Reyes-Corral, MartaSola-Idígora, Noeliade la Puerta, RocíoMontaner, JoanYbot-González, Patricia2022-10-032022-10-032021-03-03Reyes-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):2524http://hdl.handle.net/10668/4212Neonatal 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.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/Neonatal hypoxia–ischemiaNutraceuticalsNatural productsNeuroprotectionPreventionMaternal supplementationPolyphenolsOmega-3 fatty acidsVitaminsPlant-derived compoundsAsphyxiaLactationEnfermedades del recién nacidoHipoxia-isquemia encefálicaSuplementos dietéticosProductos biológicosNeuroprotecciónPolifenolesÁcidos grasos omega-3VitaminasFitoquímicosAsfixiaLactanciaMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Organisms::Eukaryota::Animals::Animal Population Groups::Animals, NewbornMedical Subject Headings::Anatomy::Nervous System::Central Nervous System::BrainMedical Subject Headings::Technology and Food and Beverages::Food and Beverages::Food::Dietary SupplementsMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Diseases::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Hypoxia, Brain::Hypoxia-Ischemia, BrainMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Protective Agents::Neuroprotective AgentsMedical Subject Headings::Check Tags::FemaleMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Amidines::Guanidines::CreatineMedical Subject Headings::Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::MelatoninMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::AntioxidantsMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Amides::Polyunsaturated Alkamides::CapsaicinMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Hydrocarbons, Cyclic::Hydrocarbons, Aromatic::Benzene Derivatives::Phenols::PolyphenolsMedical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Death::AsphyxiaMedical Subject Headings::Diseases::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Brain Damage, Chronic::Cerebral PalsyMedical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Body Temperature Changes::HypothermiaMedical Subject Headings::Diseases::Nervous System Diseases::Neurologic Manifestations::Neurobehavioral Manifestations::Intellectual DisabilityMedical Subject Headings::Persons::Persons::Parents::MothersMedical Subject Headings::Diseases::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Brain InjuriesMedical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::PhytochemicalsMedical Subject Headings::Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated::Fatty Acids, Omega-3Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Vital Statistics::Mortality::Infant MortalityMedical Subject Headings::Chemicals and Drugs::Complex Mixtures::Biological ProductsMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Amines::Quaternary Ammonium Compounds::Trimethyl Ammonium Compounds::CarnitineMedical Subject Headings::Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Postpartum Period::LactationMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Vital Statistics::MorbidityMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Carboxylic Acids::Hydroxy Acids::LactatesMedical Subject Headings::Diseases::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Epilepsy::SeizuresMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Growth Substances::Micronutrients::VitaminsMedical Subject Headings::Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Dietreview article33802413open access10.3390/ijms220525241422-0067PMC7959318