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Matrix metalloproteinase expression is related to hemorrhagic transformation after cardioembolic stroke
J Montaner1, J Alvarez-Sabín, C A Molina
1Cerebrovascular Unit, Vall d'Hebron Hospital, Barcelona, Spain. alsa@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.
Insights
Matrix metalloproteinases (MMPs) are linked to hemorrhagic transformation (HT) after stroke. Elevated baseline MMP-9 predicts late hemorrhagic infarction, while a 24-hour MMP-9 peak precedes parenchymal hematoma in cardioembolic stroke patients.
Area of Science:
- Neuroscience
- Biochemistry
- Medical Research
Background:
- Matrix metalloproteinase (MMP) expression increases in animal models of cerebral ischemia, correlating with blood-brain barrier disruption and edema.
- MMP inhibitors have shown potential in reducing hemorrhagic transformation (HT) in animal studies.
- Previous research suggests a link between MMPs and HT, but the relationship in human ischemic stroke requires further investigation.
Purpose of the Study:
- To investigate the association between matrix metalloproteinases (MMPs) and hemorrhagic transformation (HT) in patients who have experienced a human ischemic stroke.
- To determine if specific MMPs, namely MMP-2 and MMP-9, are related to the occurrence and subtypes of HT.
- To identify potential predictive markers for HT based on MMP levels.
Main Methods:
- Serial measurements of MMP-2 and MMP-9 were conducted using ELISA in 39 patients with cardioembolic strokes.
- Hemorrhagic events were classified as hemorrhagic infarction (HI) or parenchymal hematoma (PH) based on clinical and CT scan criteria.
- HT was assessed at 48 hours (early HT) and between days 5–7 (late HT) via CT scans.
Main Results:
- Hemorrhagic transformation (HT) was observed in 41% of patients, with varying frequencies of early HI, early PH, and late HI.
- MMP-2 levels were within the normal range and showed no correlation with HT.
- Elevated baseline MMP-9 levels were found in patients with HT, particularly those with late HI. A 24-hour MMP-9 peak preceded the appearance of PH.
Conclusions:
- Matrix metalloproteinases (MMPs) play a role in specific subtypes of hemorrhagic transformation (HT) following human cardioembolic stroke.
- Baseline MMP-9 levels can predict the occurrence of late hemorrhagic infarction (HI).
- A peak in MMP-9 levels at 24 hours post-stroke may precede the development of early parenchymal hematoma (PH).