Publication Date
2011
Document Type
Thesis
Committee Members
Thomas Brown (Committee Member), David Cool (Advisor), Courtney Sulentic (Committee Member)
Degree Name
Master of Science (MS)
Abstract
Organophosphorus nerve agents are amongst the most deadly chemical compounds ever synthesized. Sarin is an organophosphate (OP) ester that irreversibly forms a phosphoester bond at the active site of acetylcholinesterase and thereby induces a rapid and lethal cholinergic crisis. It remains an active threat to vulnerable civilian populations due to its ease of synthesis and known use by rogue nations and terrorist groups. Death is the most extreme consequence of sarin toxicity. Current treatments fail to provide protection against progressive cognitive impairments years after mild exposure. Q-VD-OPh is an in-vivo caspase inhibitor with potent anti-apoptotic and anti-inflammatory properties. In this pilot study, adult male C57BL/6J mice were subcutaneously injected with 0.5 LD50 sarin followed by an intraperitoneal injection of 20 mg/kg Q-VD-OPh. Mice were sacrificed at a two-day time point followed by MALDI imaging and immunohistochemical analysis of brain sections. Protein mass spectra of tissue sections subjected to organic washes yielded an increase in signal sensitivity compared to untreated sections. A non-significant upward trend in GFAP expression was observed in sarin treated animals in contrast to Q-VD-OPh animals. Statistically significant downward trends in nuclear NF-κB/p50-50 expression were observed in sarin treated animals in contrast to Q-VD-OPh animals. These trends open a window to innovative research paradigms that extend beyond the emphasis of regenerating acetylcholinesterase and managing seizures.
Page Count
90
Department or Program
Department of Pharmacology and Toxicology
Year Degree Awarded
2011
Copyright
Copyright 2011, all rights reserved. This open access ETD is published by Wright State University and OhioLINK.
