Mainali Shraddha, Nepal Gaurav, Shumilov Kirill, Webb Amy, Fadda Paolo, Mirebrahimi Darya, Hamed Mohammad, Nana-Sinkam Patrick, Worrall Bradford B, Woo Daniel, Johnson Nicholas
Department of Neurology, Virginia Commonwealth University, Richmond, VA 23298, USA.
Department of Internal Medicine, Maharajgunj Medical Campus, Tribhuvan University, Kathmandu 44600, Nepal.
Int J Mol Sci. 2025 Jan 17;26(2):747. doi: 10.3390/ijms26020747.
Acute ischemic stroke with large vessel occlusion (LVO) continues to present a considerable challenge to global health, marked by substantial morbidity and mortality rates. Although definitive diagnostic markers exist in the form of neuroimaging, their expense, limited availability, and potential for diagnostic delay can often result in missed opportunities for life-saving interventions. Despite several past attempts, research efforts to date have been fraught with challenges likely due to multiple factors, such as the inclusion of diverse stroke types, variable onset intervals, differing pathobiologies, and a range of infarct sizes, all contributing to inconsistent circulating biomarker levels. In this context, microRNAs (miRNAs) have emerged as a promising biomarker, demonstrating potential as biomarkers across various diseases, including cancer, cardiovascular conditions, and neurological disorders. These circulating miRNAs embody a wide spectrum of pathophysiological processes, encompassing cell death, inflammation, angiogenesis, neuroprotection, brain plasticity, and blood-brain barrier integrity. This pilot study explores the utility of circulating exosome-enriched extracellular vesicle (EV) miRNAs as potential biomarkers for anterior circulation LVO (acLVO) stroke. In our longitudinal prospective cohort study, we collected data from acLVO stroke patients at four critical time intervals post-symptom onset: 0-6 h, 6-12 h, 12-24 h, and 5-7 days. For comparative analysis, healthy individuals were included as control subjects. In this study, extracellular vesicles (EVs) were isolated from the plasma of participants, and the miRNAs within these EVs were profiled utilizing the NanoString nCounter system. Complementing this, a scoping review was conducted to examine the roles of specific miRNAs such as miR-140-5p, miR-210-3p, and miR-7-5p in acute ischemic stroke (AIS). This review involved a targeted PubMed search to assess their influence on crucial pathophysiological pathways in AIS, and their potential applications in diagnosis, treatment, and prognosis. The review also included an assessment of additional miRNAs linked to stroke. Within the first 6 h of symptom onset, three specific miRNAs (miR-7-5p, miR-140-5p, and miR-210-3p) exhibited significant differential expression compared to other time points and healthy controls. These miRNAs have previously been associated with neuroprotection, cellular stress responses, and tissue damage, suggesting their potential as early markers of acute ischemic stroke. This study highlights the potential of circulating miRNAs as blood-based biomarkers for hyperacute acLVO ischemic stroke. However, further validation in a larger, risk-matched cohort is required. Additionally, investigations are needed to assess the prognostic relevance of these miRNAs by linking their expression profiles with radiological and functional outcomes.
伴有大血管闭塞(LVO)的急性缺血性中风仍然给全球健康带来巨大挑战,其发病率和死亡率都很高。尽管神经影像学检查存在明确的诊断标志物,但这些检查费用高昂、可及性有限,且存在诊断延迟的可能,常常导致错失挽救生命的干预时机。尽管过去曾多次尝试,但由于多种因素,如纳入了多种中风类型、发病间隔时间不同、病理生物学各异以及梗死面积范围不同,导致循环生物标志物水平不一致,迄今的研究工作一直充满挑战。在这种背景下,微小RNA(miRNA)已成为一种有前景的生物标志物,在包括癌症、心血管疾病和神经疾病在内的各种疾病中都显示出作为生物标志物的潜力。这些循环miRNA体现了广泛的病理生理过程,包括细胞死亡、炎症、血管生成、神经保护、脑可塑性和血脑屏障完整性。这项初步研究探讨了循环中富含外泌体的细胞外囊泡(EV)miRNA作为前循环LVO(acLVO)中风潜在生物标志物的效用。在我们的纵向前瞻性队列研究中,我们在症状发作后的四个关键时间间隔收集了acLVO中风患者的数据:0 - 6小时、6 - 12小时、12 - 24小时和5 - 7天。为了进行比较分析,纳入健康个体作为对照。在这项研究中,从参与者的血浆中分离出细胞外囊泡(EV),并利用NanoString nCounter系统对这些EV中的miRNA进行分析。作为补充,还进行了一项综述,以研究特定miRNA如miR - 140 - 5p、miR - 210 - 3p和miR - 7 - 5p在急性缺血性中风(AIS)中的作用。该综述涉及有针对性地在PubMed上进行检索,以评估它们对AIS关键病理生理途径的影响,以及它们在诊断、治疗和预后方面的潜在应用。该综述还包括对与中风相关的其他miRNA的评估。在症状发作后的前6小时内,与其他时间点和健康对照相比,三种特定的miRNA(miR - 7 - 5p、miR - 140 - 5p和miR - 210 - 3p)表现出显著的差异表达。这些miRNA此前已与神经保护、细胞应激反应和组织损伤相关联,表明它们有可能作为急性缺血性中风的早期标志物。这项研究突出了循环miRNA作为超急性acLVO缺血性中风基于血液的生物标志物的潜力。然而,需要在更大的、风险匹配的队列中进行进一步验证。此外,还需要进行研究,通过将它们的表达谱与放射学和功能结果联系起来,评估这些miRNA的预后相关性。