2023
PET Imaging of Rho‐Associated Protein Kinase 2 in A Mouse Model of Alzheimer’s Disease
Zheng C, Nicholson L, Chen B, Toyonaga T, Liu M, Strittmatter S, Carson R, Huang Y, Cai Z. PET Imaging of Rho‐Associated Protein Kinase 2 in A Mouse Model of Alzheimer’s Disease. Alzheimer's & Dementia 2023, 19 DOI: 10.1002/alz.081695.Peer-Reviewed Original ResearchAPP/PS1 micePS1 miceWT miceCentral nervous systemTime-activity curvesAlzheimer's diseaseAPP/PS1 transgenic miceAPP/PS1 transgenic AD miceMouse brainAge-matched WT controlsPS1 transgenic miceAPP/PS1Transgenic AD miceDynamic PET imaging dataROCK2 protein expressionAD drug discoveryHigh tracer uptakeMin post injectionPET imaging resultsExpression levelsReference tissue model 2PET imaging dataProtein expression levelsAD miceRegional time-activity curvesDevelopment of neural repair therapy for chronic spinal cord trauma: soluble Nogo receptor decoy from discovery to clinical trial
Howard E, Strittmatter S. Development of neural repair therapy for chronic spinal cord trauma: soluble Nogo receptor decoy from discovery to clinical trial. Current Opinion In Neurology 2023, 36: 516-522. PMID: 37865850, PMCID: PMC10841037, DOI: 10.1097/wco.0000000000001205.Peer-Reviewed Original ResearchConceptsSpinal cord injuryChronic cervical spinal cord injuryCervical spinal cord injuryRecent clinical trialsCentral nervous systemClinical trialsAnimal studiesNeural repairChronic spinal cord injuryIncomplete spinal cord injuryTraumatic spinal cord injuryAdult mammalian central nervous systemContusion spinal cord injuryTreatment-naïve patientsSpinal cord traumaMammalian central nervous systemNeural repair therapiesUpper extremity strengthNonhuman primate studiesReceptor 1 pathwayNeurological recoveryNeurological deficitsCord traumaMedical therapyChronic stage
2022
Rabphilin3A reduces integrin-dependent growth cone signaling to restrict axon regeneration after trauma
Sekine Y, Kannan R, Wang X, Strittmatter SM. Rabphilin3A reduces integrin-dependent growth cone signaling to restrict axon regeneration after trauma. Experimental Neurology 2022, 353: 114070. PMID: 35398339, PMCID: PMC9555232, DOI: 10.1016/j.expneurol.2022.114070.Peer-Reviewed Original ResearchConceptsAxon regenerationModerate spinal cord contusion injurySpinal cord contusion injuryTraumatic spinal cord injuryAdult mammalian central nervous systemGrowth conesRetinal ganglion cell axonsOptic nerve crushSpinal cord crush injuryGanglion cell axonsSpinal cord injuryMammalian central nervous systemCentral nervous systemCorticospinal axon regenerationContusion injuryAxonal sproutingCrush injuryNerve crushAxonal growth conesCord injuryAxon sproutingCell axonsProximal bodyNervous systemNeural repair
2018
Diltiazem Promotes Regenerative Axon Growth
Huebner EA, Budel S, Jiang Z, Omura T, Ho TS, Barrett L, Merkel JS, Pereira LM, Andrews NA, Wang X, Singh B, Kapur K, Costigan M, Strittmatter SM, Woolf CJ. Diltiazem Promotes Regenerative Axon Growth. Molecular Neurobiology 2018, 56: 3948-3957. PMID: 30232777, PMCID: PMC6424671, DOI: 10.1007/s12035-018-1349-5.Peer-Reviewed Original ResearchConceptsL-type calcium channel blockerDorsal root gangliaCentral nervous systemChondroitin sulfate proteoglycanAxon regenerationMouse dorsal root gangliaAdult central nervous systemHuman sensory neuronsCalcium channel blockersSpinal cord injuryRat cortical culturesCord injuryAxonal regrowthRoot gangliaCortical culturesChannel blockersRegenerative propensityRegenerative axon growthSensory neuronsNervous systemPharmacological enhancersAxon growthPermanent lossSulfate proteoglycanAxotomy
2017
Regulation of axonal regeneration by the level of function of the endogenous Nogo receptor antagonist LOTUS
Hirokawa T, Zou Y, Kurihara Y, Jiang Z, Sakakibara Y, Ito H, Funakoshi K, Kawahara N, Goshima Y, Strittmatter SM, Takei K. Regulation of axonal regeneration by the level of function of the endogenous Nogo receptor antagonist LOTUS. Scientific Reports 2017, 7: 12119. PMID: 28935984, PMCID: PMC5608707, DOI: 10.1038/s41598-017-12449-6.Peer-Reviewed Original ResearchConceptsSpinal cord injuryOptic nerve crushAxonal regenerationMotor recoveryNerve crushNeural repairRetinal ganglion cell axonal regenerationAdult mammalian central nervous systemIntrinsic motor recoverySpontaneous neural repairAxonal growth inhibitorsMammalian central nervous systemCentral nervous systemNon-permissive environmentLevel of functionUntreated miceFunctional recoveryCord injuryReceptor antagonistNeuronal overexpressionNervous systemGenetic deletionViral overexpressionCrushInhibitorsIdentification of Intrinsic Axon Growth Modulators for Intact CNS Neurons after Injury
Fink KL, López-Giráldez F, Kim IJ, Strittmatter SM, Cafferty WB. Identification of Intrinsic Axon Growth Modulators for Intact CNS Neurons after Injury. Cell Reports 2017, 18: 2687-2701. PMID: 28297672, PMCID: PMC5389739, DOI: 10.1016/j.celrep.2017.02.058.Peer-Reviewed Original ResearchConceptsSpinal cord injuryCentral nervous systemFunctional recoveryIntact neuronsAdult mammalian central nervous systemPartial spinal cord injuryInjury-induced sproutingUnilateral brainstem lesionsGreater functional recoverySpontaneous functional recoveryCorticospinal motor neuronsCorticospinal tract axonsMammalian central nervous systemWild-type miceNew synapse formationGrowth modulatorsAdjacent injuryBrainstem lesionsCord injuryFunctional deficitsIntact circuitryCNS neuronsMotor neuronsCircuit plasticityNervous system
2016
Rewiring the spinal cord: Direct and indirect strategies
Dell’Anno M, Strittmatter SM. Rewiring the spinal cord: Direct and indirect strategies. Neuroscience Letters 2016, 652: 25-34. PMID: 28007647, PMCID: PMC5466898, DOI: 10.1016/j.neulet.2016.12.002.Peer-Reviewed Original ResearchConceptsSpinal cordNeural stem cellsNeural stem cell-derived neuronsTransplanted neural stem cellsNeural stem cell transplantationAdult central nervous systemLong-distance axonsNeutralization of myelinRecipient spinal cordStem cell transplantationSpinal cord injuryStem cell-derived neuronsCentral nervous systemCell-derived neuronsIntrinsic regenerative capacityPoor intrinsic regenerative capacityStem cellsNeurologic recoveryAxonal sproutingSecondary complicationsCell transplantationCord injuryAxonal regenerationGlial cellsAdult brain
2014
Progressive retinal degeneration and accumulation of autofluorescent lipopigments in Progranulin deficient mice
Hafler BP, Klein ZA, Zhou Z, Strittmatter SM. Progressive retinal degeneration and accumulation of autofluorescent lipopigments in Progranulin deficient mice. Brain Research 2014, 1588: 168-174. PMID: 25234724, PMCID: PMC4254024, DOI: 10.1016/j.brainres.2014.09.023.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCells, CulturedElectroretinographyGranulinsImmunohistochemistryIntercellular Signaling Peptides and ProteinsMice, Inbred C57BLMice, KnockoutMicroscopy, ConfocalNeuronal Ceroid-LipofuscinosesOptical ImagingPhotoreceptor Cells, VertebrateProgranulinsRetinal DegenerationRetinal Ganglion CellsConceptsProgranulin-deficient miceNeuronal ceroid lipofuscinosisAdult-onset neuronal ceroid lipofuscinosisDeficient miceRetinal degenerationCeroid lipofuscinosisRetinal ganglion cellsCentral nervous systemAutofluorescent storage materialMotor dysfunctionNeuropathological analysisGanglion cellsVision lossOptic atrophyEarly deathAutofluorescent lipopigmentsClinical observationsNervous systemDegenerative pathologyMiceDegenerationHomozygous mutationAutofluorescent materialPatientsNeuronsThe Nogo Receptor NgR1 Mediates Infection by Mammalian Reovirus
Konopka-Anstadt JL, Mainou BA, Sutherland DM, Sekine Y, Strittmatter SM, Dermody TS. The Nogo Receptor NgR1 Mediates Infection by Mammalian Reovirus. Cell Host & Microbe 2014, 15: 681-691. PMID: 24922571, PMCID: PMC4100558, DOI: 10.1016/j.chom.2014.05.010.Peer-Reviewed Original ResearchConceptsCentral nervous systemReceptor NgR1Reovirus infectionExpression of NgR1Primary cortical neuronsDistinct cell surface moleculesJunctional adhesion molecule ASoluble NgR1Cell surface moleculesNeurotropic virusesCortical neuronsMammalian reovirusesNonsusceptible cellsNervous systemNgR1Null miceSystemic spreadInfectionIndependent receptorsMultiple receptorsReovirus replicationInitial siteReovirus virionsNeuronsReceptors
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 cellsMyelin-derived ephrinB3 restricts axonal regeneration and recovery after adult CNS injury
Duffy P, Wang X, Siegel CS, Tu N, Henkemeyer M, Cafferty WB, Strittmatter SM. Myelin-derived ephrinB3 restricts axonal regeneration and recovery after adult CNS injury. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 5063-5068. PMID: 22411787, PMCID: PMC3323955, DOI: 10.1073/pnas.1113953109.Peer-Reviewed Original ResearchConceptsAxonal regenerationAxonal growthAdult mammalian central nervous systemAdult CNS injuryDorsal hemisection injurySpinal cord injuryMammalian central nervous systemWild-type miceCentral nervous systemCaudal spinal cordAxonal guidance cuesAxonal growth inhibitionLater time pointsGreater spasticityCNS traumaHemisection injuryCrush siteOptic nerveNeurological functionCNS injuryCord injuryTransection modelGrowth restrictionSpinal cordTraumatic injurySmall-molecule-induced Rho-inhibition: NSAIDs after spinal cord injury
Kopp MA, Liebscher T, Niedeggen A, Laufer S, Brommer B, Jungehulsing GJ, Strittmatter SM, Dirnagl U, Schwab JM. Small-molecule-induced Rho-inhibition: NSAIDs after spinal cord injury. Cell And Tissue Research 2012, 349: 119-132. PMID: 22350947, PMCID: PMC3744771, DOI: 10.1007/s00441-012-1334-7.Peer-Reviewed Original ResearchConceptsSpinal cord injuryCentral nervous systemAxonal plasticityCord injuryAcute spinal cord injuryExperimental spinal cord injuryNon-steroid anti-inflammatory drugsRelevant SCI modelGrowth-inhibitory environmentCNS injury modelsAnti-inflammatory drugsOligodendrocyte myelin glycoproteinRhoA inhibitionRepulsive guidance moleculeMotor recoveryAxonal sproutingPreclinical evidenceFunctional recoveryLocomotor recoverySCI modelChondroitin sulfate proteoglycanCNS injuryNeurofunctional outcomeGrowth cone collapsePossible clinical translation
2009
Axon Regeneration in the Peripheral and Central Nervous Systems
Huebner EA, Strittmatter SM. Axon Regeneration in the Peripheral and Central Nervous Systems. Results And Problems In Cell Differentiation 2009, 48: 305-360. PMID: 19582408, PMCID: PMC2846285, DOI: 10.1007/400_2009_19.Peer-Reviewed Original ResearchConceptsCentral nervous systemPeripheral nervous systemSpinal cord injuryNervous systemAxon regenerationLong-distance axon regenerationMature mammalian central nervous systemMammalian peripheral nervous systemSubstantial functional recoveryMammalian central nervous systemTraumatic brain injuryIntrinsic growth capacityFunctional recoveryCord injuryAxonal disconnectionFunctional deficitsBrain injuryRelated conditionsInjuryRegenerative successExtracellular moleculesGrowth capacityStroke
2007
Nogo receptor interacts with brain APP and Abeta to reduce pathologic changes in Alzheimer's transgenic mice.
Park JH, Strittmatter SM. Nogo receptor interacts with brain APP and Abeta to reduce pathologic changes in Alzheimer's transgenic mice. Current Alzheimer Research 2007, 4: 568-70. PMID: 18220524, PMCID: PMC2846284, DOI: 10.2174/156720507783018235.Peer-Reviewed Original ResearchConceptsTransgenic miceAlzheimer's diseasePlaque depositionAdult central nervous systemAlzheimer's transgenic miceNogo-66 receptorAmyloid β plaquesCentral nervous systemAxonal sproutingAβ accumulationΒ plaquesDystrophic neuritesPathologic changesNogo receptorNervous systemBrain APPDiseasePotential mechanistic basisMiceExpression increasesNGR modificationReceptorsNeurite responseNGRMechanistic basis
2006
Delayed Nogo receptor therapy improves recovery from spinal cord contusion
Wang X, Baughman KW, Basso DM, Strittmatter SM. Delayed Nogo receptor therapy improves recovery from spinal cord contusion. Annals Of Neurology 2006, 60: 540-549. PMID: 16958113, PMCID: PMC2855693, DOI: 10.1002/ana.20953.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxonsDisease Models, AnimalDrug Administration ScheduleDrug Therapy, CombinationFemaleInjections, IntraventricularLocomotionMyelin SheathPhosphodiesterase InhibitorsPyramidal TractsRatsRats, Sprague-DawleyRecombinant Fusion ProteinsRecovery of FunctionRolipramSpinal Cord InjuriesTime FactorsTreatment OutcomeConceptsSpinal cord contusionCord contusionSpinal cordAxonal growthHuman spinal cord injuryAdult central nervous systemBresnahan locomotor scoresFc treatment groupVehicle-treated groupTime of injuryCyclic adenosine monophosphate phosphodiesterase inhibitorSpinal cord injuryRecovery of locomotionAddition of rolipramRostral spinal cordCentral nervous systemCaudal spinal cordBeneficial behavioral effectsDelayed therapyNeurological recoveryRaphespinal axonsAcute therapyCorticospinal axonsLocomotor scoresIntracerebroventricular routeExtracellular regulators of axonal growth in the adult central nervous system
Liu BP, Cafferty WB, Budel SO, Strittmatter SM. Extracellular regulators of axonal growth in the adult central nervous system. Philosophical Transactions Of The Royal Society B Biological Sciences 2006, 361: 1593-1610. PMID: 16939977, PMCID: PMC1664666, DOI: 10.1098/rstb.2006.1891.Peer-Reviewed Original ResearchConceptsAxonal growth inhibitorsAxonal sproutingCNS injuryAdult CNSAxonal growthAdult central nervous systemAdult CNS injuryCentral nervous system functionRecovery of functionRobust axonal growthAstroglial scar formationAdult CNS axonsCentral nervous systemOligodendrocyte myelin glycoproteinNervous system functionNeurological functionPathological damageAxonal stabilityNervous systemScar formationAxonal receptorsNeuronal connectivityCNS axonsEphrin-B3Such interventions
2005
Effect of combined treatment with methylprednisolone and soluble Nogo‐66 receptor after rat spinal cord injury
Ji B, Li M, Budel S, Pepinsky RB, Walus L, Engber TM, Strittmatter SM, Relton JK. Effect of combined treatment with methylprednisolone and soluble Nogo‐66 receptor after rat spinal cord injury. European Journal Of Neuroscience 2005, 22: 587-594. PMID: 16101740, PMCID: PMC2846292, DOI: 10.1111/j.1460-9568.2005.04241.x.Peer-Reviewed Original ResearchMeSH KeywordsAnalysis of VarianceAnimalsAxonsBehavior, AnimalBiotinCells, CulturedChick EmbryoDextransDisease Models, AnimalDose-Response Relationship, DrugDrug InteractionsDrug Therapy, CombinationExploratory BehaviorFemaleGanglia, SpinalGPI-Linked ProteinsImmunoglobulin GLaminectomyMethylprednisoloneMyelin ProteinsMyelin SheathNerve RegenerationNeuronsNogo Receptor 1Pyramidal TractsRatsRats, Long-EvansReceptors, Cell SurfaceReceptors, PeptideRecombinant ProteinsRecovery of FunctionSpinal Cord InjuriesConceptsSpinal cord injuryCord injuryRat spinal cord injuryMP treatmentAdult central nervous systemThoracic dorsal hemisectionNovel experimental therapiesCorticospinal tract axonsRecovery of functionNogo-66 receptorNumber of axonsCentral nervous systemGrowth inhibitory effectsDorsal hemisectionBBB scoresAxonal sproutingFunctional recoveryBresnahan (BBB) scoringAxonal regenerationMotor neuronsExperimental therapiesMethylprednisoloneSynthetic glucocorticoidNervous systemAxonal growthChapter 26 Promoting the Regeneration of Axons within the Central Nervous System
Park J, Strittmatter S. Chapter 26 Promoting the Regeneration of Axons within the Central Nervous System. 2005, 433-xviii. DOI: 10.1016/b978-012738903-5/50027-8.Peer-Reviewed Original ResearchCentral nervous systemSpinal cord injuryNervous systemPeripheral nervous system axonsPNS Schwann cellsPermanent functional deficitsRegeneration of axonsRegenerative capacityLittle functional recoveryFunctional recoveryCell transplantationCord injuryAxonal regenerationFunctional deficitsPNS neuronsCNS gliaSchwann cellsAxon regenerationCombinatorial treatmentTransplantation studiesPromising targetAxonsKinase inhibitionInjuryProteoglycan digestion
2004
Regulating axon growth within the postnatal central nervous system
Hu F, Strittmatter SM. Regulating axon growth within the postnatal central nervous system. Seminars In Perinatology 2004, 28: 371-378. PMID: 15693393, DOI: 10.1053/j.semperi.2004.10.001.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxonsCentral Nervous SystemGPI-Linked ProteinsGrowth InhibitorsHumansHypoxiaIntracellular Signaling Peptides and ProteinsMembrane ProteinsMiceMyelin ProteinsMyelin-Associated GlycoproteinMyelin-Oligodendrocyte GlycoproteinNerve RegenerationNerve Tissue ProteinsNogo ProteinsNogo Receptor 1Receptor, Nerve Growth FactorReceptors, Cell SurfaceConceptsCentral nervous systemAxonal growthNervous systemNeuronal developmentAdult central nervous systemMature central nervous systemAxon growth inhibitorsPostnatal central nervous systemPotential therapeutic interventionsNew neuronal connectionsMyelin-derived proteinsAxonal sproutingDirect blockadeNgR proteinPostnatal brainNeuronal connectionsTherapeutic interventionsAxon growthDevelopmental hypoxiaReduced expressionMyelin proteinsHypoxic conditionsInhibitor pathwayImportant investigationCritical roleA new role for Nogo as a regulator of vascular remodeling
Acevedo L, Yu J, Erdjument-Bromage H, Miao RQ, Kim JE, Fulton D, Tempst P, Strittmatter SM, Sessa WC. A new role for Nogo as a regulator of vascular remodeling. Nature Medicine 2004, 10: 382-388. PMID: 15034570, DOI: 10.1038/nm1020.Peer-Reviewed Original ResearchConceptsSmooth muscle cellsVascular remodelingMuscle cellsVascular smooth muscle cellsCentral nervous systemIntact blood vesselsVascular injuryAxonal regenerationNeointimal proliferationMice promotesKnockout miceNervous systemVascular homeostasisFamily of proteinsVascular expansionEndothelial cellsBlood vesselsNogoNogo isoformsLipid raftsProteomic analysisN-terminusRemodelingGene transferCells