Neurodevelopment Research Group, Institute of Biomedicine of Seville, IBIS/HUVR/CSIC/US, 41013 Seville, Spain.
Department of Pharmacology, Faculty of Pharmacy, University of Seville, 41012 Seville, Spain.
Int J Mol Sci. 2021 Mar 3;22(5):2524. doi: 10.3390/ijms22052524.
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.
新生儿缺氧缺血性脑损伤（HI）是由于出生窒息或脑灌注减少导致的脑缺氧引起的脑损伤，常导致脑瘫、癫痫或智力迟钝等终身性限制后遗症。HI 仍然是全球新生儿死亡和发病的主要原因之一，目前的治疗方法有限。低温治疗已成功降低死亡率和一些残疾，但仅适用于符合严格纳入标准的新生儿亚组。鉴于导致新生儿 HI 的产科并发症具有不可预测性，预防而不是挽救 HI 脑损伤的预防性治疗方法正在成为一种治疗选择。营养保健品是饮食中存在的天然化合物或用作膳食补充剂，具有抗氧化、抗炎或抗细胞凋亡特性。本综述总结了大多数在啮齿动物模型中进行的、研究营养保健品在预防和减轻 HI 诱导的脑损伤和认知障碍中的神经保护特性的临床前体内研究。综述的天然产物包括多酚、ω-3 脂肪酸、维生素、植物衍生化合物（丹参酮、萝卜硫素和辣椒素）和内源性化合物（褪黑素、肉碱、肌酸和乳酸）。这些营养保健品在损伤发生之前给予，要么作为孕妇的饮食补充剂在怀孕期间和/或哺乳期给予，要么在 HI 诱导前给予幼崽。迄今为止，这些营养干预措施中只有极少数在人类中进行了研究，但我们提到了那些在减少成人缺血性中风方面成功的干预措施。总的来说，有大量的临床前证据支持营养保健品的神经保护特性，它们可能代表一种安全且廉价的营养策略，用于预防新生儿 HI 脑病。
