Matrix metalloproteinase expression is related to hemorrhagic transformation after cardioembolic stroke

Background and Purpose-In animal models of cerebral ischemia, matrix metall oproteinase (MMP) expression was significantly increased and related to blo od-brain barrier disruption, edema formation, and hemorrhagic transformatio n HT). MMP inhibitors reduce HT after embolic ischemia in tissue-type plasm inogen activator-treated animals. We aimed to determine the relationship be tween MMPs and HT after human ischemic stroke. Methods-Serial MMP-2 and MMP-9 determinations were performed by means of EL ISA in 39 cardioembolic strokes in the middle cerebral artery territory. He morrhagic events were classified according to clinical and CT criteria (hem orrhagic infarction [HI] and parenchymal hematoma [PH]). HT was evaluated o n 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 unr elated to HT. Increased expression of MMP-9 (normal range < 97 ng/mL) was f ound 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 lev els 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 cardioembo lic stroke. Baseline MMP-9 level predicts late HI and a 24-hour peak preced es early PH.