Surgery and anesthesia can induce an inflammatory response in the central nervous system, causing neuronal damage and dysfunction, ultimately leading to the occurrence of POCD.

① Sleep disorders can promote the expression of complement C3 and C5 in the hippocampus, activate microglia, and upregulate pro-inflammatory factors, thus worsening neuroinflammation. Pro-inflammatory factors can also promote cell apoptosis and neuron phagocytosis.

②Neuroinflammation can reversely regulate the sleep process and affect endogenous sleep regulatory molecules (such as adenosine to regulate sleep homeostasis and cytokines to promote non-rapid movement sleep), and the two form a vicious positive feedback loop.

Preoperative sleep deprivation can induce hippocampal inflammatory responses and impair cognitive abilities in aged mice. Sevoflurane anesthesia downregulates the expression of peroxisome proliferator-activated receptor γ in the hippocampus, causing neuroinflammation and leading to cognitive decline in OSA mice.

This suggests that sleep disorders, surgery, and anesthesia play a role in the development of POCD by triggering neuroinflammation, suggesting that key triggers of neuroinflammation may serve as potential targets for preventing POCD.

Due to the high basal oxygen consumption and low antioxidant levels of the brain, the nervous system is susceptible to oxidative stress, and the POCD hippocampus shows oxidative stress damage changes such as increased reactive oxygen species (ROS).

Sleep disorders can cause an imbalance between oxidative and antioxidant effects, leading to oxidative stress. Mitochondria play a central role in this process, producing ROS to cause damage. Mitochondria ROS can also regulate sleep-wake states. Increased expression of antioxidant genes shortens sleep time, and reducing ROS levels promotes wakefulness.

The interaction between sleep disorders and oxidative stress can cause cognitive-related pathological changes, such as β-amyloid deposition, and participate in the POCD process. Reducing hippocampal oxidative stress can improve postoperative cognitive function in sleep-deprived rats.

Pathological deposition of brain proteins (such as Aβ and tau protein) is a key pathological feature of various cognitive impairment diseases. Aβ deposition plays an important role in POCD and can be used as a cerebrospinal fluid biomarker to predict the occurrence of POCD.

Sleep disorders can interfere with Aβ clearance and promote Aβ accumulation. On the contrary, Aβ accumulation can also worsen sleep disorders. The sleep disorder in the background of POCD and the self-reinforcing mechanism of Aβ deposition need further verification.

Hyperphosphorylation of Tau protein is involved in the pathogenesis of PoCD. Sleep deprivation and sleep-wake cycle disorders will increase brain tau protein levels. Mice carrying pathological tau protein show changes in sleep patterns.

The lymphoid system is responsible for clearing neurotoxic compounds from the brain. Anesthetic drugs and postoperative systemic inflammation have an inhibitory effect on its function. Stabilizing the acute state of aquaporin can improve the lymphoid system and relieve POCD symptoms.

Sleep disorders can also damage lymphoid drainage, regulate AQP4 expression and affect cognitive behavior.