Department of Chemistry, The University of Kansas , Lawrence, KS, USA.
Center of BioModular Multiscale Systems for Precision Medicine, The University of Kansas , Lawrence, KS, USA.
Expert Rev Mol Diagn. 2020 Aug;20(8):771-788. doi: 10.1080/14737159.2020.1777859. Epub 2020 Jul 5.
There is a short time window (4.5 h) for the effective treatment of acute ischemic stroke (AIS), which uses recombinant tissue plasminogen activator (rt-PA). Unfortunately, this short therapeutic timeframe is a contributing factor to the relatively small number of patients (~7%) that receive rt-PA. While neuroimaging is the major diagnostic for AIS, more timely decisions could be made using a molecular diagnostic.
In this review, we survey neuroimaging techniques used to diagnose stroke and their limitations. We also highlight the potential of various molecular/cellular biomarkers, especially peripheral blood-based (. liquid biopsy) biomarkers, for diagnosing stroke to allow for precision decisions on managing stroke in a timely manner. Both protein and nucleic acid molecular biomarkers are reviewed. In particular, mRNA markers are discussed for AIS and hemorrhagic stroke diagnosis sourced from both cells and extracellular vesicles.
While there are a plethora of molecular markers for stroke diagnosis that have been reported, they have yet to be FDA-cleared. Possible reasons include the inability for these markers to appear in sufficient quantities for highly sensitive clinical decisions within the rt-PA therapeutic time.
急性缺血性脑卒中(AIS)的有效治疗时间窗口很短(4.5 小时),需要使用重组组织型纤溶酶原激活剂(rt-PA)。不幸的是,这种较短的治疗时间框架是导致接受 rt-PA 治疗的患者比例相对较小(约 7%)的一个因素。虽然神经影像学是 AIS 的主要诊断方法,但使用分子诊断可以做出更及时的决策。
在这篇综述中,我们调查了用于诊断中风的神经影像学技术及其局限性。我们还强调了各种分子/细胞生物标志物的潜力,特别是基于外周血的(液体活检)生物标志物,用于诊断中风,以便及时做出精确的决策,从而对中风进行管理。我们回顾了蛋白质和核酸分子生物标志物。特别是,讨论了源自细胞和细胞外囊泡的 AIS 和出血性中风诊断的 mRNA 标志物。
虽然已经报道了大量用于中风诊断的分子标志物,但尚未获得 FDA 批准。可能的原因包括这些标志物在 rt-PA 治疗时间内无法出现足够数量,从而无法进行高度敏感的临床决策。