Matrix metalloproteinase-9 in an exploratory trial of intravenous minocycline for acute ischemic stroke

Abstract

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.

Figures

Figure 1

Levels of MMP-9 over time in MINOS. (A) MMP-9 levels in tPA-treated and tPA-untreated subjects at each timepoint in MINOS.Box = 25 to 75% interquartile range; horizontal line = median; vertical lines = range. *p < 0.0083. (B) A representative zymogram from a MINOS patient showing MMP-9 over time.

Figure 2

Levels of MMP-9 in MINOS and comparison subjects at 24 hours. MMP-9 in tPA-treated and tPA-untreated MINOS and comparison subjects at 24 hours. Box = 25 to 75% interquartile range; horizontal line = median; vertical lines = range. *p < 0.0125.