microRNA Profile Changes in Brain, Cerebrospinal Fluid, and Blood Following Low-Level Repeated Blast Exposure in a Rat Model

大鼠模型中低强度反复冲击波暴露后大脑、脑脊液及血液中的microRNA表达谱变化

It is well documented that service members are exposed to repeated low-level blast overpressure during training with heavy weapons such as artillery, mortars and explosive breaching. Often, acute symptoms associated with these exposures are transient but cumulative effect of low-level repeated blast exposures (RBEs) can include persistent deficits in cognitive and behavioral health. Thus far, reliable diagnostic biomarkers which can guide countermeasure strategies have not been identified. In this study, rats were exposed to multiple field-relevant blast waves with 8.5 and 10 psi peak positive overpressures, applying one exposure per day for 14 consecutive days. The results indicate that miRNAs are differentially dysregulated in response to blast injuries and may represent better prognostic and diagnostic biomarkers than traditional molecules to identify blast-specific brain injury.

已有充分文献证实，军人在使用火炮、迫击炮及炸药等重型武器进行训练时，会暴露于反复的低强度冲击波超压环境中。通常情况下，与这类暴露相关的急性症状是暂时性的，但低强度反复冲击波暴露（RBEs）的累积效应可能导致认知功能与行为健康出现持续性损伤。截至目前，尚未发现可指导应对策略制定的可靠诊断生物标志物。本研究中，研究人员让大鼠暴露于多种与实际场景相关的冲击波环境中，冲击波正压峰值分别为8.5磅/平方英寸（psi）和10磅/平方英寸（psi），连续14天每天暴露1次。研究结果表明，在应对冲击波损伤时，miRNAs的表达会出现差异性失调；相较于传统分子，miRNAs或许是识别冲击波特异性脑损伤的更优预后及诊断生物标志物。

REF: Dahal S, Kakulavarapu RV, Heyburn L, et al. microRNA Profile Changes in Brain, Cerebrospinal Fluid, and Blood Following Low-Level Repeated Blast Exposure in a Rat Model. J Neurotrauma. 2025;42(17-18):1654-1661. doi:10.1089/neu.2024.0269 PMID: 39535039

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Genetic Differences Modify Anesthetic Preconditioning of Traumatic Brain Injury in Drosophila

遗传差异对果蝇创伤性脑损伤麻醉预处理效应的调控作用

Pre-clinical vertebrate models of traumatic brain injury (TBI) routinely use anesthetics for animal welfare; however, humans experience TBI without anesthetics. Therefore, translation of findings from vertebrate models to humans hinges on understanding how anesthetics influence cellular and molecular events that lead to secondary injuries following TBI. To investigate the effects of anesthetics on TBI outcomes, we used an invertebrate Drosophila melanogaster model to compare outcomes between animals exposed or not exposed to anesthetics prior to the same primary injury. The data indicate that anesthetic dose and genetic background should be considered when investigating effects of anesthetics in vertebrate TBI models, and they support use of the fly model for elucidating the mechanisms underlying anesthetic preconditioning of TBI.

在创伤性脑损伤（TBI）的临床前脊椎动物模型中，为保障动物福利，常规会使用麻醉剂；然而，人类发生创伤性脑损伤时并无麻醉剂参与。因此，要将脊椎动物模型的研究结果转化应用于人类，关键在于明确麻醉剂如何影响创伤性脑损伤后引发继发性损伤的细胞与分子事件。为探究麻醉剂对创伤性脑损伤结局的影响，本研究采用无脊椎动物黑腹果蝇模型，在相同原发性损伤条件下，对比了损伤前接触与未接触麻醉剂的果蝇的损伤结局。研究数据表明，在研究脊椎动物创伤性脑损伤模型中麻醉剂的作用时，应考虑麻醉剂剂量与遗传背景这两个因素；同时，该数据也为利用果蝇模型阐明创伤性脑损伤麻醉预处理的潜在机制提供了依据。

REF: Johnson-Schlitz D, Seidl AR, Olufs ZPG, Huang W, Wassarman DA, Perouansky M. Genetic Differences Modify Anesthetic Preconditioning of Traumatic Brain Injury in Drosophila. J Neurotrauma. 2025;42(17-18):1641-1653. doi:10.1089/neu.2024.0314 PMID: 39558897

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Mechanism of Injury and Clinical Recovery Outcomes Following Pediatric Concussion

儿童脑震荡的损伤机制与临床恢复结局

Children with concussion are injured through a variety of mechanisms, but the relationship between mechanism of injury (MOI) and recovery outcomes is unclear due to small sample sizes and varied methodological designs. Our objective was to examine the association of MOI and clinical recovery in youth with concussion using a large dataset collated from a single, multisite study. Sport-related concussions were generally associated with better symptom and quality of life scores in older children, but these differences were modest and unlikely to be clinically significant. Regardless of MOI, most children experienced clinical improvements across the first three months following concussion.

脑震荡儿童的受伤机制多种多样，但由于既往研究样本量较小且研究方法设计存在差异，损伤机制（MOI）与恢复结局之间的关联尚不明确。本研究旨在利用一项多中心研究整理的大型数据集，探讨脑震荡青少年的损伤机制与临床恢复之间的关系。研究发现，在年龄较大的儿童中，运动相关脑震荡通常与更优的症状评分及生活质量评分相关，但这些差异程度较小，不太可能具有临床意义。无论损伤机制如何，大多数儿童在脑震荡发生后的前三个月内均呈现出临床改善。

REF: Gudymenko A, Iuliano SG, Gagnon IJ, et al. Mechanism of Injury and Clinical Recovery Outcomes Following Pediatric Concussion. J Neurotrauma. 2025;42(17-18):1631-1640. doi:10.1089/neu.2024.0483 PMID: 40244878

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The Impact of Non-Pain Factors on Pain Interference Among U.S. Service Members and Veterans with Symptoms of Mild Traumatic Brain Injury

非疼痛因素对存在轻度创伤性脑损伤症状的美国军人及退伍军人疼痛干扰的影响

U.S. Service members and Veterans (SM/V) experience elevated rates of traumatic brain injury (TBI), chronic pain, and other non-pain symptoms. However, the role of non-pain factors on pain interference levels remains unclear among SM/Vs, particularly those with a history of TBI. The primary objective of this study was to identify factors that differentiate high/low pain interference, given equivalent pain intensity among U.S. SM/V participating in the ongoing Long-term Impact of Military-relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium (LIMBIC-CENC) national multi-center prospective longitudinal observational study. Non-pain factors are associated with functional limitations and disability experience among SM/V with an mTBI history. The functional effects of pain may be mediated through multiple other factors. Pain is a multi-dimensional experience that may benefit most from holistic treatment approaches that target comorbidities and build supports that promote recovery.

美国军人与退伍军人群体中，创伤性脑损伤（TBI）、慢性疼痛及其他非疼痛症状的发生率均处于较高水平。然而，在这一群体中，尤其是有创伤性脑损伤病史的人群，非疼痛因素对疼痛干扰程度的影响机制仍不明确。本研究的主要目的是：在参与“军事相关脑损伤联盟-神经创伤慢性影响联盟（LIMBIC-CENC）”这一正在进行的全国多中心前瞻性纵向观察性研究的美国军人与退伍军人中，当研究对象的疼痛强度处于同等水平时，识别出能够区分疼痛干扰程度高低的相关因素。研究发现，对于有轻度创伤性脑损伤（mTBI）病史的美国军人与退伍军人，非疼痛因素与他们的功能受限情况及残疾体验相关。疼痛对功能产生的影响可能通过多种其他因素介导。疼痛是一种多维度的感受体验，针对共病（如焦虑、睡眠障碍等）制定整体治疗方案，并建立有助于促进康复的支持体系，或许是改善疼痛问题最有效的方式。

REF: Kennedy E, Manhapra A, Miles SR, et al. The Impact of Non-Pain Factors on Pain Interference Among U.S. Service Members and Veterans with Symptoms of Mild Traumatic Brain Injury. J Neurotrauma. 2025;42(17-18):1621-1630. doi:10.1089/neu.2024.0126 PMID: 38907690

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Biofluid, Imaging, Physiological, and Functional Biomarkers of Mild Traumatic Brain Injury and Subconcussive Head Impacts

轻度创伤性脑损伤与脑震荡下头部撞击的生物流体、影像学、生理学及功能性生物标志物

Post-concussive symptoms are frequently reported by individuals who sustain mild traumatic brain injuries (mTBIs) and subconcussive head impacts, even when evidence of intracranial pathology is lacking. Current strategies used to evaluate head injuries, which primarily rely on self-report, have a limited ability to predict the incidence, severity, and duration of post-concussive symptoms that will develop in an individual patient. In addition, these self-report measures have little association with the underlying mechanisms of pathology that may contribute to persisting symptoms, impeding advancement in precision treatment for TBI. Emerging evidence suggests that biofluid, imaging, physiological, and functional biomarkers associated with mTBI and subconcussive head impacts may address these shortcomings by providing more objective measures of injury severity and underlying pathology. Interest in the use of biomarker data has rapidly accelerated, which is reflected by the recent efforts of organizations such as the National Institute of Neurological Disorders and Stroke and the National Academies of Sciences, Engineering, and Medicine to prioritize the collection of biomarker data during TBI characterization in acute-care settings. Thus, this review aims to describe recent progress in the identification and development of biomarkers of mTBI and subconcussive head impacts and to discuss important considerations for the implementation of these biomarkers in clinical practice.

发生轻度创伤性脑损伤（mTBI）和脑震荡下头部撞击的人群中，脑震荡后症状的报告率较高，即便在缺乏颅内病变证据的情况下也是如此。目前用于评估头部损伤的策略主要依赖自我报告，但其预测个体患者脑震荡后症状发生率、严重程度及持续时间的能力有限。此外，这些自我报告评估手段与可能导致症状持续的潜在病理机制关联度较低，这阻碍了创伤性脑损伤（TBI）精准治疗的发展。新的研究证据表明，与轻度创伤性脑损伤和脑震荡下头部撞击相关的生物流体、影像学、生理学及功能性生物标志物，可通过提供更客观的损伤严重程度和潜在病理评估指标，以解决上述不足。目前，人们对生物标志物数据应用的关注度迅速提升，美国国家神经疾病与中风研究所、美国国家科学院、工程院与医学院等机构近期已在急诊环境下的创伤性脑损伤特征评估中，将生物标志物数据收集列为优先事项，这一举措也体现了上述关注度的提升。因此，本综述旨在阐述轻度创伤性脑损伤和脑震荡下头部撞击生物标志物的识别与开发最新进展，并探讨在临床实践中应用这些生物标志物需重点考虑的问题。

REF: Beard K, Gauff AK, Pennington AM, Marion DW, Smith J, Sloley S. Biofluid, Imaging, Physiological, and Functional Biomarkers of Mild Traumatic Brain Injury and Subconcussive Head Impacts. J Neurotrauma. 2025;42(17-18):1601-1620. doi:10.1089/neu.2024.0136 PMID: 38943278

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Evaluating and Updating the IMPACT Model to Predict Outcomes in Two Contemporary North American Traumatic Brain Injury Cohorts

评估并更新IMPACT模型以预测两个当代北美创伤性脑损伤队列的预后

The International Mission on Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) model is a widely recognized prognostic model applied after traumatic brain injury (TBI). However, it was developed with patient cohorts that may not reflect modern practice patterns in North America. We analyzed data from two sources: the placebo arm of the phase II double-blinded, multicenter, randomized controlled trial Prehospital Tranexamic Acid for TBI (TXA) cohort and an observational cohort with similar inclusion/exclusion criteria (Predictors of Low-risk Phenotypes after Traumatic Brain Injury Incorporating Proteomic Biomarker Signatures [PROTIPS] cohort). In our comprehensive evaluation of the IMPACT model, the coefficient updated models were the best performing across all cohorts through a structured closed testing procedure. Thus, standardization of model updating procedures is needed to reproducibly determine the best performing versions of IMPACT that reflect the specific characteristics of a dataset.

创伤性脑损伤临床试验预后与分析国际项目（IMPACT）模型是创伤性脑损伤（TBI）领域应用广泛且认可度高的预后预测模型。然而，该模型的开发所依据的患者队列，可能无法反映北美地区当前的临床实践模式。本研究分析了两个来源的数据：一是II期双盲、多中心、随机对照试验“创伤性脑损伤院前使用氨甲环酸（TXA）”的安慰剂组队列（TXA队列）；二是与前者纳入/排除标准相似的观察性队列——“整合蛋白质组学生物标志物特征的创伤性脑损伤低风险表型预测因素”队列。在对IMPACT模型的综合评估中，通过结构化封闭检验流程发现，系数更新后的模型在所有队列中均表现最佳。因此，有必要对模型更新流程进行标准化，以可重复的方式确定IMPACT模型的最佳性能版本，使其能够反映特定数据集的特征。

REF: Takegami N, Torres-Espin A, Imagawa Y, et al. Evaluating and Updating the IMPACT Model to Predict Outcomes in Two Contemporary North American Traumatic Brain Injury Cohorts. J Neurotrauma. 2025;42(17-18):1585-1600. doi:10.1089/neu.2024.0158 PMID: 38984940

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Mild Traumatic Brain Injury in Older Adults: Recovery Course and Insights on Early Predictors of Outcome

老年人轻度创伤性脑损伤：恢复进程及预后早期预测因素研究

Mild traumatic brain injury (mTBI) is a growing health concern in the context of an aging population. Older adults comprise a distinct population, with an increased vulnerability for mTBI due to comorbid diseases and age-associated frailty compared with the adult population. The aim of this study was to assess the recovery course and determinants of outcome in a large cohort of older patients with mTBI. The recovery course in older patients with mTBI is dynamic and further research on factors associated with long-term outcomes in this specific patient population is imperative to enhance treatment strategies.

在人口老龄化背景下，轻度创伤性脑损伤（mTBI）已成为日益受关注的健康问题。老年人是一个独特的群体，与成年人群体相比，由于合并症以及与年龄相关的衰弱状态，他们发生轻度创伤性脑损伤的易感性更高。本研究旨在评估大规模老年轻度创伤性脑损伤患者群体的恢复进程及预后决定因素。研究发现，老年轻度创伤性脑损伤患者的恢复进程具有动态变化特征；为完善治疗策略，针对这一特定患者群体，开展与长期预后相关因素的进一步研究势在必行。

REF: Thuss NS, Bittencourt M, Balart-Sánchez SA, Spikman JM, Maurits NM, van der Naalt J. Mild Traumatic Brain Injury in Older Adults: Recovery Course and Insights on Early Predictors of Outcome. J Neurotrauma. 2025;42(17-18):1575-1584. doi:10.1089/neu.2024.0220 PMID: 39639809

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Detecting Mild Traumatic Brain Injury after Combat Deployment: Agreement Between Veterans Health Administration Clinical System and LIMBIC-CENC Research Protocol

作战部署后轻度创伤性脑损伤的检测：退伍军人健康管理局临床系统与LIMBIC-CENC研究方案的一致性分析

Identifying historical mild traumatic brain injury (TBI) is important for many clinical care reasons; however, diagnosing mild TBI is inherently challenging and utility of screening is unknown. This study compares a standardized research process to an established clinical process for screening and diagnosis of historical mild TBI during combat deployment in a military/Veteran cohort. Agreement was far higher for TBI determinations compared with the PCE screening. Significant characteristics of PLS-positive/VHA-negative mismatches included demographic variables, military service variables, and current symptom levels. Further research is needed to better understand whether there is a clinical value to adjust the VHA TBI screening process and how these characteristics could be considered. Providers should be aware that some Veterans may have undocumented, positive mild TBI histories even if they underwent screening and/or CTBIE processes.

出于多种临床诊疗目的，识别既往轻度创伤性脑损伤（TBI）具有重要意义；然而，轻度创伤性脑损伤的诊断本身存在固有挑战性，且相关筛查手段的实用性尚未明确。本研究在军人/退伍军人群体中，对比了一套标准化研究流程与一套成熟临床流程——二者均用于筛查和诊断作战部署期间发生的既往轻度创伤性脑损伤。结果显示，在创伤性脑损伤判定方面，两种流程的一致性远高于潜在创伤性脑损伤（PCE）筛查的一致性。潜在创伤性脑损伤筛查阳性但退伍军人健康管理局（VHA）诊断阴性这一不一致情况，其显著相关特征包括人口统计学变量、军旅服役相关变量及当前症状水平。未来需开展进一步研究，以更好地明确调整退伍军人健康管理局创伤性脑损伤筛查流程是否具有临床价值，以及如何考量上述特征。医疗服务提供者应注意，部分退伍军人即便接受过创伤性脑损伤筛查和/或创伤性脑损伤综合评估（CTBIE）流程，其既往轻度创伤性脑损伤病史仍可能未被记录在案（即实际为阳性病史）。

REF: Walker WC, Pogoda TK, Eppich KG, et al. Detecting Mild Traumatic Brain Injury after Combat Deployment: Agreement Between Veterans Health Administration Clinical System and LIMBIC-CENC Research Protocol. J Neurotrauma. 2025;42(17-18):1560-1574. doi:10.1089/neu.2024.0316 PMID: 39705081

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Contribution of Extracranial Injuries to GOSE Scores after Traumatic Brain Injury TBI: A TRACK-Traumatic Brain Injury Study

创伤性脑损伤（TBI）后颅外损伤对扩展格拉斯哥预后量表（GOSE）评分的影响：一项TRACK-创伤性脑损伤研究

The Glasgow Outcome Scale Extended (GOSE) is the most widely used outcome measure for hospital-based studies of traumatic brain injury (TBI). The GOSE may be administered several ways, the choice depending on the purpose of the research. In this investigation, we evaluated the effect of administering the GOSE to collect functional disability attributed to all injuries sustained (GOSE-All) or excluding the impact of extracranial injuries (GOSE-TBI). It is important for researchers, given the aims of their studies, to decide in advance whether GOSE classification should be based on the effects of all injuries sustained or excluding the effects of extracranial injuries so as to emphasize the effects of the brain injury, as well as how disability due to emotional consequences of injury and other circumstances will be scored. Instructions to the respondent and outcomes examiner need to be clear about what causes of disability are to be included. The TBI Common Data Elements should include information that reflects the method that was used to collect the GOSE data and data repositories should disclose which data collection method was used for a given study.

扩展格拉斯哥预后量表（GOSE）是在以医院为研究场景的创伤性脑损伤（TBI）研究中，应用最为广泛的预后评估工具。GOSE的实施方式多样，具体选择需依据研究目的而定。在本研究中，我们评估了两种GOSE实施方式的效果：一种是纳入患者所有损伤所致功能障碍的评估（简称GOSE-All），另一种是排除颅外损伤影响、仅评估脑损伤相关功能障碍的方式（简称GOSE-TBI）。对于研究人员而言，基于自身研究目标提前做出两项决策至关重要：其一，确定GOSE分级应基于患者所有损伤的影响，还是排除颅外损伤影响以重点凸显脑损伤的作用；其二，明确如何对损伤引发的情绪问题及其他相关情况所致的功能障碍进行评分。此外，向受访者（患者或相关人员）及结局评估者提供的指导说明，需清晰界定应纳入评估的功能障碍成因。创伤性脑损伤（TBI）通用数据元应包含能体现GOSE数据收集方法的信息，同时数据存储库需公开特定研究采用的GOSE数据收集方式。

REF: Temkin N, Barber J, Machamer J, et al. Contribution of Extracranial Injuries to GOSE Scores after Traumatic Brain Injury TBI: A TRACK-Traumatic Brain Injury Study. J Neurotrauma. 2025;42(17-18):1550-1559. doi:10.1089/neu.2024.0421 PMID: 40200868

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