Guo Shiqi, Yang Liuyue, Ding Weihua, Dagnew Tewodros Mulugeta, Gao Yuting, Wang Wei, Wang Pei, Huang Song, Ran Chongzhao, Wang Changning, Shen Le, Chen Qian, Akeju Oluwaseun, Shen Shiqian
Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts.
Massachusetts General Hospital/Harvard-MIT Health Sciences and Technology Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts.
Anesthesiology. 2025 Sep 1;143(3):625-640. doi: 10.1097/ALN.0000000000005478. Epub 2025 Mar 28.
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.
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.
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.
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.
术后谵妄（POD）是麻醉/手术后常见且严重的临床病症。尽管其临床影响已得到充分认识，但其潜在的电生理机制仍 largely 未知，这给有效治疗带来了挑战。本研究旨在调查有发生 POD 倾向的老年小鼠在麻醉/手术前后的海马神经动力学。
本研究纳入了 POD 模型的成年和老年小鼠。在 N = 10 只小鼠的基线期（手术前一天）以及麻醉/手术后 9 小时和 24 小时评估类似 POD 的行为。使用包括旷场试验、Y 迷宫、埋藏食物试验和新物体识别在内的行为学组合进行评估。在相同时间间隔内，使用高密度硅探针在清醒、受限的小鼠上进行体内慢性脑记录。为了进一步研究海马神经动力学，还进行了体内双光子钙成像。此外，对老年小鼠进行吲哚 - 3 - 丙酸（IPA）预处理，并使用电生理学和钙成像评估其对类似 POD 行为和神经活动的影响。
第一个观察结果是，与麻醉/手术后的成年小鼠相比，老年小鼠经 Z 评分测量表现出显著的类似 POD 的行为。分析显示海马神经元活动存在显著的年龄相关差异。与成年小鼠相比，手术后 9 小时，老年小鼠的锥体细胞活动显著增加，中间神经元活动减少。这些神经元动力学变化与老年小鼠类似 POD 症状的发作相关。到手术后 24 小时，老年小鼠的锥体细胞和中间神经元活动均恢复到手术前水平，这与类似 POD 行为的改善相吻合。此外，IPA 预处理调节了老年小鼠的神经元活动，减弱了锥体细胞的过度活动并部分改善了中间神经元功能障碍，这些变化与减轻的类似 POD 行为相关。
海马神经活动的改变可能显著导致脑功能障碍和类似 POD 的行为。IPA 预处理可能调节老年小鼠的神经回路失衡，潜在地降低 POD 的发生率。
