Clinical research progress of esketamine in perioperative neuroprotection: from mechanisms to therapeutic neuroprotection

During the perioperative period, factors such as ischemia-reperfusion injury, neuroinflammation, and cognitive dysfunction not only significantly affect postoperative recovery, but also are the main causes of postoperative disability and perioperative death. Esketamine is the R-enantiomer of ketamine, possessing N-methyl-D-aspartate (NMDA) receptor antagonistic activity along with multiple anti-inflammatory, anti-apoptotic, and antioxidant properties. Compared to racemic ketamine, esketamine is more potent, acts more rapidly, causes mild respiratory depression, and induces fewer adverse neuropsychiatric effects, making it a promising agent for perioperative neuroprotection. This review aims to provide a comprehensive overview of esketamine’s neuroprotective mechanisms and clinical applications in the perioperative setting, offering insights into future research directions that may advance therapeutic neuroprotection and improve surgical patient outcomes.