Iron and Hydrocephalus

  • Thomas Garton
  • Jennifer M. Strahle


The role of iron in hemorrhagic injury and the development of hydrocephalus is a hot topic in current stroke research. It is clear that iron overload is directly related to hydrocephalus, and efforts to specifically address iron in animal models and in in vitro experiments have been met with some success. Due to its ability to engage in dangerous Fenton reactions with oxygenated species like hydrogen peroxide, iron can create free radicals and reactive oxygen species capable of causing significant damage to the brain. The mechanism by which these reactions influence hydrocephalus is less well understood. Current hypotheses implicate damage to the ependymal surface and possibly motile cilia in the dysfunction of CSF dynamics. However, additional pathways may exist. Identifying mechanisms of iron-mediated ventriculomegaly is an important goal of hydrocephalus research and is one that holds significant promise with respect to our ability to improve treatment for patients suffering from hydrocephalus.


Iron Hydrocephalus Cerebrospinal fluid Hemorrhage Treatments 


  1. 1.
    Aisen P, Leibman A, Zweier J. Stoichiometric and site characteristics of the binding of iron to human transferrin. J Biol Chem. 1978;253:1930–7.PubMedGoogle Scholar
  2. 2.
    Alayash AI. Haptoglobin: old protein with new functions. Clin Chim Acta. 2011;412:493–8.PubMedCrossRefGoogle Scholar
  3. 3.
    Bao L, Avshalumov MV, Patel JC, Lee CR, Miller EW, Chang CJ, Rice ME. Mitochondria are the source of hydrogen peroxide for dynamic brain-cell signaling. J Neurosci. 2009;29:9002–10.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Biagioli M, Pinto M, Cesselli D, Zaninello M, Lazarevic D, Roncaglia P, Simone R, Vlachouli C, Plessy C, Bertin N, et al. Unexpected expression of alpha- and beta-globin in mesencephalic dopaminergic neurons and glial cells. Proc Natl Acad Sci U S A. 2009;106:15454–9.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Borda JT, Alvarez X, Mohan M, Hasegawa A, Bernardino A, Jean S, Aye P, Lackner AA. CD163, a marker of perivascular macrophages, is up-regulated by microglia in simian immunodeficiency virus encephalitis after haptoglobin-hemoglobin complex stimulation and is suggestive of breakdown of the blood-brain barrier. Am J Pathol. 2008;172:725–37.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Bradbury MW. Transport of iron in the blood-brain-cerebrospinal fluid system. J Neurochem. 1997;69:443–54.PubMedCrossRefGoogle Scholar
  7. 7.
    Calabrese V, Lodi R, Tonon C, D’Agata V, Sapienza M, Scapagnini G, Mangiameli A, Pennisi G, Stella AM, Butterfield DA. Oxidative stress, mitochondrial dysfunction and cellular stress response in Friedreich’s ataxia. J Neurol Sci. 2005;233:145–62.PubMedCrossRefGoogle Scholar
  8. 8.
    Cereghetti GM, Stangherlin A, Martins de Brito O, Chang CR, Blackstone C, Bernardi P, Scorrano L. Dephosphorylation by calcineurin regulates translocation of Drp1 to mitochondria. Proc Natl Acad Sci U S A. 2008;105:15803–8.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Chen Q, Tang J, Tan L, Guo J, Tao Y, Li L, Chen Y, Liu X, Zhang JH, Chen Z, et al. Intracerebral hematoma contributes to hydrocephalus after intraventricular hemorrhage via aggravating iron accumulation. Stroke. 2015;46:2902–8.PubMedCrossRefGoogle Scholar
  10. 10.
    Chen-Roetling J, Regan RF. Haptoglobin increases the vulnerability of CD163-expressing neurons to hemoglobin. J Neurochem. 2016;139:586–95.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Chen-Roetling J, Chen L, Regan RF. Minocycline attenuates iron neurotoxicity in cortical cell cultures. Biochem Biophys Res Commun. 2009;386:322–6.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Cho B, Choi SY, Cho HM, Kim HJ, Sun W. Physiological and pathological significance of dynamin-related protein 1 (drp1)-dependent mitochondrial fission in the nervous system. Exp Neurobiol. 2013;22:149–57.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Christian EA, Jin DL, Attenello F, Wen T, Cen S, Mack WJ, Krieger MD, McComb JG. Trends in hospitalization of preterm infants with intraventricular hemorrhage and hydrocephalus in the United States, 2000-2010. J Neurosurg. 2016;17:260–9.Google Scholar
  14. 14.
    Chun HJ, Kim DW, Yi HJ, Kim YS, Kim EH, Hwang SJ, Jwa CS, Lee YK, Ryou H. Effects of statin and deferoxamine administration on neurological outcomes in a rat model of intracerebral hemorrhage. Neurol Sci. 2012;33:289–96.PubMedCrossRefGoogle Scholar
  15. 15.
    Cui HJ, He HY, Yang AL, Zhou HJ, Wang C, Luo JK, Lin Y, Tang T. Efficacy of deferoxamine in animal models of intracerebral hemorrhage: a systematic review and stratified meta-analysis. PLoS One. 2015;10:e0127256.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Etzerodt A, Moestrup SK. CD163 and inflammation: biological, diagnostic, and therapeutic aspects. Antioxid Redox Signal. 2013;18:2352–63.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Fagan SC, Waller JL, Nichols FT, Edwards DJ, Pettigrew LC, Clark WM, Hall CE, Switzer JA, Ergul A, Hess DC. Minocycline to improve neurologic outcome in stroke (MINOS): a dose-finding study. Stroke. 2010;41:2283–7.PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Fruitier I, Garreau I, Lacroix A, Cupo A, Piot JM. Proteolytic degradation of hemoglobin by endogenous lysosomal proteases gives rise to bioactive peptides: hemorphins. FEBS Lett. 1999;447:81–6.PubMedCrossRefGoogle Scholar
  19. 19.
    Gao C, Du H, Hua Y, Keep RF, Strahle J, Xi G. Role of red blood cell lysis and iron in hydrocephalus after intraventricular hemorrhage. J Cereb Blood Flow Metab. 2014;34:1070–5.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Garton T, Keep RF, Hua Y, Xi G. Brain iron overload following intracranial haemorrhage. Stroke Vasc Neurol. 2016;1:172–84.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Garton TP, He Y, Garton HJ, Keep RF, Xi G, Strahle JM. Hemoglobin-induced neuronal degeneration in the hippocampus after neonatal intraventricular hemorrhage. Brain Res. 2016;1635:86–94.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Garton T, Keep RF, Hua Y, Xi G. CD163, a hemoglobin/haptoglobin scavenger receptor, after intracerebral hemorrhage: functions in microglia/macrophages versus neurons. Transl Stroke Res. 2017;8:612–7.PubMedCrossRefGoogle Scholar
  23. 23.
    Graversen JH, Madsen M, Moestrup SK. CD163: a signal receptor scavenging haptoglobin-hemoglobin complexes from plasma. Int J Biochem Cell Biol. 2002;34:309–14.PubMedCrossRefGoogle Scholar
  24. 24.
    Gray NK, Hentze MW. Iron regulatory protein prevents binding of the 43S translation pre-initiation complex to ferritin and eALAS mRNAs. EMBO J. 1994;13:3882–91.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Gunshin H, Allerson CR, Polycarpou-Schwarz M, Rofts A, Rogers JT, Kishi F, Hentze MW, Rouault TA, Andrews NC, Hediger MA. Iron-dependent regulation of the divalent metal ion transporter. FEBS Lett. 2001;509:309–16.PubMedCrossRefGoogle Scholar
  26. 26.
    Guo B, Yu Y, Leibold EA. Iron regulates cytoplasmic levels of a novel iron-responsive element-binding protein without aconitase activity. J Biol Chem. 1994;269:24252–60.PubMedGoogle Scholar
  27. 27.
    Guo J, Chen Q, Tang J, Zhang J, Tao Y, Li L, Zhu G, Feng H, Chen Z. Minocycline-induced attenuation of iron overload and brain injury after experimental germinal matrix hemorrhage. Brain Res. 2015;1594:115–24.PubMedCrossRefGoogle Scholar
  28. 28.
    Hatakeyama T, Okauchi M, Hua Y, Keep RF, Xi G. Deferoxamine reduces neuronal death and hematoma lysis after intracerebral hemorrhage in aged rats. Transl Stroke Res. 2013;4:546–53.PubMedCrossRefGoogle Scholar
  29. 29.
    Hill A, Shackelford GD, Volpe JJ. A potential mechanism of pathogenesis for early posthemorrhagic hydrocephalus in the premature newborn. Pediatrics. 1984;73:19–21.PubMedGoogle Scholar
  30. 30.
    Hua Y, Keep RF, Hoff JT, Xi G. Deferoxamine therapy for intracerebral hemorrhage. Acta Neurochir. 2008;105:3–6.CrossRefGoogle Scholar
  31. 31.
    Kanat A, Turkmenoglu O, Aydin MD, Yolas C, Aydin N, Gursan N, Tumkaya L, Demir R. Toward changing of the pathophysiologic basis of acute hydrocephalus after subarachnoid hemorrhage: a preliminary experimental study. World Neurosurg. 2013;80:390–5.PubMedCrossRefGoogle Scholar
  32. 32.
    Ke Y, Qian ZM. Brain iron metabolism: neurobiology and neurochemistry. Prog Neurobiol. 2007;83:149–73.PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Klein NC, Cunha BA. Tetracyclines. Med Clin North Am. 1995;79:789–801.PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Kohler E, Prentice DA, Bates TR, Hankey GJ, Claxton A, van Heerden J, Blacker D. Intravenous minocycline in acute stroke: a randomized, controlled pilot study and meta-analysis. Stroke. 2013;44:2493–9.PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Kuhn LC. Iron regulatory proteins and their role in controlling iron metabolism. Metallomics. 2015;7:232–43.PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Li L, Holscher C, Chen BB, Zhang ZF, Liu YZ. Hepcidin treatment modulates the expression of divalent metal transporter-1, ceruloplasmin, and ferroportin-1 in the rat cerebral cortex and hippocampus. Biol Trace Elem Res. 2011;143:1581–93.PubMedCrossRefPubMedCentralGoogle Scholar
  37. 37.
    Lisi S, D’Amore M, Sisto M. ADAM17 at the interface between inflammation and autoimmunity. Immunol Lett. 2014;162:159–69.PubMedCrossRefPubMedCentralGoogle Scholar
  38. 38.
    Liu L, Zeng M, Stamler JS. Hemoglobin induction in mouse macrophages. Proc Natl Acad Sci U S A. 1999;96:6643–7.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Liu R, Cao S, Hua Y, Keep RF, Huang Y, Xi G. CD163 expression in neurons after experimental intracerebral hemorrhage. Stroke. 2017;48:1369–75.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Meng H, Li F, Hu R, Yuan Y, Gong G, Hu S, Feng H. Deferoxamine alleviates chronic hydrocephalus after intraventricular hemorrhage through iron chelation and Wnt1/Wnt3a inhibition. Brain Res. 2015;1602:44–52.PubMedCrossRefGoogle Scholar
  41. 41.
    Miller JM, McAllister JP 2nd. Reduction of astrogliosis and microgliosis by cerebrospinal fluid shunting in experimental hydrocephalus. Cerebrospinal Fluid Res. 2007;4:5.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Moller HJ. Soluble CD163. Scand J Clin Lab Invest. 2012;72:1–13.PubMedCrossRefGoogle Scholar
  43. 43.
    Nemeth E, Tuttle MS, Powelson J, Vaughn MB, Donovan A, Ward DM, Ganz T, Kaplan J. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science. 2004;306:2090–3.PubMedCrossRefGoogle Scholar
  44. 44.
    O’Brien L, Hosick PA, John K, Stec DE, Hinds TD Jr. Biliverdin reductase isozymes in metabolism. Trends Endocrinol Metab. 2015;26:212–20.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Oi S, Di Rocco C. Proposal of “evolution theory in cerebrospinal fluid dynamics” and minor pathway hydrocephalus in developing immature brain. Childs Nerv Syst. 2006;22:662–9.PubMedCrossRefGoogle Scholar
  46. 46.
    Okubo S, Strahle J, Keep RF, Hua Y, Xi G. Subarachnoid hemorrhage-induced hydrocephalus in rats. Stroke. 2013;44:547–50.CrossRefGoogle Scholar
  47. 47.
    Park J, Lee DG, Kim B, Park SJ, Kim JH, Lee SR, Chang KT, Lee HS, Lee DS. Iron overload triggers mitochondrial fragmentation via calcineurin-sensitive signals in HT-22 hippocampal neuron cells. Toxicology. 2015;337:39–46.PubMedCrossRefGoogle Scholar
  48. 48.
    Qian ZM, Tang PL, Wang Q. Iron crosses the endosomal membrane by a carrier-mediated process. Prog Biophys Mol Biol. 1997;67:1–15.PubMedCrossRefGoogle Scholar
  49. 49.
    Qian M, Shen X, Wang H. The distinct role of ADAM17 in APP proteolysis and microglial activation related to Alzheimer’s disease. Cell Mol Neurobiol. 2016;36:471–82.PubMedCrossRefGoogle Scholar
  50. 50.
    Richter F, Meurers BH, Zhu C, Medvedeva VP, Chesselet MF. Neurons express hemoglobin alpha- and beta-chains in rat and human brains. J Comp Neurol. 2009;515:538–47.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Rochette L, Gudjoncik A, Guenancia C, Zeller M, Cottin Y, Vergely C. The iron-regulatory hormone hepcidin: a possible therapeutic target? Pharmacol Ther. 2015;146:35–52.PubMedCrossRefGoogle Scholar
  52. 52.
    Rogers JT, Randall JD, Cahill CM, Eder PS, Huang X, Gunshin H, Leiter L, McPhee J, Sarang SS, Utsuki T, et al. An iron-responsive element type II in the 5′-untranslated region of the Alzheimer’s amyloid precursor protein transcript. J Biol Chem. 2002;277:45518–28.PubMedCrossRefGoogle Scholar
  53. 53.
    Savman K, Nilsson UA, Blennow M, Kjellmer I, Whitelaw A. Non-protein-bound iron is elevated in cerebrospinal fluid from preterm infants with posthemorrhagic ventricular dilatation. Pediatr Res. 2001;49:208–12.PubMedCrossRefGoogle Scholar
  54. 54.
    Schaer CA, Schoedon G, Imhof A, Kurrer MO, Schaer DJ. Constitutive endocytosis of CD163 mediates hemoglobin-heme uptake and determines the noninflammatory and protective transcriptional response of macrophages to hemoglobin. Circ Res. 2006;99:943–50.PubMedCrossRefGoogle Scholar
  55. 55.
    Schelshorn DW, Schneider A, Kuschinsky W, Weber D, Kruger C, Dittgen T, Burgers HF, Sabouri F, Gassler N, Bach A, et al. Expression of hemoglobin in rodent neurons. J Cereb Blood Flow Metab. 2009;29:585–95.PubMedCrossRefGoogle Scholar
  56. 56.
    Schweizer C, Fraering PC, Kuhn LC. Ferritin H gene deletion in the choroid plexus and forebrain results in hydrocephalus. Neurochem Int. 2014;71:17–21.PubMedCrossRefGoogle Scholar
  57. 57.
    Selim M. Deferoxamine mesylate: a new hope for intracerebral hemorrhage: from bench to clinical trials. Stroke. 2009;40:S90–1.PubMedCrossRefGoogle Scholar
  58. 58.
    Selim M, Yeatts S, Goldstein JN, Gomes J, Greenberg S, Morgenstern LB, Schlaug G, Torbey M, Waldman B, Xi G, et al. Safety and tolerability of deferoxamine mesylate in patients with acute intracerebral hemorrhage. Stroke. 2011;42:3067–74.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Shamoto-Nagai M, Maruyama W, Yi H, Akao Y, Tribl F, Gerlach M, Osawa T, Riederer P, Naoi M. Neuromelanin induces oxidative stress in mitochondria through release of iron: mechanism behind the inhibition of 26S proteasome. J Neural Transm (Vienna). 2006;113:633–44.CrossRefGoogle Scholar
  60. 60.
    Siler DA, Berlow YA, Kukino A, Davis CM, Nelson JW, Grafe MR, Ono H, Cetas JS, Pike M, Alkayed NJ. Soluble epoxide hydrolase in hydrocephalus, cerebral edema, and vascular inflammation after subarachnoid hemorrhage. Stroke. 2015;46:1916–22.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Slupe AM, Merrill RA, Flippo KH, Lobas MA, Houtman JC, Strack S. A calcineurin docking motif (LXVP) in dynamin-related protein 1 contributes to mitochondrial fragmentation and ischemic neuronal injury. J Biol Chem. 2013;288:12353–65.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Strahle JM, Garton T, Bazzi AA, Kilaru H, Garton HJ, Maher CO, Muraszko KM, Keep RF, Xi G. Role of hemoglobin and iron in hydrocephalus after neonatal intraventricular hemorrhage. Neurosurgery. 2014;75:696–705; discussion 706PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Suzuki H, Muramatsu M, Tanaka K, Fujiwara H, Kojima T, Taki W. Cerebrospinal fluid ferritin in chronic hydrocephalus after aneurysmal subarachnoid hemorrhage. J Neurol. 2006;253:1170–6.PubMedCrossRefGoogle Scholar
  64. 64.
    Switzer JA, Hess DC, Ergul A, Waller JL, Machado LS, Portik-Dobos V, Pettigrew LC, Clark WM, Fagan SC. Matrix metalloproteinase-9 in an exploratory trial of intravenous minocycline for acute ischemic stroke. Stroke. 2011;42:2633–5.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Switzer JA, Sikora A, Ergul A, Waller JL, Hess DC, Fagan SC. Minocycline prevents IL-6 increase after acute ischemic stroke. Transl Stroke Res. 2012;3:363–8.PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Tan G, Liu L, He Z, Sun J, Xing W, Sun X. Role of hepcidin and its downstream proteins in early brain injury after experimental subarachnoid hemorrhage in rats. Mol Cell Biochem. 2016;418:31–8.PubMedCrossRefGoogle Scholar
  67. 67.
    Thomsen JH, Etzerodt A, Svendsen P, Moestrup SK. The haptoglobin-CD163-heme oxygenase-1 pathway for hemoglobin scavenging. Oxidative Med Cell Longev. 2013;2013:523652.CrossRefGoogle Scholar
  68. 68.
    Tyrrell R. Redox regulation and oxidant activation of heme oxygenase-1. Free Radic Res. 1999;31:335–40.PubMedCrossRefGoogle Scholar
  69. 69.
    Unno M, Matsui T, Ikeda-Saito M. Crystallographic studies of heme oxygenase complexed with an unstable reaction intermediate, verdoheme. J Inorg Biochem. 2012;113:102–9.PubMedCrossRefGoogle Scholar
  70. 70.
    Vollmer DG, Hongo K, Ogawa H, Tsukahara T, Kassell NF. A study of the effectiveness of the iron-chelating agent deferoxamine as vasospasm prophylaxis in a rabbit model of subarachnoid hemorrhage. Neurosurgery. 1991;28:27–32.PubMedCrossRefGoogle Scholar
  71. 71.
    Watchko JF. Bilirubin-induced neurotoxicity in the preterm neonate. Clin Perinatol. 2016;43:297–311.PubMedCrossRefGoogle Scholar
  72. 72.
    Wetterhall M, Bergquist J, Hillered L, Hjort K, Dahlin AP. Identification of human cerebrospinal fluid proteins and their distribution in an in vitro microdialysis sampling system. Eur J Pharm Sci. 2014;57:34–40.PubMedCrossRefGoogle Scholar
  73. 73.
    Wicher KB, Fries E. Evolutionary aspects of hemoglobin scavengers. Antioxid Redox Signal. 2010;12:249–59.PubMedCrossRefGoogle Scholar
  74. 74.
    Wong BX, Tsatsanis A, Lim LQ, Adlard PA, Bush AI, Duce JA. β-Amyloid precursor protein does not possess ferroxidase activity but does stabilize the cell surface ferrous iron exporter ferroportin. PLoS One. 2014;9:e114174.PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Wu H, Wu T, Xu X, Wang J, Wang J. Iron toxicity in mice with collagenase-induced intracerebral hemorrhage. J Cereb Blood Flow Metab. 2011;31:1243–50.PubMedCrossRefGoogle Scholar
  76. 76.
    Xie Q, Gu Y, Hua Y, Liu W, Keep RF, Xi G. Deferoxamine attenuates white matter injury in a piglet intracerebral hemorrhage model. Stroke. 2014;45:290–2.PubMedCrossRefPubMedCentralGoogle Scholar
  77. 77.
    Xu H, Tan G, Zhang S, Zhu H, Liu F, Huang C, Zhang F, Wang Z. Minocycline reduces reactive gliosis in the rat model of hydrocephalus. BMC Neurosci. 2012;13:148.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Yeatts SD, Palesch YY, Moy CS, Selim M. High dose deferoxamine in intracerebral hemorrhage (HI-DEF) trial: rationale, design, and methods. Neurocrit Care. 2013;19:257–66.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Yu Z, Persson HL, Eaton JW, Brunk UT. Intralysosomal iron: a major determinant of oxidant-induced cell death. Free Radic Biol Med. 2003;34:1243–52.PubMedCrossRefPubMedCentralGoogle Scholar
  80. 80.
    Yu Y, Zhao W, Zhu C, Kong Z, Xu Y, Liu G, Gao X. The clinical effect of deferoxamine mesylate on edema after intracerebral hemorrhage. PLoS One. 2015;10:e0122371.PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Zacharia BE, Vaughan KA, Hickman ZL, Bruce SS, Carpenter AM, Petersen NH, Deiner S, Badjatia N, Connolly ES Jr. Predictors of long-term shunt-dependent hydrocephalus in patients with intracerebral hemorrhage requiring emergency cerebrospinal fluid diversion. Neurosurg Focus. 2012;32:E5.PubMedCrossRefGoogle Scholar
  82. 82.
    Zhang AS, Enns CA. Iron homeostasis: recently identified proteins provide insight into novel control mechanisms. J Biol Chem. 2009;284:711–5.PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    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;42:3587–93.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Zhao J, Chen Z, Xi G, Keep RF, Hua Y. Deferoxamine attenuates acute hydrocephalus after traumatic brain injury in rats. Transl Stroke Res. 2014;5:586–94.PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Zhao F, Xi G, Liu W, Keep RF, Hua Y. Minocycline attenuates iron-induced brain injury. Acta Neurochir. 2016;121:361–5.CrossRefGoogle Scholar
  86. 86.
    Zhou X, Xie Q, Xi G, Keep RF, Hua Y. Brain CD47 expression in a swine model of intracerebral hemorrhage. Brain Res. 2014;1574:70–6.PubMedPubMedCentralCrossRefGoogle Scholar

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.University of Michigan, Department of NeurosurgeryAnn ArborUSA
  2. 2.Washington Univeristy in St. Louis, Department of NeurosurgerySt. LouisUSA

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