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Sex Differences in Acute Neuroinflammation after Experimental Traumatic Brain Injury Are Mediated by Infiltrating Myeloid Cells.

Abstract：

:The inflammatory response to moderate-severe controlled cortical impact (CCI) in adult male mice has been shown to exhibit greater glial activation compared with age-matched female mice. However, the relative contributions of resident microglia and infiltrating peripheral myeloid cells to this sexually dimorphic neuroinflammatory responses remains unclear. Here, 12-week-old male and female C57Bl/6 mice were subjected to sham or CCI, and brain samples were collected at 1, 3, or 7 days post-injury for flow cytometry analysis of cytokines, reactive oxygen species (ROS), and phagocytosis in resident microglia (CD45intCD11b+) versus infiltrating myeloid cells (CD45hiCD11b+). Motor (rotarod, cylinder test), affect (open field), and cognitive (Y-maze) function tests also were performed. We demonstrate that male microglia had increased phagocytic activity and higher ROS levels in the non-injured brain, whereas female microglia had increased production of tumor necrosis factor (TNF) α and interleukin (IL)-1β. Following CCI, males showed a significant influx of peripheral myeloid cells by 1 day post-injury followed by proliferation of resident microglia at 3 days. In contrast, myeloid infiltration and microglial activation responses in female CCI mice were significantly reduced. No sex differences were observed for TNFα, IL-1β, transforming growth factor β, NOX2, ROS production, or phagocytic activity in resident microglia or infiltrating cells at any time. However, across these functions, infiltrating myeloid cells were significantly more reactive than resident microglia. Female CCI mice also had improved motor function at 1 day post-injury compared with male mice. Thus, we conclude that sexually dimorphic responses to moderate-severe CCI result from the rapid activation and infiltration of pro-inflammatory myeloid cells to brain in male, but not female, mice.

journal_name

J Neurotrauma

journal_title

Journal of neurotrauma

authors

Doran SJ,Ritzel RM,Glaser EP,Henry RJ,Faden AI,Loane DJ

doi

10.1089/neu.2018.6019

subject

Has Abstract

pub_date

2019-04-01 00:00:00

pages

1040-1053

issue

eissn

0897-7151

issn

1557-9042

journal_volume

pub_type

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Sex Differences in Acute Neuroinflammation after Experimental Traumatic Brain Injury Are Mediated by Infiltrating Myeloid Cells.