title: Deep brain stimulation of the anterior nucleus of the thalamus reverses the gene expression of cytokines and their receptors as well as neuronal degeneration in epileptic rats.
abstract: Deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) is effective in seizure control. However, the mechanisms remain unclear.
  
  
  
  Sixty-four rats were randomly assigned to the control group, the kainic acid (KA) group, the sham-DBS group and the DBS group. Video-electroencephalogram (EEG) was used to monitor seizures. Quantitative real time PCR (qPCR) was applied for detecting interleukin-1 beta (IL-1β), IL-1 receptor (IL-1R), IL-6, IL-6 receptor (IL-6R), gp130, tumor necrosis factor-alpha (TNF-α), TNF-receptor 1 (TNF-R1) and TNF-receptor 2 (TNF-R2) expression 12h after the establishment of an epileptic model. The neuronal structural degeneration in the hippocampus was evaluated with transmission electron microscopy (TEM) at this same time point.
  
  
  
  The seizure frequency was 48.6% lower in the DBS group compared with the sham-DBS group (P<0.01). The expression of IL-1β, IL-1R, IL-6, IL-6R, gp130, TNF-α and TNF-R1 was elevated in both the KA and the sham group compared with the control group (all Ps<0.01). Additionally, ANT-DBS was able to reverse this gene expression pattern in the DBS group compared with the sham-DBS group (all Ps<0.01). There was no significant difference in TNF-R2 expression among the four groups. The neuronal structural degeneration in the KA group and the sham-DBS group was more severe than that in the control group (injury scores, all Ps<0.01). ANT-DBS was also capable of relieving the degeneration compared with the sham-DBS group (injury score, P<0.01).
  
  
  
  This study demonstrated that ANT-DBS can reduce seizure frequency in the early stage in epileptic rats as well as relieve the pro-inflammatory state and neuronal injury, which may be one of the most effective mechanisms of ANT-DBS against epileptogenesis.
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China. Electronic address: chenyingchuancyc@163.com.
authors.forename: Ying-Chuan
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China. Electronic address: 375449969@qq.com.
authors.forename: Guan-Yu
authors.initials: GY
authors.lastname: Zhu
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China. Electronic address: 805064590@qq.com.
authors.forename: Xiu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China. Electronic address: 173874447@qq.com.
authors.forename: Lin
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Functional Neurosurgery, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China. Electronic address: jiangyin0802@foxmail.com.
authors.forename: Yin
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Functional Neurosurgery, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China. Electronic address: zxin05@126.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China; Department of Functional Neurosurgery, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China; Beijing Key Laboratory of Neurostimulation, Beijing 100050, China. Electronic address: zjguo73@126.com.
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Zhang
mesh_terms: D000818:Animals; D020643:Anterior Thalamic Nuclei / Q000473:pathology / Q000503:physiopathology*; D016207:Cytokines / Q000378:metabolism*; D046690:Deep Brain Stimulation; D004195:Disease Models, Animal; D004569:Electroencephalography; D004827:Epilepsy / Q000150:complications / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D015870:Gene Expression / Q000502:physiology; D007608:Kainic Acid; D008297:Male; D046529:Microscopy, Electron, Transmission; D019636:Neurodegenerative Diseases / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D018121:Receptors, Cytokine / Q000378:metabolism*
chemical_list: D016207:Cytokines; D018121:Receptors, Cytokine; D007608:Kainic Acid
keywords: Anterior nucleus of the thalamus (ANT); Deep brain stimulation (DBS); Epilepsy; Inflammation; Neuronal injury