2025
Exercise and the organ-brain axis: Regulation of neurological disorders by emerging exerkines
Dai Y, Dou X, Nie B, Sun Y, Chen P, Fu C, Zhang X, Chu Y, Gao Q, Ge Y, Lin Y. Exercise and the organ-brain axis: Regulation of neurological disorders by emerging exerkines. Pharmacological Research 2025, 219: 107913. PMID: 40818821, DOI: 10.1016/j.phrs.2025.107913.Peer-Reviewed Original ResearchConceptsBlood-brain barrierCentral nervous systemBrain disordersCerebral energy metabolismImmune homeostasisPeripheral organsSynaptic plasticityFunctional alterationsNervous systemAdipose tissueNeuroprotective effectsMicroglia phenotypePeptide releaseMyokine secretionSkeletal muscleBrain homeostasisNeurological disordersDisordersRegulatory effectsBrainBrain functionSignaling moleculesEnergy metabolismHomeostasisAdaptive responseAge-dependent brain responses to mechanical stress determine resilience in a chronic lymphatic drainage impairment model
Gursky Z, Khan Z, Koundal S, Bhardwaj A, Melgarejo J, Xu K, Chen X, Lin H, Gu X, Lee H, Kipnis J, Dori Y, Tannenbaum A, Santambrogio L, Benveniste H. Age-dependent brain responses to mechanical stress determine resilience in a chronic lymphatic drainage impairment model. Journal Of Clinical Investigation 2025, 135: e182555. PMID: 40663395, PMCID: PMC12404751, DOI: 10.1172/jci182555.Peer-Reviewed Original ResearchConceptsDeep cervical lymph nodesLymph nodesContrast-enhanced magnetic resonance imagingDynamic contrast-enhanced magnetic resonance imagingCervical lymph nodesEvidence of hydrocephalusBlood-brain barrier leakageImpaired lymphatic drainageLow-grade inflammationLymphatic drainage pathwaysCerebral homeostasisMagnetic resonance imagingDCE-MRILymphatic drainageIntracranial pressureLymphatic vesselsMeningeal lymphatic vesselsLong-term mechanical stressResonance imagingBarrier leakageRatsSolute clearanceGlymphatic influxDrainage pathwaysAge groupsTyphoid toxin causes neuropathology by disrupting the blood–brain barrier
Zhao H, Catarino J, Stack G, Albizu A, Lara-Tejero M, Horvath T, Galán J. Typhoid toxin causes neuropathology by disrupting the blood–brain barrier. Nature Microbiology 2025, 10: 1340-1351. PMID: 40341334, DOI: 10.1038/s41564-025-02000-z.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBacterial ToxinsBlood-Brain BarrierDisease Models, AnimalHumansMiceNeuronsSalmonella typhiTyphoid FeverConceptsTyphoid toxinTyphoid feverBlood-brain barrierBlood brain barrier disruption in vivoDisruption in vivoManifestations of typhoid feverVirulence factorsSalmonella typhiCatalytic subunitBlood-brain barrier permeability changesToxin actionLife-threatening complicationsSevere neurological manifestationsTyphoidIn vitro modelToxinNeurological complicationsGlial cellsTherapeutic interventionsFeverToxin exposureVirulenceComplicationsNeuropathologyEncephalopathyReduced Notch signaling in hypothalamic endothelial cells mediates obesity-induced alterations in glucose uptake and insulin signaling
Zhu Y, Mehlkop O, Backes H, Cremer A, Porniece M, Klemm P, Steuernagel L, Chen W, Johnen R, Wunderlich F, Jais A, Brüning J. Reduced Notch signaling in hypothalamic endothelial cells mediates obesity-induced alterations in glucose uptake and insulin signaling. Cell Reports 2025, 44: 115522. PMID: 40186867, DOI: 10.1016/j.celrep.2025.115522.Peer-Reviewed Original ResearchConceptsShort-term HFD feedingNotch signalingIntracellular domainGlucose uptakeBrain microvascular endothelial cellsNotch intracellular domainHFD feedingDownregulation of Notch signalingHigh-fat dietBlood-brain barrierReduced Notch signalingGLUT1 expressionInsulin signalingSystemic insulin sensitivityBlood-brain barrier permeabilityNotch activationInduced expressionObesity-induced alterationsCaveolae formationPleiotropic effectsEndothelial cellsMicrovascular endothelial cellsExpressionBlood-brain barrier functionCultured brain microvascular endothelial cellsEndothelial SHANK3 regulates tight junctions in the neonatal mouse blood-brain barrier through β-Catenin signaling
Kim Y, Kim M, Kim S, Lee R, Ujihara Y, Marquez-Wilkins E, Jiang Y, Yang E, Kim H, Lee C, Park C, Kim I. Endothelial SHANK3 regulates tight junctions in the neonatal mouse blood-brain barrier through β-Catenin signaling. Nature Communications 2025, 16: 1407. PMID: 39915488, PMCID: PMC11802743, DOI: 10.1038/s41467-025-56720-1.Peer-Reviewed Original ResearchConceptsBlood-brain barrierNeuronal excitabilityB-cateninBarrier functionMouse blood-brain barrierReduced neuronal excitabilityMale mutant miceBlood-brain barrier permeabilityBrain endothelial cellsAutism spectrum disorderNeonatal micePotential therapeutic targetASD risk genesMutant miceTight junctionsImpaired sociabilityPathogenic mechanismsBrain parenchymaEndothelial cellsTherapeutic targetASD pathogenesisSHANK3Adult ageDisabling conditionMice
2024
Mesenchymal Stem Cells and Their Extracellular Vesicles: Therapeutic Mechanisms for Blood–Spinal Cord Barrier Repair Following Spinal Cord Injury
Nakazaki M, Yokoyama T, Lankford K, Hirota R, Kocsis J, Honmou O. Mesenchymal Stem Cells and Their Extracellular Vesicles: Therapeutic Mechanisms for Blood–Spinal Cord Barrier Repair Following Spinal Cord Injury. International Journal Of Molecular Sciences 2024, 25: 13460. PMID: 39769223, PMCID: PMC11677717, DOI: 10.3390/ijms252413460.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood-Brain BarrierExtracellular VesiclesHumansMesenchymal Stem Cell TransplantationMesenchymal Stem CellsSpinal CordSpinal Cord InjuriesConceptsBlood-spinal cord barrierBSCB repairMesenchymal stromal/stem cellsSpinal cord injuryMSC-EVsMesenchymal stromal/stem cell therapyBlood-spinal cord barrier integritySpinal cord homeostasisBlood-spinal cord barrier permeabilityCord injuryImpaired axonal regenerationTreating spinal cord injuryCell-free alternativeExtracellular vesiclesTight junction proteinsSpinal neural tissueBlood-brain barrierImprove patient outcomesAnti-inflammatory propertiesImmune cellsPreclinical studiesJunction proteinsSecreted extracellular vesiclesClinical trialsReduce inflammationTranscobalamin receptor antibodies in autoimmune vitamin B12 central deficiency
Pluvinage J, Ngo T, Fouassier C, McDonagh M, Holmes B, Bartley C, Kondapavulur S, Hurabielle C, Bodansky A, Pai V, Hinman S, Aslanpour A, Alvarenga B, Zorn K, Zamecnik C, McCann A, Asencor A, Huynh T, Browne W, Tubati A, Haney M, Douglas V, Louine M, Cree B, Hauser S, Seeley W, Baranzini S, Wells J, Spudich S, Farhadian S, Ramachandran P, Gillum L, Hales C, Zikherman J, Anderson M, Yazdany J, Smith B, Nath A, Suh G, Flanagan E, Green A, Green R, Gelfand J, DeRisi J, Pleasure S, Wilson M. Transcobalamin receptor antibodies in autoimmune vitamin B12 central deficiency. Science Translational Medicine 2024, 16: eadl3758. PMID: 38924428, PMCID: PMC11520464, DOI: 10.1126/scitranslmed.adl3758.Peer-Reviewed Original ResearchConceptsBlood-brain barrierCerebrospinal fluidNeurological deficitsAutoimmune neurological conditionsCohort of patientsCellular uptake of cobalaminVitamin B12B12 transportCerebrospinal fluid samplesMeasurement of vitamin B12Low-density lipoprotein receptorProgrammable phage displayImmunosuppressive treatmentIn vitro modelNeuropsychiatric lupusImmunomodulatory treatmentReceptor antibodiesClinical improvementUptake of cobalaminB12 deficiencyUnknown etiologyHematopoietic cellsTranscobalamin receptorCentral deficiencyB12 supplementation
2023
Pericytes are protective in experimental pneumococcal meningitis through regulating leukocyte infiltration and blood–brain barrier function
Teske N, Dyckhoff-Shen S, Beckenbauer P, Bewersdorf J, Engelen-Lee J, Hammerschmidt S, Kälin R, Pfister H, Brouwer M, Klein M, Glass R, van de Beek D, Koedel U. Pericytes are protective in experimental pneumococcal meningitis through regulating leukocyte infiltration and blood–brain barrier function. Journal Of Neuroinflammation 2023, 20: 267. PMID: 37978545, PMCID: PMC10655320, DOI: 10.1186/s12974-023-02938-z.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood-Brain BarrierChemokinesCytokinesHumansLeukocytesMeningitis, PneumococcalMicePericytesStreptococcus pneumoniaeZebrafishConceptsModel of pneumococcal meningitisPneumococcal meningitisLeukocyte infiltrationAnimal model of pneumococcal meningitisPrevented blood-brain barrierToll-like receptor inhibitorsDegree of leukocyte infiltrationSerotypes of Streptococcus pneumoniaeUnfavorable disease courseBlood-brain barrier disruptionHuman pericytesExperimental pneumococcal meningitisBlood-brain barrier integrityRegulating leukocyte infiltrationBlood-brain barrier functionRegulation of cerebral blood flowAdult mouse modelInfection in vivoUpregulation of chemokine expressionIncreased cerebral edemaMaintenance of blood-brain barrier integrityBlood-brain barrierCerebral blood flowMouse meningitis modelIn vitro studiesCD31 as a probable responding and gate-keeping protein of the blood-brain barrier and the risk of Alzheimer’s disease
Zhang Z, Gan Q, Han J, Tao Q, Qiu W, Madri J. CD31 as a probable responding and gate-keeping protein of the blood-brain barrier and the risk of Alzheimer’s disease. Cerebrovascular And Brain Metabolism Reviews 2023, 43: 1027-1041. PMID: 37051650, PMCID: PMC10291450, DOI: 10.1177/0271678x231170041.Peer-Reviewed Original ResearchConceptsPlatelet endothelial cell adhesion moleculeImmune cellsDisease riskBlood-brain barrier permeabilityMajor genetic risk factorBlood-brain barrierNeuronal cell injuryEndothelial cell adhesion moleculesAlzheimer's disease riskGenetic risk factorsPeripheral inflammationBrain axisAPOE4 carriersAD pathogenesisRisk factorsBarrier permeabilityAD developmentCell adhesion moleculeCell injuryImmune systemAlzheimer's diseaseCD31Transendothelial migrationPotential drug targetsAdhesion moleculesThe choroid plexus links innate immunity to CSF dysregulation in hydrocephalus
Robert S, Reeves B, Kiziltug E, Duy P, Karimy J, Mansuri M, Marlier A, Allington G, Greenberg A, DeSpenza T, Singh A, Zeng X, Mekbib K, Kundishora A, Nelson-Williams C, Hao L, Zhang J, Lam T, Wilson R, Butler W, Diluna M, Feinberg P, Schafer D, Movahedi K, Tannenbaum A, Koundal S, Chen X, Benveniste H, Limbrick D, Schiff S, Carter B, Gunel M, Simard J, Lifton R, Alper S, Delpire E, Kahle K. The choroid plexus links innate immunity to CSF dysregulation in hydrocephalus. Cell 2023, 186: 764-785.e21. PMID: 36803604, PMCID: PMC10069664, DOI: 10.1016/j.cell.2023.01.017.Peer-Reviewed Original ResearchMeSH KeywordsBlood-Brain BarrierBrainChoroid PlexusCytokine Release SyndromeHumansHydrocephalusImmunity, InnateConceptsPost-infectious hydrocephalusTLR4-dependent immune responseBlood-cerebrospinal fluid barrierSmall molecule pharmacotherapyCell cross talkPharmacological immunomodulationCytokine stormNeuroimmune disordersBrain infectionDrug treatmentImmune responseAcquired hydrocephalusHydrocephalus modelChoroid plexusFluid barrierHydrocephalusEpithelial cellsCSFMulti-omics investigationsCross talkHypersecretionHemorrhagePharmacotherapyImmunomodulationPlexus
2022
Extra-Virgin Olive Oil Enhances the Blood–Brain Barrier Function in Mild Cognitive Impairment: A Randomized Controlled Trial
Kaddoumi A, Denney T, Deshpande G, Robinson J, Beyers R, Redden D, Praticò D, Kyriakides T, Lu B, Kirby A, Beck D, Merner N. Extra-Virgin Olive Oil Enhances the Blood–Brain Barrier Function in Mild Cognitive Impairment: A Randomized Controlled Trial. Nutrients 2022, 14: 5102. PMID: 36501136, PMCID: PMC9736478, DOI: 10.3390/nu14235102.Peer-Reviewed Original ResearchMeSH KeywordsAlzheimer DiseaseAmyloid beta-PeptidesAnimalsBlood-Brain BarrierCognitive DysfunctionHumansMiceOlive OilConceptsClinical Dementia RatingMild cognitive impairmentBBB permeabilityAlzheimer's diseaseProtective effectP-tau/t-tau ratioCognitive impairmentBlood-brain barrier breakdownBlood-brain barrier functionBrain connectivityBehavioral scoresAbnormal BBB permeabilityAD mouse modelClearance of AβT-tau ratioEarly Alzheimer's diseaseFunctional brain activationSecondary outcomesBrain atrophyControlled TrialsPrimary outcomePreclinical findingsBrain amyloidBlood biomarkersBarrier breakdownRadiochemical Synthesis and Evaluation of 3‑[11C]Methyl-4-aminopyridine in Rodents and Nonhuman Primates for Imaging Potassium Channels in the CNS
Sun Y, Guehl N, Zhou Y, Takahashi K, Belov V, Dhaynaut M, Moon S, Fakhri G, Normandin M, Brugarolas P. Radiochemical Synthesis and Evaluation of 3‑[11C]Methyl-4-aminopyridine in Rodents and Nonhuman Primates for Imaging Potassium Channels in the CNS. ACS Chemical Neuroscience 2022, 13: 3342-3351. PMID: 36417797, PMCID: PMC9732819, DOI: 10.1021/acschemneuro.2c00364.Peer-Reviewed Original ResearchConceptsRegional brain time-activity curvesBrain time-activity curvesOne-tissue compartment modelBlood-brain barrierConsistent with <i>inNonhuman primatesTime-activity curvesPositron emission tomographySpinal cord injuryDemyelinated neuronsNeurological symptomsPotassium channelsNeuronal conductionBrain uptakeEmission tomographyStille cross-couplingMultiple sclerosisCord injurySlow kineticsBrain permeabilityTraumatic brainMyelin sheathStronger binding affinityNeuronsBrainNucleic Acid Delivery to the Vascular Endothelium
Reschke M, Piotrowski-Daspit AS, Pober JS, Saltzman WM. Nucleic Acid Delivery to the Vascular Endothelium. Molecular Pharmaceutics 2022, 19: 4466-4486. PMID: 36251765, PMCID: PMC10673694, DOI: 10.1021/acs.molpharmaceut.2c00653.Peer-Reviewed Original ResearchMeSH KeywordsBiological TransportBlood-Brain BarrierEndothelium, VascularGenetic TherapyNucleic AcidsChoroid plexus tissue perfusion and blood to CSF barrier function in rats measured with continuous arterial spin labeling
Lee H, Ozturk B, Stringer MS, Koundal S, MacIntosh BJ, Rothman D, Benveniste H. Choroid plexus tissue perfusion and blood to CSF barrier function in rats measured with continuous arterial spin labeling. NeuroImage 2022, 261: 119512. PMID: 35882269, PMCID: PMC9969358, DOI: 10.1016/j.neuroimage.2022.119512.Peer-Reviewed Original ResearchConceptsWater flowBlood perfusionLow-dose isofluraneCerebral blood flowClinical translational studiesAnti-diuretic hormoneContinuous arterial spinLevels of bloodMeasurement accuracyMagnetic resonance imagingArterial spin labelingCerebrospinal fluid productionAnesthetic regimensBalanced anesthesiaCerebral ventricleContinuous arterial spin labelingIsoflurane anesthesiaKey parametersSystemic administrationVentricular CSFImmune surveillanceArterial bloodBlood flowTissue perfusionChoroid plexus
2021
Neurovascular imaging with QUTE-CE MRI in APOE4 rats reveals early vascular abnormalities
Leaston J, Ferris C, Kulkarni P, Chandramohan D, van de Ven A, Qiao J, Timms L, Sepulcre J, Fakhri G, Ma C, Normandin M, Gharagouzloo C. Neurovascular imaging with QUTE-CE MRI in APOE4 rats reveals early vascular abnormalities. PLOS ONE 2021, 16: e0256749. PMID: 34449808, PMCID: PMC8396782, DOI: 10.1371/journal.pone.0256749.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApolipoprotein E4Blood-Brain BarrierBrainDisease Models, AnimalGene Knock-In TechniquesHumansMagnetic Resonance ImagingRatsConceptsVascular abnormalitiesAPOE-e4Contrast-enhanced magnetic resonance imagingBlood-brain-barrier leakageNeurovascular dysfunctionSmall vessel abnormalitiesMagnetic resonance imagingTri-synaptic circuitBlood-brain-barrierCross-sectional studyFemale ratsSignificant signal increaseHyper-vascularizationCerebrovascular abnormalitiesVessel abnormalitiesNeurovascular imagingQUTE-CEBrain volumeAnimal modelsPathological causesAbnormalitiesHistological validationImaging modalitiesResonance imagingENT2 facilitates brain endothelial cell penetration and blood-brain barrier transport by a tumor-targeting anti-DNA autoantibody
Rattray Z, Deng G, Zhang S, Shirali A, May CK, Chen X, Cuffari BJ, Liu J, Zou P, Rattray N, Johnson CH, Dubljevic V, Campbell JA, Huttner A, Baehring JM, Zhou J, Hansen JE. ENT2 facilitates brain endothelial cell penetration and blood-brain barrier transport by a tumor-targeting anti-DNA autoantibody. JCI Insight 2021, 6: e145875. PMID: 34128837, PMCID: PMC8410084, DOI: 10.1172/jci.insight.145875.Peer-Reviewed Original ResearchConceptsBlood-brain barrierAnti-DNA autoantibodiesBrain tumorsBreast cancer brain metastasesBlood-brain barrier transportBrain tumor immunotherapyCancer brain metastasesBrain endothelial cellsEndothelial cell penetrationCNS lupusNeurotoxic autoantibodiesBrain metastasesTumor immunotherapyBarrier transportAntibody-based approachesCNS penetrationAutoantibodiesEfficacy studiesOrthotopic glioblastomaEndothelial cellsTumorsCancer cellsNucleoside fluxesActionable mechanismsKey transportersRepeated infusion of mesenchymal stem cells maintain the condition to inhibit deteriorated motor function, leading to an extended lifespan in the SOD1G93A rat model of amyotrophic lateral sclerosis
Magota H, Sasaki M, Kataoka-Sasaki Y, Oka S, Ukai R, Kiyose R, Onodera R, Kocsis JD, Honmou O. Repeated infusion of mesenchymal stem cells maintain the condition to inhibit deteriorated motor function, leading to an extended lifespan in the SOD1G93A rat model of amyotrophic lateral sclerosis. Molecular Brain 2021, 14: 76. PMID: 33962678, PMCID: PMC8103621, DOI: 10.1186/s13041-021-00787-6.Peer-Reviewed Original ResearchConceptsAmyotrophic lateral sclerosisAdministration of MSCsSingle infusionMesenchymal stem cellsMotor functionGait abilityDisease progressionMotor neuronsRat modelLateral sclerosisBlood-spinal cord barrierSOD1G93A rat modelSpinal cord degenerateVehicle infusion groupHind limb functionALS rat modelStem cellsLimb functionVehicle infusionFatal disorderSurvival periodTherapeutic effectLocomotor activityInfusionProgressive deteriorationImaging the transmembrane and transendothelial sodium gradients in gliomas
Khan MH, Walsh JJ, Mihailović JM, Mishra SK, Coman D, Hyder F. Imaging the transmembrane and transendothelial sodium gradients in gliomas. Scientific Reports 2021, 11: 6710. PMID: 33758290, PMCID: PMC7987982, DOI: 10.1038/s41598-021-85925-9.Peer-Reviewed Original ResearchMeSH KeywordsBiological TransportBiomarkersBlood-Brain BarrierEnergy MetabolismGliomaMagnetic Resonance ImagingSodiumSpectrum AnalysisUnlocking Pericyte Function in the Adult Blood Brain Barrier One Cell at a Time
Nicoli S, Grutzendler J. Unlocking Pericyte Function in the Adult Blood Brain Barrier One Cell at a Time. Circulation Research 2021, 128: 511-512. PMID: 33600230, PMCID: PMC7928238, DOI: 10.1161/circresaha.121.318799.Peer-Reviewed Original ResearchPreclinical Comparison of the Blood–brain barrier Permeability of Osimertinib with Other EGFR TKIs
Colclough N, Chen K, Johnström P, Strittmatter N, Yan Y, Wrigley GL, Schou M, Goodwin R, Varnäs K, Adua SJ, Zhao M, Nguyen DX, Maglennon G, Barton P, Atkinson J, Zhang L, Janefeldt A, Wilson J, Smith A, Takano A, Arakawa R, Kondrashov M, Malmquist J, Revunov E, Vazquez-Romero A, Moein MM, Windhorst AD, Karp NA, Finlay MRV, Ward RA, Yates JWT, Smith PD, Farde L, Cheng Z, Cross DAE. Preclinical Comparison of the Blood–brain barrier Permeability of Osimertinib with Other EGFR TKIs. Clinical Cancer Research 2021, 27: 189-201. PMID: 33028591, DOI: 10.1158/1078-0432.ccr-19-1871.Peer-Reviewed Original ResearchConceptsBlood-brain barrier permeabilityBrain metastasesBrain penetranceBarrier permeabilityEGFR tyrosine kinase inhibitorsT790M resistance mutationMetastatic brain diseaseSubclinical brain metastasesSelective EGFR tyrosine kinase inhibitorOngoing clinical evaluationM resistance mutationTyrosine kinase inhibitorsBBB penetranceBrain tumor growthClinical efficacyEGFR-TKIEGFR-TKIsBrain penetrationClinical evaluationPreclinical comparisonPreclinical modelsPreclinical studiesCynomolgus macaquesOsimertinibTumor growth
This site is protected by hCaptcha and its Privacy Policy and Terms of Service apply