2019
Plexina2 and CRMP2 Signaling Complex Is Activated by Nogo-A-Liganded Ngr1 to Restrict Corticospinal Axon Sprouting after Trauma
Sekine Y, Algarate PT, Cafferty WBJ, Strittmatter SM. Plexina2 and CRMP2 Signaling Complex Is Activated by Nogo-A-Liganded Ngr1 to Restrict Corticospinal Axon Sprouting after Trauma. Journal Of Neuroscience 2019, 39: 3204-3216. PMID: 30804090, PMCID: PMC6788813, DOI: 10.1523/jneurosci.2996-18.2019.Peer-Reviewed Original ResearchConceptsCNS traumaNeural repairMouse cervical spinal cordSpinal cord traumaCervical spinal cordNon-neuronal cellsInteraction of NogoAxon growth inhibitionAxonal guidance mechanismsNeurological recoveryAxonal sproutingCNS pathwaysCord traumaFunctional recoveryAxon sproutingSpinal cordNgR1 functionUnilateral pyramidotomyAxon regenerationAdult traumaNgR1TraumaAxon growthNogoCytoplasmic mediators
2018
Human neuroepithelial stem cell regional specificity enables spinal cord repair through a relay circuit
Dell’Anno M, Wang X, Onorati M, Li M, Talpo F, Sekine Y, Ma S, Liu F, Cafferty WBJ, Sestan N, Strittmatter SM. Human neuroepithelial stem cell regional specificity enables spinal cord repair through a relay circuit. Nature Communications 2018, 9: 3419. PMID: 30143638, PMCID: PMC6109094, DOI: 10.1038/s41467-018-05844-8.Peer-Reviewed Original ResearchConceptsHuman neuroepithelial stem cellsNeuroepithelial stem cellsSpinal cord injury recoverySpinal cord injury resultsNeural stem cell transplantationStem cell transplantationSpinal cord repairOptimal cell typeStem cellsGrafted neuronsPersistent disabilityFunctional recoveryTherapeutic optionsCell transplantationHost axonsInjury resultsSpinal cordRobust engraftmentImmunodeficient miceInjury recoveryAnatomical sitesNeural elementsSpecific marker proteinsTransplantationAdherent conditions
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
Inhibition of Poly-ADP-Ribosylation Fails to Increase Axonal Regeneration or Improve Functional Recovery after Adult Mammalian CNS Injury
Wang X, Sekine Y, Byrne AB, Cafferty WB, Hammarlund M, Strittmatter SM. Inhibition of Poly-ADP-Ribosylation Fails to Increase Axonal Regeneration or Improve Functional Recovery after Adult Mammalian CNS Injury. ENeuro 2016, 3: eneuro.0270-16.2016. PMID: 28032120, PMCID: PMC5187389, DOI: 10.1523/eneuro.0270-16.2016.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxonsBenzimidazolesCells, CulturedCerebral CortexDisease Models, AnimalFemaleIsoenzymesMaleMice, 129 StrainMice, Inbred C57BLMice, TransgenicMotor ActivityNerve RegenerationOptic Nerve InjuriesPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) Polymerase InhibitorsRecovery of FunctionSpinal Cord InjuriesThoracic VertebraeConceptsOptic nerve crush injuryNerve crush injuryThoracic spinal cordAxonal regenerationSpinal cordDorsal hemisectionCrush injuryFunctional recoveryPARP inhibitorsMotor function recoveryRecovery of functionPoly (ADP-ribose) polymeraseClinical PARP inhibitorsNeurological recoveryShort hairpin RNACNS traumaCNS injuryFunction recoveryAxonal regrowthSystemic administrationPharmacodynamic actionAxon regenerationTraumatic damageTherapeutic efficacyNeurological trauma
2015
Gene-Silencing Screen for Mammalian Axon Regeneration Identifies Inpp5f (Sac2) as an Endogenous Suppressor of Repair after Spinal Cord Injury
Zou Y, Stagi M, Wang X, Yigitkanli K, Siegel CS, Nakatsu F, Cafferty WB, Strittmatter SM. Gene-Silencing Screen for Mammalian Axon Regeneration Identifies Inpp5f (Sac2) as an Endogenous Suppressor of Repair after Spinal Cord Injury. Journal Of Neuroscience 2015, 35: 10429-10439. PMID: 26203138, PMCID: PMC4510284, DOI: 10.1523/jneurosci.1718-15.2015.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxonsDisease Models, AnimalGene Knockdown TechniquesImmunohistochemistryInositol Polyphosphate 5-PhosphatasesMiceMice, Inbred C57BLMice, KnockoutNerve RegenerationPhosphoric Monoester HydrolasesRecovery of FunctionReverse Transcriptase Polymerase Chain ReactionSpinal Cord InjuriesConceptsSpinal cord injuryCord injuryEndogenous suppressorAxon regenerationNonoverlapping substrate specificityGenome-wide scaleHigh-throughput functional screensFunctional recoveryAxonal regenerationCNS axon repairSpinal cord injury researchDorsal hemisection injuryMammalian genesPI3K/AKT/mTOR pathwayCNS axon growthAKT/mTOR pathwayLipid phosphataseCorticospinal tract axonsCNS axon regenerationAdult mammalian CNSFunctional screenSubstrate specificityNovel suppressorShRNA resultsINPP5FPlasticity of Intact Rubral Projections Mediates Spontaneous Recovery of Function after Corticospinal Tract Injury
Siegel CS, Fink KL, Strittmatter SM, Cafferty WB. Plasticity of Intact Rubral Projections Mediates Spontaneous Recovery of Function after Corticospinal Tract Injury. Journal Of Neuroscience 2015, 35: 1443-1457. PMID: 25632122, PMCID: PMC4308593, DOI: 10.1523/jneurosci.3713-14.2015.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDesigner DrugsFunctional LateralityGene Expression RegulationGlial Fibrillary Acidic ProteinLocomotionMaleMiceMice, Inbred C57BLMice, TransgenicMuscle StrengthMyelin ProteinsNeuronal PlasticityNogo ProteinsPsychomotor DisordersPyramidal TractsRaphe NucleiRecovery of FunctionSpinal Cord InjuriesStereotyped BehaviorTime FactorsConceptsSpinal cord injurySpontaneous functional recoveryFunctional recoverySpontaneous recoveryIncomplete spinal cord injuryCorticospinal tract lesionsWeeks of lesionCorticospinal tract injuryNogo receptor 1Nucleus raphe magnusTract injuryRubrospinal projectionsTract lesionsCord injuryRaphe magnusCircuit rearrangementsAdult CNSCircuit plasticityLocomotor functionAdult micePharmacogenetic toolsRed nucleusRubral projectionReceptor 1Extensive sprouting
2014
Nogo limits neural plasticity and recovery from injury
Schwab ME, Strittmatter SM. Nogo limits neural plasticity and recovery from injury. Current Opinion In Neurobiology 2014, 27: 53-60. PMID: 24632308, PMCID: PMC4122629, DOI: 10.1016/j.conb.2014.02.011.Peer-Reviewed Original ResearchConceptsNeural repairCentral nervous system injuryOptic nerve injurySpinal cord traumaNervous system injuryExperience-dependent plasticityIschemic strokeNerve injuryCord traumaFunctional recoveryMultiple sclerosisSystem injuryReceptor NgR1Neural plasticityPhysiologic roleAxonal anatomyInjuryAdult mammalsMultiple studiesNogoNgR1Molecular studiesRepairSclerosisAntagonist
2012
PlexinA2 limits recovery from corticospinal axotomy by mediating oligodendrocyte-derived Sema6A growth inhibition
Shim SO, Cafferty WB, Schmidt EC, Kim BG, Fujisawa H, Strittmatter SM. PlexinA2 limits recovery from corticospinal axotomy by mediating oligodendrocyte-derived Sema6A growth inhibition. Molecular And Cellular Neuroscience 2012, 50: 193-200. PMID: 22564823, PMCID: PMC3383336, DOI: 10.1016/j.mcn.2012.04.007.Peer-Reviewed Original ResearchConceptsAxonal growthSpinal cordPellet retrieval taskCervical spinal cordWild-type miceContralateral gray matterAxon guidance cuesSevered fibersSprouted fibersAxonal sproutingCorticofugal projectionsFunctional recoveryBehavioral recoveryCNS injuryImpaired forelimbClass 3 semaphorinsCorticospinal fibersCorticospinal tractMedullary pyramidsSynaptic punctaInhibitor receptorsType miceUnilateral pyramidotomyNeuron inhibitionAdult traumaSmall-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
2011
Recovery from chronic spinal cord contusion after nogo receptor intervention
Wang X, Duffy P, McGee AW, Hasan O, Gould G, Tu N, Harel NY, Huang Y, Carson RE, Weinzimmer D, Ropchan J, Benowitz LI, Cafferty WB, Strittmatter SM. Recovery from chronic spinal cord contusion after nogo receptor intervention. Annals Of Neurology 2011, 70: 805-821. PMID: 22162062, PMCID: PMC3238798, DOI: 10.1002/ana.22527.Peer-Reviewed Original ResearchConceptsChronic spinal cord injurySpinal cord injuryContusion injuryCord injurySpinal cord contusion injuryCentral nervous system injuryBresnahan locomotor scoresOpen-field BassoSpinal hemisection injuryWeight-bearing statusSpinal cord contusionMonths of treatmentNervous system injuryMyelin-derived inhibitorCaudal spinal cordPositron emission tomographyNgR1 pathwayRaphespinal axonsSpinal contusionCord contusionHemisection injuryFunctional recoveryLocomotor scoresSystem injuryControl ratsMyelin associated inhibitors: A link between injury-induced and experience-dependent plasticity
Akbik F, Cafferty WB, Strittmatter SM. Myelin associated inhibitors: A link between injury-induced and experience-dependent plasticity. Experimental Neurology 2011, 235: 43-52. PMID: 21699896, PMCID: PMC3189418, DOI: 10.1016/j.expneurol.2011.06.006.Peer-Reviewed Original ResearchConceptsExperience-dependent plasticityAnatomical rearrangementsNogo-66 receptor 1Spinal cord injuryNeurologic recoveryFunctional recoveryInciting stimulusCNS injuryCord injuryAxonal regenerationAdult CNSInjury studiesAnimal modelsReceptor 1Common receptorPaired-ImmunoglobulinMyelinInhibitorsInjuryAnatomical growthCNSReceptorsWide spectrumExtracellular matrixGrowth inhibitorA Multi-domain Fragment of Nogo-A Protein Is a Potent Inhibitor of Cortical Axon Regeneration via Nogo Receptor 1*
Huebner EA, Kim BG, Duffy PJ, Brown RH, Strittmatter SM. A Multi-domain Fragment of Nogo-A Protein Is a Potent Inhibitor of Cortical Axon Regeneration via Nogo Receptor 1*. Journal Of Biological Chemistry 2011, 286: 18026-18036. PMID: 21454605, PMCID: PMC3093876, DOI: 10.1074/jbc.m110.208108.Peer-Reviewed Original ResearchConceptsMature cortical neuronsCortical neuronsNogo-66Axon regenerationReceptor 1Central nervous system injuryDorsal root ganglion neuronsNogo-66 receptor 1Expression of PirBMature cortical culturesNogo receptor 1Nervous system injuryNogo-A proteinImmunoglobulin-like receptorsChick dorsal root ganglion neuronsFunctional recoverySystem injuryGanglion neuronsCortical culturesPredominant receptorNgR1Genetic deletionPirBCell surface receptorsNeurons
2010
Genetic Deletion and Pharmacological Inhibition of Nogo-66 Receptor Impairs Cognitive Outcome after Traumatic Brain Injury in Mice
Hånell A, Clausen F, Björk M, Jansson K, Philipson O, Nilsson LN, Hillered L, Weinreb PH, Lee D, McIntosh TK, Gimbel DA, Strittmatter SM, Marklund N. Genetic Deletion and Pharmacological Inhibition of Nogo-66 Receptor Impairs Cognitive Outcome after Traumatic Brain Injury in Mice. Journal Of Neurotrauma 2010, 27: 1297-1309. PMID: 20486800, PMCID: PMC2942864, DOI: 10.1089/neu.2009.1255.Peer-Reviewed Original ResearchConceptsTraumatic brain injuryMossy fiber sproutingSoluble NgR1Fiber sproutingBrain injuryCortical impact injury modelEarly post-injury periodNogo-66 receptor 1Hippocampal mossy fiber sproutingBehavioral recovery processSham-injured animalsBrain-injured animalsPost-injury periodSpinal cord injuryOligodendrocyte myelin glycoproteinPharmacological neutralizationBehavioral recoveryFunctional recoveryLoss of tissueCord injuryTimm stainInjury modelMotor functionRodent modelsHistological effectsMAG and OMgp Synergize with Nogo-A to Restrict Axonal Growth and Neurological Recovery after Spinal Cord Trauma
Cafferty WB, Duffy P, Huebner E, Strittmatter SM. MAG and OMgp Synergize with Nogo-A to Restrict Axonal Growth and Neurological Recovery after Spinal Cord Trauma. Journal Of Neuroscience 2010, 30: 6825-6837. PMID: 20484625, PMCID: PMC2883258, DOI: 10.1523/jneurosci.6239-09.2010.Peer-Reviewed Original ResearchMeSH KeywordsAnalysis of VarianceAnimalsBiotinCells, CulturedDextransDisease Models, AnimalFemaleFunctional LateralityGanglia, SpinalGPI-Linked ProteinsMaleMiceMice, Inbred C57BLMice, KnockoutMutationMyelin ProteinsMyelin-Associated GlycoproteinMyelin-Oligodendrocyte GlycoproteinNerve Tissue ProteinsNeuronsNogo ProteinsPyramidal TractsReceptors, Cell SurfaceReceptors, SerotoninRecovery of FunctionSpinal Cord InjuriesConceptsAxonal growthSpinal Cord Injury StudyMutant miceGreater axonal growthGreater behavioral recoverySpinal cord traumaWild-type miceAxonal growth inhibitionHeterozygous mutant miceDeficient myelinNeurological recoveryCNS damageTriple-mutant miceBehavioral recoveryCord traumaFunctional recoveryNeurological functionMyelin inhibitorsAxonal regrowthReceptor mechanismsInjury studiesMyelin inhibitionDecoy receptorOptimal chanceMice
2009
Rho-Associated Kinase II (ROCKII) Limits Axonal Growth after Trauma within the Adult Mouse Spinal Cord
Duffy P, Schmandke A, Schmandke A, Sigworth J, Narumiya S, Cafferty WB, Strittmatter SM. Rho-Associated Kinase II (ROCKII) Limits Axonal Growth after Trauma within the Adult Mouse Spinal Cord. Journal Of Neuroscience 2009, 29: 15266-15276. PMID: 19955379, PMCID: PMC2855556, DOI: 10.1523/jneurosci.4650-09.2009.Peer-Reviewed Original ResearchMeSH KeywordsAmidesAnalysis of VarianceAnimalsAxonsBehavior, AnimalBrain InjuriesCA1 Region, HippocampalCells, CulturedCholera ToxinEnzyme InhibitorsGanglia, SpinalGene Expression RegulationMedian NeuropathyMiceMice, Inbred C57BLMice, KnockoutMyelin ProteinsNerve RegenerationNeuronsNogo ProteinsPyridinesReceptors, Calcitonin Gene-Related PeptideRhizotomyRho-Associated KinasesSpinal Cord InjuriesTime FactorsVersicansConceptsSpinal cordCNS traumaFunctional recoveryBasso Mouse Scale scoresSpinal Cord Injury StudyAxonal growthDorsal root entry zoneDorsal root ganglion neuronsAdult mouse spinal cordAxonal growth inhibitorsSpinal cord hemisectionRoot entry zoneSpinal cord injuryCaudal spinal cordMouse spinal cordDorsal hemisectionRaphespinal axonsDorsal rhizotomyCrush injuryCord hemisectionCorticospinal axonsChondroitin sulfate proteoglycanCord injuryGanglion neuronsInjury paradigmsAxon 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
2008
Nogo-66 Receptor Antagonist Peptide (NEP1-40) Administration Promotes Functional Recovery and Axonal Growth After Lateral Funiculus Injury in the Adult Rat
Cao Y, Shumsky JS, Sabol MA, Kushner RA, Strittmatter S, Hamers FP, Lee DH, Rabacchi SA, Murray M. Nogo-66 Receptor Antagonist Peptide (NEP1-40) Administration Promotes Functional Recovery and Axonal Growth After Lateral Funiculus Injury in the Adult Rat. Neurorehabilitation And Neural Repair 2008, 22: 262-278. PMID: 18056009, PMCID: PMC2853251, DOI: 10.1177/1545968307308550.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBehavior, AnimalDenervationEfferent PathwaysFemaleGPI-Linked ProteinsGrowth ConesMyelin ProteinsNerve RegenerationNeuronal PlasticityNogo Receptor 1Peptide FragmentsPyramidal TractsRaphe NucleiRatsRats, Sprague-DawleyReceptors, Cell SurfaceRecovery of FunctionRed NucleusSpinal Cord InjuriesSpinal Nerve RootsTreatment OutcomeWallerian DegenerationConceptsNEP1-40 groupDorsal root axonsRST axonsRubrospinal axonsRubrospinal tractAxonal growthNEP1-40 treatmentPromotes Functional RecoveryCervical spinal cordDorsal hemisectionForelimb usageNEP1-40Corticospinal axonsFunctional recoveryIntrathecal deliveryLateral funiculusSpinal cordMotor functionOutcome measuresAdult ratsLesion siteOperated controlsWhite matterGait analysisAxonsAxonal growth therapeutics: regeneration or sprouting or plasticity?
Cafferty WB, McGee AW, Strittmatter SM. Axonal growth therapeutics: regeneration or sprouting or plasticity? Trends In Neurosciences 2008, 31: 215-220. PMID: 18395807, PMCID: PMC2678051, DOI: 10.1016/j.tins.2008.02.004.Peer-Reviewed Original ResearchConceptsAxonal growthAstroglial scarHigh clinical significanceFunctional recoveryNeurological injuryInciting eventFunctional deficitsSpinal cordClinical significanceAdult brainLoss of functionCell lossInhibitory factorAxonal connectivityAxonal anatomyAxonal extensionMolecular interventionsMyelinScarCordInjuryBrain
2005
Experience-Driven Plasticity of Visual Cortex Limited by Myelin and Nogo Receptor
McGee AW, Yang Y, Fischer QS, Daw NW, Strittmatter SM. Experience-Driven Plasticity of Visual Cortex Limited by Myelin and Nogo Receptor. Science 2005, 309: 2222-2226. PMID: 16195464, PMCID: PMC2856689, DOI: 10.1126/science.1114362.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsChondroitin Sulfate ProteoglycansDarknessDominance, OcularElectrophysiologyGamma-Aminobutyric AcidGene TargetingGPI-Linked ProteinsMiceMice, Inbred C57BLMutationMyelin Basic ProteinMyelin ProteinsMyelin SheathMyelin-Associated GlycoproteinNeuritesNeuronal PlasticityNeuronsNogo ProteinsNogo Receptor 1Photic StimulationReceptors, Cell SurfaceSignal TransductionVisual CortexConceptsOcular dominanceOcular dominance plasticityNogo-66 receptorExperience-dependent plasticityPostnatal critical periodCritical periodFunctional recoveryAxonal regenerationMonocular deprivationNogo receptorDays postnatalVisual cortexNeural circuitryPathological traumaJuvenile ageMyelinReceptorsNGRPlasticityPostnatalCortexOMgpTraumaNogoCessation