2024
PAK1 inhibition with Romidepsin attenuates H‐reflex hyperexcitability after spinal cord injury
Kauer S, Benson C, Carrara J, Tarafder A, Ibrahim Y, Estacion M, Waxman S, Tan A. PAK1 inhibition with Romidepsin attenuates H‐reflex hyperexcitability after spinal cord injury. The Journal Of Physiology 2024, 602: 5061-5081. PMID: 39231098, DOI: 10.1113/jp284976.Peer-Reviewed Original ResearchDendritic spine dysgenesisSpinal cord injurySCI-induced spasticityRomidepsin treatmentSpine dysgenesisLoss of rate-dependent depressionCutaneous T-cell lymphomaTreatment of cutaneous T-cell lymphomaContusive spinal cord injuryT-cell lymphomaSpinal cord injury animalsCord injuryRate-dependent depressionExaggerated reflex responsesH-reflex changesSpinal cord injury mouse modelManaging spasticityReduce spasticityReporter micePreclinical utilityDrug responseRomidepsinControl cohortIntervention effectsSpinal hyperreflexiaA FAIR, open-source virtual reality platform for dendritic spine analysis
Reimer M, Kauer S, Benson C, King J, Patwa S, Feng S, Estacion M, Bangalore L, Waxman S, Tan A. A FAIR, open-source virtual reality platform for dendritic spine analysis. Patterns 2024, 5: 101041. PMID: 39568639, PMCID: PMC11573899, DOI: 10.1016/j.patter.2024.101041.Peer-Reviewed Original ResearchVirtual realityVirtual reality platformSoftware ecosystemReality platformData standardSuperior accuracyDatasetWorkflowValidation processDendritic spine morphologySpine analysisDendritic spinesReconstruction techniqueSpine lengthMethod's superior accuracyDendritic spine lengthSpine morphologyMetricsMorphological metricsNeurodataFairness
2023
Conditional Astrocyte Rac1KO Attenuates Hyperreflexia after Spinal Cord Injury
Benson C, Olson K, Patwa S, Kauer S, King J, Waxman S, Tan A. Conditional Astrocyte Rac1KO Attenuates Hyperreflexia after Spinal Cord Injury. Journal Of Neuroscience 2023, 44: e1670222023. PMID: 37963762, PMCID: PMC10851682, DOI: 10.1523/jneurosci.1670-22.2023.Peer-Reviewed Original ResearchConceptsSpinal cord injuryRate-dependent depressionΑ-motor neuronsGlutamate transporter 1Dendritic spine dysgenesisCord injurySpine dysgenesisDevelopment of SCIMild contusion spinal cord injuryAstrocytic glutamate transporter 1Glial-specific glutamate transporterContusion spinal cord injuryTransporter 1Development of hyperreflexiaMonosynaptic H-reflexDendritic spine densityPre-injury levelSpinal reflex circuitsVentral spinal cordReflex hyperexcitabilityHyperexcitability disordersFunctional recoveryGlutamate clearanceH-reflexVentral hornIncreased astrocytic GLT-1 expression in tripartite synapses is associated with SCI-induced hyperreflexia
Benson C, King J, Kauer S, Waxman S, Tan A. Increased astrocytic GLT-1 expression in tripartite synapses is associated with SCI-induced hyperreflexia. Journal Of Neurophysiology 2023, 130: 1358-1366. PMID: 37877184, PMCID: PMC10972632, DOI: 10.1152/jn.00234.2023.Peer-Reviewed Original ResearchConceptsSpinal cord injuryRate-dependent depressionTripartite synapsesGLT-1Astrocytic GLT-1 expressionChronic neurological complicationsGLT-1 expressionAstrocyte involvementChronic spasticityUninjured shamsNeurological complicationsNeuropathic painHyperexcitability disordersH-reflexPSD-95 proteinReactive astrocytesVentral hornCord injuryMuscle toneAstrocytes' roleSpinal cordSpinal circuitsSynaptic transmissionHyperreflexiaSpasticity
2022
Dendritic Spines and Pain Memory
Benson C, King J, Reimer M, Kauer S, Waxman S, Tan A. Dendritic Spines and Pain Memory. The Neuroscientist 2022, 30: 294-314. PMID: 36461773, DOI: 10.1177/10738584221138251.Peer-Reviewed Original ResearchNeuropathic painDendritic spinesSynaptic transmissionSpinal cord dorsal hornForm of painNew therapeutic approachesSurface of neuronsDorsal hornIntractable painDeep laminaePain memoryTherapeutic approachesPainNervous systemNew therapeuticsSpineMillions of peopleInjuryDiseaseRecent studiesReview articlePrevalenceNeuronsImportant role
2021
Conditional RAC1 knockout in motor neurons restores H-reflex rate-dependent depression after spinal cord injury
Benson CA, Olson KL, Patwa S, Reimer ML, Bangalore L, Hill M, Waxman SG, Tan AM. Conditional RAC1 knockout in motor neurons restores H-reflex rate-dependent depression after spinal cord injury. Scientific Reports 2021, 11: 7838. PMID: 33837249, PMCID: PMC8035187, DOI: 10.1038/s41598-021-87476-5.Peer-Reviewed Original ResearchConceptsSpinal cord injuryDendritic spine dysgenesisMotor neuronsSpine dysgenesisSCI animalsHyperexcitability disordersCord injurySpinal alpha motor neuronsVentral horn motor neuronsAbnormal dendritic spine morphologyRac1 knockoutH-reflex pathwayRate-dependent depressionAlpha motor neuronsDevelopment of spasticityAdeno-associated viralMushroom dendritic spinesSpine head sizeOverall spine lengthDendritic spine morphologyRac1 protein expressionNeuronal hyperexcitabilityMajor complicationsClinical symptomsReflex excitability
2020
Dendritic Spine Dynamics after Peripheral Nerve Injury: An Intravital Structural Study
Benson CA, Fenrich KK, Olson KL, Patwa S, Bangalore L, Waxman SG, Tan AM. Dendritic Spine Dynamics after Peripheral Nerve Injury: An Intravital Structural Study. Journal Of Neuroscience 2020, 40: 4297-4308. PMID: 32371602, PMCID: PMC7252482, DOI: 10.1523/jneurosci.2858-19.2020.Peer-Reviewed Original ResearchConceptsDendritic spine dynamicsInjury-induced painPeripheral nerve injuryNeuropathic painDorsal hornSpine dynamicsNerve injuryPeripheral nerve injury-induced painNerve injury-induced painSuperficial dorsal horn neuronsSpinal cord dorsal hornDorsal horn neuronsSuperficial dorsal hornMechanisms of painDendritic spine dysgenesisContext of injuryPostmortem tissue analysisSame dendritic branchRepeat imagingMale miceMedical conditionsEffective treatmentPainSpine dysgenesisDendritic spines
2016
Dendritic spine remodeling following early and late Rac1 inhibition after spinal cord injury: evidence for a pain biomarker
Zhao P, Hill M, Liu S, Chen L, Bangalore L, Waxman SG, Tan AM. Dendritic spine remodeling following early and late Rac1 inhibition after spinal cord injury: evidence for a pain biomarker. Journal Of Neurophysiology 2016, 115: 2893-2910. PMID: 26936986, PMCID: PMC4922610, DOI: 10.1152/jn.01057.2015.Peer-Reviewed Original ResearchConceptsSpinal cord injuryNeuropathic painDendritic spine dysgenesisDendritic spinesCord injurySpine dysgenesisDorsal horn neuronsSpine profilesDendritic spine remodelingEffective clinical translationSensory dysfunctionSignificant complicationsNociceptive systemPain biomarkersSpine remodelingClinical conditionsPreclinical studiesRac1 activityEffective treatmentPainDrug responsivenessStructural biomarkersDisease statesRac1 inhibitionBiomarkers
2014
Dendritic spine dysgenesis contributes to hyperreflexia after spinal cord injury
Bandaru SP, Liu S, Waxman SG, Tan AM. Dendritic spine dysgenesis contributes to hyperreflexia after spinal cord injury. Journal Of Neurophysiology 2014, 113: 1598-1615. PMID: 25505110, PMCID: PMC4346729, DOI: 10.1152/jn.00566.2014.Peer-Reviewed Original ResearchConceptsSpinal cord injuryLevel of injuryH-reflexCord injuryStretch reflexDendritic spinesSpinal cord motor systemSpine morphologyContusion spinal cord injuryExaggerated tendon jerksSpinal cord contributesRate-dependent depressionSpine profilesDendritic spine dysgenesisΑ-motor neuronsH-reflex testingTonic stretch reflexVelocity-dependent increaseAdult Sprague-DawleyM-wave responsesAbnormal dendritic spinesSpinal stretch reflexAbnormal spine morphologyDendritic spine morphologyReflex dysfunction
2012
Selective Corticospinal Tract Injury in the Rat Induces Primary Afferent Fiber Sprouting in the Spinal Cord and Hyperreflexia
Tan A, Chakrabarty S, Kimura H, Martin J. Selective Corticospinal Tract Injury in the Rat Induces Primary Afferent Fiber Sprouting in the Spinal Cord and Hyperreflexia. Journal Of Neuroscience 2012, 32: 12896-12908. PMID: 22973013, PMCID: PMC3499628, DOI: 10.1523/jneurosci.6451-11.2012.Peer-Reviewed Original ResearchConceptsCorticospinal tract injurySpinal cordCorticospinal tractProprioceptive afferentsAfferent fiber sproutingGray matter regionsFrequency-dependent depressionCorticospinal tract terminalsCervical spinal cordMechanisms of maladaptive plasticityMatter regionsSpinal cord projectionsSpinal cord injuryPyramidal tract sectionTract injurySpared sideAdult ratsFiber sproutingAfferent terminalsSpinal targetsMicroglial densityMuscle afferentsSpinal sensorimotor circuitsMaladaptive plasticityAfferentsMaladaptive Dendritic Spine Remodeling Contributes to Diabetic Neuropathic Pain
Tan AM, Samad OA, Fischer TZ, Zhao P, Persson AK, Waxman SG. Maladaptive Dendritic Spine Remodeling Contributes to Diabetic Neuropathic Pain. Journal Of Neuroscience 2012, 32: 6795-6807. PMID: 22593049, PMCID: PMC6622192, DOI: 10.1523/jneurosci.1017-12.2012.Peer-Reviewed Original ResearchConceptsDiabetic neuropathic painNeuropathic painDendritic spinesSpine plasticitySpine morphologyMajor public health problemDiabetes-induced changesDevelopment of painDendritic spine remodelingDendritic spine plasticitySpontaneous firing activityPublic health problemAvailable clinical treatmentsEvidence of painDendritic spine morphologyDendritic spine shapeNeuronal hyperresponsivenessRange neuronsWDR neuronsNeuron hyperexcitabilitySTZ injectionDorsal hornMechanical painChronic painDiabetic rats
2011
Rac1-regulated dendritic spine remodeling contributes to neuropathic pain after peripheral nerve injury
Tan AM, Chang YW, Zhao P, Hains BC, Waxman SG. Rac1-regulated dendritic spine remodeling contributes to neuropathic pain after peripheral nerve injury. Experimental Neurology 2011, 232: 222-233. PMID: 21963650, DOI: 10.1016/j.expneurol.2011.08.028.Peer-Reviewed Original ResearchConceptsDorsal horn neuronsPeripheral nerve injuryChronic constriction injuryWide dynamic range dorsal horn neuronsRange dorsal horn neuronsNerve injuryNeuropathic painDendritic spinesTactile allodyniaThermal hyperalgesiaSpine morphologyInjury-induced hyperexcitabilityNoxious peripheral stimuliSpinal cord injuryMushroom-shaped spinesDendritic spine developmentDendritic spine morphologyConstriction injuryHyperexcitable responsesCCI animalsNeuronal hyperexcitabilityIpsilateral hindNociceptive thresholdSpine densityCord injurySpinal cord injury, dendritic spine remodeling, and spinal memory mechanisms
Tan AM, Waxman SG. Spinal cord injury, dendritic spine remodeling, and spinal memory mechanisms. Experimental Neurology 2011, 235: 142-151. PMID: 21925174, DOI: 10.1016/j.expneurol.2011.08.026.Peer-Reviewed Original ResearchConceptsSpinal cord injuryNeuropathic painDendritic spinesChronic painCord injuryNervous systemWide dynamic range neuronsNociceptive dorsal horn neuronsDorsal horn neuronsDendritic spine remodelingRange neuronsCentral sensitizationSpinal cordSpine remodelingPainSynaptic potentiationPain researchInjuryMore effective strategiesAberrant changesLong-term memory storageSpineStructural substrateSynaptic modelNeurons
2009
Unilateral Focal Burn Injury Is Followed by Long-Lasting Bilateral Allodynia and Neuronal Hyperexcitability in Spinal Cord Dorsal Horn
Chang YW, Tan A, Saab C, Waxman S. Unilateral Focal Burn Injury Is Followed by Long-Lasting Bilateral Allodynia and Neuronal Hyperexcitability in Spinal Cord Dorsal Horn. Journal Of Pain 2009, 11: 119-130. PMID: 19744891, DOI: 10.1016/j.jpain.2009.06.009.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnalysis of VarianceAnimalsBrain InjuriesCalcitonin Gene-Related PeptideCD11b AntigenDisease Models, AnimalFunctional LateralityHyperesthesiaMaleMicrogliaP38 Mitogen-Activated Protein KinasesPainPain MeasurementPain ThresholdPhysical StimulationPosterior Horn CellsRatsSpinal CordSubstance PConceptsSpinal cord dorsal hornBurn injuryBurn injury modelBilateral allodyniaDorsal hornNeuronal hyperexcitabilityInjury modelSpinal cordDorsal horn neuronal hyperexcitabilitySecond-order sensory neuronsCentral neuropathic mechanismsIpsilateral mechanical allodyniaDorsal horn neuronsActivation of microgliaPathogenesis of painPotential therapeutic targetNovel animal modelContralateral allodyniaMechanical allodyniaNeuropathic mechanismsSpinal microgliaBilateral painMicroglial activationNerve injuryWeeks postinjuryDendritic Spine Remodeling After Spinal Cord Injury Alters Neuronal Signal Processing
Tan AM, Choi JS, Waxman SG, Hains BC. Dendritic Spine Remodeling After Spinal Cord Injury Alters Neuronal Signal Processing. Journal Of Neurophysiology 2009, 102: 2396-2409. PMID: 19692517, DOI: 10.1152/jn.00095.2009.Peer-Reviewed Original ResearchConceptsSpinal cord injuryCord injurySynaptic transmissionDorsal horn nociceptive neuronsFrequency-following abilityDendritic spine remodelingGeneration of painAction potential activationDendritic spine morphologyDendritic spine shapeAbnormal painCentral sensitizationNociceptive neuronsSpine remodelingPostsynaptic neuronsDendritic spinesSpine morphologyInput-output functionPainSoma resultsInjurySpine shapeNeuronal statesNeuronsPotential activation
2008
Neuropathic Pain Memory Is Maintained by Rac1-Regulated Dendritic Spine Remodeling after Spinal Cord Injury
Tan AM, Stamboulian S, Chang YW, Zhao P, Hains AB, Waxman SG, Hains BC. Neuropathic Pain Memory Is Maintained by Rac1-Regulated Dendritic Spine Remodeling after Spinal Cord Injury. Journal Of Neuroscience 2008, 28: 13173-13183. PMID: 19052208, PMCID: PMC6671613, DOI: 10.1523/jneurosci.3142-08.2008.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsComputer SimulationDendritic SpinesDisease Models, AnimalEnzyme ActivationEnzyme InhibitorsExcitatory Postsynaptic PotentialsHyperalgesiaLearningMaleMemoryNeuralgiaNeuronal PlasticityPain MeasurementPain ThresholdPosterior Horn CellsRac1 GTP-Binding ProteinRatsRats, Sprague-DawleySpinal Cord InjuriesSynaptic TransmissionConceptsSpinal cord injuryNeuropathic painCord injuryWide dynamic range neuronsContusion spinal cord injuryDendritic spine pathologyInjury-induced hyperexcitabilityNoxious peripheral stimuliRats 1 monthChronic neuropathic painDorsal horn neuronsDendritic spine remodelingIncreased spine densityRange neuronsSpine morphometryDH neuronsTactile allodyniaNeuronal hyperexcitabilitySCI animalsThermal hyperalgesiaSham surgerySpine densityLamina IVControl neuronsSynaptic basis
2007
Sensory afferents regenerated into dorsal columns after spinal cord injury remain in a chronic pathophysiological state
Tan A, Petruska J, Mendell L, Levine J. Sensory afferents regenerated into dorsal columns after spinal cord injury remain in a chronic pathophysiological state. Experimental Neurology 2007, 206: 257-268. PMID: 17585905, PMCID: PMC3103885, DOI: 10.1016/j.expneurol.2007.05.013.Peer-Reviewed Original ResearchConceptsSpinal cord injuryDorsal columnsChronic pathophysiological stateNerve conditioning lesionConditioning lesionRegenerating axonsCord injurySensory afferentsInjury siteFrequency-following abilityInfusion of antibodiesPathophysiological statesIntrinsic growth stateExperimental spinal cord injuryRegenerating sensory axonsReduced conduction velocityIntrinsic growth capacitySensory axon growthAxonal growthGrowth inhibitory effectSensory neuronsSpinal cordCombinatorial treatmentInhibit axonal growthRepetitive stimuli
2006
Antibodies against the NG2 Proteoglycan Promote the Regeneration of Sensory Axons within the Dorsal Columns of the Spinal Cord
Tan A, Colletti M, Rorai A, Skene J, Levine J. Antibodies against the NG2 Proteoglycan Promote the Regeneration of Sensory Axons within the Dorsal Columns of the Spinal Cord. Journal Of Neuroscience 2006, 26: 4729-4739. PMID: 16672645, PMCID: PMC6674154, DOI: 10.1523/jneurosci.3900-05.2006.Peer-Reviewed Original ResearchMeSH KeywordsAnalysis of VarianceAnimalsAntibodies, MonoclonalAntigensAxonsBlotting, WesternCD11b AntigenDisease Models, AnimalEctodysplasinsFemaleFibronectinsFluorescent Antibody TechniqueGlial Fibrillary Acidic ProteinImmunoprecipitationLaminectomyMembrane ProteinsMyelin ProteinsNerve RegenerationNeurogliaNeurons, AfferentNogo ProteinsPeripheral Nervous System DiseasesProteoglycansRatsRats, Sprague-DawleySpinal Cord InjuriesTime FactorsTumor Necrosis FactorsConceptsAnti-NG2 antibodiesNerve conditioning lesionConditioning lesionSpinal cordSensory axonsAxonal regenerationAdult rat spinal cordSite of CNS injuryRegeneration of sensory axonsNon-neutralizing antibodiesRat spinal cordSensory axon regenerationTransected adult rat spinal cordGlial scarAxon growth in vitroIntrinsic growth capacityAscending sensory axonsGrowth in vitroInhibit axon regenerationExtrinsic inhibitionAntibody treatmentDorsal columnsDorsal rootsNG2 immunoreactivityAdult neurons
2005
NG2: a component of the glial scar that inhibits axon growth
Tan A, Zhang W, Levine J. NG2: a component of the glial scar that inhibits axon growth. Journal Of Anatomy 2005, 207: 717-725. PMID: 16367799, PMCID: PMC1571583, DOI: 10.1111/j.1469-7580.2005.00452.x.Peer-Reviewed Original ResearchConceptsOligodendrocyte precursor cellsGlial scarNG2-expressing oligodendrocyte precursor cellsGrowth-inhibitory environmentSpinal cord resultsCord resultsInhibit axonal growthCNS injuryInjury siteSurface of oligodendrocyte precursor cellsPrecursor cellsAxonal regenerationAxonal regrowthChondroitin sulphate proteoglycansInjury to brainNG2ScarsInjuryAxonal growth