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Deferoxamine Reduces Neuronal Death and Hematoma Lysis After Intracerebral Hemorrhage in Aged Rats

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Abstract

Intracerebral hemorrhage (ICH) is primarily a disease of the elderly. Deferoxamine (DFX), an iron chelator, reduces long-term neurological deficits and brain atrophy after ICH in aged rats. In the present study, we investigated whether DFX can reduce acute ICH-induced neuronal death and whether it affects the endogenous response to ICH (ferritin upregulation and hematoma resolution) in aged rats. Male Fischer 344 rats (18 months old) had an intracaudate injection of 100 μL autologous whole blood into the right basal ganglia and were treated with DFX (100 mg/kg) or vehicle 2 h post-ICH and then every 12 h up to 7 days. Rats were euthanized 1, 3, or 7 days later for neuronal death and ferritin and hematoma size measurements. Plasma ferritin levels and behavioral outcome following ICH were also examined. DFX treatment significantly reduced ICH-induced neuronal death and neurological deficits. DFX also suppressed ferritin upregulation in the ipsilateral basal ganglia after ICH and hematoma lysis (hematoma volume at day 7, 13.2 ± 4.9 vs. 3.8 ± 1.2 mm3 in vehicle-treated group, p < 0.01). However, effects of DFX on plasma ferritin levels after ICH did not reach significance. In conclusion, DFX reduces neuronal death and neurological deficits after ICH in aged rats. It also affects the endogenous response to ICH.

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Acknowledgment

This study was supported by grants NS-052510, NS-057539, NS-073595, NS-079157, and NS-084049 from the National Institutes of Health (NIH). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Conflict of Interest

Tetsuhiro Hatakeyama, Masanobu Okauchi, Ya Hua, Richard F. Keep, and Guohua Xi declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Neurosurgery, University of Michigan, R5018, BSRB 109 Zina Pitcher Place, Ann Arbor, MI, 48109-2200, USA

    Tetsuhiro Hatakeyama, Masanobu Okauchi, Ya Hua, Richard F. Keep & Guohua Xi

  2. Department of Neurological Surgery, Kagawa University, Kagawa, Japan

    Tetsuhiro Hatakeyama & Masanobu Okauchi

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  1. Tetsuhiro Hatakeyama
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  2. Masanobu Okauchi
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  3. Ya Hua
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  4. Richard F. Keep
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  5. Guohua Xi
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Correspondence to Guohua Xi.

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Hatakeyama, T., Okauchi, M., Hua, Y. et al. Deferoxamine Reduces Neuronal Death and Hematoma Lysis After Intracerebral Hemorrhage in Aged Rats. Transl. Stroke Res. 4, 546–553 (2013). https://doi.org/10.1007/s12975-013-0270-5

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  • DOI: https://doi.org/10.1007/s12975-013-0270-5

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