Abstracts

Rationale: 2-deoxy-D-glucose (2DG), a glucose analogue lacking an oxygen atom at the 2-position, has been used for autoradiographic and PET measurement of regional glucose utilization based on its activity-dependent cellular uptake in response to neural activity and neurovascular coupling. 2DG also has anticonvulsant effects in vivo against 6Hz, audiogenic, and pilocarpine-induced seizures, and chronic antiepileptic effects against kindling progression consisting of ~ 2-fold slowing of kindling progression when administered at 250 mg/kg IP 30 min prior to perforant path or olfactory bulb stimulation. The goal of this study was to determine the dose-response relationship and time course of action of this “disease-modifying” effect against progression of seizures, which focally load 2DG in circuitry by increased blood flow and metabolic demand for as long as 15 minutes after a seizure. Methods: Male Sprague-Dawley rats received twice daily 1 sec trains of 60 hz stimulation in the perforant path at the lowest current intensity that evoked afterdischarges (ADs) according to standard techniques until 5 Class V seizures were evoked. 2DG was administered at doses of 25-250 mg/kg IP 30 min prior to kindling stimulation, and at 37.5 mg/kg IP immediately after, 10 min after, or 30 min after each evoked AD. Results: The progression of kindling was slowed in rats that received 2DG at 37.5 mg/kg 30 min prior to kindling stimulation compared to controls (43 ± 7.9 vs 25 ± 2.6 ADs to 1st Class V, p < 0.01). Doses of 25 mg/kg were not different from controls (22 ± 4.2 ADs, n.s.). 2-fold slowing of progression was also observed at doses of 37.5 mg/kg administered immediately AFTER or 10 minutes AFTER evoked seizures (44.5 ± 4.2 and 42 ± 4.5 ADs respectively, p ≤ 0.001). A trend toward slowing was also observed with administration 30 min AFTER seizures (38.2 ± 7 ADs, p=0.086).