Escitalopram Relieves Sleep Anxiety in Patients with Cerebral Small Vessel Disease Sleep Disorder by Downregulating the Nrf2/ARE Signaling Pathway.

Objective: Nrf2/ARE signaling pathway is reported to alleviate sleep anxiety in patients with sleep disorders. This study aimed at exploring the effect of escitalopram (ESC) on sleep anxiety in patients with cerebral small vessel disease (CSVD) and sleep disorder and its correlation with the Nrf2/ARE signaling pathway.

Methods: In the present study, we enrolled 80 CSVD patients (disease group) and 40 healthy patients (control group) in our hospital. The CSVD patients were classified into ESC treatment group and conventional treatment group and administered ESC and diazepam, respectively. After treatment, the patients' sleep quality was monitored within three months, and their symptoms were evaluated. Additionally, a mouse model of CSVD was set up, and the rats received intragastric administration of low, moderate, and high dosage of ESC or thymoquinone. The morphology of nerve cells and cognitive functions in the rat hippocampus were seen. TUNEL staining was conducted to detect nerve cell apoptosis and RT-qPCR, and Western blot analyses determined the expression levels of Nrf2 and ARE.

Results: Compared with conventional treatment group, the patients of ESC treatment group had shorter symptom improvement time and better sleep quality with a lower AHI and PSQI score. On the other hand, in the animal model, ESC treatment alleviated sleep disorders in CSVD rats, improved cognition and serum TNF-α levels, and protected nerve cells. Administration of ESC eliminated the expressions of Nrf2 and ARE and reduced nerve cell apoptosis dose-dependently. Moreover, Nrf2/ARE pathway activator (Danshensu) decreased rat sleep time and the level of serum TNF-α with more cell atrophy, while Nrf2/ARE pathway inhibitor (ML385) greatly improved sleep quality of CSVD rats.

Conclusion: ESC can effectively relieve sleep anxiety in patients with CSVD and sleep disorders through downregulating the Nrf2/ARE signaling pathway. ESC treatment increases patient's sleep time and serum TNF-α levels and attenuates nerve cell damage, further improving the patient's sleep quality.