{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:57:59Z","timestamp":1792789079225,"version":"4.5.0"},"reference-count":116,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,4,29]],"date-time":"2024-04-29T00:00:00Z","timestamp":1714348800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of University and Research","award":["2022XF7YYI"],"award-info":[{"award-number":["2022XF7YYI"]}]},{"name":"Ministry of University and Research","award":["DN. 1553 11.10.2022"],"award-info":[{"award-number":["DN. 1553 11.10.2022"]}]},{"name":"PNRR, PE12: MNESYS (PE0000006)\u2014A Multiscale integrated approach to the study of the nervous system in health and disease","award":["2022XF7YYI"],"award-info":[{"award-number":["2022XF7YYI"]}]},{"name":"PNRR, PE12: MNESYS (PE0000006)\u2014A Multiscale integrated approach to the study of the nervous system in health and disease","award":["DN. 1553 11.10.2022"],"award-info":[{"award-number":["DN. 1553 11.10.2022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Brain ischemia is one of the major causes of chronic disability and death worldwide. It is related to insufficient blood supply to cerebral tissue, which induces irreversible or reversible intracellular effects depending on the time and intensity of the ischemic event. Indeed, neuronal function may be restored in some conditions, such as transient ischemic attack (TIA), which may be responsible for protecting against a subsequent lethal ischemic insult. It is well known that the brain requires high levels of oxygen and glucose to ensure cellular metabolism and energy production and that damage caused by oxygen impairment is tightly related to the brain\u2019s low antioxidant capacity. Oxygen is a key player in mitochondrial oxidative phosphorylation (OXPHOS), during which reactive oxygen species (ROS) synthesis can occur as a physiological side-product of the process. Indeed, besides producing adenosine triphosphate (ATP) under normal physiological conditions, mitochondria are the primary source of ROS within the cell. This is because, in 0.2\u20132% of cases, the escape of electrons from complex I (NADPH-dehydrogenase) and III of the electron transport chain occurring in mitochondria during ATP synthesis leads to the production of the superoxide radical anion (O2\u2022\u2212), which exerts detrimental intracellular effects owing to its high molecular instability. Along with ROS, reactive nitrosative species (RNS) also contribute to the production of free radicals. When the accumulation of ROS and RNS occurs, it can cause membrane lipid peroxidation and DNA damage. Here, we describe the intracellular pathways activated in brain tissue after a lethal\/sub lethal ischemic event like stroke or ischemic tolerance, respectively, highlighting the important role played by oxidative stress and mitochondrial dysfunction in the onset of the two different ischemic conditions.<\/jats:p>","DOI":"10.3390\/antiox13050547","type":"journal-article","created":{"date-parts":[[2024,5,1]],"date-time":"2024-05-01T10:33:31Z","timestamp":1714559611000},"page":"547","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Oxidative Metabolism in Brain Ischemia and Preconditioning: Two Sides of the Same Coin"],"prefix":"10.3390","volume":"13","author":[{"given":"Elena","family":"D\u2019Apolito","sequence":"first","affiliation":[{"name":"Division of Pharmacology, Department of Neuroscience Reproductive Sciences and Dentistry, Federico II University of Naples, 80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Jos\u00e8","family":"Sisalli","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Federico II University of Naples, 80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Tufano","sequence":"additional","affiliation":[{"name":"Division of Pharmacology, Department of Neuroscience Reproductive Sciences and Dentistry, Federico II University of Naples, 80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucio","family":"Annunziato","sequence":"additional","affiliation":[{"name":"IRCCS Synlab SDN S.p.A, Via Gianturco 113, 80143 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Scorziello","sequence":"additional","affiliation":[{"name":"Division of Pharmacology, Department of Neuroscience Reproductive Sciences and Dentistry, Federico II University of Naples, 80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,29]]},"reference":[{"key":"ref_1","first-page":"658","article-title":"Reactive Oxygen Species: Oxidative Damage and Pathogenesis","volume":"77","author":"Bandyopadhyay","year":"1999","journal-title":"Curr. 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