{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T14:54:22Z","timestamp":1776092062894,"version":"3.50.1"},"reference-count":58,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,6,15]],"date-time":"2025-06-15T00:00:00Z","timestamp":1749945600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondecyt Regular","award":["1241502"],"award-info":[{"award-number":["1241502"]}]},{"name":"Fondecyt Regular","award":["1241626"],"award-info":[{"award-number":["1241626"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Gestational chronic hypoxia impacts prenatal development, leading to fetal growth restriction (FGR), defined as the fetus\u2019s failure to reach its genetic growth potential. Postnatal hypoxia in the cerebral tissue can induce a redox imbalance and mitochondrial dysfunction, consequently increasing neuronal death. However, these data cannot necessarily be extrapolated to prenatal hypoxia. In this regard, this study aims to describe the effect of gestational hypoxia on redox balance and apoptosis cell death mechanisms in the prefrontal cortex of guinea pigs. Ten Guinea pig (Cavia porcellus) pregnant dams were utilized in this study; five gestated in normoxia (Nx; three newborn males, and two females) and five gestated under chronic hypobaric hypoxia (Hx; two newborn males, and three females). We monitored the pregnancies by ultrasound examinations from gestational days 20 to 65 (term ~ 70). At birth, pups were euthanized, and the fetal brain was collected for cellular redox measurement, mitochondrial enzyme expression, and apoptosis assay. Gestation under hypoxia induced an imbalance in the expression of anti- and pro-oxidant enzymes, resulting in increased oxidative stress. Additionally, a decrease in cytochrome I and III expression and neuronal density in the neonatal prefrontal cortex was observed. Finally, DNA fragmentation was increased by the TUNEL assay in the brain tissue of newborns gestated under chronic hypoxia. Our findings demonstrate the association of gestational hypoxia with oxidative stress and neuronal death in newborns, which may predispose to neuronal dysfunction in adulthood.<\/jats:p>","DOI":"10.3390\/antiox14060736","type":"journal-article","created":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T14:03:11Z","timestamp":1750082591000},"page":"736","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Redox Imbalance Is Associated with Neuronal Apoptosis in the Cortex of Neonates Gestated Under Chronic Hypoxia"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1316-738X","authenticated-orcid":false,"given":"Esteban G.","family":"Figueroa","sequence":"first","affiliation":[{"name":"Laboratory of Fetal Neuroprogramming, Institute of Health Sciences, Universidad de O\u2019Higgins, Rancagua 3655000, Chile"},{"name":"Institute of Health Sciences, Universidad de O\u2019Higgins, Rancagua 3655000, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rodrigo L.","family":"Castillo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine East, Faculty of Medicine, Universidad de Chile, Santiago 7500922, Chile"},{"name":"Critical Patient Unit, Hospital del Salvador, Santiago 7500922, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4611-2748","authenticated-orcid":false,"given":"Adolfo A.","family":"Paz","sequence":"additional","affiliation":[{"name":"Laboratory of Vascular Function & Reactivity, Pathophysiology Program, ICBM, Faculty of Medicine, Universidad de Chile, Santiago 8330015, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3163-3911","authenticated-orcid":false,"given":"Mat\u00edas","family":"Monsalves-Alvarez","sequence":"additional","affiliation":[{"name":"Exercise and Rehabilitation Sciences Institute, Faculty of Rehabilitation Sciences, Universidad Andr\u00e9s Bello, Santiago 7610196, Chile"},{"name":"Geroscience Center for Brain Health and Metabolism (GERO), Santiago 7800003, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisca","family":"Salas-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Institute of Health Sciences, Universidad de O\u2019Higgins, Rancagua 3655000, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ximena","family":"Calle","sequence":"additional","affiliation":[{"name":"Institute of Health Sciences, Universidad de O\u2019Higgins, Rancagua 3655000, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tamara A.","family":"Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Laboratory of Vascular Function & Reactivity, Pathophysiology Program, ICBM, Faculty of Medicine, Universidad de Chile, Santiago 8330015, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6342-085X","authenticated-orcid":false,"given":"Emilio A.","family":"Herrera","sequence":"additional","affiliation":[{"name":"Laboratory of Vascular Function & Reactivity, Pathophysiology Program, ICBM, Faculty of Medicine, Universidad de Chile, Santiago 8330015, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alejandro","family":"Gonzal\u00e9z-Candia","sequence":"additional","affiliation":[{"name":"Laboratory of Fetal Neuroprogramming, Institute of Health Sciences, Universidad de O\u2019Higgins, Rancagua 3655000, Chile"},{"name":"Institute of Health Sciences, Universidad de O\u2019Higgins, Rancagua 3655000, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.earlhumdev.2004.10.003","article-title":"The Fetal, Neonatal, and Infant Environments-the Long-Term Consequences for Disease Risk","volume":"81","author":"Gluckman","year":"2005","journal-title":"Early Hum. Dev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1152\/physiol.00050.2005","article-title":"Intrauterine Programming of Physiological Systems: Causes and Consequences","volume":"21","author":"Fowden","year":"2006","journal-title":"Physiology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1002\/bdr2.1142","article-title":"Hypoxia: From Placental Development to Fetal Programming","volume":"109","author":"Fajersztajn","year":"2017","journal-title":"Birth Defects Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.placenta.2020.05.003","article-title":"The Placenta in Fetal Growth Restriction: What Is Going Wrong?","volume":"96","author":"Sun","year":"2020","journal-title":"Placenta"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1113\/JP271099","article-title":"The Fetal Brain Sparing Response to Hypoxia: Physiological Mechanisms","volume":"594","author":"Giussani","year":"2016","journal-title":"J. Physiol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Demirci-\u00c7eki\u00e7, S., \u00d6zkan, G., Avan, A.N., Uzunboy, S., \u00c7apano\u011flu, E., and Apak, R. (2022). Biomarkers of Oxidative Stress and Antioxidant Defense. J. Pharm. Biomed. Anal., 209.","DOI":"10.1016\/j.jpba.2021.114477"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Chen, R., Lai, U.H., Zhu, L., Singh, A., Ahmed, M., and Forsyth, N.R. (2018). Reactive Oxygen Species Formation in the Brain at Different Oxygen Levels: The Role of Hypoxia Inducible Factors. Front. Cell Dev. Biol., 6.","DOI":"10.3389\/fcell.2018.00132"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.freeradbiomed.2018.03.042","article-title":"Hypoxia, Oxidative Stress and Inflammation","volume":"125","author":"McGarry","year":"2018","journal-title":"Free Radic. Biol. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.1159\/000489450","article-title":"Upregulation of NOX2 and NOX4 Mediated by TGF-\u03b2 Signaling Pathway Exacerbates Cerebral Ischemia\/Reperfusion Oxidative Stress Injury","volume":"46","author":"Lou","year":"2018","journal-title":"Cell Physiol. Biochem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/978-3-030-04615-6_8","article-title":"Nox2 and Nox4 Participate in ROS-Induced Neuronal Apoptosis and Brain Injury During Ischemia-Reperfusion in Rats","volume":"127","author":"Wang","year":"2020","journal-title":"Acta Neurochir. Suppl."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1007\/s00484-020-02037-1","article-title":"High-Altitude Hypoxia Induced Reactive Oxygen Species Generation, Signaling, and Mitigation Approaches","volume":"65","author":"Gaur","year":"2021","journal-title":"Int. J. Biometeorol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Hu, X.Q., and Zhang, L. (2021). Hypoxia and Mitochondrial Dysfunction in Pregnancy Complications. Antioxidants, 10.","DOI":"10.3390\/antiox10030405"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Herrera, E.A., Krause, B., Ebensperger, G., Reyes, R.V., Casanello, P., Parra-Cordero, M., and Llanos, A.J. (2014). The Placental Pursuit for an Adequate Oxidant Balance between the Mother and the Fetus. Front. Pharmacol., 5.","DOI":"10.3389\/fphar.2014.00149"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"103","DOI":"10.24041\/ejmr2019.139","article-title":"Non-Enzymatic Natural Reactive Oxygen Scavengers (ROS): A Review on Structures and Mode of Action","volume":"6","author":"Ahamad","year":"2019","journal-title":"Era\u2019s J. Med. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2768365","DOI":"10.1155\/2016\/2768365","article-title":"Oxidative Stress Related Diseases in Newborns","volume":"2016","author":"Ozsurekci","year":"2016","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Panfoli, I., Candiano, G., Malova, M., De Angelis, L., Cardiello, V., Buonocore, G., and Ramenghi, L.A. (2018). Oxidative Stress as a Primary Risk Factor for Brain Damage in Preterm Newborns. Front. Pediatr., 6.","DOI":"10.3389\/fped.2018.00369"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1523\/JNEUROSCI.3989-03.2004","article-title":"Glutathione Peroxidase-Catalase Cooperativity Is Required for Resistance to Hydrogen Peroxide by Mature Rat Oligodendrocytes","volume":"24","author":"Baud","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1152\/physrev.00047.2006","article-title":"Life and Death: Metabolic Rate, Membrane Composition, and Life Span of Animals","volume":"87","author":"Hulbert","year":"2007","journal-title":"Physiol. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.2174\/1570159X19666211111141246","article-title":"Association of Oxidative Stress with Neurological Disorders","volume":"20","author":"Hassan","year":"2022","journal-title":"Curr. Neuropharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Astorga, C.R., Gonz\u00e1lez-Candia, A., Candia, A.A., Figueroa, E.G., Ca\u00f1as, D., Ebensperger, G., Reyes, R.V., Llanos, A.J., and Herrera, E.A. (2018). Melatonin Decreases Pulmonary Vascular Remodeling and Oxygen Sensitivity in Pulmonary Hypertensive Newborn Lambs. Front. Physiol., 9.","DOI":"10.3389\/fphys.2018.00185"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Candia, A.A., Jim\u00e9nez, T., Navarrete, \u00c1., Be\u00f1aldo, F., Silva, P., Garc\u00eda-Herrera, C., Sferruzzi-Perri, A.N., Krause, B.J., Gonz\u00e1lez-Candia, A., and Herrera, E.A. (2023). Developmental Ultrasound Characteristics in Guinea Pigs: Similarities with Human Pregnancy. Vet. Sci., 10.","DOI":"10.3390\/vetsci10020144"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1111\/jpi.12222","article-title":"Melatonin Reduces Oxidative Stress and Improves Vascular Function in Pulmonary Hypertensive Newborn Sheep","volume":"58","author":"Torres","year":"2015","journal-title":"J. Pineal Res."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Gonzalez-Candia, A., Veliz, M., Carrasco-Pozo, C., Castillo, R.L., C\u00e1rdenas, J.C., Ebensperger, G., Reyes, R.V., Llanos, A.J., and Herrera, E.A. (2019). Antenatal Melatonin Modulates an Enhanced Antioxidant\/pro-Oxidant Ratio in Pulmonary Hypertensive Newborn Sheep. Redox Biol., 22.","DOI":"10.1016\/j.redox.2019.101128"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1007\/s10096-023-04654-1","article-title":"Tenofovir Disoproxil Fumarate Mediates Neuronal Injury by Inducing Neurotoxicity","volume":"42","author":"Yang","year":"2023","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1097\/AOG.0b013e318212140e","article-title":"Fetal Programming of Adult Disease: Implications for Prenatal Care","volume":"117","author":"Lau","year":"2011","journal-title":"Obstet. Gynecol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1111\/j.1467-8721.2008.00544.x","article-title":"Fetal programming: Prenatal origins of health and illness","volume":"17","author":"Coe","year":"2008","journal-title":"Curr. Dir. Psychol. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.biocel.2006.07.001","article-title":"Free Radicals and Antioxidants in Normal Physiological Functions and Human Disease","volume":"39","author":"Valko","year":"2007","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1203\/00006450-198403000-00004","article-title":"Preparation for Birth into an O2-Rich Environment: The Antioxidant Enzymes in the Developing Rabbit Lung","volume":"18","author":"Frank","year":"1984","journal-title":"Pediatr. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.siny.2010.04.001","article-title":"Maturation of the Antioxidant System and the Effects on Preterm Birth","volume":"15","author":"Davis","year":"2010","journal-title":"Semin. Fetal Neonatal Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"5535","DOI":"10.1113\/JP274948","article-title":"Guinea pig models for translation of the developmental origins of health and disease hypothesis into the clinic","volume":"596","author":"Morrison","year":"2018","journal-title":"J. Physiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1007\/s10571-015-0298-z","article-title":"Modulation of Brain Glutathione Reductase and Peroxiredoxin 2 by \u03b1-Tocopheryl Phosphate","volume":"36","author":"Uchoa","year":"2016","journal-title":"Cell Mol. Neurobiol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Terraneo, L., Paroni, R., Bianciardi, P., Giallongo, T., Carelli, S., Gorio, A., and Samaja, M. (2016). Brain Adaptation to Hypoxia and Hyperoxia in Mice. Redox Biol., 11.","DOI":"10.1016\/j.redox.2016.10.018"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1152\/physrev.00044.2005","article-title":"The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology","volume":"87","author":"Bedard","year":"2007","journal-title":"Physiol. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Gonzalez-Candia, A., and Herrera, E.A. (2021). High Altitude Pregnancies and Vascular Dysfunction: Observations From Latin American Studies. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.786038"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1097\/CCM.0b013e3181cb1158","article-title":"Cyclooxygenase-2 Inhibition Provides Lasting Protection against Neonatal Hypoxic-Ischemic Brain Injury","volume":"38","author":"Fathali","year":"2010","journal-title":"Crit. Care Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s12933-016-0369-6","article-title":"Oxidative Stress, Inflammation, Endothelial Dysfunction and Incidence of Type 2 Diabetes","volume":"15","author":"Odegaard","year":"2016","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1089\/ars.2020.8093","article-title":"Hypoxic-Ischemic Encephalopathy and Mitochondrial Dysfunction: Facts, Unknowns, and Challenges","volume":"33","author":"Valez","year":"2020","journal-title":"Antioxid. Redox Signal"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/S0306-4522(00)00271-2","article-title":"Reduced Number of Neurons in the Hippocampus and the Cerebellum in the Postnatal Guinea-Pig Following Intrauterine Growth-Restriction","volume":"100","author":"Mallard","year":"2000","journal-title":"Neuroscience"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1177\/1933719110364061","article-title":"Brain Injury Caused by Chronic Fetal Hypoxemia Is Mediated by Inflammatory Cascade Activation","volume":"17","author":"Guo","year":"2010","journal-title":"Reprod. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.placenta.2016.11.012","article-title":"Review: Neuroinflammation in Intrauterine Growth Restriction","volume":"54","author":"Wixey","year":"2017","journal-title":"Placenta"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1177\/0883073821999896","article-title":"Mechanisms Underlying Neurologic Injury in Intrauterine Growth Restriction","volume":"36","author":"Wan","year":"2021","journal-title":"J. Child. Neurol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.brainres.2009.09.006","article-title":"Long-Term Cognitive Impairment and Myelination Deficiency in a Rat Model of Perinatal Hypoxic-Ischemic Brain Injury","volume":"1301","author":"Huang","year":"2009","journal-title":"Brain Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1111\/j.1460-9568.2006.04918.x","article-title":"Minocycline Attenuates Hypoxia-Ischemia-Induced Neurological Dysfunction and Brain Injury in the Juvenile Rat","volume":"24","author":"Fan","year":"2006","journal-title":"Eur. J. Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.pediatrneurol.2008.09.016","article-title":"Role of Perinatal Inflammation in Cerebral Palsy","volume":"40","author":"Girard","year":"2009","journal-title":"Pediatr. Neurol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1097\/00004647-199703000-00005","article-title":"Interleukin-8 Released into the Cerebrospinal Fluid after Brain Injury Is Associated with Blood-Brain Barrier Dysfunction and Nerve Growth Factor Production","volume":"17","author":"Kossmann","year":"1997","journal-title":"J. Cereb. Blood Flow. Metab."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.braindev.2005.06.006","article-title":"IL-1beta, IL-6 and TNF-Alpha and Outcomes of Neonatal Hypoxic Ischemic Encephalopathy","volume":"28","author":"Aly","year":"2006","journal-title":"Brain Dev."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1038\/jcbfm.2015.134","article-title":"Interleukin-1\u03b2 Transfer across the Blood\u2013Brain Barrier in the Ovine Fetus","volume":"35","author":"Sadowska","year":"2015","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s42000-018-0007-7","article-title":"Perinatal Hypoxia as a Risk Factor for Psychopathology Later in Life: The Role of Dopamine and Neurotrophins","volume":"17","author":"Giannopoulou","year":"2018","journal-title":"Hormones"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.earlhumdev.2006.09.001","article-title":"Intrauterine Growth Restriction and Circulating Neurotrophin Levels at Term","volume":"83","author":"Nikolaou","year":"2007","journal-title":"Early Hum. Dev."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.aanat.2015.02.003","article-title":"Immunoreactivity of Neurogenic Factor in the Guinea Pig Brain after Prenatal Hypoxia","volume":"200","author":"Chung","year":"2015","journal-title":"Ann. Anat."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1093\/jnen\/59.3.218","article-title":"Chronic Prenatal Exposure to Carbon Monoxide Results in a Reduction in Tyrosine Hydroxylase-Immunoreactivity and an Increase in Choline Acetyltransferase-Immunoreactivity in the Fetal Medulla: Implications for Sudden Infant Death Syndrome","volume":"59","author":"Tolcos","year":"2000","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/S0928-4680(00)00053-5","article-title":"Oxidative Stress and Apoptosis","volume":"7","author":"Kannan","year":"2000","journal-title":"Pathophysiology"},{"key":"ref_53","first-page":"963520","article-title":"ROS and Brain Diseases: The Good, the Bad, and the Ugly","volume":"2013","author":"Mitran","year":"2013","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Ultanir, S., Shetty, A.S., Constantin Badea, T., Sun, M., Wang, B., Zeng, H., and Liu, J. (2021). Effects of Prenatal Hypoxia on Nervous System Development and Related Diseases. Front. Neurosci., 15.","DOI":"10.3389\/fnins.2021.755554"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1007\/s12640-020-00270-5","article-title":"Sepsis and Cerebral Dysfunction: BBB Damage, Neuroinflammation, Oxidative Stress, Apoptosis and Autophagy as Key Mediators and the Potential Therapeutic Approaches","volume":"39","author":"Gu","year":"2021","journal-title":"Neurotox. Res."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Silva, F.F.V.e., Pad\u00edn-Iruegas, M.E., Caponio, V.C.A., Lorenzo-Pouso, A.I., Saavedra-Nieves, P., Chamorro-Petronacci, C.M., Suar\u00e9z-Pe\u00f1aranda, J., and P\u00e9rez-Say\u00e1ns, M. (2022). Caspase 3 and Cleaved Caspase 3 Expression in Tumorogenesis and Its Correlations with Prognosis in Head and Neck Cancer: A Systematic Review and Meta-Analysis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231911937"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1111\/j.1749-6632.2000.tb06226.x","article-title":"Mechanisms of Perinatal Cerebral Injury in Fetus and Newborn","volume":"900","author":"Mishra","year":"2000","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.freeradbiomed.2005.08.040","article-title":"Free Radicals, Mitochondria, and Hypoxia-Ischemia in the Developing Brain","volume":"40","author":"Blomgren","year":"2006","journal-title":"Free Radic. Biol. Med."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/14\/6\/736\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:52:27Z","timestamp":1760032347000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/14\/6\/736"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,15]]},"references-count":58,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["antiox14060736"],"URL":"https:\/\/doi.org\/10.3390\/antiox14060736","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,15]]}}}