{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T03:29:04Z","timestamp":1789010944067,"version":"build-2803163510"},"reference-count":295,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,3,3]],"date-time":"2021-03-03T00:00:00Z","timestamp":1614729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010566","name":"Consejer\u00eda de Salud y Familias, Junta de Andaluc\u00eda","doi-asserted-by":"publisher","award":["C-0025-2018"],"award-info":[{"award-number":["C-0025-2018"]}],"id":[{"id":"10.13039\/501100010566","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Consejer\u00eda de Econom\u00eda, Junta de Andaluc\u00eda","award":["DOC_01701"],"award-info":[{"award-number":["DOC_01701"]}]},{"name":"Fundaci\u00f3n Alicia Koplowitz","award":["Ayudas a proyectos de investigaci\u00f3n en neuropediatr\u00eda 2018"],"award-info":[{"award-number":["Ayudas a proyectos de investigaci\u00f3n en neuropediatr\u00eda 2018"]}]},{"name":"Spanish Stroke Research Network (INVICTUS+)","award":["RD16\/0019\/0015"],"award-info":[{"award-number":["RD16\/0019\/0015"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neonatal hypoxia\u2013ischemia (HI) is a brain injury caused by oxygen deprivation to the brain due to birth asphyxia or reduced cerebral blood perfusion, and it often leads to lifelong limiting sequelae such as cerebral palsy, seizures, or mental retardation. HI remains one of the leading causes of neonatal mortality and morbidity worldwide, and current therapies are limited. Hypothermia has been successful in reducing mortality and some disabilities, but it is only applied to a subset of newborns that meet strict inclusion criteria. Given the unpredictable nature of the obstetric complications that contribute to neonatal HI, prophylactic treatments that prevent, rather than rescue, HI brain injury are emerging as a therapeutic alternative. Nutraceuticals are natural compounds present in the diet or used as dietary supplements that have antioxidant, anti-inflammatory, or antiapoptotic properties. This review summarizes the preclinical in vivo studies, mostly conducted on rodent models, that have investigated the neuroprotective properties of nutraceuticals in preventing and reducing HI-induced brain damage and cognitive impairments. The natural products reviewed include polyphenols, omega-3 fatty acids, vitamins, plant-derived compounds (tanshinones, sulforaphane, and capsaicin), and endogenous compounds (melatonin, carnitine, creatine, and lactate). These nutraceuticals were administered before the damage occurred, either to the mothers as a dietary supplement during pregnancy and\/or lactation or to the pups prior to HI induction. To date, very few of these nutritional interventions have been investigated in humans, but we refer to those that have been successful in reducing ischemic stroke in adults. Overall, there is a robust body of preclinical evidence that supports the neuroprotective properties of nutraceuticals, and these may represent a safe and inexpensive nutritional strategy for the prevention of neonatal HI encephalopathy.<\/jats:p>","DOI":"10.3390\/ijms22052524","type":"journal-article","created":{"date-parts":[[2021,3,3]],"date-time":"2021-03-03T20:33:57Z","timestamp":1614803637000},"page":"2524","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Nutraceuticals in the Prevention of Neonatal Hypoxia\u2013Ischemia: A Comprehensive Review of their Neuroprotective Properties, Mechanisms of Action and Future Directions"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5490-0624","authenticated-orcid":false,"given":"Marta","family":"Reyes-Corral","sequence":"first","affiliation":[{"name":"Neurodevelopment Research Group, Institute of Biomedicine of Seville, IBIS\/HUVR\/CSIC\/US, 41013 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8625-0470","authenticated-orcid":false,"given":"Noelia","family":"Sola-Id\u00edgora","sequence":"additional","affiliation":[{"name":"Neurodevelopment Research Group, Institute of Biomedicine of Seville, IBIS\/HUVR\/CSIC\/US, 41013 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8996-8015","authenticated-orcid":false,"given":"Roc\u00edo","family":"de la Puerta","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, University of Seville, 41012 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan","family":"Montaner","sequence":"additional","affiliation":[{"name":"Neurovascular Research Lab, Institute of Biomedicine of Seville, IBIS\/HUVR\/CSIC\/US, 41013 Seville, Spain"},{"name":"Department of Neurology and Neurophysiology, Hospital Universitario Virgen Macarena, 41009 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7836-2659","authenticated-orcid":false,"given":"Patricia","family":"Ybot-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Neurodevelopment Research Group, Institute of Biomedicine of Seville, IBIS\/HUVR\/CSIC\/US, 41013 Seville, Spain"},{"name":"Department of Neurology and Neurophysiology, Hospital Universitario Virgen Macarena, 41009 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.phrs.2018.08.022","article-title":"Preventing childhood and lifelong disability: Maternal dietary supplementation for perinatal brain injury","volume":"139","author":"Shaw","year":"2019","journal-title":"Pharm. 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