Two percent of babies may develop complications during birth, including reduction in the level of oxygen to the brain, resulting in birth asphyxia or hypoxia, the leading cause of neonatal encephalopathy. The effect of hypoxia on the brain and development of babies is not well understood. The prognosis of infants suffering from neonatal brain damage is poor, accounting for 4 million neonatal death every year worldwide, 50% of infants will develop seizures in the neonatal period, and 70% of babies will suffer for adverse neuropsychological outcomes. Both diagnosis and treatment, however, remain a clinical challenge with current therapeutics, being effective only in a subgroup of patients and diagnostic/prognostic methods are either inaccurate or possible too late for an effective treatment. We know that babies suffering from hypoxia will develop neurological outcomes and these outcomes do not improve with current therapies. These failures may result from targeting specific neuronal proteins (e.g. Phenobarbital targets GABA-A receptor), without considering the other cells of the brain (e.g. microglia, astrocytes) or the specific nature and mechanism of the developing brain. Our new data suggests that neuroinflammation may be a key contributor to the pathophysiology of neonatal brain-damage and long-lasting neurological outcomes. We will evaluate the contribution of inflammation to the neurological outcomes after hypoxia-seizures using a model of hypoxia in neonates. In current proposal, we will use a novel comprehensive and multidisciplinary approach to analyse inflammation as main driver of neonatal brain damage by using our well-characterised mouse hypoxia model and clinical data.
Current proposal will deeply understand the pathogenesis of neonatal brain damage and, ideally, discover novel drug targets with a higher response rate, minimal side effects, longer time-window and improve neurological outcomes. Using state-of-the-art techniques, we will uncover a pathophysiological mechanism relevant for acquired neurodevelopmental disorders after perinatal asphyxia.