日時:2010年10月13日 場所:第12講堂
スタンフォード大学Neuroscience Courseにおけるカリキュラムの紹介 & Where do spontaneous seizures initiate in a rat model of temporal lobe epilepsy?
Izumi Toyoda, D.V.M. PhD student, Stanford University School of Medicine ( )
The substrate of seizure initiation in models of temporal lobe epilepsy (TLE) is not well understood. We sought to identify structures that initiate seizures in a commonly used animal model. Depth electrodes (32/rat) were used to record field potentials during spontaneous seizures in chronically epileptic pilocarpine-treated rats. Simultaneous EEG recordings were obtained from structures that are suspected to contribute to seizure initiation in TLE based on previous EEG and neuropathological studies: septum, amygdala, piriform cortex, thalamus, substantia nigra pars reticulata (SNr), entorhinal cortex, subiculum, and dorsal and ventral hippocampus. Time of electrographic seizure onset for each structure was determined using 4 measurements: by eye, the appearance of a slow wave, and the peak of summed spectral power (20-200 Hz and 200-600 Hz). The earliest time among the 4 measurements was considered to be the onset time for the structure. A total of 813 electrographic seizures were recorded (average 74/rat; 11 rats). The average incidence of non-convulsive seizures was 34% (range 0-92%/rat). In 80 seizures (10/rat) of 8 rats analyzed so far, only 10 seizures in 4 rats failed to spread to all recorded target structures. Seizure activity always was detected in the ventral hippocampus, subiculum, and entorhinal cortex. For all seizures, the average rank (earliest to latest) of onset latency was: hippocampus, subiculum, entorhinal cortex, piriform cortex, amygdala, septum, SNr, dorsomedial thalamus, and other thalamic nuclei. No single recording site consistently had the shortest onset latency within or across rats. However, in 5/8 rats, the hippocampal formation consistently had the shortest average onset latency (0.5 s); seizure activity was recorded first in subiculum (28/80 seizures), ventral hippocampus (13/80), dorsal hippocampus (11/80), or entorhinal cortex (5/80). In 2/8 rats, amygdala and amygdalo-hippocampal transition area had the shortest average onset latency (1.3 s), followed by the hippocampal formation (2.3 s). In 1/8 rats, piriform cortex had the shortest average onset latency (1.4 s), followed by the hippocampal formation (2.3 s). SNr and thalamic nuclei consistently showed long average onset latencies, 4.0 s and 4.5 s, respectively. The average onset latency from the earliest to the latest recorded seizure onset was 5.8 s; range 0.4-26.1 s. Among the structures recorded in this study, electrographic seizures spread extensively and quickly during both convulsive and non-convulsive seizures. Our data suggest that the most important substrate for seizure initiation in this rat model of TLE may be the hippocampal formation.