Open AccessP2Y6 receptor inhibition aggravates ischemic brain injury by reducing microglial phagocytosis
Author(s) -
Wen RuoXue,
Shen Hui,
Huang ShuXian,
Wang LiPing,
Li ZongWei,
Peng Peng,
Mamtilahun Muyassar,
Tang YaoHui,
Shen FanXia,
Tian HengLi,
Yang GuoYuan,
Zhang ZhiJun
Publication year - 2020
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.13296
Subject(s) - phagocytosis , microglia , receptor , neuroprotection , stroke (engine) , medicine , pharmacology , neuroscience , immunology , biology , inflammation , mechanical engineering , engineering
Abstract 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.