RT Journal Article T1 Nutraceuticals in the Prevention of Neonatal Hypoxia-Ischemia: A Comprehensive Review of their Neuroprotective Properties, Mechanisms of Action and Future Directions A1 Reyes-Corral, Marta A1 Sola-Idígora, Noelia A1 de la Puerta, Rocío A1 Montaner, Joan A1 Ybot-González, Patricia K1 Neonatal hypoxia–ischemia K1 Nutraceuticals K1 Natural products K1 Neuroprotection K1 Prevention K1 Maternal supplementation K1 Polyphenols K1 Omega-3 fatty acids K1 Vitamins K1 Plant-derived compounds K1 Asphyxia K1 Lactation K1 Enfermedades del recién nacido K1 Hipoxia-isquemia encefálica K1 Suplementos dietéticos K1 Productos biológicos K1 Neuroprotección K1 Polifenoles K1 Ácidos grasos omega-3 K1 Vitaminas K1 Fitoquímicos K1 Asfixia K1 Lactancia AB Neonatal hypoxia-ischemia (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. PB MDPI YR 2021 FD 2021-03-03 LK http://hdl.handle.net/10668/4212 UL http://hdl.handle.net/10668/4212 LA en NO Reyes-Corral M, Sola-Idígora N, de la Puerta R, Montaner J, Ybot-González P. Nutraceuticals in the Prevention of Neonatal Hypoxia-Ischemia: A Comprehensive Review of their Neuroprotective Properties, Mechanisms of Action and Future Directions. Int J Mol Sci. 2021 Mar 3;22(5):2524 DS RISalud RD Aug 8, 2025