Is adiponectin deficiency a critical factor for sevoflurane induced neurocognitive dysfunction?

Abstract

The global rise in obesity has resulted in an increase in the number of surgical procedures under general anaesthesia in this patient population. Sevoflurane is one of the most widely used volatile aesthetic agent in developed countries. Clinical evidence suggests obesity is a risk factor for cognitive dysfunction after surgery. Experimentally animals with pre-existing cerebral insults are more susceptible to the neurotoxic effects of sevoflurane compared with their normal counterparts. Nevertheless, the mechanism underlying this vulnerability in obese subjects is not fully elucidated.Obesity is associated with a significant reduction of adiponectin, an adipocyte-derived molecule with neurotrophic and anti-inflammatory properties. Adiponectin receptors are abundantly expressed in hippocampus and cortex. Moreover, adiponectin deficiency is associated with exacerbation of neuroinflammation, neuronal dysfunction and cognitive impairment in animal models of obesity and Alzheimer’s disease. Based on these observations, we hypothesize that adiponectin deficiency plays a critical role in sevoflurane induced cognitive dysfunction in obese subjects accounting for its higher incidence in this patient population. With diminished protective effects from adiponectin, sevoflurane may further exacerbate neuroinflammation by activating the proinflammatory pathways and increase the synthesis of inflammatory cytokines in the brain, leading to significant neuronal dysfunction and cognitive impairment. On the other hand, treatment with adiponectin or adiponectin receptor agonists may have therapeutic potential in minimizing the risk of postoperative cognitive impairment in obese patients undergoing surgery. As an oral adiponectin agonist is available, it can be expeditiously evaluated in clinical trials if our hypothesis is validated.