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基于质谱的创伤性脑损伤临床生物标志物发现方法

Mass Spectrometry-Based Approaches for Clinical Biomarker Discovery in Traumatic Brain Injury.

作者信息

Creech Matthew, Carvalho Lindsey, McCoy Heather, Jacobs Jon, Hinson H E

机构信息

Department of Neurology, Oregon Health and Science University, Portland OR.

Biological Sciences Division, Pacific Northwest National Laboratories, Richland, WA.

出版信息

Curr Treat Options Neurol. 2022 Dec;24(12):605-618. doi: 10.1007/s11940-022-00742-3. Epub 2022 Sep 15.

Abstract

PURPOSE OF REVIEW

Precision treatments to address the multifaceted pathophysiology of traumatic brain injury (TBI) are desperately needed, which has led to the intense study of fluid-based protein biomarkers in TBI. Mass Spectrometry (MS) is increasingly being applied to biomarker discovery and quantification in neurological disease to explore the proteome, allowing for more flexibility in biomarker discovery than commonly encountered antibody-based assays. In this narrative review, we will provide specific examples of how MS technology has advanced translational research in traumatic brain injury (TBI) focusing on clinical studies, and looking ahead to promising emerging applications of MS to the field of Neurocritical Care.

RECENT FINDINGS

Proteomic biomarker discovery using MS technology in human subjects has included the full range of injury severity in TBI, though critically ill patients can offer more options to biofluids given the need for invasive monitoring. Blood, urine, cerebrospinal fluid, brain specimens, and cerebral extracellular fluid have all been sources for analysis. Emerging evidence suggests there are distinct proteomic profiles in radiographic TBI subtypes, and that biomarkers may be used to distinguish patients sustaining TBI from healthy controls. Metabolomics may offer a window into the perturbations of ongoing cerebral insults in critically ill patients after severe TBI.

SUMMARY

Emerging MS technologies may offer biomarker discovery and validation opportunities not afforded by conventional means due to its ability to handle the complexities associated with the proteome. While MS techniques are relatively early in development in the neurosciences space, the potential applications to TBI and neurocritical care are likely to accelerate in the coming decade.

摘要

综述目的

迫切需要精准治疗来应对创伤性脑损伤(TBI)多方面的病理生理学,这促使人们对TBI中基于体液的蛋白质生物标志物展开深入研究。质谱(MS)越来越多地应用于神经疾病生物标志物的发现和定量,以探索蛋白质组,与常见的基于抗体的检测方法相比,在生物标志物发现方面具有更大的灵活性。在这篇叙述性综述中,我们将提供具体实例,说明MS技术如何推动创伤性脑损伤(TBI)的转化研究,重点关注临床研究,并展望MS在神经重症监护领域有前景的新兴应用。

最新发现

在人类受试者中使用MS技术进行蛋白质组生物标志物发现涵盖了TBI的各种损伤严重程度,不过鉴于重症患者需要侵入性监测,他们能为生物流体提供更多选择。血液、尿液、脑脊液、脑标本和脑细胞外液均为分析来源。新出现的证据表明,影像学TBI亚型存在独特的蛋白质组特征,且生物标志物可用于区分TBI患者和健康对照。代谢组学可能为重度TBI后重症患者持续脑损伤的扰动提供一个窗口。

总结

新兴MS技术因其能够处理与蛋白质组相关的复杂性,可能提供传统方法无法提供的生物标志物发现和验证机会。虽然MS技术在神经科学领域的发展相对早期,但在未来十年,其在TBI和神经重症监护方面的潜在应用可能会加速。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e70/10072855/ea44592523ec/nihms-1836927-f0001.jpg

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本文引用的文献

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Progress and challenges in mass spectrometry-based analysis of antibody repertoires.基于质谱的抗体库分析的进展与挑战
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