Alterations in Neural Connectivity following Placental Insufficiency, its Role in Neurodevelopmental Disabilities, and the Neuropreventive Effects of Broccoli Sprout Supplementation: A Potential Therapeutic Intervention

Abstract

Background Intrauterine growth restriction (IUGR) as a result of suboptimal in utero environments can cause perinatal brain injury and ultimately lead to neurodevelopmental disorders (NDD). In the developed world placental insufficiency (PI) is the leading cause of IUGR. This antepartum insult results in ischemic injury, oxidative stress, and chronic sequelae of fetal brain damage that can alter neuron development. As antepartum insults cause more than 70% of perinatal brain injury, targeting this vulnerable fetal population with a novel neuropreventive therapy can ideally reduce the severity and incidence of NDD. An established model of PI was used to explore the possible neuropreventive benefits of a natural health product; broccoli sprouts (BrSp), to treat this critical window of brain development currently without therapeutic interventions. Methods Bilateral uterine artery ligation as a model of PI was induced on day 20 of a 23-day gestation in the pregnant rat dam. Dams were randomly allocated to receive 200mg of BrSp daily from gestational day 15 until postnatal day (P) 21. On P35 animals were euthanized and brain tissue was extracted, fixed, and processed for Golgi-Cox analysis. Neurons were traced using a camera lucida and underwent Sholl analysis for dendritic length (DL), branch point analysis (BPs) for dendritic complexity, and spine density (SD) analysis as a measure of synapses. Results Our results indicate that BrSp afford neuropreventive benefits in neuronal morphology of the CA1 region of the hippocampus, specifically in the basal dendrites. This was demonstrated by reduced DL and BPs in the basal dendrites of IUGR animals that was prevented with the supplementation of BrSp. Additionally, male IUGR offspring were shown to be more significantly affected than IUGR females. Morphological assessment of the neurons in the primary motor cortex did not show an effect of IUGR, however BrSp increased both DL and BPs. This demonstrates the potential nutritive benefits of maternal BrSp consumption on the fetal brain. However, further studies will be needed to determine the effects of BrSp on the function of neurons, and various other brain regions. Conclusion The results of this study show that BrSp supplemented during late gestation and lactation can prevent alterations to the neuron caused by PI induced IUGR. These changes may contribute to the behavioural changes previously seen in this model. This suggests BrSp is an effective and novel neuropreventive approach to NDD associated with antepartum insults and perinatal brain injury.