Heme activates TLR4-mediated inflammatory injury via MyD88/TRIF signaling pathway in intracerebral hemorrhage

Lapchak PA, Araujo DM: Advances in hemorrhagic stroke therapy: conventional and novel approaches. Expert Opin Emerg Drugs 2007, 12:389–406.

Ferro JM: Update on intracerebral haemorrhage. J Neurol 2006, 253:985–999.

Hanley DF: Intraventricular hemorrhage: severity factor and treatment target in spontaneous intracerebral hemorrhage. Stroke 2009, 40:1533–1538.

Gong C, Hoff JT, Keep RF: Acute inflammatory reaction following experimental intracerebral hemorrhage in rat. Brain Res 2000, 871:57–65.

Castillo J, Dávalos A, Alvarez-Sabín J, Pumar JM, Leira R, Silva Y, Montaner J, Kase CS: Molecular signatures of brain injury after intracerebral hemorrhage. Neurology 2002, 58:624–629.

Xi G, Keep RF, Hoff JT: Pathophysiology of brain edema formation. Genetics 2002, 13:371–383.

Xi G, Keep RF, Hoff JT: Mechanisms of brain injury after intracerebral haemorrhage. Lancet Neurol 2006, 5:53–63.

Yang GY, Betz AL, Chenevert TL, Brunberg JA, Hoff JT: Experimental intracerebral hemorrhage: relationship between brain edema, blood flow, and blood-brain barrier permeability in rats. J Neurosurg 1994, 81:93–102.

Del Bigio MR, Yan HJ, Buist R, Peeling J: Experimental intracerebral hemorrhage in rats. Magnetic resonance imaging and histopathological correlates. Stroke 1996, 27:2312–2319.

Fujii Y, Tanaka R, Takeuchi S, Koike T, Minakawa T, Sasaki O: Hematoma enlargement in spontaneous intracerebral hemorrhage. J Neurosurg 1994, 80:51–57.

Rivest S: Regulation of innate immune responses in the brain. Nat Rev Immunol 2009, 9:429–439.

Hopkins PA, Sriskandan S: Mammalian: Toll-like receptors: to immunity and beyond. Clin Exp Immunol 2005, 140:395–407.

Beutler BA: TLRs and innate immunity. Blood 2009, 113:1399–1407.

Zhu J, Mohan C: Toll-like receptor signaling pathways-therapeutic opportunities. Mediators Inflamm 2010 2010, 781235.

Kawai T, Akira S: The role of pattern-recognition receptors in innate immunity: Update on Toll-like receptors. Nat Immuno 2010, 11:373–384.

Miyake K: Endotoxin recognition molecules MD-2 and toll-like receptor 4 as potential targets for therapeutic intervention of endotoxin shock. Curr Drug Targets Inflamm Allergy 2004, 3:291–297.

Takeda K, Akira S: TLR signaling pathways. Semin Immunol 2004, 16:3–9.

Buchanan MM, Hutchinson M, Watkins LR, Yin H: Toll-like receptor 4 in CNS pathologies. J Neurochem 2010, 114:13–27.

Yang QW, Xiang J, Zhou Y, Zhong Q, Li JC: Targeting HMGB1/TLR4 signaling as a novel approach to treatment of cerebral ischemia. Front Biosci (Schol Ed) 2010, 2:1081–1091.

Figueiredo RT, Fernandez PL, Mourao-Sa DS, Porto BN, Dutra FF, Alves LS, Oliveira MF, Oliveira PL, Graça-Souza AV, Bozza MT: Characterization of heme as activator of Toll-like receptor 4. J Biol Chem 2007, 282:20221–20229.

Teng W, Wang L, Xue W, Guan C: Activation of TLR4-mediated NFkappaB signaling in hemorrhagic brain in rats. Mediators Inflamm 2009 2009, 473276.

Hu YY, Huang M, Dong XQ, Xu QP, Yu WH, Zhang ZY: Ginkgolide B reduces neuronal cell apoptosis in the hemorrhagic rat brain: Possible involvement of Toll-like receptor 4/nuclear factor-kappa B pathway. J Ethnopharmacol 2011, in press.

Chen L, Zhang X, Chen-Roetling J, Regan RF: Increased striatal injury and behavioral deficits after intracerebral hemorrhage in hemopexin knockout mice. J Neurosurg 2011, 114:1159–1167.

Huang FP, Xi G, Keep RF, Hua Y, Nemoianu A, Hoff JT: Brain edema after experimental intracerebral hemorrhage: role of hemoglobin degradation products. J Neurosurg 2002, 96:287–293.

Chang CF, Chen SF, Lee TS, Lee HF, Chen SF, Shyue SK: Caveolin-1 deletion reduces early brain injury after experimental intracerebral hemorrhage. Am J Pathol 2011, 178:1749–1761.

Bond BC, Virley DJ, Cairns NJ, Hunter AJ, Moore GB, Moss SJ, Mudge AW, Walsh FS, Jazin E, Preece P: The quantification of gene expression in an animal model of brain ischaemia using TaqMan real-time RT-PCR. Brain Res Mol Brain Res 2002, 106:101–116.

Yin D, Zhou C, Kusaka I, Calvert JW, Parent AD, Nanda A, Zhang JH: Inhibition of apoptosis by hyperbaric oxygen in a rat focal cerebral ischemic model. J Cereb Blood Flow Metab 2003, 23:855–864.

Park S, Yamaguchi M, Zhou C, Calvert JW, Tang J, Zhang JH: Neurovascular protection reduces early brain injury after subarachnoid hemorrhage. Stroke 2004, 35:2412–2417.

Wu H, Chen G, Wyburn KR, Yin J, Bertolino P, Eris JM, Alexander SI, Sharland AF, Chadban SJ: TLR4 activation mediates kidney ischemia/reperfusion injury. J Clin Invest 2007, 117:2847–2859.

Zhao X, Sun G, Zhang J, Strong R, Song W, Gonzales N, Grotta JC, Aronowski J: Hematoma resolution as a target for intracerebral hemorrhage treatment: role for peroxisome proliferator-activated receptor gamma in microglia/macrophages. Ann Neurol 2007, 61:352–362.

Yang QW, Lu FL, Zhou Y, Wang L, Zhong Q, Lin S, Xiang J, Li JC, Fang CQ, Wang JZ: HMBG1 mediates ischemia-reperfusion injury by TRIF-adaptor independent Toll-like receptor 4 signaling. J Cereb Blood Flow Metab 2011, 31:593–605.

Yang QW, Li JC, Lu FL, Wen AQ, Xiang J, Zhang LL, Huang ZY, Wang JZ: Upregulated expression of toll-like receptor 4 in monocytes correlates with severity of acute cerebral infarction. J Cereb Blood Flow Metab 2008, 28:1588–1596.

Giulian D, Baker TJ: Characterization of ameboid microglia isolated from developing mammalian brain. J Neurosci 1986, 6:2163–2178.

Yang Q, Zhong Q, Cao C, Li J, Lu F, Wang J: Anti-Toll like receptor 4 monoclonal antibody attenuates cerebral ischemia-reperfusion injury. Cerebrovasc Dis 2008, 26:212–222.

Kitamura M: Control of NF-κB and inflammation by the unfolded protein response. Int Rev Immunol 2011, 30:4–15.

Chen Z, Gao C, Hua Y, Keep RF, Muraszko K, Xi G: Role of iron in brain injury after intraventricular hemorrhage. Stroke 2011, 42:465–470.

Yamamoto M, Sato S, Hemmi H, Uematsu S, Hoshino K, Kaisho T, Takeuchi O, Takeda K, Akira S: TRAM is specifically involved in the Toll-like receptor 4-mediated MyD88-independent signaling pathway. Nat Immunol 2003, 4:1144–1150.

Zhai Y, Shen XD, O'Connell R, Gao F, Lassman C, Busuttil RW, Cheng G, Kupiec-Weglinski JW: Cutting edge: TLR4 activation mediates liver ischemia/reperfusion inflammatory response via IFN regulatory factor 3-dependent MyD88-independent pathway. J Immunol 2004, 173:7115–7119.

Yang Q, Zhu P, Wang Z, Jiang J: Lipopolysaccharide upregulates the expression of Toll-like receptor 4 in human vascular endothelial cells. Chin Med J (Engl) 2002, 115:286–289.

Arumugam TV, Okun E, Tang SC, Thundyil J, Taylor SM, Woodruff TM: Toll-like receptors in ischemia-reperfusion injury. Shock 2009, 32:4–16.

Lehnardt S, Massillon L, Follett P, Jensen FE, Ratan R, Rosenberg PA, Volpe JJ, Vartanian T: Activation of innate immunity in the CNS triggers neurodegeneration through a Toll-like receptor 4-dependent pathway. Proc Natl Acad Sci USA 2003, 100:8514–8519.

Falsig J, van Beek J, Hermann C, Leist M: Molecular basis for detection of invading pathogens in the brain. J Neurosci Res 2008, 86:1434–1447.

Sloane JA, Blitz D, Margolin Z, Vartanian T: A clear and present danger: endogenous ligands of Toll-like receptors. Neuromolecular Med 2010, 12:149–163.

Wagner KR, Sharp FR, Ardizzone TD, Lu A, Clark JF: Heme and iron metabolism: role in cerebral hemorrhage. J Cereb Blood Flow Metab 2003, 23:629–652.

Darrow VC, Alvord EC Jr, Mack LA: Histologic evolution of the reactions to hemorrhage in the premature human infant's brain. A combined ultrasound and autopsy study and a comparison with the reaction in adults. Am J Pathol 1998, 130:44–58.

Macdonald RL, Weir BK: A review of hemoglobin and the pathogenesis of cerebral vasospasm. Stroke 1991, 22:971–982.

Graça-Souza AV, Arruda MA, de Freitas MS, Barja-Fidalgo C, Oliveira PL: Neutrophil activation by heme: implications for inflammatory processes. Blood 2002, 99:4160–4165.