Abstracts

We have recently reported that a single pharamacologically-induced tonic-clonic generalized seizure in immature rats resulted in permanent changes in adult hippocampal physiology (S. Meilleur et al, Epilepsia, 2003, v44(4), p507-517). We extended these results by investigating whether any long term changes would implicate an other mechanism, namely the NMDA receptors. We therefore tested whether epileptiform discharges generated following NMDA receptor activation [italic]in vitro[/italic] differed in adult rats having suffered a pentylenetetrazol-induced episode of status epilepticus (SE) when immature vs controls. We further tested for male (M) vs female (F) differences.
Generalized convulsions lasting [gt]30 min were provoked on 13 M and 10 F Sprague-Dawley rat pups on postnatal day 20 by pentylenetetrazol (PTZ, 90mg/kg). Hippocampal slices were prepared from these rats at age 6-11 months (PTZ slices) and from 10 F and 14 M na[iuml]ve rats aged 2-10 months (control slices). Slices were perfused with medium without added Mg²⁺ and the frequency of ensuing spontaneous epileptiform discharges was measured in the CA1, CA3 and dentate gyrus (DG) areas.
The severity and duration of the PTZ-induced SE in M and F pups were similar and no spontaneous behavioural seizures were observed thereafter. Perfusion of hippocampal slices with Mg²⁺-free medium induced the appearance of synchronous spontaneous interictal-like discharges in the CA1, CA3 and DG areas with similar frequencies. In each area, the frequencies were significantly elevated in PTZ vs control slices (CA1 p[lt]0.0043, CA3 p[lt]0.0001, DG p[lt]0.038). Moreover, the frequencies obtained in slices from F-PTZ rats were higher compared to those from M-PTZ rats in all areas, a difference that was significant in CA3 (p[lt]0.03). Subsequent recordings carried out exclusively in the CA3 area, indicated that spontaneous discharge frequency was higher in PTZ vs control slices from animals of both sexes (F-control 0.16[plusmn]0.01 Hz, n=33 vs F-PTZ 0.24[plusmn]0.01 Hz n=34, p=0.0001; M-control 0.14[plusmn]0.01 Hz, n=56 vs M-PTZ 0.20[plusmn]0.01 Hz n=46, p=0.0007). A comparison of the frequencies in F- vs M-control slices indicated no differences (p[gt]0.05), while a comparison of F- vs M-PTZ slices indicated significant differences (p[lt]0.04). Since the ages of the animals used to prepare slices were similar but not identical, we tested whether interictal discharge frequency was age-dependent within each group (F-control, F-PTZ, M-control, M-PTZ): results suggested no correlation.
These results suggest that a single episode of a pharmacologically-induced protracted generalized seizure or SE in juvenile rats, provokes permanent changes in adult hippocampal physiology, which furthermore appear to be more pronounced in female vs male animals. These changes are consistent with increased excitability associated with the NMDA system.
[Supported by: NSERC and Savoy Foundation for Epilepsy]