A new model of chronic temporal lobe epilepsy induced by electrical stimulation of the amygdala in rat

Spontaneous seizures are the hallmark of human epilepsy but they do not occ ur in most of the epilepsy models that are used to investigate the mechanis ms of epilepsy or to test new antiepileptic compounds. This study was desig ned to develop a new focal epilepsy model that mimics different aspects of human temporal lobe epilepsy (TLE), including the occurrence of spontaneous seizures. Self-sustained status epilepticus (SSSE) lasting for 6-20 h was induced by a 20-30 min stimulation of the lateral nucleus of the amygdala ( 100 ms train of 1 ms, 60 Hz bipolar pulses, 400 mu A, every 0.5 s). Stimula ted rats (n = 16) were monitored with a video-EEG recording system every ot her day (24 h/day) for 6 months, and every other video-EEG recording was an alyzed. Spontaneous epileptic seizures (total number 3698) were detected in 13 of the 15 animals (88%) after a latency period of 6 to 85 days (median 33 days). Four animals (31%) had frequent (697-1317) seizures and 9 animals (69%) had occasional seizures (1-107) during the 6-months follow-up period . Fifty-seven percent of the seizures occurred during daytime (lights on 07 :00-19:00 h). At the end of the follow-up period, epileptic animals demonst rated impaired spatial memory in the Morris water-maze. Histologic analysis indicated neuronal loss in the amygdala, hippocampus, and surrounding cort ical areas, and mossy fiber sprouting in the dentate gyrus. The present dat a indicate that focal stimulation of the amygdala initiates a cascade of ev ents that lead to the development of spontaneous seizures in rats. This mod el provides a new tool to better mimic different aspects of human TLE for i nvestigation of the pathogenesis of TLE or the effects of new antiepileptic compounds on status epilepticus, epileptogenesis, and spontaneous seizures . (C) 2000 Elsevier Science B.V. All rights reserved.