Electrophysiological observations in hippocampal slices from rats treated with the ketogenic diet

The electrophysiological effects of the high-fat, low-carbohydrate ketogeni c diet (KD) were assessed in normal and epileptic [kainic-acid(KA)-treated] adult rats using hippocampal slices. In the first set of experiments, norm al rats were fed the KD or a standard control diet for 6-8 weeks (beginning on postnatal day 56, P56), after which they were sacrificed for hippocampa l slices. All rats on the KD became ketotic. The baseline effects of the KD were determined by comparing extracellular measures of synaptic transmissi on and responses to evoked stimulation, and hippocampal excitability was te sted in Mg2+-free medium. There were no differences in EPSP slope, input/ou tput relationship, responses to evoked stimulation or Mg2+-free burst frequ ency between slices from control and KD-fed rats. In another set of experim ents, rats were made epileptic by intraperitoneal injection of kainic acid (KA) on P54, which caused status epilepticus followed by the development of spontaneous recurrent seizures (SRS) over the next few weeks. Two days aft er KA-induced status, rats were divided into a control-fed group and a KD-f ed group. Animals on the KD had significantly fewer SRS over the ensuing 8 weeks. In hippocampal slices from KA-treated, KD-fed rats, there were fewer evoked CA1 population spikes th an from slices of control-fed rats. These results suggest that the KD does not alter baseline electrophysiological pa rameters in normal rats. In rats made chronically epileptic by administrati on of KA, KD treatment was associated with fewer spontaneous seizures and r educed CA1 excitability in vitro. Therefore, at least part of the KD mechan ism of action may involve long-term changes in network excitability. Copyri ght (C) 1999 S. Karger AG, Basel.