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Increased expression of ferritin in cerebral cortex after human traumatic brain injury

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Abstract

Despite numerous researches and improvements in the past few years, the precise mechanisms underlying secondary brain injury after trauma remain obscure. Iron is essential for almost all types of cells, including nerve cells. However, excess of iron has been proved to contribute to the brain injury following trauma in animal models. As a key iron-handling protein in the brain, ferritin might be involved in iron-induced pathophysiological process of various brain disorders. Therefore, the current study was aimed to investigate the expression of ferritin in the human contused brain. Nineteen contused brain samples were obtained from 19 patients undergoing surgery for brain contusions 3 h–17 d after trauma, and three normal temporal pole samples from 3 patients with petroclival meningioma were collected as controls. Expression of ferritin-H-chain was measured by quantitative real-time polymerase chain reaction (PCR), western blot and immunohistochemistry, respectively. Perl’s reaction was taken for iron staining. The results showed that human traumatic brain injury (TBI) could up-regulate ferritin-H-chain in pericontusional cortex. A marked increase of ferritin was detected in the early group (≤12 h), and remained elevated for a long time till after 48 h post-injury. The location of ferritin-H-chain was found mainly at the neuron-like cells and seldom at glia-like cells. Perl’s reaction showed that most of the iron-positive cells were glia-like cells. These findings suggested that iron and ferritin might be involved in the secondary brain injury and could be therapeutic targets for patients with TBI.

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References

  1. Roth P, Farls K (2000) Pathophysiology of traumatic brain injury. Crit Care Nurs Q 23(3):14–25 quiz 65

    PubMed  CAS  Google Scholar 

  2. Khoshyomn S, Tranmer BI (2004) Diagnosis and management of pediatric closed head injury. Semin Pediatr Surg 13(2):80–86

    Article  PubMed  Google Scholar 

  3. Ziebell JM, Morganti-Kossmann MC (2010) Involvement of pro- and anti-inflammatory cytokines and chemokines in the pathophysiology of traumatic brain injury. Neurotherapeutics 7(1):22–30

    Article  PubMed  CAS  Google Scholar 

  4. Bramlett HM, Dietrich WD (2007) Progressive damage after brain and spinal cord injury: pathomechanisms and treatment strategies. Prog Brain Res 161:125–141

    Article  PubMed  Google Scholar 

  5. Helmy A, De Simoni MG, Guilfoyle MR, Carpenter KL, Hutchinson PJ (2011) Cytokines and innate inflammation in the pathogenesis of human traumatic brain injury. Prog Neurobiol 95(3):352–372

    Article  PubMed  CAS  Google Scholar 

  6. Clausen F, Marklund N, Lewen A, Enblad P, Basu S, Hillered L (2012) Interstitial F(2)-isoprostane 8-iso-PGF(2alpha) as a biomarker of oxidative stress after severe human traumatic brain injury. J Neurotrauma 29(5):766–775

    Article  PubMed  Google Scholar 

  7. Zhang QG, Laird MD, Han D, Nguyen K, Scott E, Dong Y, Dhandapani KM, Brann DW (2012) Critical role of NADPH oxidase in neuronal oxidative damage and microglia activation following traumatic brain injury. PLoS ONE 7(4):e34504

    Article  PubMed  CAS  Google Scholar 

  8. Jin W, Wang H, Yan W, Zhu L, Hu Z, Ding Y, Tang K (2009) Role of Nrf2 in protection against traumatic brain injury in mice. J Neurotrauma 26(1):131–139

    Article  PubMed  Google Scholar 

  9. Carbonell T, Rama R (2007) Iron, oxidative stress and early neurological deterioration in ischemic stroke. Curr Med Chem 14(8):857–874

    Article  PubMed  CAS  Google Scholar 

  10. Connor JR, Menzies SL, Burdo JR, Boyer PJ (2001) Iron and iron management proteins in neurobiology. Pediatr Neurol 25(2):118–129

    Article  PubMed  CAS  Google Scholar 

  11. Wagner KR, Sharp FR, Ardizzone TD, Lu A, Clark JF (2003) Heme and iron metabolism: role in cerebral hemorrhage. J Cereb Blood Flow Metab 23(6):629–652

    Article  PubMed  CAS  Google Scholar 

  12. Dennery PA, Visner G, Weng YH, Nguyen X, Lu F, Zander D, Yang G (2003) Resistance to hyperoxia with heme oxygenase-1 disruption: role of iron. Free Radic Biol Med 34(1):124–133

    Article  PubMed  CAS  Google Scholar 

  13. Chang EF, Claus CP, Vreman HJ, Wong RJ, Noble-Haeusslein LJ (2005) Heme regulation in traumatic brain injury: relevance to the adult and developing brain. J Cereb Blood Flow Metab 25(11):1401–1417

    Article  PubMed  CAS  Google Scholar 

  14. Huang FP, Xi G, Keep RF, Hua Y, Nemoianu A, Hoff JT (2002) Brain edema after experimental intracerebral hemorrhage: role of hemoglobin degradation products. J Neurosurg 96(2):287–293

    Article  PubMed  Google Scholar 

  15. Wu J, Hua Y, Keep RF, Schallert T, Hoff JT, Xi G (2002) Oxidative brain injury from extravasated erythrocytes after intracerebral hemorrhage. Brain Res 953(1–2):45–52

    Article  PubMed  CAS  Google Scholar 

  16. Lee JY, Keep RF, He Y, Sagher O, Hua Y, Xi G (2010) Hemoglobin and iron handling in brain after subarachnoid hemorrhage and the effect of deferoxamine on early brain injury. J Cereb Blood Flow Metab 30(11):1793–1803

    Article  PubMed  CAS  Google Scholar 

  17. Long DA, Ghosh K, Moore AN, Dixon CE, Dash PK (1996) Deferoxamine improves spatial memory performance following experimental brain injury in rats. Brain Res 717(1–2):109–117

    Article  PubMed  CAS  Google Scholar 

  18. Panter SS, Braughler JM, Hall ED (1992) Dextran-coupled deferoxamine improves outcome in a murine model of head injury. J Neurotrauma 9(1):47–53

    Article  PubMed  CAS  Google Scholar 

  19. Lovell MA, Robertson JD, Teesdale WJ, Campbell JL, Markesbery WR (1998) Copper, iron and zinc in Alzheimer’s disease senile plaques. J Neurol Sci 158(1):47–52

    Article  PubMed  CAS  Google Scholar 

  20. Youdim MB, Ben-Shachar D, Riederer P (1991) Iron in brain function and dysfunction with emphasis on Parkinson’s disease. Eur Neurol 31(Suppl 1):34–40

    Article  PubMed  Google Scholar 

  21. Chiueh CC (2001) Iron overload, oxidative stress, and axonal dystrophy in brain disorders. Pediatr Neurol 25(2):138–147

    Article  PubMed  CAS  Google Scholar 

  22. Koeppen AH, Dickson AC, McEvoy JA (1995) The cellular reactions to experimental intracerebral hemorrhage. J Neurol Sci 134(Suppl):102–112

    Article  PubMed  Google Scholar 

  23. 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(12):2964–2969

    Article  PubMed  CAS  Google Scholar 

  24. Levi S, Yewdall SJ, Harrison PM, Santambrogio P, Cozzi A, Rovida E, Albertini A, Arosio P (1992) Evidence of H- and L-chains have co-operative roles in the iron-uptake mechanism of human ferritin. Biochem J 288(Pt 2):591–596

    PubMed  CAS  Google Scholar 

  25. Hang CH, Chen G, Shi JX, Zhang X, Li JS (2006) Cortical expression of nuclear factor kappaB after human brain contusion. Brain Res 1109(1):14–21

    Article  PubMed  CAS  Google Scholar 

  26. Li W, Ling HP, You WC, Ji XJ, Tang Y, Zhao JB, Su XF, Hang CH (2012) Recombinant high-mobility group box 1 protein (HMGB-1) promotes myeloid differentiation primary response protein 88 (Myd88) upregulation in mouse primary cortical neurons. Neurol Sci

  27. McIntosh TK, Thomas M, Smith D, Banbury M (1992) The novel 21-aminosteroid U74006F attenuates cerebral edema and improves survival after brain injury in the rat. J Neurotrauma 9(1):33–46

    Article  PubMed  CAS  Google Scholar 

  28. Marklund N, Clausen F, Lewen A, Hovda DA, Olsson Y, Hillered L (2001) alpha-Phenyl-tert-N-butyl nitrone (PBN) improves functional and morphological outcome after cortical contusion injury in the rat. Acta Neurochir (Wien) 143(1):73–81

    Article  CAS  Google Scholar 

  29. Fukuda K, Richmon JD, Sato M, Sharp FR, Panter SS, Noble LJ (1996) Induction of heme oxygenase-1 (HO-1) in glia after traumatic brain injury. Brain Res 736(1–2):68–75

    Article  PubMed  CAS  Google Scholar 

  30. Beschorner R, Adjodah D, Schwab JM, Mittelbronn M, Pedal I, Mattern R, Schluesener HJ, Meyermann R (2000) Long-term expression of heme oxygenase-1 (HO-1, HSP-32) following focal cerebral infarctions and traumatic brain injury in humans. Acta Neuropathol 100(4):377–384

    Article  PubMed  CAS  Google Scholar 

  31. Chen Z, Gao C, Hua Y, Keep RF, Muraszko K, Xi G (2011) Role of iron in brain injury after intraventricular hemorrhage. Stroke 42(2):465–470

    Article  PubMed  Google Scholar 

  32. Okauchi M, Hua Y, Keep RF, Morgenstern LB, Xi G (2009) Effects of deferoxamine on intracerebral hemorrhage-induced brain injury in aged rats. Stroke 40(5):1858–1863

    Article  PubMed  CAS  Google Scholar 

  33. Zhang L, Hu R, Li M, Li F, Meng H, Zhu G, Lin J, Feng H (2012) Deferoxamine attenuates iron-induced long-term neurotoxicity in rats with traumatic brain injury. Neurol Sci

  34. Selim M (2009) Deferoxamine mesylate: a new hope for intracerebral hemorrhage: from bench to clinical trials. Stroke 40(3 Suppl):S90–S91

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by grants from National Natural Science Foundation, China (No. 81171170 for C.-H. Hang, No. 8100053 for M.-L. Zhou and No. 81271377 for L. Zhu) and Nature Science Foundation of Jiangsu Province, China (BK2010459).

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Authors and Affiliations

  1. Department of Neurosurgery, School of Medicine, Southern Medical University (Guangzhou), Jinling Hospital, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu Province, People’s Republic of China

    Huan-Dong Liu, Zhen-Rui Chen & Chun-Hua Hang

  2. Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu Province, People’s Republic of China

    Wei Li, Meng-Liang Zhou, Zong Zhuang, Ding-Ding Zhang, Lin Zhu & Chun-Hua Hang

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  1. Huan-Dong Liu
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  2. Wei Li
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Correspondence to Chun-Hua Hang.

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Liu, HD., Li, W., Chen, ZR. et al. Increased expression of ferritin in cerebral cortex after human traumatic brain injury. Neurol Sci 34, 1173–1180 (2013). https://doi.org/10.1007/s10072-012-1214-7

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  • DOI: https://doi.org/10.1007/s10072-012-1214-7

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