Resveratrol improves delayed r-tPA treatment outcome by reducing MMPs

• Published in: Acta neurologica Scandinavica Vol. 134; no. 1; pp. 54 - 60
• Main Authors: Chen, J., Bai, Q., Zhao, Z., Sui, H., Xie, X.
• Format: Journal Article
• Language: English
• Published: Denmark Blackwell Publishing Ltd 01-07-2016; Hindawi Limited
• Subjects: Aged; Antioxidants - administration & dosage; Clinical outcomes; Female; Fibrinolytic Agents - administration & dosage; Humans; Male; Matrix Metalloproteinase 2 - blood; Matrix Metalloproteinase 9 - blood; Middle Aged; recombinant tissue plasminogen activator; resveratrol; Stilbenes - administration & dosage; Stroke; Stroke - blood; Stroke - drug therapy; thrombolysis; Time Factors; Tissue Plasminogen Activator - administration & dosage; Treatment Outcome; recombinant tissue plasminogen activator; thrombolysis; resveratrol; stroke
• ISSN: 0001-6314; 1600-0404
• DOI: 10.1111/ane.12511

Objectives
Although recombinant tissue plasminogen activator (r‐tPA) is currently the most effective treatment for brain ischemic stroke, the 3‐h narrow therapeutic windows severely limits its clinical efficacy. We aim to investigate the effect of resveratrol on improving treatment outcomes of delayed r‐tPA administration.
Materials & methods
Patients were randomly divided according to their onset‐to‐treatment time (OTT), as early OTT or delayed OTT. Then, they were either treated with r‐tPA + placebo or with r‐tPA + resveratrol. Twenty‐four hours after the treatment, outcomes were assessed with NIH stroke scale (NIHSS), and plasma levels of MMP‐2 and MMP‐9 were also examined with ELISA.
Results
In patients receiving delayed r‐tPA treatment, co‐administration of resveratrol significantly improves their treatment outcomes compared with those receiving placebo, as indicated by improved NIHSS scores. This improved outcome was be caused by resveratrol‐induced reduction in plasma levels of both matrix metalloproteinase (MMP)‐2 and MMP‐9, as a positive correlation was observed between reductions in both MMPs and patient NIHSS scores.
Conclusions
Resveratrol could be potentially administered as an adjuvant with r‐tPA treatment, which extends the clinical therapeutic window of r‐tPA, therefore improving the outcome of patients receiving late stroke treatment.