Cargando…
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...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8474429/ https://www.ncbi.nlm.nih.gov/pubmed/34589775 http://dx.doi.org/10.1016/j.bbih.2021.100270 |
_version_ | 1784575221974433792 |
---|---|
author | Schuhmann, Michael K. Kollikowski, Alexander M. März, Alexander G. Bieber, Michael Pham, Mirko Stoll, Guido |
author_facet | Schuhmann, Michael K. Kollikowski, Alexander M. März, Alexander G. Bieber, Michael Pham, Mirko Stoll, Guido |
author_sort | Schuhmann, Michael K. |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-8474429 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-84744292021-09-28 Danger-associated molecular patterns are locally released during occlusion in hyper-acute stroke Schuhmann, Michael K. Kollikowski, Alexander M. März, Alexander G. Bieber, Michael Pham, Mirko Stoll, Guido Brain Behav Immun Health Short Communication 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. Elsevier 2021-05-25 /pmc/articles/PMC8474429/ /pubmed/34589775 http://dx.doi.org/10.1016/j.bbih.2021.100270 Text en © 2021 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Short Communication Schuhmann, Michael K. Kollikowski, Alexander M. März, Alexander G. Bieber, Michael Pham, Mirko Stoll, Guido Danger-associated molecular patterns are locally released during occlusion in 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 | Short Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8474429/ https://www.ncbi.nlm.nih.gov/pubmed/34589775 http://dx.doi.org/10.1016/j.bbih.2021.100270 |
work_keys_str_mv | AT schuhmannmichaelk dangerassociatedmolecularpatternsarelocallyreleasedduringocclusioninhyperacutestroke AT kollikowskialexanderm dangerassociatedmolecularpatternsarelocallyreleasedduringocclusioninhyperacutestroke AT marzalexanderg dangerassociatedmolecularpatternsarelocallyreleasedduringocclusioninhyperacutestroke AT biebermichael dangerassociatedmolecularpatternsarelocallyreleasedduringocclusioninhyperacutestroke AT phammirko dangerassociatedmolecularpatternsarelocallyreleasedduringocclusioninhyperacutestroke AT stollguido dangerassociatedmolecularpatternsarelocallyreleasedduringocclusioninhyperacutestroke |