Danger-associated molecular patterns are locally released during occlusion in hyper-acute stroke
Objective: Immune responses are an integral part of the complex reactions to acute cerebral ischemia and contribute to infarct expansion and tissue remodeling. Among damage-associated molecular patterns (DAMPs) the high-mobility group box 1 protein (HMGB1) and calprotectin (S100A8/A9) are released f...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-08-01
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| Series: | Brain, Behavior, & Immunity - Health |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666354621000739 |
| _version_ | 1818846770059280384 |
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| author | Michael K. Schuhmann Alexander M. Kollikowski Alexander G. März Michael Bieber Mirko Pham Guido Stoll |
| author_facet | Michael K. Schuhmann Alexander M. Kollikowski Alexander G. März Michael Bieber Mirko Pham Guido Stoll |
| author_sort | Michael K. Schuhmann |
| collection | DOAJ |
| description | Objective: Immune responses are an integral part of the complex reactions to acute cerebral ischemia and contribute to infarct expansion and tissue remodeling. Among damage-associated molecular patterns (DAMPs) the high-mobility group box 1 protein (HMGB1) and calprotectin (S100A8/A9) are released from dying cells and activate the innate immune system. Methods: To assess DAMPs concentrations and related leukocytic infiltration directly and locally in human stroke patients we performed microcatheter sampling from within the core of the occluded vascular compartment before recanalization by mechanical thrombectomy. These samples from the core of a sealed cerebral-ischemic arterial compartment were compared with systemic control samples from the internal carotid artery obtained after recanalization. Results: We found increased plasma levels of total free HMGB1 (+33%) and increased S100A8/A9 (+8%) locally within the ischemic cerebral compartment vs. systemic levels. Local concentrations of HMGB1 were associated with more extensive structural brain infarction on admission. In addition, local ischemic HMGB1 and S100A8/A9 concentrations were associated with the numbers of leukocytes that infiltrate the occluded compartment by collateral pathways. Conclusion: This is the first direct human observation of a local increase in DAMPs concentrations in a uniquely sealed vascular compartment of the ischemic cerebral circulation. These data provide an important pathophysiological link between ischemia-induced cell death and stroke-related inflammation. |
| first_indexed | 2024-12-19T05:50:50Z |
| format | Article |
| id | doaj.art-922a14da55d343368f61df2982fe234e |
| institution | Directory Open Access Journal |
| issn | 2666-3546 |
| language | English |
| last_indexed | 2024-12-19T05:50:50Z |
| publishDate | 2021-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain, Behavior, & Immunity - Health |
| spelling | doaj.art-922a14da55d343368f61df2982fe234e2022-12-21T20:33:37ZengElsevierBrain, Behavior, & Immunity - Health2666-35462021-08-0115100270Danger-associated molecular patterns are locally released during occlusion in hyper-acute strokeMichael K. Schuhmann0Alexander M. Kollikowski1Alexander G. März2Michael Bieber3Mirko Pham4Guido Stoll5Department of Neurology, University Hospital Würzburg, GermanyDepartment of Neuroradiology, University Hospital Würzburg, GermanyDepartment of Neuroradiology, University Hospital Würzburg, GermanyDepartment of Neurology, University Hospital Würzburg, GermanyDepartment of Neuroradiology, University Hospital Würzburg, GermanyDepartment of Neurology, University Hospital Würzburg, Germany; Corresponding author. Department of Neurology, University Hospital Würzburg, Josef-Schneider-Str. 11, 97080, Würzburg, Germany.Objective: Immune responses are an integral part of the complex reactions to acute cerebral ischemia and contribute to infarct expansion and tissue remodeling. Among damage-associated molecular patterns (DAMPs) the high-mobility group box 1 protein (HMGB1) and calprotectin (S100A8/A9) are released from dying cells and activate the innate immune system. Methods: To assess DAMPs concentrations and related leukocytic infiltration directly and locally in human stroke patients we performed microcatheter sampling from within the core of the occluded vascular compartment before recanalization by mechanical thrombectomy. These samples from the core of a sealed cerebral-ischemic arterial compartment were compared with systemic control samples from the internal carotid artery obtained after recanalization. Results: We found increased plasma levels of total free HMGB1 (+33%) and increased S100A8/A9 (+8%) locally within the ischemic cerebral compartment vs. systemic levels. Local concentrations of HMGB1 were associated with more extensive structural brain infarction on admission. In addition, local ischemic HMGB1 and S100A8/A9 concentrations were associated with the numbers of leukocytes that infiltrate the occluded compartment by collateral pathways. Conclusion: This is the first direct human observation of a local increase in DAMPs concentrations in a uniquely sealed vascular compartment of the ischemic cerebral circulation. These data provide an important pathophysiological link between ischemia-induced cell death and stroke-related inflammation.http://www.sciencedirect.com/science/article/pii/S2666354621000739Danger-associated molecular patternsHigh-mobility group box 1 proteinCalprotectinHyper-acute stroke |
| spellingShingle | Michael K. Schuhmann Alexander M. Kollikowski Alexander G. März Michael Bieber Mirko Pham Guido Stoll Danger-associated molecular patterns are locally released during occlusion in hyper-acute stroke Brain, Behavior, & Immunity - Health Danger-associated molecular patterns High-mobility group box 1 protein Calprotectin Hyper-acute stroke |
| title | Danger-associated molecular patterns are locally released during occlusion in hyper-acute stroke |
| title_full | Danger-associated molecular patterns are locally released during occlusion in hyper-acute stroke |
| title_fullStr | Danger-associated molecular patterns are locally released during occlusion in hyper-acute stroke |
| title_full_unstemmed | Danger-associated molecular patterns are locally released during occlusion in hyper-acute stroke |
| title_short | Danger-associated molecular patterns are locally released during occlusion in hyper-acute stroke |
| title_sort | danger associated molecular patterns are locally released during occlusion in hyper acute stroke |
| topic | Danger-associated molecular patterns High-mobility group box 1 protein Calprotectin Hyper-acute stroke |
| url | http://www.sciencedirect.com/science/article/pii/S2666354621000739 |
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