2021
Astroglial 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
Gene expression in the epileptic (EL) mouse hippocampus
Lee TS, Li AY, Rapuano A, Mantis J, Eid T, Seyfried TN, de Lanerolle NC. Gene expression in the epileptic (EL) mouse hippocampus. Neurobiology Of Disease 2020, 147: 105152. PMID: 33153970, DOI: 10.1016/j.nbd.2020.105152.Peer-Reviewed Original ResearchConceptsTemporal lobe epilepsyHuman temporal lobe epilepsySeizure focusHippocampal seizure focusRole of neurogliaExtensive neuronal lossMolecular changesEpileptic miceMicroglial activationNeuronal lossNeuron lossEl miceLobe epilepsySeizure modelHippocampal fieldsSeizure generationPathological changesPaucity of studiesMouse hippocampusAnimal modelsHeat shock proteinsNormal populationPathological processesExpression levelsEpilepsyCircadian-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 modulatorPatients
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 effects5 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
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 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
2006
Changes in glial glutamate transporters in human epileptogenic hippocampus: Inadequate explanation for high extracellular glutamate during seizures
Bjørnsen LP, Eid T, Holmseth S, Danbolt NC, Spencer DD, de Lanerolle NC. Changes in glial glutamate transporters in human epileptogenic hippocampus: Inadequate explanation for high extracellular glutamate during seizures. Neurobiology Of Disease 2006, 25: 319-330. PMID: 17112731, DOI: 10.1016/j.nbd.2006.09.014.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAmino Acid Transport System X-AGAstrocytesChildChild, PreschoolDown-RegulationEpilepsyEpilepsy, Temporal LobeExcitatory Amino Acid Transporter 1Excitatory Amino Acid Transporter 2Extracellular FluidFemaleGlutamic AcidHippocampusHumansImmunohistochemistryMaleMicroscopy, Electron, TransmissionMiddle AgedUp-RegulationConceptsTemporal lobe epilepsySclerotic hippocampusNeuronal lossExtracellular glutamateGlial glutamate transporters GLASTHigh extracellular glutamate levelsGroups of hippocampiHuman epileptogenic hippocampusLess neuronal lossExtracellular glutamate levelsGlutamate transporter GLASTGlial glutamate transportersVivo dialysis studyHigh extracellular glutamateSuch compensatory changesEpileptogenic hippocampusHippocampal sclerosisLobe epilepsySclerotic groupSeizure focusGlutamate levelsWeak immunoreactivityGLT-1Glutamate transportersHippocampus
2004
Loss of glutamine synthetase in the human epileptogenic hippocampus: possible mechanism for raised extracellular glutamate in mesial temporal lobe epilepsy
Eid T, Thomas M, Spencer D, Rundén-Pran E, Lai J, Malthankar G, Kim J, Danbolt N, Ottersen O, de Lanerolle N. Loss of glutamine synthetase in the human epileptogenic hippocampus: possible mechanism for raised extracellular glutamate in mesial temporal lobe epilepsy. The Lancet 2004, 363: 28-37. PMID: 14723991, DOI: 10.1016/s0140-6736(03)15166-5.Peer-Reviewed Original ResearchConceptsMesial temporal lobe epilepsyTemporal lobe epilepsyMTLE hippocampiLobe epilepsyExtracellular glutamateHigh extracellular glutamate concentrationsAnteromedial temporal lobeHuman epileptogenic hippocampusExtracellular glutamate accumulationResolution of seizuresExtracellular glutamate concentrationGlial glutamate transportersMeans of immunohistochemistryEpileptogenic hippocampusSurgical resectionSeizure generationGlutamate homeostasisTemporal lobeAstroglial proliferationEpileptic seizuresGlutamate transportersHippocampusTherapeutic interventionsGlutamate concentrationWestern blot
2003
A Retrospective Analysis of Hippocampal Pathology in Human Temporal Lobe Epilepsy: Evidence for Distinctive Patient Subcategories
De Lanerolle N, Kim J, Williamson A, Spencer S, Zaveri H, Eid T, Spencer D. A Retrospective Analysis of Hippocampal Pathology in Human Temporal Lobe Epilepsy: Evidence for Distinctive Patient Subcategories. Epilepsia 2003, 44: 1131-1131. DOI: 10.1046/j.1528-1157.2003.00448.x.Peer-Reviewed Original Research
2001
Disruption of Inhibition in Area CA1 of the Hippocampus in a Rat Model of Temporal Lobe Epilepsy
Denslow M, Eid T, Du F, Schwarcz R, Lothman E, Steward O. Disruption of Inhibition in Area CA1 of the Hippocampus in a Rat Model of Temporal Lobe Epilepsy. Journal Of Neurophysiology 2001, 86: 2231-2245. PMID: 11698514, DOI: 10.1152/jn.2001.86.5.2231.Peer-Reviewed Original ResearchConceptsTemporal lobe epilepsyLayer III neuronsPaired-pulse stimulationEntorhinal cortexCommissural projectionsDisruption of inhibitionHeterosynaptic inhibitionAOAA injectionPopulation spikesLobe epilepsyInhibitory functionDentate gyrusRat modelAminooxyacetic acidInhibitory interneuronsControl animalsElectrolytic lesionsTemporo-ammonic pathwayMultiple population spikesPaired-pulse inhibitionDuration of afterdischargeLoss of neuronsHigh-frequency stimulationNumber of stimulationsAbnormal physiological responsesIbotenate Injections into the Pre‐ and Parasubiculum Provide Partial Protection against Kainate‐Induced Epileptic Damage in Layer III of Rat Entorhinal Cortex
Eid T, Du F, Schwarcz R. Ibotenate Injections into the Pre‐ and Parasubiculum Provide Partial Protection against Kainate‐Induced Epileptic Damage in Layer III of Rat Entorhinal Cortex. Epilepsia 2001, 42: 817-824. PMID: 11488878, DOI: 10.1046/j.1528-1157.2001.042007817.x.Peer-Reviewed Original ResearchConceptsTemporal lobe epilepsyEntorhinal cortexLayer IIIIbotenate injectionLobe epilepsySeizure-induced damageLoss of neuronsLayer III neuronsRat entorhinal cortexEpileptic damagePartial neuroprotectionExcitatory afferentsPrimary lesionSeizure activityEntorhinal neuronsAnimal modelsIbotenate lesionsPartial protectionLesionsNeuronsKainatePresubiculumEpilepsySerial reconstructionCortex
2000
Neurons in Layer III of the Entorhinal Cortex: A Role in Epileptogenesis and Epilepsy?
SCHWARCZ R, EID T, DU F. Neurons in Layer III of the Entorhinal Cortex: A Role in Epileptogenesis and Epilepsy? Annals Of The New York Academy Of Sciences 2000, 911: 328-342. PMID: 10911883, DOI: 10.1111/j.1749-6632.2000.tb06735.x.Peer-Reviewed Original ResearchConceptsTemporal lobe epilepsyEntorhinal cortexLayer IIILobe epilepsySeizure-induced cell deathProminent excitatory inputSeizure-induced deathLayer III neuronsAminooxyacetic acidAOAA injectionPreferential lesionGABAergic neuronsNeuron lossLimbic structuresExcitatory inputsPathological changesParahippocampal structuresAnimal modelsEpilepsyNeuronsLesionsCell deathCortexDeathInjection
1999
Ultrastructure and immunocytochemical distribution of GABA in layer III of the rat medial entorhinal cortex following aminooxyacetic acid-induced seizures
Eid T, Schwarcz R, Ottersen OP. Ultrastructure and immunocytochemical distribution of GABA in layer III of the rat medial entorhinal cortex following aminooxyacetic acid-induced seizures. Experimental Brain Research 1999, 125: 463-475. PMID: 10323293, DOI: 10.1007/s002210050704.Peer-Reviewed Original ResearchConceptsTemporal lobe epilepsyEntorhinal cortexLayer IIIMedial entorhinal cortexAminooxyacetic acidGABA-immunoreactive neuronsTemporal lobe seizuresAcid-induced seizuresGABA-like immunoreactivityDifferent animal modelsHippocampal region CA1AOAA injectionSimilar neuropathologySwollen dendritesBehavioral seizuresGABA neuronsLobe epilepsyNeuronal profilesNeuropathological changesPyramidal neuronsNerve terminalsAxon terminalsRat medialDendritic spinesLight microscopic preparations
1998
Glutamate receptor subunits GluR1 and GluR2/3 distribution shows reorganization in the human epileptogenic hippocampus
De Lanerolle N, Eid T, Von Campe G, Kovacs I, Spencer D, Brines M. Glutamate receptor subunits GluR1 and GluR2/3 distribution shows reorganization in the human epileptogenic hippocampus. European Journal Of Neuroscience 1998, 10: 1687-1703. PMID: 9751141, DOI: 10.1046/j.1460-9568.1998.00171.x.Peer-Reviewed Original ResearchConceptsDentate granule cellsEpileptogenic hippocampusProximal dendritesGranule cellsGlutamate receptor subunits GluR1Human epileptogenic hippocampusControl of seizuresCA3 pyramidal neuronsTemporal lobe epilepsyDendrites of neuronsSitu hybridization histochemistrySubunit-specific antibodiesGluR1 immunoreactivitySame hippocampusFlop splice variantsHilar neuronsGlutamatergic responsesNeuronal lossLobe epilepsyPyramidal neuronsPrincipal neuronsSeizure focusSubunit GluR1Ammon's hornDendritic excrescences
1997
Neuronal damage after the injection of amino-oxyacetic acid into the rat entorhinal cortex: a silver impregnation study
Du F, Eid T, Schwarcz R. Neuronal damage after the injection of amino-oxyacetic acid into the rat entorhinal cortex: a silver impregnation study. Neuroscience 1997, 82: 1165-1178. PMID: 9466438, DOI: 10.1016/s0306-4522(97)00354-0.Peer-Reviewed Original ResearchConceptsSilver-stained neuronsTemporal lobe epilepsyEntorhinal cortexAcid injectionNeuronal damageLobe epilepsyLayer IIIProlonged seizure activitySilver impregnation studyReactive glial cellsPattern of neurodegenerationHippocampal CA1 fieldLateral amygdaloid nucleusRat entorhinal cortexAminooxyacetic acidAmino-oxyacetic acidMedial entorhinal cortexDegenerated neuronsNeuropathological consequencesDamaged neuronsSeizure activityAmygdaloid nucleusMost neuronsNeuronal deathCA1 field
1996
Afferents to the seizure-sensitive neurons in layer III of the medial entorhinal area: a tracing study in the rat
Eid T, Jorritsma-Byham B, Schwarcz R, Witter MP. Afferents to the seizure-sensitive neurons in layer III of the medial entorhinal area: a tracing study in the rat. Experimental Brain Research 1996, 109: 209-218. PMID: 8738371, DOI: 10.1007/bf00231782.Peer-Reviewed Original ResearchConceptsMedial entorhinal areaEntorhinal areaLayer IIIThalamic nucleiIontophoretic injectionVentral portionSeptum-diagonal band complexRetrograde tracer Fast BlueAnteroventral thalamic nucleusTemporal lobe epilepsyAnterograde tracing techniquesAnteromedial thalamic nucleusNucleus raphe dorsalisTracer Fast BlueLateral entorhinal areaAmino-oxyacetic acidLimbic seizuresLobe epilepsyNeuronal vulnerabilityVentrolateral hypothalamusSurgical specimensAnterograde tracerLayer IVRaphe dorsalisFast Blue
1995
Preferential neuronal loss in layer III of the medial entorhinal cortex in rat models of temporal lobe epilepsy
Du F, Eid T, Lothman E, Kohler C, Schwarcz R. Preferential neuronal loss in layer III of the medial entorhinal cortex in rat models of temporal lobe epilepsy. Journal Of Neuroscience 1995, 15: 6301-6313. PMID: 7472396, PMCID: PMC6577998, DOI: 10.1523/jneurosci.15-10-06301.1995.Peer-Reviewed Original ResearchConceptsPreferential neuronal lossTemporal lobe epilepsyNeuronal lossMedial entorhinal cortexEntorhinal cortexLayer IIILobe epilepsyRat modelIntractable temporal lobe epilepsyAcute status epilepticusLithium/pilocarpineParvalbumin-positive neuronsIntracellular calcium ion concentrationKainic acid administrationNerve cell lossAdult male ratsInjection of diazepamSurviving neuronsProlonged seizuresStatus epilepticusAcid administrationNissl stainingVentral hippocampusKainic acidPathological elevationDifferential neuronal vulnerability to amino-oxyacetate and quinolinate in the rat parahippocampal region
Eid T, Du F, Schwarcz R. Differential neuronal vulnerability to amino-oxyacetate and quinolinate in the rat parahippocampal region. Neuroscience 1995, 68: 645-656. PMID: 8577365, DOI: 10.1016/0306-4522(95)00183-j.Peer-Reviewed Original ResearchConceptsAcute behavioral seizuresBehavioral seizuresDizocilpine maleateNeuronal lossEntorhinal cortexEndogenous N-methyl-D-aspartate receptor agonistN-methyl-D-aspartate receptor antagonist dizocilpine maleateLayer IIIN-methyl-D-aspartate receptor agonistParahippocampal regionN-methyl-D-aspartate (NMDA) receptor subtypeDifferential neuronal vulnerabilityDorsal perirhinal cortexPreferential neuronal lossTemporal lobe epilepsyChloral hydrate anesthesiaLower anesthetic doseNeuropathological sequelaeLobe epilepsyNeuropathological changesLayer VNeuronal vulnerabilityPreferential degenerationAnesthetic doseReceptor agonist