Laparotomy: a non-bacterial endotoxin mouse model for investigating the impact of systemic inflammation on neuroinflammation and cognitive functions

Abstract

Background: Increasing lines of evidence have shown that systemic inflammation may contribute to neuroinflammation and accelerate the progression of neurodegenerative diseases. In this study, a non-bacterial endotoxin mouse model of laparotomy is adopted to address the systemic inflammation triggered by surgery. We aim at investigating whether laparotomy induces systemic inflammation, neuroinflammation and cellular changes such as tau phosphorylation leading to cognitive dysfunction. Method: Male wild-type C57BL/6J mice were randomly divided into two groups: control group under sevoflurane anesthesia and laparotomy group under sevoflurane anesthesia. Expression of mRNA for cytokines in the liver, frontal cortex and hippocampus was examined at 4 h and day 1 after laparotomy by quantitative RT-PCR and tau protein phosphorylation was comparatively determined on post-operative day (POD) 1 by western blot analysis. Result: First, laparotomy induced peripheral inflammation and neuroinflammation. At 4 h after laparotomy, significant increase of interleukin-1β (IL-1β) and MCP-1 were detected in the liver of the laparotomy group (p < 0.05). Expression of IL-1β was also significantly upregulated in the hippocampus after laparotomy. On POD 1, no significant differences of IL-1β, IL-6, TNF- α and MCP-1 mRNA expression were observed at the liver. It implies that the induced systemic inflammation is transient. Meanwhile, the level of IL-1β remained high in the hippocampus after surgery. Second, on POD 1, there was no significant difference in the total tau protein level between the laparotomy and control groups in the frontal cortex. It could be possible that the changes in protein expression level could not be reflected within a relatively short time period after laparotomy. Conclusion: This study reveals that laparotomy induces systemic and neural inflammation. Further studies will be performed to examine the infiltration of monocytes into the brain and cognitive dysfunction induced by laparotomy.