CpG preconditioning reduces accumulation of lysophosphatidylcholine in ischemic brain tissue after middle cerebral arter
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RESEARCH PAPER
CpG preconditioning reduces accumulation of lysophosphatidylcholine in ischemic brain tissue after middle cerebral artery occlusion Leonidas Mavroudakis 1 & Susan L. Stevens 2 & Kyle D. Duncan 1 & Mary P. Stenzel-Poore 2 & Julia Laskin 3,4 & Ingela Lanekoff 1 Received: 3 July 2020 / Revised: 8 September 2020 / Accepted: 5 October 2020 # The Author(s) 2020
Abstract Ischemic stroke is one of the major causes of death and permanent disability in the world. However, the molecular mechanisms surrounding tissue damage are complex and further studies are needed to gain insights necessary for development of treatment. Prophylactic treatment by administration of cytosine-guanine (CpG) oligodeoxynucleotides has been shown to provide neuroprotection against anticipated ischemic injury. CpG binds to Toll-like receptor 9 (TLR9) causing initialization of an inflammatory response that limits visible ischemic damages upon subsequent stroke. Here, we use nanospray desorption electrospray ionization (nano-DESI) mass spectrometry imaging (MSI) to characterize molecular effects of CpG preconditioning prior to middle cerebral artery occlusion (MCAO) and reperfusion. By doping the nano-DESI solvent with appropriate internal standards, we can study and compare distributions of phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) in the ischemic hemisphere of the brain despite the large changes in alkali metal abundances. Our results show that CpG preconditioning not only reduces the infarct size but it also decreases the degradation of PC and accumulation of LPC species, which indicates reduced cell membrane breakdown and overall ischemic damage. Our findings show that molecular mechanisms of PC degradation are intact despite CpG preconditioning but that these are limited due to the initialized inflammatory response. Keywords Ischemia . CpG preconditioning . Mass spectrometry imaging . Lysophosphatidylcholine . Phosphatidylcholine . Nano-DESI
Introduction Published in the topical collection Mass Spectrometry Imaging 2.0 with guest editors Shane R. Ellis and Tiffany Siegel Porta. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00216-020-02987-w) contains supplementary material, which is available to authorized users. * Ingela Lanekoff [email protected] 1
Department of Chemistry – BMC, Uppsala University, 75123 Uppsala, Sweden
2
Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, OR 97239, USA
3
Physical Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA
4
Department of Chemistry, Purdue University, West Lafayette, IN 47907, USA
Stroke is the fifth leading cause of death in the USA, with a death occurring on average every 3 min 35 s [1]. Ischemic stroke, accounting for 87% of all strokes, occurs after the obstruction of blood vessels supplying blood to a region of the brain. During ischemic stroke, oxygen and nutrients, such as glucose, cannot reach the brain cells in this regio
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