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Postoperative sleep disturbance (PSD) often occurs in elderly patients after major surgery and exerts harmful effects on postoperative recovery. PSD may increase the incidence of postoperative fatigue, severe anxiety and depression, pain sensitivity, and cognitive dysfunction, which can cause or aggravate neurodegenerative diseases via amyloid aggregation and tau accumulation. Exosomes are important carriers that mediate the transfer of active substances and genetic information among cells. Recent evidence has shown that exosomes are involved in the pathogenesis of end-organ morbidity caused by sleep disorders via increasing amyloid plaque formation, transmitting tau protein, regulating neuroinflammation, and increasing blood-brain barrier permeability. Additionally, exosomes may be useful for delivering therapeutic genetic materials, such as microRNAs (miRNAs) and proteins, to exert neuroprotective effects and reduce cognitive impairment. However, the molecular mechanisms underlying this process remain to be fully elucidated. This review focuses on exosome-related pathways and the modulatory role of exosomal miRNAs on the pathogenesis of sleep disturbance and neurodegeneration. Moreover, we discuss the advantages of reducing neurotoxic proteins via exosomal intervention and miRNA regulation. Future research in exosome administration may offer new insights into PSD-related pathomechanisms and therapeutics.

Roles of Exosomes and Exosomal MicroRNAs in Postoperative Sleep Disturbance