title: Low-frequency stimulation inhibits epileptogenesis by modulating the early network of the limbic system as evaluated in amygdala kindling model.
abstract: 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. (18)F-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 ± 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.
authors.affiliation: Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Department of Pharmacology, Zhejiang Province Key Laboratory of Neurobiology, School of Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhenghao
authors.initials: Z
authors.lastname: Xu
authors.forename: Hui
authors.initials: H
authors.lastname: Cheng
authors.forename: Yi
authors.initials: Y
authors.lastname: Guo
authors.forename: Cenglin
authors.initials: C
authors.lastname: Xu
authors.forename: Shuang
authors.initials: S
authors.lastname: Wang
authors.forename: Jianmin
authors.initials: J
authors.lastname: Zhang
authors.forename: Meiping
authors.initials: M
authors.lastname: Ding
authors.forename: Zhong
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001703:Biophysics; D004195:Disease Models, Animal; D004558:Electric Stimulation / Q000379:methods*; D004569:Electroencephalography; D004827:Epilepsy / Q000473:pathology* / Q000628:therapy*; D019788:Fluorodeoxyglucose F18; D007696:Kindling, Neurologic; D008032:Limbic System / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D009415:Nerve Net / Q000000981:diagnostic imaging; D049268:Positron-Emission Tomography; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D019788:Fluorodeoxyglucose F18