Preparation of Acute Human Hippocampal Slices for Electrophysiological Recordings
| Autor: | Martin Holtkamp, Larissa Kraus, Julia Onken, Laura Monni, Ulf C. Schneider, Pawel Fidzinski, Philipp Spindler |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
General Chemical Engineering Hippocampus In Vitro Techniques Hippocampal formation Sudden death General Biochemistry Genetics and Molecular Biology Temporal lobe 03 medical and health sciences Epilepsy 0302 clinical medicine medicine Humans General Immunology and Microbiology business.industry General Neuroscience Human brain Bicuculline medicine.disease Electrophysiology 030104 developmental biology medicine.anatomical_structure business Neuroscience 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Journal of Visualized Experiments. |
| ISSN: | 1940-087X |
| Popis: | Epilepsy affects about 1% of the world population and leads to a severe decrease in quality of life due to ongoing seizures as well as high risk for sudden death. Despite an abundance of available treatment options, about 30% of patients are drug-resistant. Several novel therapeutics have been developed using animal models, though the rate of drug-resistant patients remains unaltered. One of probable reasons is the lack of translation between rodent models and humans, such as a weak representation of human pharmacoresistance in animal models. Resected human brain tissue as a preclinical evaluation tool has the advantage to bridge this translational gap. Described here is a method for high quality preparation of human hippocampal brain slices and subsequent stable induction of epileptiform activity. The protocol describes the induction of burst activity during application of 8 mM KCl and 4-aminopyridin. This activity is sensitive to established AED lacosamide or novel antiepileptic candidates, such as dimethylethanolamine (DMEA). In addition, the method describes induction of seizure-like events in CA1 of human hippocampal brain slices by reduction of extracellular Mg2+ and application of bicuculline, a GABAA receptor blocker. The experimental set-up can be used to screen potential antiepileptic substances for their effects on epileptiform activity. Furthermore, mechanisms of action postulated for specific compounds can be validated using this approach in human tissue (e.g., using patch-clamp recordings). To conclude, investigation of vital human brain tissue ex vivo (here, resected hippocampus from patients suffering from temporal lobe epilepsy) will improve the current knowledge of physiological and pathological mechanisms in the human brain. |
| Databáze: | OpenAIRE |
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