Blood-brain barrier disruption in humans is independently associated with increased matrix metalloproteinase-9.
OBJECTIVE
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.
Barr
Taura L
TL
National Institute of Nursing Research, Bethesda, Md, USA. barrt@mail.nih.gov
Latour
Lawrence L
LL
Lee
Kyung-Yul
KY
Schaewe
Timothy J
TJ
Luby
Marie
M
Chang
George S
GS
El-Zammar
Ziad
Z
Alam
Shaista
S
Hallenbeck
John M
JM
Kidwell
Chelsea S
CS
Warach
Steven
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D001812:Blood-Brain Barrier / Q000201:enzymology* / Q000473:pathology*; D002561:Cerebrovascular Disorders / Q000097:blood* / Q000201:enzymology* / Q000503:physiopathology; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D011446:Prospective Studies; D015427:Reperfusion Injury / Q000097:blood / Q000201:enzymology / Q000503:physiopathology
D015415:Biomarkers; D020780:Matrix Metalloproteinase 9