2021
In vivo evidence of differential frontal cortex metabolic abnormalities in progressive and relapsing‐remitting multiple sclerosis
Swanberg KM, Prinsen H, DeStefano K, Bailey M, Kurada AV, Pitt D, Fulbright RK, Juchem C. In vivo evidence of differential frontal cortex metabolic abnormalities in progressive and relapsing‐remitting multiple sclerosis. NMR In Biomedicine 2021, 34: e4590. PMID: 34318959, DOI: 10.1002/nbm.4590.Peer-Reviewed Original ResearchConceptsProgressive multiple sclerosisRelapsing-remitting multiple sclerosisMultiple sclerosis patientsMultiple sclerosisDisease durationSclerosis patientsRelapsing-remitting multiple sclerosis patientsSignificant negative correlationAvailable disease-modifying therapiesFrontal cortex metabolismH-MRS protocolDisease-modifying therapiesHealthy control adultsN-acetyl aspartateCross-sectional analysisCortex metabolismMetabolic abnormalitiesΓ-aminobutyric acidMetabolites glutamateFrontal cortexSclerosisNegative correlationControl adultsGABAProton MRS
2020
Differential expression of the T-cell inhibitor TIGIT in glioblastoma and MS
Lucca LE, Lerner BA, Park C, DeBartolo D, Harnett B, Kumar VP, Ponath G, Raddassi K, Huttner A, Hafler DA, Pitt D. Differential expression of the T-cell inhibitor TIGIT in glioblastoma and MS. Neurology Neuroimmunology & Neuroinflammation 2020, 7: e712. PMID: 32269065, PMCID: PMC7188477, DOI: 10.1212/nxi.0000000000000712.Peer-Reviewed Original ResearchConceptsTumor-infiltrating T cellsT cellsPD-1/PD-L1Anti-TIGIT therapyExpression of CD226Expression of TIGITPostmortem CNS tissueLymphocytes of patientsFresh surgical resectionsLigand CD155TIGIT expressionSurgical resectionPD-1PD-L1CNS diseaseHealthy controlsHealthy donorsLymphocytic expressionImmune responseCNS tissueMS lesionsTIGITImmune pathwaysPatientsGlioblastoma multiforme
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 stage
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 cellsCNS demyelination and enhanced myelin-reactive responses after ipilimumab treatment
Cao Y, Nylander A, Ramanan S, Goods BA, Ponath G, Zabad R, Chiang VL, Vortmeyer AO, Hafler DA, Pitt D. CNS demyelination and enhanced myelin-reactive responses after ipilimumab treatment. Neurology 2016, 86: 1553-1556. PMID: 26984943, PMCID: PMC5573201, DOI: 10.1212/wnl.0000000000002594.Peer-Reviewed Original Research
2015
Basal Ganglia Iron in Patients with Multiple Sclerosis Measured with 7T Quantitative Susceptibility Mapping Correlates with Inhibitory Control
Schmalbrock P, Prakash RS, Schirda B, Janssen A, Yang GK, Russell M, Knopp MV, Boster A, Nicholas JA, Racke M, Pitt D. Basal Ganglia Iron in Patients with Multiple Sclerosis Measured with 7T Quantitative Susceptibility Mapping Correlates with Inhibitory Control. American Journal Of Neuroradiology 2015, 37: 439-446. PMID: 26611996, PMCID: PMC7960135, DOI: 10.3174/ajnr.a4599.Peer-Reviewed Original Research
2014
Quantitative 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 tissueMyelinMicrogliaB cells populating the multiple sclerosis brain mature in the draining cervical lymph nodes
Stern JN, Yaari G, Vander Heiden JA, Church G, Donahue WF, Hintzen RQ, Huttner AJ, Laman JD, Nagra RM, Nylander A, Pitt D, Ramanan S, Siddiqui BA, Vigneault F, Kleinstein SH, Hafler DA, O'Connor KC. B cells populating the multiple sclerosis brain mature in the draining cervical lymph nodes. Science Translational Medicine 2014, 6: 248ra107. PMID: 25100741, PMCID: PMC4388137, DOI: 10.1126/scitranslmed.3008879.Peer-Reviewed Original ResearchConceptsCervical lymph nodesCentral nervous systemB cellsCerebrospinal fluidLymph nodesMultiple sclerosisLymphoid tissueCNS of patientsCNS B cellsAntigen-experienced B cellsMultiple sclerosis brainSecondary lymphoid tissuesB cell compartmentB cell trafficB cell maturationImmunomodulatory therapyImmune infiltratesPeripheral bloodInflammatory diseasesLymphocyte transmigrationPeripheral tissuesNervous systemMembers of clonesCell maturationCell traffic
2012
Detecting cortical lesions in multiple sclerosis at 7 T using white matter signal attenuation
Bluestein KT, Pitt D, Sammet S, Zachariah CR, Nagaraj U, Knopp MV, Schmalbrock P. Detecting cortical lesions in multiple sclerosis at 7 T using white matter signal attenuation. Magnetic Resonance Imaging 2012, 30: 907-915. PMID: 22578928, PMCID: PMC3402634, DOI: 10.1016/j.mri.2012.03.006.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAlgorithmsCerebral CortexFemaleHumansImage EnhancementImage Interpretation, Computer-AssistedMagnetic Resonance ImagingMaleMiddle AgedMultiple SclerosisNerve Fibers, MyelinatedReproducibility of ResultsSensitivity and SpecificitySubtraction TechniqueYoung Adult
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
2003
Glutamate uptake by oligodendrocytes
Pitt D, Nagelmeier IE, Wilson HC, Raine CS. Glutamate uptake by oligodendrocytes. Neurology 2003, 61: 1113-1120. PMID: 14581674, DOI: 10.1212/01.wnl.0000090564.88719.37.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAstrocytesAutoradiographyBiological TransportCell SurvivalCells, CulturedDose-Response Relationship, DrugExcitatory Amino Acid Transporter 1Excitatory Amino Acid Transporter 2FemaleGene ExpressionGlutamic AcidHumansIn Situ HybridizationMaleMiddle AgedMultiple SclerosisNeurotoxinsOligodendrogliaRNA, MessengerSpinal CordTritiumTumor Necrosis Factor-alphaConceptsMS white matterEAAT-2EAAT-1White matterExtracellular glutamateGlutamate uptakePredominant cellsHuman oligodendrocytesGlutamate removalProinflammatory cytokine tumor necrosisHuman white matterNormal human white matterCommon pathologic eventGlutamate transporter expressionGlutamate receptor expressionCytokine tumor necrosisExcess extracellular glutamateInhibited glutamate uptakeHigh extracellular glutamateSubsequent overstimulationExcitotoxic damageGlutamate excitotoxicityGlutamate clearanceTumor necrosisReceptor expression
2001
Multiple sclerosis: Altered glutamate homeostasis in lesions correlates with oligodendrocyte and axonal damage
Werner P, Pitt D, Raine C. Multiple sclerosis: Altered glutamate homeostasis in lesions correlates with oligodendrocyte and axonal damage. Annals Of Neurology 2001, 50: 169-180. PMID: 11506399, DOI: 10.1002/ana.1077.Peer-Reviewed Original ResearchConceptsMultiple sclerosisAxonal damageWhite matterGlutamate excitotoxicityGlutamate homeostasisMS lesionsGlutaminase expressionMS white matterInflammatory neurologic diseasesActive MS lesionsCNS cell typesOligodendroglial pathologyNoninflammatory conditionsDystrophic axonsNeurologic diseaseGLT-1Low-level expressionAnimal modelsGlutamate transportersHomeostasis contributesLesion correlatesGlutamate transportLesionsOligodendrocytesTherapeutic import