title: Beneficial effects of sulindac in focal cerebral ischemia: a positive role in Wnt/β-catenin pathway.
abstract: BACKGROUND
  Accumulated evidences have established that inflammatory damage plays an important role in cerebral ischemic pathogenesis and may represent a target for treatment. Sulindac is well known as a nonsteroidal anti-inflammatory drug. However, little is known regarding the effect of sulindac in acute cerebral ischemia. Here, we designed this study to investigate the potential protective effects of sulindac in focal cerebral ischemia and the mechanisms underlying in vivo.
  
  
  METHODS
  Focal cerebral ischemia was induced in male Sprague-Dawley rats by permanent middle cerebral artery occlusion (pMCAO). Sulindac was administrated at dose of 4, 10, or 20mg/kg at 30 min before the operation. Neurological deficit scores, brain water content and infarct volumes were measured at 24h after pMCAO. Immunohistochemistry, western blot and reverse transcription-polymerase chain reaction were used for examining the mediators involved in Wnt/β-catenin signaling pathway, including the positive regulators dishevelled (Dvl) and β-catenin, the negative regulators adenomatous polyposis coli (APC), and P-β-catenin, as well as the downstream targets Bcl-2, Bax and claudin-5.
  
  
  RESULTS
  Compared with Vehicle group, 20mg/kg sulindac reduced neurological deficits, brain water content and infarct volumes. The same dose of sulindac upregulated the expression of Dvl, β-catenin, Bcl2 and claudin-5, and downregulated APC, P-β-catenin and Bax compared with Vehicle group.
  
  
  CONCLUSIONS
  These results showed that sulindac had a significant beneficial effect in cerebral ischemia; this effect may be correlated with the activation of the Wnt/β-catenin signaling.
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China.
authors.forename: Yinxue
authors.initials: Y
authors.lastname: Xing
authors.forename: Xiangjian
authors.initials: X
authors.lastname: Zhang
authors.forename: Kang
authors.initials: K
authors.lastname: Zhao
authors.forename: Lili
authors.initials: L
authors.lastname: Cui
authors.forename: Lina
authors.initials: L
authors.lastname: Wang
authors.forename: Lipeng
authors.initials: L
authors.lastname: Dong
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Li
authors.forename: Zongjie
authors.initials: Z
authors.lastname: Liu
authors.forename: Chaohui
authors.initials: C
authors.lastname: Wang
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Zhang
authors.forename: Chunhua
authors.initials: C
authors.lastname: Zhu
authors.forename: Huimin
authors.initials: H
authors.lastname: Qiao
authors.forename: Ye
authors.initials: Y
authors.lastname: Ji
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Cao
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D001929:Brain Edema / Q000188:drug therapy / Q000209:etiology; D020520:Brain Infarction / Q000188:drug therapy / Q000209:etiology; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D008297:Male; D009422:Nervous System Diseases / Q000209:etiology / Q000517:prevention & control; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric; D013467:Sulindac / Q000008:administration & dosage*; D060449:Wnt Signaling Pathway / Q000187:drug effects* / Q000235:genetics; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051176:beta Catenin; D013467:Sulindac