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

Title: 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. ^[1]; Stenzel-Poore, Mary P. ^[2]; Laskin, Julia ^[3];

^[1]

Uppsala Univ. (Sweden). Dept. of Chemistry
Oregon Health & Science Univ., Portland, OR (United States). Dept. of Molecular Microbiology & Immunology
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.

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Research Organization:: Pacific Northwest National Lab. (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, Vol. 413, Issue 10; ISSN 1618-2642

Publisher:: SpringerCopyright Statement

Country of Publication:: United States

Language:: English

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Related Subjects

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

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

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