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Virginia Commonwealth University

Epilepsy

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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 …


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 …


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 …