Monocyte-derived macrophages contribute to spontaneous long-term functional recovery after stroke in mice
(2016) In The 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.
(Less)
- author
- organization
- publishing date
- 2016-04-13
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Macrophage, Microglia, Monocyte, Neuroinflammation, Stroke
- in
- The Journal of Neuroscience
- volume
- 36
- issue
- 15
- pages
- 14 pages
- publisher
- Society for Neuroscience
- external identifiers
-
- scopus:84963762637
- pmid:27076418
- wos:000375129700006
- 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
- 2024-09-21 13:15:54
@article{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}}, keywords = {{Macrophage; Microglia; Monocyte; Neuroinflammation; Stroke}}, language = {{eng}}, month = {{04}}, number = {{15}}, pages = {{4182--4195}}, publisher = {{Society for Neuroscience}}, series = {{The 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}}, doi = {{10.1523/JNEUROSCI.4317-15.2016}}, volume = {{36}}, year = {{2016}}, }