Validation of the 6 Hz refractory seizure mouse model for intracerebroventricularly administered compounds
| Autor: | Joeri Van Liefferinge, Katrien Maes, Ann Massie, Jessica Coppens, Eduard Bentea, Ann Van Eeckhaut, Laura Walrave, Ilse Julia Smolders |
|---|---|
| Přispěvatelé: | Pharmaceutical and Pharmacological Sciences, Pharmaceutical Chemistry, Drug Analysis and Drug Information, Medicine and Pharmacy academic/administration, Experimental Pharmacology, Alliance for Modulation in Epilepsy |
| Rok vydání: | 2015 |
| Předmět: |
Phenytoin
Levetiracetam medicine.medical_treatment Sodium phenytoin Blood–brain barrier Capillary Permeability Cornea Epilepsy Mice Catheters Indwelling Refractory Seizures medicine Animals Injections Intraventricular Dentate gyrus medicine.disease Immunohistochemistry Piracetam Electric Stimulation Disease Models Animal medicine.anatomical_structure Anticonvulsant Neurology Blood-Brain Barrier Dentate Gyrus Anticonvulsants Neurology (clinical) Psychology Neuroscience Proto-Oncogene Proteins c-fos medicine.drug |
| Zdroj: | Epilepsy research. 115 |
| ISSN: | 1872-6844 |
| Popis: | The six hertz (6 Hz) refractory seizure model is considered an indispensable chain of the Anticonvulsant Screening Project. We here describe an adapted protocol using the intracerebroventricular (i.c.v.) delivery route, which will allow researchers to perform targetvalidation or proof-of-principle studies using promising compounds with unknown or limited blood-brain barrier permeability (e.g. neuropeptides and peptidomimetics) in this model. Seizures were induced by single application of a current intensity of 49 mA to i.c.v.-implanted NMRI mice using an ECT Unit 57800 Ugo Basile stimulator. By applying these key parameters, c-Fos immunohistochemistry revealed the recruitment of the dentate gyrus, ratifying this model as a valuable tool for testing i.c.v. administered compounds against therapy-resistant seizures. This finding was further strengthened, since i.c.v. administration of levetiracetam suppressed 6 Hz-evoked seizure severity but sodium phenytoin did not. We also propose to use "seizure duration" as an alternative, accurate parameter to express the results within this model. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect