PERIPHERAL IMMUNE INFILTRATION AND NEUROINFLAMMATORY REPROGRAMMING FOLLOWING NEONATAL HYPOXIA

Neonatal hypoxia remains a major cause of neonatal mortality and long-term neurological morbidity, yet the neuroinflammatory processes linking early hypoxic injury to later brain vulnerability remain poorly defined. Increasing evidence indicates that immune activation during critical developmental windows can shape neuroimmune function and influence responses to subsequent challenges. Here, we investigated how neonatal hypoxia modulates CNS resident and infiltrating immune responses.
Using a mouse model of global neonatal hypoxia, C57BL/6J postnatal day 7 pups were exposed to 5% oxygen for 15 minutes, and immune dynamics were characterised at acute and chronic time points using spectral flow cytometry and immunohistochemistry. Neonatal hypoxia induced a robust but temporally restricted wave of peripheral immune cell infiltration into the brain, characterised by initial recruitment of innate populations such as monocytes and neutrophils, followed by adaptive CD4+ and CD8+ T cells and B cells. These changes largely resolved within days, indicating that hypoxia does not result in sustained peripheral immune occupancy. Acute immune infiltration coincided with microglia activation and the emergence of neurodevelopmental delays. Together, these findings demonstrate that neonatal hypoxia opens a transient window of peripheral immune interaction with the developing brain that may contribute to neurological outcomes later in life.