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0-26.741-21.543-14.142-34.142l128.662-128.662c7.81-7.81 20.474-7.81 28.284 0l128.662 128.662c12.6 12.599 3.676 34.142-14.142 34.142z"></path></svg></button></li></ul></li></ul></div> <script src="//a.academia-assets.com/assets/webpack_bundles/fast_loswp-bundle-d651820c1939e5287fa830883d89f986bbe9f35a9f42a5371043c36c78a32b4f.js" defer="defer"></script><script>window.loswp = {}; window.loswp.author = 32943665; window.loswp.bulkDownloadFilterCounts = {}; window.loswp.hasDownloadableAttachment = true; window.loswp.hasViewableAttachments = true; // TODO: just use routes for this window.loswp.loginUrl = "https://www.academia.edu/login?post_login_redirect_url=https%3A%2F%2Fwww.academia.edu%2F13849329%2FAdverse_Effect_of_Cyclosporin_A_on_Barrier_Functions_of_Cerebral_Microvascular_Endothelial_Cells_After_Hypoxia_reoxygenation_Damage_In_Vitro%3Fauto%3Ddownload"; window.loswp.translateUrl = 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Alterations of the BBB function after hypoxia/reoxygenation (H/R) injury remain unclear. Cyclosporin A (CsA), a potent immunosuppressant, induces neurotoxic effects by entering the brain, although the transport of CsA across the BBB is restricted by Pglycoprotein (P-gp), a multidrug efflux pump, and tight junctions of the brain capillary endothelial cells. The aim of this study was to evaluate whether the BBB after H/R damage is vulnerable to CsA-induced BBB dysfunction. We attempted to establish a pathophysiological BBB model with immortalized mouse brain capillary endothelial (MBEC4) cells. The effects of CsA on permeability and P-gp activity of the MBEC4 cells were then examined. Exposure to hypoxia for 4 h and reoxygenation for 1 h (H/R (4 h/1 h)) produced a significant decrease in P-gp function of MBEC4 cells, without changing cell viability and permeability for sodium fluorescein and Evan's blue-albumin at 7 days after H/R (4 h/1 h). CsA-induced hyperpermeability and P-gp dysfunction in MBEC4 monolayers at 7 days after H/R (4 h/1 h) were exacerbated. The possibility that CsA penetrates the BBB with incomplete functions in the vicinity of cerebral infarcts to induce neurotoxicity has to be considered.","publication_date":"2007,,","publication_name":"Cellular and Molecular Neurobiology","grobid_abstract_attachment_id":"40754942"},"document_type":"paper","pre_hit_view_count_baseline":null,"quality":"high","language":"en","title":"Adverse Effect of Cyclosporin A on Barrier Functions of Cerebral Microvascular Endothelial Cells After Hypoxia-reoxygenation Damage In Vitro","broadcastable":true,"draft":null,"has_indexable_attachment":true,"indexable":true}}["work"]; window.loswp.workCoauthors = [32943665,32986091]; window.loswp.locale = "en"; window.loswp.countryCode = "SG"; window.loswp.cwvAbTestBucket = ""; window.loswp.designVariant = "ds_vanilla"; window.loswp.fullPageMobileSutdModalVariant = "full_page_mobile_sutd_modal"; window.loswp.useOptimizedScribd4genScript = false; window.loswp.appleClientId = 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Heart and circulatory physiology, 2003</p><p class="ds-related-work--abstract ds2-5-body-sm">Cerebral microvessel endothelial cells that form the blood-brain barrier (BBB) have tight junctions (TJs) that are critical for maintaining brain homeostasis. The effects of initial reoxygenation after a hypoxic insult (H/R) on functional and molecular properties of the BBB and TJs remain unclear. In situ brain perfusion and Western blot analyses were performed to assess in vivo BBB integrity on reoxygenation after a hypoxic insult of 6% O2 for 1 h. Model conditions [blood pressure, blood gas chemistries, cerebral blood flow (CBF), and brain ATP concentration] were also assessed to ensure consistent levels and criteria for insult. In situ brain perfusion revealed that initial reoxygenation (10 min) significantly increased the uptake of [14C]sucrose into brain parenchyma. Capillary depletion and CBF analyses indicated the perturbations were due to increased paracellular permeability rather than vascular volume changes. Hypoxia with reoxygenation (10 min) produced an increase in BBB p...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Effects of hypoxia-reoxygenation on rat blood-brain barrier permeability and tight junctional protein expression","attachmentId":99596408,"attachmentType":"pdf","work_url":"https://www.academia.edu/98172530/Effects_of_hypoxia_reoxygenation_on_rat_blood_brain_barrier_permeability_and_tight_junctional_protein_expression","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/98172530/Effects_of_hypoxia_reoxygenation_on_rat_blood_brain_barrier_permeability_and_tight_junctional_protein_expression"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="5" data-entity-id="98172527" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/98172527/Oxidative_Stress_Increases_Blood_Brain_Barrier_Permeability_and_Induces_Alterations_in_Occludin_during_Hypoxia_Reoxygenation">Oxidative Stress Increases Blood–Brain Barrier Permeability and Induces Alterations in Occludin during Hypoxia–Reoxygenation</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="38289730" href="https://independent.academia.edu/ThomasDavis24">Thomas Davis</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of Cerebral Blood Flow &amp; Metabolism, 2010</p><p class="ds-related-work--abstract ds2-5-body-sm">The blood–brain barrier (BBB) has a critical role in central nervous system homeostasis. Intercellular tight junction (TJ) protein complexes of the brain microvasculature limit paracellular diffusion of substances from the blood into the brain. Hypoxia and reoxygenation (HR) is a central component to numerous disease states and pathologic conditions. We have previously shown that HR can influence the permeability of the BBB as well as the critical TJ protein occludin. During HR, free radicals are produced, which may lead to oxidative stress. Using the free radical scavenger tempol (200 mg/kg, intraperitoneal), we show that oxidative stress produced during HR (6% O2 for 1 h, followed by room air for 20 min) mediates an increase in BBB permeability in vivo using in situ brain perfusion. We also show that these changes are associated with alterations in the structure and localization of occludin. Our data indicate that oxidative stress is associated with movement of occludin away from ...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Oxidative Stress Increases Blood–Brain Barrier Permeability and Induces Alterations in Occludin during Hypoxia–Reoxygenation","attachmentId":99596390,"attachmentType":"pdf","work_url":"https://www.academia.edu/98172527/Oxidative_Stress_Increases_Blood_Brain_Barrier_Permeability_and_Induces_Alterations_in_Occludin_during_Hypoxia_Reoxygenation","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/98172527/Oxidative_Stress_Increases_Blood_Brain_Barrier_Permeability_and_Induces_Alterations_in_Occludin_during_Hypoxia_Reoxygenation"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="6" data-entity-id="44606144" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/44606144/P_glycoprotein_expression_in_immortalised_rat_brain_endothelial_cells_comparisons_following_exogenously_applied_hydrogen_peroxide_and_after_hypoxia_reoxygenation">P-glycoprotein expression in immortalised rat brain endothelial cells: comparisons following exogenously applied hydrogen peroxide and after hypoxia-reoxygenation</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="180204303" href="https://cambridge.academia.edu/StephenHladky">Stephen Hladky</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of Neurochemistry, 2009</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"P-glycoprotein expression in immortalised rat brain endothelial cells: comparisons following exogenously applied hydrogen peroxide and after hypoxia-reoxygenation","attachmentId":65069944,"attachmentType":"pdf","work_url":"https://www.academia.edu/44606144/P_glycoprotein_expression_in_immortalised_rat_brain_endothelial_cells_comparisons_following_exogenously_applied_hydrogen_peroxide_and_after_hypoxia_reoxygenation","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/44606144/P_glycoprotein_expression_in_immortalised_rat_brain_endothelial_cells_comparisons_following_exogenously_applied_hydrogen_peroxide_and_after_hypoxia_reoxygenation"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="7" data-entity-id="16488587" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/16488587/Evaluation_of_the_MDR_MDCK_cell_line_as_a_permeability_screen_for_the_blood_brain_barrier">Evaluation of the MDR-MDCK cell line as a permeability screen for the blood–brain barrier</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="35702423" href="https://independent.academia.edu/IsmaelHidalgo2">Ismael Hidalgo</a></div><p class="ds-related-work--metadata ds2-5-body-xs">International Journal of Pharmaceutics, 2005</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Evaluation of the MDR-MDCK cell line as a permeability screen for the blood–brain barrier","attachmentId":42462749,"attachmentType":"pdf","work_url":"https://www.academia.edu/16488587/Evaluation_of_the_MDR_MDCK_cell_line_as_a_permeability_screen_for_the_blood_brain_barrier","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/16488587/Evaluation_of_the_MDR_MDCK_cell_line_as_a_permeability_screen_for_the_blood_brain_barrier"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="8" data-entity-id="18509072" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/18509072/Molecular_and_cellular_permeability_control_at_the_blood_brain_barrier">Molecular and cellular permeability control at the blood–brain barrier</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="41419345" href="https://uzh.academia.edu/KarlFrei">Karl Frei</a><span>, </span><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="38537303" href="https://unibasel.academia.edu/RegineLandmann">Regine Landmann</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Brain Research Reviews, 2001</p><p class="ds-related-work--abstract ds2-5-body-sm">The blood-brain barrier (BBB) is formed by brain capillary endothelial cells. These cells have at least three properties which distinguish them from their peripheral counterparts: (1) tight junctions (TJs) of extremely low permeability; (2) low rates of fluid-phase endocytosis; (3) specific transport and carrier molecules. In combination, these features restrict the nonspecific flux of ions, proteins, and other substances into the central nervous system (CNS) environment. The restriction protects neurons from harmful compositional fluctuations occurring in the blood and allows uptake of essential molecules. Breakdown of the BBB is associated with a variety of CNS disorders and results in aggravation of the condition. Restoration of the BBB is thus one strategy during therapy of CNS diseases. Its success depends on a precise knowledge of the structural and functional principles underlying BBB functionality. In this review we have tried to summarise the current knowledge of TJs, including information gained from non-neuronal systems, and describe selected mechanisms involved in permeability regulation.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Molecular and cellular permeability control at the blood–brain barrier","attachmentId":42164349,"attachmentType":"pdf","work_url":"https://www.academia.edu/18509072/Molecular_and_cellular_permeability_control_at_the_blood_brain_barrier","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/18509072/Molecular_and_cellular_permeability_control_at_the_blood_brain_barrier"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="9" data-entity-id="14522623" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/14522623/Effects_of_hypoxia_on_endothelial_pericytic_co_culture_model_of_the_blood_brain_barrier">Effects of hypoxia on endothelial/pericytic co-culture model of the blood–brain barrier</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="33477131" href="https://manoa-hawaii.academia.edu/KentaroHayashi">Kentaro Hayashi</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Regulatory Peptides, 2004</p><p class="ds-related-work--abstract ds2-5-body-sm">The blood–brain barrier (BBB) is composed of endothelial cells, pericytes and astrocytic foot processes. Most research for the in vitro BBB is performed endothelial cells with or without astrocytes. Hypoxia damage to the BBB induces vasogenic brain edema. We have generated a new model of the BBB with brain endothelial cells and pericytes and have examined the effects of hypoxia</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Effects of hypoxia on endothelial/pericytic co-culture model of the blood–brain barrier","attachmentId":44093728,"attachmentType":"pdf","work_url":"https://www.academia.edu/14522623/Effects_of_hypoxia_on_endothelial_pericytic_co_culture_model_of_the_blood_brain_barrier","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/14522623/Effects_of_hypoxia_on_endothelial_pericytic_co_culture_model_of_the_blood_brain_barrier"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div></div></div><div class="ds-sticky-ctas--wrapper js-loswp-sticky-ctas hidden"><div class="ds-sticky-ctas--grid-container"><div class="ds-sticky-ctas--container"><button class="ds2-5-button js-swp-download-button" data-signup-modal="{"location":"continue-reading-button--sticky-ctas","attachmentId":40754942,"attachmentType":"pdf","workUrl":null}">See full PDF</button><button class="ds2-5-button ds2-5-button--secondary js-swp-download-button" data-signup-modal="{"location":"download-pdf-button--sticky-ctas","attachmentId":40754942,"attachmentType":"pdf","workUrl":null}"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span>Download PDF</button></div></div></div><div class="ds-below-fold--grid-container"><div class="ds-work--container js-loswp-embedded-document"><div class="attachment_preview" data-attachment="Attachment_40754942" style="display: none"><div class="js-scribd-document-container"><div class="scribd--document-loading js-scribd-document-loader" style="display: block;"><img alt="Loading..." src="//a.academia-assets.com/images/loaders/paper-load.gif" /><p>Loading Preview</p></div></div><div style="text-align: center;"><div class="scribd--no-preview-alert js-preview-unavailable"><p>Sorry, preview is currently unavailable. 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class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="4" data-entity-id="36914794" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/36914794/Intercommunications_between_brain_capillary_endothelial_cells_and_glial_cells_increase_the_transcellular_permeability_of_the_blood_brain_barrier_during_ischaemia">Intercommunications between brain capillary endothelial cells and glial cells increase the transcellular permeability of the blood��brain barrier during ischaemia</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="83470149" href="https://independent.academia.edu/JBrillault">J. Brillault</a></div><p class="ds-related-work--metadata ds2-5-body-xs">2002</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Intercommunications between brain capillary endothelial cells and glial cells increase the transcellular permeability of the blood��brain barrier during ischaemia","attachmentId":56865605,"attachmentType":"pdf","work_url":"https://www.academia.edu/36914794/Intercommunications_between_brain_capillary_endothelial_cells_and_glial_cells_increase_the_transcellular_permeability_of_the_blood_brain_barrier_during_ischaemia","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" 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