Resveratrol improves delayed r-tPA treatment outcome by reducing MMPs

Acta Neurol Scand. 2016 Jul;134(1):54-60. doi: 10.1111/ane.12511. Epub 2015 Oct 12.

Abstract

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.

Keywords: recombinant tissue plasminogen activator; resveratrol; stroke; thrombolysis.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Antioxidants / administration & dosage*
  • Female
  • Fibrinolytic Agents / administration & dosage*
  • Humans
  • Male
  • Matrix Metalloproteinase 2 / blood
  • Matrix Metalloproteinase 9 / blood
  • Middle Aged
  • Resveratrol
  • Stilbenes / administration & dosage*
  • Stroke / blood
  • Stroke / drug therapy*
  • Time Factors
  • Tissue Plasminogen Activator / administration & dosage*
  • Treatment Outcome

Substances

  • Antioxidants
  • Fibrinolytic Agents
  • Stilbenes
  • Tissue Plasminogen Activator
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • MMP9 protein, human
  • Matrix Metalloproteinase 9
  • Resveratrol