Rapido Francesca, Di Franco Valeria, Tabolacci Elisabetta, Dello Russo Cinzia, Aceto Paola
Department of Anesthesia & Critical Care Medicine, Gui de Chauliac Montpellier University Hospital, Montpellier, France; Institute of Functional Genomics, Unité Mixtes de Recherche (UMR) 5203 Centre National de la Recherche Scientifique (CNRS)-Unité 1191 INSERM, University of Montpellier, Montpellier, France.
Dipartimento di Scienze dell'emergenza, Anestesiologiche e della rianimazione, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
Eur J Pharmacol. 2025 Jul 15;999:177696. doi: 10.1016/j.ejphar.2025.177696. Epub 2025 May 1.
Neuroinflammation induced by anaesthetics may negatively affect neurocognitive functions after surgery in humans. This systematic review and meta-analysis aimed to evaluate the impact of sevoflurane exposure on systemic inflammation and neuroinflammation and to assess alterations in behavioural/cognitive functions in experimental rodent models not exposed to surgery nor to other inflammatory stimuli. Databases were searched for in vivo and/or in vitro studies examining inflammation after sevoflurane exposure compared to control conditions. Inflammatory biomarkers, including interleukin (IL)-6, IL-1β, and tumor necrosis factor alfa (TNFα), at the peak time of production (primary outcomes) were investigated. The secondary outcome was to evaluate the presence of alterations in behavioural/cognitive tests. Subgroup analyses on young and adult rodents were performed for in vivo studies. Thirty-five in vivo and in vitro studies were selected. Results from meta-analyses demonstrated significant increases in the secretion peak of all inflammatory markers in vivo models. Significantly higher plasma peaks of IL-6 (SMD: 7.97, 95 % CI: 4.76-11.17), IL-1β (SMD: 5.71, 95 % CI: 1.88-9.55) and TNFα (SMD: 6.64, 95 % CI: 3.73-9.56) were found only in adult rodents exposed to sevoflurane. Similar findings were observed in brain tissue homogenates. Rodents exposed to sevoflurane exhibited significant alterations in behavioural/cognitive tests and significance persisted only in adult rodents. Sevoflurane exposure may trigger systemic inflammation and neuroinflammation in experimental rodent models with marked effects in adult rodents. Alterations in behavioural/cognitive tests suggest a potential role of sevoflurane in the development of postoperative cognitive disorders in the elderly, independently of surgery. Further research is needed in humans.
麻醉剂引起的神经炎症可能会对人类术后的神经认知功能产生负面影响。本系统评价和荟萃分析旨在评估七氟醚暴露对全身炎症和神经炎症的影响，并评估未接受手术或其他炎症刺激的实验性啮齿动物模型中行为/认知功能的变化。检索数据库以查找与对照条件相比，研究七氟醚暴露后炎症的体内和/或体外研究。研究了炎症生物标志物，包括白细胞介素（IL）-6、IL-1β和肿瘤坏死因子α（TNFα）在产生峰值时（主要结局）的情况。次要结局是评估行为/认知测试中是否存在变化。对体内研究进行了幼年和成年啮齿动物的亚组分析。选择了35项体内和体外研究。荟萃分析结果表明，体内模型中所有炎症标志物的分泌峰值均显著增加。仅在暴露于七氟醚的成年啮齿动物中发现IL-6（标准化均数差：7.97，95%置信区间：4.76-11.17）、IL-1β（标准化均数差：5.71，95%置信区间：1.88-9.55）和TNFα（标准化均数差：6.64，95%置信区间：3.73-9.56）的血浆峰值显著更高。在脑组织匀浆中也观察到类似结果。暴露于七氟醚的啮齿动物在行为/认知测试中表现出显著变化，且这种显著性仅在成年啮齿动物中持续存在。七氟醚暴露可能会在实验性啮齿动物模型中引发全身炎症和神经炎症，对成年啮齿动物有显著影响。行为/认知测试中的变化表明，七氟醚在老年人术后认知障碍的发生中可能具有潜在作用，与手术无关。需要在人类中进行进一步研究。
