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 studiesBrainNetwork-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
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
2019
Branched-Chain Amino Acids and Seizures: A Systematic Review of the Literature
Gruenbaum SE, Chen EC, Sandhu MRS, Deshpande K, Dhaher R, Hersey D, Eid T. Branched-Chain Amino Acids and Seizures: A Systematic Review of the Literature. CNS Drugs 2019, 33: 755-770. PMID: 31313139, DOI: 10.1007/s40263-019-00650-2.Peer-Reviewed Original ResearchConceptsGenetic absence epilepsyBCAA supplementationAbsence epilepsyAnimal modelsBranched-chain amino acid supplementationSystematic reviewLong-term BCAA supplementationEpilepsy experience seizuresAnti-seizure effectsEffect of BCAAMost animal modelsPossible underlying mechanismsAmino acid supplementationChain amino acidsBCAA administrationBCAA mixtureRefractory epilepsyNeuron lossSeizure disorderAntiepileptic drugsSeizure modelSeizure propagationCochrane LibrarySeizure activityKainic acidEffects of Branched-Chain Amino Acid Supplementation on Spontaneous Seizures and Neuronal Viability in a Model of Mesial Temporal Lobe Epilepsy
Gruenbaum SE, Dhaher R, Rapuano A, Zaveri HP, Tang A, de Lanerolle N, Eid T. Effects of Branched-Chain Amino Acid Supplementation on Spontaneous Seizures and Neuronal Viability in a Model of Mesial Temporal Lobe Epilepsy. Journal Of Neurosurgical Anesthesiology 2019, 31: 247-256. PMID: 29620688, PMCID: PMC6170745, DOI: 10.1097/ana.0000000000000499.Peer-Reviewed Original ResearchConceptsMesial temporal lobe epilepsyTemporal lobe epilepsyLobe epilepsySpontaneous seizuresNeuron lossSeizure propagationBranched-chain amino acid supplementationChronic oral supplementationSpontaneous recurrent seizuresEffect of BCAAPotential novel treatmentBranched-chain amino acid leucineAmino acid supplementationAcute seizuresBCAA supplementationChronic seizuresConvulsive seizuresOral supplementationRecurrent seizuresRefractory epilepsyDentate hilusNeuronal viabilityAcid supplementationImmunohistochemical analysisNovel treatments
2018
Selective deletion of glutamine synthetase in the mouse cerebral cortex induces glial dysfunction and vascular impairment that precede epilepsy and neurodegeneration
Zhou Y, Dhaher R, Parent M, Hu QX, Hassel B, Yee SP, Hyder F, Gruenbaum SE, Eid T, Danbolt NC. Selective deletion of glutamine synthetase in the mouse cerebral cortex induces glial dysfunction and vascular impairment that precede epilepsy and neurodegeneration. Neurochemistry International 2018, 123: 22-33. PMID: 30053506, PMCID: PMC8261904, DOI: 10.1016/j.neuint.2018.07.009.Peer-Reviewed Original ResearchConceptsAbnormal glutamate metabolismMouse cerebral cortexCerebral blood vesselsNovel mouse modelPostnatal week threeWeeks of ageProgressive astrogliosisVascular impairmentSpontaneous seizuresCerebral cortexGlial dysfunctionNeurovascular couplingDeficient miceSclerotic areasMouse modelEpileptic patientsApparent malformationsProgressive neurodegenerationSelective deletionGlutamate-ammonia ligaseTissue levelsGlutamate metabolismBlood vesselsWeek threeNeurodegeneration