Perioperative neurocognitive disorders: Advances in molecular mechanisms and bioactive molecules

Perioperative neurocognitive disorders (PNDs) are common complications following surgery, especially in elderly patients, and are characterized by memory loss, attention deficits, and impaired executive function. The pathogenesis of PNDs involves a complex interplay of neuroinflammation, neurotransmitter imbalance, epigenetic modifications, and gut–brain axis disruption. This review summarizes the latest findings on the mechanisms underlying PNDs, with a focus on microglial activation, interleukin imbalance, and NLRP3 inflammasome-mediated pyroptosis. We further discuss how anesthesia and surgery impair synaptic plasticity by disrupting neurotransmitter systems, particularly GABAA and NMDA receptors. Additionally, we highlight the roles of epigenetic regulation and gut microbiota dysbiosis in sustaining neuroinflammation and cognitive deficits. Finally, we explore potential therapeutic strategies, including bioactive compounds and neuroprotective agents, offering new directions for the prevention and treatment of PNDs.