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Iron-Induced Necrotic Brain Cell Death in Rats with Different Aerobic Capacity

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Abstract

Brain iron overload has a key role in brain injury after intracerebral hemorrhage (ICH). Our recent study demonstrated that ICH-induced brain injury was greater in low capacity runner (LCR) than in high capacity runner (HCR) rats. The present study examines whether iron-induced brain injury differs between LCRs and HCRs. Adult male LCR and HCR rats had an intracaudate injection of iron or saline. Rats were euthanized at 2 and at 24 h after T2 magnetic resonance imaging, and the brains were used for immunostaining and Western blotting. LCRs had more hemispheric swelling, T2 lesion volumes, blood-brain barrier disruption, and neuronal death at 24 h after iron injection (p < 0.05). Many propidium iodide (PI)-positive cells, indicative of necrotic cell death, were observed in the ipsilateral basal ganglia of both HCRs and LCRs at 2 h after iron injection. PI fluorescence intensity was higher in LCRs than in HCRs. In addition, membrane attack complex (MAC) expression was increased at 2 h after iron injection and was higher in LCRs than in HCRs. The PI-positive cells co-localized with MAC-positive cells in the ipsilateral basal ganglia. Iron induces more severe necrotic brain cell death, brain swelling, and blood-brain barrier disruption in LCR rats, which may be related with complement activation and MAC formation.

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Acknowledgments

This study was supported by grants NS-073595, NS-079157, NS-084049, OD-010950, DK-077200 and GM-104194 from the National Institutes of Health (NIH).

Conflict of Interest

Mingzhe Zheng, Hanjian Du, Wei Ni, Lauren G. Koch, Steven L. Britton, Richard F. Keep, Guohua Xi, and Ya Hua declare that they have no conflict of interest.

Compliance with Ethics Requirements

All institutional and national guidelines for the care and use of laboratory animals were followed.

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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

    Mingzhe Zheng, Hanjian Du, Wei Ni, Richard F. Keep, Guohua Xi & Ya Hua

  2. Department of Anesthesiology, University of Michigan, Ann Arbor, MI, USA

    Lauren G. Koch & Steven L. Britton

Authors
  1. Mingzhe Zheng
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  2. Hanjian Du
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  3. Wei Ni
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  7. Guohua Xi
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  8. Ya Hua
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Correspondence to Ya Hua.

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Zheng, M., Du, H., Ni, W. et al. Iron-Induced Necrotic Brain Cell Death in Rats with Different Aerobic Capacity. Transl. Stroke Res. 6, 215–223 (2015). https://doi.org/10.1007/s12975-015-0388-8

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  • DOI: https://doi.org/10.1007/s12975-015-0388-8

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