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Increased plasma and tissue MMP levels are associated with BCSFB and BBB disruption evident on post-contrast FLAIR
Ayush Batra1, Lawrence L Latour, Christl A Ruetzler
1Stroke Diagnostics and Therapeutics Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
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 mm(3). Although the percent enhancement was comparable across groups, the volume of enhancing lesion was significantly higher at 48 h (260+/-80 mm(3), 100%) in comparison to 1 h (8+/-3 mm(3), 3%) and 24 h (51 mm(3), 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.
Insights
Matrix metalloproteinases (MMPs) like MMP-2 and MMP-9 are linked to blood-brain barrier disruption after stroke. Imaging markers of barrier integrity may indirectly reflect MMP levels and hemorrhagic transformation risk.
Area of Science:
- Neuroscience
- Biochemistry
- Medical Imaging
Background:
- Matrix metalloproteinases (MMPs), specifically MMP-2 and MMP-9, play crucial roles in tissue remodeling and extracellular matrix degradation.
- Disruption of the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB) are critical events following ischemic stroke, influencing outcomes and therapeutic interventions.
Purpose of the Study:
- To investigate the relationship between matrix metalloproteinase (MMP)-2 and MMP-9 levels in tissue and blood.
- To explore the association between MMP levels and the integrity of the blood-cerebrospinal fluid barrier (BCSFB) and blood-brain barrier (BBB) using advanced imaging techniques.
Main Methods:
- Gelatin zymography was employed to quantify MMP-2 and MMP-9 levels at various time points post-experimental stroke.
- Post-contrast fluid-attenuated inversion-recovery (FLAIR) imaging was utilized to assess BCSFB and BBB disruption, evaluating ventricular and parenchymal enhancement.
Main Results:
- Elevated plasma MMP-9 correlated with BCSFB disruption at 1 hour post-reperfusion, evidenced by significant ventricular enhancement.
- Increased tissue MMP-2 and MMP-9 were associated with BBB disruption at 48 hours post-reperfusion, indicated by a larger volume of parenchymal enhancement.
Conclusions:
- Imaging markers of BCSFB and BBB integrity can serve as indirect indicators of MMP regulation in blood and brain tissue.
- The study provides a methodological framework for understanding the interplay between MMPs, barrier function, and the potential for hemorrhagic transformation after stroke.
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