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Browsing by Author "Dudek, F. Edward, advisor"

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    Status epilepticus, recurrent seizures, hippocampal damage and the estrous cycle in a model of temporal lobe epilepsy
    (Colorado State University. Libraries, 2008) Fawley, Jessica, author; Dudek, F. Edward, advisor
    Temporal lobe epilepsy is the most common form of epilepsy and is associated with hippocampal sclerosis and spontaneous recurrent seizures. These pathologies generally develop after a latent period from a precipitating brain injury, which often results in status epilepticus (SE). Sex and hormones have been reported to influence SE and mortality in both clinical and experimental settings. Temporal lobe epilepsy is also associated with an increase in reproductive disorders, which are often the result of altered pulsatile release of luteinizing hormone (LH). Gonadotropin-releasing hormone (GnRH) controls LH release; therefore, reproductive abnormalities associated with epilepsy could hypothetically involve hypothalamic disturbances, particularly to the GnRH network, resulting in altered secretion of GnRH. The aim of this dissertation was to (1) to examine the effects of SE and/or temporal lobe epilepsy on the GnRH neuronal network and (2) utilize recordings of electroencephalogram (EEG) activity to systematically quantify sex and hormone influences on SE and the subsequent recurrent seizures. I report that pilocarpine-induced SE resulted in reproductive alterations in two rodent models of temporal lobe epilepsy, which were not due to a detectable reduction in GnRH-positive neurons. There were no significant differences between the EEG parameters of SE or recurrent seizures between groups. Sex and the stage of the estrous cycle may influence pyramidal cell loss in the hippocampus at 24 h but the stage of the estrous cycle and/or sex do not seem to be predictors of long-term hippocampal damage. In summary, these data do not support the hypothesis that SE and/or temporal lobe epilepsy results in a reduction in the number of GnRH neurons or the hypothesis that sex/cycle stage influences SE, or the progression to temporal lobe epilepsy. However, these models of SE/temporal lobe epilepsy will be useful to further study temporal lobe epilepsy-associated reproductive alterations.
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    The use of chronic models of temporal lobe epilepsy in antiepileptic drug development
    (Colorado State University. Libraries, 2007) Grabenstatter, Heidi, author; Dudek, F. Edward, advisor
    A 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.