CONTEMPORARY STRATEGIES FOR ANTIOXIDANT THERAPY IN CEREBRAL ISCHEMIA AND TRAUMATIC BRAIN INJURY

Abstract

Acute cerebral insufficiency, as observed in conditions such as cerebral ischemia and traumatic brain injury (TBI), is accompanied by pronounced oxidative stress and mitochondrial dysfunction, triggering cascades of lipid peroxidation, neuroinflammation, and apoptosis. Current antioxidant therapeutic strategies focus on two main approaches: (1) direct free radical scavenging, exemplified by edaravone and the combination edaravone–dexborneol, and (2) mitochondrial-targeted interventions, including mitochondria-directed molecules and metabolic support. Between 2023 and 2025, emerging clinical evidence on edaravone–dexborneol in acute cerebral insufficiency—including meta-analyses and efficacy and safety studies—indicates potential improvements in functional outcomes when incorporated into standard therapy, particularly during early stages, with a favorable safety profile. However, international guidelines have yet to formally adopt these agents, aside from national recommendations in certain countries (e.g., Japan), underscoring the need for further multicenter randomized controlled trials and harmonization of treatment protocols. In TBI, mitochondrial-focused interventions, encompassing antioxidants and metabolic substrates, appear particularly promising, as supported by systematic reviews and observed dynamics of oxidative and nitrosative stress biomarkers in preclinical models; nevertheless, the clinical evidence remains limited and heterogeneous. This review synthesizes the mechanistic rationale, current clinical findings, and optimal therapeutic windows (first hours to days post-stroke and early to subacute phases in TBI), while outlining a framework for personalized therapy based on injury severity, reperfusion status, and patient metabolic profile.