From the Stroke Unit (J.S.-F., A.G., F.S., C.M., B.R., G.C., L.C.), Centro Hospitalar e Universitário de Coimbra; Faculdade de Medicina da Universidade de Coimbra (J.S.-F., M.C.-B., L.F., L.C.); Centro de Neurociências e Biologia Celular (J.S.-F., S.A., A.C.G., L.F.); Instituto de Ciências Nucleares Aplicadas à Saúde (C.N., M.C., C.F., A.A., M.C.-B.), Coimbra; and Genomics Unit, Biocant-Biotechnology Innovation Center (S.S., A.C.G.), Cantanhede, Portugal.
Neurology. 2018 Jan 9;90(2):e127-e134. doi: 10.1212/WNL.0000000000004801. Epub 2017 Dec 13.
To study the association among endothelial progenitor cells (EPCs), subacute blood-brain barrier (BBB) permeability, and clinical outcome after ischemic stroke, determining the micro RNAs of EPCs responsible for good clinical outcome.
We included consecutive patients with nonlacunar acute ischemic strokes in the territory of a middle cerebral artery and ages between 18 and 80 years. Clinical outcome was defined as modified Rankin Scale score at 3 months. Neuroimaging was performed at day 0 and 7 by MRI, including assessment of BBB permeability by dynamic contrast enhancement. EPCs were isolated from peripheral venous blood, quantified, and submitted to in vitro functional tests, including migratory and angiogenic assays. Stroke hemodynamics were evaluated serially by ultrasound. Statistical significance was set at < 0.05.
We included 45 patients; mean age was 70.0 ± 10.0 years. The in vitro functional properties of EPCs were associated with BBB permeability, particularly at day 7. The number of each EPC subset at both timepoints was not associated with BBB permeability. Permeability of BBB at day 7 was independently associated with improved clinical outcome (odds ratio 0.897; 95% confidence interval 0.816-0.986; = 0.025). The EPCs (CD34+ cell subset) of patients with good clinical outcome showed 24 differentially expressed miRNAs, with a common effect on adherens junction pathway.
The functional properties of EPCs are associated with enhanced subacute permeability of BBB and improved clinical outcome after acute ischemic stroke.
研究内皮祖细胞（EPC）、亚急性血脑屏障（BBB）通透性与缺血性脑卒中后临床结局之间的关系，确定与良好临床结局相关的 EPC 微小 RNA。
我们纳入了连续的大脑中动脉区域非腔隙性急性缺血性脑卒中患者，年龄在 18 至 80 岁之间。临床结局定义为 3 个月时的改良 Rankin 量表评分。神经影像学在第 0 天和第 7 天进行，包括通过动态对比增强评估 BBB 通透性。从外周静脉血中分离、定量 EPC，并进行体外功能测试，包括迁移和血管生成测定。通过超声连续评估卒中血流动力学。统计显著性设为 < 0.05。
我们纳入了 45 例患者，平均年龄为 70.0 ± 10.0 岁。EPC 的体外功能特性与 BBB 通透性相关，尤其是在第 7 天。两个时间点的每个 EPC 亚群的数量与 BBB 通透性无关。第 7 天 BBB 的通透性与改善的临床结局独立相关（比值比 0.897；95%置信区间 0.816-0.986；P=0.025）。临床结局良好的患者的 EPC（CD34+细胞亚群）显示出 24 个差异表达的 miRNA，对黏附连接途径具有共同作用。
EPC 的功能特性与急性缺血性脑卒中后亚急性 BBB 通透性增强和临床结局改善相关。
