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Cited by 100Neuroinflammation and Neurodegeneration MechanismsNeurogenesis and neuroplasticity mechanismsNeurological Disease Mechanisms and Treatments

CD11c(+) microglia promote white matter repair after ischemic stroke

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Jia, Junqiu, Zheng, Lili, Ye, Lei, Chen, Jian, Shu, Shu, Xu, Siyi, Bao, Xinyu, Xia, Shengnan +3 more·2023·Cell Death & Disease
DOI 10.1038/s41419-023-05689-0PMC PMC9958101
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Abstract

Ischemic stroke leads to white matter damage and neurological deficits. However, the characteristics of white matter injury and repair after stroke are unclear. Additionally, the precise molecular communications between microglia and white matter repair during the stroke rehabilitation phase remain elusive. In this current study, MRI DTI scan and immunofluorescence staining were performed to trace white matter and microglia in the mouse transient middle cerebral artery occlusion (tMCAO) stroke model. We found that the most serious white matter damage was on Day 7 after the ischemic stroke, then it recovered gradually from Day 7 to Day 30. Parallel to white matter recovery, we observed that microglia centered around the damaged myelin sheath and swallowed myelin debris in the ischemic areas. Then, microglia of the ischemic hemisphere were sorted by flow cytometry for RNA sequencing and subpopulation analysis. We found that CD11c + microglia increased from Day 7 to Day 30, demonstrating high phagocytotic capabilities, myelin-supportive genes, and lipid metabolism associated genes. CD11c + microglia population was partly depleted by the stereotactic injecting of rAAV2/6M-taCasp3 (rAAV2/6M-CMV-DIO-taCasp3-TEVp) into CD11c-cre mice. Selective depletion of CD11c + microglia disrupted white matter repair, oligodendrocyte maturation, and functional recovery after stroke by Rotarod test, Adhesive Removal test, and Morris Water Maze test. These findings suggest that spontaneous white matter repair occurs after ischemic stroke, while CD11c + microglia play critical roles in this white matter restorative progress.

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Sorted by citations

Authors
Jia, J., Zheng, L., Ye, L., Chen, J., Shu, S., Xu, S., Bao, X., Xia, S., Liu, R., Xu, Y., & Zhang, M.
Affiliations
  • Nanjing Drum Tower Hospital (CN)
  • Jiangsu University (CN)
  • Nanjing Brain Hospital (CN)
Corresponding author
  • Xu, Yun
  • Zhang, Meijuan
ORCID
Venue
Cell Death & Disease
Publisher
Springer Science and Business Media LLC
Published
2023-02-24
Volume
14
Issue
2
Pages
156-156
ISSN
2041-4889 (ISSN-L)
DOI
10.1038/s41419-023-05689-0
PMC
PMC9958101
OpenAlex
W4321782973
Cited by
100
References
8
Citations by year
2026: 35 · 2025: 42 · 2024: 19 · 2023: 4
FWCI
10.31
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Death and Disease (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Natural Science Foundation of China (81971112, 82130036, 81920208017)
  • Natural Science Foundation of Jiangsu Province (BK20191116)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Keywords
white matter repair, ischemic stroke, myelin phagocytosis, microglial depletion, oligodendrocyte maturation, functional recovery, lipid metabolism, myelin debris, stroke rehabilitation, transient middle cerebral artery occlusion
MeSH terms
Ischemic Stroke, Animals, Microglia, Infarction, Middle Cerebral Artery, Stroke, Mice, White Matter

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