Abstracts

RATIONALE: The search for new, effective anticonvulsant therapies that are free of side effects led us to examine the possibility that low frequency stimulation (LFS) could effectively interfere with the generation of seizures in amygdala kindled rats. Based on previous work by Gaito et al. and Veliskova et al., we tested the hypothesis that low frequency, sine wave stimulation, delivered during kindling acquisition and after development of the kindled state, would interfere with epileptogenesis and the generation of kindled seizures (SZ). At the end of this activity the participants should be able to discuss the effect of LFS on kindled seizures.
METHODS: Bipolar stainless steel electrodes were implanted bilaterally into the basolateral amygdalae of adult male Sprague-Dawley rats. All animals (n=13) were stimulated twice a day (60Hz, 1msec pulses, 400 [mu]A) for one sec. Experimental animals (n=7) received 30 sec of sine wave stimulation (1Hz, 50[mu]A) immediately before the kindling stimulus. Afterdischarge (AD) duration, the number of stimulations required to elicit the first stage 5 SZ and the number of stimulations required for each animal to become fully kindled were measured for each group. After 20 stimulations a crossover was performed. Fully kindled rats from each group were switched, so that rats in the original control group (n=5) received LFS plus the kindling stimulus and rats in the original experimental group (n=5) received only the kindling stimulus.
RESULTS: The addition of LFS to the kindling stimulus did not have a significant effect on AD duration, the number of stimulations to the first stage 5 SZ, or the number of stimulations required for the experimental rats to become fully kindled. However, the presentation of LFS significantly increased the number of times the kindling stimulus failed to elicit an AD. During the first 20 stimulations, the experimental rats exhibited an AD failure rate of 32.9% compared to an AD failure rate of 0.83% in control rats (p[lt]0.001, Student[ssquote]s t-test). After crossover, both groups of rats received additional stimulations. The failure rate in the original control group significantly increased from 0.83% to 63.3% (p[lt]0.001) while the failure rate in the original experimental group decreased from 32.9% to 9.9% (p[lt]0.01). The experimental animals did not appear to alter their behavior during the LFS.
CONCLUSIONS: These results suggest that LFS may be an effective therapy for the prevention of seizures. The observation that LFS was more effective in fully kindled animals suggests that LFS may be an effective therapy for generalized tonic-clonic seizures. LFS does not appear to have a long-lasting effect on seizure threshold as evidenced by the decrease in the AD failure rate once LFS was discontinued. Further studies are required to determine if LFS, using different intensities or durations, will be more effective than the LFS used in this study and whether LFS interferes with normal brain function.
[Supported by: NeuroPace Inc. and the New York State Department of Health to J.H.G.]; (Disclosure: Salary - Thomas Tcheng, PhD. is an employee of NeuroPace Inc., Grant - From NeuroPace, Inc. to J.H.G.)