Transcranial magnetic stimulation mitigates perioperative neurocognitive disorders by regulating the function of the glymphatic system

The incidence of perioperative neurocognitive disorders (PND) increase with age, especially within those countries facing great challenge of aging population. However, the mechanism of PND remains elusive, and the lack of precautions has resulted in extended recovery among the elderly. Transcranial magnetic stimulation (TMS) has shown promising therapeutic potential in many neurological disorders such as depression and Alzheimer’s disease. This study aimed to explore the therapeutic potential of TMS on PND mouse model and aged patients. PND mice model were established through exploratory laparotomy on aged mice. We performed Y maze test and novel object recognition test to evaluate the cognitive function after TMS treatment. Intracisternal injection and immunofluorescence staining were conducted to assess the glymphatic system function. We used ELISA, immunofluorescence staining, Western-blotting and TUNEL assay to detect neuroinflammation and neuronal loss. We examined the therapeutic effect of TMS on patients in a clinical trial. PND mice showed improved cognitive functions after TMS treatment. TMS abrogated glymphatic system dysfunction and aquaporin-4 (AQP4) translocation, the key pathological changes that lead to cognitive decline, in PND mice. Moreover, TMS alleviated neuroinflammation and apoptosis in PND mice. We further found that inhibition of glymphatic system function blocked the ameliorative effects of TMS on postoperative cognitive function, neuroinflammation, and neuronal damage. Patients who received TMS showed improved memory function 7 days after surgery and obtained better Abbreviated Mental Test Score 30 days post-operation. Our study indicates the great therapeutic potentials of TMS in anesthesia- and surgery-induced cognitive impairment and pathological changes. Trial registration ChiCTR2200057080.