Temporally irregular electrical stimulation to the epileptogenic focus delays epileptogenesis in rats |
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| Affiliation: | 1. Laboratorio de Neurofisiología del Control y la Regulación, Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría “Ramón de la Fuente Muñiz”, Calz. México-Xochimilco 101, Col. San Lorenzo Huipulco, 14370, Ciudad de México, Mexico;2. Laboratorio de Bioelectrónica, Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría “Ramón de la Fuente Muñiz”, Calz. México-Xochimilco 101, Col. San Lorenzo Huipulco, 14370, Ciudad de México, Mexico;1. Department of Medical Physics and Biomedical Engineering, University College London, UK;2. Wolfson Institute for Biomedical Research, University College London, UK;3. Department of Surgery and Cancer, Imperial College London, UK;4. UCL Queen Square Institute of Neurology, University College London, UK;1. Key Laboratory of Biomedical Engineering of Education Ministry, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, Zhejiang 310027, China;2. Neural Engineering Center, Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA;1. Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China;2. Department of Functional Neurosurgery, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China;3. Beijing Key Laboratory of Neurostimulation, Beijing, China;4. Department of Neurosurgery, Aviational General Hospital of China Medical University, Beijing, China;1. Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China;2. Department of Neurology, The Sixth People Hospital of Jinan, Jinan, China;3. School of Public Health and Family Medicine, Capital Medical University, Beijing, China;4. Beijing Neurosurgical Institute, Capital Medical University, Beijing, China;5. Department of Pharmacology and Howard Hughes Medical Institute, University of Washington, Seattle, WA, USA;6. Department of Pathology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China |
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| Abstract: | BackgroundVariation in the temporal patterns of electrical pulses in stimulation trains has opened a new field of opportunity for the treatment of neurological disorders, such as pharmacoresistant temporal lobe epilepsy. Whether this novel type of stimulation affects epileptogenesis remains to be investigated.ObjectiveThe purpose of this study was to analyze the effects of temporally irregular deep brain stimulation on kindling-induced epileptogenesis in rats.MethodsTemporally irregular deep brain stimulation was delivered at different times with respect to the kindling stimulation. Behavioral and electrographic changes on kindling acquisition were compared with a control group and a temporally regular deep brain stimulation-treated group. The propagation of epileptiform activity was analyzed with wavelet cross-correlation analysis, and interictal epileptiform discharge ratios were obtained.ResultsTemporally irregular deep brain stimulation delivered in the epileptogenic focus during the interictal period shortened the daily afterdischarge duration, slowed the progression of seizure stages, diminished the generalized seizure duration and interfered with the propagation of epileptiform activity from the seizure onset zone to the ipsi- and contralateral motor cortex. We also found a negative correlation between seizure severity and interictal epileptiform discharges in rats stimulated with temporally irregular deep brain stimulation.ConclusionThese results provide evidence that temporally irregular deep brain stimulation interferes with the establishment of epilepsy by delaying epileptogenesis by almost twice as long in kindling animals. Thus, temporally irregular deep brain stimulation could be a preventive approach against epilepsy. |
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| Keywords: | Epilepsy Deep brain stimulation Kindling Epileptogenesis Temporally irregular stimulation Random inter-pulse-interval |
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