title: Green tea polyphenols alleviate early BBB damage during experimental focal cerebral ischemia through regulating tight junctions and PKCalpha signaling.
abstract: BACKGROUND
  It has been supposed that green tea polyphenols (GTPs) have neuroprotective effects on brain damage after brain ischemia in animal experiments. Little is known regarding GTPs' protective effects against the blood-brain barrier (BBB) disruption after ischemic stroke. We investigated the effects of GTPs on the expression of claudin-5, occludin, and ZO-1, and the corresponding cellular mechanisms involved in the early stage of cerebral ischemia.
  
  
  METHODS
  Male Wistar rats were subjected to a middle cerebral artery occlusion (MCAO) for 0, 30, 60, and 120 min. GTPs (400 mg/kg/day) or vehicle was administered by intragastric gavage twice a day for 30 days prior to MCAO. At different time points, the expression of claudin-5, occludin, ZO-1, and PKCα signaling pathway in microvessel fragments of cerebral ischemic tissue were evaluated.
  
  
  RESULTS
  GTPs reduced BBB permeability at 60 min and 120 min after ischemia as compared with the vehicle group. Transmission electron microscopy also revealed that GTPs could reverse the opening of tight junction (TJ) barrier at 60 min and 120 min after MACO. The decreased mRNA and protein expression levels of claudin-5, occludin, and ZO-1 in microvessel fragments of cerebral ischemic tissue were significantly prevented by treatment with GTPs at the same time points after ischemia in rats. Furthermore, GTPs could attenuate the increase in the expression levels of PKCα mRNA and protein caused by cerebral ischemia.
  
  
  CONCLUSIONS
  These results demonstrate that GTPs may act as a potential neuroprotective agent against BBB damage at the early stage of focal cerebral ischemia through the regulation of TJ and PKCα signaling.
authors.forename: Xiaobai
authors.initials: X
authors.lastname: Liu
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Wang
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Bo
authors.initials: B
authors.lastname: Yu
authors.forename: Yunhui
authors.initials: Y
authors.lastname: Liu
authors.forename: Yixue
authors.initials: Y
authors.lastname: Xue
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D028241:Camellia sinensis / Q000737:chemistry*; D062507:Claudin-5 / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D062793:Occludin / Q000378:metabolism; D010539:Permeability; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D059808:Polyphenols / Q000494:pharmacology / Q000627:therapeutic use*; D051571:Protein Kinase C-alpha / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D020521:Stroke / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D019108:Tight Junctions / Q000187:drug effects*
chemical_list: D062507:Claudin-5; D018696:Neuroprotective Agents; D062793:Occludin; D010936:Plant Extracts; D059808:Polyphenols; D012333:RNA, Messenger; D051571:Protein Kinase C-alpha