Matrix metalloproteinase expression after human cardioembolic stroke - Temporal profile and relation to neurological impairment

Background and Purpose-Uncontrolled expression of matrix metalloproteinases (MMPs) can result in tissue injury and inflammation. In animal models of c erebral ischemia, the expression of MMP-2 and MMP-9 was significantly incre ased. However, their role in human stroke in vivo remains unknown. Therefor e, we sought to determine the temporal profile of MMP expression in patient s with acute ischemic stroke and to investigate its relationship to stroke severity, location of arterial occlusion, and total infarct volume. Methods-Serial MMP-2 and MMP-9 determinations were made in 39 patients with cardioembolic strokes that involved the middle cerebral artery territory b y means of enzyme-linked immunosorbent assay. Blood samples, transcranial D oppler recordings, and National Institutes of Health Stroke Scale (NIHSS) s cores were obtained at baseline and at 12, 24, and 48 hours after stroke on set. Infarct volume was measured with CT scanning at 48 hours. Results-No correlation was found between MMP-2 and NIHSS score at any time point, although a close relation appeared between mean MMP-9 and final NIHS S score (r=0.486, P=0.002). MMP-9 value was the only factor associated with the final NIHSS score in the multiple logistic regression model (OR 4.54, 95% Cl 1.5 to 13.75). A cut-point of MMP-9 142.18 ng/mL had a positive pred ictive value of 94.4% to assess a patient's NIHSS (<8 or greater than or eq ual to8) by the end of the study. Final MMP-2 and MMP-9 levels were signifi cantly lower when recanalization occurred (528 +/- 144.3 versus 681.4 +/- 2 39.2 ng/mL, P=0.031 for MMP-2; 110.2 +/- 100.9 versus 244.8 +/- 130 ng/mL, P=0.004 for MMP-9). A positive correlation was found between mean MMP-9 and infarct volume (r=0.385, P=0.022). Conclusions-MMPs are involved in the acute phase of human ischemic stroke. MMP-9 levels are associated with neurological deficit, middle cerebral arte ry occlusion, and infarct volume.