Adiponectin deficiency exaggerates cortical and hippocampal neuroinflammation following sevoflurane exposure

Abstract

As global obesity rate surges, so has the rate of surgical procedures for treating obese individuals. One of the more commonly used anesthetics agent is sevoflurane, but concerns have been raised over its effects on the central nervous system (CNS). Obese patients, often have associated conditions such as diabetes or metabolic syndrome, face higher risks of cognitive dysfunction after surgery due to anesthesia or surgery-related complications. However, the specific mechanisms contributing to this phenomenon have not yet been fully identified. In this context, adiponectin, a molecule derived from adipocytes and known for its anti-inflammatory and neurotrophic properties, emerges as a potential key player in understanding these adverse effects. It is plausible that the association between obesity and cognitive dysfunction is connected to reduced levels of adiponectin in obese individuals, which in turn contributes to the heightened susceptibility to cognitive impairment. We hypothesize that dysregulation of adiponectin can potentially increase the susceptibility of obese individuals to cognitive dysfunction following exposure to sevoflurane. Therefore, the current study evaluated the critical role of adiponectin deficiency in sevoflurane-induced cognitive dysfunction, 4 to 5 months old mice with adiponectin knockout genotype background were treated with sevoflurane and the impact of sevoflurane on both knockout and wild type mice were examined. Moreover, to investigate the neuroprotective effects of adiponectin supplement, adiponectin receptor agonist AdipoRON was administered to mice before sevoflurane exposure. Our results demonstrated that sevoflurane-induced cognitive impairment in adiponectin knockout mice with the modulation of neuroinflammatory response, tau phosphorylation and neuronal apoptosis. In contrast, no significant cognitive impact was observed in wild type mice. With AdipoRON treatment, adiponectin knockout mice were protected against sevoflurane-induced neuroinflammation and cognitive impairment. Our findings indicated an important role for adiponectin deficiency in accentuating neuroinflammation and cognitive impairment following sevoflurane exposure. Consequently, therapeutic strategies that can manipulate adiponectin or adiponectin receptor signaling could significantly improve post-surgical cognitive outcomes in obese patients given sevoflurane anesthesia, as well as serve as a potential treatment for perioperative neurocognitive disorders (PND).