Neonatal hyperoxia exposure causes cerebellar lesions and behavioral abnormalities in rats

In humans, fetal cerebellar development peaks during the final stages of pregnancy. Preterm infants experience hyperoxia (excessive oxygen) outside the uterus. Hyperoxia exposure causes neurological deficits in preterm infants. However, detailed mechanisms underlying hyperoxia-induced neurological deficits remain unclear. Previous studies on neurological deficits have focused on cerebral lesions. However, recently, cerebellar lesions have been observed on brain magnetic resonance imaging in preterm infants. We herein aimed to investigate behavioral and cerebellar tissue–level changes in Sprague–Dawley rat neonates exposed to 83% hyperoxia from within 24 h of birth to 14 days of age. In rats, cerebellar development peaks in the first postnatal week. We elucidated the mechanism by which hyperoxia exposure causes neurological deficits in these rats. We found that prolonged hyperoxia exposure, starting within 24 h of birth, induces behavioral impairments (such as motor, cognitive and memory, and social interaction deficits) in rats. At the tissue level, delayed granule cell migration and abnormal Purkinje cell dendritic development combined with impaired myelination were observed in the acute and chronic hyperoxia exposure phases, respectively. Thus, hyperoxia exposure may cause abnormalities in cerebellar morphology and function, resulting in neurological deficits in preterm infants.