title: Effects of hyperbaric oxygen on the expression of claudins after cerebral ischemia-reperfusion in rats.
abstract: The malfunction of tight junctions (TJs) between endothelial cells in the blood brain barrier (BBB) is the pathophysiological basis for cerebral ischemia-reperfusion (IR) injury. Claudins, major molecular elements of the TJs, play a key role in the paracellular permeability of the BBB. Although several studies have demonstrated the impact of hyperbaric oxygenation (HBO) on boosting oxygen supply and reducing infarct size, its effect and underlying mechanism on the integrity of the BBB is unknown. To study the function of HBO on claudins and the permeability of the BBB, we replicated the animal model of local cerebral IR. Using Evans blue dye, permeability of the BBB was examined. Transmission electron microscopy (TEM), immunohistochemistry, western blot, and gelatin zymography were used to detect the integrity of the BBB, the expression of claudin-1 and claudin-5, and the activity of matrix metalloproteinases (MMPs) in brain microvessel endothelium. Our data indicate that compared with the sham-operated group, IR increased permeability of the BBB to Evans blue dye (P < 0.01), peaking at 4 h. The BBB ultrastructure was disrupted and the expression of claudin-5 and claudin-1 decreased (P < 0.01) in the 4 and 72 h IR group, respectively. Increased claudin-5 and claudin-1 expression and decreased permeability of the BBB were observed in the HBO + IR group (P < 0.01) via the suppression of MMP-2 and MMP-9, respectively. Our study provides direct evidence that HBO decreases the permeability of the BBB by reducing the enzymatic activity of MMPs and augmenting the expression of claudins at different stages in cerebral IR injury.
authors.affiliation: Department of Experimental Center of Functional Subjects, College of Basic Medicine, China Medical University, Shenyang 110001, China. zhaohong1966@hotmail.com
authors.forename: Hong
authors.initials: H
authors.lastname: Zhao
authors.forename: Qianru
authors.initials: Q
authors.lastname: Zhang
authors.forename: Yixue
authors.initials: Y
authors.lastname: Xue
authors.forename: Xuexin
authors.initials: X
authors.lastname: Chen
authors.forename: Randy S
authors.initials: RS
authors.lastname: Haun
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D002545:Brain Ischemia / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D062445:Claudin-1; D062507:Claudin-5; D057167:Claudins / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation; D006931:Hyperbaric Oxygenation / Q000379:methods; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D019108:Tight Junctions / Q000235:genetics / Q000378:metabolism
chemical_list: D062445:Claudin-1; D062507:Claudin-5; D057167:Claudins; C568114:Cldn1 protein, rat; C491510:Cldn5 protein, rat; D008565:Membrane Proteins