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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| Format: | Article |
| Language: | English |
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Nature Portfolio
2020-12-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-020-78930-x |
| _version_ | 1818842533293195264 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-19T04:43:29Z |
| format | Article |
| id | doaj.art-642301be6d594791aaff0e5f015b232c |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-19T04:43:29Z |
| publishDate | 2020-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-642301be6d594791aaff0e5f015b232c2022-12-21T20:35:32ZengNature PortfolioScientific Reports2045-23222020-12-0110111210.1038/s41598-020-78930-xMetabolomic analysis and mass spectrometry imaging after neonatal stroke and cell therapies in mouse brainsEmi Tanaka0Yuko Ogawa1Ritsuko Fujii2Tomomi Shimonaka3Yoshiaki Sato4Takashi Hamazaki5Tokiko Nagamura-Inoue6Haruo Shintaku7Masahiro Tsuji8Department of Pediatrics, Osaka City University Graduate School of MedicineInstitute of Biomedical Research and InnovationDivision of Bioenergetics, Research Center for Artificial Photosynthesis, Osaka City UniversityAnalysis Division, Research Center for Artificial Photosynthesis, Osaka City UniversityDivision of Neonatology, Center for Maternal-Neonatal Care, Nagoya University HospitalDepartment of Pediatrics, Osaka City University Graduate School of MedicineDepartment of Cell Processing and Transfusion, Institute of Medical Science, The University of TokyoDepartment of Pediatrics, Osaka City University Graduate School of MedicineDepartment of Food and Nutrition, Kyoto Women’s UniversityAbstract 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.https://doi.org/10.1038/s41598-020-78930-x |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-020-78930-x |
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