Medial septal stimulation increases seizure threshold and improves cognition in epileptic rats
| Autor: | Darrin J. Lee, Kiarash Shahlaie, Arne D. Ekstrom, Ali Izadi, Aleksandr Pevzner, Gene G. Gurkoff |
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| Rok vydání: | 2018 |
| Předmět: |
Male
Deep brain stimulation medicine.medical_treatment Deep Brain Stimulation Biophysics Spatial Learning Hippocampus Prefrontal Cortex Stimulation 050105 experimental psychology lcsh:RC321-571 Rats Sprague-Dawley 03 medical and health sciences Epilepsy 0302 clinical medicine Cognition medicine Animals 0501 psychology and cognitive sciences Theta Rhythm Temporal lobe epilepsy lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Theta oscillations Medial septal nucleus Seizure threshold business.industry General Neuroscience 05 social sciences Pilocarpine medicine.disease Neuromodulation (medicine) Barnes maze Rats medicine.anatomical_structure Epilepsy Temporal Lobe Neurology (clinical) business Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Brain Stimulation, Vol 12, Iss 3, Pp 735-742 (2019) |
| ISSN: | 1876-4754 |
| Popis: | Background Temporal lobe epilepsy is most prevalent among focal epilepsies, and nearly one-third of patients are refractory to pharmacological intervention. Persistent cognitive and neurobehavioral comorbidities also occur due to the recurrent nature of seizures and medication-related side effects. Hypothesis Electrical neuromodulation is an effective strategy to reduce seizures both in animal models and clinically, but its efficacy to modulate cognition remains unclear. We hypothesized that theta frequency stimulation of the medial septum would increase septohippocampal oscillations, increase seizure threshold, and improve spatial learning in a rat model of pilocarpine-induced epilepsy. Methods Sham and pilocarpine rats were implanted with electrodes in the medial septum, hippocampus and prefrontal cortex. EEG was assessed days prior to and following stimulation. Sham and pilocarpine-treated rats received either no stimulation, continuous (throughout each behavior), or pre-task (one minute prior to each behavior) 7.7 Hz septal stimulation during the Barnes maze spatial navigation test and also during assessment of flurothyl-induced seizures. Results Both continuous and pre-task stimulation prevented epilepsy-associated reductions in theta oscillations over time. Additionally, both stimulation paradigms significantly improved spatial navigation in the Barnes maze, reducing latency and improving search strategy. Moreover, stimulation led to significant increases in seizure threshold in pilocarpine-treated rats. There was no evidence of cognitive enhancement or increased seizure threshold in stimulated sham rats. Conclusion These findings have profound implications as theta stimulation of the septum represents a single frequency and target that has the potential to both improve cognition and reduce seizures for patients with refractory epilepsy. |
| Databáze: | OpenAIRE |
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