Abstracts

RATIONALE: As many individuals with temporal lobe epilepsy remain resistant to pharmacological treatment, alternative approaches to arrest their seizures become essential. Several alternative treatments have been presented recently, including electrical brain stimulation. Previously it was reported that long trains of low frequency stimulation (LFS) retard the kindling process in rats (Gaito, 1980). However, from a clinical perspective, a more important question would be whether that stimulation could be applied effectively against a previously epileptic site. To answer that question, we assessed the effects of LFS on a kindled amygdala focus in rats that were selectively bred to be natively seizure-prone (Fast kindlers) or seizure-resistant (Slow kindlers). The objective was to measure the anti-epileptic potential of LFS.
METHODS: Under surgical anesthesia, 10 Fast and 10 Slow kindling male rats (250 g) were implanted in both amygdalae with either a twisted bipolar electrode ([lt]0.5mm tip separation) or a spaced bipolar electrode (i.e., 2 monopolar electrodes separated by 4 mm anterior to posterior). One week later, afterdischarge thresholds (ADTs) were determined, which was followed by daily kindling of one amygdala using a 2 s, 60 Hz sine wave stimulus at the local ADT intensity. After kindling and the accumulation of 6 stage-5 generalized convulsions, 5-10 additional convulsions were provoked in order to assess the stability of the local ADT. Once ADT stability was evident, a single 30 s, 1 Hz sine wave stimulus at 100 uA was delivered to the kindled site. The ADT at that site was then redetermined one min, and again 1-7 days later (without repetition of the LFS).
RESULTS: The ADTs showed no change one min after presentation of the LFS in either strain, nor were there changes in the profile of the convulsive seizures. However, one day later, a dramatic elevation (200-500%) in the ADTs occurred, which slowly abated over 3 days and returned to baseline by ~7 days. This outcome was evident with both electrode configurations and in both strains. However, in the Slow rats, the convulsive seizure profile was also altered 24 hours after LFS. Normally, without LFS, 100% of the ADTs are associated with a triggered convulsion. However, in the Slow rats after LFS, up to 30% of the ADTs did not recruit a convulsive response. Using Fluoro-Jade, histological assessment 24 hours after LFS indicated no evidence of brain injury associated with the elevated ADTs.
CONCLUSIONS: LFS of a kindled epileptic focus raises the threshold for triggering subsequent focal seizures for several days. This effect is not associated with obvious brain injury. It remains to be determined, however, whether the suppressive effects of LFS on ADTs are localized to cells at the electrode tips or represent an effect cast more broadly over the larger kindled network.
[Supported by: This work was supported by CIHR]