Niu Yixuan, Yan Jia, Jiang Hong
Department of Anesthesiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Mol Neurosci. 2022 Nov 21;15:1017578. doi: 10.3389/fnmol.2022.1017578. eCollection 2022.
Anesthesia is unavoidable in surgical procedures. However, whether the general anesthetics are neurotoxic to immature brains remains undefined. Neurodevelopmental impairment induced by anesthesia has been a critical health issue and topic of concern. This review summarizes recent progress made in clinical and preclinical studies to provide useful suggestions and potential therapeutic targets for the protection of the immature brain. On the one hand, clinical researchers continue the debate about the effect of single and multiple exposures to anesthesia on developing brains. On the other hand, preclinical researchers focus on exploring the mechanisms of neurotoxic effects of general anesthesia on immature brains and seeking novel solutions. Rodent models have always been used in preclinical studies, but it is still unclear whether the mechanisms observed in rodent models have clinical relevance. Compared with these models, non-human primates (NHPs) are more genetically similar to humans. However, few research institutions in this area can afford to use NHP models in their studies. One way to address both problems is by combining single-cell sequencing technologies to screen differential gene expression in NHPs and perform validation in rodents. The mechanism of anesthesia-induced neurotoxicity still requires further elucidation in primates.
麻醉在外科手术中是不可避免的。然而,全身麻醉剂对未成熟大脑是否具有神经毒性仍不明确。麻醉引起的神经发育障碍一直是一个关键的健康问题和关注话题。本综述总结了临床和临床前研究的最新进展,为保护未成熟大脑提供有用的建议和潜在的治疗靶点。一方面,临床研究人员继续争论单次和多次接触麻醉对发育中大脑的影响。另一方面,临床前研究人员专注于探索全身麻醉对未成熟大脑神经毒性作用的机制,并寻求新的解决方案。啮齿动物模型一直用于临床前研究,但在啮齿动物模型中观察到的机制是否具有临床相关性仍不清楚。与这些模型相比,非人灵长类动物(NHP)在基因上与人类更相似。然而,该领域很少有研究机构能够负担得起在其研究中使用NHP模型。解决这两个问题的一种方法是结合单细胞测序技术,筛选NHP中的差异基因表达,并在啮齿动物中进行验证。麻醉诱导神经毒性的机制在灵长类动物中仍需要进一步阐明。