Department of Biotechnology, College of Biomedical and Health Science, Konkuk University, Chungju, Republic of Korea.
Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
Sci Rep. 2021 Apr 16;11(1):8376. doi: 10.1038/s41598-021-87790-y.
Postoperative delirium is a common neuropsychiatric syndrome resulting a high postsurgical mortality rate and decline in postdischarge function. Extensive research has been performed on both human and animal delirium-like models due to their clinical significance, focusing on systematic inflammation and consequent neuroinflammation playing a key role in the pathogenesis of postoperative cognitive dysfunctions. Since animal models are widely utilized for pathophysiological study of neuropsychiatric disorders, this study aimed at examining the validity of the scopolamine-induced delirium-like mice model with respect to the neuroinflammatory hypothesis of delirium. Male C57BL/6 mice were treated with intraperitoneal scopolamine (2 mg/kg). Neurobehavioral tests were performed to evaluate the changes in cognitive functions, including learning and memory, and the level of anxiety after surgery or scopolamine treatment. The levels of pro-inflammatory cytokines (IL-1β, IL-18, and TNF-α) and inflammasome components (NLRP3, ASC, and caspase-1) in different brain regions were measured. Gene expression profiles were also examined using whole-genome RNA sequencing analyses to compare gene expression patterns of different mice models. Scopolamine treatment showed significant increase in the level of anxiety and impairments in memory and cognitive function associated with increased level of pro-inflammatory cytokines and NLRP3 inflammasome components. Genetic analysis confirmed the different expression patterns of genes involved in immune response and inflammation and those related with the development of the nervous system in both surgery and scopolamine-induced mice models. The scopolamine-induced delirium-like mice model successfully showed that analogous neuropsychiatric changes coincides with the neuroinflammatory hypothesis for pathogenesis of delirium.
术后谵妄是一种常见的神经精神综合征，可导致高术后死亡率和出院后功能下降。由于其临床意义，广泛研究了人类和动物的谵妄样模型，重点是系统性炎症和随之而来的神经炎症在术后认知功能障碍的发病机制中起关键作用。由于动物模型广泛用于神经精神疾病的病理生理学研究，本研究旨在检查东莨菪碱诱导的谵妄样小鼠模型在谵妄的神经炎症假说方面的有效性。雄性 C57BL/6 小鼠接受腹腔内东莨菪碱（2mg/kg）治疗。进行神经行为测试以评估手术后或东莨菪碱治疗后认知功能（包括学习和记忆）和焦虑水平的变化。测量不同脑区促炎细胞因子（IL-1β、IL-18 和 TNF-α）和炎症小体成分（NLRP3、ASC 和 caspase-1）的水平。还使用全基因组 RNA 测序分析检查基因表达谱，以比较不同小鼠模型的基因表达模式。东莨菪碱治疗显示焦虑水平显著增加，记忆和认知功能受损，与促炎细胞因子和 NLRP3 炎症小体成分水平升高有关。遗传分析证实了手术和东莨菪碱诱导的小鼠模型中涉及免疫反应和炎症的基因以及与神经系统发育相关的基因的不同表达模式。东莨菪碱诱导的谵妄样小鼠模型成功地表明，类似的神经精神变化与谵妄发病机制的神经炎症假说一致。
