{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T14:29:37Z","timestamp":1792160977215,"version":"4.4.0"},"reference-count":75,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,9,7]],"date-time":"2025-09-07T00:00:00Z","timestamp":1757203200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Universidad Nacional Mayor de San Marcos","award":["05557-2022-R\/UNMSM"],"award-info":[{"award-number":["05557-2022-R\/UNMSM"]}]},{"name":"Universidad Nacional Mayor de San Marcos","award":["PE501092497-2024"],"award-info":[{"award-number":["PE501092497-2024"]}]},{"name":"PROCIENCIA-CONCYTEC","award":["05557-2022-R\/UNMSM"],"award-info":[{"award-number":["05557-2022-R\/UNMSM"]}]},{"name":"PROCIENCIA-CONCYTEC","award":["PE501092497-2024"],"award-info":[{"award-number":["PE501092497-2024"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hypoxia at altitudes above 3000 m poses a significant threat to organ health and physiological homeostasis, particularly in metabolically active tissues such as the brain. Many of the cellular alterations induced by hypoxia are associated with the excessive generation of reactive oxygen species (ROS) and the resulting oxidative stress. In this study, we investigated the effects of exposure duration and altitude levels on oxidative homeostasis in the rat hypothalamus, cortex, hippocampus, and striatum. We assessed ROS production, malondialdehyde (MDA) levels, the antioxidant activities of superoxide dismutase (SOD), and catalase, as well as molecular biomarkers of oxidative stress, cell death, and inflammation. Our findings demonstrated that ROS, MDA and SOD levels increased across all brain regions, particularly in response to higher altitude exposure. Conversely, catalase activity decreased under the same conditions. At the molecular level, we observed overexpression of key biomarkers related to oxidative stress, cell death, and inflammation, especially at extreme altitudes. Furthermore, these effects were most pronounced in the hippocampus, cortex, and striatum. In conclusion, our data indicate that hypoxic exposure at higher altitudes significantly contributes to the oxidative disruption of brain homeostasis in rats.<\/jats:p>","DOI":"10.3390\/ijms26178714","type":"journal-article","created":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T10:27:12Z","timestamp":1757500032000},"page":"8714","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Impact of Exposure Duration to High-Altitude Hypoxia on Oxidative Homeostasis in Rat Brain Regions"],"prefix":"10.3390","volume":"26","author":[{"given":"Boris","family":"Lira-Mej\u00eda","sequence":"first","affiliation":[{"name":"GIFATA Research Group, Animal Physiology Laboratory, Faculty of Veterinary Medicine, Major National University of San Marcos, Lima 15021, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Calderon-Romero","sequence":"additional","affiliation":[{"name":"GIFATA Research Group, Animal Physiology Laboratory, Faculty of Veterinary Medicine, Major National University of San Marcos, Lima 15021, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Ordaya-Fierro","sequence":"additional","affiliation":[{"name":"GIFATA Research Group, Animal Physiology Laboratory, Faculty of Veterinary Medicine, Major National University of San Marcos, Lima 15021, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristian","family":"Medina","sequence":"additional","affiliation":[{"name":"GIFATA Research Group, Animal Physiology Laboratory, Faculty of Veterinary Medicine, Major National University of San Marcos, Lima 15021, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3962-2101","authenticated-orcid":false,"given":"Jos\u00e9-Luis","family":"Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"GIFATA Research Group, Animal Physiology Laboratory, Faculty of Veterinary Medicine, Major National University of San Marcos, Lima 15021, Peru"},{"name":"Complutox Research Group, Department of Pharmacology and Toxicology, Faculty of Veterinary, Complutense University of Madrid, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5483-4973","authenticated-orcid":false,"given":"Alejandro","family":"Romero","sequence":"additional","affiliation":[{"name":"Complutox Research Group, Department of Pharmacology and Toxicology, Faculty of Veterinary, Complutense University of Madrid, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"D\u00e1vila","sequence":"additional","affiliation":[{"name":"GIFATA Research Group, Animal Physiology Laboratory, Faculty of Veterinary Medicine, Major National University of San Marcos, Lima 15021, Peru"},{"name":"Veterinary Clinic, Faculty of Veterinary Medicine, Major National University of San Marcos, Lima 15021, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9990-4074","authenticated-orcid":false,"given":"Mariella","family":"Ramos-Gonzalez","sequence":"additional","affiliation":[{"name":"Zootecnia an Animal Production Laboratory, Faculty of Veterinary Medicine, Major National University of San Marcos, Lima 15021, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Mukandala, G., Tynan, R., Lanigan, S., and O\u2019Connor, J.J. (2016). The Effects of Hypoxia and Inflammation on Synaptic Signaling in the CNS. Brain Sci., 6.","DOI":"10.3390\/brainsci6010006"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1023\/A:1026080320034","article-title":"High altitude hypoxia: An intricate interplay of oxygen responsive macroevents and micromolecules","volume":"253","author":"Sarkar","year":"2003","journal-title":"Mol. Cell. Biochem."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Li, Z., Zhang, J., Zhang, X., Jin, Q., Zheng, X., Mo, L., and Da, Z. (2025). Oxygen metabolism abnormalities and high-altitude cerebral edema. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1555910"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4163188","DOI":"10.1155\/2022\/4163188","article-title":"Insight into the Effects of High-Altitude Hypoxic Exposure on Learning and Memory","volume":"2022","author":"Zhang","year":"2022","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Pena, E., El Alam, S., Siques, P., and Brito, J. (2022). Oxidative Stress and Diseases Associated with High-Altitude Exposure. Antioxidants, 11.","DOI":"10.3390\/antiox11020267"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.neuint.2006.06.002","article-title":"Hypobaric hypoxia induces oxidative stress in rat brain","volume":"49","author":"Maiti","year":"2006","journal-title":"Neurochem. Int."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.redox.2017.02.014","article-title":"Oxidative stress and apoptosis after acute respiratory hypoxia and reoxygenation in rat brain","volume":"12","author":"Alva","year":"2017","journal-title":"Redox Biol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Ionescu, C., Ghidersa, M., Ciobica, A., Mavroudis, I., Kazis, D., Petridis, F.E., Gorgan, D.L., and Balmus, I.M. (2025). Potential Correlation Between Molecular Biomarkers and Oxidative Stress in Traumatic Brain Injury. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26083858"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/S0301-0082(00)00011-3","article-title":"Mechanisms underlying hypoxia-induced neuronal apoptosis","volume":"62","author":"Banasiak","year":"2000","journal-title":"Prog. Neurobiol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Cui, C., Jiang, X., Wang, Y., Li, C., Lin, Z., Wei, Y., and Ni, Q. (2024). Cerebral Hypoxia-Induced Molecular Alterations and Their Impact on the Physiology of Neurons and Dendritic Spines: A Comprehensive Review. Cell. Mol. Neurobiol., 44.","DOI":"10.1007\/s10571-024-01491-4"},{"key":"ref_11","first-page":"e63852","article-title":"Hypoxia-Inducible Factor 1-Alpha (HIF-1\u03b1): An Essential Regulator in Cellular Metabolic Control","volume":"16","author":"Basheeruddin","year":"2024","journal-title":"Cureus"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/978-3-031-42003-0_6","article-title":"Pro-survival Phenotype of HIF-1\u03b1: Neuroprotection Through Inflammatory Mechanisms","volume":"1438","author":"Puchowicz","year":"2023","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1002\/jnr.24366","article-title":"The insights into molecular pathways of hypoxia-inducible factor in the brain","volume":"98","author":"Ostrowski","year":"2020","journal-title":"J. Neurosci. Res."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Guo, L., and Zhu, L. (2021). Multiple Roles of Peripheral Immune System in Modulating Ischemia\/Hypoxia-Induced Neuroinflammation. Front. Mol. Biosci., 8.","DOI":"10.3389\/fmolb.2021.752465"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1097\/00007890-199702150-00023","article-title":"Hypoxia, but not reoxygenation, induces interleukin 6 gene expression through NF-kappa B activation","volume":"63","author":"Muraoka","year":"1997","journal-title":"Transplantation"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.4049\/jimmunol.1002256","article-title":"An intact canonical NF-\u03baB pathway is required for inflammatory gene expression in response to hypoxia","volume":"186","author":"Fitzpatrick","year":"2011","journal-title":"J. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1074\/jbc.272.1.601","article-title":"Hypoxia induces cyclooxygenase-2 via the NF-kappaB p65 transcription factor in human vascular endothelial cells","volume":"272","author":"Schmedtje","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1101\/gad.13.15.1899","article-title":"BCL-2 family members and the mitochondria in apoptosis","volume":"13","author":"Gross","year":"1999","journal-title":"Genes Dev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/S0092-8674(00)80434-1","article-title":"Cytochrome c and dATP-dependent formation of Apaf-1\/caspase-9 complex initiates an apoptotic protease cascade","volume":"91","author":"Li","year":"1997","journal-title":"Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1038\/cdd.2009.16","article-title":"Role of BNIP3 and NIX in cell death, autophagy, and mitophagy","volume":"16","author":"Zhang","year":"2009","journal-title":"Cell Death Differ."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Aboouf, M.A., Thiersch, M., Soliz, J., Gassmann, M., and Schneider Gasser, E.M. (2023). The Brain at High Altitude: From Molecular Signaling to Cognitive Performance. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241210179"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1111\/j.1582-4934.2011.01258.x","article-title":"Why is the partial oxygen pressure of human tissues a crucial parameter? Small molecules and hypoxia","volume":"15","author":"Carreau","year":"2011","journal-title":"J. Cell. Mol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Zhang, K., Zhou, Y., Zhao, T., Wu, L., Huang, X., Wu, K., Xu, L., Li, D., Liu, S., and Zhao, Y. (2015). Reduced Cerebral Oxygen Content in the DG and SVZ In Situ Promotes Neurogenesis in the Adult Rat Brain In Vivo. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0140035"},{"key":"ref_24","unstructured":"Hultgren, H.N. (1997). High Altitude Medicine, Hultgren Publications."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1042\/cs0900081","article-title":"Are Himalayan Sherpas better protected against brain damage associated with extreme altitude climbs?","volume":"90","author":"Garrido","year":"1996","journal-title":"Clin. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Kottke, R., Pichler Hefti, J., Rummel, C., Hauf, M., Hefti, U., and Merz, T.M. (2015). Morphological Brain Changes after Climbing to Extreme Altitudes\u2014A Prospective Cohort Study. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0141097"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"791","DOI":"10.3357\/AMHP.6061.2022","article-title":"Attention Network Changes of High-Altitude Migrants","volume":"93","author":"An","year":"2022","journal-title":"Aerosp. Med. Hum. Perform."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1016\/j.clinph.2005.02.020","article-title":"Effects of simulated high altitude on event-related potential (P300) and auditory brain-stem responses","volume":"116","author":"Hayashi","year":"2005","journal-title":"Clin. Neurophysiol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Sch\u00f6nenberger, M.J., and Kovacs, W.J. (2015). Hypoxia signaling pathways: Modulators of oxygen-related organelles. Front. Cell Dev. Biol., 3.","DOI":"10.3389\/fcell.2015.00042"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1023\/A:1027374931887","article-title":"Superoxide production by the mitochondrial respiratory chain","volume":"17","author":"Turrens","year":"1997","journal-title":"Biosci. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/S0014-5793(01)02850-2","article-title":"The site of production of superoxide radical in mitochondrial Complex I is not a bound ubisemiquinone but presumably iron-sulfur cluster N2","volume":"505","author":"Genova","year":"2001","journal-title":"FEBS Lett."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/S0006-291X(03)00818-0","article-title":"Oxygen dependence of mitochondrial nitric oxide synthase activity","volume":"305","author":"Alvarez","year":"2003","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1152\/physrev.00026.2013","article-title":"Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release","volume":"94","author":"Zorov","year":"2014","journal-title":"Physiol. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"11715","DOI":"10.1073\/pnas.95.20.11715","article-title":"Mitochondrial reactive oxygen species trigger hypoxia-induced transcription","volume":"95","author":"Chandel","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/S1569-9048(02)00051-4","article-title":"O(2) sensing in hypoxic pulmonary vasoconstriction: The mitochondrial door re-opens","volume":"132","author":"Waypa","year":"2002","journal-title":"Respir. Physiol. Neurobiol."},{"key":"ref_36","first-page":"956","article-title":"Oxidative stress concept updated: Definitions, classifications, and regulatory pathways implicated","volume":"20","author":"Lushchak","year":"2021","journal-title":"EXCLI J."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Leveque, C., Mrakic Sposta, S., Theunissen, S., Germonpr\u00e9, P., Lambrechts, K., Vezzoli, A., Gussoni, M., Levenez, M., Laf\u00e8re, P., and Guerrero, F. (2023). Oxidative Stress Response Kinetics after 60 Minutes at Different Levels (10% or 15%) of Normobaric Hypoxia Exposure. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241210188"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1113\/expphysiol.2006.033506","article-title":"Oxygen sensing by mitochondria at complex III: The paradox of increased reactive oxygen species during hypoxia","volume":"91","author":"Guzy","year":"2006","journal-title":"Exp. Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/978-3-030-89340-8_3","article-title":"Pathological Roles of Reactive Oxygen Species in Male Reproduction","volume":"1358","author":"Chakraborty","year":"2022","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1089\/ham.2009.1057","article-title":"Role of oxidative stress and inflammation in hypoxia-induced cerebral edema: A molecular approach","volume":"11","author":"Himadri","year":"2010","journal-title":"High Alt. Med. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1007\/s12192-017-0795-8","article-title":"Oxidative protein modification alters proteostasis under acute hypobaric hypoxia in skeletal muscles: A comprehensive in vivo study","volume":"22","author":"Agrawal","year":"2017","journal-title":"Cell Stress Chaperones"},{"key":"ref_42","first-page":"540","article-title":"Effect of different altitudes on telomere length of rat peripheral blood leukocyte","volume":"65","author":"Wang","year":"2013","journal-title":"Sheng Li Xue Bao Acta Physiol. Sin."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.wem.2010.09.004","article-title":"Oxidative stress status in rats after intermittent exposure to hypobaric hypoxia","volume":"21","author":"Esteva","year":"2010","journal-title":"Wilderness Environ. Med."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Aguilar, M., Gonz\u00e1lez-Candia, A., Rodr\u00edguez, J., Carrasco-Pozo, C., Ca\u00f1as, D., Garc\u00eda-Herrera, C., Herrera, E.A., and Castillo, R.L. (2018). Mechanisms of Cardiovascular Protection Associated with Intermittent Hypobaric Hypoxia Exposure in a Rat Model: Role of Oxidative Stress. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19020366"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1089\/ham.2019.0143","article-title":"Oxidative and Endoplasmic Reticulum Stress Responses to Chronic High-Altitude Exposure During the Development of High-Altitude Pulmonary Hypertension","volume":"21","author":"Pu","year":"2020","journal-title":"High Alt. Med. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"574524","DOI":"10.1093\/ecam\/nep199","article-title":"Modulation of Hypoxia-Induced Pulmonary Vascular Leakage in Rats by Seabuckthorn (Hippophae rhamnoides L.)","volume":"2011","author":"Purushothaman","year":"2011","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.brainresbull.2008.08.026","article-title":"Modulatory effects of seabuckthorn (Hippophae rhamnoides L.) in hypobaric hypoxia induced cerebral vascular injury","volume":"77","author":"Purushothaman","year":"2008","journal-title":"Brain Res. Bull."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.molimm.2018.02.001","article-title":"Ganglioside GM1 protects against high altitude cerebral edema in rats by suppressing the oxidative stress and inflammatory response via the PI3K\/AKT-Nrf2 pathway","volume":"95","author":"Gong","year":"2018","journal-title":"Mol. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2499","DOI":"10.1007\/s00204-023-03562-9","article-title":"Reactive oxygen species, toxicity, oxidative stress, and antioxidants: Chronic diseases and aging","volume":"97","author":"Jomova","year":"2023","journal-title":"Arch. Toxicol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.expneurol.2008.01.030","article-title":"Chronic hypobaric hypoxia induced apoptosis in CA1 region of hippocampus: A possible role of NMDAR mediated p75NTR upregulation","volume":"212","author":"Hota","year":"2008","journal-title":"Exp. Neurol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1089\/ham.2024.0041","article-title":"Hypobaric Hypoxia Increased Autophagy and Apoptosis in PC12 Rat Pheochromocytoma Cells More Than Normobaric Hypoxia","volume":"26","author":"Yin","year":"2025","journal-title":"High Alt. Med. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Huan, Y., Quan, H., Jia, B., Hao, G., Shi, Z., Zhao, T., Yuan, Y., Yuan, F., Dong, Y., and Liang, G. (2023). High-altitude cerebral hypoxia promotes mitochondrial dysfunction and apoptosis of mouse neurons. Front. Mol. Neurosci., 16.","DOI":"10.3389\/fnmol.2023.1216947"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1007\/s11064-023-04080-x","article-title":"Nitronyl Nitroxide Ameliorates Hypobaric Hypoxia-Induced Cognitive Impairment in Mice by Suppressing the Oxidative Stress, Inflammatory Response and Apoptosis","volume":"49","author":"Jing","year":"2024","journal-title":"Neurochem. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"152114","DOI":"10.1016\/j.acthis.2023.152114","article-title":"Histological and cytochemical analysis of the brain under conditions of hypobaric hypoxia-induced oxygen deficiency in albino rats","volume":"125","author":"Shushanyan","year":"2023","journal-title":"Acta Histochem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.neuroscience.2022.11.009","article-title":"Keratin 18 Depletion as a Possible Mechanism for the Induction of Apoptosis and Ferroptosis in the Rat Hippocampus After Hypobaric Hypoxia","volume":"513","author":"Cui","year":"2023","journal-title":"Neuroscience"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"147987","DOI":"10.1016\/j.brainres.2022.147987","article-title":"Dynamic cerebral blood flow changes with FOXOs stimulation are involved in neuronal damage associated with high-altitude cerebral edema in mice","volume":"1790","author":"Shi","year":"2022","journal-title":"Brain Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/sj.cdd.4400810","article-title":"Hypoxia induces the expression of the pro-apoptotic gene BNIP3","volume":"8","author":"Guo","year":"2001","journal-title":"Cell Death Differ."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2673","DOI":"10.1089\/ars.2009.2730","article-title":"Mitochondrial regulation of cell survival and death during low-oxygen conditions","volume":"11","author":"Snyder","year":"2009","journal-title":"Antioxid. Redox Signal."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"137163","DOI":"10.1016\/j.neulet.2023.137163","article-title":"Time-course effects and mechanisms of hypobaric hypoxia on nervous system in mice","volume":"801","author":"Zhang","year":"2023","journal-title":"Neurosci. Lett."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"175015","DOI":"10.1016\/j.ejphar.2022.175015","article-title":"Salidroside attenuates high altitude hypobaric hypoxia-induced brain injury in mice via inhibiting NF-\u03baB\/NLRP3 pathway","volume":"925","author":"Jiang","year":"2022","journal-title":"Eur. J. Pharmacol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Wang, R., Ma, S., Yang, J., Luo, K., Qian, Q., Pan, J., Liang, K., Wang, Y., Gao, Y., and Li, M. (2024). Sodium Hydrosulfide Protects Rats from Hypobaric-Hypoxia-Induced Acute Lung Injury. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms251910734"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1186\/s12931-024-02975-z","article-title":"Curcumin-mediated enhancement of lung barrier function in rats with high-altitude-associated acute lung injury via inhibition of inflammatory response","volume":"25","author":"Yang","year":"2024","journal-title":"Respir. Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"118861","DOI":"10.1016\/j.jep.2024.118861","article-title":"Preconditioning with Ginsenoside Rg3 mitigates cardiac injury induced by high-altitude hypobaric hypoxia exposure in mice by suppressing ferroptosis through inhibition of the RhoA\/ROCK signaling pathway","volume":"337","author":"Liu","year":"2025","journal-title":"J. Ethnopharmacol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e36241","DOI":"10.1016\/j.heliyon.2024.e36241","article-title":"Network pharmacology and in vivo experimental studies reveal the protective effects of 6-hydroxygenistein against hypobaric hypoxia-induced brain injury","volume":"10","author":"Shi","year":"2024","journal-title":"Heliyon"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1038\/cr.2010.178","article-title":"Crosstalk of reactive oxygen species and NF-\u03baB signaling","volume":"21","author":"Morgan","year":"2011","journal-title":"Cell Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1038\/35094583","article-title":"Cytokines and acute neurodegeneration","volume":"2","author":"Allan","year":"2001","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"10954","DOI":"10.1073\/pnas.95.18.10954","article-title":"Cyclooxygenase-2 inhibition prevents delayed death of CA1 hippocampal neurons following global ischemia","volume":"95","author":"Nakayama","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.neubiorev.2017.01.019","article-title":"Effect of acute hypoxia on cognition: A systematic review and meta-regression analysis","volume":"74","author":"McMorris","year":"2017","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Chen, X., Zhang, J., Lin, Y., Li, Y., Wang, H., Wang, Z., Liu, H., Hu, Y., and Liu, L. (2023). Mechanism, prevention and treatment of cognitive impairment caused by high altitude exposure. Front. Physiol., 14.","DOI":"10.3389\/fphys.2023.1191058"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e41479","DOI":"10.1097\/MD.0000000000041479","article-title":"Impact of hypoxia on the hippocampus: A review","volume":"104","author":"Lu","year":"2025","journal-title":"Medicine"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/s11065-004-8159-4","article-title":"Neuropsychological functioning associated with high-altitude exposure","volume":"14","author":"Garrido","year":"2004","journal-title":"Neuropsychol. Rev."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1111\/j.1471-4159.1966.tb09873.x","article-title":"Regional studies of catecholamines in the rat brain. I. The disposition of [3H]norepinephrine, [3H]dopamine and [3H]dopa in various regions of the brain","volume":"13","author":"Glowinski","year":"1966","journal-title":"J. Neurochem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/0197-0186(90)90025-O","article-title":"Sensitive and rapid quantitation of oxygen reactive species formation in rat synaptosomes","volume":"17","author":"Lebel","year":"1990","journal-title":"Neurochem. Int."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Dasgupta, A., and Klein, K. (2014). Chapter 2\u2014Methods for Measuring Oxidative Stress in the Laboratory. Antioxidants in Food, Vitamins and Supplements, Elsevier.","DOI":"10.1016\/B978-0-12-405872-9.00002-1"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Barrios-Arpi, L., Arias, Y., Lopez-Torres, B., Ramos-Gonzalez, M., Ticli, G., Prosperi, E., and Rodr\u00edguez, J.L. (2022). In Vitro Neurotoxicity of Flumethrin Pyrethroid on SH-SY5Y Neuroblastoma Cells: Apoptosis Associated with Oxidative Stress. Toxics, 10.","DOI":"10.3390\/toxics10030131"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/17\/8714\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:41:27Z","timestamp":1760035287000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/17\/8714"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,7]]},"references-count":75,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["ijms26178714"],"URL":"https:\/\/doi.org\/10.3390\/ijms26178714","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,7]]}}}