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Potential Treatments For Malformation Associated Epilepsy, Olivia M. Bowles Jan 2016

Potential Treatments For Malformation Associated Epilepsy, Olivia M. Bowles

Theses and Dissertations

Epilepsy has been previously attributed to either increased excitation or decreased inhibition. With this closed frame of mind, modern medicine has been unable to develop a permanent treatment against the mechanisms of epilepsy. In order to treat patients with intractable seizures, especially those caused by developmental malformations, it is essential to understand the entirety of mechanisms that could possibly play a role in the abnormal cortical function. One such developmental malformation is known as polymicrogyria. Epileptogenesis occurs in an area laterally adjacent to this malformation known as the paramicrogyral region (PMR). Past studies have narrowed down the potential cause of …


Eeg Interictal Spike Detection Using Artificial Neural Networks, Howard J. Carey Iii Jan 2016

Eeg Interictal Spike Detection Using Artificial Neural Networks, Howard J. Carey Iii

Theses and Dissertations

Epilepsy is a neurological disease causing seizures in its victims and affects approximately 50 million people worldwide. Successful treatment is dependent upon correct identification of the origin of the seizures within the brain. To achieve this, electroencephalograms (EEGs) are used to measure a patient’s brainwaves. This EEG data must be manually analyzed to identify interictal spikes that emanate from the afflicted region of the brain. This process can take a neurologist more than a week and a half per patient. This thesis presents a method to extract and process the interictal spikes in a patient, and use them to reduce …


Group I Metabotropic Glutamate Receptors On Selective Cellular Subtypes In Epileptogenic Malformed Cortex, William Bruch Jan 2012

Group I Metabotropic Glutamate Receptors On Selective Cellular Subtypes In Epileptogenic Malformed Cortex, William Bruch

Theses and Dissertations

Cortical malformations from altered development are common causes of human epilepsy. The cellular mechanisms responsible for the epileptic state of cortex remain unclear and a significant portion of these cases do not respond to treatment. Previous electrophysiological recordings in the Jacobs lab in a rat polymicrogyria model indicated an increased response to group I metabotropic glutamate receptor agonists in the region adjacent to the malformation (PMZ). In addition there was a novel response in low threshold spiking (LTS) interneurons via mGluR5 activation. To determine whether cell specific expression of these receptors was altered in malformed cortex immunohistochemical stains were performed …


Age Dependent Spatial Characteristics Of Epileptiform Activity In Malformed Cortex, L. Andrew Bell Dec 2011

Age Dependent Spatial Characteristics Of Epileptiform Activity In Malformed Cortex, L. Andrew Bell

Theses and Dissertations

Developmental cortical malformations are a major cause of intractable seizures. Determining the location and timing of susceptibility for epileptiform activity is critical to identifying what mechanisms contribute to epileptogenesis in any model. Using the freeze lesion rat model of polymicrogyria, we have identified, in lesioned cortex, these two aspects of epileptogenesis. Previous studies have demonstrated that epileptiform activity cannot be evoked prior to postnatal day (P) 12, but the malformed cortex is more susceptible to seizures as early as P10. An increase in excitatory afferents to the epileptogenic zone occurs before the onset of network epileptiform activity. Whether or not …


The Effects Of Hypothermia On Status Epilepticus-Induced Acquired Epilepsy, Kristin Phillips Aug 2011

The Effects Of Hypothermia On Status Epilepticus-Induced Acquired Epilepsy, Kristin Phillips

Theses and Dissertations

Status epilepticus (SE) is a type of neurological injury characterized by continuous seizure activity and can lead to molecular and pathophysiological alterations leading to plasticity changes. SE can lead to the development of AE by the process of epileptogenesis, which is a phenomenon that describes the transformation of normal brain tissue into a hyperexcitable neuronal population. It has been demonstrated both in vivo and in vitro that calcium (Ca2+) dynamics are severely altered during and after SE, and these changes play a major role in the progression of epileptogenesis. It has also been reported that preventing the rise in intracellular …


Inhibition Of The Calcium Plateau Following In Vitro Status Epilepticus Prevents The Development Of Spontaneous Recurrent Epileptiform Discharges, Nisha Nagarkatti Sep 2009

Inhibition Of The Calcium Plateau Following In Vitro Status Epilepticus Prevents The Development Of Spontaneous Recurrent Epileptiform Discharges, Nisha Nagarkatti

Theses and Dissertations

Status epilepticus (SE) is a major clinical emergency resulting in continuous seizure activity that can cause brain injury and many molecular and pathophysiologic changes leading to neuronal plasticity. The neuronal plasticity following SE-induced brain injury can initiate epileptogenesis and lead to the ultimate expression of acquired epilepsy (AE), characterized clinically by spontaneous, recurrent seizures. Epileptogenesis is the process wherein healthy brain tissue is transformed into hyperexcitable neuronal networks that produce AE. Understanding these alterations induced by brain injury is an important clinical challenge and can lend insight into possible new therapeutic targets to halt the development of AE. Currently there …


The Role Of Inhibitory Interneurons In A Model Od Developmental Epilepsy, Patrick James Wolfgang Jan 2007

The Role Of Inhibitory Interneurons In A Model Od Developmental Epilepsy, Patrick James Wolfgang

Theses and Dissertations

Epilepsy, defined by recurrent seizures, is the one of the most prevalent neurological disorders worldwide (World Health Organization 2007). While many forms of epilepsy are well-controlled by anti-epileptogenic medications, a significant portion of patients have intractable, i.e. untreatable, seizures. The etiology of these seizures is varied, but a significant cause, particularly for patients with intractable epilepsy is developmental malformation. In these cases, an error or interruption during the development of the neocortex produces a structural alteration. Such patients may have other neurological problems, but seizures are the most common symptom. The neuronal mechanisms that link malformation and cortical hyperexcitability are …


Outcomes Of Status Epilepticus In The Elderly, Alan R. Towne Jan 2007

Outcomes Of Status Epilepticus In The Elderly, Alan R. Towne

Theses and Dissertations

Background: Status epilepticus (SE) is a serious medical condition associated with significant morbidity and mortality. Few studies have addressed this condition in the elderly. The present study examines predictors of SE mortality in this growing population.Methods: SE patients visiting the Virginia Commonwealth University Medical Center from July 1, 1989, to June 30,2006 were included in the study. Data on demographic characteristics, SE type, etiology, time to treatment and mortality were collected. Logistic regression analysis was conducted to examine the determinants of mortality due to SE. Data was stratified by age to examine the characteristics of SE among the elderly population.Results: …


Functional Redistribution Of Hippocampal Cannabinoid Cb1 Receptors In The Rat Pilocarpine Model Of Acquired Epilepsy, Katherine Winslow Falenski Jan 2006

Functional Redistribution Of Hippocampal Cannabinoid Cb1 Receptors In The Rat Pilocarpine Model Of Acquired Epilepsy, Katherine Winslow Falenski

Theses and Dissertations

Cannabinoids, such as the marijuana derivative Δ9-THC, are known to have CBl receptor-mediated anticonvulsant effects in several animal models of seizures and epilepsy, including the rat pilocarpine model of acquired epilepsy. However, the distribution of CBl receptor expression and function in brains of epileptic rats has not been characterized. Therefore, this dissertation was initiated to evaluate the effect of epileptogenesis on the distribution and function of the endogenous CBI receptor system in the rat pilocarpine model, a well-established model of acquired temporal lobe epilepsy. Using immunohistochemistry, we demonstrated that chronically epileptic rats exhibit a unique, long-term, and specific redistribution of …


Pathological Upregulation Of A Calcium-Stimulated Phosphatase, Calcineurin, In Two Models Of Neuronal Injury, Jonathan Elledge Kurz Jan 2006

Pathological Upregulation Of A Calcium-Stimulated Phosphatase, Calcineurin, In Two Models Of Neuronal Injury, Jonathan Elledge Kurz

Theses and Dissertations

Excitotoxic calcium influx and activation of calcium-regulated systems is a common event in several types of neuronal injury. This mechanism has been the focus of intense research, with the hope that a more complete understanding of how neuronal injury affects calcium-regulated systems will provide effective treatment options. This study examines one such calcium-stimulated enzyme, calcineurin, in the context of two common neurological pathologies, status epilepticus and traumatic brain injury.Status epilepticus was induced by pilocarpine injection. NMDA-dependent increases in calcineurin activity were observed in cortical and hippocampal homogenates. Upon closer examination, the most profound increases in activity were found to be …


Post-Juvenile Brain Development Modulates Seizure Characteristics And Diazepam Efficacy In The Rat Pilocarpine-Se Model, William H. Holbert Ii Jan 2005

Post-Juvenile Brain Development Modulates Seizure Characteristics And Diazepam Efficacy In The Rat Pilocarpine-Se Model, William H. Holbert Ii

Theses and Dissertations

These studies were completed to examine how status epilpeticus seizure characteristics are modulated during post-juvenile brain development. This may determine if postnatal age in rats is a better identifier of stages of post-juvenile brain development. The first study fully detailed the acute discrete seizure phase of the rat pilocarpine-SE model. Results for this study showed that Racine behavioral severity score, spike frequency, and seizure severity during the acute discrete seizure phase change in relation to post-juvenile brain developmental stages. The second study fully detailed early and late patterns of status epilepticus. Results for this study displayed modulation of time in …


Status Epilepticus Results In A Duration-Dependent Increased Protein Kinase A Activity In The Rat Pilocarpine Model, James M. Bracey Jan 2005

Status Epilepticus Results In A Duration-Dependent Increased Protein Kinase A Activity In The Rat Pilocarpine Model, James M. Bracey

Theses and Dissertations

This study was conducted to characterize cellular changes occurring during the progression of status epilepticus (SE) that could lead to the maintenance of increased membrane excitability. SE was induced by injection of pilocarpine after which rats were monitored both electrographically and behaviorally. After various lengths of time in SE, specific brain regions were isolated for biochemical study. SE resulted in an early maintenance of PKA activity in both cortical homogenate and crude synaptoplasmic membrane (crude SPM) fractions. At subsequent stages of SE there was a significant increase in PKA activity in both homogenate and crude SPM fractions. Wester blot analysis …