Abstracts

RATIONALE: It is debated whether intermittent seizures cause progressive neuronal loss. Studies have provided conflicting results, but uncertain clinical histories and seizure severities have confounded the results. In this study we examine this issue using two rat models of limbic epilepsy (kindling and post status epilepticus chronic limbic epilepsy). The two models allow for a standardized method of seizure induction and the ability to document numbers of seizures accurately.
METHODS: Adult Sprague-Dawley rats were divided into 3 groups: controls (n = 17), kindled (n=12) and chronic limbic epilepsy (CLE) (n=14). All rats received bipolar electrodes in the mid ventral hippocampus. The controls were not stimulated. The kindled animals were divided into a low frequency (1-2 stimuli/day, 3 times/week) or high frequency (8 stimuli/day, 3 times/week). The CLE rats underwent a period of electrically induced status epilepticus, after which they developed spontaneous recurrent seizures. Seizure frequency was documented by continuous EEG monitoring. CLE rats were divided into low frequency (low seizure number) and high frequency (high seizure number). All rats were also divided by age: 6 months following the first stimulation divided young and old rats. At predetermined intervals rats were perfused and prepared for histological analysis of the ventral hippocampus, which included Timm[ssquote]s staining for mossy fiber sprouting as well as stereological analysis (cell counts and regional cross sectional areas).
RESULTS: In general, kindled animals did not differ significantly from controls other than with an increase in cross sectional area in many of the hippocampal regions. Timm[ssquote]s staining was not significantly increased in kindled rats and there was no relationship between frequency or age and the degree of sprouting. The CLE animals had significant neuronal loss in multiple regions, but there was no relationship between age or seizure frequency. Timm[ssquote]s staining was greater in older rats and in rats with higher frequencies.
CONCLUSIONS: In these rat models of limbic seizures there is no evidence for progressive neuronal loss with increasing seizure frequency, although mossy fiber sprouting is increased in older CLE animals and in CLE animals with higher seizure frequencies. The findings support the hypothesis that the majority of neuronal loss occurs is a result of an initial insult rather than of a cumulative consequence of recurrent seizures.
[Supported by: This study was supported by NINDS grants NS25605 (eb) and NS38992 and NS 02808 (gm).]