Degree Type

Dissertation

Date of Award

2011

Degree Name

Doctor of Philosophy

Department

Biomedical Sciences

First Advisor

Steve A. Carlson

Abstract

Salmonella enterica serovar Saintpaul (SstpNPG) is a unique isolate capable of producing bovine encephalopathy in the presence of host neuroendocrine hormones. In vivo and in vitro molecular techniques were used to determine how specific the conditions are for the perpetuation of neuropathogenicity, to understand how the strain traversed the blood-brain barrier (BBB), to find a potential pharmacological agent that abrogated the effects of neuropathogenicity, and to assess the bacterial factors that provoke neurologic disease. In order to determine if collagenase (clg) is responsible for the traversal of the BBB, RT-PCRs were conducted to determine clg expression. Results elucidated a unique relationship between bovine stress factors and clg that could be abrogated by cilostazol, which is capable of tightening the BBB. Knock out of clg also abolished signs of neurologic disease in calves. It was also established that these neurologic deficits seen in cattle could not be reproduced in swine. In order to determine if these signs of neurologic disease could be abolished, beta-lactam antibiotics, which has been recently determined as a novel neuroprotective agent through the upregulation of glutamate transporter expression, were given as a treatment and successfully ameliorated bovine encephalopathy indicating excess extracellular glutamate as a key component. Since little CNS inflammation occurred, neurologic disease most likely resulted from signal transduction aberrations. Lipopolysaccharides (LPS) could be possible elements that provoke such effects. Considering this, LPS was blocked and/or debilitated pharmacologically, resulting in no signs of neurologic disease in calves and alluding to a potential provoker of bovine encephalopathy.

DOI

https://doi.org/10.31274/etd-180810-2062

Copyright Owner

Nalee Xiong

Language

en

Date Available

2012-04-30

File Format

application/pdf

File Size

95 pages

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