Abstract
IntroductionClearance 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.AimTo investigate whether P2Y6 receptor‐mediated microglial phagocytosis is beneficial for the debris clearance and functional recovery after ischemic stroke.ResultsThe 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.ConclusionOur 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.
Highlights
Ischemic stroke is one of the leading causes of death and adult disability around the world, which leads to massive cell death and complex pathological changes [1,2,3]
MRS2578 treatment had no effect on the expression of IL-1α, IL-1β, IL-6, IL-10, tumor necrosis factor-α (TNF-α), TGF-β and MPO after ischemic stroke, which suggested that it had no effect on the inflammation in the brain
We found that the expression of myosin light chain kinase decreased after microglial phagocytosis inhibition in ischemic mice, which suggested that myosin light chain kinase was involved in P2Y6 receptor mediated phagocytosis
Summary
Ischemic stroke is one of the leading causes of death and adult disability around the world, which leads to massive cell death and complex pathological changes [1,2,3]. The innate immune cells in the central nervous system, firstly respond to the injury and are recruited to the infarct area after ischemic stroke [5,6,7]. Activated microglia could enhance proliferation, phagocytosis, and release a series of pro-inflammatory or anti-inflammatory cytokines depending on the different phenotypes [8,9,10]. On the one hand, activated microglia can secrete a series of pro-inflammatory cytokines to aggravate the destruction of blood-brain barrier and tissue damage [4, 11]. Clearance of damaged cells is beneficial for the functional recovery after brain injury. Phagocytosis of tissue and cell debris is an important function of microglia during the development and pathological diseases. Which specific phagocytic receptor mediates microglial phagocytosis after ischemic stroke is obscure
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