Authors: Lina Wang Zhenzhong Li Xiangjian Zhang Sheng Wang Chunhua Zhu Jiangyong Miao Linyu Chen Lili Cui Huimin Qiao
Publish Date: 2013/11/19
Volume: 39, Issue: 1, Pages: 97-106
Abstract
Inflammatory damage plays an important role in cerebral ischemic pathogenesis and represents a new target for treatment of stroke Shikonin has gained attention for its prominent antiinflammatory property but up to now little is known about shikonin treatment in acute ischemic stroke The aim of this study was to evaluate the potential neuroprotective role of shikonin in cerebral ischemic injury and investigate whether shikonin modulated inflammatory responses after stroke Focal cerebral ischemia in male ICR mice was induced by transient middle cerebral artery occlusion Shikonin 10 and 25 mg/kg was administered by gavage once a day for 3 days before surgery and another dosage after operation Neurological deficit infarct volume brain edema blood–brain barrier BBB dysfunction and inflammatory mediators were evaluated at 24 and 72 h after stroke Compared with vehicle group 25 mg/kg shikonin significantly improved neurological deficit decreased infarct volume and edema both at 24 and 72 h after transient ischemic stroke our data also showed that shikonin inhibited the proinflammatory mediators including TLR4 TNFα NFκB and phosphorylation of p38MAPK in ischemic cortex In addition shikonin effectively alleviated brain leakage of Evans blue upregulated claudin5 expression and inhibited the overexpressed MMP9 in ischemic brain These results suggested that shikonin effectively protected brain against ischemic damage by regulating inflammatory responses and ameliorating BBB permeabilityThis study was funded by the National Natural Science Foundation of China 81371287 and 81072481 The authors thank technician Ruichun Liu Hongran Wu and Zhongyao Li for their technical assistance and Dr Yansu Guo Dr Weisong Duan for providing valuable suggestions
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