{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T21:44:01Z","timestamp":1794433441317,"version":"4.9.1"},"reference-count":157,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T00:00:00Z","timestamp":1736726400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:p>Ischemic stroke, which is characterized by hypoxia and ischemia, triggers a cascade of injury responses, including neurotoxicity, inflammation, oxidative stress, disruption of the blood\u2013brain barrier, and neuronal death. In this context, tryptophan metabolites and enzymes, which are synthesized through the kynurenine and 5-hydroxytryptamine pathways, play dual roles. The delicate balance between neurotoxic and neuroprotective substances is a crucial factor influencing the progression of ischemic stroke. Neuroprotective metabolites, such as kynurenic acid, exert their effects through various mechanisms, including competitive blockade of N-methyl-D-aspartate receptors, modulation of \u03b17 nicotinic acetylcholine receptors, and scavenging of reactive oxygen species. In contrast, neurotoxic substances such as quinolinic acid can hinder the development of vascular glucose transporter proteins, induce neurotoxicity mediated by reactive oxygen species, and disrupt mitochondrial function. Additionally, the enzymes involved in tryptophan metabolism play major roles in these processes. Indoleamine 2,3-dioxygenase in the kynurenine pathway and tryptophan hydroxylase in the 5-hydroxytryptamine pathway influence neuroinflammation and brain homeostasis. Consequently, the metabolites generated through tryptophan metabolism have substantial effects on the development and progression of ischemic stroke. Stroke treatment aims to restore the balance of various metabolite levels; however, precise regulation of tryptophan metabolism within the central nervous system remains a major challenge for the treatment of ischemic stroke. Therefore, this review aimed to elucidate the complex interactions between tryptophan metabolites and enzymes in ischemic stroke and develop targeted therapies that can restore the delicate balance between neurotoxicity and neuroprotection.<\/jats:p>","DOI":"10.4103\/nrr.nrr-d-24-00777","type":"journal-article","created":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T11:02:15Z","timestamp":1746529335000},"page":"466-477","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":23,"title":["Tryptophan metabolism and ischemic stroke: An intricate balance"],"prefix":"10.4103","volume":"21","author":[{"given":"Chongjie","family":"Yao","sequence":"first","affiliation":[{"name":"Rehabilitation Department, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China"},{"name":"School of Acupuncture-Moxibustion and Tuina, Shanghai University of Traditional Chinese Medicine, Shanghai, 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