Journal of Neurorestoratology最新文献_第3页

Icariin protects against intracerebral hemorrhage in mice by enhancing neuroprotection 淫羊藿苷通过增强神经保护作用来预防小鼠脑出血

IF 3.1 4区医学 Q2 CLINICAL NEUROLOGY

Journal of Neurorestoratology

Pub Date : 2025-06-18 DOI: 10.1016/j.jnrt.2025.100224

Aigerim Bizhanova , Xiangyu Zhang , Maham Mazhar , Yuanyuan Liu , Gaili Yan , Sara Xue , V. Wee Yong , Mengzhou Xue

Background

Intracerebral hemorrhage (ICH) is a major type of stroke associated with high rates of mortality and long-term disability, often leading to inflammation, brain edema, and neuronal loss. Icariin (ICA) is the primary active compound extracted from Herba epimedii, and it possesses several pharmacological effects including anti-inflammatory, antioxidant and anti-apoptotic properties. However, its neuroprotective capacity and mechanisms in ICH remain unknown. This study investigates the neuroprotective potential of ICA in an ICH mouse model.

Methods

A total of 108 C57BL/6 mice were randomly assigned to three groups: sham group (n = 36), ICH + vehicle group (n = 36), and ICH + ICA group (n = 36). ICH was induced in the ICH + Vehicle and ICH + ICA groups through injection of collagenase type VII into the basal ganglia. The ICH + ICA group was administered ICA (60 mg/kg/day) intraperitoneally for three consecutive days. Neurological assessment was conducted using the corner test and modified neurological severity scores. TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling) staining was performed to evaluate brain cell death. Brain water content, Western blot, Evans blue (EB) dye extravasation, and immunofluorescence staining were conducted 3 days post-ICH.

Results

ICA treatment significantly alleviated brain edema and enhanced neurological function in mice three days post-ICH. Immunofluorescence results revealed that ICA decreased microglia and astrocyte activation and reduced neutrophil infiltration. Western blot results demonstrated that ICA maintained blood-brain barrier (BBB) integrity by decreasing the loss of tight junction proteins, including Occludin and Zonula occludens-1. ICA also lowered matrix metalloproteinase-9 and the proinflammatory cytokines tumor necrosis factor-α and interleukin-1β. TUNEL staining showed a reduction in neuronal cell death with ICA, linked to enhanced level of the anti-apoptotic B-cell lymphoma 2 (Bcl-2) protein and reduced expression of the pro-apoptotic Bcl-2-associated X (Bax) protein.

Conclusion

ICA exhibits significant neuroprotective effects in mice following ICH by reducing neuroinflammation, maintaining BBB integrity, and attenuating brain cell death.

脑出血（ICH）是卒中的一种主要类型，与高死亡率和长期残疾相关，常导致炎症、脑水肿和神经元丢失。淫羊藿苷（Icariin， ICA）是从淫羊藿中提取的主要活性化合物，具有抗炎、抗氧化、抗细胞凋亡等药理作用。然而，其在脑出血中的神经保护能力和机制尚不清楚。本研究探讨了ICA对脑出血小鼠模型的神经保护作用。方法将108只C57BL/6小鼠随机分为假手术组（n = 36）、ICH +载药组（n = 36）和ICH + ICA组（n = 36）。采用基底节注射VII型胶原酶诱导ICH + Vehicle组和ICH + ICA组脑出血。脑出血+ ICA组给予ICA （60 mg/kg/d）腹腔注射，连续3 d。神经学评估采用角测试和改良神经学严重程度评分。TUNEL（末端脱氧核苷酸转移酶介导的dUTP缺口末端标记）染色评估脑细胞死亡。脑出血后3 d进行脑水含量、Western blot、Evans蓝（EB）染色外渗、免疫荧光染色。结果ica治疗可显著减轻脑出血后3 d小鼠脑水肿，增强神经功能。免疫荧光结果显示，ICA降低了小胶质细胞和星形胶质细胞的活化，减少了中性粒细胞的浸润。Western blot结果表明，ICA通过减少紧密连接蛋白（包括Occludin和Zonula occludens-1）的损失来维持血脑屏障（BBB）的完整性。ICA还能降低基质金属蛋白酶-9和促炎细胞因子肿瘤坏死因子-α和白细胞介素-1β。TUNEL染色显示，ICA降低了神经元细胞死亡，这与抗凋亡b细胞淋巴瘤2 （Bcl-2）蛋白水平的提高和促凋亡Bcl-2相关的X （Bax）蛋白表达的降低有关。结论ica对脑出血小鼠具有明显的神经保护作用，可减轻神经炎症，维持血脑屏障完整性，减轻脑细胞死亡。

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引用次数: 0

Therapeutic effects of glial cell-derived extracellular vesicles on ischemic stroke in rodent models: A systematic review and meta-analysis 神经胶质细胞来源的细胞外囊泡对缺血性脑卒中啮齿动物模型的治疗作用：系统回顾和荟萃分析

IF 3.1 4区医学 Q2 CLINICAL NEUROLOGY

Journal of Neurorestoratology

Pub Date : 2025-06-11 DOI: 10.1016/j.jnrt.2025.100222

Na Li , Ying Qian , Hongrui Zhang , Chenxi Tao , Ying Li , Rufan Xu , Yikun Sun , Yannan He , Yonghong Gao , Zhenhong Liu

Treating ischemic stroke (IS) presents significant challenges; however, recent advancements suggest that glial cell-derived extracellular vesicles (GD-EVs) may offer a promising therapeutic strategy. This systematic review and meta-analysis evaluated the potential benefits of GD-EVs in IS by synthesizing data from preclinical studies. The review protocol was pre-registered with PROSPERO (CRD42024541149). Comprehensive literature searches were conducted across multiple databases, including PubMed, EMBASE, Web of Science, Cochrane Library, China National Knowledge Infrastructure, VIP Database for Chinese Technical Periodicals, Wanfang Database, and SinoMed, until April 10, 2024, to identify relevant studies. Preclinical studies investigating the utilization of GD-EVs in animal models of IS were included. Study quality was assessed using the risk of bias tool from the Systematic Review Center for Laboratory Animal Experimentation. From an initial pool of 3028 studies, 11 studies met the inclusion criteria. The analysis demonstrated that GD-EVs significantly improved neurological function, as evidenced by a reduction in the modified neurological severity score (standardized mean difference [SMD]: −1.69, 95% confidence interval [CI]: −2.15 to −1.22, p < 0.00001, and I² = 0%). GD-EVs also significantly reduced infarct volume in rodent models (SMD: −4.78, 95% CI: −6.91 to −2.66, p < 0.0001, Tau² = 0.99, and I² = 42%) and decreased brain water content and the release of pro-inflammatory factors post-stroke.

The methodological rigor of the included studies indicated sufficiently high overall quality. These findings suggest that GD-EVs hold significant promise as a novel therapeutic approach for IS and warrant further preclinical investigations before translation into clinical trials.

治疗缺血性卒中（IS）面临重大挑战；然而，最近的进展表明，胶质细胞来源的细胞外囊泡（gd - ev）可能提供一种有前途的治疗策略。本系统综述和荟萃分析通过综合临床前研究数据，评估了gd - ev治疗IS的潜在益处。审查方案在PROSPERO进行了预注册（CRD42024541149）。全文检索PubMed、EMBASE、Web of Science、Cochrane Library、中国知识基础设施、中国科技期刊VIP数据库、万方数据库、中国医学信息网等数据库，检索时间截止到2024年4月10日。包括研究gd - ev在IS动物模型中的应用的临床前研究。使用来自实验动物实验系统评价中心的偏倚风险工具评估研究质量。在最初的3028项研究中，有11项研究符合纳入标准。分析表明，gd - ev显著改善了神经功能，其证据是改良神经严重程度评分的降低(标准化平均差[SMD]: - 1.69, 95%可信区间[CI]: - 2.15至- 1.22,p <；0.00001, I2 = 0%)。在啮齿类动物模型中，gd - ev也显著减少了梗死体积(SMD: - 4.78, 95% CI: - 6.91至- 2.66,p <；0.0001, Tau2 = 0.99, I2 = 42%)，脑卒中后脑含水量和促炎因子释放减少。纳入研究的方法学严谨性表明总体质量足够高。这些发现表明，gd - ev作为一种新的IS治疗方法具有重要的前景，值得在转化为临床试验之前进行进一步的临床前研究。

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引用次数: 0

Biportal endoscopy for atlantoaxial stenosis 双门静脉内窥镜治疗寰枢椎狭窄

IF 3.1 4区医学 Q2 CLINICAL NEUROLOGY

Journal of Neurorestoratology

Pub Date : 2025-06-06 DOI: 10.1016/j.jnrt.2025.100221

Guidong Shi, Yongqin Chen, Liang Wang, Haozhi Yu, Yunpeng Jiang, Lei Qi

Recent epidemiological data have revealed an increasing incidence of atlantoaxial (C1–C2) stenosis. In this study, we review the merits and limitations of traditional surgical techniques for the decompression and excision of atlantoaxial stenosis, and introduce a novel biportal endoscopy method. A retrospective analysis was conducted on 1562 cases extracted from 19 articles. These patients, diagnosed with cervical spondylotic myelopathy or cervical spondylosis with various etiologies, underwent surgery using either a posterior biportal endoscopic approach for cervical discectomy or cervical canal decompression. Additionally, we present two cases of atlantoaxial cervical spondylosis treated using the biportal endoscopy approach, yielding positive clinical and radiological outcomes. Common complications associated with spinal endoscopy surgery include dura injury, nerve root injury, hematoma, and recurrence of the condition. While endoscopic cervical spinal surgery shows promising results in terms of efficacy and safety, further detailed assessments of potential complications are necessary.

最近的流行病学资料显示寰枢椎（C1-C2）狭窄的发病率在增加。在本研究中，我们回顾了寰枢椎狭窄减压切除的传统手术技术的优点和局限性，并介绍了一种新的双门静脉内窥镜方法。回顾性分析19篇文献中1562例病例。这些被诊断为脊髓型颈椎病或各种病因的颈椎病的患者，采用后双门静脉内窥镜入路进行颈椎间盘切除术或颈椎管减压手术。此外，我们报告了两例使用双门静脉内窥镜方法治疗寰枢椎颈椎病的病例，临床和放射学结果均为阳性。脊柱内窥镜手术的常见并发症包括硬脑膜损伤、神经根损伤、血肿和疾病复发。虽然内窥镜颈椎手术在疗效和安全性方面显示出良好的结果，但对潜在并发症的进一步详细评估是必要的。

引用次数: 0

Quantitative sensory assessment in patients with spinal cord injury 脊髓损伤患者定量感觉评估

IF 3.1 4区医学 Q2 CLINICAL NEUROLOGY

Journal of Neurorestoratology

Pub Date : 2025-06-03 DOI: 10.1016/j.jnrt.2025.100220

Yan Wang, Yong-Qiang Li, Tong Yu, Zun-Cheng Zheng

引用次数: 0

Research progress in spinal cord electrical stimulation for consciousness recovery in patients with disorders of consciousness 脊髓电刺激对意识障碍患者意识恢复的研究进展

IF 3.1 4区医学 Q2 CLINICAL NEUROLOGY

Journal of Neurorestoratology

Pub Date : 2025-05-26 DOI: 10.1016/j.jnrt.2025.100219

Yingjie Li , Chaowang An , Wenling Li , Zheng Wang , Hari Shanker Sharma , Haipeng Xie , Xiaolei Song , Di Zhang , Jingwen Zhang

Disorders of consciousness (DOC) are neuropsychiatric disorders with causes that include traumatic brain injury, hypoxia, and stroke. The possibility of spontaneous recovery is low, and treatment remains a difficult problem in the frontier challenge of neuroscience and medicine. With progress in neurocritical care, the number of patients with DOC is growing. Spinal cord stimulation (SCS) can improve the level of consciousness in patients with DOC. The present article reviews the current research status and development trends of SCS in promoting consciousness recovery in patients with DOC. It also seeks to identify the frontier problems and challenges associated with this neuroregulatory technology. Through a systematic review of the relevant literature, criteria for inclusion and exclusion in SCS therapy were established, suitable patients with DOC were identified, and the effects of different stimulation frequencies on consciousness and motor function were examined. Additionally, the optimal SCS mode was investigated, and evaluation criteria, treatment mechanisms, and factors influencing effectiveness were summarized. The present review aims to guide the clinical application and research development of SCS. Although SCS has demonstrated efficacy in the treatment of DOC, responses to SCS exhibit significant individual variation. Consequently, further studies are necessary to expand the sample size for continued exploration and enhancement.

意识障碍（DOC）是一种神经精神疾病，其原因包括创伤性脑损伤、缺氧和中风。自发性恢复的可能性低，治疗仍是神经科学和医学前沿挑战的难题。随着神经危重症护理的进展，DOC患者的数量正在增加。脊髓刺激（SCS）可提高DOC患者的意识水平。现就SCS促进DOC患者意识恢复的研究现状及发展趋势进行综述。它还试图确定与这种神经调节技术相关的前沿问题和挑战。通过系统回顾相关文献，建立SCS治疗的纳入和排除标准，确定合适的DOC患者，并检查不同刺激频率对意识和运动功能的影响。并对SCS的最佳模式进行了探讨，总结了SCS的评价标准、治疗机制及影响疗效的因素。本文综述旨在指导SCS的临床应用和研究发展。虽然SCS在治疗DOC方面已被证明有效，但对SCS的反应表现出显著的个体差异。因此，需要进一步的研究来扩大样本量，以继续探索和增强。

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引用次数: 0

Modes of brain cell death and neurorestoration following stroke: Molecular mechanisms and clinical potential 脑卒中后脑细胞死亡和神经恢复的模式：分子机制和临床潜力

IF 3.1 4区医学 Q2 CLINICAL NEUROLOGY

Journal of Neurorestoratology

Pub Date : 2025-05-13 DOI: 10.1016/j.jnrt.2025.100218

Lingxiao Qi , Pingping Guo , Xiangyu Zhang , Voon Wee Yong , Mengzhou Xue

引用次数: 0

Bibliometric analysis of C7 nerve transfer surgery C7神经转移手术文献计量学分析

IF 3.1 4区医学 Q2 CLINICAL NEUROLOGY

Journal of Neurorestoratology

Pub Date : 2025-05-08 DOI: 10.1016/j.jnrt.2025.100210

Ling Yang , Yuyang Liu , Jiaxin Xie , Shemin Zhang , Hailin Jiang , Jihua Wang , Jiansen Cao , Xin Zhang , Chao Li , Ning Cao , Yaping Feng

Background

C7 nerve transfer surgery aims to bridge neural gaps and promote functional recovery in patients with central nervous system (CNS) injuries. The surgery involves transferring the C7 nerve root from the healthy side to the affected side, promoting neural plasticity and reconstructing motor control. Research on C7 nerve transfer surgery is gradually coming into the public eye, with more innovations and applications in evidence-based research and biological mechanism studies in this field.

Methods

This is the first bibliometric analysis of C7 nerve transfer surgery. Relevant articles related to the field published between 1986 and 2023 were assessed, providing an emerging theoretical basis for future advances and developments. The literature source was the Web of Science Core Collection. The publication column, author details, affiliated institutions and countries, publication year, and keywords were recorded.

Results

A total of 3,416 articles were included. The annual publications on C7 nerve transfer surgery fluctuated within a certain range. “BRAIN RESEARCH” is the journal with the most publications, and the “INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS VOLUME” is the most influential journal. GU YD is the most prolific author, with 40 articles and the highest H-index (h = 19). The top-ranking country and institution are the United States and the University of California System, producing 1,004 and 159 articles, respectively. Co-keyword cluster analysis indicates that the temporal research trends in C7 nerve transfer surgery are mainly focused on imaging examinations and long-term prognosis.

Conclusion

This study collected, visualized, and analyzed the literature in the field of C7 nerve transfer surgery over the past 47 years to map the development process and examine research frontiers, research hotspots, cutting-edge directions of clinical practice, and the therapeutic mechanisms underlying the operation.

背景：c7神经移植手术旨在弥合中枢神经系统（CNS）损伤患者的神经间隙，促进其功能恢复。手术包括将C7神经根从健康侧转移到患侧，促进神经可塑性和重建运动控制。C7神经转移手术的研究逐渐进入公众视野，在循证研究和生物机制研究方面有了更多的创新和应用。方法首次对C7神经转移手术进行文献计量学分析。评估了1986年至2023年间发表的与该领域相关的相关文章，为未来的进展和发展提供了新兴的理论基础。文献来源为Web of Science Core Collection。记录出版栏目、作者详细信息、所属机构和国家、出版年份、关键词等。结果共纳入文献3416篇。关于C7神经转移手术的年度出版物在一定范围内波动。《BRAIN RESEARCH》是发行量最大的期刊，《INTERNATIONAL journal OF RADIATION ONCOLOGY BIOLOGY PHYSICS VOLUME》是最具影响力的期刊。GU YD是最多产的作者，发表了40篇文章，h指数最高（h = 19）。排名第一的国家和大学是美国和加州大学系统，分别发表了1004篇和159篇论文。共关键词聚类分析表明，C7神经转移手术的时间研究趋势主要集中在影像学检查和远期预后方面。结论本研究对近47年来C7神经转移手术领域的文献进行收集、可视化和分析，以描绘其发展历程，考察其研究前沿、研究热点、临床实践前沿方向和手术治疗机制。

{"title":"Bibliometric analysis of C7 nerve transfer surgery","authors":"Ling Yang , Yuyang Liu , Jiaxin Xie , Shemin Zhang , Hailin Jiang , Jihua Wang , Jiansen Cao , Xin Zhang , Chao Li , Ning Cao , Yaping Feng","doi":"10.1016/j.jnrt.2025.100210","DOIUrl":"10.1016/j.jnrt.2025.100210","url":null,"abstract":"<div><h3>Background</h3><div>C7 nerve transfer surgery aims to bridge neural gaps and promote functional recovery in patients with central nervous system (CNS) injuries. The surgery involves transferring the C7 nerve root from the healthy side to the affected side, promoting neural plasticity and reconstructing motor control. Research on C7 nerve transfer surgery is gradually coming into the public eye, with more innovations and applications in evidence-based research and biological mechanism studies in this field.</div></div><div><h3>Methods</h3><div>This is the first bibliometric analysis of C7 nerve transfer surgery. Relevant articles related to the field published between 1986 and 2023 were assessed, providing an emerging theoretical basis for future advances and developments. The literature source was the Web of Science Core Collection. The publication column, author details, affiliated institutions and countries, publication year, and keywords were recorded.</div></div><div><h3>Results</h3><div>A total of 3,416 articles were included. The annual publications on C7 nerve transfer surgery fluctuated within a certain range. “BRAIN RESEARCH” is the journal with the most publications, and the “INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS VOLUME” is the most influential journal. GU YD is the most prolific author, with 40 articles and the highest H-index (h = 19). The top-ranking country and institution are the United States and the University of California System, producing 1,004 and 159 articles, respectively. Co-keyword cluster analysis indicates that the temporal research trends in C7 nerve transfer surgery are mainly focused on imaging examinations and long-term prognosis.</div></div><div><h3>Conclusion</h3><div>This study collected, visualized, and analyzed the literature in the field of C7 nerve transfer surgery over the past 47 years to map the development process and examine research frontiers, research hotspots, cutting-edge directions of clinical practice, and the therapeutic mechanisms underlying the operation.</div></div>","PeriodicalId":44709,"journal":{"name":"Journal of Neurorestoratology","volume":"13 4","pages":"Article 100210"},"PeriodicalIF":3.1,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144253832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Functional brain network discrepancies in disorders of consciousness: A brain connectivity analysis 意识障碍的功能性脑网络差异：脑连通性分析

IF 3.1 4区医学 Q2 CLINICAL NEUROLOGY

Journal of Neurorestoratology

Pub Date : 2025-04-30 DOI: 10.1016/j.jnrt.2025.100208

Xuewei Qin , Xuanling Chen , Xin Zhao , Lan Yao , Zongsheng Xu , Hongchuan Niu , Fengqiao Sun , Kai Li , Changyu Lu , Yuanli Zhao , Shengpei Wang , Xiangyang Guo , Xiaoli Li

Background

Resting-state functional magnetic resonance imaging provides insight into brain function in patients with consciousness disorders. We investigated the variability in functional brain networks in consciousness disorders with different etiologies and identified potential correlations with recovery.

Methods

In this single-center prospective observational study, we included seven patients with traumatic brain injury, seven with cerebrovascular accidents, and a healthy control group of eight participants with intraspinal space-occupying lesions. All participants underwent resting-state functional magnetic resonance imaging and were assessed using the Coma Recovery Scale-Revised. Regional homogeneity values were compared across groups to evaluate differences in functional brain activity.

Results

Patients with traumatic brain injury demonstrated increased regional homogeneity values in the right fusiform gyrus, left middle cingulum, and right inferior frontal gyrus and reduced values in the left middle temporal gyrus, right supramarginal gyrus, right supplementary motor area, right precentral gyrus, and inferior frontal gyrus. Both groups exhibited higher regional homogeneity values in subcortical nuclei compared with the healthy control group. Patients with traumatic brain injury had reduced regional homogeneity in the paracentral lobule and frontal, temporal, and supramarginal regions compared with patients with cerebrovascular accidents. Preoperative Coma Recovery Scale-Revised scores were positively correlated with regional homogeneity in the hippocampus and negatively correlated with regional homogeneity in the midline temporal region. For 3 months, both groups showed improved consciousness.

Conclusions

Regional homogeneity analysis can identify alterations in functional brain activity associated with recovery of consciousness, offering potential neuroimaging biomarkers for clinical assessment and prognosis for consciousness disorders.

背景：睡眠状态功能磁共振成像提供了对意识障碍患者脑功能的深入了解。我们研究了不同病因的意识障碍中功能性脑网络的变异性，并确定了与康复的潜在相关性。方法在这项单中心前瞻性观察研究中，我们纳入了7例外伤性脑损伤患者，7例脑血管意外患者，以及8例椎管内占位性病变的健康对照组。所有参与者接受静息状态功能磁共振成像，并使用昏迷恢复量表进行评估。区域均匀性值在各组间进行比较，以评估脑功能活动的差异。结果外伤性脑损伤患者右侧梭状回、左侧中扣带和右侧额下回的区域均匀性值升高，左侧颞中回、右侧边缘上回、右侧辅助运动区、右侧中央前回和额下回的区域均匀性值降低。与健康对照组相比，两组均表现出更高的皮质下核区域均匀性值。与脑血管意外患者相比，外伤性脑损伤患者在中央旁小叶和额叶、颞叶和边缘上区域的区域均匀性降低。术前昏迷恢复量表-修订评分与海马区域均匀性呈正相关，与颞中线区域均匀性负相关。3个月后，两组患者的意识均有所改善。结论区域均匀性分析可以识别与意识恢复相关的脑功能活动的改变，为意识障碍的临床评估和预后提供潜在的神经影像学生物标志物。

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引用次数: 0

Ischemic stroke treatment by vagus nerve stimulation: A comprehensive review of mechanisms, clinical efficacy, and future directions 迷走神经刺激治疗缺血性卒中：机制、临床疗效和未来发展方向的综合综述

IF 3.1 4区医学 Q2 CLINICAL NEUROLOGY

Journal of Neurorestoratology

Pub Date : 2025-04-30 DOI: 10.1016/j.jnrt.2025.100209

Penglang Fan , Chao Wu , Bin Liu

Vagus nerve stimulation (VNS) has emerged as a promising neuromodulatory therapy for ischemic stroke that uses multifaceted mechanisms to address acute injury and chronic recovery. This review synthesizes evidence from preclinical and clinical studies, highlighting three neuroprotective mechanisms of VNS: (1) hemodynamic optimization through cholinergic-mediated vasodilation and neurovascular coupling enhancement, (2) suppression of proinflammatory cascades via the cholinergic anti-inflammatory pathway (e.g., >60% TNF-α reduction in animal models), and (3) facilitation of neuroplasticity via brain-derived neurotrophic factor (BDNF) upregulation and reorganization of neural networks. Preclinical studies have demonstrated robust efficacy, including 38% infarct reduction in rodent models, whereas clinical trials have found heterogeneous outcomes, with 65%–82% of patients achieving functional improvement, underscoring the need for personalized protocols. Technological advancements are pivotal: noninvasive transcutaneous VNS (tVNS) offers safer alternatives to comparable acute-phase efficacy, and closed-loop systems integrating electroencephalography (EEG), functional magnetic resonance imaging (fMRI), and biomarker feedback reduce adverse effects by 37% through adaptive parameter optimization. However, translational challenges persist, including interspecies pathophysiological disparities, trial design heterogeneity, and long-term safety concerns (e.g., 28%–33% incidence of neural adaptation in chronic invasive VNS). Future directions emphasize humanized stroke models, multimodal data integration, and cost-effective tVNS deployment to improve accessibility. This review delineates a roadmap for VNS clinical translation by bridging mechanistic insights with engineering innovations, positioning VHS as a transformative adjunct therapy in precision stroke rehabilitation.

迷走神经刺激（VNS）是一种很有前途的缺血性脑卒中的神经调节治疗方法，它使用多方面的机制来解决急性损伤和慢性恢复。本文综述了临床前和临床研究的证据，重点介绍了VNS的三种神经保护机制：(1)通过胆碱能介导的血管舒张和神经血管耦合增强优化血流动力学；(2)通过胆碱能抗炎途径抑制促炎级联反应（如动物模型中TNF-α降低60%）；(3)通过脑源性神经营养因子（BDNF）上调和神经网络重组促进神经可塑性。临床前研究已经证明了强大的疗效，包括在啮齿动物模型中减少38%的梗死，而临床试验发现了不同的结果，65%-82%的患者实现了功能改善，强调了个性化方案的必要性。技术进步至关重要：无创经皮VNS （tVNS）提供了比急性期疗效更安全的替代方案，集成脑电图（EEG）、功能磁共振成像（fMRI）和生物标志物反馈的闭环系统通过自适应参数优化将不良反应减少37%。然而，翻译方面的挑战仍然存在，包括种间病理生理差异、试验设计异质性和长期安全性问题（例如，慢性侵袭性VNS中28%-33%的神经适应发生率）。未来的发展方向是强调人性化的卒中模型、多模式数据集成和高性价比的tVNS部署，以提高可及性。这篇综述描绘了VNS临床翻译的路线图，通过将机械见解与工程创新相结合，将VHS定位为精确中风康复的变革性辅助治疗。

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引用次数: 0

Repeated intrathecal injections of autologous bone marrow-derived mesenchymal stem cells for spastic cerebral palsy: Single-arm safety and preliminary efficacy clinical trial 反复鞘内注射自体骨髓间充质干细胞治疗痉挛性脑瘫：单臂安全性和初步疗效临床试验

IF 3.1 4区医学 Q2 CLINICAL NEUROLOGY

Journal of Neurorestoratology

Pub Date : 2025-04-29 DOI: 10.1016/j.jnrt.2025.100207

Mohammadhosein Akhlaghpasand , Maede Hosseinpoor , Bardia Hajikarimloo , Atieh Hajarizadeh , Maryam Golmohammadi , Roozbeh Tavanaei , Ida Mohammadi , Nastaran Ansari Noghlebari , Niloofar MohammadEbrahim , Alireza Zali , Saeed Oraee-Yazdani

Background

Cerebral palsy (CP) is the most prevalent motor disability among children, for which effective treatment options remain limited. This research sought to evaluate the safety and initial effectiveness of multiple intrathecal administrations of autologous bone marrow-derived mesenchymal stem cells (MSCs) in children with spastic CP.

Methods

A phase I, prospective, single-arm, open-label clinical trial was conducted on 16 children aged 2–12 years with spastic CP. Patients received four intrathecal injections of MSCs at monthly intervals. Safety was evaluated based on the occurrence of adverse events, while efficacy was assessed using various clinical scales, including the Gross Motor Function Classification System (GMFCS), Gross Motor Function Measure (GMFM), Berg Balance Scale (BBS), and the Modified Ashworth Scale (MAS). Assessments were conducted at baseline before treatment, and at a 12-month post-treatment follow-up.

Results

Safety assessment revealed no severe adverse events. Mild adverse events included nausea (18.75%), fatigue (12.5%), and headache (12.5%). Statistically significant improvements were observed in motor function, balance, and spasticity. GMFCS levels improved, with the proportion of patients in Level V decreasing from 62.5% to 43.75% (p = 0.0047). Total GMFM scores increased significantly from 47.01 ± 21.45 to 54.69 ± 22.62 (p < 0.001), with domain-specific improvements in lying (p = 0.002), sitting (p = 0.001), crawling (p = 0.002), standing (p = 0.004), and walking (p = 0.043). BBS scores improved from 6.75 ± 10.88 to 9.88 ± 13.60 (p = 0.001), while MAS reduced from 2.25 ± 1.18 to 1.62 ± 0.96 (p = 0.004). Functional independence improved significantly, with FIM motor scores increasing from 38.63 ± 24.35 to 47.44 ± 25.27 (p = 0.001) and cognitive scores from 57.06 ± 29.15 to 70.88 ± 26.96 (p = 0.001).

Conclusion

Repeated intrathecal injections of autologous MSCs are safe and significantly improve motor function, balance, and spasticity in children with spastic CP. These findings suggest that MSC therapy enhances functional outcomes and quality of life, though larger randomized controlled trials are needed.

背景：脑瘫（CP）是儿童中最常见的运动障碍，有效的治疗方案仍然有限。本研究旨在评估多次鞘内注射自体骨髓间充质干细胞（MSCs）治疗痉挛性CP儿童的安全性和初步有效性。方法对16名2-12岁的痉挛性CP儿童进行了I期、前瞻性、单臂、开放标签的临床试验，患者每月接受4次鞘内注射MSCs。安全性根据不良事件的发生进行评估，而疗效则使用各种临床量表进行评估，包括大运动功能分类系统（GMFCS）、大运动功能量表（GMFM）、Berg平衡量表（BBS）和改良Ashworth量表（MAS）。在治疗前基线和治疗后12个月随访时进行评估。结果安全性评估未发现严重不良事件。轻度不良事件包括恶心（18.75%）、疲劳（12.5%）和头痛（12.5%）。在运动功能、平衡和痉挛方面观察到统计学上显著的改善。GMFCS水平提高，V级患者比例从62.5%降至43.75% （p = 0.0047）。GMFM总分由47.01±21.45分显著增加至54.69±22.62分(p <；0.001)，在躺着（p = 0.002）、坐着（p = 0.001）、爬行（p = 0.002）、站立（p = 0.004）和行走（p = 0.043）方面有特定领域的改善。BBS评分从6.75±10.88提高到9.88±13.60 (p = 0.001)， MAS评分从2.25±1.18降低到1.62±0.96 （p = 0.004）。功能独立性显著改善，FIM运动评分从38.63±24.35分提高到47.44±25.27分（p = 0.001），认知评分从57.06±29.15分提高到70.88±26.96分（p = 0.001）。结论：反复鞘内注射自体间充质干细胞是安全的，可显著改善痉挛性CP患儿的运动功能、平衡和痉挛。这些研究结果表明，MSC治疗可提高功能结局和生活质量，但还需要更大规模的随机对照试验。

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引用次数: 0