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
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 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
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
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