Journal of Neurorestoratology最新文献

{"title":"Ischemic stroke treatment by vagus nerve stimulation: A comprehensive review of mechanisms, clinical efficacy, and future directions","authors":"Penglang Fan ,&nbsp;Chao Wu ,&nbsp;Bin Liu","doi":"10.1016/j.jnrt.2025.100209","DOIUrl":"10.1016/j.jnrt.2025.100209","url":null,"abstract":"<div><div>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., &gt;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.</div></div>","PeriodicalId":44709,"journal":{"name":"Journal of Neurorestoratology","volume":"13 4","pages":"Article 100209"},"PeriodicalIF":3.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144147778","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}

{"title":"Repeated intrathecal injections of autologous bone marrow-derived mesenchymal stem cells for spastic cerebral palsy: Single-arm safety and preliminary efficacy clinical trial","authors":"Mohammadhosein Akhlaghpasand ,&nbsp;Maede Hosseinpoor ,&nbsp;Bardia Hajikarimloo ,&nbsp;Atieh Hajarizadeh ,&nbsp;Maryam Golmohammadi ,&nbsp;Roozbeh Tavanaei ,&nbsp;Ida Mohammadi ,&nbsp;Nastaran Ansari Noghlebari ,&nbsp;Niloofar MohammadEbrahim ,&nbsp;Alireza Zali ,&nbsp;Saeed Oraee-Yazdani","doi":"10.1016/j.jnrt.2025.100207","DOIUrl":"10.1016/j.jnrt.2025.100207","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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% (<em>p</em> = 0.0047). Total GMFM scores increased significantly from 47.01 ± 21.45 to 54.69 ± 22.62 (<em>p</em> &lt; 0.001), with domain-specific improvements in lying (<em>p</em> = 0.002), sitting (<em>p</em> = 0.001), crawling (<em>p</em> = 0.002), standing (<em>p</em> = 0.004), and walking (<em>p</em> = 0.043). BBS scores improved from 6.75 ± 10.88 to 9.88 ± 13.60 (<em>p</em> = 0.001), while MAS reduced from 2.25 ± 1.18 to 1.62 ± 0.96 (<em>p</em> = 0.004). Functional independence improved significantly, with FIM motor scores increasing from 38.63 ± 24.35 to 47.44 ± 25.27 (<em>p</em> = 0.001) and cognitive scores from 57.06 ± 29.15 to 70.88 ± 26.96 (<em>p</em> = 0.001).</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":44709,"journal":{"name":"Journal of Neurorestoratology","volume":"13 4","pages":"Article 100207"},"PeriodicalIF":3.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144194918","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}

{"title":"Therapeutic effects of glial cell-derived extracellular vesicles on ischemic stroke in rodent models: A systematic review and meta-analysis","authors":"Na Li ,&nbsp;Ying Qian ,&nbsp;Hongrui Zhang ,&nbsp;Chenxi Tao ,&nbsp;Ying Li ,&nbsp;Rufan Xu ,&nbsp;Yikun Sun ,&nbsp;Yannan He ,&nbsp;Yonghong Gao ,&nbsp;Zhenhong Liu","doi":"10.1016/j.jnrt.2025.100222","DOIUrl":"10.1016/j.jnrt.2025.100222","url":null,"abstract":"<div><div>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, <em>p</em> &lt; 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, <em>p</em> &lt; 0.0001, Tau² = 0.99, and I² = 42%) and decreased brain water content and the release of pro-inflammatory factors post-stroke.</div><div>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.</div></div>","PeriodicalId":44709,"journal":{"name":"Journal of Neurorestoratology","volume":"13 4","pages":"Article 100222"},"PeriodicalIF":3.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144480608","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}

{"title":"The effects of weight training and Aklil-ol-Malek on histopathology and C-reactive protein, nuclear factor erythroid-derived 2-like 2 beta-site Amyloid Precursor protein cleaving enzyme1 genes expression in Alzheimer's disease model rats","authors":"Farah Nameni ,&nbsp;Mohammad Reza Amir Khan Dehkordi","doi":"10.1016/j.jnrt.2025.100206","DOIUrl":"10.1016/j.jnrt.2025.100206","url":null,"abstract":"<div><h3>Background</h3><div>Oxidative stress and neuroinflammation are key factors in the pathophysiology of Alzheimer's disease (AD). Exercise and Aklil-ol-Malek may reduce AD symptoms. Therefore, the current study investigated the effect of weight training and Aklil-ol-Malek consumption on histopathological and inflammatory changes in hippocampal tissue of male AD model rats.</div></div><div><h3>Method</h3><div>We prepared 55 8-week-old male Wistar rats and transferred them to an animal laboratory. The rats were randomly divided into five groups: healthy control group, Alzheimer's control group, Alzheimer's group + weight training, Alzheimer's group + Aklil-ol-Malek supplement, and Alzheimer's group + Aklil-ol-Malek supplement + weight training. AD was induced in the 4 groups. The weight training protocol and Aklil-ol-Malek supplementation were examined as an intervention. The designated groups were administered Aklil-ol-Malek supplements. The anesthetized rats' hippocampi were extracted for further analysis 72 hours after the last session of the protocol. After the induction of AD and supplementation, two-way analysis of variance was used to examine the differences between groups (<em>p &lt;</em> 0.05).</div></div><div><h3>Results</h3><div>The results showed a decrease in the expression of CRP and NFE2L2 genes in rats in the Aklil-ol-Malek and weight training group compared with the findings in rats in the Alzheimer's group. Changes in the expression of BACE1 were not significant in rats in the weight training with Aklil-ol-Malek group.</div></div><div><h3>Conclusion</h3><div>An intervention receiving exercise and Aklil-ol-Malek extract positively improved health and reduced AD progression. These results were likely to have been caused by the physiological effects of exercise and the antioxidant properties of Aklil-ol-Malek.</div></div>","PeriodicalId":44709,"journal":{"name":"Journal of Neurorestoratology","volume":"13 3","pages":"Article 100206"},"PeriodicalIF":3.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143898644","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}

{"title":"Advances in clinical neurorestorative treatments of Parkinson's disease","authors":"Yixuan Yin ,&nbsp;Dongning Su ,&nbsp;Joyce S.T. Lam ,&nbsp;Tao Feng","doi":"10.1016/j.jnrt.2025.100204","DOIUrl":"10.1016/j.jnrt.2025.100204","url":null,"abstract":"<div><div>Increasing dopamine levels using oral levodopa administration has been the gold standard for treating Parkinson's disease (PD), but motor complications that occur with the progression of PD seriously affect patient quality of life. Neurorestorative treatments have provided new possibilities for PD therapies. This review summarizes the recent clinical progress in several aspects of neurorestorative strategies: cell therapy, bioengineering and tissue engineering therapy, pharmacological therapy, neurostimulation/neuromodulation, and brain–computer interfaces. However, progress has mainly been related to exploratory experimental results, and more evidence is needed to further verify the safety and efficacy of these neurorestorative treatments in PD.</div></div>","PeriodicalId":44709,"journal":{"name":"Journal of Neurorestoratology","volume":"13 3","pages":"Article 100204"},"PeriodicalIF":3.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848013","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}

{"title":"The efficacy of transcutaneous auricular vagus nerve stimulation for patients with mild cognitive impairment and depressive symptoms: A case report and fMRI study","authors":"Chunlei Guo ,&nbsp;Jifei Sun ,&nbsp;Yue Ma ,&nbsp;Shanshan Gao ,&nbsp;Tianjiao Xu ,&nbsp;Qingyan Chen ,&nbsp;Lei Zhang ,&nbsp;Jiudong Cao ,&nbsp;Guolei Zhang ,&nbsp;Yang Hong ,&nbsp;Hua Yan ,&nbsp;Ge Yang ,&nbsp;Jiliang Fang","doi":"10.1016/j.jnrt.2025.100202","DOIUrl":"10.1016/j.jnrt.2025.100202","url":null,"abstract":"<div><div>This case report details a patient diagnosed with mild cognitive impairment concurrently exhibiting depressive symptoms and undergoing 24 weeks of transcutaneous vagus nerve stimulation therapy. After the 24-week treatment, the patient demonstrated notable improvement in both cognitive function and mood. Simultaneously, significant alterations were observed in the patient's temporal pole and medial orbitofrontal gyrus, regions associated with cognition and emotion. Furthermore, the patient continued to maintain a favorable status throughout the follow-up period. Therefore, transcutaneous vagus nerve stimulation may be a potential treatment for patients with mild cognitive impairment and depressive symptoms.</div></div>","PeriodicalId":44709,"journal":{"name":"Journal of Neurorestoratology","volume":"13 3","pages":"Article 100202"},"PeriodicalIF":3.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143825545","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}

{"title":"Application and progress of magnetic field therapy for spinal cord injury","authors":"Zicai Liu ,&nbsp;Zhanxiang Lin ,&nbsp;Xuejin Liu ,&nbsp;Xiuying Xie ,&nbsp;Cheng Tan","doi":"10.1016/j.jnrt.2025.100205","DOIUrl":"10.1016/j.jnrt.2025.100205","url":null,"abstract":"<div><div>Spinal cord injury (SCI), which results in severe neurological loss and multiple complications, remains a global health problem. Although SCI is a central nervous system injury, the field of related therapies has shown great promise, with breakthroughs regarding the theory of central nervous system irreparability. However, from the perspective of neuroprosthetics, the relevant basic theories are not always fully recognized or clearly understood, which poses a challenge to clinical practice guidance. Magnetic therapy technology has developed rapidly in recent years, and various magnetic therapy methods have emerged. Magnetic field therapy (MFT), with applications in SCI treatment, is considered a promising strategy for nerve repair and provides a theoretical foundation for subsequent research. MFT, including transcranial magnetic stimulation, static magnetic field, and pulsed electromagnetic field, has been used preclinically, and clinical studies have shown potential efficacy in SCI. Moreover, preclinical studies have revealed that MFT promotes nerve repair, reduces inflammatory responses, improves motor function, and enhances bladder control. They have also demonstrated that MFT is safe in human SCI patients and may improve motor function and pain control. However, its translation from preclinical studies to clinical application faces many challenges, including biological differences, determination of dose and treatment parameters, assessment of safety and side effects, and ethical and regulatory compliance. The present article aims to provide a comprehensive review of the applications and advances of MFT in SCI, to guide future research and provide a reference for clinical treatment. An in-depth discussion of MFT in the field of SCI may provide new ideas and directions for neural repair in SCI.</div></div>","PeriodicalId":44709,"journal":{"name":"Journal of Neurorestoratology","volume":"13 3","pages":"Article 100205"},"PeriodicalIF":3.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143834495","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}

{"title":"Relationship between major depression and cervical spondylosis: A two-sample bidirectional mendelian randomization study","authors":"Dingyu Du ,&nbsp;Guipeng Zhao ,&nbsp;Yukai Huang ,&nbsp;Longyi Chen,&nbsp;Jinping Liu","doi":"10.1016/j.jnrt.2025.100203","DOIUrl":"10.1016/j.jnrt.2025.100203","url":null,"abstract":"<div><h3>Background</h3><div>This study aimed to explore the causal link between cervical spondylosis (CS) and major depression (MD) using a bidirectional Mendelian randomization (MR) analysis.</div></div><div><h3>Methods</h3><div>Bidirectional MR was employed to validate the bidirectional causal relationship between CS and MD using pooled data obtained from the Integrated Epidemiology Unit Open Genome Wide Association Study (GWAS) database. MR Egger, weighted median, inverse-variance weighted (IVW), and simple mode methods were used, with priority given to IVW results. Sensitivity analyses, including heterogeneity tests, horizontal pleiotropy tests, and leave-one-out methods, were performed to confirm the stability of the MR results.</div></div><div><h3>Results</h3><div>In a forward MR analysis, a causal effect was found between MD and CS (IVW: OR &gt; 1, <em>p</em> &lt; 0.05). However, a reverse MR analysis indicated no causal relationship between CS and MD (<em>p</em> &gt; 0.05). Sensitivity analyses revealed no sample heterogeneity, no horizontal pleiotropy effect, and no significant bias, thus supporting the reliability of the MR analysis results.</div></div><div><h3>Conclusion</h3><div>This study provides evidence demonstrating that MD is causally associated with CS, whereas CS is not causally linked to MD. These findings offer novel insights into the pathogenesis of these two prevalent diseases.</div></div>","PeriodicalId":44709,"journal":{"name":"Journal of Neurorestoratology","volume":"13 3","pages":"Article 100203"},"PeriodicalIF":3.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143759582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in clinical neurorestorative treatments in brain trauma","authors":"Qian Zhou ,&nbsp;Wei Shen ,&nbsp;Liang Wen","doi":"10.1016/j.jnrt.2025.100191","DOIUrl":"10.1016/j.jnrt.2025.100191","url":null,"abstract":"<div><div>Traumatic brain injury (TBI) is a significant cause of mortality and disability globally, imposing a considerable burden on society and individuals. In recent years, neurorestorative therapies for TBI have attracted widespread attention. Despite the rapid progress in clinical neurorestorative treatments for TBI, few relevant reviews have been published. This review addresses advances in these strategies for patients with TBI, covering cellular therapies, neurostimulation therapies, brain-computer interfaces, pharmacologic therapies, and multidisciplinary therapies. This review aims to serve as a reference for clinical professionals treating patients with TBI, improving neurologic rehabilitation and outcomes for patients with TBI.</div></div>","PeriodicalId":44709,"journal":{"name":"Journal of Neurorestoratology","volume":"13 3","pages":"Article 100191"},"PeriodicalIF":3.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143621214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroinflammation and neurorestoration following stroke: Molecular mechanisms and therapeutic approaches","authors":"Liang Cao ,&nbsp;Yi Zhang ,&nbsp;Wenjun Pi ,&nbsp;Voon Wee Yong ,&nbsp;Mengzhou Xue","doi":"10.1016/j.jnrt.2025.100201","DOIUrl":"10.1016/j.jnrt.2025.100201","url":null,"abstract":"","PeriodicalId":44709,"journal":{"name":"Journal of Neurorestoratology","volume":"13 3","pages":"Article 100201"},"PeriodicalIF":3.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143734653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}