Abstracts

Rationale: Several studies measured the threshold to pentylenetetrazol (PTZ)-induced seizures in rats fed a Ketogenic Diet (KD) or subjected to calorie restriction. These studies were only based on the observation of clinical seizure symptoms and particularly the first overt myoclonia. Our purpose was to control whether the efficacy of the KD and/or calorie restriction was similar on the different electroclinical patterns of seizures induced by PTZ.Methods: Forty 50-day-old rats were divided in four weight-matched groups and fed controlled diets: Normocaloric Carbohydrate (NC), Hypocaloric Carbohydrate (HC), Normocaloric Ketogenic (NK) and Hypocaloric Ketogenic (HK). After 21 days of the selected diet, blood glucose and beta-hydroxybutyrate levels were determined and seizures were induced by continuous infusion of PTZ in the tail vein of freely-moving animals. The clinical and EEG course of the seizures were studied. Thresholds were determined for each seizure pattern and compared between the different groups. Results: The electroclinical course of PTZ-induced seizures was similar in all groups. The HK group exhibited higher thresholds than NC, HC and NK ones for most clinical features: absence (p=0.003), first overt myoclonia (p=0.028), clonic seizure (p=0.006) as well as for EEG features: first spike (p=0.036), first spike-and-wave discharge (p=0.014), subcontinuous spike-and-wave discharges (p=0.005). The NK, HC and NC groups were not statistically significantly different from each other. Blood glucose and beta-hydroxybutyrate levels were not correlated with electroclinical seizure thresholds. Furthermore, despite the interruption of PTZ infusion when the clonic seizure began, a tonic seizure occurred in some animals, with no significant difference regarding the diet.Conclusions: This approach permitted a precise electroclinical study of the course of PTZ- induced seizures. In this model, in addition to the usually studied first overt myoclonia, we clearly demonstrated in young adult rats the efficiency of a calorie restricted KD in elevating the thresholds to most electroclinical seizure patterns. We also confirmed the lack of efficiency of the KD to reduce seizure severity once the seizure has started.