原文题目：

Dr. Xiao-Ming Xu: A True Gentleman and Scholar in the Field of Spinal Cord Injury and Schwann Cell Biology

原文链接：

https://www.liebertpub.com/doi/10.1089/neu.2023.29136.inmemoriam

[REF: Dr. Xiao-Ming Xu: A True Gentleman and Scholar in the Field of Spinal Cord Injury and Schwann Cell Biology. J Neurotrauma. 2023;40(9-10):791-792. doi:10.1089/neu.2023.29136.inmemoriam PMID: 36749168]

We have received very sad news that our good friend and colleague, Dr. Xiao-Ming Xu, died peacefully after a long battle with bladder cancer. Xiao-Ming will be remembered for being an exceptional individual who did innovative research and was a leader in the field of Schwann cell biology and spinal cord injury. Over the years, we benefited from his many contributions to science and also his collaborative nature. A truly amazing individual who will be greatly missed. Since we heard the sad news, we have received many communications emphasizing his personal and professional contributions from his scientific community...

我们收到了非常悲痛的消息，我们的好朋友兼同事徐晓明博士在与膀胱癌长期抗争后安详地去世了。晓明将被人们铭记，因为他是一位进行创新研究的杰出个人，是雪旺细胞生物学和脊髓损伤领域的领军人物。多年来，我们受益于他对科学的许多贡献，也受益于他乐于合作的性格。一个真正令人赞叹的人，他将被非常怀念。自从我们听到这个不幸的消息后，我们收到了许多来自他的科学界的信件，强调他的个人和专业贡献……

Spinal cord injury (SCI) in humans frequently causes intractable chronic pain. Females are susceptible to worse pain than males, and females may show higher pain prevalence after SCI. Despite this difference in the clinical prevalence of SCI pain, few pre-clinical studies have systematically studied sex differences in SCI-elicited pain-related behaviors in rodents. Here, we leverage data from a large cohort of mice to test whether contusion SCI consistently causes pain symptoms in mice, and to establish whether female (vs. male) mice display heightened hypersensitivity after SCI. Our data suggest that thoracic contusion SCI elicits consistent and persistent pain-associated symptoms, which are more intense in female than in male mice. These results have important implications for uncovering sex-specific mechanisms and therapeutic targets to ameliorate neuropathic pain after SCI.

人类脊髓损伤(SCI)常常引起顽固性慢性疼痛。女性比男性更容易患上更严重的疼痛，女性在脊髓损伤后的疼痛患病率可能更高。尽管SCI疼痛的临床患病率存在这种差异，但很少有临床前研究系统地研究啮齿类动物SCI引起的疼痛相关行为的性别差异。在这里，我们利用来自小鼠的数据来测试SCI是否持续地导致小鼠的疼痛症状，并确定雌性(与雄性相比)小鼠在SCI后是否表现出高度的敏感性。我们的数据表明，SCI引起的雌性小鼠的疼痛相关症状比雄性小鼠更强烈。这些结果对于揭示性别特异性机制和治疗靶点以缓解脊髓损伤后神经病理性疼痛具有重要意义。

原文题目：

Upregulated 5-HT1A Receptors Regulate Lower Urinary Tract Function in Rats after Complete Spinal Cord Injury

原文链接：

https://www.liebertpub.com/doi/10.1089/neu.2022.0329

increased, and filling is accompanied by numerous non-voiding contractions (NVCs) referred to as neurogenic detrusor overactivity. Here, we investigate the expression levels of the serotonin 1A (5-HT1A) receptor in segments both rostral and caudal to the injured site, as well as the effects on micturition of blocking 5-HT1A receptor using pharmacological interventions in spinally intact rats or T8 complete SCI rats. According to the results, the neuroplasticity of the 5-HT1A receptor can be a potential therapeutic target for treatment of bladder dysfunction after SCI.

脊髓损伤常导致下尿路功能障碍，包括逼尿肌反射亢进，表现为膀胱顺应性低，基线压力升高，充盈时伴有大量非排尿收缩(NVC)，称为神经源性逼尿肌过度活动。在这里，我们研究了5-HT1A(5-HT1A)受体在损伤部位头端和尾端的表达水平，以及药物干预对脊髓完整大鼠或T8完全性脊髓损伤大鼠排尿功能的影响。结果表明，5-HT1a受体的神经可塑性可作为治疗脊髓损伤后膀胱功能障碍的潜在靶点。

recovery. This prospective monocentric longitudinal observational study investigated the extent and severity of LMN dysfunction and its impact on upper extremity motor recovery after acute cervical SCI. LMN dysfunction represents a relevant factor contributing to motor impairment and recovery in acute cervical SCI. Defined recovery mechanisms (peripheral reinnervation) may at least partially underlie spontaneous recovery in respective muscles. Therefore, assessment of LMN dysfunction could help refine prediction of motor recovery after SCI.

脊髓损伤(SCI)后瘫痪是由上下运动神经元(LMN)损伤引起的，可能会不同程度地影响神经功能的恢复。这项前瞻性单中心纵向观察研究调查了急性颈髓损伤后LMN功能障碍的程度和严重程度及其对上肢运动恢复的影响。在急性颈髓损伤中，LMN功能障碍是导致运动障碍和康复的相关因素。明确的恢复机制(外周神经再生)可能至少部分是各自肌肉自发恢复的基础。因此，对LMN功能障碍的评估有助于完善脊髓损伤后运动恢复的预测。

原文题目：

Does Older Age Affect the Likelihood to Achieve Normal Quality of Life After Traumatic Spinal Cord Injury? A Prospective Observational Cohort Study

原文链接：

https://www.liebertpub.com/doi/10.1089/neu.2022.0025

Previous studies suggest that health-related quality of life (HRQoL) is impaired after a traumatic spinal cord injury (TSCI) and may be worse with older age. This study determines whether the expectations to achieve normal HRQoL in Canadians after a TSCI is indeed influenced by older age. Overall, 39.3% of individuals displayed normal PCS, whereas 80.4% displayed normal MCS. When adjusted for confounders, older age remained significantly associated with increased likelihood of achieving normal PCS (Odds Ratio: 1.03; 95% Confidence Interval: 1.01-1.06; P = 0.002). We observed no association between age and achieving normal MCS. A significant proportion of individuals can achieve a normal HRQoL similar to their healthy peers following a TSCI, particularly for the mental component. When compared to younger individuals, older individuals are more likely to achieve normal PCS and present a similar likelihood for achieving normal MCS.

先前的研究表明，创伤性脊髓损伤(TSCI)后，健康相关的生活质量(HRQOL)会受到损害，随着年龄的增加，情况可能会更糟。这项研究确定了加拿大人在TSCI后达到正常HRQOL的期望是否确实受到年龄的影响。总体而言，39.3%的人PCS正常，而80.4%的人MCS正常。调整混杂因素后，年龄越大，PCS恢复正常的可能性越高(比值比：1.03；95%可信区间：1.01-1.06；P=0.002)。我们没有观察到年龄和达到正常的MCS之间的联系。在TSCI后，相当大比例的人可以达到与健康同龄人相似的正常HRQOL，特别是在精神方面。与年轻人相比，年长的人更有可能实现正常的PCS，并呈现出类似的实现正常MCS的可能性。

原文题目：

Major Differences in Transcriptional Alterations in Dorsal Root Ganglia Between Spinal Cord Injury and Peripheral Neuropathic Pain Models

原文链接：

https://www.liebertpub.com/doi/10.1089/neu.2022.0238

SCI, especially in regeneration-associated genes (RAGs) and long noncoding RNAs (lncRNAs).  Although only a few genes in DRG cells exhibited similar changes in expression across all the painful conditions examined here, these genes may represent a core set whose transcription in various DRG cell types is sensitive to significant bodily injury, and which may play a fundamental role in promoting neuropathic pain.

通过比较PNI和SCI模型中DRG的转录特征，可以突出感觉神经节中与疼痛相关的转录变化，这些变化不依赖于外周轴突切断或相关的效应，如外周沃勒变性。我们的大鼠胸段脊髓损伤实验的数据与已发表的来自大鼠PNI模型的完整DRG RNA-seq数据集的荟萃分析相结合。在对PNI和SCI的转录反应中发现了显著的差异，特别是在再生相关基因(RAG)和长链非编码RNA(LncRNAs)上。虽然在所有的疼痛条件下，DRG细胞中只有几个基因表现出相似的表达变化，但这些基因可能代表了其在各种DRG细胞类型中的转录对重大身体损伤敏感的核心集合，并可能在促进神经病理性疼痛方面发挥基础作用。

原文题目：

Inflammaging and Bone Loss in a Rat Model of Spinal Cord Injury

原文链接：

https://www.liebertpub.com/doi/10.1089/neu.2022.0342

skeletal health after SCI remains largely unknown. To address this, we compared bone parameters in young (3 month) and middle-aged (9 month) male and female rats with a moderate thoracic contusion injury, to age- and sex-matched sham-operated controls. Overall, this study demonstrates SCI-induced loss of bone and altered bone turnover in male and female rats that persists into the chronic phase post-injury. The sex- and age-dependent variations in bone turnover and serum cytokines, however, underscore the need to further explore both mechanisms and potential therapeutics in multiple demographics.

脊髓损伤(SCI)导致骨的显著丢失，增加了骨折和骨折后并发症的风险。不幸的是，脊髓损伤对骨骼健康的影响也可能上升，因为脊髓损伤的平均年龄已经增加，而且众所周知，年龄对骨骼有负面影响。然而，到目前为止，年龄和年龄相关的炎症对脊髓损伤后骨骼健康的影响在很大程度上仍不清楚。为了解决这一问题，我们比较了患有中度胸部挫伤的年轻(3月)和中年(9月)雄性和雌性大鼠与年龄和性别匹配的假手术对照组的骨参数。总体而言，这项研究证明了脊髓损伤导致的骨丢失和骨转换改变在雄性和雌性大鼠中持续到损伤后的慢性期。然而，骨转换和血清细胞因子随性别和年龄的变化，强调了在多个人口统计学中进一步探索机制和潜在治疗方法的必要性。

with an emphasis on diffusion-weighted imaging (DWI) markers of axonal injury and perfusion-weighted imaging of spinal cord blood flow (SCBF). Spinal cord perfusion has unique spatiotemporal dynamics compared with diffusion measures of axonal damage and highlights the importance of acute perfusion abnormalities. Perfusion and diffusion offer complementary and clinically relevant insight into physiological and structural abnormalities following spinal cord injury beyond those afforded by T1 or T2 contrasts.

创伤性脊髓损伤会导致迅速的神经元和血管损伤，需要预测性生物标记物来促进急性患者的治疗。本研究在啮齿动物模型中检测了脊髓损伤后磁共振成像(MRI)生物标志物的进展及其预测长期神经预后的能力，重点是轴突损伤的弥散加权成像(DWI)标志物和脊髓血流量的灌注加权成像(SCBF)。与轴索损伤的弥散措施相比，脊髓灌注具有独特的时空动力学，并突出了急性灌注异常的重要性。除了T1或T2对比外，灌注和弥散成像还能为脊髓损伤后的生理和结构异常提供补充和临床相关的洞察力。

This study aims to investigate the brain gray matter volume (GMV) alterations of pediatric complete thoracolumbar spinal cord injury (SCI) without fracture or dislocation (SCIWOFD) using voxel-based morphometry (VBM) analysis and assess the sensitive neuroimaging biomarkers that may be surrogate targets to enhance brain plasticity. The findings provided evidence that the brain undergoes GMV changes after pediatric SCIWOFD, which may suggest important targets for functional remodeling after SCI in children and provide valuable information for the development of novel and effective rehabilitation therapies in the future.

本研究旨在应用基于体素的形态计量学(VBM)分析方法，研究无骨折脱位的完全性胸腰段脊髓损伤(SCI)患儿脑灰质体积(GMV)的变化，并评价可能作为增强脑可塑性替代靶点的敏感神经影像生物标志物。这些结果为儿童SCIWOFD后GMV的变化提供了证据，这可能为儿童SCI后功能重塑提供重要的靶点，并为未来开发新的有效的康复治疗方法提供有价值的信息。

framework, we developed a multi-modal approach combining SXPCT, histology and correlative methods to study neurovascular architecture in normal and spinal level C4-contused mouse spinal cords (C57BL/6J mice, age 2-3 months). In conclusion, SXPCT capability to image at high resolution cellular changes in 3D enables the understanding of the relationship between hemorrhagic events and nervous structure damage in SCI.

脊髓损伤(SCI)后，功能(运动、自主或感觉)丧失的程度与神经组织损伤的严重程度相关。目前，在脊髓损伤的研究中，缺乏一种能够非侵入性地同时捕捉神经元丢失、血管损伤和周围组织重组的复杂机制的成像技术。同步辐射X射线相衬成像(SXPCT)是一种具有高对比度和空间分辨率的无损三维神经成像技术。在此框架下，我们发展了一种结合SXPCT、组织学和相关方法的多模式方法来研究正常和脊髓水平C4挫伤小鼠(C57BL/6J小鼠，2-3月龄)的神经血管构筑。总之，SXPCT以高分辨率3D成像细胞变化的能力使我们能够理解脊髓损伤中出血事件与神经结构损伤之间的关系。

After incomplete spinal cord injury (iSCI), the control of lower extremity movements may be affected by impairments in descending corticospinal tract function. Previous iSCI studies demonstrated relatively well-preserved movement control during simple alternating dorsiflections and plantar flexions albeit with severely reduced motor strength and range of motion. This task, however, required comparably limited fine motor control, impeding the sensitivity to assess the modulatory capacity of corticospinal control. Therefore, we introduced a more challenging ankle motor task necessitating complex and dynamic feedback-based movement adjustments to modulate corticospinal drive. The results, along with the walking performance, correlated well with the delta frequency shift between the regular and irregular movement task in the 38 Hz band (corticospinal drive frequency) in the iSCI group, suggesting that task performance is related to the capacity to modulate corticospinal control. The irregular movement task holds promise as a tool for revealing further insights into corticospinal control of single-joint movements. It may serve as a surrogate marker for the assessment of modulatory capacity and the integrity of corticospinal control in individuals with iSCI early after injury and throughout rehabilitation.

不完全性脊髓损伤(ISCI)后，皮质脊髓束下行功能受损可能影响对肢体运动的控制。以前的ISCI研究表明，在简单的交替背部反射和足底屈曲时，运动控制相对保存良好，尽管运动强度和运动范围严重降低。然而，这项任务需要相对有限的精细运动控制，阻碍了评估皮质脊髓控制的调节能力的敏感性。因此，我们引入了一个更具挑战性的踝关节运动任务，需要复杂和动态的基于反馈的运动调整来调节皮质脊髓驱动。结果显示，在ISCI组中，行走能力与38赫兹频段(皮质脊髓驱动频率)的规则运动任务和非规则运动任务之间的增量频移有很好的相关性，这表明任务表现与调节皮质脊髓控制的能力有关。不规则运动任务有望成为揭示皮质脊髓对单关节运动控制的进一步洞察力的工具。它可以作为评估ISCI患者早期和整个康复过程中调节能力和皮质脊髓控制完整性的替代标记物。

Spinal cord injury (SCI) frequently results in motor, sensory, and autonomic dysfunction for which there is currently no cure. Recent pre-clinical and clinical research has led to promising advances in treatment; however, therapeutics indicating promise in rodents have not translated successfully in human trials, likely due, in part, to gross anatomical and physiological differences between the species. Therefore, large animal models of SCI may facilitate the study of secondary injury processes that are influenced by scale, and may assist the translation of potential therapeutic interventions. The aim of this study was to characterize two severities of thoracic contusion SCI in female domestic pigs, measuring motor function and spinal cord lesion characteristics, over 2 weeks post-SCI. This study demonstrated graded injuries in a domestic pig strain, with outcome measures comparable to miniature pig models of contusion SCI. The model provides a vehicle for the study of SCI and potential treatments, particularly where miniature pig strains are not available and/or where small animal models are not appropriate for the research question.

脊髓损伤(SCI)经常导致运动、感觉和自主神经功能障碍，目前尚无治愈方法。最近的临床前和临床研究在治疗方面取得了有希望的进展；然而，在啮齿动物身上显示出希望的治疗方法并没有在人体试验中成功转化，可能部分原因是物种之间在解剖学和生理学上的巨大差异。因此，脊髓损伤的大动物模型可能有助于研究受规模影响的继发性损伤过程，并可能有助于潜在的治疗干预措施的转化。本研究的目的是描述雌性家猪胸部挫伤的两种严重程度，测量脊髓损伤后2周以上的运动功能和脊髓损伤特征。这项研究显示了家猪品系的分级损伤，其结果衡量标准与小型猪的挫伤脊髓损伤模型相当。该模型为研究脊髓损伤和潜在的治疗方法提供了一种工具，特别是在没有小型猪品系和/或小动物模型不适合研究问题的情况下。

Here we investigate gene-expression and physiological changes in GI peptides and hormones, as well as changes in physiological response to feeding, glucose and insulin challenge, and evaluate GI tissue cytoarchitecture after experimental SCI. Adult female mice (C57BL/6) were subjected to a severe SCI (65 kDyne) at T9, and a sham control group received laminectomy only. The SCI results in chronic elevation of fasting plasma glucose levels and an exaggerated glucose response after an oral glucose and insulin tolerance test. Mice with SCI also exhibit significant alteration in gut hormone genes, plasma levels, physiological response to prandial challenge, and cell loss and gross tissue damage in the gut. These findings demonstrate that SCI has widespread effects on the GI system contributing to component cardiometabolic disease risk factors and may inform future therapeutic and rehabilitation strategies in humans.

在这里，我们研究了实验性脊髓损伤后胃肠道多肽和激素的基因表达和生理变化，以及对摄食、葡萄糖和胰岛素刺激的生理反应的变化，并评估了实验性脊髓损伤后胃肠道组织的细胞结构。成年雌性小鼠(C57BL/6)于T9时造成严重脊髓损伤(65kdyne)，假手术对照组仅行椎板切除。脊髓损伤导致空腹血糖水平慢性升高，并在口服葡萄糖和胰岛素耐量试验后出现夸大的血糖反应。脊髓损伤小鼠在肠道激素基因、血浆水平、对进食挑战的生理反应、肠道细胞丢失和大体组织损伤方面也表现出显著的变化。这些发现表明，脊髓损伤对胃肠道系统有广泛的影响，导致心脏代谢性疾病的危险因素，并可能为人类未来的治疗和康复策略提供信息。

The use of biomarkers in spinal cord injury (SCI) research has evolved rapidly in recent years whereby most studies focused on the acute post-injury phase. Since SCI is characterized by persisting neurological impairments, the question arises whether blood biomarkers remain altered during the subacute post-injury time. Sample collection in the subacute phase might provide a better insight in the ongoing SCI specific molecular mechanism with fewer confounding factors compared with the acute phase where, amongst other complications, individuals receive a substantial amount of medication. This study aimed to determine if the temporal dynamics of serum biomarkers of neurodegeneration differ between individuals depending on their extent of neurological recovery in the transition phase between acute and chronic SCI. The trajectory of serum GFAP levels qualifies as a prognostic biomarker for neurological recovery, and facilitates monitoring of disease progression in the sub-acute post-injury phase.

近年来，生物标志物在脊髓损伤(SCI)研究中的应用发展迅速，大多数研究集中在损伤后的急性阶段。由于脊髓损伤的特点是持续性的神经损害，因此在亚急性损伤后的时间内血液生物标志物是否保持改变的问题就产生了。与急性期相比，亚急性期的样本采集可能提供对正在进行的SCI特定分子机制的更好的洞察，混杂因素更少，在急性期，患者接受大量药物治疗。本研究旨在确定在急性和慢性脊髓损伤的过渡阶段，神经退行性变的血清生物标志物的时间动态是否因个体之间的神经恢复程度而有所不同。血清GFAP水平的变化轨迹可作为神经功能恢复的预测生物标志物，并有助于监测亚急性损伤后阶段的疾病进展。

Protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) is a major signal transducer of the endoplasmic reticulum stress response (ERSR) pathway. Outcomes of PERK activation range from abrogating ER stress to induction of cell death, dependent on its level, duration, and cellular context. Current data demonstrate that after mouse spinal cord injury (SCI), acute inhibition of PERK (0-72 h) with the small molecule inhibitor GSK2656157 reduced ERSR while improving white matter sparing and hindlimb locomotion recovery. GSK2656157-treated mice showed increased numbers of oligodendrocytes at the injury epicenter. Moreover, GSK2656157 protected cultured primary mouse oligodendrocyte precursor cells from ER stress-induced cytotoxicity. These findings suggest that in the context of SCI, excessive acute activation of PERK contributes to functionally relevant white matter damage. Pharmacological inhibition of PERK is a potential strategy to protect central nervous system (CNS) white matter following acute injuries, including SCI.

蛋白激酶R(PKR)样内质网蛋白激酶(PERK)是内质网应激反应(ERSR)途径的主要信号转导分子。PERK激活的结果从消除内质网应激到诱导细胞死亡，取决于其水平、持续时间和细胞环境。目前的数据表明，小分子抑制剂GSK2656157急性抑制小鼠脊髓损伤(SCI)后，PERK(0~72h)可降低ERSR，同时促进脑白质的保留和后肢运动的恢复。GSK2656157处理的小鼠显示损伤中心的少突胶质细胞数量增加。此外，GSK2656157还可保护原代培养的小鼠少突胶质前体细胞免受内质网应激诱导的细胞毒性。这些发现表明，在脊髓损伤的背景下，PERK的过度急性激活有助于功能相关的脑白质损伤。药物抑制PERK是保护包括脊髓损伤在内的急性损伤后中枢神经系统(CNS)白质的一种潜在策略。

Spinal cord injury (SCI) affects ∼1,300,000 people living in the United States. Most research efforts have been focused on reversing paralysis, as this is arguably the most defining feature of SCI. The damage caused by SCI, however, extends past paralysis and includes other debilitating outcomes including immune dysfunction and gut dysbiosis. Recent efforts are now investigating the pathophysiology of and developing therapies for these more distal manifestations of SCI. One exciting avenue is the spinal cord-gut-immune axis, which proposes that gut dysbiosis amplifies lesion inflammation and impairs SCI recovery. This review will highlight the most recent findings regarding gut and immune dysfunction following SCI, and discuss how the central nervous system (CNS), gut, and immune system all coalesce to form a bidirectional axis that can impact SCI recovery. Finally, important considerations regarding how the spinal cord-gut-immune axis fits within the larger framework of therapeutic development (i.e., probiotics, fecal transplants, dietary modifications) will be discussed, emphasizing the lack of interdepartmental investigation and the missed opportunity to maximize therapeutic benefit in SCI.

脊髓损伤(SCI)影响着生活在美国的∼130万人。大多数研究工作都集中在逆转瘫痪上，因为这可以说是脊髓损伤最具决定性的特征。然而，脊髓损伤造成的损害不仅限于瘫痪，还包括其他令人衰弱的结果，包括免疫功能障碍和肠道生物失调。最近的努力现在正在研究这些更远端的脊髓损伤表现的病理生理学和开发治疗方法。一个令人兴奋的途径是脊髓-肠道免疫轴，它认为肠道生物失调放大了病变炎症，损害了脊髓损伤的恢复。本综述将重点介绍有关脊髓损伤后肠道和免疫功能障碍的最新研究结果，并讨论中枢神经系统(CNS)、肠道和免疫系统如何结合形成一个双向轴，从而影响脊髓损伤的恢复。最后，将讨论有关脊髓-肠道-免疫轴如何适应治疗发展(即益生菌、粪便移植、饮食修改)的更大框架的重要考虑，强调缺乏内在探索和错过了在脊髓损伤中最大限度地发挥治疗效益的机会。

People with spinal cord injury (SCI) get recurrent infections, such as urinary tract infections (UTIs) and pneumonias, that cause mortality and worsen neurological recovery. Over the past decades, researchers have proposed that post-SCI lymphopenia and decreased lymphocyte function increase susceptibility to infections and worsen neurological outcome in humans, leading to a condition called SCI-induced immune depression syndrome (SCI-IDS). In this review, we explore how SCI affects blood lymphocyte homeostasis and function in humans and rodents. Understanding how SCI affects blood lymphocytes will help the management of recurrent infections in spinal cord injured people and shed light on the clinical translation of findings in animal models to humans.

患有脊髓损伤(SCI)的人会反复感染，如尿路感染(UTIs)和肺炎，这些感染会导致死亡，并使神经恢复变差。在过去的几十年里，研究人员提出，脊髓损伤后淋巴细胞减少和淋巴细胞功能下降增加了人类感染的易感性，并恶化了神经预后，导致了一种称为脊髓损伤诱导免疫抑制综合征(SCI-IDS)的疾病。在这篇综述中，我们探讨了脊髓损伤如何影响人类和啮齿动物的血淋巴细胞稳态和功能。了解脊髓损伤是如何影响血淋巴细胞的，将有助于脊髓损伤患者反复感染的治疗，并有助于将动物模型的研究结果临床转化。

L-arginine is a semi-essential amino acid involved in a variety of physiological processes in the central nervous system (CNS). It is essential in the survival and functionality of neuronal cells. Nonetheless, L-arginine also has a dark side; it potentiates neuroinflammation and nitric oxide (NO) production, leading to secondary damage. Therefore, modulating the L-arginine metabolism is challenging because both detrimental and beneficial effects are dependent on this semi-essential amino acid. After spinal cord injury (SCI), L-arginine plays a crucial role in trauma-induced neuroinflammation and regenerative processes via the two key enzymes: nitric oxide synthase (NOS) and arginase (ARG). Studies on L-arginine metabolism using ARG and NOS inhibitors highlighted the conflicting role of this semi-essential amino acid. Similarly, L-arginine supplementation resulted in both negative and positive outcomes after SCI. However, new data indicate that arginine depletion substantially improves spinal cord regeneration after injury. Here, we review the challenging characteristics of L-arginine metabolism as a therapeutic target after SCI.

L-精氨酸是一种参与中枢神经系统多种生理过程的半必需氨基酸。它对神经细胞的存活和功能是必不可少的。尽管如此，L-精氨酸也有黑暗面：它会加剧神经炎症和一氧化氮(NO)的产生，导致二次损伤。因此，调节L-精氨酸代谢是具有挑战性的，因为有害和有益的作用都依赖于这种半必需的氨基酸。脊髓损伤后，L-精氨酸通过一氧化氮合酶和精氨酸酶两个关键酶在创伤后的神经炎症和再生过程中发挥重要作用。使用精氨酸和一氧化氮合酶抑制剂对L-精氨酸代谢的研究突出了这种半必需氨基酸的相互冲突的作用。同样，补充L-精氨酸可导致脊髓损伤后的阳性和阴性结果。然而，新的数据表明，精氨酸耗竭显著改善了脊髓损伤后的再生。在这里，我们回顾了L-精氨酸代谢作为脊髓损伤后治疗靶点的挑战性特征。

The aim of this prospective phase IIa, open-label exploratory, pre-post study was to determine the efficacy of fesoterodine (i.e., 12-week treatment period) to ameliorate autonomic dysreflexia (AD) in individuals with chronic SCI (> 1-year post-injury) at or above the sixth thoracic spinal segment, with confirmed history of AD and neurogenic detrusor overactivity (NDO). In conclusion, fesoterodine reduces the magnitude and frequency of AD, while improving LUT function and urinary incontinence-related QoL in individuals with chronic SCI without negatively affecting cognitive or bowel function.

这项IIa期开放研究的目的是确定非索特罗定(Fesoterodine) (即12周治疗期)对第六胸段或以上慢性脊髓损伤(>1年)患者自主神经反射障碍(AD)的改善效果，这些患者已确诊有AD病史和神经原性逼尿肌过度活动(NDO)。总而言之，非索特罗定可降低AD的程度和频率，同时改善慢性脊髓损伤患者的LUT功能和与尿失禁相关的生活质量，而不会对认知或肠道功能造成负面影响。

首都医科大学附属北京天坛医院神经外科博士研究生

主要研究方向为糖皮质激素在创伤性脑损伤后继发性损伤和修复的机制