Fingolimod prevents cognitive impairments following hypoxia-induced neonatal seizure by ameliorating the inflammation and oxidative stress in male and female juvenile rats

Abstract

Hypoxia-induced neonatal seizure (HINS) is associated with cognitive disorders in later life. Since the neuroinflammation following HINS leads to these deleterious effects, in the current study, the short-term outcomes of Fingolimod (FTY720) treatment as an anti-inflammatory agent was investigated in the rat model of HINS. Seizures were induced in postnatal day (P10) by exposure to 5 % O2 for 15 min. Forty-five minutes after the onset of hypoxia, pups received FTY720 (0.3 mg/kg) or normal saline for 12 consecutive days. Then, behavioral functions of the rats were assessed by commonly used tests. Subsequently, hippocampal tissue sampling at P22-P23 was done for biochemical assessments and real-time PCR. The results showed that FTY720 prevents cognitive impairments and related reduction of malondialehyde (MDA) concentration in the hippocampus of both male and female hypoxic animals. Furthermore, FTY720 administration following HINS could not prevent the decreased brain-derived neurotrophic factor (BDNF) concentration, increased nitric oxide (NO) level and decreased Interleukin-4 (IL-4) gene expression in the hippocampus of both male and female hypoxic animals. Interestingly, FTY720 showed significant interaction with sex in hippocampal Tumor necrosis factor alpha (TNF-α) gene expression and BDNF concentration. Taken together, these results suggest that FTY720 administration in the lactation period can prevent the deleterious effects of HINS on cognition in later life by ameliorating inflammation and oxidative stress in the hippocampus of both male and female juvenile rats.