2-deoxyglucose enhances epileptic tolerance evoked by transient incompletebrain ischemia in mice

The aim of the study was to assess the influence of chronic treatment with a non-metabolisable glucose analogue, 2-deoxyglucose (2-DG) at a 150 mg/kg dose on long-term epileptic tolerance (ET) evoked by 30 min bilateral carot id artery clamping (BCCA) in mice. The effects: of protein synthesis: inhib ition with cycloheximide (CHX), given in three daily doses of 2.5 mg/kg sta rting either 1 day before (peri-insult regimen) or 1 day after the priming insult (post-insult regimen), on ET development was also studied. Seizures were induced 14 days after BCCA with 3.5 mg/kg of bicuculline; this dose (C D97) evokes convulsions in 97% of normal untreated mice. BCCA resulted in d ecreased mortality, prolonged latency to the onset of generalised convulsio ns and decreased overall seizure score. CHX given in the post-insult regime n did not influence, while the peri-insult regimen abolished, all signs of BCCA-evoked ET. 2-DG treatment of sham-operated animals resulted in a model ate but significant decrease in mortality rate and a tendency toward a low er seizure score. BCCA combined with 2-DG treatment resulted in a marked de crease in mortality rate, as well as reduction in all indicators of seizure susceptibility. CHX abolished the antiepileptic effects of BCCA alone, as well as BCCA combined with 2-DG, while it did not influence the 2-DG-relate d decrease in mortality. We conclude that the development of BCCA-induced e pileptic tolerance, as well as unmasking antiepileptic effects of 2-DG by B CCA, is dependent on protein synthesis. (C) 2001 Elsevier Science B.V. All rights reserved.