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
2018
Therapeutic potential of Pak1 inhibition for pain associated with cutaneous burn injury
Guo Y, Benson C, Hill M, Henry S, Effraim P, Waxman S, Dib-Hajj S, Tan AM. Therapeutic potential of Pak1 inhibition for pain associated with cutaneous burn injury. Molecular Pain 2018, 14: 1744806918788648. PMID: 29956587, PMCID: PMC6053256, DOI: 10.1177/1744806918788648.Peer-Reviewed Original ResearchConceptsDendritic spine dysgenesisNeuropathic painSpine dysgenesisBurn injurySignificant tactile allodyniaDorsal horn neuronsChronic disease burdenActivity-dependent expressionCutaneous burn injurySecond-degree burn injuryBurn injury modelC-fos expressionPotential molecular targetsDrug discontinuationHeat hyperalgesiaTactile allodyniaDorsal hornPain outcomesChronic painNociceptive activityLower painDisease burdenInjury modelCognitive dysfunctionPain
2002
Primary motor neurons fail to up‐regulate voltage‐gated sodium channel Nav1.3/brain type III following axotomy resulting from spinal cord injury
Hains B, Black J, Waxman S. Primary motor neurons fail to up‐regulate voltage‐gated sodium channel Nav1.3/brain type III following axotomy resulting from spinal cord injury. Journal Of Neuroscience Research 2002, 70: 546-552. PMID: 12404508, DOI: 10.1002/jnr.10402.Peer-Reviewed Original ResearchConceptsSpinal cord injuryUpper motor neuronsPrimary motor cortexDorsal root gangliaMotor neuronsCord injuryMotor cortexRat primary motor cortexDorsal column transectionIpsilateral DRG neuronsCortical motor neuronsSciatic nerve transectionTraumatic head injuryFacial motor neuronsSodium channel expressionPrimary motor neuronsVoltage-gated sodium channelsPeripheral axotomyDRG neuronsNerve transectionLayer VControl brainsHead injuryRoot gangliaSpinal cord
2001
Flanking regulatory sequences of the locus encoding the murine GDNF receptor, c‐ret, directs lac Z (β‐galactosidase) expression in developing somatosensory system
Sukumaran M, Waxman S, Wood J, Pachnis V. Flanking regulatory sequences of the locus encoding the murine GDNF receptor, c‐ret, directs lac Z (β‐galactosidase) expression in developing somatosensory system. Developmental Dynamics 2001, 222: 389-402. PMID: 11747074, DOI: 10.1002/dvdy.1192.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornBase SequenceChromosome MappingCloning, MolecularConsensus SequenceDrosophila ProteinsEmbryo, MammalianGanglia, SensoryGene ExpressionGene Expression Regulation, DevelopmentalGenes, RegulatorGlial Cell Line-Derived Neurotrophic Factor ReceptorsLac OperonLectinsMiceMice, TransgenicNeurons, AfferentNociceptorsPromoter Regions, GeneticProtein Structure, TertiaryProto-Oncogene ProteinsProto-Oncogene Proteins c-retReceptor Protein-Tyrosine KinasesSpinal CordTranscription Initiation SiteConceptsRegulatory domainLac Z expressionZ expressionCell type-specific expressionDistal regulatory domainEndogenous gene expressionCis-regulatory domainsTranscription initiation siteEntire structural geneSpecific regulatory domainsLac Z reporter geneStructural geneMouse genomeLateral mesodermRegulatory sequencesCpG islandsDNA sequencesPrimitive streakReporter geneFlanking sequencesCosmid contigGene expressionSpecific expressionTransgenic mouse lineInitiation site
2000
Development of Glutamatergic Synaptic Activity in Cultured Spinal Neurons
Robert A, Howe J, Waxman S. Development of Glutamatergic Synaptic Activity in Cultured Spinal Neurons. Journal Of Neurophysiology 2000, 83: 659-670. PMID: 10669482, DOI: 10.1152/jn.2000.83.2.659.Peer-Reviewed Original ResearchMeSH Keywords2-Amino-5-phosphonovalerate6-Cyano-7-nitroquinoxaline-2,3-dioneAnimalsCells, CulturedExcitatory Amino Acid AntagonistsExcitatory Postsynaptic PotentialsFetusGlutamic AcidMagnesiumMembrane PotentialsNeuronsPatch-Clamp TechniquesQuinoxalinesRatsRats, Sprague-DawleyReceptors, AMPAReceptors, N-Methyl-D-AspartateSpinal CordSynapsesTetrodotoxinConceptsSpontaneous synaptic activityCultured spinal neuronsSynaptic activitySpinal neuronsGlutamatergic synapsesSynaptic currentsGlutamatergic synaptic activityIsoxazolepropionic acid (AMPA) receptorsSpontaneous synaptic currentsOlder neuronsSynaptic NMDARsExogenous glutamateNMDARAcid receptorsSynaptic regionNeuronsReceptor openingSignificant increaseTime courseSynapsesSequence of eventsActivityWeeksCourseReceptors
1999
The role of voltage-gated Ca2+ channels in anoxic injury of spinal cord white matter
Imaizumi T, Kocsis J, Waxman S. The role of voltage-gated Ca2+ channels in anoxic injury of spinal cord white matter. Brain Research 1999, 817: 84-92. PMID: 9889329, DOI: 10.1016/s0006-8993(98)01214-1.Peer-Reviewed Original ResearchConceptsVoltage-gated Ca2Spinal cord axonsAnoxic injuryDorsal columnsR-type voltage-gated Ca2N-type calcium channelsSpinal cord white matterRat dorsal columnsDorsal column axonsR-type Ca2Rat spinal cordCord white matterT-type channelsInflux of Ca2Dose-dependent mannerLoss of conductionAxonal conductionSpinal cordChannel blockersCalcium channelsSurface stimulationWhite matterPerfusion solutionInjuryGlass microelectrodes
1998
Transplanted Olfactory Ensheathing Cells Remyelinate and Enhance Axonal Conduction in the Demyelinated Dorsal Columns of the Rat Spinal Cord
Imaizumi T, Lankford K, Waxman S, Greer C, Kocsis J. Transplanted Olfactory Ensheathing Cells Remyelinate and Enhance Axonal Conduction in the Demyelinated Dorsal Columns of the Rat Spinal Cord. Journal Of Neuroscience 1998, 18: 6176-6185. PMID: 9698311, PMCID: PMC2605360, DOI: 10.1523/jneurosci.18-16-06176.1998.Peer-Reviewed Original ResearchConceptsDorsal column axonsRat spinal cordSpinal cordRemyelinated axonsDorsal columnsAdult rat spinal cordExtent of remyelinationTransplantation of OECsSpinal cord lesionsCell injection siteQuantitative histological analysisFunctional remyelinationCord lesionsAxonal conductionNeonatal ratsFocal injectionsConduction blockSchwann cellsConduction velocityInjection siteElectrophysiological propertiesAction potentialsAxonsHistological analysisTransplantationEndogenous NMDA-Receptor Activation Regulates Glutamate Release in Cultured Spinal Neurons
Robert A, Black J, Waxman S. Endogenous NMDA-Receptor Activation Regulates Glutamate Release in Cultured Spinal Neurons. Journal Of Neurophysiology 1998, 80: 196-208. PMID: 9658041, DOI: 10.1152/jn.1998.80.1.196.Peer-Reviewed Original ResearchMeSH Keywords2-Amino-5-phosphonovalerate6-Cyano-7-nitroquinoxaline-2,3-dioneAnimalsAnimals, NewbornBicucullineCells, CulturedExcitatory Amino Acid AntagonistsExcitatory Postsynaptic PotentialsGlutamic AcidNeuronsRatsRats, Sprague-DawleyReceptors, AMPAReceptors, N-Methyl-D-AspartateSpinal CordSynapsesTetrodotoxinTime FactorsConceptsAMPA excitatory postsynaptic currentsExcitatory postsynaptic currentsNMDA receptor activationCultured spinal neuronsNMDA receptorsSpinal neuronsPresynaptic terminalsNMDA receptor-mediated glutamatergic neurotransmissionSpontaneous excitatory postsynaptic currentsAspartate receptor activationNMDA receptor activityRelease of neurotransmittersNonsynaptic receptorsTTX applicationGlutamate releaseImmature neuronsGlutamatergic neurotransmissionPostsynaptic currentsSpinal cordReceptor activationReceptor activityQuantal sizeQuantal analysisCNS developmentElectrical activityEffects of Glucose Deprivation, Chemical Hypoxia, and Simulated Ischemia on Na+ Homeostasis in Rat Spinal Cord Astrocytes
Rose C, Waxman S, Ransom B. Effects of Glucose Deprivation, Chemical Hypoxia, and Simulated Ischemia on Na+ Homeostasis in Rat Spinal Cord Astrocytes. Journal Of Neuroscience 1998, 18: 3554-3562. PMID: 9570787, PMCID: PMC6793162, DOI: 10.1523/jneurosci.18-10-03554.1998.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornAntimetabolitesAstrocytesBenzofuransCell HypoxiaDeoxyglucoseEnergy MetabolismEnzyme InhibitorsEthers, CyclicExcitatory Amino Acid AgonistsFluorescent DyesFluorides, TopicalGlucoseGlycolysisHomeostasisIschemiaKainic AcidNeurotoxinsOuabainRatsRats, Sprague-DawleySodiumSodium AzideSodium FluorideSodium-Potassium-Exchanging ATPaseSpinal CordTetrodotoxinConceptsSpinal cord astrocytesChemical hypoxiaGlucose deprivationEnergy failureCultured spinal cord astrocytesGlutamatergic agonist kainateGlucose salineGlutamate reuptakeVivo ischemiaSpinal cordGlial functionMetabolic insultsSimulated ischemiaAgonist kainateIschemiaStandard salineAstrocytesSalineHypoxiaIntracellular ion concentrationsGlucose removalExtracellular spaceDeprivationL-lactateReperfusionNovel splice variants of the voltage-sensitive sodium channel alpha subunit
Oh Y, Waxman S. Novel splice variants of the voltage-sensitive sodium channel alpha subunit. Neuroreport 1998, 9: 1267-1272. PMID: 9631410, DOI: 10.1097/00001756-199805110-00002.Peer-Reviewed Original ResearchMeSH KeywordsAlternative SplicingAmino Acid SequenceAnimalsAnimals, NewbornAstrocytesAstrocytomaBrainBucladesineCalcimycinCells, CulturedGenetic VariationMacromolecular SubstancesModels, MolecularMolecular Sequence DataPolymerase Chain ReactionProtein ConformationRatsRats, Sprague-DawleySodium ChannelsSpinal CordUp-RegulationConceptsChannel alpha subunitNeuroblastoma cellsSpinal cord astrocytesB104 neuroblastoma cellsCultured rat astrocytesChannel mRNA expressionNovel splice variantSplice variantsSodium channel alpha subunitAlpha-subunit mRNASpinal cordCerebral astrocytesUnique regulatory pathwaysAlpha subunitRat astrocytesAstrocytesMRNA expressionSubunit mRNAsMicroM A23187Dibutyryl cAMPPremature truncationCellsExpressionRegulatory pathwaysCord
1997
Pharmacological Characterization of Na+ Influx via Voltage-Gated Na+ Channels in Spinal Cord Astrocytes
Rose C, Ransom B, Waxman S. Pharmacological Characterization of Na+ Influx via Voltage-Gated Na+ Channels in Spinal Cord Astrocytes. Journal Of Neurophysiology 1997, 78: 3249-3258. PMID: 9405543, DOI: 10.1152/jn.1997.78.6.3249.Peer-Reviewed Original ResearchConceptsSpinal cordChannel inactivationCultured spinal cordSpinal cord astrocytesEffect of veratridineSodium-binding benzofuranMicroM tetrodotoxinPharmacological characterizationAgonist kainatePharmacological inhibitionTetrodotoxinAstrocytesVeratridineCordMembrane depolarizationKainateImportant functional roleInfluxFunctional roleInhibitionCellsProminent pathwayATPase activityInactivationBaselineImmunolocalization of the Na+–Ca2+ exchanger in mammalian myelinated axons
Steffensen I, Waxman S, Mills L, Stys P. Immunolocalization of the Na+–Ca2+ exchanger in mammalian myelinated axons. Brain Research 1997, 776: 1-9. PMID: 9439790, DOI: 10.1016/s0006-8993(97)00868-8.Peer-Reviewed Original ResearchConceptsOptic nerveSpinal cordDorsal root axonsSciatic nerve sectionRat optic nerveCentral myelinated axonsCardiac type IFiner processesSimilar staining patternNerve sectionDorsal columnsSciatic nerveFrozen cryostat sectionsAnoxic injuryAxonal profilesImmunofluorescence labeling techniqueMyelinated axonsCell bodiesCryostat sectionsImportant mediatorAxonal localizationMammalian axonsNerveAxonsStaining patternRegulation of Na+ channel β1 and β2 subunit mRNA levels in cultured rat astrocytes
Oh Y, Lee Y, Waxman S. Regulation of Na+ channel β1 and β2 subunit mRNA levels in cultured rat astrocytes. Neuroscience Letters 1997, 234: 107-110. PMID: 9364509, DOI: 10.1016/s0304-3940(97)00694-0.Peer-Reviewed Original ResearchConceptsReverse transcription-polymerase chain reactionMRNA levelsSpinal cordCompetitive reverse transcription-polymerase chain reactionQuantitative competitive reverse transcription-polymerase chain reactionSpinal cord astrocytesRat optic nerveDibutyryl cAMPBeta 2 mRNACultured rat astrocytesTranscription-polymerase chain reactionBeta 1 mRNASubunit mRNA levelsNeuroblastoma cell linesOptic nerveChannel β1Cultured astrocytesRat astrocytesCalcium ionophoreAstrocytesBeta 1Chain reactionCell linesCordMRNA
1996
Manipulation of the delayed rectifier Kv1.5 potassium channel in glial cells by antisense oligodeoxynucleotides
Roy M, Saal D, Perney T, Sontheimer H, Waxman S, Kaczmarek L. Manipulation of the delayed rectifier Kv1.5 potassium channel in glial cells by antisense oligodeoxynucleotides. Glia 1996, 18: 177-184. PMID: 8915650, DOI: 10.1002/(sici)1098-1136(199611)18:3<177::aid-glia2>3.0.co;2-x.Peer-Reviewed Original ResearchConceptsGlial cellsKv1.5 channel proteinSpinal cordKv1.5 proteinCultured spinal cordTEA-insensitive currentSpinal cord astrocytesRectifier current densityPotassium channel typesAntisense oligodeoxynucleotide treatmentKv1.5 potassium channelAdult ratsCerebellar slicesChannel proteinsAstrocytesOligodeoxynucleotide treatmentPotassium channelsRectifier currentEndfoot processesSuch treatmentCurrent activationAntisense oligodeoxynucleotidesCordCellsTreatmentExpression of mRNA for a sodium channel in subfamily 2 in spinal sensory neurons
Waxman S, Black J. Expression of mRNA for a sodium channel in subfamily 2 in spinal sensory neurons. Neurochemical Research 1996, 21: 395-401. PMID: 8734431, DOI: 10.1007/bf02527702.Peer-Reviewed Original ResearchConceptsDorsal root gangliaSpinal sensory neuronsSchwann cellsDRG neuronsSensory neuronsRat dorsal root gangliaSodium channelsΒ1 subunitExpression of mRNARoot gangliaSpinal cordSitu hybridization cytochemistryNeuronsΑ-subunitAntisense riboprobesBlot analysisType IMRNACellsExpressionHigh levelsGangliaRNA blot analysisHippocampusCord
1995
Na+ channel β1 subunit mRNA expression in developing rat central nervous system
Sashihara S, Oh Y, Black J, Waxman S. Na+ channel β1 subunit mRNA expression in developing rat central nervous system. Brain Research 1995, 34: 239-250. PMID: 8750827, DOI: 10.1016/0169-328x(95)00168-r.Peer-Reviewed Original ResearchConceptsGranule cell layerCell layerRat central nervous systemBeta 1Channel beta 1 subunitRexed's lamina IXDentate granule cellsPyramidal cell layerPostnatal day 2Beta 1 expressionSpecific neuronal populationsVentral-dorsal gradientCentral nervous systemSubunit mRNA expressionVoltage-dependent sodium channelsExternal granule cell layerInternal granule cell layerDorsal hornVentral hornLamina IXSpinal cordBeta 1 subunitAdult ratsIntensity of labelingGranule cellsExpression of sodium channel α- and β-subunits in the nervous system of themyelin-deficient rat
Felts P, Black J, Waxman S. Expression of sodium channel α- and β-subunits in the nervous system of themyelin-deficient rat. Brain Cell Biology 1995, 24: 654-666. PMID: 7500121, DOI: 10.1007/bf01179816.Peer-Reviewed Original ResearchConceptsSodium channel αMale littermatesSubtype-specific riboprobesDorsal root gangliaChannel αNormal male littermatesSodium channel subunitsUnaffected male littermatesDays of ageAdult expression patternRoot gangliaSpinal cordExpression patternsAdult ratsNervous systemUnaffected littermatesSodium channelsLittermatesPattern of expressionChannel subunitsRatsGreater expressionSitu hybridization techniqueUnaffected animalsPrevious reportsNa+ channel β1 subunit mRNA: differential expression in rat spinal sensory neurons
Oh Y, Sashihara S, Black J, Waxman S. Na+ channel β1 subunit mRNA: differential expression in rat spinal sensory neurons. Brain Research 1995, 30: 357-361. PMID: 7637585, DOI: 10.1016/0169-328x(95)00052-t.Peer-Reviewed Original ResearchConceptsDRG neuronsNervous systemChannel beta 1 subunit (Na beta 1) mRNARat dorsal root ganglion neuronsCell bodiesDorsal root ganglion neuronsSubunit mRNAsBeta 1 mRNA expressionRat central nervous systemSmall DRG neuronsLarge DRG neuronsSpinal sensory neuronsPeripheral nervous systemPostnatal day 4Central nervous systemBeta 1 mRNABeta 1 subunit mRNASitu hybridization histochemistryAdult DRGGanglion neuronsSensory neuronsDay 4Hybridization histochemistryMRNA expressionNeurons
1994
Type II sodium channels in spinal cord astrocytes in situ: Immunocytochemical observations
Black J, Westenbroek R, Ransom B, Catterall W, Waxman S. Type II sodium channels in spinal cord astrocytes in situ: Immunocytochemical observations. Glia 1994, 12: 219-227. PMID: 7851989, DOI: 10.1002/glia.440120307.Peer-Reviewed Original ResearchConceptsAdult rat spinal cordRat spinal cordOptic nerveSubtype-specific sequencesSpinal cordVentral funiculusSpinal cord white matter tractsSpinal cord white matterSodium channelsSpinal cord astrocytesCord white matterWhite matter tractsType ISodium channel alphaWhite matterAstrocytesNerveImmunocytochemical methodsCordChannel alphaSodium channel IIIsoform expressionDetectable labelingType II sodium channelsImmunocytochemical observations