Mass‐spectrometry based oxidative lipidomics and lipid imaging: applications in traumatic brain injury

Abstract

Lipids, particularly phospholipids, are fundamental to central nervous system (CNS) tissue architecture and function. Endogenous polyunsaturated fatty acid chains of phospholipids possess cis-double bonds each separated by one methylene group. These phospholipids are very susceptible to free-radical attack and oxidative modifications. A combination of analytical methods including different versions of chromatography and mass spectrometry allows obtaining detailed information on the content and distribution of lipids and their oxidation products thus constituting the newly emerging field of oxidative lipidomics. It is becoming evident that specific oxidative modifications of lipids are critical to a number of cellular functions, disease states and responses to oxidative stresses. Oxidative lipidomics is beginning to provide new mechanistic insights into traumatic brain injury (TBI) which may have significant translational potential for development of therapies in acute CNS insults. In particular, selective oxidation of a mitochondria-specific phospholipid, cardiolipin, has been associated with the initiation and progression of apoptosis in injured neurons thus indicating new drug discovery targets. Further, imaging mass-spectrometry represents an exciting new opportunity for correlating maps of lipid profiles and their oxidation products with structure and neuropathology. This review is focused on these most recent advancements in the field of lipidomics and oxidative lipidomics based on the applications of mass-spectrometry and imaging mass-spectrometry as they relate to studies of phospholipids in TBI.

Alterations in phospholipidomic profile in the brain of mouse model of depression induced by chronic unpredictable stress

“…ROS formation occurs preferentially in mitochondria, and therefore it is accepted that CL is more susceptible to oxidation than other phospholipids. Moreover, because of the structural diversity of CL in brain, detecting hydroperoxide species of CL by MS is challenging, since CL oxidized species are likely to be overlap the natural brain CL species (Sparvero et al, 2010). In addition to the observed oxidation of CL, we also reported a decrease in the total content of CL after chronic unpredictable stress, which might be implicated in a decline of mitochondrial respiratory functions and ROS accumulation.…”

“…Lipid hydroperoxides are the primary products of lipid oxidation and have been used in several studies to evaluate the oxidation status of cells and/or tissues (Tyurin et al, 2008, Sparvero et al, 2010.…”

Oxidative Lipidomics Coming of Age: Advances in Analysis of Oxidized Phospholipids in Physiology and Pathology

“…MALDI imaging appears to work particularly well for easily ionized lipids (PC, PE) as well as for other metabolites or peptides (88), and studies on the lipid content of a number of animal tissues have been reported, especially in the brain and liver, which have a high lipid content; this has been comprehensively reviewed recently (35,36). As yet, very few studies in which oxidized lipids were detected have been reported (114), but Stutts et al have used sophisticated MS n methodology to image truncated carboxylate-containing PCs in rat spinal cord and show they were mainly localized to the gray matter (Fig. 11) (124), and the analysis of oxidized lipids in traumatic brain injury has been recently reviewed (114).…”

Circadian Time Structure of Circulating Plasma Lipid Components in Healthy Indians of Different Age Groups

“…Lipid metabolites are therefore considered potential biomarker candidates for disease diagnosis and drug responses. Indeed, recent lipidomic studies have shown that lipid metabolites such as eicosanoids and sphingolipids are biomarker candidates for cardiovascular events [1], traumatic brain injury [13], Alzheimer's disease [3,14], type 2 diabetes [15] and depression [16]. Blood is a commonly used biofluid for biomarker discovery because it is a ''data-rich'' source containing several thousands of hydrophilic and hydrophobic metabolites that likely reflect many complex biological processes in the body [17].…”