- 作者：Yinxue Xing ; Xiangjian Zhang ; Kang Zhao ; Lili Cui ; Lina Wang ; Lipeng Dong ; Yanhua Li ; Zongjie Liu ; Chaohui Wang ; Xiaolin Zhang ; Chunhua Zhu ; Huimin Qiao ; Ye Ji ; Xiaoyun Cao
- 关键词：Cerebral ischemia ; Sulindac ; Wnt/¦Â-catenin signaling ; Bcl-2 ; Bax ; Claudin-5
- 刊名：Brain Research
- 出版年：2012
- 出版时间：30 October, 2012
- 年：2012
- 卷：1482
- 期：Complete
- 页码：71-80
- 全文大小：1058 K
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 20 mg/kg at 30 min before the operation. Neurological deficit scores, brain water content and infarct volumes were measured at 24 h after pMCAO. Immunohistochemistry, western blot and reverse transcription-polymerase chain reaction were used for examining the mediators involved in Wnt/¦Â-catenin signaling pathway, including the positive regulators dishevelled (Dvl) and ¦Â-catenin, the negative regulators adenomatous polyposis coli (APC), and P-¦Â-catenin, as well as the downstream targets Bcl-2, Bax and claudin-5.
Results
Compared with Vehicle group, 20 mg/kg sulindac reduced neurological deficits, brain water content and infarct volumes. The same dose of sulindac upregulated the expression of Dvl, ¦Â-catenin, Bcl2 and claudin-5, and downregulated APC, P-¦Â-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/¦Â-catenin signaling.