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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.

Original publication

DOI

10.1186/s12974-018-1344-9

Type

Journal article

Journal

J Neuroinflammation

Publication Date

30/10/2018

Volume

15

Keywords

Immune cell trafficking, Neuroinflammation, Newborn, Animals, Animals, Newborn, Antibodies, Antigens, Ly, Calcium-Binding Proteins, Cytokinins, Disease Models, Animal, Functional Laterality, Green Fluorescent Proteins, Hypoxia-Ischemia, Brain, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Microfilament Proteins, Monocytes, Muramidase, Myeloid Cells, Nerve Tissue Proteins, Neutrophils