Date of Award

1-1-2017

Document Type

Masters Thesis

Degree Name

M.S.

Organizational Unit

Biological Sciences

First Advisor

Daniel A. Linseman, Ph.D.

Second Advisor

Keith Miller, Ph.D.

Third Advisor

David Patterson

Fourth Advisor

Scott Barbee

Keywords

Closed head injury, Controlled cortical impact, Cysteine, Glutathione, Traumatic Brain Injury

Abstract

Over the past three decades, traumatic brain injury (TBI) has been considered a "silent epidemic" and recognized as an emergent public health problem by the Centers for Disease Control and Prevention (CDC). TBI is defined as a bump, blow, or jolt to the head that disrupts the normal function of the brain. Due to the debilitating effects and prevalence of TBI, novel preventative treatment regimens are highly desirable in at risk populations. According to the CDC groups disproportionately affected by TBI include athletes, people aged 75+, and service men and women, among others. Here, we investigated a unique whey protein supplement, Immunocal®, to determine its ability to boost resilience of neurons prior to injury. It has been previously described that Immunocal® functions specifically by increasing levels of the essential antioxidant glutathione (GSH). We hypothesize that boosting brain levels of GSH will help ameliorate cognitive, physical, and histopathological indices of brain injury post TBI in a mouse model of closed head impact injury. We found that twice daily oral supplementation with 3.30% Immunocal® for 28-35 days prior to impact significantly improved animal motor coordination and to a lesser extent, cognitive performance. Histopathological results also demonstrated a significant effect on corpus callosum width (axonal myelination) and a decreased presence of degenerating neurons in Immunocal®-treated animals compared to untreated TBI animals. However, no effect was seen in measured clinical effects, or primary injury using MRI analysis. Finally, Immunocal® treatment prevented an ~30% reduction in the brain GSH/GSSG ratio observed in untreated TBI mice. These cumulative data suggest that Immunocal®, while unable to attenuate damage done by the primary injury, was helpful in alleviating secondary injury mechanisms in this TBI mouse model. In the future, this compound could hold promise as a preventative agent for in TBI in certain high risk populations.

Publication Statement

Copyright is held by the author. User is responsible for all copyright compliance.

Rights Holder

Elizabeth Eugenia Ignowski

Provenance

Received from ProQuest

File Format

application/pdf

Language

en

File Size

62 p.

Discipline

Biology, Molecular biology

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