2024
Pathogenic 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 polarityMultimodal measures of spontaneous brain activity reveal both common and divergent patterns of cortical functional organization
Vafaii H, Mandino F, Desrosiers-Grégoire G, O’Connor D, Markicevic M, Shen X, Ge X, Herman P, Hyder F, Papademetris X, Chakravarty M, Crair M, Constable R, Lake E, Pessoa L. Multimodal measures of spontaneous brain activity reveal both common and divergent patterns of cortical functional organization. Nature Communications 2024, 15: 229. PMID: 38172111, PMCID: PMC10764905, DOI: 10.1038/s41467-023-44363-z.Peer-Reviewed Original Research
2018
Imaging the Effects of &bgr;-Hydroxybutyrate on Peri-Infarct Neurovascular Function and Metabolism
Bazzigaluppi P, Lake EM, Beckett TL, Koletar MM, Weisspapir I, Heinen S, Mester J, Lai A, Janik R, Dorr A, McLaurin J, Stanisz GJ, Carlen PL, Stefanovic B. Imaging the Effects of &bgr;-Hydroxybutyrate on Peri-Infarct Neurovascular Function and Metabolism. Stroke 2018, 49: 2173-2181. PMID: 30354983, DOI: 10.1161/strokeaha.118.020586.Peer-Reviewed Original ResearchMeSH Keywords3-Hydroxybutyric AcidAcetoacetatesAnimalsAstrocytesBlood GlucoseBrainBrain IschemiaCell DeathCerebrovascular CirculationDisease Models, AnimalElectrophysiological PhenomenaEndothelin-1HemodynamicsMagnetic Resonance ImagingMagnetic Resonance SpectroscopyMicroinjectionsNeuronsRatsReactive Oxygen SpeciesSensorimotor CortexConceptsBody β-hydroxybutyrateFunctional recoveryMagnetic resonance imagingIschemic insultNeuronal deathResonance imagingFocal cortical strokeVehicle-administered animalsNeurological deficit scoresKetone body β-hydroxybutyrateNeuronal glucose uptakeContinuous arterial spinReduced oxidative stressPurpose Recent evidenceReactive oxygen species productionCortical microinjectionsCortical strokePostischemic hyperglycemiaDeficit scoresNeurovascular functionAcute phaseCerebrovascular reactivitySensorimotor cortexCerebral hemodynamicsEndothelin-1
2016
Modulation of the peri‐infarct neurogliovascular function by delayed COX‐1 inhibition
Lake EMR, Mester J, Thomason LA, Adams C, Bazzigaluppi P, Koletar M, Janik R, Carlen P, McLaurin J, Stanisz GJ, Stefanovic B. Modulation of the peri‐infarct neurogliovascular function by delayed COX‐1 inhibition. Journal Of Magnetic Resonance Imaging 2016, 46: 505-517. PMID: 28703413, DOI: 10.1002/jmri.25541.Peer-Reviewed Original ResearchConceptsNeuronal survivalMicroglia/macrophage recruitmentExerts multiple beneficial effectsChronic ischemic injuryAdult male ratsCOX-1 inhibitionMultiple beneficial effectsMost patientsAstrocytic activationEndothelial densityNeuronal lossChronic stageFocal ischemiaHemodynamic changesIschemic injuryAdult disabilityMacrophage recruitmentMale ratsPerfusion responseMore effective interventionsNeurogliovascular unitCOX-1Novel treatmentsPerfusionBeneficial effectsNeurovascular unit remodelling in the subacute stage of stroke recovery
Lake EMR, Bazzigaluppi P, Mester J, Thomason LAM, Janik R, Brown M, McLaurin J, Carlen PL, Corbett D, Stanisz GJ, Stefanovic B. Neurovascular unit remodelling in the subacute stage of stroke recovery. NeuroImage 2016, 146: 869-882. PMID: 27664828, DOI: 10.1016/j.neuroimage.2016.09.016.Peer-Reviewed Original ResearchConceptsPeri-lesional cortexVascular reactivityNeuronal lossSubacute stageEndothelin-1LFP activityLong-term functional outcomeLocal field potential responsesPeripheral somatosensory stimulationActivation of microgliaET-1 injectionFocal ischemic strokeFocal cerebral ischaemiaPeri-infarct zoneSensori-motor cortexSpontaneous neuronal activityAdult Sprague-DawleyField potential responsesExtended temporal windowDynamic functional changesIschemic strokeAstrocytic activationCerebral ischaemiaNeurovascular unitIschemic insult