A research group headed by Professor CHEN Zhong at Department of Pharmacology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China and Zhejiang Province Key Laboratory of Neurobiology, College of pharmaceutical sciences, Zhejiang University has recently published a research paper titled Low-frequency stimulation inhibits epileptogenesis by modulating the early network of the limbic system as evaluated in amygdala kindling model in the internationally renowned neuroscience journal Brain structure and function in June 2013. The article reported that modulation of the early network in the limbic system is crucial for the anti-epileptogenic effect of LFS in amygdaloid-kindling rats.

Low-frequency stimulation (LFS) is emerging as a new and promising option for the treatment of intractable epilepsy with the advantages of reversibility and adjustability and is relatively safer than high-frequency stimulation. However, its mechanisms of action remain unclear. In their study, they have provided the first evidence that the early stages are crucial for LFS inhibiting epileptogenesis by modulating the early network of limbic system. The hypometabolism in the limbic network may be an important biomarker for the beginning of epileptogenesis in temporal lobe epilepsy. So far, human clinical trials attempting to prevent epilepsy have been few and universally unsuccessful; one possible reason may be that the treatment was not administered within the critical period. Therefore, the hypometabolism in the limbic network may be an important biomarker for the beginning of epileptogenesis in temporal lobe epilepsy and this presents the possibility of early intervention and predictive potential in the future management of epilepsy patients.

Studying the mechanism of epileptogenesis and treatment is one of the important research directions for Professor Chen’s research group. Co-first authors of the article are Dr. Yi Wang and Dr. Zheng-hao Xu. The study was funded by the Key Project of National Natural Science Foundation of China and the Key Project of Zhejiang Provincial Natural Science Foundation.

Wang Y, Xu Z, Cheng H, Guo Y, Xu C, Wang S, Zhang J, Ding M, Chen Z.Low-frequency stimulation inhibits epileptogenesis by modulating the early network of the limbic system as evaluated in amygdala kindling model.Brain Struct Funct. 2013 Jun 11.

Source:

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.

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. 18F-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.

PMID: 23754239