{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T11:04:50Z","timestamp":1785236690897,"version":"3.55.0"},"reference-count":82,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T00:00:00Z","timestamp":1731369600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Perinatal asphyxia (PA) is a clinical condition characterized by oxygen supply suspension before, during, or immediately after birth, and it is an important risk factor for neurodevelopmental damage. Its estimated 1\/1000 live births incidence in developed countries rises to 5\u201310-fold in developing countries. Schizophrenia, cerebral palsy, mental retardation, epilepsy, blindness, and others are among the highly disabling chronic pathologies associated with PA. However, so far, there is no effective therapy to neutralize or reduce PA-induced harm. Selective regulators of estrogen activity in tissues and selective estrogen receptor modulators like raloxifene have shown neuroprotective activity in different pathological scenarios. Their effect on PA is yet unknown. The purpose of this paper is to examine whether raloxifene showed neuroprotection in an oxygen\u2013glucose deprivation\/reoxygenation astrocyte cell model. To study this issue, T98G cells in culture were treated with a glucose-free DMEM medium and incubated at 37 \u00b0C in a hypoxia chamber with 1% O2 for 3, 6, 12, and 24 h. Cultures were supplemented with raloxifene 10, and 100 nM during both glucose and oxygen deprivation and reoxygenation periods. Raloxifene 100 nM and 10 nM improved cell survival\u201465.34% and 70.56%, respectively, compared with the control cell groups. Mitochondrial membrane potential was preserved by 58.9% 10 nM raloxifene and 81.57% 100 nM raloxifene cotreatment. Raloxifene co-treatment reduced superoxide production by 72.72% and peroxide production by 57%. Mitochondrial mass was preserved by 47.4%, 75.5%, and 89% in T98G cells exposed to 6-h oxygen\u2013glucose deprivation followed by 3, 6, and 9 h of reoxygenation, respectively. Therefore, raloxifene improved cell survival and mitochondrial membrane potential and reduced lipid peroxidation and reactive oxygen species (ROS) production, suggesting a direct effect on mitochondria. In this study, raloxifene protected oxygen\u2013glucose-deprived astrocyte cells, used to mimic hypoxic\u2013ischemic brain injury. Two examiners performed the qualitative assessment in a double-blind fashion.<\/jats:p>","DOI":"10.3390\/ijms252212121","type":"journal-article","created":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T05:21:59Z","timestamp":1731388919000},"page":"12121","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Raloxifene Protects Oxygen-Glucose-Deprived Astrocyte Cells Used to Mimic Hypoxic-Ischemic Brain Injury"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6770-1678","authenticated-orcid":false,"given":"Nicol\u00e1s","family":"Toro-Urrego","sequence":"first","affiliation":[{"name":"Centro de Altos Estudios en Ciencias Humanas y de la Salud, Universidad Abierta Interamericana, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, CAECIHS, UAI-CONICET, Buenos Aires C1270AAH, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan P.","family":"Luaces","sequence":"additional","affiliation":[{"name":"Centro de Altos Estudios en Ciencias Humanas y de la Salud, Universidad Abierta Interamericana, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, CAECIHS, UAI-CONICET, Buenos Aires C1270AAH, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1589-1064","authenticated-orcid":false,"given":"Tamara","family":"Kobiec","sequence":"additional","affiliation":[{"name":"Centro de Altos Estudios en Ciencias Humanas y de la Salud, Universidad Abierta Interamericana, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, CAECIHS, UAI-CONICET, Buenos Aires C1270AAH, Argentina"},{"name":"Centro de Investigaciones en Psicolog\u00eda y Psicopedagog\u00eda (CIPP), Facultad de Psicolog\u00eda y Psicopedagog\u00eda, Pontificia Universidad Cat\u00f3lica Argentina (UCA), Buenos Aires C1107AFB, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas","family":"Udovin","sequence":"additional","affiliation":[{"name":"Centro de Altos Estudios en Ciencias Humanas y de la Salud, Universidad Abierta Interamericana, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, CAECIHS, UAI-CONICET, Buenos Aires C1270AAH, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sof\u00eda","family":"Bordet","sequence":"additional","affiliation":[{"name":"Centro de Altos Estudios en Ciencias Humanas y de la Salud, Universidad Abierta Interamericana, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, CAECIHS, UAI-CONICET, Buenos Aires C1270AAH, Argentina"},{"name":"Centro de Investigaciones en Psicolog\u00eda y Psicopedagog\u00eda (CIPP), Facultad de Psicolog\u00eda y Psicopedagog\u00eda, Pontificia Universidad Cat\u00f3lica Argentina (UCA), Buenos Aires C1107AFB, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6650-1033","authenticated-orcid":false,"given":"Matilde","family":"Otero-Losada","sequence":"additional","affiliation":[{"name":"Centro de Altos Estudios en Ciencias Humanas y de la Salud, Universidad Abierta Interamericana, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, CAECIHS, UAI-CONICET, Buenos Aires C1270AAH, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Capani","sequence":"additional","affiliation":[{"name":"Centro de Altos Estudios en Ciencias Humanas y de la Salud, Universidad Abierta Interamericana, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, CAECIHS, UAI-CONICET, Buenos Aires C1270AAH, Argentina"},{"name":"Instituto de Ciencias Biom\u00e9dicas, Facultad de Ciencias de la Salud, Universidad Aut\u00f3noma de Chile, Santiago 7500912, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1007\/s12640-010-9208-9","article-title":"Perinatal asphyxia: Current status and approaches towards neuroprotective strategies, with focus on sentinel proteins","volume":"19","author":"Morales","year":"2011","journal-title":"Neurotox Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1002\/syn.21660","article-title":"Moderate and severe perinatal asphyxia induces differential effects on cocaine sensitization in adult rats","volume":"67","author":"Galeano","year":"2013","journal-title":"Synapse"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Herrera, M.I., Udovin, L.D., Toro-Urrego, N., Kusnier, C.F., Luaces, J.P., and Capani, F. (2018). Palmitoylethanolamide ameliorates hippocampal damage and behavioral dysfunction after perinatal asphyxia in the immature rat brain. Front. Neurosci., 12.","DOI":"10.3389\/fnins.2018.00145"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Udovin, L.D., Kobiec, T., Herrera, M.I., Toro-Urrego, N., Kusnier, C.F., K\u00f6lliker-Frers, R.A., Ramos-Hryb, A.B., Luaces, J.P., Otero-Losada, M., and Capani, F. (2020). Partial Reversal of Striatal Damage by Palmitoylethanolamide Administration Following Perinatal Asphyxia. Front. Neurosci., 13.","DOI":"10.3389\/fnins.2019.01345"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.expneurol.2016.08.017","article-title":"Consequences of excessive plasticity in the hippocampus induced by perinatal asphyxia","volume":"286","author":"Saraceno","year":"2016","journal-title":"Exp. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Saraceno, G.E., Bellini, M.J., Garcia-Segura, L.M., and Capani, F. (2018). Estradiol Activates PI3K\/Akt\/GSK3 Pathway Under Chronic Neurodegenerative Conditions Triggered by Perinatal Asphyxia. Front. Pharmacol., 9.","DOI":"10.3389\/fphar.2018.00335"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1007\/s12640-017-9755-4","article-title":"Vulnerability to a Metabolic Challenge Following Perinatal Asphyxia Evaluated by Organotypic Cultures: Neonatal Nicotinamide Treatment","volume":"32","author":"Palacios","year":"2017","journal-title":"Neurotox. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.neubiorev.2017.01.042","article-title":"25 years of research on global asphyxia in the immature rat brain","volume":"75","author":"Barkhuizen","year":"2017","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1007\/s12640-018-9928-9","article-title":"Regionally Impaired Redox Homeostasis in the Brain of Rats Subjected to Global Perinatal Asphyxia: Sustained Effect up to 14 Postnatal Days","volume":"34","author":"Vio","year":"2018","journal-title":"Neurotox. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1007\/s12640-019-00064-4","article-title":"The Long-Term Impairment in Redox Homeostasis Observed in the Hippocampus of Rats Subjected to Global Perinatal Asphyxia (PA) Implies Changes in Glutathione-Dependent Antioxidant Enzymes and TIGAR-Dependent Shift Towards the Pentose Phosphate Pathways: Effect of Nicotinamide","volume":"36","author":"Bustamante","year":"2019","journal-title":"Neurotox. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2929","DOI":"10.1007\/s00213-018-4982-9","article-title":"Palmitoylethanolamide prevents neuroinflammation, reduces astrogliosis and preserves recognition and spatial memory following induction of neonatal anoxia-ischemia","volume":"235","author":"Holubiec","year":"2018","journal-title":"Psychopharmacology"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Herrera-Marschitz, M., Neira-Pena, T., Rojas-Mancilla, E., Espina-Marchant, P., Esmar, D., Perez, R., Mu\u00f1oz, V., Gutierrez-Hernandez, M., Rivera, B., and Simola, N. (2014). Perinatal asphyxia: CNS development and deficits with delayed onset. Front. Cell. Neurosci., 8.","DOI":"10.3389\/fnins.2014.00047"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"67","DOI":"10.5409\/wjcp.v5.i1.67","article-title":"Short- and long-term prognosis in perinatal asphyxia: An update","volume":"5","author":"Ahearne","year":"2016","journal-title":"World J. Clin. Pediatr."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Galeano, P., Blanco, E., Logica Tornatore, T.M.A., Romero, J.I., Holubiec, M.I., Rodr\u00edguez de Fonseca, F., and Capani, F. (2015). Life-long environmental enrichment counteracts spatial learning, reference and working memory deficits in middle-aged rats subjected to perinatal asphyxia. Front. Behav. Neurosci., 8.","DOI":"10.3389\/fnbeh.2014.00406"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1111\/epi.16912","article-title":"A combination of phenobarbital and the bumetanide derivative bumepamine prevents neonatal seizures and subsequent hippocampal neurodegeneration in a rat model of birth asphyxia","volume":"62","author":"Johne","year":"2021","journal-title":"Epilepsia"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.psychres.2018.11.023","article-title":"Maternal stress, prenatal medical illnesses and obstetric complications: Risk factors for schizophrenia spectrum disorder, bipolar disorder and major depressive disorder","volume":"271","author":"Pugliese","year":"2019","journal-title":"Psychiatry Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1847","DOI":"10.1007\/s10803-016-2717-5","article-title":"Impaired Gas Exchange at Birth and Risk of Intellectual Disability and Autism: A Meta-analysis","volume":"46","author":"Modabbernia","year":"2016","journal-title":"J. Autism Dev. Disord."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1080\/09084282.2011.643946","article-title":"Perinatal cyanosis: Long-term cognitive sequelae and behavioral consequences","volume":"1","author":"Perna","year":"2012","journal-title":"Appl. Neuropsychol. Child."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Otero-Losada, M., Capani, F., and Perez Lloret, S. (2020). Neuroactive Steroids in Hypoxic\u2013Ischemic Brain Injury: Overview and Future Directions. Neuroprotection-New Approaches Prospects, IntechOpen.","DOI":"10.5772\/intechopen.77918"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.neuroscience.2015.03.046","article-title":"Brain glucose metabolism in an animal model of depression","volume":"295","author":"Detka","year":"2015","journal-title":"Neuroscience."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/j.tins.2013.07.001","article-title":"Sugar for the brain: The role of glucose in physiological and pathological brain function","volume":"36","author":"Mergenthaler","year":"2013","journal-title":"Trends Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Chen, J., Li, M., Liu, Z., Wang, Y., and Xiong, K. (2022). Molecular mechanisms of neuronal death in brain injury after subarachnoid hemorrhage. Front. Cell. Neurosci., 16.","DOI":"10.3389\/fncel.2022.1025708"},{"key":"ref_23","first-page":"119","article-title":"Astrocytes in neurodegenerative diseases (I): Function and molecular description","volume":"30","year":"2015","journal-title":"Neurologia"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.mrfmmm.2009.08.016","article-title":"Activated astroglia during chronic inflammation in Alzheimer\u2019s disease\u2014Do they neglect their neurosupportive roles?","volume":"690","author":"Fuller","year":"2010","journal-title":"Mutat. Res."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Sifat, A.E., Nozohouri, S., Archie, S.R., Chowdhury, E.A., and Abbruscato, T.J. (2022). Brain Energy Metabolism in Ischemic Stroke: Effects of Smoking and Diabetes. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23158512"},{"key":"ref_26","first-page":"1346","article-title":"Estrogen and progesterone attenuate glutamate neurotoxicity via regulation of EAAT3 and GLT-1 in a rat model of ischemic stroke","volume":"23","author":"Nematipour","year":"2020","journal-title":"Iran. J. Basic Med. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1177\/1352458513519181","article-title":"The role of gender and sex hormones in determining the onset and outcome of multiple sclerosis","volume":"20","author":"Bove","year":"2014","journal-title":"Mult. Scler."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/j.ajog.2008.06.094","article-title":"A systematic review of the role of intrapartum hypoxia-ischemia in the causation of neonatal encephalopathy","volume":"199","author":"Graham","year":"2008","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.jsbmb.2014.07.009","article-title":"Tibolone protects T98G cells from glucose deprivation","volume":"144","author":"Cabezas","year":"2014","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"164","DOI":"10.2174\/187152411796011303","article-title":"Astrocytes: Targets for neuroprotection in stroke","volume":"11","author":"Barreto","year":"2011","journal-title":"Cent. Nerv. Syst. Agents. Med. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1001\/jama.282.7.637","article-title":"Reduction of Vertebral Fracture Risk in Postmenopausal Women with Osteoporosis Treated with Raloxifene: Results From a 3-Year Randomized Clinical Trial","volume":"282","author":"Ettinger","year":"1999","journal-title":"JAMA"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Veenman, L. (2020). Raloxifene as Treatment for Various Types of Brain Injuries and Neurodegenerative Diseases: A Good Start. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21207586"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2285","DOI":"10.1007\/s12035-017-0481-y","article-title":"Blockade of Neuroglobin Reduces Protection of Conditioned Medium from Human Mesenchymal Stem Cells in Human Astrocyte Model (T98G) Under a Scratch Assay","volume":"55","author":"Vega","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.jsbmb.2014.05.005","article-title":"Neuroprotective action of raloxifene against hypoxia-induced damage in mouse hippocampal cells depends on ER\u03b1 but not ER\u03b2 or GPR30 signalling","volume":"146","author":"Rzemieniec","year":"2015","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5144","DOI":"10.1200\/JCO.2008.21.0716","article-title":"Effects of Tamoxifen and Raloxifene on Memory and Other Cognitive Abilities: Cognition in the Study of Tamoxifen and Raloxifene","volume":"27","author":"Legault","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.jsbmb.2014.05.001","article-title":"Selective estrogen receptor modulators (SERMs) enhance neurogenesis and spine density following focal cerebral ischemia","volume":"146","author":"Khan","year":"2015","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"68","DOI":"10.2478\/amb-2022-0033","article-title":"Pathophysiology and Management Possibilities of Thyroid-Associated Depression","volume":"49","author":"Ivanov","year":"2022","journal-title":"Acta Medica Bulg."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"8215082","DOI":"10.1155\/2016\/8215082","article-title":"Roles and Mechanisms of Obstructive Sleep Apnea-Hypopnea Syndrome and Chronic Intermittent Hypoxia in Atherosclerosis: Evidence and Prospective","volume":"2016","author":"Ma","year":"2016","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Leaw, B., Nair, S., Lim, R., Thornton, C., Mallard, C., and Hagberg, H. (2017). Mitochondria, Bioenergetics and Excitotoxicity: New Therapeutic Targets in Perinatal Brain Injury. Front. Cell. Neurosci., 11.","DOI":"10.3389\/fncel.2017.00199"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"6968","DOI":"10.1021\/acsomega.2c07793","article-title":"Vanillin-Based Indolin-2-one Derivative Bearing a Pyridyl Moiety as a Promising Anti-Breast Cancer Agent via Anti-Estrogenic Activity","volume":"8","author":"Bender","year":"2023","journal-title":"ACS Omega"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Kryszczuk, M., and Kowalczuk, O. (2022). Significance of NRF2 in physiological and pathological conditions a comprehensive review. Arch. Biochem. Biophys., 730.","DOI":"10.1016\/j.abb.2022.109417"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"R431","DOI":"10.1152\/ajpregu.00361.2003","article-title":"Methods for detection of reactive metabolites of oxygen and nitrogen: In vitro and in vivo considerations","volume":"286","author":"Tarpey","year":"2004","journal-title":"Am. J. Physiology. Regul. Integr. Comp. Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2105","DOI":"10.1089\/ars.2009.2459","article-title":"The Role of NADPH Oxidase 1\u2013Derived Reactive Oxygen Species in Paraquat-Mediated Dopaminergic Cell Death","volume":"11","author":"Choi","year":"2009","journal-title":"Antioxid. Redox Signal."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Scaduto, R.C., and Grotyohann, L.W. (1999). Measurement of mitochondrial membrane potential using fluorescent rhodamine derivatives. Biophys. J., 76 Pt 1.","DOI":"10.1016\/S0006-3495(99)77214-0"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Oliva, C.R., Moellering, D.R., Gillespie, G.Y., and Griguer, C.E. (2011). Acquisition of chemoresistance in gliomas is associated with increased mitochondrial coupling and decreased ROS production. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0024665"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"874","DOI":"10.2174\/1570159X17666181206101314","article-title":"Neuroprotective Role of Hypothermia in Hypoxic-ischemic Brain Injury: Combined Therapies using Estrogen","volume":"17","author":"Herrera","year":"2019","journal-title":"Curr. Neuropharmacol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.exger.2006.06.032","article-title":"Role of astrocytes in estrogen-mediated neuroprotection","volume":"42","author":"Dhandapani","year":"2007","journal-title":"Exp. Gerontol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"8867","DOI":"10.1073\/pnas.1103833108","article-title":"Neuroprotection mediated through estrogen receptor-alpha in astrocytes","volume":"108","author":"Spence","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1515\/revneuro-2013-0055","article-title":"Possible roles of astrocytes in estrogen neuroprotection during cerebral ischemia","volume":"25","author":"Wang","year":"2014","journal-title":"Rev. Neurosci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1002\/glia.22679","article-title":"Mechanism of raloxifene-induced upregulation of glutamate transporters in rat primary astrocytes","volume":"62","author":"Karki","year":"2014","journal-title":"Glia"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2051","DOI":"10.1002\/jcp.27481","article-title":"Raloxifene attenuates oxidative stress and preserves mitochondrial function in astrocytic cells upon glucose deprivation","volume":"234","author":"Echeverria","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"114276","DOI":"10.1016\/j.bbr.2022.114276","article-title":"Adolescent raloxifene treatment in females prevents cognitive deficits in a neurodevelopmental rodent model of schizophrenia","volume":"441","author":"Hlusicka","year":"2023","journal-title":"Behav. Brain Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.cca.2015.01.026","article-title":"Role of mitochondria in apoptotic and necroptotic cell death in the developing brain","volume":"451 Pt A","author":"Thornton","year":"2015","journal-title":"Clin. Chim. Acta; Int. J. Clin. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1111\/cns.12771","article-title":"Endoplasmic reticulum stress regulates oxygen-glucose deprivation-induced parthanatos in human SH-SY5Y cells via improvement of intracellular ROS","volume":"24","author":"Wang","year":"2018","journal-title":"CNS Neurosci. Ther."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Wassink, G., Gunn, E.R., Drury, P.P., Bennet, L., and Gunn, A.J. (2014). The mechanisms and treatment of asphyxial encephalopathy. Front. Neurosci., 8.","DOI":"10.3389\/fnins.2014.00040"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1523\/JNEUROSCI.2382-06.2007","article-title":"Estrogen Regulates Bcl-w and Bim Expression: Role in Protection against \u03b2-Amyloid Peptide-Induced Neuronal Death","volume":"27","author":"Yao","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2347","DOI":"10.1016\/j.neurobiolaging.2014.03.017","article-title":"Raloxifene activates G protein-coupled estrogen receptor 1\/Akt signaling to protect dopamine neurons in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mice","volume":"35","author":"Bourque","year":"2014","journal-title":"Neurobiol. Aging"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.pneurobio.2016.06.002","article-title":"Regulation of astroglia by gonadal steroid hormones under physiological and pathological conditions","volume":"144","author":"Barreto","year":"2016","journal-title":"Prog. Neurobiol."},{"key":"ref_59","first-page":"828","article-title":"New method for studying the relationship between morphological parameters and cell viability","volume":"Volume 6150","author":"Xiong","year":"2006","journal-title":"2nd International Symposium on Advanced Optical Manufacturing and Testing Technologies: Optical Test and Measurement Technology and Equipment"},{"key":"ref_60","first-page":"124","article-title":"Morphological features of cell death","volume":"19","author":"Ziegler","year":"2004","journal-title":"News Physiol. Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1161\/CIRCRESAHA.118.310082","article-title":"Calcium signaling and reactive oxygen species in Mitochondria","volume":"122","author":"Bertero","year":"2018","journal-title":"Circ. Res."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"De Nicolo, B., Cataldi-Stagetti, E., Diquigiovanni, C., and Bonora, E. (2023). Calcium and Reactive Oxygen Species Signaling Interplays in Cardiac Physiology and Pathologies. Antioxidants, 12.","DOI":"10.3390\/antiox12020353"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.redox.2015.08.010","article-title":"Calcium and ROS: A mutual interplay","volume":"6","author":"Bertram","year":"2015","journal-title":"Redox Biol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Ryan, A.K., Rich, W., and Reilly, M.A. (2023). Oxidative stress in the brain and retina after traumatic injury. Front. Neurosci., 17.","DOI":"10.3389\/fnins.2023.1021152"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BJ20081386","article-title":"How mitochondria produce reactive oxygen species","volume":"417","author":"Murphy","year":"2009","journal-title":"Biochem. J."},{"key":"ref_66","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_67","doi-asserted-by":"crossref","unstructured":"Fang, M., Xia, F., Chen, Y., Shen, Y., Ma, L., You, C., Tao, C., and Hu, X. (2022). Role of Eryptosis in Hemorrhagic Stroke. Front. Mol. Neurosci., 15.","DOI":"10.3389\/fnmol.2022.932931"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.bbabio.2003.06.005","article-title":"The possible role of cytochrome c oxidase in stress-induced apoptosis and degenerative diseases","volume":"1655","author":"Kadenbach","year":"2004","journal-title":"Biochim. Biophys. Acta (BBA)-Bioenerg."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Zhang, Z., Huang, Q., Zhao, D., Lian, F., Li, X., and Qi, W. (2023). The impact of oxidative stress-induced mitochondrial dysfunction on diabetic microvascular complications. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1112363"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.cell.2017.09.021","article-title":"Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease","volume":"171","author":"Stockwell","year":"2017","journal-title":"Cell"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"5462","DOI":"10.1007\/s12035-017-0777-y","article-title":"Tibolone Reduces Oxidative Damage and Inflammation in Microglia Stimulated with Palmitic Acid through Mechanisms Involving Estrogen Receptor Beta","volume":"55","author":"Zamudio","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"31","DOI":"10.3109\/09513590.2014.943727","article-title":"Antioxidant effect of the active metabolites of tibolone","volume":"31","author":"Stark","year":"2015","journal-title":"Gynecol. Endocrinol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/S0006-8993(01)02781-0","article-title":"Changes in reactive oxygen species (ROS) production in rat brain during global perinatal asphyxia: An ESR study","volume":"914","author":"Capani","year":"2001","journal-title":"Brain Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.mce.2016.02.007","article-title":"17\u03b2-Estradiol alters oxidative damage and oxidative stress response protein expression in the mouse mammary gland","volume":"426","author":"Yuan","year":"2016","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Korenic, A., Boltze, J., Deten, A., Peters, M., Andjus, P., and Radenovic, L. (2014). Astrocytic mitochondrial membrane hyperpolarization following extended oxygen and glucose deprivation. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0090697"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1242\/jcs.115.6.1175","article-title":"Mitochondrial oxidative stress and cell death in astrocytes--requirement for stored Ca2+ and sustained opening of the permeability transition pore","volume":"115","author":"Jacobson","year":"2002","journal-title":"J. Cell Sci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.brainres.2016.02.006","article-title":"Therapies targeting lipid peroxidation in traumatic brain injury","volume":"1640 Pt A","author":"Anthonymuthu","year":"2016","journal-title":"Brain Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.chemphyslip.2018.04.005","article-title":"How cardiolipin peroxidation alters the properties of the inner mitochondrial membrane? Chem","volume":"214","author":"Peltomaa","year":"2018","journal-title":"Phys. Lipids"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Zhang, J., and Shi, Y. (2022). In Search of the Holy Grail: Toward a Unified Hypothesis on Mitochondrial Dysfunction in Age-Related Diseases. Cells, 11.","DOI":"10.3390\/cells11121906"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.mce.2016.05.024","article-title":"Tibolone protects astrocytic cells from glucose deprivation through a mechanism involving estrogen receptor beta and the upregulation of neuroglobin expression","volume":"433","author":"Baez","year":"2016","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/S0304-3940(00)01051-X","article-title":"Adenosine triphosphate affects interleukin -1\u03b2 release by T98G glioblastoma cells through a purinoceptor-independent mechanism","volume":"285","author":"Mancini","year":"2000","journal-title":"Neurosci. Lett."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1002\/jcp.1040990107","article-title":"T98G: An anchorage-independent human tumor cell line that exhibits stationary phase G1 arrest in vitro","volume":"99","author":"Stein","year":"1979","journal-title":"J. Cell. Physiol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/22\/12121\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:30:33Z","timestamp":1760113833000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/22\/12121"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,12]]},"references-count":82,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["ijms252212121"],"URL":"https:\/\/doi.org\/10.3390\/ijms252212121","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,12]]}}}