Protective effect of vascular endothelial growth factor (VEGF) in a rat model of status epilepticus.
Item
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Title
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Protective effect of vascular endothelial growth factor (VEGF) in a rat model of status epilepticus.
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Identifier
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AAI3325458
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identifier
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3325458
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Creator
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Nicoletti, Jamee Noelle.
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Contributor
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Adviser: Susan D. Croll
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Date
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2008
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Language
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English
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Publisher
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City University of New York.
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Subject
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Psychology, Psychobiology
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Abstract
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Epilepsy is the most common neurological disease worldwide. Current treatments involve the administration of anti-epileptic drugs (AEDs) which address seizure frequency but not etiology or resultant pathology. Neurotrophic factors have recently been explored in the treatment of epilepsy. One such neurotrophic factor, vascular endothelial growth factor (VEGF), may have potential as a therapeutic in the treatment of epilepsy. VEGF mediates several biological processes including vascular permeability, angiogenesis, and neuroprotection. Given its various functions, we sought to characterize the role of VEGF in a rat model of status epilepticus. We first investigated whether VEGF was endogenously upregulated after status epilepticus. We found that VEGF was significantly increased in neurons and glia of the hippocampus and temporal cortex 24 hours after status epilepticus. Given that VEGF is primarily known for its angiogenic properties, we next investigated if there was an increase in vascular density after status epilepticus. We found a significant increase in vascular density in the CA1 region of the hippocampus three days after status epilepticus. When we infused Flt-Fc, an immunoadhesin designed to sequester endogenous VEGF, into brain prior to status epilepticus, we found no significant difference in increased vascular density relative to controls. Since VEGF was not responsible for an increase in vascular density in our model, we hypothesized that perhaps it played a neuroprotective role. We again infused Flt-Fc or a control into brain to characterize VEGF's neuroprotective role. We found a statistically significant decrease in neuronal density in animals treated with Flt-Fc relative to controls. Thus, we concluded that endogenous VEGF did indeed play a neuroprotective role. We also investigated whether exogenous VEGF would provide additional protection to neurons. We found that animals infused with 30ng/d and 60ng/d VEGF had significantly more neurons after status epilepticus than controls. Since VEGF significantly preserved neurons after status epilepticus, we then sought to determine if it also preserved cognitive functioning. We found that VEGF preserved normal anxiety functioning but did not preserve learning and memory. Our findings that exogenous VEGF protein is neuroprotective in this paradigm suggest that it could elucidate a novel approach to cell protection in epilepsy.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
