Comparing Brain and Blood Lipidome Changes following Single and Repetitive Mild Traumatic Brain Injury in Rats

• Type of Material: Article
• Authors: Alexis N Pulliam, Emory University; Eric C Gier, Georgia Institute of Technology; David A Gaul, Georgia Institute of Technology; Samuel G Moore, Georgia Institute of Technology; Facundo M Fernández, Georgia Institute of Technology; Michelle C LaPlaca, Emory University
• Language: English
• Date: 2024-01-05
• Publisher: ACS Publications
• Publication Version: Final Published Version
• Copyright Statement: © 2024 The Authors. Published by American Chemical Society
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): https://pubs.acs.org/doi/10.1021/acschemneuro.3c00603
• Title of Journal or Parent Work: ACS Chemical Neuroscience
• Volume: 15
• Issue: 2
• Start Page: 300
• End Page: 314
• Grant/Funding Agency: National Science Foundation Graduate Research Fellowship Program; National Institute of Health; Georgia Institute of Technology
• Grant/Funding Information: The authors acknowledge support and technical help from Georgia institute of Technology Mass Spectrometry Core Facility and graphical abstract created with BioRender.com.; This material is based upon work supported by the National Science Foundation Graduate Research Fellowship Program under Grant No. (DGE-2039655: A.N.P.), and the National Institute of Health under Grant No. (T32 GM145735: A.N.P. and R01NS101909).
• Keywords: ultra-high performance mass spectrometry; Traumatic brain injury; lipidomics; blood biomarkers; brain biomarkers
• Subject - Topics: Single vs Repetitive Injury Mechanisms; Biomarker Discovery for mTBI; Lipidomic Alterations in Brain and Serum
• Research Categories: Neurosciences; Analytical chemistry; Systematic biology

Abstract

Traumatic brain injury (TBI) is a major health concern in the United States and globally, contributing to disability and long-term neurological problems. Lipid dysregulation after TBI is underexplored, and a better understanding of lipid turnover and degradation could point to novel biomarker candidates and therapeutic targets. Here, we investigated overlapping lipidome changes in the brain and blood using a data-driven discovery approach to understand lipid alterations in the brain and serum compartments acutely following mild TBI (mTBI) and the potential efflux of brain lipids to peripheral blood. The cortices and sera from male and female Sprague–Dawley rats were analyzed via ultra-high performance liquid chromatography–mass spectrometry (UHPLC-MS) in both positive and negative ion modes following single and repetitive closed head impacts. The overlapping lipids in the data sets were identified with an in-house data dictionary for investigating lipid class changes. MS-based lipid profiling revealed overall increased changes in the serum compartment, while the brain lipids primarily showed decreased changes. Interestingly, there were prominent alterations in the sphingolipid class in the brain and blood compartments after single and repetitive injury, which may suggest efflux of brain sphingolipids into the blood after TBI. Genetic algorithms were used for predictive panel selection to classify injured and control samples with high sensitivity and specificity. These overlapping lipid panels primarily mapped to the glycerophospholipid metabolism pathway with Benjamini–Hochberg adjusted q-values less than 0.05. Collectively, these results detail overlapping lipidome changes following mTBI in the brain and blood compartments, increasing our understanding of TBI-related lipid dysregulation while identifying novel biomarker candidates.