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01-08-2014 | Review Article

Iron and Intracerebral Hemorrhage: From Mechanism to Translation

Authors: Xiao-Yi Xiong, Jian Wang, Zhong-Ming Qian, Qing-Wu Yang

Published in: Translational Stroke Research | Issue 4/2014

Abstract

Intracerebral hemorrhage (ICH) is a leading cause of morbidity and mortality around the world. Currently, there is no effective medical treatment available to improve functional outcomes in patients with ICH due to its unknown mechanisms of damage. Increasing evidence has shown that the metabolic products of erythrocytes are the key contributor of ICH-induced secondary brain injury. Iron, an important metabolic product that accumulates in the brain parenchyma, has a detrimental effect on secondary injury following ICH. Because the damage mechanism of iron during ICH-induced secondary injury is clear, iron removal therapy research on animal models is effective. Although many animal and clinical studies have been conducted, the exact metabolic pathways of iron and the mechanisms of iron removal treatments are still not clear. This review summarizes recent progress concerning the iron metabolism mechanisms underlying ICH-induced injury. We focus on iron, brain iron metabolism, the role of iron in oxidative injury, and iron removal therapy following ICH, and we suggest that further studies focus on brain iron metabolism after ICH and the mechanism for iron removal therapy.

Wang J. Preclinical and clinical research on inflammation after intracerebral hemorrhage. Prog Neurobiol. 2010;92(4):463–77.PubMedCentralPubMed

Mayer SA, Rincon F. Treatment of intracerebral haemorrhage. Lancet Neurol. 2005;4(10):662–72.PubMed

Sutherland GR, Auer RN. Primary intracerebral hemorrhage. J Clin Neurosci. 2006;13(5):511–7.PubMed

Chaudhary N, Gemmete JJ, Thompson BG, Xi G, Pandey AS. Iron-potential therapeutic target in hemorrhagic stroke. World Neurosurg. 2013;79(1):7–9.PubMed

Ke Y, Qian ZM. Brain iron metabolism: neurobiology and neurochemistry. Prog Neurobiol. 2007;83(3):149–73.PubMed

Hua Y, Nakamura T, Keep RF, Wu J, Schallert T, Hoff JT, et al. Long-term effects of experimental intracerebral hemorrhage: the role of iron. J Neurosurg. 2006;104(2):305–12.PubMed

Wu J, Hua Y, Keep RF, Nakamura T, Hoff JT, Xi G. Iron and iron-handling proteins in the brain after intracerebral hemorrhage. Stroke. 2003;34(12):2964–9.PubMed

Wang J, Doré S. Heme oxygenase-1 exacerbates early brain injury after intracerebral haemorrhage. Brain. 2007;130(6):1643–52.PubMedCentralPubMed

Maines MD. The heme oxygenase system: a regulator of second messenger gases. Annu Rev Pharmacol Toxicol. 1997;37(1):517–54.PubMed

10.

Xi G, Keep RF, Hoff JT. Mechanisms of brain injury after intracerebral haemorrhage. Lancet Neurol. 2006;5(1):53–63.PubMed

11.

Keep RF, Hua Y, Xi G. Intracerebral haemorrhage: mechanisms of injury and therapeutic targets. Lancet Neurol. 2012;11(8):720–31.PubMed

12.

Jin H, Wu G, Hu S, Hua Y, Keep RF, Wu J, et al. T2 and T2* magnetic resonance imaging sequences predict brain injury after intracerebral hemorrhage in rats. Acta Neurochir Suppl. 2013;18:151–5.

13.

Wang W, Di X, D'Agostino RB, Torti SV, Torti FM. Excess capacity of the iron regulatory protein system. J Biol Chem. 2007;282(34):24650–9.PubMed

14.

Crichton RR, Wilmet S, Legssyer R, Ward RJ. Molecular and cellular mechanisms of iron homeostasis and toxicity in mammalian cells. J Inorg Biochem. 2002;91(1):9–18.PubMed

15.

Ganz T, Nemeth E. Hepcidin and iron homeostasis. Biochimica et biophysica acta. 2012;1823(9):1434–43.PubMedCentralPubMed

16.

Galy B, Ferring-Appel D, Becker C, Gretz N, Gröne H-J, Schümann K, et al. Iron regulatory proteins control a mucosal block to intestinal iron absorption. Cell Rep. 2013;3(3):844–57.PubMed

17.

Anderson GJ, Frazer DM, McLaren GD. Iron absorption and metabolism. Curr Opin Gastroenterol. 2009;25(2):129–35.PubMed

18.

Knutson MD. Iron-sensing proteins that regulate hepcidin and enteric iron absorption. Annu Rev Nutr. 2010;30:149–71.PubMed

19.

Schümann K, Moret R, Künzle H, Kühn LC. Iron regulatory protein as an endogenous sensor of iron in rat intestinal mucosa. EurJ Biochem. 1999;260(2):362–72.

20.

Mastrogiannaki M, Matak P, Keith B, Simon MC, Vaulont S, Peyssonnaux C. HIF-2α, but not HIF-1α, promotes iron absorption in mice. J Clin Invest. 2009;119(5):1159.PubMedCentralPubMed

21.

Shah YM, Matsubara T, Ito S, Yim S-H, Gonzalez FJ. Intestinal hypoxia-inducible transcription factors are essential for iron absorption following iron deficiency. Cell Metab. 2009;9(2):152–64.PubMedCentralPubMed

22.

Taylor M, Qu A, Anderson ER, Matsubara T, Martin A, Gonzalez FJ, et al. Hypoxia-inducible factor-2α mediates the adaptive increase of intestinal ferroportin during iron deficiency in mice. Gastroenterology. 2011;140(7):2044–55.PubMedCentralPubMed

23.

Nemeth E, Tuttle MS, Powelson J, Vaughn MB, Donovan A, Ward DM, et al. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science. 2004;306(5704):2090–3.PubMed

24.

Rolfs A, Hediger MA. Metal ion transporters in mammals: structure, function and pathological implications. J Physiol. 1999;518(1):1–12.PubMedCentralPubMed

25.

Goldman BS, Kranz RG. ABC transporters associated with cytochrome c biogenesis. Res microbiol. 2001;152(3):323–9.PubMed

26.

Malecki EA, Devenyi AG, Beard JL, Connor JR. Existing and emerging mechanisms for transport of iron and manganese to the brain. J Neurosci Res. 1999;56(2):113.PubMed

27.

Moos T, Morgan EH. Transferrin and transferrin receptor function in brain barrier systems. Cell Mol Neurobiol. 2000;20(1):77–95.PubMed

28.

Bradbury M. Transport of iron in the blood–brain–cerebrospinal fluid system. J Neurochem. 1997;69(2):443–54.PubMed

29.

Talukder M, Takeuchi T, Harada E. Receptor-mediated transport of lactoferrin into the cerebrospinal fluid via plasma in young calves. J Vet Med Sci. 2003;65(9):957–64.PubMed

30.

Ji B, Maeda J, Higuchi M, Inoue K, Akita H, Harashima H, et al. Pharmacokinetics and brain uptake of lactoferrin in rats. Life Sci. 2006;78(8):851–5.PubMed

31.

Qian ZM, Morgan EH. Changes in the uptake of transferrin-free and transferrin-bound iron during reticulocyte maturation in vivo and in vitro. Biochim Biophys Acta. 1992;1135(1):35–43.PubMed

32.

Qian ZM, Tang PL, Morgan EH. Effect of lipid peroxidation on transferrin-free iron uptake by rabbit reticulocytes. Biochim Biophys Acta. 1996;1310(3):293–302.PubMed

33.

Deane R, Zheng W, Zlokovic BV. Brain capillary endothelium and choroid plexus epithelium regulate transport of transferrin-bound and free iron into the rat brain. J Neurochem. 2004;88(4):813–20.PubMedCentralPubMed

34.

Li H, Qian ZM. Transferrin/transferrin receptor-mediated drug delivery. Med Res Rev. 2002;22(3):225–50.PubMed

35.

Rouault TA, Cooperman S. Brain iron metabolism. Semin pediatr neurol. 2006;13(3):142–8.PubMed

36.

Hahn P, Qian Y, Dentchev T, Chen L, Beard J, Harris ZL, et al. Disruption of ceruloplasmin and hephaestin in mice causes retinal iron overload and retinal degeneration with features of age-related macular degeneration. Proc Natl Acad Sci U S A. 2004;101(38):13850–5.PubMedCentralPubMed

37.

Qian ZM, Chang YZ, Zhu L, Yang L, Du JR, Ho KP, et al. Development and iron‐dependent expression of hephaestin in different brain regions of rats. J Cell Biochem. 2007;102(5):1225–33.PubMed

38.

Moos T. Brain iron homeostasis. Dan Med Bull. 2002;49(4):279.PubMed

39.

los Monteros D, Espinosa A, Kumar S, Scully S, Cole R, de Vellis J. Transferrin gene expression and secretion by rat brain cells in vitro. J Neurosci Res. 1990;25(4):576–80.

40.

Moos T, Morgan EH. Evidence for low molecular weight, non-transferrin-bound iron in rat brain and cerebrospinal fluid. J Neurosci Res. 1998;54(4):486–94.PubMed

41.

Qian ZM, Shen X. Brain iron transport and neurodegeneration. Trends Mol Med. 2001;7(3):103–8.PubMed

42.

Attieh ZK, Mukhopadhyay CK, Seshadri V, Tripoulas NA, Fox PL. Ceruloplasmin ferroxidase activity stimulates cellular iron uptake by a trivalent cation-specific transport mechanism. J Biol Chem. 1999;274(2):1116–23.PubMed

43.

Hulet S, Hess E, Debinski W, Arosio P, Bruce K, Powers S, et al. Characterization and distribution of ferritin binding sites in the adult mouse brain. J Neurochem. 1999;72(2):868–74.PubMed

44.

Hulet S, Heyliger S, Powers S, Connor J. Oligodendrocyte progenitor cells internalize ferritin via clathrin-dependent receptor mediated endocytosis. J Neurosci Res. 2000;61(1):52–60.PubMed

45.

Ke Y, Qian ZM. Iron misregulation in the brain: a primary cause of neurodegenerative disorders. Lancet Neurol. 2003;2(4):246–53.PubMed

46.

Rouault TA. Systemic iron metabolism: a review and implications for brain iron metabolism. Pediatr Neurol. 2001;25(2):130–7.PubMed

47.

Crowe A, Morgan EH. Iron and transferrrin uptake by brain and cerebrospinal fluid in the rat. Brain Res. 1992;592(1):8–16.PubMed

48.

Descamps L, Dehouck M-P, Torpier G, Cecchelli R. Receptor-mediated transcytosis of transferrin through blood–brain barrier endothelial cells. Am J Physiol. 1996;270(4):H1149–58.PubMed

49.

REGAN RF, PANTER S. Hemoglobin potentiates excitotoxic injury in cortical cell culture. J Neurotrauma. 1996;13(4):223–31.PubMed

50.

Goldstein L, Teng ZP, Zeserson E, Patel M, Regan RF. Hemin induces an iron-dependent, oxidative injury to human neuron-like cells. J Neurosci Res. 2003;73(1):113–21.PubMed

51.

Cooper CE. Nitric oxide and iron proteins. Biochim Biophys Acta. 1999;1411(2):290–309.PubMed

52.

Nakamura T, Keep RF, Hua Y, Hoff JT, Xi G. Oxidative DNA injury after experimental intracerebral hemorrhage. Brain Res. 2005;1039(1):30–6.PubMed

53.

Zaman K, Ryu H, Hall D, O'Donovan K, Lin K-I, Miller MP, et al. Protection from oxidative stress–induced apoptosis in cortical neuronal cultures by iron chelators is associated with enhanced dna binding of hypoxia-inducible factor-1 and atf-1/creb and increased expression of glycolytic enzymes, p21waf1/cip1, and erythropoietin. J Neurosci. 1999;19(22):9821–30.PubMed

54.

Tanji K, Imaizumi T, Matsumiya T, Itaya H, Fujimoto K, Cui X-F, et al. Desferrioxamine, an iron chelator, upregulates cyclooxygenase-2 expression and prostaglandin production in a human macrophage cell line. Biochim Biophys Acta. 2001;1530(2):227–35.PubMed

55.

Willmore JL, Ballinger Jr WE, Boggs W, Sypert GW, Rubin JJ. Dendritic alterations in rat isocortex within an iron-induced chronic epileptic focus. Neurosurg. 1980;7(2):142–6.

56.

Reid SA, Sypert GW, Boggs WM, Willmore LJ. Histopathology of the ferric-induced chronic epileptic focus in cat: a Golgi study. Exp Neurol. 1979;66(2):205–19.PubMed

57.

Connor JR, Menzies SL. Relationship of iron to oligondendrocytes and myelination. Glia. 1996;17(2):83–93.PubMed

58.

Kondo Y, Ogawa N, Asanuma M, Ota Z, Mori A. Regional differences in late-onset iron deposition, ferritin, transferrin, astrocyte proliferation, and microglial activation after transient forebrain ischemia in rat brain. J Cereb Blood Flow Metab. 1995;15(2):216–26.PubMed

59.

Dwork A, Schon E, Herbert J. Nonidentical distribution of transferrin and ferric iron in human brain. Neuroscience. 1988;27(1):333–45.PubMed

60.

Wagner KR, Sharp FR, Ardizzone TD, Lu A, Clark JF. Heme and iron metabolism&colon; role in cerebral hemorrhage. J Cereb Blood Flow Metab. 2003;23(6):629–52.PubMed

61.

Connor JR, Menzies SL. Cellular management of iron in the brain. J Neurol Sci. 1995;134:33–44.PubMed

62.

Connor JR, Menzies SL, Burdo JR, Boyer PJ. Iron and iron management proteins in neurobiology. Pediatr Neurol. 2001;25(2):118–29.PubMed

63.

Zhao F, Hua Y, He Y, Keep RF, Xi G. Minocycline-induced attenuation of iron overload and brain injury after experimental intracerebral hemorrhage. Stroke. 2011;42(12):3587–93.PubMedCentralPubMed

64.

Kaur C, Ling E. Increased expression of transferrin receptors and iron in amoeboid microglial cells in postnatal rats following an exposure to hypoxia. Neurosci Lett. 1999;262(3):183–6.PubMed

65.

Djeha A, Perez-Arellano J-L, Hayes SL, Oria R, Simpson RJ, Raja KB, et al. Cytokine-mediated regulation of transferrin synthesis in mouse macrophages and human T lymphocytes. Blood. 1995;85(4):1036–42.PubMed

66.

She H, Xiong S, Lin M, Zandi E, Giulivi C, Tsukamoto H. Iron activates NF-κB in Kupffer cells. Am J Physiol Gastrointest Liver Physiol. 2002;283(3):G719–26.PubMed

67.

Mehdiratta M, Kumar S, Hackney D, Schlaug G, Selim M. Association between serum ferritin level and perihematoma edema volume in patients with spontaneous intracerebral hemorrhage. Stroke. 2008;39(4):1165–70.PubMed

68.

de la Ossa NP, Sobrino T, Silva Y, Blanco M, Millán M, Gomis M, et al. Iron-related brain damage in patients with intracerebral hemorrhage. Stroke. 2010;41(4):810–3.

69.

Ghosh S, Hevi S, Chuck SL. Regulated secretion of glycosylated human ferritin from hepatocytes. Blood. 2004;103(6):2369–76.PubMed

70.

Tran TN, Eubanks SK, Schaffer KJ, Zhou CY, Linder MC. Secretion of ferritin by rat hepatoma cells and its regulation by inflammatory cytokines and iron. Blood. 1997;90(12):4979–86.PubMed

71.

Sibille JC, Kondo H, Aisen P. Interactions between isolated hepatocytes and Kupffer cells in iron metabolism: a possible role for ferritin as an iron carrier protein. Hepatology. 1988;8(2):296–301.PubMed

72.

Cohen LA, Gutierrez L, Weiss A, Leichtmann-Bardoogo Y, Zhang D-L, Crooks DR, et al. Serum ferritin is derived primarily from macrophages through a nonclassical secretory pathway. Blood. 2010;116(9):1574–84.PubMed

73.

Gutteridge J. Hydroxyl radicals, iron, oxidative stress, and neurodegeneration. Ann NY Acad Sci. 1994;738(1):201–13.PubMed

74.

Thompson KJ, Shoham S, Connor JR. Iron and neurodegenerative disorders. Brain Res Bull. 2001;55(2):155–64.PubMed

75.

Zecca L, Youdim MB, Riederer P, Connor JR, Crichton RR. Iron, brain ageing and neurodegenerative disorders. Nat Rev Neurosci. 2004;5(11):863–73.PubMed

76.

Gu Y, Hua Y, Keep RF, Morgenstern LB, Xi G. Deferoxamine reduces intracerebral hematoma-induced iron accumulation and neuronal death in piglets. Stroke. 2009;40(6):2241–3.PubMedCentralPubMed

77.

Nakamura T, Keep RF, Hua Y, Schallert T, Hoff JT, Xi G. Deferoxamine-induced attenuation of brain edema and neurological deficits in a rat model of intracerebral hemorrhage. J Neurosurg. 2004;100(4):672–8.PubMed

78.

Warkentin LM, Auriat AM, Wowk S, Colbourne F. Failure of deferoxamine, an iron chelator, to improve outcome after collagenase-induced intracerebral hemorrhage in rats. Brain Res. 2010;1309:95–103.PubMed

79.

Auriat AM, Silasi G, Wei Z, Paquette R, Paterson P, Nichol H, et al. Ferric iron chelation lowers brain iron levels after intracerebral hemorrhage in rats but does not improve outcome. Exp Neurol. 2012;234(1):136–43.PubMed

80.

Selim M. Deferoxamine mesylate: a new hope for intracerebral hemorrhage: from bench to clinical trials. Stroke. 2009;40(3 suppl 1):S90–1.PubMed

81.

Regan RF, Rogers B. Delayed treatment of hemoglobin neurotoxicity. J neurotrauma. 2003;20(1):111–20.PubMed

82.

Okauchi M, Hua Y, Keep RF, Morgenstern LB, Xi G. Effects of deferoxamine on intracerebral hemorrhage-induced brain injury in aged rats. Stroke. 2009;40(5):1858–63.PubMedCentralPubMed

83.

Song S, Hua Y, Keep R, He Y, Wang J, Wu J. Deferoxamine reduces brain swelling in a rat model of hippocampal intracerebral hemorrhage. Acta Neurochir Suppl. 2008;105:13–8.PubMed

84.

Wu H, Wu T, Xu X, Wang J, Wang J. Iron toxicity in mice with collagenase-induced intracerebral hemorrhage. J Cereb Blood Flow Metab. 2010;31(5):1243–50.PubMedCentralPubMed

85.

Wan S, Hua Y, Keep R, Hoff J, Xi G. Deferoxamine reduces CSF free iron levels following intracerebral hemorrhage. Acta Neurochir Suppl. 2006;96:199–202.PubMed

86.

Rosenberg GA, Mun-Bryce S, Wesley M, Kornfeld M. Collagenase-induced intracerebral hemorrhage in rats. Stroke. 1990;21(5):801–7.PubMed

87.

Paraskevaidis IA, Iliodromitis EK, Vlahakos D, Tsiapras DP, Nikolaidis A, Marathias A, et al. Deferoxamine infusion during coronary artery bypass grafting ameliorates lipid peroxidation and protects the myocardium against reperfusion injury: immediate and long-term significance. Eur Heart J. 2005;26(3):263–70.PubMed

88.

Selim M, Yeatts S, Goldstein J, Gomes J, Greenberg S, Morgenstern L, et al. Deferoxamine Mesylate in Intracerebral Hemorrhage Investigators. Safety and tolerability of deferoxamine mesylate in patients with acute intracerebral hemorrhage. Stroke. 2011;42:3067–74.PubMedCentralPubMed

89.

Grenier D, Huot M-P, Mayrand D. Iron-chelating activity of tetracyclines and its impact on the susceptibility of Actinobacillus actinomycetemcomitans to these antibiotics. Antimicrob Agents Ch. 2000;44(3):763–6.

90.

Chen-Roetling J, Chen L, Regan RF. Minocycline attenuates iron neurotoxicity in cortical cell cultures. Biochem Biophys Res Commun. 2009;386(2):322–6.PubMedCentralPubMed

91.

Murata Y, Rosell A, Scannevin RH, Rhodes KJ, Wang X, Lo EH. Extension of the thrombolytic time window with minocycline in experimental stroke. Stroke. 2008;39(12):3372–7.PubMedCentralPubMed

92.

Alano CC, Kauppinen TM, Valls AV, Swanson RA. Minocycline inhibits poly (ADP-ribose) polymerase-1 at nanomolar concentrations. Proc Natl Acad Sci U S A. 2006;103(25):9685–90.PubMedCentralPubMed

93.

Wasserman JK, Schlichter LC. Minocycline protects the blood–brain barrier and reduces edema following intracerebral hemorrhage in the rat. Exp Neurol. 2007;207(2):227–37.PubMed

94.

Power C, Henry S, Del Bigio MR, Larsen PH, Corbett D, Imai Y, et al. Intracerebral hemorrhage induces macrophage activation and matrix metalloproteinases. Ann Neurol. 2003;53(6):731–42.PubMed

95.

Arosio P, Levi S. Ferritin, iron homeostasis, and oxidative damage. Free Radical Bio Med. 2002;33(4):457–63.

96.

Meyron-Holtz EG, Ghosh MC, Iwai K, LaVaute T, Brazzolotto X, Berger UV, et al. Genetic ablations of iron regulatory proteins 1 and 2 reveal why iron regulatory protein 2 dominates iron homeostasis. EMBO J. 2004;23(2):386–95.PubMedCentralPubMed

97.

Hu J, Connor JR. Demonstration and characterization of the iron regulatory protein in human brain. J Neurochem. 1996;67(2):838–44.PubMed

98.

Pantopoulos K. Iron metabolism and the IRE/IRP regulatory system: an update. Ann N Y Acad Sci. 2004;1012(1):1–13.PubMed

99.

Hentze MW, Caughman SW, Rouault TA, Barriocanal JG, Dancis A, Harford JB, et al. Identification of the iron-responsive element for the translational regulation of human ferritin mRNA. Science. 1987;238(4833):1570–3.PubMed

100.

Casey JL, Hentze MW, Koeller DM, Caughman SW, Rouault TA, Klausner RD, et al. Iron-responsive elements: regulatory RNA sequences that control mRNA levels and translation. Science. 1988;240(4854):924–8.PubMed

101.

Gunshin H, Allerson CR, Polycarpou-Schwarz M, Rofts A, Rogers JT, Kishi F, et al. Iron-dependent regulation of the divalent metal ion transporter. FEBS Lett. 2001;509(2):309–16.PubMed

102.

Donovan A, Brownlie A, Zhou Y, Shepard J, Pratt SJ, Moynihan J, et al. Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter. Nature. 2000;403(6771):776–81.PubMed

103.

Guo B, Phillips JD, Yu Y, Leibold EA. Iron regulates the intracellular degradation of iron regulatory protein 2 by the proteasome. J Biol Chem. 1995;270(37):21645–51.PubMed

104.

Galy B, Ferring-Appel D, Kaden S, Gröne H-J, Hentze MW. Iron regulatory proteins are essential for intestinal function and control key iron absorption molecules in the duodenum. Cell Metab. 2008;7(1):79–85.PubMed

105.

Smith SR, Ghosh MC, Ollivierre-Wilson H, Hang Tong W, Rouault TA. Complete loss of iron regulatory proteins 1 and 2 prevents viability of murine zygotes beyond the blastocyst stage of embryonic development. Blood Cells Mol Dis. 2006;36(2):283–7.PubMed

106.

Chen M, Awe OO, Chen-Roetling J, Regan RF. Iron regulatory protein-2 knockout increases perihematomal ferritin expression and cell viability after intracerebral hemorrhage. Brain Res. 2010;1337:95–103.PubMedCentralPubMed

107.

Regan RF, Chen M, Li Z, Zhang X, Benvenisti-Zarom L, Chen-Roetling J. Neurons lacking iron regulatory protein-2 are highly resistant to the toxicity of hemoglobin. Neurobiol Dis. 2008;31(2):242–9.PubMedCentralPubMed

108.

Santamaria R, Irace C, Festa M, Maffettone C, Colonna A. Induction of ferritin expression by oxalomalate. Biochim Biophys Acta. 2004;1691(2):151–9.PubMed

109.

LaVaute T, Smith S, Cooperman S, Iwai K, Land W, Meyron-Holtz E, et al. Targeted deletion of the gene encoding iron regulatory protein-2 causes misregulation of iron metabolism and neurodegenerative disease in mice. Nat Genet. 2001;27(2):209–14.PubMed

110.

Festa M, Colonna A, Pietropaolo C, Ruffo A. Oxalomalate, a competitive inhibitor of aconitase, modulates the RNA-binding activity of iron-regulatory proteins. Biochem J. 2000;348:315–20.PubMedCentralPubMed

111.

Schroeder SE, Reddy MB, Schalinske KL. Retinoic acid modulates hepatic iron homeostasis in rats by attenuating the RNA-binding activity of iron regulatory proteins. J Nutr. 2007;137(12):2686–90.PubMed

112.

Qureshi AI, Mendelow AD, Hanley DF. Intracerebral haemorrhage. Lancet. 2009;373(9675):1632–44.PubMedCentralPubMed

113.

Allkemper T, Tombach B, Schwindt W, Kugel H, Schilling M, Debus O, et al. Acute and subacute intracerebral hemorrhages: comparison of MR imaging at 1.5 and 3.0 T—initial experience. Radiology. 2004;232(3):874–81.PubMed

Title: Iron and Intracerebral Hemorrhage: From Mechanism to Translation
Authors: Xiao-Yi Xiong
Jian Wang
Zhong-Ming Qian
Qing-Wu Yang
Publication date: 01-08-2014
Publisher: Springer US
Published in: Translational Stroke Research / Issue 4/2014
Print ISSN: 1868-4483
Electronic ISSN: 1868-601X
DOI: https://doi.org/10.1007/s12975-013-0317-7

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Springer Medicine

Iron and Intracerebral Hemorrhage: From Mechanism to Translation

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