Introduction: The effect of recombinant human follistatin-1 and phenytoin alone and their combined treatment on maximal electroshock seizures, the level of cytokines and apoptotic factors in the prefrontal cortex and hippocampus, the level of lactate in the blood and these two brain regions, as well as the histopathology of the hippocampus of mice, was investigated.
Methods: Mice (n=6) intraperitoneally received saline, follistatin-1 (10, 100, and 1000 μg/kg), phenytoin (35 mg/kg) alone, and a combination of follistatin-1 (100 μg/kg) and phenytoin (35 mg/kg) two hours before seizure (50 mA, 0.2 sec) induction. The levels of tumor growth factor-beta (TGF-β), interleukin-6 (IL-6), caspase-3, and lactate in the prefrontal cortex and hippocampus samples were determined. The serum lactate level and the percentage of dead mice were also measured. The viability of hippocampal neurons was evaluated after hematoxylin and eosin (H&E) and crystal violet staining.
Results: The administration of follistatin-1 (100 and 1000 μg/kg) and phenytoin alone decreased the severity of seizures, caspase-3, and TGF-β levels, and increased the level of IL-6 in the brain areas. Follistatin-1 decreased the level of lactate in the blood and brain areas compared to the control group. Follistatin-1 (100 μg/kg) was able to intensify the effect of phenytoin on seizures and all the measured parameters without increasing the deaths of mice.
Conclusion: ollistatin-1 alone acts as an anticonvulsant, and plus phenytoin is a fruitful combination therapy for reducing seizures and providing hippocampal protection.