Abstracts

The consequences of atypical febrile seizures on brain development remain poorly understood. It has been shown that patients with mesial temporal lobe epilepsy and a history of atypical febrile seizures in early life have a reduction of cerebral volume. Recently, we have demonstrated that a localized cortical microgyrus predisposes immature rats to atypical hyperthermic seizures (HS). The purpose of this study is to investigate the effect of HS in lesioned rats on the total cerebral volume (TCV) of the developing brain. Freeze lesions (focal microgyri) were induced in the right fronto-parietal cortex of rats on postnatal day (P)1. HS were then induced at P10 by exposure to moderately-heated dry air. The TCVs were then estimated at P12, P22 and at P[gt]60 using the method of water immersion volumetry. To evaluate the impact of the HS on the asymmetry between the hemispheres; hemispheric volumes at P22 were estimated using the Cavalieri method after having sectioned the brains and determined the area of each section using the public domain NIH Image program. The degree of hemispheric asymmetry was estimated by calculating a ratio between the volumes of the right and left hemispheres. Controls were sham-operated and na[iuml]ve rats with and without HS (non-lesioned controls) and rats that only received the lesion (lesioned controls). At all ages, there was no difference in the TCV between non-lesion control groups. The TCV of lesioned controls (mean [plusmn] SD cm3; 0.65 [plusmn] 0.06, n=8) differed from non-lesioned controls only at P12 where it was significantly smaller (0.76 [plusmn] 0.06, n=26, P[lt]0.001). Although at P12 the TCV of lesioned rats with HS and lesioned controls were similar, the TCV of the former was significantly reduced at P22 (0.96 [plusmn] 0.05, n=28) vs. (1.01 [plusmn] 0.05, n=22, P[lt]0.005) and at P[gt]60 (1.28 [plusmn] 0.08, n=7) vs (1.46 [plusmn] 0.11, n=7, P[lt]0.01), respectively. Regarding the ratio of the volumes between the hemispheres, there was no difference between the non-lesion controls therefore these results were pooled. This ratio, in lesioned rats with HS (0.96 [plusmn] 0.04, n=9) was significantly smaller than that observed in these controls (1.00 [plusmn] 0.04, n=17, P[lt]0.05). Lesioned controls had a smaller ratio than non-lesioned controls but this was not statistically different. Our results show a progressive loss of cerebral volume and greater hemispheric asymmetry compared to controls in lesioned rats following HS. This indicates that atypical HS lead to an abnormality in brain growth. These results are in line with studies supporting that atypical febrile seizures may have adverse affects on the developing brain. (Supported by The Hospital for Sick Children Foundation, Epilepsy Canada / CIHR, The Ste-Justine Research Foundation)