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
Ventricular-subventricular zone stem cell niche adaptations in a mouse model of post-infectious hydrocephalus
Herman J, Rittenhouse N, Mandino F, Majid M, Wang Y, Mezger A, Kump A, Kadian S, Lake E, Verardi P, Conover J. Ventricular-subventricular zone stem cell niche adaptations in a mouse model of post-infectious hydrocephalus. Frontiers In Neuroscience 2024, 18: 1429829. PMID: 39145299, PMCID: PMC11322059, DOI: 10.3389/fnins.2024.1429829.Peer-Reviewed Original ResearchPost-infectious hydrocephalusVentricular-subventricular zoneInfluenza virusMouse modelMouse-adapted influenza virusIntact ependymaStem cellsPostnatal day 4Stem cell numbersStem cell nicheCell-to-cell transmissionOlfactory bulbMultiorgan hemorrhageLateral ventricleIntracerebroventricular injectionVentriculomegalyEmbryonic dayVentricular systemDay 4Cell nicheNo significant reductionHydrocephalusSignificant reductionVentricleCell numberPathogenic variants in autism gene KATNAL2 cause hydrocephalus and disrupt neuronal connectivity by impairing ciliary microtubule dynamics
DeSpenza T, Singh A, Allington G, Zhao S, Lee J, Kiziltug E, Prina M, Desmet N, Dang H, Fields J, Nelson-Williams C, Zhang J, Mekbib K, Dennis E, Mehta N, Duy P, Shimelis H, Walsh L, Marlier A, Deniz E, Lake E, Constable R, Hoffman E, Lifton R, Gulledge A, Fiering S, Moreno-De-Luca A, Haider S, Alper S, Jin S, Kahle K, Luikart B. Pathogenic variants in autism gene KATNAL2 cause hydrocephalus and disrupt neuronal connectivity by impairing ciliary microtubule dynamics. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2314702121. PMID: 38916997, PMCID: PMC11228466, DOI: 10.1073/pnas.2314702121.Peer-Reviewed Original ResearchConceptsCongenital hydrocephalusCerebral ventriculomegalyPathogenic variantsPrefrontal pyramidal neuronsGenetic subsets of patientsDevelopment of ventriculomegalyRadial gliaSubsets of patientsHigh-frequency firingNeuronal connectivityHeterozygous germline variantsAutism spectrum disorderVentricular-subventricular zoneMicrotubule dynamicsImpaired spermatogenesisCSF shuntingExcitatory driveMicrotubule-severing ATPasePyramidal neuronsDisrupt neuronal connectivityGermline variantsVentriculomegalyCSF homeostasisDisrupt microtubule dynamicsPlanar cell polarityTRIM71 mutations cause a neurodevelopmental syndrome featuring ventriculomegaly and hydrocephalus
Duy P, Jux B, Zhao S, Mekbib K, Dennis E, Dong W, Nelson-Williams C, Mehta N, Shohfi J, Juusola J, Allington G, Smith H, Marlin S, Belhous K, Monteleone B, Schaefer G, Pisarska M, Vásquez J, Estrada-Veras J, Keren B, Mignot C, Flore L, Palafoll I, Alper S, Lifton R, Haider S, Moreno-De-Luca A, Jin S, Kolanus W, Kahle K. TRIM71 mutations cause a neurodevelopmental syndrome featuring ventriculomegaly and hydrocephalus. Brain 2024, 147: 4292-4305. PMID: 38833623, PMCID: PMC11629693, DOI: 10.1093/brain/awae175.Peer-Reviewed Original ResearchCongenital hydrocephalusCerebral ventriculomegalyStructural brain defectsCohort of patientsAnalysis of human embryosNeurodevelopmental syndromeCorpus callosum dysgenesisWhite matter hypoplasiaSingle-cell transcriptome analysisNeural stem cellsDysmorphic featuresTransmitted variantsPatient cohortVentriculomegalyNHL domainCross-sectional analysisLin-41Subcellular localizationBrain defectsDevelopmental delayHuman embryosProcessing bodiesHomologous positionsPatientsStem cellsBiomechanical instability of the brain–CSF interface in hydrocephalus
Duy P, Mehta N, Kahle K. Biomechanical instability of the brain–CSF interface in hydrocephalus. Brain 2024, 147: 3274-3285. PMID: 38798141, PMCID: PMC11449143, DOI: 10.1093/brain/awae155.Peer-Reviewed Original ResearchBrain-CSF interfaceBrain parenchymaPost-hemorrhagic hydrocephalusLow intracranial pressureAbnormal biomechanical propertiesNormal pressure hydrocephalusPost-infectiousCongenital hydrocephalusImpaired neurodevelopmentCommunicating hydrocephalusCSF homeostasisBiomechanical instabilityHydrocephalusIntracranial pressureAnimal studiesPressure hydrocephalusArachnoid granulationsPrimary derangementBrain surgeryStudy of hydrocephalusAge groupsCSF reabsorptionVentriculomegalyVentricleSecondary enlargement184 PTEN Mutations Portend Cerebral Ventriculomegaly With Autism-Like Deficits in Cortical Circuitry
DeSpenza T, Kizlitug E, Allington G, Barson D, O'Connor D, Robert S, Mekbib K, Singh A, Phan D, Nanda P, Mandino F, Constable T, Lake E, Carter B, Gunel M, Lifton R, Luikart B, Kahle K. 184 PTEN Mutations Portend Cerebral Ventriculomegaly With Autism-Like Deficits in Cortical Circuitry. Neurosurgery 2024, 70: 46-46. DOI: 10.1227/neu.0000000000002809_184.Peer-Reviewed Original ResearchWhole-exome sequencingFetal ventriculomegalyCongenital hydrocephalusExome sequencingChoroid plexus hyperplasiaMutated genesCa2+ imagingMutant mouse modelsPTEN mutantsHuman fetal brainPten mutant miceSporadic CHCerebral ventriculomegalyCSF diversionObstructive hydrocephalusCH patientsCSF secretionPharmacological mTORC1 inhibitionNeurodevelopmental assessmentRadiographic biomarkersFetal brainPTEN mutationsAqueductal stenosisPTEN deletionVentriculomegaly
2021
Intraventricular CSF Turbulence in Pediatric Communicating Hydrocephalus
Duy PQ, Kahle KT. Intraventricular CSF Turbulence in Pediatric Communicating Hydrocephalus. Neurology 2021, 97: 246-247. PMID: 34031199, PMCID: PMC8589266, DOI: 10.1212/wnl.0000000000012237.Peer-Reviewed Original ResearchConceptsProgressive macrocephalyCSF turbulenceLower extremity motor functionDiffuse cortical atrophyExtremity motor functionMild neurocognitive impairmentCommunicating hydrocephalusVentriculoperitoneal shuntCortical atrophyIntracranial hemorrhagePhysical examinationPostoperative imagingComplete resolutionIntracranial pressureMotor functionHead circumferenceOpen myelomeningoceleNeurocognitive impairmentMild decreaseCSF flowVentriculomegalyMacrocephaly
2015
Apathy, ventriculomegaly and neurocognitive improvement following shunt surgery in normal pressure hydrocephalus
Peterson KA, Housden CR, Killikelly C, DeVito EE, Keong NC, Savulich G, Czosnyka Z, Pickard JD, Sahakian BJ. Apathy, ventriculomegaly and neurocognitive improvement following shunt surgery in normal pressure hydrocephalus. British Journal Of Neurosurgery 2015, 30: 38-42. PMID: 25968325, DOI: 10.3109/02688697.2015.1029429.Peer-Reviewed Original ResearchConceptsNormal pressure hydrocephalusMini-Mental State ExaminationApathy Evaluation ScaleGeriatric Depression ScaleShunt surgeryApathetic symptomsPressure hydrocephalusBicaudate ratioSubcortical atrophyCaudate atrophyFunctional outcomeGDS scoresNeurocognitive improvementDepression ScaleCognitive recoveryLevel of apathyState ExaminationVentriculomegalySurgerySymptomsCognitive outcomesHydrocephalusAtrophyEvaluation ScaleGoal-directed behavior
2013
Ventriculomegaly associated with ependymal gliosis and declines in barrier integrity in the aging human and mouse brain
Shook BA, Lennington JB, Acabchuk RL, Halling M, Sun Y, Peters J, Wu Q, Mahajan A, Fellows DW, Conover JC. Ventriculomegaly associated with ependymal gliosis and declines in barrier integrity in the aging human and mouse brain. Aging Cell 2013, 13: 340-350. PMID: 24341850, PMCID: PMC3954884, DOI: 10.1111/acel.12184.Peer-Reviewed Original ResearchConceptsAged humansPeriventricular tissueVentricle enlargementGlial scarringEpendymal cell lossEpendymal cell liningPeriventricular gliosisReactive gliosisHistological featuresDegenerative lossLateral ventricleGliosisMouse modelVentricular expansionVentricle liningAquaporin-4Barrier integrityEpendymal cellsLateral ventricle surfaceCell lossMouse brainVentriculomegalyCell liningMiceScarring
2009
Ventricular dilation and elevated aqueductal pulsations in a new experimental model of communicating hydrocephalus
Wagshul M, McAllister J, Rashid S, Li J, Egnor M, Walker M, Yu M, Smith S, Zhang G, Chen J, Benveniste H. Ventricular dilation and elevated aqueductal pulsations in a new experimental model of communicating hydrocephalus. Experimental Neurology 2009, 218: 33-40. PMID: 19348801, DOI: 10.1016/j.expneurol.2009.03.034.Peer-Reviewed Original ResearchConceptsVentricular dilationAqueductal flowVentricular volumeInjection of kaolinNew experimental modelCSF pulsatilityClinical presentationMild ventriculomegalyVentricular sizeBasal cisternsChronic elevationAbnormal pulsationsCerebral aqueductHydrocephalic animalsEffective treatmentAdult ratsIntact controlsNormal levelsHydrocephalusExperimental modelT MRIRatsMonth periodVentriculomegalyDilation
2002
A1 adenosine receptor activation induces ventriculomegaly and white matter loss
Turner CP, Yan H, Schwartz M, Othman T, Rivkees SA. A1 adenosine receptor activation induces ventriculomegaly and white matter loss. Neuroreport 2002, 13: 1199-1204. PMID: 12151769, DOI: 10.1097/00001756-200207020-00026.Peer-Reviewed Original ResearchMeSH KeywordsAdenosineAnimalsAnimals, NewbornBody WeightCell CountCerebral CortexCerebral VentriclesDrug CombinationsDrug InteractionsGTP-Binding ProteinsGuanosine 5'-O-(3-Thiotriphosphate)HippocampusMicroscopy, ElectronMyelin Basic ProteinNerve DegenerationNerve Fibers, MyelinatedNeurogliaNeuronsPresynaptic TerminalsPurinergic P1 Receptor AgonistsPurinergic P1 Receptor AntagonistsRatsRats, Sprague-DawleyReceptors, Purinergic P1TelencephalonTheophyllineConceptsWhite matter lossAdenosine receptor activationActivation of A1ARPostnatal day 3White matter volumeReceptor-G protein couplingMyelin basic proteinNeuronal lossAgonist treatmentNeonatal ratsN6-cyclopentyladenosineA1AR activationMatter volumeDay 3Adenosine receptorsReceptor activationBrain formationPD 4A1ARReduced expressionProtein couplingQuantitative electron microscopyVentriculomegalyBasic proteinBrain
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