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To help understand the role of HIF-1α in neonatal hypoxic-ischemic brain injury, mice with" /> <title>(PDF) HIF-1α-Deficient Mice Have Increased Brain Injury after Neonatal Hypoxia-Ischemia | Donna Ferriero - Academia.edu</title> <link rel="canonical" href="https://www.academia.edu/125338047/HIF_1%CE%B1_Deficient_Mice_Have_Increased_Brain_Injury_after_Neonatal_Hypoxia_Ischemia" /> <script async src="https://www.googletagmanager.com/gtag/js?id=G-5VKX33P2DS"></script> <script> window.dataLayer = window.dataLayer || []; function gtag(){dataLayer.push(arguments);} gtag('js', new Date()); gtag('config', 'G-5VKX33P2DS', { cookie_domain: 'academia.edu', send_page_view: false, }); gtag('event', 'page_view', { 'controller': "single_work", 'action': "show", 'controller_action': 'single_work#show', 'logged_in': 'false', 'edge': 'unknown', // Send nil if there is no A/B test bucket, in case some records get logged // with missing data - that way we can distinguish between the two cases. // ab_test_bucket should be of the form <ab_test_name>:<bucket> 'ab_test_bucket': null, }) </script> <script> var $controller_name = 'single_work'; var $action_name = "show"; var $rails_env = 'production'; var $app_rev = '49879c2402910372f4abc62630a427bbe033d190'; var $domain = 'academia.edu'; var $app_host = "academia.edu"; var $asset_host = "academia-assets.com"; var $start_time = new Date().getTime(); var $recaptcha_key = "6LdxlRMTAAAAADnu_zyLhLg0YF9uACwz78shpjJB"; var $recaptcha_invisible_key = "6Lf3KHUUAAAAACggoMpmGJdQDtiyrjVlvGJ6BbAj"; var $disableClientRecordHit = false; </script> <script> window.require = { config: function() { return function() {} } } </script> <script> window.Aedu = window.Aedu || {}; window.Aedu.hit_data = null; window.Aedu.serverRenderTime = new Date(1732416541000); window.Aedu.timeDifference = new Date().getTime() - 1732416541000; </script> <script type="application/ld+json">{"@context":"https://schema.org","@type":"ScholarlyArticle","abstract":"Evidence suggests that the activation of the transcription factor hypoxia-inducible factor 1α (HIF-1α) may promote cell survival in hypoxic or ischemic brain. To help understand the role of HIF-1α in neonatal hypoxic-ischemic brain injury, mice with conditional neuron-specific inactivation of HIF-1α underwent hypoxia-ischemia (HI). Mice heterozygous for Cre recombinase under the control of the calcium/calmodulin-dependent kinase II promoter were bred with homozygous ‘floxed’ HIF-1α transgenic mice. The resulting litters produced mice with a forebrain predominant neuronal deletion of HIF-1α (HIF-1αΔ/Δ), as well as littermates without the deletion. In order to verify reduction of HIF-1α at postnatal day 7, HIF-1αΔ/Δ and wild-type mice were exposed to a hypoxic stimulus (8% oxygen) or room air for 1 h, followed by immediate collection of brain cortices for determination of HIF-1α expression. Results of Western blotting of mouse cortices exposed to hypoxia stimulus or room air confirmed...","author":[{"@context":"https://schema.org","@type":"Person","name":"Donna Ferriero"}],"contributor":[],"dateCreated":"2024-11-06","dateModified":null,"datePublished":"2009-01-01","headline":"HIF-1α-Deficient Mice Have Increased Brain Injury after Neonatal Hypoxia-Ischemia","inLanguage":"en","keywords":["Endocrinology","Genetics","Cognitive Science","Biology","Developmental neuroscience","Medicine","Internal Medicine","Anoxia","Cerebral Cortex","Female","Animals","Male","Cytoprotection","Brain injury","Fluorescent Antibody Technique","Analysis of Variance","Calmodulin","Cell Survival","Forebrain","Hypoxia inducible factor"],"locationCreated":null,"publication":"Developmental Neuroscience","publisher":{"@context":"https://schema.org","@type":"Organization","name":"S. 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window.loswp.shouldDetectTimezone = true; window.loswp.shouldShowBulkDownload = true; window.loswp.showSignupCaptcha = false window.loswp.willEdgeCache = false; window.loswp.work = {"work":{"id":125338047,"created_at":"2024-11-06T12:38:20.395-08:00","from_world_paper_id":260807233,"updated_at":"2024-11-06T13:02:04.472-08:00","_data":{"abstract":"Evidence suggests that the activation of the transcription factor hypoxia-inducible factor 1α (HIF-1α) may promote cell survival in hypoxic or ischemic brain. To help understand the role of HIF-1α in neonatal hypoxic-ischemic brain injury, mice with conditional neuron-specific inactivation of HIF-1α underwent hypoxia-ischemia (HI). Mice heterozygous for Cre recombinase under the control of the calcium/calmodulin-dependent kinase II promoter were bred with homozygous ‘floxed’ HIF-1α transgenic mice. The resulting litters produced mice with a forebrain predominant neuronal deletion of HIF-1α (HIF-1αΔ/Δ), as well as littermates without the deletion. In order to verify reduction of HIF-1α at postnatal day 7, HIF-1αΔ/Δ and wild-type mice were exposed to a hypoxic stimulus (8% oxygen) or room air for 1 h, followed by immediate collection of brain cortices for determination of HIF-1α expression. Results of Western blotting of mouse cortices exposed to hypoxia stimulus or room air confirmed...","publisher":"S. Karger AG","publication_date":"2009,,","publication_name":"Developmental Neuroscience"},"document_type":"paper","pre_hit_view_count_baseline":null,"quality":"high","language":"en","title":"HIF-1α-Deficient Mice Have Increased Brain Injury after Neonatal Hypoxia-Ischemia","broadcastable":false,"draft":null,"has_indexable_attachment":true,"indexable":true}}["work"]; window.loswp.workCoauthors = [33003560]; window.loswp.locale = "en"; window.loswp.countryCode = "SG"; window.loswp.cwvAbTestBucket = ""; window.loswp.designVariant = "ds_vanilla"; window.loswp.fullPageMobileSutdModalVariant = "control"; window.loswp.useOptimizedScribd4genScript = false; window.loswp.appleClientId = 'edu.academia.applesignon';</script><script defer="" src="https://accounts.google.com/gsi/client"></script><div class="ds-loswp-container"><div class="ds-work-card--grid-container"><div class="ds-work-card--container js-loswp-work-card"><div class="ds-work-card--cover"><div class="ds-work-cover--wrapper"><div class="ds-work-cover--container"><button class="ds-work-cover--clickable js-swp-download-button" data-signup-modal="{"location":"swp-splash-paper-cover","attachmentId":119400357,"attachmentType":"pdf"}"><img alt="First page of “HIF-1α-Deficient Mice Have Increased Brain Injury after Neonatal Hypoxia-Ischemia”" class="ds-work-cover--cover-thumbnail" src="https://0.academia-photos.com/attachment_thumbnails/119400357/mini_magick20241106-1-keq246.png?1730925508" /><img alt="PDF Icon" class="ds-work-cover--file-icon" src="//a.academia-assets.com/assets/single_work_splash/adobe.icon-574afd46eb6b03a77a153a647fb47e30546f9215c0ee6a25df597a779717f9ef.svg" /><div class="ds-work-cover--hover-container"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span><p>Download Free PDF</p></div><div class="ds-work-cover--ribbon-container">Download Free PDF</div><div class="ds-work-cover--ribbon-triangle"></div></button></div></div></div><div class="ds-work-card--work-information"><h1 class="ds-work-card--work-title">HIF-1α-Deficient Mice Have Increased Brain Injury after Neonatal Hypoxia-Ischemia</h1><div class="ds-work-card--work-authors ds-work-card--detail"><a class="ds-work-card--author js-wsj-grid-card-author ds2-5-body-md ds2-5-body-link" data-author-id="33003560" href="https://ucsf.academia.edu/DonnaFerriero"><img alt="Profile image of Donna Ferriero" class="ds-work-card--author-avatar" src="//a.academia-assets.com/images/s65_no_pic.png" />Donna Ferriero</a></div><p class="ds-work-card--detail ds2-5-body-sm">2009, Developmental Neuroscience</p><p class="ds-work-card--work-abstract ds-work-card--detail ds2-5-body-md">Evidence suggests that the activation of the transcription factor hypoxia-inducible factor 1α (HIF-1α) may promote cell survival in hypoxic or ischemic brain. To help understand the role of HIF-1α in neonatal hypoxic-ischemic brain injury, mice with conditional neuron-specific inactivation of HIF-1α underwent hypoxia-ischemia (HI). Mice heterozygous for Cre recombinase under the control of the calcium/calmodulin-dependent kinase II promoter were bred with homozygous ‘floxed’ HIF-1α transgenic mice. The resulting litters produced mice with a forebrain predominant neuronal deletion of HIF-1α (HIF-1αΔ/Δ), as well as littermates without the deletion. In order to verify reduction of HIF-1α at postnatal day 7, HIF-1αΔ/Δ and wild-type mice were exposed to a hypoxic stimulus (8% oxygen) or room air for 1 h, followed by immediate collection of brain cortices for determination of HIF-1α expression. Results of Western blotting of mouse cortices exposed to hypoxia stimulus or room air confirmed...</p><div class="ds-work-card--button-container"><button class="ds2-5-button js-swp-download-button" data-signup-modal="{"location":"continue-reading-button--work-card","attachmentId":119400357,"attachmentType":"pdf","workUrl":"https://www.academia.edu/125338047/HIF_1%CE%B1_Deficient_Mice_Have_Increased_Brain_Injury_after_Neonatal_Hypoxia_Ischemia"}">See full PDF</button><button class="ds2-5-button ds2-5-button--secondary js-swp-download-button" data-signup-modal="{"location":"download-pdf-button--work-card","attachmentId":119400357,"attachmentType":"pdf","workUrl":"https://www.academia.edu/125338047/HIF_1%CE%B1_Deficient_Mice_Have_Increased_Brain_Injury_after_Neonatal_Hypoxia_Ischemia"}"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span>Download PDF</button></div></div></div></div><div data-auto_select="false" 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genes","attachmentId":109131491,"attachmentType":"pdf","work_url":"https://www.academia.edu/111658974/Oxygen_treatment_after_experimental_hypoxia_ischemia_in_neonatal_rats_alters_the_expression_of_HIF_1%CE%B1_and_its_downstream_target_genes","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/111658974/Oxygen_treatment_after_experimental_hypoxia_ischemia_in_neonatal_rats_alters_the_expression_of_HIF_1%CE%B1_and_its_downstream_target_genes"><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="6329384" 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/6329384/HIF_1_alpha_inhibition_ameliorates_neonatal_brain_damage_after_hypoxic_ischemic_injury">HIF-1 alpha inhibition ameliorates neonatal brain damage after hypoxic-ischemic injury</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="9851264" href="https://independent.academia.edu/jadhavvikram">vikram jadhav</a></div><p class="ds-related-work--abstract ds2-5-body-sm">Background Hypoxia-inducible-factor-1alpha (HIF-1α) has been considered as a regulator of both prosurvival and prodeath pathways in the nervous system. This study was designed to elucidate the role of HIF-1α in neonatal hypoxia-ischemia (HI) brain injury. Methods 2-methoxyestradiol (2ME2), a HIF-1α inhibitor, was tested at different dosages (1.5, 15 and 150 mg/kg) and a therapeutic window was tested by administrating 2-methoxyestradiol (15 mg/kg) immediately or 3 hours after the induction of a hypoxic ischemic injury. Infarct size using TTC staining and brain edema were measured at 48 hours post hypoxia-ischemia. Blood-brain barrier (BBB) permeability was examined by IgG staining. Vascular endothelial growth factor (VEGF) and HIF-1α expression and distribution were studied by immunohistochemistry and western blotting analysis. Findings 2ME2 exhibited dose-dependent neuroprotection by decreasing infarct volume and attenuating brain edema. 2ME2 also attenuated BBB disruption, and decreased HIF-1α and vascular endothelial growth factor (VEGF) expression. The neuroprotection, however, was lost when 2ME2 was administered 3 hours after neonatal HI. Conclusion The study shows that the acute inhibition of HIF-1α is neuroprotective in neonatal hypoxic-ischemic injury by preserving BBB integrity and reducing brain edema.</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":"HIF-1 alpha inhibition ameliorates neonatal brain damage after hypoxic-ischemic injury","attachmentId":48914844,"attachmentType":"pdf","work_url":"https://www.academia.edu/6329384/HIF_1_alpha_inhibition_ameliorates_neonatal_brain_damage_after_hypoxic_ischemic_injury","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/6329384/HIF_1_alpha_inhibition_ameliorates_neonatal_brain_damage_after_hypoxic_ischemic_injury"><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="13449499" 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/13449499/Role_of_hypoxia_inducible_factor_1_in_hypoxia_induced_ischemic_tolerance_in_neonatal_rat_brain">Role of hypoxia-inducible factor-1 in hypoxia-induced ischemic tolerance in neonatal rat brain</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="32675304" href="https://ucdavis.academia.edu/FrankSharp">Frank Sharp</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Annals of Neurology, 2000</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":"Role of hypoxia-inducible factor-1 in hypoxia-induced ischemic tolerance in neonatal rat brain","attachmentId":45333804,"attachmentType":"pdf","work_url":"https://www.academia.edu/13449499/Role_of_hypoxia_inducible_factor_1_in_hypoxia_induced_ischemic_tolerance_in_neonatal_rat_brain","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/13449499/Role_of_hypoxia_inducible_factor_1_in_hypoxia_induced_ischemic_tolerance_in_neonatal_rat_brain"><span class="ds2-5-text-link__content">View PDF</span><span 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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/13978488/HIF_1alpha_cytoplasmic_accumulation_is_associated_with_cell_death_in_old_rat_cerebral_cortex_exposed_to_intermittent_hypoxia">HIF-1alpha cytoplasmic accumulation is associated with cell death in old rat cerebral cortex exposed to intermittent hypoxia</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="33022572" href="https://uniteramo.academia.edu/CinziaRapino">Cinzia Rapino</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Aging Cell, 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":"HIF-1alpha cytoplasmic accumulation is associated with cell death in old rat cerebral cortex exposed to 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IDENTIFICATION OF GENES THAT MIGHT CONTRIBUTE TO HYPOXIA-INDUCED ISCHEMIC TOLERANCE</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="32675304" href="https://ucdavis.academia.edu/FrankSharp">Frank Sharp</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of Biological Chemistry, 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":"Brain Genomic Response following Hypoxia and Re-oxygenation in the Neonatal Rat. 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data-entity-id="17765764" 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/17765764/Hypoxia_driven_proliferation_of_embryonic_neural_stem_progenitor_cells_role_of_hypoxia_inducible_transcription_factor_1%CE%B1">Hypoxia-driven proliferation of embryonic neural stem/progenitor cells - role of hypoxia-inducible transcription factor-1α</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="37670715" href="https://independent.academia.edu/XiaominWang1">Xiaomin Wang</a></div><p class="ds-related-work--metadata ds2-5-body-xs">FEBS Journal, 2008</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":"Hypoxia-driven proliferation of embryonic neural stem/progenitor cells - role 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data-entity-id="13948694" 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/13948694/Signaling_pathway_involved_in_hypoxia_inducible_factor_1%CE%B1_regulation_in_hypoxic_ischemic_cortical_neurons_in_vitro">Signaling pathway involved in hypoxia-inducible factor-1α regulation in hypoxic-ischemic cortical neurons in vitro</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="33003560" href="https://ucsf.academia.edu/DonnaFerriero">Donna Ferriero</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Neuroscience Letters, 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":"Signaling pathway involved in hypoxia-inducible factor-1α regulation in hypoxic-ischemic 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Dadak</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Molecular and Cellular Biology, 2003</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":"Hypoxia-Induced Gene Expression Occurs Solely through the Action of Hypoxia-Inducible Factor 1 (HIF-1 ): Role of Cytoplasmic Trapping of HIF-2 ","attachmentId":52286028,"attachmentType":"pdf","work_url":"https://www.academia.edu/32020650/Hypoxia_Induced_Gene_Expression_Occurs_Solely_through_the_Action_of_Hypoxia_Inducible_Factor_1_HIF_1_Role_of_Cytoplasmic_Trapping_of_HIF_2_","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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