2022
Dorsal bed nucleus of stria terminalis in depressed and nondepressed temporal lobe epilepsy patients
Dhaher R, Bronen RA, Spencer L, Colic L, Brown F, Mian A, Sandhu M, Pittman B, Spencer D, Blumberg HP, Altalib H. Dorsal bed nucleus of stria terminalis in depressed and nondepressed temporal lobe epilepsy patients. Epilepsia 2022, 63: 2561-2570. PMID: 35883245, DOI: 10.1111/epi.17377.Peer-Reviewed Original ResearchConceptsTemporal lobe epilepsyDorsal bed nucleusTLE patientsEpilepsy patientsBed nucleusHC subjectsStria terminalisTemporal lobe epilepsy patientsMini International Neuropsychiatric InterviewMagnetic resonance imaging (MRI) scansTreatment-resistant depressionComprehensive Epilepsy CenterHealthy control subjectsStructural magnetic resonance imaging (MRI) scansResonance imaging scansNumber of patientsCase-control studyInternational Neuropsychiatric InterviewMajor depressive disorderCommon comorbid disordersHuman clinical studiesEpilepsy centersLobe epilepsyComorbid depressionControl subjects
2021
Small loci of astroglial glutamine synthetase deficiency in the postnatal brain cause epileptic seizures and impaired functional connectivity
Farina MG, Sandhu MRS, Parent M, Sanganahalli BG, Derbin M, Dhaher R, Wang H, Zaveri HP, Zhou Y, Danbolt NC, Hyder F, Eid T. Small loci of astroglial glutamine synthetase deficiency in the postnatal brain cause epileptic seizures and impaired functional connectivity. Epilepsia 2021, 62: 2858-2870. PMID: 34536233, PMCID: PMC9006438, DOI: 10.1111/epi.17072.Peer-Reviewed Original ResearchConceptsPostnatal brainFunctional connectivityContinuous video-electroencephalographic recordingSpontaneous recurrent seizuresPathogenesis of epilepsyGlutamine synthetase deficiencyVideo-electroencephalographic recordingsSpecific animal modelsEx vivo studySeizure thresholdAdult patientsRecurrent seizuresFocal epilepsyAdeno-associated virusHippocampal formationAnimal modelsFocal mannerEpileptic seizuresGS deficiencySmall lociSynthetase deficiencyEpilepsyGradual returnVivo studiesBrainIncreased branched‐chain amino acids at baseline and hours before a spontaneous seizure in the human epileptic brain
Ong C, Damisah EC, Gruenbaum SE, Dhaher R, Deng Y, Sandhu MRS, Zaveri HP, Spencer DD, Eid T. Increased branched‐chain amino acids at baseline and hours before a spontaneous seizure in the human epileptic brain. Epilepsia 2021, 62: e88-e97. PMID: 33949690, PMCID: PMC11259155, DOI: 10.1111/epi.16920.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAmino Acids, Branched-ChainBrain ChemistryChildChild, PreschoolChromatography, High Pressure LiquidDrug Resistant EpilepsyElectrocorticographyElectroencephalographyEpilepsies, PartialExtracellular SpaceFemaleGlutamic AcidHumansIsoleucineMaleMicrodialysisMiddle AgedSeizuresTandem Mass SpectrometryYoung AdultConceptsSpontaneous seizuresDrug-resistant focal epilepsyExtracellular brain glutamateHuman epileptic brainBranched-chain amino acidsBranched chain amino acids valineRefractory epilepsyBrain microdialysisGlutamatergic neurotransmissionFocal epilepsySeizure onsetBrain glutamateEpileptic brainHuman patientsSeizuresBrain regionsDialysis samplesMammalian targetEpilepsyLiquid chromatography-tandem mass spectrometryBaselineBCAAIntracranial electroencephalographyChromatography-tandem mass spectrometryPatientsAstroglial Glutamine Synthetase and the Pathogenesis of Mesial Temporal Lobe Epilepsy
Sandhu MRS, Gruenbaum BF, Gruenbaum SE, Dhaher R, Deshpande K, Funaro MC, Lee TW, Zaveri HP, Eid T. Astroglial Glutamine Synthetase and the Pathogenesis of Mesial Temporal Lobe Epilepsy. Frontiers In Neurology 2021, 12: 665334. PMID: 33927688, PMCID: PMC8078591, DOI: 10.3389/fneur.2021.665334.Peer-Reviewed Original ResearchMesial temporal lobe epilepsyAstroglial glutamine synthetaseTemporal lobe epilepsyLobe epilepsyIntractable mesial temporal lobe epilepsyAstrocytic glutamine synthetaseDepressive-like featuresPathogenesis of epilepsyType of epilepsyDiscrete brain regionsNeocortical epilepsyHippocampal neuronsEpilepsyBrain regionsGlutamate-ammonia ligaseLaboratory animalsPathogenesisPossible roleExperimental inhibitionGlutamine synthetaseEnzyme glutamine synthetaseDysfunctionSeizuresAstrocytesSyndromeNetwork-Related Changes in Neurotransmitters and Seizure Propagation During Rodent Epileptogenesis
Dhaher R, Gruenbaum SE, Sandhu MRS, Ottestad-Hansen S, Tu N, Wang Y, Lee TW, Deshpande K, Spencer DD, Danbolt NC, Zaveri HP, Eid T. Network-Related Changes in Neurotransmitters and Seizure Propagation During Rodent Epileptogenesis. Neurology 2021, 96: e2261-e2271. PMID: 33722994, PMCID: PMC8166437, DOI: 10.1212/wnl.0000000000011846.Peer-Reviewed Original ResearchConceptsSpontaneous seizuresSeizure propagationSeizure focusMesial temporal lobe epilepsyExtracellular brain levelsTemporal lobe epilepsyExtracellular glutamate levelsRelevant rodent modelsGlutamine synthetase inhibitor methionine sulfoximineTransporter subtype 1Contralateral hippocampusLobe epilepsyBrain levelsBrain microdialysisExtracellular GABANeurotransmitter levelsSeizure initiationGlutamate levelsSeizure onsetEpilepsy networkRodent modelsSubtype 1EpileptogenesisHippocampusBrain regions
2020
Circadian-Like Rhythmicity of Extracellular Brain Glutamate in Epilepsy
Sandhu MRS, Dhaher R, Gruenbaum SE, Raaisa R, Spencer DD, Pavlova MK, Zaveri HP, Eid T. Circadian-Like Rhythmicity of Extracellular Brain Glutamate in Epilepsy. Frontiers In Neurology 2020, 11: 398. PMID: 32499751, PMCID: PMC7242976, DOI: 10.3389/fneur.2020.00398.Peer-Reviewed Original ResearchMesial temporal lobe epilepsyExtracellular brain glutamateSeizure onset regionTemporal lobe epilepsyType of epilepsyExcitatory neurotransmitter glutamateSeizure onset areaTranslational rodent modelEpileptogenic hippocampusLobe epilepsyIntracerebral microdialysisExtracellular glutamateBrain glutamateIndividual patientsRodent modelsControl animalsNeurotransmitter glutamateExtracellular levelsEpilepsySeizuresOnset areaCircadian-like rhythmGlutamateEssential modulatorPatientsOral glutamine supplementation increases seizure severity in a rodent model of mesial temporal lobe epilepsy
Dhaher R, Chen EC, Perez E, Rapuano A, Sandhu MRS, Gruenbaum SE, Deshpande K, Dai F, Zaveri HP, Eid T. Oral glutamine supplementation increases seizure severity in a rodent model of mesial temporal lobe epilepsy. Nutritional Neuroscience 2020, 25: 64-69. PMID: 31900092, PMCID: PMC8970572, DOI: 10.1080/1028415x.2019.1708568.Peer-Reviewed Original ResearchConceptsMesial temporal lobe epilepsyOral glutamine supplementationSeverity of seizuresTemporal lobe epilepsyGlutamine supplementationSeizure severityLobe epilepsyRefractory mesial temporal lobe epilepsyMale Sprague-DawleySeizure frequencyConvulsive seizuresSeizure propagationEpilepsy modelSprague-DawleyEffective treatmentRodent modelsSeizuresSupplementationSeverityPotential roleEpilepsyFunction mutationsHippocampusGlutamine synthetaseDays
2019
Branched-Chain Amino Acids and Seizures: A Systematic Review of the Literature
Gruenbaum SE, Chen EC, Sandhu MRS, Deshpande K, Dhaher R, Hersey D, Eid T. Branched-Chain Amino Acids and Seizures: A Systematic Review of the Literature. CNS Drugs 2019, 33: 755-770. PMID: 31313139, DOI: 10.1007/s40263-019-00650-2.Peer-Reviewed Original ResearchConceptsGenetic absence epilepsyBCAA supplementationAbsence epilepsyAnimal modelsBranched-chain amino acid supplementationSystematic reviewLong-term BCAA supplementationEpilepsy experience seizuresAnti-seizure effectsEffect of BCAAMost animal modelsPossible underlying mechanismsAmino acid supplementationChain amino acidsBCAA administrationBCAA mixtureRefractory epilepsyNeuron lossSeizure disorderAntiepileptic drugsSeizure modelSeizure propagationCochrane LibrarySeizure activityKainic acidEffects of Branched-Chain Amino Acid Supplementation on Spontaneous Seizures and Neuronal Viability in a Model of Mesial Temporal Lobe Epilepsy
Gruenbaum SE, Dhaher R, Rapuano A, Zaveri HP, Tang A, de Lanerolle N, Eid T. Effects of Branched-Chain Amino Acid Supplementation on Spontaneous Seizures and Neuronal Viability in a Model of Mesial Temporal Lobe Epilepsy. Journal Of Neurosurgical Anesthesiology 2019, 31: 247-256. PMID: 29620688, PMCID: PMC6170745, DOI: 10.1097/ana.0000000000000499.Peer-Reviewed Original ResearchConceptsMesial temporal lobe epilepsyTemporal lobe epilepsyLobe epilepsySpontaneous seizuresNeuron lossSeizure propagationBranched-chain amino acid supplementationChronic oral supplementationSpontaneous recurrent seizuresEffect of BCAAPotential novel treatmentBranched-chain amino acid leucineAmino acid supplementationAcute seizuresBCAA supplementationChronic seizuresConvulsive seizuresOral supplementationRecurrent seizuresRefractory epilepsyDentate hilusNeuronal viabilityAcid supplementationImmunohistochemical analysisNovel treatments
2018
Selective deletion of glutamine synthetase in the mouse cerebral cortex induces glial dysfunction and vascular impairment that precede epilepsy and neurodegeneration
Zhou Y, Dhaher R, Parent M, Hu QX, Hassel B, Yee SP, Hyder F, Gruenbaum SE, Eid T, Danbolt NC. Selective deletion of glutamine synthetase in the mouse cerebral cortex induces glial dysfunction and vascular impairment that precede epilepsy and neurodegeneration. Neurochemistry International 2018, 123: 22-33. PMID: 30053506, PMCID: PMC8261904, DOI: 10.1016/j.neuint.2018.07.009.Peer-Reviewed Original ResearchConceptsAbnormal glutamate metabolismMouse cerebral cortexCerebral blood vesselsNovel mouse modelPostnatal week threeWeeks of ageProgressive astrogliosisVascular impairmentSpontaneous seizuresCerebral cortexGlial dysfunctionNeurovascular couplingDeficient miceSclerotic areasMouse modelEpileptic patientsApparent malformationsProgressive neurodegenerationSelective deletionGlutamate-ammonia ligaseTissue levelsGlutamate metabolismBlood vesselsWeek threeNeurodegeneration2235 15N-Leucine transport across the blood brain barrier is significantly impaired in the glutamine synthetase-inhibited brain
Gruenbaum S, Dhaher R, Behar K, Zaveri H, Erfe M, Eid T. 2235 15N-Leucine transport across the blood brain barrier is significantly impaired in the glutamine synthetase-inhibited brain. Journal Of Clinical And Translational Science 2018, 2: 1-1. PMCID: PMC6808188, DOI: 10.1017/cts.2018.37.Peer-Reviewed Original ResearchIpsilateral hippocampusDentate gyrusAstroglial glutamine synthetaseMicrodialysis guide cannulaBlood-brain barrierImmune system dysfunctionRight dentate gyrusBilateral dentate gyrusL-type amino acid transporterBrief isoflurane anesthesiaArtificial extracellular fluidSignificant increaseGlutamine concentrationImportant therapeutic targetBilateral microdialysis probesAmino acid influxMethionine sulfoximineContralateral hippocampusLiver diseaseBrain ammoniaSynaptic glutamateBrain barrierSystem dysfunctionGuide cannulaIsoflurane anesthesia5 Oral Administration of Branched-Chain Amino Acids Results in Increased Seizure Threshold and Loss of Hippocampal Neurons in a Rodent Model of Mesial Temporal Lobe Epilepsy
Gruenbaum S, Dhaher R, Rapuano A, Tang A, Eid T. 5 Oral Administration of Branched-Chain Amino Acids Results in Increased Seizure Threshold and Loss of Hippocampal Neurons in a Rodent Model of Mesial Temporal Lobe Epilepsy. American Journal Of Clinical Pathology 2018, 149: s165-s166. DOI: 10.1093/ajcp/aqx149.374.Peer-Reviewed Original ResearchMesial temporal lobe epilepsyTemporal lobe epilepsyBCAA ingestionSeizure thresholdSpontaneous seizuresDays of drinkingRodent modelsLobe epilepsyDentate hilusControl ratsControl groupHilar neuron lossIncreased seizure thresholdInjection of pentylenetetrazoleSingle intraperitoneal injectionRight dentate gyrusRelevant rodent modelsGlutamine synthetase inhibitor methionine sulfoximineBranched-chain amino acid leucineBCAA groupInduced seizuresOral supplementationNeuron lossEpileptic ratsDentate gyrus
2017
2092
Gruenbaum S, Dhaher R, Rapuano A, Eid T. 2092. Journal Of Clinical And Translational Science 2017, 1: 56-56. PMCID: PMC6798929, DOI: 10.1017/cts.2017.200.Peer-Reviewed Original ResearchTemporal lobe epilepsyDays of drinkingDentate hilusBCAA groupNeuronal viabilityControl groupHilar neuron lossHilar neuronal lossRight dentate gyrusRelevant rodent modelsRole of BCAABCAA ingestionNeuronal lossSpontaneous seizuresLobe epilepsyNeuron lossSeizure activityChronic ingestionDentate gyrusInfusion siteHilar regionRodent modelsMethionine sulfoximineNeurochemical modulationRats