title: Radiation-induced blood-brain barrier damages: an in vitro study.
abstract: A radiation-induced blood-brain barrier (BBB) breakdown has been supposed to explain the acute radiation syndrome and the delayed brain radiation injury, but it has been clearly demonstrated only at high doses. In a previous study (Diserbo et al., 2002), we showed that non-lethal total body irradiation produced an early transient increase in BBB permeability in rats but the underlying mechanisms of radiation-induced BBB breakdown remain unclear. In the present work, the effects of ionizing radiation were studied on an in vitro BBB model. Gamma irradiation induced an increase in [(14)C]-sucrose BBB permeability that can be detected 72 h after exposure at doses up to 4 Gy. This increase was more important 8 days after irradiation and could be limited by dexamethasone treatment. An increase in fluorescein and FITC-dextrans (4 kDa/70 kDa) permeability was also observed, which can be related to a substantial opening of endothelial cell tight-junctions but without massive modification of tight-junction protein (ZO-1, ZO-2, claudin-5, occludin) immunolabeling even 8 days after 25 Gy exposure. Formation of actin stress fibers occurred in endothelial cells 8 days after 25 Gy exposure. A progressive decrease in cellular density associated with a simultaneous spreading of the endothelial cells was also observed after irradiation. Anti-γH2AX immunolabeling was used to investigate both DNA double-strand break induction and repair rates in endothelial cells. It revealed long-lasting DNA double-strand breaks after gamma irradiation. A better understanding and awareness of these phenomena are essential for designing appropriate pharmacotherapy in radiation-therapy and treatment of accidental overexposure.
authors.affiliation: Département Effets Biologiques des Rayonnements, IRBA-CRSSA, 24 avenue des maquis du Grésivaudan, F-38700 La Tronche, France. wfmail2005-lab@yahoo.com
authors.forename: William
authors.initials: W
authors.lastname: Fauquette
authors.forename: Christine
authors.initials: C
authors.lastname: Amourette
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Dehouck
authors.forename: Michel
authors.initials: M
authors.lastname: Diserbo
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects*; D002199:Capillary Permeability / Q000502:physiology / Q000528:radiation effects; D002417:Cattle; D002478:Cells, Cultured; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D019108:Tight Junctions / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects