新表达的SUR1调节的NC（Ca-ATP）通道介导缺血性中风后的脑水肿。
Newly expressed SUR1-regulated NC(Ca-ATP) channel mediates cerebral edema after ischemic stroke.
作者信息
Simard J Marc, Chen Mingkui, Tarasov Kirill V, Bhatta Sergei, Ivanova Svetlana, Melnitchenko Ludmila, Tsymbalyuk Natalya, West G Alexander, Gerzanich Volodymyr
机构信息
Department of Neurosurgery, School of Medicine, University of Maryland at Baltimore, 22 South Greene Street, Suite 12SD, Baltimore, Maryland 21201-1595, USA.
出版信息
Nat Med. 2006 Apr;12(4):433-40. doi: 10.1038/nm1390. Epub 2006 Mar 19.
Pathological conditions in the central nervous system, including stroke and trauma, are often exacerbated by cerebral edema. We recently identified a nonselective cation channel, the NC(Ca-ATP) channel, in ischemic astrocytes that is regulated by sulfonylurea receptor 1 (SUR1), is opened by depletion of ATP and, when opened, causes cytotoxic edema. Here, we evaluated involvement of this channel in rodent models of stroke. SUR1 protein and mRNA were newly expressed in ischemic neurons, astrocytes and capillaries. Upregulation of SUR1 was linked to activation of the transcription factor Sp1 and was associated with expression of functional NC(Ca-ATP) but not K(ATP) channels. Block of SUR1 with low-dose glibenclamide reduced cerebral edema, infarct volume and mortality by 50%, with the reduction in infarct volume being associated with cortical sparing. Our findings indicate that the NC(Ca-ATP) channel is crucially involved in development of cerebral edema, and that targeting SUR1 may provide a new therapeutic approach to stroke.
包括中风和创伤在内的中枢神经系统病理状况，常常因脑水肿而加剧。我们最近在缺血性星形胶质细胞中鉴定出一种非选择性阳离子通道，即NC（Ca - ATP）通道，它受磺脲类受体1（SUR1）调控，因ATP耗竭而开放，开放时会导致细胞毒性水肿。在此，我们评估了该通道在啮齿动物中风模型中的作用。SUR1蛋白和mRNA在缺血性神经元、星形胶质细胞和毛细血管中重新表达。SUR1的上调与转录因子Sp1的激活有关，并与功能性NC（Ca - ATP）通道而非K（ATP）通道的表达相关。低剂量格列本脲阻断SUR1可使脑水肿、梗死体积和死亡率降低50%，梗死体积的减小与皮质保留有关。我们的研究结果表明，NC（Ca - ATP）通道在脑水肿的发展中起关键作用，靶向SUR1可能为中风提供一种新的治疗方法。
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