Abstract：
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.
摘要：
脓毒症相关性脑病(SAE),脓毒症常见的神经系统并发症，是由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死亡率和发病率过高。尽管具有高发病率的临床相关性，对其急性/慢性发病机制和治疗管理都缺乏了解。更好地理解SAE背后的分子机制可以提供更好地增强治疗功效的工具。越来越多的证据表明，某些类型的非凋亡调节细胞死亡（RCD），比如铁中毒，焦亡,和自噬,有助于SAE。靶向这些类型的RCD可以为针对SAE的未来治疗提供有意义的靶标。本文综述了非凋亡性RCD导致SAE发病的核心机制。我们专注于能够抑制RCD的新兴类型的治疗化合物，并描述了它们对SAE的有益药理作用。在这篇综述中，我们认为非凋亡性RCD的药理抑制可能是针对SAE的潜在治疗策略。
