Related Experiment Video
Updated: Aug 30, 2026
Automated Impactor for Contusive Spinal Cord Injury Model in Mice
Published on: January 19, 2024
An adverse role for matrix metalloproteinase 12 after spinal cord injury in mice
Jennifer E A Wells1, Tiffany K Rice, Robert K Nuttall
1Department of Clinical Neurosciences, Faculty of Medicine, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
Abstract:
We investigated the role of matrix metalloproteinases (MMPs) in acute spinal cord injury (SCI). Transcripts encoding 22 of the 23 known mammalian MMPs were measured in the mouse spinal cord at various time points after injury. Although there were significant changes in the expression levels of multiple MMPs, MMP-12 was increased 189-fold over normal levels, the highest of all MMPs examined. To evaluate the role of MMP-12 in SCI, spinal cord compression was performed in wild-type (WT) and MMP-12 null mice. Behavioral analyses were conducted for 4 weeks using the Basso-Beattie-Bresnahan (BBB) locomotor rating scale as well as the inclined plane test. The results show that MMP-12 null mice exhibited significantly improved functional recovery compared with WT controls. Twenty-eight days after injury, the BBB score in the MMP-12 group was 7, representing extensive movement of all three hindlimb joints, compared with 4 in the WT group, representing only slight movement of these joints. Furthermore, MMP-12 null mice showed recovery of hindlimb strength more rapidly than control mice, with significantly higher inclined plane scores on days 14 and 21 after SCI. Mechanistically, there was decreased permeability of the blood-spinal barrier and reduced microglial and macrophage density in MMP-12 null mice compared with WT controls. This is the first study to profile the expression patterns of a majority of the known MMPs after spinal cord compression. The data indicate that MMP-12 expression after spinal cord trauma is deleterious and contributes to the development of secondary injury in SCI.
Insights
Matrix metalloproteinase-12 (MMP-12) plays a detrimental role in acute spinal cord injury (SCI). Inhibiting MMP-12 in mice significantly improved locomotor recovery and reduced secondary injury after SCI.
Area of Science:
- Neuroscience
- Biochemistry
- Immunology
Background:
- Matrix metalloproteinases (MMPs) are implicated in tissue remodeling and inflammation.
- Their precise role in acute spinal cord injury (SCI) remains incompletely understood.
- MMP-12 expression is significantly upregulated following spinal cord trauma.
Purpose of the Study:
- To investigate the functional role of MMP-12 in the acute phase of spinal cord injury.
- To determine the impact of MMP-12 deficiency on locomotor recovery and secondary injury mechanisms.
Main Methods:
- Profiling of 22 mammalian MMP transcripts in mouse spinal cord post-injury.
- Induction of spinal cord compression in wild-type (WT) and MMP-12 null mice.
- Behavioral assessment using the Basso-Beattie-Bresnahan (BBB) scale and inclined plane test.
- Histological analysis of blood-spinal barrier permeability and immune cell infiltration.
Main Results:
- MMP-12 expression increased 189-fold in injured spinal cords, the highest among all MMPs studied.
- MMP-12 null mice demonstrated significantly improved locomotor recovery (higher BBB scores) and hindlimb strength compared to WT controls.
- Absence of MMP-12 led to reduced blood-spinal barrier permeability and decreased microglial/macrophage infiltration.
Conclusions:
- MMP-12 expression following spinal cord trauma is detrimental.
- Targeting MMP-12 may represent a therapeutic strategy to mitigate secondary injury and enhance functional recovery after SCI.
- This study provides the first comprehensive MMP expression profile and highlights MMP-12 as a key contributor to SCI pathogenesis.
