Electrophysiologic analysis of a chronic seizure model after unilateral hippocampal KA injection

Purpose: Unilateral intrahippocampal injections of kainic acid (KA) in rats produce spontaneous recurrent limbic seizures and morphologic changes in h ippocampus that resemble hippocampal sclerosis in patients with medically r efractory mesial temporal lobe epilepsy (MTLE), that form of temporal lobe epilepsy (TLE) associated with hippocampal sclerosis. Interictal in vivo el ectrophysiologic studies have revealed high-frequency (250-500 Hz) oscillat ions, termed fast ripples (FRs). These oscillations may uniquely occur in o r adjacent to the site of hippocampal KA injection, in areas that generate spontaneous seizures. Similar field potentials also have been demonstrated in the epileptogenic region of patients with TLE. We have now characterized ictal electrographic patterns in this rat model for comparison with those in human TLE and begun to evaluate the role of FRs in the transition to ict us in the KA-treated rat. Methods: Rats received unilateral intrahippocampal injections of KA and, af ter the development of spontaneous seizures, were implanted with multiple f ixed and moveable microelectrodes for single unit, field potential, and EEG recording. They were then monitored by using video-EEG telemetry for sever al weeks to capture and evaluate electrographic and behavioral seizure type s. Results were correlated with Timm's stain demonstration of mossy fiber s prouting. Results: Low-voltage fast (LVF) and hypersynchronous electrographic ictal-o nset patterns were seen in the KA-treated rat that resembled similar ictal- onset patterns in patients with TLE. Hypersynchronous, but not LVF, ictal d ischarges were associated with recurrent FRs. As in the human, hypersynchro nous ictal onsets originated predominantly in hippocampus, whereas LVF icta l onsets more often involved extrahippocampal structures. LVF ictal onsets occurred during wakefulness or paradoxical sleep and were usually associate d with motor behavior, whereas hypersynchronous ictal onsets occurred durin g slow-wave sleep or periods of immobility and were not associated with mot or behavior unless there was transition to another ictal electrographic pat tern. Mossy fiber sprouting did not correlate with the frequency of ictal E EG discharges exhibited by each rat but was greater in those rats that demo nstrated frequent behavioral seizures, Conclusions: The electrographic features of spontaneous seizures in the KA- treated rat resemble those of patients with medically refractory TLE with r espect to EEG pattern and localization. Our data suggest that hypersynchron ous ictal onsets represent epileptogenic disturbances in hippocampal circui ts, whereas LVF ictal onsets may involve extrahippocampal areas having more direct connections to the motor system. Hypersynchronous seizures may invo lve the same neuronal mechanisms that generate interictal FRs.