Protective effect of dapsone on cognitive impairment induced by propofol involves hippocampal autophagy

Abstract Post-operative cognitive dysfunction (POCD) is a commonly seen postoperative complication in elderly patients and its underlying mechanisms are still unclear. Autophagy, a degradation mechanism of cellular components, is required for cell survival and many physiological processes. Although propofol is one of the most commonly used intravenous anesthetics, investigations into its mechanisms and effects on cognition in aged rodents are relatively scarce. In this study, we evaluate the influence of propofol on learning and memory, and identify the potential role of hippocampal autophagy in propofol-induced cognitive alterations in aged rats. The results demonstrate that 4 h propofol exposure significantly impaired cognitive performance through the inhibition of hippocampal autophagy. Diaminodiphenyl sulfone (dapsone, DDS), which was used as an anti-leprosy drug, has been found to have neuroprotective effects. We have previously demonstrated that DDS can improve surgical stress induced depression- and anxiety-like behavior. We therefore aimed to investigate the effects of DDS on propofol-induced cognitive dysfunction and associated hippocampal autophagy responses. Pretreatment with 5 mg/kg or 10 mg/kg body weight DDS significantly improved the behavioral disorder and upregulated the inhibited autophagic response in aged rats. Our exploration is the first to establish an in vivo link between central autophagy and cognitive dysfunction in aged hippocampus after propofol anesthesia and demonstrate that the prophylactic effect of DDS on the cognitive impairment induced by propofol involves autophagy. These findings may imply a potential novel target for the treatment in patients with propofol anesthesia-induced cognitive impairment.