2020
Oral 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
2017
Network evolution in mesial temporal lobe epilepsy revealed by diffusion tensor imaging
Wang H, Huang Y, Coman D, Munbodh R, Dhaher R, Zaveri HP, Hyder F, Eid T. Network evolution in mesial temporal lobe epilepsy revealed by diffusion tensor imaging. Epilepsia 2017, 58: 824-834. PMID: 28378878, PMCID: PMC5429866, DOI: 10.1111/epi.13731.Peer-Reviewed Original ResearchConceptsMesial temporal lobe epilepsyDiffusion tensor imagingTemporal lobe epilepsyFractional anisotropyLobe epilepsyAstroglial glutamine synthetaseEntorhinal-hippocampal areaEpileptogenic hippocampal formationNumerous brain regionsMultiple brain areasBrain diffusion tensor imagingLater time pointsInfused ratsEpileptogenic processCorpus callosumEpileptogenesisHippocampal formationBrain areasImaging biomarkersEarly identificationBrain regionsRatsTensor imagingFA changesTime points
2016
Progressive neuronal activation accompanies epileptogenesis caused by hippocampal glutamine synthetase inhibition
Albright B, Dhaher R, Wang H, Harb R, Lee TW, Zaveri H, Eid T. Progressive neuronal activation accompanies epileptogenesis caused by hippocampal glutamine synthetase inhibition. Experimental Neurology 2016, 288: 122-133. PMID: 27769717, PMCID: PMC5547560, DOI: 10.1016/j.expneurol.2016.10.007.Peer-Reviewed Original ResearchConceptsMesial temporal lobe epilepsyNeuronal activationHippocampal formationHuman mesial temporal lobe epilepsyAnterior olfactory areaEntorhinal-hippocampal areaProcess of epileptogenesisC-Fos immunohistochemistryTemporal lobe epilepsyTypes of seizuresGlutamine synthetase inhibitionSurgical resectionPiriform cortexSeizure severityLobe epilepsyHippocampal astrocytesEpilepsy developmentEpileptogenic processElectroencephalogram monitoringOlfactory areasPharmacological interventionsSeizure phenotypeBed nucleusMidline thalamusStria terminalis50 Hz hippocampal stimulation in refractory epilepsy: Higher level of basal glutamate predicts greater release of glutamate
Cavus I, Widi GA, Duckrow RB, Zaveri H, Kennard JT, Krystal J, Spencer DD. 50 Hz hippocampal stimulation in refractory epilepsy: Higher level of basal glutamate predicts greater release of glutamate. Epilepsia 2016, 57: 288-297. PMID: 26749134, DOI: 10.1111/epi.13269.Peer-Reviewed Original ResearchConceptsBasal glutamate levelsRefractory epilepsyGlutamate effluxBasal glutamateGlutamate levelsElectrical stimulationEpileptic hippocampusGlutamate releaseSeizure groupHz stimulationBrain glutamate releaseHippocampus of patientsStimulation-induced increaseEpilepsy monitoring unitStimulation-induced changesEpileptogenic hippocampusInduced seizuresSeizure inductionSpontaneous seizuresInterictal levelsGlutamate increaseAtrophic hippocampusElectroencephalography evaluationHippocampal stimulationHippocampal electrodes
2015
Inhibition of glutamine synthetase in the central nucleus of the amygdala induces anhedonic behavior and recurrent seizures in a rat model of mesial temporal lobe epilepsy
Gruenbaum SE, Wang H, Zaveri HP, Tang AB, Lee TS, Eid T, Dhaher R. Inhibition of glutamine synthetase in the central nucleus of the amygdala induces anhedonic behavior and recurrent seizures in a rat model of mesial temporal lobe epilepsy. Epilepsy & Behavior 2015, 51: 96-103. PMID: 26262937, PMCID: PMC4663049, DOI: 10.1016/j.yebeh.2015.07.015.Peer-Reviewed Original ResearchMeSH KeywordsAmygdalaAnalysis of VarianceAnhedoniaAnimalsBrainCentral Amygdaloid NucleusComorbidityDepressive DisorderDisease Models, AnimalElectroencephalographyEnzyme InhibitorsEpilepsy, Temporal LobeGlutamate-Ammonia LigaseHippocampusMaleMethionine SulfoximineNeuronsRatsRats, Sprague-DawleySeizuresConceptsMesial temporal lobe epilepsyTemporal lobe epilepsyRecurrent seizuresLobe epilepsyCentral nucleusMale Sprague-Dawley ratsPrevalence of depressionSprague-Dawley ratsGlutamine synthetase inhibitor methionine sulfoximineMeasures of anhedoniaRight CeA.Seizure activityAnhedonic behaviorDentate gyrusMedial amygdalaSucrose preferenceRat modelCommon causeAstrocytic enzymeBasolateral amygdalaLateral amygdalaOsmotic pumpPatientsEpilepsyAmygdala
2012
Evidence for astrocytes as a potential source of the glutamate excess in temporal lobe epilepsy
Perez EL, Lauritzen F, Wang Y, Lee TS, Kang D, Zaveri HP, Chaudhry FA, Ottersen OP, Bergersen LH, Eid T. Evidence for astrocytes as a potential source of the glutamate excess in temporal lobe epilepsy. Neurobiology Of Disease 2012, 47: 331-337. PMID: 22659305, PMCID: PMC3392431, DOI: 10.1016/j.nbd.2012.05.010.Peer-Reviewed Original ResearchConceptsTemporal lobe epilepsyRecurrent seizuresConcentration of glutamateHippocampal formationLobe epilepsyExtracellular glutamateRefractory temporal lobe epilepsyEpileptogenic hippocampal formationExtracellular brain glutamateSubset of patientsSaline-treated ratsStart of infusionRatio of glutamateExcessive glutamateGlutamate excessBrain glutamateExtracellular brainAstrocytesExcessive releaseGS deficiencyRatsSeizuresGlutamateSeparate groupsEpilepsy
2009
The development of recurrent seizures after continuous intrahippocampal infusion of methionine sulfoximine in rats A video-intracranial electroencephalographic study
Wang Y, Zaveri HP, Lee TS, Eid T. The development of recurrent seizures after continuous intrahippocampal infusion of methionine sulfoximine in rats A video-intracranial electroencephalographic study. Experimental Neurology 2009, 220: 293-302. PMID: 19747915, PMCID: PMC2989153, DOI: 10.1016/j.expneurol.2009.08.034.Peer-Reviewed Original ResearchConceptsMesial temporal lobe epilepsyHuman mesial temporal lobe epilepsyRecurrent seizuresNeuronal lossPartial seizuresPathophysiology of mTLEDiffuse neuronal lossSaline-treated animalsTemporal lobe epilepsyMinimal neuronal lossGlutamine synthetase inhibitor methionine sulfoximineEpileptogenic hippocampusHippocampal sclerosisLobe epilepsyElectroencephalogram monitoringStage IElectrophysiological mechanismsSeizuresElectroencephalographic studiesDays durationIntrahippocampal infusionHippocampusInfusionMethionine sulfoximineIntracranial EEG
2008
Decreased hippocampal volume on MRI is associated with increased extracellular glutamate in epilepsy patients
Cavus I, Pan JW, Hetherington HP, Abi‐Saab W, Zaveri HP, Vives KP, Krystal JH, Spencer SS, Spencer DD. Decreased hippocampal volume on MRI is associated with increased extracellular glutamate in epilepsy patients. Epilepsia 2008, 49: 1358-1366. PMID: 18410365, DOI: 10.1111/j.1528-1167.2008.01603.x.Peer-Reviewed Original ResearchConceptsTemporal lobe epilepsyHippocampal volumeClinical factorsHippocampal atrophyEpileptogenic hippocampusGABA levelsNeurochemical levelsElevated extracellular glutamate levelsContralateral hippocampal volumeIntracranial EEG evaluationMedication-resistant epilepsyRefractory TLE patientsHigh seizure frequencyRelevant clinical factorsSmaller hippocampal volumesExtracellular glutamate levelsFebrile seizure historyTreatment of epilepsySeizure frequencyLobe epilepsySeizure historyTLE patientsAtrophic hippocampusGlutamate levelsExtracellular glutamateNeurometabolism in human epilepsy
Pan JW, Williamson A, Cavus I, Hetherington HP, Zaveri H, Petroff OA, Spencer DD. Neurometabolism in human epilepsy. Epilepsia 2008, 49: 31-41. PMID: 18304254, PMCID: PMC3657747, DOI: 10.1111/j.1528-1167.2008.01508.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrain DiseasesBrain MappingCarbon IsotopesDominance, CerebralElectrodes, ImplantedElectroencephalographyEpilepsyGamma-Aminobutyric AcidGlucoseHippocampusHumansLimbic SystemMagnetic Resonance SpectroscopyMetabolic DiseasesMicrodialysisMitochondrial DiseasesNeural PathwaysNeuronsPositron-Emission TomographyRatsSynaptic TransmissionConceptsNeurometabolic dysfunctionMagnetic resonance spectroscopic imagingHuman epilepsyEpileptic brainHippocampal resectionSclerotic hippocampusPathophysiologic aspectsEpileptogenic processMicrodialysis measuresExtracellular glutamateEpileptic dysfunctionEnergetic dysfunctionHuman studiesDysfunctionNeurotransmitter cyclingNoninvasive functional imagingProfound decreaseMitochondrial injuryBrain functionEpilepsyFunctional imagingMetabolic imagingBrainIntracranial EEGNeurometabolismRecurrent seizures and brain pathology after inhibition of glutamine synthetase in the hippocampus in rats
Eid T, Ghosh A, Wang Y, Beckström H, Zaveri HP, Lee TS, Lai JC, Malthankar-Phatak GH, de Lanerolle NC. Recurrent seizures and brain pathology after inhibition of glutamine synthetase in the hippocampus in rats. Brain 2008, 131: 2061-2070. PMID: 18669513, PMCID: PMC2724901, DOI: 10.1093/brain/awn133.Peer-Reviewed Original ResearchConceptsMesial temporal lobe epilepsyMesial temporal sclerosisRecurrent seizuresTemporal sclerosisBrain pathologyIntractable mesial temporal lobe epilepsyTemporal lobe epilepsyGlutamine synthetase deficiencyNovel animal modelContinuous microinfusionHippocampal atrophyLobe epilepsyGlutamate excessNeuropathological featuresExtracellular glutamateHippocampal neuronsAnimal modelsTherapeutic interventionsHippocampusSeizuresSclerosisSynthetase deficiencyMinimal injuryPatientsRats
2003
A Retrospective Analysis of Hippocampal Pathology in Human Temporal Lobe Epilepsy: Evidence for Distinctive Patient Subcategories
De Lanerolle NC, Kim JH, Williamson A, Spencer SS, Zaveri HP, Eid T, Spencer DD. A Retrospective Analysis of Hippocampal Pathology in Human Temporal Lobe Epilepsy: Evidence for Distinctive Patient Subcategories. Epilepsia 2003, 44: 677-687. PMID: 12752467, DOI: 10.1046/j.1528-1157.2003.32701.x.Peer-Reviewed Original ResearchMeSH KeywordsAdultApoptosisCell CountCulture TechniquesDentate GyrusDynorphinsElectroencephalographyEpilepsy, Temporal LobeEvoked PotentialsFemaleFollow-Up StudiesHippocampusHumansImmunoenzyme TechniquesInterneuronsMaleNeuronsNeuropeptide YReference ValuesRetrospective StudiesSclerosisSomatostatinSubstance PTreatment OutcomeConceptsIntractable temporal lobe epilepsyTemporal lobe epilepsyDentate granule cellsLobe epilepsySurgical outcomesNeuronal lossNeuronal densityGranule cellsDentate gyrusNonsclerotic hippocampiRetrospective analysisHippocampal subfieldsHuman temporal lobe epilepsyBasis of pathophysiologyEvidence of sclerosisSignificant neuronal lossExtensive neuronal lossSharp electrode recordingsPatient subcategoriesSignificant hyperexcitabilityAutopsy controlsHippocampal pathologyNeuropeptide YImmunohistochemical characteristicsSubstance P
2001
Distinguishing Subtypes of Temporal Lobe Epilepsy with Background Hippocampal Activity
Zaveri H, Duckrow R, De Lanerolle N, Spencer S. Distinguishing Subtypes of Temporal Lobe Epilepsy with Background Hippocampal Activity. Epilepsia 2001, 42: 725-730. PMID: 11422326, DOI: 10.1046/j.1528-1157.2001.00500.x.Peer-Reviewed Original ResearchConceptsMesial temporal sclerosisTemporal lobe epilepsyLobe epilepsySurgical outcomesIntractable temporal lobe epilepsyPoor surgical outcomesGood surgical outcomeMedial temporal structuresMedial temporal lobeDelta band powerTemporal sclerosisRetrospective studyHippocampal tissueBackground EEGSeizure onsetIndividual patientsSurgical proceduresIntracranial monitoringTemporal lobeGamma frequency bandClinical observationsPatientsAnterior hippocampusCell lossSubtypes