title: Neuroprotective effect of bicyclol in rat ischemic stroke: down-regulates TLR4, TLR9, TRAF6, NF-κB, MMP-9 and up-regulates claudin-5 expression.
abstract: BACKGROUND
  Inflammatory damage aggravates the cerebral ischemic pathological process and may pave a new way for treatment. Bicyclol has been proved to elicit a series of biologic effects through its anti-inflammatory property in treating hepatitis and hepatic ischemic/reperfusion injury. Whether this protective effect applies to cerebral ischemic injury, we therefore investigated the potential neuroprotective role of bicyclol and the underlying mechanisms.
  
  
  METHODS
  Male Sprague-Dawley rats were randomly assigned to five groups: permanent middle cerebral artery occlusion (pMCAO), Vehicle (pMCAO+0.5% sodium carboxymethylcellulose), By-L (Vehicle+bicyclol 50 mg/kg), By-H (Vehicle+bicyclol 100 mg/kg) and Sham operated group. Bicyclol was administered intragastrically once a day for 3 days, after 1h of bicyclol pretreatment on the third day; rat brain ischemia was induced by pMCAO. Neurological deficit, infarct volume, and brain edema were measured at 24 h after stroke. Immunohistochemistry, Western blot and real-time quantitative PCR were used to detect the expression of TLR4, TLR9, TRAF6, NF-κB and MMP-9, claudin-5.
  
  
  RESULTS
  Compared with pMCAO group, bicyclol significantly ameliorated neurological deficit, decreased infarct volume and edema, and down-regulated the expression of TLR4, TLR9, TRAF6, NF-κB and MMP-9 (P<0.05). Meanwhile, the expression of claudin-5 was increased (P<0.05).
  
  
  CONCLUSIONS
  Bicyclol has neuroprotective effect on cerebral ischemia, and this protection may be through down-regulating TLR4, TLR9, TRAF6, NF-κB, MMP-9 and up-regulating claudin-5 expression.
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, 215 Hepingxi Road, Shijiazhuang, Hebei 050000, PR China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Baosheng
authors.initials: B
authors.lastname: Fu
authors.forename: Xiangjian
authors.initials: X
authors.lastname: Zhang
authors.forename: Linyu
authors.initials: L
authors.lastname: Chen
authors.forename: Lan
authors.initials: L
authors.lastname: Zhang
authors.forename: Xumeng
authors.initials: X
authors.lastname: Zhao
authors.forename: Xue
authors.initials: X
authors.lastname: Bai
authors.forename: Chunhua
authors.initials: C
authors.lastname: Zhu
authors.forename: Lili
authors.initials: L
authors.lastname: Cui
authors.forename: Lina
authors.initials: L
authors.lastname: Wang
mesh_terms: D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D062507:Claudin-5 / Q000378:metabolism; D015536:Down-Regulation; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism* / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D001713:Biphenyl Compounds; D062507:Claudin-5; C491510:Cldn5 protein, rat; D016328:NF-kappa B; D018696:Neuroprotective Agents; D048029:TNF Receptor-Associated Factor 6; C495347:Tlr4 protein, rat; C489640:Tlr9 protein, rat; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; C477843:bicyclol; D020780:Matrix Metalloproteinase 9
keywords: Bicyclol; Ischemic stroke; NF-κB; Protection; TLR4; TRAF6