2024
Single-Cell Transcriptomic Analyses of Brain Parenchyma in Patients With New-Onset Refractory Status Epilepticus (NORSE)
Hanin A, Zhang L, Huttner A, Plu I, Mathon B, Bielle F, Navarro V, Hirsch L, Hafler D. Single-Cell Transcriptomic Analyses of Brain Parenchyma in Patients With New-Onset Refractory Status Epilepticus (NORSE). Neurology Neuroimmunology & Neuroinflammation 2024, 11: e200259. PMID: 38810181, PMCID: PMC11139018, DOI: 10.1212/nxi.0000000000200259.Peer-Reviewed Original ResearchConceptsNew-onset refractory status epilepticusTemporal lobe epilepsyGABAergic neuronsExcitatory neuronsInfiltrating macrophagesProportion of GABAergic neuronsChronic temporal lobe epilepsyRefractory status epilepticusInhibitory GABAergic neuronsSingle-cell transcriptome analysisDecreased expression of genesDegree of demyelinationImmune disturbancesNeuronal excitabilityImmune dysregulationNew-onsetStatus epilepticusPoor outcomeRefractory epilepsyHealthy childrenMicroglial reactivitySingle-nucleus RNA sequencingNLRP3 inflammasome activationInflammatory responseLobe epilepsy
2023
Chromosome instability and aneuploidy in the mammalian brain
Albert O, Sun S, Huttner A, Zhang Z, Suh Y, Campisi J, Vijg J, Montagna C. Chromosome instability and aneuploidy in the mammalian brain. Chromosome Research 2023, 31: 32. PMID: 37910282, PMCID: PMC10833588, DOI: 10.1007/s10577-023-09740-w.Peer-Reviewed Original ResearchConceptsChromosome instabilityExcess of chromosomesRole of aneuploidyNon-transformed cellsSomatic tissuesDiploid setChromosomal countsAneuploid cellsChromosomal alterationsMammalian brainCancer cellsAneuploidyCellsAging processChromosomesDevelopmental disordersPresent understandingSpecific consequencesDNAValuable insightsFuture research effortsBroad rangeHallmarkStructural modificationsAnti-seed PNAs targeting multiple oncomiRs for brain tumor therapy
Wang Y, Malik S, Suh H, Xiao Y, Deng Y, Fan R, Huttner A, Bindra R, Singh V, Saltzman W, Bahal R. Anti-seed PNAs targeting multiple oncomiRs for brain tumor therapy. Science Advances 2023, 9: eabq7459. PMID: 36753549, PMCID: PMC9908025, DOI: 10.1126/sciadv.abq7459.Peer-Reviewed Original ResearchConceptsConvection-enhanced deliveryHigh recurrence rateOrthotopic mouse modelBrain tumor therapyTreatment of glioblastomaRecurrence ratePoor survivalLethal malignancyMouse modelGBM progressionTumor cellsGlioblastomaTumor therapyBioadhesive nanoparticlesOncomiRSurvivalTreatmentSeed regionMalignancyTemozolomideTherapy
2022
Analysis of somatic mutations in 131 human brains reveals aging-associated hypermutability
Bae T, Fasching L, Wang Y, Shin JH, Suvakov M, Jang Y, Norton S, Dias C, Mariani J, Jourdon A, Wu F, Panda A, Pattni R, Chahine Y, Yeh R, Roberts RC, Huttner A, Kleinman JE, Hyde TM, Straub RE, Walsh CA, Urban A, Leckman J, Weinberger D, Vaccarino F, Abyzov A, Walsh C, Park P, Sestan N, Weinberger D, Moran J, Gage F, Vaccarino F, Gleeson J, Mathern G, Courchesne E, Roy S, Chess A, Akbarian S, Bizzotto S, Coulter M, Dias C, D’Gama A, Ganz J, Hill R, Huang A, Khoshkhoo S, Kim S, Lee A, Lodato M, Maury E, Miller M, Borges-Monroy R, Rodin R, Zhou Z, Bohrson C, Chu C, Cortes-Ciriano I, Dou Y, Galor A, Gulhan D, Kwon M, Luquette J, Sherman M, Viswanadham V, Jones A, Rosenbluh C, Cho S, Langmead B, Thorpe J, Erwin J, Jaffe A, McConnell M, Narurkar R, Paquola A, Shin J, Straub R, Abyzov A, Bae T, Jang Y, Wang Y, Molitor C, Peters M, Linker S, Reed P, Wang M, Urban A, Zhou B, Zhu X, Pattni R, Serres Amero A, Juan D, Lobon I, Marques-Bonet T, Solis Moruno M, Garcia Perez R, Povolotskaya I, Soriano E, Antaki D, Averbuj D, Ball L, Breuss M, Yang X, Chung C, Emery S, Flasch D, Kidd J, Kopera H, Kwan K, Mills R, Moldovan J, Sun C, Zhao X, Zhou W, Frisbie T, Cherskov A, Fasching L, Jourdon A, Pochareddy S, Scuderi S. Analysis of somatic mutations in 131 human brains reveals aging-associated hypermutability. Science 2022, 377: 511-517. PMID: 35901164, PMCID: PMC9420557, DOI: 10.1126/science.abm6222.Peer-Reviewed Original ResearchConceptsTranscription factorsSomatic mutationsPutative transcription factorEnhancer-like regionSingle nucleotide mutationsWhole-genome sequencingGene regulationSomatic duplicationGenome sequencingDamaging mutationsBackground mutagenesisMutationsHypermutabilityClonal expansionMotifDiseased brainPotential linkVivo clonal expansionMutagenesisGenesDuplicationSequencingRegulation
2020
A Rare Case of a Pediatric Medullary Intracranial Germinoma
Seifert K, Huttner A, Malhotra A. A Rare Case of a Pediatric Medullary Intracranial Germinoma. World Neurosurgery 2020, 138: 137-140. PMID: 32147555, DOI: 10.1016/j.wneu.2020.02.147.Peer-Reviewed Original ResearchMRI-Guided Laser Interstitial Thermal Therapy for Radiation Necrosis in Previously Irradiated Brain Arteriovenous Malformations
Hong CS, Cord BJ, Kundishora AJ, Elsamadicy AA, Beckta JM, Huttner A, Chiang VL, Matouk CC. MRI-Guided Laser Interstitial Thermal Therapy for Radiation Necrosis in Previously Irradiated Brain Arteriovenous Malformations. Practical Radiation Oncology 2020, 10: e298-e303. PMID: 32068154, DOI: 10.1016/j.prro.2020.02.003.Peer-Reviewed Original Research
2018
Integrative functional genomic analysis of human brain development and neuropsychiatric risks
Li M, Santpere G, Imamura Kawasawa Y, Evgrafov OV, Gulden FO, Pochareddy S, Sunkin SM, Li Z, Shin Y, Zhu Y, Sousa AMM, Werling DM, Kitchen RR, Kang HJ, Pletikos M, Choi J, Muchnik S, Xu X, Wang D, Lorente-Galdos B, Liu S, Giusti-Rodríguez P, Won H, de Leeuw C, Pardiñas AF, Hu M, Jin F, Li Y, Owen M, O’Donovan M, Walters J, Posthuma D, Reimers M, Levitt P, Weinberger D, Hyde T, Kleinman J, Geschwind D, Hawrylycz M, State M, Sanders S, Sullivan P, Gerstein M, Lein E, Knowles J, Sestan N, Willsey A, Oldre A, Szafer A, Camarena A, Cherskov A, Charney A, Abyzov A, Kozlenkov A, Safi A, Jones A, Ashley-Koch A, Ebbert A, Price A, Sekijima A, Kefi A, Bernard A, Amiri A, Sboner A, Clark A, Jaffe A, Tebbenkamp A, Sodt A, Guillozet-Bongaarts A, Nairn A, Carey A, Huttner A, Chervenak A, Szekely A, Shieh A, Harmanci A, Lipska B, Carlyle B, Gregor B, Kassim B, Sheppard B, Bichsel C, Hahn C, Lee C, Chen C, Kuan C, Dang C, Lau C, Cuhaciyan C, Armoskus C, Mason C, Liu C, Slaughterbeck C, Bennet C, Pinto D, Polioudakis D, Franjic D, Miller D, Bertagnolli D, Lewis D, Feng D, Sandman D, Clarke D, Williams D, DelValle D, Fitzgerald D, Shen E, Flatow E, Zharovsky E, Burke E, Olson E, Fulfs E, Mattei E, Hadjimichael E, Deelman E, Navarro F, Wu F, Lee F, Cheng F, Goes F, Vaccarino F, Liu F, Hoffman G, Gürsoy G, Gee G, Mehta G, Coppola G, Giase G, Sedmak G, Johnson G, Wray G, Crawford G, Gu G, van Bakel H, Witt H, Yoon H, Pratt H, Zhao H, Glass I, Huey J, Arnold J, Noonan J, Bendl J, Jochim J, Goldy J, Herstein J, Wiseman J, Miller J, Mariani J, Stoll J, Moore J, Szatkiewicz J, Leng J, Zhang J, Parente J, Rozowsky J, Fullard J, Hohmann J, Morris J, Phillips J, Warrell J, Shin J, An J, Belmont J, Nyhus J, Pendergraft J, Bryois J, Roll K, Grennan K, Aiona K, White K, Aldinger K, Smith K, Girdhar K, Brouner K, Mangravite L, Brown L, Collado-Torres L, Cheng L, Gourley L, Song L, Ubieta L, Habegger L, Ng L, Hauberg M, Onorati M, Webster M, Kundakovic M, Skarica M, Reimers M, Johnson M, Chen M, Garrett M, Sarreal M, Reding M, Gu M, Peters M, Fisher M, Gandal M, Purcaro M, Smith M, Brown M, Shibata M, Brown M, Xu M, Yang M, Ray M, Shapovalova N, Francoeur N, Sjoquist N, Mastan N, Kaur N, Parikshak N, Mosqueda N, Ngo N, Dee N, Ivanov N, Devillers O, Roussos P, Parker P, Manser P, Wohnoutka P, Farnham P, Zandi P, Emani P, Dalley R, Mayani R, Tao R, Gittin R, Straub R, Lifton R, Jacobov R, Howard R, Park R, Dai R, Abramowicz S, Akbarian S, Schreiner S, Ma S, Parry S, Shapouri S, Weissman S, Caldejon S, Mane S, Ding S, Scuderi S, Dracheva S, Butler S, Lisgo S, Rhie S, Lindsay S, Datta S, Souaiaia T, Roychowdhury T, Gomez T, Naluai-Cecchini T, Beach T, Goodman T, Gao T, Dolbeare T, Fliss T, Reddy T, Chen T, Hyde T, Brunetti T, Lemon T, Desta T, Borrman T, Haroutunian V, Spitsyna V, Swarup V, Shi X, Jiang Y, Xia Y, Chen Y, Jiang Y, Wang Y, Chae Y, Yang Y, Kim Y, Riley Z, Krsnik Z, Deng Z, Weng Z, Lin Z, Li Z. Integrative functional genomic analysis of human brain development and neuropsychiatric risks. Science 2018, 362 PMID: 30545854, PMCID: PMC6413317, DOI: 10.1126/science.aat7615.Peer-Reviewed Original ResearchConceptsIntegrative functional genomic analysisFunctional genomic analysisCell typesGene coexpression modulesDistinct cell typesCell type-specific dynamicsGenomic basisEpigenomic reorganizationEpigenomic landscapeEpigenomic regulationGenomic analysisCoexpression modulesIntegrative analysisHuman brain developmentFetal transitionHuman neurodevelopmentGenetic associationCellular compositionNeuropsychiatric riskBrain developmentNeurodevelopmental processesGenesTraitsPostnatal developmentNeuropsychiatric disorders
2017
The aged rhesus macaque manifests Braak stage III/IV Alzheimer's‐like pathology
Paspalas CD, Carlyle BC, Leslie S, Preuss TM, Crimins JL, Huttner AJ, van Dyck C, Rosene DL, Nairn AC, Arnsten AFT. The aged rhesus macaque manifests Braak stage III/IV Alzheimer's‐like pathology. Alzheimer's & Dementia 2017, 14: 680-691. PMID: 29241829, PMCID: PMC6178089, DOI: 10.1016/j.jalz.2017.11.005.Peer-Reviewed Original ResearchConceptsLate-onset Alzheimer's diseaseCortical pathologyEntorhinal cortexAnimal modelsBraak stage III/IVAlzheimer's diseaseStage III/IVRhesus macaquesProgression of tauAlzheimer-like pathologyPrimary visual cortexSequence of tauDorsolateral prefrontal cortexTau pathologyPreventive strategiesAssociation cortexVisual cortexPrefrontal cortexCortexPathologyDiseaseOld animalsProtein kinase A (PKA) phosphorylationGenetic insultsMacaquesDisappearing Leukoencephalopathy
Chan AM, Huttner A, Baehring J. Disappearing Leukoencephalopathy. Clinical Neuroradiology 2017, 28: 455-459. PMID: 29196778, DOI: 10.1007/s00062-017-0650-4.Peer-Reviewed Original ResearchAntiviral CD8 T cells induce Zika-virus-associated paralysis in mice
Jurado KA, Yockey LJ, Wong PW, Lee S, Huttner AJ, Iwasaki A. Antiviral CD8 T cells induce Zika-virus-associated paralysis in mice. Nature Microbiology 2017, 3: 141-147. PMID: 29158604, PMCID: PMC5780207, DOI: 10.1038/s41564-017-0060-z.Peer-Reviewed Original ResearchConceptsCentral nervous systemZIKV infectionZika virusT cellsNeurological complicationsNervous systemBlood-brain barrier breakdownAntiviral CD8 T cellsHigh viral burdenIFNAR knockout miceCD8 T cellsEffector T cellsSusceptible mouse modelBlood-brain barrierNon-haematopoietic cellsSite of infectionIFNAR1 deficiencyViral burdenNeurological manifestationsGuillain-BarréBarrier breakdownMouse modelKnockout miceAstrocytes resultsAntiviral activitySurface chemistry governs cellular tropism of nanoparticles in the brain
Song E, Gaudin A, King AR, Seo YE, Suh HW, Deng Y, Cui J, Tietjen GT, Huttner A, Saltzman WM. Surface chemistry governs cellular tropism of nanoparticles in the brain. Nature Communications 2017, 8: 15322. PMID: 28524852, PMCID: PMC5454541, DOI: 10.1038/ncomms15322.Peer-Reviewed Original ResearchConceptsSurface chemistryDifferent surface chemistriesDrug deliveryNanoparticlesNanoparticle designChemistryTherapeutic efficacyAssociation rateFunctionalizationCentral nervous systemConvection-enhanced deliverySignificant uptakeBrain interstitiumOrthotopic modelNervous systemNeurological diseasesAdverse toxicityCellular tropismExtent of internalizationCellular depositionBrainCell populationsDepositionPropertiesGlioblastoma
2016
Distribution of polymer nanoparticles by convection-enhanced delivery to brain tumors
Saucier-Sawyer JK, Seo YE, Gaudin A, Quijano E, Song E, Sawyer AJ, Deng Y, Huttner A, Saltzman WM. Distribution of polymer nanoparticles by convection-enhanced delivery to brain tumors. Journal Of Controlled Release 2016, 232: 103-112. PMID: 27063424, PMCID: PMC4893898, DOI: 10.1016/j.jconrel.2016.04.006.Peer-Reviewed Original ResearchConceptsConvection-enhanced deliveryBlood-brain barrierBrain-penetrating nanoparticlesIntracranial tumorsBrain tumorsGlioblastoma multiformeHealthy brainMain tumor massFatal brain tumorPresence of tumorBrain tumor treatmentLocal recurrenceInfusion sitePeritumoral tissuesTumor massCED infusionIndividual tumorsTumorsNecrotic regionsTumor treatmentLocal administrationHeterogeneous distribution patternAdministrationBrainCell targeting
2015
A 15‐year‐old girl with a rapidly progressing tumor‐like lesion
Keung B, Huttner A. A 15‐year‐old girl with a rapidly progressing tumor‐like lesion. Neuropathology 2015, 35: 497-501. PMID: 26011248, DOI: 10.1111/neup.12207.Peer-Reviewed Original Research
2014
B cells populating the multiple sclerosis brain mature in the draining cervical lymph nodes
Stern JN, Yaari G, Vander Heiden JA, Church G, Donahue WF, Hintzen RQ, Huttner AJ, Laman JD, Nagra RM, Nylander A, Pitt D, Ramanan S, Siddiqui BA, Vigneault F, Kleinstein SH, Hafler DA, O'Connor KC. B cells populating the multiple sclerosis brain mature in the draining cervical lymph nodes. Science Translational Medicine 2014, 6: 248ra107. PMID: 25100741, PMCID: PMC4388137, DOI: 10.1126/scitranslmed.3008879.Peer-Reviewed Original ResearchConceptsCervical lymph nodesCentral nervous systemB cellsCerebrospinal fluidLymph nodesMultiple sclerosisLymphoid tissueCNS of patientsCNS B cellsAntigen-experienced B cellsMultiple sclerosis brainSecondary lymphoid tissuesB cell compartmentB cell trafficB cell maturationImmunomodulatory therapyImmune infiltratesPeripheral bloodInflammatory diseasesLymphocyte transmigrationPeripheral tissuesNervous systemMembers of clonesCell maturationCell trafficCoherent Raman tissue imaging in the brain.
Saar BG, Freudiger CW, Xu X, Huttner A, Kesari S, Young G, Xie XS. Coherent Raman tissue imaging in the brain. Cold Spring Harbor Protocols 2014, 2014: pdb.top081695. PMID: 24786507, DOI: 10.1101/pdb.top081695.Peer-Reviewed Original ResearchConceptsMultiphoton-excited fluorescenceCRS imagingCRS techniqueCoherent anti-Stokes RamanCoherent Raman scattering techniquesAnti-Stokes RamanLabel-free chemical imagingLabel-free imagingClass of moleculesDrug moleculesRaman scattering techniqueVibrational signaturesChemical imagingFluorescent moleculesScattering techniquesRaman scatteringHigh spatial resolutionMolecular speciesMultiphoton microscopySimilar imaging parametersEndogenous fluorophoresMoleculesSpatial resolutionFluorescent labelingInstrumentation requirements
2011
Spatio-temporal transcriptome of the human brain
Kang HJ, Kawasawa YI, Cheng F, Zhu Y, Xu X, Li M, Sousa AM, Pletikos M, Meyer KA, Sedmak G, Guennel T, Shin Y, Johnson MB, Krsnik Ž, Mayer S, Fertuzinhos S, Umlauf S, Lisgo SN, Vortmeyer A, Weinberger DR, Mane S, Hyde TM, Huttner A, Reimers M, Kleinman JE, Šestan N. Spatio-temporal transcriptome of the human brain. Nature 2011, 478: 483-489. PMID: 22031440, PMCID: PMC3566780, DOI: 10.1038/nature10523.Peer-Reviewed Original Research
1998
Chimeric brains generated by intraventricular transplantation of fetal human brain cells into embryonic rats
Brüstle O, Choudhary K, Karram K, Hüttner A, Murray K, Dubois-Dalcq M, McKay R. Chimeric brains generated by intraventricular transplantation of fetal human brain cells into embryonic rats. Nature Biotechnology 1998, 16: 1040-1044. PMID: 9831032, DOI: 10.1038/3481.Peer-Reviewed Original ResearchConceptsFetal human brain cellsCentral nervous systemHuman brain cellsBrain cellsNervous systemEmbryonic ratsNeural cell migrationIntraventricular transplantationCerebral ventricleNeural chimerasFunctional nervous systemChimeric brainsHuman neural developmentNeural developmentRatsCell migrationBrainCellsRodent cellsUnique modelHuman cellsTransplantationAstrocytesVentricleChimerism