Discovery of Lipidome Alterations Following Traumatic Brain Injury via High-Resolution Metabolomics.

Published

Journal Article

Traumatic brain injury (TBI) can occur across wide segments of the population, presenting in a heterogeneous manner that makes diagnosis inconsistent and management challenging. Biomarkers offer the potential to objectively identify injury status, severity, and phenotype by measuring the relative concentrations of endogenous molecules in readily accessible biofluids. Through a data-driven, discovery approach, novel biomarker candidates for TBI were identified in the serum lipidome of adult male Sprague-Dawley rats in the first week following moderate controlled cortical impact (CCI). Serum samples were analyzed in positive and negative modes by ultraperformance liquid chromatography-mass spectrometry (UPLC-MS). A predictive panel for the classification of injured and uninjured sera samples, consisting of 26 dysregulated species belonging to a variety of lipid classes, was developed with a cross-validated accuracy of 85.3% using omniClassifier software to optimize feature selection. Polyunsaturated fatty acids (PUFAs) and PUFA-containing diacylglycerols were found to be upregulated in sera from injured rats, while changes in sphingolipids and other membrane phospholipids were also observed, many of which map to known secondary injury pathways. Overall, the identified biomarker panel offers viable molecular candidates representing lipids that may readily cross the blood-brain barrier (BBB) and aid in the understanding of TBI pathophysiology.

Full Text

Duke Authors

Cited Authors

  • Hogan, SR; Phan, JH; Alvarado-Velez, M; Wang, MD; Bellamkonda, RV; Fernández, FM; LaPlaca, MC

Published Date

  • June 2018

Published In

Volume / Issue

  • 17 / 6

Start / End Page

  • 2131 - 2143

PubMed ID

  • 29671324

Pubmed Central ID

  • 29671324

Electronic International Standard Serial Number (EISSN)

  • 1535-3907

International Standard Serial Number (ISSN)

  • 1535-3893

Digital Object Identifier (DOI)

  • 10.1021/acs.jproteome.8b00068

Language

  • eng