High-risk preterm infants are affected by a higher incidence of cognitive developmental deficits due to the unavoidable risk factor of
oxygen toxicity.
Caffeine is known to have a protective effect in preventing
bronchopulmonary dysplasia associated with improved neurologic outcomes, although very early initiation of
therapy is controversial. In this study, we used newborn rats in an
oxygen injury model to test the hypothesis that near-birth
caffeine administration modulates neuronal maturation and differentiation in the hippocampus of the developing brain. For this purpose, newborn Wistar rats were exposed to 21% or 80%
oxygen on the day of birth for 3 or 5 days and treated with vehicle or
caffeine (10 mg/kg/48 h). Postnatal exposure to 80%
oxygen resulted in a drastic reduction of associated neuronal mediators for radial glia, mitotic/postmitotic neurons, and impaired cell-cycle regulation, predominantly persistent even after recovery to room air until postnatal day 15. Systemic
caffeine administration significantly counteracted the effects of
oxygen insult on neuronal maturation in the hippocampus. Interestingly, under normoxia,
caffeine inhibited the transcription of neuronal mediators of maturing and mature neurons. The early administration of
caffeine modulated
hyperoxia-induced decreased neurogenesis in the hippocampus and showed neuroprotective properties in the neonatal rat
oxygen toxicity model.