浙江中医药大学Cenglin Xu等研究人员合作发现，低频刺激海马下托可预防颞叶癫痫的广泛继发性癫痫发生。该项研究成果于2024年1月20日在线发表在《神经科学通报》杂志上。

研究人员旨在小鼠模型中测试低频刺激（LFS）对继发性癫痫发生的影响。通过连续激起刺激，在原发灶的对侧和同侧区域模拟继发性癫痫的发生。与未处理小鼠相比，在右侧CA3刺激的小鼠在对侧CA3和同侧内侧皮层都表现出更高的癫痫易感性，并且刺激过程加快。在右侧CA3的原发性刺激过程中，在同侧海马下托施用LFS可有效防止对侧CA3和同侧内侧皮层的继发性癫痫发生，这些继发性病灶的癫痫发作易感性降低，刺激过程减慢。只有在原发性癫痫发生时使用才有效。

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，而对继发灶产生的抑制作用有关。这些结果表明，在海马下托上使用LFS是颞叶癫痫广泛继发性癫痫发生的有效预防策略，并将海马下托作为一个具有潜在转化意义的靶点。

据悉，继发性癫痫发生的特点是癫痫易感性增加，并倾向于在原发灶以外产生癫痫样活动。它是癫痫药物抵抗和手术失败的主要原因之一，但目前仍缺乏有效的治疗方法。

附：英文原文

Title: Low-frequency Stimulation at the Subiculum Prevents Extensive Secondary Epileptogenesis in Temporal Lobe Epilepsy

Author: Shen, Yujia, Gong, Yiwei, Da, Xiaoli, Gao, Shajing, Zhang, Shuo, Sun, Minjuan, Yang, Yuanzhi, Qiu, Xiaoyun, Li, Menghan, Zheng, Yang, Fei, Fan, Wang, Yi, Chen, Zhong, Xu, Cenglin

Issue&Volume: 2024-01-20

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.

DOI: 10.1007/s12264-023-01173-z

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