Research current and Future of Biomarkers of brain injury
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摘要: 创伤性脑损伤(traumatic brain injury,TBI)是最常见的后天脑损伤,大约43%的TBI幸存者也伴随慢性残疾,其致死、致残率高。TBI可因直接打击、缺血缺氧性脑损伤、细胞因子、炎性介质等机制诱发神经元死亡。如何早期、快速、准确地诊断TBI,对指导临床治疗和判断预后起着极为重要的作用。目前临床上诊断TBI主要依赖格拉斯哥昏迷评分(Glasgow coma scale,GCS)和颅脑CT、核磁共振成像(MRI)等影像学检查。但近年来,随着疾病生物标志物的研究和液体活检技术的进步,相关的TBI损伤生物标志物逐渐走向临床,为TBI的早期诊断、动态监测和预后评估提供重要的辅助手段。TBI发生发展过程中产生了大量生物分子标志物,这些标志物在损伤早期就可出现在血清和脑脊液中,其敏感性和特异性往往比影像学检查更具优势,深入研究TBI后生物分子标志物的变化及其规律,有助于弥补传统诊断方式的不足,为TBI的治疗提供新的依据和线索。本文对部分比较有前景的TBI相关生物标志物-常规生化标志物、脑组织损伤类标志物、继发性损伤效应标志物、神经病变人群易感基因、游离核酸等新兴分子诊断标志物的研究进展进行了综述,并对TBI实验室精准诊断的发展方向进行了展望,以期为寻找适用于临床的TBI相关的生物标志物、研发相关临床实验室诊断新技术提供参考依据。Abstract: Traumatic brain injury(TBI) is the most common acquired brain injury. About 43% of TBI survivors are also accompanied by chronic disabilities, and their death and disability rates are high. Neuronal cell death could be induced by the following mechanisms,such as direct attack,hypoxic-ischemic brain injury, cytokines,inflammatory mediators after TBI. How to diagnose TBI early, quickly and accurately plays an extremely important role in guiding clinical treatment and judging prognosis. The current clinical diagnosis mainly depends on Glasgow Coma Score(GCS) and clinical imaging such as craniocerebral CT and magnetic resonance imaging(MRI).But in recent years, with the development of disease markers and liquid biopsy technology, TBI related biomarkers are expected to clinical application, providing important diagnostic value for early diagnosis, dynamic monitoring and evaluation the prognosis. A large number of bio-molecular markers are generated during the development of TBI,Biomedical markers of TBI appear early in the serum and cerebro-spinal fluid with a higher sensitivity and specificity than image examination. An intensive study of the change regularity of biomarkers after TBI is of important significance for clinical therapy.It provides a new basis and clue for the treatment of TBI. Some promising TBI biomarkers are summarized in this paper, including conventional biomarkers, brain tissue injury markers, secondary injury markers, and emerging molecular diagnostic markers such as susceptible genes and cell free nucleic acids. And, the development direction of accurate laboratory diagnosis of TBI is also forecasted. This review is organized in order to provide reference for TBI related biomarkers and development for new clinical laboratory diagnostic techniques.
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Key words:
- Traumatic brain injury(TBI) /
- Biomarkers /
- Molecular diagnosis /
- Laboratory diagnosis
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