Differential temporal expression of matrix metalloproteinases after spinal cord injury: relationship to revascularization and wound healing.

OBJECT: Matrix metalloproteinases (MMPs), particularly MMP-9/gelatinase B, promote early inflammation and barrier disruption after spinal cord injury (SCI). Early blockade of MMPs after injury provides neuroprotection and improves motor outcome. There is recent evidence, however, that MMP-9 and MMP-2/gelatinase A participate in later wound healing in the injured cord. The authors therefore examined the activity of these gelatinases during revascularization and glial scar formation in the contused murine spinal cord. METHODS: Gelatinase activity was evaluated using gelatin zymography 24 hours after a mild, moderate, or severe contusion injury. The active form of MMP-2 was not detected, whereas MMP-9 activity was evident in all SCI groups and rose with increasing injury severity. The temporal expression of gelatinases was then examined using gelatin zymography after a moderate SCI. The active form of MMP-9 was most prominent at 1 day, extended through the early period of revascularization, and returned to control by 14 days. The active form of MMP-2 appeared at 7 days postinjury and remained elevated compared with that documented in sham-treated mice for at least 21 days. Increased MMP-2 activity coincided with both revascularization and glial scar formation. Using in situ zymography, gelatinolytic activity was detected in the meninges, vascular elements, glia, and macrophage-like cells in the injured cord. Results of immunolabeling confirmed the presence of gelatinase in vessels during revascularization and in reactive astrocytes associated with glial scar formation. CONCLUSIONS: These findings suggest that although MMP-9 and -2 exhibit overlapping expression during revascularization, the former is associated with acute injury responses and the latter with formation of a glial scar.