1 Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, Maryland.
2 Aristea Translational Medicine Corporation, Park City, Utah.
J Neurotrauma. 2019 Apr 1;36(7):975-987. doi: 10.1089/neu.2018.5898. Epub 2018 Oct 25.
Traumatic brain injury (TBI) is a major cause of injury-related death throughout the world and lacks effective treatment. Surviving TBI patients often develop neuropsychiatric symptoms, and the molecular mechanisms underlying the neuronal damage and recovery following TBI are not well understood. Extracellular vesicles (EVs) are membranous nanoparticles that are divided into exosomes (originating in the endosomal/multi-vesicular body [MVB] system) and microvesicles (larger EVs produced through budding of the plasma membrane). Both types of EVs are generated by all cells and are secreted into the extracellular environment, and participate in cell-to-cell communication and protein and RNA delivery. EVs enriched for neuronal origin can be harvested from peripheral blood samples and their contents quantitatively examined as a window to follow potential changes occurring in brain. Recent studies suggest that the levels of exosomal proteins and microRNAs (miRNAs) may represent novel biomarkers to support the clinical diagnosis and potential response to treatment for neurological disorders. In this review, we focus on the biogenesis of EVs, their molecular composition, and recent advances in research of their contents as potential diagnostic tools for TBI.
创伤性脑损伤(TBI)是全世界导致伤害相关死亡的主要原因,目前缺乏有效的治疗方法。幸存的 TBI 患者常出现神经精神症状,且 TBI 后神经元损伤和恢复的分子机制尚不清楚。细胞外囊泡(EVs)是膜性纳米颗粒,可分为外泌体(起源于内体/多泡体[MVB]系统)和微泡(通过质膜出芽产生的较大 EVs)。这两种类型的 EVs 均由所有细胞产生,并分泌到细胞外环境中,参与细胞间通讯以及蛋白质和 RNA 的传递。可从外周血样本中提取富含神经元来源的 EVs,并对其内容物进行定量检测,以作为观察大脑中潜在变化的窗口。最近的研究表明,外泌体蛋白和 microRNAs(miRNAs)的水平可能代表新的生物标志物,以支持神经疾病的临床诊断和潜在的治疗反应。在本综述中,我们重点关注 EVs 的生物发生、分子组成以及其内容物作为 TBI 潜在诊断工具的最新研究进展。