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dc.contributor.authorKundrick, Erica
dc.date.accessioned2020-01-15T12:50:08Z
dc.date.available2020-01-15T12:50:08Z
dc.date.issued2019en_US
dc.identifier.urihttp://hdl.handle.net/10713/11616
dc.description2019
dc.descriptionToxicology
dc.descriptionUniversity of Maryland, Baltimore
dc.descriptionM.S.
dc.description.abstractIn rodents, exposure to chemical warfare nerve agent soman leads to status epilepticus and extensive neuronal loss. Mice and rats are less sensitive to nerve agent toxicity compared to primates since high levels of plasma carboxylesterase, which acts as a bioscavenger against soman, increase resistance of these rodents to organophosphorus poisoning. One objective of this research project was to determine the LD50s of soman in female plasma carboxylesterase knockout (ES1-/-) mice at the different stages of their estrous cycle and to compare toxicity across estrous and with male mice. Female mice in estrus were less susceptible to the soman lethality compared to female mice in proestrus and to male mice. The second objective was to evaluate dose-response effects of delayed midazolam treatment in soman-exposed ES1-/- mice. Delayed midazolam dose-dependently increased survival and reduced seizure severity but did not prevent epileptogenesis or brain pathology in seizure-sensitive brain regions, independent of sex.
dc.subjectToxicology
dc.subjectNeurosciences
dc.subject.meshFemaleen_US
dc.subject.meshMice, Knockouten_US
dc.subject.meshMidazolam--therapeutic useen_US
dc.subject.meshSoman--adverse effectsen_US
dc.titleSex differences in soman-induced toxicity and response to medical countermeasures in serum carboxylesterase knockout miceen_US
dc.typedissertationen_US
dc.date.updated2020-01-08T23:01:47Z
dc.language.rfc3066en
dc.contributor.advisorPereira, Edna F. R.
dc.contributor.advisorLumley, Lucille A.
dc.contributor.orcid0000-0002-4222-1528en_US
refterms.dateFOA2020-01-15T12:50:08Z


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