Zheng Xiaoyu, Xiang Qian, Dong Xiaoxu, Shen Yang, Fang Wei, Yang Hongna
Shandong University, Jinan 250012, Shandong, China.
Department of Critical Care Medicine, Shandong Provincial Hospital, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250000, Shandong, China. Corresponding author: Yang Hongna, Email:
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2024 Aug;36(8):892-896. doi: 10.3760/cma.j.cn121430-20231109-00959.
Sepsis-associated encephalopathy (SAE) is the most common neurological complication of sepsis, with an incidence of up to 70% in sepsis, and contributes to the increased mortality and disability in sepsis. To date, the exact pathogenesis of SAE is not clear. Most of current researches indicated that blood-brain barrier (BBB) dysfunction, active neuroinflammation, glial cell over activation as well as cerebral microcirculation dysfunction contributed to the pathophysiology of SAE. BBB, as a complex cellular structure between the central nervous system and the peripheral system, strictly controls the entrance and discharge of substances and plays an important role in maintaining the balance between biochemical system and immune system of central system. During the progress of sepsis, inflammatory cytokines and reactive oxygen species resulting from peripheral system directly or indirectly resulted in the damage to the integrity and structure of BBB, which helped above species easily enter into the central system. Above these damages caused glial cell activation (microglia and astrocyte), the imbalance of neurotransmitters, mitochondrial dysfunction and neural apoptosis, which also reversely contributed to the damage to the integrity and permeability of BBB via decreasing the expression of tight junctional protein between cells. Therefore, this review focuses on the structural and functional changes of BBB in SAE, and how these changes lead to the development of SAE, in order to seek a BBB-targeted therapy for SAE.
脓毒症相关性脑病(SAE)是脓毒症最常见的神经并发症,在脓毒症中的发生率高达70%,并导致脓毒症患者死亡率和致残率增加。迄今为止,SAE的确切发病机制尚不清楚。目前大多数研究表明,血脑屏障(BBB)功能障碍、活跃的神经炎症、胶质细胞过度激活以及脑微循环功能障碍参与了SAE的病理生理过程。血脑屏障作为中枢神经系统与外周系统之间的一种复杂细胞结构,严格控制物质的进出,在维持中枢系统生化系统和免疫系统平衡方面发挥着重要作用。在脓毒症进展过程中,外周系统产生的炎性细胞因子和活性氧直接或间接导致血脑屏障完整性和结构受损,促使上述物质轻易进入中枢系统。上述损伤引起胶质细胞(小胶质细胞和星形胶质细胞)激活、神经递质失衡、线粒体功能障碍和神经细胞凋亡,这些反过来又通过降低细胞间紧密连接蛋白的表达,导致血脑屏障完整性和通透性受损。因此,本综述聚焦于SAE中血脑屏障的结构和功能变化,以及这些变化如何导致SAE的发生发展,以期寻找针对血脑屏障的SAE治疗方法。