Defense Date
2024
Document Type
Thesis
Degree Name
Master of Science
Department
Anatomy & Neurobiology
First Advisor
Dr. Kimberle Jacobs
Abstract
In this study, the effects of several drug treatments on epileptiform activity in the freeze lesion (FL) mouse model of epilepsy have been evaluated and compared. The FL model replicates the histopathology and epileptiform activity that occurs in humans with the developmental cortical malformation of polymicrogyria (PMG). While Gabapentin is already used in a clinical setting to treat seizures, there are other alternatives that have not been fully tested. Rapamycin, for instance, has been shown to reduce seizures in other models of epilepsy. It is an inhibitor of the mammalian target of rapamycin (mTOR) pathway, which regulates the function of many organs of the body. MTEP has also been shown to have an anticonvulsant effect in certain forms of epilepsy. MTEP is an mGlu5 receptor antagonist. These drugs were delivered in a frame of time that is specific to this study and medically relevant. The age of the mouse at the time of injection corresponded in cortical development with a term human infant, which is the earliest age at which assessment and treatment of PMG would be likely to occur.
To compare the effectiveness of these drugs, local field potential recordings were made using brain slices collected from the somatosensory cortex of FL and Sham lesioned mice with and without the specific drug treatments. It was hypothesized that the incidence of epileptiform activity in the rapamycin, MTEP, and gabapentin treated FL mice will be significantly reduced compared to the FL mice without drug treatment.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
8-12-2024