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Critical appraisal of a hybrid SSVEP–AO–MI paradigm for motor rehabilitation: Considerations for clinical translation 对运动康复的混合SSVEP-AO-MI模式的批判性评价:临床翻译的考虑
IF 3.4 4区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2026-01-13 DOI: 10.1016/j.jnrt.2026.100268
Parth Aphale, Himanshu Shekhar, Shashank Dokania
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引用次数: 0
The spring of China's national policy in clinical cell (somatic cell) therapy for neurorestoration 中国的春季国家政策在临床细胞(体细胞)治疗中用于神经修复
IF 3.4 4区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2026-01-09 DOI: 10.1016/j.jnrt.2026.100267
Hongyun Huang
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引用次数: 0
Lycium barbarum polysaccharide promotes motor function recovery in rats after spinal cord injury by regulating macrophage /microglial polarization 枸杞多糖通过调节巨噬细胞/小胶质细胞极化促进脊髓损伤大鼠运动功能恢复
IF 3.4 4区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2025-11-13 DOI: 10.1016/j.jnrt.2025.100264
Dun-Xu Hu , Er-Ke Gao , Jia-Yi Zhang , Jun-Bo Chen , De-Jing Zhang , Peng-Tian Zhao , Zhi-Qi Wang , Jun-Jin Li , Zhi-Jian Wei , Tao Zhang

Background

Macrophage and microglial polarization are key drivers of localised inflammatory responses following spinal cord injury (SCI). The equilibrium between the anti-inflammatory and pro-inflammatory effects mediated by polarised cells plays a critical role in influencing neurological recovery post-SCI. Lycium barbarum polysaccharide (LBP), a bioactive compound derived from Lycium barbarum, has shown potential in modulating inflammatory responses and enhancing neurofunctional recovery, yet its underlying mechanisms are still not fully understood.

Methods

We selected 48 adult female rats as the experimental subjects for the in vivo study. Random assignment placed the rats into three distinct groups (n ​= ​16): Sham, SCI, and SCI ​+ ​LBP. A rat spinal cord contusion model was utilised to evaluate the therapeutic effects of LBP on histological repair and locomotor recovery following SCI. Inflammatory cytokine levels at the injury site were quantified. In vitro, a lipopolysaccharide (LPS)-induced bone marrow-derived macrophage (BMDM) model was employed to assess the anti-inflammatory effects of LBP, with subsequent analysis of inflammatory mediator profiles and macrophage M1/M2 polarization status.

Results

LBP treatment significantly improved hindlimb motor function and enhanced nerve conduction capacity in SCI rats, accompanied by reduced histological damage. Moreover, LBP substantially downregulated pro-inflammatory cytokine expression at the injury site. Mechanistically, LBP suppressed M1 polarization while promoting M2 polarization of macrophages and microglia.

Conclusion

LBP offers neuroprotective effects by mitigating post-SCI inflammatory responses via modulation of macrophage and microglial polarization to an anti-inflammatory phenotype. These results provide preclinical evidence for the potential application of LBP as a treatment for SCI.
巨噬细胞和小胶质细胞极化是脊髓损伤(SCI)后局部炎症反应的关键驱动因素。极化细胞介导的抗炎和促炎作用之间的平衡在影响脊髓损伤后神经恢复中起关键作用。枸杞多糖(Lycium barbarum多糖,LBP)是一种从枸杞中提取的生物活性化合物,具有调节炎症反应和促进神经功能恢复的潜力,但其潜在机制尚不完全清楚。方法选择48只成年雌性大鼠作为实验对象进行体内研究。将大鼠随机分为三组(n = 16): Sham组、SCI组和SCI + LBP组。采用大鼠脊髓挫伤模型,评价LBP对脊髓损伤后组织修复和运动恢复的治疗作用。量化损伤部位的炎症细胞因子水平。在体外,采用脂多糖(LPS)诱导的骨髓源性巨噬细胞(BMDM)模型来评估LBP的抗炎作用,随后分析炎症介质谱和巨噬细胞M1/M2极化状态。结果slbp治疗可显著改善脊髓损伤大鼠后肢运动功能,增强神经传导能力,减轻组织损伤。此外,LBP显著下调了损伤部位的促炎细胞因子表达。在机制上,LBP抑制了巨噬细胞和小胶质细胞的M1极化,同时促进了M2极化。结论lbp通过调节巨噬细胞和小胶质细胞极化到抗炎表型,减轻脊髓损伤后的炎症反应,具有神经保护作用。这些结果为LBP作为脊髓损伤治疗的潜在应用提供了临床前证据。
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引用次数: 0
Clinical diagnostic and therapeutic guidelines for ischemic stroke neurorestoration (2024 China version) 缺血性脑卒中神经修复临床诊疗指南(2024中文版)
IF 3.4 4区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2025-11-12 DOI: 10.1016/j.jnrt.2025.100263
Xiaoling Guo , Qun Xue , Jianhua Zhao , Yang Yu , Yi Yang , HanCheng Qiu , Wei Zhang , Lin Chen , Liqun Ren , Jing Liu , Ping Zhang , Siquan Liang , Gengsheng Mao , Linsen Mu , Dezhong Liu , Chuanqiang Qu , Haitao Xi , Hongyan Han , Zhenchuan Liu , Juehua Zhu , Hongyun Huang
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引用次数: 0
CXCL14–CXCR4-mediated platelet migration across the blood–brain barrier and subsequent microglia and astrocyte activation in arterial baroreflex dysfunction 在动脉反射功能障碍中,cxcl14 - cxcr4介导的血小板跨血脑屏障迁移和随后的小胶质细胞和星形胶质细胞激活
IF 3.4 4区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2025-10-25 DOI: 10.1016/j.jnrt.2025.100255
Ruimin Chen , Fengbao Chen , Rui Tan , Bowen Shen , Lili Yang , Yunting Wang , Tianyang Guo , Xiuli Jing , Xiaoli Lu , Xinbo Li , Yongfeng Gao , Xiaomin Zhao

Background

Arterial baroreflex (ABR) dysfunction is linked to various central nervous system disorders and is associated with platelet accumulation in the brain, contributing to neuroinflammation. However, the mechanisms for platelets crossing the blood–brain barrier (BBB) and the role of platelets in ABR dysfunction remain poorly understood. We hypothesize that CXCL14–CXCR4 signaling facilitates platelet migration across the BBB and promotes glial activation in the context of ABR dysfunction.

Methods

ABR dysfunction was induced in Sprague Dawley rats via sinoaortic denervation (SAD). Four weeks post-surgery, 12 rats were randomly divided into two groups (n ​= ​6 per group; Sham and SAD). An additional 18 were divided into three groups (n ​= ​6 per group; Sham, SAD, and SAD ​+ ​clopidogrel). Platelet infiltration in the brain was assessed by immunohistochemistry. Levels of CXCL14 in the brain were evaluated using immunohistochemistry, western blotting, and enzyme-linked immunosorbent assays. CXCR4 levels on platelets was detected by flow cytometry. We constructed an in vitro BBB model to study platelet migration across the BBB. Platelets were co-cultured with BV2 cells and C6 cells, and the levels of inflammatory factors were measured using enzyme-linked immunosorbent assays. Polarization was assessed by immunofluorescence.

Results

Immunofluorescence revealed significant platelet infiltration in ABR dysfunction model rat brains. In vitro BBB models and in vivo experiments confirmed increased platelet migration in ABR-dysfunctional rats. Further analysis showed elevated levels of the chemokine CXCL14 in brain tissue and increased CXCR4 abundance on platelets. In vitro assays demonstrated that platelet migration across the model BBB was driven by CXCL14 and was significantly reduced by inhibitors targeting CXCL14 (neutralizing antibody), CXCR4 (AMD3100), G-protein signaling (pertussis toxin), PI3K signaling (LY294002), and actin polymerization (cytochalasin B). Moreover, CXCL14 stimulation enhanced the phosphorylation of neural Wiskott–Aldrich syndrome protein (N-WASP), a key regulator of cytoskeletal dynamics. Migrating platelets also promoted the polarization of microglia and astrocytes toward pro-inflammatory M1 and A1 phenotypes, respectively. Treatment with clopidogrel, a platelet inhibitor, suppressed platelet migration and glial activation.

Conclusion

Our findings indicate that the CXCL14–CXCR4 axis mediates platelet migration across the BBB in states of ABR dysfunction via G-protein and PI3K-dependent pathways, ultimately triggering glial activation. Our study provides new insights into the mechanisms of platelet migration and neuroinflammation associated with ABR dysfunction.
材料压力反射(ABR)功能障碍与各种中枢神经系统疾病有关,并与大脑血小板积聚有关,从而导致神经炎症。然而,血小板穿越血脑屏障(BBB)的机制以及血小板在ABR功能障碍中的作用仍然知之甚少。我们假设在ABR功能障碍的情况下,CXCL14-CXCR4信号传导促进血小板跨血脑屏障迁移并促进胶质细胞激活。方法采用窦主动脉去神经(SAD)诱导大鼠sabr功能障碍。术后4周,12只大鼠随机分为两组(Sham和SAD每组n = 6)。另外18人被分为三组(每组n = 6人;Sham, SAD和SAD +氯吡格雷)。免疫组化法观察脑组织血小板浸润情况。使用免疫组织化学、western blotting和酶联免疫吸附法评估脑内CXCL14的水平。流式细胞术检测血小板CXCR4水平。我们构建了体外血脑屏障模型来研究血小板在血脑屏障中的迁移。将血小板与BV2细胞和C6细胞共培养,采用酶联免疫吸附法测定炎症因子水平。免疫荧光法测定极化。结果免疫荧光显示ABR功能障碍模型大鼠脑内有明显的血小板浸润。体外血脑屏障模型和体内实验证实,abr功能障碍大鼠血小板迁移增加。进一步分析显示脑组织中趋化因子CXCL14水平升高,血小板中CXCR4丰度增加。体外实验表明,血小板在模型血脑屏障上的迁移由CXCL14驱动,并被靶向CXCL14(中和抗体)、CXCR4 (AMD3100)、g蛋白信号(百日毒)、PI3K信号(LY294002)和肌动蛋白聚合(细胞chalasin B)的抑制剂显著降低。此外,CXCL14刺激增强了神经Wiskott-Aldrich综合征蛋白(N-WASP)的磷酸化,N-WASP是细胞骨架动力学的关键调节因子。迁移的血小板也促进小胶质细胞和星形胶质细胞分别向促炎M1和A1表型极化。氯吡格雷治疗,一种血小板抑制剂,抑制血小板迁移和神经胶质活化。结论研究结果表明,在ABR功能障碍状态下,CXCL14-CXCR4轴通过g蛋白和pi3k依赖通路介导血小板跨血脑屏障迁移,最终触发胶质细胞激活。我们的研究为血小板迁移和与ABR功能障碍相关的神经炎症机制提供了新的见解。
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引用次数: 0
Network pharmacology analysis of energy metabolism-related genes in ischemic stroke targeted by Herba Siegesbeckiae 荆芥靶向缺血性脑卒中能量代谢相关基因的网络药理学分析
IF 3.4 4区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2025-10-22 DOI: 10.1016/j.jnrt.2025.100254
Wenjuan Cong , Xiaojing Yuan , Yuwen Hao , Huimin Jia , Wenjun Jiang , Qiang Gao , Xiaoqian Lv , Hongyou Yang , Yaoting Zheng , Hao Zhang , Haoyue Chen , Ling Zheng , Chao Pang , Yilin Sun , Yi Zhang , Xuanxuan Ge , Zuncheng Zheng , Xiaoyu Wang

Objective

Ischemic stroke (IS), a leading cause of disability and mortality worldwide, results from cerebral vascular occlusion and is associated with profound energy metabolism disorders, including oxidative phosphorylation, glycolysis, and fatty acid metabolism. Herba Siegesbeckiae (HS), a traditional Chinese medicinal herb, has shown neuroprotective potential by modulating metabolic and inflammatory pathways,but its mechanisms in IS remain unclear.

Methods

Active compounds of HS were identified from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. Potential targets were predicted using GeneCards, DisGeNET, and SwissTargetPrediction and filtered for genes related to energy metabolism in IS. A protein-protein interaction network was constructed using STRING and analyzed with Cytoscape 3.9.1 Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed with the clusterProfiler package in R,and molecular docking with AutoDock Vina evaluated compounds-target affinities.

Results

Nine active compounds and 252 potential target genes were identified. Among 21 core targets, IL6, CYP3A4, and PPARG showed the highest network centrality. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated enrichment in inflammatory regulation, lipid metabolism, and oxidative stress-related pathways. Molecular docking showed strong binding affinities, with hederagenin demonstrating the most stable interaction with CYP3A4.

Conclusion

HS may regulate energy metabolism in IS through multi-target, multi-pathway mechanisms, exerting neuroprotective effects via anti-inflammatory and metabolic regulation.
缺血性卒中(IS)是世界范围内致残和死亡的主要原因,由脑血管闭塞引起,并与深度能量代谢紊乱相关,包括氧化磷酸化、糖酵解和脂肪酸代谢。传统中草药荆芥(HS)通过调节代谢和炎症通路显示出神经保护潜力,但其在IS中的机制尚不清楚。方法从中药系统药理学数据库和分析平台中鉴定其有效成分。使用GeneCards、DisGeNET和SwissTargetPrediction预测潜在靶标,并过滤IS中与能量代谢相关的基因。使用STRING构建蛋白-蛋白相互作用网络,使用Cytoscape 3.9.1 Gene Ontology和京都基因百科全书进行分析,使用R中的clusterProfiler软件包进行富集分析,并与AutoDock Vina进行分子对接,评估化合物-靶点亲和力。结果共鉴定出9个活性化合物和252个潜在靶基因。在21个核心靶点中,IL6、CYP3A4和PPARG的网络中心性最高。基因本体和京都基因与基因组百科全书富集分析表明,在炎症调节、脂质代谢和氧化应激相关途径中富集。分子对接表现出较强的结合亲和力,其中hederagenin与CYP3A4的相互作用最稳定。结论hs可能通过多靶点、多途径调节IS的能量代谢,通过抗炎和代谢调节发挥神经保护作用。
{"title":"Network pharmacology analysis of energy metabolism-related genes in ischemic stroke targeted by Herba Siegesbeckiae","authors":"Wenjuan Cong ,&nbsp;Xiaojing Yuan ,&nbsp;Yuwen Hao ,&nbsp;Huimin Jia ,&nbsp;Wenjun Jiang ,&nbsp;Qiang Gao ,&nbsp;Xiaoqian Lv ,&nbsp;Hongyou Yang ,&nbsp;Yaoting Zheng ,&nbsp;Hao Zhang ,&nbsp;Haoyue Chen ,&nbsp;Ling Zheng ,&nbsp;Chao Pang ,&nbsp;Yilin Sun ,&nbsp;Yi Zhang ,&nbsp;Xuanxuan Ge ,&nbsp;Zuncheng Zheng ,&nbsp;Xiaoyu Wang","doi":"10.1016/j.jnrt.2025.100254","DOIUrl":"10.1016/j.jnrt.2025.100254","url":null,"abstract":"<div><h3>Objective</h3><div>Ischemic stroke (IS), a leading cause of disability and mortality worldwide, results from cerebral vascular occlusion and is associated with profound energy metabolism disorders, including oxidative phosphorylation, glycolysis, and fatty acid metabolism. <em>Herba Siegesbeckiae</em> (HS), a traditional Chinese medicinal herb, has shown neuroprotective potential by modulating metabolic and inflammatory pathways,but its mechanisms in IS remain unclear.</div></div><div><h3>Methods</h3><div>Active compounds of HS were identified from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. Potential targets were predicted using GeneCards, DisGeNET, and SwissTargetPrediction and filtered for genes related to energy metabolism in IS. A protein-protein interaction network was constructed using STRING and analyzed with Cytoscape 3.9.1 Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed with the clusterProfiler package in R,and molecular docking with AutoDock Vina evaluated compounds-target affinities.</div></div><div><h3>Results</h3><div>Nine active compounds and 252 potential target genes were identified. Among 21 core targets, IL6, CYP3A4, and PPARG showed the highest network centrality. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated enrichment in inflammatory regulation, lipid metabolism, and oxidative stress-related pathways. Molecular docking showed strong binding affinities, with hederagenin demonstrating the most stable interaction with CYP3A4.</div></div><div><h3>Conclusion</h3><div>HS may regulate energy metabolism in IS through multi-target, multi-pathway mechanisms, exerting neuroprotective effects via anti-inflammatory and metabolic regulation.</div></div>","PeriodicalId":44709,"journal":{"name":"Journal of Neurorestoratology","volume":"14 1","pages":"Article 100254"},"PeriodicalIF":3.4,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145684846","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
Clinical guideline for neurorestorative therapy in pediatric cerebral palsy (2024 China version) 小儿脑瘫神经修复治疗临床指南(2024中文版)
IF 3.4 4区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2025-10-19 DOI: 10.1016/j.jnrt.2025.100253
Zhonghai Li , Kwok-Fai So , Lin Chen , Shiqing Feng , Yong Hu , Liming Cheng , Xinlin Hou , Dong Li , Weimin Huang , Jiujun Qiu , Guoqiang Cheng , Jun Wang , Tonghuan Li , Weipeng Liu , Chao Han , Xin Guan , Yachen Wang , Lili Du , Hongyun Huang , Jing Liu
Cerebral palsy (CP) is a common pediatric neuromotor disorder that is characterized by persistent impairments in movement, muscle tone, and posture. It is frequently associated with sensory, cognitive, and behavioral comorbidities. This guideline presents evidence-based recommendations for neurorestorative therapy in pediatric CP, developed through a systematic review of 44 studies (including randomized controlled trials, cohort studies, and systematic reviews) published up to December 31, 2024. Recommendations were graded according to the Oxford Centre for Evidence-Based Medicine Levels of Evidence. Key recommendations include the use of the Gross Motor Function Classification System for precise motor dysfunction grading, neuroimaging-supported diagnostic criteria, and a multidisciplinary neurorestorative treatment approach. This approach encompasses cell therapy (Grade B), pharmacological management (Grades B–C), surgical interventions (Grade B), neuromodulation (Grade B), structured rehabilitation (Grade B), and psychological support (Grade C). The guideline also advocates for a multi-tiered prevention strategy targeting primary, secondary, and tertiary levels. By emphasizing evidence-based, individualized, and multidisciplinary care, this guideline aims to optimize neurorestorative outcomes and improve quality of life for children with CP, while encouraging ongoing research and periodic updates as new evidence emerges.
脑瘫(CP)是一种常见的儿童神经运动障碍,其特征是运动、肌肉张力和姿势的持续损伤。它通常与感觉、认知和行为合并症有关。本指南通过对截至2024年12月31日发表的44项研究(包括随机对照试验、队列研究和系统评价)的系统综述,提出了儿童CP神经修复治疗的循证建议。建议是根据牛津循证医学证据水平进行分级的。主要建议包括使用大运动功能分类系统进行精确的运动功能分级,神经影像学支持的诊断标准,以及多学科神经恢复性治疗方法。该方法包括细胞治疗(B级)、药物管理(B - C级)、手术干预(B级)、神经调节(B级)、结构康复(B级)和心理支持(C级)。该指南还倡导针对初级、二级和三级采取多层次预防战略。通过强调循证、个体化和多学科护理,本指南旨在优化CP患儿的神经修复结果和改善生活质量,同时鼓励持续研究和定期更新新证据。
{"title":"Clinical guideline for neurorestorative therapy in pediatric cerebral palsy (2024 China version)","authors":"Zhonghai Li ,&nbsp;Kwok-Fai So ,&nbsp;Lin Chen ,&nbsp;Shiqing Feng ,&nbsp;Yong Hu ,&nbsp;Liming Cheng ,&nbsp;Xinlin Hou ,&nbsp;Dong Li ,&nbsp;Weimin Huang ,&nbsp;Jiujun Qiu ,&nbsp;Guoqiang Cheng ,&nbsp;Jun Wang ,&nbsp;Tonghuan Li ,&nbsp;Weipeng Liu ,&nbsp;Chao Han ,&nbsp;Xin Guan ,&nbsp;Yachen Wang ,&nbsp;Lili Du ,&nbsp;Hongyun Huang ,&nbsp;Jing Liu","doi":"10.1016/j.jnrt.2025.100253","DOIUrl":"10.1016/j.jnrt.2025.100253","url":null,"abstract":"<div><div>Cerebral palsy (CP) is a common pediatric neuromotor disorder that is characterized by persistent impairments in movement, muscle tone, and posture. It is frequently associated with sensory, cognitive, and behavioral comorbidities. This guideline presents evidence-based recommendations for neurorestorative therapy in pediatric CP, developed through a systematic review of 44 studies (including randomized controlled trials, cohort studies, and systematic reviews) published up to December 31, 2024. Recommendations were graded according to the Oxford Centre for Evidence-Based Medicine Levels of Evidence. Key recommendations include the use of the Gross Motor Function Classification System for precise motor dysfunction grading, neuroimaging-supported diagnostic criteria, and a multidisciplinary neurorestorative treatment approach. This approach encompasses cell therapy <em>(Grade B)</em>, pharmacological management <em>(Grades B–C)</em>, surgical interventions <em>(Grade B)</em>, neuromodulation <em>(Grade B)</em>, structured rehabilitation <em>(Grade B)</em>, and psychological support <em>(Grade C)</em>. The guideline also advocates for a multi-tiered prevention strategy targeting primary, secondary, and tertiary levels. By emphasizing evidence-based, individualized, and multidisciplinary care, this guideline aims to optimize neurorestorative outcomes and improve quality of life for children with CP, while encouraging ongoing research and periodic updates as new evidence emerges.</div></div>","PeriodicalId":44709,"journal":{"name":"Journal of Neurorestoratology","volume":"13 6","pages":"Article 100253"},"PeriodicalIF":3.4,"publicationDate":"2025-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145466322","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
Asynchronous co-culture enhances neuronal differentiation in CRISPR/Cas9-engineered NURR1 reporter induced neural stem cells 异步共培养增强CRISPR/ cas9工程NURR1报告基因诱导的神经干细胞的神经元分化
IF 3.4 4区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2025-09-24 DOI: 10.1016/j.jnrt.2025.100252
Deqiang Han , Xueyao Wang , Shuili Jing , Tianqi Zheng , Yuan Wang , Yuanzhang Tang , Zhiguo Chen

Background

Parkinson's disease (PD) is caused by the gradual degeneration of dopaminergic neurons in the midbrain, resulting in severe motor impairments. Stem cell-based neurorestorative therapies present considerable therapeutic promise; however, major challenges remain, such as variability in lineage specification, limited long-term graft survival, and the absence of effective real-time techniques to monitor differentiation processes. Overcoming these obstacles necessitates innovative strategies to address cellular heterogeneity and enhance the efficacy of neurorestorative interventions.

Methods

We engineered a NURR1-driven dopaminergic reporter in induced neural stem cells (iNSCs) through CRISPR/Cas9-mediated knock-in of ZsGreen. The differentiation capacity of reporter iNSCs was validated via in vitro spontaneous differentiation. Transcriptomic profiling was performed to compare fluorescence-sorted differentiation-committed (ZsGreen+) and non-committed (ZsGreen) subpopulations with biological triplicates. To enhance neuronal differentiation efficiency, we developed a stage-specific asynchronous co-culture system that combined early-stage (day 5) and mid-stage (day 8) differentiating iNSC populations. Optimized iNSC-derived dopaminergic precursors were transplanted into striatum of sixteen male SCID-Beige mice (6–8 weeks old), which were randomly assigned to two groups: one receiving co-cultured cells (n ​= ​8) and the other receiving non-co-cultured cells (n ​= ​8). Graft survival and differentiation were subsequently assessed.

Results

The reporter system allowed real-time tracking of dopaminergic differentiation from iNSCs without affecting their differentiation potential. Transcriptome analysis showed specific activation of neurorestorative pathways in ZsGreen+ ​cells, including processes such as neurogenesis, neuronal maturation, axonal guidance, and cell projection organization. Asynchronous co-culture markedly enhanced the neuronal yield from iNSC-derived dopaminergic precursors compared with standard approaches. Transplantation in vivo confirmed stable engraftment and differentiation into TH-positive cells within the host striatal tissue.

Conclusion

The NURR1-ZsGreen reporter system provides a functional platform to resolve lineage specification heterogeneity and optimize differentiation protocols. The identified neurorestorative pathways, together with the asynchronous co-culture strategy, collectively address critical barriers in cell replacement-based neurorestorative therapy.
帕金森病(PD)是由中脑多巴胺能神经元的逐渐退化引起的,导致严重的运动障碍。基于干细胞的神经修复疗法具有相当大的治疗前景;然而,主要的挑战仍然存在,如谱系规格的可变性,有限的长期移植物存活,以及缺乏有效的实时技术来监测分化过程。克服这些障碍需要创新的策略来解决细胞异质性和提高神经修复干预的功效。方法通过CRISPR/ cas9介导的ZsGreen敲入,在诱导神经干细胞(iNSCs)中构建nurr1驱动的多巴胺能报告基因。通过体外自发分化验证了报告细胞的分化能力。进行转录组学分析,比较荧光分类的分化承诺(ZsGreen+)和非承诺(ZsGreen -)亚群与生物三倍体。为了提高神经元分化效率,我们开发了一个阶段特异性的异步共培养系统,将早期(第5天)和中期(第8天)分化的iNSC群体结合起来。将优化后的insc来源的多巴胺能前体移植到16只雄性SCID-Beige小鼠(6-8周龄)的纹状体中,随机分为两组:一组接受共培养细胞(n = 8),另一组接受非共培养细胞(n = 8)。随后评估移植物存活和分化。结果该报告系统在不影响其分化潜能的情况下,可以实时跟踪iNSCs的多巴胺能分化情况。转录组分析显示,ZsGreen+细胞的神经修复通路特异性激活,包括神经发生、神经元成熟、轴突引导和细胞投射组织等过程。与标准方法相比,异步共培养显著提高了insc来源的多巴胺能前体的神经元产量。体内移植证实在宿主纹状体组织内稳定植入并分化为th阳性细胞。结论NURR1-ZsGreen报告系统为解决谱系规格异质性和优化分化方案提供了功能平台。已确定的神经修复途径,以及异步共培养策略,共同解决了基于细胞替代的神经修复治疗的关键障碍。
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引用次数: 0
Efficacy and safety of argatroban in acute branch atheromatous disease: A retrospective observational study 阿加曲班治疗急性支动脉粥样硬化的疗效和安全性:一项回顾性观察研究
IF 3.4 4区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2025-09-13 DOI: 10.1016/j.jnrt.2025.100251
Min Chang, Ruifang Ren, Dewei Zhu, Jun Zhao, Xu Li, Meiyang Yu, Ping Zhang, Haiqing Yan

Background

To evaluate the efficacy and safety of argatroban combined with dual antiplatelet therapy (DAPT) for treating acute branch atheromatous disease-related cerebral infarction.

Methods

A retrospective study was conducted of 127 stroke patients admitted to the Department of Neurology at the First Affiliated Hospital of Xinxiang Medical University from January 2022 to December 2023. Patients were divided into two groups: the argatroban group with 44 individuals (who initially received argatroban therapy and subsequently received DAPT) and the DAPT group with 83 individuals (who received treatment with aspirin combined with clopidogrel). Therapeutic effects were evaluated using the National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale, and Activities of Daily Living scores before and after treatment.

Results

After propensity score matching, 37 patients were included per group. The argatroban group showed higher rates of “basic cure,” 3-month modified Rankin Scale score ≤1, and NIHSS score reduction ≥2, and had a lower recurrence rate (p ​< ​0.05). No adverse events were observed. Multivariate logistic regression confirmed a lower recurrence rate in the argatroban group. Subgroup analysis revealed better outcomes in older patients (higher NIHSS reduction ≥2) and in young/middle-aged patients with mild branch atheromatous disease (higher cure rate, lower incidence of early neurological deterioration) (p ​< ​0.05).

Conclusion

Argatroban combined with DAPT in the acute phase improves cure rates, promotes neurological recovery, enhances short-term prognosis, reduces recurrence, and does not increase adverse reactions such as bleeding.
背景评价阿加曲班联合双重抗血小板疗法(DAPT)治疗急性支动脉粥样硬化相关脑梗死的疗效和安全性。方法对2022年1月至2023年12月新乡医科大学第一附属医院神经内科收治的127例脑卒中患者进行回顾性研究。患者分为两组:阿加曲班组44例(最初接受阿加曲班治疗,随后接受DAPT治疗)和DAPT组83例(接受阿司匹林联合氯吡格雷治疗)。治疗前后采用美国国立卫生研究院卒中量表(NIHSS)、改良Rankin量表和日常生活活动评分评估治疗效果。结果倾向评分匹配后,每组纳入37例患者。阿加曲班组“基本治愈率”较高,3个月改良Rankin量表评分≤1分,NIHSS评分降低≥2分,复发率较低(p < 0.05)。未观察到不良事件。多因素logistic回归证实阿加曲班组复发率较低。亚组分析显示,老年患者(NIHSS降低≥2)和中青年轻度分支动脉粥样硬化患者(治愈率较高,早期神经功能恶化发生率较低)预后较好(p < 0.05)。结论急性期阿加曲班联合DAPT可提高治愈率,促进神经功能恢复,改善短期预后,减少复发率,且不增加出血等不良反应。
{"title":"Efficacy and safety of argatroban in acute branch atheromatous disease: A retrospective observational study","authors":"Min Chang,&nbsp;Ruifang Ren,&nbsp;Dewei Zhu,&nbsp;Jun Zhao,&nbsp;Xu Li,&nbsp;Meiyang Yu,&nbsp;Ping Zhang,&nbsp;Haiqing Yan","doi":"10.1016/j.jnrt.2025.100251","DOIUrl":"10.1016/j.jnrt.2025.100251","url":null,"abstract":"<div><h3>Background</h3><div>To evaluate the efficacy and safety of argatroban combined with dual antiplatelet therapy (DAPT) for treating acute branch atheromatous disease-related cerebral infarction.</div></div><div><h3>Methods</h3><div>A retrospective study was conducted of 127 stroke patients admitted to the Department of Neurology at the First Affiliated Hospital of Xinxiang Medical University from January 2022 to December 2023. Patients were divided into two groups: the argatroban group with 44 individuals (who initially received argatroban therapy and subsequently received DAPT) and the DAPT group with 83 individuals (who received treatment with aspirin combined with clopidogrel). Therapeutic effects were evaluated using the National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale, and Activities of Daily Living scores before and after treatment.</div></div><div><h3>Results</h3><div>After propensity score matching, 37 patients were included per group. The argatroban group showed higher rates of “basic cure,” 3-month modified Rankin Scale score ≤1, and NIHSS score reduction ≥2, and had a lower recurrence rate (<em>p</em> ​&lt; ​0.05). No adverse events were observed. Multivariate logistic regression confirmed a lower recurrence rate in the argatroban group. Subgroup analysis revealed better outcomes in older patients (higher NIHSS reduction ≥2) and in young/middle-aged patients with mild branch atheromatous disease (higher cure rate, lower incidence of early neurological deterioration) (<em>p</em> ​&lt; ​0.05).</div></div><div><h3>Conclusion</h3><div>Argatroban combined with DAPT in the acute phase improves cure rates, promotes neurological recovery, enhances short-term prognosis, reduces recurrence, and does not increase adverse reactions such as bleeding.</div></div>","PeriodicalId":44709,"journal":{"name":"Journal of Neurorestoratology","volume":"14 1","pages":"Article 100251"},"PeriodicalIF":3.4,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145571144","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
The 2024 yearbook of Neurorestoratology 2024年神经修复学年鉴
IF 3.4 4区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2025-09-11 DOI: 10.1016/j.jnrt.2025.100250
Hongyun Huang , Paul R. Sanberg , Hari Shanker Sharma , John R. Bach , Hooshang Saberi , Ashok K. Shetty , Ali Otom , Almudena Ramon-Cueto , Damien Kuffler , Xiaoling Guo , Mengzhou Xue , Dario Siniscalco , Edgardo O. Alvarez , Ziad Alhawamdeh , Russell J. Andrews , Gustavo A. Moviglia , Shiqing Feng , Liyan Qiao
In the year 2024, the continuous novel advances in the field of Neurorestoratology have reflected the exploring pathogenesis and neurorestorative mechanisms of the neurodegenerative diseases. Clinical therapeutic neurorestorative explorations have demonstrated exciting results benefiting patients with neuro-psychiatric diseases through various therapeutic strategies, including neuromodulation and brain-computer interfaces, cell therapies, neurorestorative surgery as well as pharmaceutical therapy, and intensive training. More randomized clinical trials of neurorestorative treatments have been conducted and demonstrated positive results, which will be further translated into routine clinical practice. Here we compile the most relevant studies with the sole idea of contributing to the improvement of quality of life of people suffering from neurological disorders. This yearbook emphasizes and summarizes some of the most relevant reserach in the field of Neurorestoratology, evidenced by published articles in original impact journals during 2024.
2024年,神经修复学领域不断取得新进展,反映了神经退行性疾病的发病机制和神经修复机制的探索。临床治疗性神经修复探索通过各种治疗策略,包括神经调节和脑机接口,细胞治疗,神经修复手术以及药物治疗和强化训练,展示了令人兴奋的结果,使神经精神疾病患者受益。更多的神经修复治疗的随机临床试验已经开展并取得了积极的结果,这些结果将进一步转化为常规临床实践。在这里,我们汇集了最相关的研究,唯一的想法是为改善神经系统疾病患者的生活质量做出贡献。本年鉴强调并总结了神经修复学领域的一些最相关的研究,这些研究是由2024年在原始影响期刊上发表的文章所证明的。
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Journal of Neurorestoratology
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