Ceruloplasmin protects injured spinal cord from iron-mediated oxidative damage

Khizr I. Rathore, Bradley J. Kerr, Adriana Redensek, Rubèn López-Vales, Young Jeong Suh, Prem Ponka, Samuel David

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

CNS injury-induced hemorrhage and tissue damage leads to excess iron, which can cause secondary degeneration. The mechanisms that handle this excess iron are not fully understood. We report that spinal cord contusion injury (SCI) in mice induces an "iron homeostatic response" that partially limits iron-catalyzed oxidative damage. We show that ceruloplasmin (Cp), a ferroxidase that oxidizes toxic ferrous iron, is important for this process. SCI in Cp-deficient mice demonstrates that Cp detoxifies and mobilizes iron and reduces secondary tissue degeneration and functional loss. Our results provide new insights into how astrocytes and macrophages handle iron after SCI. Importantly, we show that iron chelator treatment has a delayed effect in improving locomotor recovery between 3 and 6 weeks after SCI. These data reveal important aspects of the molecular control of CNS iron homeostasis after SCI and suggest that iron chelator therapy may improve functional recovery after CNS trauma and hemorrhagic stroke.

Original languageEnglish (US)
Pages (from-to)12736-12747
Number of pages12
JournalJournal of Neuroscience
Volume28
Issue number48
DOIs
StatePublished - Nov 26 2008
Externally publishedYes

Keywords

  • CNS injury
  • Free radicals
  • Hemorrhage
  • Inflammation
  • Iron chelation
  • Macrophage

ASJC Scopus subject areas

  • Neuroscience(all)

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