2023
TMEM106B Puncta Is Increased in Multiple Sclerosis Plaques, and Reduced Protein in Mice Results in Delayed Lipid Clearance Following CNS Injury
Shafit-Zagardo B, Sidoli S, Goldman J, DuBois J, Corboy J, Strittmatter S, Guzik H, Edema U, Arackal A, Botbol Y, Merheb E, Nagra R, Graff S. TMEM106B Puncta Is Increased in Multiple Sclerosis Plaques, and Reduced Protein in Mice Results in Delayed Lipid Clearance Following CNS Injury. Cells 2023, 12: 1734. PMID: 37443768, PMCID: PMC10340176, DOI: 10.3390/cells12131734.Peer-Reviewed Original ResearchConceptsAxonal damageMultiple sclerosisRelapsing-remitting multiple sclerosisHypomorphic miceExperimental autoimmune encephalomyelitisRelapsing-remitting MSNormal-appearing white matterMultiple sclerosis plaquesWhite matter plaquesNon-neurologic controlsWild-type miceBrains of individualsLipid droplet accumulationAutoimmune encephalomyelitisMyelin oligodendrocyteCNS injuryLipid clearanceSpinal cordNeuronal integrityTransmembrane protein 106BWhite matterAlzheimer's diseaseMice resultsDroplet accumulationPlaques
2022
Translational PET Imaging of Spinal Cord Injury with the Serotonin Transporter Tracer [11C]AFM
Fang H, Rossano S, Wang X, Nabulsi N, Kelley B, Fowles K, Ropchan J, Strittmatter SM, Carson RE, Huang Y. Translational PET Imaging of Spinal Cord Injury with the Serotonin Transporter Tracer [11C]AFM. Molecular Imaging And Biology 2022, 24: 560-569. PMID: 35020138, PMCID: PMC9550197, DOI: 10.1007/s11307-021-01698-7.Peer-Reviewed Original ResearchConceptsSpinal cord injurySpinal cordHealthy ratsHuman spinal cordCord injurySerotonin transporterRat modelRodent modelsPET imagingTranslational PET imagingSCI rat modelIntact spinal cordSpinal cord caudalRodent spinal cordSerotonin transporter tracerUse of PETCervical uptakeSERT changesSCI animalsSCI patientsPresynaptic serotonin transporterCord caudalAxon damageSerotonin systemSERT radioligand
2021
B-cells expressing NgR1 and NgR3 are localized to EAE-induced inflammatory infiltrates and are stimulated by BAFF
Bakhuraysah MM, Theotokis P, Lee JY, Alrehaili AA, Aui PM, Figgett WA, Azari MF, Abou-Afech JP, Mackay F, Siatskas C, Alderuccio F, Strittmatter SM, Grigoriadis N, Petratos S. B-cells expressing NgR1 and NgR3 are localized to EAE-induced inflammatory infiltrates and are stimulated by BAFF. Scientific Reports 2021, 11: 2890. PMID: 33536561, PMCID: PMC7858582, DOI: 10.1038/s41598-021-82346-6.Peer-Reviewed Original ResearchConceptsExperimental autoimmune encephalomyelitisEAE-induced miceB cellsB-cell activating factorMeningeal B cellsLumbosacral spinal cordSecretion of immunoglobulinsG0/G1 phaseImmune cell signalingNeurological progressionAutoimmune encephalomyelitisInflammatory infiltrateAxonal dystrophyCentral nervous system myelinSpinal cordRecombinant BAFFActivating factorNgR1Score 1BAFFBAFF stimulationInfiltratesNgR3System myelinG1 phase
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 conditionsThe nociceptin receptor inhibits axonal regeneration and recovery from spinal cord injury
Sekine Y, Siegel CS, Sekine-Konno T, Cafferty WBJ, Strittmatter SM. The nociceptin receptor inhibits axonal regeneration and recovery from spinal cord injury. Science Signaling 2018, 11 PMID: 29615517, PMCID: PMC6179440, DOI: 10.1126/scisignal.aao4180.Peer-Reviewed Original ResearchConceptsSpinal cord injuryCord injuryAxonal regenerationMid-thoracic spinal cordTraumatic spinal cord injuryPartial neurological recoveryTraumatic CNS injuryDorsal hemisectionNeurological recoveryPeptide nociceptinCNS injuryAxon sproutingORL1 agonistSelective blockadeSpinal cordLocomotor functionNociceptin receptorAxon regenerationNeural repairPrimary neuronsNgR1 proteinAxonal growthNull miceMRNA expressionORL1
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 brainInhibition 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
Comprehensive Corticospinal Labeling with mu-crystallin Transgene Reveals Axon Regeneration after Spinal Cord Trauma in ngr1−/− Mice
Fink KL, Strittmatter SM, Cafferty WB. Comprehensive Corticospinal Labeling with mu-crystallin Transgene Reveals Axon Regeneration after Spinal Cord Trauma in ngr1−/− Mice. Journal Of Neuroscience 2015, 35: 15403-15418. PMID: 26586827, PMCID: PMC4649010, DOI: 10.1523/jneurosci.3165-15.2015.Peer-Reviewed Original ResearchMeSH KeywordsAmidinesAnalysis of VarianceAnimalsAxonsBiotinCrystallinsDextransDisease Models, AnimalFunctional LateralityGene Expression RegulationGlial Fibrillary Acidic ProteinGPI-Linked ProteinsLuminescent ProteinsMiceMice, Inbred C57BLMice, TransgenicMu-CrystallinsMyelin ProteinsNerve RegenerationNogo Receptor 1Pyramidal TractsReceptors, Cell SurfaceRecovery of FunctionSpinal Cord InjuriesConceptsCorticospinal tractCST axonsTransgenic miceMotor tractsDextran amineFunctional deficitsSpinal cordAxon regenerationSpinal Cord Injury StudySpontaneous axon regenerationSpinal cord traumaNogo receptor 1Permanent functional deficitsPersistent functional deficitsBilateral pyramidotomyDorsal hemisectionMidthoracic cordCord traumaMotor pathwaysAdult CNSCST regenerationInjury studiesLesion siteRegenerating fibersNeural repair
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 testing
2013
Multimodal exercises simultaneously stimulating cortical and brainstem pathways after unilateral corticospinal lesion
Harel NY, Yigitkanli K, Fu Y, Cafferty WB, Strittmatter SM. Multimodal exercises simultaneously stimulating cortical and brainstem pathways after unilateral corticospinal lesion. Brain Research 2013, 1538: 17-25. PMID: 24055330, PMCID: PMC3873870, DOI: 10.1016/j.brainres.2013.07.012.Peer-Reviewed Original ResearchConceptsBrainstem pathwaysMultimodal exerciseCorticospinal tractTraining groupContext of injuryCST pathwayAnatomical outcomesCST injuryPostural exercisesCorticospinal lesionsCollateral sproutingCST lesionElectrophysiological assessmentSpinal cordPhysical exerciseGait kinematicsLimb performanceSynaptic strengthLesionsSubcortical circuitsFiber densityMiceInjuryFurther studiesExercise
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 cellsPlexinA2 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 traumaMyelin-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 injury
2011
Inosine Augments the Effects of a Nogo Receptor Blocker and of Environmental Enrichment to Restore Skilled Forelimb Use after Stroke
Zai L, Ferrari C, Dice C, Subbaiah S, Havton LA, Coppola G, Geschwind D, Irwin N, Huebner E, Strittmatter SM, Benowitz LI. Inosine Augments the Effects of a Nogo Receptor Blocker and of Environmental Enrichment to Restore Skilled Forelimb Use after Stroke. Journal Of Neuroscience 2011, 31: 5977-5988. PMID: 21508223, PMCID: PMC3101108, DOI: 10.1523/jneurosci.4498-10.2011.Peer-Reviewed Original ResearchConceptsIntrinsic growth potentialUnilateral strokeSpinal cordLayer 5 pyramidal neuronsForelimb motor areaSimilar functional improvementEnvironmental enrichmentCause of disabilitySkilled forelimb useEffect of treatmentUndamaged cortexReceptor blockersDenervated sidePreoperative levelsNEP1-40Stroke patientsPyramidal neuronsUndamaged hemisphereSkilled reachingTreatment optionsDenervated areaIntact hemisphereReceptor antagonistClinical trialsFunctional improvement
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 paradigmsInosine 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 growth
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
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 route