IRCCS Fondazione Don Carlo Gnocchi ONLUS, 20148 Milano, Italy.
Dipartimento di Medicina Molecolare e Traslazionale, Università degli Studi di Brescia, 25122 Brescia, Italy.
Int J Mol Sci. 2023 Apr 27;24(9):7937. doi: 10.3390/ijms24097937.
The inflammatory, reparative and regenerative mechanisms activated in ischemic stroke patients immediately after the event cooperate in the response to injury, in the restoration of functions and in brain remodeling even weeks after the event and can be sustained by the rehabilitation treatment. Nonetheless, patients' response to treatments is difficult to predict because of the lack of specific measurable markers of recovery, which could be complementary to clinical scales in the evaluation of patients. Considering that Extracellular Vesicles (EVs) are carriers of multiple molecules involved in the response to stroke injury, in the present study, we have identified a panel of EV-associated molecules that (i) confirm the crucial involvement of EVs in the processes that follow ischemic stroke, (ii) could possibly profile ischemic stroke patients at the beginning of the rehabilitation program, (iii) could be used in predicting patients' response to treatment. By means of a multiplexing Surface Plasmon Resonance imaging biosensor, subacute ischemic stroke patients were proven to have increased expression of vascular endothelial growth factor receptor 2 (VEGFR2) and translocator protein (TSPO) on the surface of small EVs in blood. Besides, microglia EVs and endothelial EVs were shown to be significantly involved in the intercellular communications that occur more than 10 days after ischemic stroke, thus being potential tools for the profiling of patients in the subacute phase after ischemic stroke and in the prediction of their recovery.
在缺血性中风事件发生后立即,激活的炎症、修复和再生机制在损伤反应、功能恢复和脑重塑中协同作用,甚至在事件发生后数周内仍然可以通过康复治疗维持。尽管如此,由于缺乏恢复的具体可测量标志物,患者对治疗的反应难以预测,这些标志物可以在评估患者时与临床量表互补。考虑到细胞外囊泡(EVs)是参与中风损伤反应的多种分子的载体,在本研究中,我们已经鉴定了一组与 EV 相关的分子,这些分子 (i) 证实了 EVs 在缺血性中风后发生的过程中的关键作用,(ii) 可能在康复计划开始时对缺血性中风患者进行分类,(iii) 可用于预测患者对治疗的反应。通过多重表面等离子体共振成像生物传感器,证明亚急性缺血性中风患者血液中小 EV 表面的血管内皮生长因子受体 2 (VEGFR2) 和转位蛋白 (TSPO) 的表达增加。此外,小胶质细胞 EV 和内皮细胞 EV 被证明在缺血性中风后 10 天以上的细胞间通讯中显著参与,因此是缺血性中风后亚急性期患者分类和预测其恢复的潜在工具。