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 synthetaseDysfunctionSeizuresAstrocytesSyndrome
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