Abstract
There is a need to develop animal models to study postoperative delirium. Inattention is one of the symptoms of delirium. Increases in the levels of α-synuclein and S100β have been reported to be associated with delirium. Therefore, we set out to determine the effects of surgery plus general anesthesia on the behavioral changes (including loss of attention) in mice and on the levels of α-synuclein and S100β in the brain tissues of these mice. C57BL/6J mice (2- to 8-months-old) had a simple laparotomy plus isoflurane anesthesia. The behavioral changes, including attention level and the speed of movements, were determined 12, 24, and 48 h after the surgery plus anesthesia in the mice. The levels of α-synuclein and S100β in the cortex of these mice following the surgery plus anesthesia were determined by Western blot analysis. We found that there was a loss of attention at 24, but not 12 or 48 h following the surgery plus anesthesia (49% ± 5 vs. 33% ± 2.9, P = 0.011, N = 12) in the mice without significantly affecting the speed of their movements. There were increases in the levels of total α-synuclein (139% ± 33.5 vs. 100% ± 13.7, P = 0.037, N = 6) and S100β (142% ± 7.7 vs. 100% ± 6, P = 0.002, N = 6) in the cortex of the mice 12 h following the surgery plus anesthesia. These findings suggested that the surgery plus isoflurane anesthesia might induce behavioral and biochemical/cellular changes associated with delirium. We could use the surgery plus anesthesia in mice to develop an animal model to study postoperative delirium.
Highlights
The surgery plus anesthesia did not significantly alter the speed of movement (Figure 1D, P = 0.788, Student’s t-test, N = 12 in each group) in the mice 24 h after the surgery plus anesthesia. These results showed that the surgery plus anesthesia did not impair the locomotor activity of the mice, and that the surgery plus anesthesia-induced loss of attention was not the result of impairment of the locomotor activity in the mice
The surgery plus anesthesia did not increase the S100β level in the cortex of the mice as compared to the sham condition 24 h after the surgery plus anesthesia (Figures 3C,D). These data suggested that the surgery plus anesthesia enhanced the S100β levels in the brain tissue of mice in a time-dependent manner. In this system-establishment pilot study, we assessed whether surgery plus anesthesia was able to induce the behavioral changes and biochemical/cellular changes that are potentially associated with delirium
We found that the surgery plus anesthesia might induce behavioral changes including reduction in the attention levels in the mice 24, but not 12 or 48 h after the surgery plus anesthesia
Summary
Postoperative delirium, a common postoperative complication (Marcantonio et al, 1994; Liu and Leung, 2000), has independent and adverse effects on short- and long-term mortality and morbidity, including poor functional recovery, postoperative cognitive dysfunction, deterioration in quality of life, and increased costs of medical care (Inouye, 2006; Ansaloni et al, 2010; Jankowski et al, 2011; Saczynski et al, 2012, reviewed in Deiner and Silverstein, 2009; Vasilevskis et al, 2012). The neuropathogenesis and targeted intervention(s) for postoperative delirium remain largely to be determined, partially owing to the lack of animal models to study postoperative delirium. The establishment of animal model(s) to study postoperative delirium, Anesthesia, surgery, and attention would likely facilitate investigations into the neuropathogenesis of postoperative delirium, and could lead to the development of targeted intervention(s). Few animal models related to the study of delirium have been established. The attentional setshifting task (AST), another potential animal model that could be used to study delirium (Culley et al, 2014), includes tests of discrimination problems, which are based on stimulus dimensions (e.g., odor and intra-and extra-dimensional cues). It has been suggested that AST is similar to the Wisconsin Card Sorting Test (WCST) (Culley et al, 2014), a test used clinically to detect impairments in attention and executive function due to prefrontal cortex damage or dysfunction in patients (Bourne and Milner, 1963; Roberts et al, 1988)
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