title: Mass spectrometry imaging of biomarker lipids for phagocytosis and signalling during focal cerebral ischaemia.
abstract: Focal cerebral ischaemia has an initial phase of inflammation and tissue injury followed by a later phase of resolution and repair. Mass spectrometry imaging (desorption electrospray ionization and matrix assisted laser desorption ionization) was applied on brain sections from mice 2 h, 24 h, 5d, 7d, and 20d after permanent focal cerebral ischaemia. Within 24 h, N-acyl-phosphatidylethanolamines, lysophosphatidylcholine, and ceramide accumulated, while sphingomyelin disappeared. At the later resolution stages, bis(monoacylglycero)phosphate (BMP(22:6/22:6)), 2-arachidonoyl-glycerol, ceramide-phosphate, sphingosine-1-phosphate, lysophosphatidylserine, and cholesteryl ester appeared. At day 5 to 7, dihydroxy derivates of docosahexaenoic and docosapentaenoic acid, some of which may be pro-resolving mediators, e.g. resolvins, were found in the injured area, and BMP(22:6/22:6) co-localized with the macrophage biomarker CD11b, and probably with cholesteryl ester. Mass spectrometry imaging can visualize spatiotemporal changes in the lipidome during the progression and resolution of focal cerebral inflammation and suggests that BMP(22:6/22:6) and N-acyl-phosphatidylethanolamines can be used as biomarkers for phagocytizing macrophages/microglia cells and dead neurones, respectively.
authors.affiliation: Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
authors.forename: Mette M B
authors.initials: MM
authors.lastname: Nielsen
authors.affiliation: Department of Neurobiology Research, University of Southern Denmark, J. B. Winsløws Vej 21, DK-5000, Odense, Denmark.
authors.forename: Kate L
authors.initials: KL
authors.lastname: Lambertsen
authors.affiliation: Department of Neurobiology Research, University of Southern Denmark, J. B. Winsløws Vej 21, DK-5000, Odense, Denmark.
authors.forename: Bettina H
authors.initials: BH
authors.lastname: Clausen
authors.affiliation: Department of Neurobiology Research, University of Southern Denmark, J. B. Winsløws Vej 21, DK-5000, Odense, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Meyer
authors.affiliation: Institute of Inorganic and Analytical Chemistry, Justus Liebig University, Heinrich-Buff-Ring 17, D-35392, Giessen, Germany.
authors.forename: Dhaka R
authors.initials: DR
authors.lastname: Bhandari
authors.affiliation: National Research Centre for the Working Environment, Lersø Parkallé 105, DK-2100, Copenhagen, Denmark.
authors.forename: Søren T
authors.initials: ST
authors.lastname: Larsen
authors.affiliation: Department of Biomedical Sciences, University of Copenhagen, Blegdamsvej 3, DK-2200, Copenhagen, Denmark.
authors.forename: Steen S
authors.initials: SS
authors.lastname: Poulsen
authors.affiliation: Institute of Inorganic and Analytical Chemistry, Justus Liebig University, Heinrich-Buff-Ring 17, D-35392, Giessen, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Spengler
authors.affiliation: Department of Pharmacy, University of Copenhagen, Universitetsparken 2, DK-2100, Copenhagen, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Janfelt
authors.affiliation: Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
authors.forename: Harald S
authors.initials: HS
authors.lastname: Hansen
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000737:chemistry; D015415:Biomarkers / Q000737:chemistry*; D002545:Brain Ischemia / Q000000981:diagnostic imaging* / Q000378:metabolism*; D039481:CD11b Antigen / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000737:chemistry; D004789:Enzyme Activation; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism; D007249:Inflammation; D008055:Lipids / Q000737:chemistry; D008264:Macrophages / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D010587:Phagocytosis; D010740:Phospholipases / Q000737:chemistry; D015398:Signal Transduction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D015415:Biomarkers; D039481:CD11b Antigen; D008055:Lipids; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D010740:Phospholipases