2021
Exogenous 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 efficacy
2020
Depletion of CD4 T cells provides therapeutic benefits in aged mice after ischemic stroke
Harris NM, Roy-O'Reilly M, Ritzel RM, Holmes A, Sansing LH, O'Keefe LM, McCullough LD, Chauhan A. Depletion of CD4 T cells provides therapeutic benefits in aged mice after ischemic stroke. Experimental Neurology 2020, 326: 113202. PMID: 31954116, PMCID: PMC7059209, DOI: 10.1016/j.expneurol.2020.113202.Peer-Reviewed Original ResearchConceptsIP-10 levelsMiddle cerebral artery occlusionCD4 T cellsT cellsIschemic strokeStroke patientsIsotype controlBrain-infiltrating T cellsCD4 T-cell depletionCerebral artery occlusionT-cell depletionAged mouse modelAged male micePro-inflammatory factorsT cell dysfunctionPro-inflammatory cytokinesAnti-CD4 antibodiesAged stroke patientsIgG isotype controlCD4 treatmentDepletion antibodyArtery occlusionExperimental strokeStroke onsetSham surgery
2019
Transforming 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