Acta pharmacologica Sinica, 2017-11, Vol.38 (11), p.1425-1434
2017
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- Autor(en) / Beteiligte
- Titel
- Age-related differences in interferon regulatory factor-4 and -5 signaling in ischemic brains of mice
- Ist Teil von
- Acta pharmacologica Sinica, 2017-11, Vol.38 (11), p.1425-1434
- Ort / Verlag
- London: Nature Publishing Group UK
- Erscheinungsjahr
- 2017
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Stroke is a disease that mainly affects the elderly and modeling stroke in aged animals is clinically more relevant. The inflammatory responses to stroke are a fundamental pathological procedure where microglial activation plays an important role. Interferon regulatory factor-5 （IRF5） and IRF4 regulate M$ and M2 activation of macrophages, respectively, in peripheral inflammation; but it is unknown whether IRF5/IRF4 are also involved in cerebral inflammatory responses to stroke and whether age-related differences of the IRF5/IRF4 signaling exist in the ischemic brain. Here, we investigated the impacts of aging on IRF5/IRF4 signaling and post- stroke inflammation in mice. Both young （9-12 weeks） and aged （18 months） male mice were subject to middle cerebral artery occlusion （MCAO）. Morphological and biochemical changes in the ischemic brains and behavior deficits were assessed on 1, 3, and 7 d post-stroke. After MCAO, the aged mice showed smaller infarct sizes but worse behavior deficits than young mice. Young mice had significantly more IRF4/CD206 double positive microglia in the ischemic brains, whereas the aged mice had more IRF5＋ and MHC11＋ microglia after stroke than their counterparts. In addition, serum pro-inflammatory cytokines （TNF-α, iNOS, IL-6） were more robustly up-regulated in aged mice, whereas serum anti-inflammatory cytokine （TGF-β, IL-4, IL-10） levels were higher in young mice compared to their counterparts after MCAO. Our results demonstrate that aging has a significant effect on stroke outcomes in mice, which is most likely mediated by age-specific inflammatory responses.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1671-4083eISSN: 1745-7254DOI: 10.1038/aps.2017.122Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5672072
- Format
- –
- Schlagworte
- Activation, Age, Age Factors, Aging - metabolism, Aging - pathology, Animals, Behavior, Animal, Biomedical and Life Sciences, Biomedicine, Brain - metabolism, Brain - pathology, Brain - physiopathology, Cell activation, Cerebral blood flow, Cytokines, Cytokines - blood, Disease Models, Animal, Geriatrics, Immunology, Infarction, Middle Cerebral Artery - metabolism, Infarction, Middle Cerebral Artery - physiopathology, Infarction, Middle Cerebral Artery - psychology, Inflammation, Inflammation Mediators - blood, Interferon, Interferon regulatory factor, Interferon regulatory factor 4, Interferon Regulatory Factors - metabolism, Interleukin 10, Interleukin 4, Interleukin 6, Internal Medicine, Ischemia, Macrophages, Male, Medical Microbiology, Mice, Mice, Inbred C57BL, Microglia, Microglia - metabolism, Myeloid Differentiation Factor 88 - metabolism, Neurological diseases, Nitric-oxide synthase, Occlusion, Older people, Original, original-article, Pharmacology/Toxicology, Rodents, Signal Transduction, Stroke, Time Factors, Tumor necrosis factor, Tumor necrosis factor-α, Vaccine