The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
Monocyte-Derived Macrophages Contribute to Spontaneous Long-Term Functional Recovery after Stroke in Mice
Open accessAbstract
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 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. SIGNIFICANCE STATEMENT For decades, any involvement of circulating immune cells in CNS repair was completely denied. Only over the past few years has involvement of monocyte-derived macrophages (MDMs) in CNS repair received appreciation. We show here, for the first time, that MDMs recruited to the injured brain early after ischemic stroke contribute to long-term spontaneous functional recovery through inflammation-resolving activity. Our data raise the possibility that inadequate recruitment of MDMs to the brain after stroke underlies the incomplete functional recovery seen in patients and that boosting homing of MDMs with an anti-inflammatory bias to the injured brain tissue may be a new therapeutic approach to promote long-term improvement after stroke.
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Cites
Monocyte and macrophage heterogeneity
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Microglia in the adult brain arise from Ly-6ChiCCR2+ monocytes only under defined host conditions
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Temporal and Spatial Dynamics of Cerebral Immune Cell Accumulation in Stroke
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“DOI:10.1523/JNEUROSCI.4317-15.2016 Copyright © 2016 the authors 0270-6474/16/364182-14$15.00/0 Significance Statement For decades, any involvement of circulating immune cells in CNS repair was completely denied.”
BackgroundInfluentialWetzler, C., Kämpfer, H., Stallmeyer, B., Pfeilschifter, J., & Frank, S. (2000) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.2000.00029.x · Cited by 584
Dealing with danger in the CNS: the response of the immune system to injury
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Functional differences between microglia and monocytes after ischemic stroke
Ritzel, R. M., Patel, A. R., Grenier, J. M., Crapser, J., Verma, R., Jellison, E. R., & McCullough, L. D. (2015) · Journal of Neuroinflammation · doi:10.1186/s12974-015-0329-1 · Cited by 295
Macrophages prevent hemorrhagic infarct transformation in murine stroke models
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Cited by
Signaling pathways involved in ischemic stroke: molecular mechanisms and therapeutic interventions
Qin, C., Yang, S., Chu, Y.-H., Zhang, H., Pang, X.-W., Chen, L., Zhou, L.-Q., Chen, M., Tian, D.-S., & Wang, W. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01064-1 · Cited by 939
Immune responses to stroke: mechanisms, modulation, and therapeutic potential.
Iadecola, C., Buckwalter, M. S., & Anrather, J. (2020) · Journal of Clinical Investigation · doi:10.1172/jci135530 · Cited by 853
Neuroimmunology of Traumatic Brain Injury: Time for a Paradigm Shift
Jassam, Y. N., Izzy, S., Whalen, M., McGavern, D. B., & El Khoury, J. (2017) · Neuron · doi:10.1016/j.neuron.2017.07.010 · Cited by 799
ApoE4: an emerging therapeutic target for Alzheimer’s disease
Safieh, M., Korczyn, A. D., & Michaelson, D. M. (2019) · BMC Medicine · doi:10.1186/s12916-019-1299-4 · Cited by 449
Systemic inflammation impairs microglial Aβ clearance through NLRP3 inflammasome
Tejera, D., Mercan, D., Sanchez‐Caro, J. M., Hanan, M., Greenberg, D., Soreq, H., Latz, E., Golenbock, D., & Heneka, M. T. (2019) · The EMBO Journal · doi:10.15252/embj.2018101064 · Cited by 351
Metadata
- Authors
- Wattananit, S., Tornero, D., Graubardt, N., Memanishvili, T., Monni, E., Tatarishvili, J., Miskinyte, G., Ge, R., Ahlenius, H., Lindvall, O., Schwartz, M., & Kokaia, Z.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2016-04-13
- Volume
- 36
- Issue
- 15
- Pages
- 4182-4195
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- OpenAlex
- W2340192487
- Cited by
- 353
- References
- 12
- FWCI
- 17.96
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Wattananit, S., Tornero, D., Graubardt, N., Memanishvili, T., Monni, E., Tatarishvili, J., Miskinyte, G., Ge, R., Ahlenius, H., Lindvall, O., Schwartz, M., & Kokaia, Z. (2016). Monocyte-Derived Macrophages Contribute to Spontaneous Long-Term Functional Recovery after Stroke in Mice. The Journal of Neuroscience. https://doi.org/10.1523/jneurosci.4317-15.2016
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
