Nutritional Supplementation Reduces Lesion Size and Neuroinflammation in a Sex-Dependent Manner in a Mouse Model of Perinatal Hypoxic-Ischemic Brain Injury.

Perinatal hypoxia-ischemia (HI) is a major cause of neonatal brain injury, leading to long-term neurological impairments. Medical nutrition can be rapidly implemented in the clinic, making it a viable intervention to improve neurodevelopment after injury. The omega-3 (n-3) fatty acids docosahexaenoic acid (DHA, 22:6n-3) and eicosapentaenoic acid (EPA, 20:5n-3), uridine monophosphate (UMP) and choline have previously been shown in rodents to synergistically enhance brain phospholipids, synaptic components and cognitive performance. The objective of this study was to test the efficacy of an experimental diet containing DHA, EPA, UMP, choline, iodide, zinc, and vitamin B12 in a mouse model of perinatal HI. Male and female C57Bl/6 mice received the experimental diet or an isocaloric control diet from birth. Hypoxic ischemic encephalopathy was induced on postnatal day 9 by ligation of the right common carotid artery and systemic hypoxia. To assess the effects of the experimental diet on long-term motor and cognitive outcome, mice were subjected to a behavioral test battery. Lesion size, neuroinflammation, brain fatty acids and phospholipids were analyzed at 15 weeks after HI. The experimental diet reduced lesion size and neuroinflammation specifically in males. In both sexes, brain n-3 fatty acids were increased after receiving the experimental diet. The experimental diet also improved novel object recognition, but no significant effects on motor performance were observed. Current data indicates that early life nutritional supplementation with a combination of DHA, EPA, UMP, choline, iodide, zinc, and vitamin B12 may provide neuroprotection after perinatal HI.

Postnatal Nutrition to Improve Brain Development in the Preterm Infant: A Systematic Review From Bench to Bedside.

Background: Preterm infants are at high risk for Encephalopathy of Prematurity and successive adverse neurodevelopmental outcome. Adequate nutrition is crucial for healthy brain development. Maternal breast milk is first choice of post-natal enteral nutrition for preterm infants. However, breast milk contains insufficient nutrient quantities to meet the greater nutritional needs of preterm infants, meaning that supplementation is recommended. Aim: To provide an overview of current literature on potential nutritional interventions for improvement of neurodevelopmental outcome in preterm infants, by taking a bench to bedside approach from pre-clinical models of neonatal brain injury to randomized controlled clinical trials (RCTs) in preterm infants. Methods: Separate clinical and pre-clinical searches were performed in Medline and Embase for English written papers published between 08/2008 and 08/2018 that studied a single nutritional component. Papers were included if one of the following components was studied: lipids, carbohydrates, proteins, vitamins, minerals, probiotics, prebiotics, oligosaccharides, fatty acids, or amino acids, with brain injury, brain development or neurodevelopmental outcome as outcome measure in preterm infants (gestational age <32 weeks and/or birth weight <1,500 g) or in animal models of neonatal brain injury. Results: In total, 2,671 pre-clinical studies and 852 RCTs were screened, of which 24 pre-clinical and 22 RCTs were included in this review. In these trials supplementation with amino acids and protein, lipids, probiotics (only clinical), prebiotics (only clinical), vitamins, and minerals was studied. All included pre-clinical studies show positive effect of supplementation on brain injury and/or neurodevelopment. Although some nutrients, such as glutamine, show promising short term outcome in clinical studies, no evident long term effect of any supplemented nutrient was found. Main limitations were inclusion of studies no older than 10 years at time of search and studies that focused on single nutritional components only. Conclusion: Even though many pre-clinical trials demonstrate promising effects of different nutritional interventions on reducing brain injury and/or improving neurodevelopmental outcome, these positive effects have so far not evidently been demonstrated in RCTs. More clinically relevant animal models and long term follow up after clinical trials are needed to move novel nutritional therapies from bench to bedside of preterm infants.