Siyi Wang, Lei Qi, Xinqi Huang, Chunxue Wu, Jialin Du, Qing Xue, Jinghui Liu, Yuanhong Chen, Liankun Ren
Aims
Autoscopic phenomena (AP) are distinct manifestations of epileptic seizure semiology and are also identified in diverse psychiatric disorders. Our study aimed to map the brain AP network and characterize its multimodal signatures.
Methods
By performing lesion network mapping using the human connectome dataset (n = 1000), we investigated the brain AP network derived from 25 cases of AP caused by distributed focal brain lesions (n = 19) and direct electrical stimulation (DES) (n = 6). We further studied the multimodal signatures of the AP network, including exploring spatial correlation with human cortical developmental and evolutionary expansions, neurotransmitters, and electrophysiological rhythms.
Results
We mapped a common AP network primarily involving the bilateral angular gyrus, posterior medial cortex, intraparietal sulcus, cuneus, fusiform and insula. Specifically, the bilateral thalamic pulvinar were identified as subcortical hubs. We further found a significant negative correlation between the AP network and developmental and evolutionary expansions. Particularly, the spatial density of norepinephrine transporter and the alpha frequency band power were significantly positively correlated with the AP network.
Conclusion
Our study identified a common brain AP network and uncovered its multimodal signatures. These findings may clarify the network mechanisms underpinning AP, providing novel insights into bodily self-consciousness.
{"title":"Brain Network Signature of Autoscopic Phenomena in Humans","authors":"Siyi Wang, Lei Qi, Xinqi Huang, Chunxue Wu, Jialin Du, Qing Xue, Jinghui Liu, Yuanhong Chen, Liankun Ren","doi":"10.1111/cns.70635","DOIUrl":"https://doi.org/10.1111/cns.70635","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Autoscopic phenomena (AP) are distinct manifestations of epileptic seizure semiology and are also identified in diverse psychiatric disorders. Our study aimed to map the brain AP network and characterize its multimodal signatures.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>By performing lesion network mapping using the human connectome dataset (<i>n</i> = 1000), we investigated the brain AP network derived from 25 cases of AP caused by distributed focal brain lesions (<i>n</i> = 19) and direct electrical stimulation (DES) (<i>n</i> = 6). We further studied the multimodal signatures of the AP network, including exploring spatial correlation with human cortical developmental and evolutionary expansions, neurotransmitters, and electrophysiological rhythms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We mapped a common AP network primarily involving the bilateral angular gyrus, posterior medial cortex, intraparietal sulcus, cuneus, fusiform and insula. Specifically, the bilateral thalamic pulvinar were identified as subcortical hubs. We further found a significant negative correlation between the AP network and developmental and evolutionary expansions. Particularly, the spatial density of norepinephrine transporter and the alpha frequency band power were significantly positively correlated with the AP network.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study identified a common brain AP network and uncovered its multimodal signatures. These findings may clarify the network mechanisms underpinning AP, providing novel insights into bodily self-consciousness.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 11","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70635","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145385142","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}
To explore the emotion recognition (ER) abilities among temporal lobe epilepsy (TLE) patients with different levels of depression.
Methods
This observational study was conducted during December 2021 and November 2022, including 71 healthy controls (HCs) and 93 TLE patients. Based on the scores of the Beck Depression Index, the patients were divided into four groups (no/mild/moderate/severe depression). All participants finished the Faux pas task (FPT), watched the dynamic facial expression task and recognized the emotion (anger, disgust, happiness, or sadness) with the recording of eye movements. The accuracy of ER was recorded. The percentage of fixation in interested areas (IA) and fixation counts in IA were selected and analyzed.
Results
TLE patients without depression had significantly lower FPT scores (p = 0.001) and accuracy ratios of dynamic facial ER (p = 0.039) than HCs. Patients with severe depression had significantly more fixation percentages and fixation counts in the nose than patients with no/mild/moderate depression (p < 0.05).
Conclusion
The recording of eye movement provides more accurate and objective biobehavioral indicators for distinguishing TLE patients with severe depression, which has great practical significance for early monitoring and intervention.
{"title":"More Fixations in Static Facial Regions During Emotion Recognition Among TLE Patients With Severe Depression","authors":"Haojun Yang, Qiong Zhang, Kailing Huang, Li Feng","doi":"10.1111/cns.70636","DOIUrl":"10.1111/cns.70636","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To explore the emotion recognition (ER) abilities among temporal lobe epilepsy (TLE) patients with different levels of depression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This observational study was conducted during December 2021 and November 2022, including 71 healthy controls (HCs) and 93 TLE patients. Based on the scores of the Beck Depression Index, the patients were divided into four groups (no/mild/moderate/severe depression). All participants finished the Faux pas task (FPT), watched the dynamic facial expression task and recognized the emotion (anger, disgust, happiness, or sadness) with the recording of eye movements. The accuracy of ER was recorded. The percentage of fixation in interested areas (IA) and fixation counts in IA were selected and analyzed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>TLE patients without depression had significantly lower FPT scores (<i>p</i> = 0.001) and accuracy ratios of dynamic facial ER (<i>p</i> = 0.039) than HCs. Patients with severe depression had significantly more fixation percentages and fixation counts in the nose than patients with no/mild/moderate depression (<i>p</i> < 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The recording of eye movement provides more accurate and objective biobehavioral indicators for distinguishing TLE patients with severe depression, which has great practical significance for early monitoring and intervention.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 10","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70636","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145385422","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}
Anti-AMPAR encephalitis is a rare antibody-mediated disorder, and its clinicoradiological profile is incompletely defined. We aimed to characterize the clinical presentation and cerebral metabolic patterns of Chinese adults with anti-AMPAR encephalitis using 18F-FDG PET/CT.
Methods
From August 2016 to August 2022, we retrospectively identified patients from two neurology centers who were positive for anti-AMPAR antibodies in serum and/or cerebrospinal fluid. Demographic data, presenting symptoms, MRI and 18F-FDG PET/CT findings (Discovery Elite, GE Healthcare), treatment regimens, and outcomes were extracted and analyzed.
Results
Eight patients (four women) were included; median age was 53 years (range 37–63). Anti-AMPA2R antibodies were detected in seven cases and anti-AMPA1R antibodies in one. Limbic manifestations dominated, particularly cognitive decline and abnormal behavior; severe disease necessitated intensive care support in one patient, who nonetheless achieved a good outcome. Malignancy was documented in three individuals (lung carcinoma, hepatocellular carcinoma, and thymoma), and three harbored additional neural autoantibodies. MRI was abnormal in five patients (62.5%). All five subjects who underwent 18F-FDG PET/CT displayed prefrontal hypometabolism; three also showed posterior cingulate hypometabolism. Focal hypermetabolism was observed in the right temporal lobe (one case) and in the left thalamus (one case).
Conclusion
Anti-AMPAR encephalitis usually presents as limbic encephalitis and is marked by prefrontal and posterior cingulate hypometabolism on 18F-FDG PET/CT. In some instances, hypermetabolism was observed in the basal ganglia or temporal lobes, possibly reflecting the local blood flow.
目的：抗ampar脑炎是一种罕见的抗体介导的疾病，其临床放射学特征尚不完全明确。我们的目的是利用18F-FDG PET/CT表征中国成人抗ampar脑炎的临床表现和脑代谢模式。方法：从2016年8月至2022年8月，我们回顾性筛选了来自两个神经病学中心的血清和/或脑脊液中抗ampar抗体阳性的患者。提取并分析了人口统计数据、表现症状、MRI和18F-FDG PET/CT结果（Discovery Elite, GE Healthcare）、治疗方案和结果。结果：纳入8例患者（女性4例）；中位年龄为53岁（37-63岁）。抗ampa2r抗体7例，抗ampa1r抗体1例。以边缘表现为主，尤其是认知能力下降和行为异常；一名患者病情严重，需要重症监护支持，但仍取得了良好的结果。恶性肿瘤有3例（肺癌、肝细胞癌和胸腺瘤），其中3例携带额外的神经自身抗体。MRI异常5例（62.5%）。所有接受18F-FDG PET/CT检查的5名受试者均显示前额叶代谢低下；3例还显示后扣带代谢低下。局灶性高代谢出现在右侧颞叶（1例）和左侧丘脑（1例）。结论：抗ampar脑炎多表现为边缘脑炎，18F-FDG PET/CT表现为前额叶和后扣带代谢低下。在某些情况下，在基底神经节或颞叶观察到高代谢，可能反映了局部血流量。
{"title":"18F-FDG PET/CT Reveals Characteristic Prefrontal-Posterior Cingulate Hypometabolism in anti-AMPAR Encephalitis to Understand Cerebral Function: Insights From an Eight-Patient Cohort","authors":"Hengri Cong, Leilei yuan, Pei Zheng, Xuan Xu, Wenyue Dong, DeCai Tian, Linlin Yin, Yueta Ma, Tian Song, Yanxue Zhao, Yun Xu, Mengting Zhang, Baitao Liu, Guoqiang Chang, Ke Sun, Wenping Ma, Lin Ai, Wangshu Xu","doi":"10.1111/cns.70633","DOIUrl":"10.1111/cns.70633","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>Anti-AMPAR encephalitis is a rare antibody-mediated disorder, and its clinicoradiological profile is incompletely defined. We aimed to characterize the clinical presentation and cerebral metabolic patterns of Chinese adults with anti-AMPAR encephalitis using <sup>18</sup>F-FDG PET/CT.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>From August 2016 to August 2022, we retrospectively identified patients from two neurology centers who were positive for anti-AMPAR antibodies in serum and/or cerebrospinal fluid. Demographic data, presenting symptoms, MRI and <sup>18</sup>F-FDG PET/CT findings (Discovery Elite, GE Healthcare), treatment regimens, and outcomes were extracted and analyzed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Eight patients (four women) were included; median age was 53 years (range 37–63). Anti-AMPA2R antibodies were detected in seven cases and anti-AMPA1R antibodies in one. Limbic manifestations dominated, particularly cognitive decline and abnormal behavior; severe disease necessitated intensive care support in one patient, who nonetheless achieved a good outcome. Malignancy was documented in three individuals (lung carcinoma, hepatocellular carcinoma, and thymoma), and three harbored additional neural autoantibodies. MRI was abnormal in five patients (62.5%). All five subjects who underwent <sup>18</sup>F-FDG PET/CT displayed prefrontal hypometabolism; three also showed posterior cingulate hypometabolism. Focal hypermetabolism was observed in the right temporal lobe (one case) and in the left thalamus (one case).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Anti-AMPAR encephalitis usually presents as limbic encephalitis and is marked by prefrontal and posterior cingulate hypometabolism on <sup>18</sup>F-FDG PET/CT. In some instances, hypermetabolism was observed in the basal ganglia or temporal lobes, possibly reflecting the local blood flow.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 10","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70633","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145385443","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}
Xuan Xu, Sha-Sha Fan, Jiang Li, Hao Wu, Junwen He, Yang He, Xiang-Yu Meng, Yin Shen
Aims
Alzheimer's disease (AD) is a devastating neurodegenerative disorder where mitochondrial dysfunction is increasingly recognized as pivotal, yet its comprehensive molecular underpinnings remain incompletely understood. This study aimed to systematically identify and validate mitochondria-related biomarkers associated with AD risk and brain resilience, thus elucidating the molecular mechanisms underpinning mitochondrial dysfunction in AD.
Methods
We innovatively integrated a multi-omics approach, encompassing genomics, DNA methylation, RNA-sequencing, and miRNA profiles from the ROSMAP and ADNI cohorts (sample sizes ranging from 638 to 2090 per omic layer). Additionally, we applied 10 distinct machine learning methods to robustly identify and validate critical mitochondrial biomarkers relevant to AD progression. Subsequent validation was performed using a two-tiered approach: an in vivo AD mouse model to establish phenotypic relevance and an in vitro H2O2-induced oxidative stress model in HT22 cells to provide direct mechanistic validation.
Results
Our computational analyses identified key biomarkers such as hsa-miR-129-5p and SLC6A12 as pivotal regulators and highlighted the importance of the tricarboxylic acid (TCA) cycle. Experimentally, our AD mouse model exhibited significant cognitive deficits and brain remodeling, linked to a specific transcriptomic signature. Our in vitro model functionally recapitulated mitochondrial dysfunction and oxidative stress. Crucially, a cross-model analysis revealed a core signature of seven genes (including APOE, CDKN1A, and CLOCK) consistently dysregulated in both the cognitively impaired mouse brain and in neuronal cells subjected to direct oxidative insult. This provides powerful functional evidence linking our computationally derived targets, such as mitochondrial-epistatic genes (CLOCK), to AD-relevant pathology.
Conclusion
These functionally validated findings provide deeper insights into the complex mitochondrial regulatory mechanisms involved in AD pathogenesis, offering robust biomarkers and novel potential avenues for developing targeted therapeutic strategies to address this challenging neurodegenerative disease.
{"title":"Integrated Multi-Omics Analysis and Cross-Model Validation Reveal Mitochondrial Signatures in Alzheimer's Disease","authors":"Xuan Xu, Sha-Sha Fan, Jiang Li, Hao Wu, Junwen He, Yang He, Xiang-Yu Meng, Yin Shen","doi":"10.1111/cns.70634","DOIUrl":"10.1111/cns.70634","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Alzheimer's disease (AD) is a devastating neurodegenerative disorder where mitochondrial dysfunction is increasingly recognized as pivotal, yet its comprehensive molecular underpinnings remain incompletely understood. This study aimed to systematically identify and validate mitochondria-related biomarkers associated with AD risk and brain resilience, thus elucidating the molecular mechanisms underpinning mitochondrial dysfunction in AD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We innovatively integrated a multi-omics approach, encompassing genomics, DNA methylation, RNA-sequencing, and miRNA profiles from the ROSMAP and ADNI cohorts (sample sizes ranging from 638 to 2090 per omic layer). Additionally, we applied 10 distinct machine learning methods to robustly identify and validate critical mitochondrial biomarkers relevant to AD progression. Subsequent validation was performed using a two-tiered approach: an in vivo AD mouse model to establish phenotypic relevance and an in vitro H<sub>2</sub>O<sub>2</sub>-induced oxidative stress model in HT22 cells to provide direct mechanistic validation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our computational analyses identified key biomarkers such as hsa-miR-129-5p and <i>SLC6A12</i> as pivotal regulators and highlighted the importance of the tricarboxylic acid (TCA) cycle. Experimentally, our AD mouse model exhibited significant cognitive deficits and brain remodeling, linked to a specific transcriptomic signature. Our in vitro model functionally recapitulated mitochondrial dysfunction and oxidative stress. Crucially, a cross-model analysis revealed a core signature of seven genes (including <i>APOE</i>, <i>CDKN1A</i>, and <i>CLOCK</i>) consistently dysregulated in both the cognitively impaired mouse brain and in neuronal cells subjected to direct oxidative insult. This provides powerful functional evidence linking our computationally derived targets, such as mitochondrial-epistatic genes (<i>CLOCK</i>), to AD-relevant pathology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These functionally validated findings provide deeper insights into the complex mitochondrial regulatory mechanisms involved in AD pathogenesis, offering robust biomarkers and novel potential avenues for developing targeted therapeutic strategies to address this challenging neurodegenerative disease.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 10","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12559030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145375515","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}
Electroencephalogram (EEG) signals are crucial for brain–computer interface research but are highly susceptible to noise contamination, necessitating effective denoising. While deep learning has been widely applied, its “black-box” nature limits interpretability. In contrast, traditional model-based methods like Low-Rank Recovery (LRR) offer strong interpretability by decomposing signals into low-rank and sparse components.
Objective
This paper aims to develop an interpretable deep-learning model for EEG denoising that combines the performance of deep learning with the interpretability of traditional LRR methods.
Methods
We propose LRR-Unet, a deep unfolding network that transforms the traditional iterative LRR algorithm into a neural network architecture. Specifically, the time-consuming Singular Value Decomposition (SVD) and sparse optimization processes in LRR are replaced with learnable neural network modules.
Results
Extensive experiments demonstrate that LRR-Unet outperforms other state-of-the-art models in removing ocular and electromyographic artifacts, achieving superior performance on both quantitative and qualitative metrics. Furthermore, in downstream classification tasks, EEG signals preprocessed with LRR-Unet yield better results across various evaluation indicators.
Conclusion
The proposed LRR-Unet provides an effective and interpretable solution for EEG denoising. Its superiority in denoising performance and practical utility in enhancing downstream application performance is validated through comprehensive experiments.
{"title":"LRR-UNet: A Deep Unfolding Network With Low-Rank Recovery for EEG Signal Denoising","authors":"Xiaoxiong Yue, Liangfu Lu, Haipeng Liu, Yunliang Zang","doi":"10.1111/cns.70632","DOIUrl":"10.1111/cns.70632","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Electroencephalogram (EEG) signals are crucial for brain–computer interface research but are highly susceptible to noise contamination, necessitating effective denoising. While deep learning has been widely applied, its “black-box” nature limits interpretability. In contrast, traditional model-based methods like Low-Rank Recovery (LRR) offer strong interpretability by decomposing signals into low-rank and sparse components.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This paper aims to develop an interpretable deep-learning model for EEG denoising that combines the performance of deep learning with the interpretability of traditional LRR methods.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We propose LRR-Unet, a deep unfolding network that transforms the traditional iterative LRR algorithm into a neural network architecture. Specifically, the time-consuming Singular Value Decomposition (SVD) and sparse optimization processes in LRR are replaced with learnable neural network modules.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Extensive experiments demonstrate that LRR-Unet outperforms other state-of-the-art models in removing ocular and electromyographic artifacts, achieving superior performance on both quantitative and qualitative metrics. Furthermore, in downstream classification tasks, EEG signals preprocessed with LRR-Unet yield better results across various evaluation indicators.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The proposed LRR-Unet provides an effective and interpretable solution for EEG denoising. Its superiority in denoising performance and practical utility in enhancing downstream application performance is validated through comprehensive experiments.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 10","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12559029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145375675","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}
Yang Liu, Zihan Zhang, Zihan Jing, Binbin Sun, Hong Zhao, Yan Wang, Mao Li, Dehao Li, Dengfa Zhao, Hongmei Cheng, Min Su, Haoyang Hu, Ruozhuo Liu, Shengyuan Yu, Fei Yang
Background
Critical illness polyneuropathy (CIP) is a common cause of weakness in critically ill patients, and early diagnosis and treatment are essential. Conventional comprehensive electrophysiological testing requires 60–90 min and can be invasive, limiting its utility in the intensive care setting. This study aimed to develop a rapid, efficient, and minimally invasive diagnostic model for CIP.
Methods
Patients who met the inclusion criteria were recruited from the intensive care units (ICU) of the First Medical Center and Fifth Medical Center of the PLA General Hospital and Nanfang Hospital. To identify the optimal diagnostic model, we compared several machine learning approaches, including K-nearest neighbor, support vector machine with radial basis function (SVM-RBF), SVM with Gaussian kernel, random forest, and extreme gradient boosting (XGB), using all electrophysiological features. These were also compared with nerve conduction studies of the peroneal and sural nerves. To construct a rapid diagnostic model, different feature combinations were assessed across the machine learning methods. Model performance was evaluated using cross-validated areas under the receiver operating characteristic curve (AUCs).
Results
Of 14,768 admissions screened, 134 patients with CIP and 135 matched controls were included. In total, 41 electrophysiological features were analyzed. Feature ranking revealed that the distal compound muscle action potential (CMAP) of the peroneal nerve contributed most to diagnostic accuracy. After comparison, the SVM-RBF method was selected to establish the final diagnostic model. The optimal model, based on seven electrophysiological features of the peroneal and ulnar nerves (proximal latency, distal latency, and CMAP amplitude), achieved an AUC of 0.93, which was comparable to the all-feature XGB model (AUC = 0.95). In the independent validation set, the rapid diagnostic model maintained strong performance (AUC = 0.88), similar to the all-feature model (AUC = 0.90).
Conclusion
We developed a rapid diagnostic model for CIP using the SVM-RBF method and seven electrophysiological features from the peroneal and ulnar nerves. This model enables efficient, minimally invasive, and timely diagnosis of CIP in critically ill patients. The source code and related scripts are available at [https://github.com/PLAGH-Neuro-Yang/RDM-CIP].
{"title":"Rapid Diagnostic Model for Critical Illness Polyneuropathy Based on Electrophysiological Data","authors":"Yang Liu, Zihan Zhang, Zihan Jing, Binbin Sun, Hong Zhao, Yan Wang, Mao Li, Dehao Li, Dengfa Zhao, Hongmei Cheng, Min Su, Haoyang Hu, Ruozhuo Liu, Shengyuan Yu, Fei Yang","doi":"10.1111/cns.70631","DOIUrl":"10.1111/cns.70631","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Critical illness polyneuropathy (CIP) is a common cause of weakness in critically ill patients, and early diagnosis and treatment are essential. Conventional comprehensive electrophysiological testing requires 60–90 min and can be invasive, limiting its utility in the intensive care setting. This study aimed to develop a rapid, efficient, and minimally invasive diagnostic model for CIP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients who met the inclusion criteria were recruited from the intensive care units (ICU) of the First Medical Center and Fifth Medical Center of the PLA General Hospital and Nanfang Hospital. To identify the optimal diagnostic model, we compared several machine learning approaches, including K-nearest neighbor, support vector machine with radial basis function (SVM-RBF), SVM with Gaussian kernel, random forest, and extreme gradient boosting (XGB), using all electrophysiological features. These were also compared with nerve conduction studies of the peroneal and sural nerves. To construct a rapid diagnostic model, different feature combinations were assessed across the machine learning methods. Model performance was evaluated using cross-validated areas under the receiver operating characteristic curve (AUCs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 14,768 admissions screened, 134 patients with CIP and 135 matched controls were included. In total, 41 electrophysiological features were analyzed. Feature ranking revealed that the distal compound muscle action potential (CMAP) of the peroneal nerve contributed most to diagnostic accuracy. After comparison, the SVM-RBF method was selected to establish the final diagnostic model. The optimal model, based on seven electrophysiological features of the peroneal and ulnar nerves (proximal latency, distal latency, and CMAP amplitude), achieved an AUC of 0.93, which was comparable to the all-feature XGB model (AUC = 0.95). In the independent validation set, the rapid diagnostic model maintained strong performance (AUC = 0.88), similar to the all-feature model (AUC = 0.90).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We developed a rapid diagnostic model for CIP using the SVM-RBF method and seven electrophysiological features from the peroneal and ulnar nerves. This model enables efficient, minimally invasive, and timely diagnosis of CIP in critically ill patients. The source code and related scripts are available at [https://github.com/PLAGH-Neuro-Yang/RDM-CIP].</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 10","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12541361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342278","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}
The pathogenesis of anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDAR encephalitis)-associated seizures remains elusive.
Methods
Mice were injected with GluN1359–378 peptide to construct a model of anti-NMDAR encephalitis. Next, the expression of NMDAR antibodies (NMDAR-Ab) was detected in serum samples. The electroencephalograms (EEGs) of mice were recorded. Afterward, neuronal action potentials (APs) and miniature excitatory postsynaptic currents (mEPSCs) were examined following exposure to serum derived from model mice. The expression levels of subunits of the NMDA receptor (GluN1, GluN2B) and glutamate vesicular transporter 1 (Vglut1) were quantified via Western blot analysis. Additionally, mice were injected with pentylenetetrazol (PTZ) to construct an in vivo model of status epilepticus (SE). Lastly, neurons exposed to mouse serum were incubated in a magnesium-free solution (Mg2+-free) for 1, 2, and 3 h, and APs were assessed.
Results
Following the administration of immunogenic peptide GluN1359–378, serum NMDAR-Ab was detected. EEG recording revealed that 68.75% (11/16) of mice receiving GluN1359–378 exhibited epileptiform discharges. Moreover, the frequency of neuronal APs and mEPSCs following exposure to serum derived from mice receiving GluN1359–378 was increased. The surface expression level of the GluN1 protein was significantly decreased, whereas that of the total Vglut1 protein was increased. Moreover, the seizure latency of mice receiving GluN1359–378 was significantly shortened. Finally, after 1 to 2 h of incubation with Mg2+-free solution, the frequency of neuronal APs following exposure to serum derived from mice receiving GluN1359–378 was increased.
Conclusion
To the best of our knowledge, this is the first study to demonstrate that increased glutamate release may increase seizure susceptibility in patients with anti-NMDAR encephalitis.
背景：抗n -甲基- d -天冬氨酸受体脑炎（抗nmdar脑炎）相关癫痫发作的发病机制尚不清楚。方法：小鼠注射GluN1359-378肽，建立抗nmdar脑炎模型。接下来，检测血清样品中NMDAR抗体（NMDAR- ab）的表达。记录小鼠脑电图。随后，暴露于模型小鼠血清后，检测神经元动作电位（APs）和微型兴奋性突触后电流（mEPSCs）。Western blot检测NMDA受体GluN1、GluN2B和谷氨酸囊泡转运蛋白1 （Vglut1）亚基的表达水平。另外，给小鼠注射戊四唑（PTZ），建立小鼠体内癫痫持续状态（SE）模型。最后，将暴露于小鼠血清中的神经元在无镁溶液（无Mg2+）中孵育1、2和3小时，并评估ap。结果：给予免疫原性肽GluN1359-378后，检测血清nmda - ab。脑电记录显示68.75%（11/16）小鼠接受GluN1359-378后出现癫痫样放电。此外，暴露于GluN1359-378小鼠血清后，神经元ap和mEPSCs的频率增加。GluN1蛋白的表面表达量显著降低，而Vglut1总蛋白的表面表达量显著升高。此外，服用GluN1359-378的小鼠癫痫发作潜伏期明显缩短。最后，与无Mg2+溶液孵育1至2小时后，暴露于GluN1359-378小鼠血清后神经元ap的频率增加。结论：据我们所知，这是第一个证明谷氨酸释放增加可能增加抗nmdar脑炎患者癫痫易感性的研究。
{"title":"Elevated Release of Presynaptic Glutamate: The Potential Pathogenesis of Anti-NMDAR Encephalitis-Associated Seizures","authors":"Hongmi Huang, Yifei Huang, Sijun Li, Ying Wu, Shengyu Yang, Yuan Wu","doi":"10.1111/cns.70585","DOIUrl":"10.1111/cns.70585","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The pathogenesis of anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDAR encephalitis)-associated seizures remains elusive.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Mice were injected with GluN1<sub>359–378</sub> peptide to construct a model of anti-NMDAR encephalitis. Next, the expression of NMDAR antibodies (NMDAR-Ab) was detected in serum samples. The electroencephalograms (EEGs) of mice were recorded. Afterward, neuronal action potentials (APs) and miniature excitatory postsynaptic currents (mEPSCs) were examined following exposure to serum derived from model mice. The expression levels of subunits of the NMDA receptor (GluN1, GluN2B) and glutamate vesicular transporter 1 (Vglut1) were quantified via Western blot analysis. Additionally, mice were injected with pentylenetetrazol (PTZ) to construct an in vivo model of status epilepticus (SE). Lastly, neurons exposed to mouse serum were incubated in a magnesium-free solution (Mg<sup>2+</sup>-free) for 1, 2, and 3 h, and APs were assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Following the administration of immunogenic peptide GluN1<sub>359–378</sub>, serum NMDAR-Ab was detected. EEG recording revealed that 68.75% (11/16) of mice receiving GluN1<sub>359–378</sub> exhibited epileptiform discharges. Moreover, the frequency of neuronal APs and mEPSCs following exposure to serum derived from mice receiving GluN1<sub>359–378</sub> was increased. The surface expression level of the GluN1 protein was significantly decreased, whereas that of the total Vglut1 protein was increased. Moreover, the seizure latency of mice receiving GluN1<sub>359–378</sub> was significantly shortened. Finally, after 1 to 2 h of incubation with Mg<sup>2+</sup>-free solution, the frequency of neuronal APs following exposure to serum derived from mice receiving GluN1<sub>359–378</sub> was increased.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>To the best of our knowledge, this is the first study to demonstrate that increased glutamate release may increase seizure susceptibility in patients with anti-NMDAR encephalitis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 10","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70585","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145306486","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}
Yaye Wang, Wenjia Zhu, Qing Liu, Xinmei Wen, Nairong Xie, Haoran Liu, Zhangyan Geng, Yuting Jiang, Li Di, Min Wang, Yan Lu, Jianying Duo, Yue Huang, Yu Qian, Qinyao Liu, Congwen Lv, Yuwei Da
<div> <section> <h3> Background</h3> <p>Efgartigimod is a neonatal Fc receptor (FcRn) antagonist that reduces pathogenic IgG and improves clinical symptoms in generalized myasthenia gravis (gMG). However, its immunomodulatory effects on innate and adaptive immune cells beyond IgG depletion are rarely reported.</p> </section> <section> <h3> Objective</h3> <p>This study aimed to investigate clinical and immunological responses during the initial treatment cycle of efgartigimod in naive acetylcholine receptor antibody-positive (AChR-Ab+) gMG patients, with a focus on peripheral immune cell dynamics.</p> </section> <section> <h3> Methods</h3> <p>We conducted a longitudinal study between October 23, 2023, and December 10, 2024, based on the database of the Clinical Cohort Study of Myasthenia Gravis at Xuanwu Hospital, Capital Medical University. Seventeen naive AChR-Ab+ gMG patients were enrolled after applying strict inclusion and exclusion criteria and received a four-dose regimen of efgartigimod. Clinical efficacy was evaluated using Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores. Serum total IgG and AChR antibody levels were measured. Peripheral immune cell profiling included leukocytes, neutrophils, monocytes, platelets, and natural killer (NK) cells, as well as T and B cell subsets analyzed by flow cytometry. Longitudinal changes were assessed using linear mixed-effects models.</p> </section> <section> <h3> Results</h3> <p>All patients achieved clinical improvement, accompanied by significant reductions in serum total IgG and AChR antibody levels. Neutrophil and leukocyte counts progressively increased and peaked at Week 3 (<i>p</i> < 0.05), whereas monocyte and platelet counts remained relatively stable throughout all visits. CD4+ and CD8+ T cells decreased transiently at Week 2 and partially recovered by Week 3 (<i>p</i> = 0.091 and <i>p</i> = 0.005). The CD4/CD8 ratio remained stable. NK cells showed a temporary decrease at Week 2 with a borderline significant time effect (<i>p</i> = 0.050), followed by partial recovery. Plasmablast proportions significantly increased at Week 2 (<i>p</i> < 0.05), with a parallel trend in memory B cells. A transient increase in regulatory T cells was observed at Week 1 (<i>p</i> < 0.05). Similar immune changes were observed in sensitivity analysis without corticosteroid use.</p> </section> <section> <h3> Conclusion</h3> <p>This study provides the fi
{"title":"Dynamic Changes in Peripheral Immune Cells During Efgartigimod Treatment in Naive Generalized Myasthenia Gravis","authors":"Yaye Wang, Wenjia Zhu, Qing Liu, Xinmei Wen, Nairong Xie, Haoran Liu, Zhangyan Geng, Yuting Jiang, Li Di, Min Wang, Yan Lu, Jianying Duo, Yue Huang, Yu Qian, Qinyao Liu, Congwen Lv, Yuwei Da","doi":"10.1111/cns.70627","DOIUrl":"10.1111/cns.70627","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Efgartigimod is a neonatal Fc receptor (FcRn) antagonist that reduces pathogenic IgG and improves clinical symptoms in generalized myasthenia gravis (gMG). However, its immunomodulatory effects on innate and adaptive immune cells beyond IgG depletion are rarely reported.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to investigate clinical and immunological responses during the initial treatment cycle of efgartigimod in naive acetylcholine receptor antibody-positive (AChR-Ab+) gMG patients, with a focus on peripheral immune cell dynamics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a longitudinal study between October 23, 2023, and December 10, 2024, based on the database of the Clinical Cohort Study of Myasthenia Gravis at Xuanwu Hospital, Capital Medical University. Seventeen naive AChR-Ab+ gMG patients were enrolled after applying strict inclusion and exclusion criteria and received a four-dose regimen of efgartigimod. Clinical efficacy was evaluated using Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores. Serum total IgG and AChR antibody levels were measured. Peripheral immune cell profiling included leukocytes, neutrophils, monocytes, platelets, and natural killer (NK) cells, as well as T and B cell subsets analyzed by flow cytometry. Longitudinal changes were assessed using linear mixed-effects models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>All patients achieved clinical improvement, accompanied by significant reductions in serum total IgG and AChR antibody levels. Neutrophil and leukocyte counts progressively increased and peaked at Week 3 (<i>p</i> < 0.05), whereas monocyte and platelet counts remained relatively stable throughout all visits. CD4+ and CD8+ T cells decreased transiently at Week 2 and partially recovered by Week 3 (<i>p</i> = 0.091 and <i>p</i> = 0.005). The CD4/CD8 ratio remained stable. NK cells showed a temporary decrease at Week 2 with a borderline significant time effect (<i>p</i> = 0.050), followed by partial recovery. Plasmablast proportions significantly increased at Week 2 (<i>p</i> < 0.05), with a parallel trend in memory B cells. A transient increase in regulatory T cells was observed at Week 1 (<i>p</i> < 0.05). Similar immune changes were observed in sensitivity analysis without corticosteroid use.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study provides the fi","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 10","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12518786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285062","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}
Glioblastoma (GBM) represents the most prevalent primary malignant brain tumor. Temozolomide (TMZ) is the primary chemotherapeutic agent administered following surgical resection. However, the emergence of TMZ resistance in patients undergoing chemotherapy significantly diminishes its efficacy. To date, the majority of preclinical studies have been unsuccessful in effectively overcoming TMZ resistance. Prior research has suggested that the KIF4A gene may serve as a prognostic indicator for patients with GBM. Nevertheless, the precise mechanism by which KIF4A contributes to TMZ resistance remains to be elucidated.
Methods
In order to simulate the in vivo growth environment of glioblastoma, transwell co-culture and hypoxia induction were employed. Functional experiments were then conducted in order to verify the effects of KIF4A and HIF1A on the proliferation, migration, invasion, and angiogenic ability of GBM cells. Western blot analysis was employed to determine the protein levels of KIF4A, HIF1A, and VEGFA in GBM cells. ELISA was employed to determine the secreted protein levels of VEGFA and MMP9 in GBM cells. A prognostic model was utilized to assess the clinical utility of the pathway. The intercellular resistance to temozolomide was determined through the use of colony formation assays, flow cytometry, and immunofluorescence. The intercellular communication medium and its mechanism were analyzed by electron microscopy, particle size measurement, and WB experiments. Finally, a xenograft tumor model was utilized to investigate the in vivo function of KIF4A.
Results
KIF4A promotes the malignant progression of glioblastoma by regulating the HIF1A/VEGFA axis. GBM cells secrete exosomes to regulate the temozolomide resistance of astrocytes and the expression level of HIF1A/VEGFA protein, thereby making glioblastoma more resistant.
Conclusion
This study provides a new idea for antagonizing temozolomide resistance in glioblastoma. KIF4A promotes malignant progression of glioblastoma and transmission of TMZ resistance in the tumor microenvironment through the HIF1A/VEGFA axis.
{"title":"KIF4A Promotes Glioblastoma Malignant Progression and Transmission of Temozolomide Resistance in the Tumor Microenvironment via the HIF1A/VEGFA Axis","authors":"Xinan Shen, Honglei Cheng, Yihan Xia, Jiarong Zheng, Qiliang Peng, Zhicheng Zhang, Nanheng Yin, Yongshun Liu, Jun Dong, Yuntian Shen","doi":"10.1111/cns.70550","DOIUrl":"10.1111/cns.70550","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Glioblastoma (GBM) represents the most prevalent primary malignant brain tumor. Temozolomide (TMZ) is the primary chemotherapeutic agent administered following surgical resection. However, the emergence of TMZ resistance in patients undergoing chemotherapy significantly diminishes its efficacy. To date, the majority of preclinical studies have been unsuccessful in effectively overcoming TMZ resistance. Prior research has suggested that the KIF4A gene may serve as a prognostic indicator for patients with GBM. Nevertheless, the precise mechanism by which KIF4A contributes to TMZ resistance remains to be elucidated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In order to simulate the in vivo growth environment of glioblastoma, transwell co-culture and hypoxia induction were employed. Functional experiments were then conducted in order to verify the effects of KIF4A and HIF1A on the proliferation, migration, invasion, and angiogenic ability of GBM cells. Western blot analysis was employed to determine the protein levels of KIF4A, HIF1A, and VEGFA in GBM cells. ELISA was employed to determine the secreted protein levels of VEGFA and MMP9 in GBM cells. A prognostic model was utilized to assess the clinical utility of the pathway. The intercellular resistance to temozolomide was determined through the use of colony formation assays, flow cytometry, and immunofluorescence. The intercellular communication medium and its mechanism were analyzed by electron microscopy, particle size measurement, and WB experiments. Finally, a xenograft tumor model was utilized to investigate the in vivo function of KIF4A.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>KIF4A promotes the malignant progression of glioblastoma by regulating the HIF1A/VEGFA axis. GBM cells secrete exosomes to regulate the temozolomide resistance of astrocytes and the expression level of HIF1A/VEGFA protein, thereby making glioblastoma more resistant.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study provides a new idea for antagonizing temozolomide resistance in glioblastoma. KIF4A promotes malignant progression of glioblastoma and transmission of TMZ resistance in the tumor microenvironment through the HIF1A/VEGFA axis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 10","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12518161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285027","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}
Qi Wu, Fangzhou Liu, Min Gu, Junjie Wei, Guotao Lu, Li Qian, Xiaobo Li, Weijuan Gong
Aims
Myeloid-derived suppressor cells (MDSCs) are elevated in Parkinson's disease (PD), but their functional role remains unclear. This study investigated whether GSDMD deficiency enhances the immunosuppressive activity of granulocytic MDSCs (G-MDSCs) to mitigate PD progression.
Methods
Flow cytometry and Western blot analyzed G/M-MDSCs in 37 PD patients and 21 controls. An MPTP-induced PD mouse model was used to assess GSDMD-deficient G-MDSCs through behavioral tests, immunohistochemistry, and adoptive transfer experiments. The NLRP3 inhibitor ACT001 was evaluated for therapeutic potential.
Results
PD patients and MPTP-treated mice showed increased peripheral G-MDSCs with reduced NLRP3/GSDMD activation. GSDMD knockout mice exhibited attenuated PD symptoms, reversed by MDSCs depletion. Adoptive transfer of GSDMD-deficient G-MDSCs suppressed microglial activation and improved motor function. ACT001 enhanced G-MDSCs immunosuppression and alleviated PD pathology.
Conclusion
GSDMD deficiency promotes immunosuppressive G-MDSCs that inhibit neuroinflammation and PD progression. Targeting GSDMD to modulate MDSCs' function represents a novel therapeutic strategy for PD.
{"title":"GSDMD-Deficient G-MDSCs Exert Profoundly Suppressive Activity to Relieve MPTP-Induced Parkinson's Disease","authors":"Qi Wu, Fangzhou Liu, Min Gu, Junjie Wei, Guotao Lu, Li Qian, Xiaobo Li, Weijuan Gong","doi":"10.1111/cns.70626","DOIUrl":"10.1111/cns.70626","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Myeloid-derived suppressor cells (MDSCs) are elevated in Parkinson's disease (PD), but their functional role remains unclear. This study investigated whether GSDMD deficiency enhances the immunosuppressive activity of granulocytic MDSCs (G-MDSCs) to mitigate PD progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Flow cytometry and Western blot analyzed G/M-MDSCs in 37 PD patients and 21 controls. An MPTP-induced PD mouse model was used to assess GSDMD-deficient G-MDSCs through behavioral tests, immunohistochemistry, and adoptive transfer experiments. The NLRP3 inhibitor ACT001 was evaluated for therapeutic potential.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>PD patients and MPTP-treated mice showed increased peripheral G-MDSCs with reduced NLRP3/GSDMD activation. GSDMD knockout mice exhibited attenuated PD symptoms, reversed by MDSCs depletion. Adoptive transfer of GSDMD-deficient G-MDSCs suppressed microglial activation and improved motor function. ACT001 enhanced G-MDSCs immunosuppression and alleviated PD pathology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>GSDMD deficiency promotes immunosuppressive G-MDSCs that inhibit neuroinflammation and PD progression. Targeting GSDMD to modulate MDSCs' function represents a novel therapeutic strategy for PD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 10","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12518779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285106","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}
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