Localized transmeningeal muscimol prevents neocortical seizures in rats and nonhuman primates: Therapeutic implications
| Autor: | Nandor Ludvig, Hans von Gizycki, Hai M. Tang, Ruben Kuzniecky, Geza Medveczky, Orrin Devinsky, Shirn L. Baptiste, Jean Charchaflieh |
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| Rok vydání: | 2009 |
| Předmět: |
Male
Neocortex Electroencephalography Subarachnoid Space chemistry.chemical_compound Epilepsy Drug Delivery Systems Seizures Convulsion medicine Animals Rats Long-Evans Neurotransmitter GABA Agonists Saimiri Analysis of Variance Dose-Response Relationship Drug Fourier Analysis medicine.diagnostic_test Muscimol business.industry Feeding Behavior medicine.disease Acetylcholine Rats Disease Models Animal medicine.anatomical_structure Neurology chemistry Anesthesia Neurology (clinical) medicine.symptom Subarachnoid space business medicine.drug |
| Zdroj: | Epilepsia. 50:678-693 |
| ISSN: | 1528-1167 0013-9580 |
| DOI: | 10.1111/j.1528-1167.2008.01914.x |
| Popis: | Summary Purpose: To determine whether muscimol delivered epidurally or into the subarachnoid space can prevent and/or terminate acetylcholine (Ach)–induced focal neocortical seizures at concentrations not affecting behavior and background electroencephalography (EEG) activity. Methods: Rats (n = 12) and squirrel monkeys (n = 3) were chronically implanted with an epidural or subarachnoid drug delivery device, respectively, over the right frontal/parietal cortex, with adjacent EEG electrodes. Recordings were performed in behaving rats and chaired monkeys. Via the implants, either a control solution (artificial cerebrospinal fluid, ACSF) or muscimol (0.25–12.5 mm) was delivered locally as a “pretreatment,” followed by the similar delivery of a seizure-inducing concentration of Ach. In five additional rats, the quantities of food-pellets consumed during epidural ACSF and muscimol (2.5 mm) exposures were measured. In a last group of four rats, muscimol (0.8–2.5 mm) was delivered epidurally during the ongoing, Ach-induced EEG seizure. Results: In contrast to ACSF pretreatments, epidural muscimol pretreatment in rats completely prevented the seizures at and above 2.5 mm. In the monkeys, subarachnoid muscimol pretreatments at 2.5 mm completely prevented the focal-seizure–inducing effect of Ach, whereas similar deliveries of ACSF did not affect the seizures. Furthermore, 2.5 mm epidural muscimol left the eating behavior of rats intact and caused only slight changes in the EEG power spectra. Finally, muscimol delivery during Ach-induced EEG seizures terminated the seizure activity within 1–3 min. Conclusions: The results of this study suggest that muscimol is a viable candidate for the transmeningeal pharmacotherapy of intractable focal epilepsy. |
| Databáze: | OpenAIRE |
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