Mode-dependent effect of high-frequency electrical stimulation of the anterior thalamic nucleus on amygdala-kindled seizures in rats

Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao 266071, PR China.
Neuroscience (Impact Factor: 3.33). 05/2012; 217:113-22. DOI: 10.1016/j.neuroscience.2012.05.009
Source: PubMed

ABSTRACT Deep brain stimulation (DBS) is an emerging treatment of epilepsy. Anterior nucleus of the thalamus (ANT) is considered to be an attractive target due to its close connection to the limbic structures and wide regions of neocortex. The present study aimed to investigate the effects of high frequency stimulation (HFS) targeting the ANT on amygdala-kindled seizures in Wistar rats in two different stimulation modes i.e. pre-treatment and post-treatment stimulations, mimicking the scheduled and responsive stimulations in clinical use respectively. When fully-kindled seizures were achieved by daily amygdala kindling (1 s train of 1 ms pulses at 60 Hz), HFS (15 min train of 100 μs pulses at 150 Hz and 450-800 μA) was applied in two modes for 10 days. Bilateral post-treatment with HFS reduced the incidence of generalized seizures and the mean behavioral seizure stage and shortened average afterdischarge duration (ADD) and generalized seizure duration (GSD), while bilateral pre-treatment with HFS resulted in a similar but much weaker inhibition of seizures. On the other hand, we also found the two stimulation modes both increased the afterdischarge threshold (ADT) and the differences of current intensity between ADT and generalized seizure threshold (GST) i.e. Δ(GST-ADT). However, Δ(GST-ADT) increased by at least 20 μA in bilateral post-treatment group, while less in bilateral pre-treatment group. Additionally, unilateral post-treatment with HFS failed to inhibit seizures. Our data show that anti-epileptic effect of bilateral post-treatment with HFS of ANT is much stronger than that of bilateral pre-treatment HFS, indicating bilateral responsive stimulation might be more appropriate for clinical anti-epileptic treatment of ANT HFS.

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Available from: Jin-Tai Yu, Aug 24, 2015
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    • "Several studies using traditional kindling in different anatomical targets have evaluated the inhibitory effect of low frequency stimulation [19] [20] [21] [22] [23] and high-frequency stimulation [24] [25] [26]. Few reports have been carried out in hippocampus using RK model [25] [27] [28], moreover for its role in epileptogenesis [29] [30] [31]. "
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    ABSTRACT: Epilepsy is one of the most common serious neurological disorders. Pharmacoresistant epilepsy patients are poorly con-trolled or their seizures are refractory to drug treatment. Resective surgery is frequently a promising therapy in this population, however, not all the patients meet the eligibility criteria for the surgical treatment. Deep brain stimulation has been investigated in clinical studies and animal studies as an alternative treatment, but the optimal stimulation pa-rameters remain an issue. The present study was designed to investigate the effect of unilateral high-frequency stimula-tion (HFS) of hippocampus on seizure development by using the hippocampal rapid kindling method (hRK) in rats, and compared the results with those of low-frequency stimulation previously published by our group. We used male Wistar rats implanted with electrodes in the ventral hippocampus. All rats underwent hRK (biphasic square wave pulses, 20 Hz for 10 seconds) during three consecutive days (twelve stimulations per day). The control group (hRK; n = 7) received only RK stimulus, while the treated group (HFS-hRK; n = 9) received also HFS (biphasic square wave pulses, 130 Hz for 30 seconds) immediately before the RK stimulus, during three consecutive days. At the end of behavioral testing 78% (p < 0.01) of the animals receiving HFS treatment were still not fully kindled staying in stages 0 -III (p < 0.01). HFS group needed a higher number of stimulations to achieve stage III (p < 0.05) with respect to control group. How-ever, no significant differences in the cumulative daily afterdischarge duration were observed. HFS did not present sig-nificant differences compared with LFS in any of studied parameters. The findings suggest that unilateral HFS applied on hippocampus effectively inhibited the epileptogenic process induced by hippocampal rapid kindling. According to the comparative results about hippocampal rapid kindled animals stimulated with HFS and LFS (5 Hz), we found no conclusive information on which treatment is most efficient.
    Neuroscience & Medicine 01/2013; 4(02):71-76. DOI:10.4236/nm.2013.42011
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    ABSTRACT: PURPOSE: Bilateral electrical stimulation of anterior nuclei of thalamus (ANT) has shown promising effects on epileptic seizures. However, bilateral implantation increases the risk of surgical complications and side effects. This study was undertaken to access the effectiveness of a stimulation paradigm involving high frequency and low intensity currents to stimulate the left ANT in rats. METHODS: Male Sprague-Dawley rats were implanted with electroencephalogram (EEG) electrodes, and an additional concentric bipolar stimulation electrode into either the left or right ANT. The stimulus was a train of pulses (90μs duration each) delivered with a frequency of 200Hz and a current intensity of 50μA. Thalamic stimuli were started 1h before the first intraperitoneal pilocarpine injection (i.p., 300mg/kg), and were applied for 5h. RESULTS: EEG documented seizure activity and status epilepticus (SE) developed in 87.5% of rats treated with no ANT stimulation after a single dose of pilocarpine. Left ANT stimulation significantly increased the tolerance threshold for pilocarpine-induced EEG seizure activity; 20% of rats developed their EEG documented seizure activity after receiving the first dose, whereas 50%, 10% and 20% of rats did not develop seizure activity until they had received the 2nd, 3rd and 4th pilocarpine injection at 1-h intervals. Moreover, left thalamic stimulation reduced the occurrences of both EEG documented seizure activity and SE induced by single-dose pilocarpine to 25%. However, our result demonstrated that little effect on the occurrence rate of seizures and SE was found when rats received right ANT stimulation. CONCLUSIONS: These results suggest that continuously 5-h left ANT stimulation with high frequency and low intensity currents, beginning from 1h before the pilocarpine administration, may successfully reduce the occurrence rate of EEG documented seizure activity and SE development in rats.
    Seizure 01/2013; 34(3). DOI:10.1016/j.seizure.2012.12.015 · 2.06 Impact Factor
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    ABSTRACT: The anterior thalamic nuclei (ATN), a central component of Papez' circuit, are generally assumed to be key constituents of the neural circuits responsible for certain categories of learning and memory. Supporting evidence for this contention is that damage to either of two brain regions, the medial temporal lobe and the medial diencephalon, is most consistently associated with anterograde amnesia. Within these respective regions, the hippocampal formation and the ATN (anteromedial, anteroventral, and anterodorsal) are the particular structures of interest. The extensive direct and indirect hippocampal-anterior thalamic interconnections and the presence of theta-modulated cells in both sites further support the hypothesis that these structures constitute a neuronal network crucial for memory and cognition. The major tool in understanding how the brain processes information is the analysis of neuronal output at each hierarchical level along the pathway of signal propagation coupled with neuroanatomical studies. Here, we discuss the electrophysiological properties of cells in the ATN with an emphasis on their role in spatial navigation. In addition, we describe neuroanatomical and functional relationships between the ATN and hippocampal formation.
    Frontiers in Systems Neuroscience 08/2013; 7:45. DOI:10.3389/fnsys.2013.00045
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