Matrix metalloproteinase expression is related to hemorrhagic transformation after cardioembolic stroke.
OBJECTIVE
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.
Montaner
J
J
Cerebrovascular Unit, Vall d'Hebron Hospital, Barcelona, Spain. alsa@hg.vhebron.es
Alvarez-Sabín
J
J
Molina
C A
CA
Anglés
A
A
Abilleira
S
S
Arenillas
J
J
Monasterio
J
J
D000368:Aged; D000369:Aged, 80 and over; D002543:Cerebral Hemorrhage / Q000097:blood / Q000150:complications / Q000201:enzymology*; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D020766:Intracranial Embolism / Q000097:blood / Q000150:complications / Q000201:enzymology*; D016015:Logistic Models; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood*; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012016:Reference Values; D018570:Risk Assessment; D012720:Severity of Illness Index; D020521:Stroke / Q000097:blood / Q000150:complications / Q000201:enzymology*; D014057:Tomography, X-Ray Computed; D017585:Ultrasonography, Doppler, Transcranial
D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9