Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang 11004, China.
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY 11439, USA.
Biomed Pharmacother. 2024 May;174:116453. doi: 10.1016/j.biopha.2024.116453. Epub 2024 Mar 20.
Sepsis-associated encephalopathy (SAE), a common neurological complication of sepsis, is a heterogenous complex clinical syndrome caused by the dysfunctional response of a host to infection. This dysfunctional response leads to excess mortality and morbidity worldwide. Despite clinical relevance with high incidence, there is a lack of understanding for its both its acute/chronic pathogenesis and therapeutic management. A better understanding of the molecular mechanisms behind SAE may provide tools to better enhance therapeutic efficacy. Mounting evidence indicates that some types of non-apoptotic regulated cell death (RCD), such as ferroptosis, pyroptosis, and autophagy, contribute to SAE. Targeting these types of RCD may provide meaningful targets for future treatments against SAE. This review summarizes the core mechanism by which non-apoptotic RCD leads to the pathogenesis of SAE. We focus on the emerging types of therapeutic compounds that can inhibit RCD and delineate their beneficial pharmacological effects against SAE. Within this review we suggest that pharmacological inhibition of non-apoptotic RCD may serve as a potential therapeutic strategy against SAE.
脓毒症相关性脑病（SAE）是脓毒症的一种常见神经系统并发症，是宿主对感染的功能失调反应引起的异质性复杂临床综合征。这种功能失调的反应导致全球范围内的死亡率和发病率增加。尽管具有很高的发病率和临床相关性，但人们对其急性/慢性发病机制和治疗管理缺乏了解。更好地了解 SAE 背后的分子机制可能为更好地提高治疗效果提供工具。越来越多的证据表明，某些类型的非细胞凋亡性调控细胞死亡（RCD），如铁死亡、细胞焦亡和自噬，与 SAE 有关。针对这些类型的 RCD 可能为治疗 SAE 提供有意义的靶点。本综述总结了非细胞凋亡性 RCD 导致 SAE 发病机制的核心机制。我们重点介绍了可以抑制 RCD 的新兴治疗化合物类型，并阐述了它们对 SAE 的有益的药理学作用。在本综述中，我们提出抑制非细胞凋亡性 RCD 可能是治疗 SAE 的一种潜在治疗策略。
