Investigating the mechanism of protective effects of fingolimod administration following hypoxia-induced neonatal seizures in adult male and female rats: the possible role of brain-derived neurotrophic factor and nitric oxide

Hypoxia-induced neonatal seizures activate neuroinflammatory and oxidative stress mechanisms and lead to brain damage. Therefore, considering the high sensitivity of the immature brain to anaerobic metabolism during hypoxia, the purpose of this study is to investigate the mechanism of the protective effects of fingolimod in modulation of complications caused by neonatal seizures induced by hypoxia in puberty.

In this study, 40 male and female wistar rats were divided into 4 groups: 1. control-saline, 2. control-fingolimod, 3. hypoxia-saline and 4. hypoxia-fingolimod. Neonatal seizures were induced 10 days after birth by placing the neonates in hypoxia chamber for 15 minutes. In different experimental groups, fingolimod or saline were injected from the 10th to the 21st day after birth. Then, 60 days after birth, hippocampus samples were extracted and used for biochemical evaluations.

The results of this study showed that fingolimod significantly prevents the increased concentration of brain-derived neurotrophic factor and nitric oxide in the hippocampus of both male and female hypoxia groups (p < 0.05). Although this decrement was not significant in hypoxia-fingolimod female group.

Administration of fingolimod can modulate complications caused by neonatal seizures, possibly through decreasing the expression of brain-derived nerve growth factor and the compensatory effect of nitric oxide during puberty.