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 ResearchMeSH KeywordsAnimalsAstrocytesBrainEpilepsyGlial Fibrillary Acidic ProteinGlutamate-Ammonia LigaseGlutamineHumansMetabolic DiseasesMiceSeizuresConceptsPostnatal 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 studiesBrain
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
2018
Astrocytes and Glutamine Synthetase in Epileptogenesis
Eid T, Lee T, Patrylo P, Zaveri HP. Astrocytes and Glutamine Synthetase in Epileptogenesis. Journal Of Neuroscience Research 2018, 97: 1345-1362. PMID: 30022509, PMCID: PMC6338538, DOI: 10.1002/jnr.24267.Peer-Reviewed Original ResearchConceptsMesial temporal lobe epilepsyTemporal lobe epilepsyLobe epilepsyAstrocytic glutamine synthetaseRole of astrocytesPotassium channel Kir4.1Important causative factorExcitatory amino acid transporters EAAT1Antiepileptogenic interventionsEpileptogenic insultAntiepileptogenic therapiesEpilepsy developmentChannel Kir4.1Aquaporin-4EpilepsyCausative factorsTransporters EAAT1New targetsSuch interventionsTransporters MCT1DysfunctionAstrocytesMetabolic mechanismsGlutamine synthetaseDownstream effects
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 terminalis
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 pumpPatientsEpilepsyAmygdalaEffects of site-specific infusions of methionine sulfoximine on the temporal progression of seizures in a rat model of mesial temporal lobe epilepsy
Dhaher R, Wang H, Gruenbaum SE, Tu N, Lee TS, Zaveri HP, Eid T. Effects of site-specific infusions of methionine sulfoximine on the temporal progression of seizures in a rat model of mesial temporal lobe epilepsy. Epilepsy Research 2015, 115: 45-54. PMID: 26220375, PMCID: PMC4677790, DOI: 10.1016/j.eplepsyres.2015.05.005.Peer-Reviewed Original ResearchConceptsMesial temporal lobe epilepsyTemporal lobe epilepsyRecurrent seizuresLateral ventricleLobe epilepsyDentate gyrusEntorhinal cortexDeep entorhinal cortexEntorhinal-hippocampal areaWeek recording periodSite-specific infusionPhosphate-buffered salineDays of infusionAdult laboratory ratsRecording periodMethionine sulfoximineSeizure severitySeizure activitySevere seizuresMetabolism of glutamateRat modelSynaptic transmissionAnatomical distributionHippocampal formationAngular bundle
2008
Recurrent 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 ResearchMeSH KeywordsAnimalsElectroencephalographyEpilepsy, Temporal LobeGlutamate-Ammonia LigaseGlutathioneHippocampusMaleMethionine SulfoximineModels, AnimalRatsRats, Sprague-DawleyRecurrenceConceptsMesial 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