2025
CCL21-CCR7 blockade prevents neuroinflammation and degeneration in Parkinson’s disease models
Leser F, Júnyor F, Pagnoncelli I, Delgado A, Medeiros I, Nóbrega A, Andrade B, de Lima M, da Silva N, Jacob L, Boyé K, Geraldo L, de Souza A, Maron-Gutierrez T, Castro-Faria-Neto H, Follmer C, Braga C, Neves G, Eichmann A, Romão L, Lima F. CCL21-CCR7 blockade prevents neuroinflammation and degeneration in Parkinson’s disease models. Journal Of Neuroinflammation 2025, 22: 31. PMID: 39894839, PMCID: PMC11789347, DOI: 10.1186/s12974-024-03318-x.Peer-Reviewed Original ResearchConceptsMouse model of PDModel of PDMouse modelDopaminergic neuronsNeuron-microglia communicationNeuron-glia communicationParkinson's diseaseCCR7-dependent mannerMicroglial cell activationCCR7 expressionCCL21-CCR7Progressive degenerative diseaseCCR7 receptorMicroglial cell migrationInflammatory profileChemokine CCL21Cell activationCCL21Therapeutic strategiesChemokine inhibitorsTherapeutic implicationsMicroglial activationReceptor pathwayCCR7Behavioral deficits
2024
Neuroinflammatory history results in overlapping transcriptional signatures with heroin exposure in the nucleus accumbens and alters responsiveness to heroin in male rats
Floris G, Zanda M, Dabrowski K, Daws S. Neuroinflammatory history results in overlapping transcriptional signatures with heroin exposure in the nucleus accumbens and alters responsiveness to heroin in male rats. Translational Psychiatry 2024, 14: 500. PMID: 39702361, PMCID: PMC11659471, DOI: 10.1038/s41398-024-03203-4.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBehavior, AnimalHeroinLipopolysaccharidesMaleNeuroinflammatory DiseasesNucleus AccumbensRatsRats, Sprague-DawleyTranscriptomeConceptsResponse to heroinNucleus accumbensHeroin exposureOpioid use disorderSelf-administrationHeroin self-administrationMesolimbic dopamine systemOpioid-induced behaviorsMolecular neuroadaptationsDopamine systemOpioid rewardHeroin intakeBehavioral effectsUse disorderPsychiatric researchLipopolysaccharide (LPS)-induced neuroinflammationPreclinical modelsBehavioral ramificationsSensitivity to opioidsOpioid heroinHeroinMale ratsAccumbensHeightened immune responseNeuroinflammationIntrathecal lactate dehydrogenase A inhibitors FX11 and oxamate alleviate chronic constriction injury-induced nociceptive sensitization through neuroinflammation and angiogenesis
Cheng H, Chen N, Chen W, Wu Z, Sun Y, Teng W, Su F, Sung C, Wen Z. Intrathecal lactate dehydrogenase A inhibitors FX11 and oxamate alleviate chronic constriction injury-induced nociceptive sensitization through neuroinflammation and angiogenesis. The Journal Of Headache And Pain 2024, 25: 207. PMID: 39587478, PMCID: PMC11590346, DOI: 10.1186/s10194-024-01916-x.Peer-Reviewed Original ResearchConceptsLactate dehydrogenase ANeuropathic painNociceptive sensitizationLDHA inhibitorsTreat neuropathic painType of painUpregulation of glycolysisCCI-induced neuroinflammationCentral nervous systemBackgroundNeuropathic painNeuropathic ratsSpinal roleNociceptive behaviorBlood vessel growthImmunohistochemical analysisControl inflammationPainEffective treatmentConclusionIn conclusionHIF-1aCellular mechanismsNervous systemTherapeutic targetVessel growthWestern blottingMaresin-1 Ameliorates Sepsis-Induced Microglial Activation Through Modulation of the P38 MAPK Pathway
Dai M, Sun S, Dai Y, Dou X, Yang J, Chen X, Yang D, Lin Y. Maresin-1 Ameliorates Sepsis-Induced Microglial Activation Through Modulation of the P38 MAPK Pathway. Neurochemical Research 2024, 50: 26. PMID: 39565476, DOI: 10.1007/s11064-024-04280-z.Peer-Reviewed Original ResearchConceptsSepsis-induced neuroinflammationM1-type microgliaPro-inflammatory markersPhosphorylation of p38 MAPKP38 MAPK pathwayP38 MAPKDysregulated immune response to infectionMouse cecum ligationImmune response to infectionExpression of pro-inflammatory markersInhibited phosphorylation of p38 MAPKInduce neuronal degenerationMAPK pathwayPuncture (CLP)-induced sepsis modelPotential therapeutic roleP38 MAPK inhibitor SB203580Combination of SB203580Response to infectionMicroglial cell markersLife-threatening diseaseMAPK inhibitor SB203580Co-administrationCell markersCLP modelCecum ligationVEGF-C prophylaxis favors lymphatic drainage and modulates neuroinflammation in a stroke model
Boisserand L, Geraldo L, Bouchart J, Kamouh M, Lee S, Sanganahalli B, Spajer M, Zhang S, Lee S, Parent M, Xue Y, Skarica M, Yin X, Guegan J, Boyé K, Leser F, Jacob L, Poulet M, Li M, Liu X, Velazquez S, Singhabahu R, Robinson M, Askenase M, Osherov A, Sestan N, Zhou J, Alitalo K, Song E, Eichmann A, Sansing L, Benveniste H, Hyder F, Thomas J. VEGF-C prophylaxis favors lymphatic drainage and modulates neuroinflammation in a stroke model. Journal Of Experimental Medicine 2024, 221: e20221983. PMID: 38442272, PMCID: PMC10913814, DOI: 10.1084/jem.20221983.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDrainageIschemic StrokeMiceNeuroinflammatory DiseasesStrokeVascular Endothelial Growth Factor CConceptsVascular endothelial growth factor-CDeep cervical lymph nodesCentral nervous systemEffect of vascular endothelial growth factor-CMeningeal lymphatic vesselsAmeliorated motor performanceCervical lymph nodesIschemic strokeVEGF-C overexpressionIncreased BDNF signalingAcute ischemic strokeBrain cellsIncreased CSF drainageIschemic stroke outcomesModel of ischemic strokeMouse model of ischemic strokeImmune surveillanceCSF drainageLymph nodesFluid drainageNucleus RNA sequencingLymphatic growthLymphatic drainageMouse modelBDNF signalingSiponimod Attenuates Neuronal Cell Death Triggered by Neuroinflammation via NFκB and Mitochondrial Pathways
Gurrea-Rubio M, Wang Q, Mills E, Wu Q, Pitt D, Tsou P, Fox D, Mao-Draayer Y. Siponimod Attenuates Neuronal Cell Death Triggered by Neuroinflammation via NFκB and Mitochondrial Pathways. International Journal Of Molecular Sciences 2024, 25: 2454. PMID: 38473703, PMCID: PMC10931690, DOI: 10.3390/ijms25052454.Peer-Reviewed Original ResearchConceptsSecondary progressive MSRelapsing-remitting MSCentral nervous systemMultiple sclerosisProgressive MSModulator of sphingosine-1-phosphateCytokine tumor necrosis factor-alphaEffects of siponimodTumor necrosis factor-alphaHeterogeneous clinical courseBouts of inflammationNeuroprotective effectsPreclinical animal modelsAutoimmune demyelinating diseaseNecrosis factor-alphaMitochondrial oxidative phosphorylationHuman induced pluripotent stem cell (iPSC)-derived neuronsSphingosine-1-phosphateCytokine signaling pathwaysClinical courseLive cell analysisProgressive diseaseOral treatmentMitochondrial pathwayFactor-alpha
2023
Development and Pharmacochemical Characterization Discover a Novel Brain-Permeable HDAC11-Selective Inhibitor with Therapeutic Potential by Regulating Neuroinflammation in Mice
Bai P, Liu Y, Yang L, Ding W, Mondal P, Sang N, Liu G, Lu X, Ho T, Zhou Y, Wu R, Birar V, Wilks M, Tanzi R, Lin H, Zhang C, Li W, Shen S, Wang C. Development and Pharmacochemical Characterization Discover a Novel Brain-Permeable HDAC11-Selective Inhibitor with Therapeutic Potential by Regulating Neuroinflammation in Mice. Journal Of Medicinal Chemistry 2023, 66: 16075-16090. PMID: 37972387, PMCID: PMC12080345, DOI: 10.1021/acs.jmedchem.3c01491.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainHistone Deacetylase InhibitorsHistone DeacetylasesMiceNeuralgiaNeuroinflammatory DiseasesConceptsPositron emission tomographyNeuropathic painHDAC11 inhibitorsInhibition of HDAC11Histone deacetylase 11Pharmacokinetic/pharmacodynamic evaluationNeuroimmune functionMouse modelPharmacological inhibitionBrain uptakeEmission tomographyTherapeutic potentialNeurological indicationsPainTherapeutic targetHDAC11Regulating neuroinflammationNeurological disordersDrug developmentMiceInhibitorsHDAC isoformsCarbon-11Metabolic propertiesBrainSelf-Reported Neuropsychiatric Post–COVID-19 Condition and CSF Markers of Neuroinflammation
Farhadian S, Reisert H, McAlpine L, Chiarella J, Kosana P, Yoon J, Spudich S. Self-Reported Neuropsychiatric Post–COVID-19 Condition and CSF Markers of Neuroinflammation. JAMA Network Open 2023, 6: e2342741. PMID: 37948085, PMCID: PMC10638645, DOI: 10.1001/jamanetworkopen.2023.42741.Peer-Reviewed Original ResearchTargeting PGLYRP1 promotes antitumor immunity while inhibiting autoimmune neuroinflammation
Schnell A, Huang L, Regan B, Singh V, Vonficht D, Bollhagen A, Wang M, Hou Y, Bod L, Sobel R, Chihara N, Madi A, Anderson A, Regev A, Kuchroo V. Targeting PGLYRP1 promotes antitumor immunity while inhibiting autoimmune neuroinflammation. Nature Immunology 2023, 24: 1908-1920. PMID: 37828379, PMCID: PMC10864036, DOI: 10.1038/s41590-023-01645-4.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD8-Positive T-LymphocytesCytokinesEncephalomyelitis, Autoimmune, ExperimentalHumansImmunotherapyInflammationMiceNeoplasmsNeuroinflammatory DiseasesTumor MicroenvironmentConceptsPeptidoglycan recognition protein 1T cellsMyeloid cellsGenetic deletionPotent antitumor immune responsesCo-inhibitory moleculesExperimental autoimmune encephalomyelitisAntitumor immune responseImmune checkpoint blockadePromising targetSuccessful treatment optionT cell functionCentral nervous systemT cell activationMultiple human cancersAutoimmune neuroinflammationAntitumor immunityAutoimmune encephalomyelitisCheckpoint blockadeCheckpoint moleculesEffector phenotypeAutoimmune diseasesProinflammatory moleculesTissue inflammationTreatment optionsEffects of anti‐tau immunotherapy on reactive microgliosis, cerebral endotheliopathy, and cognitive function in an experimental model of cerebral malaria
Ndunge O, Shikani H, Dai M, Freeman B, Desruisseaux M. Effects of anti‐tau immunotherapy on reactive microgliosis, cerebral endotheliopathy, and cognitive function in an experimental model of cerebral malaria. Journal Of Neurochemistry 2023, 167: 441-460. PMID: 37814468, PMCID: PMC10596299, DOI: 10.1111/jnc.15972.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainCognitionDisease Models, AnimalHumansImmunotherapyMalaria, CerebralMiceMice, Inbred C57BLNeurodegenerative DiseasesNeuroinflammatory Diseasestau ProteinsConceptsNeural cell injuryCerebral malariaExperimental CMCell injuryUninfected micePHF-1Cell activationNeurodegenerative diseasesAbnormal regulationExperimental modelAnti-tau immunotherapyTau-targeting therapiesExperimental cerebral malariaGlial cell activationPlasmodium berghei ANKAPlasmodium berghei NK65Abnormal tau phosphorylationSubsequent neurocognitive impairmentSignificant memory impairmentNeural cell damageMicrovascular congestionPbA infectionInflammatory markersBerghei ANKANeurological deficitsCD4dimCD8bright T cells are inversely associated with neuro-inflammatory markers among people with HIV
Albalawi Y, Shull T, Virdi A, Subra C, Mitchell J, Slike B, Jian N, Krebs S, Sacdalan C, Ratnaratorn N, Hsu D, Phanuphak N, Spudich S, Trautmann L, Al-Harthi L. CD4dimCD8bright T cells are inversely associated with neuro-inflammatory markers among people with HIV. AIDS 2023, 38: 1-7. PMID: 37792358, PMCID: PMC10715695, DOI: 10.1097/qad.0000000000003743.Peer-Reviewed Original ResearchMeSH KeywordsCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCognitionHIV InfectionsHumansNeuroinflammatory DiseasesConceptsCombination antiretroviral therapyT cellsWeeks 0CD4-CD8Cerebrospinal fluidImmune activationSoluble markersSuppressive combination antiretroviral therapyPeripheral blood T cellsNeuro-inflammatory markersSubset of CD8Anti-inflammatory propertiesBlood T cellsConfidence intervalsPlasma of peopleT-cell typeCART initiationCSF neopterinPlasma RANTESAntiretroviral therapyWeek 24IP-10IL-6Lumbar punctureIL-8Postinfectious Inflammation, Autoimmunity, and Obsessive-Compulsive Disorder: Sydenham Chorea, Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infection, and Pediatric Acute-Onset Neuropsychiatric Disorder
Vreeland A, Calaprice D, Or-Geva N, Frye R, Agalliu D, Lachman H, Pittenger C, Pallanti S, Williams K, Ma M, Thienemann M, Gagliano A, Mellins E, Frankovich J. Postinfectious Inflammation, Autoimmunity, and Obsessive-Compulsive Disorder: Sydenham Chorea, Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infection, and Pediatric Acute-Onset Neuropsychiatric Disorder. Developmental Neuroscience 2023, 45: 361-374. PMID: 37742615, DOI: 10.1159/000534261.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutoantibodiesAutoimmunityChildChoreaHumansInflammationNeuroinflammatory DiseasesObsessive-Compulsive DisorderStreptococcal InfectionsConceptsPediatric acute-onset neuropsychiatric syndromeObsessive-compulsive disorderGroup A streptococciSydenham's choreaNeuropsychiatric disordersStreptococcal infectionAcute-onset obsessive-compulsive disorderPediatric autoimmune neuropsychiatric disorders associated with streptococcal infectionsAssociated with streptococcal infectionsAnimal modelsPediatric autoimmune neuropsychiatric disordersAnti-neuronal autoantibodiesAutoimmune neuropsychiatric disordersTriggered by infectionModulate neuronal activityRandomized clinical trialsNeuropsychiatric syndromeNeuropsychiatric manifestationsRheumatologic diseasesClinical trialsA streptococciNeural antigensBasal gangliaClinical syndromeNeuronal activityVery-long-chain fatty acids induce glial-derived sphingosine-1-phosphate synthesis, secretion, and neuroinflammation
Chung H, Ye Q, Park Y, Zuo Z, Mok J, Kanca O, Tattikota S, Lu S, Perrimon N, Lee H, Bellen H. Very-long-chain fatty acids induce glial-derived sphingosine-1-phosphate synthesis, secretion, and neuroinflammation. Cell Metabolism 2023, 35: 855-874.e5. PMID: 37084732, PMCID: PMC10160010, DOI: 10.1016/j.cmet.2023.03.022.Peer-Reviewed Original ResearchConceptsExperimental autoimmune encephalomyelitisMultiple sclerosisAdministration of fingolimodFunctions of S1PNF-κB activationSphingosine-1-phosphate (S1P) synthesisS1P receptor antagonistsElevated VLCFAAutoimmune encephalomyelitisFatty acidsMacrophage infiltrationReceptor antagonistImmune cellsMouse modelTreatment avenuesVLCFA levelsFly gliaLong-chain fatty acidsGliaS1P pathwayS1PNeuroinflammationFingolimodVLCFAAbundant fatty acids18F-Labeled o‑aminopyridyl alkynyl radioligands targeting colony-stimulating factor 1 receptor for neuroinflammation imaging
An X, Wang J, Tong L, Zhang X, Fu H, Zhang J, Xie H, Huang Y, Jia H. 18F-Labeled o‑aminopyridyl alkynyl radioligands targeting colony-stimulating factor 1 receptor for neuroinflammation imaging. Bioorganic & Medicinal Chemistry 2023, 83: 117233. PMID: 36933438, DOI: 10.1016/j.bmc.2023.117233.Peer-Reviewed Original ResearchConceptsBrain of lipopolysaccharideMale ICR miceModerate brain uptakeFactor 1 receptorColony-stimulating factor 1 receptorBrain uptakeICR miceGBq/Metabolic stability studiesID/Neuroinflammation imagingMouse brainBiodistribution studiesNanomolar inhibitory potencyReceptor ligandsMiceInhibitory potencySpecific bindingBrainCSF-1RRadiochemical purityMolar activityNeuroinflammation in Obsessive-Compulsive Disorder Sydenham Chorea, Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections, and Pediatric Acute Onset Neuropsychiatric Syndrome
Vreeland A, Thienemann M, Cunningham M, Muscal E, Pittenger C, Frankovich J. Neuroinflammation in Obsessive-Compulsive Disorder Sydenham Chorea, Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections, and Pediatric Acute Onset Neuropsychiatric Syndrome. Psychiatric Clinics Of North America 2023, 46: 69-88. PMID: 36740356, DOI: 10.1016/j.psc.2022.11.004.Peer-Reviewed Original ResearchMeSH KeywordsAutoimmune DiseasesChildChoreaHumansInflammationNeuroinflammatory DiseasesObsessive-Compulsive DisorderStreptococcal InfectionsConceptsPediatric acute-onset neuropsychiatric syndromePediatric autoimmune neuropsychiatric disordersAutoimmune neuropsychiatric disordersSydenham's choreaStreptococcal infectionNeuroinflammatory diseasesNeuropsychiatric syndromeNeuropsychiatric disordersSource of inflammationObsessive-compulsive disorderRheumatological diseasesBasal gangliaClinical trialsClinical dataMajor manifestationsDiagnostic biomarkersImmune systemDisordersDiseaseBehavioral disordersInflammationChoreaSyndromeInfectionFuture studies
2022
Impact of resilience, social support, and personality traits in patients with neuroinflammatory diseases during the COVID-19 pandemic
Jakimovski D, Kavak KS, Longbrake EE, Levit E, Perrone CM, Bar-Or A, Benedict RH, Riley CS, De Jager PL, Venkatesh S, Walker ELS, Xia Z, Weinstock-Guttman B, Collaborative M. Impact of resilience, social support, and personality traits in patients with neuroinflammatory diseases during the COVID-19 pandemic. Multiple Sclerosis And Related Disorders 2022, 68: 104235. PMID: 36283322, PMCID: PMC9548342, DOI: 10.1016/j.msard.2022.104235.Peer-Reviewed Original ResearchNeuroinflammation in neuronopathic Gaucher disease: Role of microglia and NK cells, biomarkers, and response to substrate reduction therapy
Boddupalli CS, Nair S, Belinsky G, Gans J, Teeple E, Nguyen TH, Mehta S, Guo L, Kramer ML, Ruan J, Wang H, Davison M, Kumar D, Vidyadhara D, Zhang B, Klinger K, Mistry PK. Neuroinflammation in neuronopathic Gaucher disease: Role of microglia and NK cells, biomarkers, and response to substrate reduction therapy. ELife 2022, 11: e79830. PMID: 35972072, PMCID: PMC9381039, DOI: 10.7554/elife.79830.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomarkersGaucher DiseaseGlucosylceramidaseGlycosphingolipidsKiller Cells, NaturalMiceMicrogliaNeuroinflammatory DiseasesPilot ProjectsConceptsNeuronopathic Gaucher diseaseAmelioration of neuroinflammationNK cellsGaucher diseaseSerum neurofilament light chainInvolvement of microgliaActivation of microgliaRole of microgliaProminent pathological featureNeurofilament light chainBlood-derived macrophagesRare neurodegenerative disorderGlucosylceramide synthaseNeuroinflammation pathwaysSerum NFMicroglia activationNeuronal injuryImmune infiltratesImproved survivalBrain macrophagesPathological featuresGD patientsClinical trialsMacrophage compartmentPatient managementNervous 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 ResearchDimethyl Fumarate Reduces Inflammation in Chronic Active Multiple Sclerosis Lesions
Zinger N, Ponath G, Sweeney E, Nguyen TD, Lo CH, Diaz I, Dimov A, Teng L, Zexter L, Comunale J, Wang Y, Pitt D, Gauthier SA. Dimethyl Fumarate Reduces Inflammation in Chronic Active Multiple Sclerosis Lesions. Neurology Neuroimmunology & Neuroinflammation 2022, 9: e1138. PMID: 35046083, PMCID: PMC8771666, DOI: 10.1212/nxi.0000000000001138.Peer-Reviewed Original ResearchConceptsChronic active lesionsGlatiramer acetateRim lesionsHuman microgliaDimethyl fumarateMultiple sclerosisActive lesionsChronic active multiple sclerosis lesionsEffects of DMFActive multiple sclerosis lesionsClass III evidenceMarkers of inflammationRelapsing-remitting MSRetrospective observational studyQuantitative susceptibility mappingMultiple sclerosis lesionsActivation stateTreatment-induced changesMRI quantitative susceptibility mappingMicroglial activityGlial activityInflammatory activationMicroglial cellsObservational studyMS lesionsWorsening physical functioning in patients with neuroinflammatory disease during the COVID-19 pandemic
Levit E, Cohen I, Dahl M, Edwards K, Weinstock-Guttman B, Ishikawa T, Kavak K, Leavitt V, Nelson K, Onomichi K, Bar-Or A, Perrone C, Riley C, Venkatesh S, De Jager PL, Xia Z, Longbrake EE, Collaborative M. Worsening physical functioning in patients with neuroinflammatory disease during the COVID-19 pandemic. Multiple Sclerosis And Related Disorders 2022, 58: 103482. PMID: 35016114, PMCID: PMC8742609, DOI: 10.1016/j.msard.2021.103482.Peer-Reviewed Original ResearchConceptsPhysical functionDepression scoresCOVID-19 pandemicPhysical disabilityNeurological inflammatory diseasesMajor academic medical centerAcademic medical centerHigher baseline levelsLack of diseaseDisease durationStudy entryTherapy useNeuroinflammatory diseasesMale genderInflammatory diseasesPhysical functioningMedical CenterMood symptomsDepressive symptomsSmall cohortBaseline levelsSerial surveysSignificant depressionOlder ageWorse depression
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