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Spine (Phila Pa 1976). 2008 Aug 1;33(17):E576-9. doi: 10.1097/BRS.0b013e31817ecc87.

Inhibition of MMP2/MMP9 after spinal cord trauma reduces apoptosis.

Author information

1
Division of Orthopaedic Surgery, Veterans Affairs Medical Center, San Francisco, CA, USA.

Abstract

STUDY DESIGN:

Randomized controlled trial.

OBJECTIVE:

To characterize the increase in gelatinase A (MMP2) activity after spinal cord injury (SCI) in the mouse model, and the effects of MMP2/MMP9 inhibition on apoptotic cells.

SUMMARY OF BACKGROUND DATA:

Clinical consequences of SCI are due to a series of secondary injury cascades. Matrix metalloproteinases are thought play a key role in this, leading to apoptotic cell death.

METHODS:

SCI via a drop tower in mice was used. MMP2 beta-gal reporter mice were used to quantify the level of MMP2 after SCI. In a follow-up experiment, mice which underwent SCI were randomized to daily SQ injections of MMP2/MMP9 inhibitor versus placebo. MMP2 levels were quantified and histology was performed with TUNEL and Luxol fast blue staining.

RESULTS:

MMP2 transcription was significantly upregulated after SCI, by the beta-gal assay. Inhibition of MMP2/MMP9 activity after SCI led to statistically significant decreases in apoptosis within the zone of injury. There was a trend towards preservation of myelin by preserved luxol fast blue staining.

CONCLUSION:

After SCI, MMP2 is upregulated along with neuron and glial cells apoptosis. The level of apoptosis could be reduced with MMP2/MMP9 inhibition. This supports MMP2 as cause for apoptosis after SCI with the potential for therapeutic intervention as apoptosis can be reduced with MMP2 inhibition.

PMID:
18670324
DOI:
10.1097/BRS.0b013e31817ecc87
[Indexed for MEDLINE]

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