2022
The Stroke Preclinical Assessment Network: Rationale, Design, Feasibility, and Stage 1 Results
Lyden PD, Bosetti F, Diniz MA, Rogatko A, Koenig JI, Lamb J, Nagarkatti KA, Cabeen RP, Hess DC, Kamat PK, Khan MB, Wood K, Dhandapani K, Arbab AS, Leira EC, Chauhan AK, Dhanesha N, Patel RB, Kumskova M, Thedens D, Morais A, Imai T, Qin T, Ayata C, Boisserand LSB, Herman AL, Beatty HE, Velazquez SE, Diaz-Perez S, Sanganahalli BG, Mihailovic JM, Hyder F, Sansing LH, Koehler RC, Lannon S, Shi Y, Karuppagounder SS, Bibic A, Akhter K, Aronowski J, McCullough LD, Chauhan A, Goh A, Siddiqui S, Sheth K, Matouk C, Cruz C, Zhou J, Dawson V, Dawson T, Liang J, van Zijl P, Zeiler S, Taylor Kimberly W, Erdogan T, Yu L, Mandeville J, Whittier J. The Stroke Preclinical Assessment Network: Rationale, Design, Feasibility, and Stage 1 Results. Stroke 2022, 53: 1802-1812. PMID: 35354299, PMCID: PMC9038686, DOI: 10.1161/strokeaha.121.038047.Peer-Reviewed Original ResearchConceptsPreclinical assessmentStroke treatmentCandidate treatmentMiddle cerebral artery occlusion (MCAO) surgeryClinical stroke trialsSuccessful stroke treatmentInclusion/exclusion criteriaStroke clinical trialsClinical trial designYoung male animalsComorbid diseasesOcclusion surgeryCerebral ischemiaNeurological disabilityComorbid conditionsStroke trialsProtocol adherenceBlinded assessmentSuch therapyClinical trialsClinical studiesExclusion criteriaTrial designAged animalsOutcome assessmentMaximizing Brain Health After Hemorrhagic Stroke: Bugher Foundation Centers of Excellence
Sheth KN, Anderson CD, Biffi A, Dlamini N, Falcone GJ, Fox CK, Fullerton HJ, Greenberg SM, Hemphill JC, Kim A, Kim H, Ko NU, Roland JL, Sansing LH, van Veluw SJ, Rosand J. Maximizing Brain Health After Hemorrhagic Stroke: Bugher Foundation Centers of Excellence. Stroke 2022, 53: 1020-1029. PMID: 35109678, PMCID: PMC8885885, DOI: 10.1161/strokeaha.121.036197.Peer-Reviewed Original ResearchBedside detection of intracranial midline shift using portable magnetic resonance imaging
Sheth KN, Yuen MM, Mazurek MH, Cahn BA, Prabhat AM, Salehi S, Shah JT, By S, Welch EB, Sofka M, Sacolick LI, Kim JA, Payabvash S, Falcone GJ, Gilmore EJ, Hwang DY, Matouk C, Gordon-Kundu B, RN AW, Petersen N, Schindler J, Gobeske KT, Sansing LH, Sze G, Rosen MS, Kimberly WT, Kundu P. Bedside detection of intracranial midline shift using portable magnetic resonance imaging. Scientific Reports 2022, 12: 67. PMID: 34996970, PMCID: PMC8742125, DOI: 10.1038/s41598-021-03892-7.Peer-Reviewed Original ResearchConceptsMidline shiftNeuroscience intensive care unitCare measurementYale-New Haven HospitalValuable bedside toolIntensive care unitPoor clinical outcomeBrain-injured patientsMass effectNew Haven HospitalMagnetic resonance imagingClinical outcomesIll patientsCare unitStroke patientsFunctional outcomeBedside toolObservational studyBedside detectionImaging examsPatientsResonance imagingPortable MRIImaging suiteSignificant concordance
2021
Portable, bedside, low-field magnetic resonance imaging for evaluation of intracerebral hemorrhage
Mazurek MH, Cahn BA, Yuen MM, Prabhat AM, Chavva IR, Shah JT, Crawford AL, Welch EB, Rothberg J, Sacolick L, Poole M, Wira C, Matouk CC, Ward A, Timario N, Leasure A, Beekman R, Peng TJ, Witsch J, Antonios JP, Falcone GJ, Gobeske KT, Petersen N, Schindler J, Sansing L, Gilmore EJ, Hwang DY, Kim JA, Malhotra A, Sze G, Rosen MS, Kimberly WT, Sheth KN. Portable, bedside, low-field magnetic resonance imaging for evaluation of intracerebral hemorrhage. Nature Communications 2021, 12: 5119. PMID: 34433813, PMCID: PMC8387402, DOI: 10.1038/s41467-021-25441-6.Peer-Reviewed Original ResearchConceptsMagnetic resonance imagingNIH Stroke ScaleIntracerebral hemorrhageHematoma volumeYale-New Haven HospitalStroke care pathwayConventional magnetic resonance imagingBoard-certified neuroradiologistsNew Haven HospitalResource-limited settingsStroke ScaleClinical outcomesLow-field magnetic resonance imagingCare pathwayLow-field magnetic resonanceRadiological examinationConventional neuroimagingAdvanced MRI technologiesResonance imagingCases of disagreementHemorrhageMRI technologyPortable MRINeuroimagingMagnetic resonanceDivergent 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 ResearchConceptsMonocyte-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 macrophagesLongitudinal transcriptomics define the stages of myeloid activation in the living human brain after intracerebral hemorrhage
Askenase MH, Goods BA, Beatty HE, Steinschneider AF, Velazquez SE, Osherov A, Landreneau MJ, Carroll SL, Tran TB, Avram VS, Drake RS, Gatter GJ, Massey JA, Karuppagounder SS, Ratan RR, Matouk CC, Sheth KN, Ziai WC, Parry-Jones AR, Awad IA, Zuccarello M, Thompson RE, Dawson J, Hanley DF, Love JC, Shalek AK, Sansing LH, Barrer S, MacKenzie L, Jonczak K, Bussinger P, Nakaji P, Wright S, Honea N, Zomorodi A, James M, Yeh E, Galicich W, Bergman T, France K, Leiphart J, Ramesh S, Brennan T, Huang J, Ziai W, White M, Camarata P, Abraham M, Gorup J, Reimer R, Freeman W, Williams C, Edwards E, Pollack A, Terry J, Shoen A, Jahromi B, Maas M, Yip B, Amidei C, Muñoz L, Lopez G, Holtz R, Gupta G, Rybinnik I, Moccio M, Lovick D, Brion B, Titus K, Jallo J, Rincon F, Pigott K, Boyden L, Dougherty J, Harrigan M, Miller D, Nelson L, Thompson G, Rajajee V, Pandey A, Ball R, Carlson A, Tran H, Alchbli A, James R, Jerde A, Taussky P, Ansari S, Neate C, Martinez J, Letsinger J, Fagatele L, Eaquinto C, Matouk C, Sheth K, Sansing L, Ryall L, Kunze K, Mampre D, Jasak S, Abdul-Rahim A, Abou-Hamden A, Abraham M, Ahmed A, Alba C, Aldrich E, Ali H, Altschul D, Amin-Hanjani S, Anderson C, Anderson D, Ansari S, Antezana D, Ardelt A, Arikan F, Awad R, Baguena M, Baker A, Barrer S, Barzo P, Becker K, Bergman T, Betz J, Bistran-Hall A, Boström A, Braun J, Brindley P, Broaddus W, Brown R, Buki A, Bulters D, Camarata P, Cao B, Cao Y, Carhuapoma J, Carlson A, Caron J, Carrion-Penagos J, Chalela J, Chang T, Chicoine M, Chorro I, Chowdhry S, Cobb C, Corral L, Csiba L, Davies J, Dawson J, Díaz A, Derdeyn C, Diringer M, Dlugash R, Dodd R, Ecker R, Economas T, Enriquez P, Ezer E, Fan Y, Feng H, Franz D, Freeman W, Fusco M, Galicich W, Gandhi D, Gelea M, Goldstein J, Gonzalez A, Grabarits C, Greenberg S, Gregson B, Gress D, Gu E, Gupta G, Hall C, Hanley D, Hao Y, Harnof S, Harrigan M, Hernandez F, Hoesch R, Hoh B, Houser J, Hu R, Huang J, Huang Y, Hussain M, Insinga S, Jadhav A, Jaffe J, Jahromi B, Jallo J, James M, James R, Janis S, Jankowitz B, Jeon E, Jichici D, Jonczak K, Jonker B, Karlen N, Kase C, Keric N, Kerz T, Kitagawa R, Knopman J, Koenig C, Krishnamurthy S, Kumar A, Kureshi I, Laidlaw J, Lakhanpal A, Lane K, Latorre J, LeDoux D, Lees K, Leifer D, Leiphart J, Lenington S, Li Y, Lopez G, Lovick D, Lumenta C, Luo J, Maas M, MacDonald J, MacKenzie L, Madan V, Majkowski R, Major O, Malhorta R, Malkoff M, Mangat H, Maswadeh A, Matouk C, Mayo S, McArthur K, McBee N, McCaul S, Medow J, Mendelow A, Mezey G, Mighty J, Miller D, Mitchell P, Mohan K, Money P, Mould W, Muir K, Muñoz L, Nakaji P, Nee A, Nekoovaght-Tak S, Nyquist P, O’Kane R, Okasha M, O'Kelly C, Ostapkovich N, Pandey A, Parry-Jones A, Patel H, Perla K, Pollack A, Polster S, Pouratian N, Quinn T, Rajajee V, Reddy K, Rehman M, Reimer R, Rincon F, Rosenblum M, Rybinnik I, Sanchez B, Sansing L, Sarabia R, Schneck M, Schuerer L, Schul D, Schweitzer J, Seder D, Seyfried D, Sheth K, Spiotta A, Stadnik A, Stechison M, Sugar E, Szabo K, Tamayo G, Tanczos K, Taussky P, Teitelbaum J, Terry J, Testai F, Thomas K, Thompson C, Thompson G, Thompson R, Torner J, Tran H, Tucker K, Ullman N, Ungar L, Unterberg A, Varelas P, Vargas N, Vatter H, Venkatasubramanian C, Vermillion K, Vespa P, Vollmer D, Wang W, Wang Y, Wang Y, Wen J, Whitworth L, Willis B, Wilson A, Wolfe S, Wrencher M, Wright S, Xu Y, Yanase L, Yenokyan G, Yi X, Yu Z, Ziai W, Zomorodi A, Zuccarello M. Longitudinal transcriptomics define the stages of myeloid activation in the living human brain after intracerebral hemorrhage. Science Immunology 2021, 6 PMID: 33891558, PMCID: PMC8252865, DOI: 10.1126/sciimmunol.abd6279.Peer-Reviewed Original ResearchConceptsIntracerebral hemorrhageHypoxia-inducible factorMyeloid activationBrain injuryImmune responseAnti-inflammatory circuitsSubtypes of strokeAnti-inflammatory factorsInflammatory gene expressionPositive patient outcomesMonocytes/macrophagesDynamics of inflammationAcute sterile injuryLongitudinal transcriptional profilingHuman brainNeurological recoveryMyeloid responseProinflammatory profileImmune resolutionPatient cohortImmune factorsClinical trialsPatient outcomesSterile injuryProstaglandin E
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 ResearchConceptsIntracerebral 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 metabolitesTransforming growth factor-β promotes basement membrane fibrosis, alters perivascular cerebrospinal fluid distribution, and worsens neurological recovery in the aged brain after stroke
Howe MD, Furr JW, Munshi Y, Roy-O’Reilly M, Maniskas ME, Koellhoffer EC, d’Aigle J, Sansing LH, McCullough LD, Urayama A. Transforming growth factor-β promotes basement membrane fibrosis, alters perivascular cerebrospinal fluid distribution, and worsens neurological recovery in the aged brain after stroke. GeroScience 2019, 41: 543-559. PMID: 31721012, PMCID: PMC6885082, DOI: 10.1007/s11357-019-00118-7.Peer-Reviewed Original ResearchConceptsPoor functional recoveryFunctional recoveryExperimental strokeAstrocyte activationStroke patientsAged brainCultured astrocytesSerum TGF-β levelsTGF-β receptor inhibitionPotential new treatment strategyGlial scar developmentElderly stroke patientsTGF-β levelsPoor functional outcomeOxygen-glucose deprivationCerebrospinal fluid distributionNew treatment strategiesPrimary cultured astrocytesExogenous TGF-β stimulationBasement membraneTGF-β stimulationNeurological recoveryElderly patientsSerum levelsFunctional outcome
2009
Prior antiplatelet use does not affect hemorrhage growth or outcome after ICHSYMBOL
Sansing LH, Messe SR, Cucchiara BL, Cohen SN, Lyden PD, Kasner SE. Prior antiplatelet use does not affect hemorrhage growth or outcome after ICHSYMBOL. Neurology 2009, 72: 1397-1402. PMID: 19129506, PMCID: PMC2677505, DOI: 10.1212/01.wnl.0000342709.31341.88.Peer-Reviewed Original ResearchMeSH KeywordsAgedBrainBrain EdemaCausalityCerebral HemorrhageDisease ProgressionDrug-Related Side Effects and Adverse ReactionsFemaleHumansIatrogenic DiseaseImage Processing, Computer-AssistedMagnetic Resonance ImagingMaleMiddle AgedOutcome Assessment, Health CarePlatelet Aggregation InhibitorsProspective StudiesTomography, X-Ray ComputedTreatment OutcomeConceptsAntiplatelet medication useAntiplatelet medicationsIntracerebral hemorrhageSpontaneous intracerebral hemorrhageHemorrhage expansionMedication useClinical outcomesICH onsetHemorrhage growthTime of ICHVolume of ICHInitial ICH volumeIntracerebral hemorrhage onsetPrior antiplatelet usePlacebo-controlled trialRecent clinical trialsAssociation of useGrowth of ICHAntiplatelet useEdema growthOral anticoagulationRankin scorePlacebo armCerebral hemorrhageMultivariable analysis