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Neuroinflammation after Intracerebral Hemorrhage and Potential Therapeutic Targets
Spontaneous intracerebral hemorrhage (ICH) is a catastrophic illness causing significant morbidity and mortality. Despite advances in surgical technique addressing primary brain injury caused by ICH, little progress has been made treating the subsequent inflammatory cascade. Pre-clinical studies hav...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Korean Stroke Society
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7005353/ https://www.ncbi.nlm.nih.gov/pubmed/32027790 http://dx.doi.org/10.5853/jos.2019.02236 |
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author | Tschoe, Christine Bushnell, Cheryl D. Duncan, Pamela W. Alexander-Miller, Martha A. Wolfe, Stacey Q. |
author_facet | Tschoe, Christine Bushnell, Cheryl D. Duncan, Pamela W. Alexander-Miller, Martha A. Wolfe, Stacey Q. |
author_sort | Tschoe, Christine |
collection | PubMed |
description | Spontaneous intracerebral hemorrhage (ICH) is a catastrophic illness causing significant morbidity and mortality. Despite advances in surgical technique addressing primary brain injury caused by ICH, little progress has been made treating the subsequent inflammatory cascade. Pre-clinical studies have made advancements identifying components of neuroinflammation, including microglia, astrocytes, and T lymphocytes. After cerebral insult, inflammation is initially driven by the M1 microglia, secreting cytokines (e.g., interleukin-1β [IL-1β] and tumor necrosis factor-α) that are involved in the breakdown of the extracellular matrix, cellular integrity, and the blood brain barrier. Additionally, inflammatory factors recruit and induce differentiation of A1 reactive astrocytes and T helper 1 (Th1) cells, which contribute to the secretion of inflammatory cytokines, augmenting M1 polarization and potentiating inflammation. Within 7 days of ICH ictus, the M1 phenotype coverts to a M2 phenotype, key for hematoma removal, tissue healing, and overall resolution of inflammation. The secretion of anti-inflammatory cytokines (e.g., IL-4, IL-10) can drive Th2 cell differentiation. M2 polarization is maintained by the secretion of additional anti-inflammatory cytokines by the Th2 cells, suppressing M1 and Th1 phenotypes. Elucidating the timing and trigger of the anti-inflammatory phenotype may be integral in improving clinical outcomes. A challenge in current translational research is the absence of an equivalent disease animal model mirroring the patient population and comorbid pathophysiologic state. We review existing data and describe potential therapeutic targets around which we are creating a bench to bedside translational research model that better reflects the pathophysiology of ICH patients. |
format | Online Article Text |
id | pubmed-7005353 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Korean Stroke Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-70053532020-02-13 Neuroinflammation after Intracerebral Hemorrhage and Potential Therapeutic Targets Tschoe, Christine Bushnell, Cheryl D. Duncan, Pamela W. Alexander-Miller, Martha A. Wolfe, Stacey Q. J Stroke Review Spontaneous intracerebral hemorrhage (ICH) is a catastrophic illness causing significant morbidity and mortality. Despite advances in surgical technique addressing primary brain injury caused by ICH, little progress has been made treating the subsequent inflammatory cascade. Pre-clinical studies have made advancements identifying components of neuroinflammation, including microglia, astrocytes, and T lymphocytes. After cerebral insult, inflammation is initially driven by the M1 microglia, secreting cytokines (e.g., interleukin-1β [IL-1β] and tumor necrosis factor-α) that are involved in the breakdown of the extracellular matrix, cellular integrity, and the blood brain barrier. Additionally, inflammatory factors recruit and induce differentiation of A1 reactive astrocytes and T helper 1 (Th1) cells, which contribute to the secretion of inflammatory cytokines, augmenting M1 polarization and potentiating inflammation. Within 7 days of ICH ictus, the M1 phenotype coverts to a M2 phenotype, key for hematoma removal, tissue healing, and overall resolution of inflammation. The secretion of anti-inflammatory cytokines (e.g., IL-4, IL-10) can drive Th2 cell differentiation. M2 polarization is maintained by the secretion of additional anti-inflammatory cytokines by the Th2 cells, suppressing M1 and Th1 phenotypes. Elucidating the timing and trigger of the anti-inflammatory phenotype may be integral in improving clinical outcomes. A challenge in current translational research is the absence of an equivalent disease animal model mirroring the patient population and comorbid pathophysiologic state. We review existing data and describe potential therapeutic targets around which we are creating a bench to bedside translational research model that better reflects the pathophysiology of ICH patients. Korean Stroke Society 2020-01 2020-01-31 /pmc/articles/PMC7005353/ /pubmed/32027790 http://dx.doi.org/10.5853/jos.2019.02236 Text en Copyright © 2020 Korean Stroke Society This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Review Tschoe, Christine Bushnell, Cheryl D. Duncan, Pamela W. Alexander-Miller, Martha A. Wolfe, Stacey Q. Neuroinflammation after Intracerebral Hemorrhage and Potential Therapeutic Targets |
title | Neuroinflammation after Intracerebral Hemorrhage and Potential Therapeutic Targets |
title_full | Neuroinflammation after Intracerebral Hemorrhage and Potential Therapeutic Targets |
title_fullStr | Neuroinflammation after Intracerebral Hemorrhage and Potential Therapeutic Targets |
title_full_unstemmed | Neuroinflammation after Intracerebral Hemorrhage and Potential Therapeutic Targets |
title_short | Neuroinflammation after Intracerebral Hemorrhage and Potential Therapeutic Targets |
title_sort | neuroinflammation after intracerebral hemorrhage and potential therapeutic targets |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7005353/ https://www.ncbi.nlm.nih.gov/pubmed/32027790 http://dx.doi.org/10.5853/jos.2019.02236 |
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