Therapeutic potential of hypoxic conditioning technology in post-stroke rehabilitation: from molecular and physiological mechanisms to clinical practice (narrative review)

Acute cerebrovascular accident remains one of the leading causes of disability and mortality, with persistent risks of developing and progressing cognitive and functional impairments even in the late recovery period. The urgency of this issue drives the search for innovative approaches to rehabilitation and quality-of-life improvement in such patients. Interval hypoxic conditioning technology, particularly in the form of intermittent hypoxic–hyperoxic training, represents a promising non-pharmacological approach capable of enhancing neuroplasticity, synaptogenesis, and cerebral hemodynamics. The aim of this review is to analyze the therapeutic potential of intermittent hypoxic–hyperoxic training in the context of post-acute cerebrovascular accident rehabilitation, including its effects on molecular adaptation mechanisms, angiogenesis, and functional recovery. Methodology involved a systematic search in PubMed, Scopus, eLIBRARY.RU, and other databases, focusing on studies related to hypoxic preconditioning, neuroprotection, and clinical outcomes. The results demonstrate that intermittent hypoxic–hyperoxic training activates HIF-1α–dependent pathways, stimulating angiogenesis through VEGF and neurogenesis via BDNF, as confirmed by both experimental and clinical data. Moderate intermittent hypoxia (9%–16% O₂) optimizes the redox balance, suppresses proinflammatory cytokines (IL-6, TNF-α), and enhances antioxidant defense through Nrf2, correlating with reduced ischemic damage. Clinically, intermittent hypoxic–hyperoxic training procedures improve cognitive function (memory, attention) and motor performance, especially when combined with aerobic training, increasing exercise tolerance (e.g., 15%–20% improvement in the six-minute walk test) and quality of life. Cardioprotective effects include normalization of blood pressure and reduction of oxidative stress markers (malondialdehyde), which is particularly relevant for patients with multimorbidity. Integration of intermittent hypoxic–hyperoxic training into multimodal rehabilitation programs contributes to synergistic effects, enhancing neurovascular remodeling. Despite its promise, further optimization of personalized protocols considering age and comorbidities, as well as randomized trials to assess long-term safety, are required. This review addresses neurologists, molecular biologists, and rehabilitation specialists, highlighting the translational potential of intermittent hypoxic–hyperoxic training into clinical practice given further validation of its efficacy.