title: Alteration in P-glycoprotein at the blood-brain barrier in the early period of MCAO in rats.
abstract: OBJECTIVE
  The aim of this work was to investigate the alteration in P-glycoprotein (P-gp) at the blood-brain barrier (BBB) after middle cerebral artery occlusion (MCAO) in rats.
  
  
  METHODS
  Permanent MCAO was verified via 2,3,5-triphenyltetrazolium staining and hematoxylin-eosin staining. The expression of P-gp, matrix metalloproteinase-2 (MMP-2), MMP-9, claudin-5, tumour necrosis factor-α (TNF-α) and nitric oxide synthase (NOS) at the BBB was evaluated using western blot or immunostaining analysis. The content of fluorescein sodium (NaF), rhodamine-123 and nimodipine in ischaemic brain tissues was determined using high-performance liquid chromatography.
  
  
  RESULTS
  Elevated expression of P-gp at the BBB and decreased concentration of P-gp substrates in the ischaemic brain tissues were observed within 4 h after MCAO. However, at 6 h after MCAO, the concentration of P-gp substrates in the ischaemic hemisphere began to rise even though the expression of P-gp was still increased. Moreover, the expression of claudin-5 was decreased; contrarily, the expression of MMP-2, MMP-9, TNF-α as well as NOS gradually increased within 6 h after MCAO.
  
  
  CONCLUSIONS
  P-gp plays a crucial role in limiting the entrance of agents into the brain after MCAO and the specific regulation of P-gp expression/activity may provide an important approach for the improvement of pharmacotherapy in ischaemic stroke.
authors.affiliation: Key Laboratory of Natural Medicine and Immune Engineering, Henan University, Kaifeng, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Cen
authors.forename: Lu
authors.initials: L
authors.lastname: Liu
authors.forename: Ming-Shan
authors.initials: MS
authors.lastname: Li
authors.forename: Ling
authors.initials: L
authors.lastname: He
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Wang
authors.forename: Yan-Qing
authors.initials: YQ
authors.lastname: Liu
authors.forename: Meng
authors.initials: M
authors.lastname: Liu
authors.forename: Bian-Sheng
authors.initials: BS
authors.lastname: Ji
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002545:Brain Ischemia / Q000378:metabolism*; D062507:Claudin-5 / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D062507:Claudin-5; D014409:Tumor Necrosis Factor-alpha; D019001:Nitric Oxide Synthase; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9