Alexis Pulliam
BME PhD Defense Presentation

Date: 2024-07-12
Time: 9:00 am
Location / Meeting Link: https://gatech.zoom.us/j/95392165561/ U A Whitaker Biomedical Engr-165 - 1214 Classroom BME

Committee Members:
Michelle LaPlaca, PhD (advisor); Facundo Fernández, PhD; Levi Wood, PhD; Susan Margulies, PhD; Edward Botchwey, PhD


Title: Identifying Lipid Biomarkers and Potential Efflux Routes after Mild Traumatic Brain Injury

Abstract:
Traumatic brain injury (TBI) is a heterogenous disease that affects millions of people worldwide. The vast majority of TBI incidences are classified as mild and prevalent in contact sports both recreationally and professionally, and military populations. Current methods to diagnose TBI rely heavily on self-reported criterion, which may lead to misdiagnosis in milder injuries. There is a need for quantitative metric to accurately diagnose TBI. Biomarkers have emerged in last couple of decades and shown strong predictive power in patient outcome, especially in the moderate-to-severe injury phenotypes, but mixed result in milder injuries. Lipids may serve as ideal biomarker of TBI due to the brain’s high lipid content and lipophilic nature of the blood brain barrier. The work presented in this thesis sought to investigate lipidome alterations in the brain and the blood and understand the contribution of the glymphatic system to biomarker efflux. A clinically relevant closed head injury model was used to integrate lipid and cytokine alterations after single and repetitive mTBI (Aim 1). I found a reduction of pro-inflammatory cytokines in the brain that correlated with lipid decrease after repetitive mild TBI and lipid increase after single mild (TB). Compare the lipidome alteration in the brain and blood compartments after single and repetitive mTBI (Aim 2). I identified overlapping lipids in the brain and blood compartments and found greater changes in the serum compared to the brain, identified brain-specific lipids that elevated in the serum, and identified lipid biomarker panels that discriminate between injury and sham control with overlapping pathways. Lastly, I examined the contribution of the glymphatic system on surrogate biomarkers and endogenous biomarker release from the brain to peripheral tissues (Aim 3). I found TBI alters fluid flow, evidence of size dependent flux in the brain, and the elevation of endogenous biomarkers in the nasal tissue compartment.