Increased Plasma and Tissue MMP Levels are Associated with BCSFB and BBB Disruption Evident on Post-Contrast FLAIR after Experimental Stroke

Abstract

In this study, we examined the relationship between tissue and blood levels of matrix metalloproteinase (MMP)-2 and MMP-9 through gelatin zymography at multiple time points after experimental stroke. We additionally investigated the association between these levels and the evidence of blood–cerebrospinal fluid (CSF) barrier (BCSFB) and blood–brain barrier (BBB) disruption on post-contrast fluid-attenuated inversion-recovery (FLAIR) imaging. Increased plasma MMP-9 was associated with BCSFB disruption at 1h post-reperfusion. Ventricular enhancement ipsilateral to the stroke was 500±100%, significantly higher than sham, 24, and 48 h groups. Increased tissue MMP-2 and MMP-9 were associated with BBB disruption at 48 h post-reperfusion. Parenchymal enhancement was 60±20% for a volume equivalent to 260±80 mm3. Although the percent enhancement was comparable across groups, the volume of enhancing lesion was significantly higher at 48 h (260±80 mm3, 100%) in comparison to 1 h (8±3 mm3, 3%) and 24 h (51 mm3, 18%). These findings support the use of imaging markers of BCSFB and BBB status as indirect measures of MMP regulation in the blood and brain tissue. The methods presented herein should be useful in understanding the link between MMPs, barrier integrity, and subsequent hemorrhagic transformation.