Plasma Lipid Metabolism is altered in Acute Mild Traumatic Brain Injury

Abstract

Background and ObjectivesLipids are the source of signaling and inflammatory molecules that may contribute to trauma pathology. Accordingly, we examined levels of lipid species and a lipolytic enzyme activity in a one‐month longitudinal study of acute mild traumatic brain injury (mTBI).MethodsWe recruited mTBI patients (n=21) and non‐head trauma controls (CT, n=9), aged 18–50 years from the emergency department of the Huntington Memorial Hospital (Pasadena, CA). Symptom progression was observed within days of injury (W1), and four weeks thereafter (W4). Plasma lipids collected at W1 and W4 were extracted and unesterified (UFA) and esterified fatty acids (EFA) quantified using negative ion/chemical ionization gas chromatography/mass spectrometry. Plasma glycerophospholipids (GP) and sphingolipids (SP) were analyzed using liquid chromatography‐tandem mass spectrometry. Plasma phospholipase A2 (PLA2) activity was determined using a fluorescence‐based activity assay.ResultsmTBI participants' plasma at W1 had higher levels of 24 UFA species that included seven saturated fatty acids (SAFA), seven monounsaturated fatty acids (MUFA), four omega‐3, and six omega‐6 polyunsaturated fatty acids (PUFA). The sum of all SAFAs, MUFAs, omega‐3 PUFAs, omega‐6 PUFAs, and PUFAs were higher in mTBI plasma at W1. For EFA at W1, two omega‐6 (homo‐g‐C20:3n‐6, C22:4n‐6), one omega‐3 (C20:5n‐3), the sum of omega‐3 PUFAs, and the omega‐3 to omega‐6 ratios (omega‐3 index) were lower in mTBI than in CT. At W4, esterified C19:0 and C22:3n‐3 levels were lower while C24:1 was higher in mTBI compared with CT. The UFA to EFA ratio that estimates endogenous lipolysis of fatty acids was higher in mTBI than CT for three SAFAs, two MUFAs, two omega‐6, two omega‐3, and the ratio of the sum of UFAs to the sum EFAs. Calcium‐dependent PLA2 activity was higher in mTBI plasma at W1 but not at W4. mTBI PLA2 activity at W1 positively correlated with most UFA species except C18:2n‐6 and C18:3n‐6 but correlated only with two UFA (C20:1, C22:1) in CT. PLA2 activity negatively correlated with seven EFA species.ConclusionsOur data showing higher UFA, UFA to EFA ratios, and correlation of UFA with PLA2 indicate excessive lipolysis in early mTBI. A lower omega‐3 index suggests the excessive oxidative breakdown of omega‐3 in mTBI. We propose that early intervention using strategies that reduce lipolysis may attenuate tissue damage linked to mTBI. Additionally, measurements of fatty acid fluctuations may be useful in discovering new therapies and monitoring resolution of mTBI.Support or Funding InformationFinancial support provided by the D.O.D. grant W81XWH‐13‐1‐0005. Thao Tran, David Strickland, Betty Chung, Darlene Royal, and David Buennagel assisted with data collection and patient recruitment.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.