CNS Neuroscience & Therapeutics最新文献_第2页

An Integrated QSM-Radiomics Nomogram With Clinical and Imaging Markers for Stratifying Cognitive Impairment in Hypertension 综合qsm -放射组学图与临床和影像学标志物对高血压患者认知功能障碍的分层。

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2026-01-30 DOI: 10.1002/cns.70769

Yu Su, Tingting Liu, Chengjun Dong, Limin Ge, Tianxiang Li, Zhiqing Zhang, Yihan Zhang, Chungao Li, Jie Zhao, Chuansheng Zheng, E. Mark Haacke, Wenjun Wu, Lixia Wang

Background

Hypertensive cognitive impairment is associated with increased iron deposition in deep gray matter. This study aimed to evaluate the potential clinical application of quantitative susceptibility mapping (QSM)-based radiomics for stratifying cognitive impairment in hypertensive patients.

Methods

We prospectively enrolled 178 hypertensive patients who underwent QSM examination and categorized them into cognitive impairment group and normal cognition group. The workflow included: (1) Precise 3D segmentation and susceptibility quantification of the basal ganglia; (2) Initial radiomics feature extraction from the target regions, followed by optimal feature selection via variance thresholding, maximum relevance minimum redundancy (mRMR) algorithm, and LASSO regression; (3) Construction of a multiparametric model integrating radiomics scores and clinical risk factors. The model's performance was assessed by receiver operating characteristic (ROC) curve and its clinical utility for stratification was further evaluated using decision curve analysis (DCA).

Results

The multi-region radiomics model demonstrated superior diagnostic performance in the training cohort (AUC = 0.812), significantly outperforming the QSM and WMH models (AUCs = 0.620 and 0.688, respectively). In the validation cohort, clinically meaningful improvements were observed (ΔAUC = 0.117 and 0.136, respectively). The combined model, which integrated Radscore, susceptibility values, WMH scores, age, and education level, achieved the highest discriminability in both the training (AUC = 0.860) and validation cohorts (AUC = 0.872). DCA further indicated that the nomogram derived from the combined model provided the greatest net clinical benefit for stratifying hypertensive cognitive impairment.

Conclusion

A nomogram integrating QSM-based radiomics with clinical and imaging markers accurately stratified hypertensive cognitive impairment, offering an objective tool for early risk assessment.

背景：高血压认知障碍与深部灰质铁沉积增加有关。本研究旨在评估基于定量易感性制图（QSM）的放射组学在高血压患者认知功能障碍分层中的潜在临床应用。方法：前瞻性纳入178例接受QSM检查的高血压患者，将其分为认知障碍组和认知正常组。工作流程包括：(1)基底节区精确的三维分割和敏感性量化；(2)从目标区域提取放射组学初始特征，然后通过方差阈值分割、mRMR算法和LASSO回归进行最优特征选择；(3)构建放射组学评分与临床危险因素相结合的多参数模型。采用受试者工作特征（ROC）曲线评价模型的性能，采用决策曲线分析（DCA）进一步评价模型在分层中的临床应用。结果：多区域放射组学模型在训练队列中表现出优越的诊断性能（AUC = 0.812），显著优于QSM和WMH模型（AUC分别为0.620和0.688）。在验证队列中，观察到有临床意义的改善（ΔAUC分别= 0.117和0.136）。综合Radscore、敏感性值、WMH评分、年龄和受教育程度的联合模型在训练队列（AUC = 0.860）和验证队列（AUC = 0.872）中具有最高的判别性。DCA进一步表明，由联合模型得出的nomogram为高血压认知障碍分层提供了最大的净临床效益。结论：基于qsm的放射组学与临床和影像学标志物相结合的nomogram可准确分层高血压认知功能障碍，为早期风险评估提供客观工具。

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引用次数: 0

Geometric Microstructural Characteristics of White Matter Differentiate Patients With Facial Dyskinesias and Palsy 面部运动障碍和面瘫患者的白质几何显微结构特征鉴别。

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2026-01-28 DOI: 10.1002/cns.70733

Hua Zhu, Aocai Yang, Jixin Luan, Manxi Xu, Bing Liu, Kuan Lv, Pianpian Hu, Amir Shmuel, Haogang Zhu, Zhen Yuan, Ni Shu, Jian Cheng, Guolin Ma

Purpose

The heterogeneous and homogeneous clinical manifestations of peripheral facial palsy (FP), hemifacial spasm (HFS), and Meige's syndrome (MS) complicate the differentiation of diagnoses for these facial motor diseases. To comprehensively investigate the white matter microstructural characteristics in patients with facial dyskinesias and palsy using geometric and integrity metrics in DTI.

Material and Methods

In this prospective study conducted from September 2020 to January 2022, patients with FP, HFS, and MS, as well as sex-matched healthy control subjects, underwent 3.0 T MRI. Geometric metrics (i.e., splay, bend, twist, and total distortion) based on “Director Field Analysis” and fractional anisotropy (FA) and mean diffusivity (MD) were calculated from DTI data. Cross-sectional tract-based spatial statistics were performed among FP, HFS, MS patients, and healthy controls. The correlation between disease severity and DTI metrics was evaluated. Additionally, the geometric microstructural properties combining FA and MD were used to classify FP, HFS, and MS patients using machine learning methods.

Results

Geometric metrics and FA/MD were widely altered across white matter in FP and HFS patients compared with healthy controls. However, in MS patients only DFA metrics were significantly altered. FA and DFA values strongly correlated with the severity of facial movement disorder in FP patients. Combing conventional FA/MD value with DFA metrics enabled the diagnostic differentiation of FP and HFS from MS.

Conclusion

Our findings demonstrated that the geometric microstructural information of white matter fibers could provide novel insight into the underlying pathological changes in facial dyskinesias and palsy.

目的：周围性面瘫（FP）、半面肌痉挛（HFS）和梅格综合征（MS）的临床表现具有异质性和同质性，使这些面肌运动疾病的诊断鉴别复杂化。应用DTI的几何指标和完整性指标全面探讨面部运动障碍和瘫痪患者的白质微结构特征。材料和方法：本前瞻性研究于2020年9月至2022年1月进行，对FP、HFS和MS患者以及性别匹配的健康对照进行3.0 T MRI检查。基于“定向场分析”、分数各向异性（FA）和平均扩散系数（MD），计算几何指标（即张开、弯曲、扭转和总畸变）。在FP、HFS、MS患者和健康对照中进行基于横断面的空间统计。评估疾病严重程度与DTI指标之间的相关性。此外，结合FA和MD的几何微观结构特性，使用机器学习方法对FP， HFS和MS患者进行分类。结果：与健康对照相比，FP和HFS患者的白质几何指标和FA/MD发生了广泛的改变。然而，在MS患者中，只有DFA指标有显著改变。FA和DFA值与FP患者面部运动障碍的严重程度密切相关。将常规FA/MD值与DFA指标相结合，可以区分FP和HFS与ms的诊断。结论：我们的研究结果表明，白质纤维的几何微结构信息可以为了解面部运动障碍和瘫痪的潜在病理变化提供新的见解。

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引用次数: 0

TTBK2-Driven Ciliogenesis Is Required for Intrinsic Neuronal Regeneration After Spinal Cord Injury ttbk2驱动的纤毛发生是脊髓损伤后内在神经元再生所必需的。

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2026-01-24 DOI: 10.1002/cns.70763

Renfeng Zhang, Su Pan, Zhenwei Tian, Haorui Du, Jintao Wang, Xiaoyu Yang, Zhiping Qi

Background

The primary cilium (PC) is a pivotal organelle for neuronal signaling and development, while tau tubulin kinase 2 (TTBK2) is a key initiator of ciliogenesis. However, the role of TTBK2 in spinal neurons during spinal cord injury (SCI) and subsequent neural repair remains unclear.

Methods

We manipulated TTBK2 expression in spinal neurons using adenovirus-mediated overexpression and knockdown in vitro. Transcriptomic profiling (RNA-sequencing) and RT-qPCR were employed to explore the potential regulatory pathways at the molecular level. In vivo, Ttbk2^fl/fl-Rosa-CreERT2^+/− conditional knockout mice were subjected to a spinal cord hemisection model. Behavioral assays, immunofluorescence, and biotinylated dextran amine (BDA) tracing were conducted to assess neuronal survival, axonal regeneration, and circuit reorganization.

Results

Here, we demonstrated that intact activity of TTBK2 in PC promoted neural survival, axonal regeneration, and neural circuit remodeling. However, loss of TTBK2 impaired PC function and hindered recovery after SCI.

Conclusions

These findings extend the role of PCs beyond neurodevelopment, demonstrating that the TTBK2–PC functions as an endogenous repair mechanism after SCI. Targeting this pathway may provide novel therapeutic strategies for enhancing neural regeneration.

背景：初级纤毛（PC）是神经元信号传导和发育的关键细胞器，而tau微管蛋白激酶2 （TTBK2）是纤毛发生的关键启动器。然而，在脊髓损伤（SCI）和随后的神经修复过程中，TTBK2在脊髓神经元中的作用尚不清楚。方法：利用腺病毒介导的TTBK2过表达和敲低技术，在体外调控TTBK2在脊髓神经元中的表达。利用转录组学分析（rna测序）和RT-qPCR在分子水平上探索潜在的调控途径。在体内，Ttbk2fl/fl-Rosa-CreERT2+/-条件敲除小鼠进行脊髓半切模型。通过行为分析、免疫荧光和生物素化右旋糖酐胺（BDA）示踪来评估神经元存活、轴突再生和回路重组。结果：在这里，我们证明了TTBK2在PC中的完整活性促进了神经存活、轴突再生和神经回路重塑。然而，TTBK2的缺失损害了脊髓损伤后的PC功能，阻碍了脊髓损伤后的恢复。结论：这些发现将pc的作用扩展到神经发育之外，表明TTBK2-PC在脊髓损伤后作为内源性修复机制发挥作用。靶向这一通路可能为增强神经再生提供新的治疗策略。

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引用次数: 0

Therapeutic Hypothermia Alleviates Hydrocephalus and Neurological Dysfunction Post Intraventricular Hemorrhage by Enhancing Drainage of Glymphatic-Meningeal Lymphatic-Deep Cervical Lymphatic System 通过加强淋巴-脑膜淋巴-颈深淋巴系统引流，治疗性低温减轻脑室内出血后脑积水和神经功能障碍。

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2026-01-24 DOI: 10.1002/cns.70740

Yijian Yang, Qian Ouyang, Yaxin Sun, Aijun Liang, Junqiang Wang, Kaiyue Wang, Yexin Yuan, Zhikun Liu, Jun Huang, Zhiping Zhang, Libin Wang, Yang Yuan, Cheng Wang, Zhangjie Su, Qinghua Zhang, Liyang Zhang, Gelei Xiao

Aims

Intraventricular hemorrhage (IVH) has a high mortality and disability rate and poses significant clinical challenges, which often leads to hydrocephalus and neurological dysfunction. Emerging evidence implicates dysfunction of the glymphatic-meningeal lymphatic-deep cervical lymphatic system in the pathogenesis of post-IVH hydrocephalus. Therapeutic hypothermia (TH) holds promise for mitigating these sequelae. This study investigates the potential of TH to ameliorate IVH-induced hydrocephalus and neurological dysfunction, while elucidating its underlying mechanisms.

Methods

Rat models of IVH are established by intraventricular injection of autologous blood. TH, deep cervical lymph nodes (dCLNs) ligation, and intraperitoneal injection of AMPK inhibitor are used to intervene.

Results

In rat models of IVH, TH alleviates neurological dysfunction and attenuates hydrocephalus and pathology damage. TH protects physiological function and maintains normal structure of the glymphatic system. TH improves function and structure of the meningeal lymphatic system and promotes drainage of the deep cervical lymphatic system. TH upregulates RTN3, facilitates phosphorylation of AMPK, and suppresses ERS. All the above effects are reversed by ligation of dCLNs and AMPK inhibitor.

Conclusion

TH alleviates hydrocephalus and neurological dysfunction post IVH by enhancing drainage of the glymphatic-meningeal lymphatic-deep cervical lymphatic system. The RTN3/AMPK/ERS pathway may be the proposed mechanism mediating this effect. TH is expected to become a novel therapeutic strategy for IVH.

目的：脑室内出血（IVH）死亡率和致残率高，是临床面临的重大挑战，常导致脑积水和神经功能障碍。新出现的证据暗示淋巴-脑膜淋巴-颈深淋巴系统在ivh后脑积水发病机制中的功能障碍。治疗性低温（TH）有望减轻这些后遗症。本研究探讨了TH改善ivh诱导的脑积水和神经功能障碍的潜力，同时阐明了其潜在机制。方法：采用脑室内注射自体血建立大鼠IVH模型。采用TH、颈深淋巴结（dCLNs）结扎、AMPK抑制剂腹腔注射进行干预。结果：在IVH大鼠模型中，TH可减轻神经功能障碍，减轻脑积水和病理损害。TH保护生理功能，维持淋巴系统的正常结构。TH改善脑膜淋巴系统的功能和结构，促进颈深淋巴系统的引流。TH上调RTN3，促进AMPK磷酸化，抑制ERS。通过连接dcln和AMPK抑制剂，上述所有作用都被逆转。结论：TH可增强淋巴-脑膜淋巴-颈深淋巴系统引流，减轻IVH后脑积水和神经功能障碍。RTN3/AMPK/ERS通路可能是介导这种作用的机制。TH有望成为IVH的一种新的治疗策略。

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引用次数: 0

Exploring the Fecal Microbiome Dysbiosis and Its Plasma Metabolome Determinants in Advanced Parkinson's Disease With Motor Complications 探讨伴有运动并发症的晚期帕金森病患者粪便微生物群失调及其血浆代谢组决定因素。

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2026-01-23 DOI: 10.1002/cns.70750

Shuangjie Qian, Jialong Hou, Xi Xiong, Qi Duan, Tao Jiang, Yi Zheng, Weiwei Quan, Jiaxue Xu, Keke Chen, Jingjing Qian, Hongchang Gao, Chenglong Xie

Background

Parkinson's disease with motor complications (PD-MC) lacks effective diagnostic and therapeutic strategies. The perturbations of the gut microbiota and plasma metabolites are closely associated with the etiopathogenesis of PD. However, whether fecal microbiome dysbiosis and changed plasma metabolites are involved in PD progression, particularly in the development of PD-MC, is still unclear.

Methods

In this study, we performed an extensive multiomics analysis involving 108 PD patients for 16S rRNA gut microbiome profiling and 246 PD patients for plasma nontargeted metabolomics. Our findings revealed distinct gut microbiota and plasma metabolites associated with PD-MC. Utilizing these discriminative features, we developed a multivariate diagnostic model for PD-MC. The relationships between differential metabolites and microorganisms were evaluated using Spearman correlation analysis. Functional interpretation of the key metabolites was conducted through enrichment and pathway analysis, employing the KEGG and SMPDB databases.

Results

PD-MC patients had distinct gut microbial signatures as compared with PD without motor complications (PD-NMC) individuals and were increased in fecal Lactobacillus, Limosilactobacillus, Bifidobacterium, and Ligilactobacillus genera along with depleted Agathobacter. Moreover, metabolomic analysis revealed the differences in plasma 3-deoxysappanchalcone (3-DSC), 1,3-Dimethyluracil (1,3-DTl), Leucine, and N-Acetylisoleucine (N-AIL), Dodec-6-enoic acid (D-6-E), N-butyl Oleate (N-BO), and 4-hydroxyundecanoic acid (4-HUA) in PD-MC compared to PD-NMC. Spearman correlation analysis showed that the fecal microbiota aberrations in PD-MC patients were linked to plasma metabolic changes, indicating the association between key microbial populations and metabolomic profiles in PD-MC.

Conclusions

This study underscores the value of employing integrated multiomics profiling of the fecal microbiome and plasma metabolome to enhance the mechanistic understanding of PD-MC and to identify potential diagnostic biomarkers.

背景：帕金森病伴运动并发症（PD-MC）缺乏有效的诊断和治疗策略。肠道菌群和血浆代谢物的紊乱与PD的发病密切相关。然而，粪便微生物群失调和血浆代谢物的改变是否参与PD的进展，特别是PD- mc的发展，尚不清楚。方法：在这项研究中，我们对108名PD患者进行了广泛的多组学分析，进行了16S rRNA肠道微生物组分析，并对246名PD患者进行了血浆非靶向代谢组学分析。我们的研究结果揭示了与PD-MC相关的不同肠道微生物群和血浆代谢物。利用这些判别特征，我们开发了PD-MC的多变量诊断模型。采用Spearman相关分析评价差异代谢物与微生物之间的关系。利用KEGG和SMPDB数据库，通过富集和通路分析对关键代谢物进行功能解释。结果：与没有运动并发症的PD- nmc患者相比，PD- mc患者具有明显的肠道微生物特征，并且粪便中乳酸杆菌、乳酸杆菌、双歧杆菌和乳酸杆菌属的数量增加，同时Agathobacter的数量减少。此外，代谢组学分析显示PD-MC与PD-NMC血浆中3-脱氧葡查尔酮（3-DSC）、1,3-二甲基尿嘧啶（1,3- dtl）、亮氨酸和n -乙酰异亮氨酸（N-AIL）、十二-6-烯酸（D-6-E）、n -丁基油酸（N-BO）和4-羟基十一烷酸（4-HUA）的差异。Spearman相关分析显示，PD-MC患者的粪便微生物群畸变与血浆代谢变化有关，表明PD-MC患者的关键微生物群与代谢组学特征之间存在关联。结论：本研究强调了利用粪便微生物组和血浆代谢组的综合多组学分析来增强PD-MC的机制理解和识别潜在的诊断生物标志物的价值。

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引用次数: 0

Peripheral Signatures of Multidimensional Pathology in Symptomatic and Asymptomatic Creutzfeldt–Jakob Disease 有症状和无症状克雅氏病多维病理的外周特征。

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2026-01-23 DOI: 10.1002/cns.70765

Zhong-Yun Chen, Min Chu, Yi-Hao Wang, Rui Liu, Jing Zhang, Ai-ling Yue, Hua Lu, Qian-qian He, Jia-hui Hou, Yu-fei Chen, Hong Ye, Li-Yong Wu

Background

Plasma markers of neuronal injury in Creutzfeldt–Jakob disease (CJD) are established, but peripheral biomarkers reflecting glial activation, synaptic dysfunction, and vascular impairment remain less explored. We systematically assessed these markers in symptomatic CJD and asymptomatic PRNP mutation carriers to improve diagnosis and identify early pathophysiology.

Methods

This prospective cohort study recruited CJD, frontotemporal dementia (FTD), healthy controls (HCs), and preclinical familial CJD pedigrees. Sixteen plasma proteins representing neuronal injury, glial activation, synaptic function, and vascular/BBB integrity were measured. Analyses included group differences, discriminative performance, clinical/imaging correlations, and longitudinal trajectories.

Results

We enrolled 130 CJD patients, 145 FTD, 70 HCs, 16 asymptomatic PRNP carriers (4–6 years follow-up, 4 converters), and 16 non-carrier family controls. In symptomatic CJD, plasma NfL, t-tau, and GFAP were strongly elevated, each showing excellent discriminative performance (AUCs > 0.93 vs. HCs and > 0.82 vs. FTD). We also observed alterations in vascular/BBB markers, with VCAM-1 levels elevated and significantly associated with both clinical decline and DWI hyperintensity. In asymptomatic carriers, biomarker levels remained largely normal and stable preclinically. Notably, two G114V carriers showed mild pre-symptomatic elevations in NfL and GFAP, and one exhibited a slight VCAM-1 increase before clinical onset; all changes exceeded the 90th percentile of control values. E200K and T188K carriers showed no pre-onset changes.

Conclusions

Plasma biomarkers in CJD may reflect multisystem involvement, with neuronal markers showing strong discriminative potential and vascular proteins indicating possible BBB dysfunction. In asymptomatic carriers, minor changes may occur only near onset in those with relatively slow-progressing mutations.

背景：克雅氏病（Creutzfeldt-Jakob disease， CJD）神经元损伤的血浆标志物已经建立，但反映神经胶质激活、突触功能障碍和血管损伤的外周生物标志物仍然很少被探索。我们在有症状的CJD和无症状的PRNP突变携带者中系统地评估了这些标记物，以提高诊断和识别早期病理生理。方法：这项前瞻性队列研究招募了克雅氏病、额颞叶痴呆（FTD）、健康对照（hc）和临床前家族性克雅氏病谱系。测量了代表神经元损伤、神经胶质活化、突触功能和血管/血脑屏障完整性的16种血浆蛋白。分析包括组间差异、鉴别表现、临床/影像学相关性和纵向轨迹。结果：我们招募了130名CJD患者，145名FTD患者，70名hc患者，16名无症状PRNP携带者（随访4-6年，4名转化者）和16名非携带者家族对照。在有症状的CJD中，血浆NfL、t-tau和GFAP均显著升高，分别表现出优异的鉴别性能（auc为> 0.93 vs. hc, > 0.82 vs. FTD）。我们还观察到血管/血脑屏障标志物的改变，VCAM-1水平升高，与临床衰退和DWI高强度显著相关。在无症状携带者中，生物标志物水平在临床前基本保持正常和稳定。值得注意的是，两名G114V携带者在症状前表现出轻微的NfL和GFAP升高，一名在临床发病前表现出轻微的VCAM-1升高；所有变化均超过控制值的第90个百分位数。E200K和T188K携带者未见发病前变化。结论：血浆生物标志物可能反映了克雅氏病的多系统参与，神经元标志物具有很强的鉴别潜力，血管蛋白表明可能存在血脑屏障功能障碍。在无症状携带者中，轻微的变化可能只发生在那些进展相对缓慢的突变的发病附近。

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引用次数: 0

Pyroptosis in Peripheral Neuropathy: From Molecular Mechanisms to Therapeutic Targeting 周围神经病变的焦亡：从分子机制到治疗靶向。

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2026-01-23 DOI: 10.1002/cns.70760

Jinhuan Wei, Mingyue Liuyuan, Zhixin Ye, Xueying Wang, Xueli Zhou, Yifan Shan, Cheng He, Chunting Zhu, Chicheng Zhou, Jingyin Bao, Yonghui Zhang, Gang Chen

Background

Peripheral neuropathy (PN) is a common consequence of peripheral nervous system (PNS) disorders, yet its effective treatment remains a significant clinical challenge. Pyroptosis, an inflammatory form of programmed cell death (PCD) triggered by gasdermin A–E (GSDMA-E), contributes to the pathogenesis of PN and represents a promising therapeutic target. While reviews of pyroptosis in other diseases are extensive, comprehensive reviews focusing on PN are lacking.

Method

We systematically searched PubMed, Scopus, Web of Science, and Google Scholar (1986–2025). Only original studies investigating pyroptosis in PN were included.

Results

This review first consolidates established evidence, highlighting a context-dependent dual role of pyroptosis in PN. Its detrimental effects in chronic pain involve canonical (caspase-1/GSDMD) or noncanonical pathways (e.g., caspase-4/5/11/GSDMD, caspase-3/GSDME, caspase-8/GSDMC), often initiated by inflammasomes (e.g., NOD-like receptor family pyrin domain containing 3 [NLRP3]). Conversely, its beneficial, tumoricidal role is leveraged in neuroblastoma. Preclinically, diverse inhibitors—including NLRP3 inhibitors (e.g., MCC950), caspase-1 inhibitors (e.g., VX-765), and P2X7R antagonists (e.g., Brilliant Blue G)—alleviate pain and promote nerve repair, while pyroptosis inducers (e.g., axitinib) combat chemoresistant tumors. We then identify critical knowledge gaps and emerging frontiers. The roles of most gasdermins (GSDMA, GSDMB, GSDMC) in PN are unknown. We explore the emerging concept of PANoptosis (crosstalk among pyroptosis, apoptosis, and necroptosis) as a novel conceptual framework for PNS pathologies, where shared molecular hubs may amplify neuroinflammation. Furthermore, despite promising strategies like combination therapy and drug repurposing, a significant translational gap exists, with no current clinical trials specifically targeting pyroptosis for PN.

Conclusion and Perspective

Targeting pyroptosis is a novel therapeutic avenue for PN. This review synthesizes current mechanistic understanding, evaluates preclinical therapeutic strategies, and delineates crucial future directions, including elucidating gasdermin diversity, validating PANoptosis, and bridging the translational divide, thereby accelerating their application for patients suffering from PN.

背景：周围神经病变（PN）是周围神经系统（PNS）疾病的常见后果，但其有效治疗仍然是一个重大的临床挑战。焦亡是一种由气皮蛋白a - e （GSDMA-E）引发的程序性细胞死亡（PCD）的炎症形式，有助于PN的发病机制，是一个有希望的治疗靶点。虽然对其他疾病的焦亡的综述很广泛，但缺乏对PN的全面综述。方法：系统检索PubMed、Scopus、Web of Science和谷歌Scholar（1986-2025）。仅纳入了研究PN焦亡的原始研究。结果：这篇综述首先巩固了已有的证据，强调了焦亡在PN中依赖于环境的双重作用。它在慢性疼痛中的有害作用涉及典型（caspase-1/GSDMD）或非典型途径（如caspase-4/5/11/GSDMD、caspase-3/GSDME、caspase-8/GSDMC），通常由炎症小体（如nod样受体家族pyrin结构域3 [NLRP3]）启动。相反，其有益的杀瘤作用在神经母细胞瘤中发挥作用。临床前，多种抑制剂——包括NLRP3抑制剂（如MCC950）、caspase-1抑制剂（如VX-765）和P2X7R拮抗剂（如Brilliant Blue G）——可以缓解疼痛并促进神经修复，而焦死诱导剂（如阿西替尼）可以对抗化疗耐药肿瘤。然后，我们确定关键的知识差距和新兴的前沿。大多数gasdermins （GSDMA， GSDMB， GSDMC）在PN中的作用尚不清楚。我们将PANoptosis（焦亡、凋亡和坏死之间的串扰）这一新兴概念作为PNS病理的新概念框架进行探讨，其中共享的分子中心可能会放大神经炎症。此外，尽管联合治疗和药物再利用等有希望的策略，但存在显著的翻译差距，目前没有专门针对焦亡治疗PN的临床试验。结论与展望：靶向性焦亡是治疗PN的新途径。这篇综述综合了目前的机制理解，评估了临床前治疗策略，并描绘了关键的未来方向，包括阐明gasdermin多样性，验证PANoptosis，弥合翻译鸿沟，从而加速它们在PN患者中的应用。

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引用次数: 0

The Cerebellar Connectome Disruptions in Ischemic Stroke 缺血性中风中的小脑连接体中断。

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2026-01-23 DOI: 10.1002/cns.70759

Xiuqin Wang, Tongyue Li, Jinhui Wang, Yanhui Fu, Zhenqiang Ma, Xiaoyan Wu, Yiying Wang, Yufeng Zang, Yulin Song, Yating Lv

Background

Supratentorial focal lesions following ischemic stroke can lead to crossed cerebellar diaschisis (CCD). However, it remains unclear how CCD affects the functional connectivity between the cerebellum and the rest of the brain in ischemic stroke patients.

Methods

This case–control study involved resting-state fMRI data from 65 patients with basal ganglia ischemic stroke (Stroke) and 72 healthy controls (HC). Cerebral, cerebellar, and cerebrocerebellar inter-module functional connectivity in both 7-module and 17-module conditions were calculated and compared between the Stroke and HC groups. Spearman correlation analyses were further conducted to examine the relationships between connectivity alterations and both stroke severity and lesion size in Stroke patients.

Results

The Stroke patients exhibited disrupted inter-module functional connectivity, characterized by increased intra-hemispheric and decreased inter-hemispheric connectivity between cerebral modules, increased inter-module connectivity in the cerebellum, and reduced connectivity between ipsilesional cerebral modules and cerebellar modules while increasing connectivity between contralesional cerebral modules and cerebellar modules. Moreover, these connectivity changes, particularly disruptions in the cerebellar connectome, may be associated with lesion size and stroke severity in Stroke patients.

Conclusions

These findings highlight the importance of cerebellar connectome disruptions in ischemic stroke, which may provide valuable insights into the disease's underlying brain mechanisms.

背景：缺血性脑卒中后幕上局灶性病变可导致交叉小脑水溶（CCD）。然而，目前尚不清楚CCD如何影响缺血性中风患者小脑和大脑其他部分之间的功能连接。方法：本病例对照研究包括65例基底节区缺血性脑卒中（卒中）患者和72例健康对照（HC）的静息状态fMRI数据。计算并比较卒中组和HC组在7模块和17模块条件下的大脑、小脑和脑小脑模块间功能连通性。进一步进行Spearman相关分析，检验脑卒中患者连通性改变与脑卒中严重程度和病变大小之间的关系。结果：脑卒中患者表现为脑模块间功能连接中断，表现为脑模块间半球内连接增加，半球间连接减少，小脑模块间连接增加，同侧脑模块与小脑模块间连接减少，对侧脑模块与小脑模块间连接增加。此外，这些连通性的改变，特别是小脑连接组的破坏，可能与中风患者的病变大小和中风严重程度有关。结论：这些发现强调了缺血性卒中中小脑连接体中断的重要性，这可能为该疾病的潜在脑机制提供有价值的见解。

{"title":"The Cerebellar Connectome Disruptions in Ischemic Stroke","authors":"Xiuqin Wang, Tongyue Li, Jinhui Wang, Yanhui Fu, Zhenqiang Ma, Xiaoyan Wu, Yiying Wang, Yufeng Zang, Yulin Song, Yating Lv","doi":"10.1002/cns.70759","DOIUrl":"10.1002/cns.70759","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Supratentorial focal lesions following ischemic stroke can lead to crossed cerebellar diaschisis (CCD). However, it remains unclear how CCD affects the functional connectivity between the cerebellum and the rest of the brain in ischemic stroke patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This case–control study involved resting-state fMRI data from 65 patients with basal ganglia ischemic stroke (Stroke) and 72 healthy controls (HC). Cerebral, cerebellar, and cerebrocerebellar inter-module functional connectivity in both 7-module and 17-module conditions were calculated and compared between the Stroke and HC groups. Spearman correlation analyses were further conducted to examine the relationships between connectivity alterations and both stroke severity and lesion size in Stroke patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The Stroke patients exhibited disrupted inter-module functional connectivity, characterized by increased intra-hemispheric and decreased inter-hemispheric connectivity between cerebral modules, increased inter-module connectivity in the cerebellum, and reduced connectivity between ipsilesional cerebral modules and cerebellar modules while increasing connectivity between contralesional cerebral modules and cerebellar modules. Moreover, these connectivity changes, particularly disruptions in the cerebellar connectome, may be associated with lesion size and stroke severity in Stroke patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings highlight the importance of cerebellar connectome disruptions in ischemic stroke, which may provide valuable insights into the disease's underlying brain mechanisms.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12828662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146027952","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}

引用次数: 0

Function of the Human Cingulate Cortex: A Brainnetome Atlas-Based Study via Cortical Electrical Stimulation in Patients With Epilepsy 人类扣带皮层的功能：一项基于脑网络图谱的癫痫患者皮质电刺激研究。

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2026-01-23 DOI: 10.1002/cns.70768

Qinqin Deng, Mengyang Wang, Guanpeng Chen, Xiongfei Wang, Zhaofen Yan, Huajun Yang, Yujiao Yang, Minghui Wang, Mengyi Guo, Zhonghua Xiong, Nan Guan, Jian Zhou, Yuguang Guan, Guoming Luan, Tianfu Li, Jing Wang

Objective

This study aimed to systematically map the functional organization of the cingulate gyrus using cortical electrical stimulation (CES) guided by the Brainnetome Atlas.

Methods

We retrospectively analyzed CES data from 234 patients with drug-resistant epilepsy who underwent stereoelectroencephalography (SEEG) implantation in the cingulate cortex. A total of 1141 stimulation sites across seven cingulate subregions (A23d, A24rv, A32p, A23v, A24cd, A23c, A32sg) were examined. Responses were categorized into somatosensory, motor, autonomic, vestibular, visual, emotional, memory, and pain-related phenomena.

Results

Key findings included: (1) Somatosensory responses (n = 99) were widely distributed, with motor responses localized to middle-posterior subregions (A23c/A24rv/A24cd); (2) Autonomic (n = 58) and emotional (n = 15) responses showed broad distribution, with ventral MCC (A24rv) as an affective hub; (3) Pain responses (n = 30) involved both anterior (affective) and posterior (spatial) subregions; (4) Memory deficits (n = 8) specifically localized to posterior cingulate (A23d); (5) Visual (n = 13) and vestibular (n = 51) responses clustered in posterior and middle-posterior regions, respectively.

Conclusion

This study provides a systematic functional mapping of the cingulate gyrus using the Brainnetome Atlas, demonstrating its integrated role in diverse neurological functions. The findings advance understanding of cingulate pathophysiology and have implications for surgical planning in epilepsy.

目的：利用脑网图谱引导下的皮质电刺激（CES）技术，系统地绘制扣带回的功能组织。方法：我们回顾性分析234例在扣带皮层植入立体脑电图（SEEG）的耐药癫痫患者的CES数据。共检测了7个扣带亚区（A23d、A24rv、A32p、A23v、A24cd、A23c、A32sg）的1141个刺激位点。反应分为躯体感觉、运动、自主神经、前庭神经、视觉、情绪、记忆和疼痛相关现象。结果：主要发现包括：(1)体感反应（n = 99）分布广泛，运动反应集中于中后侧亚区（A23c/A24rv/A24cd）；(2)自主反应（n = 58）和情绪反应（n = 15）分布广泛，以腹侧MCC （A24rv）为情感中枢；(3)疼痛反应（n = 30）涉及前（情感）和后（空间）亚区；(4)特定于后扣带（A23d）的记忆缺陷（n = 8）；(5)视觉反应（n = 13）和前庭反应（n = 51）分别聚集在后侧和中后侧区域。结论：本研究利用脑网图谱对扣带回进行了系统的功能定位，证明了其在多种神经功能中的综合作用。这些发现促进了对扣带病理生理的理解，并对癫痫的手术计划有指导意义。

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引用次数: 0

BETMB: A Dual-Target Compound for Synergistic Suppression of Neuronal Hyperexcitability in Refractory Epilepsy via Concurrent Modulation of Nav Channels and GABAA Receptors 通过同时调节Nav通道和GABAA受体协同抑制难治性癫痫神经元高兴奋性的双靶点化合物。

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2026-01-23 DOI: 10.1002/cns.70766

Di Zhang, Kai Li, Yingying Zhang, Yao Nie, Yue Li, Rui Li, Xin Wang, Shengjun Mao

Aims

This study aims to evaluate 5-(but-1-en-1-yl)-1,2,3-trimethoxybenzene (BETMB) as a novel dual-target anti-seizure agent for refractory epilepsy and elucidate the synergistic neuroelectrophysiological mechanism between Na_V channels and GABA_A receptors.

Methods

Whole-cell patch-clamp recordings characterized BETMB's dual-target activity. Antiseizure efficacy was assessed in maximal electroshock (MES), pentylenetetrazole (PTZ), and kainic acid (KA) models. Cognitive function in chronic KA mice was evaluated using the Morris water maze (MWM). Histopathological, immunohistochemical, and Western blot analyses explored neuroprotection. Synergy between Na_V and GABA_AR modulation was systematically investigated using both an in vitro Mg²⁺-free model of neuronal hyperexcitability and an in silico model of cortical spreading depolarization (CSD).

Results

BETMB acted as a GABA_AR positive allosteric modulator (EC₅₀ = 93.2 μM) and a state-dependent Na_V blocker (K_I = 1.9 μM). It significantly suppressed seizures across models, improved cognition in chronic epilepsy, and modulated downstream expression of GABRA1, NR2B, and BDNF-pAKT-CREB signaling. Synergistic Na_V and GABA_AR modulation completely abolished ictal-like discharges in Mg²⁺-free cellular models and prevented CSD initiation in computational simulations.

Conclusion

BETMB is a promising dual-target therapy for refractory epilepsy, supported by the first electrophysiological evidence that dual modulation of GABA_AR and Na_V synergistically suppresses neuronal hyperexcitability. Beyond epilepsy, this finding may also extend to CSD-related conditions such as stroke, traumatic brain injury, and migraine.

目的：本研究旨在评价5-（丁-1-烯-1-基）-1,2,3-三甲氧基苯（BETMB）作为一种新型双靶点抗难治性癫痫药物的作用，并阐明NaV通道与GABAA受体之间的协同神经电生理机制。方法：全细胞膜片钳记录表征BETMB的双靶点活性。在最大电击（MES）、戊四唑（PTZ）和kainic酸（KA）模型中评估抗癫痫效果。采用Morris水迷宫（MWM）评价慢性KA小鼠的认知功能。组织病理学、免疫组织化学和Western blot分析探讨了神经保护作用。通过体外无Mg2+神经元高兴奋性模型和皮质扩张性去极化（CSD）模型，系统地研究了NaV和GABAAR调节之间的协同作用。结果：BETMB具有GABAAR阳性变构调节剂（EC50 = 93.2 μM）和状态依赖性NaV阻滞剂（KI = 1.9 μM）的作用。它显著抑制了所有模型的癫痫发作，改善了慢性癫痫的认知，并调节了GABRA1、NR2B和BDNF-pAKT-CREB信号的下游表达。协同NaV和GABAAR调制完全消除了无Mg2+细胞模型中的初始样放电，并在计算模拟中阻止了CSD的启动。结论：BETMB是治疗难治性癫痫的一种很有前景的双靶点疗法，首次得到GABAAR和NaV双调节协同抑制神经元高兴奋性的电生理证据支持。除了癫痫，这一发现也可能延伸到与脑脊病相关的疾病，如中风、创伤性脑损伤和偏头痛。

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引用次数: 0