Neuroscience Bulletin 2024年第5期︱特别刊：癫痫中的新机制、药物靶点和治疗方法-上海格索普生物科技有限公司

本文部分内容转自神经科学通报英文版

该封面图由格索普生物制图团队创作

本期专辑的封面文章来自浙江中医药大学药学院陈忠教授和徐层林研究员研究团队题为“Low-Frequency Stimulation at the Subiculum Prevents Extensive Secondary Epileptogenesis in Temporal Lobe Epilepsy”的研究论文。研究团队前期系列研究证实，低频电刺激海马下托可有效延缓第一灶点颞叶癫痫全面性发作和耐药性的形成，提示其可能也是防治灶点转移的有效策略。因此，本研究通过在小鼠右侧海马CA3给予电点燃刺激来诱导癫痫第一灶点形成，之后分别在对侧海马和同侧内嗅皮层给以电点燃刺激建立了颞叶癫痫对侧及同侧灶点转移的动物模型，并考察低频电刺激第一灶点同侧海马下托对颞叶癫痫灶点转移的作用。研究结果表明低频电刺激海马下托可以有效延缓颞叶癫痫第二灶点的形成，并且这种效果可能与抑制了癫痫形成过程中第一灶点至第二灶点之间突触可塑性的增强从而降低了第二灶点的神经兴奋有关。详情请点击“上线文章长摘要”。

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https://link.springer.com/article/10.1007/s12264-023-01173-z

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Abstract

Secondary epileptogenesis is characterized by increased epileptic susceptibility and a tendency to generate epileptiform activities outside the primary focus. It is one of the major resultants of pharmacoresistance and failure of surgical outcomes in epilepsy, but still lacks effective treatments. Here, we aimed to test the effects of low-frequency stimulation (LFS) at the subiculum for secondary epileptogenesis in a mouse model. Here, secondary epileptogenesis was simulated at regions both contralateral and ipsilateral to the primary focus by applying successive kindling stimuli. Mice kindled at the right CA3 showed higher seizure susceptibilities at both the contralateral CA3 and the ipsilateral entorhinal cortex and had accelerated kindling processes compared with naive mice. LFS at the ipsilateral subiculum during the primary kindling progress at the right CA3 effectively prevented secondary epileptogenesis at both the contralateral CA3 and the ipsilateral entorhinal cortex, characterized by decreased seizure susceptibilities and a retarded kindling process at those secondary foci. Only application along with the primary epileptogenesis was effective. Notably, the effects of LFS on secondary epileptogenesis were associated with its inhibitory effect at the secondary focus through interfering with the enhancement of synaptic connections between the primary and secondary foci. These results imply that LFS at the subiculum is an effective preventive strategy for extensive secondary epileptogenesis in temporal lobe epilepsy and present the subiculum as a target with potential translational importance.

摘要

继发性癫痫发生的特点是癫痫易感性增加，并有在原发灶外产生癫痫样活动的趋势。它是癫痫药物耐药性和手术失败的主要结果之一，但仍缺乏有效的治疗方法。在这里，我们旨在测试低频刺激（LFS）在小鼠模型中对继发性癫痫发生的影响。在这里，通过施加连续的点燃刺激，在主病灶的对侧和同侧区域模拟继发性癫痫发生。在右侧CA3点燃的小鼠在对侧CA3和同侧内嗅皮层都表现出更高的癫痫易感性，并且与未点燃的小鼠相比，点燃过程加快。在右侧CA3的初次点燃过程中，同侧下托的LFS有效地阻止了对侧CA3和同侧内嗅皮层的继发性癫痫发生，其特征是这些继发灶的癫痫易感性降低和点燃过程延迟。只有在原发性癫痫发生的同时应用才有效。值得注意的是，LFS对继发性癫痫发生的影响与其通过干扰原发灶和继发灶之间突触连接的增强对继发灶的抑制作用有关。这些结果表明，下托LFS是颞叶癫痫广泛继发性癫痫发生的有效预防策略，并将下托作为具有潜在转化重要性的靶点。

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Neuroscience Bulletin 2024年第5期︱特别刊：癫痫中的新机制、药物靶点和治疗方法

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