Nature Medicine
- 12, 433 - 440 (2006)
Published online: 19 March 2006; | doi:10.1038/nm1390
Newly expressed SUR1-regulated NCCa-ATP channel mediates cerebral edema after ischemic strokeJ Marc Simard1, 2, 3, Mingkui Chen1, Kirill V Tarasov1, Sergei Bhatta1, Svetlana Ivanova1, Ludmila Melnitchenko1, Natalya Tsymbalyuk1, G Alexander West4 & Volodymyr Gerzanich11
Department of Neurosurgery, School of Medicine, University of Maryland at Baltimore, 22 South Greene Street, Suite 12SD, Baltimore, Maryland 21201-1595, USA. 2
Department of Pathology, School of Medicine, University of Maryland at Baltimore, 22 South Greene Street, Suite 12SD, Baltimore, Maryland 21201-1595, USA. 3
Department of Physiology, School of Medicine, University of Maryland at Baltimore, 22 South Greene Street, Suite 12SD, Baltimore, Maryland 21201-1595, USA. 4
Department of Neurological Surgery, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239-3098, USA.
Correspondence should be addressed to J Marc Simard msimard@surgery1.umaryland.edu 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 NCCa-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 NCCa-ATP but not KATP 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 NCCa-ATP channel is crucially involved in development of cerebral edema, and that targeting SUR1 may provide a new therapeutic approach to stroke.
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