Social isolation (SI) increases ischemic injury and significantly delays recovery after experimental stroke. Changes in circulating microRNAs (miRNAs) have been implicated in several neurological disorders, including stroke. However, potential biomarkers to elucidate the mechanisms that underlie the detrimental effects of post-stroke isolation are unknown. Aged C57BL/6 male and female mice (18–20 months) were subjected to a 60-min middle cerebral artery occlusion followed by reperfusion and were assigned to either isolation (SI) or continued pair housing (PH) immediately after stroke. On day 15, mice were sacrificed, and plasma samples were collected for miRNAome analysis. Top candidate miRNAs and their biological functions were identified using integrated bioinformatics. The miRNAome analysis revealed a total of 21 differentially expressed miRNAs across both sexes with fold change of 3 or higher. Within the female cohort, miR-206-3p, -376a-3p, -34b-5p, -133a-5p, -466f, and -671-3p were highly altered relative to the PH housing condition. Similarly in males, miR-376c-3p, -181d-5p, -712-5p, -186-5p, -21a-3p, -30d-3p, -495-3p, -669c-5p, -335-5p, -429-3p, -31-3p, and -217-5p were identified. Following Kyoto Encyclopedia of Genes and Genomes analysis, the identified miRNAs effected distinct subset of pathways within sexes. Interactional network analysis revealed miR-495-3p (male) and miR-34b-5p (female) as pivotal nodes that targeted the largest subset of genes. We identified several sex-specific miRNAs as candidate biomarkers for post-stroke SI in aged male and female mice. Additionally, these results suggest that there is potential to use plasma-based circulating miRNAs as a source of novel biomarkers to identify biological pathways involved in post-stroke SI.

社会隔离 (SI) 会增加缺血性损伤并显着延迟实验性中风后的恢复。循环 microRNA (miRNA) 的变化与几种神经系统疾病有关，包括中风。然而，阐明中风后隔离有害影响机制的潜在生物标志物尚不清楚。对老年 C57BL/6 雄性和雌性小鼠（18-20 个月）进行 60 分钟的大脑中动脉闭塞，然后再灌注，并在中风后立即被分配到隔离 (SI) 或继续配对住房 (PH)。在第 15 天，处死小鼠，收集血浆样本进行 miRNAome 分析。使用综合生物信息学鉴定出最佳候选 miRNA 及其生物学功能。miRNAome 分析显示，共有 21 个差异表达的 miRNAs 跨性别，倍数变化为 3 或更高。在女性队列中，miR-206-3p、-376a-3p、-34b-5p、-133a-5p、-466f 和 -671-3p 相对于 PH 住房条件发生了很大变化。同样在男性中，miR-376c-3p、-181d-5p、-712-5p、-186-5p、-21a-3p、-30d-3p、-495-3p、-669c-5p、-335-5p、识别出 -429-3p、-31-3p 和 -217-5p。根据京都基因百科全书和基因组分析，鉴定出的 miRNA 影响了性别内不同的通路子集。交互网络分析显示 miR-495-3p（雄性）和 miR-34b-5p（雌性）是靶向最大基因子集的关键节点。我们确定了几种性别特异性 miRNA 作为老年雄性和雌性小鼠中风后 SI 的候选生物标志物。此外，