Low-frequency stimulation inhibits epileptogenesis by modulating the early network of the limbic system as evaluated in amygdala kindling model

被引:27
作者
Wang, Yi [1 ]
Xu, Zhenghao [1 ]
Cheng, Hui [2 ]
Guo, Yi [2 ]
Xu, Cenglin [1 ]
Wang, Shuang [2 ]
Zhang, Jianmin [2 ]
Ding, Meiping [2 ]
Chen, Zhong [1 ,2 ]
机构
[1] Zhejiang Univ, Coll Pharmaceut Sci,Minist Hlth China, Sch Med,Key Lab Med Neurobiol, Zhejiang Prov Key Lab Neurobiol,Dept Pharmacol, Hangzhou 310058, Zhejiang, Peoples R China
[2] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Epilepsy Ctr,Dept Neurol, Hangzhou 310058, Zhejiang, Peoples R China
基金
中国国家自然科学基金;
关键词
Brain stimulation; Low-frequency stimulation; Epileptogenesis; Early network; MicroPET; DEEP BRAIN-STIMULATION; LITHIUM-PILOCARPINE MODEL; THERAPEUTIC TIME-WINDOW; TEMPORAL-LOBE EPILEPSY; ANTIEPILEPTIC DRUGS; EPILEPTIFORM SYNCHRONIZATION; GLUCOSE-UTILIZATION; METABOLIC-CHANGES; DELTA ACTIVITY; RAT-BRAIN;
D O I
10.1007/s00429-013-0594-7
中图分类号
R602 [外科病理学、解剖学]; R32 [人体形态学];
学科分类号
100101 ;
摘要
Low-frequency stimulation (LFS) is emerging as a new option for the treatment of epilepsy. The present study was designed to determine whether there is a crucial period for the treatment of epileptogenesis with LFS. LFS was delivered at different time-points to evaluate its anti-epileptogenic effect on amygdala-kindling rats. F-18-fluorodeoxyglucose small-animal positron-emission tomography (microPET) and multi-channel EEG recording (MER) were used to investigate the dynamics of brain networks during epileptogenesis and LFS treatment. Interestingly, LFS delivered in the first 7 days significantly retarded the progression of behavioral seizure stages and shortened the afterdischarge duration (ADD), LFS delivered throughout the whole process resulted in similar effects. However, if LFS was delivered at the beginning of seizure stage 2 or 3 (5 +/- A 0.3 days during kindling acquisition), it had no anti-epileptogenic effect and even prolonged the ADD and enhanced synchronization of the EEGs. MicroPET study revealed a notable hypometabolism in the amygdala, piriform cortex, entorhinal cortex and other regions in the limbic system during the period from seizure stage 0 to stage 2 or 3. The glucose metabolism in those regions was specifically increased by LFS. MER further verified that an early network of afterdischarge spread was formed in those brain regions during kindling acquisition. Thus, we provided direct evidence that modulation of the early network in the limbic system is crucial for the anti-epileptogenic effect of LFS in amygdaloid-kindling rats.
引用
收藏
页码:1685 / 1696
页数:12
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