Author ORCID Identifier

0000-0002-9548-9288

Date of Graduation

8-2018

Document Type

Dissertation (PhD)

Program Affiliation

Cell and Regulatory Biology

Degree Name

Doctor of Philosophy (PhD)

Advisor/Committee Chair

David Loose, Ph.D.

Committee Member

Ruth Heidelberger, M.D., Ph.D.

Committee Member

Darren Boehning, Ph.D.

Committee Member

Michelle Hook, Ph.D.

Committee Member

Edgar T. Walters, Ph.D.

Abstract

Spinal cord injury is a devastating disease that researchers have had very limited success in treating. In addition to interrupted innervation, spinal cord injury causes pathologic changes in a multitude of organ systems. Male infertility is one such complication that is particularly devastating because the patient population is predominantly young men. Our lab has previously shown that the blood testis barrier breaks down after spinal cord injury. This dissertation shows the local metabolomic and mRNA changes that spinal cord injury causes within the testes using a Sprague Dawley rat model, including the elevation in eicosanoids, increased oxidative stress, chronically elevated unconjugated bile acids, altered immune cell populations, acutely decreased testosterone production, and acute elevations in lysolipids. In addition, we show promising and long lasting attenuation of many of these changes with early treatment with licofelone, a dual cox/lox inhibitor, including attenuation of bile acid levels, lysolipids, inflammation, and oxidative stress. This indicates a promising avenue for future research into alleviating this symptom of a devastating injury.

Keywords

Spinal Cord Injury, male infertility, testes, inflammation, oxidative stress, metabolomics, mRNA, rat model

Available for download on Thursday, January 03, 2019

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