Low frequency stimulation decreases seizure activity in a mutation model of epilepsy.
OBJECTIVE
To investigate brain electrical activity in Q54 mice that display spontaneous seizures because of a gain-of-function mutation of the Scn2a sodium channel gene, and to evaluate the efficacy of low frequency deep brain stimulation (DBS) for seizure frequency reduction.


METHODS
Electroencephalography (EEG), electromyography (EMG), and hippocampal deep electrodes were implanted into Q54 mice expressing an epileptic phenotype (n = 6). Chronic six channel recordings (wideband, 0.1-300 Hz) were stored 24 h a day for more than 12 days. Low frequency stimulation (LFS) (3 Hz, square wave, biphasic, 100 μs, 400 μA) was applied to the ventral hippocampal commissure (VHC) in alternating 5 min cycles (on or off) 24 h a day for a period of 4 days.


RESULTS
LFS (3 Hz) resulted in a significant reduction in seizure frequency and duration (21% and 35%, p < 0.05), when applied to the VHC of epileptic Q54 mice (n = 6). Seizure frequency was not directly affected by stimulation state ("on" vs. "off").


CONCLUSIONS
LFS applied at a frequency of 3 Hz significantly reduced seizure frequency and duration in the Q54 model. Furthermore, the reduction of seizure frequency and duration by LFS was not immediate but had a delayed and lasting effect, supporting complex, indirect mechanisms of action.
Kile
Kara Buehrer
KB
Neural Engineering Center, Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Tian
Nan
N
Durand
Dominique M
DM
D000818:Animals; D001921:Brain / Q000502:physiology*; D046690:Deep Brain Stimulation / Q000379:methods; D004195:Disease Models, Animal; D004558:Electric Stimulation / Q000379:methods*; D004567:Electrodes, Implanted; D004569:Electroencephalography / Q000706:statistics & numerical data; D004827:Epilepsy / Q000235:genetics* / Q000517:prevention & control; D006624:Hippocampus / Q000502:physiology*; D006801:Humans; D007696:Kindling, Neurologic / Q000235:genetics / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics* / Q000502:physiology; D062551:NAV1.2 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics*; D012640:Seizures / Q000235:genetics / Q000517:prevention & control; D015222:Sodium Channels / Q000235:genetics*
D062551:NAV1.2 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568251:SCN2A protein, human; C000654500:Scn2a protein, mouse; D015222:Sodium Channels