I.P. Pavlov Journal of Higher Nervous ActivityI.P. Pavlov Journal of Higher Nervous ActivityЖурнал высшей нервной деятельности им. И.П. Павлова0044-46773034-5316The Russian Academy of Sciences68750610.31857/S0044467725040023ОБЗОРЫ И ТЕОРЕТИЧЕСКИЕ СТАТЬИResearch ArticlePeriodic hypoxia: physiological effects and possible molecular mechanismsПериодическая гипоксия: физиологические эффекты и возможные молекулярные механизмыSimonenkoS. D.СимоненкоС. Д.
Russian Federation

Biology faculty

Биологический факультет

nglevitskaya@gmail.comSebentsovaЕ. A.СебенцоваЕ. А.
Russian Federation

Biology faculty

Биологический факультет

nglevitskaya@gmail.comKabiolskyI. A.КабиольскийИ. А.
Russian Federation

Biology faculty

Биологический факультет

nglevitskaya@gmail.comLevitskayaN. G.ЛевицкаяН. Г.
Russian Federation

Biology faculty

Биологический факультет

nglevitskaya@gmail.comLomonosov Moscow State UniversityМосковский государственный университет им. М.В. ЛомоносоваNational Research Centre “Kurchatov Institute”Национальный исследовательский центр «Курчатовский институт»150820257543974191407202514072025Copyright ©; 2025, Russian Academy of SciencesCopyright ©; 2025, Российская академия наук2025Russian Academy of SciencesРоссийская академия наукhttps://transsyst.ru/0044-4677/article/view/687506

Periodic hypoxia includes periods of low oxygen content, interspersed with periods of reoxygenation. Periodic hypoxia is usually associated with pathological conditions and is considered as a negative stimulus leading to disorders of cognitive functions, the cardiovascular system, respiration and metabolism. It is the most important pathophysiological element of sleep apnea syndrome, which is accompanied by the development of inflammation and oxidative stress. On the other hand, periodic hypoxia, unrelated to sleep apnea, has a positive or negative effect on the body, depending on the intensity, duration and number and frequency of hypoxic exposures. In medicine, periodic hypoxia is used to improve health and enhance performance and is a non-pharmacological treatment for a number of diseases. The goal of the present review is to summarize clinical and experimental data on the effect of periodic hypoxemic hypoxia on the adult body. Special attention is paid to the effect of periodic hypoxia on cognitive functions. The review discusses the molecular mechanisms by which periodic hypoxia can trigger a cascade of intracellular reactions leading to either beneficial or pathological effects.

Периодическая гипоксия включает в себя периоды пониженного содержания кислорода, перемежающиеся периодами реоксигенации. Периодическая гипоксия обычно ассоциируется с патологическими состояниями и рассматривается как негативный стимул, приводящий к нарушениям когнитивных функций, работы сердечно-сосудистой системы, дыхания и обмена веществ. Она является важнейшим патофизиологическим элементом синдрома апноэ во сне, который сопровождается развитием воспаления и окислительным стрессом. С другой стороны, периодическая гипоксия, не связанная с апноэ сна, оказывает положительное или отрицательное влияние на организм в зависимости от интенсивности, продолжительности, количества и частоты гипоксических воздействий. В медицине контролируемая интервальная гипоксия используется для улучшения здоровья и повышения работоспособности и является немедикаментозным средством лечения ряда заболеваний. Целью представленного обзора является обобщение клинических и экспериментальных данных о влиянии периодической гипоксемической гипоксии на взрослый организм. Особое внимание уделено влиянию периодической гипоксии на когнитивные функции. В обзоре обсуждаются молекулярные механизмы, с помощью которых периодическая гипоксия может запускать каскад внутриклеточных реакций, приводящих либо к благоприятным, либо к патологическим эффектам.

periodic hypoxiahypoxia-inducible factorsnuclear factor NF-kBoxidative stressinflammationcognitive functionsпериодическая гипоксияфакторыиндуцируемые гипоксиейядерный фактор NF-κBокислительный стрессвоспалениекогнитивные функцииРоссийский научный фондRussian Science Foundation24-25-00097Барбашова З.И. Акклиматизация к гипоксии и ее физиологические механизмы. М., Л.: изд-во АН СССР. 1960. 216 с.Бондаренко Н.Н., Хомутов Е.В., Ряполова Т.Л., Кишеня М.С., Игнатенко Т.С., Толстой В.А., Евтушенко И.С., Туманова С.В. Молекулярно-клеточные механизмы ответа организма на гипоксию. Ульяновский медико-биологический журнал. 2023. 2: 6–29. (Bondarenko N.N., Khomutov E.V., Ryapolova T.L., Kishenya M.S., Ignatenko T.S., Tolstoy V.A., Evtushenko I.S., Tumanova S.V. Molecular and cellular mechanisms of hypoxic response. Ul'yanovskiy mediko-biologicheskiy zhurnal. 2023; 2: 6–29. (in Russian).Глазачев О.С., Геппе Н.А., Тимофеев Ю.С., Самарцева В.Г., Дудник Е.Н., Запара М.А., Чебышева С.Н. Индикаторы индивидуальной устойчивости к гипоксии – путь оптимизации применения гипоксических тренировок у детей. Рос. Вестн. Перинатол. и педиатр. 2020. 65(4): 78–84. (Glazachev O.S., Geppe N.A., Timofeev Yu.S., Samartseva V.G., Dudnik E.N., Zapara M.A., Chebysheva S.N. Indicators of individual hypoxia resistance – a way to optimize hypoxic training for children. Ros. Vestn. Perinatol. i Pediatr. 2020; 65(4): 78–84 (in Russian).Евсеева М.А., Евсеев А.В., Правдивцев В.А., Шабанов П.Д. Механизмы развития острой гипоксии и пути ее фармакологической коррекции. Обзоры по клин. фармакол. и лекарств. терапии. 2008. 6: 3–25. (Evseeva M., Evseev A., Pravdivtsev W., Shabanov P. Mechanisms of development of acute hypoxia and its pharmacologic correction. Rev Clin Pharmacol and Drug Therap. 2008. 6: 3–25. (In Russian).Зинько М.Ю., Рыбникова Е.A. Перекрестная адаптация: от Ф.З. Меерсона до наших дней. Часть 1. Адаптация, перекрестная адаптация и перекрестная сенсибилизация. Успехи физиологических наук. 2019. 50(4): 3–13. (Zenko M.Y., Rybnikova E.A. Cross Adaptation: from F.Z. Meerson to the Modern State of the Problem. Part 1. Adaptation, Cross-Adaptation and Cross-Sensitization. Uspekhi Fiziologicheskikh Nauk. 2019. 50(4): 3–13. (In Russian).Зинько М.Ю., Рыбникова Е.A. Гипоксическая адаптация и тренировка: исторические, биомедицинские и спортивные аспекты. Авиакосмическая и экологическая медицина. 2021. 55(1): 20–26. (Zen’ko M.Yu., Rybnikova Е.А. Hypoxic adaptation and training: historic, biomedical and sport aspects. Journal of Aerospace and Environmental Medicine. 2021. 55(1): 20–26. (In Russian).Игнатенко Г.А., Багрий А.Э., Игнатенко Т.С. Толстой В.А., Евтушенко И.С., Михайличенко Е.С. Возможности и перспективы применения гипокситерапии в кардиологии. Архивъ внутренней медицины. 2023. 13(4): 245–252. (Ignatenko G.A., Bagriy A.E., Ignatenko T.S. Tolstoy V.A., Evtushenko I.S., Mykhailichenko E.S. Possibilities and Prospects of Hypoxitherapy Application in Cardiology. The Russian Archives of Internal Medicine. 2023. 13(4): 245–252. (In Russian).Петров И.Р. Кислородное голодание головного мозга (экспериментальные материалы). Л.: Медгиз. Ленинградское отделение, 1949. 211 с.Приходько В.А., Селизарова Н.О., Оковитый С.В. Молекулярные механизмы развития гипоксии и адаптации к ней. Часть I. Архив патологии. 2021. 83(2): 52–61. (Prikhodko V.A., Selizarova N.O., Okovityi S.V. Molecular mechanisms for hypoxia development and adaptation to it. Part I. Archive of Pathology. 2021. 83(2): 52–61. (In Russian).Сариева К.В., Лянгузов А.Ю., Галкина О.В., Ветровой О.В. Влияние тяжелой гипоксии на HIF1- и Nrf2-опосредованные механизмы антиоксидантной защиты в неокортексе крыс. Нейрохимия. 2019. 36(2): 128–139 (Sarieva K.V., Lyanguzov A.Yu., Galkina O.V., Vetrovoy O.V. The Effect of Severe Hypoxia on HIF1- and Nrf2-Mediated Mechanisms of Antioxidant Defense in the Rat Neocortex. Neurochem. J. 2019. 13: 145–155).Семенов Д.Г., Беляков А.В. Гипоксическое кондиционирование как стимул формирования гипоксической толерантности мозга. Успехи физиологических наук. 2023. 54(2): 3–19. (Semenov D.G., Belyakov A.V. Hypoxic conditioning as a stimulus for the formation of hypoxic tolerance in the brain. Uspekhi Fiziologicheskikh Nauk. 2023. 54(2): 3–19. (In Russian).Albrecht M., Zitta K., Groenendaal F., van Bel F., Peeters-Scholte C. Neuroprotective strategies following perinatal hypoxia-ischemia: Taking aim at NOS. Free Radic. Biol. Med. 2019. 142: 123–131.Almendros I., Farré R., Planas A.M., Torres M., Bonsignore M.R., Navajas D., Montserrat J.M. Tissue oxygenation in brain, muscle, and fat in a rat model of sleep apnea: differential effect of obstructive apneas and intermittent hypoxia. Sleep. 2011. 34(8): 1127–1133.Almendros I., Wang Y., Becker L., Lennon F.E., Zheng J., Coats B.R., Schoenfelt K.S., Carreras A., Hakim F., Zhang S.X., Farré R., Gozal D. Intermittent hypoxia-induced changes in tumor-associated macrophages and tumor malignancy in a mouse model of sleep apnea. Am. J. Respir. Crit. Care Med. 2014. 189(5): 593–601.Angelo M.F., Aguirre A., Avilés Reyes R.X., Villarreal A., Lukin J., Melendez M., Vanasco V., Barker P., Alvarez S., Epstein A., Jerusalinsky D., Ramos A.J. The proinflammatory RAGE/NF-κB pathway is involved in neuronal damage and reactive gliosis in a model of sleep apnea by intermittent hypoxia. PLoS One. 2014. 9(9): e107901Angerer P., Nowak D. Working in permanent hypoxia for fire protection-impact on health. Int. Arch. Occup. Environ. Health. 2003. 76(2): 87–102.Attaway A.H., Bellar A., Mishra S., Karthikeyan M., Sekar J., Welch N., Musich R., Singh S.S., Kumar A., Menon A., King J., Langen R., Webster J., Scheraga R.G., Rochon K., Mears J., Naga Prasad S.V., Hatzoglou M., Chakraborty A.A., Dasarathy S. Adaptive exhaustion during prolonged intermittent hypoxia causes dysregulated skeletal muscle protein homeostasis. J Physiol. 2023. 601(3): 567–606.Balduini W., Carloni S., Buonocore G. Autophagy in hypoxia-ischemia induced brain injury. J. Matern. Fetal. Neonatal. Med. 2012. 25(1): 30–34.Banasiak K.J., Xia Y., Haddad G.G. Mechanisms underlying hypoxia-induced neuronal apoptosis. Prog. Neurobiol. 2000. 62(3): 215–249.Bao X., Liu H., Liu H.Y., Long Y., Tan J.W., Zhu Z.M. The effect of intermittent hypoxia training on migraine: a randomized controlled trial. Am J Transl Res. 2020. 12(7): 4059–4065.Baranova K.A., Zenko M.Y., Rybnikova E.A. Influence of Interval Hypoxic Training in Different Regimes on the Blood Parameters of Rats. J. Evol. Biochem. Phys. 2024. 60: 306–315.Basovich S.N. The role of hypoxia in mental development and in the treatment of mental disorders: a review. Biosci. Trends. 2010. 4(6): 288–296.Behrendt T., Bielitzki R., Behrens M., Glazachev O.S., Schega L. Effects of Intermittent Hypoxia-Hyperoxia Exposure Prior to Aerobic Cycling Exercise on Physical and Cognitive Performance in Geriatric Patients – A Randomized Controlled Trial. Front Physiol. 2022. 13: 899096.Bibel M., Barde Y.A. Neurotrophins: key regulators of cell fate and cell shape in the vertebrate nervous system. Genes Dev. 2000. 14(23): 2919–2937.Borkum J.M. Migraine Triggers and Oxidative Stress: A Narrative Review and Synthesis. Headache. 2016. 56(1): 12–35.Burtscher J., Mallet R.T., Burtscher M., Millet G.P. Hypoxia and brain aging: Neurodegeneration or neuroprotection? Ageing Research Reviews. 2021. 68: 101343.Burtscher J., Citherlet T., Camacho-Cardenosa A., Camacho-Cardenosa M., Raberin A., Krumm B., Hohenauer E., Egg M., Lichtblau M., Müller J., Rybnikova E.A., Gatterer H., Debevec T., Baillieul S., Manferdelli G., Behrendt T., Schega L., Ehrenreich H., Millet G.P., Gassmann M., Schwarzer C., Glazachev O., Girard O., Lalande S., Hamlin M., Samaja M., Hüfner K., Burtscher M., Panza G., Mallet R.T. Mechanisms underlying the health benefits of intermittent hypoxia conditioning. J Physiol. 2024a. 602(21): 5757–5783.Burtscher J., Raberin A., Brocherie F., Malatesta D., Manferdelli G., Citherlet T., Krumm B., Bourdillon N., Antero J., Rasica L., Burtscher M., Millet G.P. Recommendations for Women in Mountain Sports and Hypoxia Training/Conditioning. Sports Med. 2024b. 54(4): 795–811.Car H., Oksztel R., Nadlewska A., Wiśniewski K. Baclofen prevents hypoxia-induced consolidation impairment for passive avoidance in rats. Pharmacol. Res. 2001. 44(4): 329–335.Carissimi A., Martinez D., Kim L.J., Fiori C.Z., Vieira L.R., Rosa D.P., Pires G.N. Intermittent hypoxia, brain glyoxalase-1 and glutathione reductase-1, and anxiety-like behavior in mice. Braz J Psychiatry. 2018. 40(4): 376–381.Chandrasekaran B., Fernandes S. “Exercise with facemask; Are we handling a devil’s sword?” – A physiological hypothesis. Med Hypotheses. 2020. 144: 110002.Chen L.M., Kuo W.W., Yang J.J., Wang S.G., Yeh Y.L., Tsai F.J., Ho Y J., Chang M.H., Huang C.Y., Lee S.D. Eccentric cardiac hypertrophy was induced by long-term intermittent hypoxia in rats. Experimental physiology. 2007. 92(2): 409–416.Chen A., Xiong L.J., Tong Y., Mao M. The neuroprotective roles of BDNF in hypoxic ischemic brain injury. Biomed. Rep. 2013. 1(2): 167–176.Chen S.D., Wu C.L., Hwang W.C., Yang D.I. More Insight into BDNF against Neurodegeneration: Anti-Apoptosis, Anti-Oxidation, and Suppression of Autophagy. Int. J. Mol. Sci. 2017. 18(3): 545.Chen R., Lai U.H., Zhu L., Singh A., Ahmed M., Forsyth N.R. Reactive Oxygen Species Formation in the Brain at Different Oxygen Levels: The Role of Hypoxia Inducible Factors. Front. Cell Dev. Biol. 2018. 6: 132.Chen P.S., Chiu W.T., Hsu P.L., Lin S.C., Peng I.C., Wang C.Y., Tsai S.J. Pathophysiological implications of hypoxia in human diseases. J. Biomed. Sci. 2020. 27(1) :63.Chen L., Ren S.Y., Li R.X., Liu K., Chen J.F., Yang Y.J., Deng Y.B., Wang H.Z., Xiao L., Mei F., Wang F. Chronic Exposure to Hypoxia Inhibits Myelinogenesis and Causes Motor Coordination Deficits in Adult Mice. Neurosci. Bull. 2021. 37(10): 1397–1411.Chen L., Gao Y., Li Y., Wang C., Chen D., Gao Y., Ran X. Severe Intermittent Hypoxia Modulates the Macrophage Phenotype and Impairs Wound Healing Through Downregulation of HIF-2α. Nat. Sci. Sleep. 2022. 14: 1511–1520.Coimbra-Costa D., Alva N., Duran M., Carbonell T., Rama R. Oxidative stress and apoptosis after acute respiratory hypoxia and reoxygenation in rat brain. Redox. Biol. 2017. 12: 216–225.Cui C., Jiang X., Wang Y., Li C., Lin Z., Wei Y., Ni Q. Cerebral Hypoxia-Induced Molecular Alterations and Their Impact on the Physiology of Neurons and Dendritic Spines: A Comprehensive Review. Cell Mol. Neurobiol. 2024. 44 (1): 58.Dallas M., Boycott H.E., Atkinson L., Miller A., Boyle J.P., Pearson H.A., Peers C. Hypoxia suppresses glutamate transport in astrocytes. J. Neurosci. 2007. 27 (15): 3946–3955.Damgaard V., Mariegaard J., Lindhardsen J.M., Ehrenreich H., Miskowiak K.W. Neuroprotective Effects of Moderate Hypoxia: A Systematic Review. Brain Sci. 2023. 13 (12): 1648.D’Arcy M.S. Cell death: a review of the major forms of apoptosis, necrosis and autophagy. Cell Biol. Int. 2019. 43 (6): 582–592.Della Rocca Y., Fonticoli L., Rajan T.S., Trubiani O., Caputi S., Diomede F., Pizzicannella J., Marconi G.D. Hypoxia: molecular pathophysiological mechanisms in human diseases. J Physiol Biochem. 2022. 78(4): 739–752.Dengler V.L., Galbraith M., Espinosa J.M. Transcriptional regulation by hypoxia inducible factors. Crit. Rev. Biochem. Mol. Biol. 2014. 49 (1): 1–15.Drager L.F., Yao Q., Hernandez K.L., Shin M.K., Bevans-Fonti S., Gay J., Sussan T.E., Jun J.C., Myers A.C., Olivecrona G., Schwartz A.R., Halberg N., Scherer P.E., Semenza G.L., Powell D.R., Polotsky V.Y. Chronic intermittent hypoxia induces atherosclerosis via activation of adipose angiopoietin-like 4. Am. J. Respir. Crit. Care Med. 2013. 188 (2): 240–248.Dumitrascu R., Heitmann J., Seeger W., Weissmann N., Schulz R. Obstructive sleep apnea, oxidative stress and cardiovascular disease: lessons from animal studies. Oxid. Med. Cell Longevity. 2013. 2013: 234631.Fan J., Fan X., Li Y., Guo J., Xia D., Ding L., Zheng Q., Wang W., Xue F., Chen R., Liu S., Hu L., Gong Y. Blunted inflammation mediated by NF-κB activation in hippocampus alleviates chronic normobaric hypoxia-induced anxiety-like behavior in rats. Brain Res. Bull. 2016. 122: 54–61.Farré R., Rotger M., Montserrat J.M., Calero G., Navajas D. Collapsible upper airway segment to study the obstructive sleep apnea/hypopnea syndrome in rats. Respir. Physiol. Neurobiol. 2003. 136. (2-3): 199–209.Farré R., Montserrat J.M., Gozal D., Almendros I., Navajas D. Intermittent Hypoxia Severity in Animal Models of Sleep Apnea. Front. Physiol. 2018. 9: 1556.Frank F., Faulhaber M., Messlinger K., Accinelli C., Peball M., Schiefecker A., Kaltseis K., Burtscher M., Broessner G. Migraine and aura triggered by normobaric hypoxia. Cephalalgia. 2020. 40 (14). 1561–1573.Frank F., Kaltseis K., Filippi V., Broessner G. Hypoxia-related mechanisms inducing acute mountain sickness and migraine. Front. Physiol. 2022. 13: 994469.Fukutomi T., Takagi K., Mizushima T., Ohuchi N., Yamamoto M. Kinetic, thermodynamic, and structural characterizations of the association between Nrf2-DLGex degron and Keap1. Mol Cell Biol. 2014. 34(5): 832–846.Fulco C.S., Rock P.B., Cymerman A. Improving athletic performance: is altitude residence or altitude training helpful? Aviat. Space Environ. Med. 2000. 71 (2): 162–171.Gabryelska A., Turkiewicz S., Ditmer M., Gajewski A., Białasiewicz P., Strzelecki D., Chałubiński M., Sochal M. Evaluation of the Continuous Positive Airway Pressure Effect on Neurotrophins’ Gene Expression and Protein Levels. Int J Mol Sci. 2023. 24(23): 16599.Glazachev O.S., Kryzhanovskaya S.Y., Zapara M.A., Dudnik E.N., Samartseva V.G., Susta D. Safety and Efficacy of Intermittent Hypoxia Conditioning as a New Rehabilitation/ Secondary Prevention Strategy for Patients with Cardiovascular Diseases: A Systematic Review and Meta-analysis. Curr Cardiol Rev. 2021. 17(6): e051121193317.Gozal D., Daniel J.M., Dohanich G.P. Behavioral and anatomical correlates of chronic episodic hypoxia during sleep in the rat. J. Neurosci. 2001. 21 (7): 2442–2450.Halder S.K., Milner R. Mild hypoxia triggers transient blood-brain barrier disruption: a fundamental protective role for microglia. Acta Neuropathol. Commun. 2020. 8 (1): 175.Heinrich E.C., Tift M.S. Lessons in immune adaptations to hypoxia revealed by comparative and evolutionary physiology. BMC Biol. 2023. 21 (1): 295.Heinzer R., Vat S., Marques-Vidal P., Marti-Soler H., Andries D., Tobback N., Mooser V., Preisig M., Malhotra A., Waeber G., Vollenweider P., Tafti M., Haba-Rubio J. Prevalence of sleep-disordered breathing in the general population: the HypnoLaus study. Lancet Respir. Med. 2015. 3 (4): 310–318.Helan M., Aravamudan B., Hartman W.R., Thompson M.A., Johnson B.D., Pabelick C.M., Prakash Y.S. BDNF secretion by human pulmonary artery endothelial cells in response to hypoxia. J Mol Cell Cardiol. 2014. 68: 89–97.Hu C., Huang Y., Wu L., Zhao H., Pac Soo C., Lian Q., Ma D. Apoptosis and necroptosis occur in the different brain regions of hippocampus in a rat model of hypoxia asphyxia. Int. J. Neurosci. 2021. 131 (9): 843–853.Hunyor I., Cook K.M. Models of intermittent hypoxia and obstructive sleep apnea: molecular pathways and their contribution to cancer. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2018. 315 (4): R669–R687.Iturriaga R., Moya E.A., Del Rio R. Inflammation and oxidative stress during intermittent hypoxia: the impact on chemoreception. Exp. Physiol. 2015. 100 (2): 149–155.Jiang B., Wei H. Oxygen therapy strategies and techniques to treat hypoxia in COVID-19 patients. Eur. Rev. Med. Pharmacol. Sci. 2020. 24 (19): 10239–10246.Kim L.J., Martinez D., Fiori C.Z., Baronio D., Kretzmann N.A., Barros H.M. Hypomyelination, memory impairment, and blood-brain barrier permeability in a model of sleep apnea. Brain Res. 2015. 1597: 28–36.Kisielinski K., Giboni P., Prescher A., Klosterhalfen B., Graessel D., Funken S., Kempski O., Hirsch O. Is a Mask That Covers the Mouth and Nose Free from Undesirable Side Effects in Everyday Use and Free of Potential Hazards? Int. J. Environ. Res. Public Health. 2021. 18 (8): 4344.Kisielinski K., Hirsch O., Wagner S., Wojtasik B., Funken S., Klosterhalfen B., Kanti Manna S., Prescher A., Sukul P., Sönnichsen A. Physio-metabolic and clinical consequences of wearing face masks-Systematic review with meta-analysis and comprehensive evaluation. Front. Public Health. 2023. 11: 1125150.Krueger K., Catanese L., Scholz H. Intermittent hypoxia: Friend and foe. Acta Physiol. (Oxf). 2019. 226 (2): e13276.Kung S.C., Shen Y.C., Chang E.T., Hong Y.L., Wang L.Y. Hypercapnia impaired cognitive and memory functions in obese patients with obstructive sleep apnoea. Sci Rep. 2018. 8(1): 17551.Lahousse L., Tiemeier H., Ikram M.A., Brusselle G.G. Chronic obstructive pulmonary disease and cerebrovascular disease: A comprehensive review. Respir. Med. 2015. 109 (11): 1371–1380.Lai M.C., Yang S.N. Perinatal hypoxic-ischemic encephalopathy. J. Biomed. Biotechnol. 2011. 2011: 609813.Leconte C., Léger M., Boulouard M., Tixier E., Fréret T., Bernaudin M., Schumann-Bard P. Repeated mild hypoxic exposures decrease anxiety-like behavior in the adult mouse together with an increased brain adrenomedullin gene expression. Behav. Brain Res. 2012. 230 (1): 78–84.Lee K.H. Cha M., Lee B.H. Neuroprotective Effect of Antioxidants in the Brain. Int. J. Mol. Sci. 2020a. 21 (19): 7152.Lee J.M., Grabb M.C., Zipfel G.J., Choi D.W. Brain tissue responses to ischemia. J. Clin. Invest. 2000b. 106 (6): 723–731.Lee S., Li G., Liu T., Tse G. COVID-19: Electrophysiological mechanisms underlying sudden cardiac death during exercise with facemasks. Med. Hypotheses. 2020c. 144: 110177.Lei L., Feng J., Wu G., Wei Z., Wang J.Z., Zhang B., Liu R., Liu F., Wang X., Li H.L. HIF-1α Causes LCMT1/PP2A Deficiency and Mediates Tau Hyperphosphorylation and Cognitive Dysfunction during Chronic Hypoxia. Int. J. Mol. Sci. 2022. 23 (24): 16140.Li Y., Tan M.S., Jiang T., Tan L. Microglia in Alzheimer’s disease. Biomed. Res. Int. 2014. 2014: 437483.Li Z., Wang S., Gong C., Hu Y., Liu J., Wang W., Chen Y., Liao Q., He B., Huang Y., Luo Q., Zhao Y., Xiao Y. Effects of Environmental and Pathological Hypoxia on Male Fertility. Front. Cell Dev. Biol. 2021. 9: 725933.Ling J., Yu Q., Li Y., Yuan X., Wang X., Liu W., Guo T., Duan Y., Li L. Edaravone Improves Intermittent Hypoxia-Induced Cognitive Impairment and Hippocampal Damage in Rats. Biol. Pharm. Bull. 2020. 43 (8): 1196–1201.Liu H., Qiu H., Yang J., Ni J., Le W. Chronic hypoxia facilitates Alzheimer’s disease through demethylation of γ-secretase by downregulating DNA methyltransferase 3b. Alzheimers Dement. 2016. 12 (2): 130–143.Liu Q., Palmgren V.A.C., Danen E.H., Le Dévédec S.E. Acute vs. chronic vs. intermittent hypoxia in breast Cancer: a review on its application in in vitro research. Mol. Biol. Rep. 2022. 49 (11): 10961–10973.Lv R., Liu X., Zhang Y., Dong N., Wang X., He Y., Yue H., Yin Q. Pathophysiological mechanisms and therapeutic approaches in obstructive sleep apnea syndrome. Signal. Transduct. Target Ther. 2023. 8 (1): 218.Luo Z., Tian M., Yang G., Tan Q., Chen Y., Li G., Zhang Q., Li Y., Wan P., Wu J. Hypoxia signaling in human health and diseases: implications and prospects for therapeutics. Signal Transduct Target Ther. 2022. 7(1): 218.Lyamina N.P., Lyamina S.V., Senchiknin V.N., Mallet R.T., Downey H.F., Manukhina E.B. Normobaric hypoxia conditioning reduces blood pressure and normalizes nitric oxide synthesis in patients with arterial hypertension. J. Hypertens. 2011. 29 (11): 2265–2272.Mabry S., Bradshaw J.L., Gardner J.J., Wilson E.N., Cunningham R.L. Sex-dependent effects of chronic intermittent hypoxia: implication for obstructive sleep apnea. Biol. Sex Differ. 2024. 15 (1): 38.Marques K.L., Rodrigues V., Balduci C.T.N., Montes G.C., Barradas P.C., Cunha-Rodrigues M.C. Emerging therapeutic strategies in hypoxic-ischemic encephalopathy: a focus on cognitive outcomes. Front. Pharmacol. 2024. 15: 1347529.Mallet R.T., Manukhina E.B., Ruelas S.S., Caffrey J.L., Downey H.F. Cardioprotection by intermittent hypoxia conditioning: evidence, mechanisms, and therapeutic potential. Am J Physiol Heart Circ Physiol. 2018. 315(2): H216–H232.Martinez C.A., Jiramongkol Y., Bal N., Alwis I., Nedoboy P.E., Farnham M.M.J., White M.D., Cistulli P.A., Cook K.M. Intermittent hypoxia enhances the expression of hypoxia inducible factor HIF1A through histone demethylation. J Biol Chem. 2022. 298 (11): 102536.Mastino P., Rosati D., de Soccio G., Romeo M., Pentangelo D., Venarubea S., Fiore M., Meliante P.G., Petrella C., Barbato C., Minni A. Oxidative Stress in Obstructive Sleep Apnea Syndrome: Putative Pathways to Hearing System Impairment. Antioxidants (Basel). 2023. 12(7): 1430.McMorris T., Hale B.J., Barwood M., Costello J., Corbett J. Effect of acute hypoxia on cognition: A systematic review and meta-regression analysis. Neurosci. Biobehav. Rev. 2017. 74: 225–232.Meng S.X., Wang B., Li W.T. Intermittent hypoxia improves cognition and reduces anxiety-related behavior in APP/PS1 mice. Brain Behav. 2020. 10(2): e01513.Nair D., Ramesh V., Li R.C., Schally A.V., Gozal D. Growth hormone releasing hormone (GHRH) signaling modulates intermittent hypoxia-induce oxidative stress and cognitive decline in mouse. J. Neurochem. 2013. 127 (4): 1–4.Nanduri J., Yuan G., Kumar G.K., Semenza G.L., Prabhakar N.R. Transcriptional responses to intermittent hypoxia. Respir Physiol Neurobiol. 2008. 164 (1-2): 277–281.Nanduri J., Wang N., Yuan G., Khan S.A., Souvannakitti D., Peng Y.J., Kumar G.K., Garcia J.A., Prabhakar N.R. Intermittent hypoxia degrades HIF-2alpha via calpains resulting in oxidative stress: implications for recurrent apnea-induced morbidities. Proc. Natl. Acad. Sci. USA. 2009. 106 (4): 1199–1204.Nanduri J., Vaddi D.R., Khan S.A., Wang N., Makerenko V., Prabhakar N.R. Xanthine oxidase mediates hypoxia-inducible factor-2α degradation by intermittent hypoxia. PLoS One. 2013. 8 (10): e75838.Nanduri J., Semenza G.L., Prabhakar N.R. Epigenetic changes by DNA methylation in chronic and intermittent hypoxia. Am. J. Physiol. Lung Cell Mol. Physiol. 2017. 313 (6): L1096–L1100.Nanduri J., Wang N.., Wang BL., Prabhakar N.R. Lysine demethylase KDM6B regulates HIF-1α-mediated systemic and cellular responses to intermittent hypoxia. Physiol. Genomics. 2021. 53(9): 385–394.Navarrete-Opazo A., Mitchell G.S. Therapeutic potential of intermittent hypoxia: a matter of dose. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2014. 307(10): R1181–R1197.Nisar A., Khan S., Li W., Hu L., Samarawickrama P.N., Gold N.M., Zi M., Mehmood S.A., Miao J., He Y. Hypoxia and aging: molecular mechanisms, diseases, and therapeutic targets. MedComm (2020). 2024. 5(11): e786.Olaithe M., Bucks R.S., Hillman D.R., Eastwood P.R. Cognitive deficits in obstructive sleep apnea: Insights from a meta-review and comparison with deficits observed in COPD, insomnia, and sleep deprivation. Sleep Med. Rev. 2018. 38: 39–49.Panza G.S., Burtscher J., Zhao F. Intermittent hypoxia: a call for harmonization in terminology. J Appl Physiol (1985). 2023. 135(4): 886–890.Paoletti P., Bellone C., Zhou Q. NMDA receptor subunit diversity: impact on receptor properties, synaptic plasticity and disease. Nat. Rev. Neurosci. 2013. 14(6): 383–400.Park J., Jung S., Kim S.M., Park I.Y., Bui N.A., Hwang G.S., Han I.O. Repeated hypoxia exposure induces cognitive dysfunction, brain inflammation, and amyloidβ/p-Tau accumulation through reduced brain O-GlcNAcylation in zebrafish. J. Cereb. Blood Flow Metab. 2021. 41(11): 3111–3126.Peng Y.J., Yuan G., Khan S., Nanduri J., Makarenko V.V., Reddy V.D., Vasavda C., Kumar G.K., Semenza G.L., Prabhakar N.R. Regulation of hypoxia-inducible factor-α isoforms and redox state by carotid body neural activity in rats. J. Physiol. 2014. 592(17): 3841–3858.Peppard P.E., Young T., Palta M., Skatrud J. Prospective study of the association between sleep-disordered breathing and hypertension. N. Engl. J. Med. 2000. 342(19): 1378–1384.Pham K., Parikh K., Heinrich E.C. Hypoxia and Inflammation: Insights From High-Altitude Physiology. Front. Physiol. 2021. 12: 676782.Piešová M., Mach M. Impact of perinatal hypoxia on the developing brain. Physiol. Res. 2020. 69(2): 199–213.Pisoschi A.M., Pop A. The role of antioxidants in the chemistry of oxidative stress: A review. Eur J Med Chem. 2015. 97: 55–74.Prabhakar N.R. Oxygen sensing during intermittent hypoxia: cellular and molecular mechanisms. J. Appl. Physiol. 2001. 90(5): 1986-1994.Prabhakar N.R., Semenza G.L. Oxygen Sensing and Homeostasis. Physiology (Bethesda). 2015. 30(5): 340–348.Pregnolato S., Chakkarapani E., Isles A.R., Luyt K. Glutamate Transport and Preterm Brain Injury. Front. Physiol. 2019. 10: 417.Puri S., Panza G., Mateika J.H. A comprehensive review of respiratory, autonomic and cardiovascular responses to intermittent hypoxia in humans. Exp. Neurol. 2021. 341: 113709.Rahman A., Tabassum T., Araf Y., Al Nahid A., Ullah M.A., Hosen M.J. Silent hypoxia in COVID-19: pathomechanism and possible management strategy. Mol. Biol. Rep. 2021. 48(4): 3863–3869.Rapino C., Bianchi G., Di Giulio C., Centurione L., Cacchio M., Antonucci A., Cataldi A. HIF-1alpha cytoplasmic accumulation is associated with cell death in old rat cerebral cortex exposed to intermittent hypoxia. Aging Cell. 2005. 4(4): 177–185.Reinke C., Bevans-Fonti S., Drager L.F., Shin M.K., Polotsky V.Y. Effects of different acute hypoxic regimens on tissue oxygen profiles and metabolic outcomes. J. Appl. Physiol. 2011. 111(3): 881–890.Richard N.A., Koehle M.S. Differences in cardio-ventilatory responses to hypobaric and normobaric hypoxia: a review. Aviat. Space Environ. Med. 2012. 83(7): 677–684.Row B.W. Intermittent hypoxia and cognitive function: implications from chronic animal models. Advances in experimental medicine and biology. 2007. 618: 51–67.Rybnikova E., Vataeva L., Tyulkova E., Gluschenko T., Otellin V., Pelto-Huikko M., Samoilov M.O. Mild hypoxia preconditioning prevents impairment of passive avoidance learning and suppression of brain NGFI-A expression induced by severe hypoxia. Behav. Brain Res. 2005. 160(1): 107–114.Rybnikova, E., Samoilov M. Current insights into the molecular mechanisms of hypoxic pre- and postconditioning using hypobaric hypoxia. 2015. Front. Neurosci. 9: 388.Rybnikova E.A., Nalivaeva N.N., Zenko M.Y., Baranova K.A. Intermittent Hypoxic Training as an Effective Tool for Increasing the Adaptive Potential, Endurance and Working Capacity of the Brain. Front Neurosci. 2022. 16: 941740.Ryan S. Adipose tissue inflammation by intermittent hypoxia: mechanistic link between obstructive sleep apnoea and metabolic dysfunction. J. Physiol. 2017. 595(8): 2423–2430.Salyha N., Oliynyk I. Hypoxia modeling techniques: A review. Heliyon. 2023. 9(2): e13238Schoorlemmer G.H., Rossi M.V., Tufik S., Cravo S.L. A new method to produce obstructive sleep apnoea in conscious unrestrained rats. Exp Physiol. 2011. 96(10): 1010–1018.Segal R.A., Takahashi H., McKay R.D. Changes in neurotrophin responsiveness during the development of cerebellar granule neurons. Neuron. 1992. 9(6): 1041–1052.Semenza G.L. HIF-1: mediator of physiological and pathophysiological responses to hypoxia. J Appl Physiol (1985). 2000. 88(4): 1474–1480.Semenza G.L. Hypoxia-inducible factors in physiology and medicine. Cell. 2012. 149: 399–40.Semenza G.L., Prabhakar N.R. The role of hypoxia-inducible factors in carotid body (patho) physiology. J. Physiol. 2018. 596(15): 2977–2983.Serebrovskaya T.V. Intermittent hypoxia research in the former Soviet Union and the commonwealth of independent States: history and review of the concept and selected applications. High Alt Med Biol. 2002. 3(2): 205–221.Serebrovskaya T.V., Manukhina E.B., Smith M.L., Downey H.F., Mallet R.T. Intermittent hypoxia: cause of or therapy for systemic hypertension? Exp. Biol. Med. (Maywood). 2008. 233(6): 627–650.Serebrovska Z.O., Serebrovska T.V., Kholin V.A., Tumanovska L.V., Shysh A.M., Pashevin D.A., Goncharov S.V., Stroy D., Grib O.N., Shatylo V.B., Bachinskaya N.Y., Egorov E., Xi L., Dosenko V.E. Intermittent Hypoxia-Hyperoxia Training Improves Cognitive Function and Decreases Circulating Biomarkers of Alzheimer’s Disease in Patients with Mild Cognitive Impairment: A Pilot Study. Int. J. Mol. Sci. 2019. 20(21): 5405.Serebrovskaya T.V., Xi L. Intermittent hypoxia training as non-pharmacologic therapy for cardiovascular diseases: Practical analysis on methods and equipment. Exp Biol Med (Maywood). 2016. 241(15): 1708–1723.Serebrovska Z.O., Xi L., Tumanovska L.V., Shysh A.M., Goncharov S.V., Khetsuriani M., Kozak T.O., Pashevin D.A., Dosenko V.E., Virko S.V., Kholin V.A., Grib O.N., Utko N.A., Egorov E., Polischuk A.O., Serebrovska T.V. Response of Circulating Inflammatory Markers to Intermittent Hypoxia-Hyperoxia Training in Healthy Elderly People and Patients with Mild Cognitive Impairment. Life (Basel). 2022. 12(3): 432.Setia R., Dogra M., Handoo A., Yadav R., Thangavel G.P., Rahman A.E. Use of face mask by blood donors during the COVID-19 pandemic: Impact on donor hemoglobin concentration: A bane or a boon. Transfus. Apher. Sci. 2021. 60(4): 103160.Sforza E., Roche F. Chronic intermittent hypoxia and obstructive sleep apnea: an experimental and clinical approach. Hypoxia (Auckl). 2016. 4: 99–108.Shao G., Gao C.Y., Lu G.W. Alterations of hypoxia-inducible factor-1 alpha in the hippocampus of mice acutely and repeatedly exposed to hypoxia. Neurosignals. 2005. 14(5): 255–261.Shobatake R., Ota H., Takahashi N., Ueno S., Sugie K., Takasawa S. The Impact of Intermittent Hypoxia on Metabolism and Cognition. Int. J. Mol. Sci. 2022. 23(21): 12957.Simonson T.S., Baker T.L., Banzett R.B., Bishop T., Dempsey J.A., Feldman J.L., Guyenet P.G., Hodson E.J., Mitchell G.S., Moya E.A., Nokes B.T., Orr J.E., Owens R.L., Poulin M., Rawling J.M., Schmickl C.N., Watters J.J., Younes M., Malhotra A. Silent hypoxaemia in COVID-19 patients. J. Physiol. 2021. 599(4): 1057–1065.Singh K.K., Chaubey G., Chen J.Y., Suravajhala P. Decoding SARS-CoV-2 hijacking of host mitochondria in COVID-19 pathogenesis. Am. J Physiol. Cell Physiol. 2020. 319(2): C258–C267.Smerdon D. The effect of masks on cognitive performance. Proc. Natl. Acad. Sci. USA. 2022. 119 (49): e2206528119.Smith K.A., Waypa G.B., Schumacker P.T. Redox signaling during hypoxia in mammalian cells. Redox Biol. 2017. 13: 228–234.Solleiro-Villavicencio H., Rivas-Arancibia S. Effect of Chronic Oxidative Stress on Neuroinflammatory Response Mediated by CD4+T Cells in Neurodegenerative Diseases. Front. Cell Neurosci. 2018. 12: 114.Somers V.K., Kara T., Xie J. Progressive Hypoxia: A Pivotal Pathophysiologic Mechanism of COVID-19 Pneumonia. Mayo Clin Proc. 2020. 95 (11): 2339-2342.Stefano G.B., Ptacek R., Ptackova H., Martin A., Kream R.M. Selective Neuronal Mitochondrial Targeting in SARS-CoV-2 Infection Affects Cognitive Processes to Induce ‘Brain Fog’ and Results in Behavioral Changes that Favor Viral Survival. Med. Sci. Monit. 2021. 27: e930886.Sukhanova I.A., Sebentsova E.A., Levitskaya N.G. The acute and delayed effects of perinatal hypoxic brain damage in children and in model experiments with rodents. Neurochemical Journal. 2016. 10(4): 258–272.Sukul P., Bartels J., Fuchs P., Trefz P., Remy R., Rührmund L., Kamysek S., Schubert J.K., Miekisch W. Effects of COVID-19 protective face masks and wearing durations on respiratory haemodynamic physiology and exhaled breath constituents. Eur Respir J. 2022. 60(3): 2200009.Takeda Y., Kimura F., Takasawa S. Possible Molecular Mechanisms of Hypertension Induced by Sleep Apnea Syndrome/Intermittent Hypoxia. Life (Basel). 2024. 14(1): 157.Tang S., Zhu J., Zhao D., Mo H., Zeng Z., Xiong M., Dong M., Hu K. Effects of the excitation or inhibition of basal forebrain cholinergic neurons on cognitive ability in mice exposed to chronic intermittent hypoxia. Brain Res Bull. 2020. 164: 235–248.Turovskaya M.V., Gaidin S.G., Vedunova M.V., Babaev A.A., Turovsky E.A. BDNF Overexpression Enhances the Preconditioning Effect of Brief Episodes of Hypoxia, Promoting Survival of GABAergic Neurons. Neurosci Bull. 2020. 36(7): 733–760.van Uden P., Kenneth N.S., Rocha S. Regulation of hypoxia-inducible factor-1alpha by NF-kappaB. Biochem. J. 2008. 412(3): 477–484.Veasey S. Insight from animal models into the cognitive consequences of adult sleep-disordered breathing. ILAR J. 2009. 50(3): 307–311.Velescu D.R., Marc M.S., Traila D., Pescaru C.C., Hogea P., Suppini N., Crisan A.F., Wellmann N., Oancea C. A Narrative Review of Self-Reported Scales to Evaluate Depression and Anxiety Symptoms in Adult Obstructive Sleep Apnea Patients. Medicina (Kaunas). 2024. 60(2): 261.Vetrovoy O., Sarieva K., Lomert E., Nimiritsky P., Eschenko N., Galkina O., Lyanguzov A., Tyulkova E., Rybnikova E. Pharmacological HIF1 Inhibition Eliminates Downregulation of the Pentose Phosphate Pathway and Prevents Neuronal Apoptosis in Rat Hippocampus Caused by Severe Hypoxia. J Mol Neurosci. 2020. 70(5): 635–646.Vlahopoulos S.A. Aberrant control of NF-κB in cancer permits transcriptional and phenotypic plasticity, to curtail dependence on host tissue: molecular mode. Cancer Biol. Med. 2017. 14(3): 254–270.Voirin A.C., Chatard M., Briançon-Marjollet A., Pepin J.L., Perek N., Roche F. Loss of Blood-Brain Barrier Integrity in an In Vitro Model Subjected to Intermittent Hypoxia: Is Reversion Possible with a HIF-1α Pathway Inhibitor? Int. J. Mol. Sci. 2023. 24(5): 5062.Wang X., Cui L., Ji X. Cognitive impairment caused by hypoxia: from clinical evidences to molecular mechanisms. Metab. Brain Dis. 2022. 37(1): 51–66.Wang Y., Zhang Q., Ma Q., Wang Q., Huang D., Ji X. Intermittent hypoxia preconditioning can attenuate acute hypoxic injury after a sustained normobaric hypoxic exposure: A randomized clinical trial. CNS Neurosci. Ther. 2024. 30(3): e14662.Watts M.E., Pocock R., Claudianos C. Brain Energy and Oxygen Metabolism: Emerging Role in Normal Function and Disease. Front. Mol. Neurosci. 2018. 1: 216.Wei Y., Giunta S., Xia S. Hypoxia in Aging and Aging-Related Diseases: Mechanism and Therapeutic Strategies. Int. J. Mol. Sci. 2022. 23(15): 8165.Xinliang Z., Achkasov E.E., Gavrikov L.K., Yuchen L., Zhang C., Dudnik E.N., Rumyantseva O., Beeraka N.M., Glazachev O.S. Assessing the importance and safety of hypoxia conditioning for patients with occupational pulmonary diseases: A recent clinical perspective. Biomed Pharmacother. 2024. 178: 117275.Yeo E.J. Hypoxia and aging. Exp. Mol. Med. 2019. 51(6): 1–15.Yohannes A.M., Chen W., Moga A.M., Leroi I., Connolly M.J. Cognitive Impairment in Chronic Obstructive Pulmonary Disease and Chronic Heart Failure: A Systematic Review and Meta-analysis of Observational Studies. J. Am. Med. Dir. Assoc. 2017. 18(5): 451.e1–451.e11.Yu L., Chen Y., Wang W., Xiao Z., Hong Y. Multi-Vitamin B Supplementation Reverses Hypoxia-Induced Tau Hyperphosphorylation and Improves Memory Function in Adult Mice. J. Alzheimers Dis. 2016. 54(1): 297–306.Yuan G., Nanduri J., Khan S., Semenza G.L., Prabhakar N.R. Induction of HIF-1alpha expression by intermittent hypoxia: involvement of NADPH oxidase, Ca2+ signaling, prolyl hydroxylases, and mTOR. J. Cell Physiol. 2008. 217(3): 674–685.Zhang Q., Zhao W., Li S., Ding Y., Wang Y., Ji X. Intermittent Hypoxia Conditioning: A Potential Multi-Organ Protective Therapeutic Strategy. Int J Med Sci. 2023a. 20(12): 1551–1561.Zhang Z., Kalra H., Delzell M.C., Jedlicka C.R., Vasilyev M., Vasileva A., Tomasson M.H., Bates M.L. CORP: Sources and degrees of variability in whole animal intermittent hypoxia experiments. J. Appl. Physiol. 2023b. 134(5): 1207–1215.Zhang G., Yang G., Zhou Y., Cao Z., Yin M., Ma L., Fan M., Zhao Y.Q., Zhu L. Intermittent hypoxia training effectively protects against cognitive decline caused by acute hypoxia exposure. Pflugers Arch. 2024. 476(2): 197–210.Zheng C., Poon E.T., Wan K., Dai Z., Wong S.H. Effects of Wearing a Mask During Exercise on Physiological and Psychological Outcomes in Healthy Individuals: A Systematic Review and Meta-Analysis. Sports Med. 2023. 53(1): 125–150.Zhou Z., Zhao Q., Huang Y., Meng S., Chen X., Zhang G., Chi Y., Xu D., Yin Z., Jiang H., Yu L., Wang H. Berberine ameliorates chronic intermittent hypoxia-induced cardiac remodelling by preserving mitochondrial function, role of SIRT6 signalling. J. Cell Mol. Med. 2024. 28(12): e18407.Zhu L.L., Zhao T., Li H.S., Zhao H., Wu L.Y., Ding A.S., Fan W.H., Fan M. Neurogenesis in the adult rat brain after intermittent hypoxia. Brain Res. 2005. 1055(1–2): 1–6Zhu X.H., Yan H.C., Zhang J., Qu H.D., Qiu X.S., Chen L., Li S.J., Cao X., Bean J.C., Chen L.H., Qin X.H., Liu J.H., Bai X.C., Mei L., Gao T.M. Intermittent hypoxia promotes hippocampal neurogenesis and produces antidepressant-like effects in adult rats. J. Neurosci. 2010. 30: 12653–12663.Zhu J., Tang S., Zhao D., Zeng Z., Mo H., Hu K. Orexin A improves the cognitive impairment induced by chronic intermittent hypoxia in mice. Brain Res Bull. 2021. 173: 203–210.Zoccal D.B., Vieira B.N., Mendes L.R., Evangelista A.B., Leirão I.P. Hypoxia sensing in the body: An update on the peripheral and central mechanisms. Exp. Physiol. 2024. 109(4): 461–469.