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Estrogen Reduces Iron-Mediated Brain Edema and Neuronal Death

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Brain Edema XIV

Part of the book series: Acta Neurochirurgica Supplementum ((NEUROCHIRURGICA,volume 106))

Abstract

Our previous studies found that 17-β estradiol attenuates edema formation after intracerebral hemorrhage (ICH). As brain iron overload occurs after ICH and contributes to ICH-induced brain injury, the present study examined the effects of estrogen on iron-induced brain injury in vivo and in vitro.

There were two sets of experiments in this study. In the first set, male Sprague-Dawley rats were pretreated with 17-β estradiol or vehicle prior to an intracerebral injection of ferrous iron. Ferrous iron was injected into the right caudate and the rats were killed 24 h later for brain edema measurement. In the second set, primary cultured neurons were pretreated with different doses of 17-β estradiol or vehicle for 24 h. The cells were then exposed to ferrous iron for 48 h when culture medium was collected for lactate dehydrogenase measurement. Neuronal death was also assessed by live/dead cell assay.

Estrogen pretreatment reduced brain water content (p < 0.01) 24 h after iron injection. Estrogen also protected against iron-induced cell death in cultured neurons. Estrogen reduces iron-induced brain edema in vivo and neuronal death in vitro suggesting estrogen could be a potential therapeutic agent for ICH.

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Reference

  1. Behan M, Zabka AG, Mitchell GS (2002) Age and gender effects on serotonin-dependent plasticity in respiratory motor control. Resp Physiol Neurobiol 131:65–77

    Article  CAS  Google Scholar 

  2. Felberg RA, Grotta JC, Shirzadi AL, Strong R, Narayana P, Hill-Felberg SJ, Aronowski J (2002) Cell death in experimental intracerebral hemorrhage: the “black hole” model of hemorrhagic damage. Ann Neurol 51:517–524

    Article  PubMed  Google Scholar 

  3. Garcia-Segura LM, Azcoitia I, DonCarlos LL (2001) Neuroprotection by estradiol. Prog Neurobiol 63:29–60

    Article  PubMed  CAS  Google Scholar 

  4. Gerlach M, Ben-Shachar D, Riederer P, Youdim MB (1994) Altered brain metabolism of iron as a cause of neurodegenerative diseases? J Neurochem 63:793–807

    Article  PubMed  CAS  Google Scholar 

  5. Hua Y, Nakamura T, Keep RF, Wu J, Schallert T, Hoff JT, Xi G (2006) Long-term effects of experimental intracerebral hemorrhage: the role of iron. J Neurosurg 104:305–312

    Article  PubMed  CAS  Google Scholar 

  6. Hurn PD, Brass LM (2003) Estrogen and stroke: a balanced analysis. Stroke 34:338–341

    Article  PubMed  Google Scholar 

  7. Hurn PD, Macrae IM (2000) Estrogen as a neuroprotectant in stroke. J Cereb Blood Flow Metab 20:631–652

    Article  PubMed  CAS  Google Scholar 

  8. Jiang Y, Wu J, Hua Y, Keep RF, Xiang J, Hoff JT, Xi G (2002) Thrombin-receptor activation and thrombin-induced brain tolerance. J Cereb Blood Flow Metab 22:404–410

    Article  PubMed  CAS  Google Scholar 

  9. Nakamura T, Hua Y, Keep RF, Park JW, Xi G, Hoff JT (2005) Estrogen therapy for experimental intracerebral hemorrhage in rats. J Neurosurg 103:97–103

    Article  PubMed  CAS  Google Scholar 

  10. Nakamura T, Keep RF, Hua Y, Hoff JT, Xi G (2005) Oxidative DNA injury after experimental intracerebral hemorrhage. Brain Res 1039:30–36

    Article  PubMed  CAS  Google Scholar 

  11. Nakamura T, Keep RF, Hua Y, Schallert T, Hoff JT, Xi G (2004) Deferoxamine-induced attenuation of brain edema and neurological deficits in a rat model of intracerebral hemorrhage. J Neurosurg 100:672–678

    Article  PubMed  CAS  Google Scholar 

  12. Nakamura T, Xi G, Hua Y, Schallert T, Hoff JT, Keep RF (2004) Intracerebral hemorrhage in mice: model characterization and application for genetically modified mice. J Cereb Blood Flow Metab 24:487–494

    Article  PubMed  Google Scholar 

  13. Rau SW, Dubal DB, Bottner M, Gerhold LM, Wise PM (2003) Estradiol attenuates programmed cell death after stroke-like injury. J Neurosci 23:11420–11426

    PubMed  CAS  Google Scholar 

  14. Ropper AH (1986) Lateral displacement of the brain and level of consciousness in patients with an acute hemispheral mass. N Eng J Med 314:953–958

    Article  CAS  Google Scholar 

  15. Ropper AH, King RB (1984) Intracranial pressure monitoring in comatose patients with cerebral hemorrhage. Arch Neurol 41:725–728

    Article  PubMed  CAS  Google Scholar 

  16. Santizo RA, Anderson S, Ye S, Koenig HM, Pelligrino DA (2000) Effects of estrogen on leukocyte adhesion after transient forebrain ischemia. Stroke 31:2231–2235

    Article  PubMed  CAS  Google Scholar 

  17. Wise PM, Dubal DB, Wilson ME, Rau SW, Bottner M, Rosewell KL (2001) Estradiol is a protective factor in the adult and aging brain: understanding of mechanisms derived from in vivo and in vitro studies. Brain Res – Brain Res Rev 37:313–319

    Article  PubMed  CAS  Google Scholar 

  18. Wu J, Hua Y, Keep RF, Nakamura T, Hoff JT, Xi G (2003) Iron and iron-handling proteins in the brain after intracerebral hemorrhage. Stroke 34:2964–2969

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  20. Zazulia AR, Diringer MN, Derdeyn CP, Powers WJ (1999) Progression of mass effect after intracerebral hemorrhage. Stroke 30:1167–1173

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This study was supported by grants NS-017760, NS-039866, and NS-057539 from the National Institutes of Health (NIH), and 0755717Z and 0840016N from American Heart Asso-ciation (AHA). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or AHA.

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Correspondence to Y. Hua .

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Gu, Y., Xi, G., Liu, W., Keep, R.F., Hua, Y. (2010). Estrogen Reduces Iron-Mediated Brain Edema and Neuronal Death. In: Czernicki, Z., Baethmann, A., Ito, U., Katayama, Y., Kuroiwa, T., Mendelow, D. (eds) Brain Edema XIV. Acta Neurochirurgica Supplementum, vol 106. Springer, Vienna. https://doi.org/10.1007/978-3-211-98811-4_29

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  • DOI: https://doi.org/10.1007/978-3-211-98811-4_29

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  • Print ISBN: 978-3-211-98758-2

  • Online ISBN: 978-3-211-98811-4

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