Featured Publications
A fluoro-Nissl dye identifies pericytes as distinct vascular mural cells during in vivo brain imaging
Damisah EC, Hill RA, Tong L, Murray KN, Grutzendler J. A fluoro-Nissl dye identifies pericytes as distinct vascular mural cells during in vivo brain imaging. Nature Neuroscience 2017, 20: 1023-1032. PMID: 28504673, PMCID: PMC5550770, DOI: 10.1038/nn.4564.Peer-Reviewed Original ResearchImaging and optogenetic modulation of vascular mural cells in the live brain
Tong L, Hill RA, Damisah EC, Murray KN, Yuan P, Bordey A, Grutzendler J. Imaging and optogenetic modulation of vascular mural cells in the live brain. Nature Protocols 2020, 16: 472-496. PMID: 33299155, DOI: 10.1038/s41596-020-00425-w.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAnimalsBlood CirculationBrainFemaleMaleMice, TransgenicMyocytes, Smooth MuscleOptical ImagingOptogeneticsPericytesConceptsRegional cerebral blood flowMural cellsBlood-brain barrier maintenanceCerebral ischemia mouse modelAge-related neurodegenerative diseasesCerebral blood flowSmooth muscle cell physiologyBrain blood vesselsIschemia mouse modelVascular mural cellsBrain microvesselsHigh-resolution intravital imagingVascular disordersMouse modelBlood flowMuscle cell physiologyTransgenic miceCalcium transientsAlzheimer's diseaseCalcium imagingCell subtypesBarrier maintenanceNeurodegenerative diseasesTwo-photon optogeneticsBlood vesselsLong-term dendritic spine stability in the adult cortex
Grutzendler J, Kasthuri N, Gan WB. Long-term dendritic spine stability in the adult cortex. Nature 2002, 420: 812-816. PMID: 12490949, DOI: 10.1038/nature01276.Peer-Reviewed Original ResearchConceptsLayer 5 pyramidal neuronsAxo-dendritic synapsesFilopodia-like dendritic protrusionsPrimary visual cortexVisual cortex developmentDendritic spine stabilityTwo-photon imaging techniquePyramidal neuronsDendritic specializationsAdult cortexYoung miceSpine eliminationAdult miceOne-month intervalsNervous systemTransgenic miceSpine stabilityVisual cortexDendritic protrusionsMammalian brainCortex developmentAdult animalsSpineMiceYoung animalsATP mediates rapid microglial response to local brain injury in vivo
Davalos D, Grutzendler J, Yang G, Kim JV, Zuo Y, Jung S, Littman DR, Dustin ML, Gan WB. ATP mediates rapid microglial response to local brain injury in vivo. Nature Neuroscience 2005, 8: 752-758. PMID: 15895084, DOI: 10.1038/nn1472.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsApyraseAstrocytesBrainBrain InjuriesCell CommunicationChemotaxisConnexinsGliosisGreen Fluorescent ProteinsMiceMice, TransgenicMicrogliaPhagocytosisPurinergic P2 Receptor AntagonistsReaction TimeReceptors, Purinergic P2Receptors, Purinergic P2Y1Signal TransductionConceptsRapid microglial responseMicroglial processesMicroglial responseBrain injuryG protein-coupled purinergic receptorsLocal brain injuryTraumatic brain injurySite of injuryPrincipal immune cellsPresence of apyraseParenchymal microgliaImmune cellsLocal injectionPurinergic receptorsBaseline motilityIntact brainTwo-photon imagingChannel inhibitorsMouse cortexInjuryExtracellular ATPMicrogliaEnzyme apyraseAstrocytesChemotactic responseAngiophagy Prevents Early Embolus Washout But Recanalizes Microvessels Through Embolus Extravasation
Grutzendler J, Murikinati S, Hiner B, Ji L, Lam CK, Yoo T, Gupta S, Hafler BP, Adelman RA, Yuan P, Rodriguez G. Angiophagy Prevents Early Embolus Washout But Recanalizes Microvessels Through Embolus Extravasation. Science Translational Medicine 2014, 6: 226ra31. PMID: 24598589, DOI: 10.1126/scitranslmed.3006585.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainCerebrovascular CirculationCoronary CirculationEmbolismFibrinFibrinolysisFundus OculiGreen Fluorescent ProteinsHemodynamicsHumansKidney TubulesLungMacrophagesMiceMice, TransgenicMicrocirculationMicrogliaMicroscopy, Electron, TransmissionMicrovesselsMonocytesPhagocytosisRetinaRetinal VesselsThrombosisConceptsBlood flow reestablishmentHours of occlusionVascular occlusive disordersDifferent therapeutic strategiesEmbolic occlusionOcclusive disordersVessel recanalizationAlveolar spaceTherapeutic strategiesTherapeutic targetHemodynamic pressureFibrinolytic systemPerivascular spacesEmboliRenal tubulesBlood clotsMicrovascular wallMost human organsOcclusionLungExtravasationKidneyEndotheliumMicrovasculatureWashoutIn vivo imaging of oligodendrocytes with sulforhodamine 101
Hill RA, Grutzendler J. In vivo imaging of oligodendrocytes with sulforhodamine 101. Nature Methods 2014, 11: 1081-1082. PMID: 25357236, PMCID: PMC4539948, DOI: 10.1038/nmeth.3140.Peer-Reviewed Original Research
2021
Caveolae-mediated Tie2 signaling contributes to CCM pathogenesis in a brain endothelial cell-specific Pdcd10-deficient mouse model
Zhou HJ, Qin L, Jiang Q, Murray KN, Zhang H, Li B, Lin Q, Graham M, Liu X, Grutzendler J, Min W. Caveolae-mediated Tie2 signaling contributes to CCM pathogenesis in a brain endothelial cell-specific Pdcd10-deficient mouse model. Nature Communications 2021, 12: 504. PMID: 33495460, PMCID: PMC7835246, DOI: 10.1038/s41467-020-20774-0.Peer-Reviewed Original ResearchConceptsCerebral cavernous malformationsCCM lesionsSmooth muscle actin-positive pericytesEndothelial cell lossRegions of brainCCM pathogenesisPost-capillary venulesCerebral hemorrhagePharmacological blockadeVascular abnormalitiesEC-specific deletionCavernous malformationsMouse modelCell lossMicrovascular bedGenetic deletionLesion formationLesionsVascular dynamicsBarrier functionMicrovascular structureTwo-photon microscopyTie2PathogenesisMice
2018
Activation of pial and dural macrophages and dendritic cells by cortical spreading depression
Schain AJ, Melo‐Carrillo A, Borsook D, Grutzendler J, Strassman AM, Burstein R. Activation of pial and dural macrophages and dendritic cells by cortical spreading depression. Annals Of Neurology 2018, 83: 508-521. PMID: 29394508, PMCID: PMC5965700, DOI: 10.1002/ana.25169.Peer-Reviewed Original ResearchConceptsBlood-brain barrierDendritic cellsDural macrophagesImmune cellsAnatomical relationshipMigratory dendritic cellsAnn NeurolTRPV1 axonsMeningeal nociceptorsHead painMigraine attacksNociceptor activationSubarachnoid spaceMeningeal macrophagesMacrophagesCortical eventsAxonsActivationAuraDuraDepressionMinutesCellsCellular eventsCSD
2017
Oxalate-curcumin–based probe for micro- and macroimaging of reactive oxygen species in Alzheimer’s disease
Yang J, Zhang X, Yuan P, Yang J, Xu Y, Grutzendler J, Shao Y, Moore A, Ran C. Oxalate-curcumin–based probe for micro- and macroimaging of reactive oxygen species in Alzheimer’s disease. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: 12384-12389. PMID: 29109280, PMCID: PMC5703278, DOI: 10.1073/pnas.1706248114.Peer-Reviewed Original ResearchConceptsCerebral amyloid angiopathyAD brainAlzheimer's diseaseTwo-photon imagingNIRF imagingAmyloid-beta plaquesROS levelsIrreversible neurodegenerative disorderAD pathological conditionsAge-related increaseReactive oxygen species levelsAmyloid angiopathyBeta plaquesOxygen species levelsDrug treatmentHealthy brainNeurodegenerative disordersDiseaseOxidative stressHigh ROS levelsPathological conditionsReactive oxygen speciesBrainFluorescence imaging probeOxygen species
2016
Attenuation of β-Amyloid Deposition and Neurotoxicity by Chemogenetic Modulation of Neural Activity
Yuan P, Grutzendler J. Attenuation of β-Amyloid Deposition and Neurotoxicity by Chemogenetic Modulation of Neural Activity. Journal Of Neuroscience 2016, 36: 632-641. PMID: 26758850, PMCID: PMC4710779, DOI: 10.1523/jneurosci.2531-15.2016.Peer-Reviewed Original ResearchMeSH KeywordsAlzheimer DiseaseAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAnimalsCalcium-Binding ProteinsClozapineDesigner DrugsDisease Models, AnimalHumansInsulysinLysosome-Associated Membrane GlycoproteinsMaleMiceMice, TransgenicMicrofilament ProteinsNerve Tissue ProteinsNeurotoxicity SyndromesPresenilin-1Proto-Oncogene Proteins c-fosStyrenesTransduction, GeneticConceptsAmyloid plaquesAlzheimer's diseaseNeuronal activityAmyloid depositionDisease miceNeural activityAD-like mouse modelNeural activity reductionΒ-amyloid depositionAlzheimer's disease miceNovel therapeutic approachesPotential therapeutic strategyViral-mediated deliveryChemogenetic modulationSynaptic lossAβ depositionSynaptic pathologyNeural hyperactivityAmyloid pathologyAxonal dystrophyDendritic fieldsChronic attenuationDesigner receptorsTherapeutic approachesMouse model
2014
A bifunctional curcumin analogue for two-photon imaging and inhibiting crosslinking of amyloid beta in Alzheimer's disease
Zhang X, Tian Y, Yuan P, Li Y, Yaseen MA, Grutzendler J, Moore A, Ran C. A bifunctional curcumin analogue for two-photon imaging and inhibiting crosslinking of amyloid beta in Alzheimer's disease. Chemical Communications 2014, 50: 11550-11553. PMID: 25134928, PMCID: PMC4617557, DOI: 10.1039/c4cc03731f.Peer-Reviewed Original ResearchModulation of oligodendrocyte generation during a critical temporal window after NG2 cell division
Hill RA, Patel KD, Goncalves CM, Grutzendler J, Nishiyama A. Modulation of oligodendrocyte generation during a critical temporal window after NG2 cell division. Nature Neuroscience 2014, 17: 1518-1527. PMID: 25262495, PMCID: PMC4275302, DOI: 10.1038/nn.3815.Peer-Reviewed Original Research
2011
Multicolor time-stamp reveals the dynamics and toxicity of amyloid deposition
Condello C, Schain A, Grutzendler J. Multicolor time-stamp reveals the dynamics and toxicity of amyloid deposition. Scientific Reports 2011, 1: 19. PMID: 22355538, PMCID: PMC3216507, DOI: 10.1038/srep00019.Peer-Reviewed Original ResearchConceptsPlaque burdenAmyloid depositionAlzheimer's diseaseAD mouse modelPlaque enlargementClinicopathological studyNeuritic dystrophyPathogenic rolePostmortem studiesAmyloid plaquesNew plaquesConsequent neurotoxicityMouse modelOld plaquesQuantitative confocal imagingCognitive statusPlaquesPlaque expansionOld animalsAmyloid-binding dyesNeurotoxicityDiseasePoor correlationBurdenCritical determinant
2010
Thinned-skull cranial window technique for long-term imaging of the cortex in live mice
Yang G, Pan F, Parkhurst CN, Grutzendler J, Gan WB. Thinned-skull cranial window technique for long-term imaging of the cortex in live mice. Nature Protocols 2010, 5: 201-208. PMID: 20134419, PMCID: PMC4690457, DOI: 10.1038/nprot.2009.222.Peer-Reviewed Original ResearchConceptsTwo-photon laser scanning microscopyHigh optical resolutionThinned-skull cranial windowImportant experimental toolOptical resolutionLiving brainCranial window techniqueLive miceLong-term imagingCranial windowExperimental toolInvasive approachAvoids exposureFunctional changesCortical structuresLongitudinal imagingPathological conditionsCortexBrainLaser scanning microscopyScanning microscopyMiceImagingMicroscopyResolution
2007
Various Dendritic Abnormalities Are Associated with Fibrillar Amyloid Deposits in Alzheimer's Disease
GRUTZENDLER J, HELMIN K, TSAI J, GAN W. Various Dendritic Abnormalities Are Associated with Fibrillar Amyloid Deposits in Alzheimer's Disease. Annals Of The New York Academy Of Sciences 2007, 1097: 30-39. PMID: 17413007, DOI: 10.1196/annals.1379.003.Peer-Reviewed Original ResearchConceptsAmyloid depositsAlzheimer's diseasePSAPP miceFibrillar amyloid depositsAmyloid depositionDendritic abnormalitiesHuman AD tissueFibrillar amyloid depositionHuman AD brainsTransgenic mouse modelHuman postmortem brainDystrophic neuritesSpine lossAD brainAD tissueAmyloid plaquesCommon abnormalityMouse modelPostmortem brainsDendritic spinesNeuronal circuitsVaricosity formationSynaptic structureDiseaseDendritic branches
2004
Fibrillar amyloid deposition leads to local synaptic abnormalities and breakage of neuronal branches
Tsai J, Grutzendler J, Duff K, Gan WB. Fibrillar amyloid deposition leads to local synaptic abnormalities and breakage of neuronal branches. Nature Neuroscience 2004, 7: 1181-1183. PMID: 15475950, DOI: 10.1038/nn1335.Peer-Reviewed Original ResearchConceptsFibrillar amyloid depositionAmyloid depositionAlzheimer's diseaseTransgenic mouse modelImportance of preventionFibrillar amyloid depositsSpine lossNearby axonsNeuronal labelingEarly clearanceLarge varicositiesAmyloid plaquesMouse modelNeuronal circuitryAmyloid depositsTwo-photon imagingNeuronal connectionsSynaptic abnormalitiesNeuronal branchesPermanent disruptionPlaquesDiseaseAtrophyVaricositiesPathogenesis