Featured Publications
TREM2 Haplodeficiency in Mice and Humans Impairs the Microglia Barrier Function Leading to Decreased Amyloid Compaction and Severe Axonal Dystrophy
Yuan P, Condello C, Keene CD, Wang Y, Bird TD, Paul SM, Luo W, Colonna M, Baddeley D, Grutzendler J. TREM2 Haplodeficiency in Mice and Humans Impairs the Microglia Barrier Function Leading to Decreased Amyloid Compaction and Severe Axonal Dystrophy. Neuron 2016, 90: 724-739. PMID: 27196974, PMCID: PMC4898967, DOI: 10.1016/j.neuron.2016.05.003.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseAxonal dystrophyAmyloid depositsAD-like miceHuman AD tissueLate-onset Alzheimer's diseaseNovel therapeutic strategiesTREM2 deficiencyTau hyperphosphorylationAD tissueMicroglia processesPharmacological modulationCompact plaquesTherapeutic strategiesHigh-resolution confocalTREM2 mutationsTREM2Barrier functionMiceGreater surface exposureAmyloid fibrilsHaplodeficiencyPlaquesDiseaseDystrophyLong-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 animalsTREM2 Haplodeficiency in Mice and Humans Impairs the Microglia Barrier Function Leading to Decreased Amyloid Compaction and Severe Axonal Dystrophy
Yuan P, Condello C, Keene CD, Wang Y, Bird TD, Paul SM, Luo W, Colonna M, Baddeley D, Grutzendler J. TREM2 Haplodeficiency in Mice and Humans Impairs the Microglia Barrier Function Leading to Decreased Amyloid Compaction and Severe Axonal Dystrophy. Neuron 2016, 92: 252-264. PMID: 27710785, DOI: 10.1016/j.neuron.2016.09.016.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 endotheliumMicroemboliExtravasationFibrinolysisVesselsRecanalizationEmboliPatientsStrokeEndotheliumMiceBloodBrainWeeksClots
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
2016
Label-free Confocal Reflectance and 2-photon Microscopy of Myelinated Axons and Microvasculature in Live Mice
Grutzendler J. Label-free Confocal Reflectance and 2-photon Microscopy of Myelinated Axons and Microvasculature in Live Mice. 2016, bw4b.2. DOI: 10.1364/brain.2016.bw4b.2.Peer-Reviewed Original Research
2013
Perturbed neural activity disrupts cerebral angiogenesis during a postnatal critical period
Whiteus C, Freitas C, Grutzendler J. Perturbed neural activity disrupts cerebral angiogenesis during a postnatal critical period. Nature 2013, 505: 407-411. PMID: 24305053, PMCID: PMC3947100, DOI: 10.1038/nature12821.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornBlood VesselsCapillariesCell ProliferationCerebral CortexCerebrovascular CirculationDendritic SpinesEndothelial CellsFemaleHypoxia, BrainInterneuronsMaleMiceMicrocirculationNeovascularization, PathologicNeovascularization, PhysiologicNeurogliaNeuronsNG-Nitroarginine Methyl EsterNitric OxideNitric Oxide SynthaseOxygenSignal TransductionTime FactorsVibrissae
2012
In Vivo Imaging of Cerebral Microvascular Plasticity from Birth to Death
Harb R, Whiteus C, Freitas C, Grutzendler J. In Vivo Imaging of Cerebral Microvascular Plasticity from Birth to Death. Cerebrovascular And Brain Metabolism Reviews 2012, 33: 146-156. PMID: 23093067, PMCID: PMC3597363, DOI: 10.1038/jcbfm.2012.152.Peer-Reviewed Original ResearchConceptsVascular stabilityYoung adult miceFirst postnatal monthDegenerative neurological disordersVessel formationHypoxia-induced angiogenesisCerebral functionPostnatal monthAdult brainAdult miceIntact brainMicrovascular plasticityNeurological disordersFirst monthMicrovessel formationOlder adultsMetabolic challengesTwo-photon microscopyNew vesselsBaseline turnoverLong-term adaptive responsesIndividual microvesselsMiceVivo patternBrain
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
Long-term two-photon transcranial imaging of synaptic structures in the living brain.
Grutzendler J, Gan WB. Long-term two-photon transcranial imaging of synaptic structures in the living brain. Cold Spring Harbor Protocols 2007, 2007: pdb.prot4766. PMID: 21357119, DOI: 10.1101/pdb.prot4766.Peer-Reviewed Original ResearchLiving brainNeurological disease modelsMouse brain areasIndividual dendritic spinesAxonal varicositiesFrontal cortexDendritic spinesBrain areasTherapeutic interventionsSynaptic structureFunctional changesNeuronal structuresTranscranial imagingTwo-photon microscopyDisease modelsBrainLiving mouseSensitive toolImaging approachMemory processesImagingSomatosensoryVaricositiesCortexMice