Multimodal imaging of hemorrhagic transformation biomarkers in an ischemic stroke model.
Hemorrhagic transformation of ischemic stroke has devastating consequences, with high mortality and poor functional outcomes. Animal models of ischemic stroke also demonstrate the potential for hemorrhagic transformation, which complicates biochemical characterization, treatment studies, and hinders...
| Main Authors: | , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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OXFORD UNIV PRESS
2022
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| Online Access: | http://hdl.handle.net/20.500.11937/92983 |
| _version_ | 1848765683200950272 |
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| author | Pushie, M.J. Messmer, M. Sylvain, N.J. Heppner, J. Newton, J.M. Hou, H. Hackett, Mark Kelly, M.E. Peeling, L. |
| author_facet | Pushie, M.J. Messmer, M. Sylvain, N.J. Heppner, J. Newton, J.M. Hou, H. Hackett, Mark Kelly, M.E. Peeling, L. |
| author_sort | Pushie, M.J. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Hemorrhagic transformation of ischemic stroke has devastating consequences, with high mortality and poor functional outcomes. Animal models of ischemic stroke also demonstrate the potential for hemorrhagic transformation, which complicates biochemical characterization, treatment studies, and hinders poststroke functional outcomes in affected subjects. The incidence of hemorrhagic transformation of ischemic stroke in animal model research is not commonly reported. The postmortem brain of such cases presents a complex milieu of biomarkers due to the presence of healthy cells, regions of varying degrees of ischemia, dead and dying cells, dysregulated metabolites, and blood components (especially reactive Fe species released from lysed erythrocytes). To improve the characterization of hemorrhage biomarkers on an ischemic stroke background, we have employed a combination of histology, X-ray fluorescence imaging (XFI), and Fourier transform infrared (FTIR) spectroscopic imaging to assess 122 photothrombotic (ischemic) stroke brains. Rapid freezing preserves brain biomarkers in situ and minimizes metabolic artifacts due to postmortem ischemia. Analysis revealed that 25% of the photothrombotic models had clear signs of hemorrhagic transformation. The XFI and FTIR metabolites provided a quantitative method to differentiate key metabolic regions in these models. Across all hemorrhage cases, it was possible to consistently differentiate otherwise healthy tissue from other metabolically distinct regions, including the ischemic infarct, the ischemic penumbra, blood vessels, sites of hemorrhage, and a region surrounding the hemorrhage core that contained elevated lipid oxidation. Chemical speciation of deposited Fe demonstrates the presence of heme-Fe and accumulation of ferritin. |
| first_indexed | 2025-11-14T11:39:09Z |
| format | Journal Article |
| id | curtin-20.500.11937-92983 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-14T11:39:09Z |
| publishDate | 2022 |
| publisher | OXFORD UNIV PRESS |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-929832023-08-28T01:16:05Z Multimodal imaging of hemorrhagic transformation biomarkers in an ischemic stroke model. Pushie, M.J. Messmer, M. Sylvain, N.J. Heppner, J. Newton, J.M. Hou, H. Hackett, Mark Kelly, M.E. Peeling, L. Science & Technology Life Sciences & Biomedicine Biochemistry & Molecular Biology hemorrhage stroke FTIR imaging XFI Fe speciation oxidative damage BRAIN-BARRIER PERMEABILITY ION HOMEOSTASIS IRON HEME SPECTROSCOPY CALCIUM INJURY FTIR imaging Fe speciation XFI hemorrhage oxidative damage stroke Animals Biomarkers Brain Ischemia Hemorrhage Humans Ischemic Stroke Multimodal Imaging Stroke Animals Humans Brain Ischemia Hemorrhage Stroke Multimodal Imaging Biomarkers Ischemic Stroke Hemorrhagic transformation of ischemic stroke has devastating consequences, with high mortality and poor functional outcomes. Animal models of ischemic stroke also demonstrate the potential for hemorrhagic transformation, which complicates biochemical characterization, treatment studies, and hinders poststroke functional outcomes in affected subjects. The incidence of hemorrhagic transformation of ischemic stroke in animal model research is not commonly reported. The postmortem brain of such cases presents a complex milieu of biomarkers due to the presence of healthy cells, regions of varying degrees of ischemia, dead and dying cells, dysregulated metabolites, and blood components (especially reactive Fe species released from lysed erythrocytes). To improve the characterization of hemorrhage biomarkers on an ischemic stroke background, we have employed a combination of histology, X-ray fluorescence imaging (XFI), and Fourier transform infrared (FTIR) spectroscopic imaging to assess 122 photothrombotic (ischemic) stroke brains. Rapid freezing preserves brain biomarkers in situ and minimizes metabolic artifacts due to postmortem ischemia. Analysis revealed that 25% of the photothrombotic models had clear signs of hemorrhagic transformation. The XFI and FTIR metabolites provided a quantitative method to differentiate key metabolic regions in these models. Across all hemorrhage cases, it was possible to consistently differentiate otherwise healthy tissue from other metabolically distinct regions, including the ischemic infarct, the ischemic penumbra, blood vessels, sites of hemorrhage, and a region surrounding the hemorrhage core that contained elevated lipid oxidation. Chemical speciation of deposited Fe demonstrates the presence of heme-Fe and accumulation of ferritin. 2022 Journal Article http://hdl.handle.net/20.500.11937/92983 10.1093/mtomcs/mfac007 English OXFORD UNIV PRESS unknown |
| spellingShingle | Science & Technology Life Sciences & Biomedicine Biochemistry & Molecular Biology hemorrhage stroke FTIR imaging XFI Fe speciation oxidative damage BRAIN-BARRIER PERMEABILITY ION HOMEOSTASIS IRON HEME SPECTROSCOPY CALCIUM INJURY FTIR imaging Fe speciation XFI hemorrhage oxidative damage stroke Animals Biomarkers Brain Ischemia Hemorrhage Humans Ischemic Stroke Multimodal Imaging Stroke Animals Humans Brain Ischemia Hemorrhage Stroke Multimodal Imaging Biomarkers Ischemic Stroke Pushie, M.J. Messmer, M. Sylvain, N.J. Heppner, J. Newton, J.M. Hou, H. Hackett, Mark Kelly, M.E. Peeling, L. Multimodal imaging of hemorrhagic transformation biomarkers in an ischemic stroke model. |
| title | Multimodal imaging of hemorrhagic transformation biomarkers in an ischemic stroke model. |
| title_full | Multimodal imaging of hemorrhagic transformation biomarkers in an ischemic stroke model. |
| title_fullStr | Multimodal imaging of hemorrhagic transformation biomarkers in an ischemic stroke model. |
| title_full_unstemmed | Multimodal imaging of hemorrhagic transformation biomarkers in an ischemic stroke model. |
| title_short | Multimodal imaging of hemorrhagic transformation biomarkers in an ischemic stroke model. |
| title_sort | multimodal imaging of hemorrhagic transformation biomarkers in an ischemic stroke model. |
| topic | Science & Technology Life Sciences & Biomedicine Biochemistry & Molecular Biology hemorrhage stroke FTIR imaging XFI Fe speciation oxidative damage BRAIN-BARRIER PERMEABILITY ION HOMEOSTASIS IRON HEME SPECTROSCOPY CALCIUM INJURY FTIR imaging Fe speciation XFI hemorrhage oxidative damage stroke Animals Biomarkers Brain Ischemia Hemorrhage Humans Ischemic Stroke Multimodal Imaging Stroke Animals Humans Brain Ischemia Hemorrhage Stroke Multimodal Imaging Biomarkers Ischemic Stroke |
| url | http://hdl.handle.net/20.500.11937/92983 |