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Dysfunction of Inflammation-Resolving Pathways Is Associated with Postoperative Cognitive Decline in Elderly Mice.
Behavioural Brain Research ( IF 2.7 ) Pub Date : 2020-02-27 , DOI: 10.1016/j.bbr.2020.112538
Moxuan Gong 1 , Gongming Wang 1 , Guodong Li 2 , Jie Liu 3 , Panpan Sun 4 , Lichi Xu 1 , Jingjing Li 1 , Yanjing Guo 1 , Mengyuan Zhang 1
Affiliation  

BACKGROUND Postoperative cognitive dysfunction (POCD) refers to a reversible, perioperative mental disorder. POCD increases the likelihood of postoperative complications and the risk for postoperative mortality, typically among elderly patients (age 65 or older). The importance of the cholinergic anti-inflammatory pathway (CAP) in resolving neuro-inflammatory and cognitive decline caused by sterile trauma has been recognized. We speculate that the POCD in elderly mice is associated with dysfunction of CAP. METHODS Mice were assigned to several groups (n = 5 in each group): AM (adult mice) Sham, AM (adult mice) Surgery, EM (elderly mice) Sham, EM (elderly mice) Surgery, and EM-P (elderly mice with PNU) Surgery. At 24 h after surgery, assessed the cognitive levels. Pro-inflammatory cytokines in peripheral blood and splenic monocytes (TNF-α, IL-6 and IL-10) were assessed by ELISA and qPCR. Levels of M2 macrophages in hippocampus were visualized by immunofluorescence. Detecting CD11b/c+α7 nAChR+ cells in the spleens with flow cytometry. RESULTS At postoperative 24 hours, elderly mice exhibited significantly increased POCD compared with adult mice. The proinflammatory factor TNF-α and IL-6 were higher among elderly surgery mice (EM) compared with adult surgery (AM) and elderly-P surgery mice (EM-P); the anti-inflammatory factor IL-10 and M2 macrophages were lower among EM surgery mice compared with AM surgery and EM-P surgery mice. The CD11b/c+α7 nAChR+ population of splenocytes was reduced in the EM surgery mice. CONCLUSIONS The exaggerated and persistent cognitive decline and inflammatory response among elderly mice were associated with dysfunction of CAP, and these phenomena were reversed by α7nAch receptor agonists.

中文翻译:

炎症解决途径的功能障碍与老年小鼠的术后认知能力下降有关。

背景术后认知功能障碍(POCD)是指一种可逆的围手术期精神障碍。POCD 会增加术后并发症的可能性和术后死亡的风险,尤其是在老年患者(65 岁或以上)中。胆碱能抗炎通路 (CAP) 在解决无菌性创伤引起的神经炎症和认知能力下降方面的重要性已得到认可。我们推测老年小鼠的 POCD 与 CAP 的功能障碍有关。方法 将小鼠分为几组(每组 n = 5):AM(成年小鼠)Sham、AM(成年小鼠)Surgery、EM(老年小鼠)Sham、EM(老年小鼠)Surgery 和 EM-P(老年小鼠) PNU 的小鼠)手术。在手术后 24 小时,评估认知水平。外周血和脾单核细胞中的促炎细胞因子(TNF-α,IL-6 和 IL-10) 通过 ELISA 和 qPCR 进行评估。通过免疫荧光观察海马中 M2 巨噬细胞的水平。用流式细胞术检测脾脏中的 CD11b/c+α7 nAChR+ 细胞。结果 在术后 24 小时,与成年小鼠相比,老年小鼠的 POCD 显着增加。与成年手术小鼠(AM)和老年P手术小鼠(EM-P)相比,老年手术小鼠(EM)的促炎因子TNF-α和IL-6较高;与AM手术和EM-P手术小鼠相比,EM手术小鼠的抗炎因子IL-10和M2巨噬细胞较低。在 EM 手术小鼠中,CD11b/c+α7 nAChR+ 脾细胞群减少。结论老年小鼠过度且持续的认知能力下降和炎症反应与CAP功能障碍有关,
更新日期:2020-02-27
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