Back to Search
Start Over
Ceruloplasmin protects injured spinal cord from iron-mediated oxidative damage.
- Source :
-
The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2008 Nov 26; Vol. 28 (48), pp. 12736-47. - Publication Year :
- 2008
-
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.
- Subjects :
- Animals
Antioxidants pharmacology
Antioxidants therapeutic use
Ceruloplasmin therapeutic use
Disease Models, Animal
Hemorrhage complications
Hemorrhage physiopathology
Iron metabolism
Iron Metabolism Disorders etiology
Iron Metabolism Disorders physiopathology
Mice
Mice, Inbred C57BL
Mice, Knockout
Neurons drug effects
Neurons metabolism
Neurons pathology
Neuroprotective Agents pharmacology
Neuroprotective Agents therapeutic use
Oxidative Stress physiology
Recovery of Function drug effects
Recovery of Function physiology
Spinal Cord drug effects
Spinal Cord metabolism
Spinal Cord physiopathology
Spinal Cord Injuries complications
Spinal Cord Injuries physiopathology
Treatment Outcome
Ceruloplasmin pharmacology
Hemorrhage drug therapy
Iron toxicity
Iron Metabolism Disorders drug therapy
Oxidative Stress drug effects
Spinal Cord Injuries drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1529-2401
- Volume :
- 28
- Issue :
- 48
- Database :
- MEDLINE
- Journal :
- The Journal of neuroscience : the official journal of the Society for Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 19036966
- Full Text :
- https://doi.org/10.1523/JNEUROSCI.3649-08.2008