Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-7773
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dc.contributor.authorZehendner, Christoph M.-
dc.contributor.authorLibrizzi, Laura-
dc.contributor.authorHedrich, Jana-
dc.contributor.authorBauer, Nina M.-
dc.contributor.authorAngamo, Eskedar A.-
dc.contributor.authorde Curtis, Marco-
dc.contributor.authorLuhmann, Heiko-
dc.date.accessioned2022-09-15T07:58:39Z-
dc.date.available2022-09-15T07:58:39Z-
dc.date.issued2013
dc.identifier.urihttps://openscience.ub.uni-mainz.de/handle/20.500.12030/7788-
dc.description.abstractRe-canalization of cerebral vessels in ischemic stroke is pivotal to rescue dysfunctional brain areas that are exposed to moderate hypoxia within the penumbra from irreversible cell death. Goal of the present study was to evaluate the effect of moderate hypoxia followed by reoxygenation (MHR) on the evolution of reactive oxygen species (ROS) and blood-brain barrier (BBB) integrity in brain endothelial cells (BEC). BBB integrity was assessed in BEC in vitro and in microvessels of the guinea pig whole brain in situ preparation. Probes were exposed to MHR (2 hours 67-70 mmHg O2, 3 hours reoxygenation, BEC) or towards occlusion of the arteria cerebri media (MCAO) with or without subsequent reperfusion in the whole brain preparation. In vitro BBB integrity was evaluated using trans-endothelial electrical resistance (TEER) and transwell permeability assays. ROS in BEC were evaluated using 2',7'-dichlorodihydrofluorescein diacetate (DCF), MitoSox and immunostaining for nitrotyrosine. Tight-junction protein (TJ) integrity in BEC, stainings for nitrotyrosine and FITC-albumin extravasation in the guinea pig brain preparation were assessed by confocal microscopy. Diphenyleneiodonium (DPI) was used to investigate NADPH oxidase dependent ROS evolution and its effect on BBB parameters in BEC. MHR impaired TJ proteins zonula occludens 1 (ZO-1) and claudin 5 (Cl5), decreased TEER, and significantly increased cytosolic ROS in BEC. These events were blocked by the NADPH oxidase inhibitor DPI. MCAO with or without subsequent reoxygenation resulted in extravasation of FITC-albumin and ROS generation in the penumbra region of the guinea pig brain preparation and confirmed BBB damage. BEC integrity may be impaired through ROS in MHR on the level of TJ and the BBB is also functionally impaired in moderate hypoxic conditions followed by reperfusion in a complex guinea pig brain preparation. These findings suggest that the BBB is susceptible towards MHR and that ROS play a key role in this process.en_GB
dc.description.sponsorshipDFG, Open Access-Publizieren Universität Mainz / Universitätsmedizinde
dc.language.isoengde
dc.rightsCC BY*
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/*
dc.subject.ddc610 Medizinde_DE
dc.subject.ddc610 Medical sciencesen_GB
dc.titleModerate hypoxia followed by reoxygenation results in blood-brain barrier breakdown via oxidative stress-dependent tight-junction protein disruptionen_GB
dc.typeZeitschriftenaufsatzde
dc.identifier.doihttp://doi.org/10.25358/openscience-7773-
jgu.type.dinitypearticleen_GB
jgu.type.versionPublished versionde
jgu.type.resourceTextde
jgu.organisation.departmentFB 04 Medizinde
jgu.organisation.number2700-
jgu.organisation.nameJohannes Gutenberg-Universität Mainz-
jgu.rights.accessrightsopenAccess-
jgu.journal.titlePLoS onede
jgu.journal.volume8de
jgu.journal.issue12de
jgu.pages.alternativee82823de
jgu.publisher.year2013-
jgu.publisher.namePLoSde
jgu.publisher.placeLawrence, Kan.de
jgu.publisher.urihttp://dx.doi.org/10.1371/journal.pone.0082823de
jgu.publisher.issn1932-6203de
jgu.organisation.placeMainz-
jgu.identifier.pmid24324834
jgu.subject.ddccode610de
opus.date.modified2018-08-02T10:00:44Z
opus.subject.dfgcode00-000
opus.organisation.stringFB 04: Medizin: Institut für Physiologie und Pathophysiologiede_DE
opus.identifier.opusid25528
opus.importsourcepubmed
opus.institute.number0403
opus.metadataonlyfalse
opus.type.contenttypeKeinede_DE
opus.type.contenttypeNoneen_EN
opus.affiliatedZehendner, Christoph M.
opus.affiliatedHedrich, Jana
opus.affiliatedLuhmann, Heiko
jgu.publisher.doi10.1371/journal.pone.0082823de
jgu.organisation.rorhttps://ror.org/023b0x485-
Appears in collections:DFG-OA-Publizieren (2012 - 2017)

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