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dc.rights.licenseopenen_US
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorMORA, Pierre
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorHOLLIER, Pierre-Louis
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorGUIMBAL, Sarah
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorABELANET, Alice
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorDIOP, Aïssata
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorCORNUAULT, Lauriane
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorCOUFFINHAL, Thierry
dc.contributor.authorHORNG, Sam
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorGADEAU, Alain-Pierre
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorRENAULT, Marie-Ange
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorCHAPOULY, Candice
dc.date.accessioned2021-03-04T11:13:18Z
dc.date.available2021-03-04T11:13:18Z
dc.date.issued2020-01-01
dc.identifier.issn1545-7885en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/26432
dc.description.abstractEnInflammation of the central nervous system (CNS) induces endothelial blood-brain barrier (BBB) opening as well as the formation of a tight junction barrier between reactive astrocytes at the Glia Limitans. We hypothesized that the CNS parenchyma may acquire protection from the reactive astrocytic Glia Limitans not only during neuroinflammation but also when BBB integrity is compromised in the resting state. Previous studies found that astrocyte-derived Sonic hedgehog (SHH) stabilizes the BBB during CNS inflammatory disease, while endothelial-derived desert hedgehog (DHH) is expressed at the BBB under resting conditions. Here, we investigated the effects of endothelial Dhh on the integrity of the BBB and Glia Limitans. We first characterized DHH expression within endothelial cells at the BBB, then demonstrated that DHH is down-regulated during experimental autoimmune encephalomyelitis (EAE). Using a mouse model in which endothelial Dhh is inducibly deleted, we found that endothelial Dhh both opens the BBB via the modulation of forkhead box O1 (FoxO1) transcriptional activity and induces a tight junctional barrier at the Glia Limitans. We confirmed the relevance of this glial barrier system in human multiple sclerosis active lesions. These results provide evidence for the novel concept of "chronic neuroinflammatory tolerance" in which BBB opening in the resting state is sufficient to stimulate a protective barrier at the Glia Limitans that limits the severity of subsequent neuroinflammatory disease. In summary, genetic disruption of the BBB generates endothelial signals that drive the formation under resting conditions of a secondary barrier at the Glia Limitans with protective effects against subsequent CNS inflammation. The concept of a reciprocally regulated CNS double barrier system has implications for treatment strategies in both the acute and chronic phases of multiple sclerosis pathophysiology.
dc.language.isoENen_US
dc.subject.enAdherens Junctions
dc.subject.enAnimals
dc.subject.enAntigens
dc.subject.enCD
dc.subject.enAstrocytes
dc.subject.enBlood-Brain Barrier
dc.subject.enCadherins
dc.subject.enCapillary Permeability
dc.subject.enClaudin-5
dc.subject.enDown-Regulation
dc.subject.enEncephalomyelitis
dc.subject.enAutoimmune
dc.subject.enExperimental
dc.subject.enEndothelial Cells
dc.subject.enFemale
dc.subject.enHedgehog Proteins
dc.subject.enHumans
dc.subject.enMice
dc.subject.enMice
dc.subject.enInbred C57BL
dc.subject.enMice
dc.subject.enKnockout
dc.subject.enMultiple Sclerosis
dc.subject.enNeuroglia
dc.subject.enTight Junctions
dc.title.enBlood-brain barrier genetic disruption leads to protective barrier formation at the Glia Limitans.
dc.title.alternativePLoS Biolen_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1371/journal.pbio.3000946en_US
dc.subject.halSciences du Vivant [q-bio]/Médecine humaine et pathologie
dc.identifier.pubmed33253145en_US
bordeaux.journalPlos Biologyen_US
bordeaux.pagee3000946en_US
bordeaux.volume18en_US
bordeaux.hal.laboratoriesBiologie des maladies cardiovasculaires - U1034en_US
bordeaux.issue11en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.import.sourcepubmed
hal.identifierhal-03424158
hal.version1
hal.date.transferred2021-11-10T11:56:08Z
hal.exporttrue
workflow.import.sourcepubmed
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