CNS Neuroscience & Therapeutics最新文献

{"title":"Fracture Risk Associated With Dimethyl Fumarate Treatment in Multiple Sclerosis Patients: Population Heterogeneity and Temporal Patterns","authors":"Dongdong He,&nbsp;Jingkai Di,&nbsp;Peirui Jiang,&nbsp;Lujia Liu,&nbsp;Feida Wang,&nbsp;Chuan Xiang","doi":"10.1111/cns.70612","DOIUrl":"https://doi.org/10.1111/cns.70612","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Dimethyl fumarate (DMF) is currently recommended as a first-line therapy for multiple sclerosis (MS). Investigating its adverse events (AEs) holds significant clinical importance. This study aimed to explore the association between DMF and fracture-related AEs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Data from the FDA Adverse Event Reporting System (FAERS) database (Q1 2004 to Q3 2024) were analyzed using disproportionality analysis. Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Information Component (IC), and Empirical Bayes Geometric Mean (EBGM) were employed to identify and characterize AEs. Age- and gender-specific subgroup analyses were conducted to evaluate AE patterns. Additionally, Weibull distribution analysis was performed to assess the temporal relationship of AE onset.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Overall, spinal fusion fracture (ROR = 13.13, 95% CI: 1.73–99.86) and coccyx fracture (ROR = 3.05, 95% CI: 1.92–4.86) exhibited the strongest signals. Gender and age heterogeneity were observed in DMF-associated fracture risks. Female patients showed the highest signals for spinal fusion bone fracture (ROR = 13.13) and coccyx fracture (ROR = 2.80), while males predominantly exhibited patella (ROR = 4.94) and scapula fractures (ROR = 3.68). Age stratification revealed elevated risks of forearm fracture (ROR = 10.29, 95% CI: 4.24–24.96) and ankle fracture (ROR = 5.63, 95% CI: 4.32–7.35) in elderly patients, whereas younger populations displayed diverse multi-site fractures. Time-to-onset (TTO) analysis indicated that 63.62% of fractures occurred within the first 2 years of the treatment cycle, with a median onset time of 506 days. Weibull distribution modeling indicated that DMF's failure pattern aligned with an early failure-type curve.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>DMF use is associated with an increased risk of fracture-related AEs, with demographic variations in susceptibility. This study provides critical insights into the safety profile of DMF in MS management, underscoring the need for vigilance in high-risk populations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70612","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145037575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deer Antler S-Adenosylmethionine Ameliorates Depression-Like Behaviors and Neuroinflammation in CUMS Mice","authors":"Yongjian Liu,&nbsp;Chenyang Han,&nbsp;Li Guo,&nbsp;Wenyan Li,&nbsp;Shasha wu,&nbsp;Jian Sheng,&nbsp;Liping Zhai,&nbsp;Heping Shen,&nbsp;Genghuan Wang","doi":"10.1111/cns.70569","DOIUrl":"https://doi.org/10.1111/cns.70569","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To investigate the effects and mechanisms of S-adenosylmethionine (SAM) from deer antler on improving depression-like behaviors in chronic unpredictable mild stress (CUMS) mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The CUMS method was used to establish a mouse depression model. The relationship between SAM and HIF-1α was analyzed by small molecule-protein docking and molecular dynamics simulation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Network pharmacology analysis showed that the effect of SAM is related to HIF-1α. When shRNA-HIF-1α was used to silence the expression of HIF-1α, the effect of SAM was inhibited. The improvement of depression-like behaviors in mice was not significant, and inflammatory factors were no longer further downregulated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>SAM can improve depression-like behaviors in CUMS mice and enhance their mobility. SAM inhibits neuroinflammation and glycolysis, and also suppresses the activation of microglia.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70569","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repopulating Microglia Suppress Peripheral Immune Cell Infiltration to Promote Poststroke Recovery","authors":"Ligen Shi,&nbsp;Lingxiao Lu,&nbsp;Jun Hu,&nbsp;Jiarui Chen,&nbsp;Qia Zhang,&nbsp;Ziyang Jin,&nbsp;Zhen Wang,&nbsp;Zhe Zheng,&nbsp;Jianmin Zhang","doi":"10.1111/cns.70565","DOIUrl":"10.1111/cns.70565","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Sustained neuroinflammation following ischemic stroke impedes post-injury tissue repairment and neurological functional recovery. Developing innovative therapeutic strategies that simultaneously suppress detrimental inflammatory cascades and facilitate neurorestorative processes is critical for improving long-term rehabilitation outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We employed a microglia depletion-repopulation paradigm by administering PLX5622 for 7 days post-ischemia; followed by a 7-day withdrawal period to allow microglia repopulation. Single-cell transcriptomics, behavioral testing, cytokine arrays, flow cytometry, and immunofluorescence were used to assess the effects of microglia repopulation and delineate the transition of reshaped immune microenvironment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>PLX5622 administration reshaped the poststroke immune microenvironment, promoting neurofunctional recovery. Repopulated microglia adopted a homeostatic phenotype, increasing homeostatic states by ~14.36% and reducing pro-inflammatory states by ~20.17%. This reshaped environment suppressed T cell exhaustion, limited neutrophil terminal differentiation, and promoted a phagocytic macrophage phenotype. Furthermore, we identified that these transitions in infiltrating immune cells may be driven by reduced chemokine production, enhanced blood–brain barrier (BBB) integrity, and transcriptional reprogramming.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Transient microglial depletion and repopulation via PLX5622 during the acute phase post stroke facilitate the recovery of neurological function. This immunomodulatory strategy offers a promising and clinically translationally relevant approach to enhance functional recovery following ischemic brain injury.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70565","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Individualized Frequency-Dependent Stimulation to the Anterior Nucleus of the Thalamus May Improve Antiepileptic Effects in Patients With Focal Epilepsy","authors":"Ying Gao,&nbsp;Hao Yan,&nbsp;Xueyuan Wang,&nbsp;Guiliang Hao,&nbsp;Liang Qiao,&nbsp;Wei Shu,&nbsp;Duanyu Ni,&nbsp;Guoguang Zhao,&nbsp;Liankun Ren,&nbsp;Tao Yu","doi":"10.1111/cns.70611","DOIUrl":"10.1111/cns.70611","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>A total of 30% of individuals with epilepsy are resistant to drug treatment. Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) shows promise for treating drug-resistant epilepsy (DRE), but further research is needed to optimize DBS parameters, including stimulation frequency. This study aimed to reveal the optimal frequency for ANT-DBS by testing the real-time effects of various stimulation frequencies on the ANT among patients undergoing stereoelectroencephalography (SEEG) electrode implantation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Eleven patients (8 males; mean age, 24.2 years; mean epilepsy duration, 13.5 years) were enrolled. Postoperative electrode reconstruction identified ANT contacts for bipolar stimulation between 10 Hz and 100 Hz at 10-Hz increments, with a 1-min interval between stimuli. The effects were analyzed on the basis of spike count, power spectral density, and causal flow.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our study revealed that ANT stimulation suppresses seizure focus activity and modulates brain network dynamics, with the effects varying by individual characteristics and frequency. Stimulation at 10–70 Hz reduced spikes (&gt; 50%) and PSD (<i>p</i> &lt; 0.05) in the epileptogenic region while also influencing network connectivity between the epileptogenic zone and adjacent cortical regions, including the frontal, temporal, and insular lobes, as well as the overall brain network.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Instead of using a fixed high frequency for ANT-DBS, the optimal frequency should be selected for each patient. Patients who do not respond well to high-frequency ANT-DBS can use a lower frequency, such as 10–70 Hz.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70611","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Visuomotor Training to Enhance Proprioception of Contralateral Wrist Based on the Cross-Transfer Effect","authors":"Yizhao Wang,&nbsp;Liping Huang,&nbsp;Zhuang Wang,&nbsp;Ting Liu","doi":"10.1111/cns.70504","DOIUrl":"10.1111/cns.70504","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Neurological diseases such as stroke or Parkinson's disease are often accompanied by weakening or loss of proprioception, which seriously affects the motor control ability of the patients. However, proprioception rehabilitation is challenging due to the pain caused by impaired joints and the hard efforts that patients have to make during training. This study investigated the cross-transfer effect of short-term visuomotor training to the untrained wrist from the trained wrist, from both views of behavioral results and brain activity analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Thirty healthy volunteers aged 25.53 ± 4.95 years were recruited for this study. They were randomly assigned into two groups: the visuomotor (<i>n</i> = 15) group performed visuomotor training (VM group) and the conventional training (<i>n</i> = 15) group (CT group) performed flexion and extension training on the right wrist. Behavioral tests (movement accuracy error, MAE) were performed both before and after training, with electroencephalogram (EEG) recorded. The movement-related cortical potentials (MRCPs), event-related potentials (ERPs) and event-related spectral perturbation (ERSP) were calculated in the test session before and after training.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Behavioral results showed that after visuomotor training of the right wrist on the VM group, the mean MAE of both the right wrist and untrained left wrist were reduced (<i>p</i> &lt; 0.05) after training. EEG topography showed reduced brain activity as the behavioral test task became familiar. ERPs showed a decrease in amplitude during the behavioral test for both trained and untrained wrist movements. MRCPs latency significantly increased at C3 and C4 while amplitude decreased at C3 and Cz for the right wrist; latency significantly increased at C3 while amplitude decreased at Cz for the left wrist. Increased power at CP3 for the right wrist and CP4 for the left wrist in α-frequency ERSP after VM was observed; reduced power in β-frequency ERSP after VM was observed for both wrists. For the CT group, the mean MAE of the trained right wrist increased (<i>p</i> &lt; 0.05) after training, while the untrained left wrist showed no statistical significance. No significant energy changes corresponding to the left/right wrist were observed in EEG topography after training. There was a noticeable decrease in ERPs amplitude at the central and parietal regions for both the left and right wrists. The MRCPs latency significantly increased at C3 for the right wrist; however, the latency and amplitude did not significantly change for the left wrist. Dec","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70504","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Heterogeneity in Vestibular Migraine Using Individualized Differential Structural Covariance Network Analysis","authors":"Wen Chen,&nbsp;Hongru Zhao,&nbsp;Lingling Dai,&nbsp;Xing Xiong,&nbsp;Qifang Feng,&nbsp;Jun Ke,&nbsp;Chunhong Hu","doi":"10.1111/cns.70599","DOIUrl":"https://doi.org/10.1111/cns.70599","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The high heterogeneity in vestibular migraine (VM) complicates understanding its precise pathophysiological mechanisms and identifying potential biomarkers. This study investigated the heterogeneity in VM using a newly proposed method called Individualized Differential Structural Covariance Network (IDSCN) analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Structural T1-weighted MRI scans were performed on 55 patients with VM and 65 healthy controls, and an IDSCN was constructed for each patient. We studied the extent of heterogeneity in the IDSCNs, summarized the distribution of differential edges, and clustered the patients into subtypes with the shared differential edges. Imaging–clinical association analyses were conducted on both the subtype classification and the differential edges exhibiting significant inter-subtype differences.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients with VM demonstrated notable heterogeneity in the number of significantly altered IDSCN edges, while sharing several common differential connections that were mainly distributed among the parietal, subcortical, and cerebellar regions. Two robust and distinct neuroanatomical subtypes of VM were identified, which were associated with headache frequency. The differential edge between the left paracentral lobule and right pallidum was associated with both headache frequency and occurrence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings indicate the importance of considering individual differences in VM research and may offer insights for precise diagnosis and individualized treatment of the disease.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70599","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145007951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotective Effects of Transcranial Pulsed Current Stimulation: Modulation of Microglial Polarization in Traumatic Brain Injury","authors":"Peng Yao,&nbsp;Bingkai Ren,&nbsp;Qianhui Zhou,&nbsp;Yang Bai,&nbsp;Zhen Feng","doi":"10.1111/cns.70606","DOIUrl":"https://doi.org/10.1111/cns.70606","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Traumatic brain injury (TBI), a prevalent neurological disorder worldwide, is marked by varying degrees of neurological dysfunction. A key contributor to secondary damage and impediments in the repair process is the unregulated activation of microglia, which triggers neuroinflammation. Emerging evidence highlights the therapeutic potential of transcranial pulsed current stimulation (tPCS) in mitigating neurological deficits. However, despite these promising neuroprotective effects, its role and exact mechanisms in TBI remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Herein, a mouse model of TBI was established, and daily 30-min tPCS treatments were administered for five consecutive days. Subsequently, we conducted comprehensive assessments of neurological function, microglial activation status, and neuroplasticity in the treated subjects. Additionally, a co-culture system of BV2 and HT22 cells was developed, using LPS to activate microglia, to explore potential neuroprotective mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our findings revealed that tPCS plays a crucial role in mitigating neuroinflammation and promoting neurological recovery following TBI. The underlying mechanism likely involves tPCS enhancing orexin-A (OX-A) expression, which subsequently suppresses the NF-κB pathway and promotes the expression of neurorepair-related markers. In vitro experiments further clarified these findings, demonstrating that OX-A effectively inhibited LPS-induced M1 microglial polarization and promoted a shift towards the M2 phenotype. Furthermore, OX-A significantly reduced intracellular ROS production and microglia-induced neuronal apoptosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings indicate that tPCS regulates microglial phenotype via the OX-A/NF-κB pathway, thereby suppressing neuroinflammation and enhancing neuroplasticity. These results provide a new perspective for the rehabilitation of individuals with TBI.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70606","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145007904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered Sensorimotor Cortical Activities During Forearm Movement in Humans With Spinal Cord Injury","authors":"Bo Li,&nbsp;Honghao Liu,&nbsp;Guanghui Li,&nbsp;Yiran Lang,&nbsp;Rongyu Tang,&nbsp;Fengbao Yang","doi":"10.1111/cns.70601","DOIUrl":"https://doi.org/10.1111/cns.70601","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Decoding the motor intention by electroencephalography to control external devices is an effective method of helping spinal cord injury (SCI) patients to regain motor function. Still, SCI patients have much lower accuracy in the decoding of motor intentions compared to healthy individuals, which severely hampers the clinical application. However, the underlying neural mechanisms are still unknown. The aim of this paper is to investigate changes in cortical activities after SCI, which are direct determinants of motor decoding performance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed source localization analyses to investigate the changes in motor-related cortical regions after SCI. Moreover, we measured the power spectral density values and event-related spectral perturbation values to assess the characteristics of the changes in cortical potentials.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that motor-related independent component clusters decreased while attempting upper limb movement after SCI. Additionally, the activities in the sensorimotor cortex obviously attenuated after SCI. theta, alpha, and beta band power modulation obviously altered in SCI individuals. Furthermore, the latency of the largest power increase or decrease between SCI and healthy individuals demonstrated obvious differences.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings revealed changes in motor-related cortical areas after SCI, which were crucial for improving the accuracy of motor intention decoding and advancing the clinical application.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70601","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145007905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of P62/Nrf2/Keap1 Signaling Pathway in Lead-Induced Neurological Dysfunction","authors":"Dongjie Peng,&nbsp;Peiqi Wei,&nbsp;Zhenning Li,&nbsp;Ruokun Wei,&nbsp;Huishuai Li,&nbsp;Shaojun Li","doi":"10.1111/cns.70566","DOIUrl":"https://doi.org/10.1111/cns.70566","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Lead (Pb) exposure is recognized for its contribution to the development of neurodegenerative diseases. However, the precise mechanisms underlying Pb-induced neurological dysfunction remain elusive. This study aimed to investigate the role of oxidative stress and the autophagy-related P62/kelch like ECH-associated protein 1 (Keap1)/Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in neuronal impairment caused by Pb.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>By employing both in vivo and in vitro approaches, we explored the involvement of the P62/Nrf2/Keap1 pathway in Pb-induced neurotoxicity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our findings demonstrated that Pb exposure triggers excessive production of reactive oxygen species (ROS), upregulates Keap1 protein expressions, promotes Nrf2 degradation, and inhibits expression of antioxidant proteins such as heme Oxygenase-1 (HO-1) and glutathione peroxidase (GPx), resulting in oxidative damage in neurons. Furthermore, we observed that the autophagy protein P62 disrupts the normal autophagy process by interacting with the Nrf2/Keap1 axis, leading to an accumulation of Tau, a protein associated with Alzheimer's disease (AD), ultimately resulting in neurodegeneration. However, treatment with the antioxidant N-acetylcysteine, Nrf2 activator Artemisitene, and autophagy activator Rapamycin attenuated these detrimental changes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The P62/Nrf2/Keap1 pathway mediates Pb-induced neuronal dysfunction and highlights its potential as a therapeutic target for mitigating the neurodegenerative effects associated with Pb exposure.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70566","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144998670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Language Functional Connectivity Alterations During Resting State in Brain Arteriovenous Malformation Patients","authors":"Xiaofeng Deng,&nbsp;Qiji Shi,&nbsp;Zekun Han,&nbsp;Shuo Wang,&nbsp;Yong Cao,&nbsp;Xiaolin Chen,&nbsp;Yan Zhang,&nbsp;Bo Wang,&nbsp;Minyu Jian,&nbsp;Fangrong Zong,&nbsp;Jizong Zhao","doi":"10.1111/cns.70602","DOIUrl":"https://doi.org/10.1111/cns.70602","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Unruptured brain arteriovenous malformations (AVMs) typically do not cause aphasia, even when the traditional language areas are affected by the nidus. We attempted to elucidate its language reorganization mechanism by analyzing the alterations in functional connectivity using functional connectivity (FC) and track-weighted static functional connectivity (TW-sFC) approaches.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This cross-sectional study prospectively enrolled patients with AVMs involving left-hemisphere language areas and healthy controls. All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging scans. Conventional FC analysis was used to investigate the spatially segregated functional connectivity in the gray matter, and the TW-sFC method was applied to explore the functional connectivity constrained by the white matter.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>34 AVM patients with lesions involving the left cerebral hemisphere and 27 healthy subjects were included. FC analysis findings revealed decreased FC intensity between the left-hemisphere language-associated regions and their right-hemisphere homologs in AVM patients. Additionally, increased FC intensity was observed between the anterior cingulate cortex (ACC) and the language-related areas in bilateral cerebellar hemispheres (lobule VIII, VIIb, Crus I, and Crus II). The TW-sFC results demonstrated increased intensity in multiple right-hemisphere fiber bundles, the left anterior thalamic radiation (ATR) and the callosum.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Three factors may contribute to maintaining intact language function in AVM patients, including the weakened inhibitory effect from the left dominant cerebral hemisphere over the right cerebral hemisphere leading to activation of the potential language functions of the right cerebral hemisphere (inter-cerebral connection reorganization), the functional upregulation of the cerebral language areas by cerebellar language-related brain regions via ACC (cerebrocerebellar connection reorganization), as well as the enhanced functions of the brain areas surrounding the lesion in the left cerebral hemisphere (intracerebral connection reorganization).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>This study is registered in the Chinese Trial Registry (clinical trial number: ChiCTR1900020993)</p>\u0000 ","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70602","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144998681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}