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The use of chronic models of temporal lobe epilepsy in antiepileptic drug development

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dc.contributor.authorGrabenstatter, Heidi, author
dc.contributor.authorDudek, F. Edward, advisor
dc.date.accessioned2024-03-13T19:53:49Z
dc.date.available2024-03-13T19:53:49Z
dc.date.issued2007
dc.description.abstractA chronic animal model with altered ion channels, transmitter receptors and/or neural circuitry similar to temporal lobe epilepsy (TLE) may be useful in the discovery of new antiepileptic drugs (AEDs). The hypothesis was that rats with kainate-induced epilepsy are pharmacosensitive to AEDs, but high doses do not block all spontaneous seizures (i.e., these rats are "pharmacoresistant"). A repeated-measures cross-over protocol was used to show single intraperitoneal injections of topiramate, RWJ-333369, and carbamazepine reduced the frequency of spontaneous motor seizures. The same protocol with administration of 30 mg/kg and 100 mg/kg carbamazepine in specially-formulated food pellets was as effective as intraperitoneal injections, and 100 mg/kg carbamazepine administered in food three times per day completely suppressed motor seizures in 50% of the animals for a prolonged time period (i.e., 24 h) while reducing any stress to the animals. Video-EEG showed carbamazepine preferentially reduced spontaneous convulsive seizures compared to nonconvulsive seizures at 100 mg/kg, reduced seizure duration in some animals at 100 mg/kg, and caused a subtle decrease in the maximum frequency of population spikes during seizures at 30 mg/kg. These data suggest that animal models of TLE with spontaneous seizures can be used efficiently to test AEDs, and that this repeated-measures cross-over protocol is amenable to both dose-effect and time-course-of-recovery studies for the direct comparison of AEDs. This approach can provide statistical power to compensate for seizure clusters and variability across animals. These experiments also show that rats with kainate-induced epilepsy are pharmacosensitive to standard and experimental AEDs; additional studies are required to determine if this model is also pharmacoresistant.
dc.format.mediumborn digital
dc.format.mediumdoctoral dissertations
dc.identifierETDF_Grabenstatter_2007_3266371.pdf
dc.identifier.urihttps://hdl.handle.net/10217/237759
dc.languageEnglish
dc.language.isoeng
dc.publisherColorado State University. Libraries
dc.relation.ispartof2000-2019
dc.rightsCopyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright.
dc.rights.licensePer the terms of a contractual agreement, all use of this item is limited to the non-commercial use of Colorado State University and its authorized users.
dc.subjectantiepileptic drugs
dc.subjectcarbamazepine
dc.subjectdrug development
dc.subjectepilepsy
dc.subjectkaninic acid
dc.subjectRWJ-333369
dc.subjectspontaneous seizures
dc.subjecttemporal lobe epilepsy
dc.subjecttopiramate
dc.subjectneurology
dc.subjectpharmacology
dc.subjectneurosciences
dc.titleThe use of chronic models of temporal lobe epilepsy in antiepileptic drug development
dc.typeText
dcterms.rights.dplaThis Item is protected by copyright and/or related rights (https://rightsstatements.org/vocab/InC/1.0/). You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).
thesis.degree.disciplineBiomedical Sciences
thesis.degree.grantorColorado State University
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy (Ph.D.)

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