Brief suppression of Abcc8 prevents autodestruction of spinal cord after trauma.
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.
Simard
J Marc
JM
Department of Neurosurgery, University of Maryland School of Medicine, 22 South Greene Street, Suite S12D, Baltimore, MD 21201-1595, USA. msimard@smail.umaryland.edu
Woo
S Kyoon
SK
Norenberg
Michael D
MD
Tosun
Cigdem
C
Chen
Zheng
Z
Ivanova
Svetlana
S
Tsymbalyuk
Orest
O
Bryan
Joseph
J
Landsman
Douglas
D
Gerzanich
Volodymyr
V
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
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
Philos Trans R Soc Lond B Biol Sci. 2009 Jan 27;364(1514):257-67
18990670
Exp Neurol. 1996 Jun;139(2):244-56
8654527
Pflugers Arch. 2007 Feb;453(5):703-18
16897043
Ann N Y Acad Sci. 1999;890:366-84
10668443
Nat Med. 2006 Apr;12(4):433-40
16550187
J Neurosci. 2003 Sep 17;23(24):8568-77
13679426
J Mol Cell Cardiol. 2005 Jun;38(6):945-9
15910879
Lab Invest. 1978 Sep;39(3):236-53
713489
J Neurotrauma. 1998 Aug;15(8):645-53
9726263
Stroke. 2007 Sep;38(9):2526-30
17673715
J Neurosci. 2007 Oct 31;27(44):11782-92
17978014
J Neurotrauma. 1995 Feb;12(1):1-21
7783230
J Cereb Blood Flow Metab. 2009 Feb;29(2):317-30
18854840
Stroke. 2009 Feb;40(2):604-9
19023097
Lancet Neurol. 2007 Mar;6(3):258-68
17303532
Exp Neurol. 1999 May;157(1):19-42
10222106
Pflugers Arch. 1999 Apr;437(5):652-60
10087141
Endocr Rev. 2008 May;29(3):265-91
18436707
Pflugers Arch. 1999 Feb;437(3):400-8
9914396
Magn Reson Med. 2000 Apr;43(4):594-600
10748436
J Neurotrauma. 1997 Apr;14(4):235-48
9151772
Brain. 2006 Dec;129(Pt 12):3249-69
17071951
Curr Opin Struct Biol. 2007 Aug;17(4):412-8
17723295
Nat Med. 2009 Feb;15(2):185-91
19169264
J Neurosurg. 1997 Mar;86(3):483-92
9046306
Expert Rev Mol Med. 2009 Mar 23;11:e10
19302730
J Neurosurg. 1991 Jul;75(1):15-26
2045903
J Neurosci Methods. 2003 Nov 30;130(1):53-63
14583404
J Neurosurg. 1987 Apr;66(4):595-603
3104553
J Neurotrauma. 2006 May;23(5):635-59
16689667
J Clin Invest. 2007 Aug;117(8):2105-13
17657312
No Shinkei Geka. 1993 Jan;21(1):45-51
8426687
Spinal Cord. 2006 Sep;44(9):523-9
16389270
Circ Res. 2008 Feb 1;102(2):164-76
18239147
J Biol Chem. 1999 Jun 25;274(26):18261-70
10373428
J Biol Chem. 2000 Mar 31;275(13):9270-7
10734066
Curr Opin Pharmacol. 2008 Feb;8(1):42-9
18032110