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Published in: Neurological Sciences 10/2015

01-10-2015 | Original Article

Serum hepcidin concentrations correlate with serum iron level and outcome in patients with intracerebral hemorrhage

Authors: Xiao-Yi Xiong, Jing Chen, Wen-Yao Zhu, Ting Zhao, Qi Zhong, Kai Zhou, Zhao-You Meng, Yan-Chun Wang, Peng-Fei Wang, Huang Fang, Qing-Wu Yang

Published in: Neurological Sciences | Issue 10/2015

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Abstract

Iron plays a detrimental role in the intracerebral hemorrhage (ICH)-induced brain damage, while hepcidin is the most important iron-regulated hormone. Here, we investigate the association between serum hepcidin and serum iron, outcome in patients with ICH. Serum samples of 81 cases with ICH were obtained on consecutive days to detect the levels of hepcidin, iron, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). The National Institutes of Health Stroke Scale score (NIHSS) was measured at admission and on days 7 and 30, and the modified Rankin Scale (mRS) score was evaluated at 3 months after ICH. Additionally, the correlations of serum hepcidin with serum iron and the mRS score were analyzed by a generalized linear model. Higher serum hepcidin levels were detected in patients with poor outcomes (P < 0.001), and the mRS score increased by a mean of 1.135 points (95 % CI 1.021–1.247, P < 0.001) for every serum hepcidin quartile after adjusting for other prognostic variables. Pearson correlation analysis showed that serum hepcidin was negatively correlated with serum iron (r = −0.5301, P < 0.001), and a significantly lower concentration of serum iron was found in patients with poor outcomes (P = 0.007). Additionally, serum hepcidin was independently correlated with mRS scores of ICH patients (OR 1.115, 95 % CI 0.995–1.249, P = 0.021). Our results suggest that serum hepcidin is closely related to the outcome of patients with ICH and may be a biological marker for outcome prediction.
Literature
1.
go back to reference Keep RF, Hua Y, Xi G (2012) Intracerebral haemorrhage: mechanisms of injury and therapeutic targets. Lancet Neurol 11:720–731CrossRefPubMed Keep RF, Hua Y, Xi G (2012) Intracerebral haemorrhage: mechanisms of injury and therapeutic targets. Lancet Neurol 11:720–731CrossRefPubMed
2.
go back to reference Xiong XY, Wang J, Qian ZM, Yang QW (2014) Iron and intracerebral hemorrhage: from mechanism to translation. Transl Stroke Res 5:429–441CrossRefPubMed Xiong XY, Wang J, Qian ZM, Yang QW (2014) Iron and intracerebral hemorrhage: from mechanism to translation. Transl Stroke Res 5:429–441CrossRefPubMed
3.
4.
go back to reference Gu Y, Hua Y, He Y, Wang L, Hu H, Keep RF et al (2011) Iron accumulation and DNA damage in a pig model of intracerebral hemorrhage. Acta Neurochir Suppl 111:123–128CrossRefPubMed Gu Y, Hua Y, He Y, Wang L, Hu H, Keep RF et al (2011) Iron accumulation and DNA damage in a pig model of intracerebral hemorrhage. Acta Neurochir Suppl 111:123–128CrossRefPubMed
5.
go back to reference Nakamura T, Keep RF, Hua Y, Hoff JT, Xi G (2005) Oxidative DNA injury after experimental intracerebral hemorrhage. Brain Res 1039:30–36CrossRefPubMed Nakamura T, Keep RF, Hua Y, Hoff JT, Xi G (2005) Oxidative DNA injury after experimental intracerebral hemorrhage. Brain Res 1039:30–36CrossRefPubMed
6.
go back to reference Gu Y, Hua Y, Keep RF, Morgenstern LB, Xi G (2009) Deferoxamine reduces intracerebral hematoma-induced iron accumulation and neuronal death in piglets. Stroke 40:2241–2243PubMedCentralCrossRefPubMed Gu Y, Hua Y, Keep RF, Morgenstern LB, Xi G (2009) Deferoxamine reduces intracerebral hematoma-induced iron accumulation and neuronal death in piglets. Stroke 40:2241–2243PubMedCentralCrossRefPubMed
7.
go back to reference 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 100:672–678CrossRefPubMed 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 100:672–678CrossRefPubMed
8.
go back to reference Auriat AM, Silasi G, Wei Z, Paquette R, Paterson P, Nichol H et al (2012) Ferric iron chelation lowers brain iron levels after intracerebral hemorrhage in rats but does not improve outcome. Exp Neurol 234:136–143CrossRefPubMed Auriat AM, Silasi G, Wei Z, Paquette R, Paterson P, Nichol H et al (2012) Ferric iron chelation lowers brain iron levels after intracerebral hemorrhage in rats but does not improve outcome. Exp Neurol 234:136–143CrossRefPubMed
9.
go back to reference Zhao F, Hua Y, He Y, Keep RF, Xi G (2011) Minocycline-induced attenuation of iron overload and brain injury after experimental intracerebral hemorrhage. Stroke 42:3587–3593PubMedCentralCrossRefPubMed Zhao F, Hua Y, He Y, Keep RF, Xi G (2011) Minocycline-induced attenuation of iron overload and brain injury after experimental intracerebral hemorrhage. Stroke 42:3587–3593PubMedCentralCrossRefPubMed
10.
go back to reference Xi G, Strahle J, Hua Y, Keep RF (2014) Progress in translational research on intracerebral hemorrhage: is there an end in sight? Prog Neurobiol 115:45–63CrossRefPubMed Xi G, Strahle J, Hua Y, Keep RF (2014) Progress in translational research on intracerebral hemorrhage: is there an end in sight? Prog Neurobiol 115:45–63CrossRefPubMed
11.
go back to reference 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 34:2964–2969CrossRefPubMed 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 34:2964–2969CrossRefPubMed
13.
go back to reference Ganz T, Nemeth E (2012) Hepcidin and iron homeostasis. BBA-Mo Cell Res 1823:1434–1443 Ganz T, Nemeth E (2012) Hepcidin and iron homeostasis. BBA-Mo Cell Res 1823:1434–1443
14.
go back to reference Nemeth E, Tuttle MS, Powelson J, Vaughn MB, Donovan A, Ward DM et al (2004) Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 306:2090–2093CrossRefPubMed Nemeth E, Tuttle MS, Powelson J, Vaughn MB, Donovan A, Ward DM et al (2004) Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 306:2090–2093CrossRefPubMed
15.
go back to reference Mecklenburg I, Reznik D, Fasler-Kan E, Drewe J, Beglinger C, Hruz P (2014) Serum hepcidin concentrations correlate with ferritin in patients with inflammatory bowel disease. J Crohns Colitis 8:1392–1397CrossRefPubMed Mecklenburg I, Reznik D, Fasler-Kan E, Drewe J, Beglinger C, Hruz P (2014) Serum hepcidin concentrations correlate with ferritin in patients with inflammatory bowel disease. J Crohns Colitis 8:1392–1397CrossRefPubMed
16.
go back to reference Mehdiratta M, Kumar S, Hackney D, Schlaug G, Selim M (2008) Association between serum ferritin level and perihematoma edema volume in patients with spontaneous intracerebral hemorrhage. Stroke 39:1165–1170CrossRefPubMed Mehdiratta M, Kumar S, Hackney D, Schlaug G, Selim M (2008) Association between serum ferritin level and perihematoma edema volume in patients with spontaneous intracerebral hemorrhage. Stroke 39:1165–1170CrossRefPubMed
17.
go back to reference de la Ossa NP, Sobrino T, Silva Y, Blanco M, Millán M, Gomis M et al (2010) Iron-related brain damage in patients with intracerebral hemorrhage. Stroke 41:810–813CrossRef de la Ossa NP, Sobrino T, Silva Y, Blanco M, Millán M, Gomis M et al (2010) Iron-related brain damage in patients with intracerebral hemorrhage. Stroke 41:810–813CrossRef
18.
go back to reference Steiner T, Kaste M, Katse M, Forsting M, Mendelow D, Kwiecinski H et al (2005) Recommendations for the management of intracranial haemorrhage-part I: spontaneous intracerebral haemorrhage. Cerebrovasc Dis (Basel, Switz) 22:294–316 Steiner T, Kaste M, Katse M, Forsting M, Mendelow D, Kwiecinski H et al (2005) Recommendations for the management of intracranial haemorrhage-part I: spontaneous intracerebral haemorrhage. Cerebrovasc Dis (Basel, Switz) 22:294–316
19.
go back to reference Zhou Y, Xiong KL, Lin S, Zhong Q, Lu FL, Liang H et al (2010) Elevation of high-mobility group protein box-1 in serum correlates with severity of acute intracerebral hemorrhage. Mediat Inflamm 2010:2010 Zhou Y, Xiong KL, Lin S, Zhong Q, Lu FL, Liang H et al (2010) Elevation of high-mobility group protein box-1 in serum correlates with severity of acute intracerebral hemorrhage. Mediat Inflamm 2010:2010
20.
go back to reference Fang H, Chen J, Lin S, Wang P, Wang Y, Xiong X et al (2014) CD36-mediated hematoma absorption following intracerebral hemorrhage: negative regulation by TLR4 signaling. J Immunol 192:5984–5992PubMedCentralCrossRefPubMed Fang H, Chen J, Lin S, Wang P, Wang Y, Xiong X et al (2014) CD36-mediated hematoma absorption following intracerebral hemorrhage: negative regulation by TLR4 signaling. J Immunol 192:5984–5992PubMedCentralCrossRefPubMed
21.
go back to reference Kothari RU, Brott T, Broderick JP, Barsan WG, Sauerbeck LR, Zuccarello M et al (1996) The ABCs of measuring intracerebral hemorrhage volumes. Stroke 27:1304–1305CrossRefPubMed Kothari RU, Brott T, Broderick JP, Barsan WG, Sauerbeck LR, Zuccarello M et al (1996) The ABCs of measuring intracerebral hemorrhage volumes. Stroke 27:1304–1305CrossRefPubMed
22.
go back to reference Urrutia P, Aguirre P, Esparza A, Tapia V, Mena NP, Arredondo M et al (2013) Inflammation alters the expression of DMT1, FPN1 and hepcidin, and it causes iron accumulation in central nervous system cells. J Neurochem 126:541–549CrossRefPubMed Urrutia P, Aguirre P, Esparza A, Tapia V, Mena NP, Arredondo M et al (2013) Inflammation alters the expression of DMT1, FPN1 and hepcidin, and it causes iron accumulation in central nervous system cells. J Neurochem 126:541–549CrossRefPubMed
23.
go back to reference Thomas C, Kobold U, Balan S, Roeddiger R, Thomas L (2011) Serum hepcidin-25 may replace the ferritin index in the Thomas plot in assessing iron status in anemic patients. Int J Lab Hematol 33:187–193CrossRefPubMed Thomas C, Kobold U, Balan S, Roeddiger R, Thomas L (2011) Serum hepcidin-25 may replace the ferritin index in the Thomas plot in assessing iron status in anemic patients. Int J Lab Hematol 33:187–193CrossRefPubMed
Metadata
Title
Serum hepcidin concentrations correlate with serum iron level and outcome in patients with intracerebral hemorrhage
Authors
Xiao-Yi Xiong
Jing Chen
Wen-Yao Zhu
Ting Zhao
Qi Zhong
Kai Zhou
Zhao-You Meng
Yan-Chun Wang
Peng-Fei Wang
Huang Fang
Qing-Wu Yang
Publication date
01-10-2015
Publisher
Springer Milan
Published in
Neurological Sciences / Issue 10/2015
Print ISSN: 1590-1874
Electronic ISSN: 1590-3478
DOI
https://doi.org/10.1007/s10072-015-2266-2

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