The effect of sevoflurane on cognitive and synaptic function

Abstract

Advances in surgical and anaesthetic care have improved long term survival after surgery but in doing so have uncovered incidentally the phenomenon of postoperative cognitive dysfunction (POCD). The mechanisms underlying the development of POCD is still not fully elucidated but is currently thought to involve systemic inflammation induced surgical trauma, leading to neuroinflammation. As surgery almost always requires to be performed under anaesthesia, it is of great interest to evaluate any effects and/or interaction, if any, between anaesthesia and surgically induced systemic inflammation has on cognitive and synaptic function. This in turn might provide insights into the development and progression of POCD. Young adult C57BL/6N male mice were exposed to sevoflurane, with or without concomitant lipopolysaccharide injection. Sevoflurane was chosen for anaesthesia as it is widely used in clinical practice and lipopolysaccharide was chosen to mimic surgically induced systemic inflammation in order to avoid postoperative pain associated motor impairment that might interference with motor based cognitive testing. The results show that sevoflurane anaesthesia at clinically relevant concentrations is associated with short-term impairment of working memory and changes in synaptic function in the enriched synaptosomal fraction of the frontal cortex. There was an additive effect of the two treatments on systemic inflammation and neuroinflammation but these were not translated into significant changes in cognitive and synaptic function. Overall, there was a lack of strong evidence to support an important contribution of sevoflurane towards the development of POCD using this animal model.