Abstracts

RATIONALE: To analyze if differences in the acute phase of convulsive status epilepticus (SE) at different maturational stages might be a reason for less extensive neuronal damage in immature brain.
METHODS: SE was induced by LiCl-pilocarpine (40 mg/kg i.p.) in 12- (P12) and 25-day-old rats (P25) with implanted cortical and hippocampal electrodes. Video-EEG monitoring was performed for 24 (P12) or 48 (P25) hours. To decrease mortality, animals received a single dose of paraldehyde (0.3 and/or 0.6 ml/kg in the two age groups, respectively) after 2 hours of SE. Because of dependence of P12 rats on the mother, EEG recording was repeatedly interrupted and the pups were given back to the nest for 3h. Then the registration continued. After the end of registration, the brains were used for histology. Neuronal damage was detected by Nissl- and Fluoro Jade-B staining.
RESULTS: SE was elicited in all animals. Motor seizures slowly subsided in the younger animals whereas they were violent in the 25-day-old ones. Reaction to paraldehyde varied among individual animals; motor seizures were always more affected than EEG phenomena. Ictal epileptic activity reappeared even in the rats with excellent reaction to paraldehyde. Nongeneralized epileptic EEG activity was common in the P12 rats and formed more than 60% of ictal activity. In addition, number and duration of ictal phases was lower than in P25 rats but the total duration of seizures was much longer than the minimum necessary for marked consequences in adult rats (1 hour). FJB labelled neurons were detected in both age groups. In P12 rats, degenerating neurons were found in several telencephalic and diencephalic structures in all animals. Anterior cortical and/or medial nuclei of the amygdala and the CA1 field of the hippocampus were mostly affected. In the thalamus, FJB-labelled neurons consistently occurred in the mediodorsal and laterodorsal nuclei. No damage was detected in Nissl-stained sections. In P25 rats, neuronal degeneration was more apparent and more extensive than in P12 rats. Degenerating neurons were found in all neocortical areas with prevalence in infragranular layers. Among subcortical structures, extensive damage was evident in the septum, in the bed nc., in the posterior half of the piriform cortex, in the endopiriform area and in all superficial and deep amygdalar nc. In the hippocampus, degenerated neurons occurred in the CA1, the CA3 and in the hilus of the dentate gyrus. Thalamic mediodorsal, laterodorsal and lateroposterior nc., nc. reuniens, dorsal nc. of the lateral geniculate body and medial geniculate body were affected. Decrease in Nissl staining of neurons was found in 4 of 8 rats in the piriform cortex, CA1 and CA3 of the hippocampus and the deep amygdalar nuclei.
CONCLUSIONS: Poor generalization of epileptic activity and low electroclinical correlation during SE in P12 compared to P25 animals might play a role in development of less extensive damage of immature brain after SE.
[Supported by: Grant Agency of the Ministry of Health of the Czech Republic - grant No. NF 6474-3]; (Disclosure: Honoraria - Pavel Mares - speaker for Glaxo Wellcome, Janssen Cilag, Sanofi and Desitin at local meetings)