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 journalArticle

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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)
JournalStroke
Volume41
Issue number3
DOIs
StatePublished - Mar 2010

Fingerprint

Matrix Metalloproteinase 9
Blood-Brain Barrier
Reperfusion Injury
Stroke
Tissue Inhibitor of Metalloproteinase-1
Matrix Metalloproteinase 1
Logistic Models
Odds Ratio
Confidence Intervals
Matrix Metalloproteinase Inhibitors
Cerebral Hemorrhage
Gadolinium
Matrix Metalloproteinases
Cerebrospinal Fluid
Enzyme-Linked Immunosorbent Assay

Keywords

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

ASJC Scopus subject areas

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

Cite this

Barr, T. L., Latour, L. L., Lee, K. Y., Schaewe, T. J., Luby, M., Chang, G. S., ... Warach, S. (2010). Blood-brain barrier disruption in humans is independently associated with increased matrix metalloproteinase-9. Stroke, 41(3). https://doi.org/10.1161/STROKEAHA.109.570515

Blood-brain barrier disruption in humans is independently associated with increased matrix metalloproteinase-9. / Barr, Taura L.; Latour, Lawrence L.; Lee, Kyung Yul; Schaewe, Timothy J.; Luby, Marie; Chang, George S.; El-Zammar, Ziad; Alam, Shaista; Hallenbeck, John M.; Kidwell, Chelsea S.; Warach, Steven.

In: Stroke, Vol. 41, No. 3, 03.2010.

Research output: Contribution to journalArticle

Barr, TL, Latour, LL, Lee, KY, Schaewe, TJ, Luby, M, Chang, GS, El-Zammar, Z, Alam, S, Hallenbeck, JM, Kidwell, CS & Warach, S 2010, 'Blood-brain barrier disruption in humans is independently associated with increased matrix metalloproteinase-9', Stroke, vol. 41, no. 3. https://doi.org/10.1161/STROKEAHA.109.570515
Barr, Taura L. ; Latour, Lawrence L. ; Lee, Kyung Yul ; Schaewe, Timothy J. ; Luby, Marie ; Chang, George S. ; El-Zammar, Ziad ; Alam, Shaista ; Hallenbeck, John M. ; Kidwell, Chelsea S. ; Warach, Steven. / Blood-brain barrier disruption in humans is independently associated with increased matrix metalloproteinase-9. In: Stroke. 2010 ; Vol. 41, No. 3.
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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.",
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AU - Luby, Marie

AU - Chang, George S.

AU - El-Zammar, Ziad

AU - Alam, Shaista

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