Postoperative delirium is a common neuro psychiatric 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.
Fig: Experimental design and procedure. (A) Scopolamine (2 mg/kg) or vehicle was injected intraperitoneally. Mice were subjected to abdominal surgery by clipping superior mesenteric artery and rubbing intestines. All mouse brains were isolated, and brain sub-regions, such as hippocampus, prefrontal cortex, and amygdala, were analyzed after surgery or scopolamine treatment. (B) Mice in surgery group and sham group performed behavioral test at 4 and 5 day post-surgery. Mice in both vehicle and scopolamine-treated groups performed behavioral test at 1 day before scopolamine or vehicle treatment, and 30 min after scopolamine or vehicle treatment.
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.
Cheon, S.Y., Koo, BN., Kim, S.Y. et al. Scopolamine promotes neuroinflammation and delirium-like neuropsychiatric disorder in mice. Sci Rep 11, 8376 (2021). https://doi.org/10.1038/s41598-021-87790-y