title: Targeting heme oxygenase after intracerebral hemorrhage.
abstract: Intracerebral hemorrhage (ICH) is the primary event in approximately 10% of strokes, and has higher rates of morbidity and mortality than ischemic stroke. Experimental evidence suggests that the toxicity of hemoglobin and its degradation products contributes to secondary injury that may be amenable to therapeutic intervention. Hemin, the oxidized form of heme, accumulates in intracranial hematomas to cytotoxic levels. The rate limiting step of its breakdown is catalyzed by the heme oxygenase (HO) enzymes, which consist of inducible HO-1 and constitutively-expressed HO-2. The effect of these enzymes on perihematomal injury and neurological outcome has been investigated in ICH models using both genetic and pharmacological approaches to alter their expression, with variable results reported. These findings are summarized and reconciled in this review; therapeutic strategies that may optimize HO expression and activity after ICH are described.
authors: Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA, USA.
authors: Jing
authors: J
authors: Chen-Roetling
authors: Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA, USA.
authors: Xiangping
authors: X
authors: Lu
authors: Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA, USA.
authors: Raymond F
authors: RF
authors: Regan
keywords: intracerebral hemorrhage; iron; oxidative stress; stroke; subarachnoid hemorrhage
references: Cell Mol Biol (Noisy-le-grand). 2000 May;46(3):597-608
references: 10872746
references: Biomarkers. 2009 Nov;14(7):493-501
references: 19863188
references: Neuron. 1995 Oct;15(4):867-73
references: 7576635
references: Drug Metab Dispos. 1999 Oct;27(10 ):1214-9
references: 10497150
references: J Neurotrauma. 2003 Jan;20(1):111-20
references: 12614593
references: J Neurosci. 2002 Jul 15;22(14):5848-55
references: 12122047
references: Biochem Biophys Res Commun. 2004 May 21;318(1):88-94
references: 15110757
references: J Neurochem. 2009 Jul;110(2):469-85
references: 19457088
references: J Neurosurg. 2000 Jun;92(6):1016-22
references: 10839264
references: Anesthesiology. 2008 Aug;109 (2):260-8
references: 18648235
references: Lancet Neurol. 2006 Jan;5(1):53-63
references: 16361023
references: J Neurotrauma. 2004 Aug;21(8):1017-30
references: 15319001
references: Nature. 2001 Jan 11;409(6817):198-201
references: 11196644
references: Free Radic Res. 2014 Feb;48(2):200-5
references: 24164169
references: Neurology. 1999 Jan 15;52(2):266-72
references: 9932942
references: Ann N Y Acad Sci. 2004 Mar;1012:14-26
references: 15105252
references: Free Radic Biol Med. 1990;9(1):5-10
references: 2210440
references: Blood. 2001 Mar 1;97(5):1306-13
references: 11222374
references: J Biol Chem. 2007 Jul 13;282(28):20621-33
references: 17430897
references: Redox Rep. 2009;14 (6):228-35
references: 20003707
references: J Biol Chem. 2010 Sep 10;285(37):28874-82
references: 20610401
references: Free Radic Biol Med. 2003 Oct 15;35(8):872-81
references: 14556851
references: J Cereb Blood Flow Metab. 2008 Mar;28(3):516-25
references: 17726491
references: Adv Ther. 2008 Sep;25(9):842-57
references: 18777015
references: J Neurosurg. 1993 Aug;79(2):252-5
references: 8331409
references: Neurobiol Dis. 2014 Oct;70:245-51
references: 24952361
references: J Cereb Blood Flow Metab. 2005 Nov;25(11):1466-75
references: 15902196
references: J Biol Chem. 1968 Feb 10;243(3):465-75
references: 4966113
references: BMC Res Notes. 2014 Aug 22;7:561
references: 25149897
references: Neurochem Int. 2012 Apr;60(5):488-94
references: 22342655
references: Neuroscience. 2008 Sep 9;155(4):1133-41
references: 18674596
references: Brain. 2007 Jun;130(Pt 6):1643-52
references: 17525142
references: Eur J Biochem. 1974 Mar 15;43(1):73-8
references: 4209590
references: J Cereb Blood Flow Metab. 2009 May;29(5):953-64
references: 19277051
references: Neuropharmacology. 2011 Feb-Mar;60(2-3):423-31
references: 21034753
references: Ann N Y Acad Sci. 2004 Mar;1012:237-51
references: 15105270
references: Pharmacol Rev. 2008 Mar;60(1):79-127
references: 18323402
references: Blood. 2006 Jan 1;107(1):373-80
references: 16189277
references: J Neurosurg. 2002 Feb;96(2):287-93
references: 11838803
references: Neurocrit Care. 2008;9(1):139-52
references: 18058257
references: J Cereb Blood Flow Metab. 1998 May;18(5):559-69
references: 9591848
references: J Neurochem. 2010 Aug;114(4):1063-73
references: 20497302
references: Neurobiol Dis. 2006 Jun;22(3):473-6
references: 16459095
references: J Cereb Blood Flow Metab. 2001 Jul;21(7):804-10
references: 11435792
references: Ann Intern Med. 2005 Mar 15;142(6):439-50
references: 15767622
references: Acta Neurochir Suppl. 2006;96:232-6
references: 16671461
references: J Clin Invest. 1981 Sep;68(3):672-7
references: 7276166
references: J Neurosci Methods. 2013 Jun 15;216(2):128-36
references: 23583700
references: BMC Neurosci. 2004 Sep 17;5:34
references: 15377391
references: J Neurosurg. 2007 Mar;106(3):428-35
references: 17367065