Document Detail


Blood-brain barrier disruption in humans is independently associated with increased matrix metalloproteinase-9.
MedLine Citation:
PMID:  20035078     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-12-24
Journal Detail:
Title:  Stroke; a journal of cerebral circulation     Volume:  41     ISSN:  1524-4628     ISO Abbreviation:  Stroke     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-02-23     Completed Date:  2010-04-05     Revised Date:  2013-05-31    
Medline Journal Info:
Nlm Unique ID:  0235266     Medline TA:  Stroke     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e123-8     Citation Subset:  IM    
Affiliation:
National Institute of Nursing Research, Bethesda, Md, USA. barrt@mail.nih.gov
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
Biological Markers / 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
Grant Support
ID/Acronym/Agency:
Z01 NS003043-01/NS/NINDS NIH HHS; Z01 NS003044-01/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Biological Markers; EC 3.4.24.35/Matrix Metalloproteinase 9
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