Papini Melissa G, Avila André N, Fitzgerald Melinda, Hellewell Sarah C
Curtin Medical School, Faculty of Health Sciences, Curtin University, Perth, Australia.
Curtin Health Innovation Research Institute, Curtin University, Perth, Australia.
J Neurotrauma. 2025 Apr;42(7-8):640-667. doi: 10.1089/neu.2024.0039. Epub 2024 Aug 21.
Mild traumatic brain injury (mTBI) is the most common form of traumatic brain injury. Post-concussive symptoms typically resolve after a few weeks although up to 20% of people experience these symptoms for >3 months, termed persistent post-concussive symptoms (PPCS). Subtle white matter (WM) microstructural damage is thought to underlie neurological and cognitive deficits experienced post-mTBI. Evidence suggests that diffusion magnetic resonance imaging (dMRI) and blood-based biomarkers could be used as surrogate markers of WM organization. We conducted a scoping review according to PRISMA-ScR guidelines, aiming to collate evidence for the use of dMRI and/or blood-based biomarkers of WM organization, in mTBI and PPCS, and document relationships between WM biomarkers and symptoms. We focused specifically on biomarkers of axonal or myelin integrity post-mTBI. Biomarkers excluded from this review therefore included the following: astroglial, perivascular, endothelial, and inflammatory markers. A literature search performed across four databases, EMBASE, Scopus, Google Scholar, and ProQuest, identified 100 records: 68 analyzed dMRI, 28 assessed blood-based biomarkers, and 4 used both. Blood biomarker studies commonly assessed axonal cytoskeleton proteins (i.e., tau); dMRI studies assessed measures of WM organization (i.e., fractional anisotropy). Significant biomarker alterations were frequently associated with heightened symptom burden and prolonged recovery time post-injury. These data suggest that dMRI and blood-based biomarkers may be useful proxies of WM organization, although few studies assessed these complementary measures in parallel, and the relationship between modalities remains unclear. Further studies are warranted to assess the benefit of a combined biomarker approach in evaluating alterations to WM organization after mTBI.
轻度创伤性脑损伤（mTBI）是创伤性脑损伤最常见的形式。脑震荡后症状通常在几周后缓解，尽管高达20%的人会在3个月以上出现这些症状，称为持续性脑震荡后症状（PPCS）。人们认为，细微的白质（WM）微观结构损伤是mTBI后出现神经和认知缺陷的基础。有证据表明，扩散磁共振成像（dMRI）和血液生物标志物可作为WM组织的替代标志物。我们根据PRISMA-ScR指南进行了一项范围综述，旨在整理mTBI和PPCS中使用dMRI和/或基于血液的WM组织生物标志物的证据，并记录WM生物标志物与症状之间的关系。我们特别关注mTBI后轴突或髓鞘完整性的生物标志物。因此，本综述排除的生物标志物包括以下几种：星形胶质细胞、血管周围、内皮细胞和炎症标志物。在四个数据库EMBASE、Scopus、谷歌学术和ProQuest中进行的文献检索共识别出100条记录：68条分析了dMRI，28条评估了基于血液的生物标志物，4条同时使用了两者。血液生物标志物研究通常评估轴突细胞骨架蛋白（即tau）；dMRI研究评估WM组织的测量指标（即分数各向异性）。生物标志物的显著改变通常与受伤后症状负担加重和恢复时间延长有关。这些数据表明，dMRI和基于血液的生物标志物可能是WM组织的有用替代指标，尽管很少有研究同时评估这些互补措施，且不同检测方法之间的关系仍不明确。有必要进一步开展研究，以评估联合生物标志物方法在评估mTBI后WM组织改变方面的益处。
