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Response of Neuroinflammatory and Neurodegenerative Markers Following Sub-lethal Sarin Exposure and Subsequent Treatment via an in-vivo Caspase Inhibitor

Chmura, Douglas F.
http://rave.ohiolink.edu/etdc/view?acc_num=wright1324414961

Abstract Details

2011, Master of Science (MS), Wright State University, Pharmacology and Toxicology.
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.
David Cool, PhD (Advisor)
Thomas Brown, PhD (Committee Member)
Courtney Sulentic, PhD (Committee Member)
90 p.
Pharmacology; Toxicology
pharmacology

Recommended Citations

Citations

  • Chmura, D. F. (2011). Response of Neuroinflammatory and Neurodegenerative Markers Following Sub-lethal Sarin Exposure and Subsequent Treatment via an in-vivo Caspase Inhibitor [Master's thesis, Wright State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=wright1324414961

    APA Style (7th edition)

  • Chmura, Douglas. Response of Neuroinflammatory and Neurodegenerative Markers Following Sub-lethal Sarin Exposure and Subsequent Treatment via an in-vivo Caspase Inhibitor. 2011. Wright State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=wright1324414961.

    MLA Style (8th edition)

  • Chmura, Douglas. "Response of Neuroinflammatory and Neurodegenerative Markers Following Sub-lethal Sarin Exposure and Subsequent Treatment via an in-vivo Caspase Inhibitor." Master's thesis, Wright State University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=wright1324414961

    Chicago Manual of Style (17th edition)

wright1324414961
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© 2011, all rights reserved.
This open access ETD is published by Wright State University and OhioLINK.