CpG preconditioning reduces accumulation of lysophosphatidylcholine in ischemic brain tissue after middle cerebral artery occlusion

Mavroudakis, Leonidas; Stevens, Susan L.; Duncan, Kyle D.; Stenzel-Poore, Mary P.; Laskin, Julia; Lanekoff, Ingela

doi:10.1007/s00216-020-02987-w

CpG preconditioning reduces accumulation of lysophosphatidylcholine in ischemic brain tissue after middle cerebral artery occlusion

Journal Article · Mon Oct 19 00:00:00 EDT 2020 · Analytical and Bioanalytical Chemistry

DOI:https://doi.org/10.1007/s00216-020-02987-w· OSTI ID:1815711

Mavroudakis, Leonidas ^[1]; Stevens, Susan L. ^[2]; Duncan, Kyle D. ^[3]; Stenzel-Poore, Mary P. ^[2]; Laskin, Julia ^[4]; ^[3]

Uppsala Univ. (Sweden). Dept. of Chemistry; OSTI
Oregon Health & Science Univ., Portland, OR (United States). Dept. of Molecular Microbiology & Immunology
Uppsala Univ. (Sweden). Dept. of Chemistry
Pacific Northwest National Lab. (PNNL), Richland, WA (United States). Physical Sciences Division; Purdue Univ., West Lafayette, IN (United States). Dept. of Chemistry

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.

View Accepted Manuscript (DOE)

Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division

Grant/Contract Number:: AC05-76RL01830

OSTI ID:: 1815711

Journal Information:: Analytical and Bioanalytical Chemistry, Journal Name: Analytical and Bioanalytical Chemistry Journal Issue: 10 Vol. 413; ISSN 1618-2642

Publisher:: SpringerCopyright Statement

Country of Publication:: United States

Language:: English

References (50)

Imaging mass spectrometry McDonnell, Liam A.; Heeren, Ron M. A. Mass Spectrometry Reviews, Vol. 26, Issue 4 https://doi.org/10.1002/mas.20124	journal	January 2007
Direct profiling of phospholipids and lysophospholipids in rat brain sections after ischemic stroke: Profiling of lipids in in rat brain after ischemic stroke Wang, Hay-Yan J.; Liu, Cheng Bin; Wu, Hsuan-Wen Rapid Communications in Mass Spectrometry, Vol. 24, Issue 14 https://doi.org/10.1002/rcm.4620	journal	June 2010
MALDI-mass spectrometry imaging of desalted rat brain sections reveals ischemia-mediated changes of lipids Wang, Hay-Yan J.; Wu, Hsuan-Wen; Tsai, Ping-Ju Analytical and Bioanalytical Chemistry, Vol. 404, Issue 1 https://doi.org/10.1007/s00216-012-6077-5	journal	May 2012
Ischemic stroke: experimental models and reality Sommer, Clemens J. Acta Neuropathologica, Vol. 133, Issue 2 https://doi.org/10.1007/s00401-017-1667-0	journal	January 2017
Membrane breakdown in acute and chronic neurodegeneration: focus on choline-containing phospholipids Klein, J. Journal of Neural Transmission, Vol. 107, Issue 8-9 https://doi.org/10.1007/s007020070051	journal	August 2000
Integrated MALDI-MS imaging and LC–MS techniques for visualizing spatiotemporal metabolomic dynamics in a rat stroke model Irie, Miho; Fujimura, Yoshinori; Yamato, Mayumi Metabolomics, Vol. 10, Issue 3 https://doi.org/10.1007/s11306-013-0588-8	journal	October 2013
Metabolomics facilitates the discovery of metabolic biomarkers and pathways for ischemic stroke: a systematic review Ke, Chaofu; Pan, Chen-Wei; Zhang, Yuxia Metabolomics, Vol. 15, Issue 12 https://doi.org/10.1007/s11306-019-1615-1	journal	November 2019
Preclinical Development of a Prophylactic Neuroprotective Therapy for the Preventive Treatment of Anticipated Ischemia-Reperfusion Injury Bahjat, Frances Rena; Alexander West, G.; Kohama, Steven G. Translational Stroke Research, Vol. 8, Issue 4 https://doi.org/10.1007/s12975-017-0532-8	journal	April 2017
MALDI Mass Spectrometric Imaging of Lipids in Rat Brain Injury Models Hankin, Joseph A.; Farias, Santiago E.; Barkley, Robert M. Journal of The American Society for Mass Spectrometry, Vol. 22, Issue 6 https://doi.org/10.1007/s13361-011-0122-z	journal	April 2011
Towards High-Resolution Tissue Imaging Using Nanospray Desorption Electrospray Ionization Mass Spectrometry Coupled to Shear Force Microscopy Nguyen, Son N.; Sontag, Ryan L.; Carson, James P. Journal of The American Society for Mass Spectrometry, Vol. 29, Issue 2 https://doi.org/10.1007/s13361-017-1750-8	journal	July 2017
Positional distribution and turnover of fatty acids in phosphatidic acid, phosphoinositides, phosphatidylcholine and phosphatidylethanolamine in rat brain in vivo Baker, R. R.; Thompson, W. Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, Vol. 270, Issue 4 https://doi.org/10.1016/0005-2760(72)90114-2	journal	August 1972
Mechanisms of ischemic brain damage Doyle, Kristian P.; Simon, Roger P.; Stenzel-Poore, Mary P. Neuropharmacology, Vol. 55, Issue 3 https://doi.org/10.1016/J.NEUROPHARM.2008.01.005	journal	September 2008
Positional distribution of fatty acids in glycerophosphatides of bovine gray matter Yabuuchi, Hyakuji; O'Brien, John S. Journal of Lipid Research, Vol. 9, Issue 1 https://doi.org/10.1016/S0022-2275(20)43144-X	journal	January 1968
Quantification of low molecular weight compounds by MALDI imaging mass spectrometry – A tutorial review Rzagalinski, Ignacy; Volmer, Dietrich A. Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Vol. 1865, Issue 7 https://doi.org/10.1016/j.bbapap.2016.12.011	journal	July 2017
Toll-like receptor signaling in endogenous neuroprotection and stroke Marsh, B. J.; Williams-Karnesky, R. L.; Stenzel-Poore, M. P. Neuroscience, Vol. 158, Issue 3 https://doi.org/10.1016/j.neuroscience.2008.07.067	journal	February 2009
Imaging mass spectrometry revealed the production of lyso-phosphatidylcholine in the injured ischemic rat brain Koizumi, S.; Yamamoto, S.; Hayasaka, T. Neuroscience, Vol. 168, Issue 1 https://doi.org/10.1016/j.neuroscience.2010.03.056	journal	June 2010
Preconditioning in neuroprotection: From hypoxia to ischemia Li, Sijie; Hafeez, Adam; Noorulla, Fatima Progress in Neurobiology, Vol. 157 https://doi.org/10.1016/j.pneurobio.2017.01.001	journal	October 2017
Recent advances in ambient mass spectrometry imaging Xue, Jinjuan; Bai, Yu; Liu, Huwei TrAC Trends in Analytical Chemistry, Vol. 120 https://doi.org/10.1016/j.trac.2019.115659	journal	November 2019
Ultrahighly Sensitive in Situ Metabolomic Imaging for Visualizing Spatiotemporal Metabolic Behaviors Miura, Daisuke; Fujimura, Yoshinori; Yamato, Mayumi Analytical Chemistry, Vol. 82, Issue 23 https://doi.org/10.1021/ac101998z	journal	November 2010
Robust Data Processing and Normalization Strategy for MALDI Mass Spectrometric Imaging Fonville, Judith M.; Carter, Claire; Cloarec, Olivier Analytical Chemistry, Vol. 84, Issue 3 https://doi.org/10.1021/ac201767g	journal	January 2012
Tissue Imaging Using Nanospray Desorption Electrospray Ionization Mass Spectrometry Laskin, Julia; Heath, Brandi S.; Roach, Patrick J. Analytical Chemistry, Vol. 84, Issue 1 https://doi.org/10.1021/ac2021322	journal	December 2011
Automated Platform for High-Resolution Tissue Imaging Using Nanospray Desorption Electrospray Ionization Mass Spectrometry Lanekoff, Ingela; Heath, Brandi S.; Liyu, Andrey Analytical Chemistry, Vol. 84, Issue 19 https://doi.org/10.1021/ac301909a	journal	September 2012
Imaging Nicotine in Rat Brain Tissue by Use of Nanospray Desorption Electrospray Ionization Mass Spectrometry Lanekoff, Ingela; Thomas, Mathew; Carson, James P. Analytical Chemistry, Vol. 85, Issue 2 https://doi.org/10.1021/ac302308p	journal	December 2012
High-Speed Tandem Mass Spectrometric in Situ Imaging by Nanospray Desorption Electrospray Ionization Mass Spectrometry Lanekoff, Ingela; Burnum-Johnson, Kristin; Thomas, Mathew Analytical Chemistry, Vol. 85, Issue 20 https://doi.org/10.1021/ac401760s	journal	September 2013
Shotgun Approach for Quantitative Imaging of Phospholipids Using Nanospray Desorption Electrospray Ionization Mass Spectrometry Lanekoff, Ingela; Thomas, Mathew; Laskin, Julia Analytical Chemistry, Vol. 86, Issue 3 https://doi.org/10.1021/ac403931r	journal	January 2014
1,5-Diaminonaphthalene Hydrochloride Assisted Laser Desorption/Ionization Mass Spectrometry Imaging of Small Molecules in Tissues Following Focal Cerebral Ischemia Liu, Huihui; Chen, Rui; Wang, Jiyun Analytical Chemistry, Vol. 86, Issue 20 https://doi.org/10.1021/ac5034566	journal	October 2014
High Spatial Resolution Imaging of Mouse Pancreatic Islets Using Nanospray Desorption Electrospray Ionization Mass Spectrometry Yin, Ruichuan; Kyle, Jennifer; Burnum-Johnson, Kristin Analytical Chemistry, Vol. 90, Issue 11 https://doi.org/10.1021/acs.analchem.8b00161	journal	April 2018
Quantitative Mass Spectrometry Imaging of Prostaglandins as Silver Ion Adducts with Nanospray Desorption Electrospray Ionization Duncan, Kyle D.; Fang, Ru; Yuan, Jia Analytical Chemistry, Vol. 90, Issue 12 https://doi.org/10.1021/acs.analchem.8b00350	journal	April 2018
Lipid Coverage in Nanospray Desorption Electrospray Ionization Mass Spectrometry Imaging of Mouse Lung Tissues Nguyen, Son N.; Kyle, Jennifer E.; Dautel, Sydney E. Analytical Chemistry, Vol. 91, Issue 18 https://doi.org/10.1021/acs.analchem.9b02045	journal	August 2019
Proof of Concept: Pharmacological Preconditioning with a Toll-like Receptor Agonist Protects against Cerebrovascular Injury in a Primate Model of Stroke Bahjat, Frances Rena; Williams-Karnesky, Rebecca L.; Kohama, Steven G. Journal of Cerebral Blood Flow & Metabolism, Vol. 31, Issue 5 https://doi.org/10.1038/jcbfm.2011.6	journal	December 2010
High spatial resolution imaging of biological tissues using nanospray desorption electrospray ionization mass spectrometry Yin, Ruichuan; Burnum-Johnson, Kristin E.; Sun, Xiaofei Nature Protocols, Vol. 14, Issue 12 https://doi.org/10.1038/s41596-019-0237-4	journal	November 2019
Distinguishing core from penumbra by lipid profiles using Mass Spectrometry Imaging in a transgenic mouse model of ischemic stroke Mulder, I. A.; Ogrinc Potočnik, N.; Broos, L. A. M. Scientific Reports, Vol. 9, Issue 1 https://doi.org/10.1038/s41598-018-37612-5	journal	January 2019
Toll-Like Receptor 9: A New Target of Ischemic Preconditioning in the Brain Stevens, Susan L.; Ciesielski, Thomas MP; Marsh, Brenda J. Journal of Cerebral Blood Flow & Metabolism, Vol. 28, Issue 5 https://doi.org/10.1038/sj.jcbfm.9600606	journal	January 2008
Nanospray desorption electrospray ionization: an ambient method for liquid-extraction surface sampling in mass spectrometry Roach, Patrick J.; Laskin, Julia; Laskin, Alexander The Analyst, Vol. 135, Issue 9 https://doi.org/10.1039/c0an00312c	journal	January 2010
Spatially resolved analysis of glycolipids and metabolites in living Synechococcus sp. PCC 7002 using nanospray desorption electrospray ionization Lanekoff, Ingela; Geydebrekht, Oleg; Pinchuk, Grigoriy E. The Analyst, Vol. 138, Issue 7 https://doi.org/10.1039/c3an36716a	journal	January 2013
Matrix effects in biological mass spectrometry imaging: identification and compensation Lanekoff, Ingela; Stevens, Susan L.; Stenzel-Poore, Mary P. The Analyst, Vol. 139, Issue 14 https://doi.org/10.1039/c4an00504j	journal	January 2014
Quantitative mass spectrometry imaging of small-molecule neurotransmitters in rat brain tissue sections using nanospray desorption electrospray ionization Bergman, Hilde-Marléne; Lundin, Erik; Andersson, Malin The Analyst, Vol. 141, Issue 12 https://doi.org/10.1039/c5an02620b	journal	January 2016
Profiling and quantifying endogenous molecules in single cells using nano-DESI MS Bergman, Hilde-Marléne; Lanekoff, Ingela The Analyst, Vol. 142, Issue 19 https://doi.org/10.1039/c7an00885f	journal	January 2017
ProteoWizard: open source software for rapid proteomics tools development Kessner, Darren; Chambers, Matt; Burke, Robert Bioinformatics, Vol. 24, Issue 21 https://doi.org/10.1093/bioinformatics/btn323	journal	July 2008
Visualization by mass spectrometry of 2‐dimensional changes in rat brain lipids, including N ‐acylphosphatidylethanolamines, during neonatal brain ischemia Janfelt, Christian; Wellner, Niels; Leger, Pierre‐Louis The FASEB Journal, Vol. 26, Issue 6 https://doi.org/10.1096/fj.11-201152	journal	March 2012
Middle Cerebral Artery Occlusion Model in Rodents: Methods and Potential Pitfalls Liu, Fudong; McCullough, Louise D. Journal of Biomedicine and Biotechnology, Vol. 2011 https://doi.org/10.1155/2011/464701	journal	January 2011
Regional brain calcium changes in the rat middle cerebral artery occlusion model of ischemia. Rappaport, Z. H.; Young, W.; Flamm, E. S. Stroke, Vol. 18, Issue 4 https://doi.org/10.1161/01.STR.18.4.760	journal	July 1987
Degradation of phospholipid molecular species during experimental cerebral ischemia in rats. Goto, Y.; Okamoto, S.; Yonekawa, Y. Stroke, Vol. 19, Issue 6 https://doi.org/10.1161/01.STR.19.6.728	journal	June 1988
Heart Disease and Stroke Statistics—2020 Update: A Report From the American Heart Association Virani, Salim S.; Alonso, Alvaro; Benjamin, Emelia J. Circulation, Vol. 141, Issue 9 https://doi.org/10.1161/CIR.0000000000000757	journal	March 2020
Inflammation and the Emerging Role of the Toll-Like Receptor System in Acute Brain Ischemia Marsh, B. J.; Stevens, S. L.; Hunter, B. Stroke, Vol. 40, Issue 3, Supplement 1 https://doi.org/10.1161/STROKEAHA.108.534917	journal	December 2008
Remote Ischemic Preconditioning for Cerebral and Cardiac Protection During Carotid Endarterectomy: Results From a Pilot Randomized Clinical Trial Walsh, Stewart R.; Nouraei, S. A.; Tang, Tjun Y. Vascular and Endovascular Surgery, Vol. 44, Issue 6 https://doi.org/10.1177/1538574410369709	journal	May 2010
Global changes in phospholipids identified by MALDI MS in rats with focal cerebral ischemia Shanta, Selina Rahman; Choi, Chang Soon; Lee, Jeong Hwa Journal of Lipid Research, Vol. 53, Issue 9 https://doi.org/10.1194/jlr.M022558	journal	September 2012
A simple desalting method for direct MALDI mass spectrometry profiling of tissue lipids Wang, Hay-Yan J.; Liu, Cheng Bin; Wu, Hsuan-Wen Journal of Lipid Research, Vol. 52, Issue 4 https://doi.org/10.1194/jlr.d013060	journal	April 2011
The Role of Phospholipases, Cyclooxygenases, and Lipoxygenases in Cerebral Ischemic/Traumatic Injuries Phillis, John W.; O'Regan, Michael H. Critical Reviews in Neurobiology, Vol. 15, Issue 1 https://doi.org/10.1615/CritRevNeurobiol.v15.i1.30	journal	January 2003
Imaging of Stroke: Part 2, Pathophysiology at the Molecular and Cellular Levels and Corresponding Imaging Changes Kanekar, Sangam G.; Zacharia, Thomas; Roller, Rebecca American Journal of Roentgenology, Vol. 198, Issue 1 https://doi.org/10.2214/AJR.10.7312	journal	January 2012

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Nano-DESI
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
59 BASIC BIOLOGICAL SCIENCES
CpG preconditioning
Ischemia
Lysophosphatidylcholine
Mass spectrometry imaging
Phosphatidylcholine

CpG preconditioning reduces accumulation of lysophosphatidylcholine in ischemic brain tissue after middle cerebral artery occlusion

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References (50)

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