Sexual dimorphism in immune mediated preterm brain injury.

Around the world, 15 million babies are born too soon (before 37 weeks gestation) each year. Advances in intensive care have improved survival rates for preterm infants but the developing brain remains vulnerable to injury during this period. Brain injury among survivors can result in difficulties with learning, behaviour, memory and communication. These problems persist lifelong and there are no treatments available to improve long-term outcomes.

Male infants have an increased risk of developing cerebral palsy, intellectual disability, and psychiatric disorders when compared with female infants born at the same gestational age. The reasons for this are unknown but several lines of evidence suggest there are sex differences in the vulnerability of the developing brain to the damaging effects of infection in early life. Human studies are needed to advance our understanding of the underlying biology in order to develop successful treatments to protect the developing brain.

Through an experimental approach combining stem cell technology, advanced brain scans (MRI) and post-mortem brain tissue, I will determine how infection affects early brain development and characterise sex differences. I will use human stem cells to generate male and female immune cells (microglia), study their responses to infection, and examine how they interact with developing brain cells (neurons) in 3D mini brains, called organoids. To understand how infection can affect the developing brain differently in male and female infants, I will also study brain growth and development using advanced neonatal brain MRI scans and brain tissue from preterm infants who do not survive.

The overarching aim of this programme of research is to identify sex-specific therapies that promote healthy brain development after preterm birth.