Effects of Ketogenic Diet on Corneal Kindling Mouse Model

Abstract

Abstract Aim/objective: Corneal kindling mouse test is a model of decreasing the seizure threshold after repetitive subchronical electrical stimuli. Ketogenic diet (KD) is used for the treatment of children with pharmacoresistant epilepsy since more than 100 years. Surprisingly, very few studies testing the effect of the KD in corneal kindling test were published. The aim of this study was to evaluate the effect of the KD on the seizure activity in corneal kindling mouse model. Methods: 50 adult male ICR mice (25-35 g) were randomly distributed in four groups, as follows: group 1 – standard diet (SD) treated controls (n = 10); group 2 – KD treated (n = 10), group 3 – kindled mice on SD treatment (n = 15); group 4 – kindled mice on KD treatment (n = 15). The diet was started at day one, one week before the start of the kindling and it continued for four weeks. At the end of the experiment, kindled mice were challenged with 6-Hz test and their behavior was assessed. Results: In kindled mice on SD the seizure latency time significantly decreased at days 14, 21 and 28. Mice on KD displayed relatively constant seizure latency during the experiment. At day 28 the duration of provoked seizures was statistically higher as compared with mice on KD (median values 101 vs 2 sec, p < 0.05). Blood ketone levels were statistically higher (p < 0.05), and blood glucose level was statistically lower (p < 0.05) in the KD treated group, as compared with SD treated mice. Conclusion: KD effectively suppressed the seizure activity in corneal kindling test. Further studies are needed for elucidating the molecular mechanisms which can explain this effect.