Locomotor Recovery in Spinal Cord Injury Can Be Assessed Using Weight-Bearing

利用负重法评估脊髓损伤后的运动功能恢复

Spinal cord injury (SCI) can result in partial or full paralysis, depending on the level and completeness of injury. Locomotor function is often used as a measure of recovery and treatment outcomes. The Basso, Beattie, and Bresnahan scale and Basso Mouse Scale (BMS) are gold standards used in rodent SCI studies to evaluate changes in locomotor recovery. However, these scoring systems are observer-dependent measures that may be affected by the presence of an experimenter, particularly in studies where blinding is difficult. We observed a shift in body weight early after injury, with increased surface area and weight placement to the front paws and the trunk/tail region. Concurrently, there was a reduction in rear paw surface area and weight placement. As functional recovery occurred over time, there was a shift toward reduced weight placement on the front paws. As with locomotor recovery, these changes did not return to preinjury levels. We also found that the rate and degree to which mice shifted weight onto front paws depended on injury severity. Importantly, changes in weight distribution and surface area showed a strong correlation with BMS scores, suggesting that the observer-independent ADWB test is a viable measure to assess changes in locomotor function over time after SCI.

脊髓损伤（SCI）的损伤节段与损伤程度不同，可导致患者出现部分性或完全性瘫痪。运动功能常被用作评估脊髓损伤后功能恢复及治疗效果的核心指标。Basso-Beattie-Bresnahan（BBB）运动功能评分量表与Basso小鼠运动功能评分量表（BMS），是啮齿类动物脊髓损伤研究中用于评估运动功能恢复变化的金标准。但上述评分体系均属于观察者依赖性评估方法，其结果可能会受到实验人员在场的干扰，在难以实施设盲操作的研究中，这种干扰尤为明显。本研究观察到，小鼠在脊髓损伤早期会出现体重分布的偏移：前爪与躯干/尾部区域的承重面积及承重占比均显著增加，而后爪的承重面积与承重占比则相应降低。随着时间推移，小鼠的运动功能逐渐恢复，其前爪的承重占比也随之下降。但与运动功能恢复的规律一致，上述各项指标均未能恢复至损伤前水平。研究同时发现，小鼠前爪承重占比的偏移速率与偏移程度，与脊髓损伤的严重程度密切相关。值得注意的是，体重分布与承重面积的变化情况，与BMS评分具有显著的相关性。这提示，自动体重分布（ADWB）检测法作为一种不依赖观察者的评估手段，可有效用于动态监测脊髓损伤后小鼠的运动功能变化。

REF: Bannerman CA, Knezic M, Segal JP, et al. Locomotor Recovery in Spinal Cord Injury Can Be Assessed Using Weight-Bearing. J Neurotrauma. 2025;42(23-24):2282-2288. doi:10.1177/08977151251380704 PMID: 40982320

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Acute Opioid Administration Undermines Recovery after SCI: Adverse Effects Are Not Restricted to Morphine

急性期阿片类药物给药会削弱脊髓损伤后的功能恢复：其不良影响并非仅限于吗啡

Previous studies have shown that administration of high doses of morphine in the acute phase of spinal cord injury (SCI) significantly undermines locomotor recovery and increases symptoms of chronic pain in a rat spinal contusion model. Similarly, SCI patients treated with high doses of opioid for the first 24 h postinjury have increased symptoms of chronic pain 1 year later. Whether these adverse effects are driven by morphine only or all opioids compromise recovery after SCI, however, is unknown. Based on our previous findings we hypothesized that activation of the kappa opioid receptor (KOR) is key in the morphine-induced attenuation of locomotor recovery after SCI. Thus, we posited that opioids that engage KOR-mediated signaling pathways (morphine, oxycodone) would undermine recovery, and clinically relevant opioids with less KOR activity (fentanyl and buprenorphine) would not. To test this, we compared the effects of the clinically relevant opioids on locomotor recovery and pain in a male rat spinal contusion model. This study provides critical insight into pain management strategies in the acute phase of SCI and potential long-term consequences of early opioid administration.

既往研究表明，在大鼠脊髓挫伤模型中，于脊髓损伤（SCI）急性期给予大剂量吗啡，会显著削弱大鼠的运动功能恢复，并加重其慢性疼痛症状。与之相似，脊髓损伤患者若在伤后24小时内接受大剂量阿片类药物治疗，其慢性疼痛症状在1年后也会明显加重。但目前尚不明确，此类不良影响是仅由吗啡导致，还是所有阿片类药物均会对脊髓损伤后的修复进程产生不利作用。基于既往研究结果，本研究提出假设：κ阿片受体（KOR）的激活，是吗啡抑制脊髓损伤后运动功能恢复的关键机制。据此我们推测，能够激活κ阿片受体介导信号通路的阿片类药物（吗啡、羟考酮）会削弱脊髓损伤后的修复进程，而在临床上广泛应用且对κ阿片受体作用较弱的阿片类药物（芬太尼、丁丙诺啡）则不会产生该负面效应。为验证这一假设，本研究以雄性大鼠脊髓挫伤模型为研究对象，对比分析了上述几种临床常用阿片类药物对大鼠运动功能恢复及疼痛症状的影响。该研究为脊髓损伤急性期的疼痛管理策略制定，以及早期使用阿片类药物可能产生的远期影响，提供了关键参考依据。

REF: Rau J, Joseph R, Weise L, et al. Acute Opioid Administration Undermines Recovery after SCI: Adverse Effects Are Not Restricted to Morphine. J Neurotrauma. 2025;42(23-24):2265-2281. doi:10.1089/neu.2024.0375 PMID: 39912807

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Complete High Thoracic Spinal Cord Injury Causes Bowel Dysfunction in Mice

小鼠高位胸段完全性脊髓损伤致肠功能障碍

Bowel dysfunction, is a prevalent and life-impacting comorbidity of spinal cord injury (SCI) with no long-term treatment available. SCI-induced colon changes including motility and fibrosis are understudied as are strategies to address SCI bowel dysfunction. This need remains partly due to the lack of a mouse model that recapitulates the human condition. We hypothesized that a high thoracic spinal transection in mice would trigger bowel dysfunction with coincident colon pathology similar to humans and rats after SCI. Collectively, the findings demonstrate bowel dysfunction immediately after injury that continues in the distal colon over time. Establishing this mouse model enables further interrogation using transgenic models.

肠道功能障碍是脊髓损伤（SCI）一种高发且严重影响患者生活质量的并发症，目前尚无长期有效治疗方案。脊髓损伤引发的结肠功能改变（包括结肠动力异常与纤维化），以及针对脊髓损伤后肠道功能障碍的干预策略，均属于研究薄弱领域。上述研究缺口的存在，部分原因在于缺乏能够模拟人类病理状态的小鼠模型。本研究假设，对小鼠实施高位胸段脊髓横断术，可诱导其出现肠道功能障碍，并伴随与人类及大鼠脊髓损伤后相似的结肠病理改变。综合研究结果表明，脊髓损伤后会立即出现肠道功能障碍，且该症状会随时间推移持续存在于远端结肠。该小鼠模型的成功构建，为借助转基因模型开展后续深入研究奠定了基础。

REF: Wireman OH, Sams EL, Richey LE, et al. Complete High Thoracic Spinal Cord Injury Causes Bowel Dysfunction in Mice. J Neurotrauma. 2025;42(23-24):2254-2264. doi:10.1089/neu.2024.0277 PMID: 40179002

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Passive Hindlimb Cycling Enhances Tolerance of Cardiac Electrical Conduction in Rats with Spinal Cord Injuries

被动后肢蹬车训练提升脊髓损伤大鼠的心脏电传导耐受性

High-level spinal cord injury (SCI) often disrupts supraspinal control of sympathetic input to the heart. The resulting imbalance in the autonomic nervous system increases the risk of developing cardiac arrhythmias. It was previously demonstrated that passive hindlimb cycling (PHLC) effectively maintains or improves bodily function including cardiovascular performance following SCI. However, it remains unclear whether the exercise can affect cardiac electrical disorders. To address this specific question, we complemented a complete SCI at a high-thoracic level in rats and then performed PHLC for 5 or 10 weeks. The results suggest that activity-based training for the long term improves autonomic balance to enhance tolerance of cardiac electrical conduction following SCI.

高位脊髓损伤（SCI）常导致脊髓上中枢对心脏交感神经传入的调控功能受损，由此引发的自主神经系统失衡会增加心律失常的发生风险。已有研究证实，被动后肢蹬车训练（PHLC）可有效维持或改善脊髓损伤后的机体功能，其中包括心血管功能。但该训练方式能否改善心脏电传导异常，目前尚不明确。为解答这一特定问题，本研究构建了大鼠高位胸段完全性脊髓损伤模型，随后对模型大鼠实施为期5周或10周的被动后肢蹬车训练。研究结果表明，长期的基于活动的训练可改善脊髓损伤后的自主神经平衡，进而提升心脏电传导耐受性。

REF: Cusimano M, Tom VJ, Houle JD, Hou S. Passive Hindlimb Cycling Enhances Tolerance of Cardiac Electrical Conduction in Rats with Spinal Cord Injuries. J Neurotrauma. 2025;42(23-24):2242-2253. doi:10.1089/neu.2025.0021 PMID: 40227565

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Economic Optimization Through Adherence to Best Practice Guidelines: A Decision Analysis of Traumatic Spinal Cord Injury Care Pathways in Australia

遵循最佳实践指南实现经济效益优化：澳大利亚创伤性脊髓损伤诊疗路径的决策分析

Traumatic spinal cord injuries (TSCIs) have significant health, economic, and social effects on individuals, families, and society. In this economic analysis modeling study, we used record-linked administrative patient data from New South Wales, Australia, to construct a decision tree model to compare the economic cost of acute care for patients with TSCI under current clinical pathways with an optimal care (consensus guidelines-informed) modeled pathway. The findings highlight the economic case for adherence to best practice care guidelines at the healthcare system level to inform future healthcare planning for patients with TSCI.

创伤性脊髓损伤（TSCI）对患者个人、家庭及社会均会产生显著的健康、经济与社会层面影响。在本项经济学建模分析研究中，研究团队采用澳大利亚新南威尔士州的关联病历行政数据，构建决策树模型，对比分析了现行临床路径下创伤性脊髓损伤患者急性期诊疗的经济成本，以及基于共识指南制定的优化诊疗路径的模拟成本。研究结论从医疗系统层面，论证了遵循最佳实践诊疗指南的经济学价值，可为创伤性脊髓损伤患者未来的医疗资源规划提供参考依据。

REF: Vaikuntam BP, Sharwood LN, Connelly LB, Middleton JW. Economic Optimization Through Adherence to Best Practice Guidelines: A Decision Analysis of Traumatic Spinal Cord Injury Care Pathways in Australia. J Neurotrauma. 2025;42(23-24):2228-2241. doi:10.1089/neu.2023.0674 PMID: 40227758

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Alterations in Topological Structure and Modular Interactions in Pediatric Patients with Complete Spinal Cord Injury: A Functional Brain Network Study

完全性脊髓损伤患儿脑功能网络的拓扑结构与模块连接改变研究

Traumatic complete spinal cord injury (CSCI) leads to severe impairment of sensory-motor function, and patients often suffer from neuropsychological deficits such as anxiety, depression, and cognitive deficits, which involve different brain functional modules. However, the alterations in modular organization and the interactions between these modules in pediatric patients with CSCI remain unclear. In this study, a total of 70 participants, including 34 pediatric CSCI patients and 36 healthy controls (HCs) aged 6 to 12 years, underwent whole-brain resting-state functional MRI. The findings suggest that functional network and modular alterations chiefly occur in emotional cognition and vision-associated regions, emphasizing the importance to focus on their psychocognitive well-being and providing evidence for visual-feedback related rehabilitation strategies.

创伤性完全性脊髓损伤（CSCI）可导致严重的感觉运动功能障碍，患者常并发焦虑、抑郁及认知障碍等神经心理缺损症状，上述症状的发生涉及脑内不同的功能模块。但目前，儿童完全性脊髓损伤患者脑功能模块的组织模式改变及模块间的相互作用机制仍有待阐明。本研究共纳入70名受试者，包括34例年龄在6～12岁的儿童完全性脊髓损伤患者，以及36名同年龄段的健康对照者（HCs），所有受试者均接受全脑静息态功能磁共振成像检查。研究结果表明，脑功能网络及模块的异常改变主要集中于情绪认知与视觉相关脑区；该结论强调了关注患儿心理认知健康状态的重要性，并为基于视觉反馈的康复治疗策略提供了循证依据。

REF: Wang Y, Wang L, Yang B, et al. Alterations in Topological Structure and Modular Interactions in Pediatric Patients with Complete Spinal Cord Injury: A Functional Brain Network Study. J Neurotrauma. 2025;42(23-24):2217-2227. doi:10.1089/neu.2024.0560 PMID: 40329834

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Perineuronal Net Changes Reveal a Distinct Right and Left Spinal Phrenic Circuit

神经元周围网的形态改变揭示脊髓膈神经通路存在左右侧特异性差异

Respiratory failure is one of the greatest causes of morbidity and mortality after cervical lesions, the most common type of spinal cord injury (SCI). Fortunately, several pre-clinical and clinical studies have shown spontaneous, but limited, respiratory recovery after injury. However, there are still many unanswered questions about what is driving this recovery, so there is a growing need to further elucidate the neuroplastic potential of the phrenic network. Here, we investigated the structural plasticity of the right and left phrenic networks by analyzing perineuronal net (PNN) changes after a C2 hemisection (C2Hx) in mice. Overall, this work underscores the importance of studying neuroplasticity and how it holds the potential to help improve outcomes for individuals living with SCI.

呼吸衰竭是颈髓损伤最主要的致残与致死原因之一，而颈髓损伤也是脊髓损伤（SCI）中最常见的类型。值得庆幸的是，多项临床前与临床研究表明，损伤后患者可出现自发性呼吸功能恢复，但恢复程度有限。不过，关于驱动该恢复过程的具体机制，目前仍存在诸多未解之谜，因此，进一步阐明膈神经网络的神经可塑性潜力的需求日益迫切。本研究通过分析小鼠C2节段脊髓半切损伤（C2Hx）后神经元周围网（PNN）的形态变化，探究了双侧膈神经网络的结构可塑性。综上，本研究强调了开展神经可塑性研究的重要意义，以及该研究在改善脊髓损伤患者预后方面的潜在价值。

REF: Sánchez-Ventura J, Schardien KA, Fortino T, Zholudeva LV, Lane MA, Udina E. Perineuronal Net Changes Reveal a Distinct Right and Left Spinal Phrenic Circuit. J Neurotrauma. 2025;42(23-24):2204-2216. doi:10.1089/neu.2024.0597 PMID: 40435933

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Cardiovascular and Locomotor Recovery Following Hindlimb Muscle Stretching of Rodents with a Clinically Relevant Model of Spinal Cord Injury

基于临床相关脊髓损伤模型的啮齿动物后肢肌肉牵伸干预对心血管及运动功能恢复的影响

Physical therapy stretching remains one of the most prevalent therapies for patients with spinal cord injury (SCI); however, we have previously shown that daily hindlimb muscle stretching of rats following a T10 SCI significantly disrupts their hindlimb locomotor function, likely through maladaptive sprouting of nociceptive afferents and modulation of lumbar spinal circuitry. Despite these clinically significant findings, mid-thoracic contusion models do not represent a majority of clinical injuries and are not effective for modeling the loss of cardiovascular control and autonomic complications that patients with higher level SCI experience. Therefore, the objective of the current study was to examine the effects of hindlimb stretching on the locomotor and cardiovascular function of rats with a T2 SCI. Overall, these results indicate that hindlimb stretching following a high-thoracic SCI does not appear to aberrantly modulate lumbar spinal circuitry as has been shown in low thoracic injuries. Additionally, stretching combined with a T2 SCI does not result in cardiovascular dysfunction, although future work must be conducted to determine whether stretching triggers autonomic events and maladaptive plasticity near the spinal lesion.

物理治疗牵伸仍是脊髓损伤（SCI）患者最常用的治疗手段之一；然而，我们既往的研究表明，大鼠T10节段脊髓损伤后，每日进行后肢肌肉牵伸会显著破坏其后肢运动功能，其作用机制可能与伤害性传入纤维的异常出芽以及腰段脊髓环路的调控改变相关。尽管上述研究结论具有重要临床意义，但胸中段脊髓挫伤模型并不能模拟大多数临床损伤病例，且无法有效复现高位脊髓损伤患者常见的心血管调节功能丧失及自主神经并发症。因此，本研究旨在探讨后肢肌肉牵伸对T2节段脊髓损伤大鼠运动功能及心血管功能的影响。综合研究结果可见，与胸下段脊髓损伤模型的表现不同，胸上段脊髓损伤后实施后肢肌肉牵伸，并未对腰段脊髓环路产生异常调控作用。此外，T2节段脊髓损伤联合后肢肌肉牵伸干预并未引发心血管功能障碍，但后续仍需开展进一步研究，明确该干预是否会在脊髓损伤灶附近诱发自主神经异常反应及病理性可塑性改变。

REF: Forston M, Cesarz G, Wood D, Shum-Siu A, Magnuson D. Cardiovascular and Locomotor Recovery Following Hindlimb Muscle Stretching of Rodents with a Clinically Relevant Model of Spinal Cord Injury. J Neurotrauma. 2025;42(23-24):2191-2203. doi:10.1089/neu.2024.0349 PMID: 40522712

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Predictive Factors Affecting the Need for Mechanical Ventilation in Acute Traumatic Cervical Spinal Cord Injury

影响急性创伤性颈脊髓损伤患者机械通气需求的预测因素

Acute traumatic cervical spinal cord injuries (TCSCI) are associated with significant mortality and morbidity, particularly when complicated by neurogenic respiratory failure. While upper cervical-level injuries are established risk factors for mechanical ventilation, patients with acute injuries below the fifth cervical level without significant chest trauma may also require ventilatory support. However, reliable early predictors remain unclear. This study aims to identify the primary predictors of early mechanical ventilation needs in patients with acute TCSCI. The study found that patients with >25% cervical spinal cord compression had significantly poorer outcomes compared to those with ≤25% compression, including longer hospital stays, lower survival rates, worse pre-treatment neurological status, and higher complication rates. Surgical treatment, particularly the posterior approach, was more common in the >25% compression group; however, post-treatment neurological improvement was observed only in cases of grade 2 degree compression, not grades 3 and 4 in CT and MRI. In contrast, the ≤25% compression group demonstrated better outcomes, with greater post-treatment improvement.

急性创伤性颈脊髓损伤（TCSCI）可导致极高的病死率与病残率，合并神经源性呼吸衰竭时情况尤为严重。尽管高位颈髓损伤已被明确列为机械通气的危险因素，但颈5节段以下的急性损伤患者，即便未合并严重胸部创伤，也可能需要呼吸支持。然而，目前临床上仍缺乏可靠的早期预测指标。本研究旨在明确急性创伤性颈脊髓损伤患者早期机械通气需求的主要预测因素。研究结果显示，颈脊髓受压程度＞25%的患者，其预后显著劣于受压程度≤25%的患者，具体表现为住院时间更长、生存率更低、治疗前神经功能状态更差，且并发症发生率更高。受压程度＞25%的患者更常接受手术治疗，且以后路手术入路为主；但仅在颈脊髓受压程度为2级的患者中观察到治疗后神经功能改善，而在CT及MRI评估为3级、4级受压的患者中未出现该改善趋势。相比之下，受压程度≤25%的患者预后更佳，治疗后神经功能改善幅度更大。

REF: Chaisawasthomrong C, Boongird A. Predictive Factors Affecting the Need for Mechanical Ventilation in Acute Traumatic Cervical Spinal Cord Injury. J Neurotrauma. 2025;42(23-24):2178-2190. doi:10.1089/neu.2025.0006 PMID: 40560002

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