Anticonvulsant profile of a balanced ketogenic diet in acute mouse seizure models.
Anticonvulsant effects of the ketogenic diet (KD) have been reported in the mouse, although previous studies did not control for intake of vitamins, minerals and antioxidants. The aim of this study was to examine the effects of balanced ketogenic and control diets in acute mouse seizure models. The behavior in four mouse seizure models, plasma d-beta-hydroxybutyrate (d-BHB) and glucose levels were determined after feeding control diet, 4:1 and 6:1 KDs with matched vitamins, minerals and antioxidants. Feeding 4:1 and 6:1 KDs ad lib to 3-week-old (adolescent) mice resulted in 1.2-2.2mM d-BHB in plasma, but did not consistently change glucose levels. The 6:1 KD reproducibly elevated the CC50 (current that initiates seizures in 50% mice tested) in the 6-Hz model after 14 days of feeding to adolescent CD1 mice. Higher plasma d-BHB levels correlated with anticonvulsant effects. Despite ketosis, no consistent anticonvulsant effects of KDs were found in the fluorothyl or pentylenetetrazole CD1 mouse models. The 4:1 KD was neither anticonvulsant nor neuroprotective in hippocampus in the C3H mouse kainate model. Taken together, the KD's anticonvulsant effect was limited to the 6-Hz model, required chronic feeding with 6:1 fat content, and was independent from lowering plasma glucose.
Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, 1300 Coulter, Amarillo, TX 79106, United States.
Ramakrishna
R
Samala
Sarah
S
Willis
Karin
K
Borges
D020155:3-Hydroxybutyric Acid / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003292:Convulsants / Q000009:adverse effects; D055423:Diet, Ketogenic / Q000379:methods*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000009:adverse effects; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D007659:Ketones / Q000097:blood; D051379:Mice; D008903:Minerals / Q000008:administration & dosage; D012640:Seizures / Q000097:blood / Q000178:diet therapy* / Q000209:etiology / Q000517:prevention & control*; D013997:Time Factors; D014815:Vitamins / Q000008:administration & dosage
D000975:Antioxidants; D001786:Blood Glucose; D003292:Convulsants; D007659:Ketones; D008903:Minerals; D014815:Vitamins; D020155:3-Hydroxybutyric Acid