Ketogenic diet: effects on expression of kindled seizures and behavior in adult rats.
OBJECTIVE
Despite use of the ketogenic diet (KD) for >75 years its effectiveness or mechanism of action has been examined in few animal studies. Using the kindling model of epilepsy, we tested the anticonvulsant effectiveness and behavioral consequences of an experimental KD in adult rats.


METHODS
Rats fully kindled from the amygdala were divided into KD-fed or standard rat diet-fed groups; diet treatment continued for 5 weeks. The KD approximated at 4:1 ("classic") ketogenic diet and consisted (by weight) of 70% fat, 14% protein, no carbohydrate, and appropriate vitamins, minerals and fiber; 92% of energy provided was contributed by fat and 8% was contributed by protein. Afterdischarge threshold and duration (ADT, ADD) and stage 5 seizure threshold and duration (ST, SD) were assessed weekly for 5 weeks. During week 3, learning and memory were tested by the water maze and the behavioral response to a novel environment was assessed by the open field test.


RESULTS
Rats receiving the KD became ketonemic and had weight gains similar to those of control rats. As compared with rats receiving a standard diet, those fed the KD had an elevated ADT and ST for the first 2 weeks of treatment. The control and KD-fed groups did not differ with regard to ADD or SD at any time during the study, and both groups performed similarly in the water maze and open field test.


CONCLUSIONS
In the kindling model, the KD afforded transient protection against the focal generation of kindled seizures but not seizure spread. Rats that received the KD did not perform differently from control-fed rats on spatial learning or exploratory behavior tasks. Our results provide a promising model for study of the anticonvulsant mechanisms of ketosis.
Hori
A
A
Department of Neurology, Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Tandon
P
P
Holmes
G L
GL
Stafstrom
C E
CE
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004041:Dietary Fats / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004569:Electroencephalography / Q000187:drug effects; D005106:Exploratory Behavior / Q000187:drug effects; D005526:Food, Formulated; D007657:Ketone Bodies / Q000096:biosynthesis; D007662:Ketosis / Q000209:etiology*; D007696:Kindling, Neurologic / Q000187:drug effects* / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000178:diet therapy / Q000209:etiology / Q000517:prevention & control*; D013037:Spatial Behavior / Q000187:drug effects
D004041:Dietary Fats; D007657:Ketone Bodies