A NOVEL ELECTRICAL STIMULATION PARADIGM FOR THE SUPPRESSION OF EPILEPTIFORM ACTIVITY IN ANIN VIVOMODEL OF MESIAL TEMPORAL LOBE STATUS EPILEPTICUS

Abstract

In this study, we present a novel low-frequency electrical stimulation paradigm for mesial temporal lobe epilepsy (MTLE). The paradigm utilizes the hippocampal commissure as a unique stimulation target to simultaneously influence large portions of the bilateral hippocampal network. When applied to an acute rat model of MTLE, animals that received stimulation exhibited an 88% reduction in the signal power of the bilateral epileptiform activity relative to the control group. In addition, the stimulation entrained the hippocampal network's spontaneous epileptiform activity and disrupted its bilateral synchrony.

Seizure reduction through interneuron-mediated entrainment using low frequency optical stimulation

“…Electrical stimulation has been shown to be an effective method to suppress seizures by more that 85% in in vitro (Toprani and Durand, 2013a) and in vivo (Zhang et al , 2009; Xu et al , 2010; Rashid et al , 2012; Tang and Durand, 2012) animals models and in humans patients (Koubeissi et al , 2013). However, it remains unclear and a subject of great debate whether the therapeutic effect results from activation of specific neural populations or from stimulation of glial cells, passing axons, or afferent inputs to the target neurons.…”

Suppression of acute seizures by theta burst electrical stimulation of the hippocampal commissure using a closed-loop system

“…The mechanisms of low frequency stimulationmediated seizure suppressions may also be involved in the seizure suppression by eTBS. Low frequency electrical stimulation in the ventral hippocampal commissure was effective in suppressing status epilepticus in an animal model (Tang and Durand, 2012) and was due to GABA B -mediated hyperpolarization caused by the synchronous firing of a large number of pyramidal cells (Toprani and Durand, 2013). Therefore, the effects of eTBS may involve mechanisms of both low and high frequency stimulations.…”

Mechanism of highly synchronized bilateral hippocampal activity

“…All locations were relative to bregma. Accurate placement could be confirmed by recording antidromic evoked potentials in CA3 from VHC stimulation (Tang and Durand, 2012). Artificial cerebrospinal fluid (ACSF) was warmed to 37 °C and applied to the exposed skull.…”

“…To generate unilateral seizure activity, ACSF containing 25 mM 4-aminopyridine (4-AP) was injected into the CA1 region at a rate of 0.1 μl/min (Bahar et al, 2006; Tang and Durand, 2012). The injection was 1.0 μl at the start of the first hour and 0.5 μl during subsequent hours for a total of seven hours.…”

“…The bilateral delay was calculated by using cross-correlation, which was performed on the onset section of the ictal data segments (Tang and Durand, 2012). These segments were detected by visually analyzing the raw signal traces and spectrum (LabChart software, AD Instruments, Colorado Springs, CO, USA).…”