Author ORCID Identifier
Date Available
12-20-2024
Year of Publication
2023
Degree Name
Doctor of Philosophy (PhD)
Document Type
Doctoral Dissertation
College
Arts and Sciences
Department/School/Program
Chemistry
First Advisor
Dr. Mark A. Lovell
Abstract
Traumatic brain injury (TBI) continues to be a significant cause of morbidity and mortality worldwide. Despite significant progress in understanding the complex pathophysiology of TBI, the underlying mechanisms remain poorly understood. The primary brain damage is acute and irreversible. However, secondary brain injuries often develop gradually over months to years, creating an opportunity for critical therapeutic interventions. In the past decade, research on TBI biomarkers has seen significant progress. This progress has been driven by the diverse nature of TBI pathologies and the challenges they present for evaluation, management, and prognosis. TBI biomarker proteins resulting from axonal, neuronal, or glial cell injuries have been extensively studied and widely used. However, their detection in peripheral blood specimens may be limited due to difficulties in crossing the blood-brain barrier in sufficient quantities. Even with the advances made in TBI research, there remains a clinical need to develop and identify novel TBI biomarkers that can address these limitations and provide more accurate and accessible diagnostic tools.
In Chapter 2, we used a lateral flow device (LFD) developed in our lab to measure the blood levels of ubiquitinated visinin-like protein 1 (ubVILIP-1) in athletes from the University of Kentucky. ubVILIP-1 levels were measured at baseline, after general exercises, contact practices, and after a potential sports-related concussion (SRC). This study allows us to investigate the usefulness of an LFD to detect blood levels of ubVILIP-1 as a mild TBI (mTBI) biomarker. In order to understand cellular level alternations of VILIP-1 and ubVILIP-1 following a mild injury we subjected SY5Y neuroblastoma cells to mechanically induced stretch injury and an oxygen-glucose deprivation/reoxygenation model for investigation. In addition, we employed Nifedipine as a calcium channel blocker to determine if Ca2+ influx into the intracellular environment after an injury leads to ubiquitination of VILIP-1.
Digital Object Identifier (DOI)
https://doi.org/10.13023/etd.2023.484
Funding Information
- Validation of a Point of Care Diagnostic Test for Sports-Related Concussion (NINDS-R01NS104289)
- Commercialization of a Rapid Blood Test for Traumatic Brain Injury (NINDS-1R41NS102118)
- Validation of a Point of Care Diagnostic for Traumatic Brain Injury (NINDS-1R21NS099781)
Recommended Citation
wu, yueming, "INVESTIGATING VISININ-LIKE PROTEIN 1 AND UBIQUITINATED VISININ-LIKE PROTEIN 1 AS MILD TRAUMATIC BRAIN INJURY BIOMARKERS" (2023). Theses and Dissertations--Chemistry. 185.
https://uknowledge.uky.edu/chemistry_etds/185
Included in
Analytical Chemistry Commons, Biochemistry Commons, Investigative Techniques Commons, Molecular and Cellular Neuroscience Commons
