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

Wattananit, Somsak LU ; Tornero, Daniel LU ; Graubardt, Nadine; Memanishvili, Tamar LU ; Monni, Emanuela LU ; Tatarishvili, Jemal LU ; Miskinyte, Giedre LU ; Ge, Ruimin LU ; Ahlenius, Henrik LU and Lindvall, Olle LU , et al. (2016) In Journal of Neuroscience 36(15). p.4182-4195
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... (More)

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.

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Contribution to journal
publication status
published
subject
keywords
Macrophage, Microglia, Monocyte, Neuroinflammation, Stroke
in
Journal of Neuroscience
volume
36
issue
15
pages
14 pages
publisher
Society for Neuroscience
external identifiers
  • Scopus:84963762637
ISSN
0270-6474
DOI
10.1523/JNEUROSCI.4317-15.2016
language
English
LU publication?
yes
id
e613880e-7a66-423d-8bcb-2628ecf0410a
date added to LUP
2016-05-12 13:33:14
date last changed
2016-11-27 04:40:20
@misc{e613880e-7a66-423d-8bcb-2628ecf0410a,
  abstract     = {<p>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.</p>},
  author       = {Wattananit, Somsak and Tornero, Daniel and Graubardt, Nadine and Memanishvili, Tamar and Monni, Emanuela and Tatarishvili, Jemal and Miskinyte, Giedre and Ge, Ruimin and Ahlenius, Henrik and Lindvall, Olle and Schwartz, Michal and Kokaia, Zaal},
  issn         = {0270-6474},
  keyword      = {Macrophage,Microglia,Monocyte,Neuroinflammation,Stroke},
  language     = {eng},
  month        = {04},
  number       = {15},
  pages        = {4182--4195},
  publisher    = {ARRAY(0x9da0020)},
  series       = {Journal of Neuroscience},
  title        = {Monocyte-derived macrophages contribute to spontaneous long-term functional recovery after stroke in mice},
  url          = {http://dx.doi.org/10.1523/JNEUROSCI.4317-15.2016},
  volume       = {36},
  year         = {2016},
}