title: Epigallocatechin Gallate Extends the Therapeutic Window of Recombinant Tissue Plasminogen Activator Treatment in Ischemic Rats.
abstract: BACKGROUND
  Ischemic stroke is the leading cause of death and disability worldwide. To date, recombinant tissue plasminogen activator (rt-PA) remains the only safe and effective pharmaceutical treatment for brain ischemia, but delayed rt-PA administration leads to hyperperfusion, which severely limits its clinical efficacy.
  
  
  METHODS
  In this study, we investigated the effect of epigallocatechin gallate (EGCG) in extending the therapeutic window of rt-PA using a rat middle cerebral artery occlusion (MCAO) model.
  
  
  RESULTS
  Simultaneous treatment of EGCG and rt-PA significantly recovered the neurobehavioral deficit, when administered even 4 hours after MCAO. Pathological examinations on the ischemic brain samples revealed that EGCG significantly alleviated the common side effects of delayed rt-PA treatment, including brain infarction, cerebral edema, and blood-brain barrier disruption. We further found that EGCG exerted its protective functions against delayed rt-PA through upregulation of plasminogen activator inhibitor-1, as well as downregulation of matrix metalloproteinases.
  
  
  CONCLUSIONS
  Our study has demonstrated for the first time in vivo results supporting the potential of EGCG to be coadministered with rt-PA, to extend its therapeutic window in treating acute brain ischemia.
authors: Department of Neurology, Wuxi People's Hospital, Wuxi, China. Electronic address: ypyou2@163.com.
authors: Yi-Ping
authors: YP
authors: You
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000503:physiopathology; D001929:Brain Edema / Q000188:drug therapy / Q000209:etiology; D002392:Catechin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D005786:Gene Expression Regulation / Q000187:drug effects; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010539:Permeability / Q000187:drug effects; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D055139:Sensory Gating / Q000187:drug effects; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D005343:Fibrinolytic Agents; D018696:Neuroprotective Agents; D017395:Plasminogen Activator Inhibitor 1; D002392:Catechin; C045651:epigallocatechin gallate; D010959:Tissue Plasminogen Activator; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1
keywords: Epigallocatechin gallate (EGCG); middle cerebral artery occlusion; recombinant tissue plasminogen activator (rt-PA); thrombolysis