Monocyte-derived macrophages contribute to spontaneous long-term functional recovery after stroke in mice

Research output: Contribution to journalArticle

Abstract

Stroke is a leading cause of disability and currently lacks effective therapy enabling long-term functional recovery. Ischemic brain injury causes local inflammation, which involves both activated resident microglia and infiltrating immune cells, including monocytes. Monocyte-derived macrophages (MDMs) exhibit a high degree of functional plasticity. Here, we determined the role of MDMs in longterm spontaneous functional recovery after middle cerebral artery occlusion in mice. Analyses by flow cytometry and immunocytochemistry revealed that monocytes home to the stroke-injured hemisphere., and that infiltration peaks 3 d after stroke. At day 7, half of the infiltratingMDMsexhibited a bias toward a proinflammatory phenotype and the other half toward an anti-inflammatory phenotype, but during the subsequent 2 weeks, MDMs with an anti-inflammatory phenotype dominated. Blocking monocyte recruitment using the anti-CCR2 antibody MC-21 during the first week after stroke abolished long-term behavioral recovery, as determined in corridor and staircase tests, and drastically decreased tissue expression of anti-inflammatory genes, including TGFβ, CD163, and Ym1. Our results show that spontaneously recruited monocytes to the injured brain early after the insult contribute to long-term functional recovery after stroke.

Details

Authors
Organisations
External organisations
  • Weizmann Institute of Science Israel
  • Ivane Javakhishvili Tbilisi State University
  • Mahidol University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurology

Keywords

  • Macrophage, Microglia, Monocyte, Neuroinflammation, Stroke
Original languageEnglish
Pages (from-to)4182-4195
Number of pages14
JournalJournal of Neuroscience
Volume36
Issue number15
Publication statusPublished - 2016 Apr 13
Publication categoryResearch
Peer-reviewedYes