Year of Publication

2015

Degree Name

Doctor of Philosophy (PhD)

Document Type

Doctoral Dissertation

College

Medicine

Department

Anatomy and Neurobiology

First Advisor

Dr. James W. Geddes

Abstract

Traumatic brain and spinal cord injury continue to be substantial clinical problems with few available treatment strategies. Individuals who are at a greater risk for sustaining a central nervous system (CNS) injury, such as professional athletes and military personnel, may benefit from a prophylactic supplement that would intervene in the neurodegenerative pathways immediately following injury. The high demand for selenium within the central nervous system, as well as the synthesis of selenoproteins by neurons and astrocytes suggests a critical role of selenium within the brain and spinal cord. Studies were designed to test the efficacy of enriched dietary selenium status in providing neuroprotective benefits in rodent models of spinal cord and traumatic brain injury. Levels of selenium storage within the CNS are increased relative to the amount of selenium present in the diet, indicating that selenium compounds effectively cross the blood brain barrier.

In a model of moderate severity spinal cord contusion injury, dietary selenium supplementation reduced the number of days until recovery of independent bladder function following injury. These benefits did not translate to improvements in locomotor function during open field testing or reduction in overall lesion volume in the injured animal groups. Examination of gene expression changes 24 hours after spinal cord injury revealed that dietary selenium enrichment increased expression of genes involved in DNA repair, mitochondrial respiration, and transcriptional regulation. By expanding the scope of these studies to include models of traumatic brain injury, these data show the importance of selenium in the cortex as well. In particular, when compared to diets deficient in selenium, higher levels of dietary selenium improve spatial memory performance and mitochondrial respiration. The results of this dietary study show modest improvements following both traumatic brain and spinal cord injury and suggest that while selenium enrichment may not have a profound effect on the secondary injury cascade immediately following injury, the presence of adequate dietary selenium is critical for mitochondrial respiration. Together the results of these studies suggest that dietary supplementation may play a subtle role in injury mechanisms within the CNS and warrant further investigation.

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