Hypoxia-induced changes of seizure susceptibility in immature rats are modified by vigabatrin.

Abstract

The effects of hypoxia on susceptibility to pentylenetetrazol (PTZ)-induced seizures were assessed in juvenile rats. Animals at postnatal (P) day 25 were exposed to hypobaric hypoxia (simulated altitude of 7000 m) for 8 h PTZ in a dose of 100 mg/kg was injected 1, 3 or 7 days later and latency, pattern and severity of seizures were registered. Mortality due to seizures was also evaluated. Two seizure types were evaluated: minimal mostly clonic seizures (mMS) and generalized tonic clonic seizures (GTCS). To study protective effects of vigabatrin (600 mg/kg, i.p.), drug was injected either 24 h before or immediately after hypoxia exposure. Non-hypoxic animals of corresponding age were used for comparison as controls. In non-hypoxic controls, administration of vigabatrin had pro-convulsive effects in intervals from 3 days up to 1 week - incidence of GTCS increased by 56-57%. Hypoxia exposure resulted to increased seizure susceptibility three days later, incidence of generalized tonic clonic seizures increased by 60% and latency to both seizure types shorter than in non-hypoxic controls. Also, mortality due to seizures was higher (by 58%). In other intervals, there was no difference between hypoxic and non-hypoxic animals. Vigabatrin administered 24 h before hypoxia led to significant decrease of seizure-induced mortality in intervals 1 and 3 days. Administration of vigabatrin immediately after hypoxia exposure resulted in decreased seizure severity when assessed 3 days later. Our data suggest that hypobaric hypoxia transiently increases seizure susceptibility. This effect is partially abolished by vigabatrin administered after hypoxia exposure.