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
2015
Intravitreal Delivery of Human NgR-Fc Decoy Protein Regenerates Axons After Optic Nerve Crush and Protects Ganglion Cells in Glaucoma ModelsNgR-Fc Rescues Ganglion Cells in Glaucoma
Wang X, Lin J, Arzeno A, Choi JY, Boccio J, Frieden E, Bhargava A, Maynard G, Tsai JC, Strittmatter SM. Intravitreal Delivery of Human NgR-Fc Decoy Protein Regenerates Axons After Optic Nerve Crush and Protects Ganglion Cells in Glaucoma ModelsNgR-Fc Rescues Ganglion Cells in Glaucoma. Investigative Ophthalmology & Visual Science 2015, 56: 1357-1366. PMID: 25655801, PMCID: PMC4338631, DOI: 10.1167/iovs.14-15472.Peer-Reviewed Original ResearchConceptsOptic nerve crushFluro-GoldNerve crushAxonal regenerationGanglion cellsOptic nerve crush injuryRetinal ganglion cell degenerationRGC axonal regenerationNerve crush injuryDisease-modifying therapiesGanglion cell degenerationDecoy proteinMicrobead modelVitreal spaceIntravitreal treatmentRGC densityAxonal sproutingCrush injuryGlaucoma modelNeuroprotective effectsAnterior chamberControl ratsVision lossAnterograde labelingBolus administration
2014
Human NgR-Fc Decoy Protein via Lumbar Intrathecal Bolus Administration Enhances Recovery from Rat Spinal Cord Contusion
Wang X, Yigitkanli K, Kim CY, Sekine-Konno T, Wirak D, Frieden E, Bhargava A, Maynard G, Cafferty WB, Strittmatter SM. Human NgR-Fc Decoy Protein via Lumbar Intrathecal Bolus Administration Enhances Recovery from Rat Spinal Cord Contusion. Journal Of Neurotrauma 2014, 31: 1955-1966. PMID: 24964223, PMCID: PMC4245872, DOI: 10.1089/neu.2014.3355.Peer-Reviewed Original ResearchConceptsSpinal cord injuryTraumatic spinal cord injurySpinal cord contusionNeurological recoveryCord contusionRat spinal cord contusionSpinal contusion injuryLumbar intrathecal spaceLumbar spinal cordContinuous intracerebroventricular infusionRodent SCI modelsPercentage of ratsRaphespinal axonsContusion injuryAdministration regimenSCI modelContinuous infusionCord injuryIntracerebroventricular infusionIntrathecal spaceSpinal cordPreclinical modelsEffective treatmentWalking tasksClinical testingDiffusion Tensor Imaging as a Predictor of Locomotor Function after Experimental Spinal Cord Injury and Recovery
Kelley BJ, Harel NY, Kim CY, Papademetris X, Coman D, Wang X, Hasan O, Kaufman A, Globinsky R, Staib LH, Cafferty WB, Hyder F, Strittmatter SM. Diffusion Tensor Imaging as a Predictor of Locomotor Function after Experimental Spinal Cord Injury and Recovery. Journal Of Neurotrauma 2014, 31: 1362-1373. PMID: 24779685, PMCID: PMC4120934, DOI: 10.1089/neu.2013.3238.Peer-Reviewed Original ResearchConceptsSpinal cord injuryDiffusion tensor imagingCord injuryAxonal integrityLocomotor functionExperimental spinal cord injuryTraumatic spinal cord injuryFemale Sprague-Dawley ratsTensor imagingFractional anisotropyFunctional recovery assessmentSpinal cord contusionLimited functional recoveryLong-term disabilityQuantitative diffusion tensor imagingRodent SCI modelsSprague-Dawley ratsSpinal cord morphologyWhite matter pathologyCaudal spinal cordWhite matter integrityInjury epicenterMidthoracic laminectomyCord contusionPrimary outcome
2012
Axonal regeneration induced by blockade of glial inhibitors coupled with activation of intrinsic neuronal growth pathways
Wang X, Hasan O, Arzeno A, Benowitz LI, Cafferty WB, Strittmatter SM. Axonal regeneration induced by blockade of glial inhibitors coupled with activation of intrinsic neuronal growth pathways. Experimental Neurology 2012, 237: 55-69. PMID: 22728374, PMCID: PMC3418451, DOI: 10.1016/j.expneurol.2012.06.009.Peer-Reviewed Original ResearchConceptsRetinal ganglion cellsAxonal regenerationPharmacological approachesCrush injuryChondroitin sulfate proteoglycanInjury siteNeural repairOptic nerve crush injuryDorsal root ganglion neuronsNgr1-/- miceNerve crush injurySciatic nerve axotomySpinal cord injury sitePrimary afferent fibersEffective pharmacological approachSpinal cord injuryAdult mammalian neuronsIntrinsic growth potentialGlial inhibitorsTriple therapyNerve axotomyViral gene therapyWT miceAfferent fibersCNS injury
2009
Inosine Alters Gene Expression and Axonal Projections in Neurons Contralateral to a Cortical Infarct and Improves Skilled Use of the Impaired Limb
Zai L, Ferrari C, Subbaiah S, Havton LA, Coppola G, Strittmatter S, Irwin N, Geschwind D, Benowitz LI. Inosine Alters Gene Expression and Axonal Projections in Neurons Contralateral to a Cortical Infarct and Improves Skilled Use of the Impaired Limb. Journal Of Neuroscience 2009, 29: 8187-8197. PMID: 19553458, PMCID: PMC2856695, DOI: 10.1523/jneurosci.0414-09.2009.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxonsBrain InfarctionCerebral CortexComplement C1qComplement C3Disease Models, AnimalExtremitiesFunctional LateralityGene Expression RegulationHeat-Shock ProteinsImmunohistochemistryInjections, IntraventricularInosineNeuronsOligonucleotide Array Sequence AnalysisProteasome Endopeptidase ComplexRatsRats, Sprague-DawleyRecovery of FunctionRNA, MessengerTreatment OutcomeUbiquitinationConceptsUndamaged neuronsSpinal cordSynaptic bouton-like structuresImpaired limbAlters gene expressionCorticospinal tract axonsSpecific cortical areasBouton-like structuresCortical infarctsCorticospinal neuronsDenervated sideUnaffected hemisphereAxon collateralsSensorimotor cortexBrain damageBrain injuryInjury modelLaser capture microdissectionAxonal projectionsGene expressionCortical areasDenervated halfComplement cascadeNeuronsAxon growthIbuprofen Enhances Recovery from Spinal Cord Injury by Limiting Tissue Loss and Stimulating Axonal Growth
Wang X, Budel S, Baughman K, Gould G, Song KH, Strittmatter SM. Ibuprofen Enhances Recovery from Spinal Cord Injury by Limiting Tissue Loss and Stimulating Axonal Growth. Journal Of Neurotrauma 2009, 26: 81-95. PMID: 19125588, PMCID: PMC2913782, DOI: 10.1089/neu.2007.0464.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnti-Inflammatory Agents, Non-SteroidalAxotomyChick EmbryoDisease Models, AnimalEfferent PathwaysFemaleGrowth ConesGrowth InhibitorsIbuprofenMiceNerve RegenerationNIH 3T3 CellsPyramidal TractsRaphe NucleiRatsRats, Sprague-DawleyRhoA GTP-Binding ProteinSpinal CordSpinal Cord InjuriesConceptsSpinal cord injuryAxonal sproutingCord injuryAxonal regenerationAxon regenerationNonsteroidal anti-inflammatory drugsComplete spinal cord transectionWeight-bearing statusSpinal cord contusionRecovery of ratsSpinal cord traumaTreatment of miceAdministration of ibuprofenSpinal cord transectionAnti-inflammatory drugsCorticospinal axon regenerationAction of ibuprofenRaphespinal axonsSpinal contusionCord contusionCord traumaMicroglial reactionChondroitin sulfate proteoglycanCord transectionCorticospinal fibers
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 analysisAxons
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 routeSelective temporal and regional alterations of Nogo-A and small proline-rich repeat protein 1A (SPRR1A) but not Nogo-66 receptor (NgR) occur following traumatic brain injury in the rat
Marklund N, Fulp CT, Shimizu S, Puri R, McMillan A, Strittmatter SM, McIntosh TK. Selective temporal and regional alterations of Nogo-A and small proline-rich repeat protein 1A (SPRR1A) but not Nogo-66 receptor (NgR) occur following traumatic brain injury in the rat. Experimental Neurology 2006, 197: 70-83. PMID: 16321384, PMCID: PMC2849132, DOI: 10.1016/j.expneurol.2005.08.029.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlotting, WesternBrainBrain InjuriesCell CountCornified Envelope Proline-Rich ProteinsDensitometryFunctional LateralityGPI-Linked ProteinsHippocampusImmunohistochemistryMaleMembrane ProteinsMicrotubule-Associated ProteinsMyelin ProteinsNogo ProteinsNogo Receptor 1OligodendrogliaRatsRats, Sprague-DawleyReceptors, Cell SurfaceThalamusConceptsTraumatic brain injurySmall proline-rich repeat protein 1ANogo-66 receptorBrain injuryIpsilateral cortexReticular thalamusNeuN cellsLateral fluid percussion brain injuryTraumatic central nervous system injuryFluid percussion brain injuryAxonal outgrowthCentral nervous system injuryIpsilateral external capsuleOligodendrocyte marker RIPNeuN-positive cellsNeuronal marker NeuNExpression of NogoNervous system injuryWhite matter tractsImportant brain regionsNgR expressionPoor regenerative capacitySPRR1A expressionWestern blot analysisSystem injury
2004
Blockade of Nogo-66, Myelin-Associated Glycoprotein, and Oligodendrocyte Myelin Glycoprotein by Soluble Nogo-66 Receptor Promotes Axonal Sprouting and Recovery after Spinal Injury
Li S, Liu BP, Budel S, Li M, Ji B, Walus L, Li W, Jirik A, Rabacchi S, Choi E, Worley D, Sah DW, Pepinsky B, Lee D, Relton J, Strittmatter SM. Blockade of Nogo-66, Myelin-Associated Glycoprotein, and Oligodendrocyte Myelin Glycoprotein by Soluble Nogo-66 Receptor Promotes Axonal Sprouting and Recovery after Spinal Injury. Journal Of Neuroscience 2004, 24: 10511-10520. PMID: 15548666, PMCID: PMC6730300, DOI: 10.1523/jneurosci.2828-04.2004.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxonsEvoked Potentials, MotorFemaleGPI-Linked ProteinsInjections, SpinalMotor ActivityMyelin ProteinsMyelin-Associated GlycoproteinMyelin-Oligodendrocyte GlycoproteinNogo ProteinsNogo Receptor 1OligodendrogliaPeptide FragmentsRatsRats, Sprague-DawleyReceptors, Cell SurfaceReceptors, PeptideRecombinant Fusion ProteinsSerotoninSolubilitySpinal CordSpinal Cord InjuriesConceptsAxonal sproutingTraumatic spinal cord injurySpinal-injured ratsSpinal cord injuryAdult mammalian CNSNogo-66 receptorOligodendrocyte myelin glycoproteinMyelin associated glycoproteinRaphespinal fibersLocomotor recoveryCord injurySpinal injuryMammalian CNSNgR functionTherapeutic potentialAxonal growthNogo-66Myelin glycoproteinInjuryMyelin proteinsImproved locomotionViral blockadeBlockadeFc proteinSproutingNogo Receptor Antagonism Promotes Stroke Recovery by Enhancing Axonal Plasticity
Lee JK, Kim JE, Sivula M, Strittmatter SM. Nogo Receptor Antagonism Promotes Stroke Recovery by Enhancing Axonal Plasticity. Journal Of Neuroscience 2004, 24: 6209-6217. PMID: 15240813, PMCID: PMC6729662, DOI: 10.1523/jneurosci.1643-04.2004.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxonsBehavior, AnimalDisease Models, AnimalGPI-Linked ProteinsInfarction, Middle Cerebral ArteryMaleMiceMice, KnockoutMyelin ProteinsNeuronal PlasticityNogo ProteinsNogo Receptor 1RatsRats, Sprague-DawleyReceptors, Cell SurfaceReceptors, PeptideRecombinant Fusion ProteinsRecovery of FunctionStrokeTreatment OutcomeConceptsAxonal plasticityStroke recoveryIpsilateral cervical spinal cordMiddle cerebral artery occlusionFocal brain infarctionCerebral artery occlusionCervical spinal cordComplex motor functionContralateral red nucleusUndamaged cortexBrain infarctionArtery occlusionIschemic strokeAxonal sproutingIntracerebroventricular administrationArterial occlusionPharmacological blockadeMotor functionSpinal cordControl animalsRed nucleusAxonal connectionsBehavioral improvementMutant miceStroke
2003
Rho Kinase Inhibition Enhances Axonal Regeneration in the Injured CNS
Fournier AE, Takizawa BT, Strittmatter SM. Rho Kinase Inhibition Enhances Axonal Regeneration in the Injured CNS. Journal Of Neuroscience 2003, 23: 1416-1423. PMID: 12598630, PMCID: PMC6742251, DOI: 10.1523/jneurosci.23-04-01416.2003.Peer-Reviewed Original ResearchMeSH KeywordsADP Ribose TransferasesAmidesAnimalsAxonsBotulinum ToxinsCells, CulturedChick EmbryoEnzyme InhibitorsFemaleGanglia, SpinalIntracellular Signaling Peptides and ProteinsMotor ActivityMyelin ProteinsNerve RegenerationNeuritesNogo ProteinsPC12 CellsProtein Serine-Threonine KinasesPyridinesRatsRats, Sprague-DawleyRho GTP-Binding ProteinsRho-Associated KinasesSpinal Cord InjuriesConceptsAxonal regenerationAdult ratsNeurite outgrowthCorticospinal tract lesionsNeurite outgrowth inhibitorChick DRG neuronsRho-kinase inhibitionCST fibersDRG neuronsCST lesionLocomotor recoveryTract lesionsSpinal cordOutgrowth inhibitorInhibits neurite outgrowthNogo-66Activity levelsMyelinKinase inhibitionLesionsActivation of RhoRatsC3 transferaseInhibition of p160ROCKInhibitors
2002
Nogo-66 receptor antagonist peptide promotes axonal regeneration
GrandPré T, Li S, Strittmatter SM. Nogo-66 receptor antagonist peptide promotes axonal regeneration. Nature 2002, 417: 547-551. PMID: 12037567, DOI: 10.1038/417547a.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAxonsBinding, CompetitiveCentral Nervous SystemCulture Media, ConditionedFemaleGPI-Linked ProteinsGrowth ConesMolecular Sequence DataMotor ActivityMyelin ProteinsMyelin SheathNerve RegenerationNeuritesNogo Receptor 1Peptide FragmentsProtein Structure, TertiaryRatsRats, Sprague-DawleyReceptors, Cell SurfaceSpinal Cord InjuriesConceptsCentral nervous systemAxonal regenerationNogo-66NEP1-40Antagonist peptideAxonal outgrowthNogo-66 receptorPotential therapeutic agentCorticospinal tract regenerationAxonal outgrowth inhibitionCNS myelin inhibitionSignificant axon growthIntrathecal administrationFunctional recoveryCNS injuryCorticospinal tractOutgrowth inhibitorCompetitive antagonistNervous systemMyelin inhibitionTherapeutic agentsAxon growthMonoclonal antibodiesAdult mammalsNogo
2000
Brain‐Derived Neurotrophic Factor Induces Excitotoxic Sensitivity in Cultured Embryonic Rat Spinal Motor Neurons Through Activation of the Phosphatidylinositol 3‐Kinase Pathway
Fryer H, Wolf D, Knox R, Strittmatter S, Pennica D, O'Leary R, Russell D, Kalb R. Brain‐Derived Neurotrophic Factor Induces Excitotoxic Sensitivity in Cultured Embryonic Rat Spinal Motor Neurons Through Activation of the Phosphatidylinositol 3‐Kinase Pathway. Journal Of Neurochemistry 2000, 74: 582-595. PMID: 10646509, DOI: 10.1046/j.1471-4159.2000.740582.x.Peer-Reviewed Original ResearchConceptsHerpes simplex virusBrain-derived neurotrophic factorNeurotrophic factorMotor neuronsGlial-derived neurotrophic factorRat spinal motor neuronsEffects of BDNFRat motor neuronsSpinal motor neuronsActivation of TrkBPI3K pathwayExcitotoxic deathNeurotrophin-3Receptor p75NTRBDNFSimplex virusIntracellular Ca2Cardiotrophin-1NeuronsReceptor-mediated cell deathK pathwayPI3KDominant negative p85 subunitTrkBCell death
1999
Excitotoxic Death of a Subset of Embryonic Rat Motor Neurons In Vitro
Fryer HJ, Knox RJ, Strittmatter SM, Kalb RG. Excitotoxic Death of a Subset of Embryonic Rat Motor Neurons In Vitro. Journal Of Neurochemistry 1999, 72: 500-513. PMID: 9930721, DOI: 10.1046/j.1471-4159.1999.0720500.x.Peer-Reviewed Original ResearchMeSH Keywords6-Cyano-7-nitroquinoxaline-2,3-dioneAlpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic AcidAnimalsCalciumCalcium ChannelsCalcium Channels, L-TypeCell Culture TechniquesCell DeathCells, CulturedDizocilpine MaleateDose-Response Relationship, DrugExcitatory Amino Acid AgonistsExcitatory Amino Acid AntagonistsFemaleGlutamic AcidGlutamineGlycineKainic AcidMembrane PotentialsMotor NeuronsN-MethylaspartateNerve Tissue ProteinsNeurotoxinsPotassiumPregnancyRatsRats, Sprague-DawleyReceptors, AMPAReceptors, Kainic AcidReceptors, N-Methyl-D-AspartateSpinal CordConceptsGlutamate receptor agonistsMotor neuronsReceptor agonistNon-NMDA glutamate receptor agonistsIntracellular Ca2Agonist-evoked intracellular Ca2Specific glutamate receptor agonistsIonotropic glutamate receptor activationReceptor subtype-specific antagonistsSpinal cord motor neuronsSubtype-specific antagonistsCultured motor neuronsGlutamate receptor expressionRat motor neuronsMost motor neuronsGlutamate receptor activationL-type Ca2Subunit-specific antibodiesTime-dependent mannerReceptor phenotypeChannel antagonistsReceptor expressionNeurotoxic effectsRoute of entryExtracellular Ca2
1997
Neuronal and Non-Neuronal Collapsin-1 Binding Sites in Developing Chick Are Distinct from Other Semaphorin Binding Sites
Takahashi T, Nakamura F, Strittmatter S. Neuronal and Non-Neuronal Collapsin-1 Binding Sites in Developing Chick Are Distinct from Other Semaphorin Binding Sites. Journal Of Neuroscience 1997, 17: 9183-9193. PMID: 9364065, PMCID: PMC6573609, DOI: 10.1523/jneurosci.17-23-09183.1997.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAvian ProteinsAxonsBinding SitesCells, CulturedCentral Nervous SystemChick EmbryoDNA, ComplementaryFetal ProteinsGanglia, SpinalGlycoproteinsLungMembrane ProteinsMesodermMiceMotor NeuronsMultigene FamilyNerve Growth FactorsNerve Tissue ProteinsNeuronsNeurotrophin 3Organ SpecificityRatsRats, Sprague-DawleyReceptors, Cell SurfaceRecombinant Fusion ProteinsSemaphorin-3AConceptsFusion proteinBinding sitesGrowth conesDRG neuronsNon-neuronal tissuesExtracellular proteinsF fusion proteinSemaphorin familyDRG growth conesProteinLow nanomolar affinityMajor blood vesselsLigand familyBrainstem neuronsSympathetic neuronsNanomolar affinityNervous systemAxonal pathsBiological activityBlood vesselsNeuronsFamilySitesMesenchymeSemaphorins