Matrix metalloproteinases: Potential therapeutic target in spinal cord injury

Mediators of extracellular matrix proteins degradation, the matrix metallop roteinases (MMPs), involved in inflammation as well as facilitation of proc ess outgrowth of oligodendrocytes are interesting targets for neural repair . Recent data reported their activation after seizures, cerebral ischemia a nd spinal cord injury. The present study was designed to localize at cellul ar level the gelatinase activity by in situ zymography in a rat spinal cord contusion model. The kinetic of gelatinase activation was monitored by in sire zymography on 20 mum cryostat sections. The fluorescein-quenched DQ ge latin digestion yielded cleaved fluorescent peptides enabling the detection of gelatinase activity at cellular level. Twenty four hours and 48 h after injury, a strong gelatinase activity was detected at the lesion site in an d around vascular structures and infiltrated cells. A preincubation with ei ther MMP-2 or MMP-9 antibodies significantly decreases the gelatinase activ ity pattern, suggesting the involvement of at least both MMPs. Our results are consistent with a role for MMPs in the blood spinal barrier disruption, the leukocytes infiltration, the disruption of the extracellular matrix an d the clearance of debris.