title: Calorie-restricted ketogenic diet increases thresholds to all patterns of pentylenetetrazol-induced seizures: critical importance of electroclinical assessment.
abstract: OBJECTIVE
  Thresholds to pentylenetetrazol (PTZ) seizures were usually based only on clinical symptoms. Our purpose was to use electroclinical patterns to assess the efficacy of a ketogenic and/or calorie-restricted diet on PTZ-induced seizures.
  
  
  METHODS
  Forty 50-day-old rats were divided in four weight-matched groups and fed controlled diets: normocalorie carbohydrate (NC), hypocalorie carbohydrate (HC), normocalorie ketogenic (NK), and hypocalorie ketogenic (HK). After 21 days, blood glucose and beta-hydroxybutyrate levels were determined and seizures were induced by continuous infusion of PTZ. The clinical and EEG thresholds to each seizure pattern were 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 the other ones for most clinical features: absence (p = 0.003), first overt myoclonia (p = 0.028), clonic seizure (p = 0.006), and for EEG features: first spike (p = 0.036), first spike-and-wave discharge (p = 0.014), subcontinuous spike-and-wave discharges (p = 0.005). NK, HC, and NC groups were not significantly different from each other. Blood glucose and beta-hydroxybutyrate levels were not correlated with electroclinical seizure thresholds. After the clonic seizure, despite stopping PTZ infusion, a tonic seizure occurred in some animals, without significant difference regarding the diet.
  
  
  CONCLUSIONS
  This approach permitted a precise study of the electroclinical course of PTZ-induced seizures. In addition to the usually studied first overt myoclonia, we clearly demonstrated the efficiency of a calorie restricted KD in elevating thresholds to most electroclinical seizure patterns. We confirmed the lack of efficiency of the KD to reduce seizure severity once the seizure has started.
authors.affiliation: INSERM U 666, 67085 Strasbourg, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Raffo
authors.forename: Jennifer
authors.initials: J
authors.lastname: François
authors.forename: Arielle
authors.initials: A
authors.lastname: Ferrandon
authors.forename: Estelle
authors.initials: E
authors.lastname: Koning
authors.forename: Astrid
authors.initials: A
authors.lastname: Nehlig
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000502:physiology; D031204:Caloric Restriction / Q000379:methods*; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology; D004040:Dietary Carbohydrates / Q000008:administration & dosage / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage / Q000378:metabolism; D004195:Disease Models, Animal; D004569:Electroencephalography / Q000706:statistics & numerical data*; D002149:Energy Intake; D004827:Epilepsy / Q000139:chemically induced* / Q000178:diet therapy / Q000503:physiopathology*; D007662:Ketosis / Q000209:etiology / Q000378:metabolism*; D008297:Male; D010433:Pentylenetetrazole; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001786:Blood Glucose; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D020155:3-Hydroxybutyric Acid; D010433:Pentylenetetrazole