Aunoy Poddar

The development of the infant brain is a dynamic, intricate process that can be disrupted by oxygen deprivation, a frequent cause of long-term neurological disability. This proposal will generate gene expression profiles from normal and hypoxic human neonatal brain tissues and establish a piglet in vitro system to model effects of reduced oxygen levels on the subventricular zone in the developing infant brain. The findings from this research will enhance our understanding of neonatal hypoxic injury and guide future efforts towards therapeutic interventions.

The development of the infant brain is a dynamic, intricate process that, when disrupted, can lead to long-term neurological disability. In humans, new inhibitory interneurons (INs) continue to be born and migrate extensively from the subventricular zone into specific cortical destinations late in gestation and into postnatal life. One common injury that occurs during late gestation and early infancy, is neonatal hypoxic injury (HI). HI is commonly associated with white matter injury, which has led to prior studies focusing on the myelinating cells of the brain – oligodendrocytes. Considering the growing awareness that INs migrate through the white matter and the frequency and clinical outcomes of HI, it is critical to understand the impact of hypoxia on late migrating INs. To overcome the limited access to neonatal human brain tissue, we have developed an innovative model system using the piglet brain. Using the piglet model, we have identified preliminary effects of low oxygen conditions on migration Ins. We observe a substantial decrease of IN marker expression after 24-hour exposure to low oxygen; however, ten days after acute exposure there is recovery of marker expression. Our next steps are to find the mechanisms underlying this loss and recovery by conducting RNA profiling of INs in the piglet model and human brain tissue of deceased infants who experienced HI at birth. The findings from this research will enhance our understanding of neonatal hypoxic injury and guide future efforts towards therapeutic interventions.