Featured Publications
Targeted two-photon chemical apoptotic ablation of defined cell types in vivo
Hill RA, Damisah EC, Chen F, Kwan AC, Grutzendler J. Targeted two-photon chemical apoptotic ablation of defined cell types in vivo. Nature Communications 2017, 8: 15837. PMID: 28621306, PMCID: PMC5501159, DOI: 10.1038/ncomms15837.Peer-Reviewed Original ResearchConceptsCell deathNucleic acid-binding dyeVivo functional consequencesCell type differencesPattern of apoptosisDose-dependent apoptosisComplex organismsMitochondrial fissionFluorescent proteinUnderstanding of mechanismsCell typesCell clearanceFunctional consequencesIndividual cellsDiverse organsDistinct populationsApoptosisMouse brainZebrafishMajor bottleneckNeural plasticityOrganismsSpeciesProteinApoptoticA 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 StatementsConceptsRegional 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 vesselsLifelong cortical myelin plasticity and age-related degeneration in the live mammalian brain
Hill RA, Li AM, Grutzendler J. Lifelong cortical myelin plasticity and age-related degeneration in the live mammalian brain. Nature Neuroscience 2018, 21: 683-695. PMID: 29556031, PMCID: PMC5920745, DOI: 10.1038/s41593-018-0120-6.Peer-Reviewed Original ResearchConceptsMyelin degenerationYears of ageAge-related degenerationMyelin plasticityMyelin remodelingNeural processing speedBrain pathogenesisOligodendrocyte deathUnmyelinated axonsAxonal myelinMyelin coverageStructural remodelingMouse cortexMammalian brainPeak myelinationOligodendrocyte generationIndividual axonsMyelinating oligodendrocytesMyelin distributionDegenerationMyelin internodesNetwork homeostasisAxonsStructural plasticityRemodelingATP 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 responseMicroglia constitute a barrier that prevents neurotoxic protofibrillar Aβ42 hotspots around plaques
Condello C, Yuan P, Schain A, Grutzendler J. Microglia constitute a barrier that prevents neurotoxic protofibrillar Aβ42 hotspots around plaques. Nature Communications 2015, 6: 6176. PMID: 25630253, PMCID: PMC4311408, DOI: 10.1038/ncomms7176.Peer-Reviewed Original ResearchAngiophagy 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 organsOcclusionLungExtravasationKidneyEndotheliumMicrovasculatureWashoutLabel-free in vivo imaging of myelinated axons in health and disease with spectral confocal reflectance microscopy
Schain AJ, Hill RA, Grutzendler J. Label-free in vivo imaging of myelinated axons in health and disease with spectral confocal reflectance microscopy. Nature Medicine 2014, 20: 443-449. PMID: 24681598, PMCID: PMC3981936, DOI: 10.1038/nm.3495.Peer-Reviewed Original ResearchIn 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 ResearchAngiophagy
Grutzendler J. Angiophagy. Stroke 2013, 44: s84-s86. PMID: 23709741, DOI: 10.1161/strokeaha.112.678730.Peer-Reviewed Original ResearchEmbolus extravasation is an alternative mechanism for cerebral microvascular recanalization
Lam CK, Yoo T, Hiner B, Liu Z, Grutzendler J. Embolus extravasation is an alternative mechanism for cerebral microvascular recanalization. Nature 2010, 465: 478-482. PMID: 20505729, PMCID: PMC2879083, DOI: 10.1038/nature09001.Peer-Reviewed Original ResearchConceptsAge-related cognitive disordersBlood vesselsPossible therapeutic targetAged miceBlood flowTherapeutic targetCognitive disordersMice showBlood clotsEndothelial cellsUnderlying endotheliumMicroemboliExtravasationFibrinolysisVesselsRecanalizationEmboliPatientsStrokeEndotheliumMiceBloodBrainWeeksClotsRegional Blood Flow in the Normal and Ischemic Brain Is Controlled by Arteriolar Smooth Muscle Cell Contractility and Not by Capillary Pericytes
Hill RA, Tong L, Yuan P, Murikinati S, Gupta S, Grutzendler J. Regional Blood Flow in the Normal and Ischemic Brain Is Controlled by Arteriolar Smooth Muscle Cell Contractility and Not by Capillary Pericytes. Neuron 2015, 87: 95-110. PMID: 26119027, PMCID: PMC4487786, DOI: 10.1016/j.neuron.2015.06.001.Peer-Reviewed Original ResearchConceptsSmooth muscle cellsCerebral blood flowBlood flowCapillary pericytesArteriolar smooth muscle cellsBlood flow regulationRegional blood flowNormal brain functionSmooth muscle actinSmooth muscle cell contractilityMuscle cell contractilityPericyte constrictionIschemic brainBrain ischemiaMicrovascular occlusionNeurovascular couplingMicrovascular diametersWhisker stimulationMuscle actinMuscle cellsBrain functionMajor causePathological conditionsPericytesVascular tree
2022
KCNJ8/ABCC9-containing K-ATP channel modulates brain vascular smooth muscle development and neurovascular coupling
Ando K, Tong L, Peng D, Vázquez-Liébanas E, Chiyoda H, He L, Liu J, Kawakami K, Mochizuki N, Fukuhara S, Grutzendler J, Betsholtz C. KCNJ8/ABCC9-containing K-ATP channel modulates brain vascular smooth muscle development and neurovascular coupling. Developmental Cell 2022, 57: 1383-1399.e7. PMID: 35588738, DOI: 10.1016/j.devcel.2022.04.019.Peer-Reviewed Original ResearchConceptsK-ATP channel functionVascular smooth muscle cell differentiationChannel functionSmooth muscle cell differentiationMuscle cell differentiationVascular smooth muscle developmentSmooth muscle developmentVSMC developmentHuman central nervous system disordersMuscle developmentVSMC differentiationCentral nervous system disordersCell differentiationChemical inhibitionVoltage-dependent calcium channelsATP-sensitive potassium channelsFunction mutationsCell progenitorsK-ATP channelsCerebral blood flowCell culture modelMolecular causesNervous system disordersIntracellular CaVasoconstrictive capacity
2021
Unlocking Pericyte Function in the Adult Blood Brain Barrier One Cell at a Time
Nicoli S, Grutzendler J. Unlocking Pericyte Function in the Adult Blood Brain Barrier One Cell at a Time. Circulation Research 2021, 128: 511-512. PMID: 33600230, PMCID: PMC7928238, DOI: 10.1161/circresaha.121.318799.Peer-Reviewed Original ResearchCaveolae-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
2019
Cellular Control of Brain Capillary Blood Flow: In Vivo Imaging Veritas
Grutzendler J, Nedergaard M. Cellular Control of Brain Capillary Blood Flow: In Vivo Imaging Veritas. Trends In Neurosciences 2019, 42: 528-536. PMID: 31255380, PMCID: PMC7386067, DOI: 10.1016/j.tins.2019.05.009.Peer-Reviewed Original ResearchConceptsCapillary blood flowBlood flowBrain capillary blood flowRegional cerebral blood flowCerebral blood flowRed blood cell deformabilityBlood cell deformabilityMicrovascular perfusionNeurovascular couplingMicrovascular flowBrain metabolitesMural cellsLevel-dependent changesNeural activationVessel diameterMicrovascular treeNeural activityCell deformabilityCell controlDirect visualizationMethodological standardsVasomotilityPerfusionControlUncovering the biology of myelin with optical imaging of the live brain
Hill RA, Grutzendler J. Uncovering the biology of myelin with optical imaging of the live brain. Glia 2019, 67: 2008-2019. PMID: 31033062, PMCID: PMC6744352, DOI: 10.1002/glia.23635.Peer-Reviewed Original Research
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
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