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- W3178730132 abstract "Abstract BackgroundPostsynaptic density 93 (PSD-93) plays an important role in ischemic brain injury by mediating neurotoxicity and neuroinflammation. Different photypes of microglia perform an important role in ischemic crerbral injury and repair. Blocking the combination of PSD-93 and CX3C chemokine ligand 1 (CX3CL1) is beneficial in acute ischemic stroke, but the underlying mechanism remains unclear. MethodsMiddle cerebral artery occlusion (MCAO) model was established in male C57BL/6 mice. The peptide Tat-CX3CL1 (357-395aa) which disturbing the interaction of PSD-93 and CX3CL1 was used in this study to explore the mechanism of its neuroprotective effect. The production and secretion of cytokines associated with M1 and M2 type of microglia was detected by PCR and ELISA, respectively. Neurologic damage was evaluated by behavior, triphenyl tetrazolium chloride staining, and brain water content. MBP and SMI32 double immunostaining were used to detect white matter injury and double staining for Iba1 and CD68 to assess M1 type microglia polarization. ResultsThe cytokines level of M1 phenotype cytokines was increased at 6 h after stroke and peaked at 24 h after perfusion. However, the cytokines level of M2 phenotype was decreased at 6 h and 24 h following reperfusion. The Tat-CX3CL1 (357-395aa) facilitated microglial polarization from M1 type to M2 type by reducing the production of soluble CX3CL1. Furthermore, ADAM17 inhibitor GW280264x could restrain the polarization of microglia from M1 to M2 via reducing soluble CX3CL1 formation. Moreover, Tat-CX3CL1 (357-395aa) attenuated long-term cognitive deficits and improved white matter integrity. ConclusionsBlocking the binding between CX3CL1 and PSD-93 by Tat-CX3CL1 (357-395aa) could facilitate the functional recovery after ischemic stroke by promoting M1 to M2 microglial polarization transformation. Tat-CX3CL1 (357-395aa) may be a potent agent for ischemic stroke treatment." @default.
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- W3178730132 date "2021-07-14" @default.
- W3178730132 modified "2023-09-27" @default.
- W3178730132 title "Blocking PSD-93-CX3CL1 Interaction Promotes the Phenotypic Transformation of Microglia During Acute Ischemic Stroke" @default.
- W3178730132 doi "https://doi.org/10.21203/rs.3.rs-687096/v1" @default.
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