2024
Sex Modifies the Severity and Outcome of Spontaneous Intracerebral Hemorrhage
Rivier C, Renedo D, Marini S, Magid‐Bernstein J, de Havenon A, Rosand J, Hanley D, Ziai W, Mayer S, Woo D, Sansing L, Sheth K, Anderson C, Falcone G. Sex Modifies the Severity and Outcome of Spontaneous Intracerebral Hemorrhage. Annals Of Neurology 2024 PMID: 39499118, DOI: 10.1002/ana.27123.Peer-Reviewed Original ResearchRisk of hematoma expansionHighest risk of hematoma expansionRisk of poor outcomesIntracerebral hemorrhageHematoma expansionHigh riskMale sexPoor outcomeOutcome of spontaneous intracerebral hemorrhageClinical characteristics of patientsStudies of intracerebral hemorrhageNon-traumatic intracerebral hemorrhageIndividual patient data meta-analysisPatient data meta-analysisSpontaneous intracerebral hemorrhageSingle-center studyIntracerebral hemorrhage patientsHigh risk of expansionCharacteristics of patientsIntracerebral hemorrhage severityPoor functional outcomeRandomized clinical trialsData meta-analysisHemorrhage volumeClinical characteristicsDisparities in Healthcare Interactions After Intracerebral Hemorrhage: Evidence from the REDUCE Trial (P3-5.020)
Zabinska J, Taylor C, Peasley E, Lalwani D, Schwartz A, Falcone G, Sansing L, Arora R, Mena-Hurtado C, De Havenon A, Okpala M, Bushnell C, Mullen M, Cohen J, Cohen D, Messe S, Forman R, Sheth K. Disparities in Healthcare Interactions After Intracerebral Hemorrhage: Evidence from the REDUCE Trial (P3-5.020). Neurology 2024, 102 DOI: 10.1212/wnl.0000000000206241.Peer-Reviewed Original Research
2023
Trained immunity induced by high‐salt diet impedes stroke recovery
Lin T, Jiang D, Chen W, Lin J, Zhang X, Chen C, Hsu C, Lai L, Chen P, Yang K, Sansing L, Chang C. Trained immunity induced by high‐salt diet impedes stroke recovery. EMBO Reports 2023, 24: e57164. PMID: 37965920, PMCID: PMC10702837, DOI: 10.15252/embr.202357164.Peer-Reviewed Original ResearchConceptsInnate immune memoryMonocyte-derived macrophagesStroke recoveryInflammatory responseBone marrowImmune memoryHigh-salt dietCause of morbidityInitial inflammatory responsePotential therapeutic targetLoss of Nr4a1Stroke outcomeStroke brainIntracerebral hemorrhageBrain recoverySterile inflammationHealthy miceTissue injurySevere formTherapeutic targetAlternative activationImmune primingReparative functionsProgenitor cellsNR4A familyClinical Trial Protocol for BEACH: A Phase 2a Study of MW189 in Patients with Acute Nontraumatic Intracerebral Hemorrhage
Avadhani R, Ziai W, Thompson R, Mould W, Lane K, Nanni A, Iacobelli M, Sharrock M, Sansing L, Van Eldik L, Hanley D. Clinical Trial Protocol for BEACH: A Phase 2a Study of MW189 in Patients with Acute Nontraumatic Intracerebral Hemorrhage. Neurocritical Care 2023, 40: 807-815. PMID: 37919545, PMCID: PMC10959780, DOI: 10.1007/s12028-023-01867-2.Peer-Reviewed Original ResearchIntracerebral hemorrhageNontraumatic intracerebral hemorrhageCerebral edemaFunctional outcomeCause mortalitySymptom onsetAcute central nervous system injuryAcute spontaneous intracerebral hemorrhageEnd pointCentral nervous system injuryDays post randomizationExploratory end pointsPhase 2a studyPlacebo-controlled trialSecondary end pointsAcute brain injuryAcute intracerebral hemorrhageFuture larger trialsPhase 1 studyPerihematomal edema volumeNervous system injurySpontaneous intracerebral hemorrhageInflammatory cytokine concentrationsRate of deathClinical trial protocolRole of Inflammatory Processes in Hemorrhagic Stroke
Ohashi S, DeLong J, Kozberg M, Mazur-Hart D, van Veluw S, Alkayed N, Sansing L. Role of Inflammatory Processes in Hemorrhagic Stroke. Stroke 2023, 54: 605-619. PMID: 36601948, DOI: 10.1161/strokeaha.122.037155.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsHemorrhagic strokeIntracerebral hemorrhageInflammatory processCerebral amyloid angiopathy-related haemorrhageAngiopathy-related hemorrhageRole of inflammationCerebral amyloid angiopathyInflammatory immune responseEffective therapeutic strategyCentral nervous systemBrain residentAmyloid angiopathyImmune cellsTissue injuryCommon causeImmune responseHemorrhageTherapeutic strategiesNervous systemMajor subtypesDisease pathologyStrokeOlder individualsTissue recoveryDeadliest form
2022
Association of Chronic Kidney Disease With Risk of Intracerebral Hemorrhage
Vanent KN, Leasure AC, Acosta JN, Kuohn LR, Woo D, Murthy SB, Kamel H, Messé SR, Mullen MT, Cohen JB, Cohen DL, Townsend RR, Petersen NH, Sansing LH, Gill TM, Sheth KN, Falcone GJ. Association of Chronic Kidney Disease With Risk of Intracerebral Hemorrhage. JAMA Neurology 2022, 79: 911-918. PMID: 35969388, PMCID: PMC9379821, DOI: 10.1001/jamaneurol.2022.2299.Peer-Reviewed Original Research2022 Guideline for the Management of Patients With Spontaneous Intracerebral Hemorrhage: A Guideline From the American Heart Association/American Stroke Association
Greenberg SM, Ziai WC, Cordonnier C, Dowlatshahi D, Francis B, Goldstein JN, Hemphill JC, Johnson R, Keigher KM, Mack WJ, Mocco J, Newton EJ, Ruff IM, Sansing LH, Schulman S, Selim MH, Sheth KN, Sprigg N, Sunnerhagen KS, Association O. 2022 Guideline for the Management of Patients With Spontaneous Intracerebral Hemorrhage: A Guideline From the American Heart Association/American Stroke Association. Stroke 2022, 53: e282-e361. PMID: 35579034, DOI: 10.1161/str.0000000000000407.Peer-Reviewed Original ResearchCerebral Hemorrhage: Pathophysiology, Treatment, and Future Directions
Magid-Bernstein J, Girard R, Polster S, Srinath A, Romanos S, Awad IA, Sansing LH. Cerebral Hemorrhage: Pathophysiology, Treatment, and Future Directions. Circulation Research 2022, 130: 1204-1229. PMID: 35420918, PMCID: PMC10032582, DOI: 10.1161/circresaha.121.319949.Peer-Reviewed Original ResearchConceptsMechanism of injuryIntracerebral hemorrhageUltra-early hemostatic therapyInflammatory brain injuryCurrent treatment strategiesIron-induced injuryAnticoagulant useHemostatic therapyHemorrhagic strokeHypertension managementICH therapySurgical managementHigh morbidityPrimary preventionFunctional outcomeICH managementBrain injuryClinical trialsTreatment strategiesPrognostic biomarkerDevastating formDisease pathobiologyInjuryInvasive surgeryOxidative stress8 Mechanisms of Damage After Cerebral Hemorrhage
Aronowski J, Sansing L, Xi G, Zhang J. 8 Mechanisms of Damage After Cerebral Hemorrhage. 2022, 92-102.e9. DOI: 10.1016/b978-0-323-69424-7.00008-9.ChaptersIntracerebral hemorrhageBrain damageTreatment of ICHPathogenesis of ICHPre-clinical animal modelsIschemic brain injuryNeurovascular unitCerebral hemorrhageSecondary injuryBrain injuryAnimal modelsTherapeutic interventionsOxidative stressPromising targetHemorrhageInjuryMechanisms of damageNoxious componentsDamageInflammationPathogenesisPathobiologyBlood
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 resonanceChronic Kidney Disease is Associated with Higher Risk and Worse Outcome after Spontaneous Intracerebral Hemorrhage (2729)
Leasure A, Vanent K, Acosta J, Woo D, Murthy S, Kamel H, Cohen J, Townsend R, Petersen N, Sansing L, Gill T, Sheth K, Falcone G. Chronic Kidney Disease is Associated with Higher Risk and Worse Outcome after Spontaneous Intracerebral Hemorrhage (2729). Neurology 2021, 96 DOI: 10.1212/wnl.96.15_supplement.2729.Peer-Reviewed Original ResearchDivergent 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 macrophagesObstructive Sleep Apnea as a Risk Factor for Intracerebral Hemorrhage
Geer JH, Falcone GJ, Vanent KN, Leasure AC, Woo D, Molano JR, Sansing LH, Langefeld CD, Pisani MA, Yaggi HK, Sheth KN. Obstructive Sleep Apnea as a Risk Factor for Intracerebral Hemorrhage. Stroke 2021, 52: 1835-1838. PMID: 33827242, PMCID: PMC8085039, DOI: 10.1161/strokeaha.120.033342.Peer-Reviewed Original ResearchConceptsObstructive sleep apneaRisk factorsBerlin questionnaireIntracerebral hemorrhageSleep apneaEthnic/Racial VariationsHigher body mass indexMultivariable logistic regression modelBody mass indexIntracerebral hemorrhage riskCase-control studyExposure of patientsLogistic regression analysisLogistic regression modelsOSA statusHemorrhage riskMass indexHeart diseaseNontraumatic ICHRacial variationApneaHemorrhageRegression analysisICHRegression modelsEndothelial cell secreted VEGF-C enhances NSC VEGFR3 expression and promotes NSC survival
Matta R, Feng Y, Sansing LH, Gonzalez AL. Endothelial cell secreted VEGF-C enhances NSC VEGFR3 expression and promotes NSC survival. Stem Cell Research 2021, 53: 102318. PMID: 33836422, PMCID: PMC8243729, DOI: 10.1016/j.scr.2021.102318.Peer-Reviewed Original ResearchLeukocyte dynamics after intracerebral hemorrhage in a living patient reveal rapid adaptations to tissue milieu
Goods BA, Askenase MH, Markarian E, Beatty HE, Drake RS, Fleming I, DeLong JH, Philip NH, Matouk CC, Awad IA, Zuccarello M, Hanley DF, Love JC, Shalek AK, Sansing LH, Investigators T. Leukocyte dynamics after intracerebral hemorrhage in a living patient reveal rapid adaptations to tissue milieu. JCI Insight 2021, 6: e145857. PMID: 33749664, PMCID: PMC8026179, DOI: 10.1172/jci.insight.145857.Peer-Reviewed Original ResearchConceptsIntracerebral hemorrhageAcute brain injurySystemic immune responsesBrain tissue injuryHigh mortality rateLocal cellular responseAcute injuryTreatment optionsIntracerebral eventsBrain injuryCerebral hematomaLeukocyte responseTissue injuryT cellsImmune responseCT scanMortality rateDevastating formImmune dynamicsTherapeutic interventionsLeukocyte dynamicsBrain tissuePatientsInvasive surgeryInjuryAssociation of Serum IL-6 (Interleukin 6) With Functional Outcome After Intracerebral Hemorrhage
Leasure AC, Kuohn LR, Vanent KN, Bevers MB, Kimberly WT, Steiner T, Mayer SA, Matouk CC, Sansing LH, Falcone GJ, Sheth KN. Association of Serum IL-6 (Interleukin 6) With Functional Outcome After Intracerebral Hemorrhage. Stroke 2021, 52: 1733-1740. PMID: 33682454, PMCID: PMC8085132, DOI: 10.1161/strokeaha.120.032888.Peer-Reviewed Original ResearchConceptsIL-6 levelsPerihematomal edema volumeIntracerebral hemorrhageIL-6Edema volumeFunctional outcomeICH locationICH volumeTreatment groupsSerum IL-6 levelsBaseline ICHAcute brain injuryLarge intracerebral hemorrhageSerum IL-6Predictors of outcomeSpontaneous intracerebral hemorrhageRankin ScalePoor outcomeProinflammatory cytokinesTrial populationBrain injurySecondary analysisStrong associationFast trialsOutcomesAdmission Hemoglobin Levels Are Associated With Functional Outcome in Spontaneous Intracerebral Hemorrhage
Acosta JN, Leasure AC, Kuohn LR, Both CP, Petersen NH, Sansing LH, Matouk CC, Testai F, Langefeld CD, Woo D, Kamel H, Murthy SB, Qureshi A, Mayer SA, Sheth KN, Falcone GJ. Admission Hemoglobin Levels Are Associated With Functional Outcome in Spontaneous Intracerebral Hemorrhage. Critical Care Medicine 2021, 49: 828-837. PMID: 33591003, PMCID: PMC8611893, DOI: 10.1097/ccm.0000000000004891.Peer-Reviewed Original ResearchConceptsAdmission hemoglobin levelsHemoglobin levelsNontraumatic intracerebral hemorrhageIntracerebral hemorrhageHematoma volumePoor outcomeHematoma expansionIntracerebral hemorrhage patientsPredictors of outcomeSpontaneous intracerebral hemorrhageIndividual patient dataHigher hemoglobin levelsAdmission hematoma volumeExposure of interestDose-response analysisAdmission hemoglobinRankin ScalePrimary outcomeHemorrhage patientsFunctional outcomeRepeat CTClinical trialsObservational studyHemorrhage sizeBetter outcomesLongitudinal 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 EIntracerebral Hemorrhage with Intraventricular Extension Associated with Loss of Consciousness at Symptom Onset
Witsch J, Falcone GJ, Leasure AC, Matouk C, Endres M, Sansing L, Woo D, Sheth KN. Intracerebral Hemorrhage with Intraventricular Extension Associated with Loss of Consciousness at Symptom Onset. Neurocritical Care 2021, 35: 418-427. PMID: 33479920, PMCID: PMC8578176, DOI: 10.1007/s12028-020-01180-2.Peer-Reviewed Original ResearchConceptsLoss of consciousnessIntraventricular hemorrhageIntracerebral hemorrhageSymptom onsetICH onsetUnfavorable outcomeAdmission Glasgow Coma ScoreAdmission systolic blood pressureOnset of ICHGlasgow Coma ScoreSystolic blood pressureSpontaneous intracerebral hemorrhageAdmission serum glucoseThousand seven hundredVolumetric CT measurementsBackgroundIn patientsComa ScoreBlood pressureMedical chartsICH volumeMental statusSerum glucoseICH casesInclusion criteriaPatients
2020
Plasma neurofilament light predicts mortality in patients with stroke
Gendron TF, Badi MK, Heckman MG, Jansen-West KR, Vilanilam GK, Johnson PW, Burch AR, Walton RL, Ross OA, Brott TG, Miller TM, Berry JD, Nicholson KA, Wszolek ZK, Oskarsson BE, Sheth KN, Sansing LH, Falcone GJ, Cucchiara BL, Meschia JF, Petrucelli L. Plasma neurofilament light predicts mortality in patients with stroke. Science Translational Medicine 2020, 12 PMID: 33177179, PMCID: PMC9534269, DOI: 10.1126/scitranslmed.aay1913.Peer-Reviewed Original ResearchConceptsBlood neurofilament lightNeurofilament lightStroke typeNeuroaxonal injuryHigher NfL concentrationsMini-Mental State ExaminationStroke brain injuryAcute cerebral infarctionModified Rankin ScaleEarly ischemic injuryNontraumatic intracerebral hemorrhageNIH Stroke ScaleBrain tissue damagePlasma neurofilament lightIntracranial hemorrhage volumeClinical trial efficiencyBlood biomarker studiesStroke therapeuticsCause mortalityStroke ScaleCerebral infarctionRankin ScaleFunctional disabilityIntracerebral hemorrhageIschemic injury