Antiepileptic effect of low-frequency electrical stimulation is waveform-dependent in hippocampal kindled mice

Abstract

To investigate whether the waveform of electrical stimulus affects the antiepileptic effect of focal low-frequency stimulation (LFS). The antiepileptic effects of the LFS in sine, monophase square and biphase square waves were investigated in hippocampal kindled mice, respectively. Compared to the control group, sine wave focal LFS (30 s) inhibited seizure stages (2.85 ± 0.27 vs 4.75 ± 0.12, P<0.05), lowered incidence of generalized seizures (53.6% vs 96.5%, P<0.01) and reduced afterdischarge durations [(16.2 2 ± 1.69)s vs (30.29 ± 1.12)s, P<0.01] in hippocampal kindled mice, while monophase or biphase square wave LFS (30 s) showed no antiepileptic effect. Monophase square LFS (15 min) inhibited seizure stages (3.58 ± 0.16, P<0.05) and incidence of generalized seizures (66.7%,P<0.01), but had weaker inhibitory effect on hippocampal afterdischarge durations than sine wave LFS. In addition, pre-treatment and 3 s but not 10 s post-treatment with sine wave LFS resulted in suppression of evoked seizures (P<0.05 or P<0.01). The antiepileptic effect of LFS is dependent on its waveform. Sine wave may be optimal for closed-loop LFS treatment of epilepsy.