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Matrix metalloproteinase-9 in an exploratory trial of intravenous minocycline for acute ischemic stroke
Jeffrey A Switzer1, David C Hess, Adviye Ergul
1Department of Neurology, Medical College of Georgia, 1122 15th Street, Augusta, GA 30912, USA. jswitzer@georgiahealth.edu
Background And Purpose:
Plasma matrix metalloproteinase-9 levels predict posttissue plasminogen activator (tPA) hemorrhage.
Methods:
The authors investigated the effect of minocycline on plasma matrix metalloproteinase-9 in acute ischemic stroke in the Minocycline to Improve Neurological Outcome in Stroke (MINOS) trial and a comparison group.
Results:
Matrix metalloproteinase-9 level decreased at 72 hours compared with baseline in MINOS (tPA, P=0.0022; non-tPA, P=0.0066) and was lower than in the non-MINOS comparison group at 24 hours (tPA, P<0.0001; non-tPA, P=0.0019).
Conclusions:
Lower plasma matrix metalloproteinase-9 was seen among tPA-treated subjects in the MINOS trial. Combining minocycline with tPA may prevent the adverse consequences of thrombolytic therapy through suppression of matrix metalloproteinase-9 activity.
Insights
Minocycline reduced matrix metalloproteinase-9 (MMP-9) levels in acute ischemic stroke patients treated with tissue plasminogen activator (tPA). This suggests minocycline may prevent hemorrhage associated with tPA therapy.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Plasma matrix metalloproteinase-9 (MMP-9) levels are known predictors of post-tissue plasminogen activator (tPA) hemorrhage.
- Matrix metalloproteinase-9 plays a role in the breakdown of the extracellular matrix, potentially contributing to hemorrhagic transformation after stroke treatment.
Purpose of the Study:
- To investigate the effect of minocycline on plasma MMP-9 levels in patients with acute ischemic stroke.
- To determine if minocycline influences MMP-9 levels in the context of tPA treatment.
Main Methods:
- The study involved the Minocycline to Improve Neurological Outcome in Stroke (MINOS) trial and a comparison group.
- Plasma MMP-9 levels were measured at baseline and at 72 hours in MINOS participants (tPA and non-tPA treated).
- MMP-9 levels were compared between the MINOS trial and a non-MINOS comparison group at 24 hours.
Main Results:
- Matrix metalloproteinase-9 levels significantly decreased at 72 hours compared to baseline in both tPA (P=0.0022) and non-tPA (P=0.0066) treated patients within the MINOS trial.
- At 24 hours, MMP-9 levels were significantly lower in the MINOS group compared to the non-MINOS comparison group, both for tPA (P<0.0001) and non-tPA (P=0.0019) treated patients.
- A notable reduction in plasma MMP-9 was observed in tPA-treated subjects within the MINOS trial.
Conclusions:
- Lower plasma MMP-9 levels were observed in tPA-treated subjects participating in the MINOS trial.
- Combining minocycline with tPA may offer a protective effect against adverse consequences of thrombolytic therapy by suppressing MMP-9 activity.
- Minocycline shows potential as an adjunctive therapy to reduce the risk of hemorrhage following tPA treatment in acute ischemic stroke.
