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

Author(s): Dang AB, Tay BK, Kim HT, Nauth A, Alfonso-Jaume MA, Lovett DH

Affiliation(s): Division of Orthopaedic Surgery, Veterans Affairs Medical Center, San Francisco, CA, USA.

Publication date & source: 2008-08-01, Spine., 33(17):E576-9.

Publication type: Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.

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.