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.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Reference
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
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
Garcia-Segura LM, Azcoitia I, DonCarlos LL (2001) Neuroprotection by estradiol. Prog Neurobiol 63:29–60
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
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
Hurn PD, Brass LM (2003) Estrogen and stroke: a balanced analysis. Stroke 34:338–341
Hurn PD, Macrae IM (2000) Estrogen as a neuroprotectant in stroke. J Cereb Blood Flow Metab 20:631–652
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
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
Nakamura T, Keep RF, Hua Y, Hoff JT, Xi G (2005) Oxidative DNA injury after experimental intracerebral hemorrhage. Brain Res 1039:30–36
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
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
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
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
Ropper AH, King RB (1984) Intracranial pressure monitoring in comatose patients with cerebral hemorrhage. Arch Neurol 41:725–728
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
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
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
Xi G, Keep RF, Hoff JT (2006) Mechanisms of brain injury after intracerebral haemorrhage. Lancet Neurol 5:53–63
Zazulia AR, Diringer MN, Derdeyn CP, Powers WJ (1999) Progression of mass effect after intracerebral hemorrhage. Stroke 30:1167–1173
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.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2010 Springer-Verlag/Wien
About this paper
Cite this paper
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
Download citation
DOI: https://doi.org/10.1007/978-3-211-98811-4_29
Published:
Publisher Name: Springer, Vienna
Print ISBN: 978-3-211-98758-2
Online ISBN: 978-3-211-98811-4
eBook Packages: MedicineMedicine (R0)