CNS Neuroscience & Therapeutics最新文献

{"title":"Sensory Afferent Neural Circuits Mediate Electroacupuncture to Improve Swallowing Function in a Post-Stroke Dysphagia Mouse Model","authors":"Yong Dai,&nbsp;Jiahui Hu,&nbsp;Qianqian Wang,&nbsp;Jia Qiao,&nbsp;Yueqin Tian,&nbsp;Chao Li,&nbsp;Jiemei Chen,&nbsp;Fei Zhao,&nbsp;Xinya Li,&nbsp;Chunyan Liu,&nbsp;Ruihuan Pan,&nbsp;Haining Ou,&nbsp;Nenggui Xu,&nbsp;Hongmei Wen,&nbsp;Zulin Dou,&nbsp;Qiuping Ye","doi":"10.1111/cns.70514","DOIUrl":"https://doi.org/10.1111/cns.70514","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Electroacupuncture (EA) has been reported to improve post-stroke dysphagia (PSD) effectively. However, the underlying afferent neural circuit and neurological mechanism involved in improving PSD remain poorly understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A PSD mouse model was established via the photochemical embolization method. Laser scatter contrast imaging was used to evaluate blood perfusion. Videofluoroscopic swallowing study, flexible endoscopic evaluation swallowing, and electromyography were used to assess the swallowing function. Neuronal activities and neuron types were detected by immunofluorescence. Synaptic connections between the nucleus tractus solitarii (NTS), the ventral posteromedial thalamic nucleus (VPM), and the primary sensory cortex (S1) were verified by neural tracing. Finally, photogenetic, chemogenetic, and in vivo electromyography or electrophysiological records were used to explore the possible afferent neural circuits of EA therapy for PSD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>EA treatment potentiated the blood perfusion of CV23 and S1, improved the area under the curve, pharyngeal transit time, and vocal fold mobility in PSD model mice. EA also activated neuronal activities in VPM, while chemical genetic inhibition of VPM attenuated the swallowing function of EA enhanced in PSD mice. Neural tracing revealed the presence of direct synaptic connections in the neural circuit of NTS-VPM-S1, and excitatory neurons were the predominant type of synaptic projection. Activation of this circuit improved the swallowing function in PSD mice, whereas its inhibition impaired the swallowing function; this effect was reversible by EA-CV23.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings uncover the importance of sensory afferent neural circuits NTS-VPM-S1 in driving the protective effect of EA-CV23 against dysphagia and thus reveal a potential strategy for PSD intervention.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70514","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144705531","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":"S-Propargyl-Cysteine Attenuates Stroke Heterogeneity via Promoting Protective Autophagy Across Multiple Neural Cell Types: Insights From Single-Cell Sequencing","authors":"Xiaoming Xin,&nbsp;Lei Miao,&nbsp;Lei Ci,&nbsp;Yun Wang,&nbsp;Zhiguo Zhang,&nbsp;Lingguo Meng,&nbsp;Jia Qi,&nbsp;Yicheng Mao,&nbsp;Yi-Zhun Zhu","doi":"10.1111/cns.70399","DOIUrl":"https://doi.org/10.1111/cns.70399","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Introduction&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Stroke, predominantly ischemic, is a leading cause of mortality and disability worldwide. Despite advances in intervention strategies, effective treatments to mitigate neurological injury post-ischemic stroke remain limited. Hydrogen sulfide (H&lt;sub&gt;2&lt;/sub&gt;S), a gas signaling molecule, has been implicated in neuroprotection, but its role in stroke is controversial. S-propargyl-cysteine (SPRC), an H&lt;sub&gt;2&lt;/sub&gt;S donor, has shown great potential in protecting against neurological injuries, but its mechanisms in ischemic stroke are not fully understood. This study investigates the neuroprotective potential of SPRC and its mechanisms, focusing on the interplay between H&lt;sub&gt;2&lt;/sub&gt;S and autophagy in modulating the cerebral microenvironment post-stroke.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We conducted a comprehensive single-cell RNA sequencing analysis on ischemic brain tissue to elucidate the cellular heterogeneity and specific responses related to H&lt;sub&gt;2&lt;/sub&gt;S synthesis and autophagy. We utilized the GEO repository dataset GSE174574, applying stringent filtering and batch effect correction using the Harmony R package. Cellular subpopulations were identified using established markers, and H&lt;sub&gt;2&lt;/sub&gt;S and autophagy scores were calculated using the JASMINE package. We also measured serum H&lt;sub&gt;2&lt;/sub&gt;S levels, evaluated the pharmacodynamics of SPRC in rats, and constructed a cerebral ischemia–reperfusion (I/R) injury model to assess the neuroprotective effects of SPRC. Additionally, we examined the role of SPRC in CBS and 3-MST knockout mice to determine the dependency on these H&lt;sub&gt;2&lt;/sub&gt;S synthetases.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Our findings revealed a dysregulation in the expression of H&lt;sub&gt;2&lt;/sub&gt;S and autophagy-related genes in central nervous system cells, particularly in neurons, following stroke. SPRC administration significantly improved neurological behavior, metabolic activity, reduced brain infarction size, and ameliorated ultrastructure changes in stroke-affected rats. Interestingly, SPRC continued to provide neuroprotection even after the knockdown of CBS and 3-MST, indicating a CBS/3-MST-independent mechanism. Furthermore, SPRC preserved the endogenous H&lt;sub&gt;2&lt;/sub&gt;S level and strongly upregulated protective autophagy.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This study is the first to reveal the neuroprotection of SPRC in cerebral I/R injury in a classical enzymatic CBS/3-MST independent manner. The potential cellular and molecular mechanisms may rely on ","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70399","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688039","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":"Transcranial iTBS Combined With Trans-Spinal iTBS Targeting PDE1A/cAMP/PKA Axis Regulates Neural Regeneration After Spinal Cord Injury","authors":"Yingxue Fu,&nbsp;Xianbin Wang,&nbsp;Xingyu Chen,&nbsp;Shuang Wu","doi":"10.1111/cns.70525","DOIUrl":"https://doi.org/10.1111/cns.70525","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To explore the impact of intermittent theta burst stimulation (iTBS) treatment at various targets on spinal cord injury (SCI), as well as the effects of dual-target iTBS therapy on neurological functional recovery in rats with SCI and its underlying mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using an improved Allen's method, an incomplete C6 SCI model was established. Postoperatively, the rats with SCI underwent transcranial iTBS, trans-spinal iTBS, or dual-target iTBS. Neurological functional recovery and synaptic function following SCI were evaluated through behavioral tests, footprint analysis, electrophysiological assessments, pathological staining, transmission electron microscopy, Golgi staining, and immunofluorescence staining. The expression of relevant proteins and genes was assessed using Western blotting and qRT-PCR. Proteomic and metabolomic sequencing analyses of spinal cord tissue from each group were conducted to investigate specific mechanisms. Additionally, lentivirus was used to infect primary neurons to elucidate the effect of PDE1A. Furthermore, lentivirus was applied to SCI rats to explore the influence of PDE1A on neurological and synaptic functions following SCI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared with the single-target iTBS group, dual-target iTBS treatment significantly improved motor function and reduced the damaged area of the spinal cord in SCI rats. Following dual-target iTBS intervention, SCI rats exhibited improvements in neural function and synaptic function. Sequencing analysis identified the protein PDE1A present in all groups, and the protein interaction network revealed that PDE1A is involved in the cAMP signaling pathway, with an increase in PDE1A expression observed after SCI. Additionally, inhibiting PDE1A promoted the expression of cAMP and protein kinase cAMP-activated catalytic subunit alpha (PRKACA) in primary neurons, thereby facilitating synapse function in primary neurons. Inhibition of PDE1A also improved neural connection and synaptic reconstruction in SCI rats.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Compared with single-target iTBS treatment, dual-target iTBS treatment promotes the recovery of motor function and spinal cord tissue repair more effectively in SCI rats. Dual-target iTBS may promote neural regeneration and synaptic remodeling after SCI by regulating the PDE1A-cAMP-PKA signaling pathway, thereby improving neurological dysfunction.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70525","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144687894","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":"Glymphatic Function as a Prognostic Biomarker in Prolonged Disorders of Consciousness","authors":"Dian-Wei Wu,&nbsp;Chang-Geng Song,&nbsp;Rong Chen,&nbsp;Jing-Jing Zhao,&nbsp;Ying-Chi Zhang,&nbsp;Xuan Wang,&nbsp;Zhong-Qing Sun,&nbsp;Xiao-Gang Kang,&nbsp;Qiong Gao,&nbsp;Wen Jiang","doi":"10.1111/cns.70526","DOIUrl":"https://doi.org/10.1111/cns.70526","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The glymphatic system is a major waste clearance system in the central nervous system. We aim to investigate the glymphatic function and its prognostic values in patients with prolonged disorders of consciousness (pDoC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a prospective and explorative cohort study including 40 patients with pDoC and 20 healthy controls. Glymphatic function was measured with the global and regional blood-oxygen-level-dependent and cerebrospinal fluid (BOLD-CSF) couplings, characterized by time-lags and strengths of the couplings. The clinical outcome was defined as improvement and no improvement in consciousness 6 months after enrollment, determined via a structured telephone follow-up based on the Coma Recovery Scale-Revised (CRS-R) score.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients with pDoC exhibited significantly delayed time-lags in BOLD-CSF coupling (<i>p</i> &lt; 0.05) and significantly reduced coupling strengths (<i>p &lt;</i> 0.05) when compared to healthy controls. Follow-up studies indicated that shorter global BOLD-CSF coupling time-lags can predict an improved consciousness 6 months after enrollment, with an area under the receiver operating characteristic curve of 0.837, a sensitivity of 82.4%, and an accuracy of 85.7% using a cutoff point of 7.5.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The glymphatic system was impaired in patients with pDoC, and its function, measured by BOLD-CSF coupling, can serve as a novel prognostic biomarker.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70526","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144687952","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":"Anatomical Versus Functional Methods for Hippocampal Subfields Segmentation: Letter to the Editor Regarding the Manuscript “Altered Hippocampal Subfields Functional Connectivity in Benign Paroxysmal Positional Vertigo Patients With Residual Dizziness: A Resting-State fMRI Study”","authors":"Kwangsun Yoo,&nbsp;Eek-Sung Lee","doi":"10.1111/cns.70521","DOIUrl":"https://doi.org/10.1111/cns.70521","url":null,"abstract":"&lt;p&gt;We have read with great interest the recent article by Chen et al. titled “Altered Hippocampal Subfields Functional Connectivity in Benign Paroxysmal Positional Vertigo Patients With Residual Dizziness: A Resting-State fMRI Study” published in CNS Neuroscience &amp; Therapeutics [&lt;span&gt;1&lt;/span&gt;]. This study provides valuable insights into the role of hippocampal connectivity in the mechanism of residual dizziness following BPPV. We would like to offer methodological considerations regarding the authors' approach to hippocampal subfield segmentation.&lt;/p&gt;&lt;p&gt;There are two primary methods for hippocampal subfield segmentation: an anatomical method based on cytoarchitectonic probabilistic atlases, and a functional method based on the anterior–posterior (A-P) axis of the hippocampus. While the authors used anatomical segmentation with cytoarchitectonic atlases, this approach is limited by current imaging resolution [&lt;span&gt;2&lt;/span&gt;]. Their analysis involved hippocampal subfield segmentation on 3 T MRI images, followed by functional connectivity analysis using specific subfield ROIs as seeds. Since most hippocampal layers except the dentate gyrus are less than 2 mm thick, it is difficult to avoid the partial volume effect [&lt;span&gt;3&lt;/span&gt;]. Additionally, the authors defined Cornu Ammonis (CA) as a single region, despite distinct cellular properties and connectivity patterns across CA1 to CA3 subfields [&lt;span&gt;4, 5&lt;/span&gt;]. This unified characterization of CA subregions introduces methodological concerns, particularly in the form of partial volume effects and signal mixing between subfields, which could potentially generate spurious connectivity findings [&lt;span&gt;6&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;From a functional perspective, the hippocampus exhibits a clear anterior–posterior axis organization, as demonstrated by recent research [&lt;span&gt;7&lt;/span&gt;] that challenges the traditional view of this structure as uniformly organized. Single-nucleus RNA sequencing studies have revealed systematic gradients in gene expression, demonstrating distinct cellular and molecular signatures that differentiate the anterior from the posterior hippocampus. This molecular heterogeneity is paralleled by differential connectivity patterns, with the anterior hippocampus linking to limbic and prefrontal networks for emotional and memory processing, while the posterior portion connects with parietal and occipital cortices for spatial and visual functions [&lt;span&gt;8&lt;/span&gt;]. In support of this perspective, our research in persistent postural-perceptual dizziness (PPPD) patients validates the A-P axis-based segmentation approach, revealing decreased functional connectivity between the anterior hippocampus and several regions [&lt;span&gt;9&lt;/span&gt;]. Task fMRI studies have further corroborated these findings, demonstrating distinct patterns of activation and interregional synchrony along the hippocampal long axis during cognitive tasks [&lt;span&gt;10&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;In conclusion, while defining ROIs based on cytoarch","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70521","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681097","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":"Targeting PD-L1 for Ischemic Stroke Recovery: Age-Dependent Modulation of Immune and BBB Pathways","authors":"Hang Hang,&nbsp;Can Xu,&nbsp;Likun Wang,&nbsp;Cuiying Liu,&nbsp;Rongping Zhang,&nbsp;Guofeng Wu,&nbsp;Heng Zhao","doi":"10.1111/cns.70523","DOIUrl":"https://doi.org/10.1111/cns.70523","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Aging has a profound impact on the pathophysiology of ischemic stroke and the effectiveness of therapeutic interventions. This study aims to evaluate the therapeutic efficacy of programmed death-ligand 1 (PD-L1) monoclonal antibody (mAb) in modulating immune responses and neurovascular repair following ischemic stroke, with a focus on age-dependent differences.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Young and aged mice were subjected to middle cerebral artery occlusion (MCAO) followed by PD-L1 mAb treatment. RNA sequencing, immunofluorescence, and molecular analyses were employed to assess immune modulation, blood–brain barrier (BBB) integrity, and functional recovery.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>RNA sequencing revealed significant differential gene expression in ischemic brain tissues, with CD274 (PD-L1) prominently upregulated among immune checkpoint-related genes in young mice. Immunofluorescence confirmed PD-L1 expression in microglia/macrophages, with significantly higher upregulation in young mice. PD-L1 mAb treatment showed superior efficacy in young mice, significantly reducing infarct volume, enhancing neurological recovery, and preserving BBB integrity through greater upregulation of tight junction proteins such as ZO-1, Claudin-5, and Occludin compared to aged mice. It also more effectively reduced neuroinflammation, apoptosis, and pro-inflammatory cytokines (TNF-α, IL-1β), eliciting stronger spleen responses in young mice. These findings underscore the age-dependent advantages of PD-L1-targeted therapies for ischemic stroke recovery.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>PD-L1 plays a critical role in ischemic stroke recovery, with PD-L1 mAb treatment demonstrating age-dependent therapeutic efficacy by enhancing BBB integrity, reducing neuroinflammation and apoptosis, and modulating peripheral immune responses.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70523","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144687959","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":"Ptbp1 Knockdown in Glial Cells Promotes Motor and Sensory Function Recovery After Peripheral Nerve Injury","authors":"Honghao Song,&nbsp;Lei Peng,&nbsp;Dashuang Chen,&nbsp;Xiaoyi Fan,&nbsp;Tong Hua,&nbsp;Ruifeng Ding,&nbsp;Mengqiu Deng,&nbsp;Qianbo Chen,&nbsp;Mei Yang,&nbsp;Hongbin Yuan","doi":"10.1111/cns.70531","DOIUrl":"https://doi.org/10.1111/cns.70531","url":null,"abstract":"<p><b>Background:</b> Peripheral nerve injury (PNI) frequently causes persistent sensory and motor deficits with limited therapeutic options. While Ptbp1-mediated astrocyte reprogramming shows promise in central nervous system repair, its role in PNI—particularly regarding spinal cord astrocytes and dorsal root ganglia (DRG) satellite glial cells (SGCs)—remains unexplored.<b>Aims:</b> This study aimed to determine whether Ptbp1 knockdown in glial cells enhances functional recovery after sciatic nerve injury (SNI) by dual mechanisms: (1) converting spinal cord astrocytes to motor neurons and polarizing them toward neuroprotective A2 phenotype, and (2) activating regenerative signaling pathways in DRG SGCs.<b>Materials &amp; Methods:</b> C57BL/6J mice underwent SNI followed by intrathecal injection of AAV-GFAP-CasRx-Ptbp1 (targeting Ptbp1 in astrocytes/SGCs) or control virus. Primary astrocytes and SGCs were transfected with Ptbp1 siRNA in vitro. Assessments included functional recovery (Basso Mouse Scale, Louisville Swim Score, Hargreaves test, von Frey assay), axonal regeneration (HE/β3-tubulin/SCG-10 staining), transcriptome/ATAC sequencing, and molecular analyses (immunofluorescence for DCX/Islet1/ntng2-NGL-2; Western blot for Ptbp1/GDNF/C3).<b>Results:</b> Ptbp1 was upregulated in spinal cord astrocytes and DRG SGCs post-SNI. Its knockdown accelerated motor/sensory functional recovery and axonal regeneration. Mechanistically, in the spinal cord, Ptbp1 depletion induced astrocyte-to-motor neuron conversion (upregulation of DCX/Islet1/Map2) and polarized astrocytes toward A2 phenotype (upregulation of S100a10/GDNF; downregulation of C3). In DRG, it activated the ntng2/NGL-2 pathway in SGCs, enhancing sensory axon regeneration (upregulation of ATF3/GAP43). Ntng2 blockade abolished sensory regeneration, confirming pathway dependence.<b>Discussion:</b> Ptbp1 knockdown promotes PNI repair through spatially distinct mechanisms: spinal cord astrocyte reprogramming/A2 polarization synergizes with DRG SGC-mediated ntng2/NGL-2 activation. While astrocyte-to-neuron conversion was limited, dominant A2 polarization provided neuroprotection. The absence of SGC transdifferentiation highlights cell-type-specific responses. Limitations include low conversion efficiency and interspecies regenerative differences.<b>Conclusion:</b> Targeting Ptbp1 in glial cells accelerates PNI recovery by dual regenerative mechanisms: motor function restoration via astrocyte-derived neuron replenishment and A2 polarization, coupled with sensory repair through ntng2/NGL-2 pathway activation. This establishes Ptbp1 as a promising therapeutic target for nerve injuries.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70531","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144687928","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":"Genetic Associations of Clonal Hematopoiesis With Cardioembolic Stroke: Insights From Genome-Wide Mendelian Randomization, Bulk RNA, Single-Cell RNA Sequencing","authors":"Haozhou Tan,&nbsp;Feng Zhu,&nbsp;Han Yan,&nbsp;Fangfang Li,&nbsp;Yang Yao,&nbsp;Ying Li,&nbsp;Qian Feng","doi":"10.1111/cns.70515","DOIUrl":"https://doi.org/10.1111/cns.70515","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Ischemic stroke (IS), a major global health concern, is associated with aging-related clonal hematopoiesis of indeterminate potential (CHIP), though their mechanistic connection remains unclear. This study explores the causal CHIP-IS relationship, key genetic drivers, and potential therapies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Genetic markers for CHIP were selected as instrumental variables and analyzed through bidirectional two-sample Mendelian randomization (MR) using GWAS data from IS cohorts. Functional annotation of significant loci was performed via FUMA, while transcriptomic datasets from GEO underwent differential expression analysis, weighted gene co-expression network construction, and machine learning-driven biomarker discovery. Protein–protein interaction networks and single-cell RNA sequencing (scRNA-seq) were employed to elucidate cellular mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>MR analysis revealed a significant causal association between CHIP and cardioembolic stroke (CES) risk (OR = 70.15, 95% CI = 2.03–2428.52, <i>p</i> = 0.02). PARP1 and CD3G emerged as hub genes connecting CHIP to IS pathogenesis, validated through multi-omics integration. Fourteen feature genes were identified, and potential therapeutic drugs targeting this pathway were discovered. scRNA-seq analysis further demonstrated downregulation of CD3G in T cells post-IS, disrupting immune cell communication and differentiation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study provides robust genetic evidence for CHIP-mediated predisposition to CES and identifies PARP1 and CD3G as critical therapeutic targets. The integration of machine learning and single-cell genomics offers novel insights into immune dysregulation in IS, paving the way for precision prevention strategies in CHIP patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70515","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144687895","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":"Uncovering the Associations of LILRB4 Genotypes With Parkinson's Disease: From Clinical Traits to Potential Pathologies","authors":"Yuting Zhou,&nbsp;Yaqing Li,&nbsp;Qiqing He,&nbsp;Zhen Kong,&nbsp;Ran Yu,&nbsp;Xin Yu,&nbsp;Anmu Xie","doi":"10.1111/cns.70522","DOIUrl":"https://doi.org/10.1111/cns.70522","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Leukocyte immunoglobulin-like receptor B4 (LILRB4) has been shown to be associated with susceptibility to neurodegenerative diseases. This study was aimed at investigating the relationships between &lt;i&gt;LILRB4&lt;/i&gt; and the risk of developing PD, as well as its clinical characteristics and pathology.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Method&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We analyzed 197 healthy controls and 606 PD patients from the Parkinson's Progression Marker Initiative (PPMI) study. The associations of &lt;i&gt;LILRB4&lt;/i&gt; loci with image data, CSF biomarkers, and clinical scales at baseline were assessed using multiple linear models.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Dopamine transporter (DAT)-SPECT results showed that the striatal binding ratios (SBR) in the right caudate (&lt;i&gt;β&lt;/i&gt; = 0.160, 95% CI = 0.076–0.244, &lt;i&gt;P&lt;/i&gt;&lt;sub&gt;c&lt;/sub&gt; = 0.002), right putamen (&lt;i&gt;β&lt;/i&gt; = 0.135, 95% CI = 0.057–0.214, &lt;i&gt;P&lt;/i&gt;&lt;sub&gt;c&lt;/sub&gt; = 0.009), anterior right putamen (&lt;i&gt;β&lt;/i&gt; = 0.156, 95% CI = 0.073–0.240, &lt;i&gt;P&lt;/i&gt;&lt;sub&gt;c&lt;/sub&gt; = 0.003) and left caudate (&lt;i&gt;β&lt;/i&gt; = 0.121, 95% CI = 0.038–0.2050, &lt;i&gt;P&lt;/i&gt;&lt;sub&gt;c&lt;/sub&gt; = 0.048) were positively associated with &lt;i&gt;LILRB4&lt;/i&gt;. Meanwhile, &lt;i&gt;LILRB4&lt;/i&gt; was associated with reductions in semantic fluency (&lt;i&gt;β&lt;/i&gt; = −2.135, 95% CI = −3.225 to 1.046, &lt;i&gt;P&lt;/i&gt;&lt;sub&gt;c&lt;/sub&gt; = 0.001) and impairments in nigrostriatal white matter (WM) microstructure as assessed by diffusion tensor imaging (DTI) (right rostral of substantia nigra (SN), &lt;i&gt;β&lt;/i&gt; = −0.026, 95% CI = −0.030 to 0.013, &lt;i&gt;P&lt;/i&gt;&lt;sub&gt;c&lt;/sub&gt; = 0.002; right middle SN, &lt;i&gt;β&lt;/i&gt; = −0.021, 95% CI = −0.033 to 0.009, &lt;i&gt;P&lt;/i&gt;&lt;sub&gt;c&lt;/sub&gt; = 0.012). These associations were more prominent in females (DAT in right caudate, &lt;i&gt;β&lt;/i&gt; = 0.246, 95% CI = 0.099–0.392, &lt;i&gt;P&lt;/i&gt;&lt;sub&gt;c&lt;/sub&gt; = 0.013; DTI in right middle of SN, &lt;i&gt;β&lt;/i&gt; = −0.025 95% CI = −0.040 to 0.010, &lt;i&gt;P&lt;/i&gt;&lt;sub&gt;c&lt;/sub&gt; = 0.021), but less pronounced in males (DAT in right caudate, &lt;i&gt;p&lt;/i&gt; = 0.036, &lt;i&gt;P&lt;/i&gt;&lt;sub&gt;c&lt;/sub&gt; = 0.396; DTI in right rostral of SN, &lt;i&gt;β&lt;/i&gt; = −0.025 95% CI = −0.041 to 0.008, &lt;i&gt;P&lt;/i&gt;&lt;sub&gt;c&lt;/sub&gt; = 0.021). Interestingly, in females, we also observed associations between &lt;i&gt;LILRB4&lt;/i&gt; and higher CSF α-synuclein levels (&lt;i&gt;β&lt;/i&gt; = 0.177, 95% CI = 0.062–0.292, &lt;i&gt;p&lt;/i&gt; = 3.280E−03, &lt;i&gt;P&lt;/i&gt;&lt;sub&gt;c&lt;/sub&gt; = 0.036) and worse cognitive performance (Activity of Daily Living scale, &lt;i&gt;β&lt;/i&gt; = −2.073, 95% CI = −3.446 to 0.699, &lt;i&gt;P&lt;/i&gt;&lt;sub&gt;c&lt;/sub&gt; = 0.025; Semantic Fluency test, &lt;i&gt;β&lt;/i&gt; = −2.508 95% CI = −4.255 to 0.761, &lt;i&gt;P&lt;/i&gt;&lt;sub&gt;c&lt;/sub&gt; = 0.032). Although our results suggested that dopamine and its metabolites, astrocyte markers, and inflammation-related molecules were associated with","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70522","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688023","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":"Age-Related Anatomical Changes in Carotid Artery Stenosis and Its Impact on Postoperative Complications in Stenting and Endarterectomy","authors":"Xiao Zhang,&nbsp;Jia Zhou,&nbsp;Renjie Yang,&nbsp;Jiaqi Jin,&nbsp;Yong Zeng,&nbsp;Shuaiwei Guo,&nbsp;Jiayao Li,&nbsp;Yixin Sun,&nbsp;Zixuan Xing,&nbsp;Shengyan Cui,&nbsp;Xinyu Yang,&nbsp;Xiangyu Li,&nbsp;Wenjing Li,&nbsp;Xiaoli Min,&nbsp;Liqun Jiao,&nbsp;Tao Wang","doi":"10.1111/cns.70527","DOIUrl":"https://doi.org/10.1111/cns.70527","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Carotid artery stenosis increases the risk of ischemic stroke, with carotid endarterectomy (CEA) and carotid artery stenting (CAS) as primary interventions. Age-related vascular changes may contribute to complications. This study aimed to evaluate the impact of age-related vascular changes on postoperative complications and procedural outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective cohort of 470 patients who underwent CAS or CEA from January 2020 to November 2021 was analyzed. Demographics, anatomical characteristics, and postoperative complications were assessed. Correlation, regression analyses, and machine learning models were applied to identify predictors of adverse outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Postoperative complications occurred in 64.9% of CAS and 75.2% of CEA patients. Older age correlated with larger CCA diameter, shorter clavicle-to-bifurcation distance, and increased tortuosity of both CCA and ICA. Several age-related anatomical changes were significantly linked to higher complication rates in both procedures. In CAS, key predictors included symptomatic stenosis, aortic arch variation, CCA ostial lesions, and CCA diameter (<i>p</i> &lt; 0.05). A logistic regression model predicted CAS complications effectively (AUC = 0.82).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study highlights significant age-related changes in carotid artery anatomy and their impact on postoperative complications. These findings underscore the importance of considering age-related vascular remodeling to enhance patient selection and optimize surgical outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 7","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70527","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688133","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}