title: Adrenomedullin improves the blood-brain barrier function through the expression of claudin-5.
abstract: OBJECTIVE
  Brain vascular endothelial cells secret Adrenomedullin (AM) has multifunctional biological properties. AM affects cerebral blood flow and blood-brain barrier (BBB) function. We studied the role of AM on the permeability and tight junction proteins of brain microvascular endothelial cells (BMEC).
  
  
  METHODS
  BMEC were isolated from rats and a BBB in vitro model was generated. The barrier functions were studied by measuring the transendothelial electrical resistance (TEER) and the permeability of sodium fluorescein and Evans' blue albumin. The expressions of tight junction proteins were analyzed using immunocytochemistry and immunoblotting.
  
  
  RESULTS
  AM increased TEER of BMEC monolayer dose-dependently. Immunocytochemistry revealed that AM enhanced the claudin-5 expression at a cell-cell contact site in a dose-dependent manner. Immunoblotting also showed an overexpression of claudin-5 in AM exposure.
  
  
  CONCLUSIONS
  AM therefore inhibits the paracellular transport in a BBB in vitro model through claudin-5 overexpression.
authors.affiliation: Department of Neurosurgery, Nagasaki University School of Medicine, Nagasaki, Japan. mahonda-nsu@umin.ac.jp
authors.forename: Masaru
authors.initials: M
authors.lastname: Honda
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Nakagawa
authors.forename: Kentaro
authors.initials: K
authors.lastname: Hayashi
authors.forename: Naoki
authors.initials: N
authors.lastname: Kitagawa
authors.forename: Keisuke
authors.initials: K
authors.lastname: Tsutsumi
authors.forename: Izumi
authors.initials: I
authors.lastname: Nagata
authors.forename: Masami
authors.initials: M
authors.lastname: Niwa
mesh_terms: D053607:Adrenomedullin / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D001812:Blood-Brain Barrier / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D002560:Cerebrovascular Circulation; D062507:Claudin-5; D017097:Electric Impedance; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow
chemical_list: D062507:Claudin-5; C491510:Cldn5 protein, rat; D008565:Membrane Proteins; D053607:Adrenomedullin