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Updated: May 30, 2026
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Modulating neuroinflammation and cognitive function in postoperative cognitive dysfunction via CCR5-GPCRs-Ras-MAPK
Zheng Qi1, Junlin Peng1, Haitao Wang1
1Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Aims:
Postoperative cognitive dysfunction (POCD) is prevalent among the elderly, characterized primarily by cognitive decline after surgery. This study aims to explore how extracellular vesicles (EVs) derived from BV2 microglial cells, with and without the C-C chemokine receptor type 5 (CCR5), affect neuroinflammation, neuronal integrity, and cognitive function in a POCD mouse model.
Methods:
We collected EVs from LPS-stimulated BV2 cells expressing CCR5 (EVsM1) and from BV2 cells with CCR5 knockdown (EVsM1-CCR5). These were administered to POCD-induced mice. Protein interactions between CCR5, G-protein-coupled receptors (GPCRs), and Ras were analyzed using structure-based docking and co-immunoprecipitation (Co-IP). We assessed the phosphorylation of p38 and Erk, the expression of synaptic proteins PSD95 and MAP2, and conducted Morris Water Maze tests to evaluate cognitive function.
Results:
Structure-based docking and Co-IP confirmed interactions between CCR5, GPR, and Ras, suggesting a CCR5-GPCRs-Ras-MAPK pathway involvement in neuroinflammation. EVsM1 heightened neuroinflammation, reduced synaptic integrity, and impaired cognitive function in POCD mice. In contrast, EVsM1-CCR5 reduced neuroinflammatory markers, preserved synaptic proteins, enhanced dendritic spine structure, and improved cognitive outcomes.
Conclusion:
EVsM1 induced neuroinflammation via the CCR5-GPCRs-Ras-MAPK pathway, with EVsM1-CCR5 showing protective effects on POCD progression, suggesting a new therapeutic strategy for POCD management via targeted modification of microglial EVs.
Insights
Extracellular vesicles (EVs) from microglia with C-C chemokine receptor type 5 (CCR5) worsen postoperative cognitive dysfunction (POCD). Modifying these EVs to reduce CCR5 protects against POCD, offering a new therapeutic strategy.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Postoperative cognitive dysfunction (POCD) is a common and serious condition affecting elderly patients after surgery.
- Microglia play a critical role in neuroinflammation and neuronal integrity, processes implicated in POCD.
- Extracellular vesicles (EVs) are emerging as key mediators of intercellular communication in the central nervous system.
Purpose of the Study:
- To investigate the role of C-C chemokine receptor type 5 (CCR5) on microglial extracellular vesicles (EVs) in the pathogenesis of POCD.
- To determine how EVs derived from BV2 microglial cells with or without CCR5 influence neuroinflammation, neuronal integrity, and cognitive function in a POCD mouse model.
Main Methods:
- EVs were collected from BV2 microglial cells expressing CCR5 (EVsM1) and from BV2 cells with CCR5 knockdown (EVsM1-CCR5).
- These EVs were administered to mice subjected to POCD induction.
- Protein interactions, neuroinflammation markers, synaptic protein expression, dendritic spine morphology, and cognitive function (Morris Water Maze) were assessed.
Main Results:
- Interactions between CCR5, G-protein-coupled receptors (GPCRs), and Ras were confirmed, implicating the CCR5-GPCRs-Ras-MAPK pathway in neuroinflammation.
- EVsM1 exacerbated neuroinflammation, reduced synaptic integrity, and impaired cognitive function in POCD mice.
- Conversely, EVsM1-CCR5 attenuated neuroinflammation, preserved synaptic proteins and dendritic spines, and improved cognitive performance.
Conclusions:
- Microglial EVs mediate neuroinflammation and cognitive decline in POCD through the CCR5-GPCRs-Ras-MAPK pathway.
- Reducing CCR5 expression on microglial EVs confers neuroprotection and ameliorates POCD.
- Targeted modification of microglial EVs represents a promising therapeutic avenue for managing POCD.
