Recent studies have shown that exposure to hyperoxia in infant rats leads to extensive apoptotic degeneration in the cortex and white matter of the developing brain. Besides its antiepileptic effects, topiramate exerts neuroprotective effects in animal models of stroke, hypoxia ischemia, excitotoxic insults, and status epilepticus. In the present study, we investigated the effects of topiramate against hyperoxia-induced neurodegeneration in the developing brain. Eighteen Wistar rat pups were divided into three groups: control group, hyperoxia+phosphate buffered saline treated group and hyperoxia+topiramate treated group. Hyperoxia groups were exposed to 80% oxygen (n=12) in plexiglas chambers in which the oxygen concentration was monitored twice daily from birth until postnatal day five. The hyperoxia+topiramate group received an intraperitoneal injection of topiramate at a dose of 80 mg/kg/day. At postnatal day 5, all animals were killed. Neuronal cell death and apoptosis were evaluated. Histopathological examination showed that topiramate significantly diminished apoptosis in the CA1 region and dentate gyrus of hippocampus. Topiramate may offer a therapeutic potential for neuroprotection under conditions of hyperoxic brain injury.

The effects of maternal diet on the neuroimmune responses of the offspring remain to be elucidated. We investigated the impact of maternal ketogenic diet (KD) on the NLRP3 inflammasome response in the offspring’s brain. C57BL/6 female mice were randomly allocated into standard diet (SD) and ketogenic diet (KD) groups for 30 days. After mating, the presence of sperm in the vaginal smear was considered day 0 of pregnancy, and female mice continued their respective diets during pregnancy and the lactation period. Following birth, pups were further allocated into two groups and given either LPS or intraperitoneal saline on postnatal (PN) days 4, 5 and 6; they were sacrificed on PN11 or PN21. Neuronal densities were significantly lower globally in the KD group when compared to the SD group at PN11. Neuronal density in the prefrontal cortex (PFC) and dentate gyrus (DG) regions were also significantly lower in the KD group when compared to the SD group at PN21. Following administration of LPS, the decrease in the neuronal count was more prominent in the SD group when compared to the KD group in the PFC and DG regions at PN11 and PN21. NLRP3 and IL-1β were higher in the KD group than in the SD group at PN21 in the PFC, CA1 and DG regions, and were significantly lower in the DG region of the KD group especially when compared to the SD group following LPS. Results of our study reveal that maternal KD negatively affects the offspring’s brain in the mouse model. The effects of KD exhibited regional variations. On the other hand, in the presence of KD exposure, NLRP3 expression after LPS injection was lower in the DG and CA1 areas but not in the PFC when compared to SD group. Further experimental and clinical studies are warranted to elucidate the molecular mechanisms underlying the impact of antenatal KD exposure and regional discrepancies on the developing brain.