Mitra Biswadev, Rau Thomas F, Surendran Nanda, Brennan James H, Thaveenthiran Prasanthan, Sorich Edmond, Fitzgerald Mark C, Rosenfeld Jeffrey V, Patel Sarjubhai A
Emergency & Trauma Centre, The Alfred Hospital, Australia; National Trauma Research Institute, The Alfred Hospital, Australia; Department of Epidemiology & Preventive Medicine, Monash University, Australia.
Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, MT, USA.
J Clin Neurosci. 2017 Apr;38:37-42. doi: 10.1016/j.jocn.2016.12.009. Epub 2017 Jan 20.
Prediction of post-concussive syndrome after apparent mild traumatic brain injury (TBI) and subsequent cognitive recovery remains challenging, with substantial limitations of current methods of cognitive testing. This pilot study aimed to determine if levels of micro ribonucleic acids (RNAs) circulating in plasma are altered following TBI, and if changes to levels of such biomarkers over time could assist in determination of prognosis after TBI. Patients were enrolled after TBI on presentation to the Emergency Department and allocated to three groups: A - TBI (physical trauma to the head), witnessed loss of consciousness, amnesia, GCS=15, a normal CT Brain and a recorded first pass after post-traumatic amnesia (PTA) scale; B TBI, witnessed LOC, amnesia, GCS=15, a normal CT brain and a PTA scale test fail and: C - TBI and initial GCS <13 on arrival to the ED. Venous blood was collected at three time points (arrival, day 5 and day 30). Isolation of cell-free total RNA was then assayed using a custom miRNA PCR array. Two micro-RNAs, mir142-3p and mir423-3p demonstrated potential clinical utility differentiating patients after mild head injury into those at greater risk of developing amnesia and therefore, post-concussive syndromes. In addition, these miRNA demonstrated a decrease in expression over time, possibly indicative of brain healing after the injury. Further evaluation of these identified miRNA markers with larger patient cohorts, correlation with clinical symptoms and analysis over longer time periods are essential next steps in developing objective markers of severity of TBI.
在明显的轻度创伤性脑损伤(TBI)后预测脑震荡后综合征以及随后的认知恢复仍然具有挑战性,当前认知测试方法存在重大局限性。这项前瞻性研究旨在确定创伤性脑损伤后血浆中循环的微小核糖核酸(RNA)水平是否发生改变,以及这些生物标志物水平随时间的变化是否有助于确定创伤性脑损伤后的预后。患者在创伤性脑损伤后到急诊科就诊时入组,并分为三组:A组 - 创伤性脑损伤(头部受到物理创伤),有昏迷、失忆见证,格拉斯哥昏迷量表(GCS)=15,脑部CT正常,创伤后失忆(PTA)量表记录首次通过;B组 - 创伤性脑损伤,有昏迷、失忆见证,GCS=15,脑部CT正常,PTA量表测试未通过;C组 - 创伤性脑损伤,到达急诊科时初始GCS<13。在三个时间点(到达时、第5天和第30天)采集静脉血。然后使用定制的miRNA PCR阵列检测无细胞总RNA的分离情况。两种微小RNA,mir142-3p和mir423-3p显示出潜在的临床效用,可将轻度头部损伤后的患者区分为发生失忆进而发生脑震荡后综合征风险更高的患者。此外,这些miRNA的表达随时间下降,这可能表明损伤后脑组织正在愈合。使用更大的患者队列对这些已鉴定的miRNA标记物进行进一步评估、与临床症状进行相关性分析以及在更长时间段内进行分析,是开发创伤性脑损伤严重程度客观标记物的关键下一步。