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Peripheral myeloid cells contribute to brain injury in male neonatal mice
BACKGROUND: Neonatal brain injury is increasingly understood to be linked to inflammatory processes that involve specialised CNS and peripheral immune interactions. However, the role of peripheral myeloid cells in neonatal hypoxic-ischemic (HI) brain injury remains to be fully investigated. METHODS:...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6208095/ https://www.ncbi.nlm.nih.gov/pubmed/30376851 http://dx.doi.org/10.1186/s12974-018-1344-9 |
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author | Smith, Peter L. P. Mottahedin, Amin Svedin, Pernilla Mohn, Carl-Johan Hagberg, Henrik Ek, Joakim Mallard, Carina |
author_facet | Smith, Peter L. P. Mottahedin, Amin Svedin, Pernilla Mohn, Carl-Johan Hagberg, Henrik Ek, Joakim Mallard, Carina |
author_sort | Smith, Peter L. P. |
collection | PubMed |
description | BACKGROUND: Neonatal brain injury is increasingly understood to be linked to inflammatory processes that involve specialised CNS and peripheral immune interactions. However, the role of peripheral myeloid cells in neonatal hypoxic-ischemic (HI) brain injury remains to be fully investigated. METHODS: We employed the Lys-EGFP-ki mouse that allows enhanced green fluorescent protein (EGFP)-positive mature myeloid cells of peripheral origin to be easily identified in the CNS. Using both flow cytometry and confocal microscopy, we investigated the accumulation of total EGFP(+) myeloid cells and myeloid cell subtypes: inflammatory monocytes, resident monocytes and granulocytes, in the CNS for several weeks following induction of cerebral HI in postnatal day 9 mice. We used antibody treatment to curb brain infiltration of myeloid cells and subsequently evaluated HI-induced brain injury. RESULTS: We demonstrate a temporally biphasic pattern of inflammatory monocyte and granulocyte infiltration, characterised by peak infiltration at 1 day and 7 days after hypoxia-ischemia. This occurs against a backdrop of continuous low-level resident monocyte infiltration. Antibody-mediated depletion of circulating myeloid cells reduced immune cell accumulation in the brain and reduced neuronal loss in male but not female mice. CONCLUSION: This study offers new insight into sex-dependent central-peripheral immune communication following neonatal brain injury and merits renewed interest in the roles of granulocytes and monocytes in lesion development. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12974-018-1344-9) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6208095 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-62080952018-11-16 Peripheral myeloid cells contribute to brain injury in male neonatal mice Smith, Peter L. P. Mottahedin, Amin Svedin, Pernilla Mohn, Carl-Johan Hagberg, Henrik Ek, Joakim Mallard, Carina J Neuroinflammation Research BACKGROUND: Neonatal brain injury is increasingly understood to be linked to inflammatory processes that involve specialised CNS and peripheral immune interactions. However, the role of peripheral myeloid cells in neonatal hypoxic-ischemic (HI) brain injury remains to be fully investigated. METHODS: We employed the Lys-EGFP-ki mouse that allows enhanced green fluorescent protein (EGFP)-positive mature myeloid cells of peripheral origin to be easily identified in the CNS. Using both flow cytometry and confocal microscopy, we investigated the accumulation of total EGFP(+) myeloid cells and myeloid cell subtypes: inflammatory monocytes, resident monocytes and granulocytes, in the CNS for several weeks following induction of cerebral HI in postnatal day 9 mice. We used antibody treatment to curb brain infiltration of myeloid cells and subsequently evaluated HI-induced brain injury. RESULTS: We demonstrate a temporally biphasic pattern of inflammatory monocyte and granulocyte infiltration, characterised by peak infiltration at 1 day and 7 days after hypoxia-ischemia. This occurs against a backdrop of continuous low-level resident monocyte infiltration. Antibody-mediated depletion of circulating myeloid cells reduced immune cell accumulation in the brain and reduced neuronal loss in male but not female mice. CONCLUSION: This study offers new insight into sex-dependent central-peripheral immune communication following neonatal brain injury and merits renewed interest in the roles of granulocytes and monocytes in lesion development. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12974-018-1344-9) contains supplementary material, which is available to authorized users. BioMed Central 2018-10-30 /pmc/articles/PMC6208095/ /pubmed/30376851 http://dx.doi.org/10.1186/s12974-018-1344-9 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Smith, Peter L. P. Mottahedin, Amin Svedin, Pernilla Mohn, Carl-Johan Hagberg, Henrik Ek, Joakim Mallard, Carina Peripheral myeloid cells contribute to brain injury in male neonatal mice |
title | Peripheral myeloid cells contribute to brain injury in male neonatal mice |
title_full | Peripheral myeloid cells contribute to brain injury in male neonatal mice |
title_fullStr | Peripheral myeloid cells contribute to brain injury in male neonatal mice |
title_full_unstemmed | Peripheral myeloid cells contribute to brain injury in male neonatal mice |
title_short | Peripheral myeloid cells contribute to brain injury in male neonatal mice |
title_sort | peripheral myeloid cells contribute to brain injury in male neonatal mice |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6208095/ https://www.ncbi.nlm.nih.gov/pubmed/30376851 http://dx.doi.org/10.1186/s12974-018-1344-9 |
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