Melatonin reverses neuroinflammation-induced postoperative cognitive dysfunction via microglial exosomes

Postoperative cognitive dysfunction (POCD) induced by surgical anesthesia is closely related to activated microglia-mediated central nervous inflammation. Melatonin is beneficial in the prevention and treatment of postoperative cognitive dysfunction (POD), but the specific mechanism is not clear. Previous studies have demonstrated that melatonin can not only promote exosome production, but also change the quality and content of exosome-delivered substances, which act on neurons and exert anti-inflammatory repair effects. We hypothesize that melatonin improves postoperative cognitive dysfunction by attenuating microglial M1 type activation, inducing microglial exosome release and acting on neurons to exert central anti-inflammatory repair. In this study, we used a rat POCD model and a neuroinflammatory cell model to explore the molecular mechanism by which melatonin improves postoperative cognitive dysfunction. Our study confirms that melatonin promotes microglial polarization to M2 type, increases microglial exosome release, and improves the ability of exosomes to regulate neuronal mitochondria, helping to reverse POCD-like behavior in rats. These data extend the hierarchies of melatonin action and provide new theoretical support for the POCD preventive and therapeutic effects of melatonin.