Journal
JOURNAL OF NEUROSCIENCE
Volume 36, Issue 15, Pages 4182-4195Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.4317-15.2016
Keywords
macrophage; microglia; monocyte; neuroinflammation; stroke
Categories
Funding
- European Union Project TargetBraIn [279017]
- Swedish Research Council
- AFA Foundation
- Ragnar Soderberg Foundation
- Swedish Government Initiative for Strategic Research Areas (StemTherapy)
- Program of Strategic Scholarships for Frontier Research Network, Thailand's Office of the Higher Education Commission
- Shota Rustaveli National Science Foundation (Tbilisi, Georgia)
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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 long-term 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 infiltrating MDMs exhibited 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 TGF beta, 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.
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