Adjuvant neuroprotective therapies for acute ischemic stroke in the reperfusion era: a comparative narrative review of clinical evidence for edaravone, edaravone-dexborneol, and butylphthalide.

Reperfusion therapies, including intravenous thrombolysis and endovascular treatment (EVT), are central to acute ischemic stroke (AIS) management; however, ischemia-reperfusion 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%, p = 0.05), 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.