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 hyperreflexia
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
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
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