Defense Date

2011

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Pharmacology & Toxicology

First Advisor

Robert DeLorenzo

Abstract

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 Ca2+ ([Ca2+]i) immediately following injury (the Ca2+ plateau) prevents the plasticity changes and ultimate development of epilepsy. Currently, there are no treatments available that can be administered following an injury to prevent the development of AE. Therefore it is clinically important to develop a therapy that can be administered after an injury to block epileptogenesis. Hypothermia is a potential therapeutic intervention. Hypothermia is used clinically to provide neuroprotection following various neurological insults such as stroke and traumatic brain injury (TBI). However, no studies have been performed to evaluate the therapeutic potential of hypothermia following SE. Hypothermia provides protection via multiple mechanisms, one of which includes modulating excitotoxic neurotransmission. It is believed to reduce Ca2+ influx by reducing NMDA receptor activation. It is unclear how hypothermia affects Ca2+ through other modes of entry. This dissertation evaluates the effects of hypothermia on the Ca2+ plateau and demonstrates the novel finding that hypothermia induced post-SE blocks the development of the Ca2+ plateau and reduces the development of AE.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

August 2011

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