Dysregulated Hippocampal Fatty Acid Metabolism Following Intermittent Hypoxemia-induced Neonatal Brain Injury is Rescued by Treatment with Acetate – Normoxia vs Intermittent Hypoxia – Sex Difference Analysis

The brain is a lipid-rich organ that experiences rapid growth and development after birth in a period hallmarked by extensive lipid synthesis. We still lack a fundamental understanding of lipid metabolism during this critical time of brain development and how these dynamics occur in infants born extremely preterm (<28 weeks of gestation) suffering from brain injuries. Using an established model of neonatal brain injury due to intermittent hypoxemia, we recapitulated hippocampal-dependent cognitive impairments and examined the extent of changes in the brain’s lipid and protein profile. Specifically, proteomic analysis was performed in microdissected hippocampus from postnatal day (P) 11 male and female mice that underwent intermittent hypoxia (IHx) from P1 to P11 or serve as normoxia (Nx) controls. Our results show that the most significantly downregulated proteins belong to the metabolism pathway and within the metabolism pathway, metabolism of lipids was one of the top three most downregulated pathways.