School of Medicine and Health Sciences Poster Presentations
Effects of Low-Frequency Stimulation of Anterior Piriform Cortex on Kainate-Induced Seizures in Rats
Poster Number
265
Document Type
Poster
Publication Date
3-2016
Abstract
RATIONALE: Recent evidence in animals and humans suggests that low-frequency stimulation (LFS) has significant antiseizure properties. The anterior piriform cortex (APC) has been demonstrated to be a highly susceptible seizure-trigger zone, and may be critical for the initiation and propagation of seizures originating from cortical and limbic foci. We studied the effect of LFS of the APC on seizure frequency, severity, and duration in the kainate seizure model in rats.
METHODS: Adult Sprague-Dawley rats (n=7; Hilltop Lab Animals Inc, Scottdale, PA) were implanted with tripolar electrodes in the left APC, and recording electrodes bilaterally in the hippocampal CA3 regions. Rats were monitored continuously with video-EEG for the emergence of spontaneous recurrent seizures after induction of status epilepticus by intraperitoneal kainic acid injections (KA). After emergence of spontaneous seizures, animals underwent 2 weeks of baseline recordings to determine seizure frequency and duration. Then, LFS of the APC was applied 60-min on, 15-min off, for two weeks with 1 Hz biphasic square waves, each 0.1 ms in duration, at 200 µA. Another period of 2 weeks of video-EEG monitoring was done after the cessation of LFS. Changes in total and severe seizure frequency, between baseline, LFS, and post-LFS were analyzed using random effects Poisson regression model with a random intercept. Also We analyzed changes in seizure duration by using a random effects model based on log.
RESULTS:
During LFS, seizures decreased by 37% compared with the baseline, but this was not significant. Between post-LFS and baseline, where there was a 95% reduction in the rate of seizure frequency (p=0.003). Additionally, there was an absence of severe seizures during the post-LFS period in relation to baseline. There was a 17 second decrease in median total seizure duration during LFS compared to baseline with a p-value trending toward significance (p=0.065). During the post-LFS period, only one seizure was recorded.
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CONCLUSIONS: Electrical stimulation for treatment of epilepsy has shown limited benefit when compared to remarkable benefits in other neurologic and psychiatric disorders. While LFS has been underutilized, our findings suggest that LFS of the APC significantly reduced the severity and frequency of seizures in a well studied animal model, and to have a lasting carry-over effect.
SOURCES OF FUNDING: The study was made possible by the startup funds from the George Washington University and pilot grant from Clinical and Translational Science Institute at Children’s National. Both sources of funding are for MZK.
Creative Commons License
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Open Access
1
Effects of Low-Frequency Stimulation of Anterior Piriform Cortex on Kainate-Induced Seizures in Rats
RATIONALE: Recent evidence in animals and humans suggests that low-frequency stimulation (LFS) has significant antiseizure properties. The anterior piriform cortex (APC) has been demonstrated to be a highly susceptible seizure-trigger zone, and may be critical for the initiation and propagation of seizures originating from cortical and limbic foci. We studied the effect of LFS of the APC on seizure frequency, severity, and duration in the kainate seizure model in rats.
METHODS: Adult Sprague-Dawley rats (n=7; Hilltop Lab Animals Inc, Scottdale, PA) were implanted with tripolar electrodes in the left APC, and recording electrodes bilaterally in the hippocampal CA3 regions. Rats were monitored continuously with video-EEG for the emergence of spontaneous recurrent seizures after induction of status epilepticus by intraperitoneal kainic acid injections (KA). After emergence of spontaneous seizures, animals underwent 2 weeks of baseline recordings to determine seizure frequency and duration. Then, LFS of the APC was applied 60-min on, 15-min off, for two weeks with 1 Hz biphasic square waves, each 0.1 ms in duration, at 200 µA. Another period of 2 weeks of video-EEG monitoring was done after the cessation of LFS. Changes in total and severe seizure frequency, between baseline, LFS, and post-LFS were analyzed using random effects Poisson regression model with a random intercept. Also We analyzed changes in seizure duration by using a random effects model based on log.
RESULTS:
During LFS, seizures decreased by 37% compared with the baseline, but this was not significant. Between post-LFS and baseline, where there was a 95% reduction in the rate of seizure frequency (p=0.003). Additionally, there was an absence of severe seizures during the post-LFS period in relation to baseline. There was a 17 second decrease in median total seizure duration during LFS compared to baseline with a p-value trending toward significance (p=0.065). During the post-LFS period, only one seizure was recorded.
.
CONCLUSIONS: Electrical stimulation for treatment of epilepsy has shown limited benefit when compared to remarkable benefits in other neurologic and psychiatric disorders. While LFS has been underutilized, our findings suggest that LFS of the APC significantly reduced the severity and frequency of seizures in a well studied animal model, and to have a lasting carry-over effect.
SOURCES OF FUNDING: The study was made possible by the startup funds from the George Washington University and pilot grant from Clinical and Translational Science Institute at Children’s National. Both sources of funding are for MZK.
Comments
Presented at: GW Research Days 2016