We previously reported that postsynaptic density-93 mediates neuron-microglia crosstalk by interacting with amino acids 357–395 of C-X3-C motif chemokine ligand 1(CX3 CL1) to induce microglia polarization. More impor...We previously reported that postsynaptic density-93 mediates neuron-microglia crosstalk by interacting with amino acids 357–395 of C-X3-C motif chemokine ligand 1(CX3 CL1) to induce microglia polarization. More importantly, the peptide Tat-CX3 CL1(comprising amino acids 357–395 of CX3 CL1) disrupts the interaction between postsynaptic density-93 and CX3 CL1, reducing neurological impairment and exerting a protective effect in the context of acute ischemic stroke. However, the mechanism underlying these effects remains unclear. In the current study, we found that the pro-inflammatory M1 phenotype increased and the anti-inflammatory M2 phenotype decreased at different time points. The M1 phenotype increased at 6 hours after stroke and peaked at 24 hours after perfusion, whereas the M2 phenotype decreased at 6 and 24 hours following reperfusion. We found that the peptide Tat-CX3 CL1(357–395 aa) facilitates microglial polarization from M1 to M2 by reducing the production of soluble CX3 CL1. Furthermore, the a disintegrin and metalloprotease domain 17(ADAM17) inhibitor GW280264 x, which inhibits metalloprotease activity and prevents CX3 CL1 from being sheared into its soluble form, facilitated microglial polarization from M1 to M2 by inhibiting soluble CX3 CL1 formation. Additionally, Tat-CX3 CL1(357–395 aa) attenuated long-term cognitive deficits and improved white matter integrity as determined by the Morris water maze test at 31–34 days following surgery and immunofluorescence staining at 35 days after stroke, respectively. In conclusion, Tat-CX3 CL1(357–395 aa) facilitates functional recovery after ischemic stroke by promoting microglial polarization from M1 to M2. Therefore, the Tat-CX3 CL1(357–395 aa) is a potential therapeutic agent for ischemic stroke.展开更多
目的探讨泛免疫炎症值(pan-immune inflammation value,PIV)和白细胞分化抗原93(cluster of Differentiation 93,CD93)在病毒性脑炎(viral encephalitis,VE)、自身免疫性脑炎(autoimmune encephalitis,AE)中的应用价值。方法回顾性选取2...目的探讨泛免疫炎症值(pan-immune inflammation value,PIV)和白细胞分化抗原93(cluster of Differentiation 93,CD93)在病毒性脑炎(viral encephalitis,VE)、自身免疫性脑炎(autoimmune encephalitis,AE)中的应用价值。方法回顾性选取2023年1月-2025年1月在南阳市中心医院就诊的160例急性期脑炎患者,其中VE患者74例,纳入VE组,AE患者86例,纳入AE组。比较两组临床特征及PIV、CD93水平,采用受试者工作特征(receiver operating characteristic curve,ROC)曲线评价各项指标鉴别AE和VE的效能。结果两组在发病形式、发病半球、前驱症状、影像学累及颞叶等临床体征上差异有统计学意义(P<0.05);VE组血清CD93、淋巴细胞绝对值显著低于AE组,中性粒细胞绝对值、单核细胞绝对值、PIV值显著高于AE组(P<0.05);两组血小板计数水平相当(P>0.05);多因素logistic回归分析显示,发病形式、前驱症状、血清CD93以及PIV值均是鉴别VE、AE的有效指标(P<0.05);ROC结果显示,单一指标诊断时,血清CD93的曲线下面积(area under the curve,AUC)高于PIV(0.936 vs 0.689),诊断的敏感度及特异度均高于PIV(85.29%vs 75.00%;90.27%vs 54.00%),二者联合诊断效能显著高于单一诊断,其AUC值、敏感度、特异度分别为0.976、95.00%、88.00%(P<0.05)。结论血清CD93和PIV是鉴别VE与AE的有效指标,二者联合诊断效能显著优于单一指标,敏感度和特异度均较高。展开更多
基金supported by the National Natural Science Foundation of China,Nos. 82071304 (to QXZ), 81671149 (to QXZ),and 81971179 (to XML)the Natural Science Foundation of Jiangsu Province,Nos. BK20191463 (to XML) and BK20161167 (to QXZ)。
文摘We previously reported that postsynaptic density-93 mediates neuron-microglia crosstalk by interacting with amino acids 357–395 of C-X3-C motif chemokine ligand 1(CX3 CL1) to induce microglia polarization. More importantly, the peptide Tat-CX3 CL1(comprising amino acids 357–395 of CX3 CL1) disrupts the interaction between postsynaptic density-93 and CX3 CL1, reducing neurological impairment and exerting a protective effect in the context of acute ischemic stroke. However, the mechanism underlying these effects remains unclear. In the current study, we found that the pro-inflammatory M1 phenotype increased and the anti-inflammatory M2 phenotype decreased at different time points. The M1 phenotype increased at 6 hours after stroke and peaked at 24 hours after perfusion, whereas the M2 phenotype decreased at 6 and 24 hours following reperfusion. We found that the peptide Tat-CX3 CL1(357–395 aa) facilitates microglial polarization from M1 to M2 by reducing the production of soluble CX3 CL1. Furthermore, the a disintegrin and metalloprotease domain 17(ADAM17) inhibitor GW280264 x, which inhibits metalloprotease activity and prevents CX3 CL1 from being sheared into its soluble form, facilitated microglial polarization from M1 to M2 by inhibiting soluble CX3 CL1 formation. Additionally, Tat-CX3 CL1(357–395 aa) attenuated long-term cognitive deficits and improved white matter integrity as determined by the Morris water maze test at 31–34 days following surgery and immunofluorescence staining at 35 days after stroke, respectively. In conclusion, Tat-CX3 CL1(357–395 aa) facilitates functional recovery after ischemic stroke by promoting microglial polarization from M1 to M2. Therefore, the Tat-CX3 CL1(357–395 aa) is a potential therapeutic agent for ischemic stroke.
文摘目的探讨泛免疫炎症值(pan-immune inflammation value,PIV)和白细胞分化抗原93(cluster of Differentiation 93,CD93)在病毒性脑炎(viral encephalitis,VE)、自身免疫性脑炎(autoimmune encephalitis,AE)中的应用价值。方法回顾性选取2023年1月-2025年1月在南阳市中心医院就诊的160例急性期脑炎患者,其中VE患者74例,纳入VE组,AE患者86例,纳入AE组。比较两组临床特征及PIV、CD93水平,采用受试者工作特征(receiver operating characteristic curve,ROC)曲线评价各项指标鉴别AE和VE的效能。结果两组在发病形式、发病半球、前驱症状、影像学累及颞叶等临床体征上差异有统计学意义(P<0.05);VE组血清CD93、淋巴细胞绝对值显著低于AE组,中性粒细胞绝对值、单核细胞绝对值、PIV值显著高于AE组(P<0.05);两组血小板计数水平相当(P>0.05);多因素logistic回归分析显示,发病形式、前驱症状、血清CD93以及PIV值均是鉴别VE、AE的有效指标(P<0.05);ROC结果显示,单一指标诊断时,血清CD93的曲线下面积(area under the curve,AUC)高于PIV(0.936 vs 0.689),诊断的敏感度及特异度均高于PIV(85.29%vs 75.00%;90.27%vs 54.00%),二者联合诊断效能显著高于单一诊断,其AUC值、敏感度、特异度分别为0.976、95.00%、88.00%(P<0.05)。结论血清CD93和PIV是鉴别VE与AE的有效指标,二者联合诊断效能显著优于单一指标,敏感度和特异度均较高。
