title: Mechanisms underlying the perifocal neuroprotective effect of the Nrf2-ARE signaling pathway after intracranial hemorrhage.
abstract: BACKGROUND
  It has been found that nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2-ARE) signaling pathway plays a role in antioxidative response, anti-inflammatory response, and neuron-protection in intracerebral hemorrhage (ICH). The aim of this study is to explore mechanisms underlying the perifocal neuroprotective effect of the Nrf2-ARE signaling pathway after ICH.
  
  
  METHODS
  There were a total of 90 rats with basal ganglia hemorrhage, which were randomly divided into the following four groups: ICH (Sprague-Dawley rats with autologous femoral arterial blood injection into the basal ganglia), sulforaphane (SFN) (SFN was intraperitoneally administered into rats), retinoic acid (RA) (RA was intraperitoneally administered into rats), and dimethyl sulfoxide (the rats were treated with dimethyl sulfoxide). We observed the neurological score of the rats in the different groups, and collected brain tissues for immunofluorescence, Western blot, and reverse transcription polymerase chain reaction to detect expression of Nrf2, heme oxygenase (HO-1), nuclear factor-κB (NF-κB), and tumor necrosis factor-α (TNF-α).
  
  
  RESULTS
  The results indicated that neurological dysfunction of rats was significantly improved in the SFN group, and the expressions of Nrf2 and HO-1 in tissues surrounding the hemorrhage were increased. Also, the level of NF-κB and TNF-α were reduced compared to the ICH group. The RA group exhibited more severe neurological dysfunction and lower levels of Nrf2 and HO-1 than the SFN and ICH groups. Compared to the ICH group, the NF-κB and TNF-α expression in the RA groups was increased. In conclusion, RA inhibits Nrf2 dissociation and translocation into nucleus, thereby suppressing the anti-inflammatory effect of Nrf2-ARE signaling pathway. The activation of Nrf2-ARE signaling pathway by SFN can elevate expression of antioxidant enzyme HO-1, reduce perifocal inflammatory response after ICH, and thus may play a neuroprotective role.
  
  
  CONCLUSIONS
  The results suggest that Nrf2-ARE signaling pathway may serve as a new target for treatment of perifocal inflammatory injury caused by ICH.
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Nanchang University, Nanchang, People's Republic of China ; Department of Neurology, Affiliated Hospital of Jiujiang University, Jiujiang, People's Republic of China.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Yin
authors.affiliation: Department of Neurology, Affiliated Hospital of Jiujiang University, Jiujiang, People's Republic of China.
authors.forename: Zhi-Ying
authors.initials: ZY
authors.lastname: Chen
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Nanchang University, Nanchang, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Nanchang University, Nanchang, People's Republic of China ; Department of Neurology, The Sixth Hospital of Wuhan, Wuhan, People's Republic of China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Neurology, Affiliated Hospital of Jiujiang University, Jiujiang, People's Republic of China.
authors.forename: Bing
authors.initials: B
authors.lastname: Bao
mesh_terms: D000818:Animals; D061745:Antioxidant Response Elements / Q000502:physiology*; D015153:Blotting, Western; D002543:Cerebral Hemorrhage / Q000503:physiopathology*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004195:Disease Models, Animal; D051547:Heme Oxygenase-1 / Q000378:metabolism; D017879:Isothiocyanates / Q000494:pharmacology; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D000066829:Neuroprotection / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D013454:Sulfoxides; D014212:Tretinoin / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D017879:Isothiocyanates; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; D013454:Sulfoxides; D014409:Tumor Necrosis Factor-alpha; D014212:Tretinoin; D051547:Heme Oxygenase-1; C016766:sulforaphane; D004121:Dimethyl Sulfoxide
keywords: NF-E2-related factor 2; antioxidant response elements; cerebral hemorrhage; injuries