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Metalloproteinase increases in the injured rat spinal cord
R C de Castro1, C L Burns, D J McAdoo
1Department of Human Biological Chemistry and Genetics and the Marine Biomedical Institute, The University of Texas Medical Branch, Galveston 77555, USA.
Abstract:
Up-regulation of matrix metalloproteinases MMP-9 and MMP-2 after injury to the spinal cord (SCI) is demonstrated. MMP-9 activity maximized at 12-24 h, and MMP-2 rose at 5 days post-injury. MMP-3 was not detectable by zymographic analysis, so its level of expression was, at most, very low. The level of tissue inhibitor of metalloproteinases in the spinal cord was not altered by injury, perhaps permitting increased MMP-9 and MMP-2 activities in situ. Ablating them with an antibody demonstrated that infiltrating neutrophils were the principal source of MMP-9 activity after spinal cord injury, suggesting that neutrophils utilize that proteinase in responding to spinal cord injury. MMP-9 and MMP-2 probably contribute to breakdown of the extracellular matrix following SCI.
Insights
Matrix metalloproteinases MMP-9 and MMP-2 increase after spinal cord injury (SCI), with neutrophils being a key source of MMP-9. These enzymes likely contribute to extracellular matrix breakdown, impacting recovery.
Area of Science:
- Biochemistry
- Neuroscience
- Immunology
Background:
- Spinal cord injury (SCI) triggers complex molecular responses.
- Matrix metalloproteinases (MMPs) are enzymes involved in tissue remodeling and degradation.
- Understanding MMP roles in SCI is crucial for developing therapeutic strategies.
Purpose of the Study:
- To investigate the expression and activity of specific matrix metalloproteinases (MMPs) following spinal cord injury.
- To identify the cellular sources of MMPs, particularly MMP-9, in the injured spinal cord.
- To assess the potential contribution of MMPs to extracellular matrix breakdown after SCI.
Main Methods:
- Zymographic analysis was used to detect MMP-9 and MMP-2 activity.
- Levels of MMP-3 were assessed, though found to be very low.
- Immunohistochemistry or antibody-mediated ablation was employed to identify the cellular origin of MMP-9.
Main Results:
- Matrix metalloproteinases MMP-9 and MMP-2 showed increased activity post-SCI.
- MMP-9 activity peaked at 12-24 hours, while MMP-2 levels rose by 5 days.
- Infiltrating neutrophils were identified as the primary source of MMP-9 activity.
- Tissue inhibitor of metalloproteinases levels remained unchanged, potentially allowing increased MMP activity.
Conclusions:
- Neutrophils are a significant source of MMP-9 following spinal cord injury.
- MMP-9 and MMP-2 likely play a role in the degradation of the extracellular matrix after SCI.
- These findings suggest MMPs as potential therapeutic targets for mitigating secondary damage in SCI.