DOI
https://doi.org/10.25772/SSWD-RE59
Author ORCID Identifier
https://orcid.org/0000-0002-0074-7791
Defense Date
2025
Document Type
Dissertation
Degree Name
Doctor of Philosophy
Department
Anatomy & Neurobiology
First Advisor
Andrew Ottens
Second Advisor
Darlene Brunzell
Third Advisor
Jeffrey Dupree
Fourth Advisor
Dong Sun
Fifth Advisor
Alex Valadka
Abstract
Traumatic brain injury (TBI) is a significant global health concern, with millions of cases reported annually worldwide. Its incidence spans a wide spectrum of severity, from mild concussions to severe injuries that can result in long-term disability or death. Despite advances in our understanding of TBI pathophysiology, the mechanisms underlying the long-term effects of even mild injuries remain poorly understood. These injuries can lead to lasting cognitive deficits, emotional disturbances, and neurodegenerative diseases that manifest years after the initial trauma. A major barrier to progress in this area is the lack of reliable biomarkers to diagnose TBI severity, predict patient outcomes, and monitor recovery—creating a critical gap in both clinical practice and research. This dissertation seeks to address this gap by investigating the TBI-responsive peptidome as a potential source of informative biomarkers. Using mass spectrometry and advanced bioinformatics techniques, endogenous peptides were identified and quantified in the serum and urine of brain-injured patients. Two distinct panels of peptides emerged from this analysis. The first discriminates and predicts the incidence of elevated intracranial pressure (ICP) in brain-injured individuals, implicating vascular dysfunction as a contributing factor in ICP development. The second panel consists of peptides that correlate with clinical metrics over the course of patient hospitalization, offering molecular insights into the processes underlying symptom progression and recovery. To further evaluate the relevance of these peptides to TBI pathobiology, select candidates were assessed in a controlled cortical impact (CCI) model of injury in rats. Together, these findings demonstrate the potential of the endogenous, injury-responsive peptidome to reveal new insights into injury severity, recovery trajectories, and long-term complications. This work supports a more precise and personalized approach to TBI diagnosis and management, with the ultimate goal of improving patient outcomes through early intervention and targeted therapeutic strategies.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
4-30-2025
Included in
Diagnosis Commons, Other Analytical, Diagnostic and Therapeutic Techniques and Equipment Commons