Ceruloplasmin Protects Injured Spinal Cord from Iron-mediated Oxidative Damage

Overview

Journal J Neurosci

Specialty Neurology

Date 2008 Nov 28

PMID 19036966

Citations 51

Authors

Khizr I Rathore

Bradley J Kerr

Adriana Redensek

Ruben Lopez-Vales

Suh Young Jeong

Prem Ponka

Samuel David

Affiliations

Soon will be listed here.

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.

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