Luteolin and micronized luteolin show antiseizure effects in developing zebrafish

Abstract Seizure is one of the most frequent neurological emergencies among neonates. Seizures during neurodevelopment could promote epileptogenesis by triggering inflammatory cascades and potentiating mTOR signaling. Epileptogenesis contemplates disrupted neurogenesis and neurodegeneration; and culminates in epilepsy. Epileptic patients suffer from unpredictable and recurrent seizures, which lead to social, psychological, and cognitive impairment. In this context, developing efficient treatments to manage neonatal seizures is compulsory. Here, we aimed to investigate the antiseizure and neuroprotective potential of luteolin and micronized luteolin in zebrafish larvae at 5 days post-fertilization. Both luteolin and micronized luteolin reduced the occurrence of each seizure stage and slowed the seizure development. Furthermore, there were no residual effects on larvae motor function 24 hours after the pentylenetetrazole-induced seizures. Finally, the expression level of genes related to the inflammatory response (interleukin-1β, interleukin-6, and TNF-α), mTOR signaling (p70S6Ka and p70S6Kb), neurogenesis (BDNF), and apoptosis (caspase-3) were not altered 24 hours after the seizure occurrence. In conclusion, our study demonstrates for the first time that luteolin and micronized luteolin present antiseizure effects in developing zebrafish. The data encourage further investigations looking to new approaches to neonatal seizure management.