2023
Embracing Heterogeneity in The Multicenter Stroke Preclinical Assessment Network (SPAN) Trial
Morais A, Locascio J, Sansing L, Lamb J, Nagarkatti K, Imai T, van Leyen K, Aronowski J, Koenig J, Bosetti F, Lyden P, Ayata C, Bosetti F, Koenig J, Lyden P, Lamb J, Nagarkatti K, Hess D, Kamat P, Khan M, Dhandapani K, Arbab A, Siddiqui S, Smith C, Nisar M, Leira E, Chauhan A, Dhanesha N, Patel R, Kumskova M, Thedens D, Wang K, Ayata C, Morais A, Imai T, Qin T, Jin X, Erdogan T, Yu L, Mandeville J, Kimberly W, Whittier J, Lo E, Arai K, Van Leyen K, Sansing L, Hyder F, Mihailovic J, Sanganahalli B, Diaz-Perez S, Velazquez S, Beatty H, Johnson C, Herman A, Boisserand L, Immakavar E, Koehler R, Dawson T, Dawson V, Shi Y, Avery B, Lannon S, Bibic A, Akhter K, Karuppagounder S, Aronowski J, McCullough L, Obertas L, Goh A, Huang S, Chauhan A. Embracing Heterogeneity in The Multicenter Stroke Preclinical Assessment Network (SPAN) Trial. Stroke 2023, 54: 620-631. PMID: 36601951, PMCID: PMC9870939, DOI: 10.1161/strokeaha.122.040638.Peer-Reviewed Original ResearchConceptsTotal anesthesia durationAnesthesia durationIndependent predictorsMultivariable analysisClinical trialsTransient focal cerebral ischemiaFocal cerebral ischemiaCerebral blood flowLaser Doppler flowCentralized randomizationModified intentionTreat populationExperimental strokeCerebral ischemiaDoppler flowRodent modelsMCAOBlood flowNetwork trialFlow dropPreclinical trialsMouse cohortsStudy designTrialsTrial onset
2021
International Post Stroke Epilepsy Research Consortium (IPSERC): A consortium to accelerate discoveries in preventing epileptogenesis after stroke
Mishra NK, Engel J, Liebeskind DS, Sharma VK, Hirsch LJ, Kasner SE, French JA, Devinsky O, Friedman A, Dawson J, Quinn TJ, Selim M, de Havenon A, Yasuda CL, Cendes F, Benninger F, Zaveri HP, Burneo JG, Srivastava P, Singh M, Bhatia R, Vishnu VY, Bentes C, Ferro J, Weiss S, Sivaraju A, Kim JA, Galovic M, Gilmore EJ, Pitkänen A, Davis K, Sansing LH, Sheth KN, Paz JT, Singh A, Sheth S, Worrall BB, Grotta JC, Casillas-Espinos PM, Chen Z, Nicolo JP, Yan B, Kwan P, Consortium F. International Post Stroke Epilepsy Research Consortium (IPSERC): A consortium to accelerate discoveries in preventing epileptogenesis after stroke. Epilepsy & Behavior 2021, 127: 108502. PMID: 34968775, DOI: 10.1016/j.yebeh.2021.108502.Peer-Reviewed Original ResearchExogenous inter-α inhibitor proteins prevent cell death and improve ischemic stroke outcomes in mice
McCullough LD, Roy-O’Reilly M, Lai YJ, Patrizz A, Xu Y, Lee J, Holmes A, Kraushaar DC, Chauhan A, Sansing LH, Stonestreet BS, Zhu L, Kofler J, Lim YP, Venna VR. Exogenous inter-α inhibitor proteins prevent cell death and improve ischemic stroke outcomes in mice. Journal Of Clinical Investigation 2021, 131: e144898. PMID: 34580244, PMCID: PMC8409590, DOI: 10.1172/jci144898.Peer-Reviewed Original ResearchConceptsInter-α inhibitor proteinsIschemic strokeStroke outcomeStroke modelComplement activationBeneficial effectsMultiple stroke modelsNeutralization of histonesPost-stroke administrationIschemic stroke outcomeExperimental ischemic strokeIschemic stroke patientsExperimental stroke modelsModel of sepsisPotential therapeutic candidateExcess complement activationIaIp levelsStroke onsetStroke patientsProinflammatory cytokinesAged miceExtracellular histonesClinical relevanceTherapeutic candidateTherapeutic efficacyDivergent Functions of Tissue-Resident and Blood-Derived Macrophages in the Hemorrhagic Brain
Chang CF, Goods BA, Askenase MH, Beatty HE, Osherov A, DeLong JH, Hammond MD, Massey J, Landreneau M, Love JC, Sansing LH. Divergent Functions of Tissue-Resident and Blood-Derived Macrophages in the Hemorrhagic Brain. Stroke 2021, 52: 1798-1808. PMID: 33840225, PMCID: PMC8085165, DOI: 10.1161/strokeaha.120.032196.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainCell ProliferationDisease Models, AnimalIntracranial HemorrhagesMacrophagesMiceMicrogliaPhagocytosisConceptsMonocyte-derived macrophagesIntracerebral hemorrhageT cell proliferationCore transcriptional programDifferential gene expressionDistinct transcriptional signaturesBone marrow-derived macrophagesAntigen-specific T cell proliferationTranscriptional programsCD4 T cell proliferationLongitudinal transcriptomic analysisVivo phagocytosis assaysTranscriptomic analysisDivergent functionsMarrow-derived macrophagesMHCII genesTissue-resident microgliaAntigen-presenting capabilityAutologous blood injectionGene expressionPrimary microglia culturesInnate immune cellsPhagocytosis of debrisTranscriptional signatureBlood-derived macrophages
2020
Aging exacerbates neutrophil pathogenicity in ischemic stroke
Roy-O'Reilly MA, Ahnstedt H, Spychala MS, Munshi Y, Aronowski J, Sansing LH, McCullough LD. Aging exacerbates neutrophil pathogenicity in ischemic stroke. Aging 2020, 12: 436-461. PMID: 31927534, PMCID: PMC6977697, DOI: 10.18632/aging.102632.Peer-Reviewed Original ResearchConceptsIschemic stroke patientsIschemic strokeNeutrophil-activating cytokineStroke patientsNeutrophil functionNeutrophil reactive oxygen speciesPoor post-stroke outcomesDepletion of neutrophilsPro-inflammatory functionsStrong risk factorExperimental mouse modelPost-stroke outcomesHigher stroke mortalityStroke outcomePoor outcomeFunctional outcomeStroke mortalityLong-term benefitsRisk factorsSpecific monoclonal antibodiesNeutrophil trafficTissue injuryYoung miceAged subjectsMouse model
2019
Bexarotene Enhances Macrophage Erythrophagocytosis and Hematoma Clearance in Experimental Intracerebral Hemorrhage
Chang CF, Massey J, Osherov A, Angenendt da Costa LH, Sansing LH. Bexarotene Enhances Macrophage Erythrophagocytosis and Hematoma Clearance in Experimental Intracerebral Hemorrhage. Stroke 2019, 51: 612-618. PMID: 31826730, PMCID: PMC7135897, DOI: 10.1161/strokeaha.119.027037.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBexaroteneBrainCerebral HemorrhageDisease Models, AnimalErythrocytesHematomaMacrophagesMicrogliaPhagocytosisConceptsIntracerebral hemorrhageBexarotene treatmentFunctional recoveryHematoma clearanceRetinoid X receptor agonistExperimental intracerebral hemorrhageX receptor agonistMacrophage TNF productionMarrow-derived macrophagesNeurological recoveryNeurobehavioral recoveryNeurological deficitsAutologous bloodBrain recoveryHematoma volumeReceptor agonistTherapeutic effectMacrophage expressionTNF productionMouse modelVivo phagocytosisMacrophage phenotypeFlow cytometryHistological analysisErythrocyte metabolites