Amiodarone Improves Locomotor Function in Experimental Spinal Cord Injury by Reducing Secondary Axonal Degeneration and White Matter Atrophy

胺碘酮通过减轻继发性轴突变性与白质萎缩改善实验性脊髓损伤后的运动功能

Secondary loss of initially spared white and grey matter is a major driver of morbidity after spinal cord injury (SCI). Current treatments have not substantially changed in decades and are limited to surgical decompression and blood pressure management. White matter atrophy after SCI is primarily caused by secondary axonal degeneration (SAD), which is triggered by maladaptive axonal uptake of sodium and calcium through a multitude of ion channels and transporters. While specific inhibitors have been studied, none have been translated into clinical use, in part due to the diverse array of involved channels. Here, we studied whether amiodarone, an FDA-approved antiarrhythmic drug that exerts pleotropic inhibition of multiple sodium and calcium channels, might be neuro- and axonoprotective after SCI precisely because of its broad inhibitory profile. Overall, these data identify amiodarone as a potentially axonoprotective agent that could be repurposed to treat secondary injury after SCI.

脊髓损伤（SCI）后，初始未受损白质与灰质发生继发性丢失，是造成各类并发症的核心诱因。数十年来，临床干预手段并无实质性革新，仅局限于手术减压与血流动力学调控。脊髓损伤后的白质萎缩主要由继发性轴突变性（SAD）引发；该病理过程中，多种离子通道与转运体异常介导钠、钙离子内流，诱发轴突适应性损伤。现有研究虽已针对各类特异性通道抑制剂开展探索，但尚无药物完成临床转化，部分原因在于参与损伤通路的离子通道种类繁杂。本研究选用经美国食品药品监督管理局（FDA）批准的抗心律失常药物胺碘酮开展实验，该药可广谱抑制多种钠、钙通道；我们旨在验证，正是凭借这种广泛的通道抑制效应，胺碘酮能够在脊髓损伤后发挥神经与轴突保护作用。综合实验结果表明，胺碘酮具备潜在的轴突保护活性，有望实现老药新用，用于干预脊髓损伤后的继发性损伤。

REF: Stokum JA, Wilhelmy B, Bragança C, et al. Amiodarone Improves Locomotor Function in Experimental Spinal Cord Injury by Reducing Secondary Axonal Degeneration and White Matter Atrophy. J Neurotrauma. 2026;43(9-10):816-826. doi:10.1177/08977151251400735 PMID: 41314966

由人工翻译修正

Validation of A Wireless Telemetric Bladder Pressure Monitoring System in Traumatic Thoracic Spinal Cord Injury in Yucatan Minipigs

无线遥测膀胱压力监测系统在尤卡坦小型猪创伤性胸段脊髓损伤模型中的应用验证

Neurogenic lower urinary tract dysfunction (NLUTD) is a major cause of morbidity and reduced quality of life after spinal cord injury (SCI). In pre-clinical research, small and large animal models such as rats, dogs, and minipigs have been used to investigate NLUTD through urodynamic studies (UDS) such as conventional filling cystometry. Although filling cystometry is currently considered the gold standard for bladder monitoring in pre-clinical research, this approach has several well-recognized limitations. The aim of this study was to develop and evaluate the feasibility of an implantable, radiotelemetric system for monitoring bladder pressure in a Yucatan minipig model of SCI. The telemetry system appeared to be a reliable and accurate method for assessing bladder pressure and allowed for an evaluation of urodynamics in a pig model of SCI for several months. The application of this method could enable a more detailed in vivo evaluation of NLUTD after SCI and a better understanding of micturition behavior during natural-filling, ambulatory urodynamics.

神经源性下尿路功能障碍（NLUTD）是脊髓损伤（SCI）后导致患者并发症高发、生活质量下降的主要原因。临床前研究常选用大鼠、犬、小型猪等大小动物模型，借助常规充盈膀胱测压等尿动力学检查（UDS）开展神经源性下尿路功能障碍相关探究。尽管充盈膀胱测压目前被视作临床前研究中膀胱功能监测的金标准，但该检测手段存在多项公认的缺陷。本研究旨在搭建一套可植入式无线遥测监测系统，并验证其在尤卡坦小型猪脊髓损伤模型中监测膀胱压力的可行性。该遥测系统可稳定、精准地检测膀胱压力，能够对脊髓损伤猪模型开展长达数月的尿动力学评估。该技术的应用有助于在体更细致地研究脊髓损伤后的神经源性下尿路功能障碍，同时更充分地了解自然充盈、动态行走状态下动物的排尿行为。

REF: Doelman AW, Ethridge J, Streijger F, et al. Validation of A Wireless Telemetric Bladder Pressure Monitoring System in Traumatic Thoracic Spinal Cord Injury in Yucatan Minipigs. J Neurotrauma. 2026;43(9-10):800-815. doi:10.1177/08977151251389956 PMID: 41269117

由人工翻译修正

Administration of a Novel Peptide Derived From Thrombospondin Repeat Sequences Enhances Recovery after Cervical Spinal Cord Injury

源自血小板反应蛋白重复序列的新型多肽给药可促进颈段脊髓损伤后的功能恢复

Spinal cord injury (SCI) is a debilitating condition resulting in the loss of sensorimotor functioning at and below the site of injury. Despite advances in the treatment and management of SCI, there are no current approved pharmacological therapies to augment motor function and functional recovery. NX210c is a 12-amino acid peptide derived from thrombospondin type 1 (TSP1) repeat sequences from the subcommissural organ-spondin protein. TSPs are glycoproteins present in the extracellular matrix, mediating cell–cell and cell–matrix interactions and axon pathfinding. NX210c was previously shown to improve axonal regeneration and functional recovery in thoracic SCI. The aim of this study was to evaluate the ability of NX210c to promote functional recovery and tissue repair in a traumatic cervical SCI rat model. To conclude, NX210c mitigates various aspects of SCI, including motor function and tissue preservation, with preferential results being obtained with the delayed initial administration of NX210c at 8 h post-injury.

脊髓损伤（SCI）是一种致残性疾病，会造成损伤平面及以下节段的感觉与运动功能丧失。尽管脊髓损伤的救治与综合管理手段已有诸多进展，但目前尚无获批的药物疗法能够改善运动功能、促进整体功能恢复。NX210c是一种由12个氨基酸构成的多肽，提取自连合下器-脊索蛋白中的1型血小板反应蛋白（TSP1）重复序列。血小板反应蛋白是存在于细胞外基质内的糖蛋白，可介导细胞间、细胞与基质间的相互作用，并参与轴突导向过程。既往研究已证实，NX210c能够促进胸段脊髓损伤后的轴突再生与功能恢复。本研究旨在探究NX210c对创伤性颈髓损伤大鼠模型的功能恢复及组织修复的作用。综上，NX210c可从多方面改善脊髓损伤后的病理损伤，既能改善运动功能，又可保护神经组织；其中，伤后8小时延迟首次给药的方案疗效最优。

REF: Punjani N, Lemarchant S, Altamentova S, et al. Administration of a Novel Peptide Derived From Thrombospondin Repeat Sequences Enhances Recovery after Cervical Spinal Cord Injury. J Neurotrauma. 2026;43(9-10):785-799. doi:10.1177/08977151251392233 PMID: 41335520

由人工翻译修正

Netrin-1 Therapy Restores Partial Hindlimb Movement in a Rat Model of High-Severity Chronic Spinal Cord Injury

轴突导向因子1（Netrin-1）治疗可恢复重度慢性脊髓损伤大鼠模型的部分后肢运动功能

Spinal trauma caused by contusion or compression is the leading cause of spinal cord injury (SCI) worldwide. These injuries frequently progress to a chronic phase, especially in cases of severe damage. This process results in permanent impairment, affecting both physiological functions and voluntary motor control below the lesion level. At cellular level, the formation of a glial scar, which delineates the cystic cavity, interrupts the connectivity between the central nervous system (CNS) and muscles, as well as the neural communication between the peripheral and CNSs. This process, combined with the CNS inability to promote its self-repair to prevent the progression to a chronic phase, contributes to the exacerbation of spinal cord damage, resulting in a devastating pathology. Currently, there is no effective medical treatment to address the consequences of this condition, apart from physiotherapy, which has variable success depending on the type of injury and the degree of neural tissue preservation in the affected spinal cord. Considering this last, the development of new strategies to promote neuronal repair is essential for reversing this pathology in the future. Therefore, we propose Netrin-1—a developmental guidance molecule known to direct corticospinal tract (CST) growth during CNS development—as a potential therapeutic approach for enhancing neuronal repair in severe chronic SCI. The findings support its use as potential therapeutic strategy in future human clinical trials.

挫伤或压迫所致脊柱创伤是全球范围内脊髓损伤（SCI）最主要的诱因。这类损伤往往会进展至慢性阶段，重度损伤病例尤为如此，最终造成永久性功能缺损，累及损伤平面以下的各项生理功能与自主运动控制能力。细胞层面上，界定囊腔边界的胶质瘢痕会切断中枢神经系统（CNS）与肌肉之间的信号连接，同时阻断中枢神经系统和外周神经系统的神经通讯。加之中枢神经系统自身缺乏有效的自我修复机制，无法阻止损伤向慢性阶段进展，多重因素叠加会持续加重脊髓损伤，形成破坏性极强的病理状态。目前，除物理康复治疗外，尚无能够根治该类损伤后遗症的有效药物疗法；而康复治疗的疗效差异较大，取决于损伤类型以及受损脊髓内神经组织的残存程度。鉴于此，研发可促进神经元修复的新型干预策略，是未来逆转该类病理损伤的关键。为此，本研究提出将轴突导向因子Netrin-1作为重度慢性脊髓损伤的潜在修复治疗手段。Netrin-1是一种发育调控导向分子，在中枢神经系统发育阶段可调控皮质脊髓束（CST）的生长延伸。本研究结果证实，Netrin-1具备作为治疗方案的潜力，有望后续开展人体临床试验。

REF: Schmidt J, Uceda A, Sgariglia A, Battagino R, Quintá HR. Netrin-1 Therapy Restores Partial Hindlimb Movement in a Rat Model of High-Severity Chronic Spinal Cord Injury. J Neurotrauma. 2026;43(9-10):762-784. doi:10.1177/08977151251387696 PMID: 41163574

由人工翻译修正

Reassessing the Role of Machine Learning in Clinical Prediction: A Benchmark of Predicting Walking Function after Spinal Cord Injury

重新审视机器学习在临床预测中的应用价值：脊髓损伤后行走功能预测的基准测评

In light of growing biomedical data, machine learning (ML) models offer tremendous potential for personalized prediction in medicine. However, the additional value provided by these computational tools should always be critically evaluated. Using the example of predicting walking ability after spinal cord injury (SCI), we highlight a popular scenario in which data-driven predictions are feasible but not clinically meaningful, as the task can be performed equally well by humans. Our results show that prediction of walking function following SCI, if described through a binary label, does not benefit from ML, as ensembles of clinical experts and researchers each achieve performance similar to a range of ML models and an established clinical prediction rule. This highlights two key considerations in clinical applications of data-driven prediction models in SCI: first, the importance of carefully choosing clinical outcome measures to target in a prediction task to achieve a true benefit, and second, the necessity of benchmarking human performance on specific tasks to determine whether meaningful differences are present.

随着生物医学数据体量持续增长，机器学习（ML）模型在医学个体化预后预测领域展现出巨大应用潜力。但我们必须审慎评估这类计算工具所能提供的额外临床价值。本文以脊髓损伤（SCI）后行走能力预测为例，阐释一类普遍存在的研究情形：尽管基于数据的预测模型在技术层面具备可行性，却缺乏实际临床意义，因为临床医师人工判断即可达到同等预测效果。本研究结果显示，若仅采用二分类指标评估脊髓损伤患者远期行走功能，机器学习模型并无增益；多名临床专家与科研人员组成的人工评判团队，其预测效能与多种机器学习集成模型、成熟临床预测规则水平相当。该结论明确了将数据驱动预测模型应用于脊髓损伤临床时的两大核心考量：其一，开展预测研究需审慎选择临床结局评价指标，确保模型能产生真实临床获益；其二，必须以人工评判效能作为基准参照，判定模型是否具备有统计学/临床意义的性能优势。

REF: Bugajska J, Lukas LP, Rupp R, et al. Reassessing the Role of Machine Learning in Clinical Prediction: A Benchmark of Predicting Walking Function after Spinal Cord Injury. J Neurotrauma. 2026;43(9-10):749-761. doi:10.1177/08977151251386008 PMID: 41163583

由人工翻译修正

Modulatory Effect of Norepinephrine on Cardiorespiratory Improvement, Spinal Microenvironment and Gene Expression Following Mid-Cervical Spinal Cord Contusion in Rats

去甲肾上腺素对大鼠颈中段脊髓挫伤后心肺功能改善、脊髓微环境及基因表达的调控作用

Maintaining the arterial blood pressure within an appropriate range following acute spinal cord injury is crucial for neurological recovery. However, the therapeutic efficacy and underlying mechanism of hemodynamic management remain to be determined. The present study aimed to investigate the modulatory effect of norepinephrine on cardiorespiratory function, spinal cord microenvironment, and gene expression following cervical spinal cord injury. The results demonstrated that hemodynamic management using norepinephrine effectively improves cardiorespiratory function and modulates the spinal microenvironment following cervical spinal cord injury.

急性脊髓损伤后维持动脉血压在适宜区间，对神经功能恢复至关重要。但血流动力学调控的治疗效果及其潜在作用机制尚不明确。本研究旨在探究去甲肾上腺素对颈髓损伤后心肺功能、脊髓微环境与基因表达的调控作用。研究结果证实，采用去甲肾上腺素实施血流动力学管理，可有效改善颈髓损伤后的心肺功能，并调节脊髓局部微环境。

REF: Chen RY, Lee KZ. Modulatory Effect of Norepinephrine on Cardiorespiratory Improvement, Spinal Microenvironment and Gene Expression Following Mid-Cervical Spinal Cord Contusion in Rats. J Neurotrauma. 2026;43(9-10):732-748. doi:10.1177/08977151251384976 PMID: 41051980

由人工翻译修正

Acute Administration of Ampakine CX1739 after Cervical Spinal Cord Injury

颈段脊髓损伤后即刻给予安帕金CX1739

Treatment with a positive allosteric AMPA receptor modulator (“ampakine”) can improve respiratory muscle activation and bladder function after sub-acute (days) to chronic (weeks to months) spinal cord injury (SCI). Prior studies of SCI and excitotoxicity provide evidence that ampakines may also promote neuroprotection. We hypothesized that initiating daily low-dose treatment with the low-impact ampakine CX1739 acutely after SCI would be neuroprotective and promote recovery. We conclude that ampakine CX1739 (5 mg/kg) given daily over 0–14 days post-SCI provides no discernible benefit, and acute ampakine treatment is contraindicated, in contrast to delayed dosing paradigms. Ampakine treatment should be reserved for the subacute and chronic SCI conditions, beyond the acute period of glutamate-related neurotoxicity. These results will be particularly important in determining the optimal timing of ampakine administration as CX1739 progresses in clinical trials.

AMPA受体正向变构调节剂（安帕金类药物）干预，可改善亚急性期（伤后数天）至慢性期（伤后数周至数月）脊髓损伤（SCI）后的呼吸肌激活功能与膀胱功能。既往针对脊髓损伤及兴奋毒性的研究证实，安帕金类药物同样具备神经保护作用。本研究提出假说：于脊髓损伤急性期即刻启动低剂量安帕金CX1739每日给药方案，可发挥神经保护效应并促进神经功能恢复。本研究结论：脊髓损伤后0～14天每日给予5 mg/kg剂量的安帕金CX1739未见明确获益；与延期给药方案不同，急性期使用安帕金治疗存在用药禁忌。安帕金类药物仅适用于脊髓损伤亚急性期及慢性期，应避开谷氨酸介导神经毒性的急性期窗口。随着CX1739逐步推进临床试验，该研究结果对确定安帕金类药物最佳给药时机具有重要指导价值。

REF: Fusco AF, Rana S, Macintyre MM, et al. Acute Administration of Ampakine CX1739 after Cervical Spinal Cord Injury. J Neurotrauma. 2026;43(9-10):715-731. doi:10.1177/08977151251382939 PMID: 41051937

由人工翻译修正

Three-Dimensional Design and Implementation of a Dual Compartment Imaging Chamber to Assess Effects of Hypertonic Saline on Periaxonal Swelling and Axonal Spheroid Formation Following Cervical Contusive Spinal Cord Injury in Real Time

三维设计并搭建双腔成像舱：实时观察高渗盐水对颈髓挫伤后轴周水肿与轴突球状体形成的影响

Contusive and compressive spinal cord injury (SCI) induces pathological changes to spinal cord white matter (WM) including periaxonal swelling and resultant disruption of the axomyelinic interface, axonal swelling/spheroid formation, and secondary axonal transection. To further our knowledge of the role of vascular edema in these pathological changes to WM, we designed, and three-dimensional (3D) printed a dual-compartment imaging chamber separated by a semipermeable membrane to mimic and manipulate interstitial and vascular fluid compartments in real time. We hypothesized that hypertonic saline (HTS) applied to the “vascular” chamber would osmotically shift fluid out of the periaxonal space and preserve myelinated fibers after SCI. Our findings suggest that low-dose hypertonic solutions may have a protective effect in part by mitigating periaxonal swelling and thereby potentially reducing the occurrence of axonal spheroids within these denuded regions. These results enhance understanding of secondary axonal degeneration mechanisms and hold promise for targeted therapeutic interventions to improve outcomes in SCI.

挫伤性、压迫性脊髓损伤（SCI）会造成脊髓白质（WM）发生多种病理改变，包括轴周水肿、随之引发的轴突-髓鞘界面破坏、轴突肿胀/轴突球状体形成，以及继发性轴突断裂。为进一步探究血管源性水肿在脊髓白质上述病理损伤中发挥的作用，本研究设计并三维（3D）打印了一套双腔成像舱；舱体内部由半透膜分隔，能够实时模拟并调控组织液腔室与血管液腔室。我们提出假说：向“血管侧”腔室施加高渗盐水（HTS），可借助渗透压将液体从轴周间隙吸出，在脊髓损伤后保护有髓神经纤维。本研究结果表明，低剂量高渗溶液存在神经保护效应，其部分作用机制为减轻轴周水肿，进而有望减少髓鞘剥离区域内轴突球状体的产生。该研究结果加深了人们对继发性轴突变性机制的理解，也为研发靶向干预手段、改善脊髓损伤患者预后提供了重要研究前景。

REF: Cortez-Thomas F, Ames SO, Alli S, Jones E, Stirling DP. Three-Dimensional Design and Implementation of a Dual Compartment Imaging Chamber to Assess Effects of Hypertonic Saline on Periaxonal Swelling and Axonal Spheroid Formation Following Cervical Contusive Spinal Cord Injury in Real Time. J Neurotrauma. 2026;43(9-10):704-714. doi:10.1089/neu.2024.0454 PMID: 40045759

由人工翻译修正

Biofluid Biomarkers of Acute Traumatic Spinal Cord Injury: A Systematic Review

急性创伤性脊髓损伤的体液生物标志物：系统综述

Traumatic spinal cord injury (TSCI) is a debilitating disease that results in a heterogeneous set of symptoms. This includes secondary inflammatory mechanisms, which can perpetuate injury to the spinal cord, as well as negatively affect other organ systems. Standard prognostication, such as magnetic resonance imaging, is cumbersome and provides limited resolution; thus, the development of prognostic biofluid tests is of significant clinical importance. The current study systematically reviewed biomarker studies following acute (within 24 h) TSCI. Four databases were searched for this systematic review, PubMed/MEDLINE, Cochrane (OvidSP), Web of Science, and Scopus, resulting in 702 articles to be screened by two independent reviewers. Thirty-two studies met inclusion criteria and were included in the systemic review. About 116 total markers were examined, and 66.4% were found to be associated with TSCI with three major utilities: diagnostic, injury severity, and prognostics. Results generated from the current study highlight discrepancies between biofluids and recommend biomarkers for clinical utility. Future research should associate these acute biomarkers with long-term outcomes using predictive modeling, in addition to curating a clinical TSCI database for optimal prognostication. As TSCI outcomes are variable and impact many systems, the curation of preventative and interventional treatment strategies is crucial.

创伤性脊髓损伤（TSCI）是一类致残性疾病，临床表现复杂多样。疾病进程中会继发炎症反应，该反应不仅会持续加重脊髓损伤，还会累及机体其他器官系统。目前临床常用的预后评估手段（如磁共振成像）操作繁琐，且评估效能有限。因此，研发基于生物体液的预后检测方法具备重要的临床价值。本研究针对伤后24小时内的急性创伤性脊髓损伤，开展生物标志物相关研究的系统综述。本综述检索了四大文献数据库：PubMed/MEDLINE、OvidSP平台考克兰图书馆、Web of Science及Scopus，初步检索得到702篇文献，由两名研究人员独立完成文献筛选。最终有32项研究符合纳入标准，被纳入本次系统综述。研究共纳入分析116种生物标志物，其中66.4%的标志物被证实与创伤性脊髓损伤具有相关性，主要应用于三大方向：疾病诊断、损伤严重程度评估与预后判断。本研究结果揭示了不同生物体液标志物的应用差异，并筛选出具备临床应用价值的候选标志物。后续研究可构建预测模型，分析上述急性期生物标志物与患者远期预后的关联；同时建议搭建创伤性脊髓损伤临床数据库，以实现更精准的预后评估。创伤性脊髓损伤患者的预后个体差异较大，且病变可累及全身多系统，因此制定完善的预防与干预治疗策略至关重要。

REF: Schaeffer EA, Levy AS, Errante EL, et al. Biofluid Biomarkers of Acute Traumatic Spinal Cord Injury: A Systematic Review. J Neurotrauma. 2026;43(9-10):689-703. doi:10.1177/08977151251401222 PMID: 41334695

由人工翻译修正