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Intracerebral Hemorrhage Research pp 101–105Cite as

Red Blood Cell Lysis and Brain Tissue-Type Transglutaminase Upregulation in a Hippocampal Model of Intracerebral Hemorrhage

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Part of the book series: Acta Neurochirurgica Supplementum ((NEUROCHIRURGICA,volume 111))

Abstract

Red blood cell (RBC) lysis and iron release contribute to intracerebral hemorrhage (ICH)-induced brain injury. Tissue-type transglutaminase (tTG), which has a role in neurodegeneration, is upregulated after ICH. The current study investigated the effect of RBC lysis and iron release on brain tTG levels and neuronal death in a rat model of ICH. This study had three parts: (1) Male Sprague-Dawley rats received an intrahippocampal injection of 10 μL of either packed RBCs or lysed RBCs; (2) rats had a 10 μL injection of either saline, hemoglobin or FeCl2; (3) rats received a 10 μL injection of hemoglobin and were treated with an iron chelator, deferoxamine or vehicle. All rats were killed 24 h later, and the brains were sectioned for tTG and Fluoro-Jade C staining. Lysed but not packed RBCs caused marked tTG upregulation (p < 0.05) and neuronal death (p < 0.05) in the ipsilateral hippocampus CA-1 region. Both hemoglobin and iron mimicked the effects of lysed RBCs, resulting in tTG expression and neuronal death (p < 0.05). Hemoglobin-induced tTG upreglution and neuronal death were reduced by deferoxamine (p < 0.05). These results indicate that RBC lysis and iron toxicity contribute to neurodegeneration after ICH.

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References

  1. Qureshi AI, Tuhrim S, Broderick JP, Batjer HH, Hondo H, Hanley DF (2001) Spontaneous intracerebral hemorrhage. N Engl J Med 344:1450–1460

    Article  PubMed  CAS  Google Scholar 

  2. Mendelow AD, Gregson BA, Fernandes HM, Murray GD, Teasdale GM, Hope DT, Karimi A, Shaw MD, Barer DH (2005) Early surgery versus initial conservative treatment in patients with spontaneous supratentorial intracerebral haematomas in the International Surgical Trial in Intracerebral Haemorrhage (STICH): a randomised trial. Lancet 365:387–397

    PubMed  Google Scholar 

  3. Okauchi M, Xi G, Keep RF, Hua Y (2009) Tissue-type transglutaminase and the effects of cystamine on intracerebral hemorrhage-induced brain edema and neurological deficits. Brain Res 1249:229–236

    Article  PubMed  CAS  Google Scholar 

  4. Xi G, Keep RF, Hoff JT (1998) Erythrocytes and delayed brain edema formation following intracerebral hemorrhage in rats. J Neurosurg 89:991–996

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

    Article  PubMed  CAS  Google Scholar 

  7. Citron BA, Suo Z, SantaCruz K, Davies PJ, Qin F, Festoff BW (2002) Protein crosslinking, tissue transglutaminase, alternative splicing and neurodegeneration. Neurochem Int 40:69–78

    Article  PubMed  CAS  Google Scholar 

  8. Lesort M, Tucholski J, Miller ML, Johnson GV (2000) Tissue transglutaminase: a possible role in neurodegenerative diseases. Prog Neurobiol 61:439–463

    Article  PubMed  CAS  Google Scholar 

  9. Gu Y, Hua Y, Keep RF, Morgenstern LB, Xi G (2009) Deferoxamine reduces intracerebral hematoma-induced iron accumulation and neuronal death in piglets. Stroke 40:2241–2243

    Article  PubMed  CAS  Google Scholar 

  10. Song S, Hua Y, Keep RF, Hoff JT, Xi G (2007) A new hippocampal model for examining intracerebral hemorrhage-related neuronal death: effects of deferoxamine on hemoglobin-induced neuronal death. Stroke 38:2861–2863

    Article  PubMed  Google Scholar 

  11. Schmued LC, Albertson C, Slikker W Jr (1997) Fluoro-Jade: a novel fluorochrome for the sensitive and reliable histochemical localization of neuronal degeneration. Brain Res 751:37–46

    Article  PubMed  CAS  Google Scholar 

  12. Fesus L (1998) Transglutaminase-catalyzed protein cross-linking in the molecular program of apoptosis and its relationship to neuronal processes. Cell Mol Neurobiol 18:683–694

    Article  PubMed  CAS  Google Scholar 

  13. Festoff BW, SantaCruz K, Arnold PM, Sebastian CT, Davies PJ, Citron BA (2002) Injury-induced “switch” from GTP-regulated to novel GTP-independent isoform of tissue transglutaminase in the rat spinal cord. J Neurochem 81:708–718

    Article  PubMed  CAS  Google Scholar 

  14. Tolentino PJ, DeFord SM, Notterpek L, Glenn CC, Pike BR, Wang KK, Hayes RL (2002) Up-regulation of tissue-type transglutaminase after traumatic brain injury. J Neurochem 80:579–588

    Article  PubMed  CAS  Google Scholar 

  15. Tolentino PJ, Waghray A, Wang KK, Hayes RL (2004) Increased expression of tissue-type transglutaminase following middle cerebral artery occlusion in rats. J Neurochem 89:1301–1307

    Article  PubMed  CAS  Google Scholar 

  16. Tucholski J, Roth KA, Johnson GV (2006) Tissue transglutaminase overexpression in the brain potentiates calcium-induced hippocampal damage. J Neurochem 97:582–594

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  18. Campisi A, Caccamo D, Li Volti G, Curro M, Parisi G, Avola R, Vanella A, Ientile R (2004) Glutamate-evoked redox state alteration are involved in tissue transglutaminase upregulation in primary astrocyte cultures. FEBS Lett 578:80–84

    Article  PubMed  CAS  Google Scholar 

  19. Curro M, Condello S, Caccamo D, Ferlazzo N, Parisi G, Ientile R (2009) Homocysteine-induced toxicity increases TG2 expression in neuron2a cells. Amino Acids 36:725–730

    Article  PubMed  CAS  Google Scholar 

  20. Luciani A, Villella VR, Vasaturo A, Giardino I, Raia V, Pettoello-Mantovani M, D’Apolito M, Guido S, Leal T, Quaratino S, Maiuri L (2009) SUMOylation of tissue transglutaminase as link between oxidative stress and inflammation. J Immunol 183:2775–2784

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

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

Conflict of interest statement We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Department of Neurosurgery, University of Michigan, Ann Arbor, MI, USA

    Fan Zhao, Shuijiang Song, Wenquan Liu, Richard F. Keep & Guohua Xi

  2. Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China

    Fan Zhao

  3. Department of Neurology, The Second Affiliated Hospital, Zhejiang University, Hangzhou, China

    Shuijiang Song

  4. Department of Neurosurgery, University of Michigan, Room 5018 BSRB, 109 Zina Pitcher Place, 48109-2200, Ann Arbor, MI, USA

    Ya Hua

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  1. Fan Zhao
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  2. Shuijiang Song
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  3. Wenquan Liu
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  4. Richard F. Keep
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  5. Guohua Xi
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  6. Ya Hua
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Corresponding author

Correspondence to Ya Hua .

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Editors and Affiliations

  1. , Neurosurgery, Physiology, Loma Linda University, Campus Street 11041, Loma Linda, 92530, USA

    John Zhang

  2. School of Medicine, Dept. Neurosurgery, Loma Linda University, Anderson St. 11234, Loma Linda, 92354, California, USA

    Austin Colohan

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© 2011 Springer-Verlag/Wien

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Zhao, F., Song, S., Liu, W., Keep, R.F., Xi, G., Hua, Y. (2011). Red Blood Cell Lysis and Brain Tissue-Type Transglutaminase Upregulation in a Hippocampal Model of Intracerebral Hemorrhage. In: Zhang, J., Colohan, A. (eds) Intracerebral Hemorrhage Research. Acta Neurochirurgica Supplementum, vol 111. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0693-8_16

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  • DOI: https://doi.org/10.1007/978-3-7091-0693-8_16

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  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-7091-0692-1

  • Online ISBN: 978-3-7091-0693-8

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