Date Presented

Spring 4-2011

Document Type

Thesis

Access Type

1

Degree Name

Bachelor of Science

Department

Biomedical Science

First Advisor

Dr. Judith K. Muir

Second Advisor

Dr. David Freier

Third Advisor

Dr. Nancy Cowden

Abstract

Traumatic brain injury (TBI) is a major cause of death and permanent disability in the United States. Approximately 1.7 million cases of TBI are reported annually. After an injury to the head, excessive glutamate, an excitatory neurotransmitter, is released into the extracellular fluid resulting in the excitotoxic death of neuronal tissue. Recent studies have suggested neurosteroids, may serve as an effective means by which to modulate excitotoxicity via the excitatory neurotransmitter alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). Using mixed astrocyte-neuronal cell cultures (14-16 DIV) exposed to increasing concentrations of AMPA as the model for TBI, the experiments examined the effect of the neurosteroids, pregnenolone sulfate (PS) and dehydropiandrosterone sulfate (DHEAS), on the AMPA-mediated cell death using the lactate dehydrogenase (LDH) assay. In order to observe reactivity of neurosteroids on the specific receptor, AMPA, MK-801, an NMDA antagonist was incorporated into the experimental design. Experimental results concluded pregnenolone sulfate attenuates AMPA-mediated excitotoxicity in a dose-dependent manner, while dehydropiandrosterone sulfate provides a lesser degree of protection from excitotoxicity at higher concentrations in vitro. Neurosteroids may serve as a viable means by which to limit excitotoxic effects on the brain of an individual that has suffered from a TBI.

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