Esketamine Prevents Postoperative Emotional and Cognitive Dysfunction by Suppressing Microglial M1 Polarization and Regulating the BDNF-TrkB Pathway in Ageing Rats with Preoperative Sleep Disturbance
Yuxin Wen, Jiawen Xu, Jiahong Shen, Zili Tang, Shuxin Li, Qun Zhang, Jiaqi Li, Jianliang Sun
Molecular Neurobiology January 15, 2024 DOI: 10.1007/s12035-023-03860-4 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Aged mice |
| Intervention | Esketamine |
| Topics | Esketamine Ketamine |
| Citations | 57 |
| Key points | Esketamine reversed postoperative depression and cognitive dysfunction caused by preoperative sleep disturbance by inhibiting microglial M1 polarization and restoring BDNF-TrkB signaling and hippocampal synaptic plasticity. |
Abstract
Postoperative depression (POD) and postoperative cognitive dysfunction (POCD) have placed heavy burden on patients’ physical and mental health in recent years. Sleep disturbance before surgery is a common phenomenon that has been increasingly believed to affect patients’ recovery, especially in aged patients, while little attention has been paid to sleep disruption before surgery and the potential mechanism remains ambiguous. Ketamine has been reported to attenuate POCD after cardiac surgery and elicit rapid-acting and sustained antidepressant actions. The present study aimed to clarify the effect of esketamine’s (the S-enantiomer of ketamine) protective effects and possible mechanisms of action in POCD and POD. Our results showed that sleep disturbance before surgery exacerbated microglial M1 polarization and microglial BDNF-TrkB signalling dysfunction induced by surgery, resulting in postoperative emotional changes and cognitive impairments. Notably, treatment with esketamine reversed the behavioural abnormalities through inhibiting the M1 polarization of microglia and the inflammatory response thus improving BDNF-TrkB signalling in vivo and vitro. In addition, esketamine administration also reversed the impaired hippocampal synaptic plasticity which has been perturbed by sleep disturbance and surgery. These findings warrant further investigations into the interplay of esketamine and may provide novel ideas for the implication of preoperative preparations and the prevention of postoperative brain-related complications.
Comparable studies
Other preclinical and animal studies on esketamine, most cited first.
Citations in the library
Cited by 11
- The effect of low-dose esketamine on maternal depression after cesarean delivery. Journal of psychosomatic obstetrics and gynaecology December 1, 2025
- Effects of Esketamine on Postoperative Delirium and Postoperative Cognitive Function in Elderly Gastrointestinal Tumor Patients with Preoperative Anxiety Drug Design, Development and Therapy October 1, 2025
- Esketamine alleviates cognitive impairment signs induced by modified electroconvulsive therapy in a depression rat model via the KLF4/p38 MAPK pathway. Journal of Affective Disorders May 1, 2025
- Effect of Esketamine on Postoperative Delirium and Inflammatory Response in Patients Undergoing Off-Pump Coronary Artery Bypass Grafting: A Randomized Controlled Study. Journal of Cardiothoracic and Vascular Anesthesia April 10, 2025
- Efficacy of esketamine after cesarean section for women with symptoms of prenatal depression: A randomized controlled trial. Psychiatry Research November 16, 2025
and 6 more in the library
Cites 9
- R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Translational Psychiatry September 1, 2015
- Taming the Ketamine Tiger Anesthesiology August 6, 2010
- Rapid‐acting antidepressant ketamine, its metabolites and other candidates: A historical overview and future perspective Psychiatry and Clinical Neurosciences June 19, 2019
- Essential role of microglial transforming growth factor-β1 in antidepressant actions of (R)-ketamine and the novel antidepressant TGF-β1 Translational Psychiatry January 27, 2020
- Esketamine alleviates postoperative depression-like behavior through anti-inflammatory actions in mouse prefrontal cortex. Journal of Affective Disorders April 1, 2022
and 4 more in the library