Scopolamine-Induced Delirium Promotes Neuroinflammation and Neuropsychiatric Disorder in Mice

Abstract

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 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 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-1ꞵ, 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 mice model successfully showed that analogous neuropsychiatric changes coincides with the neuroinflammatory hypothesis for pathogenesis of delirium.

Long-term scopolamine treatment altered locomotor, exploratory and anxiety-like behaviours of albino rats

“…The observed hyperactivity and increased exploration suggested that rats were less anxious in the maze. This is supported by Walsh and Cummins [43], Jafarian et al [22] and Cheon et al [10] who demonstrated that a high frequency of the number of peripheral square crossing and rearing in open field test indicating increased locomotor activity and/or a lower level of anxiety. In addition, Walsh and Cummins [43] and Stanford [39] reported that rats spent most of their time in the central area and explore more in open field test reflect a low level of anxiety.…”

“…Control group; injected with saline intraperitoneally (i.p); and Scopolamine hydrobromide-treated group (SCO) administered SCO at a dose of 2 mg/kg, i.p. dissolved in saline solution [5,10] daily for seven weeks.…”

“…Furthermore, serotonin is included in the behaviour performance and mood regulation, due to its therapeutic effectiveness and extended treatment of anxiety disorders with selective serotonin reuptake inhibitors [31]. Most studies proved that short term use of SCO in treatment caused anxiety in rats and mice [10,22], however, there is little information about the effect of long term treatment SCO on rats, behaviour and anxiety. Therefore, we aimed to investigate the effect of long term SCO treatment on locomotor, exploratory and anxiety-like behaviours of rats using open field test and measurement of brain serotonin levels.…”