SEIZURE PRECONDITIONING DOES NOT PREVENT EPILEPTOGENESIS AFTER STATUS EPILEPTICUS IN RATS
Abstract number :
2.059
Submission category :
Year :
2005
Submission ID :
5363
Source :
www.aesnet.org
Presentation date :
12/3/2005 12:00:00 AM
Published date :
Dec 2, 2005, 06:00 AM
Authors :
1,2Alexei Kondratyev, 2Karen Gale, and 2John Gale
Recent evidence suggests that prevention of neural damage occurring shortly after a prolonged seizure episode may not prevent the later development of epilepsy. Pre-exposure of rats to brief, non-injurious seizures evoked by minimal electroconvulsive shock (ECS) protects against neural damage in the aftermath of status epilepticus (SE). This model allows us to dissociate the effects of brain damage caused by severe seizures from the effects unrelated to neurodegeneration. Here we demonstrate that spontaneous seizures evoked by SE are not prevented by ECS preconditioning. Minimal ECS was applied to rats via corneal electrodes which induced minimal limbic motor seizures lasting 5-10 sec. A single ECS treatment session consisted of the ECS seizure, given at 0, 30, and 60 min. Daily sessions were given for 7 days. Control (sham) animals received the same handling and contact with the electrodes, but no current was passed. SE was induced by kainic acid 24 hr after the last ECS and terminated after 2 hr with diazepam. Only rats exhibiting continuous SE consisting of full limbic motor seizures were included in the studies. All comparisons were made between rats that were precisely matched for intensity and duration of seizures. All rats were implanted with the epidural EEG electrodes and the video-EEG monitoring was performed following SE termination using a telemetry system. An electrographic seizure was defined as a high-frequency ([gt]5Hz) high amplitude ([gt]2x baseline) discharge lasting for at least 5 sec. Paroxysmal EEG activity (isolated sharp waves, spindles, or high amplitude bursts of [lt]5 sec) was classified as interictal activity. Animals in both groups (SE and ECS+SE) developed spontaneous seizures. Moreover, all ECS preconditioned animals (with or without spontaneous seizures) displayed frequent episodes of abnormal EEG activity, characterized by prolonged periods of low amplitude synchronized activity [sim] 4 Hz which was not observed in the non-preconditioned animals. The animals from the non-preconditioned SE group that did not develop spontaneous seizures, displayed isolated brief ([lt]5 sec) episodes of synchronized activity (i.e. spindles). Our data suggest that neuroprotective seizure preconditioning before SE does not prevent the development of spontaneous seizure activity. Moreover, the pattern of EEG activity in the preconditioned group may be indicative of more severe abnormalities in these animals. We have previously demonstrated that pre-exposure to chronic ECS resulted in a sustained increase in the levels of neurotrophic factors, and it is possible that upregulation of these factors may facilitate the progression of epileptogenesis. These results highlight the importance of factors other than injury in controlling the long-term morbidity and mortality associated with exposure to the initial episode of prolonged seizure. (Supported by NIH grants MH02040, NS20576 and T32 HD07459.)