Electro-Acupuncture Therapy Alleviates Post-Stroke Insomnia by Regulating Sirt1 and the Nrf2-ARE Pathway

Post-stroke insomnia (PSI) is a common complication following stroke, which seriously affects patients' life quality. Electro-acupuncture (EA) is an innovative form of traditional Chinese acupuncture that combines electricity with needles to achieve the prevention and treatment of diseases. However, there is limited understanding regarding the treatment mechanism of EA in PSI. In our study, we aimed to investigate the role of EA on PSI development. Our study findings indicated that the quality of sleep, levels of neurotransmitters 5-hydroxytryptamine (5-HT) and gamma-aminobutyric acid (γ-GABA), and antioxidant levels showed significant improvement following EA treatment in PSI clinical samples and rat models, while the levels of pro-inflammatory factor interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), and astrocyte damage were notably reduced. Furthermore, it was discovered that the levels of sirtuin 1 (Sirt1) were reduced in PSI, a condition that was significantly ameliorated by EA treatment. Additionally, the inhibition of Sirt1 caused a marked elevation in astrocyte apoptosis, inflammatory response, and oxidative stress. Besides, the nuclear factor E2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway was deactivated in the PSI rat model and Sirt1-silenced cells. However, the suppressive impact was successfully counteracted by EA or estazolam (ES), and the overexpression of Nrf2 partially alleviated the increase in apoptosis, inflammation, and oxidative stress caused by Sirt1 knockdown. Taken together, these findings indicated that EA improved sleep quality and silenced Sirt1-induced apoptosis, inflammation, and oxidative stress in PSI by activating the Nrf2-ARE pathway.