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Stroke. 2001;32:2762-2767
doi: 10.1161/hs1201.99512
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(Stroke. 2001;32:2762.)
© 2001 American Heart Association, Inc.


Original Contributions

Matrix Metalloproteinase Expression Is Related to Hemorrhagic Transformation After Cardioembolic Stroke

J. Montaner, MD; J. Alvarez-Sabín, MD; C.A. Molina, MD; A. Anglés, MD; S. Abilleira, MD; J. Arenillas, MD J. Monasterio, MD

From the Cerebrovascular Unit (J. Montaner, J.A.-S., C.A.M., S.A., J.A.) and Hemostasia Research Unit (A.A., J. Monasterio), Vall d’Hebron Hospital, Barcelona, Spain.

Correspondence to Dr Joan Montaner, Unidad Cerebrovascular, Servicio de Neurología (6a planta, Hospital General), Hospital Vall d’Hebron, Pg Vall d’Hebron 119-129, 08035 Barcelona, Spain. E-mail alsa{at}hg.vhebron.es

Background and Purpose In animal models of cerebral ischemia, matrix metalloproteinase (MMP) expression was significantly increased and related to blood-brain barrier disruption, edema formation, and hemorrhagic transformation (HT). MMP inhibitors reduce HT after embolic ischemia in tissue-type plasminogen activator-treated animals. We aimed to determine the relationship between MMPs and HT after human ischemic stroke.

Methods Serial MMP-2 and MMP-9 determinations were performed by means of ELISA in 39 cardioembolic strokes in the middle cerebral artery territory. Hemorrhagic events were classified according to clinical and CT criteria (hemorrhagic infarction [HI] and parenchymal hematoma [PH]). HT was evaluated on CT at 48 hours (early HT) and again between day 5 and 7 (late HT).

Results HT was present in 41% of the patients (43.75% early HI, 25% early PH and 31.25% late HI). MMP-2 values were within normal range and were unrelated to HT. Increased expression of MMP-9 (normal range <97 ng/mL) was found among patients with and without HT (159.3±82 versus 143.9±112.6 ng/mL; P=0.64). According to HT subtypes, the highest baseline MMP-9 levels corresponded to patients with late HI (240.4±111.2 versus 102.5±76.7 ng/mL for all other patients, P=0.002). Baseline MMP-9 was the only variable associated with late HI in the multiple logistic regression model (OR 9; CI 1.46, 55.24; P=0.010). Peak of MMP-9 at the 24-hour time point (250.6 ng/mL) was found before appearance of PH.

Conclusions MMPs are involved in some subtypes of HT after human cardioembolic stroke. Baseline MMP-9 level predicts late HI and a 24-hour peak precedes early PH.


Key Words: cerebral ischemia • embolism, cerebral • hematoma, parenchymal • hemorrhagic stroke • matrix metalloproteinase




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