Effects of Docosahexaenoic Acid and Sex on Inflammatory Markers, Phagocytic Capacity, and Oxidative Stress After Controlled Cortical Impact in Rat Pups

二十二碳六烯酸及性别对幼鼠控制性皮质撞击损伤后炎症标志物、吞噬能力与氧化应激的影响

Traumatic brain injury (TBI) is a leading cause of acquired neurological disability in children of both sexes. Little is known about sex-dependent differences in oxidative stress and inflammatory response, two important variables in the developing brain after TBI. Using controlled cortical impact (CCI) in 17-day-old male rats to model pediatric TBI, we showed that docosahexaenoic acid (DHA) improved neurological outcomes and decreased markers of post-injury day 1 (D1) oxidative stress and D3 pro-inflammatory microglial activation. Collectively, in males DHA was associated with increased phagocytosis and inflammation-resolving protein expression together with decreased ROS in macrophages after CCI, markers often associated with neuroprotection. In females, DHA had opposite effects on ROS in CCI macrophages. Contrary to our hypothesis, DHA affected CON microglia. We present preliminary data showing that DHA affected phospholipid abundance for some specific classes in both sexes and, in males only, for others. Our findings raise the importance of using sex-matched injured and control subjects when researching putative neurotherapeutics targeting inflammation and oxidative stress after pediatric TBI.

创伤性脑损伤（TBI）是儿童后天性神经功能残疾的首要病因，男女儿童均可发病。氧化应激与炎症反应是发育期脑损伤后两个关键病理变量，但二者是否存在性别差异，目前尚不明确。本研究采用控制性皮质撞击（CCI）对出生17日雄性幼鼠建立儿童创伤性脑损伤模型，结果证实：二十二碳六烯酸（DHA）可改善神经功能预后，并降低伤后第1天（D1）氧化应激标志物、减少伤后第3天（D3）促炎型小胶质细胞活化水平。综合结果显示：雄性幼鼠发生控制性皮质撞击损伤后，DHA可促进巨噬细胞吞噬功能、上调炎症消退蛋白表达，并降低活性氧（ROS）水平，上述指标多与神经保护效应密切相关；而在雌性幼鼠中，DHA对损伤后巨噬细胞活性氧水平呈现相反调控作用。与研究假设不符的是，DHA同样对空白对照组小胶质细胞产生影响。初步研究数据表明：DHA可改变雌雄幼鼠部分特定类别磷脂丰度，另有部分磷脂类别仅在雄性幼鼠中受DHA调控。本研究结果提示：在研发靶向儿童创伤性脑损伤炎症与氧化应激的潜在神经治疗药物时，采用性别匹配的损伤组与对照组研究对象尤为重要。

REF: Schober ME, Terry CR, Monts JK, Jones GC, Ritzel RM, Loane DJ. Effects of Docosahexaenoic Acid and Sex on Inflammatory Markers, Phagocytic Capacity, and Oxidative Stress After Controlled Cortical Impact in Rat Pups. J Neurotrauma. 2026;43(7-8):660-679. doi:10.1177/08977151251393989 PMID: 42093200

由人工翻译修正

YAP Regulates Microglial Anti-Inflammatory Responses and Alleviates Cognitive Impairment Through the IL-33/ST2 Pathway after Traumatic Brain Injury

YAP通过IL-33/ST2通路调控小胶质细胞抗炎反应并减轻创伤性脑损伤后的认知功能障碍

Traumatic brain injury (TBI) is a neurological disease that seriously endangers human life and has a poor prognosis. In particular, neuroinflammation during secondary injury after TBI affects the course of TBI, and interleukin-33 (IL-33) plays an important regulatory role in neuroinflammation after TBI. Meanwhile, the Yes-associated protein (YAP) can influence the prognosis after TBI. In this study, we explored whether the upregulation of YAP in astrocytes can enhance the protective effect of IL-33 against neuroinflammation after TBI. Above all, we found that YAP produced by astrocytes regulates microglial anti-inflammatory responses through the IL-33/ST2 pathway, thereby improving cognitive function after TBI.

创伤性脑损伤（TBI）是一种严重危及人类生命且预后不良的神经系统疾病。其中，创伤性脑损伤后继发性损伤阶段的神经炎症可影响疾病进程，而白细胞介素-33（IL-33）在创伤性脑损伤后的神经炎症中发挥重要调控作用。同时，Yes相关蛋白（YAP）可影响创伤性脑损伤患者的远期预后。本研究探讨星形胶质细胞中YAP上调是否能够增强IL-33对创伤性脑损伤后神经炎症的保护作用。研究最终发现：星形胶质细胞分泌的YAP可通过IL-33/ST2通路调控小胶质细胞的抗炎反应，进而改善创伤性脑损伤后的认知功能。

REF: Zhao R, Gao SQ, Wang X, et al. YAP Regulates Microglial Anti-Inflammatory Responses and Alleviates Cognitive Impairment Through the IL-33/ST2 Pathway after Traumatic Brain Injury. J Neurotrauma. 2026;43(7-8):641-659. doi:10.1177/08977151251401226 PMID: 41371749

由人工翻译修正

A Ferret Model of Blast-Induced Traumatic Brain Injury with Biochemical and Neurobehavioral Outcome Measures

具备生化及神经行为学结局评价指标的爆炸致创伤性脑损伤雪貂模型

Although blast-induced traumatic brain injury (bTBI) is considered as the signature injury of recent combat operations such as Operations Iraqi Freedom and Enduring Freedom, no precise biomechanical and biological mechanisms of injury have been identified. Consequently, to date, there are no FDA-approved countermeasures for the treatment of bTBI. Animal models that are highly translatable to humans are required for studying the injury mechanisms underlying bTBI. As a small animal with a gyrencephalic cerebral cortex, the ferret has been increasingly used for studying the mechanisms of neurological disorders in recent years, especially for mechanically induced brain injuries such as traumatic brain injury. In this study, we used a ferret model to understand both biochemical and neurobehavioral outcome measures following closely coupled blast exposure at ∼19 psi. Overall, we observed changes in biochemical and neurobehavioral outcomes after blast exposure that together suggest that ferret is a potentially valuable animal model for understanding the mechanism of bTBI and developing effective countermeasures.

爆炸致创伤性脑损伤（bTBI）被认为是伊拉克自由行动、持久自由行动等近代军事行动中的标志性损伤，但其确切的损伤生物力学与生物学机制至今尚未阐明。因此，目前尚无经美国食品药品监督管理局（FDA）批准的爆炸致创伤性脑损伤防治干预手段。研究爆炸致创伤性脑损伤的潜在损伤机制，亟需构建高度可向人类转化的动物模型。雪貂作为具有脑回型大脑皮层的小型实验动物，近年来已越来越多地用于神经系统疾病机制研究，尤其适用于创伤性脑损伤等机械性脑损伤相关研究。本研究采用雪貂模型，在约19磅/平方英寸（psi）近距离冲击波暴露条件下，探究损伤后的生化及神经行为学评价指标变化。总体结果显示，冲击波暴露后雪貂出现明显的生化与神经行为学指标改变，提示雪貂是研究爆炸致创伤性脑损伤机制、研发有效防治措施极具潜力的实验动物模型。

REF: Phuyal G, Govindarajulu MY, Al-Lami A, et al. A Ferret Model of Blast-Induced Traumatic Brain Injury with Biochemical and Neurobehavioral Outcome Measures. J Neurotrauma. 2026;43(7-8):625-640. doi:10.1177/08977151251395742 PMID: 41250846

由人工翻译修正

Three-Month Outcomes of Traumatic Brain Injury in the General Population: A Sunnybrook Traumatic Brain Injury Cohort Study

普通人群创伤性脑损伤的三个月预后：桑尼布鲁克创伤性脑损伤队列研究

Traumatic brain injury (TBI) is common, disabling, and a growing public health concern. There are limited large-scale studies providing insight into factors associated with recovery in the general TBI population. Our aim was to identify factors associated with concussion/TBI symptom severity and return-to-work. In one of the largest observational studies of general population concussion/TBI patients to date, we found that psychiatric symptoms and litigation status were significantly associated with symptoms at 3 months, while factors related to the injury severity were not. We also observed a decoupling of factors that impact symptom score outcomes from return-to-work outcomes. These results have important implications for the management of at-risk TBI subpopulations and wider public policy considerations.

创伤性脑损伤（TBI）十分常见、致残率高，且已成为日益突出的公共卫生问题。目前能够阐明普通创伤性脑损伤人群康复相关影响因素的大规模研究仍较为匮乏。本研究旨在筛选与脑震荡/创伤性脑损伤症状严重程度及重返工作岗位相关的影响因素。本研究是目前针对普通人群脑震荡/创伤性脑损伤规模最大的观察性研究之一。结果发现：精神心理症状及诉讼状态与伤后3个月的症状严重程度显著相关，而损伤严重程度相关因素并无明显关联。研究还发现，影响症状评分预后的因素与影响复工结局的因素相互独立、彼此分离。该研究结果对创伤性脑损伤高危亚群的临床管理及公共卫生政策制定均具有重要参考意义。

REF: Ure RJ, Kiss A, Mikolić A, et al. Three-Month Outcomes of Traumatic Brain Injury in the General Population: A Sunnybrook Traumatic Brain Injury Cohort Study. J Neurotrauma. 2026;43(7-8):618-624. doi:10.1177/08977151251394006 PMID: 41213600

由人工翻译修正

Parental and Family Functioning as Predictors of Longitudinal Trajectories of Postconcussive Symptoms Following Pediatric Mild Traumatic Brain Injury: An Advancing Concussion Assessment in Pediatrics Study

父母及家庭对儿童轻型创伤性脑损伤后脑震荡症状纵向变化轨迹的预测作用：儿科脑震荡评估进展研究

The family environment plays an important role in children’s recovery from traumatic brain injury (TBI); however, parental and family factors have not been examined in-depth in pediatric mild TBI (mTBI). Existing research on postconcussive symptoms (PCS) typically employs conventional statistical analyses that assume that children with mTBI are a homogenous group. However, children may display distinct trajectories of PCS across time after mTBI. Group-based multitrajectory modeling can identify latent clusters of individuals following similar trajectories across multiple indicators of an outcome. This study sought to: (1) identify trajectories of PCS after mTBI in children, and (2) examine their association with parental and family functioning. Participants were 506 children and adolescents aged 8- to 16-years-old who were recruited during emergency department (ED) visits within 48 h of injury at five Pediatric Emergency Research Canada hospitals. Parental adjustment, protectiveness, and social support were independent predictors of trajectory membership after adjusting for demographic and injury characteristics. The identification of different symptom trajectories and specific aspects of parental and family functioning as predictors of these trajectories provides guidance for developing family-based treatments and targeting treatments to children at risk for poor recovery.

家庭环境在儿童创伤性脑损伤（TBI）的康复过程中发挥着重要作用，但目前针对儿童轻型创伤性脑损伤（mTBI），尚未对父母及家庭相关因素开展深入研究。现有关于脑震荡后症状（PCS）的研究多采用传统统计分析方法，默认将轻型创伤性脑损伤患儿视为同质性群体。事实上，患儿在受伤后的脑震荡后症状会随时间呈现不同的演变轨迹。分组多轨迹模型可根据多项结局指标，识别具有相似症状变化规律的潜在亚组人群。本研究旨在：（1）划分儿童轻型创伤性脑损伤后脑震荡后症状的演变轨迹类型；（2）探讨父母功能、家庭功能与各症状轨迹类型之间的关联。研究共纳入506名8～16岁儿童及青少年，受试者均于受伤48小时内前往加拿大五家儿科急诊研究合作医院急诊科就诊入组。在校正人口学特征及损伤相关特征后发现：父母适应能力、过度保护倾向及社会支持是症状轨迹分组的独立预测因素。本研究明确了脑震荡后症状存在不同演变轨迹，并证实父母与家庭功能的特定维度可预测轨迹类型，可为制定以家庭为基础的干预方案、精准针对康复预后不良高危患儿开展个体化治疗提供理论依据。

REF: Chadwick L, Madigan S, Callahan BL, et al. Parental and Family Functioning as Predictors of Longitudinal Trajectories of Postconcussive Symptoms Following Pediatric Mild Traumatic Brain Injury: An Advancing Concussion Assessment in Pediatrics Study. J Neurotrauma. 2026;43(7-8):605-617. doi:10.1177/08977151251393718 PMID: 41218796

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Quality of Life and Psychological Health after Recovery From Disorders of Consciousness: A Traumatic Brain Injury Model Systems Study

意识障碍患者康复后的生活质量与心理健康：一项创伤性脑损伤模型系统研究

Patients with disorders of consciousness (DoC) resulting from severe traumatic brain injury (TBI) may recover consciousness and independence years later. There is a prevailing belief that recovery, when limited to the restoration of independence in activities of daily living, will be accompanied by poor self-reported quality of life (QOL) and psychological health. This perception may influence early clinical decision-making related to the provision of life-sustaining treatment and access to specialized rehabilitation. In this observational study, we utilized data from the multisite TBI Model Systems (TBIMS) to evaluate the outcomes of QOL (Satisfaction With Life Scale [SWLS]), anxiety (Generalized Anxiety Disorder-7 Scale [GAD-7]), and depression (Patient Health Questionnaire-9 [PHQ-9]) in participants who were admitted to inpatient rehabilitation with DoC and recovered the ability to provide self-report on these measures by 1 year post-TBI. The findings challenge the assumption that recovery from DoC is associated with poor QOL and psychological health. Clinicians should be aware that patients with a broad range of residual disability after DoC are unlikely to report dissatisfaction with life or have significant anxiety and depression up to 5 years post-TBI.

重度创伤性脑损伤（TBI）所致意识障碍（DoC）患者，可能在数年后恢复意识与生活自理能力。目前普遍观点认为：若患者仅恢复日常生活自理能力，其自评生活质量（QOL）与心理健康水平往往较差。这种固有认知可能会影响早期临床决策，包括生命支持治疗的实施以及专科康复资源的准入分配。本项观察性研究依托多中心创伤性脑损伤模型系统（TBIMS）数据库开展，纳入因意识障碍入住康复病房、且在脑损伤后1年内恢复自评能力的受试者，评估其生活质量（生活满意度量表SWLS）、焦虑程度（广泛性焦虑障碍7项量表GAD-7）及抑郁程度（患者健康问卷9项量表PHQ-9）结局。研究结果推翻了“意识障碍康复后必然伴随生活质量低下、心理健康状况不佳”的传统假设。临床医生应认识到：意识障碍康复后即便遗留不同程度功能残疾，患者在伤后长达5年内，大多并不会出现生活不满意、明显焦虑或抑郁情绪。

REF: Gilmore N, Murtaugh B, Bogdanova Y, et al. Quality of Life and Psychological Health after Recovery From Disorders of Consciousness: A Traumatic Brain Injury Model Systems Study. J Neurotrauma. 2026;43(7-8):594-604. doi:10.1177/08977151251392589 PMID: 42093198

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Guideline Adherence and Outcome in Neurosurgical Treatment of Traumatic Acute Subdural Hematoma

创伤性急性硬膜下血肿神经外科治疗的指南依从性与预后

An acute subdural hematoma (ASDH) is the most common focal injury in traumatic brain injury (TBI) and a major cause of death and morbidity worldwide. The decision to perform neurosurgical evacuation of the ASDH is complex. The Brain Trauma Foundation (BTF) issued guidelines in 2006, recommending evacuation for ASDHs >1 cm or with >5 mm midline shift regardless of patients’ Glasgow Coma Scale (GCS) score, and in cases of neurological deterioration, abnormal pupillary reaction, or high intracranial pressure (ICP). Despite their global recognition, the evidence supporting these guidelines is weak. This study assesses adherence to BTF guidelines in a European cohort and determines the effect on mortality and functional outcomes. Overall adherence to BTF guidelines for surgical ASDH management was low. The current surgical thresholds do not align with clinical practice. Elderly patients and those with severe TBI were less likely to be treated per guidelines. Incorporating patient age, GCS and hematoma volume into the guidelines may enhance their relevance and adherence in clinical practice.

急性硬膜下血肿（ASDH）是创伤性脑损伤（TBI）中最常见的局灶性损伤，也是全球致死、致残的主要原因之一。是否对急性硬膜下血肿实施神经外科血肿清除术，临床决策十分复杂。脑创伤基金会（BTF）于2006年发布相关指南，推荐对血肿厚度＞1 cm或中线移位＞5 mm的急性硬膜下血肿患者，无论格拉斯哥昏迷量表（GCS）评分高低，均行手术清除；同时适用于神经功能恶化、瞳孔反射异常或颅内压（ICP）升高的患者。尽管该指南已获得全球认可，但支撑其推荐意见的研究证据仍较薄弱。本研究基于欧洲人群队列，评估临床对脑创伤基金会指南的依从性，并分析其对患者死亡率及功能预后的影响。结果显示，临床对急性硬膜下血肿手术治疗相关BTF指南的总体依从性偏低，现行手术干预阈值与临床实际诊疗现状并不匹配。老年患者及重度创伤性脑损伤患者更难按照指南标准接受规范治疗。在指南制定中纳入患者年龄、格拉斯哥昏迷量表评分及血肿体积等指标，或可提升指南的临床适用性与临床依从性。

REF: Singh RD, Corper SA, Vreeburg RJG, et al. Guideline Adherence and Outcome in Neurosurgical Treatment of Traumatic Acute Subdural Hematoma. J Neurotrauma. 2026;43(7-8):585-593. doi:10.1177/08977151251387172 PMID: 41174921

由人工翻译修正

Differential DNA Methylation of the Brain-Derived Neurotrophic Factor Gene is Observed after Pediatric Traumatic Brain Injury Compared with Orthopedic Injury

儿童创伤性脑损伤相较于骨科损伤后，脑源性神经营养因子基因存在差异性DNA甲基化

Pediatric traumatic brain injury (TBI) triggers biological changes that may differ from those observed in non-brain injuries. Brain-derived neurotrophic factor (BDNF) DNA methylation (DNAm) may serve as a novel, dynamic biomarker of the brain’s response and help identify TBI-specific epigenetic patterns relevant to later recovery. Therefore, the purpose of this study was to examine whether BDNF DNAm differed between children with TBI and those with orthopedic injury (OI, comparison group) acutely and over time. The findings suggest that BDNF DNAm differs between children with TBI and those with OI, particularly in the acute period. BDNF DNAm differences may reflect early biological responses that are specific to TBI.

儿童创伤性脑损伤（TBI）会引发一系列生物学改变，且这类改变与非脑部损伤存在差异。脑源性神经营养因子（BDNF）基因的DNA甲基化（DNAm）可作为反映脑部应激反应的新型动态生物标志物，同时有助于识别与后期康复相关、创伤性脑损伤特有的表观遗传特征。因此，本研究旨在探讨创伤性脑损伤患儿与骨科损伤（OI，对照组）患儿的BDNF 基因DNA甲基化水平在急性期及随访过程中是否存在差异。研究结果显示，创伤性脑损伤患儿与骨科损伤患儿的BDNF基因DNA甲基化存在差异，尤以急性期最为显著。BDNF基因DNA甲基化差异或可反映创伤性脑损伤所特有的早期生物学应答特征。

REF: Heinsberg LW, Kesbhat A, Petersen B, et al. Differential DNA Methylation of the Brain-Derived Neurotrophic Factor Gene is Observed after Pediatric Traumatic Brain Injury Compared with Orthopedic Injury. J Neurotrauma. 2026;43(7-8):575-584. doi:10.1177/08977151251400737 PMID: 41376515 PMCID: PMC12990021

由人工翻译修正

Alterations in CSF Amyloid-β and Tau Biomarkers in Former College and Professional American Football Players: Findings from the DIAGNOSE CTE Research Project

美国大学及职业橄榄球运动员脑脊液β淀粉样蛋白与Tau生物标志物的变化：DIAGNOSE CTE研究结果

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to repetitive head impacts (RHIs), characterized by tau tangles around small blood vessels at the depths of the sulci. Currently, CTE can be diagnosed only postmortem, but can present with an array of cognitive, behavioral, mood, and motor symptoms. However, traumatic brain injury is also associated with increased risk of Alzheimer’s disease (AD) and may lead to comorbid neuropathology. Characterization of the in vivo biomarkers of CTE is a necessary next step to facilitate accurate diagnoses. We examined the profile of cerebrospinal fluid (CSF) biomarkers of amyloid-β, total tau (tTau), and phospho-tau (pTau) in a cohort of former professional (PRO, n = 100) and college (COL, n = 40) football players at high risk of CTE compared to asymptomatic unexposed controls (UE, n = 43). The findings of significant associations of reduced CSF Aβ levels with RHI in elite football players are in line with recent postmortem studies; however, the lack of relationship with CSF tTau and pTau species observed to be altered in the setting of AD suggests that the pathological features of CTE reflected in fluid biomarkers are complex and require further study. The overlapping comorbid age-dependent features of neurodegeneration that occur in those at risk for CTE suggest that tau pathology in CTE is not reliably reflected by currently available fluid biomarkers and that the use of multiple biomarkers related to the compound characteristics of CTE may be required for early detection.

慢性创伤性脑病（CTE）是一种与反复头部撞击（RHI）暴露相关的神经退行性疾病，其病理特征为脑沟深部小血管周围出现Tau蛋白缠结。目前，慢性创伤性脑病仅能通过尸检确诊，但患者可表现出一系列认知、行为、情绪及运动功能障碍症状。此外，创伤性脑损伤还会升高阿尔茨海默病（AD）的患病风险，并可能引发共病神经病理改变。明确慢性创伤性脑病的在体生物标志物，是实现精准诊断亟需推进的下一步研究方向。本研究纳入高患病风险的前职业橄榄球运动员（PRO组，n=100）与前大学橄榄球运动员（COL组，n=40），以无头部撞击暴露史的无症状健康人群作为对照组（UE组，n=43），检测其脑脊液（CSF）中β淀粉样蛋白、总Tau蛋白（tTau）及磷酸化Tau蛋白（pTau）的标志物表达谱。研究发现，精英橄榄球运动员脑脊液β淀粉样蛋白水平降低与反复头部撞击存在显著关联，该结果与近期尸检研究结论一致；但在阿尔茨海默病中存在异常改变的脑脊液总Tau蛋白、磷酸化Tau蛋白，本研究未发现其与反复头部撞击存在相关性。这提示，体液标志物所反映的慢性创伤性脑病病理特征十分复杂，仍需进一步深入研究。慢性创伤性脑病高危人群存在神经退行性病变的年龄相关性重叠共病特征，说明现有体液标志物尚不能可靠反映慢性创伤性脑病的Tau蛋白病理改变；若要实现早期筛查，或许需要联合使用多种与慢性创伤性脑病复合病理特征相关的生物标志物。

REF: Jansson D, Shofer J, Colasurdo E, et al. Alterations in CSF Amyloid-β and Tau Biomarkers in Former College and Professional American Football Players: Findings from the DIAGNOSE CTE Research Project. J Neurotrauma. 2026;43(7-8):559-574. doi:10.1177/08977151251390520 PMID: 41612558 PMCID: PMC13130387

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