Stromelysin‐1 (MMP‐3) is critical for intracranial bleeding after t‐PA treatment of stroke in mice

摘要: Summary. Background: Tissue-type plasminogen activator (t-PA) is approved for treatment of ischemic stroke patients, but it may increase the risk intracranial bleeding (ICB). Matrix metalloproteinases (MMPs), which can be activated through plasminogen/plasmin system, contribute to ICB after stroke. Objectives: To explore contribution plasminogen, MMP-3 and MMP-9 associated with t-PA Methods: Using a thrombotic middle cerebral artery occlusion (MCA-O) model, was studied in mice genetic deficiencies (Plg−/−), stromelysin-1 (MMP-3−/−), or gelatinase B (MMP-9−/−) their corresponding wild-type (WT) littermates. The induction also C57BL/6 WT mice. Results: ICB induced by (10 mg kg−1) significantly less than Plg−/− (P < 0.05) MMP-3−/− not MMP-9−/− Furthermore, administration broad-spectrum MMP inhibitor GM6001 reduced MMP-3+/+ mice, had no effect on expression enhanced at hemisphere; placebo treatment, expressed only neurons, whereas up-regulated endothelial cells treatment. Although brain, amount distribution were comparable without Conclusions: Our data gene-deficient thus suggest that are relatively more important increased