Matrix Metalloproteinase-9 Facilitates Glial Scar Formation in the Injured Spinal Cord

The Journal of Neuroscience, 2008 · DOI: 10.1523/JNEUROSCI.2287-08.2008 · Published: December 10, 2008

Simple Explanation

After a spinal cord injury, a glial scar forms, which becomes a major impediment to the regeneration of axons. This scar is largely composed of reactive astrocytes that migrate to the injury site. This study found that mice with spinal cord injuries who express MMPs developed a more severe glial scar and enhanced expression of chondroitin sulfate proteoglycans. This indicates a more inhibitory environment for axonal regeneration, compared to MMP-9 null mice. The research provides direct evidence that MMP-9 is essential for both the formation of an inhibitory glial scar and the migration of astrocytes, which is mediated by the cytoskeleton. Thus, MMP-9 could be a valuable target for reducing glial scarring after spinal cord injury.

Study Duration

42 d postinjury

Participants

Male MMP-9 null and wild-type mice, weighing 30–35 g (4–6 months of age)

Evidence Level

Not specified

Key Findings

1
Wild-type mice developed a more severe glial scar compared to MMP-9 null mice after spinal cord injury, indicating MMP-9's role in glial scar formation.
2
Wild-type mice exhibited higher CSPG immunoreactivity than MMP-9 null mice, suggesting that MMP-9 governs the formation of a complex and inhibitory glial scar.
3
MMP-9 modulates astrocyte migration by regulating actin-cytoskeleton organization.

Research Summary

This study investigates the role of MMP-9 in glial scar formation and astrocyte migration following spinal cord injury. The findings suggest that MMP-9 facilitates glial scar formation and astrocyte migration in vitro. Experiments showed that spinal cord-injured wild-type mice developed a more severe and inhibitory glial scar than injured MMP-9 null mice. The absence of MMP-9 also altered actin-cytoskeleton organization. The study concludes that MMP-9 contributes to glial scar formation by promoting astrocyte migration, suggesting it as a potential therapeutic target to reduce glial scarring after spinal cord injury.

Practical Implications

Therapeutic Target

MMP-9 may be a promising therapeutic target to reduce glial scarring during wound healing after spinal cord injury.

Understanding Scar Formation

MMP-9 governs the formation of a complex and inhibitory glial scar in the injured spinal cord.

Cytoskeleton Regulation

MMP-9 modulates astrocyte migration likely through a CD44-dependent process, thereby stimulating intracellular signaling that affects the assembly and distribution of actin cytoskeleton.

Study Limitations

1
The specific mechanisms by which MMP-9 modulates astrocyte migration are not well understood.
2
Additional research with MMP conditional knock-outs and selective MMP inhibitors is needed.
3
The study acknowledges that some CSPGs, normally susceptible to MMP-9, may be upregulated in MMP-9 null mice, while others decrease.

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