Blocking postsynaptic density-93 binding to C-X3-C motif chemokine ligand 1 promotes microglial phenotypic transformation during acute ischemic stroke

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.

重组组织型纤溶酶原激活剂动脉溶栓联合血管内治疗对早期急性脑梗死的疗效观察

目的探析重组组织型纤溶酶原激活剂(rt-PA)动脉溶栓联合血管内治疗发病时间6 h内急性脑梗死(ACI)的临床疗效。方法选取2017年2月—2019年3月徐州医科大学第二附属医院收治的发病<6 h ACI患者160例,按照患者及家属对治疗方案的选择意愿分组,观察组采取rt-PA+血管内支架成形术治疗,对照组采取rt-PA动脉溶栓,每组80例。比较两组术前、术后24 h、7 d、3个月NIHSS评分、ADL评分,观察患者血管再通情况,记录不良反应及临床预后。结果两组不同时间点的NIHSS评分和ADL评分有差异(P<0.05),两组的NIHSS评分和ADL评分有差异(P<0.05),两组的NIHSS评分和ADL评分变化趋势有差异(P<0.05)。观察组血管再通率为100%(完全再通76例,部分再通5例),对照组血管再通率为95%(完全再通62例,部分再通14例,未通4例),两组血管再通率比较差异有统计学意义(P<0.05)。观察组术后仅2例再发脑梗死,未出现死亡病例,对照组术后12例再发脑梗死,且4例因脑梗死伴脑疝死亡,两组预后比较差异有统计学意义(P<0.05)。结论ACI发病6 h内采取rt-PA联合血管内支架成形术治疗可提高溶栓效果,促进神经功能恢复,改善预后,安全性良好。但受血管内介入治疗技术及术前准备耗时等因素的影响,可能会延长溶栓处理时间,抵消早期动脉溶栓的优势,建议视患者病情制订个体化溶栓治疗方案。