{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T05:28:11Z","timestamp":1786512491539,"version":"build-2736575974"},"reference-count":65,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hangzhou City Science and Technology Special Project to Support the Development of Biomedicine and Health Industries","award":["2024WJC098"],"award-info":[{"award-number":["2024WJC098"]}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p>\n                    Reperfusion therapies, including intravenous thrombolysis and endovascular treatment (EVT), are central to acute ischemic stroke (AIS) management; however, ischemia\u2013reperfusion injury may limit recovery despite successful recanalization. This structured narrative review compares the clinical evidence, safety signals, and mechanistic literature for edaravone, butylphthalide (NBP), and the fixed-dose combination edaravone-dexborneol (EDB) as adjunctive neuroprotective approaches. The evidence base is heterogeneous with respect to population, background reperfusion treatment, outcome timing, and geographical setting. In TASTE-2, EDB administered before EVT was associated with a modest increase in 90-day functional independence versus placebo (55.0% vs. 49.6%,\n                    <jats:italic>p<\/jats:italic>\n                    \u202f=\u202f0.05), without an apparent safety signal; bridging alteplase was permitted in a subset of participants. In the BAST trial, NBP improved the prespecified 90-day functional outcome versus placebo among patients receiving intravenous thrombolysis and\/or EVT (56.7% vs. 44.0%). Observational studies and meta-analyses provide supportive but non-confirmatory evidence for edaravone. Network meta-analyses generate relative rankings at individual endpoints, but indirect comparisons and differing outcome networks preclude definitive between-agent selection. Mechanistic studies indicate overlapping antioxidant, anti-inflammatory, mitochondrial, and neurovascular effects rather than exclusive pathway regulation. Biomarker and imaging approaches, including exploratory GFAP and UCH-L1 measurements, are promising research tools but are not yet validated for treatment selection in AIS. Accordingly, these agents should be regarded as candidates for further evidence-informed adjunctive use; future trials are needed to define reproducible patient-selection and treatment-timing strategies.\n                  <\/jats:p>","DOI":"10.3389\/fneur.2026.1899933","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T04:42:53Z","timestamp":1786509773000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Adjuvant neuroprotective therapies for acute ischemic stroke in the reperfusion era: a comparative narrative review of clinical evidence for edaravone, edaravone-dexborneol, and butylphthalide"],"prefix":"10.3389","volume":"17","author":[{"given":"Weiqing","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Neurology, First People's Hospital of Jiande City","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junsen","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Scientific Research, First People's Hospital of Jiande City","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"e70705","DOI":"10.1002\/brb3.70705","article-title":"Current advancement and patient outcomes in reperfusion brain injuries after stroke: a comparative analysis of thrombolysis and thrombectomy","volume":"15","author":"Ayomide","year":"2025","journal-title":"Brain Behav"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"450","DOI":"10.11477\/mf.1416202358","article-title":"Therapeutic strategies for ischemic stroke","volume":"75","author":"Nagata","year":"2023","journal-title":"Brain 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