Ying-Chuan Chen1, Guan-Yu Zhu2, Xiu Wang3, Lin Shi4, Yin Jiang5, Xin Zhang6, Jian-Guo Zhang7. 1. Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China. Electronic address: chenyingchuancyc@163.com. 2. Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China. Electronic address: 375449969@qq.com. 3. Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China. Electronic address: 805064590@qq.com. 4. Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China. Electronic address: 173874447@qq.com. 5. Department of Functional Neurosurgery, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China. Electronic address: jiangyin0802@foxmail.com. 6. Department of Functional Neurosurgery, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China. Electronic address: zxin05@126.com. 7. 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.
Abstract
BACKGROUND: Deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) is effective in seizure control. However, the mechanisms remain unclear. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
BACKGROUND: Deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) is effective in seizure control. However, the mechanisms remain unclear. METHODS: 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. RESULTS: 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). CONCLUSIONS: This study demonstrated that ANT-DBS can reduce seizure frequency in the early stage in epilepticrats 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.