title: Resveratrol improves delayed r-tPA treatment outcome by reducing MMPs.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Neurology, Pudong People's Hospital, Shanghai, China.
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Neurology, Pudong People's Hospital, Shanghai, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Bai
authors.affiliation: Department of Radiology, Pudong People's Hospital, Shanghai, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Radiology, Pudong People's Hospital, Shanghai, China.
authors.forename: H
authors.initials: H
authors.lastname: Sui
authors.affiliation: Department of Radiology, Pudong People's Hospital, Shanghai, China.
authors.forename: X
authors.initials: X
authors.lastname: Xie
mesh_terms: D000368:Aged; D000975:Antioxidants / Q000008:administration & dosage*; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage*; D020521:Stroke / Q000097:blood / Q000188:drug therapy*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000975:Antioxidants; D005343:Fibrinolytic Agents; D013267:Stilbenes; D010959:Tissue Plasminogen Activator; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D000077185:Resveratrol
keywords: recombinant tissue plasminogen activator; resveratrol; stroke; thrombolysis