The evaluation of the contributory roles of anaesthesia and neuroinflammation to the development of postoperative cognitive dysfunction

Abstract

Postoperative Cognitive Dysfunction (POCD) occurs more frequently in the elderly patients scheduled for elective major non-cardiac surgery. Neuroinflammation and abnormal tau phosphorylation have been regarded as the main characteristics in series of neurodegenerative diseases. The development and pathogenesis of POCD is multifactorial, it remains elusive whether POCD is related more to anaesthetic neurotoxicity or surgical co-morbidities. So far, no reliable and effective therapy strategy has been identified. SD rats and C57 mice were included for three sets of experiments to evaluate the contributory roles of anaesthesia and peripheral surgery to the development of POCD. Firstly, abnormal tau phosphorylation was examined after propofol and dexmedetomidine intravenous infusion in rats for 2 hours. Secondly, ibuprofen was administrated in young C57 mice following laparotomy under sevoflurane anaesthesia to determine if cognition improvement due to its anti-inflammatory function, and associated with attenuating tau phosphorylation. Thirdly, the effect of varenicline was evaluated by detecting tau phosphorylation and DNA damage induced by laparotomy in aged C57 mice. The results show that the neurotoxic effect of intravenous anaesthesia limits their usage in the further peripheral surgery, since the latter causes remarkable cognitive impairment in both young and aged mice associated with the contribution by neuroinflammation and tau phosphorylation, particularly DNA damage in aged brain. Ibuprofen and varenicline provide effective neuroprotective effect by reversing these changes. JAK/STAT signaling pathway is involved in these processes. All these point out potential therapy strategies for POCD with uncovering its specific pathological characteristics.