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

作者：Shiqi Guo, Liuyue Yang, Weihua Ding, Tewodros Mulugeta Dagnew, Yuting Gao, Wei Wang, Pei Wang, Song Huang, Chongzhao Ran, Changning Wang, Le Shen, Qian Chen, Oluwaseun Akeju, Shiqian Shen · 发表于：Anesthesiology · 年份：2025 · DOI：10.1097/aln.0000000000005478 · 被引用次数：9 · 研究领域：Intensive Care Unit Cognitive Disorders、Anesthesia and Sedative Agents、Anesthesia and Neurotoxicity Research

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 exhibit...