Zou Shuang, Gong Yiwei, Yan Mengqi, Yuan Zhijian, Sun Minjuan, Zhang Shuo, Yang Yuanzhi, Guo Xiongfeng, Huang Lan, Fei Fan, Wang Yi, Chen Zhong, Xu Cenglin
Zhejiang Key Laboratory of Neuropsychopharmacology, the Second Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Xinhua Hospital), School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.
Department of Pharmacy, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China.
CNS Neurosci Ther. 2025 Feb;31(2):e70265. doi: 10.1111/cns.70265.
The limited efficacy and very restricted antiseizure range of current deep brain stimulation (DBS) targets highlight the need to find an optimal target for managing various seizure types. Here, we aimed to investigate the efficacy of DBS on the ventromedial hypothalamus (VMH) in the different types of experimental epileptic seizures.
The efficacy of DBS was examined in various epileptic seizure models, and the potential mechanisms were investigated by using in vivo calcium signal recording and optogenetics.
The c-fos expression was significantly increased in the glutamatergic neurons of VMH (VMH) following seizures. Then, 1-Hz low-frequency stimulation (LFS) at the VMH successfully attenuated the seizure severities across models of epilepsy, including the maximal electroshock, the pentylenetetrazol, the absence seizure, the cortical or hippocampal kainic acid-induced acute seizure, and the hippocampal-kindling models. The in vivo calcium imaging recordings revealed that LFS could inhibit the activities of the VMH. Optogenetic inhibition of VMH mirrored LFS's antiseizure impact. Further anterograde viral tracing confirmed the extensive distributed projections of VMH, which may compose the circuitry basis of the broad-spectral efficacy of LFS.
These findings demonstrate that VMH-LFS is a broad-spectrum treatment approach for different seizure types by decreasing VMH activity.
当前脑深部电刺激（DBS）靶点的疗效有限且抗癫痫范围非常狭窄，这凸显了寻找治疗各种癫痫类型的最佳靶点的必要性。在此，我们旨在研究DBS对不同类型实验性癫痫发作中腹内侧下丘脑（VMH）的疗效。
在各种癫痫发作模型中检测DBS的疗效，并通过体内钙信号记录和光遗传学研究其潜在机制。
癫痫发作后，VMH的谷氨酸能神经元中c-fos表达显著增加。然后，在VMH处进行1赫兹低频刺激（LFS）成功减轻了多种癫痫模型的发作严重程度，包括最大电休克、戊四氮、失神发作、皮质或海马海人酸诱导的急性发作以及海马点燃模型。体内钙成像记录显示LFS可抑制VMH的活动。VMH的光遗传学抑制反映了LFS的抗癫痫作用。进一步的顺行病毒示踪证实了VMH广泛分布的投射，这可能构成了LFS广谱疗效的电路基础。
这些发现表明，VMH-LFS通过降低VMH活性是一种针对不同癫痫类型的广谱治疗方法。
