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Brain Ceruloplasmin Expression After Experimental Intracerebral Hemorrhage and Protection Against Iron-Induced Brain Injury

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Abstract

Ceruloplasmin (CP) is an essential ferroxidase that is involved in maintaining iron homeostasis by oxidizing toxic ferrous iron (Fe2+) to less-toxic ferric iron (Fe3+). CP has been well studied in many neurodegenerative diseases, but there has not been an in-depth investigation in intracerebral hemorrhage (ICH). This research investigated brain CP expression in rats after ICH and the effect of CP on Fe2+-induced brain injury. This study had two parts: first, rats had injection of autologous blood into the right basal ganglia and the time course of CP expression in the brain examined (protein and mRNA). Second, rats had an injection of either Fe2+ in saline, Fe2+ plus CP in saline, or saline alone into the right basal ganglia. All rats in the second part had T2-weighted magnetic resonance imaging, and behavioral tests before the brains were harvested for immunohistochemistry and Western blotting. We found that CP was expressed on neurons and astrocytes in both cortex and basal ganglia after ICH. The time course showed that ICH induced CP expression increased from 4 h to 7 days, peaking at day 3. Whether the brain itself can produce CP was confirmed by RT-PCR. Exogenous CP reduced Fe2+-induced T2 lesions, blood-brain barrier disruption, brain cell death, and neurological deficits. These results suggest a role of CP in potentially reducing ICH-induced brain injury.

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Funding

This work was supported by grants NS-091545, NS-090925, NS-096917, and NS-106746 from the National Institutes of Health (NIH).

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Authors and Affiliations

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

    Hongwei Liu, Ya Hua, Richard F. Keep & Guohua Xi

  2. Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China

    Hongwei Liu

Authors
  1. Hongwei Liu
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  2. Ya Hua
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  3. Richard F. Keep
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  4. Guohua Xi
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Correspondence to Guohua Xi.

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The authors declare that they have no conflict of interest.

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

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Liu, H., Hua, Y., Keep, R.F. et al. Brain Ceruloplasmin Expression After Experimental Intracerebral Hemorrhage and Protection Against Iron-Induced Brain Injury. Transl. Stroke Res. 10, 112–119 (2019). https://doi.org/10.1007/s12975-018-0669-0

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  • DOI: https://doi.org/10.1007/s12975-018-0669-0

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