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

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

Research output: Contribution to journalArticlepeer-review

134 Scopus citations

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 ∼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:s: 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.

Original languageEnglish (US)
Pages (from-to)e123-e128
JournalStroke
Volume41
Issue number3
DOIs
StatePublished - Mar 2010

Keywords

  • Acute cerebrovascular event
  • Blood-brain barrier
  • Matrix metalloproteinase-9

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing

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