Adrenomedullin Improves the Blood–Brain Barrier Function Through the Expression of Claudin-5

• DOI: 10.1007/s10571-006-9028-x
• Publication Date: 2006-04-19T19:12:42Z
• Authors: Masaru Honda; Shinsuke Nakagawa; Kentaro Hayashi; Naoki Kitagawa; Keisuke Tsutsumi; Izumi Nagata; Masami Niwa
• Keywords: Male; 0303 health sciences; Endothelial Cells; Membrane Proteins; Permeability; Rats; Adrenomedullin; 03 medical and health sciences; Blood-Brain Barrier; Regional Blood Flow; Cerebrovascular Circulation; Electric Impedance; Animals; Claudin-5; Endothelium, Vascular; Rats, Wistar; Cells, Cultured

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).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.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.AM therefore inhibits the paracellular transport in a BBB in vitro model through claudin-5 overexpression.