Therapeutic Potential of Hypoxic Conditioning Technology in Post-Stroke Recovery: From Molecular and Physiological Mechanisms to Clinical Practice (A Narrative Review)



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Abstract

Acute cerebral circulatory failure (ACCF) remains one of the leading causes of disability and mortality, retaining the risks of development and progression of cognitive and functional impairment even in the late recovery period. The acuteness of the problem actualizes the necessity to search for innovative approaches to rehabilitation and maintenance of a satisfactory quality of life for such patients. The technology of hypoxic conditioning (HC) in interval modes, in particular, in the form of a course of procedures of interval hypoxic-hyperoxic exposures (IHHE), is a promising non-pharmacological approach capable of potentiating the processes of neuroplasticity, synaptogenesis, and cerebral hemodynamics. This review aims to analyse the therapeutic potential of IHHE in the context of post-ACCF rehabilitation, including its effects on molecular mechanisms of adaptation, angiogenesis and functional recovery. The methodology includes a systematic search in PubMed, Scopus, eLIBRARY.RU and other databases, with a focus on studies related to hypoxic preconditioning, neuroprotection and clinical outcomes. The results demonstrate that IHHE activates HIF-1α-dependent pathways, stimulating angiogenesis via VEGF and neurogenesis via BDNF, which is supported by experimental and clinical data. Moderate hypoxia (9-16% O₂) optimizes redox balance by suppressing pro-inflammatory cytokines (IL-6, TNF-α) and enhancing antioxidant defence via Nrf2, which correlates with a reduction in ischaemic damage volume. Clinically, IGGE improves cognitive performance (memory, attention) and motor function, especially when combined with aerobic exercise training, improving exercise tolerance (15-20% increase in 6MWT distance) and quality of life. Cardioprotective effects include normalization of blood pressure and reduction of oxidative stress markers (malonyl dialdehyde), which is significant in patients with polymorbidity. Integrating IHHE into multimodal rehabilitation programmes promotes synergistic methods, enhancing neurovascular remodeling. Although promising, optimization of personalized protocols, considering age and comorbid pathologies, and randomized trials to assess long-term safety are required. This review is addressed to neurologists, molecular biologists and rehabilitation specialists, emphasising the translational potential of IHHE into clinical practice, subject to further validation of its efficacy.

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About the authors

Malachi Nyamukondiwa

I.M. Sechenov First Moscow State Medical University of the Ministry of Health of Russia (Sechenov University)

Author for correspondence.
Email: nmalachi8@gmail.com
ORCID iD: 0000-0002-9834-2505

PhD student

Russian Federation, I.M. Sechenov First Moscow State Medical University (Sechenov University), 8 Trubezkaya Str., b. 2, Moscow, 119991, Russian Federation

Elizaveta Sergeevna Koneva

I.M. Sechenov First Moscow State Medical University of the Ministry of Health of Russia (Sechenov University)

Email: elizaveta.coneva@yandex.ru
ORCID iD: 0000-0002-9859-194X
SPIN-code: 8200-2155

Doctor of Medical Sciences, Associate Professor, Professor

Russian Federation, 8 Trubezkaya Str., b. 2, Moscow, 119991, Russian Federation; 2 Otradnoye, b. 1., Krasnogorsk, 143442, Moscow region, Russian Federation

Oleg Stanislavovich Glazachev

I.M. Sechenov First Moscow State Medical University of the Ministry of Health of Russia (Sechenov University)

Email: glazachev@mail.ru
ORCID iD: 0000-0001-9960-6608
SPIN-code: 6168-2110

Doctor of Medical Sciences, Professor, Professor

Russian Federation, 8 Trubezkaya Str., b. 2, Moscow, 119991, Russian Federation

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СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
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СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ЭЛ № ФС 77 - 80650 от 15.03.2021 г.