Metabolomic analysis and mass spectrometry imaging after neonatal stroke and cell therapies in mouse brains

Abstract Ischemic brain injury provokes complex, time-dependent downstream pathways that ultimately lead to cell death. We aimed to demonstrate the levels of a wide range of metabolites in brain lysates and their on-tissue distribution following neonatal stroke and cell therapies. Postnatal day 12 m...

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Autores principales:	Emi Tanaka, Yuko Ogawa, Ritsuko Fujii, Tomomi Shimonaka, Yoshiaki Sato, Takashi Hamazaki, Tokiko Nagamura-Inoue, Haruo Shintaku, Masahiro Tsuji
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/642301be6d594791aaff0e5f015b232c
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spelling	oai:doaj.org-article:642301be6d594791aaff0e5f015b232c2021-12-02T12:42:19ZMetabolomic analysis and mass spectrometry imaging after neonatal stroke and cell therapies in mouse brains10.1038/s41598-020-78930-x2045-2322https://doaj.org/article/642301be6d594791aaff0e5f015b232c2020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78930-xhttps://doaj.org/toc/2045-2322Abstract Ischemic brain injury provokes complex, time-dependent downstream pathways that ultimately lead to cell death. We aimed to demonstrate the levels of a wide range of metabolites in brain lysates and their on-tissue distribution following neonatal stroke and cell therapies. Postnatal day 12 mice underwent middle cerebral artery occlusion (MCAO) and were administered 1 × 105 cells after 48 h. Metabolomic analysis of the injured hemisphere demonstrated that a variety of amino acids were significantly increased and that tricarboxylic acid cycle intermediates and some related amino acids, such as glutamate, were decreased. With the exception of the changes in citric acid, neither mesenchymal stem/stromal cells nor CD34+ cells ameliorated these changes. On-tissue visualization with matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) imaging revealed that the signal intensity of glutamate was significantly decreased in the infarct area, consistent with the metabolomic analysis, while its intensity was significantly increased in the peri-infarct area after MCAO. Although cell therapies did not ameliorate the changes in metabolites in the infarct area, mesenchymal stem cells ameliorated the increased levels of glutamate and carnitine in the peri-infarct area. MALDI-MS imaging showed the location-specific effect of cell therapies even in this subacute setting after MCAO. These methodologies may be useful for further investigation of possible treatments for ischemic brain injury.Emi TanakaYuko OgawaRitsuko FujiiTomomi ShimonakaYoshiaki SatoTakashi HamazakiTokiko Nagamura-InoueHaruo ShintakuMasahiro TsujiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-12 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Emi Tanaka Yuko Ogawa Ritsuko Fujii Tomomi Shimonaka Yoshiaki Sato Takashi Hamazaki Tokiko Nagamura-Inoue Haruo Shintaku Masahiro Tsuji Metabolomic analysis and mass spectrometry imaging after neonatal stroke and cell therapies in mouse brains
description	Abstract Ischemic brain injury provokes complex, time-dependent downstream pathways that ultimately lead to cell death. We aimed to demonstrate the levels of a wide range of metabolites in brain lysates and their on-tissue distribution following neonatal stroke and cell therapies. Postnatal day 12 mice underwent middle cerebral artery occlusion (MCAO) and were administered 1 × 105 cells after 48 h. Metabolomic analysis of the injured hemisphere demonstrated that a variety of amino acids were significantly increased and that tricarboxylic acid cycle intermediates and some related amino acids, such as glutamate, were decreased. With the exception of the changes in citric acid, neither mesenchymal stem/stromal cells nor CD34+ cells ameliorated these changes. On-tissue visualization with matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) imaging revealed that the signal intensity of glutamate was significantly decreased in the infarct area, consistent with the metabolomic analysis, while its intensity was significantly increased in the peri-infarct area after MCAO. Although cell therapies did not ameliorate the changes in metabolites in the infarct area, mesenchymal stem cells ameliorated the increased levels of glutamate and carnitine in the peri-infarct area. MALDI-MS imaging showed the location-specific effect of cell therapies even in this subacute setting after MCAO. These methodologies may be useful for further investigation of possible treatments for ischemic brain injury.
format	article
author	Emi Tanaka Yuko Ogawa Ritsuko Fujii Tomomi Shimonaka Yoshiaki Sato Takashi Hamazaki Tokiko Nagamura-Inoue Haruo Shintaku Masahiro Tsuji
author_facet	Emi Tanaka Yuko Ogawa Ritsuko Fujii Tomomi Shimonaka Yoshiaki Sato Takashi Hamazaki Tokiko Nagamura-Inoue Haruo Shintaku Masahiro Tsuji
author_sort	Emi Tanaka
title	Metabolomic analysis and mass spectrometry imaging after neonatal stroke and cell therapies in mouse brains
title_short	Metabolomic analysis and mass spectrometry imaging after neonatal stroke and cell therapies in mouse brains
title_full	Metabolomic analysis and mass spectrometry imaging after neonatal stroke and cell therapies in mouse brains
title_fullStr	Metabolomic analysis and mass spectrometry imaging after neonatal stroke and cell therapies in mouse brains
title_full_unstemmed	Metabolomic analysis and mass spectrometry imaging after neonatal stroke and cell therapies in mouse brains
title_sort	metabolomic analysis and mass spectrometry imaging after neonatal stroke and cell therapies in mouse brains
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/642301be6d594791aaff0e5f015b232c
work_keys_str_mv	AT emitanaka metabolomicanalysisandmassspectrometryimagingafterneonatalstrokeandcelltherapiesinmousebrains AT yukoogawa metabolomicanalysisandmassspectrometryimagingafterneonatalstrokeandcelltherapiesinmousebrains AT ritsukofujii metabolomicanalysisandmassspectrometryimagingafterneonatalstrokeandcelltherapiesinmousebrains AT tomomishimonaka metabolomicanalysisandmassspectrometryimagingafterneonatalstrokeandcelltherapiesinmousebrains AT yoshiakisato metabolomicanalysisandmassspectrometryimagingafterneonatalstrokeandcelltherapiesinmousebrains AT takashihamazaki metabolomicanalysisandmassspectrometryimagingafterneonatalstrokeandcelltherapiesinmousebrains AT tokikonagamurainoue metabolomicanalysisandmassspectrometryimagingafterneonatalstrokeandcelltherapiesinmousebrains AT haruoshintaku metabolomicanalysisandmassspectrometryimagingafterneonatalstrokeandcelltherapiesinmousebrains AT masahirotsuji metabolomicanalysisandmassspectrometryimagingafterneonatalstrokeandcelltherapiesinmousebrains
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Metabolomic analysis and mass spectrometry imaging after neonatal stroke and cell therapies in mouse brains

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