认知功能衰退
神经炎症
术后认知功能障碍
认知
炎症
肿瘤坏死因子α
医学
海马体
细胞因子
机制(生物学)
生物信息学
免疫学
神经科学
心理学
内科学
生物
疾病
痴呆
精神科
认识论
哲学
作者
Niccolò Terrando,Claudia Monaco,Daqing Ma,Brian M. J. Foxwell,Marc Feldmann,Mervyn Maze
标识
DOI:10.1073/pnas.1014557107
摘要
Cognitive decline following surgery in older individuals is a major clinical problem of uncertain mechanism; a similar cognitive decline also follows severe infection, chemotherapy, or trauma and is currently without effective therapy. A variety of mechanisms have been proposed, and exploring the role of inflammation, we recently reported the role of IL-1β in the hippocampus after surgery in mice with postoperative cognitive dysfunction. Here, we show that TNF-α is upstream of IL-1 and provokes its production in the brain. Peripheral blockade of TNF-α is able to limit the release of IL-1 and prevent neuroinflammation and cognitive decline in a mouse model of surgery-induced cognitive decline. TNF-α appears to synergize with MyD88, the IL-1/TLR superfamily common signaling pathway, to sustain postoperative cognitive decline. Taken together, our results suggest a unique therapeutic potential for preemptive treatment with anti-TNF antibody to prevent surgery-induced cognitive decline.
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