EPIGENETIC SHAPING OF HIPPOCAMPAL VULNERABILITY IN PERINATAL ASPHYXIA IN RAT

Abstract

Hypoxic-ischemic encephalopathy secondary to asphyxia at birth is a leading cause of neonatal morbidity with early- and long-term consequences, especially on more vulnerable areas of the brain, such as hippocampus. Asphyxia severity can be influenced by concurrent maternal factors, like dietary factors, that could either mitigate or aggravate it. Trans-resveratrol (tRESV), a polyphenol with powerful antioxidant properties present in food and accessible as a maternal dietary supplement, is a potential neuroprotective candidate in case of excitotoxic mechanisms triggered by asphyxia in the neonate brain. Our group investigated the epigenetic mechanisms of brain injury and inflammation involved in asphyxia in immature brain and examined the effects of tRESV when present as a dietary habit in maternal daily intake. We used an experimental asphyxia model consisting in a 90-min exposure to hypoxia and hypercapnia in postnatal day 6 Wistar rats taken from mothers with/without tRESV supplement. The levels of hippocampal S-100B protein, interleukin 1 beta (IL-1b) and tumour necrosis factor alpha (TNFα) were measured at 24-48 hours. Also, we determined the expression of selected microRNAs (miR15a, miR124, miR132, miR134, and miR146) 24 h post-asphyxia, to investigate the epigenetic hippocampal response triggered by asphyxia and tRESV supplement. We report here an epigenetic mechanism involved in the hippocampal response to asphyxia and a neuroprotective effect of tRESV, sustained by a reduction in post-asphyxia neural inflammation and injury, with an increased tolerance to asphyxia and a potential influence on neuronal maturation. Our results encourage the use of tRESV in the maternal diet for its protective potential on the offspring’s post-asphyxia outcome and prompt to further exploration of maternal diet influence on neonatal brain pathology, with subsequent impact on the quality of life.