EVALUATING THE SPATIAL INFLAMMATORY PROFILE OF NEONATAL HYPOXIA AND ITS CONTRIBUTIONS TO NEUROLOGICAL OUTCOMES

Neonatal hypoxia is a medical condition resulting from the deprivation of oxygen to a newborn infant lasting long enough to cause harm, usually to the brain. It remains a serious condition that causes significant mortality and morbidity, including seizures. Outcomes for babies suffering from neonatal hypoxia and seizures are particularly poor, with 1 million neonatal deaths per year worldwide and survivors developing long-lasting neurological disorders (e.g., cerebral palsy, epilepsy, learning disabilities). Current diagnostics and treatment have limitations; it is an unmet medical need to better understand the pathophysiology of neonatal hypoxia to find novel diagnostic tools that can support more effective treatments.

We evaluate spatial and temporal pathophysiology using a mouse model of neonatal hypoxia (C57BL/6J postnatal day 7 pups exposed to 5% oxygen for 15 minutes). T1- and T2-weighted scans were obtained using a 9.4T MRI machine 72 hours and 5 weeks after hypoxia. These timepoints correspond with early childhood and puberty; stages at which we expect neurodevelopmental changes to peak. A battery of neurological and behavioural tests was also carried out at the same timepoints. Hypoxia mice were divided into two groups: one untreated and another treated with an anti-inflammatory compound (MCC950 administered 2 weeks post-hypoxia) and compared with control littermates. Untreated hypoxia mice display increased cytotoxic oedema in the hippocampus in the acute and chronic timepoints, showing that the inflammatory process may be persistent over time. This volume of oedema also correlates strongly with behavioural deficits. MCC-treated hypoxia mice display similar anatomical and behavioural outcomes to controls.