Extracellular vesicle signalling in perioperative neurocognitive disorders

Perioperative neurocognitive disorders (PND), including postoperative delirium, delayed neurocognitive recovery, and postoperative neurocognitive disorder, are important complications in older and vulnerable surgical patients. These conditions are associated with prolonged hospitalization, reduced functional recovery, greater healthcare utilization, and worse longer-term outcomes. Current evidence indicates that PND is not driven by a single mechanism. Instead, systemic inflammation, neurovascular dysfunction, blood-brain barrier injury, glial activation, innate immune signalling, and synaptic injury are all thought to contribute. However, the pathways by which peripheral perioperative stress is translated into sustained postoperative brain dysfunction remain incompletely understood. Extracellular vesicles (EVs) have attracted increasing attention in this context. As lipid bilayer-enclosed particles carrying proteins, lipids, and nucleic acids, EVs are involved in intercellular and inter-organ communication and may provide a mechanistic link between surgical injury and downstream cerebral responses. Emerging evidence suggests that EV-associated signals may participate in the progression from peripheral inflammation and vascular stress to blood-brain barrier dysfunction, neuroinflammation, complement-related synaptic injury, and neuronal dysfunction. In parallel, EV-associated cargo may offer a biologically informative peripheral signal for perioperative studies. This review summarizes the biological basis of EV signalling, major methodological issues relevant to EV research, and current clinical and experimental evidence linking EV-associated signals to PND. It also discusses source-specific EV populations and their potential relevance to perioperative brain injury.