Li Yun, Long Siwen, Yu Jiafeng, Feng Jingyu, Meng Shuqi, Li Yize, Zhao Lina, Yu Yonghao
Department of Anesthesiology, The Second Hospital of Tianjin Medical University, Tianjin, 300211, China.
Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin, 300052, China.
Mol Neurobiol. 2025 Mar 19. doi: 10.1007/s12035-025-04851-3.
Older adults with anesthesia and surgery often suffer from postoperative cognitive dysfunction (POCD), which puts a heavy burden on rehabilitation. Preoperative sleep disorder, a common phenomenon in elderly anesthesia patients, is closely associated with POCD, but the underlying mechanism is still not fully understood. Hippocampal gamma-aminobutyric acid (GABA)ergic neurotransmission has been reported to play an important role in sleep disorder and cognitive impairment. The aim of this study was to elucidate the effect of preoperative acute sleep deprivation (SD) on anesthesia/surgery-induced POCD and the potential mechanism of hippocampal GABAergic neurotransmission. In the aged (18-20-month-old) male mice, we used a rotating rod to deprive sleep for 24 h and induced a POCD model using sevoflurane exposure combined with laparotomy exploration. A sequential set of behavioral tests, including open field test (OFT), Y-maze, and novel object recognition (NOR), was conducted to assess cognitive performances. In vivo magnetic resonance imaging (MRI) technique was used to observe hippocampal axonal microstructural changes. The levels of GABAergic neurotransmitter markers glutamic acid decarboxylase (GAD) 67, vesicular GABA transporter (VGAT), GABA transporter (GAT)-1, and GABA in the hippocampus were detected with enzyme-linked immunosorbent assay (ELISA). The reactivity of GABAergic neurons and neuronal damage in different subregions of the hippocampus were observed by immunofluorescence and Nissl staining, respectively. Compared the anesthesia/surgery (A/S) mice, 24-h SD combined with A/S induced shorter stay time in the central area of the open field, less the percent of novel arm preference in the Y maze, and lower recognition index in the NOR, as well as significantly enhanced hippocampal GABAergic neurotransmission, decreased hippocampal axonal integrity and density, and increased GAD67 reactivity and reduced the number of neurons in hippocampal CA1. Preoperative 24-h SD exacerbated anesthesia/surgery-induced POCD in aged mice, with the cumulative effect of abnormal GABAergic neurotransmission and neuronal damage in the hippocampus.
接受麻醉和手术的老年人常患有术后认知功能障碍（POCD），这给康复带来了沉重负担。术前睡眠障碍是老年麻醉患者的常见现象，与POCD密切相关，但其潜在机制仍未完全明确。据报道，海马γ-氨基丁酸（GABA）能神经传递在睡眠障碍和认知障碍中起重要作用。本研究旨在阐明术前急性睡眠剥夺（SD）对麻醉/手术诱导的POCD的影响以及海马GABA能神经传递的潜在机制。在老年（18 - 20月龄）雄性小鼠中，我们使用转棒剥夺睡眠24小时，并通过七氟醚暴露联合剖腹探查诱导POCD模型。进行了一系列行为测试，包括旷场试验（OFT）、Y迷宫和新物体识别（NOR），以评估认知表现。采用体内磁共振成像（MRI）技术观察海马轴突微观结构变化。用酶联免疫吸附测定（ELISA）检测海马中GABA能神经递质标志物谷氨酸脱羧酶（GAD）67、囊泡GABA转运体（VGAT）、GABA转运体（GAT）-1和GABA的水平。分别通过免疫荧光和尼氏染色观察海马不同亚区GABA能神经元的反应性和神经元损伤情况。与麻醉/手术（A/S）小鼠相比，24小时SD联合A/S导致在旷场中央区域的停留时间缩短、Y迷宫中新臂偏好百分比降低、NOR中的识别指数降低，以及海马GABA能神经传递显著增强、海马轴突完整性和密度降低、GAD67反应性增加以及海马CA1区神经元数量减少。术前24小时SD加剧了老年小鼠麻醉/手术诱导的POCD，其具有海马中GABA能神经传递异常和神经元损伤的累积效应。
