Blood-brain barrier disruption in humans is independently associated with increased matrix metalloproteinase-9.

Abstract

BACKGROUND AND PURPOSE:

Matrix metalloproteinases (MMP) may play a role in blood-brain barrier (BBB) disruption after ischemic stroke. We hypothesized that plasma concentrations of MMP-9 are associated with a marker of BBB disruption in patients evaluated for acute stroke.

METHODS:

Patients underwent MRI on presentation and approximately 24 hours later. The MRI marker, termed hyperintense acute reperfusion injury marker (HARM), is gadolinium enhancement of cerebrospinal fluid on fluid-attenuated inversion recovery MRI. Plasma MMP-9 and tissue inhibitor of matrix metalloproteinase-1 were measured by enzyme-linked immunosorbent assay. Logistic regression models tested for predictors of HARM on 24-hour follow-up scans separately for MMP-9 and the ratio of MMP-9 to TIMP-1.

RESULTS:

For the 41 patients enrolled, diagnoses were: acute ischemic cerebrovascular syndrome, 33 (80.6%); intracerebral hemorrhage, 6 (14.6%); stroke mimic, 1 (2.4%); and no stroke, 1 (2.4%). HARM was present in 17 (41.5%) patients. In model 1, HARM was associated with baseline plasma MMP-9 concentration (odds ratio [OR], 1.01; 95% confidence interval [CI], 1.001-1.019; P=0.033). In model 2, HARM was associated with the ratio of MMP-9 to tissue inhibitor of matrix metalloproteinase-1 (OR, 4.94; 95% CI, 1.27-19.14; P=0.021).

CONCLUSIONS:

Baseline MMP-9 was a significant predictor of HARM at 24-hour follow-up, supporting the hypothesis that MMP-9 is associated with BBB disruption. If the association between MMP-9 and BBB disruption is confirmed in future studies, HARM may be a useful imaging marker to evaluate MMP-9 inhibition in ischemic stroke and other populations with BBB disruption.

• Authors: Taura L Barr, Lawrence L Latour, Kyung-Yul Lee, Timothy J Schaewe, Marie Luby, George S Chang, Ziad El-Zammar, Shaista Alam, John M Hallenbeck, Chelsea S Kidwell, Steven Warach
• Journal: Stroke (Stroke) Vol. 41 Issue 3 Pg. e123-8 (Mar 2010) ISSN: 1524-4628 [Electronic] United States
• PMID: 20035078 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Matrix Metalloproteinase 9

Topics

• Adult
• Aged
• Aged, 80 and over
• Biomarkers (blood)
• Blood-Brain Barrier (enzymology, pathology)
• Cerebrovascular Disorders (blood, enzymology, physiopathology)
• Enzyme Activation (physiology)
• Female
• Follow-Up Studies
• Humans
• Male
• Matrix Metalloproteinase 9 (blood)
• Middle Aged
• Prospective Studies
• Reperfusion Injury (blood, enzymology, physiopathology)