对胼胝体的低频刺激可通过γ-氨基丁酸 B 型受体和缓慢过极化后介导的组织兴奋性降低来抑制大脑皮层的癫痫样活动。

IF 6.6 1区 医学 Q1 CLINICAL NEUROLOGY Epilepsia Pub Date : 2024-10-19 DOI:10.1111/epi.18135
Nrupen Pakalapati, Chia-Chu Chiang, Dominique M Durand
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引用次数: 0

摘要

目的:脑深部刺激,尤其是针对纤维束的低频刺激(LFS),已成为治疗耐药性癫痫(DRE)和全身性癫痫的一种潜在疗法,这两种疾病都给治疗带来了巨大挑战。当对胼胝体(CC)等纤维束施加 LFS 时,可弥散地抑制大脑皮层的癫痫发作。然而,LFS抑制大脑皮层癫痫活动的具体过程仍不清楚。本研究在啮齿动物冠状脑切片中研究了LFS对CC皮层抗癫痫作用的机制:方法:建立了一个体外 4-氨基吡啶(4-AP)皮层癫痫发作模型。对 LFS 刺激参数进行了优化,以便在应用于 CC 时在大脑皮层产生最大的抗癫痫效果。在人工脑脊液、4-AP以及各种特异性和非特异性γ-氨基丁酸B型(GABAB)和慢超极化后(sAHP)拮抗剂存在的情况下,测量了LFS对组织兴奋性和癫痫发作时间百分比的影响:LFS能明显抑制大脑皮层的癫痫发作活动,最佳频率为5赫兹(76.5%)。LFS 期间的组织兴奋性在很大的刺激间期范围内都会降低,在 200 毫秒时降低幅度最大。值得注意的是,组织兴奋性在 1000 毫秒时仍保持低迷。在使用 GABAB 拮抗剂的情况下,LFS 对癫痫发作的抑制作用减弱(B 拮抗剂),这表明有一种不同的抗癫痫机制在起作用。在施用 sAHP 拮抗剂后,癫痫发作的减少再次减弱(B 拮抗剂,LFS 未能提供任何有意义的癫痫发作减少):CC的LFS可在大脑皮层产生抗癫痫作用,其机制已被充分理解,可作为DRE患者手术干预的替代方案。
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Low-frequency stimulation of corpus callosum suppresses epileptiform activity in the cortex through γ-aminobutyric acid type B receptor and slow afterhyperpolarization-mediated reduction in tissue excitability.

Objective: Deep brain stimulation, particularly low-frequency stimulation (LFS) targeting fiber tracts, has emerged as a potential therapy for drug-resistant epilepsy (DRE) and for generalized epilepsy, both of which pose significant treatment challenges. LFS diffusely suppresses seizures in the cortex when applied to fiber tracts like the corpus callosum (CC). Nevertheless, the specific processes responsible for suppressing epileptic activity in the cortex induced by LFS remain unclear. This study investigates the mechanisms underlying the antiepileptic effect in the cortex of LFS of the CC in coronal rodent brain slices.

Methods: An in vitro 4-aminopyridine (4-AP) seizure model of cortical seizures was generated. LFS stimulation parameters were optimized to provide the largest antiepileptic effect in the cortex when applied to the CC. Changes to tissue excitability and percent time spent seizing were measured due to LFS in artificial cerebrospinal fluid, 4-AP, and in the presence of various specific and nonspecific γ-aminobutyric acid type B (GABAB) and slow afterhyperpolarization (sAHP) antagonists.

Results: LFS significantly suppressed seizure activity in the cortex, with an optimal frequency of 5 Hz (76.5%). Tissue excitability during LFS reduces across a wide range of interstimulus intervals, with a maximum reduction at 200 ms. Notably, the tissue excitability remains depressed at 1000 ms. LFS, in the presence of GABAB antagonists, had diminished seizure reduction (<15%) and failed to reduce tissue excitability in the 50-400-ms range. Tissue excitability measured with paired pulses in the 600-1000-ms range was depressed in the presence of GABAB antagonists, suggesting a different antiepileptic mechanism was active. Upon administering sAHP antagonists, seizure reduction was once again diminished (<15%). Upon administration of both sAHP and GABAB antagonists, LFS failed to provide any meaningful seizure reduction (<5%).

Significance: LFS of the CC provides an antiepileptic effect in the cortex with well-understood mechanisms and could be an alternative to surgical intervention for patients suffering from DRE.

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来源期刊
Epilepsia
Epilepsia 医学-临床神经学
CiteScore
10.90
自引率
10.70%
发文量
319
审稿时长
2-4 weeks
期刊介绍: Epilepsia is the leading, authoritative source for innovative clinical and basic science research for all aspects of epilepsy and seizures. In addition, Epilepsia publishes critical reviews, opinion pieces, and guidelines that foster understanding and aim to improve the diagnosis and treatment of people with seizures and epilepsy.
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