Guedes Vivian A, Devoto Christina, Leete Jacqueline, Sass Delia, Acott Jedidiah D, Mithani Sara, Gill Jessica M
National Institute of Nursing Research, National Institutes of Health, Bethesda, MD, United States.
Front Neurol. 2020 Jul 16;11:663. doi: 10.3389/fneur.2020.00663. eCollection 2020.
Traumatic brain injury (TBI) is a heterogeneous condition, associated with diverse etiologies, clinical presentations and degrees of severity, and may result in chronic neurobehavioral sequelae. The field of TBI biomarkers is rapidly evolving to address the many facets of TBI pathology and improve its clinical management. Recent years have witnessed a marked increase in the number of publications and interest in the role of extracellular vesicles (EVs), which include exosomes, cell signaling, immune responses, and as biomarkers in a number of pathologies. Exosomes have a well-defined lipid bilayer with surface markers that reflect the cell of origin and an aqueous core that contains a variety of biological material including proteins (e.g., cytokines and growth factors) and nucleic acids (e.g., microRNAs). The presence of proteins associated with neurodegenerative changes such as amyloid-β, α-synuclein and phosphorylated tau in exosomes suggests a role in the initiation and propagation of neurological diseases. However, mechanisms of cell communication involving exosomes in the brain and their role in TBI pathology are poorly understood. Exosomes are promising TBI biomarkers as they can cross the blood-brain barrier and can be isolated from peripheral fluids, including serum, saliva, sweat, and urine. Exosomal content is protected from enzymatic degradation by exosome membranes and reflects the internal environment of their cell of origin, offering insights into tissue-specific pathological processes. Challenges in the clinical use of exosomal cargo as biomarkers include difficulty in isolating pure exosomes, variable yields of the isolation processes, quantification of vesicles, and lack of specificity of exosomal markers. Moreover, there is no consensus regarding nomenclature and characteristics of EV subtypes. In this review, we discuss current technical limitations and challenges of using exosomes and other EVs as blood-based biomarkers, highlighting their potential as diagnostic and prognostic tools in TBI.
创伤性脑损伤（TBI）是一种异质性疾病，与多种病因、临床表现和严重程度相关，可能导致慢性神经行为后遗症。TBI生物标志物领域正在迅速发展，以应对TBI病理学的诸多方面并改善其临床管理。近年来，关于细胞外囊泡（EVs）的出版物数量显著增加，人们对其在包括外泌体、细胞信号传导、免疫反应以及在多种病理学中作为生物标志物的作用的兴趣也明显增强。外泌体具有明确的脂质双层，其表面标志物反映了来源细胞，还有一个水性核心，其中包含多种生物物质，包括蛋白质（如细胞因子和生长因子）和核酸（如微小RNA）。外泌体中存在与神经退行性变化相关的蛋白质，如淀粉样β蛋白、α-突触核蛋白和磷酸化tau蛋白，这表明其在神经疾病的发生和发展中发挥作用。然而，大脑中涉及外泌体的细胞通讯机制及其在TBI病理学中的作用尚不清楚。外泌体有望成为TBI生物标志物，因为它们可以穿过血脑屏障，并且可以从外周液体中分离出来，包括血清、唾液、汗液和尿液。外泌体内容物受到外泌体膜的保护，免受酶降解，并反映其来源细胞的内部环境，为组织特异性病理过程提供见解。将外泌体货物用作生物标志物在临床应用中面临的挑战包括难以分离纯外泌体、分离过程的产量可变、囊泡的定量以及外泌体标志物缺乏特异性。此外，关于EV亚型的命名和特征尚无共识。在本综述中，我们讨论了将外泌体和其他EVs用作血液生物标志物的当前技术局限性和挑战，强调了它们作为TBI诊断和预后工具的潜力。
