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Updated: Dec 26, 2025
Assessing Retinal Microglial Phagocytic Function In Vivo Using a Flow Cytometry-based Assay
Published on: October 18, 2016
P2Y6 receptor inhibition aggravates ischemic brain injury by reducing microglial phagocytosis
Ruo-Xue Wen1, Hui Shen1, Shu-Xian Huang1
1Shanghai JiaoTong Affiliated Sixth People's Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
Introduction:
Clearance of damaged cells and debris is beneficial for the functional recovery after ischemic brain injury. However, the specific phagocytic receptor that mediates microglial phagocytosis after ischemic stroke is unknown.
Aim:
To investigate whether P2Y6 receptor-mediated microglial phagocytosis is beneficial for the debris clearance and functional recovery after ischemic stroke.
Results:
The expression of the P2Y6 receptor in microglia increased within 3 days after transient middle cerebral artery occlusion. Inhibition of microglial phagocytosis by the selective inhibitor MRS2578 enlarged the brain atrophy and edema volume after ischemic stroke, subsequently aggravated neurological function as measured by modified neurological severity scores and Grid walking test. MRS2578 treatment had no effect on the expression of IL-1α, IL-1β, IL-6, IL-10, TNF-α, TGF-β, and MPO after ischemic stroke. Finally, we found that the expression of myosin light chain kinase decreased after microglial phagocytosis inhibition in the ischemic mouse brain, which suggested that myosin light chain kinase was involved in P2Y6 receptor-mediated phagocytosis.
Conclusion:
Our results indicate that P2Y6 receptor-mediated microglial phagocytosis plays a beneficial role during the acute stage of ischemic stroke, which can be a therapeutic target for ischemic stroke.
Insights
The P2Y6 receptor facilitates microglial phagocytosis, crucial for clearing debris after ischemic stroke. Inhibiting this receptor worsens brain injury and neurological deficits, highlighting its therapeutic potential.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Clearance of cellular debris is vital for recovery following ischemic brain injury.
- The specific microglial phagocytic receptor involved in post-stroke debris clearance remains unidentified.
Purpose of the Study:
- To investigate the role of the P2Y6 receptor in microglial phagocytosis after ischemic stroke.
- To determine if P2Y6 receptor-mediated phagocytosis benefits debris clearance and functional recovery.
Main Methods:
- Transient middle cerebral artery occlusion model in mice.
- Administration of a selective P2Y6 receptor inhibitor (MRS2578).
- Assessment of brain atrophy, edema, neurological function, and inflammatory markers.
Main Results:
- P2Y6 receptor expression increased in microglia within 3 days post-occlusion.
- Inhibition of microglial phagocytosis via MRS2578 exacerbated brain atrophy, edema, and neurological deficits.
- Myosin light chain kinase expression decreased upon phagocytosis inhibition, suggesting its involvement in P2Y6-mediated phagocytosis.
Conclusions:
- P2Y6 receptor-mediated microglial phagocytosis plays a beneficial role in the acute phase of ischemic stroke.
- Targeting the P2Y6 receptor presents a potential therapeutic strategy for ischemic stroke treatment.
