2022
Type IV Pili Are a Critical Virulence Factor in Clinical Isolates of Paenibacillus thiaminolyticus
Hehnly C, Shi A, Ssentongo P, Zhang L, Isaacs A, Morton S, Streck N, Erdmann-Gilmore P, Tolstoy I, Townsend R, Limbrick D, Paulson J, Ericson J, Galperin M, Schiff S, Broach J. Type IV Pili Are a Critical Virulence Factor in Clinical Isolates of Paenibacillus thiaminolyticus. MBio 2022, 13: e02688-22. PMID: 36374038, PMCID: PMC9765702, DOI: 10.1128/mbio.02688-22.Peer-Reviewed Original ResearchConceptsPostinfectious hydrocephalusClinical isolatesVirulence factorsCritical virulence factorPotential virulence factorsPoor long-term outcomesPrevention of hydrocephalusLong-term outcomesBacterial pathogensDevastating sequelaeNeonatal sepsisMiddle-income countriesNeonatal infectionSurgical interventionReference strainsNovel bacterial pathogensAfrican cohortBeta-lactamase genesChildhood mortalityHydrocephalusTherapeutic targetInfectionVirulent strainDevastating diseaseWhole-genome sequencingThermal effects on neurons during stimulation of the brain
Kim T, Kadji H, Whalen A, Ashourvan A, Freeman E, Fried S, Tadigadapa S, Schiff S. Thermal effects on neurons during stimulation of the brain. Journal Of Neural Engineering 2022, 19: 056029. PMID: 36126646, PMCID: PMC9855718, DOI: 10.1088/1741-2552/ac9339.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiophysicsBrainElectric ConductivityElectric StimulationElectrodesMammalsNeuronsConceptsThermal effectsJoule heatingMagnetic coilsRate dependencyElectrical interactionsSmall thermal effectsTemperature changesDissipation of energyNumerical modelingRange of frequenciesThermal energyMagnetic fieldDC drivingMagnetic inductionElectrical currentStatic magnetic fieldSmall temperature increaseTemperature increaseAccurate modulationCoilEnergy depositionHeatingConductorsTransient effectsElectrode
2021
Spreading depression as an innate antiseizure mechanism
Tamim I, Chung D, de Morais A, Loonen I, Qin T, Misra A, Schlunk F, Endres M, Schiff S, Ayata C. Spreading depression as an innate antiseizure mechanism. Nature Communications 2021, 12: 2206. PMID: 33850125, PMCID: PMC8044138, DOI: 10.1038/s41467-021-22464-x.Peer-Reviewed Original ResearchConceptsFocal neocortical seizuresSystemic kainic acidCentral nervous systemVivo mouse modelAntiseizure mechanismsAntiseizure effectsSeizure generalizationFocal seizuresSD occurrenceNeocortical seizuresKainic acidBrain injuryMouse modelNervous systemSeizuresNeurological disordersProlonged depolarizationSDDepressionBicucullineMigraineInjury
2020
Paenibacillus infection with frequent viral coinfection contributes to postinfectious hydrocephalus in Ugandan infants
Paulson J, Williams B, Hehnly C, Mishra N, Sinnar S, Zhang L, Ssentongo P, Mbabazi-Kabachelor E, Wijetunge D, von Bredow B, Mulondo R, Kiwanuka J, Bajunirwe F, Bazira J, Bebell L, Burgoine K, Couto-Rodriguez M, Ericson J, Erickson T, Ferrari M, Gladstone M, Guo C, Haran M, Hornig M, Isaacs A, Kaaya B, Kangere S, Kulkarni A, Kumbakumba E, Li X, Limbrick D, Magombe J, Morton S, Mugamba J, Ng J, Olupot-Olupot P, Onen J, Peterson M, Roy F, Sheldon K, Townsend R, Weeks A, Whalen A, Quackenbush J, Ssenyonga P, Galperin M, Almeida M, Atkins H, Warf B, Lipkin W, Broach J, Schiff S. Paenibacillus infection with frequent viral coinfection contributes to postinfectious hydrocephalus in Ugandan infants. Science Translational Medicine 2020, 12 PMID: 32998967, PMCID: PMC7774825, DOI: 10.1126/scitranslmed.aba0565.Peer-Reviewed Original ResearchConceptsPostinfectious hydrocephalusCSF samplesPIH casesPotential causative organismsCerebrospinal fluid accumulationCytomegalovirus coinfectionUgandan infantsNeonatal sepsisSurgical palliationNeonatal infectionInfant casesOptimal treatmentInfant cohortCommon causeCausative organismPediatric hydrocephalusFluid accumulationHydrocephalusAnaerobic bacterial isolatesControl casesInfectionFacultative anaerobic bacterial isolatesInfantsParasitic DNADiseaseInflammation in acquired hydrocephalus: pathogenic mechanisms and therapeutic targets
Karimy JK, Reeves BC, Damisah E, Duy PQ, Antwi P, David W, Wang K, Schiff SJ, Limbrick DD, Alper SL, Warf BC, Nedergaard M, Simard JM, Kahle KT. Inflammation in acquired hydrocephalus: pathogenic mechanisms and therapeutic targets. Nature Reviews Neurology 2020, 16: 285-296. PMID: 32152460, PMCID: PMC7375440, DOI: 10.1038/s41582-020-0321-y.Peer-Reviewed Original ResearchConceptsPosthaemorrhagic hydrocephalusPostinfectious hydrocephalusNeurosurgical disordersPathogenic mechanismsToll-like receptor 4Pathogenesis of hydrocephalusImportant protective responseEpendymal denudationCommon neurosurgical disorderSustained inflammationInflammatory mediatorsNeuroinflammatory conditionsImmune cellsReceptor 4Therapeutic approachesReparative inflammationCerebrospinal fluidCSF pathwaysHydrocephalusTherapeutic targetInflammationTherapeutic interventionsBrain ventriclesProtective responsePhysical irritants
2018
A Brain–Heart Biomarker for Epileptogenesis
Bahari F, Ssentongo P, Schiff S, Gluckman B. A Brain–Heart Biomarker for Epileptogenesis. Journal Of Neuroscience 2018, 38: 8473-8483. PMID: 30150365, PMCID: PMC6158692, DOI: 10.1523/jneurosci.1130-18.2018.Peer-Reviewed Original ResearchConceptsBrain-heart interactionsBiomarkers of epileptogenesisDevelopment of epilepsyAutonomic cardiac activityIdentification of patientsPostinjury epilepsyPreventable sequelaeFirst seizureBrain insultsCortical dischargesMale miceEpileptogenesisMurine modelMouse modelCardiac rhythmReliable biomarkersEpilepsyChronic measurementTreatment developmentBiomarkersSuch treatmentCardiac activityTherapeutic purposesBrain activityPatientsControl of Spreading Depression with Electrical Fields
Whalen A, Xiao Y, Kadji H, Dahlem M, Gluckman B, Schiff S. Control of Spreading Depression with Electrical Fields. Scientific Reports 2018, 8: 8769. PMID: 29884896, PMCID: PMC5993812, DOI: 10.1038/s41598-018-26986-1.Peer-Reviewed Original ResearchConceptsElectric fieldField polarityDC electric fieldElectric field polarityElectrical controlOptical imagingPropagation pathIntrinsic optical imagingOpposite signDepression propagatesElectrical fieldField terminationElectro-chemical gradientPropagation velocityPropagatesFieldTraumatic brain injuryPropagationConfinementMore superficial layersDepression propagationBrain injurySynaptic transmissionBrain slicesWavesChanges in Ugandan Climate Rainfall at the Village and Forest Level
Ssentongo P, Muwanguzi A, Eden U, Sauer T, Bwanga G, Kateregga G, Aribo L, Ojara M, Mugerwa W, Schiff S. Changes in Ugandan Climate Rainfall at the Village and Forest Level. Scientific Reports 2018, 8: 3551. PMID: 29476058, PMCID: PMC5824879, DOI: 10.1038/s41598-018-21427-5.Peer-Reviewed Original ResearchConceptsDaily rainfall estimatesShort-term anomaliesRainfall estimatesRainfall decreaseHistorical rainfallAtmospheric AdministrationNational OceanographicAverage rainfallRainfallComplete recordsAgricultural regionsBwindi ForestAfrican continentSouthwest UgandaOverall decreaseAgriculture productionWestern UgandaSignificant implicationsWildlife habitatOceanographicContinentARC2AnomaliesGorilla habitatForest level
2017
A Murine Model to Study Epilepsy and SUDEP Induced by Malaria Infection
Ssentongo P, Robuccio A, Thuku G, Sim D, Nabi A, Bahari F, Shanmugasundaram B, Billard M, Geronimo A, Short K, Drew P, Baccon J, Weinstein S, Gilliam F, Stoute J, Chinchilli V, Read A, Gluckman B, Schiff S. A Murine Model to Study Epilepsy and SUDEP Induced by Malaria Infection. Scientific Reports 2017, 7: 43652. PMID: 28272506, PMCID: PMC5341121, DOI: 10.1038/srep43652.Peer-Reviewed Original ResearchConceptsCerebral malariaAnimal modelsStrain combinationsPrevention of epilepsySuch animal modelsSubsequent epilepsyNeurological sequelaeAdjunctive therapyPathophysiological mechanismsMalaria infectionUnexpected deathMurine modelEpilepsyPreclinical researchSUDEPMalariaGenetic backgroundMultiple miceEpileptogenesisSequelaeTherapyInfectionMiceSurvivorsPrevention
2015
Role of Multiple-Scale Modeling of Epilepsy in Seizure Forecasting
Kuhlmann L, Grayden D, Wendling F, Schiff S. Role of Multiple-Scale Modeling of Epilepsy in Seizure Forecasting. Journal Of Clinical Neurophysiology 2015, 32: 220-226. PMID: 26035674, PMCID: PMC4455036, DOI: 10.1097/wnp.0000000000000149.Peer-Reviewed Original Research
2014
Oxygen and seizure dynamics: II. Computational modeling
Wei Y, Ullah G, Ingram J, Schiff S. Oxygen and seizure dynamics: II. Computational modeling. Journal Of Neurophysiology 2014, 112: 213-223. PMID: 24671540, PMCID: PMC4064403, DOI: 10.1152/jn.00541.2013.Peer-Reviewed Original ResearchConceptsSeizure eventsTissue oxygen pressureIntense neuronal firingSeizure patternsInhibitory neuronsNeuronal firingEpileptic seizuresSeizuresElectrophysiological recordingsOxygen metabolismSeizure dynamicsMetabolic energy consumptionEnergy metabolismExcitatoryMicroenvironment dynamicsRecent studiesOxygen and seizure dynamics: I. Experiments
Ingram J, Zhang C, Cressman J, Hazra A, Wei Y, Koo Y, Žiburkus J, Kopelman R, Xu J, Schiff S. Oxygen and seizure dynamics: I. Experiments. Journal Of Neurophysiology 2014, 112: 205-212. PMID: 24598521, PMCID: PMC4064411, DOI: 10.1152/jn.00540.2013.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCA1 Region, HippocampalMaleOxygenPyramidal CellsRatsRats, Sprague-DawleySeizuresConceptsEpileptiform activityRat hippocampal slicesLayer-specific patternsSeizure-like eventsSeizure-like stateSpontaneous seizure-like eventsHippocampal slicesSeizure onsetNeuronal interplayCellular excitabilitySeizure dynamicsEndogenous hypoxiaGreater reductionO2 utilizationHypoxiaElectrical recordingsSeizuresCA1ExcitabilityPyramidaleRapid Eye Movement Sleep and Hippocampal Theta Oscillations Precede Seizure Onset in the Tetanus Toxin Model of Temporal Lobe Epilepsy
Sedigh-Sarvestani M, Thuku G, Sunderam S, Parkar A, Weinstein S, Schiff S, Gluckman B. Rapid Eye Movement Sleep and Hippocampal Theta Oscillations Precede Seizure Onset in the Tetanus Toxin Model of Temporal Lobe Epilepsy. Journal Of Neuroscience 2014, 34: 1105-1114. PMID: 24453303, PMCID: PMC3898281, DOI: 10.1523/jneurosci.3103-13.2014.Peer-Reviewed Original ResearchConceptsRapid eye movement (REM) sleepNonrapid eye movement sleepEye movement sleepHippocampal theta rhythmState of vigilanceTemporal lobe epilepsyMovement sleepSeizure onsetLobe epilepsySeizure susceptibilityTheta rhythmChronic spontaneous seizuresNatural behavioral statesTetanus toxin modelHalf of baselineSpontaneous seizuresSeizure rateVentral hippocampusToxin modelSeizuresSurvival analysisTetanus toxinTherapeutic potentialREM boutsProminent theta
2013
Frequency dependence of behavioral modulation by hippocampal electrical stimulation
La Corte G, Wei Y, Chernyy N, Gluckman B, Schiff S. Frequency dependence of behavioral modulation by hippocampal electrical stimulation. Journal Of Neurophysiology 2013, 111: 470-480. PMID: 24198322, PMCID: PMC3921403, DOI: 10.1152/jn.00523.2013.Peer-Reviewed Original ResearchFRET excited ratiometric oxygen sensing in living tissue
Ingram J, Zhang C, Xu J, Schiff S. FRET excited ratiometric oxygen sensing in living tissue. Journal Of Neuroscience Methods 2013, 214: 45-51. PMID: 23333398, PMCID: PMC3664065, DOI: 10.1016/j.jneumeth.2013.01.002.Peer-Reviewed Original ResearchMeSH Keywords4-AminopyridineAnimalsColoring AgentsComputer SystemsConvulsantsFluorescence Resonance Energy TransferGlassHippocampusIn Vitro TechniquesLuminescent MeasurementsMetal NanoparticlesMicroelectrodesOrganoplatinum CompoundsOximetryOxygen ConsumptionPorphyrinsPyramidal CellsQuantum DotsRatsRats, Sprague-DawleySingle-Cell AnalysisConceptsInterstitial oxygen concentrationGlass substratesPolymer matrixBiocompatible sensorsInert polymer matrixDynamic analysisOptical sensorsMatrix consistingTemporal resolutionSensorsMillisecond temporal resolutionOxygen concentrationQuantum dotsMatrixRatiometric oxygenFluorescence resonance energy transferEnergy transferSynchronization and desynchronization in epilepsy: controversies and hypotheses
Jiruska P, de Curtis M, Jefferys J, Schevon C, Schiff S, Schindler K. Synchronization and desynchronization in epilepsy: controversies and hypotheses. The Journal Of Physiology 2013, 591: 787-797. PMID: 23184516, PMCID: PMC3591697, DOI: 10.1113/jphysiol.2012.239590.Peer-Reviewed Original ResearchConceptsNeuronal firingPathophysiology of epilepsyFunctional brain disordersEnd of seizureEpileptiform phenomenaLocal field potentialsLarge neuronal populationsNeuronal populationsNon-firing neuronsBrain disordersSeizuresSpecific inhibitoryEpilepsyExcitatory interactionsNeuronal networksRecent evidenceField potentialsHypersynchronous statesExcessive synchronizationFiring
2012
Seizures as imbalanced up states: excitatory and inhibitory conductances during seizure-like events
Žiburkus J, Cressman J, Schiff S. Seizures as imbalanced up states: excitatory and inhibitory conductances during seizure-like events. Journal Of Neurophysiology 2012, 109: 1296-1306. PMID: 23221405, PMCID: PMC3602838, DOI: 10.1152/jn.00232.2012.Peer-Reviewed Original ResearchConceptsSeizure-like eventsO-LM cellsPyramidal cellsInhibitory conductanceOriens-lacunosum moleculare (O-LM) interneuronsNeuronal network hyperexcitabilityExcitability of interneuronsCA1 pyramidal cellsInhibitory synaptic conductancesNetwork hyperexcitabilityRecurrent seizuresMoleculare interneuronsSeizure initiationNeural network activityRat hippocampusExtracellular magnesiumSynaptic barragesFiring patternsSeizuresExcitatoryCellular subtypesSynaptic conductancesInterneuronsNetwork activityCell typesReconstructing Mammalian Sleep Dynamics with Data Assimilation
Sedigh-Sarvestani M, Schiff S, Gluckman B. Reconstructing Mammalian Sleep Dynamics with Data Assimilation. PLOS Computational Biology 2012, 8: e1002788. PMID: 23209396, PMCID: PMC3510073, DOI: 10.1371/journal.pcbi.1002788.Peer-Reviewed Original ResearchConceptsUnscented Kalman filterData assimilationData assimilation frameworkParameter estimation methodNonlinear computational modelSleep-wake regulatory networkAssimilation frameworkUnknown parametersHidden variablesCovariance inflationNoisy variablesSlow dynamicsSparse measurementsComputational modelModel parametersKalman filterModel statesEstimation methodSimulation studyComplex systemsOptimal variablesFilter modelUKF frameworkModel variablesPartial observabilityModulation of hippocampal rhythms by subthreshold electric fields and network topology
Berzhanskaya J, Chernyy N, Gluckman B, Schiff S, Ascoli G. Modulation of hippocampal rhythms by subthreshold electric fields and network topology. Journal Of Computational Neuroscience 2012, 34: 369-389. PMID: 23053863, PMCID: PMC3549326, DOI: 10.1007/s10827-012-0426-4.Peer-Reviewed Original ResearchConceptsPyramidal cellsGamma rhythmsHippocampal rhythmsSubthreshold electric fieldsSpecific synaptic connectivityExact cellular mechanismsExcitatory contactsSynaptic circuitryBasket cellsLines of resultsArea CA1Inhibitory connectivityInterneuron typesSynaptic connectivityInterneuron classesHippocampal functionNeuron typesNeuronal morphologyTheta/gamma ratioCognitive functionTheta frequencyCellular mechanismsNeural activityElectrophysiological dataNovel roleThe role of inhibition in oscillatory wave dynamics in the cortex
Xiao Y, Huang X, Van Wert S, Barreto E, Wu J, Gluckman B, Schiff S. The role of inhibition in oscillatory wave dynamics in the cortex. European Journal Of Neuroscience 2012, 36: 2201-2212. PMID: 22805065, PMCID: PMC4410882, DOI: 10.1111/j.1460-9568.2012.08132.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBicucullineCarbacholEpilepsies, PartialGABA-A Receptor AgonistsGABA-A Receptor AntagonistsGABA-B Receptor AgonistsGABA-B Receptor AntagonistsMaleMembrane PotentialsModels, NeurologicalNeocortexNeural InhibitionPicrotoxinRatsRats, Sprague-DawleyReceptors, AMPAReceptors, GABA-AReceptors, GABA-BReceptors, N-Methyl-D-AspartateTheta RhythmConceptsGABAergic inhibitionNeocortical brain slicesVoltage-sensitive dye imagingSprague-Dawley ratsPresence of carbacholConcentration-dependent mannerGABAB antagonistGABAA receptorsBrain slicesTheta frequency oscillationsPharmacological methodsDye imagingCortical oscillationsRole of inhibitionBicucullineDisinhibitionGABAATheta oscillationsCortexBasic spatiotemporal patternsInhibitionNeural information processingCarbacholMental tasksAntagonist