Journal
JOURNAL OF NEUROINFLAMMATION
Volume 15, Issue -, Pages -Publisher
BMC
DOI: 10.1186/s12974-018-1344-9
Keywords
Neuroinflammation; Newborn; Immune cell trafficking
Categories
Funding
- Swedish Medical Research Council [VR 2012-2992, 2015-02493]
- European Union grant FP7 (Neurobid) [HEALTH-F2-2009-241778]
- ERA-net (EU) [VR 529-2014-7551]
- Swedish Brain Foundation [FO 2017-0063, FO2015-0004]
- Leducq foundation [DSRR_P34404]
- NIH [1RO1HL139685-01]
- Torsten Soderberg Foundation
- Cerebral Palsy Alliance Australia
- Stroke-Riksforbundet
- Ahlen Foundation
- Wilhelm and Martina Lundgren Foundation
- [ALFGBG-142881]
- [137601]
- [ALFGBG-426401]
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BackgroundNeonatal 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.MethodsWe 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.ResultsWe demonstrate a temporally biphasic pattern of inflammatory monocyte and granulocyte infiltration, characterised by peak infiltration at 1day and 7days 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.ConclusionThis 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.
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