Diagnostic Potential of Neural Exosome Cargo as Biomarkers for Acute Brain Injury.
Diagnostic Potential of Neural Exosome Cargo as Biomarkers for Acute Brain Injury.
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神经外泌体货物作为急性脑损伤生物标志物的诊断潜力。
DOI：
10.1002/acn3.499
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发表时间：
2018-01
影响因子：
5.3
通讯作者：
Menkiti O
中科院分区：
文献类型：
--
作者：
Goetzl L;Merabova N;Darbinian N;Martirosyan D;Poletto E;Fugarolas K;Menkiti O
从外周血样本中纯化的神经元外泌体已被提出作为急性脑损伤的诊断工具，但从未在临床上进行过测试。我们假设外泌体蛋白生物标志物在急性缺氧脑损伤后会随着时间的推移而改变，并预测对治疗的反应。突触素（SYNPO）是一种存在于突触后棘中的肌动蛋白相关蛋白，与突触素、神经元特异性烯醇化酶和线粒体细胞色素c氧化酶一样，被认为是一种潜在的生物标志物。对急性缺氧缺血性脑病开始治疗后8、10和14小时采集的新生儿样本进行了二次分析（n = 14）。从血清中纯化神经元外泌体，并使用标准ELISA方法定量测定蛋白质水平。主要研究结果为住院时间（LOS）、癫痫药物出院（DCMED）和综合神经影像学评分（NIS）。神经元外泌体SYNPO在8至14小时之间的变化斜率似乎是所有三种临床研究结果中最有希望的生物标志物。SYNPO与LOS高度相关（- 0.91,P < 0.001）。无DCMED的6/8患者SYNPO增高，有DCMED的5/5患者SYNPO变差或中性（P = 0.02）。所有4例NIS异常的新生儿SYNPO均为中性或降低（P = 0.055）。其他候选生物标志物与结果无关。该报告提供了第一个临床证据，证明神经外泌体在急性脑损伤后的外周循环中翻转速度足够快，可以用作“肌钙蛋白样”测试。最佳采样和生物标志物可能因脑损伤类型而异。
Neuronal exosomes purified from peripheral blood samples have been proposed as diagnostic tool in the setting of acute brain injury but never tested clinically. We hypothesized that exosome protein biomarkers would change over time following acute hypoxic brain injury and would predict response to therapy. Synaptopodin (SYNPO), an actin‐associated protein present in postsynaptic spines, was evaluated as a potential biomarker as well as: synaptophysin, neuron‐specific enolase, and mitochondrial cytochrome c oxidase. A secondary analysis was performed on neonatal samples collected at 8, 10, and 14 h after the initiation of therapeutic‐controlled hypothermia for acute hypoxic–ischemic encephalopathy (n = 14). Neuronal exosomes were purified from serum and protein levels were quantified using standard ELISA methods. The primary study outcomes were length of stay (LOS), discharge on seizure medication (DCMED), and composite neuroimaging score (NIS). The slope of change in neuronal exosome SYNPO between 8 and 14 h appeared to be the most promising biomarker for all three clinical study outcomes. SYNPO was highly correlated with LOS (−0.91, P < 0.001). SYNPO increased in 6/8 without DCMED and was worse or neutral in 5/5 with DCMED (P = 0.02). All four neonates with an abnormal NIS had neutral or decreasing SYNPO (P = 0.055). Other candidate biomarkers were not associated with outcomes. This report provides the first clinical evidence that neural exosomes turn over rapidly enough in the peripheral circulation to be used as a “troponin‐like” test following acute brain injury. Optimal sampling and biomarkers likely vary with type of brain injury.
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影响因子：
4.6
作者：
Ko J;Hemphill MA;Gabrieli D;Wu L;Yelleswarapu V;Lawrence G;Pennycooke W;Singh A;Meaney DF;Issadore D
通讯作者：
Issadore D
影响因子：
3.7
作者：
Chiva-Blanch G;Suades R;Crespo J;Peña E;Padró T;Jiménez-Xarrié E;Martí-Fàbregas J;Badimon L
通讯作者：
Badimon L
影响因子：
4
作者：
Chivet M;Hemming F;Pernet-Gallay K;Fraboulet S;Sadoul R
通讯作者：
Sadoul R
DOI：
10.1083/jcb.139.1.193
发表时间：
1997-10-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Mundel P;Heid HW;Mundel TM;Krüger M;Reiser J;Kriz W
通讯作者：
Kriz W
影响因子：
9.9
作者：
Goetzl, Edward J.;Boxer, Adam;Kapogiannis, Dimitrios
通讯作者：
Kapogiannis, Dimitrios