Abstracts

Surgical resection of mesial temporal structures is an effective treatment of medically intractable mesial temporal lobe epilepsy (MTLE). However, dominant hippocampus resection may ensue with postoperative verbal memory deficit that warrants surgical alternatives to resection attempts. Based on the principle of multiple subpial transections, we developed in the kainate (KA) model of MTLE in mice, a technique of intrahippocampal transection, to disrupt longitudinally projecting axonal circuits that may play a role in generation and propagation of seizures. C57BL/6 adult mice were stereotactically injected with KA (1 nmol in 50 nl) in the right dorsal hippocampus and equiped for hippocampal and cortical EEG recording. Two hippocampal electrodes were placed along the longitudinal axis of the hippocampus, 1.4 mm apart, with the anterior one located at the site of KA injection. Three weeks later, when spontaneous recurrent focal discharges occurred, an intrahippocampal transection was stereotactically performed in the transversal plan between the 2 hippocampal electrodes. Seizures were quantified on EEG recordings before transection and during the following 3 weeks. Animals with such transections were compared to sham operated animals and animals with electrolytic lesion of the hippocampus. Upon completion of experiments, histological controls were performed to ascertain the hippocampal sclerosis (neuronal loss, gliosis, mossy fiber sprouting and granule cell dispersion), the position of the electrodes and the extent of the transection. After a complete hippocampal transection (n=6), no seizures were recorded at the hippocampal electrode located posterior to the transection, whereas discharges persisted at the KA focus, with a reduction of their occurrence and an increase of their duration. After partial hippocampal transection (n=6) discharges, without modification of their occurrence and duration, were recorded at both hippocampal electrodes, as well as in the sham group (n=6). After hippocampal electrolytic lesion (n=6), no discharges were recorded at both hippocampal electrodes. Complete intrahippocampal transversal transection stops diffusion of discharges within the hippocampus. Moreover, such transections also modify the generation of focal discharges, which are less frequent and of a longer duration as compared to controls. These results suggest a role of longitudinally projecting axonal circuits of the hippocampus in the generation and the diffusion of seizures in this model of MTLE. (Supported by Inserm, Fondation pour la Recherche Medicale, Societe Francaise de Neurochirurgie and Fondation Francaise pour la Recherche sur l[apos]Epilepsie.)