Cargando…

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:...

Descripción completa

Detalles Bibliográficos
Autores principales: Smith, Peter L. P., Mottahedin, Amin, Svedin, Pernilla, Mohn, Carl-Johan, Hagberg, Henrik, Ek, Joakim, Mallard, Carina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
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
_version_ 1783366650423148544
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
work_keys_str_mv AT smithpeterlp peripheralmyeloidcellscontributetobraininjuryinmaleneonatalmice
AT mottahedinamin peripheralmyeloidcellscontributetobraininjuryinmaleneonatalmice
AT svedinpernilla peripheralmyeloidcellscontributetobraininjuryinmaleneonatalmice
AT mohncarljohan peripheralmyeloidcellscontributetobraininjuryinmaleneonatalmice
AT hagberghenrik peripheralmyeloidcellscontributetobraininjuryinmaleneonatalmice
AT ekjoakim peripheralmyeloidcellscontributetobraininjuryinmaleneonatalmice
AT mallardcarina peripheralmyeloidcellscontributetobraininjuryinmaleneonatalmice