Blood Inflammatory Exosomes with Age Prime Microglia through Complement Signaling for Negative Stroke Outcomes

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dc.contributor.advisorJin, Kunlin
dc.contributor.committeeMemberForster, Michael J.
dc.contributor.committeeMemberYang, Shaohua
dc.contributor.committeeMemberShi, Xiangrong
dc.contributor.committeeMemberCunningham, J. Thomas
dc.creatorZhang, Hongxia
dc.creator.orcid0000-0003-1594-6707 (Zhang, Hongxia)
dc.date.accessioned2021-05-13T21:17:30Z
dc.date.available2021-05-13T21:17:30Z
dc.date.issued2020-05
dc.description.abstractThe systemic inflammatory milieu plays an important role in the age-related decline of functional integrity, but its contribution to age-related disease (e.g., stroke) remains largely unknown. Here, we found that activated complement molecules (C1q, C3a, C3b) in serum exosomes increased with age, whereas CD46, a C3b/C4b-inactivating factor, was higher in serum exosomes from young rats. These serum inflammatory exosomes passed the blood-brain barrier and primed the microglial response that led to exacerbation of synaptic loss and motor deficits after ischemic stroke via microglial C3a receptor (C3aR). When aged rats were exposed to serum exosomes from young rats, microglia-mediated synaptic loss was reduced and motor deficits after stroke were improved. Administration of C3aR inhibitor or microglial depletion attenuated synaptic loss associated with the treatment of serum exosome from aged rats, in parallel with improved post-stroke outcome. Our data suggest that peripheral circulating old exosomes act as inflammatory mediators and influence ischemic stroke outcome through a complement-microglia axis.
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/20.500.12503/30759
dc.language.isoen
dc.subjectaging
dc.subjectcomplement
dc.subjectischemic stroke
dc.subjectmicroglia
dc.subjectneuroinflammation
dc.subjectneuroplasticity
dc.subject.meshAging
dc.subject.meshMicroglia
dc.subject.meshIschemic Stroke
dc.titleBlood Inflammatory Exosomes with Age Prime Microglia through Complement Signaling for Negative Stroke Outcomes
dc.typeThesis
dc.type.materialtext
thesis.degree.departmentGraduate School of Biomedical Sciences
thesis.degree.disciplinePharmacology and Neuroscience
thesis.degree.grantorUniversity of North Texas Health Science Center at Fort Worth
thesis.degree.nameDoctor of Philosophy

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