PDF(Pubmed)
Abstract：
OBJECTIVE: Deep brain stimulation (DBS) is a promising approach for the treatment of epilepsy. However, the optimal target for DBS and underlying mechanisms are still not clear. Here, we compared the therapeutic effects of DBS on distinct septal subregions, aimed to find the precise targets of septal DBS and related mechanisms for the clinical treatment.
METHODS: Assisted by behavioral test, electroencephalography (EEG) recording and analyzing, selectively neuronal manipulation and immunohistochemistry, we assessed the effects of DBS on the three septal subregions in kainic acid (KA)-induced mouse seizure model.
RESULTS: DBS in the medial septum (MS) not only delayed generalized seizure (GS) development, but reduced the severity; DBS in the vertical diagonal band of Broca (VDB) only reduced the severity of GS, while DBS in the horizontal diagonal band of Broca (HDB) subregion showed no anti-seizure effect. Notably, DBS in the MS much more efficiently decreased abnormal activation of hippocampal neurons. EEG spectrum analysis indicated that DBS in the MS and VDB subregions mainly increased the basal hippocampal low-frequency (delta and theta) rhythm. Furthermore, ablation of cholinergic neurons in the MS and VDB subregions blocked the anti-seizure and EEG-modulating effects of septal DBS, suggesting the seizure-alleviating effect of DBS was dependent on local cholinergic neurons.
CONCLUSIONS: DBS in the MS and VDB, rather than HDB, attenuates hippocampal seizure by activation of cholinergic neurons-augmented hippocampal delta/theta rhythm. This may be of great therapeutic significance for the clinical treatment of epilepsy with septal DBS.
CONCLUSIONS: The optical target of deep brain stimulation in the septum is still not clear. This study demonstrated that stimulation in the medial septum and vertical diagonal band of Broca subregions, but not the horizontal diagonal band of Broca, could alleviate hippocampal seizure through cholinergic neurons-augmented hippocampal delta/theta rhythm. This study may shed light on the importance of precise regulation of deep brain stimulation therapy in treating epileptic seizures.
METHODS: Assisted by behavioral test, electroencephalography (EEG) recording and analyzing, selectively neuronal manipulation and immunohistochemistry, we assessed the effects of DBS on the three septal subregions in kainic acid (KA)-induced mouse seizure model.
RESULTS: DBS in the medial septum (MS) not only delayed generalized seizure (GS) development, but reduced the severity; DBS in the vertical diagonal band of Broca (VDB) only reduced the severity of GS, while DBS in the horizontal diagonal band of Broca (HDB) subregion showed no anti-seizure effect. Notably, DBS in the MS much more efficiently decreased abnormal activation of hippocampal neurons. EEG spectrum analysis indicated that DBS in the MS and VDB subregions mainly increased the basal hippocampal low-frequency (delta and theta) rhythm. Furthermore, ablation of cholinergic neurons in the MS and VDB subregions blocked the anti-seizure and EEG-modulating effects of septal DBS, suggesting the seizure-alleviating effect of DBS was dependent on local cholinergic neurons.
CONCLUSIONS: DBS in the MS and VDB, rather than HDB, attenuates hippocampal seizure by activation of cholinergic neurons-augmented hippocampal delta/theta rhythm. This may be of great therapeutic significance for the clinical treatment of epilepsy with septal DBS.
CONCLUSIONS: The optical target of deep brain stimulation in the septum is still not clear. This study demonstrated that stimulation in the medial septum and vertical diagonal band of Broca subregions, but not the horizontal diagonal band of Broca, could alleviate hippocampal seizure through cholinergic neurons-augmented hippocampal delta/theta rhythm. This study may shed light on the importance of precise regulation of deep brain stimulation therapy in treating epileptic seizures.
摘要：
目的：脑深部电刺激（DBS）是治疗癫痫的一种有前途的方法。然而,DBS的最佳目标和潜在机制仍不清楚。这里,我们比较了DBS对不同间隔亚区的治疗效果，旨在寻找间隔DBS的精确靶点及相关机制,为临床治疗提供依据。
方法：在行为测试的辅助下，脑电图（EEG）记录和分析，选择性神经元操作和免疫组织化学，在海藻酸（KA）诱导的小鼠癫痫模型中，我们评估了DBS对三个间隔亚区的影响。
结果：内侧隔（MS）中的DBS不仅延迟了全身癫痫（GS）的发展，但降低了严重程度；Broca（VDB）的垂直对角带中的DBS仅降低了GS的严重程度，而Broca（HDB）亚区水平对角带中的DBS没有表现出抗癫痫作用。值得注意的是,MS中的DBS更有效地降低了海马神经元的异常激活。EEG频谱分析表明，MS和VDB亚区的DBS主要增加了基底海马低频（δ和θ）节律。此外，MS和VDB亚区胆碱能神经元的消融阻断了间隔DBS的抗癫痫发作和脑电图调节作用，提示DBS的癫痫缓解作用依赖于局部胆碱能神经元。
结论：MS和VDB中的DBS，而不是HDB，通过激活胆碱能神经元增强的海马δ/θ节律来减轻海马癫痫发作。这对于临床上使用间隔DBS治疗癫痫可能具有重要的治疗意义。
结论：脑隔膜深部刺激的光学目标仍不清楚。这项研究表明，在Broca亚区的内侧隔膜和垂直对角线带的刺激，但不是Broca的水平对角带,可以通过胆碱能神经元增强的海马δ/θ节律减轻海马癫痫发作。这项研究可能揭示了精确调节深部脑刺激治疗在治疗癫痫发作中的重要性。
方法：在行为测试的辅助下，脑电图（EEG）记录和分析，选择性神经元操作和免疫组织化学，在海藻酸（KA）诱导的小鼠癫痫模型中，我们评估了DBS对三个间隔亚区的影响。
结果：内侧隔（MS）中的DBS不仅延迟了全身癫痫（GS）的发展，但降低了严重程度；Broca（VDB）的垂直对角带中的DBS仅降低了GS的严重程度，而Broca（HDB）亚区水平对角带中的DBS没有表现出抗癫痫作用。值得注意的是,MS中的DBS更有效地降低了海马神经元的异常激活。EEG频谱分析表明，MS和VDB亚区的DBS主要增加了基底海马低频（δ和θ）节律。此外，MS和VDB亚区胆碱能神经元的消融阻断了间隔DBS的抗癫痫发作和脑电图调节作用，提示DBS的癫痫缓解作用依赖于局部胆碱能神经元。
结论：MS和VDB中的DBS，而不是HDB，通过激活胆碱能神经元增强的海马δ/θ节律来减轻海马癫痫发作。这对于临床上使用间隔DBS治疗癫痫可能具有重要的治疗意义。
结论：脑隔膜深部刺激的光学目标仍不清楚。这项研究表明，在Broca亚区的内侧隔膜和垂直对角线带的刺激，但不是Broca的水平对角带,可以通过胆碱能神经元增强的海马δ/θ节律减轻海马癫痫发作。这项研究可能揭示了精确调节深部脑刺激治疗在治疗癫痫发作中的重要性。
