Resveratrol improves delayed r-tPA treatment outcome by reducing MMPs

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.