Abstracts

Using MRI at 17.6 Tesla, we have studied structural changes that occur during the latent period of epileptogenesis in an animal model of mesial temporal lobe epilepsy (MTLE) and correlated these changes with histological analysis., Five 50-day-old adult Sprague-Dawley male rats were anesthesized and implanted with stimulating electrodes to induce self-sustained status epilepticus in 4 out of 5 rats. Subsequently, rats were video monitored to capture spontaneous seizures. After eight weeks, the animals were sacrificed, transcardially perfused, and the intact fixed brains imaged in vitro at 17.6 Tesla. After imaging, brains were processed for histology and stained with Fluoro-Jade C, Timm, GFAP, Black Gold and Perl iron stains to correlate structural changes with those observed with MRI., Three of 5 rats presented with observable spontaneous seizures during the epileptogenic period. These rats showed significantly decreased T2 in the pyramidal cell layer CA1 of the hippocampus and the dorsal thalamic nuclei bilaterally [Fig. 1]. One presented with a cavity and increased T2 in the parahippocampal gyrus on the contralateral side of stimulation. No T2 changes were observed in the frontal cortices of these seizing rats. The two rats with no observable seizures either hadn[apos]t been stimulated or had stimulating electrode placement in the dorsal thalamus instead of the hippocampus. These rats showed no significant T2 abnormalities in any brain region. Histological analysis has been completed for one of the seizing rats and revealed mossy fiber sprouting around the dentate gyrus bilaterally, iron deposition in the dorsal thalamus and demyelination and astrocytic proliferation in the CA1 and CA3 hippocampal regions., These results suggest that there may be a correlation between T2 changes in the parahippocampal gyrus and the hippocampus (related to mossy fiber sprouting and gliosis on histology) and the seizure activity of animal models of MTLE. Future work will correlate these changes with in vivo MRI at different time points after electrical stimulation and structural changes using specific histological methods.[figure1], (Supported by NIH grant R01 EB004752, the Wilder Epilepsy Research Center and University of Florida Alumni Foundation.)