【摘 要】
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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 f
【机 构】
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Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China“,
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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 M1 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 MHCll+ microglia after stroke than their counterparts.In addition,serum pro-inflammatory cytokines (TNF-αx,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.
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