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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\u2019s 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.<\/jats:p>","DOI":"10.3389\/fphar.2026.1960869","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T05:36:28Z","timestamp":1789709788000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical research progress of esketamine in perioperative neuroprotection: from mechanisms to therapeutic neuroprotection"],"prefix":"10.3389","volume":"17","author":[{"given":"Hua","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, People\u2019s Hospital of Longhua","place":["ShenZhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ce","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, People\u2019s Hospital of Longhua","place":["ShenZhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"YingDong","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, People\u2019s Hospital of Longhua","place":["ShenZhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, People\u2019s Hospital of Longhua","place":["ShenZhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1007\/s44446-026-00101-2","article-title":"Phytochemicals with potential NMDAR-inhibitory activities: a review of neuroprotective mechanisms against excitotoxicity","volume":"34","author":"Alamoudi","year":"2026","journal-title":"Saudi Pharm. 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