Supragranular mossy fiber sprouting is not necessary for spontaneous seizures in the intrahippocampal kainate model of epilepsy in the rat.

Abstract

In a previous study, we suggested a dissociation between spontaneous recurrent epileptic seizures (SRS) and hippocampal supragranular mossy fiber sprouting (MFS) in the pilocarpine model of epilepsy (PILO). One possible explanation, would be that SRS in the PILO model do not originate in the hippocampus and thus would not depend on MFS. In the present study, we investigated whether MFS is necessary for the SRS that develop after a small intrahippocampal dose of kainic acid (KA), a model where seizures are more likely to start in the hippocampus. Intrahippocampal injections of KA were performed in rats, with and without the concomitant administration of cycloheximide (CHX) (0.5 microg of KA and 6 microg of CHX). After injection, recording electrodes were positioned in the same stereotaxic location. Here again, CHX was able to completely block (5/8 animals) MFS, visualized by neo-Timm staining, without altering the frequency and intensity of spontaneous ictal and interictal EEG events. From these data, we can conclude that, in the intra-hippocampal KA model, MFS is not necessary for the occurrence of ictal events. We suggest that CHX can be used together with classic epileptogenic agents, as a means to study temporal lobe epilepsy (TLE) without the contributing effect of MFS--as seen in TLE patients with mass lesions in the lateral temporal lobe.