2024
Quantitative susceptibility mapping is more sensitive and specific than phase imaging in detecting chronic active multiple sclerosis lesion rims: pathological validation
Gillen K, Nguyen T, Dimov A, Kovanlikaya I, Luu H, Demmon E, Markowitz D, Bagnato F, Pitt D, Gauthier S, Wang Y. Quantitative susceptibility mapping is more sensitive and specific than phase imaging in detecting chronic active multiple sclerosis lesion rims: pathological validation. Brain Communications 2024, 7: fcaf011. PMID: 39916751, PMCID: PMC11800486, DOI: 10.1093/braincomms/fcaf011.Peer-Reviewed Original ResearchPhase imagesQuantitative susceptibility mappingPerls' stainPredictive valueLesion rimFrequency of clinical relapsesNegative predictive valuePositive predictive valuePathological validationDecreased brain volumeProgression to disabilityQuantitative susceptibility mapping imagesClinical relapseBrain volumeMicroglial markersGold standardLesionsMultiple sclerosis lesionsParamagnetic rimMap images
2022
Phenotyping Of Multiple Sclerosis Lesions According To Innate Immune Cell Activation Using TSPO-PET (S26.003)
Nylund M, Sucksdorff M, Matilainen M, Polvinen E, Tuisku J, Airas L. Phenotyping Of Multiple Sclerosis Lesions According To Innate Immune Cell Activation Using TSPO-PET (S26.003). Neurology 2022, 98 DOI: 10.1212/wnl.98.18_supplement.2547.Peer-Reviewed Original ResearchDimethyl Fumarate Reduces Inflammation in Chronic Active Multiple Sclerosis Lesions
Zinger N, Ponath G, Sweeney E, Nguyen TD, Lo CH, Diaz I, Dimov A, Teng L, Zexter L, Comunale J, Wang Y, Pitt D, Gauthier SA. Dimethyl Fumarate Reduces Inflammation in Chronic Active Multiple Sclerosis Lesions. Neurology Neuroimmunology & Neuroinflammation 2022, 9: e1138. PMID: 35046083, PMCID: PMC8771666, DOI: 10.1212/nxi.0000000000001138.Peer-Reviewed Original ResearchConceptsChronic active lesionsGlatiramer acetateRim lesionsHuman microgliaDimethyl fumarateMultiple sclerosisActive lesionsChronic active multiple sclerosis lesionsEffects of DMFActive multiple sclerosis lesionsClass III evidenceMarkers of inflammationRelapsing-remitting MSRetrospective observational studyQuantitative susceptibility mappingMultiple sclerosis lesionsActivation stateTreatment-induced changesMRI quantitative susceptibility mappingMicroglial activityGlial activityInflammatory activationMicroglial cellsObservational studyMS lesions
2021
QSM is an imaging biomarker for chronic glial activation in multiple sclerosis lesions
Gillen KM, Mubarak M, Park C, Ponath G, Zhang S, Dimov A, Levine‐Ritterman M, Toro S, Huang W, Amici S, Kaunzner UW, Gauthier SA, Guerau‐de‐Arellano M, Wang Y, Nguyen TD, Pitt D. QSM is an imaging biomarker for chronic glial activation in multiple sclerosis lesions. Annals Of Clinical And Translational Neurology 2021, 8: 877-886. PMID: 33704933, PMCID: PMC8045922, DOI: 10.1002/acn3.51338.Peer-Reviewed Original ResearchConceptsNormal-appearing white matterMyeloid cellsLesion rimReactive oxygen speciesQuantitative susceptibility mappingChronic active lesionsChronic glial activationPro-inflammatory cytokinesBlood-brain barrierWhite matter lesionsAdjacent normal-appearing white matterMultiple sclerosis lesionsGlial activationActivated microgliaHistopathological correlatesChronic inflammationActive lesionsCytokine productionMatter lesionsMS lesionsWhite matterHuman-induced pluripotent stem cellsSclerosis lesionsLesionsLesion perimeter
2019
The landscape of myeloid and astrocyte phenotypes in acute multiple sclerosis lesions
Park C, Ponath G, Levine-Ritterman M, Bull E, Swanson EC, De Jager PL, Segal BM, Pitt D. The landscape of myeloid and astrocyte phenotypes in acute multiple sclerosis lesions. Acta Neuropathologica Communications 2019, 7: 130. PMID: 31405387, PMCID: PMC6689891, DOI: 10.1186/s40478-019-0779-2.Peer-Reviewed Original ResearchConceptsMultiple sclerosis lesionsLesion rimAstrocyte phenotypeMyeloid cellsSclerosis lesionsActive multiple sclerosis lesionsAcute multiple sclerosis lesionsGlial activation markersActive MS lesionsNovel therapeutic targetDifferent lesion stagesPredominant cell typeAcute demyelinationDemyelinating lesionsCell typesActivation markersChronic inflammationDistinct myeloidCell-extrinsic factorsGlial cellsPhenotypic subsetsLesion stageGlial phenotypeMS lesionsLesion cellsMultiplexed imaging of immune cells in staged multiple sclerosis lesions by mass cytometry
Ramaglia V, Sheikh-Mohamed S, Legg K, Park C, Rojas OL, Zandee S, Fu F, Ornatsky O, Swanson EC, Pitt D, Prat A, McKee TD, Gommerman JL. Multiplexed imaging of immune cells in staged multiple sclerosis lesions by mass cytometry. ELife 2019, 8: e48051. PMID: 31368890, PMCID: PMC6707785, DOI: 10.7554/elife.48051.Peer-Reviewed Original ResearchConceptsMultiple sclerosisMS disease activityT-cell phenotypeMass cytometryTypes of lymphocytesMultiple sclerosis lesionsNatalizumab cessationDisease activityMS patientsInflammatory lesionsImmune cellsSpinal cordLesion morphometryMS lesionsB cellsLesion typeSclerosis lesionsLesionsBlood vesselsCell phenotypeFunctional stateCytometryCellular contentCell-cell interactionsPhenotype
2018
Quantitative susceptibility mapping identifies inflammation in a subset of chronic multiple sclerosis lesions
Kaunzner UW, Kang Y, Zhang S, Morris E, Yao Y, Pandya S, Rua S, Park C, Gillen KM, Nguyen TD, Wang Y, Pitt D, Gauthier SA. Quantitative susceptibility mapping identifies inflammation in a subset of chronic multiple sclerosis lesions. Brain 2018, 142: 133-145. PMID: 30561514, PMCID: PMC6308309, DOI: 10.1093/brain/awy296.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntigens, CDAntigens, Differentiation, MyelomonocyticBrainCarbon RadioisotopesChronic DiseaseCross-Sectional StudiesFemaleHumansInflammationIronIsoquinolinesMacrophagesMagnetic Resonance ImagingMaleMicrogliaMiddle AgedMultiple SclerosisPositron-Emission TomographyRetrospective StudiesYoung AdultConceptsChronic active lesionsMultiple sclerosisChronic lesionsActive lesionsMultiple sclerosis lesionsHyperintense rimQuantitative susceptibility mappingChronic active multiple sclerosis lesionsSclerosis lesionsChronic multiple sclerosis lesionsActive multiple sclerosis lesionsPersistent inflammatory activityProgressive multiple sclerosisMicroglia/macrophagesInnate immune activationEarly disease stagesTranslocator proteinGreater tissue damagePost-mortem studiesProgressive patientsActivated microgliaInflammatory activityPersistent inflammationImmune activationDisease stageThe Role of Astrocytes in Multiple Sclerosis
Ponath G, Park C, Pitt D. The Role of Astrocytes in Multiple Sclerosis. Frontiers In Immunology 2018, 9: 217. PMID: 29515568, PMCID: PMC5826071, DOI: 10.3389/fimmu.2018.00217.Peer-Reviewed Original ResearchConceptsRole of astrocytesImmune cell accessCentral nervous systemMultiple sclerosis lesionsAstrocyte activationMultiple sclerosisGlial scarAstrocyte functionMS treatmentMS lesionsNervous systemAstrocytesSclerosis lesionsLesion formationFunctional polarizationLesionsCell accessSclerosisInflammationPathogenesisSignificance and In Vivo Detection of Iron-Laden Microglia in White Matter Multiple Sclerosis Lesions
Gillen KM, Mubarak M, Nguyen TD, Pitt D. Significance and In Vivo Detection of Iron-Laden Microglia in White Matter Multiple Sclerosis Lesions. Frontiers In Immunology 2018, 9: 255. PMID: 29515576, PMCID: PMC5826076, DOI: 10.3389/fimmu.2018.00255.Peer-Reviewed Original ResearchConceptsCentral nervous systemChronic active lesionsMultiple sclerosisActive lesionsWhite matterWhite matter MS lesionsQuantitative susceptibility mappingNovel MS therapiesResident immune cellsChronic inflammatory activityWhite matter lesionsMyeloid cell activationAdjacent white matterWhite matter multiple sclerosis lesionsChronic tissue damageMultiple sclerosis lesionsMS therapyInflammatory activityMagnetic resonance imaging techniquesChronic inflammationMatter lesionsAged brainImmune cellsMyelin phagocytosisChronic diseases
2016
Myelin phagocytosis by astrocytes after myelin damage promotes lesion pathology
Ponath G, Ramanan S, Mubarak M, Housley W, Lee S, Sahinkaya FR, Vortmeyer A, Raine CS, Pitt D. Myelin phagocytosis by astrocytes after myelin damage promotes lesion pathology. Brain 2016, 140: 399-413. PMID: 28007993, PMCID: PMC5841057, DOI: 10.1093/brain/aww298.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAnimalsAnimals, NewbornAstrocytesCell ProliferationCells, CulturedChild, PreschoolCultureCytokinesDemyelinating Autoimmune Diseases, CNSEndocytosisFemaleHumansHydrazonesMacrophagesMaleMiddle AgedMyelin SheathPhagocytosisRatsRats, Sprague-DawleyStrokeTime FactorsTransforming Growth Factor betaConceptsMyelin injuryMyelin phagocytosisMyelin debrisMultiple sclerosis lesionsMultiple sclerosisLesion pathologySclerosis lesionsAcute multiple sclerosis lesionsCentral nervous system pathologyProgressive multifocal leukoencephalopathyNervous system pathologySecretion of chemokinesNF-κB activationElevated chemokine expressionHypertrophic astrocytesMost astrocytesMyelin uptakeMultifocal leukoencephalopathyFirst-line responseAcute lesionsMyelin damageReactive astrocytesChemokine expressionAstroglial responseImmune cellsQuantitative Susceptibility Mapping and R2* Measured Changes during White Matter Lesion Development in Multiple Sclerosis: Myelin Breakdown, Myelin Debris Degradation and Removal, and Iron Accumulation
Zhang Y, Gauthier SA, Gupta A, Chen W, Comunale J, Chiang G, Zhou D, Askin G, Zhu W, Pitt D, Wang Y. Quantitative Susceptibility Mapping and R2* Measured Changes during White Matter Lesion Development in Multiple Sclerosis: Myelin Breakdown, Myelin Debris Degradation and Removal, and Iron Accumulation. American Journal Of Neuroradiology 2016, 37: 1629-1635. PMID: 27256856, PMCID: PMC5018433, DOI: 10.3174/ajnr.a4825.Peer-Reviewed Original ResearchConceptsMyelin breakdownQuantitative susceptibility mappingExpanded Disability Status Scale scoreEarly active MS lesionsDisability Status Scale scoreIron accumulationDifferent enhancing patternStatus Scale scoreActive MS lesionsWhite matter lesionsMultiple sclerosis lesionsDisease durationChronic lesionsEarly chronicMatter lesionsMultiple sclerosisActive lesionsMyelin debrisMS lesionsLesion changesScale scoreLesion typeSclerosis lesionsLesionsLesion development
2014
Dynamics of sodium channel Nav1.5 expression in astrocytes in mouse models of multiple sclerosis
Pappalardo LW, Liu S, Black JA, Waxman SG. Dynamics of sodium channel Nav1.5 expression in astrocytes in mouse models of multiple sclerosis. Neuroreport 2014, 25: 1208-1215. PMID: 25144393, PMCID: PMC4159404, DOI: 10.1097/wnr.0000000000000249.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAstrocytesEncephalomyelitis, Autoimmune, ExperimentalImmunohistochemistryLumbar VertebraeMice, BiozziMice, Inbred C57BLMotor CortexMultiple Sclerosis, Chronic ProgressiveMultiple Sclerosis, Relapsing-RemittingNAV1.5 Voltage-Gated Sodium ChannelSeverity of Illness IndexSpinal CordUp-RegulationConceptsExperimental autoimmune encephalomyelitisCentral nervous systemMultiple sclerosisNervous systemChronic multiple sclerosis lesionsNav1.5 expressionPhases of relapsePeriods of remissionGlial scar formationResponse of astrocytesSeverity of diseasePotential therapeutic targetMultiple sclerosis lesionsVoltage-gated sodium channel Nav1.5Autoimmune encephalomyelitisNeuroinflammatory pathologiesIntracellular Ca levelsReactive astrogliosisGlial scarInflammatory pathologyMouse modelImmunohistochemical analysisScar formationTherapeutic targetAstrocytesQuantitative susceptibility mapping (QSM) of white matter multiple sclerosis lesions: Interpreting positive susceptibility and the presence of iron
Wisnieff C, Ramanan S, Olesik J, Gauthier S, Wang Y, Pitt D. Quantitative susceptibility mapping (QSM) of white matter multiple sclerosis lesions: Interpreting positive susceptibility and the presence of iron. Magnetic Resonance In Medicine 2014, 74: 564-570. PMID: 25137340, PMCID: PMC4333139, DOI: 10.1002/mrm.25420.Peer-Reviewed Original ResearchConceptsMultiple sclerosisQuantitative susceptibility mappingIron depositionMS brain tissueMicroglia/macrophagesWhite matter multiple sclerosis lesionsPresence of myelinMultiple sclerosis lesionsSubstantial iron depositionChronic inflammationMS lesionsSclerosis lesionsLesionsBrain tissueMyelinMicroglia
2013
Quantitative Susceptibility Mapping of Multiple Sclerosis Lesions at Various Ages
Chen W, Gauthier SA, Gupta A, Comunale J, Liu T, Wang S, Pei M, Pitt D, Wang Y. Quantitative Susceptibility Mapping of Multiple Sclerosis Lesions at Various Ages. Radiology 2013, 271: 183-92. PMID: 24475808, PMCID: PMC4263629, DOI: 10.1148/radiol.13130353.Peer-Reviewed Original ResearchConceptsNormal-appearing white matterMS lesionsMultiple sclerosis lesionsEnhanced lesionsQuantitative susceptibility mappingMR examinationsSclerosis lesionsConventional magnetic resonance imagingMagnetic resonance imagingT2-weighted imagesMS patientsPathophysiologic featuresCerebrospinal fluidOnline supplemental materialWhite matterLesionsQSM imagesResonance imagingPatientsMR imagingThree-dimensional gradient-echo sequenceGradient echo sequenceMonthsBonferroni correctionAgeAscl1/Mash1 Promotes Brain Oligodendrogenesis during Myelination and Remyelination
Nakatani H, Martin E, Hassani H, Clavairoly A, Maire CL, Viadieu A, Kerninon C, Delmasure A, Frah M, Weber M, Nakafuku M, Zalc B, Thomas JL, Guillemot F, Nait-Oumesmar B, Parras C. Ascl1/Mash1 Promotes Brain Oligodendrogenesis during Myelination and Remyelination. Journal Of Neuroscience 2013, 33: 9752-9768. PMID: 23739972, PMCID: PMC3892435, DOI: 10.1523/jneurosci.0805-13.2013.Peer-Reviewed Original ResearchConceptsOligodendrocyte precursor cellsNeonatal periodCortical oligodendrocyte precursor cellsOligodendrocyte developmentCortical subventricular zoneSubventricular zone progenitorsMultiple sclerosis lesionsMyelin-forming cellsPostnatal cortexRemyelination processFocal demyelinationCorpus callosumSubventricular zoneOPC differentiationPostnatal brainMouse modelAscl1 functionOligodendrogenesisOPC developmentSclerosis lesionsASCL1 expressionCortical progenitorsRemyelinationProneural transcription factorsOligodendrocytesIron Is a Sensitive Biomarker for Inflammation in Multiple Sclerosis Lesions
Mehta V, Pei W, Yang G, Li S, Swamy E, Boster A, Schmalbrock P, Pitt D. Iron Is a Sensitive Biomarker for Inflammation in Multiple Sclerosis Lesions. PLOS ONE 2013, 8: e57573. PMID: 23516409, PMCID: PMC3597727, DOI: 10.1371/journal.pone.0057573.Peer-Reviewed Original ResearchConceptsMyelin-laden macrophagesMS patientsSecondary progressive MS patientsProgressive MS patientsSecondary progressive MSMultiple sclerosis patientsMacrophages/microgliaWhite matter lesionsHuman macrophage culturesIron-containing macrophagesMultiple sclerosis lesionsImportant clinical informationHuman cultured macrophagesActive relapsingDemyelinating lesionsDisease-relevant processesProgressive MSDemyelinated lesionsSclerosis patientsMultiple sclerosisMatter lesionsM1 polarizationImmunohistochemical examinationMyelin phagocytosisProinflammatory polarization
2012
Limiting multiple sclerosis related axonopathy by blocking Nogo receptor and CRMP-2 phosphorylation
Petratos S, Ozturk E, Azari MF, Kenny R, Lee JY, Magee KA, Harvey AR, McDonald C, Taghian K, Moussa L, Aui P, Siatskas C, Litwak S, Fehlings MG, Strittmatter SM, Bernard CC. Limiting multiple sclerosis related axonopathy by blocking Nogo receptor and CRMP-2 phosphorylation. Brain 2012, 135: 1794-1818. PMID: 22544872, PMCID: PMC3589918, DOI: 10.1093/brain/aws100.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnalysis of VarianceAnimalsAntibodiesAxonsCD3 ComplexCell Line, TumorDemyelinating DiseasesDisease Models, AnimalEncephalomyelitis, Autoimmune, ExperimentalFemaleGene Expression RegulationGlycoproteinsGPI-Linked ProteinsGreen Fluorescent ProteinsHumansImmunoprecipitationIntercellular Signaling Peptides and ProteinsMaleMiceMice, Inbred C57BLMice, KnockoutMiddle AgedMultiple SclerosisMutationMyelin ProteinsMyelin-Oligodendrocyte GlycoproteinNerve DegenerationNerve Tissue ProteinsNeuroblastomaNeurofilament ProteinsNogo Receptor 1Optic NervePeptide FragmentsPhosphorylationReceptors, Cell SurfaceRetinal Ganglion CellsSeverity of Illness IndexSilver StainingSpinal Cordtau ProteinsTime FactorsTransduction, GeneticTubulinConceptsExperimental autoimmune encephalomyelitisAutoimmune encephalomyelitisMyelin oligodendrocyte glycoproteinMultiple sclerosisAxonal degenerationSpinal cordChronic active multiple sclerosis lesionsOptic nerve axonal degenerationNogo-66 receptor 1CRMP-2Axonal growth inhibitorsCollapsin response mediator protein 2Improved clinical outcomesSpinal cord neuronsRetinal ganglion cellsResponse mediator protein 2Central nervous systemViable therapeutic targetAdeno-associated viral vectorMultiple sclerosis lesionsClinical outcomesOptic nerveCord neuronsOligodendrocyte glycoproteinGanglion cells
2010
Imaging Cortical Lesions in Multiple Sclerosis With Ultra–High-Field Magnetic Resonance Imaging
Pitt D, Boster A, Pei W, Wohleb E, Jasne A, Zachariah CR, Rammohan K, Knopp MV, Schmalbrock P. Imaging Cortical Lesions in Multiple Sclerosis With Ultra–High-Field Magnetic Resonance Imaging. JAMA Neurology 2010, 67: 812-818. PMID: 20625086, DOI: 10.1001/archneurol.2010.148.Peer-Reviewed Original ResearchConceptsCortical lesion detectionCortical lesionsMultiple sclerosisLesion typeCortical multiple sclerosis lesionsBrain tissueCortical lesion typesMultiple sclerosis tissueAutopsied brain tissueInversion recoveryMagnetic resonance imagingMultiple sclerosis lesionsCorresponding histological sectionsLesion detectionMyelin basic proteinHypointense ringUndetected lesionsImmunohistochemical analysisSclerosis lesionsLesionsResonance imagingSensitivity of T2SclerosisMagnetic resonance imagesLesion visibility
2005
29 Blocking the Axonal Injury Cascade Neuroprotection in Multiple Sclerosis and Its Models
Waxman S, Lo A. 29 Blocking the Axonal Injury Cascade Neuroprotection in Multiple Sclerosis and Its Models. 2005, 435-449. DOI: 10.1016/b978-012738761-1/50030-4.Peer-Reviewed Original ResearchExperimental autoimmune encephalomyelitisWhite matter injuryAxonal injuryChannel blockersNitric oxideNon-glucocorticoid steroidsCalcium channel blockersHuman multiple sclerosis lesionsSodium channel blockersMultiple sclerosis lesionsEffects of drugsAutoimmune encephalomyelitisMS pathologyOptic nerveMultiple sclerosisFunctional outcomeNeuroprotective agentsΓ-aminobutyric acidHypoxic injuryPathological evidenceSpinal nervesSpinal cordAdrenergic receptorsVivo preparationSclerosis lesions
2004
4 Molecular Mimicry in Multiple Sclerosis Role of MHC-Altered Peptide Ligands (MAPL)
Lim D, Hafler D. 4 Molecular Mimicry in Multiple Sclerosis Role of MHC-Altered Peptide Ligands (MAPL). 2004, 45-55. PMCID: PMC7151874, DOI: 10.1016/b978-044451271-0.50004-1.Peer-Reviewed Original ResearchMicrobial peptidesMolecular mimicryMimicry hypothesisMolecular mechanismsMultiple sclerosisMolecular mimicry hypothesisDisease entityMajor pathogenic mechanismAttractive hypothesisMimicryPeptide ligandsMyelin proteinsSingle disease entityPathogenic mechanismsMultiple sclerosis lesionsCross-reacting antigenDirect evidenceDisease stageT cellsPeptidesSclerosis lesionsProteinDifferent disordersImmunological studiesMechanism
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