2022
Cellular recovery after prolonged warm ischaemia of the whole body
Andrijevic D, Vrselja Z, Lysyy T, Zhang S, Skarica M, Spajic A, Dellal D, Thorn SL, Duckrow RB, Ma S, Duy PQ, Isiktas AU, Liang D, Li M, Kim SK, Daniele SG, Banu K, Perincheri S, Menon MC, Huttner A, Sheth KN, Gobeske KT, Tietjen GT, Zaveri HP, Latham SR, Sinusas AJ, Sestan N. Cellular recovery after prolonged warm ischaemia of the whole body. Nature 2022, 608: 405-412. PMID: 35922506, PMCID: PMC9518831, DOI: 10.1038/s41586-022-05016-1.Peer-Reviewed Original ResearchConceptsSingle-nucleus transcriptomic analysesSpecific gene expression patternsCellular recoveryGene expression patternsCellular processesMammalian cellsTranscriptomic analysisLarge mammalsExpression patternsCellular repair processesCell deathComprehensive resourceUnderappreciated potentialPhysiological challengesTissue integrityRepair processSpecific changesPorcine brainMammalsOrgansMultiple organs
2021
International Post Stroke Epilepsy Research Consortium (IPSERC): A consortium to accelerate discoveries in preventing epileptogenesis after stroke
Mishra NK, Engel J, Liebeskind DS, Sharma VK, Hirsch LJ, Kasner SE, French JA, Devinsky O, Friedman A, Dawson J, Quinn TJ, Selim M, de Havenon A, Yasuda CL, Cendes F, Benninger F, Zaveri HP, Burneo JG, Srivastava P, Singh M, Bhatia R, Vishnu VY, Bentes C, Ferro J, Weiss S, Sivaraju A, Kim JA, Galovic M, Gilmore EJ, Pitkänen A, Davis K, Sansing LH, Sheth KN, Paz JT, Singh A, Sheth S, Worrall BB, Grotta JC, Casillas-Espinos PM, Chen Z, Nicolo JP, Yan B, Kwan P, Consortium F. International Post Stroke Epilepsy Research Consortium (IPSERC): A consortium to accelerate discoveries in preventing epileptogenesis after stroke. Epilepsy & Behavior 2021, 127: 108502. PMID: 34968775, DOI: 10.1016/j.yebeh.2021.108502.Peer-Reviewed Original ResearchSmall 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
Effects 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
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
2014
5-Aminovaleric acid suppresses the development of severe seizures in the methionine sulfoximine model of mesial temporal lobe epilepsy
Dhaher R, Damisah EC, Wang H, Gruenbaum SE, Ong C, Zaveri HP, Gruenbaum BF, Eid T. 5-Aminovaleric acid suppresses the development of severe seizures in the methionine sulfoximine model of mesial temporal lobe epilepsy. Neurobiology Of Disease 2014, 67: 18-23. PMID: 24632421, PMCID: PMC4035438, DOI: 10.1016/j.nbd.2014.03.006.Peer-Reviewed Original ResearchConceptsMesial temporal lobe epilepsyTemporal lobe epilepsyNumber of seizuresLobe epilepsyHippocampal formationMesial temporal lobe seizuresSevere typeEntorhinal-hippocampal areaExpression of seizuresStages of seizuresTemporal lobe seizuresDorsal hippocampal formationLocalization-related epilepsyMale Sprague-DawleyPotential therapeutic targetSeizure frequencyAlzet pumpsRacine scaleSevere seizuresSecond surgerySprague-DawleyPump placementMethionine sulfoximineGlutamine-glutamateTherapeutic target
2013
Altered Network Timing in the CA3-CA1 Circuit of Hippocampal Slices from Aged Mice
Kanak DJ, Rose GM, Zaveri HP, Patrylo PR. Altered Network Timing in the CA3-CA1 Circuit of Hippocampal Slices from Aged Mice. PLOS ONE 2013, 8: e61364. PMID: 23593474, PMCID: PMC3620228, DOI: 10.1371/journal.pone.0061364.Peer-Reviewed Original ResearchConceptsCA3-CA1 circuitCA1 stratum pyramidaleSharp-wave ripplesAged miceStratum pyramidaleHippocampal slicesAge groupsCarbachol-induced gamma oscillationsSpontaneous sharp wavesCA1 stratum radiatumGamma oscillationsStratum oriensUnidentified neuronsAged neuronsStratum radiatumCA1 subregionNeuronal activityAdult miceSharp wavesUnit activityRipple oscillationsCollateral responsesMiceCA3Pyramidale
2012
Evidence for astrocytes as a potential source of the glutamate excess in temporal lobe epilepsy
Perez EL, Lauritzen F, Wang Y, Lee TS, Kang D, Zaveri HP, Chaudhry FA, Ottersen OP, Bergersen LH, Eid T. Evidence for astrocytes as a potential source of the glutamate excess in temporal lobe epilepsy. Neurobiology Of Disease 2012, 47: 331-337. PMID: 22659305, PMCID: PMC3392431, DOI: 10.1016/j.nbd.2012.05.010.Peer-Reviewed Original ResearchConceptsTemporal lobe epilepsyRecurrent seizuresConcentration of glutamateHippocampal formationLobe epilepsyExtracellular glutamateRefractory temporal lobe epilepsyEpileptogenic hippocampal formationExtracellular brain glutamateSubset of patientsSaline-treated ratsStart of infusionRatio of glutamateExcessive glutamateGlutamate excessBrain glutamateExtracellular brainAstrocytesExcessive releaseGS deficiencyRatsSeizuresGlutamateSeparate groupsEpilepsy
2011
Altered expression of brain monocarboxylate transporter 1 in models of temporal lobe epilepsy
Lauritzen F, Perez EL, Melillo ER, Roh JM, Zaveri HP, Lee TS, Wang Y, Bergersen LH, Eid T. Altered expression of brain monocarboxylate transporter 1 in models of temporal lobe epilepsy. Neurobiology Of Disease 2011, 45: 165-176. PMID: 21856423, PMCID: PMC3351090, DOI: 10.1016/j.nbd.2011.08.001.Peer-Reviewed Original ResearchConceptsTemporal lobe epilepsyMonocarboxylate transporter 1Hippocampal formationLobe epilepsyAnimal modelsModel of TLEPathogenesis of TLEHuman temporal lobe epilepsyPathophysiology of TLETransporter 1Epileptogenic hippocampal formationNonepileptic control animalsPerforant pathway stimulationRecurrent limbic seizuresRelevant rat modelGlutamine synthetase deficiencyLimbic seizuresAntiepileptic drugsBrain metabolismEpileptogenic brainMicrovessel densityRat modelValproic acidControl animalsMCT1 expression
2009
The development of recurrent seizures after continuous intrahippocampal infusion of methionine sulfoximine in rats A video-intracranial electroencephalographic study
Wang Y, Zaveri HP, Lee TS, Eid T. The development of recurrent seizures after continuous intrahippocampal infusion of methionine sulfoximine in rats A video-intracranial electroencephalographic study. Experimental Neurology 2009, 220: 293-302. PMID: 19747915, PMCID: PMC2989153, DOI: 10.1016/j.expneurol.2009.08.034.Peer-Reviewed Original ResearchConceptsMesial temporal lobe epilepsyHuman mesial temporal lobe epilepsyRecurrent seizuresNeuronal lossPartial seizuresPathophysiology of mTLEDiffuse neuronal lossSaline-treated animalsTemporal lobe epilepsyMinimal neuronal lossGlutamine synthetase inhibitor methionine sulfoximineEpileptogenic hippocampusHippocampal sclerosisLobe epilepsyElectroencephalogram monitoringStage IElectrophysiological mechanismsSeizuresElectroencephalographic studiesDays durationIntrahippocampal infusionHippocampusInfusionMethionine sulfoximineIntracranial EEG
2008
Neurometabolism in human epilepsy
Pan JW, Williamson A, Cavus I, Hetherington HP, Zaveri H, Petroff OA, Spencer DD. Neurometabolism in human epilepsy. Epilepsia 2008, 49: 31-41. PMID: 18304254, PMCID: PMC3657747, DOI: 10.1111/j.1528-1167.2008.01508.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrain DiseasesBrain MappingCarbon IsotopesDominance, CerebralElectrodes, ImplantedElectroencephalographyEpilepsyGamma-Aminobutyric AcidGlucoseHippocampusHumansLimbic SystemMagnetic Resonance SpectroscopyMetabolic DiseasesMicrodialysisMitochondrial DiseasesNeural PathwaysNeuronsPositron-Emission TomographyRatsSynaptic TransmissionConceptsNeurometabolic dysfunctionMagnetic resonance spectroscopic imagingHuman epilepsyEpileptic brainHippocampal resectionSclerotic hippocampusPathophysiologic aspectsEpileptogenic processMicrodialysis measuresExtracellular glutamateEpileptic dysfunctionEnergetic dysfunctionHuman studiesDysfunctionNeurotransmitter cyclingNoninvasive functional imagingProfound decreaseMitochondrial injuryBrain functionEpilepsyFunctional imagingMetabolic imagingBrainIntracranial EEGNeurometabolismRecurrent 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
2007
Neocortical and Thalamic Spread of Amygdala Kindled Seizures
Blumenfeld H, Rivera M, Vasquez JG, Shah A, Ismail D, Enev M, Zaveri HP. Neocortical and Thalamic Spread of Amygdala Kindled Seizures. Epilepsia 2007, 48: 254-262. PMID: 17295618, DOI: 10.1111/j.1528-1167.2006.00934.x.Peer-Reviewed Original ResearchConceptsFrontal cortexMedial thalamusInterictal periodNervous systemSimultaneous field potential recordingsAmygdala-Kindled SeizuresResult of kindlingDevelopment of epilepsyNetwork plasticityField potential recordingsSeizure durationBehavioral seizuresMotor seizuresKindled SeizuresAmygdala kindlingEpilepsy modelSeizuresKindlingPotential recordingsNeocortical circuitsCortexBehavioral severityWeak stimulationThalamusPossible role