title: Candesartan improves ischemia-induced impairment of the blood-brain barrier in vitro.
abstract: Candesartan has been reported to have a protective effect on cerebral ischemia in vivo and in human ischemic stroke. We studied the direct effects of candesartan on blood-brain barrier (BBB) function with our in vitro monolayer model generated using rat brain capillary endothelial cells (RBECs). The in vitro BBB model was subjected to normoxia or 6-h oxygen glucose deprivation (OGD)/24-h reoxygenation, with or without candesartan. 6-h OGD/24-h reoxygenation decreased transendothelial electrical resistance and increased the endothelial permeability for sodium fluorescein in RBEC monolayers. Candesartan (10 nM) improved RBEC barrier dysfunction induced by 6-h OGD/24-h reoxygenation. Immunostaining and immunoblotting analysis indicated that the effect of candesartan on barrier function under 6-h OGD/24-h reoxygenation was not related to the expression levels of tight junction proteins. However, candesartan affected RBEC morphological changes induced by 6-h OGD/24-h reoxygenation. We analyzed oxidative stress and cell viability using chemical reagents. Candesartan improved cell viability following 6-h OGD/24-h reoxygenation, whereas candesartan had no effect on oxidative stress. These results show that candesartan directly improves cell function and viability of brain capillary endothelial cells under OGD/reoxygenation, suggesting that the protective effects of candesartan on ischemic stroke are related to protection of the BBB.
authors.affiliation: Department of Neurosurgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
authors.forename: Gohei
authors.initials: G
authors.lastname: So
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Nakagawa
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Morofuji
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hiu
authors.forename: Kentaro
authors.initials: K
authors.lastname: Hayashi
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Tanaka
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Suyama
authors.forename: Maria A
authors.initials: MA
authors.lastname: Deli
authors.forename: Izumi
authors.initials: I
authors.lastname: Nagata
authors.forename: Takayuki
authors.initials: T
authors.lastname: Matsuo
authors.forename: Masami
authors.initials: M
authors.lastname: Niwa
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000473:pathology*; D002545:Brain Ischemia / Q000473:pathology*; D002470:Cell Survival / Q000187:drug effects; D017097:Electric Impedance; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology*; D062725:Tight Junction Proteins / Q000378:metabolism; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism
chemical_list: D001562:Benzimidazoles; D001713:Biphenyl Compounds; D009566:Nitrates; D009573:Nitrites; D017382:Reactive Oxygen Species; D013777:Tetrazoles; D062725:Tight Junction Proteins; C081643:candesartan