Yao Zhun, Zhao Yuanrui, Lu Liping, Xu Song, Li Yinping, Yu Zhui
Department of Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan 430060, China.
Department of Pathophysiology, Hubei Province Key Laboratory of Allergy and Immunology, Taikang Medical School (School of Basic Medical Sciences), Wuhan University, Wuhan 430060, China.
Resusc Plus. 2025 May 26;24:100993. doi: 10.1016/j.resplu.2025.100993. eCollection 2025 Jul.
Post-cardiac arrest brain injury (PCABI) is the leading cause of death and disability after resuscitation. This study aimed to investigate the pathogenesis and novel biomarkers for monitoring the progression and early prognostication of PCABI.
Mouse model of PCABI was induced by hyperkalemia-induced asystole and successful resuscitation. Young adult male C57BL/6 mice were randomized into sham-operation or asystole/resuscitation. The sham-operated mice were selected as control. Neurological examinations were performed at 24 h after resuscitation, and three groups were set: control ( = 4), severe PCABI ( = 3), and mild PCABI ( = 3). Cerebral cortexes were collected for data-independent acquisition-proteomic analyses. The pathogenesis and potential biomarkers were identified through the pairwise comparisons of three subgroups and subsequent bioinformatics analyses. Human serum proteomes profiles, extracted from a published work of the second analysis of TTM-trial, were used for joint analyses to identify the common and clinically relevant biomarkers at the same timepoint. Experimental and external validation were performed to verify the association between novel biomarkers and neural death in PCABI.
The proteomic analysis identified and quantified 7,745 proteins. The most prominent proteomic changes were related to response to external stimulus, stress response, regulation of biological and metabolic process, endomembrane system, and inflammatory response in the PCABI progression. 10 potential biomarkers were identified by the pairwise comparisons of three groups, and lipocalin-2 and angiotensinogen are common biomarkers with human studies at 24 h after resuscitation. Experimental validation verified that lipocalin-2 was closely associated with neurodegeneration in PCABI.
Stress, inflammatory, and metabolic responses play important roles in the progression of PCABI. Lipocalin-2 is a novel biomarker for monitoring and early neuroprognostication at 24 h after resuscitation.
心脏骤停后脑损伤（PCABI）是复苏后死亡和残疾的主要原因。本研究旨在探讨PCABI的发病机制以及用于监测其进展和早期预后的新型生物标志物。
通过高钾血症诱导的心搏停止和成功复苏建立PCABI小鼠模型。将年轻成年雄性C57BL/6小鼠随机分为假手术组或心搏停止/复苏组。选择假手术小鼠作为对照。复苏后24小时进行神经学检查，并分为三组：对照组（n = 4）、重度PCABI组（n = 3）和轻度PCABI组（n = 3）。收集大脑皮层进行数据非依赖采集-蛋白质组学分析。通过三个亚组的两两比较及后续生物信息学分析确定发病机制和潜在生物标志物。从已发表的TTM试验二次分析工作中提取的人血清蛋白质组图谱用于联合分析，以在同一时间点鉴定共同的和临床相关的生物标志物。进行实验和外部验证以证实新型生物标志物与PCABI中神经死亡之间的关联。
蛋白质组学分析鉴定并定量了7745种蛋白质。在PCABI进展过程中，最显著的蛋白质组学变化与对外界刺激的反应、应激反应、生物和代谢过程的调节、内膜系统及炎症反应有关。通过三组的两两比较确定了10种潜在生物标志物，其中脂钙蛋白-2和血管紧张素原是复苏后24小时与人体研究共有的生物标志物。实验验证证实脂钙蛋白-2与PCABI中的神经变性密切相关。
应激、炎症和代谢反应在PCABI进展中起重要作用。脂钙蛋白-2是复苏后24小时监测和早期神经预后评估的新型生物标志物。
