2025
PTEN mutations impair CSF dynamics and cortical networks by dysregulating periventricular neural progenitors
DeSpenza T, Kiziltug E, Allington G, Barson D, McGee S, O’Connor D, Robert S, Mekbib K, Nanda P, Greenberg A, Singh A, Duy P, Mandino F, Zhao S, Lynn A, Reeves B, Marlier A, Getz S, Nelson-Williams C, Shimelis H, Walsh L, Zhang J, Wang W, Prina M, OuYang A, Abdulkareem A, Smith H, Shohfi J, Mehta N, Dennis E, Reduron L, Hong J, Butler W, Carter B, Deniz E, Lake E, Constable R, Sahin M, Srivastava S, Winden K, Hoffman E, Carlson M, Gunel M, Lifton R, Alper S, Jin S, Crair M, Moreno-De-Luca A, Luikart B, Kahle K. PTEN mutations impair CSF dynamics and cortical networks by dysregulating periventricular neural progenitors. Nature Neuroscience 2025, 28: 536-557. PMID: 39994410, DOI: 10.1038/s41593-024-01865-3.Peer-Reviewed Original ResearchConceptsNeural progenitor cellsCongenital hydrocephalusCSF dynamicsIncreased CSF productionDe novo mutationsFrequent monogenic causeEverolimus treatmentCSF shuntingNonsurgical treatmentPTEN mutationsAqueductal stenosisInhibitory interneuronsVentriculomegalyProgenitor cellsChoroid plexusMonogenic causeCortical networksIncreased survivalBrain ventriclesCortical deficitsNeural progenitorsGene PTENCSF productionNkx2.1PTEN
2024
CC2D1A causes ciliopathy, intellectual disability, heterotaxy, renal dysplasia, and abnormal CSF flow
Kim A, Sakin I, Viviano S, Tuncel G, Aguilera S, Goles G, Jeffries L, Ji W, Lakhani S, Kose C, Silan F, Oner S, Kaplan O, Group M, Ergoren M, Mishra-Gorur K, Gunel M, Sag S, Temel S, Deniz E. CC2D1A causes ciliopathy, intellectual disability, heterotaxy, renal dysplasia, and abnormal CSF flow. Life Science Alliance 2024, 7: e202402708. PMID: 39168639, PMCID: PMC11339347, DOI: 10.26508/lsa.202402708.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainCerebrospinal FluidCiliaCiliopathiesFemaleFibroblastsHumansIntellectual DisabilityKidneyMaleMutationPedigreeXenopusConceptsDevelopmental disabilitiesIntellectual disabilityPatient-derived fibroblastsMidbrain regionsBrain developmentDefective ciliogenesisCSF circulationDisabilityCSF flowAbnormal CSF flowNervous system developmentMutant tadpolesCiliated tissuesMultiple model systemsVariant functionPronephric ductUnrelated familiesCC2D1AExpression patternsCiliogenesisRenal dysplasiaLeft-right organizerFunctional analysisDisease mechanismsBrainElucidating a new path of CSF transport in the CNS
Benveniste H, Thomas J. Elucidating a new path of CSF transport in the CNS. The Lancet Neurology 2024, 23: 553-554. PMID: 38760087, PMCID: PMC11700482, DOI: 10.1016/s1474-4422(24)00164-9.Peer-Reviewed Original Research
2023
Intrathecal delivery of nanoparticle PARP inhibitor to the cerebrospinal fluid for the treatment of metastatic medulloblastoma
Khang M, Lee J, Lee T, Suh H, Lee S, Cavaliere A, Rushing A, Geraldo L, Belitzky E, Rossano S, de Feyter H, Shin K, Huttner A, Roussel M, Thomas J, Carson R, Marquez-Nostra B, Bindra R, Saltzman W. Intrathecal delivery of nanoparticle PARP inhibitor to the cerebrospinal fluid for the treatment of metastatic medulloblastoma. Science Translational Medicine 2023, 15: eadi1617. PMID: 37910601, PMCID: PMC11078331, DOI: 10.1126/scitranslmed.adi1617.Peer-Reviewed Original ResearchConceptsCerebrospinal fluidDelivery of drugsEffective therapyTherapeutic indexPARP inhibitorsBlood-brain barrierSite of tumorRapid systemic clearanceXenograft mouse modelSolvent evaporation processAdministration of substancesLeptomeningeal spreadIntrathecal deliveryLeptomeningeal metastasesBrain penetrationSystemic clearanceTumor regressionPolymer nanoparticlesMetastatic medulloblastomaMouse modelPediatric medulloblastomaDrug accumulationCSF turnoverEncapsulated drugsPET imagingCharacterization and diagnosis spectrum of patients with cerebrospinal fluid pleocytosis
Dyckhoff-Shen S, Bewersdorf J, Teske N, Völk S, Pfister H, Koedel U, Klein M. Characterization and diagnosis spectrum of patients with cerebrospinal fluid pleocytosis. Infection 2023, 52: 219-229. PMID: 37656347, PMCID: PMC10811117, DOI: 10.1007/s15010-023-02087-8.Peer-Reviewed Original ResearchMeSH KeywordsCentral Nervous System InfectionsCerebrospinal FluidHumansLeukocyte CountLeukocytosisMeningitis, BacterialRetrospective StudiesConceptsCerebrospinal fluid pleocytosisCerebrospinal fluid cell countBacterial meningitisCerebrospinal fluidCNS infectionCell countElevated white blood cell countResultsThe most common etiologyMethodsA retrospective cohort studyNeoplastic diseaseAutoimmune CNS diseaseWhite blood cell countRetrospective cohort studySpectrum of patientsCharacteristics of patientsBlood cell countCerebrospinal fluid proteinAbnormal mental statusLaboratory featuresCSF pleocytosisCSF leukocytesLaboratory parametersClinical presentationNuchal rigidityCommon etiologies
2022
Impaired neurogenesis alters brain biomechanics in a neuroprogenitor-based genetic subtype of congenital hydrocephalus
Duy PQ, Weise SC, Marini C, Li XJ, Liang D, Dahl PJ, Ma S, Spajic A, Dong W, Juusola J, Kiziltug E, Kundishora AJ, Koundal S, Pedram MZ, Torres-Fernández LA, Händler K, De Domenico E, Becker M, Ulas T, Juranek SA, Cuevas E, Hao LT, Jux B, Sousa AMM, Liu F, Kim SK, Li M, Yang Y, Takeo Y, Duque A, Nelson-Williams C, Ha Y, Selvaganesan K, Robert SM, Singh AK, Allington G, Furey CG, Timberlake AT, Reeves BC, Smith H, Dunbar A, DeSpenza T, Goto J, Marlier A, Moreno-De-Luca A, Yu X, Butler WE, Carter BS, Lake EMR, Constable RT, Rakic P, Lin H, Deniz E, Benveniste H, Malvankar NS, Estrada-Veras JI, Walsh CA, Alper SL, Schultze JL, Paeschke K, Doetzlhofer A, Wulczyn FG, Jin SC, Lifton RP, Sestan N, Kolanus W, Kahle KT. Impaired neurogenesis alters brain biomechanics in a neuroprogenitor-based genetic subtype of congenital hydrocephalus. Nature Neuroscience 2022, 25: 458-473. PMID: 35379995, PMCID: PMC9664907, DOI: 10.1038/s41593-022-01043-3.Peer-Reviewed Original ResearchConceptsCongenital hydrocephalusCerebral ventricular dilatationPrimary defectNeuroepithelial cell differentiationRisk genesCerebrospinal fluid homeostasisWhole-exome sequencingNeuroepithelial stem cellsCortical hypoplasiaReduced neurogenesisVentricular dilatationVentricular enlargementCH mutationsPrenatal hydrocephalusDisease heterogeneityBrain surgeryCSF circulationHydrocephalusGenetic subtypesFluid homeostasisNeuroepithelial cellsNovo mutationsBrain transcriptomicsStem cellsCell differentiationNervous system consequences of COVID-19
Spudich S, Nath A. Nervous system consequences of COVID-19. Science 2022, 375: 267-269. PMID: 35050660, DOI: 10.1126/science.abm2052.Peer-Reviewed Original Research
2021
Cerebrospinal fluid CD4+ T cell infection in humans and macaques during acute HIV-1 and SHIV infection
Sharma V, Creegan M, Tokarev A, Hsu D, Slike BM, Sacdalan C, Chan P, Spudich S, Ananworanich J, Eller MA, Krebs SJ, Vasan S, Bolton DL. Cerebrospinal fluid CD4+ T cell infection in humans and macaques during acute HIV-1 and SHIV infection. PLOS Pathogens 2021, 17: e1010105. PMID: 34874976, PMCID: PMC8683024, DOI: 10.1371/journal.ppat.1010105.Peer-Reviewed Original ResearchConceptsT-cell infectionCentral nervous systemAcute HIV-1HIV-1 replicationCerebrospinal fluidT cellsHIV-1Peripheral bloodViral reservoirCell infectionBroad immune activationCerebrospinal fluid CD4CNS viral reservoirCSF T cellsHIV-1 cureActive viral transcriptionLong-term inflammationViral RNACSF CD4Early neuroinflammationAntiretroviral therapyHuman cerebrospinal fluidAcute infectionImmune activationCNS compartmentCerebrospinal Fluid Viral Load Across the Spectrum of Untreated Human Immunodeficiency Virus Type 1 (HIV-1) Infection: A Cross-Sectional Multicenter Study
Ulfhammer G, Edén A, Antinori A, Brew BJ, Calcagno A, Cinque P, De Zan V, Hagberg L, Lin A, Nilsson S, Oprea C, Pinnetti C, Spudich S, Trunfio M, Winston A, Price RW, Gisslén M. Cerebrospinal Fluid Viral Load Across the Spectrum of Untreated Human Immunodeficiency Virus Type 1 (HIV-1) Infection: A Cross-Sectional Multicenter Study. Clinical Infectious Diseases 2021, 75: 493-502. PMID: 34747481, PMCID: PMC9427147, DOI: 10.1093/cid/ciab943.Peer-Reviewed Original ResearchConceptsCSF HIV RNAWhite blood cell countPlasma HIV RNAUntreated human immunodeficiency virus type 1 (HIV-1) infectionHuman immunodeficiency virus type 1 (HIV-1) infectionCSF white blood cell countVirus type 1 infectionHIV RNACopies/mLType 1 infectionMulticenter studyOpportunistic central nervous system infectionsCerebrospinal fluid HIV RNACerebrospinal fluid viral loadHigher CSF HIV RNALog10 copies/mLCentral nervous system infectionCross-sectional multicenter studyHIV RNA quantificationNervous system infectionTreatment-naive adultsBlood cell countLarge multicenter studyCNS compartmentalizationCSF discordanceNormal childhood brain growth and a universal sex and anthropomorphic relationship to cerebrospinal fluid
Peterson M, Cherukuri V, Paulson J, Ssentongo P, Kulkarni A, Warf B, Monga V, Schiff S. Normal childhood brain growth and a universal sex and anthropomorphic relationship to cerebrospinal fluid. Journal Of Neurosurgery Pediatrics 2021, 28: 458-468. PMID: 34243147, PMCID: PMC8594737, DOI: 10.3171/2021.2.peds201006.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAlgorithmsAnalysis of VarianceAnthropometryBody WeightBrainCerebrospinal FluidChildChild DevelopmentChild, PreschoolCohort StudiesFemaleFunctional LateralityHumansHydrocephalusInfantInfant, NewbornMagnetic Resonance ImagingMaleOrgan SizePopulationReference StandardsSex CharacteristicsConceptsBrain growthBrain volumeFluid accumulationRatio of brainHealthy pediatric subjectsTotal brain volumeAge 18 yearsYears of ageRegional brain volumesNormal brain growthAge-dependent relationshipCSF accumulationPediatric subjectsChildhood diseasesCerebrospinal fluidCSF volumeCongenital disorderVolume trajectoriesEarly childhoodNormative growth curvesNumerous conditionsSexMagnetic resonanceBrain sizeDisparate volumetric fluid shifts across cerebral tissue compartments with two different anesthetics
Ozturk BO, Monte B, Koundal S, Dai F, Benveniste H, Lee H. Disparate volumetric fluid shifts across cerebral tissue compartments with two different anesthetics. Fluids And Barriers Of The CNS 2021, 18: 1. PMID: 33407650, PMCID: PMC7788828, DOI: 10.1186/s12987-020-00236-x.Peer-Reviewed Original ResearchConceptsMagnetic resonance imagingApparent diffusion coefficientCerebrospinal fluidGlymphatic transportSprague-Dawley female ratsLow-dose isofluraneCrossover study designRepetitive magnetic resonance imagingDawley female ratsTissue compartmentsVolume statusAnesthesia groupBasal cisternsDiffusion-weighted imagesDexmFemale ratsParenchymal expansionHeart rateGlymphatic systemDifferent anestheticsIsofluraneTissue statusResonance imagingFluid shiftsCSF compartment
2020
In Xenopus ependymal cilia drive embryonic CSF circulation and brain development independently of cardiac pulsatile forces
Dur AH, Tang T, Viviano S, Sekuri A, Willsey HR, Tagare HD, Kahle KT, Deniz E. In Xenopus ependymal cilia drive embryonic CSF circulation and brain development independently of cardiac pulsatile forces. Fluids And Barriers Of The CNS 2020, 17: 72. PMID: 33308296, PMCID: PMC7731788, DOI: 10.1186/s12987-020-00234-z.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainCerebrospinal FluidCiliaEpendymaHeartLarvaPulsatile FlowTomography, Optical CoherenceXenopusConceptsCSF circulationOptical coherence tomographyCSF flowVentricular systemEpendymal ciliaCoherence tomographyBrain developmentCross-sectional imaging modalitiesBrain ventricular systemEarly time pointsVentricular morphologyCerebral ventricleRespiratory forceConclusionsOur dataCerebrospinal fluidChoroid plexusVentricular spaceCardiac forceEmbryonic brainPulsatile forcesDeadly diseaseTime pointsImaging modalitiesOCT imagingPathological expansionMinimal detection of cerebrospinal fluid escape after initiation of antiretroviral therapy in acute HIV-1 infection.
Handoko R, Chan P, Jagodzinski L, Pinyakorn S, Ubolyam S, Phanuphak N, Sacdalan C, Kroon E, Dumrongpisutikul N, Paul R, Valcour V, Ananworanich J, Vasan S, Spudich S. Minimal detection of cerebrospinal fluid escape after initiation of antiretroviral therapy in acute HIV-1 infection. AIDS 2020, 35: 777-782. PMID: 33306551, PMCID: PMC7969409, DOI: 10.1097/qad.0000000000002786.Peer-Reviewed Original ResearchMeSH KeywordsAnti-Retroviral AgentsCerebrospinal FluidHIV InfectionsHIV-1HumansProspective StudiesRNA, ViralThailandViral LoadConceptsAcute HIV-1 infectionHIV-1 RNACentral nervous systemCSF escapeAntiretroviral therapyHIV-1 infectionWeek 96Week 24HIV-1CSF HIV-1 RNAInitiation of ARTLong-term neurological outcomePlasma HIV-1 RNAWeeks of ARTProspective cohort studyPersistence of HIVHIV-1 persistenceLevels of CSFYears of treatmentHIV-1 replicationNeurological outcomeCohort studyVoluntary counselingChronic infectionEarly treatmentGlymphatic Cerebrospinal Fluid and Solute Transport Quantified by MRI and PET Imaging
Benveniste H, Lee H, Ozturk B, Chen X, Koundal S, Vaska P, Tannenbaum A, Volkow ND. Glymphatic Cerebrospinal Fluid and Solute Transport Quantified by MRI and PET Imaging. Neuroscience 2020, 474: 63-79. PMID: 33248153, PMCID: PMC8149482, DOI: 10.1016/j.neuroscience.2020.11.014.Peer-Reviewed Original ResearchThe glymphatic system and its role in cerebral homeostasis
Benveniste H, Elkin R, Heerdt P, Koundal S, Xue Y, Lee H, Wardlaw J, Tannenbaum A. The glymphatic system and its role in cerebral homeostasis. Journal Of Applied Physiology 2020, 129: 1330-1340. PMID: 33002383, PMCID: PMC7792843, DOI: 10.1152/japplphysiol.00852.2019.Peer-Reviewed Original ResearchLow cerebrospinal fluid volume and the risk for post-lumbar puncture headaches
Droby A, Omer N, Gurevich T, Kestenbaum M, Mina Y, Cedarbaum JM, Aizenstein O, Giladi N, Mirelman A, Thaler A. Low cerebrospinal fluid volume and the risk for post-lumbar puncture headaches. Journal Of The Neurological Sciences 2020, 417: 117059. PMID: 32739500, DOI: 10.1016/j.jns.2020.117059.Peer-Reviewed Original ResearchMeSH KeywordsCerebrospinal FluidHumansMagnetic Resonance ImagingNervous System DiseasesPilot ProjectsPost-Dural Puncture HeadacheSpinal PunctureConceptsPost-LP headachePost-lumbar puncture headacheLow CSF volumeT1-weighted imagesCerebrospinal fluidCSF volumePuncture headacheDisease-modifying clinical trialsLow cerebrospinal fluid (CSF) volumePatient-related factorsGradient-echo T1-weighted imagesCerebrospinal fluid volumeLP headacheAdverse eventsMedical workupClinical trialsBrain MRINeurological conditionsHeadacheMRI scansT MR scannerWhite matterCSF collectionGray matterPilot studyA rare case of HIV CNS escape in a patient previously considered a viral controller
Magid-Bernstein J, Guo CY, Chow FC, Thakur KT. A rare case of HIV CNS escape in a patient previously considered a viral controller. International Journal Of STD & AIDS 2020, 31: 694-698. PMID: 32538333, DOI: 10.1177/0956462420922452.Peer-Reviewed Original ResearchConceptsViral controllersViral suppressionFungal CNS infectionsNon-HIV infectionsPerinatal HIV infectionHuman immunodeficiency virus ribonucleic acid levelsCentral nervous systemRibonucleic acid levelsCNS infectionsHIV RNAHIV infectionRare caseCerebrospinal fluidNervous systemAcid levelsInfectionYoung menIndependent replicationHIVPatientsSuppressionSettingOptimal Mass Transport with Lagrangian Workflow Reveals Advective and Diffusion Driven Solute Transport in the Glymphatic System
Koundal S, Elkin R, Nadeem S, Xue Y, Constantinou S, Sanggaard S, Liu X, Monte B, Xu F, Van Nostrand W, Nedergaard M, Lee H, Wardlaw J, Benveniste H, Tannenbaum A. Optimal Mass Transport with Lagrangian Workflow Reveals Advective and Diffusion Driven Solute Transport in the Glymphatic System. Scientific Reports 2020, 10: 1990. PMID: 32029859, PMCID: PMC7004986, DOI: 10.1038/s41598-020-59045-9.Peer-Reviewed Original Research
2019
Defining cerebrospinal fluid HIV RNA escape: editorial review AIDS.
Winston A, Antinori A, Cinque P, Fox HS, Gisslen M, Henrich TJ, Letendre S, Persaud D, Price RW, Spudich S. Defining cerebrospinal fluid HIV RNA escape: editorial review AIDS. AIDS 2019, 33 Suppl 2: s107-s111. PMID: 31790376, DOI: 10.1097/qad.0000000000002252.Peer-Reviewed Original ResearchThe microbiota regulate neuronal function and fear extinction learning
Chu C, Murdock M, Jing D, Won T, Chung H, Kressel A, Tsaava T, Addorisio M, Putzel G, Zhou L, Bessman N, Yang R, Moriyama S, Parkhurst C, Li A, Meyer H, Teng F, Chavan S, Tracey K, Regev A, Schroeder F, Lee F, Liston C, Artis D. The microbiota regulate neuronal function and fear extinction learning. Nature 2019, 574: 543-548. PMID: 31645720, PMCID: PMC6818753, DOI: 10.1038/s41586-019-1644-y.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnti-Bacterial AgentsAutistic DisorderBloodCalciumCerebrospinal FluidCuesDendritic SpinesExtinction, PsychologicalFearFecesGerm-Free LifeIndicanMaleMetabolomicsMiceMice, Inbred BALB CMice, Inbred C57BLMicrobiotaNeural InhibitionNeurogliaNeuronsPhenylpropionatesPrefrontal CortexSchizophreniaTranscriptomeVagus NerveConceptsFear extinction learningMedial prefrontal cortexExtinction learningMicrobiota-derived signalsPrefrontal cortexNeuropsychiatric disordersAdult miceSusceptibility to neuropsychiatric disordersInfluence many physiological processesGerm-free adult miceTranscranial two-photon imagingMicrobiota-derived compoundsSingle-nucleus RNA sequencingGerm-free miceComplex consortiaMulticellular organismsPostsynaptic dendritic spinesBrain healthBrain functionRNA sequencingMicrobiotaIn adulthoodGene expressionNeuronal activityPostnatal neurodevelopment
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