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Heme oxygenase-1 stabilizes the blood–spinal cord barrier and limits oxidative stress and white matter damage in the acutely injured murine spinal cord.
- Source :
-
Journal of Cerebral Blood Flow & Metabolism . May2007, Vol. 27 Issue 5, p1010-1021. 12p. 8 Black and White Photographs, 2 Graphs. - Publication Year :
- 2007
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Abstract
- We hypothesized that heme oxygenase (HO)-1, the inducible form of HO, represents an important defense against early oxidative injury in the traumatized spinal cord by stabilizing the blood–spinal cord barrier and limiting the infiltration of leukocytes. To test this hypothesis, we first examined the immunoexpression of HO-1 and compared barrier permeability and leukocyte infiltration in spinal cord-injured HO-1-deficient (+/−) and wild-type (WT, +/+) mice. Heme oxygenase was expressed in both endothelial cells and glia of the injured cord. Barrier disruption to luciferase and infiltration of neutrophils were significantly greater in the HO-1+/− than WT mice at 24 h postinjury (P≤0.019 and =0.049, respectively). We next examined by Western immunoblots the generation of 4-hydroxynoneal (HNE) and malondialdehyde (MDA), major products of lipid peroxidation, in the injured epicenter. There was a significant increase in 10 kDa HNE- and MDA-modified proteins in the HO-1+/− as compared with WT mice (P=0.037 and 0.043, respectively). Finally, we compared the degradation of myelin basic protein (MBP), an indicator of white matter damage, in the HO-1+/− and WT mice by Western immunoblots. There was significantly greater degradation of MBP in the HO-1+/− compared with WT mice (P=0.049). Together, these findings show that HO-1 modulates oxidative stress and white matter injury in the acutely injured spinal cord. This modulation may be partially attributed to the ability of HO-1 to stabilize the blood–spinal cord barrier and limit neutrophil infiltration.Journal of Cerebral Blood Flow & Metabolism (2007) 27, 1010–1021. doi:10.1038/sj.jcbfm.9600412; published online 18 October 2006 [ABSTRACT FROM AUTHOR]
- Subjects :
- *HEME oxygenase
*SPINAL cord
*LEUCOCYTES
*CELLS
*WESTERN immunoblotting
*LIPIDS
Subjects
Details
- Language :
- English
- ISSN :
- 0271678X
- Volume :
- 27
- Issue :
- 5
- Database :
- Academic Search Index
- Journal :
- Journal of Cerebral Blood Flow & Metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 24816000
- Full Text :
- https://doi.org/10.1038/sj.jcbfm.9600412