Date of Award

2006

Document Type

Thesis

Department

Biology

First Advisor

Dr. Lori Hensley

Second Advisor

Dr. Randall Wight

Third Advisor

Dr. Krista Peppers

Abstract

Multiple sclerosis (MS) is a neurodegenerative disease characterized by an autoimmune attack against myelin sheaths in the central nervous system (CNS). Resulting debilitations vary from sensory, motor, and coordination abnormalities to visual difficulties as well as bowel, bladder, sexual, and cognitive dysfunction (Fox, 2006). Mitoxantrone (Novantrone) is an FDAapproved drug used to treat the secondary-progressive form ofMS due to its demonstrated immunosuppressive properties. While the mechanism of action of mitoxantrone is not yet well understood, and is limited in its use due to cardiotoxicity, the aim of this study was to determine the effect of mitoxantrone on microglial and astrocyte activation as a measure of the inflammatory response. Enzyme-linked immunosorbent assays (ELISA) showed that lipopolysaccharide (LPS) stimulates markers of activation including nitric oxide (NO), interleukin-1-beta (IL-l b), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) in N9 cultured microglia, and moreover, that mitoxantrone inhibits these effects in a dosedependent manner.

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