Fiber tract stimulation can reduce epileptiform activity in an in-vitro bilateral hippocampal slice preparation.

Fiber tract stimulation can reduce epileptiform activity in an in-vitro bilateral hippocampal slice preparation.
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DOI:
10.1016/j.expneurol.2012.10.022
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发表时间:
2013-02
影响因子:
5.3
通讯作者:
Durand DM
Durand DM
中科院分区:
医学2区
文献类型:
--
作者:
Toprani S;Durand DM

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内侧颞叶癫痫(MTLE)是一种常见的医学难治性神经系统疾病,已经用灰质电刺激治疗,但成功率有限。然而,刺激连接大脑中动脉的白色物质束可以使治疗效果和范围最大化。我们测试了低频刺激(LFS)的一种新的目标,使同时靶向双边海马:腹侧海马连合(VHC)与一种新的体外切片制备含有双边海马连接的VHC。本研究的目的是了解海马的相互作用在癫痫发作的传播和减少连合纤维束刺激的作用。LFS应用于VHC,因为细胞外和细胞内记录技术与信号处理相结合,以估计癫痫的几个度量,包括:(1)癫痫发作活动占用的总时间(%);(2)癫痫发作持续时间(s);(3)每分钟癫痫发作次数(#);(4)发作功率(V2 Hz −1);以及(5)发作间期频谱(V2 Hz −1)。双侧癫痫样活动在此准备是高度相关的脑电活动。将LFS应用于VHC以幅度和频率依赖性方式降低治疗期间癫痫的所有指标。本研究对VHC LFS减少双侧癫痫发作的机制提供了一些见解,包括去极化阻滞,LTD/LTP和GABAA不参与。重要的是,增强的刺激后1-Hz尖峰与持久的癫痫发作减少相关,并且两者都通过经由VHC靶向双侧大脑皮层而增强。因此,通过VHC中的单个电极刺激双侧前屈肌可以提供有效的MTLE治疗。
Mesial temporal lobe epilepsy (MTLE) is a common medically refractory neurological disease that has been treated with electrical stimulation of gray matter with limited success. However, stimulation of a white matter tract connecting the hippocampi could maximize treatment efficacy and extent. We tested low-frequency stimulation (LFS) of a novel target that enables simultaneous targeting of bilateral hippocampi: the ventral hippocampal commissure (VHC) with a novel in-vitro slice preparation containing bilateral hippocampi connected by the VHC. The goal of this study is to understand the role of hippocampal interplay in seizure propagation and reduction by commissural fiber tract stimulation. LFS is applied to the VHC as extracellular and intracellular recording techniques are combined with signal processing to estimate several metrics of epilepsy including: (1) total time occupied by seizure activity (%); (2) seizure duration (s); (3) seizures per minute (#); and (4) power in the ictal (V2Hz−1); as well as (5) interictal spectra (V2Hz−1). Bilateral epileptiform activity in this preparation is highly correlated between hippocampi. Application of LFS to the VHC reduces all metrics of epilepsy during treatment in an amplitude and frequency dependent manner. This study lends several insights into the mechanisms of bilateral seizure reduction by LFS of the VHC, including that depolarization blocking, LTD/LTP and GABAA are not involved. Importantly, enhanced post-stimulation 1-Hz spiking correlates with long-lasting seizure reduction and both are heightened by targeting bilateral hippocampi via the VHC. Therefore, stimulating bilateral hippocampi via a single electrode in the VHC may provide an effective MTLE treatment.
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