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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 
 STROKE, Vol.41(3) : 123-128, 2010 
Journal Title
Issue Date
Adult ; Aged ; Aged, 80 and over ; Biomarkers/blood ; Blood-Brain Barrier/enzymology* ; Blood-Brain Barrier/pathology* ; Cerebrovascular Disorders/blood* ; Cerebrovascular Disorders/enzymology* ; Cerebrovascular Disorders/physiopathology ; Enzyme Activation/physiology ; Female ; Follow-Up Studies ; Humans ; Male ; Matrix Metalloproteinase 9/blood* ; Middle Aged ; Prospective Studies ; Reperfusion Injury/blood ; Reperfusion Injury/enzymology ; Reperfusion Injury/physiopathology
matrix metalloproteinase-9 ; acute cerebrovascular event ; blood–brain barrier
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.
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1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers
Yonsei Authors
Lee, Kyung Yul(이경열) ORCID logo https://orcid.org/0000-0001-5585-7739
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