Abstracts

Rationale: The effects of hypoxia on susceptibility to pentylenetetrazol (PTZ)-induced seizures and the effects of vigabatrin as an antiepileptic drug increasing brain GABA levels were assessed in juvenile rats. Methods: Animals at postnatal day 25 were exposed to hypobaric hypoxia (simulated altitude of 7,000 m) for 8 h. PTZ in a dose of 100 mg/kg was injected 1, 3 or 7 days later and pattern (minimal clonic and generalized tonic-clonic seizures), latency and severity of seizures were registered. Mortality due to seizures was also evaluated. To study protective effects of vigabatrin (600 mg/kg, i.p.), drug was injected either 24h before or immediately after hypoxia exposure. Animals injected with vigabatrin after hypoxia were tested only at an interval of 3 days. Groups of nonhypoxic animals of corresponding age were always used for comparison as controls – one injected only with PTZ, the other with vigbatrin and PTZ. Results: No signs of convulsions were observed during exposure to hypoxia. Hypoxia exposure resulted in increased seizure susceptibility three days later, incidence of generalized tonic-clonic seizures increased by 60% and latency to both seizure types was shorter than in nonhypoxic controls. Also, mortality due to seizures was higher (by 58%). At other intervals, there was no difference between hypoxic and nonhypoxic animals. In nonhypoxic controls, administration of vigabatrin had proconvulsant effects in intervals of 3 days and 1 week – incidence of generalized tonic-clonic seizures increased by 56-57%. Vigabatrin administered 24h before hypoxia did not significantly change the incidence of the two types of seizures. On the contrary, an incidence of complete tonic phase was decreased 1 day after hypoxia and seizure severity was lower than in hypoxic controls when assessed 3 days later. In addition, vigabatrin pretreatment led to a significant decrease of seizure-induced mortality in intervals 1 and 3 days. Vigabatrin administered after hypoxia decreased the incidence of complete tonic phase and mortality.Conclusions: Our data suggest that hypobaric hypoxia transiently increases seizure susceptibility. This effect is partially suppressed by vigabatrin administered after hypoxia exposure. The proconvulsant effect of vigabatrin observed in nonhypoxic rats was not observed in hypoxic animals. Supported by a grant No. 304/05/2582 of the Grant Agency of the Czech Republic.