Differential inflammatory effects in the brain and post operative cognitive performance from surgical trauma when compared with anaesthesia exposure without surgery

Abstract

Background and Goal of Study: Postoperative cognitive dysfunction (POCD) is associated with abnormal tau protein phosphorylation and neuroinflammation, findings commonly seen with Alzheimer’s Disease1,2 This study investigates the contribution of surgical trauma as compare with anaesthesia exposure alone to the development of this condition. Materials and methods: Young wild type C57BL/6N mice were divided into control (CON) sevoflurane only (SEVO) and laparotomy (LAP) groups. Cognitive function was assessed by Y-maze analysis and locomotor activity by the Open Field test on postoperative day 14. Inflammatory cytokine mRNA expression from the liver, frontal cortex and hippocampus were assessed by q-PCR at 4h and 24h. Brain tissues were collected for Western-Blot analysis and immunoflurescent staining. Normalized band intensities were analyzed by One-Way ANOVA followed by Turkey’s post hoc test. Results and discussion: No dif ferences were seen for locomotor activity but latency and error number were significantly increased in LAP compared with SEVO (n=10-11, p <0.01 and p <0.05 respectively) in Y-maze test. Hepatic mRNA levels of IL-1β, TNF-α, IL-8 and MCP-1 were significantly increased at 4h in LAP compared with SEVO and CON. IL-1β was elevated in the frontal cortex, as was IL-8 in the hippocampus at 4h in LAP (n= 6-8, p <0.05). Immunoflurescent positive intensity of GFAP labeled astrocyte was higher in LAP compared with SEVO at the DG region of hippocampus. There were also more activated microglia (IBA-1 labeled) in CA1 and DG regions of the hippocampus. These results indicate that both peripheral and neuroinflammation and astrocytes and microglia activation are more pronounced following trauma compared with sevoflurane exposure alone and this corresponds to delayed cognitive impairment. Conclusion(s): These data further support that POCD is a condition that is more related to surgical trauma than to anaesthesia exposure. References: 1. Iqbal, K., et al Curr Alzheimer Res, 2010. 7(8): p. 656-64. 2. Run, X., et al J Alzheimers Dis, 2010. 22 Suppl 3: p. 49-55. 3. Wan, Y., et al Anesthesiology, 2007. 106(3): p. 436-43. Acknowledgements: This work is supported in part by the HKU