Mechanisms and therapeutic potential of hyperbaric oxygen inducing autophagy in cerebral ischemia-reperfusion injury.

Cerebral ischemia-reperfusion injury (CIRI) is a complex pathological process involving oxidative stress, inflammation, and dysregulated autophagy. Hyperbaric oxygen therapy (HBO) has emerged as a promising intervention that mitigates neuronal injury by modulating autophagy. This review summarizes current evidence on the mechanisms of HBO through the AMPK-mTOR, HIF-1α-mTOR, and PI3K-AKT pathways, emphasizing its dual role in either promoting cell survival or exacerbating injury depending on autophagic flux. Preclinical studies demonstrate that HBO upregulates LC3-II and Beclin-1 while downregulating p62, indicating enhanced autophagy, whereas clinical trials (e.g., OPENS-2) suggest synergistic effects when combined with endovascular therapy. However, challenges remain regarding the lack of standardized biomarkers and optimal treatment parameters. Future research should focus on integrating HBO with specific autophagy modulators and conducting large-scale randomized controlled trials to validate its therapeutic potential in CIRI.