2020
A Static Self-Directed Method for Generating Brain Organoids from Human Embryonic Stem Cells.
Boisvert EM, Means RE, Michaud M, Thomson JJ, Madri JA, Katz SG. A Static Self-Directed Method for Generating Brain Organoids from Human Embryonic Stem Cells. Journal Of Visualized Experiments 2020 PMID: 32202516, PMCID: PMC7245934, DOI: 10.3791/60379.Peer-Reviewed Original ResearchConceptsEmbryonic stem cellsCell typesStem cellsIntrinsic developmental cuesHuman embryonic stem cellsHuman pluripotent stem cellsBrain organoidsBrain cell typesPluripotent stem cellsBasement membrane matrixMultiple cell typesDevelopmental cuesUse of organoidsExogenous growth factorsQuantitative reverse transcription polymerase chain reactionMultitude of diseasesHuman brain organoidsOrganoid growthSingle cellsReal-time quantitative reverse transcription polymerase chain reactionSpatial organizationOrganoidsGenetic disordersGrowth factorReverse transcription-polymerase chain reaction
2019
Minocycline mitigates the effect of neonatal hypoxic insult on human brain organoids
Boisvert EM, Means RE, Michaud M, Madri JA, Katz SG. Minocycline mitigates the effect of neonatal hypoxic insult on human brain organoids. Cell Death & Disease 2019, 10: 325. PMID: 30975982, PMCID: PMC6459920, DOI: 10.1038/s41419-019-1553-x.Peer-Reviewed Original ResearchConceptsNeonatal hypoxic injuryBrain developmentEfficacy of minocyclineLow birth weightUse of minocyclineEffects of hypoxiaNormal brain developmentCerebral organoid modelHuman brain organoidsLater time pointsAnimal model systemsNeonatal hypoxicDevastating causeCerebral palsySignificant morbidityHuman brain developmentNeurological consequencesBirth weightHypoxic injuryNeuronal deathCortical neuronsInjury resultsGlial cellsForebrain markersPotential treatment
2014
Adhesion Molecule-Mediated Hippo Pathway Modulates Hemangioendothelioma Cell Behavior
Tsuneki M, Madri JA. Adhesion Molecule-Mediated Hippo Pathway Modulates Hemangioendothelioma Cell Behavior. Molecular And Cellular Biology 2014, 34: 4485-4499. PMID: 25266662, PMCID: PMC4248725, DOI: 10.1128/mcb.00671-14.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDApoptosisBrainCadherinsCaspase 3Cell Line, TumorCell ProliferationHemangioendotheliomaHippo Signaling PathwayImidazolesInhibitor of Apoptosis ProteinsLIM Domain ProteinsMiceMice, Inbred C57BLNaphthoquinonesPlatelet Endothelial Cell Adhesion Molecule-1Protein Serine-Threonine KinasesRepressor ProteinsRNA, Small InterferingSignal TransductionSurvivinConceptsHippo pathwayCell adhesion moleculeAjuba expressionCell proliferationAdhesion moleculesSmall interference RNA transfectionEffector caspase-3Murine hemangioendothelioma cellsPromoter interactionsApoptotic mechanismsMolecule modulationCell behaviorContact inhibitionEndothelial cell proliferationRNA transfectionVE-cadherinCaspase-3Microvascular endothelial cell proliferationApoptosisHemangioendothelioma cellsPathwayCell culturesProliferationEndothelial cell adhesion moleculesExpression
2011
GSK-3β: a signaling pathway node modulating neural stem cell and endothelial cell interactions
Li Q, Michaud M, Canosa S, Kuo A, Madri JA. GSK-3β: a signaling pathway node modulating neural stem cell and endothelial cell interactions. Angiogenesis 2011, 14: 173-185. PMID: 21253820, DOI: 10.1007/s10456-011-9201-9.Peer-Reviewed Original ResearchMeSH KeywordsAminophenolsAnimalsBasic Helix-Loop-Helix Transcription FactorsBeta CateninBrainCell CommunicationCell DifferentiationCell MovementCell ProliferationEndothelial CellsEnzyme ActivationGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaHypoxia-Inducible Factor 1, alpha SubunitIntercellular Signaling Peptides and ProteinsMaleMaleimidesMiceMice, Inbred C57BLNeovascularization, PhysiologicNeural Stem CellsNeurogenesisPhosphorylationPhosphoserineReceptor Cross-TalkSignal TransductionSolubilitySpecies SpecificityConceptsNeural stem cellsNotch-1 expressionHIF-1αGSK-3βSDF-1III-tubulinStem cellsPremature infant populationMicrovascular endothelial cellsGSK-3β activationCD1 levelsEndothelial cell interactionsNeurogenic areasVascular proliferationInfant populationGSK-3β inhibitorTherapeutic potentialSVZ tissueGreater angiogenesisHIF-2αMouse strainsΒ-catenin participatesEndothelial cellsReciprocal modulation
2008
Matrix Metalloproteinase 9 Facilitates West Nile Virus Entry into the Brain
Wang P, Dai J, Bai F, Kong KF, Wong SJ, Montgomery RR, Madri JA, Fikrig E. Matrix Metalloproteinase 9 Facilitates West Nile Virus Entry into the Brain. Journal Of Virology 2008, 82: 8978-8985. PMID: 18632868, PMCID: PMC2546894, DOI: 10.1128/jvi.00314-08.Peer-Reviewed Original ResearchConceptsMatrix metalloproteinase-9Blood-brain barrierWest Nile virusWNV entryMetalloproteinase-9MMP9 expressionWNV infectionIntact blood-brain barrierBlood-brain barrier permeabilityBrain viral loadWest Nile virus entryEvans blue leakageMosquito-borne encephalitisWest Nile encephalitisLethal WNV challengeWild-type miceCentral nervous systemType IV collagen degradationPeripheral viremiaViral loadLeukocyte infiltrateInflammatory cytokinesLikely multifactorialBarrier permeabilityHost cytokines
2007
Modeling the neurovascular niche: Murine strain differences mimic the range of responses to chronic hypoxia in the premature newborn
Li Q, Michaud M, Stewart W, Schwartz M, Madri JA. Modeling the neurovascular niche: Murine strain differences mimic the range of responses to chronic hypoxia in the premature newborn. Journal Of Neuroscience Research 2007, 86: 1227-1242. PMID: 18092360, PMCID: PMC2644407, DOI: 10.1002/jnr.21597.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornApoptosisBlotting, WesternBrainCell ProliferationDisease Models, AnimalGene ExpressionHematopoiesis, ExtramedullaryHumansHypoxia, BrainImmunohistochemistryImmunoprecipitationInfant, NewbornInfant, PrematureIntercellular Signaling Peptides and ProteinsMiceMice, Inbred C57BLNitric OxideStem CellsConceptsNeural progenitor cellsChronic hypoxiaSubventricular zonePreterm birth resultsLow baseline levelsHypoxia-induced levelsNeurogenic responseNeurovascular nicheHypoxic insultBlunted responseBirth resultsC57BL/6 pupsBaseline levelsMotor disabilityMouse strainsGrowth factorVariable recoveryHypoxiaProgenitor cellsPupsRecent evidenceSignificant cognitiveHypoxicApoptotic responseResponse
2006
Modeling the neurovascular niche: VEGF‐ and BDNF‐mediated cross‐talk between neural stem cells and endothelial cells: An in vitro study
Li Q, Ford MC, Lavik EB, Madri JA. Modeling the neurovascular niche: VEGF‐ and BDNF‐mediated cross‐talk between neural stem cells and endothelial cells: An in vitro study. Journal Of Neuroscience Research 2006, 84: 1656-1668. PMID: 17061253, DOI: 10.1002/jnr.21087.Peer-Reviewed Original ResearchMeSH KeywordsAnalysis of VarianceAnimalsAnimals, NewbornBrainBrain-Derived Neurotrophic FactorCell CommunicationCell ProliferationCells, CulturedCoculture TechniquesEndothelial CellsEnzyme-Linked Immunosorbent AssayGreen Fluorescent ProteinsMiceMice, Inbred C57BLMice, TransgenicMicroscopy, Electron, TransmissionModels, BiologicalNerve Tissue ProteinsNeuronsNitric OxidePlatelet Endothelial Cell Adhesion Molecule-1Stem CellsVascular Endothelial Growth Factor AConceptsBrain-derived neurotrophic factorBrain-derived endothelial cellsNeural stem cellsNeurovascular nicheTube formationResident neural stem cellsEndothelial cellsCell-derived soluble factorsVascular endothelial growth factorStem cellsNitric oxide scavengerEndothelial growth factorPaucity of dataExogenous NO donorNeurotrophic factorStem cell modulationVascular tube formationCell modulationENOS activationNO donorSoluble factorsGrowth factorNeuronal differentiationReciprocal modulationInduction
2004
MMP‐2 null mice exhibit an early onset and severe experimental autoimmune encephalomyelitis due to an increase in MMP‐9 expression and activity
Esparza J, Kruse M, Lee J, Michaud M, Madri JA. MMP‐2 null mice exhibit an early onset and severe experimental autoimmune encephalomyelitis due to an increase in MMP‐9 expression and activity. The FASEB Journal 2004, 18: 1682-1691. PMID: 15522913, DOI: 10.1096/fj.04-2445com.Peer-Reviewed Original ResearchMeSH KeywordsAge of OnsetAnimalsBasement MembraneBlood-Brain BarrierBrainCD3 ComplexCell MovementEncephalomyelitis, Autoimmune, ExperimentalEnzyme ActivationGene Expression Regulation, EnzymologicMatrix Metalloproteinase 14Matrix Metalloproteinase 2Matrix Metalloproteinase 9Matrix Metalloproteinases, Membrane-AssociatedMetalloendopeptidasesMiceMice, KnockoutT-Lymphocyte SubsetsT-LymphocytesConceptsMMP-2 KO miceExperimental autoimmune encephalomyelitisMMP-9 expressionAutoimmune encephalomyelitisEarly onsetWT miceKO miceMMP-9Bone marrowSevere experimental autoimmune encephalomyelitisMMP-2 null miceSimilar early onsetWT bone marrowClinical disease scoresMMP-2-deficient miceKO bone marrowMatrix metalloproteinase-2MT1-MMP expressionEndothelial cell monolayersSevere diseaseDisease scoreMetalloproteinase-2Collagen type IVMMP-2Matrix metalloproteinaseParacrine and Autocrine Functions of Brain-derived Neurotrophic Factor (BDNF) and Nerve Growth Factor (NGF) in Brain-derived Endothelial Cells*
Kim H, Li Q, Hempstead BL, Madri JA. Paracrine and Autocrine Functions of Brain-derived Neurotrophic Factor (BDNF) and Nerve Growth Factor (NGF) in Brain-derived Endothelial Cells*. Journal Of Biological Chemistry 2004, 279: 33538-33546. PMID: 15169782, DOI: 10.1074/jbc.m404115200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBlotting, WesternBrainBrain-Derived Neurotrophic FactorCaspase 3CaspasesCell Line, TransformedCerebral CortexEndothelial CellsEnzyme ActivationEnzyme InhibitorsFlow CytometryGene Expression RegulationHypoxiaImmunohistochemistryImmunosorbent TechniquesMAP Kinase Kinase KinasesMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Mitogen-Activated Protein KinasesNerve Growth FactorPhosphoinositide-3 Kinase InhibitorsPhosphorylationRatsReceptor, Nerve Growth FactorReceptor, trkBReceptors, Nerve Growth FactorRecombinant Fusion ProteinsRecombinant ProteinsTransfectionVascular Endothelial Growth Factor Receptor-2ConceptsBrain-derived neurotrophic factorEndogenous brain-derived neurotrophic factorBrain-derived endothelial cellsNerve growth factorEndothelial cellsNeurotrophic factorAutocrine functionExpression of BDNFCentral nervous system (CNS) endotheliumPro-nerve growth factorGrowth factorExpression of TrkBNormoxic conditionsCentral nervous systemBDNF levelsBDNF expressionBDNF responseTrkB phosphorylationNervous systemTrkBSurvival/apoptosisCell survival/apoptosisRobust angiogenesisAkt pathwayInhibitor of phosphatidylinositol
2000
Distinct roles for matrix metalloproteinase-2 and α4 integrin in autoimmune T cell extravasation and residency in brain parenchyma during experimental autoimmune encephalomyelitis
Graesser D, Mahooti S, Madri J. Distinct roles for matrix metalloproteinase-2 and α4 integrin in autoimmune T cell extravasation and residency in brain parenchyma during experimental autoimmune encephalomyelitis. Journal Of Neuroimmunology 2000, 109: 121-131. PMID: 10996214, DOI: 10.1016/s0165-5728(00)00275-7.Peer-Reviewed Original ResearchConceptsMatrix metalloproteinase-2Auto-reactive T cellsExpression of alpha4T cellsMetalloproteinase-2Human multiple sclerosisExperimental autoimmune encephalomyelitisT cell extravasationMMP-2 inductionCentral nervous systemAutoimmune encephalomyelitisMultiple sclerosisAutoimmune diseasesBrain parenchymaNervous systemΑ4 integrinAlpha4 integrinsCell extravasationIndependent roleEAEAlpha4Basement membrane matrixInductionDistinct rolesIntegrins
1997
An in vitro three-dimensional coculture model of cerebral microvascular angiogenesis and differentiation
Ment L, Stewart W, Scaramuzzino D, Madri J. An in vitro three-dimensional coculture model of cerebral microvascular angiogenesis and differentiation. In Vitro Cellular & Developmental Biology - Animal 1997, 33: 684-691. PMID: 9358284, DOI: 10.1007/s11626-997-0126-y.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornAstrocytesBrainCell DifferentiationCoculture TechniquesDogsEndothelium, VascularEnzyme ActivationFibronectinsImmunohistochemistryLamininMicrocirculationMicroscopy, ConfocalMicroscopy, FluorescenceModels, BiologicalNeovascularization, PhysiologicRatsRNA, MessengerUrokinase-Type Plasminogen ActivatorConceptsAstrocyte coculturesThree-dimensional cocultureBrain microvascular endothelial cellsNewborn beagle pupsPostnatal day 1Microvascular endothelial cellsNeonatal rat forebrainCell typesPlasminogen activator activityPreterm birthMicrovascular responsesBeagle pupsThree-dimensional coculture modelDay 1Rat forebrainGlial processesEndothelial proliferationMicrovascular angiogenesisEndothelial cellsCoculture modelPlasminogen zymographyOnly low levelsExtracellular matrix componentsTube formationCocultureT cell adhesion to endothelial cells and extracellular matrix is modulated upon transendothelial cell migration.
Romanic A, Graesser D, Baron J, Visintin I, Janeway C, Madri J. T cell adhesion to endothelial cells and extracellular matrix is modulated upon transendothelial cell migration. Laboratory Investigation 1997, 76: 11-23. PMID: 9010446.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainCell AdhesionCell MovementCells, CulturedCollagenEncephalomyelitis, Autoimmune, ExperimentalEndothelium, VascularExtracellular MatrixFibronectinsFlow CytometryIntegrin alpha4beta1IntegrinsIntercellular Adhesion Molecule-1Interleukin-2Lymphocyte Function-Associated Antigen-1MiceMice, Inbred StrainsMyelin Basic ProteinPeptide FragmentsReceptors, Lymphocyte HomingReceptors, Very Late AntigenRecombinant ProteinsT-LymphocytesUp-RegulationVascular Cell Adhesion Molecule-1ConceptsAdhesion molecule-1T cellsMolecule-1Recombinant vascular cell adhesion molecule-1Recombinant intercellular adhesion molecule-1Experimental autoimmune encephalomyelitis (EAE) miceLate activation antigen-4Vascular cell adhesion molecule-1Intercellular adhesion molecule-1Cell adhesion molecule-1T cell migrationExtracellular matrixCell migrationTransendothelial cell migrationAntigen-4Integrin surface expressionInflammatory responseCD4 expressionBrain sectionsT cell adhesionPerivascular tissueEndothelial cellsIntegrin expressionCell-ECM interactionsSurface expression
1994
Extracellular Matrix‐Degrading Proteinases in the Nervous System
Romanic A, Madri J. Extracellular Matrix‐Degrading Proteinases in the Nervous System. Brain Pathology 1994, 4: 145-156. PMID: 8061860, DOI: 10.1111/j.1750-3639.1994.tb00825.x.Peer-Reviewed Original ResearchConceptsCell-ECM interactionsExtracellular matrixMatrix-degrading proteinasesNeuronal cell migrationExtracellular matrix-degrading proteinasesCell migrationNervous systemECM degradationNeurite outgrowthCell proliferationDrug designProteolytic activityNew insightsPathological conditionsBrain tumor growthTumor growthMatrix metalloproteinasesProteinasesForm of therapyCentral nervous systemInhibitorsPlasminogen activatorTraffickingLeukocyte traffickingNerve demyelination
1993
Surface expression of alpha 4 integrin by CD4 T cells is required for their entry into brain parenchyma.
Baron JL, Madri JA, Ruddle NH, Hashim G, Janeway CA. Surface expression of alpha 4 integrin by CD4 T cells is required for their entry into brain parenchyma. Journal Of Experimental Medicine 1993, 177: 57-68. PMID: 7678116, PMCID: PMC2190872, DOI: 10.1084/jem.177.1.57.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalBrainCD4-Positive T-LymphocytesCell Adhesion MoleculesCell MovementClone CellsEncephalomyelitis, Autoimmune, ExperimentalIntercellular Adhesion Molecule-1MiceMice, Inbred BALB CMyelin Basic ProteinReceptors, Very Late AntigenVascular Cell Adhesion Molecule-1ConceptsAlpha 4 integrinsExperimental autoimmune encephalomyelitisAdhesion molecule-1T cellsBrain parenchymaT cell linesEncephalitogenic clonesAlpha 4Surface expressionMolecule-1Recombinant vascular cell adhesion molecule-1T helper type 1 clonesCD4 T cell linesCloned T cell linesTh1 cytokine interleukin-2Vascular cell adhesion molecule-1Intercellular adhesion molecule-1Cell adhesion molecule-1Tumor necrosis factor betaTh1 T cellsEffector T cellsCD4 T cellsMajor pathogenic factorT cell entryNecrosis factor beta
1992
Indomethacin promotes germinal matrix microvessel maturation in the newborn beagle pup.
Ment L, Stewart W, Ardito T, Huang E, Madri J. Indomethacin promotes germinal matrix microvessel maturation in the newborn beagle pup. Stroke 1992, 23: 1132-1137. PMID: 1636188, DOI: 10.1161/01.str.23.8.1132.Peer-Reviewed Original ResearchConceptsNewborn beagle pupsPostnatal day 2Germinal matrixPostnatal ageBeagle pupsIntraventricular hemorrhageVessel densityDay 2Postnatal day 1Laminin depositionMechanism of actionMicrovessel maturationStudy medicationBeta 1 integrinImmunohistochemical studyPostnatal dayDose i.Animal studiesDay 1IndomethacinNewborn pupsHemorrhageBasement membrane depositionBuffered formalinCollagen staining