Kim Jong-Ho, Park Songyi, Jung Harry, Lee Eun-Hae, Lee Eun-Seo, Lee Jae-Jun, Sohn Jong-Hee
Department of Anesthesiology and Pain Medicine, Chuncheon Sacred Heart Hospital, College of Medicine, Hallym University, Chuncheon 24253, Republic of Korea.
Institute of New Frontier Research, College of Medicine, Hallym University, Chuncheon 24252, Republic of Korea.
Int J Mol Sci. 2025 Jun 14;26(12):5718. doi: 10.3390/ijms26125718.
Perioperative neurocognitive disorder (PND) is a concern following anesthesia, particularly in individuals at risk for Alzheimer's disease (AD). This study compared the cognitive and pathological effects of propofol and remimazolam in a mouse model with AD following surgery. Five-month-old male ApoE4-KI mice underwent abdominal surgery under either propofol (170 mg/kg) or remimazolam (85 mg/kg) anesthesia. Cognitive function was assessed using the Morris water maze and Y-maze, and neuronal apoptosis and amyloid-beta (Aβ) deposition in the CA3 and dentate gyrus (DG) of the hippocampus were evaluated preoperatively and at 2, 4, and 7 days postoperatively. Both groups showed similar postoperative cognitive functions, with increased relative escape latency at day 2 and decreased relative spontaneous alternation at days 4 and 7. However, the neuropathological analysis revealed that propofol-induced significantly more neuronal death in the CA3 (days 4 and 7) and DG (days 2, 4, and 7), and greater Aβ accumulation in the CA3 (days 2 and 4) and DG (days 2 and 7) compared to remimazolam ( < 0.05). Propofol was associated with more pronounced neuropathologic changes in the hippocampus compared to remimazolam. These findings suggest remimazolam may be a safer anesthetic for patients at risk for neurodegenerative disorders, as it is associated with less severe hippocampal pathology, which is characteristic of AD.
围手术期神经认知障碍（PND）是麻醉后令人担忧的问题，尤其是在有患阿尔茨海默病（AD）风险的个体中。本研究比较了丙泊酚和瑞马唑仑在AD小鼠手术模型中的认知和病理影响。五个月大的雄性ApoE4-KI小鼠在丙泊酚（170mg/kg）或瑞马唑仑（85mg/kg）麻醉下接受腹部手术。使用莫里斯水迷宫和Y迷宫评估认知功能，并在术前以及术后第2、4和7天评估海马体CA3区和齿状回（DG）中的神经元凋亡和β淀粉样蛋白（Aβ）沉积。两组术后认知功能相似，术后第2天相对逃避潜伏期增加，术后第4天和第7天相对自发交替减少。然而，神经病理学分析显示，与瑞马唑仑相比，丙泊酚在CA3区（术后第4天和第7天）和DG区（术后第2、4和7天）诱导的神经元死亡显著更多，并且在CA3区（术后第2天和第4天）和DG区（术后第2天和第7天）的Aβ积累更多（P<0.05）。与瑞马唑仑相比，丙泊酚与海马体更明显的神经病理变化有关。这些发现表明，瑞马唑仑可能是神经退行性疾病风险患者更安全的麻醉剂，因为它与不太严重的海马体病理变化有关，而海马体病理变化是AD的特征。
