期刊
NEUROSCIENCE LETTERS
卷 506, 期 1, 页码 1-6出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2011.11.027
关键词
Middle cerebral artery occlusion; Cyclopamine; Glioma-associated oncogene homolog 1; Patched-1; Superoxide dismutase 1
资金
- National Natural Science Foundation of China [30700254]
- Hebei Province [C2010000564, 10276104D]
Oxidative and cytotoxic damage play an important role in cerebral ischemic pathogenesis and may represent a target for treatment. Recent studies have indicated that sonic hedgehog (Shh) signaling could protect neurons against oxidative stress by increasing superoxide dismutase 1 (SOD1) activity. Glioma-associated oncogene homolog 1 (Gli1) and patched-1 (Ptch1) are both components and transcriptional targets of the Shh pathway. Here, we designed this study to determine the effect of inhibition of Shh pathway on the development of cerebral ischemia injury. Male. Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion (pMCAO). Cyclopamine (0.18 mg/kg), the classical inhibitor of Shh signaling, was stereotactic injected into the lateral cerebral ventricle immediately after pMCAO. At 24 h neurological deficit was evaluated using a modified six point scale; brain water content was measured: infarct size was analyzed with 2,3,5-triphenyltetrazolium chloride (Tit). Immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR), Western Blotting and activity assay were used to analyze the expression of Gli1. Ptch1 and SOD1. Compared with Vehicle group, cyclopamine down-regulated Gli1, Ptch1 and SOD1 in pMCAO-affected brain tissue (P<0.05), and increased infarct volume (P<0.05), brain water content (P<0.05) and behavioral deficits (P<0.05). Collectively, the present results suggest that inhibition of Shh signaling pathway exacerbated rat ischemic damage caused by pMCAO, which may be correlated with down-regulated expression of Gli1, Ptch1 and SOD1. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据