Montelukast, a cysteinyl leukotriene receptor-1 antagonist, attenuates chronic brain injury after focal cerebral ischaemia in mice and rats

被引:51
作者
Zhao, Rui [1 ,2 ]
Shi, Wen-Zhen [1 ]
Zhang, Yong-Mei [3 ,4 ]
Fang, San-Hua [1 ]
Wei, Er-Qing [1 ]
机构
[1] Zhejiang Univ, Dept Pharmacol, Sch Med, Hangzhou 310058, Zhejiang, Peoples R China
[2] Zhejiang Univ, Dept Pharm, Sir Run Run Shaw Hosp, Sch Med, Hangzhou 310058, Zhejiang, Peoples R China
[3] Xuzhou Med Coll, Dept Physiol, Xuzhou, Jiangsu, Peoples R China
[4] Xuzhou Med Coll, Dept Neurobiol, Xuzhou, Jiangsu, Peoples R China
关键词
antagonist; cysteinyl leukotriene receptor 1; focal cerebral ischaemia; montelukast; neuroprotection; KAPPA-B ACTIVATION; OXYGEN-GLUCOSE DEPRIVATION; FREE-RADICAL SCAVENGER; ASTROCYTE PROLIFERATION; SODIUM MK-0476; PRANLUKAST; ASTHMA; EXPRESSION; STROKE; CELLS;
D O I
10.1111/j.2042-7158.2010.01238.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Objectives Previously we demonstrated the neuroprotective effect of montelukast, a cysteinyl leukotriene receptor-1 (CysLT(1)) antagonist, on acute brain injury after focal cerebral ischaemia in mice. In this study, we have determined its effect on chronic brain injury after focal cerebral ischaemia in mice and rats. Methods After transient focal cerebral ischaemia was induced by middle cerebral artery occlusion, montelukast was intraperitoneally injected in mice or orally administered to rats for five days. Behavioural dysfunction, brain infarct volume, brain atrophy and neuron loss were determined to evaluate brain lesions. Key findings Montelukast (0.1 mg/kg) attenuated behavioural dysfunction, brain infarct volume, brain atrophy and neuron loss in mice, which was similar to pranlukast, another CysLT(1) receptor antagonist. Oral montelukast (0.5 mg/kg) was effective in rats and was more effective than edaravone, a free radical scavenger. Conclusion Montelukast protected mice and rats against chronic brain injury after focal cerebral ischaemia, supporting the therapeutic potential of CysLT(1) receptor antagonists.
引用
收藏
页码:550 / 557
页数:8
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