CNS Neuroscience & Therapeutics最新文献

{"title":"Association Between Argatroban and Outcomes of Branch Atheromatous Disease: A Propensity-Matched Analysis From MRI-Based Study","authors":"Shengde Li,&nbsp;Haizhou Hu,&nbsp;Yaping Zhou,&nbsp;Ping Zhang,&nbsp;Guofang Chen,&nbsp;Hongying Bai,&nbsp;Bin Liu,&nbsp;Lixin Zhou,&nbsp;Yicheng Zhu,&nbsp;Bin Peng,&nbsp;Jun Ni,&nbsp;BAD-study investigators","doi":"10.1111/cns.70467","DOIUrl":"https://doi.org/10.1111/cns.70467","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Purpose</h3>\u0000 \u0000 <p>Argatroban is widely used for patients with acute branch atheromatous disease (BAD)-related stroke, but its efficacy remains unclear. This study aims to evaluate its clinical outcomes in this patient population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A prospective, MRI-based cohort (BAD-study) was conducted across 20 hospitals in China from June 2021 to June 2023, enrolling patients aged 18–80 years with BAD-related stroke within 72 h of onset. Patients were divided into two groups: Argatroban and non-argatroban. The primary outcome was an excellent outcome, defined as a modified Rankin Scale (mRS) score of 0–1 at 90 days. Secondary outcomes included good outcome (mRS 0–2), mRS score, Barthel Index score at 90 days, and NIHSS score at 7 days. Logistic regression analyses were performed to assess the association between argatroban and outcomes after propensity score matching (PSM).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 467 patients were included, with a median age of 60 years and a median NIHSS score of 4 at admission. Eighty-six patients (18.4%) were in the argatroban group, and 381 patients (81.6%) were in the non-argatroban group. After PSM, excellent outcomes occurred in 60.0% of the argatroban group and 64.2% of the non-argatroban group (odds ratio [OR] = 0.84, 95% CI: 0.47–1.49, <i>p</i> = 0.542). Argatroban was not significantly associated with secondary outcomes and remained ineffective in sensitivity analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Argatroban was not associated with excellent outcome at 90 days in patients with acute BAD-related stroke. Our study suggests that the risks and benefits of argatroban need reevaluation in patients with BAD-related stroke.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70467","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144308942","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":"Dopaminergic Neuron-Derived AIMP1 Promotes Neurodegeneration via CD23-Dependent Microglial Activation","authors":"Qinqin Wang,&nbsp;Hao Yu,&nbsp;Xunan Yuan,&nbsp;Ruolin Li,&nbsp;Xuezhi Li,&nbsp;Shu Yin,&nbsp;Xiaodan Ma,&nbsp;Xinmiao Wang","doi":"10.1111/cns.70472","DOIUrl":"https://doi.org/10.1111/cns.70472","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Parkinson's disease (PD), the second most prevalent age-associated neurodegenerative disorder, is characterized by the degeneration and loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SN). Among the intricate pathophysiological processes of PD, chronic neuroinflammation has emerged as a pivotal hallmark in the pathogenesis of PD. The aminoacyl tRNA synthetase complex has been reported to play an important role in modulating the immune response and associated diseases. Nevertheless, the specific functions and implications of the complex in PD remain largely unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Enzyme-linked immunosorbent assay (ELISA) was used to investigate levels of AIMP1 and TNF-α. An in vivo PD model was constructed by administering 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice. A PD cell model was established by treating SH-SY5Y cells with 1-methyl-4-phenylpyridinium (MPP⁺). Pole test was performed to assess the motor function of mice. DA neuron survival and microglia activation were detected by immunofluorescence. Western blot and qPCR were used to detect the levels of tyrosine hydroxylase (TH) and inflammatory cytokines. RNA-Seq analysis was performed to explore possible mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The levels of AIMP1, a co-factor of the aminoacyl tRNA synthetase complex, were significantly elevated in the blood of PD patients. <i>Aimp1</i> knockout or knockdown remarkably improved the viability of DA neurons in the MPTP-induced mouse model of PD. <i>Aimp1</i> deficiency reduced microglial activation in PD mice. RNA-Seq analysis revealed that AIMP1 promoted microglial inflammatory response. Moreover, the AIMP1-induced microglial activation was CD23 dependent.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Collectively, our findings indicate that AIMP1 derived from DA neurons exacerbates neuroinflammation, promotes the death of DA neurons and contributes to the development of PD. This study offers novel insights into the molecular mechanisms underlying PD and blocking the AIMP1-CD23 signaling pathway potentially serves as a therapeutic strategy for PD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70472","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292256","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":"Role of MS4A7 in Regulating Microglial Polarization and Neuroinflammation in Spinal Cord Injury via the cGAS-STING-NLRP3 Axis","authors":"Xiangrui Li,&nbsp;Junpeng Liu,&nbsp;Youliang Deng,&nbsp;Fang Xing,&nbsp;Xihua Lu,&nbsp;Zhen Zhang,&nbsp;Changsheng Li","doi":"10.1111/cns.70390","DOIUrl":"https://doi.org/10.1111/cns.70390","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background and Objectives&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Spinal cord injury (SCI) leads to debilitating neurological deficits primarily due to the inflammatory response triggered by secondary injury mechanisms. Microglial activation and polarization significantly influence this response, with pro-inflammatory (M1) polarization exacerbating damage and anti-inflammatory (M2) polarization promoting repair. MS4A7, a membrane-bound protein involved in immune regulation, has been implicated in inflammation, but its role in SCI remains unexplored. This study investigates the function of MS4A7 in modulating microglial polarization and its downstream effects on the inflammatory response in SCI, focusing on the cGAS-STING-NLRP3 axis.&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;A combination of in vivo and in vitro approaches, including mouse SCI models and BV2 microglial cells, was employed. Differential gene expression analysis was conducted using the GSE93561 dataset. MS4A7 expression was modulated using shRNA and overexpression plasmids. Microglial polarization was assessed via immunofluorescence, RT-qPCR, and ELISA for M1 (iNOS, IL-1β, TNF-α) and M2 (Arg1, IL-10, CD206) markers. Pyroptosis and inflammasome activation were examined using PI staining, LDH release, and NLRP3/GSDMD assays. The role of the cGAS-STING pathway was evaluated using activators (diABZI) and inhibitors (C-176), and NLRP3 inflammasome activity was pharmacologically inhibited with MCC950.&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;MS4A7 was significantly upregulated in SCI tissues (&lt;i&gt;p&lt;/i&gt; &lt; 0.01). Knockdown of MS4A7 reduced M1 markers (iNOS, IL-1β, and TNF-α) and increased M2 markers (Arg1, IL-10, and CD206), promoting anti-inflammatory polarization (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). Conversely, MS4A7 overexpression enhanced M1 polarization and pyroptosis through the NLRP3 inflammasome. In vivo, MS4A7 knockdown improved locomotor recovery (BMS score, &lt;i&gt;p&lt;/i&gt; &lt; 0.05) and alleviated pain-related behaviors (PWL and PWT, &lt;i&gt;p&lt;/i&gt; &lt; 0.01). The cGAS-STING pathway mediated NLRP3 activation, with pharmacological inhibition mitigating pro-inflammatory effects and favoring tissue repair.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;In this study, we found that MS4A7 exacerbates inflammation and promotes M1 polarization via the cGAS-STING-NLRP3 axis in SCI. Targeting MS4A7 and its associated pathways offers potential therapeutic strategies to mitigate neuroinflammation and enhance recovery. These findings provide new insights into the molecular mechanisms underlying SCI pathophysiology an","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70390","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292255","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":"mGluR5 in Pyramidal Neurons in the Hippocampus Mediates Chronic Stress-Induced Memory Deficits","authors":"Hong-Cheng Lu,&nbsp;Zhuo-Jun Du,&nbsp;Hao Chen,&nbsp;Ting Guo,&nbsp;Shu-Cai Yang,&nbsp;Xin Li","doi":"10.1111/cns.70477","DOIUrl":"https://doi.org/10.1111/cns.70477","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Chronic stress causes variable profiles of physiological deficits, including mood disorders, sleep disorders, and memory deficits. However, the neural mechanisms and potential drug targets of chronic stress-induced memory deficit remain elusive.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study aimed to explore the function and regulatory mechanisms of metabotropic glutamate receptor 5 (mGluR5) in chronic stress-induced memory deficit and investigate the potential therapeutic target for stress-related memory deficit.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Behavioral tests were used to assess the effects of chronic stress on memory. Electrophysiological recordings were conducted to examine the synaptic inputs after chronic stress. RNA sequencing was employed to achieve transcriptional alterations in the hippocampus after stress or mGluR5 knockdown. Enrichment analysis was performed to identify the downstream effector of chronic stress-induced memory deficits.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Chronic restraint stress (CRS) impairs hippocampal-dependent memory and electrophysiological recordings reveal that chronic stress impairs synaptic inputs. Subsequently, we observe that the mGluR5 level declines after CRS, which is an important molecule for learning and memory. mGluR5 knockdown induces memory deficits and impairs synaptic inputs. Enhancement of mGluR5 activity by CDPPB could restore chronic stress-induced memory deficits and rescue impaired synaptic inputs. Furthermore, we identify that pituitary adenylyl cyclase activating peptide (PACAP) is down-regulated after CRS and mGluR5 knockdown. PACAP application could restore the impaired inhibitory synaptic inputs after CRS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These results illuminate that the mGluR5 mediates chronic stress-induced memory deficits, which may provide promising strategies for treating stress-related memory deficits.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70477","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144273199","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":"5-HT7R Deficiency Alleviates ADP-Heptose-Induced Cognitive Impairment via Inhibiting Ferroptosis and Neuroinflammation in Mice","authors":"Xiao Zou,&nbsp;Yu-Xin Yang,&nbsp;Bing-Jie Yue,&nbsp;Han-Yinan Yang,&nbsp;Yan-Rong Yang,&nbsp;Meng-Yang Li,&nbsp;Ou Du,&nbsp;Gan Qiao,&nbsp;Yi-Jin Wu,&nbsp;Jun-Rong Du,&nbsp;Fang-Yi Long","doi":"10.1111/cns.70455","DOIUrl":"https://doi.org/10.1111/cns.70455","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>ADP-heptose (ADP-hep), a soluble intermediate in the biosynthesis of lipopolysaccharide in Gram-negative bacteria, is known to trigger inflammation. Our research suggests that 5-hydroxytryptamine receptor 7 (5-HT₇R) could serve as a potential pattern recognition receptor (PRR) for ADP-hep, yet the precise mechanism of ADP-hep's regulation on 5-HT₇R remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Based on the results of mRNA sequencing analysis, this study took ferroptosis of neurons and microglia as a starting point to explore the role and underlying mechanisms of ADP-hep/5-HT₇R signaling in mediating neuroinflammation and cognitive impairment in mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that 5-HT₇R may act as a potential PRR for ADP-hep and potentially bind to ADP-hep. 5-HT₇R deficiency significantly ameliorated cognitive dysfunction induced by ADP-hep in mice, as well as ferroptosis mediated by the p53/cystine-glutamate antiporter (xCT)/glutathione peroxidase 4 (GPX4) signaling pathway and its associated key markers. Furthermore, 5-HT₇R deficiency inhibited ferroptosis in neurons and M2-type microglia, mitigated the decline in the proportion of M2-type microglia, and subsequently suppressed the inflammatory microenvironment to promote neuronal survival, thereby exerting neuroprotective effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In summary, 5-HT₇R deficiency promotes cognitive recovery by alleviating the neuronal and microglial ferroptosis triggered by ADP-hep, subsequently dampening the inflammatory microenvironment to support neuronal viability. These findings provide a novel perspective and approach for the development of innovative therapeutic strategies for the treatment of cognitive impairment-related diseases.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70455","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264625","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":"Efficacy and Safety of Hormone Replacement Combined With Escitalopram in the Treatment of Chronic Insomnia in Perimenopausal Women: A Randomized Controlled Trial","authors":"Hui Chen,&nbsp;Shufang Wu,&nbsp;Hongbin Chen,&nbsp;Guiying Zeng,&nbsp;Weiwei Wu,&nbsp;Xinyan Chen,&nbsp;Xiujuan Chen,&nbsp;Ronghua Chen,&nbsp;Yingchun Xiao","doi":"10.1111/cns.70470","DOIUrl":"https://doi.org/10.1111/cns.70470","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To explore the efficacy of Femoston plus escitalopram for perimenopausal women with chronic insomnia and the relevant biomarkers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 166 patients randomly received: escitalopram plus placebo (Escitalopram Group), Femoston plus placebo (Hormone Group), and Femoston plus escitalopram (Combined Group) for 3 months and followed for 2, 4, 8, and 12 weeks. The primary efficacy endpoint was changes in Pittsburgh Sleep Quality Index Scale (PSQI), Insomnia Severity Index Scale (ISI), and Epworth Sleepiness Scale (ESS) scores at week 12 from baseline. Secondary endpoints included changes in the Modified Kupperman Menopausal Index Scale (KMI) scores, blood 5-HT neurotransmitters and their receptor, and blood sex hormone levels during the treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared with baseline levels, all groups displayed increased serum 5-HT levels and decreased serum FSH levels, with more significant changes in the combined group. Compared with the other two groups, the combined group reported a gradual increase in serum E2 levels and a gradual decrease in serum LH levels, and the lowest KMI, ESS, ISI, and PSQI scores at weeks 4 and 12. The PSQI score was negatively correlated with serum 5-HT and E2 and positively correlated with serum FSH and LH levels, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Femoston plus escitalopram improves chronic insomnia in perimenopausal women. Serum levels of 5-HT, E2, FSH, and LH may objectively indicate the clinical severity of chronic insomnia in this population.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70470","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144273198","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":"Task-Evoked Theta Oscillation Dysregulation Underlies Attention Network Deficits in Left Temporal Lobe Drug-Resistant Epilepsy","authors":"Changqing Zhan,&nbsp;Qiao Wang,&nbsp;Wenyu Wang,&nbsp;Na Pan,&nbsp;Jieju Feng,&nbsp;Zonghan Yang,&nbsp;Shizao Fei,&nbsp;Zongsheng Chen,&nbsp;Yingnian Chen","doi":"10.1111/cns.70450","DOIUrl":"https://doi.org/10.1111/cns.70450","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study investigated the neural mechanisms of left temporal lobe drug-resistant epilepsy (DRE) with attention network dysfunction using the attention network test (ANT) and synchronous electroencephalography (EEG).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study enrolled three cohorts: 20 patients with left temporal lobe drug-resistant epilepsy (DRE group), 20 left temporal lobe drug-sensitive epilepsy (DSE group) patients, and 20 age-/sex-matched healthy controls (Ctrl group). Participants completed standardized ANT tasks while scalp EEG was recorded at a 1000 Hz sampling rate. We computed power spectral density (PSD) of neural oscillations from ANT-task EEG epochs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>DRE patients exhibited significantly impaired network efficiency across executive control (EC), alerting, and orienting networks. Compared to the Ctrl group, both DRE and DSE groups demonstrated reduced frontal theta PSDs in EC, alerting, and orienting networks (all <i>p</i> &lt; 0.001), with the DRE group showing greater deficits than the DSE group in the EC network (<i>p</i> &lt; 0.001). Additionally, Significant correlations emerged between frontal theta PSD and behavior in Ctrl (EC_{_effect}: <i>r</i> = −0.659, <i>p</i> = 0.002; Alerting_{_effect}: <i>r</i> = 0.690, <i>p</i> = 0.001; Orienting_{_effect}: <i>r</i> = 0.649, <i>p</i> = 0.002) and DSE (EC_{_effect}: <i>r</i> = −0.595, <i>p</i> = 0.006; Alerting_{_effect}: <i>r</i> = 0.592, <i>p</i> = 0.006; Orienting_{_effect}: <i>r</i> = 0.588, <i>p</i> = 0.006). In the DRE group, however, The theta band PSDs of the attention network show no significant correlation with behavioral response effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Drug-resistant epilepsy patients have dysfunctional attention network behavior and decreased theta band PSDs in the frontal lobe. It is possible that decreased theta oscillations in the frontal lobe may contribute to ANT behavior dysfunction in drug-resistant epilepsy patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70450","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264420","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":"Clinical and Functional Connectivity Markers in Prediction of Hallucinations in Parkinson's Disease","authors":"Guanglu Li,&nbsp;Mengxue Jiang,&nbsp;Xin Chen,&nbsp;Panpan Hu,&nbsp;Jun Liu,&nbsp;Kai Wang","doi":"10.1111/cns.70432","DOIUrl":"https://doi.org/10.1111/cns.70432","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Longitudinal studies addressing the predictive value of brain network connectivity in PD hallucinations are lacking. This study investigated whether functional connectivity markers could predict PD hallucinations independently of clinical markers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study used data from the Parkinson's Progression Marker Initiative, a longitudinal multicenter study that aims to identify biomarkers of PD progression. One hundred and three newly diagnosed PD patients (mean age 63.10 ± 9.70 years, 65 males) underwent clinical assessments and functional MRI scanning at baseline. Independent component analysis was used to explore intra-network and inter-network functional connectivity differences between PD patients who developed hallucinations and those who did not during the 2-year follow-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Twenty patients developed hallucinations during the follow-up. At baseline, significantly decreased connectivity within the dorsal attention network (<i>t</i> = −6.65 ~ −4.90, <i>p</i> &lt; 0.05, FWE corrected) and increased connectivity within the default mode network (<i>t</i> = 6.16 ~ 7.78, <i>p</i> &lt; 0.05, FWE corrected) were detected in PD patients who developed hallucinations compared to those who did not. Additionally, PD patients with hallucinations exhibited significantly decreased functional connectivity between the dorsal attention network and the visual network at baseline (<i>t</i> = −3.31, <i>p</i> = 0.02, FWE corrected). Binary regression analysis revealed that significant predictors of PD hallucinations included the presence of EDS (OR = 6.928, <i>p</i> = 0.022), the presence of autonomic dysfunction (OR = 6.531, <i>p</i> = 0.012), FC within the DMN (OR = 5.587, <i>p</i> = 0.006), FC within the DAN (OR = 0.217, <i>p</i> = 0.041), and FC between the DAN and VIS (OR = 0.004, <i>p</i> = 0.019) at baseline.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The findings provide evidence that disrupted brain network connectivity is associated with a greater risk of future hallucinations in PD. This may aid in the early identification of PD patients at risk of hallucinations and provide a basis for the development of new therapies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70432","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144245028","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":"Free Water-Corrected Fractional Anisotropy in Normal-Appearing White Matter as a Potential Neuroimaging Biomarker for Attention and Executive Function Impairment in Cerebral Small Vessel Disease","authors":"Qingyang Fu,&nbsp;Yage Qiu,&nbsp;Ying Hu,&nbsp;Yuanzheng Wang,&nbsp;Yao Wang,&nbsp;Wentao Hu,&nbsp;Qun Xu,&nbsp;Yawen Sun,&nbsp;Yan Zhou","doi":"10.1111/cns.70475","DOIUrl":"https://doi.org/10.1111/cns.70475","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To investigate the relationship between white matter integrity changes and attention/executive function in cerebral small vessel disease (CSVD), focusing on tract-specific alterations over stages and identifying key neuroimaging markers affecting cognitive decline.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 170 CSVD patients, including 103 Vascular Cognitive Impairment (VaMCI) and 67 with no cognitive impairment (NCI) underwent MRI and neuropsychological assessments. Neuroimaging metrics included quantitative susceptibility (QS), free water (FW), FW-corrected fractional anisotropy (FAt) and FW-corrected mean diffusivity (MDt) in white matter hyperintensities (WMH) and normal-appearing white matter (NAWM). WMH volume, gray/white matter volume, lacunar infarcts (LI) volume and counts were also included. Partial correlations were conducted to assess neuroimaging-cognition relationships, and random forest analysis was employed to determine the relative importance of these indices, with a particular focus on white matter tracts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The VaMCI group exhibited decreased NAWM FAt and white matter volume, increased NAWM QS, WMH volume, LI volume and counts when compared to the NCI group. NAWM/WMH FAt positively associated with attention/executive function, whereas NAWM/WMH QS, FW, MDt, WMH volume, and LI metrics negatively correlated. Notably, NAWM FAt was the most significant variable, especially in frontal white matter tracts and thalamic radiation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>NAWM FAt significantly impacts attention/executive function in CSVD, particularly in the frontal lobe and thalamic radiation, and may serve as an early potential neuroimaging biomarker for cognitive decline.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70475","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144245009","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":"Dual Roles of Autophagy in Radiation-Induced Brain Injury: Mechanistic Insights and Therapeutic Implications","authors":"Jiayu Tian,&nbsp;Yanna Mao,&nbsp;Dandan Liu,&nbsp;Tao Li,&nbsp;Lihuan Shi,&nbsp;Yafeng Wang,&nbsp;Changlian Zhu","doi":"10.1111/cns.70464","DOIUrl":"https://doi.org/10.1111/cns.70464","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cranial radiotherapy, while essential for treating brain tumors, often leads to radiation-induced brain injury, a debilitating condition marked by cognitive decline and neuronal damage. Autophagy, a key cellular process for recycling damaged organelles and proteins, has emerged as both a protective and detrimental player in radiation-induced brain injury.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This review systematically explores the dualistic role of autophagy in radiation-induced brain injury, synthesizing insights on its interplay with apoptosis, ferroptosis, neuroinflammation, oxidative stress, the blood–brain barrier, mitophagy, endoplasmic reticulum stress, and mitochondrial biogenesis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>While autophagy supports neuronal resilience by mitigating oxidative and inflammatory stress, excessive or dysregulated autophagy can lead to autophagic cell death and exacerbate injury. Pharmacological modulators such as mTOR inhibitors, AMP-activated protein kinase activators, demonstrate therapeutic potential in preclinical settings.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>By elucidating the mechanistic underpinnings of autophagy in radiation-induced brain injury, this review underscores its dual roles and therapeutic relevance, offering a foundation for targeted interventions that optimize autophagic balance to protect brain function postradiotherapy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70464","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144245010","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}