Extracellular vesicles as distinct biomarker reservoirs for mild traumatic brain injury diagnosis.
Extracellular vesicles as distinct biomarker reservoirs for mild traumatic brain injury diagnosis.
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DOI：
10.1093/braincomms/fcab151
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发表时间：
2021
影响因子：
4.8
通讯作者：
Issadore D
中科院分区：
文献类型：
--
作者：
Beard K;Yang Z;Haber M;Flamholz M;Diaz-Arrastia R;Sandsmark D;Meaney DF;Issadore D
轻度创伤性脑损伤目前还没有明确的分子诊断小组来确认损伤或指导治疗。目前创伤性脑损伤的生物标志物主要依赖于检测血液中与退行性神经元相关的循环蛋白，这在轻度创伤性脑损伤中不太常见，或者与多种组织产生的广泛炎症级联反应有关，因此不是脑特异性的。为了解决这个问题，我们进行了一项观察性队列研究，旨在测量血浆和脑源性细胞外囊泡两个区室中的蛋白质面板，并提出以下假设：(i)每个区室提供独立的诊断信息；（ii）算法结合这些区室准确分类临床轻度创伤性脑损伤。我们使用轻度（格拉斯哥昏迷评分13-15分）创伤性脑损伤患者（n = 47）和健康和骨科对照（n = 46）的血浆样本来评估脑源性细胞外囊泡和血浆中的生物标志物，对这一假设进行了评估。我们利用Track Etched Magnetic Nanopore技术，结合单分子阵列（single molecule Array）超灵敏数字酶联免疫吸附测定技术，基于GluR2的表达，从血浆中分离出脑源性细胞外囊泡。我们量化了与两类外伤性脑损伤病理相关的细胞外囊泡包装和血浆生物标志物水平：神经变性和神经元/胶质损伤（泛素c末端水解酶L1、胶质纤维酸蛋白、神经丝光和Tau）和炎症（白细胞介素-6、白细胞介素-10和肿瘤坏死因子α）。我们发现GluR2+细胞外囊泡与血浆中的生物标志物分布不同。作为概念验证，我们发现使用一组由血浆和GluR2+细胞外囊泡组成的生物标志物，可以准确地将受伤患者与非受伤患者进行分类。Beard等人报告说，使用一种新型纳米流体装置捕获的循环脑源性细胞外囊泡含有与创伤性脑损伤传统血浆生物标志物不同的分子信息。他们证明，通过算法将两个隔室的生物标志物结合起来，可能会提供一种临床上有用的、信息丰富的脑损伤分类方法。
Mild traumatic brain injury does not currently have a clear molecular diagnostic panel to either confirm the injury or to guide its treatment. Current biomarkers for traumatic brain injury rely mainly on detecting circulating proteins in blood that are associated with degenerating neurons, which are less common in mild traumatic brain injury, or with broad inflammatory cascades which are produced in multiple tissues and are thus not brain specific. To address this issue, we conducted an observational cohort study designed to measure a protein panel in two compartments—plasma and brain-derived extracellular vesicles—with the following hypotheses: (i) each compartment provides independent diagnostic information and (ii) algorithmically combining these compartments accurately classifies clinical mild traumatic brain injury. We evaluated this hypothesis using plasma samples from mild (Glasgow coma scale scores 13–15) traumatic brain injury patients (n = 47) and healthy and orthopaedic control subjects (n = 46) to evaluate biomarkers in brain-derived extracellular vesicles and plasma. We used our Track Etched Magnetic Nanopore technology to isolate brain-derived extracellular vesicles from plasma based on their expression of GluR2, combined with the ultrasensitive digital enzyme-linked immunosorbent assay technique, Single-Molecule Array. We quantified extracellular vesicle-packaged and plasma levels of biomarkers associated with two categories of traumatic brain injury pathology: neurodegeneration and neuronal/glial damage (ubiquitin C-terminal hydrolase L1, glial fibrillary acid protein, neurofilament light and Tau) and inflammation (interleukin-6, interleukin-10 and tumour necrosis factor alpha). We found that GluR2+ extracellular vesicles have distinct biomarker distributions than those present in the plasma. As a proof of concept, we showed that using a panel of biomarkers comprised of both plasma and GluR2+ extracellular vesicles, injured patients could be accurately classified versus non-injured patients. Abbreviated summary Beard et al. report that circulating brain-derived extracellular vesicles captured using a novel nanofluidic device contain distinct molecular information from conventional plasma biomarkers of traumatic brain injury. They demonstrate that algorithmically combining biomarkers from both compartments may provide a clinically useful, information-rich method of classifying brain injury.
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影响因子：
46.9
作者：
Alvarez-Erviti, Lydia;Seow, Yiqi;Wood, Matthew J. A.
通讯作者：
Wood, Matthew J. A.
DOI：
10.5114/ceji.2018.74871
发表时间：
2018
期刊：
Central-European journal of immunology
影响因子：
--
作者：
Binkowska AM;Michalak G;Pilip S;Kopacz M;Słotwiński R
通讯作者：
Słotwiński R
DOI：
10.1126/science.aau6977
发表时间：
2020-02-07
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kalluri R;LeBleu VS
通讯作者：
LeBleu VS
影响因子：
48
作者：
Bazarian, Jeffrey J.;Biberthaler, Peter;Jagoda, Andy S.
通讯作者：
Jagoda, Andy S.
影响因子：
3.4
作者：
Acarin, L;González, B;Castellano, B
通讯作者：
Castellano, B