title: Brief suppression of Abcc8 prevents autodestruction of spinal cord after trauma.
abstract: Spinal cord injury (SCI) is typically complicated by progressive hemorrhagic necrosis, an autodestructive process of secondary injury characterized by progressive enlargement of a hemorrhagic contusion during the first several hours after trauma. We assessed the role of Abcc8, which encodes sulfonylurea receptor 1 (SUR1), in progressive hemorrhagic necrosis. After SCI, humans and rodents exhibited similar regional and cellular patterns of up-regulation of SUR1 and Abcc8 messenger RNA. Elimination of SUR1 in Abcc8(-/-) mice and in rats given antisense oligodeoxynucleotide against Abcc8 prevented progressive hemorrhagic necrosis, yielded significantly better neurological function, and resulted in lesions that were one-fourth to one-third the size of those in control animals. The beneficial effects of Abcc8 suppression were associated with prevention of oncotic (necrotic) death of capillary endothelial cells. Suppression of Abcc8 with antisense oligodeoxynucleotide after SCI presents an opportunity for reducing the devastating sequelae of SCI.
authors.affiliation: Department of Neurosurgery, University of Maryland School of Medicine, 22 South Greene Street, Suite S12D, Baltimore, MD 21201-1595, USA. msimard@smail.umaryland.edu
authors.forename: J Marc
authors.initials: JM
authors.lastname: Simard
authors.forename: S Kyoon
authors.initials: SK
authors.lastname: Woo
authors.forename: Michael D
authors.initials: MD
authors.lastname: Norenberg
authors.forename: Cigdem
authors.initials: C
authors.lastname: Tosun
authors.forename: Zheng
authors.initials: Z
authors.lastname: Chen
authors.forename: Svetlana
authors.initials: S
authors.lastname: Ivanova
authors.forename: Orest
authors.initials: O
authors.lastname: Tsymbalyuk
authors.forename: Joseph
authors.initials: J
authors.lastname: Bryan
authors.forename: Douglas
authors.initials: D
authors.lastname: Landsman
authors.forename: Volodymyr
authors.initials: V
authors.lastname: Gerzanich
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D005905:Glyburide / Q000494:pharmacology; D006470:Hemorrhage / Q000150:complications / Q000473:pathology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009336:Necrosis; D024661:Potassium Channels, Inwardly Rectifying / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016372:RNA, Antisense / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011955:Receptors, Drug / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016329:Sp1 Transcription Factor / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000473:pathology* / Q000503:physiopathology / Q000517:prevention & control*; D064233:Sulfonylurea Receptors; D016896:Treatment Outcome
chemical_list: C577507:ABCC8 protein, human; D018528:ATP-Binding Cassette Transporters; C577508:Abcc8 protein, mouse; C577509:Abcc8 protein, rat; D024661:Potassium Channels, Inwardly Rectifying; D016372:RNA, Antisense; D012333:RNA, Messenger; D011955:Receptors, Drug; D016329:Sp1 Transcription Factor; D064233:Sulfonylurea Receptors; D005905:Glyburide
references.citation: Philos Trans R Soc Lond B Biol Sci. 2009 Jan 27;364(1514):257-67
references.pmid: 18990670
references.citation: Exp Neurol. 1996 Jun;139(2):244-56
references.pmid: 8654527
references.citation: Pflugers Arch. 2007 Feb;453(5):703-18
references.pmid: 16897043
references.citation: Ann N Y Acad Sci. 1999;890:366-84
references.pmid: 10668443
references.citation: Nat Med. 2006 Apr;12(4):433-40
references.pmid: 16550187
references.citation: J Neurosci. 2003 Sep 17;23(24):8568-77
references.pmid: 13679426
references.citation: J Mol Cell Cardiol. 2005 Jun;38(6):945-9
references.pmid: 15910879
references.citation: Lab Invest. 1978 Sep;39(3):236-53
references.pmid: 713489
references.citation: J Neurotrauma. 1998 Aug;15(8):645-53
references.pmid: 9726263
references.citation: Stroke. 2007 Sep;38(9):2526-30
references.pmid: 17673715
references.citation: J Neurosci. 2007 Oct 31;27(44):11782-92
references.pmid: 17978014
references.citation: J Neurotrauma. 1995 Feb;12(1):1-21
references.pmid: 7783230
references.citation: J Cereb Blood Flow Metab. 2009 Feb;29(2):317-30
references.pmid: 18854840
references.citation: Stroke. 2009 Feb;40(2):604-9
references.pmid: 19023097
references.citation: Lancet Neurol. 2007 Mar;6(3):258-68
references.pmid: 17303532
references.citation: Exp Neurol. 1999 May;157(1):19-42
references.pmid: 10222106
references.citation: Pflugers Arch. 1999 Apr;437(5):652-60
references.pmid: 10087141
references.citation: Endocr Rev. 2008 May;29(3):265-91
references.pmid: 18436707
references.citation: Pflugers Arch. 1999 Feb;437(3):400-8
references.pmid: 9914396
references.citation: Magn Reson Med. 2000 Apr;43(4):594-600
references.pmid: 10748436
references.citation: J Neurotrauma. 1997 Apr;14(4):235-48
references.pmid: 9151772
references.citation: Brain. 2006 Dec;129(Pt 12):3249-69
references.pmid: 17071951
references.citation: Curr Opin Struct Biol. 2007 Aug;17(4):412-8
references.pmid: 17723295
references.citation: Nat Med. 2009 Feb;15(2):185-91
references.pmid: 19169264
references.citation: J Neurosurg. 1997 Mar;86(3):483-92
references.pmid: 9046306
references.citation: Expert Rev Mol Med. 2009 Mar 23;11:e10
references.pmid: 19302730
references.citation: J Neurosurg. 1991 Jul;75(1):15-26
references.pmid: 2045903
references.citation: J Neurosci Methods. 2003 Nov 30;130(1):53-63
references.pmid: 14583404
references.citation: J Neurosurg. 1987 Apr;66(4):595-603
references.pmid: 3104553
references.citation: J Neurotrauma. 2006 May;23(5):635-59
references.pmid: 16689667
references.citation: J Clin Invest. 2007 Aug;117(8):2105-13
references.pmid: 17657312
references.citation: No Shinkei Geka. 1993 Jan;21(1):45-51
references.pmid: 8426687
references.citation: Spinal Cord. 2006 Sep;44(9):523-9
references.pmid: 16389270
references.citation: Circ Res. 2008 Feb 1;102(2):164-76
references.pmid: 18239147
references.citation: J Biol Chem. 1999 Jun 25;274(26):18261-70
references.pmid: 10373428
references.citation: J Biol Chem. 2000 Mar 31;275(13):9270-7
references.pmid: 10734066
references.citation: Curr Opin Pharmacol. 2008 Feb;8(1):42-9
references.pmid: 18032110