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Correction to: Neck Collar with Mild Jugular Vein Compression Ameliorates Brain Activation Changes During a Working Memory Task after a Season of High School Football; DOI: 10.1089/neu.2016.4834. 更正为轻度颈静脉压迫颈圈可改善高中橄榄球赛季后工作记忆任务中的大脑激活变化;DOI: 10.1089/neu.2016.4834。
IF 3.9 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-12-01 Epub Date: 2024-11-12 DOI: 10.1089/neu.2016.4834.correx
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引用次数: 0
Correction to: High School Sports-Related Concussion, and the Effect of a Jugular Vein Compression Collar: A Prospective Longitudinal Investigation of Neuroimaging and Neurofunctional Outcomes; DOI: 10.1089/neu.2021.0141. 更正为高中生运动相关脑震荡和颈静脉压迫颈圈的影响:神经影像学和神经功能结果的前瞻性纵向调查》;DOI: 10.1089/neu.2021.0141。
IF 3.9 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-12-01 Epub Date: 2024-11-11 DOI: 10.1089/neu.2021.0141.correx
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引用次数: 0
Volumetric Assessment of Traumatic Intracranial Hematomas: Is ABC/2 Reliable? 外伤性颅内血肿的体积评估:ABC/2 是否可靠?
IF 3.9 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-12-01 Epub Date: 2024-09-04 DOI: 10.1089/neu.2024.0248
Alexander Fletcher-Sandersjöö, Anders Lewén, Anders Hånell, David W Nelson, Marc Maegele, Mikael Svensson, Bo-Michael Bellander, Per Enblad, Eric Peter Thelin, Teodor Svedung Wettervik

Accurate measurement of traumatic intracranial hematoma volume is important for assessing disease progression and prognosis, as well as for serving as an important end-point in clinical trials aimed at preventing hematoma expansion. While the ABC/2 formula has traditionally been used for volume estimation in spontaneous intracerebral hemorrhage, its adaptation to traumatic hematomas lacks validation. This study aimed to compare the accuracy of ABC/2 with computer-assisted volumetric analysis (CAVA) in estimating the volumes of traumatic intracranial hematomas. We performed a dual-center observational study that included adult patients with moderate-to-severe traumatic brain injury. Volumes of intracerebral, subdural (SDHs), and epidural hematomas from admission computed tomography scans were measured using ABC/2 and CAVA, and compared using the Wilcoxon signed-rank test, Spearman's rank correlation, Lin's concordance correlation coefficient (CCC), and Bland-Altman plots. Prognostic significance for outcomes was evaluated through logistic and linear regression models. In total, 1,179 patients with 1,543 hematomas were included. Despite a high correlation (Spearman coefficients between 0.95 and 0.98) and excellent concordance (Lin's CCC from 0.89 to 0.96) between ABC/2 and CAVA, ABC/2 overestimated hematoma volumes compared with CAVA, in some instances exceeding 50 ml. Bland-Altman analysis highlighted wide limits of agreement, especially in SDH. While both methods demonstrated comparable accuracy in predicting outcomes, CAVA was slightly better at predicting craniotomies and midline shift. We conclude that while ABC/2 provides a generally reliable volumetric assessment suitable for descriptive purposes and as baseline variables in studies, CAVA should be the gold standard in clinical situations and studies requiring more precise volume estimations, such as those using hematoma expansion as an outcome.

准确测量外伤性颅内血肿体积对于评估疾病进展和预后非常重要,同时也是旨在防止血肿扩大的临床试验的重要终点。传统上,ABC/2 公式一直用于自发性脑内出血的血肿体积估算,但其对创伤性血肿的适应性还缺乏验证。本研究旨在比较 ABC/2 公式与计算机辅助容积分析(CAVA)在估计外伤性颅内血肿体积方面的准确性。我们进行了一项双中心观察研究,研究对象包括中重度脑外伤成年患者。我们使用 ABC/2 和 CAVA 测量了入院 CT 扫描中的脑内血肿 (ICH)、硬膜下血肿 (SDH) 和硬膜外血肿 (EDH) 的体积,并使用 Wilcoxon 符号秩检验、Spearman 等级相关性、Lin 一致性相关系数 (CCC) 和 Bland-Altman 图进行了比较。通过逻辑和线性回归模型评估了预后的重要性。共纳入了 1,179 名患者,1,543 个血肿。尽管ABC/2和CAVA之间具有很高的相关性(Spearman系数介于0.95和0.98之间)和很好的一致性(Lin's CCC介于0.89和0.96之间),但与CAVA相比,ABC/2高估了血肿体积,在某些情况下超过了50毫升。Bland-Altman分析强调了两者之间的差异,尤其是在SDH方面。虽然两种方法预测结果的准确性相当,但 CAVA 在预测开颅手术和中线移位方面略胜一筹。我们的结论是,虽然 ABC/2 提供的容积评估基本可靠,适合用于描述性目的和作为研究中的基线变量,但在需要更精确容积估计的临床情况和研究中,如将血肿扩大作为结果的研究中,CAVA 应成为金标准。
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引用次数: 0
Association Between Impulsivity, Self-Harm, Suicidal Ideation, and Suicide Attempts in Patients with Traumatic Brain Injury. 脑外伤患者的冲动、自残、自杀意念和自杀企图之间的关系。
IF 3.9 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-12-01 Epub Date: 2024-09-05 DOI: 10.1089/neu.2024.0167
Liliana Ladner, Tyler Shick, Srijan Adhikari, Eric Marvin, Justin Weppner, Anita Kablinger

Traumatic brain injury (TBI) affects over 48 million people worldwide each year. Suicide is common in TBI, and there are several known contributing factors, including severe TBI, depression, alcohol use, and male sex. Impulsivity, or the tendency to act quickly with little thought, may be an early predictor of suicidality following TBI. The purpose of this study was to evaluate the risk of suicidality in patients with a prior history of impulsivity following a TBI. Using de-identified electronic health records from the TriNetX U.S. Collaborative Network with Natural Language Processing, three cohorts were generated: the impulsivity TBI cohort (I+TBI+) included subjects with a diagnosis of impulsivity before a diagnosis of TBI; the no impulsivity TBI cohort (I-TBI+) included patients with TBI but no impulsivity; the impulsivity no TBI cohort (I+TBI-) included patients with impulsivity but TBI. Two analyses were conducted, including analysis 1 (impulsivity TBI vs. no impulsivity TBI) and analysis 2 (impulsivity TBI vs. impulsivity no TBI). Patients were 1:1 matched by age, sex, race, ethnicity, psychiatric diagnoses, and antidepressant use. Outcomes included a diagnosis of self-harm, suicidal ideation, or a suicide attempt within 1 year after the index event. The all-time incidence of each outcome was assessed across different age categories. The chi-square test (categorical variables) and t-test (numerical variables) were used to assess for differences between groups. A total of 1,292,776 patients with TBI were identified in the study. After 1:1 matching, there were 20,694 patients (mean [standard deviation, SD] age, 48.1 [21.8]; 8,424 females [40.7%]) with impulsivity and TBI (I+TBI+), 1,272,082 patients (mean [SD] age, 46.0 [23.1]; 562,705 females [44.2%]) with TBI alone (I-TBI+), and 90,669 patients (mean [SD] age, 43.7 [22.6]; 45,188 females [49.8%]) with impulsivity alone (I+TBI-). Within the first year after a TBI, patients with impulsivity were more likely to exhibit self-harm (p < 0.001), suicidal ideation (p < 0.001), or a suicide attempt (p < 0.001). Compared with patients with TBI without impulsivity, those with impulsivity had a 4-fold increase in the incidence of self-harm (2.81% vs. 0.63%), an 8-fold increase in suicidal ideation (52.42% vs. 6.41%), and a 21-fold increase in suicide attempts (32.02% vs. 1.50%). This study suggests that impulsivity diagnosed before a TBI may increase the risk of post-traumatic suicidality, with a 4-fold increased risk of self-harm, an 8-fold increased risk of suicidal ideation and a 21-fold increased risk of suicide attempts. This characterizes a group of at-risk individuals who may benefit from early psychiatric support and targeted interventions following a TBI.

全世界每年有超过 4800 万人受到创伤性脑损伤(TBI)的影响。自杀在创伤性脑损伤中很常见,已知的诱因包括严重创伤性脑损伤、抑郁、酗酒和男性。冲动,即不假思索地迅速行动的倾向,可能是创伤后自杀的早期预测因素。本研究的目的是评估有冲动倾向的创伤性脑损伤(TBI)患者的自杀风险。研究人员利用TriNetX美国协作网络的去标识电子健康记录和自然语言处理技术,生成了三个队列:冲动性TBI队列(I+TBI+)包括在诊断出TBI之前就诊断出冲动性的受试者;无冲动性TBI队列(I-TBI+)包括有TBI但无冲动性的患者;无冲动性TBI队列(I+TBI-)包括有冲动性但有TBI的患者。共进行了两项分析,包括分析 1(有冲动性 TBI 与无冲动性 TBI)和分析 2(有冲动性 TBI 与无冲动性 TBI)。患者的年龄、性别、种族、民族、精神病诊断和抗抑郁药使用情况均按 1:1 的倾向得分匹配。结果包括自残诊断、自杀意念或指数事件后一年内的自杀企图。每种结果的历时发生率均按不同年龄类别进行评估。采用卡方检验(分类变量)和 t 检验(数值变量)来评估组间差异。研究共确定了 1,292,776 名创伤性脑损伤患者。经过 1:1 倾向评分匹配后,有 20,694 名患者(平均 [SD] 年龄,48.1 [21.8];8,424 名女性 [40.7%])患有冲动和 TBI(I+TBI+),1,272,082 名患者(平均 [SD] 年龄,46.0[23.1];562 705 名女性[44.2%]),以及 90 669 名患者(平均[标码]年龄为 43.7 [22.6];45 188 名女性[49.8%])仅有冲动倾向(I+TBI-)。在创伤性脑损伤后的第一年内,有冲动倾向的患者更有可能出现自残(P < 0.001)、自杀意念(P < 0.001)或自杀未遂(P < 0.001)。与没有冲动倾向的创伤性脑损伤患者相比,有冲动倾向的患者自残的发生率增加了四倍(2.81% vs. 0.63%),自杀意念增加了八倍(52.42% vs. 6.41%),自杀企图增加了二十一倍(32.02% vs. 1.50%)。这项研究表明,创伤性脑损伤前诊断出的冲动症可能会增加创伤后自杀的风险,自残风险增加四倍,自杀意念风险增加八倍,自杀未遂风险增加二十一倍。这是一组高危人群的特征,他们可能受益于创伤性脑损伤后的早期精神支持和有针对性的干预措施。
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引用次数: 0
Repetitive Mild Closed-Head Injury Induced Synapse Loss and Increased Local BOLD-fMRI Signal Homogeneity. 重复性轻度闭头损伤会导致突触缺失,并增加局部 BOLD-fMRI 信号的均匀性。
IF 3.9 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-12-01 Epub Date: 2024-09-20 DOI: 10.1089/neu.2024.0095
Marija Markicevic, Francesca Mandino, Takuya Toyonaga, Zhengxin Cai, Arman Fesharaki-Zadeh, Xilin Shen, Stephen M Strittmatter, Evelyn M R Lake

Repeated mild head injuries due to sports, or domestic violence and military service are increasingly linked to debilitating symptoms in the long term. Although symptoms may take decades to manifest, potentially treatable neurobiological alterations must begin shortly after injury. Better means to diagnose and treat traumatic brain injuries requires an improved understanding of the mechanisms underlying progression and means through which they can be measured. Here, we employ a repetitive mild traumatic brain injury (rmTBI) and chronic variable stress mouse model to investigate emergent structural and functional brain abnormalities. Brain imaging is achieved with [18F]SynVesT-1 positron emission tomography, with the synaptic vesicle glycoprotein 2A ligand marking synapse density and BOLD (blood-oxygen-level-dependent) functional magnetic resonance imaging (fMRI). Animals were scanned six weeks after concluding rmTBI/Stress procedures. Injured mice showed widespread decreases in synaptic density coupled with an increase in local BOLD-fMRI synchrony detected as regional homogeneity. Injury-affected regions with higher synapse density showed a greater increase in fMRI regional homogeneity. Taken together, these observations may reflect compensatory mechanisms following injury. Multimodal studies are needed to provide deeper insights into these observations.

由于运动、家庭暴力或服兵役导致的反复轻微头部损伤,越来越多地与长期衰弱症状联系在一起。虽然症状可能需要几十年才能显现,但潜在的可治疗的神经生物学改变必须在受伤后不久就开始。要想更好地诊断和治疗脑外伤,就必须更好地了解脑外伤进展的内在机制和测量方法。在这里,我们采用重复性轻度闭头损伤(rmTBI)和慢性可变应激(CVS)小鼠模型来研究新出现的大脑结构和功能异常。脑成像是通过[18F]SynVesT-1正电子发射断层扫描和BOLD(血氧水平依赖性)功能磁共振成像(fMRI)实现的,突触小泡糖蛋白2A配体标记突触密度。在rmTBI/应激程序结束六周后对动物进行扫描。受伤小鼠的突触密度普遍下降,同时局部 BOLD-fMRI 同步性增加,表现为区域同质性。突触密度较高的受损伤区域显示出更高的 fMRI 区域同质性。综合来看,这些观察结果可能反映了损伤后的代偿机制。要深入了解这些观察结果,还需要进行多模态研究。
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引用次数: 0
The White Matter Fiber Tract Deforms Most in the Perpendicular Direction During In Vivo Volunteer Impacts. 白质纤维束在体内志愿者撞击过程中垂直方向的变形最大。
IF 3.9 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-12-01 Epub Date: 2024-08-30 DOI: 10.1089/neu.2024.0183
Zhou Zhou, Christoffer Olsson, T Christian Gasser, Xiaogai Li, Svein Kleiven

White matter (WM) tract-related strains are increasingly used to quantify brain mechanical responses, but their dynamics in live human brains during in vivo impact conditions remain largely unknown. Existing research primarily looked into the normal strain along the WM fiber tracts (i.e., tract-oriented normal strain), but it is rarely the case that the fiber tract only endures tract-oriented normal strain during impacts. In this study, we aim to extend the in vivo measurement of WM fiber deformation by quantifying the normal strain perpendicular to the fiber tract (i.e., tract-perpendicular normal strain) and the shear strain along and perpendicular to the fiber tract (i.e., tract-oriented shear strain and tract-perpendicular shear strain, respectively). To achieve this, we combine the three-dimensional strain tensor from the tagged magnetic resonance imaging with the diffusion tensor imaging (DTI) from an open-access dataset, including 44 volunteer impacts under two head loading modes, i.e., neck rotations (N = 30) and neck extensions (N = 14). The strain tensor is rotated to the coordinate system with one axis aligned with DTI-revealed fiber orientation, and then four tract-related strain measures are calculated. The results show that tract-perpendicular normal strain peaks are the largest among the four strain types (p < 0.05, Friedman's test). The distribution of tract-related strains is affected by the head loading mode, of which laterally symmetric patterns with respect to the midsagittal plane are noted under neck extensions, but not under neck rotations. Our study presents a comprehensive in vivo strain quantification toward a multifaceted understanding of WM dynamics. We find that the WM fiber tract deforms most in the perpendicular direction, illuminating new fundamentals of brain mechanics. The reported strain images can be used to evaluate the fidelity of computational head models, especially those intended to predict fiber deformation under noninjurious conditions.

白质(WM)纤维束相关应变越来越多地被用于量化大脑的机械反应,但它们在活体撞击条件下的动态变化在很大程度上仍不为人所知。现有研究主要研究沿白质纤维束的正常应变(即面向纤维束的正常应变),但在撞击过程中纤维束仅承受面向纤维束的正常应变的情况很少见。在本研究中,我们旨在通过量化垂直于纤维束的法向应变(即纤维束垂直法向应变)以及沿纤维束和垂直于纤维束的剪切应变(即纤维束导向剪切应变和纤维束垂直剪切应变)来扩展体内 WM 纤维变形的测量。为此,我们将标记磁共振成像的三维应变张量与弥散张量成像(DTI)相结合,后者来自一个开放获取的数据集,包括 44 名志愿者在两种头部加载模式下受到的撞击,即颈部旋转(30 人)和颈部伸展(14 人)。将应变张量旋转到坐标系,坐标系的一个轴与 DTI 显示的纤维方向对齐,然后计算出四个束相关的应变测量值。结果显示,在四种应变类型中,束垂直正常应变峰值最大(P < 0.05,Friedman 检验)。束相关应变的分布受头部加载模式的影响,其中颈部伸展时相对于中矢状面的横向对称模式明显,而颈部旋转时则不明显。我们的研究提出了一种全面的活体应变量化方法,旨在从多方面了解 WM 的动态变化。我们发现 WM 纤维束在垂直方向上变形最大,这揭示了大脑力学的新基础。所报告的应变图像可用于评估头部计算模型的保真度,尤其是那些旨在预测非损伤条件下纤维变形的模型。
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引用次数: 0
Safety and Feasibility of Early Activity-Based Therapy Following Severe Traumatic Spinal Cord Injury: Results from a Single-Arm Pilot Trial. 严重创伤性脊髓损伤后早期活动治疗的安全性和可行性:来自单臂试验的结果。
IF 3.9 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-11-29 DOI: 10.1089/neu.2024.0297
Antoine Dionne, David Magnuson, Andréane Richard-Denis, Yvan Petit, Dorothy Barthélémy, Francis Bernard, Jean-Marc Mac-Thiong

Early activity-based therapy (E-ABT) has the potential to decrease complications and radically improve neurofunctional recovery following traumatic spinal cord injury (TSCI). Unfortunately, E-ABT after TSCI has never been attempted in humans due to practical obstacles and potential safety concerns. This study aims to report on the safety and feasibility outcomes of the Protocol for Rapid Onset of Mobilization in Patients with Traumatic SCI (PROMPT-SCI) trial: the first-ever trial of E-ABT in critically ill patients who suffered a severe TSCI. To do so, 45 patients with severe TSCI were recruited to participate in the PROMPT-SCI trial between April 2021 and August 2023. The intervention consisted of daily 30-min sessions of motor-assisted in-bed leg cycling for 14 days, starting within 48 h of early surgery (≈72 h from the initial trauma). Adverse events were closely monitored, and completion rates were evaluated. Out of the 45 participants, 36 (80%) completed a full and safe session within 48 h of surgery and all participants managed to achieve this outcome within 72 h of surgery. Over the full 14-day protocol, the average completion rate of sessions was 87.2 ± 22.7% (range: 7.1-100.0%). A total of three patients were mechanically ventilated during the protocol and all three had 100% completion of sessions. Frequent reasons for unattempted/incomplete sessions were scheduling conflicts with activities related to care (e.g., bronchoscopy) and fatigue/uncontrolled pain before initiating cycling. We also report no neurological deterioration caused by cycling and no major adverse event recorded during or between sessions. In conclusion, this study suggests that E-ABT can be safely initiated within 48-72 h after a severe TSCI with no major adverse event. In the form of daily passive in-bed leg cycling, E-ABT is also acceptable for target users, and feasible over the course of the first weeks after the initial trauma, as shown by our excellent rate of completed sessions (87%). The present results also suggest that improved collaboration with intensive care unit staff, including intensivists and nurses, could improve these rates even further.

早期活动治疗(E-ABT)具有减少并发症和从根本上改善创伤性脊髓损伤(TSCI)后神经功能恢复的潜力。不幸的是,由于实际障碍和潜在的安全问题,TSCI后的E-ABT从未在人体中进行过尝试。本研究旨在报告创伤性脊髓损伤患者快速起搏方案(PROMPT-SCI)试验的安全性和可行性结果:这是首个E-ABT在严重创伤性脊髓损伤危重患者中的试验。为此,在2021年4月至2023年8月期间招募了45名重度TSCI患者参加PROMPT-SCI试验。干预包括每天30分钟的运动辅助床上腿部骑行,持续14天,从早期手术48小时内开始(距初始创伤约72小时)。密切监测不良事件,并评估完成率。在45名参与者中,36名(80%)在手术后48小时内完成了完整且安全的疗程,所有参与者都在手术后72小时内达到了这一结果。在整个14天的治疗方案中,疗程的平均完成率为87.2±22.7%(范围:7.1-100.0%)。在治疗过程中,总共有3名患者进行了机械通气,并且所有3名患者都100%完成了治疗。未尝试/不完整疗程的常见原因是与护理相关的活动(如支气管镜检查)和开始骑行前的疲劳/不受控制的疼痛冲突。我们也报告了骑行期间或间隔期间没有记录的神经系统恶化和主要不良事件。总之,本研究表明,E-ABT可以在严重TSCI后48-72小时内安全启动,无重大不良事件。以每日被动床内腿部循环的形式,E-ABT对于目标用户也是可以接受的,并且在初始创伤后的第一周内是可行的,正如我们出色的完成率(87%)所示。目前的结果还表明,改善与重症监护病房工作人员的合作,包括重症监护医生和护士,可以进一步提高这些比率。
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引用次数: 0
Analysis of Concussions with Persisting Symptoms Caused by Motor Vehicle Crashes in 136 Vehicle Occupants Shows that Females Are Vulnerable Road Users. 对 136 名乘车者因机动车碰撞造成的脑震荡持续症状的分析表明,女性是易受伤害的道路使用者。
IF 3.9 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-11-27 DOI: 10.1089/neu.2024.0207
Charles H Tator, Olivia F T Scott, Benjamin S Elkin, Emma Prentice, Umar Muhammad, Mozhgan Khodadadi, Qixuan Li, Ella Huszti, Maria Carmela Tartaglia

At the Canadian Concussion Centre, we treated 136 patients from 2000 to 2020 who sustained concussion plus persisting concussion symptoms (C+PCS) as motor vehicle occupants involved in motor vehicle crashes (MVCs). This center specializes in the treatment of patients with C+PCS. The objective of the present study was to identify strategies for preventing concussion among vehicle occupants involved in MVC. Indeed, this is the first study focused on C+PCS in MVC occupants, and our main purpose was to evaluate the effectiveness of onboard concussion prevention strategies. In this retrospective, consecutive cohort of 136 patients with C+PCS, we examined the patients' demographic and injury features in relation to the nature of the MVC including speed, direction of impact, and availability, deployment, and effectiveness of onboard occupant safety measures including seatbelts, head restraints, and airbags. The most frequent combination of factors was a belted female driver of an automobile struck from behind by another automobile. Surprisingly, the entire patient cohort comprised more females (69.1%) than males (30.9%), and rear-end collision was the most common type in females. Most injured occupants of both sexes were wearing seatbelts, but only a minority of the crashes caused airbag deployment. The seven most common symptoms were headache (84.6%), anxiety (72.8%), sensitivity to light (70.6%), memory problems (69.9%), sensitivity to noise (66.2%), irritability (56.6%), and depression (55.9%). Whiplash was a frequent associated injury in both sexes. Complete recovery from C+PCS was rare, and most patients with known follow-up continued to suffer from persisting symptoms for months to years. The median symptom duration for all 136 patients was 30.0 months (interquartile range: 16.8-56.0 months). Based on these findings, we conclude that females are indeed vulnerable road users with respect to C+PCS, and our literature search showed that there had been some previous evidence of increased injury risk of other injuries in female occupants. We recommend that additional prevention strategies are required to reduce the post-crash acceleration-deceleration "bobble-head" movement of the head on trunk causing both concussion and whiplash as has been accomplished in auto racing. Also, these prevention measures must be investigated in crash studies that include low-to-high speed rear-end collisions using anthropometrically appropriate models of male and female occupants reflecting the range of sizes of both sexes. There is a need for more concussion brain injury prevention research focusing on the vulnerability of female occupants, which has not been sufficiently addressed even though the deficiency was identified many years ago. The sex inequity of current onboard motor vehicle concussion brain injury prevention measures especially with respect to females should be addressed by governments and the automobile and insurance industries.

在加拿大脑震荡中心(Canadian Concussion Centre),我们从 2000 年到 2020 年共治疗了 136 名脑震荡合并持续脑震荡症状(C+PCS)的患者,他们都是机动车碰撞(MVC)事故中的机动车乘员。该中心专门治疗 C+PCS 患者。本研究的目的是确定预防机动车碰撞事故中车内人员脑震荡的策略。事实上,这是第一项针对机动车交通事故中 C+PCS 乘员的研究,我们的主要目的是评估车载脑震荡预防策略的有效性。在这项对 136 名 C+PCS 患者进行的回顾性连续队列研究中,我们研究了患者的人口统计学特征和受伤特征与 MVC 性质的关系,包括速度、撞击方向以及车载乘员安全措施(包括安全带、头枕和安全气囊)的可用性、部署和有效性。最常见的因素组合是系有安全带的女性驾驶员被另一辆汽车从后面撞击。令人惊讶的是,整个患者群体中女性(69.1%)多于男性(30.9%),而追尾碰撞是女性最常见的类型。大多数受伤的男女乘员都系了安全带,但只有少数撞车事故导致安全气囊打开。最常见的七种症状是头痛(84.6%)、焦虑(72.8%)、对光线敏感(70.6%)、记忆问题(69.9%)、对噪音敏感(66.2%)、易怒(56.6%)和抑郁(55.9%)。在男女患者中,鞭打是一种常见的相关损伤。从 C+PCS 中完全恢复的情况很少见,大多数已知随访患者的症状持续数月至数年不等。所有 136 名患者的症状持续时间中位数为 30.0 个月(四分位间范围:16.8-56.0 个月)。基于这些研究结果,我们得出结论:女性确实是容易受到 C+PCS 伤害的道路使用者。我们建议,需要采取更多的预防策略,以减少碰撞后头部在躯干上的加速-减速 "摇头晃脑 "运动造成脑震荡和鞭打,这在汽车比赛中已经实现。此外,这些预防措施必须在碰撞研究中进行调查,其中包括低速到高速的追尾碰撞,使用人体测量学上适当的男性和女性乘员模型,以反映两性的体型范围。有必要针对女性乘员的脆弱性开展更多脑震荡脑损伤预防研究,尽管多年前就发现了这一不足,但至今仍未得到充分解决。政府、汽车业和保险业应解决目前车载脑震荡预防措施的性别不平等问题,特别是对女性的不平等。
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引用次数: 0
Identification of a Therapeutic Window for Neurovascular Unit Repair after Experimental Spinal Cord Injury. 实验性脊髓损伤后神经血管单元修复治疗窗口的确定
IF 3.9 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-11-26 DOI: 10.1089/neu.2024.0233
Vanessa Hubertus, Lea Meyer, Lilly Waldmann, Laurens Roolfs, Nima Taheri, Katharina Kersting, Emily von Bronewski, Melina Nieminen-Kelhä, Irina Kremenetskaia, Christian Uhl, Kim C Fiedler, Jan-Erik Ode, Andre Rex, Harald Prüß, Asylkhan Rakhymzhan, Anja E Hauser, Raluca Niesner, Frank L Heppner, Michael G Fehlings, Peter Vajkoczy
<p><p>Traumatic spinal cord injury (SCI) is a devastating condition for which effective neuroregenerative and neuroreparative strategies are lacking. The post-traumatic disruption of the blood-spinal cord barrier (BSCB) as part of the neurovascular unit (NVU) is one major factor in the complex pathophysiology of SCI, which is associated with edema, inflammation, and cell death in the penumbra regions of the spinal cord adjacent to the lesion epicenter. Thus, the preservation of an intact NVU and vascular integrity to facilitate the regenerative capacity following SCI is a desirable therapeutic target. This study aims to identify a therapeutic window of opportunity for NVU repair after SCI by characterizing the timeframe of its post-traumatic disintegration and reintegration with implications for functional spinal cord recovery. Following thoracic clip-compression SCI or sham injury, adult C57BL/6J mice were followed up from one to 28 days. At one, three, seven, 14, and 28 days after SCI/sham, seven-Tesla magnetic resonance imaging (MRI), neurobehavioral analysis (Basso mouse scale, Tally subscore, CatWalk® gait analysis), and following sacrifice immunohistochemistry were performed, assessing vessel permeability via Evans blue (EVB) extravasation, (functional) vessel density, and NVU integrity. Thy1-yellow fluorescent protein+ mice were additionally implanted with a customized spinal window chamber and received longitudinal <i>in vivo</i> two-photon excitation imaging (2PM) with the injection of rhodamine-B-isothiocyanate-dextran for the combined imaging of axons and vasculature up to 14 days after SCI/sham injury. Post-traumatic edema formation as assessed by MRI volumetry peaked at one to three days after injury, while EVB permeability quantification revealed a thoroughly injured BSCB up to 14 days after SCI. Partial regeneration of functional vasculature via endogenous revascularization was detected after one to four weeks, however, with only 50-54% of existing vessels regaining functional perfusion. Longitudinal <i>in vivo</i> 2PM visualized the progressive degeneration of initially preserved spinal cord axons in the peri-traumatic zone after SCI while displaying a rarefication of functionally perfused vessels up to two weeks after injury. Neurobehavioral recovery started after one week but remained impaired over the whole observation period of four weeks after SCI. With this study, a therapeutic window to address the impaired NVU starting from the first days to two weeks after SCI is identified. A number of lines of evidence including <i>in vivo</i> 2PM, assessment of NVU integrity, and neurobehavioral assessments point to the critical nature of targeting the NVU to enhance axonal preservation and regeneration after SCI. Continuous multifactorial therapy applications targeting the integrity of the NVU over the identified therapeutic window of opportunity appears promising to ameliorate functional vessel perseverance and the spinal cord's rege
创伤性脊髓损伤(SCI)是一种破坏性疾病,目前尚缺乏有效的神经再生和神经恢复策略。作为神经血管单元(NVU)一部分的血脊髓屏障(BSCB)在创伤后受到破坏,是导致脊髓损伤(SCI)复杂病理生理学的一个主要因素,它与邻近病灶中心的脊髓半影区的水肿、炎症和细胞死亡有关。因此,在脊髓损伤后保持完整的NVU和血管完整性以促进再生能力是一个理想的治疗目标。本研究旨在通过描述创伤后NVU解体和重新整合的时间框架,确定脊髓损伤后NVU修复的治疗机会窗口,从而对脊髓功能恢复产生影响。在胸椎夹压型 SCI 或假性损伤后,对成年 C57BL/6J 小鼠进行了 1 到 28 天的随访。在脊髓损伤/假性损伤后的1、3、7、14和28天,对小鼠进行七特斯拉磁共振成像(MRI)、神经行为分析(巴索小鼠量表、Tally子评分、CatWalk®步态分析),并在小鼠牺牲后进行免疫组化,通过埃文斯蓝(EVB)外渗评估血管通透性、(功能性)血管密度和NVU完整性。此外,还为Thy1-黄色荧光蛋白+小鼠植入了定制的脊髓开窗室,并在脊髓损伤/胫骨损伤后14天内注射罗丹明-B-异硫氰酸-右旋糖酐,进行纵向体内双光子激发成像(2PM),对轴突和血管进行联合成像。核磁共振成像容积评估显示,创伤后水肿的形成在损伤后一到三天达到高峰,而EVB通透性定量分析显示,BSCB在SCI损伤后14天内彻底损伤。然而,一至四周后,通过内源性血管再通检测到功能性血管的部分再生,仅有50-54%的现有血管恢复了功能性灌注。纵向活体 2PM 观察到,脊髓损伤后创伤周围区域最初保留的脊髓轴突逐渐退化,同时显示功能性灌注血管在损伤后两周内稀少。神经行为的恢复从一周后开始,但在脊髓损伤后四周的整个观察期内仍然存在障碍。通过这项研究,确定了从 SCI 后最初几天到两周开始治疗受损的 NVU 的治疗窗口。包括体内 2PM、NVU 完整性评估和神经行为评估在内的一系列证据表明,针对 NVU 的治疗对于增强 SCI 后轴突的保存和再生至关重要。在已确定的治疗机会窗口期,针对 NVU 完整性的持续性多因素疗法似乎有望改善功能性血管的持久性和脊髓的再生能力。
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引用次数: 0
Genetic Differences Modify Anesthetic Preconditioning of Traumatic Brain Injury in Drosophila. 遗传差异可改变果蝇创伤性脑损伤的麻醉预处理。
IF 3.9 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-11-19 DOI: 10.1089/neu.2024.0314
Dena Johnson-Schlitz, Amanda R Seidl, Zachariah P G Olufs, Wen Huang, David A Wassarman, Misha Perouansky

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. Using a common laboratory fly line, w1118, we found that exposure to the volatile anesthetics isoflurane or sevoflurane, but not ether, prior to TBI produced a dose-dependent reduction in mortality within 24 h following TBI. Thus, isoflurane and sevoflurane precondition w1118 flies to deleterious effects of TBI. To examine the effects of genetic differences on anesthetic preconditioning of TBI, we repeated the experiment with the Drosophila Genetic Reference Panel (DGRP) collection of genetically diverse, inbred fly lines. Pre-exposure to either isoflurane or sevoflurane revealed a wide range of preconditioning levels among 171 and 144 DGRP lines, respectively, suggesting a genetic component for variation in anesthetic preconditioning of mortality following TBI. Finally, genome-wide association study analyses identified single-nucleotide polymorphisms in genes associated with isoflurane or sevoflurane preconditioning of TBI. Several of the genes, including the fly ortholog of mammalian Calcium Voltage-Gated Subunit Alpha1 D (CACNA1D), are highly expressed in neurons and are functionally linked to both anesthetics and TBI. These 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.

创伤性脑损伤(TBI)的脊椎动物临床前模型通常使用麻醉剂,以保障动物福利;然而,人类在经历 TBI 时却不使用麻醉剂。因此,将脊椎动物模型的研究结果转化为人类的研究结果取决于了解麻醉剂如何影响细胞和分子事件,从而导致创伤性脑损伤后的继发性损伤。为了研究麻醉剂对创伤性脑损伤结果的影响,我们使用了无脊椎动物黑腹果蝇模型来比较在相同的原发性损伤之前暴露或未暴露于麻醉剂的动物之间的结果。通过使用一种常见的实验蝇品系 w1118,我们发现在创伤性脑损伤前接触异氟醚或七氟醚等挥发性麻醉剂(而非乙醚)会使创伤性脑损伤后 24 小时内的死亡率呈剂量依赖性下降。因此,异氟烷和七氟烷可使w1118苍蝇在创伤性脑损伤后出现有害影响。为了研究基因差异对创伤性脑损伤麻醉预处理的影响,我们用果蝇基因参考组(DGRP)收集的基因多样的近交系果蝇重复了该实验。在预暴露于异氟醚或七氟烷的情况下,171 个 DGRP 品系和 144 个 DGRP 品系的预处理水平差异很大,这表明创伤性脑损伤后死亡率的麻醉预处理存在遗传因素。最后,全基因组关联研究分析发现了与异氟烷或七氟烷对创伤性脑损伤的预处理相关的单核苷酸多态性基因。其中几个基因,包括哺乳动物钙电压门控亚基 Alpha1 D(CACNA1D)的苍蝇同源基因,在神经元中高度表达,在功能上与麻醉剂和创伤性脑损伤有关。这些数据表明,在研究麻醉剂对脊椎动物创伤性脑损伤模型的影响时,应考虑麻醉剂的剂量和遗传背景,并支持使用苍蝇模型来阐明创伤性脑损伤的麻醉预处理机制。
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引用次数: 0
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Journal of neurotrauma
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