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Deep Brain Stimulation Increases Seizure Threshold by Altering REM Sleep and Delta Powers During NREM Sleep.
Frontiers in Neurology ( IF 3.4 ) Pub Date : 2020-08-12 , DOI: 10.3389/fneur.2020.00752
Hsin-Tzu Tseng , Yi-Tse Hsiao , Pei-Lu Yi , Fang-Chia Chang

We previously demonstrated that seizure occurrences at different zeitgeber times alter sleep and circadian rhythm differently. On the other hand, the synchronized delta wave of electroencephalogram (EEG) during non-rapid eye movement (NREM) sleep facilitates seizure, while the desynchronized EEG of rapid eye movement (REM) sleep suppresses it. We also elucidated that unilateral deep brain stimulation (DBS) of the anterior nucleus of thalamus (ANT) suppresses seizure recurrence. In the present study, we intraperitoneally injected pentylenetetrazol (PTZ, 40 mg/kg) for 14 consecutive days (PTZ kindling) to induce spontaneous seizure in rats, and a 30-min (delivered 10 min before each PTZ injection) or a 3-h DBS of unilateral ANT (delivered 1 h before each PTZ injection) was applied to suppress seizure. The frequency of DBS stimulation was 200 Hz and the electrical current consisted of biphasic square pulses with 50-μA intensity, 100-μs pulse width, and 4.1-ms stimulation interval. Our results found that PTZ-induced spontaneous seizure did not cause a significant change in the quantity of NREM sleep but suppressed the amount of REM sleep. Unilateral ANT DBS prolonged the onset latency of ictal seizure, decreased the spontaneous seizure duration, and increased the survival rate but did not change the amplitude of epileptiform EEGs during ictal period. Unilateral ANT DBS did not significantly alter NREM sleep but increased the amount of REM sleep. An analysis of the spectrograms of fast Fourier transform indicated that the intensities of all frequencies were enhanced during the PTZ-induced ictal period and the subsequent spontaneous seizure. Thirty minutes of unilateral ANT DBS suppressed the augmentation of low-frequency (<10 Hz) intensities during the spontaneous seizure induced by PTZ kindling. We further found that consecutive injections of PTZ progressively increased the enhancement of the delta powers during NREM sleep, whereas unilateral ANT DBS inhibited this progressive enhancement. It was also noticed that 30 min of ANT DBS exhibited a better efficacy in epilepsy suppression than 3 h of ANT DBS. These results elucidated that unilateral ANT DBS enhanced the seizure threshold by increasing the amount of REM sleep and decreasing the progressive enhancement of delta power during NREM sleep to suppress spontaneous seizure recurrences in PTZ kindling-induced epileptic rats.

中文翻译:

深部脑刺激通过改变快速眼动睡眠和非快速眼动睡眠期间的德尔塔功率来提高癫痫阈值。

我们之前证明,不同时间的癫痫发作对睡眠和昼夜节律的影响不同。另一方面,非快速眼动(NREM)睡眠期间脑电图(EEG)的同步δ波促进癫痫发作,而快速眼动(REM)睡眠期间的去同步脑电图则抑制癫痫发作。我们还阐明,丘脑前核(ANT)的单侧深部脑刺激(DBS)可抑制癫痫复发。在本研究中,我们连续14天腹腔注射戊四氮(PTZ,40 mg/kg)(PTZ点燃)以诱导大鼠自发性癫痫发作,并注射30分钟(每次注射PTZ前10分钟)或3分钟h 单侧 ANT 的 DBS(每次 PTZ 注射前 1 小时给药)用于抑制癫痫发作。DBS 刺激频率为 200 Hz,电流由强度为 50 μA、脉冲宽度为 100 μs、刺激间隔为 4.1 ms 的双相方脉冲组成。我们的结果发现,PTZ 诱导的自发性癫痫发作不会导致 NREM 睡眠时间的显着变化,但会抑制 REM 睡眠时间。单侧ANT DBS可延长发作潜伏期,缩短自发性发作持续时间,提高生存率,但不改变发作期癫痫样脑电图振幅。单侧 ANT DBS 并未显着改变 NREM 睡眠,但增加了 REM 睡眠时间。快速傅里叶变换频谱图分析表明,在 PTZ 诱发的发作期和随后的自发性癫痫发作期间,所有频率的强度均增强。30 分钟的单侧 ANT DBS 抑制了 PTZ 点燃引起的自发癫痫发作期间低频(<10 Hz)强度的增强。我们进一步发现,连续注射 PTZ 逐渐增加 NREM 睡眠期间 delta 功率的增强,而单侧 ANT DBS 抑制这种逐渐增强。还注意到 30 分钟的 ANT DBS 比 3 小时的 ANT DBS 表现出更好的癫痫抑制功效。这些结果阐明,单侧 ANT DBS 通过增加 REM 睡眠时间和减少 NREM 睡眠期间 delta 功率的逐渐增强来提高癫痫阈值,从而抑制 PTZ 引火诱发的癫痫大鼠的自发性癫痫发作复发。
更新日期:2020-08-12
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