5-hydroxydecanoate before NaHS administration. In addition, we detected the levels of oxidative products and the activities of antioxidant enzymes in brain tissue.
  
  
  RESULTS
  Administration of NaHS significantly increased the H2S level of brain tissue in TBI-challenged rats. The TBI-challenged animals exhibited significant brain injuries, characterized by an increase of blood-brain barrier permeability, brain edema, and lesion volume, as well as neurologic dysfunction, which were significantly ameliorated by NaHS treatment. However, the protective effects of H2S in TBI could be abolished by the mitoK(ATP) channel blocker 5-hydroxydecanoate. Moreover, we found that NaHS treatment increased endogenous antioxidant enzymatic activities and decreased oxidative product levels in brain tissue of TBI-challenged rats.
  
  
  CONCLUSIONS
  Exogenous H2S administered at an appropriate dose can exert a protective effect against TBI via activation of mitoK(ATP) channels and reduction of oxidative stress.
authors.affiliation: Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Xiing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, People's Republic of China.
authors.forename: Xiaofan
authors.initials: X
authors.lastname: Jiang
authors.forename: Yi
authors.initials: Y
authors.lastname: Huang
authors.forename: Wei
authors.initials: W
authors.lastname: Lin
authors.forename: Dakuan
authors.initials: D
authors.lastname: Gao
authors.forename: Zhou
authors.initials: Z
authors.lastname: Fei
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000503:physiopathology; D001929:Brain Edema / Q000453:epidemiology; D001930:Brain Injuries / Q000503:physiopathology* / Q000517:prevention & control*; D006862:Hydrogen Sulfide / Q000494:pharmacology / Q000627:therapeutic use*; D015994:Incidence; D008297:Male; D023421:Models, Animal; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; D006862:Hydrogen Sulfide
keywords: Hydrogen sulfide; Oxidative stress; Traumatic brain injury; mitoK(ATP) channels