Effects of levetiracetam on hyperoxia-related injury in immature brain

Effects of levetiracetam on hyperoxia-related injury in immature brain Background: Oxygen therapy widely being used in neonatal intensive care units causes neuronal apoptosis in developing brain. Levetiracetam (LEV) is a new generation antiepileptic drug with insufficient data on its use in newborns. The neuroprotective effects of LEV have been reported in some other brain injury animal models but there is no study evaluating its effects on hyperoxic immature brain injury. Objective: The aim of this study was to investigate the possible neuroprotective effects of LEV on hyperoxia-induced immature brain damage. Methods: A total of 24 Wistar-albino rat pups were used. Rat pups were separated into three groups. Two groups subjected to hyperoxia (80-90% oxygen) from postnatal sixth day to tenth day. Hyperoxia groups were treated with LEV or normal saline. Control group rats stayed in normooxic conditions and treated with normal salin. The immunohistochemistry procedure was performed for active Caspase-3 for neuronal apoptosis and vascular endothelial growth factor (VEGF) for angiogenesis in frontal, parietal and occipital regions. Marked cell percentage was calculated. To assess antioxidant status, catalase and thiol blood levels were investigated. Results: No significant decrease in apoptosis with LEV treatment was observed in any of the areas examined in the hyperoxia+LEV group, but only a significant increase in apoptosis was observed in the parietal region compared to the control group. VEGF levels were increased by hyperoxia in all regions examined and decreased with LEV treatment except for frontal region but these differences are not significant. Catalase levels in the hyperoxia groups were decreased compared to the control normoxia group, while in the group treated with LEV, increased and closed to normal values. However, this difference between groups did not reach a statistically significant level. Thiol levels were not significantly different between the groups. Conclusions: In this study, we couldn't obtain any evidence about neuroprotective effect of LEV against hyperoxia-induced damage in immature brain. More clinical and preclinical studies are needed to improve the neurocognitive outcomes of premature infants. Keywords: Immature brain, Hyperoxia, Neuroprotection, Levetiracetam