Cited by 86Intracerebral and Subarachnoid Hemorrhage ResearchNeuroinflammation and Neurodegeneration MechanismsExtracellular vesicles in disease

CX3CL1/CX3CR1 axis attenuates early brain injury via promoting the delivery of exosomal microRNA-124 from neuron to microglia after subarachnoid hemorrhage

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Chen, Xiao, Jiang, Ming, Li, Haiying, Wang, Yang, Shen, Haitao, Li, Xiang, Zhang, Yunhai, Wu, Jiang +2 more·2020·Journal of Neuroinflammation

Abstract

Background: Microglial activation-mediated neuroinflammation is a major contributor to early brain injury (EBI) after subarachnoid hemorrhage (SAH). MicroRNA-124 (miR-124) is the most abundant miRNAs in the central nervous system (CNS) and plays a vital role in microglial activation by targeting protein CCAAT-enhancer-binding protein α (C/EBPα). It has been reported that the CX3CL1/CX3CR1 axis is involved in the delivery of miR-124 from neurons to microglia. Methods: An experimental rat SAH model was established by injecting autologous arterial blood into the prechiasmatic cistern, and cultured primary neurons and microglia were exposed to oxyhemoglobin to mimic SAH in vitro. We additionally exploited specific expression plasmids encoding CX3CL1 and CX3CR1. Results: We observed significant decreases in CX3CL1 and CX3CR1 in the brain tissues of SAH patients. We also observed decreases in the levels of CX3CL1 in neurons and CX3CR1 in microglia after SAH in rats. Moreover, microglia exhibited an activated phenotype with macrophage-like morphology and high levels of CD45 and major histocompatibility complex (MHC) class II after SAH. After overexpression of CX3CL1/CX3CR1, the level of CD45 and MHC class II and the release of inflammatory factors tumor necrosis factor α, interleukin 1α and complement 1q were significantly decreased. There was also increased neuronal degeneration and behavior dysfunction after SAH, both of which were inhibited by CX3CL1/CX3CR1 overexpression. Additionally, we found that the delivery of exosomal miR-124 from neurons to microglia was significantly reduced after SAH, accompanied by an increase in C/EBPα expression, and was inhibited by CX3CL1/CX3CR1 overexpression. In conclusion, the CX3CL1/CX3CR1 axis may play protective roles after SAH by promoting the delivery of exosomal miR-124 to microglia and attenuate microglial activation and neuroinflammation. Conclusions: CX3CL1/CX3CR1 axis may be a potential intervention target for the inhibition of SAH-induced EBI by promoting exosome transport of miR-124 to microglia.

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Authors
Chen, X., Jiang, M., Li, H., Wang, Y., Shen, H., Li, X., Zhang, Y., Wu, J., Yu, Z., & Chen, G.
Affiliations
  • First Affiliated Hospital of Soochow University (CN)
  • University of Science and Technology of China (CN)
  • Chinese Academy of Sciences (CN)
Corresponding author
  • Yu, Zhengquan
  • Chen, Gang
Venue
Journal of Neuroinflammation
Published
2020-07-14
Volume
17
Issue
1
Pages
209-209
ISSN
1742-2094 (ISSN-L)
OpenAlex
W3043084564
Cited by
85
References
63
Citations by year
2026: 9 · 2025: 9 · 2024: 18 · 2023: 18 · 2022: 22 · 2021: 9
FWCI
6.34
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuroinflammation (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 (81830036, 81771255, 81971106)
  • National Key R&D Program of China (2017YFC0110304)
  • Natural Science Foundation of Jiangsu Province (BK20170363, BK20180204)
  • Gusu Health Personnel Training Project (GSWS2019030)
Topics
  • Health Sciences › Medicine › Neurology › Intracerebral and Subarachnoid Hemorrhage Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
Keywords
subarachnoid hemorrhage, early brain injury, neuron-microglia communication, microglial activation, neuroinflammation, C/EBPα, neuroprotection, MHC class II, CD45, TNF-α, interleukin-1 alpha, neurodegeneration
MeSH terms
CX3C Chemokine Receptor 1, Adult, Aged, Aged, 80 and over, Animals, Brain Injuries, Cells, Cultured, Female, Humans, Male, Middle Aged, Neurons, Subarachnoid Hemorrhage, Rats, Sprague-Dawley, Microglia, Gene Transfer Techniques, MicroRNAs, Rats, Chemokine CX3CL1, Exosomes

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