UBC Theses and Dissertations
MicroRNA biomarkers for acute traumatic spinal cord injury Tigchelaar, Seth Stravers
Spinal cord injury is a devastating condition with variability in injury mechanisms and neurologic recovery. Spinal cord impairment is measured and classified by a widely accepted standard neurologic examination, however this examination is extremely challenging to conduct due to the fact that patients are often sedated, unconscious, or have multiple injuries. The lack of objective diagnostic or prognostic tools is a barrier for clinical trials. Biological markers (biomarkers) are promising as they represent an unbiased approach to classify injury severity and predict neurologic outcome. MicroRNAs are attractive biomarker candidates in neurological disorders due to their stability in biological fluids, conservation between humans and model mammals, and tissue specificity. These features of microRNAs motivated my research to identify the changes in expression of microRNAs following different injury severities in human patients with spinal cord injury, as well as in a large animal model of spinal cord injury using pigs. In Chapter 1, I provide background on the diagnosis and prognosis of spinal cord injury and discuss the current status of biomarkers for spinal cord injury. In Chapter 2, I provide the historical context for the use of animal models for studying spinal cord injury and review the current status of such animal models and injury paradigms in spinal cord injury research. In Chapter 3, I used a porcine model of thoracic spinal cord injury to study the effects of injury severity on microRNA expression. I identified a set of microRNAs that are diagnostic for injury severity and prognostic for behavioural and histological outcome. In Chapter 4, I identified changes in microRNA expression following acute spinal cord injury in a cohort of 44 human patients. I identified a set of microRNAs that are diagnostic for baseline injury severity and prognostic for neurologic outcome. These data describe the alterations in the microRNA profiles following acute spinal cord injury and identify a common set of microRNAs that can be used as diagnostic and prognostic tools. Furthermore, the data obtained and analyzed in pigs and humans with spinal cord injury provides a reference data set for future work as well as for correlative pig-human investigations.
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