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

Area of Science:

• Neuroscience
• Biochemistry
• Biomarker Discovery

Background:

• Traumatic brain injury (TBI) presents heterogeneous symptoms, complicating diagnosis and management.
• Biomarkers in biofluids offer objective assessment of TBI status, severity, and phenotype.

Purpose of the Study:

• To identify novel serum lipid biomarker candidates for TBI using a data-driven discovery approach.
• To develop a predictive panel for classifying injured and uninjured samples.

Main Methods:

• Serum samples from adult male Sprague-Dawley rats post-controlled cortical impact (CCI) were analyzed using ultra-high-performance liquid chromatography-mass spectrometry (UPLC-MS).
• OmniClassifier software was employed for feature selection to build a predictive panel.
• Analysis included both positive and negative ion modes.

Main Results:

• A panel of 26 dysregulated lipid species was identified, achieving 85.3% cross-validated accuracy in classifying injured versus uninjured samples.
• Upregulation of polyunsaturated fatty acids (PUFAs) and PUFA-containing diacylglycerols was observed in injured rats.
• Alterations in sphingolipids and membrane phospholipids, potentially linked to secondary injury pathways, were also noted.

Conclusions:

• The identified serum lipid panel shows potential as objective biomarkers for TBI.
• These lipid candidates may cross the blood-brain barrier (BBB) and contribute to understanding TBI pathophysiology.
• This discovery aids in developing more consistent TBI diagnosis and management strategies.