Accumulation of Bioactive lipids in LPS-induced Neuroinflammation models: MSI Biomarkers


I Berrueta Razo1; H Boutin1; A McMahon1; N Lockyer1P J Hart2
1 University of Manchester, UK;  2 Medicines Discovery Catapult, UK


Mass Spectrometry Imaging (MSI) enables the in-situ identification of a vast array of chemicals that could help develop a better understanding of intricate biological mechanisms and processes. Among these biological processes, the inflammation process is of particular interest due to the complex cascade of immunological and physiological factors occurring during the inflammatory response. 

Here, MSI was applied to the analysis of brain sections from neuroinflammation rat models treated with Lipopolysaccharides (LPS). We aim to identify active lipid species that accumulate during the inflammation process and the possible ion signatures associated with the presence of activated microglia cells. Several N-acyl-phosphatidylethanolamines and fatty acyls were identified within the inflammation region with SIMS and DESI imaging.  Lipid groups such as Acylcarnitines, Lysophosphocholines and Sphingolipids were identified with MALDI-MS. In particular, long-chain carnitines were detected with MALDI-MSI mainly present surrounding the inflammation area. The signal from these specific molecules identified using the MSI techniques were found to be higher within the inflammation regions of the brain treated with LPS and are therefore thought to have the potential to act as biological active lipids during the inflammation processes. 

This study demonstrates that different MSI modalities provide complementary molecular information regarding the neurochemistry associated with inflammation. This in turn may assist in the identification of possible targets for therapeutic intervention and potential biomarkers for use during efficacy studies.

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