PMID- 18854840 OWN - NLM STAT- MEDLINE DCOM- 20090223 LR - 20220317 IS - 1559-7016 (Electronic) IS - 0271-678X (Print) IS - 0271-678X (Linking) VI - 29 IP - 2 DP - 2009 Feb TI - Glibenclamide reduces inflammation, vasogenic edema, and caspase-3 activation after subarachnoid hemorrhage. PG - 317-30 LID - 10.1038/jcbfm.2008.120 [doi] AB - Subarachnoid hemorrhage (SAH) causes secondary brain injury due to vasospasm and inflammation. Here, we studied a rat model of mild-to-moderate SAH intended to minimize ischemia/hypoxia to examine the role of sulfonylurea receptor 1 (SUR1) in the inflammatory response induced by SAH. mRNA for Abcc8, which encodes SUR1, and SUR1 protein were abundantly upregulated in cortex adjacent to SAH, where tumor-necrosis factor-alpha (TNFalpha) and nuclear factor (NF)kappaB signaling were prominent. In vitro experiments confirmed that Abcc8 transcription is stimulated by TNFalpha. To investigate the functional consequences of SUR1 expression after SAH, we studied the effect of the potent, selective SUR1 inhibitor, glibenclamide. We examined barrier permeability (immunoglobulin G, IgG extravasation), and its correlate, the localization of the tight junction protein, zona occludens 1 (ZO-1). SAH caused a large increase in barrier permeability and disrupted the normal junctional localization of ZO-1, with glibenclamide significantly reducing both effects. In addition, SAH caused large increases in markers of inflammation, including TNFalpha and NFkappaB, and markers of cell injury or cell death, including IgG endocytosis and caspase-3 activation, with glibenclamide significantly reducing these effects. We conclude that block of SUR1 by glibenclamide may ameliorate several pathologic effects associated with inflammation that lead to cortical dysfunction after SAH. FAU - Simard, J Marc AU - Simard JM AD - Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, Maryland 21201-1595, USA. msimard@smail.umaryland.edu FAU - Geng, Zhihua AU - Geng Z FAU - Woo, S Kyoon AU - Woo SK FAU - Ivanova, Svetlana AU - Ivanova S FAU - Tosun, Cigdem AU - Tosun C FAU - Melnichenko, Ludmila AU - Melnichenko L FAU - Gerzanich, Volodymyr AU - Gerzanich V LA - eng GR - R01 NS061808/NS/NINDS NIH HHS/United States GR - NS048260/NS/NINDS NIH HHS/United States GR - R01 HL082517/HL/NHLBI NIH HHS/United States GR - NS061808/NS/NINDS NIH HHS/United States GR - HL082517/HL/NHLBI NIH HHS/United States GR - R01 NS048260/NS/NINDS NIH HHS/United States GR - R01 HL082517-02/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20081015 PL - United States TA - J Cereb Blood Flow Metab JT - Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism JID - 8112566 RN - 0 (ATP-Binding Cassette Transporters) RN - 0 (Abcc8 protein, rat) RN - 0 (Potassium Channels, Inwardly Rectifying) RN - 0 (Receptors, Drug) RN - 0 (Sulfonylurea Receptors) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 3.4.22.- (Caspase 3) RN - SX6K58TVWC (Glyburide) SB - IM EIN - J Cereb Blood Flow Metab. 2009 Apr;29(4):872 MH - ATP-Binding Cassette Transporters/genetics/metabolism MH - Animals MH - Blood-Brain Barrier/drug effects MH - Brain Edema/*drug therapy/*enzymology/pathology MH - Carotid Artery Injuries MH - Carotid Artery, Internal MH - Caspase 3/*metabolism MH - Enzyme Activation/drug effects MH - Glyburide/*therapeutic use MH - Hypoxia/pathology MH - Inflammation/*drug therapy/enzymology/pathology MH - Male MH - Potassium Channels, Inwardly Rectifying/genetics/metabolism MH - Rats MH - Rats, Wistar MH - Receptors, Drug/genetics/metabolism MH - Subarachnoid Hemorrhage/*drug therapy/*enzymology/pathology MH - Sulfonylurea Receptors MH - Tumor Necrosis Factor-alpha/pharmacology MH - Up-Regulation/genetics PMC - PMC2740919 MID - NIHMS128907 EDAT- 2008/10/16 09:00 MHDA- 2009/02/24 09:00 PMCR- 2009/09/10 CRDT- 2008/10/16 09:00 PHST- 2008/10/16 09:00 [pubmed] PHST- 2009/02/24 09:00 [medline] PHST- 2008/10/16 09:00 [entrez] PHST- 2009/09/10 00:00 [pmc-release] AID - jcbfm2008120 [pii] AID - 10.1038/jcbfm.2008.120 [doi] PST - ppublish SO - J Cereb Blood Flow Metab. 2009 Feb;29(2):317-30. doi: 10.1038/jcbfm.2008.120. Epub 2008 Oct 15.