{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T16:02:12Z","timestamp":1791734532853,"version":"4.3.4"},"reference-count":82,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T00:00:00Z","timestamp":1646697600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>The morphology of the hippocampus and amygdala can be significantly affected by a long-term hypoxia-induced inflammatory response. Cardiorespiratory fitness (CRF) has a significant effect on the neuroplasticity of the hippocampus and amygdala by countering inflammation. However, the role of CRF is still largely unclear at high altitudes. Here, we investigated brain limbic volumes in participants who had experienced long-term hypoxia exposure in Tibet (3680 m), utilizing high-resolution structural images to allow the segmentation of the hippocampus and amygdala into their constituent substructures. We recruited a total of 48 participants (48 males; aged = 20.92 \u00b1 1.03 years) to undergo a structural 3T MRI, and the levels of maximal oxygen uptake (VO2max) were measured using a cardiorespiratory function test. Inflammatory biomarkers were also collected. The participants were divided into two groups according to the levels of median VO2max, and the analysis showed that the morphological indexes of subfields of the hippocampus and amygdala of the lower CRF group were decreased when compared with the higher CRF group. Furthermore, the multiple linear regression analysis showed that there was a higher association with inflammatory factors in the lower CRF group than that in the higher CRF group. This study suggested a significant association of CRF with hippocampus and amygdala volume, which may be related to hypoxic stress in high-altitude environments. A better CRF reduced physiological stress and a decrease in the inflammatory response was observed, which may be related to the increased oxygen transport capacity of the body.<\/jats:p>","DOI":"10.3390\/brainsci12030359","type":"journal-article","created":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T12:35:37Z","timestamp":1646742937000},"page":"359","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Changes in Hippocampus and Amygdala Volume with Hypoxic Stress Related to Cardiorespiratory Fitness under a High-Altitude Environment"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4525-3629","authenticated-orcid":false,"given":"Zhi-Xin","family":"Wang","sequence":"first","affiliation":[{"name":"Plateau Brain Science Research Center, Tibet University\/South China Normal University, Lhasa 850012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8104-9145","authenticated-orcid":false,"given":"Rui","family":"Su","sequence":"additional","affiliation":[{"name":"Plateau Brain Science Research Center, Tibet University\/South China Normal University, Lhasa 850012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Li","sequence":"additional","affiliation":[{"name":"Plateau Brain Science Research Center, Tibet University\/South China Normal University, Lhasa 850012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Dang","sequence":"additional","affiliation":[{"name":"Plateau Brain Science Research Center, Tibet University\/South China Normal University, Lhasa 850012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong-Ao","family":"Zeng","sequence":"additional","affiliation":[{"name":"Plateau Brain Science Research Center, Tibet University\/South China Normal University, Lhasa 850012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Mei","family":"Chen","sequence":"additional","affiliation":[{"name":"Plateau Brain Science Research Center, Tibet University\/South China Normal University, Lhasa 850012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Guo","family":"Wu","sequence":"additional","affiliation":[{"name":"Management Department, Tibet Police College, Lhasa 850012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"De-Long","family":"Zhang","sequence":"additional","affiliation":[{"name":"Plateau Brain Science Research Center, Tibet University\/South China Normal University, Lhasa 850012, China"},{"name":"Key Laboratory of Brain, Cognition and Education Sciences, Center for Studies of Psychological Application, Guangdong Key Laboratory of Mental Health and Cognitive Science, Ministry of Education, School of Psychology, South China Normal University, Guangzhou 510631, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai-Lin","family":"Ma","sequence":"additional","affiliation":[{"name":"Plateau Brain Science Research Center, Tibet University\/South China Normal University, Lhasa 850012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Roach, R.C., Wagner, P.D., and Hackett, P.H. (1999). The Hypoxic Brain. Hypoxia: Into the Next Millennium, Springer.","DOI":"10.1007\/978-1-4615-4711-2"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.brainres.2018.04.026","article-title":"Hypobaric hypoxia impairs cued and contextual fear memory in rats","volume":"1692","author":"Kumari","year":"2018","journal-title":"Brain Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.jchemneu.2008.07.003","article-title":"High altitude memory impairment is due to neuronal apoptosis in hippocampus, cortex and striatum","volume":"36","author":"Maiti","year":"2008","journal-title":"J. Chem. Neuroanat."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Zhang, J., Zhang, H., Li, J., Chen, J., Han, Q., Lin, J., Yang, T., and Fan, M. (2013). Adaptive Modulation of Adult Brain Gray and White Matter to High Altitude: Structural MRI Studies. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0068621"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"17417","DOI":"10.1038\/s41598-018-34706-y","article-title":"Aging of stimulus-driven and goal-directed attentional processes in young immigrants with long-term high altitude exposure in Tibet: An ERP study","volume":"8","author":"Ma","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1038\/s41598-017-18886-7","article-title":"Competition among the attentional networks due to resource reduction in Tibetan indigenous residents: Evidence from event-related potentials","volume":"8","author":"Zhang","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1152\/physrev.00041.2006","article-title":"Physiology and Neurobiology of Stress and Adaptation: Central Role of the Brain","volume":"87","author":"McEwen","year":"2007","journal-title":"Physiol. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Rybnikova, E., and Nalivaeva, N. (2021). Glucocorticoid-Dependent Mechanisms of Brain Tolerance to Hypoxia. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22157982"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"6986983","DOI":"10.1155\/2017\/6986983","article-title":"Effect of Hypoxic Injury in Mood Disorder","volume":"2017","author":"Zhao","year":"2017","journal-title":"Neural Plast."},{"key":"ref_10","unstructured":"Gainey, S.J. (2017). Hypoxic immunomodulation results in increased disease risk and altered behavior via non-canonical pathways. [Ph.D. Thesis, University of Illinois at Urbana-Champaign]."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jns.2010.06.002","article-title":"Why mesial temporal lobe epilepsy with hippocampal sclerosis is progressive: Uncontrolled inflammation drives disease progression?","volume":"296","author":"Yang","year":"2010","journal-title":"J. Neurol. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.neuron.2014.01.043","article-title":"Microglial CR3 Activation Triggers Long-Term Synaptic Depression in the Hippocampus via NADPH Oxidase","volume":"82","author":"Zhang","year":"2014","journal-title":"Neuron"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1089\/neu.2011.1867","article-title":"Post-Traumatic Hypoxia Exacerbates Neuronal Cell Death in the Hippocampus","volume":"29","author":"Feng","year":"2012","journal-title":"J. Neurotrauma"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1212\/WNL.0000000000003584","article-title":"Neuropathology of SUDEP","volume":"88","author":"Michalak","year":"2017","journal-title":"Neurology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1089\/ars.2014.6122","article-title":"Critical Role of Endoplasmic Reticulum Stress in Chronic Intermittent Hypoxia-Induced Deficits in Synaptic Plasticity and Long-Term Memory","volume":"23","author":"Xu","year":"2015","journal-title":"Antioxid. Redox Signal."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/j.bbr.2010.01.007","article-title":"Long-term losses of amygdala corticotropin-releasing factor neurons are associated with behavioural outcomes following neonatal hypoxia-ischemia","volume":"208","author":"Carty","year":"2010","journal-title":"Behav. Brain Res."},{"key":"ref_17","unstructured":"Watson, R.R. (2014). Chapter 4\u2014Lifestyle Factors Affecting Abdominal Obesity in Children and Adolescents: Risks and Benefits. Nutrition in the Prevention and Treatment of Abdominal Obesity, Academic Press."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.1016\/j.neuroimage.2011.08.032","article-title":"Cardiorespiratory fitness is positively correlated with cerebral white matter integrity in healthy seniors","volume":"59","author":"Johnson","year":"2012","journal-title":"NeuroImage"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1002\/bjs.5197","article-title":"The role of cardiopulmonary fitness and its genetic influences on surgical outcomes","volume":"93","author":"Lee","year":"2005","journal-title":"Br. J. Surg."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1001\/archpsyc.57.10.925","article-title":"Glucocorticoids and Hippocampal Atrophy in Neuropsychiatric Disorders","volume":"57","author":"Sapolsky","year":"2000","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.euroneuro.2009.08.003","article-title":"Regulation of adult neurogenesis by stress, sleep disruption, exercise and inflammation: Implications for depression and antidepressant action","volume":"20","author":"Lucassen","year":"2010","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1007\/s11682-014-9325-9","article-title":"Cardiorespiratory fitness is associated with brain structure, cognition, and mood in a middle-aged cohort at risk for Alzheimer\u2019s disease","volume":"9","author":"Boots","year":"2014","journal-title":"Brain Imaging Behav."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"9311","DOI":"10.1038\/s41598-021-88452-9","article-title":"Understanding the role of aerobic fitness, spatial learning, and hippocampal subfields in adolescent males","volume":"11","author":"Prathap","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1002\/hipo.20547","article-title":"Aerobic fitness is associated with hippocampal volume in elderly humans","volume":"19","author":"Erickson","year":"2009","journal-title":"Hippocampus"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.bbr.2012.05.012","article-title":"Aerobic fitness relates to learning on a virtual Morris Water Task and hippocampal volume in adolescents","volume":"233","author":"Herting","year":"2012","journal-title":"Behav. Brain Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.nlm.2014.12.005","article-title":"Running exercise delays neurodegeneration in amygdala and hippocampus of Alzheimer\u2019s disease (APP\/PS1) transgenic mice","volume":"118","author":"Lin","year":"2015","journal-title":"Neurobiol. Learn. Mem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1589\/jpts.23.271","article-title":"The Effect of Electrical Stimulation on Blood Lactate after Anaerobic Muscle Fatigue Induced in Taekwondo Athletes","volume":"23","author":"Seo","year":"2011","journal-title":"J. Phys. Ther. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Heath, E.H. (2005). ACSM\u2019s Guidelines for Exercise Testing and Prescription, Lippincott Williams & Wilkins. [7th ed.].","DOI":"10.1249\/01.mss.0000189073.33400.04"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1186\/cc5142","article-title":"High-altitude physiology and pathophysiology: Implications and relevance for intensive care medicine","volume":"11","author":"Grocott","year":"2007","journal-title":"Crit. Care"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"S140","DOI":"10.1513\/AnnalsATS.201701-043OT","article-title":"Exercise testing, supplemental oxygen, and hypoxia","volume":"14","author":"Ward","year":"2017","journal-title":"Ann. Am. Thorac. Soc."},{"key":"ref_31","first-page":"332","article-title":"Red blood cells in sports: Effects of exercise and training on oxygen supply by red blood cells","volume":"4","year":"2013","journal-title":"Front. Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1055\/s-2007-1021020","article-title":"Red Blood Cell Function in Hypoxia at Altitude and Exercise","volume":"15","author":"Kleppe","year":"1994","journal-title":"Int. J. Sports Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1097\/JES.0b013e3181aa64d7","article-title":"Regulatory Mechanisms of Cerebral Blood Flow during Exercise: New Concepts","volume":"37","author":"Ogoh","year":"2009","journal-title":"Exerc. Sport Sci. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1111\/j.1365-2044.2009.05983.x","article-title":"Cardiopulmonary exercise testing as a risk assessment method in non cardio-pulmonary surgery: A systematic review","volume":"64","author":"Smith","year":"2009","journal-title":"Anaesthesia"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1249\/00003677-198600140-00012","article-title":"Cardiovascular adaptation to exercise at high altitude","volume":"14","author":"Grover","year":"1986","journal-title":"Exerc. Sport Sci. Rev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1093\/ajcn\/78.6.1141","article-title":"Variability of measured resting metabolic rate","volume":"78","author":"Haugen","year":"2003","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_37","first-page":"217","article-title":"Differences in the morphological and physiological charac-teristics of senior and junior elite Czech judo athletes","volume":"11","author":"Mala","year":"2015","journal-title":"Arch. Budo"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.neuroimage.2015.04.042","article-title":"A computational atlas of the hippocampal formation using ex vivo, ultra-high resolution MRI: Application to adaptive segmentation of in vivo MRI","volume":"115","author":"Iglesias","year":"2015","journal-title":"NeuroImage"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.neuroimage.2017.04.046","article-title":"High-resolution magnetic resonance imaging reveals nuclei of the human amygdala: Manual segmentation to automatic atlas","volume":"155","author":"Saygin","year":"2017","journal-title":"NeuroImage"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1007\/s12264-021-00761-1","article-title":"Oxygen Metabolism-induced Stress Response Underlies Heart\u2013brain Interaction Governing Human Consciousness-breaking and Attention","volume":"38","author":"Xue","year":"2021","journal-title":"Neurosci. Bull."},{"key":"ref_41","unstructured":"Liu, S., Zhao, Y., Ren, Q., Gong, G., Zhang, D., Shao, K., Lin, P., Yuan, Y., Dai, T., and Zhang, Y. (2022, February 25). Research Square 2021. Available online: https:\/\/assets.researchsquare.com\/files\/rs-900442\/v1\/7c67881d-baba-4d40-b494-bd49d882bd54.pdf?c=1632165377."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"10166","DOI":"10.1038\/s41598-019-46687-7","article-title":"Structural MRI at 7T reveals amygdala nuclei and hippocampal subfield volumetric association with Major Depressive Disorder symptom severity","volume":"9","author":"Brown","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. R. Stat. Soc. Ser. B"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1017\/S0033291713001529","article-title":"Pre- and perinatal hypoxia associated with hippocampus\/amygdala volume in bipolar disorder","volume":"44","author":"Haukvik","year":"2013","journal-title":"Psychol. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.brainres.2010.08.049","article-title":"A neuroimaging investigation of the association between aerobic fitness, hippocampal volume, and memory performance in preadolescent children","volume":"1358","author":"Chaddock","year":"2010","journal-title":"Brain Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1080\/02640414.2011.647706","article-title":"Childhood aerobic fitness predicts cognitive performance one year later","volume":"30","author":"Chaddock","year":"2012","journal-title":"J. Sports Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.neuroscience.2018.07.050","article-title":"Is Objectively Assessed Sedentary Behavior, Physical Activity and Cardiorespiratory Fitness Linked to Brain Plasticity Outcomes in Old Age?","volume":"388","author":"Engeroff","year":"2018","journal-title":"Neuroscience"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"112488","DOI":"10.1016\/j.bbr.2020.112488","article-title":"Exercise effects on brain and behavior in healthy mice, Alzheimer\u2019s disease and Parkinson\u2019s disease model\u2014A systematic review and meta-analysis","volume":"383","author":"Daniele","year":"2020","journal-title":"Behav. Brain Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1037\/0033-2909.130.4.601","article-title":"Psychological Stress and the Human Immune System: A Meta-Analytic Study of 30 Years of Inquiry","volume":"130","author":"Segerstrom","year":"2004","journal-title":"Psychol. Bull."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.brainresbull.2015.10.009","article-title":"Developmental minocycline treatment reverses the effects of neonatal immune activation on anxiety- and depression-like behaviors, hippocampal inflammation, and HPA axis activity in adult mice","volume":"120","author":"Majidi","year":"2016","journal-title":"Brain Res. Bull."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"eaai7696","DOI":"10.1126\/scisignal.aai7696","article-title":"Astrocyte-shed extracellular vesicles regulate the peripheral leukocyte response to inflammatory brain lesions","volume":"10","author":"Dickens","year":"2017","journal-title":"Sci. Signal."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.bbr.2008.02.043","article-title":"Long-term consequences of soman poisoning in mice: Part 1. Neuropathology and neuronal regeneration in the amygdala","volume":"191","author":"Collombet","year":"2008","journal-title":"Behav. Brain Res."},{"key":"ref_53","first-page":"1837","article-title":"Selective Neuronal Necrosis Associated with Status Epilepticus: MR Findings","volume":"21","author":"Men","year":"2000","journal-title":"Am. J. Neuroradiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.brainres.2012.07.046","article-title":"Ketamine reduces neuronal degeneration and anxiety levels when administered during early life-induced status epilepticus in rats","volume":"1474","author":"Loss","year":"2012","journal-title":"Brain Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"338","DOI":"10.36295\/ASRO.2019.221144","article-title":"Correlation between Improve Lung Function with Decrease of Eosinophil Levels in Atopic Asthma Persistent After Asthma Exercise","volume":"22","author":"Handayani","year":"2019","journal-title":"Ann. Trop. Med. Public Heal."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"130","DOI":"10.3858\/emm.2012.44.2.008","article-title":"Identification of novel peptides that stimulate human neutrophils","volume":"44","author":"Bae","year":"2012","journal-title":"Exp. Mol. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1016\/j.injury.2007.09.016","article-title":"The systemic inflammatory response induced by trauma is reflected by multiple phenotypes of blood neutrophils","volume":"38","author":"Pillay","year":"2007","journal-title":"Injury"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/S0165-0173(98)00015-0","article-title":"The role of the complement system in traumatic brain injury","volume":"27","author":"Stahel","year":"1998","journal-title":"Brain Res. Rev."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/S0165-5728(00)00183-1","article-title":"Local neutrophil influx following lateral fluid-percussion brain injury in rats is associated with accumulation of complement activation fragments of the third component (C3) of the complement system","volume":"105","author":"Keeling","year":"2000","journal-title":"J. Neuroimmunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1253\/circj.CJ-15-0464","article-title":"Reactive Oxygen Species in Endothelial Function: From Disease to Adaptation","volume":"79","author":"Craige","year":"2015","journal-title":"Circ. J."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1152\/japplphysiol.01262.2001","article-title":"Lymphocyte apoptosis after exhaustive and moderate exercise","volume":"93","author":"Mooren","year":"2002","journal-title":"J. Appl. Physiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1152\/jappl.1996.81.3.1213","article-title":"Capacity of circulating neutrophils to produce reactive oxygen species after exhaustive exercise","volume":"81","author":"Suzuki","year":"1996","journal-title":"J. Appl. Physiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1080\/02640410802409683","article-title":"Antioxidant regulatory mechanisms in neutrophils and lymphocytes after intense exercise","volume":"27","author":"Ferrer","year":"2009","journal-title":"J. Sports Sci."},{"key":"ref_64","first-page":"81","article-title":"The Effects of Stress on Physical Activity and Exercise","volume":"44","author":"Sinha","year":"2013","journal-title":"Sports Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1017\/S0029665110001928","article-title":"Physical activity, exercise and low-grade systemic inflammation","volume":"69","author":"Cunningham","year":"2010","journal-title":"Proc. Nutr. Soc."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"3883","DOI":"10.1021\/acs.jproteome.6b00733","article-title":"AltitudeOmics: Red Blood Cell Metabolic Adaptation to High Altitude Hypoxia","volume":"15","author":"Nemkov","year":"2016","journal-title":"J. Proteome Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.bcmd.2006.10.161","article-title":"Red blood cell senescence and neocytolysis in humans after high altitude acclimatization","volume":"38","author":"Risso","year":"2007","journal-title":"Blood Cells Mol. Dis."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.12659\/MSM.889694","article-title":"Elevated red blood cell distri-bution width and inflammation in printing workers","volume":"19","author":"Celik","year":"2013","journal-title":"Med. Sci. Monit."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"917","DOI":"10.2217\/bmm-2017-0041","article-title":"Search for Alzheimer\u2019s disease biomarkers in blood cells: Hypotheses-driven approach","volume":"11","author":"Wojsiat","year":"2017","journal-title":"Biomarkers Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"537","DOI":"10.3233\/JAD-2010-101485","article-title":"Neuronal Hemoglobin is Reduced in Alzheimer\u2019s Disease, Argyrophilic Grain Disease, Parkinson\u2019s Disease, and Dementia with Lewy Bodies","volume":"23","author":"Ferrer","year":"2011","journal-title":"J. Alzheimers Dis."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/jcbfm.2008.152","article-title":"Expression of Hemoglobin in Rodent Neurons","volume":"29","author":"Schelshorn","year":"2008","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"616834","DOI":"10.1155\/2015\/616834","article-title":"Crosstalk between Red Blood Cells and the Immune System and Its Impact on Atherosclerosis","volume":"2015","author":"Buttari","year":"2015","journal-title":"BioMed. Res. Int."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.cca.2005.01.003","article-title":"Adaptations of the antioxidant system in erythrocytes of trained adult rats: Impact of intermittent hypobaric-hypoxia at two altitudes","volume":"140","author":"Devi","year":"2005","journal-title":"Comp. Biochem. Physiol. Part C Toxicol. Pharmacol."},{"key":"ref_74","first-page":"293","article-title":"Papel protector de la bilirrubina en el ser humano","volume":"24","author":"Velasco","year":"2009","journal-title":"Rev. Colomb. Gastroenterolog\u00eda"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/BF01553710","article-title":"Bilirubinemia and intravascular hemolysis during acclimatization to high altitude","volume":"21","author":"Altland","year":"1977","journal-title":"Int. J. Biometeorol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1007\/s00431-018-3245-4","article-title":"Changes in bilirubin in infants with hypoxic\u2013ischemic encephalopathy","volume":"177","author":"Dani","year":"2018","journal-title":"Eur. J. Pediatr."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.mcn.2011.06.008","article-title":"Selective vulnerability of rat brain regions to unconjugated bilirubin","volume":"48","author":"Vaz","year":"2011","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1080\/00362177985380171","article-title":"Effect of bilirubin on the fungicidal capacity of human neutrophils","volume":"17","author":"Thong","year":"1979","journal-title":"Med. Mycol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"6190609","DOI":"10.1155\/2016\/6190609","article-title":"Hyperbilirubinemia Protects against Aging-Associated Inflammation and Metabolic Deterioration","volume":"2016","author":"Zelenka","year":"2016","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2318","DOI":"10.1016\/j.joms.2019.05.023","article-title":"Severe Sleep Apnea Associated with Increased Systemic Inflammation and Decreased Serum Bilirubin","volume":"77","author":"Friedlander","year":"2019","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.1016\/j.biochi.2012.04.026","article-title":"Intracellular accumulation of bilirubin as a defense mechanism against increased oxidative stress","volume":"94","author":"Zelenka","year":"2012","journal-title":"Biochimie"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1152\/japplphysiol.00351.2017","article-title":"Epigenomics and human adaptation to high altitude","volume":"123","author":"Julian","year":"2017","journal-title":"J. Appl. 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