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Hippocampal Neural Dynamics and Postoperative Delirium-like Behavior in Aged Mice

文献类型：期刊论文

作者Guo, Shiqi4,5; Yang, Liuyue4,5; Ding, Weihua4,5; Dagnew, Tewodros Mulugeta3; Gao, Yuting4,5; Wang, Wei4,5; Wang, Pei4,5; Huang, Song4,5; Ran, Chongzhao3,4; Wang, Changning3
刊名ANESTHESIOLOGY
出版日期2025-09-01
卷号143期号:3页码:625-640
ISSN号0003-3022
DOI10.1097/ALN.0000000000005478
通讯作者Shen, Shiqian(sshen2@mgh.harvard.edu)
英文摘要Background:Postoperative delirium (POD) is a common and serious clinical condition that occurs after anesthesia/surgery. While its clinical impact is well recognized, the underlying electrophysiologic mechanisms remain largely unknown, posing challenges for effective treatment. This study aims to investigate hippocampal neural dynamics before and after anesthesia/surgery in aged mice, which have a tendency to develop POD.Methods:This study included adult and aged mice with a POD model. POD-like behavior was assessed in N = 10 mice at baseline (the day before surgery), as well as at 9 h and 24 h after anesthesia/surgery. A behavioral battery, including the open field test, Y maze, buried food test, and novel object recognition, was used for assessment. In vivo chronic brain recordings were performed on awake, restrained mice using a high-density silicon probe during the same time intervals. To further investigate hippocampal neural dynamics, in vivo two-photon calcium imaging was also conducted. Additionally, aged mice were pretreated with indole-3-propionic acid (IPA), and its effects on POD-like behavior and neural activity were evaluated using electrophysiology and calcium imaging.Results:The first observation was that aged mice exhibited significant POD-like behavior, as measured by Z scores, compared to adult mice after anesthesia/surgery. Analysis revealed significant age-related differences in hippocampal neuronal activities. At 9 h after surgery, aged mice exhibited a marked increase in pyramidal cell activity and a reduction in interneuron activity compared to adult mice. These changes in neuronal dynamics were associated with the onset of POD-like symptoms in aged mice. By 24 h after surgery, both pyramidal cell and interneuron activity in aged mice had returned to presurgery levels, which coincided with an improvement in POD-like behavior. Additionally, IPA pretreatment modulated neuronal activity in aged mice, attenuating pyramidal cell hyperactivity and partially ameliorating interneuron dysfunction, changes associated with mitigated POD-like behavior.Conclusions:Alterations in hippocampal neural activity may significantly contribute to brain dysfunction and POD-like behavior. IPA pretreatment may modulate neural circuit imbalances in aged mice, potentially mitigating POD incidence.
WOS关键词PERIOPERATIVE DELIRIUM ; RISK ; FRAMEWORK ; DEMENTIA ; SURGERY ; EEG
资助项目National Institutes of Health (Bethesda, Maryland)[R35GM128692] ; National Institutes of Health (Bethesda, Maryland)[R01AG070141] ; National Institutes of Health (Bethesda, Maryland)[R01AG082775] ; National Science Foundation[EAGER 2334666] ; National Academy of Medicine (Washington, D.C. ) Healthy Longevity Global Competition Catalyst Award ; Eleanor and Miles Shore Faculty Development Award (Harvard Medical School, Boston, Massachusetts)
WOS研究方向Anesthesiology
语种英语
WOS记录号WOS:001554565300021
出版者LIPPINCOTT WILLIAMS & WILKINS
源URL[http://119.78.100.183/handle/2S10ELR8/321306]  
专题中国科学院上海药物研究所
通讯作者Shen, Shiqian
作者单位1.Shanghai Inst Mat Med, Zhongshan Inst Drug Discovery, Zhongshan Tsuihang New Di, Guangdong, Peoples R China
2.Chinese Acad Med Sci, Peking Union Hosp, Dept Anesthesia, Beijing, Peoples R China
3.Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Harvard MIT Hlth Sci & Technol Martinos Ctr Biomed, Charlestown, MA USA
4.Harvard Med Sch, 149 13th St, Charlestown, MA 02129 USA
5.Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Charlestown, MA USA
推荐引用方式
GB/T 7714		 Guo, Shiqi,Yang, Liuyue,Ding, Weihua,et al. Hippocampal Neural Dynamics and Postoperative Delirium-like Behavior in Aged Mice[J]. ANESTHESIOLOGY,2025,143(3):625-640.
APA Guo, Shiqi.,Yang, Liuyue.,Ding, Weihua.,Dagnew, Tewodros Mulugeta.,Gao, Yuting.,...&Shen, Shiqian.(2025).Hippocampal Neural Dynamics and Postoperative Delirium-like Behavior in Aged Mice.ANESTHESIOLOGY,143(3),625-640.
MLA Guo, Shiqi,et al."Hippocampal Neural Dynamics and Postoperative Delirium-like Behavior in Aged Mice".ANESTHESIOLOGY 143.3(2025):625-640.

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来源：上海药物研究所

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