Abstracts

Anticonvulsant effects of the ketogenic diet seem dependent on high fat and low carbohydrate availability that results in the development of ketosis along with a modest reduction in serum glucose levels. However, it remains unclear if low glucose levels alone can decrease neuronal excitability and have anticonvulsant effects. Glucose depletion attenuates seizure activity in in vitro models whereas both proconvulsant and anticonvulsant effects have been reported in in vivo models (1,2). In the present study we sought to clarify the influence of glucose in regulating seizure susceptibility in vivo by simulating glucose deprivation with 2-deoxyglucose (2-DG), a structural analog of glucose that does not undergo glycolysis., Anticonvulsant effects of 2-DG were assessed in amygdala-kindled rats and in Swiss mice in the intravenous pentylenetetrazol (PTZ) and kainic acid models, and in the electroconvulsive threshold (ECT) and 6 Hz models. 2-DG (125 - 500 mg/kg) was administered intraperitoneally 30 min before seizure testing., In amygdala-kindled rats, 2-DG had no effect on afterdischarge threshold, afterdischarge duration, behavioral seizure score and behavioral seizure duration. In mice, administration of 2-DG had no effect on seizure threshold in the PTZ test and was slightly proconvulsant in the kainic acid model. It had no effect on ECT. Only in the 6 Hz seizure test did 2-DG cause a small, yet significant, dose-dependent elevation in seizure threshold., In contrast to a prior study using olfactory bulb and perforant path kindling (2), we did not find 2-DG to have potent anticonvulsant efficacy in the various in vivo seizure models we studied. Our findings suggest that low glucose availability plays a limited role in the seizure protection conferred by the ketogenic diet.
1. Kirchner, A., Veliskova, J. & Velisek, L. Differential effects of low glucose concentrations on seizures and epileptiform activity in vivo and in vitro. Eur. J. Neurosci. 23:1512-1522, 2006.
2. Stafstrom, C., Kriegler, S., Valley, M., Ockuly, J., Roopra, A. & Sutula, T. 2-Deoxyglucose exerts anticonvulsant and antiepileptic actions in experimental epilepsy models. Epilepsia 46 (Suppl. 8), 268[ndash]269, 2005., (Supported by NINDS, NIH.)