2023
The early days of ex vivo 1H, 13C, and 31P nuclear magnetic resonance in the laboratory of Dr. Robert G. Shulman from 1975 to 1995
Rothman D, Behar K, Petroff O, Shulman R. The early days of ex vivo 1H, 13C, and 31P nuclear magnetic resonance in the laboratory of Dr. Robert G. Shulman from 1975 to 1995. NMR In Biomedicine 2023, 36: e4879. PMID: 36424353, DOI: 10.1002/nbm.4879.Peer-Reviewed Original Research
2006
Neuronal–Glial Glucose Oxidation and Glutamatergic–GABAergic Function
Hyder F, Patel AB, Gjedde A, Rothman DL, Behar KL, Shulman RG. Neuronal–Glial Glucose Oxidation and Glutamatergic–GABAergic Function. Cerebrovascular And Brain Metabolism Reviews 2006, 26: 865-877. PMID: 16407855, DOI: 10.1038/sj.jcbfm.9600263.Peer-Reviewed Original ResearchConceptsGamma-amino butyric acid (GABA) neuronsNeuronal glucose oxidationGlutamate-glutamine cyclingRelease of lactateGlucose oxidationNeuronal oxidationGlial uptakeGABAergic neuronsGlutamate uptakeGliaNeuronsGlycolytic ATPLactateGlucoseTotal glucoseVivo rateIsoelectricityCulture studiesATPNeurotransmittersUptake
2001
In Vivo Nuclear Magnetic Resonance Studies of Glutamate-γ-Aminobutyric Acid-Glutamine Cycling in Rodent and Human Cortex: the Central Role of Glutamine
Behar K, Rothman D. In Vivo Nuclear Magnetic Resonance Studies of Glutamate-γ-Aminobutyric Acid-Glutamine Cycling in Rodent and Human Cortex: the Central Role of Glutamine. Journal Of Nutrition 2001, 131: 2498s-2504s. PMID: 11533301, DOI: 10.1093/jn/131.9.2498s.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsGamma-aminobutyric acidGlutamate-GABACortical glucose utilizationCortical electrical activityNet glutamine synthesisCerebral cortexInhibitory neurotransmitterMajor excitatoryBrain glutamateGlutamine synthesisNeurotransmitter glutamateRodent cortexGlucose utilizationHuman cortexGlutamine cycleElectrical activityCortexCentral roleGlutamine cyclingCommon mechanismGlucose oxidationGlutamateVivo nuclear magnetic resonance studiesRodentsGlutamine
1999
In vivo nuclear magnetic resonance spectroscopy studies of the relationship between the glutamate--glutamine neurotransmitter cycle and functional neuroenergetics
Rothman D, Sibson N, Hyder F, Shen J, Behar K, Shulman R. In vivo nuclear magnetic resonance spectroscopy studies of the relationship between the glutamate--glutamine neurotransmitter cycle and functional neuroenergetics. Philosophical Transactions Of The Royal Society B Biological Sciences 1999, 354: 1165-1177. PMID: 10466144, PMCID: PMC1692640, DOI: 10.1098/rstb.1999.0472.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsGlutamate-glutamine cycleNerve terminalsNeurotransmitter cycleGlucose metabolismBlood oxygenation level-dependent magnetic resonance imagingLevel-dependent magnetic resonance imagingBrain glucose oxidationCortical glucose metabolismMagnetic resonance spectroscopy studyCortex of ratsMagnetic resonance imagingFunctional imaging studiesSpecific neuronal activityOxidative glucose metabolismGlial cellsNeuronal activityResonance imagingImaging studiesHuman cortexBrain functionBrain activityRatsCortexGlucose oxidationGlutamateDetermination of the rate of the glutamate/glutamine cycle in the human brain by in vivo 13C NMR
Shen J, Petersen K, Behar K, Brown P, Nixon T, Mason G, Petroff O, Shulman G, Shulman R, Rothman D. Determination of the rate of the glutamate/glutamine cycle in the human brain by in vivo 13C NMR. Proceedings Of The National Academy Of Sciences Of The United States Of America 1999, 96: 8235-8240. PMID: 10393978, PMCID: PMC22218, DOI: 10.1073/pnas.96.14.8235.Peer-Reviewed Original ResearchConceptsGlutamate/glutamine cycleGlutamine cycleCerebral cortexMin/Rat cerebral cortexVivo 13C NMR spectraGlucose oxidation ratesHuman brainGlucose oxidationGlutamatergic activityRat modelTricarboxylic acid cycle rateParietal lobeHuman cortexCortexTime courseBrainGlutamine synthesisMajor metabolic fluxCycle rateTricarboxylic acid cycleHigh levelsInfusionRatsAcid cycleNew NMR measurements in epilepsy. Measuring brain GABA in patients with complex partial seizures.
Petroff O, Behar K, Rothman D. New NMR measurements in epilepsy. Measuring brain GABA in patients with complex partial seizures. Advances In Neurology 1999, 79: 939-45. PMID: 10514877.Peer-Reviewed Original Research
1998
Vigabatrin increases human brain homocarnosine and improves seizure control
Petroff O, Mattson R, Behar K, Hyder F, Rothman D. Vigabatrin increases human brain homocarnosine and improves seizure control. Annals Of Neurology 1998, 44: 948-952. PMID: 9851440, DOI: 10.1002/ana.410440614.Peer-Reviewed Original ResearchConceptsGamma-aminobutyric acidSeizure controlGABA concentrationAddition of vigabatrinLow-dose vigabatrinImproved seizure controlMean GABA concentrationAntiepileptic drug vigabatrinInhibitory neuromodulatorDaily doseGABAergic neuronsGABA levelsLarge dosesHomocarnosine concentrationsVigabatrinDrug vigabatrinHomocarnosinePatientsHuman brainMagnetic resonance spectroscopyControlNeuromodulatorsNeuronsDoseDosesFunctional Energy Metabolism:In vivo 13C-NMR Spectroscopy Evidence for Coupling of Cerebral Glucose Consumption and Gl utamatergic Neuronal Activity
Sibson N, Shen J, Mason G, Rothman D, Behar K, Shulman R. Functional Energy Metabolism:In vivo 13C-NMR Spectroscopy Evidence for Coupling of Cerebral Glucose Consumption and Gl utamatergic Neuronal Activity. Developmental Neuroscience 1998, 20: 321-330. PMID: 9778568, DOI: 10.1159/000017327.Peer-Reviewed Original ResearchConceptsRat brain cortexGlucose metabolismBrain cortexNeurotransmitter cyclingTotal glucose oxidationGlutamatergic synaptic activityCerebral glucose consumptionCerebral glucose metabolismFunctional activityFunctional imaging methodsGlucose oxidationOxidative glucose metabolismGlutamate neurotransmitter cyclingSynaptic activityNeuronal activityMild anesthesiaGlutamine synthesisMammalian brainNeurotransmitter releaseGlutamate cyclingEEG activityAmmonia metabolismNeurophysiological basisDetoxification componentsVivo results
1997
Homocarnosine and the measurement of neuronal pH in patients with epilepsy
Rothman D, Behar K, Prichard J, Petroff O. Homocarnosine and the measurement of neuronal pH in patients with epilepsy. Magnetic Resonance In Medicine 1997, 38: 924-929. PMID: 9402193, DOI: 10.1002/mrm.1910380611.Peer-Reviewed Original Research
1996
The13C isotope and nuclear magnetic resonance: unique tools for the study of brain metabolism
Mason G, Behar K, Lai J. The13C isotope and nuclear magnetic resonance: unique tools for the study of brain metabolism. Metabolic Brain Disease 1996, 11: 283-313. PMID: 8979250, DOI: 10.1007/bf02029492.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsHuman Brain γ‐Aminobutyric Acid Levels and Seizure Control Following Initiation of Vigabatrin Therapy
Petroff O, Behar K, Mattson R, Rothman D. Human Brain γ‐Aminobutyric Acid Levels and Seizure Control Following Initiation of Vigabatrin Therapy. Journal Of Neurochemistry 1996, 67: 2399-2404. PMID: 8931472, DOI: 10.1046/j.1471-4159.1996.67062399.x.Peer-Reviewed Original ResearchConceptsBrain GABA contentImproved seizure controlBrain GABA levelsSeizure controlVigabatrin treatmentGABA levelsDaily doseAntiepileptic drugsOccipital lobeBrain gamma-aminobutyric acid (GABA) concentrationsGABA concentrationHuman brain GABA levelsGABA contentGamma-aminobutyric acid concentrationΓ-aminobutyric acid (GABA) levelsComplex partial seizuresNovel antiepileptic drugBrain GABA concentrationsSeizure frequencyPartial seizuresVigabatrin therapySustained elevationHuman occipital lobeGABA synthesisAcid levelsLow brain GABA level is associated with poor seizure control
Petroff O, Rothman D, Behar K, Mattson R. Low brain GABA level is associated with poor seizure control. Annals Of Neurology 1996, 40: 908-911. PMID: 9007096, DOI: 10.1002/ana.410400613.Peer-Reviewed Original ResearchConceptsLower GABA levelsBrain GABA levelsLower brain GABA levelsPoor seizure controlGABA levelsSeizure controlRecent seizuresGamma-aminobutyric acid concentrationComplex partial seizuresPartial seizuresEpileptic syndromesEpileptic focusOccipital lobeCerebrospinal fluidPatientsSeizuresSignificant associationMagnetic resonanceVivo measurementsSurface coilLevelsEpilepsySyndromeGABAAcid concentrationHuman brain GABA levels rise rapidly after initiation of vigabatrin therapy
Petroff O, Rothman D, Behar K, Collins T, Mattson R. Human brain GABA levels rise rapidly after initiation of vigabatrin therapy. Neurology 1996, 47: 1567-1571.. PMID: 8960747, DOI: 10.1212/wnl.47.6.1567.Peer-Reviewed Original ResearchConceptsBrain GABA levelsBrain GABASingle oral doseOral doseGABA levelsSide effectsHuman brain GABA levelsEffective antiepileptic medicationsHours of administrationAntiepileptic medicationsVigabatrin therapyDay dosingIntractable epilepsySerial measurementsOccipital cortexVigabatrinDay 8Day 5GABAGABA transaminasePatientsDoseNext dayHuman brainMagnetic resonance spectroscopyShort echo time proton magnetic resonance spectroscopic imaging of macromolecule and metabolite signal intensities in the human brain
Hwang J, Graham G, Behar K, Alger J, Prichard J, Rothman D. Short echo time proton magnetic resonance spectroscopic imaging of macromolecule and metabolite signal intensities in the human brain. Magnetic Resonance In Medicine 1996, 35: 633-639. PMID: 8722812, DOI: 10.1002/mrm.1910350502.Peer-Reviewed Original ResearchConceptsSubacute stroke patientsProton magnetic resonance spectroscopicProton magnetic resonance spectroscopic imagingMagnetic resonance spectroscopic imagingStroke patientsHealthy subjectsMagnetic resonance spectroscopicMetabolite signal intensitiesBrain regionsPathological conditionsMacromolecule resonancesHuman brainBrainSignal intensitySubjectsRecovery timeSpectroscopic imagingPatientsHuman brain GABA levels rise after initiation of vigabatrin therapy but fail to rise further with increasing dose
Petroff O, Rothman D, Behar K, Mattson R. Human brain GABA levels rise after initiation of vigabatrin therapy but fail to rise further with increasing dose. Neurology 1996, 46: 1459-1463. PMID: 8628502, DOI: 10.1212/wnl.46.5.1459.Peer-Reviewed Original ResearchThe effect of gabapentin on brain gamma‐aminobutyric acid in patients with epilepsy
Petroff O, Rothman D, Behar K, Lamoureux D, Mattson R. The effect of gabapentin on brain gamma‐aminobutyric acid in patients with epilepsy. Annals Of Neurology 1996, 39: 95-99. PMID: 8572673, DOI: 10.1002/ana.410390114.Peer-Reviewed Original ResearchConceptsGamma-aminobutyric acidBrain GABA levelsGABA levelsHuman brain GABA levelsBrain gamma-aminobutyric acidHigh-dose gabapentinAntiepileptic drug treatmentEffect of gabapentinPartial epilepsy patientsTreatment of epilepsyMechanism of actionAdjunctive therapyStandard dosesDrug treatmentEpilepsy patientsOccipital cortexGabapentinPatientsClinical useEpilepsyHuman brainMagnetic resonanceTreatmentMagnetic resonance spectroscopyVivo measurements
1995
Initial Observations on Effect of Vigabatrin on In Vivo 1H Spectroscopic Measurements of γ‐Aminobutyric Acid, Glutamate, and Glutamine in Human Brain
Petroff O, Rothman D, Behar K, Mattson R. Initial Observations on Effect of Vigabatrin on In Vivo 1H Spectroscopic Measurements of γ‐Aminobutyric Acid, Glutamate, and Glutamine in Human Brain. Epilepsia 1995, 36: 457-464. PMID: 7614922, DOI: 10.1111/j.1528-1157.1995.tb00486.x.Peer-Reviewed Original ResearchConceptsGamma-aminobutyric acidGABA levelsMumol/Antiepileptic drugsOccipital GABA levelsEffective antiepileptic drugEffects of vigabatrinStandard medicationStandard doseΓ-aminobutyric acidHealthy subjectsEpileptic patientsVigabatrinPatientsGABA transaminaseHuman cerebrumNoninvasive measurementHuman brainBrainGlutamateInitial observationsMedicationsCerebrumLevelsDoseSimultaneous Determination of the Rates of the TCA Cycle, Glucose Utilization, α-Ketoglutarate/Glutamate Exchange, and Glutamine Synthesis in Human Brain by NMR
Mason G, Gruetter R, Rothman D, Behar K, Shulman R, Novotny E. Simultaneous Determination of the Rates of the TCA Cycle, Glucose Utilization, α-Ketoglutarate/Glutamate Exchange, and Glutamine Synthesis in Human Brain by NMR. Cerebrovascular And Brain Metabolism Reviews 1995, 15: 12-25. PMID: 7798329, DOI: 10.1038/jcbfm.1995.2.Peer-Reviewed Original ResearchVigabatrin: effect on brain GABA levels measured by nuclear magnetic resonance spectroscopy
Mattson R, Petroff O, Rothman D, Behar K. Vigabatrin: effect on brain GABA levels measured by nuclear magnetic resonance spectroscopy. Acta Neurologica Scandinavica. Supplementum 1995, 92: 27-30. PMID: 7495186, DOI: 10.1111/j.1600-0404.1995.tb00496.x.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsBrain GABA levelsGABA levelsBrain concentrationsNerve terminalsAdministration of vigabatrinClear dose-response relationshipLevels of GABAPartial epileptic seizuresAnti-epilepsy drugsPresynaptic nerve terminalsDose-response relationshipConcentration of GABASecondary generalizationClinical effectsClinical outcomesVigabatrin administrationClinical trialsPatient responseClinical studiesSynaptic transmissionBaseline valuesOptimal doseVigabatrin levelsVigabatrinEpileptic seizures
1994
Analysis of macromolecule resonances in 1H NMR spectra of human brain
Behar K, Rothman D, Spencer D, Petroff O. Analysis of macromolecule resonances in 1H NMR spectra of human brain. Magnetic Resonance In Medicine 1994, 32: 294-302. PMID: 7984061, DOI: 10.1002/mrm.1910320304.Peer-Reviewed Original Research