title: Low-frequency stimulation in anterior nucleus of thalamus alleviates kainate-induced chronic epilepsy and modulates the hippocampal EEG rhythm.
abstract: High-frequency stimulation (HFS) of the anterior nucleus of thalamus (ANT) is a new and alternative option for the treatment of intractable epilepsy. However, the responder rate is relatively low. The present study was designed to determine the effect of low-frequency stimulation (LFS) in ANT on chronic spontaneous recurrent seizures and related pathological pattern in intra-hippocampal kainate mouse model. We found that LFS (1 Hz, 100 μs, 300 μA), but not HFS (100 Hz, 100 μs, 30 μA), in bilateral ANT significantly decreased the frequency of spontaneous recurrent seizures, either non-convulsive focal seizures or tonic-clonic generalized seizures. The anti-epileptic effect persisted for one week after LFS cessation, which manifested as a long-term inhibition of the frequency of seizures with short (20-60 s) and intermediate duration (60-120 s). Meanwhile, LFS decreased the frequency of high-frequency oscillations (HFOs) and interictal spikes, two indicators of seizure severity, whereas HFS increased the HFO frequency. Furthermore, LFS decreased the power of the delta band and increased the power of the gamma band of hippocampal background EEG. In addition, LFS, but not HFS, improved the performance of chronic epileptic mice in objection-location task, novel objection recognition and freezing test. These results provide the first evidence that LFS in ANT alleviates kainate-induced chronic epilepsy and cognitive impairment, which may be related to the modulation of the hippocampal EEG rhythm. This may be of great therapeutic significance for clinical treatment of epilepsy with deep brain stimulation.
authors.affiliation: Department of Pharmacology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, College of Pharmaceutical Sciences, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, College of Pharmaceutical Sciences, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Liang
authors.affiliation: Department of Pharmacology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, College of Pharmaceutical Sciences, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Cenglin
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Pharmacology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, College of Pharmaceutical Sciences, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, College of Pharmaceutical Sciences, School of Medicine, Zhejiang University, Hangzhou, China; Epilepsy Center, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Yifang
authors.initials: Y
authors.lastname: Kuang
authors.affiliation: College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
authors.forename: Zhenghao
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Epilepsy Center, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Epilepsy Center, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Wang
authors.affiliation: Epilepsy Center, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. Electronic address: gaofeng7607@sina.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.affiliation: Department of Pharmacology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, College of Pharmaceutical Sciences, School of Medicine, Zhejiang University, Hangzhou, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Epilepsy Center, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. Electronic address: chenzhong@zju.edu.cn.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000818:Animals; D020643:Anterior Thalamic Nuclei / Q000502:physiology*; D046690:Deep Brain Stimulation / Q000379:methods*; D004569:Electroencephalography / Q000379:methods*; D004827:Epilepsy / Q000139:chemically induced / Q000503:physiopathology / Q000628:therapy*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D007608:Kainic Acid / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D007608:Kainic Acid
keywords: Anterior nucleus of thalamus; Chronic epilepsy; EEG rhythm; Low-frequency stimulation; Spontaneous recurrent seizures