Abstracts

The ketogenic diet is a high-fat, low-carbohydrate, low-protein diet that is anticonvulsant in drug-resistant epileptic children. Furthermore, it is anticonvulsive and neuroprotective in experimental brain injury in rodents, although its mechanism of action is still unknown. Our hypothesis is that the ketogenic diet leads to changes of brain metabolism and neurotransmitter levels reflected in the chemical composition of the extracellular fluid in the brain., Three week-old C3Heb/Fe mice (Jackson Labs) were fed the ketogenic diet (Harlan-Teklad TD.06233) or control diet (TD.06232) with matched amounts of minerals and vitamins [italic]ad lib[/italic] for 2-4 weeks. The latency to flurothyl-induced seizures was measured after 3 weeks of feeding. We are using i[italic]n vivo[/italic] microdialysis to measure metabolic intermediates and neurotransmitters in the hippocampus of mice on the different diets. The CMA 600 microanalyser is used to measure glucose, lactate and glutamate., Weight gain of both groups was similar, but mice on the ketogenic diet had significantly higher serum beta-hydroxybutyrate levels than control mice (2.7-fold, n=10 mice each, p[lt]0.05). Latency to flurothyl-induced tonic seizures was significantly increased (10%) by the ketogenic diet (n=10 mice each, p[lt]0.05). Preliminary microdialysis data suggests that the glucose/lactate ratio in the brain extracellular fluid is altered significantly in ketotic mice (p[lt]0.05 unpaired two-sided t-test). Mice on the control diet showed a glucose/lactate ratio of 1.5 [underline]+[/underline] 0.2 (mean [underline]+[/underline] standard deviation; n=3), whereas ketogenic mice had a ratio of 3.4 [underline]+ [/underline]0.7 (n=3). We are in the process to measure the absolute concentrations of glucose, lactate and glutamate in the brain extracellular fluid by microdialysis using the zero-flow method., In summary, our preliminary data indicate that brain energy metabolism is altered in mice on the ketogenic diet, which may contribute to protecting the brain from seizures and brain damage., (Supported by TTUHSC.)