Effect of Deep Brain Stimulation for Epilepsy in the Rat Model of Temporal Lobe Epilepsy
Date Issued
2012
Date
2012
Author(s)
Kao, I-Feng
Abstract
Epilepsy is a chronic neurological disease which affects people of all ages and distributes worldwide. Current strategy for treating epilepsy includes medication, resective surgery and vagus nerve stimulation. In spite of these treatments, there are about one third of epileptic patients who still suffer from uncontrollable seizures. Refractory epilepsy is another name for any type of epilepsy that is resistant to medication. Recently, deep brain stimulation of anterior thalamic nucleus (ATN DBS) has been proposed as a promising therapy for refractory epilepsy. There are four main questions for DBS: (1) How to stimulate the brain? (2) Where is the stimulation target? (3) What is the stimulation parameter? (4) When should one start to stimulate the brain? On one hand, the approved stimulation target for epilepsy is ATN only. On the other hand, the stimulation parameters seem to be a high frequency and a high current. For now, there is no optimal stimulation for DBS on epilepsy treatment so far.
The way to stimulate the brain could be continuous or intermittent and be open-looped or closed-looped. The closed-looped stimulation is starting the stimulation when the cue of seizure attack appears. In order to figure out the suitable stimulation paradigm for a closed-looped stimulation system, we use the pilocarpine-induced epileptic rat model. Advantages of pilocarpine-induced epilepsy are simulation of human temporal lobe epilepsy and a predictable seizure onset.
In this study, electroencephalogram (EEG) was the primary tool for monitoring and identifying seizure. Video-recording was an additional tool. The experiment started on Day one: the rats received EEG electrode with or without DBS electrode implantation.The DBS electrode was introduced to the left anterior thalamic nucleus. On Day eight, all rats were intraperitoneally injected with 280-290 mg/kg pilocarpineto induce seizures. Stimulation began at different time points before pilocarpine administration. The stimulation parameters were 200 Hz, 50 μA and the pulse width 90 μs. Our results showed 60 minutes pre-stimulation successfully suppressed seizure activity. The effects of suppressionincluded an increased seizure threshold, a delayed electrographic and behavioral seizure onset, and a decreased number of rats developed seizure and status epilepticus. In the histopathological findings, only mild inflammation was noted around the implanted site. We conclude that with high stimulation frequency, low stimulation current and prolongedstimulation duration, unilateral ATN DBS could be able to suppress seizures without severe tissue damages.
Subjects
epilepsy
deep brain stimulation (DBS)
anterior thalamic nucleus (ATN)
rat model of temporal lobe epilepsy
SDGs
Type
thesis
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