Abstracts

Brain stimulation is currently being examined as a new therapy for epilepsy. In a previous study, low frequency stimulation (LFS) using sine waves was shown to significantly decrease the incidence of stage 5 seizures in amygdala-kindled rats. In this study, the effect of LFS using sine waves was examined in hippocampal-kindled rats to determine whether LFS would effectively decrease the incidence of seizures initiated in a brain area other than the amygdala. LFS using sine waves was also compared to the effect of LFS using square waves on the incidence of stage 5 seizures in hippocampal-kindled rats.
Bipolar electrodes were surgically implanted bilaterally into the hippocampae of adult male Sprague Dawley rats. After recovery, afterdischarge (AD) thresholds were determined and the kindling process was initiated. The kindling stimulus was 60Hz, 1msec pulse, sine wave for 2sec. The current intensity was 50[mu]A greater than AD threshold. All animals were stimulated twice per day until fully kindled. Two groups of animals were tested. Group 1 animals received pre-emptive LFS using sine waves (1Hz, 50[mu]A) for 30sec each kindling stimulation. Group 2 animals received pre-emptive LFS using square waves (1Hz, 50[mu]A, 1msec biphasic pulse) for 15min each kindling stimulus. LFS using square waves was also tested in animals in the which the current of the kindling stimulation was lowered to 10[mu]A.
The hippocampal-kindled animals in Group 1 exhibited stage 5 seizures 100% of the time in response to the kindling stimulus alone. Pre-emptive LFS using sine waves significantly decreased the incidence of stage 5 seizures to 70% (p[lt] 0.001, Student[apos]s t-test). The animals in Group 2 also exhibited a stage 5 seizure 100% of the time in response to the kindling stimulus alone. However, pre-emptive square wave LFS only decreased the incidence of stage 5 seizures to 83% which was not significant (p[gt] 0.05). These animals were retested using a kindling stimulus in which the current was lowered to 10[mu]A. Lowering the current of the kindling stimulus did not result in a significant decrease in the incidence of stage 5 seizures after LFS using square waves.
Pre-emptive LFS using sine waves significantly decreased the incidence of stage 5 kindled seizures in hippocampal-kindled rats. This demonstrates that the effect of LFS on kindled seizures is not unique to seizures initiated in the amygdala and supports the hypothesis that LFS using sine waves may be an effective therapy for pharmacoresistant seizures. LFS using square wave stimulation, similar to what has been shown to induce long-term depression (LTP) or depotentiation, does not appear to be as effective as sine wave stimulation against kindled seizures initiated in the hippocampus. However, LFS using square waves may become more effective with different stimulus parameters.
[Supported by: Research grants to JHG from NeuroPace, Inc. and the CURE Foundation.]