title: The effects of hyperbaric air and hyperbaric oxygen on blood-brain barrier integrity in rats.
abstract: Hyperbaric oxygen (HBO) treatment yields conflicting results on blood-brain barrier (BBB) integrity under various pathological conditions and the effects of HBO on healthy brain is poorly understood. In this experimental study, the effects of HBO on BBB integrity were investigated in comparison with hyperbaric air (HBA) in intact rats. Four sessions of HBA or HBO were applied to intact rats in 24h. BBB integrity was functionally and structurally evaluated by determining extravasation of Evans blue (EB) dye and horseradish peroxidase (HRP) tracers. In immunohistochemical evaluation, relative staining intensity for occludin, a tight junction (TJ) protein, and aquaporin 4 (AQP4), a water-channel protein, was detected in the barrier type of microvessels of brain by image analysis. BBB permeability to EB dye significantly increased in animals in HBO treatment group compared to those in HBA and control groups (p<0.05). The immunoreactivity of occludin, a tight junction protein, remained essentially unaltered in capillaries of hippocampus in all groups. In animals exposed to HBO, AQP4 immunoreactivity significantly increased in parietal cortex compared to those in HBA and control groups (p<0.01). Ultrastructurally, frequent vesicles containing HRP reaction products were observed in capillary endothelial cells in cerebral cortex and hippocampus of rats subjected to both HBA and HBO. Our results indicate that the HBO administration to intact rats increased BBB permeability to both EB and HRP while HBA increased only HRP extravasation in these animals. The results of this study suggest that HBA also impairs the BBB integrity in intact rats as well as HBO.
authors.affiliation: Department of Underwater and Hyperbaric Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Nihal Gunes
authors.initials: NG
authors.lastname: Cevik
authors.forename: Nurcan
authors.initials: N
authors.lastname: Orhan
authors.forename: Canan Ugur
authors.initials: CU
authors.lastname: Yilmaz
authors.forename: Nadir
authors.initials: N
authors.lastname: Arican
authors.forename: Bulent
authors.initials: B
authors.lastname: Ahishali
authors.forename: Mutlu
authors.initials: M
authors.lastname: Kucuk
authors.forename: Mehmet
authors.initials: M
authors.lastname: Kaya
authors.forename: Akin Savas
authors.initials: AS
authors.lastname: Toklu
mesh_terms: D000388:Air; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000648:ultrastructure*; D001921:Brain / Q000378:metabolism / Q000648:ultrastructure*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000648:ultrastructure*; D005260:Female; D006931:Hyperbaric Oxygenation / Q000379:methods*; D051381:Rats; D017208:Rats, Wistar
keywords: Aquaporin 4; Blood–brain barrier; Evans blue; Horseradish peroxidase; Hyperbaric air; Hyperbaric oxygen; Occludin