Longitudinal Analysis of Sleep-Wake States in Neonatal Rats Subjected to Hypoxia-Ischemia

OBJECTIVE: Sleep is necessary for brain maturation in infants. Perinatal hypoxic-ischemic encephalopathy (HIE) is a major cause of chronic neurological disease in infants. Although the developmental changes of electroencephalogram (EEG) in human newborns have been described, little is known about the EEG normal maturation characteristics in rodents and the changes in sleep-awake states caused by hypoxia-ischemia (HI). This study aimed to investigate the pathological response of sleep-wake states in neonatal rats with HIE. METHODS: We constructed HIE and sham models on postnatal day (P) 3 rats and continuously monitored them using electroencephalography and electromyography for up to P12. The distribution of sleep-wake states was analyzed to estimate the effects of HIE. RESULTS: Compared with the sham group, the HI group showed lower rapid eye movement (REM) sleep percentage, but wake percentage and frequency was higher during P4-P12. The frequency of REM and non-rapid eye movement (NREM) sleep increased and the duration of REM and NREM sleep decreased after HI induction. However, it gradually returned to the normal level with an increase in daytime. CONCLUSION: HI damage alters the sleep-wake patterns during early neural development. The findings provide a comprehensive assessment of serial sleep-wake state recordings in neonatal rats from P4-P12.