Abstracts

RATIONALE: Rat models of temporal lobe epilepsy (TLE) in which recurrent spontaneous seizures develop after a chemically or electrically induced generalized (convulsive) status epilepticus (SE) are increasingly used for studies on pathomechanisms of epileptogenesis. An episode of SE in humans often leads to a highly characteristic pattern of neuronal loss that is seen later in life when patients develop TLE. The question whether this neurodegeneration is cause or consequence of the progression of epilepsy is still controversially discussed. McIntyre et al. (Brain Res. 250, 53-63, 1982) previously described a model of partial SE which is based on the electrical stimulation of the basolateral amygdala (BLA) for 60 minutes. We developed a modified protocol which led to three different types of self sustained SE (duration 1-20 h): partial (focal), focal with some generalized seizures, or generalized. Our study had the following aims: (1) comparison of neurodegeneration in the three types of SE; (2) correlation between the extent of neuronal loss and the occurrence of spontaneous recurrent seizures.
METHODS: The following stimulus was used for BLA stimulation: 100 ms trains of 1 ms, 50 Hz bipolar square-wave pulses, 700 [mu]A, every 0.5 sec, for 25 min. A similar protocol has recently been published for SE induction via the lateral nucleus of the amygdala (Nissinen et al., Epilepsy Res. 38, 177-205, 2000). Rats were perfused either 48 h (acute condition) or after development of spontaneous seizures. For the evaluation of neurodegeneration brain sections were Nissl-stained.
RESULTS: After a SE-duration of at least 2 h, neurodegeneration occurred ipsilateral to the stimulation site in most regions of the limbic system and specific thalamic nuclei independent of the type of SE. The occurrence of neuronal loss in the pyramidal cell layers of the hippocampus was correlated with the number of generalized seizures during SE. Neurodegeneration in regions of the contralateral hemisphere could only be detected in animals with generalized seizures during SE. Preliminary results indicate that all animals with neurodegeneration showed spontaneous seizures, but not all animals with spontaneous seizures showed neurodegeneration.
CONCLUSIONS: This model provides an interesting tool to study epileptogenesis and brain damage after different types of SE. The results of the present study suggest that there is no correlation between the extent of neurodegeneration and the occurrence of spontaneous recurrent seizures.
Support: Deutsche Forschungsgemeinschaft.