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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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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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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