CNS Neuroscience & Therapeutics最新文献

{"title":"Possible GABAkine-Mediated Sedative-Like Antidepressant Effects of Phytol: Molecular Interventions Through In Vitro, In Vivo and In Silico Approaches","authors":"Md. Torequl Islam,&nbsp;Jannatul Ferdous,&nbsp;Md. Sakib Al Hasan,&nbsp;Md. Shimul Bhuia,&nbsp;Irfan Aamer Ansari,&nbsp;Siddique Akber Ansari,&nbsp;Md. Amirul Islam,&nbsp;Md. Saifuzzaman","doi":"10.1111/cns.70350","DOIUrl":"10.1111/cns.70350","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>A previous report suggests that phytol (PHY) may exert its antidepressant effects in mice, possibly through GABA_A receptor interaction pathways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>We aimed to check its antidepressant effect with possible molecular mechanisms through behavioral and <i>in silico</i> studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>For this, adult mice were randomly divided into different groups (<i>n</i> = 6), namely control (vehicle), standards (DZP: diazepam at 2 mg/kg, FLU: flumazenil at 0.1 mg/kg, FLUX: fluoxetine at 20 mg/kg), PHY (25, 50, and 75 mg/kg), and combined groups (PHY-75 with DZP-2 and/or FLU-0.1, and FLUX-20). Thirty minutes after treatment, each animal was subjected to tail suspension and forced swimming tests, and their immobility time (IMT) was counted for 5 min. In silico studies were performed with the GABA_A receptor α1, α2, α3, α5, and γ2 subunits and 5HT_1A to investigate possible molecular mechanisms. Additionally, in vitro GABA activity of PHY and/or reference drugs was also performed by using the colorimetric method.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The results demonstrated that PHY and/or DZP significantly (<i>p</i> &lt; 0.05) and concentration-dependently inhibited GABA, while FLU alone or its combination with PHY reversed it. In mice, PHY dose-dependently reduced the IMT in both protocols, while FLUX-20 showed lower IMT compared to the control and DZP, indicating elevated locomotion in mice. It showed a reduced IMT value in male animals than in female animals. In both sexes, PHY at 75 mg/kg significantly (<i>p</i> &lt; 0.05) increased the IMT values with DZP-2, while reducing this parameter with FLU-0.1. <i>In silico</i> studies demonstrated that PHY exhibited higher binding affinities with the α2 and α3 subunits of the GABA_A and 5HT_1A receptors by −6.5, −7.2 and 6.7 kcal/mol, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Taken together, PHY exerted sedative-<i>like</i> antidepressant effects in mice and modulated the effects of GABAergic drugs DZP and FLU and serotonergic drug FLUX. PHY may be a potential candidate for the management of depression.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668586","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":"Asparagine Endopeptidase Inhibition Attenuates Tissue Plasminogen Activator-Induced Brain Hemorrhagic Transformation After Ischemic Stroke","authors":"Guanfeng Xie,&nbsp;Gege Jiang,&nbsp;Liqin Huang,&nbsp;Shangqi Sun,&nbsp;Xiaoyi Li,&nbsp;Bingjie Wu,&nbsp;Hualong Wang,&nbsp;Zhentao Zhang,&nbsp;Keqiang Ye,&nbsp;Ying Yu,&nbsp;Jing Xiong","doi":"10.1111/cns.70345","DOIUrl":"10.1111/cns.70345","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;Thrombolytic treatment with tissue plasminogen activator (tPA) is one of the approved pharmacological therapies for acute ischemic stroke. However, the use of tPA is limited due to hemorrhagic transformation (HT) and the narrow therapeutic time window. Previous studies demonstrated that asparagine endopeptidase (AEP), a widely expressed pH-dependent endo-lysosomal cysteine protease, can induce neuronal death during ischemia-reperfusion injury. But whether AEP is engaged in HT during ischemia-reperfusion injury is unclear. In the current study, we expanded the role of AEP on HT after delayed tPA administration.&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;In order to investigate the effects of AEP on HT after delayed tPA administration following ischemic stroke, the middle cerebral artery occlusion/reperfusion (MCAO/R) was performed in wild-type (WT) and AEP knockout (KO) transgenic mice, followed by delayed administration of tPA (10 mg/kg, 3 h after occlusion). Additionally, we explored the potential of R13, a specific TrkB agonist with a strong inhibitory impact on AEP, to mitigate injury induced by tPA. 24 h after tPA administration, the following parameters were assessed: infarct volume, behavioral tests, hemorrhagic levels, Evans blue leakage, tight and adherens junction protein expression, blood–brain barrier (BBB) function, cerebral vascular structure, matrix metalloproteinases (MMPs), and BBB-regulated protein low-density lipoprotein receptor-related protein 1 (LRP-1) expression. To construct an in vitro model to examine the effects of AEP on ischemia-reperfusion injury after tPA treatment, human umbilical vein endothelial cells (HUVECs) were exposed to 4 h of oxygen–glucose deprivation (OGD), followed by treatment with tPA (500 ng/mL). 7,8-dihydroxyflavone (7,8-DHF), a natural TrkB agonist with an inhibitory effect on AEP, was applied before OGD.&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;Compared with tPA-treated WT mice, AEP KO mice treated with tPA showed improved infarct volume, neurological function, brain edema, brain hemoglobin levels, Evans blue leakage, vascular tight junctions, and basement membrane structure combined with reduced AEP expression and activity within the peri-infarct area. In addition, the mice treated with R13 exhibited protective effects on the BBB. Furthermore, we found that the expression of MMP2, MMP9, and LRP-1 in the brain was inhibited by both AEP knockout and R13 treatment. Moreover, HUVECs treated with 7,8-DHF showed improvements in tight and adherens junction proteins and suppressed levels of MMP2, MMP9, and LRP-1.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 ","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668583","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":"Malignant Cells Beyond the Tumor Core: The Non-Negligible Factor to Overcome the Refractory of Glioblastoma","authors":"Yuyang Zhou,&nbsp;Qilin He,&nbsp;Guanglong Huang,&nbsp;Pei Ouyang,&nbsp;Hai Wang,&nbsp;Jiapeng Deng,&nbsp;Pengyu Chen,&nbsp;Xuan Liang,&nbsp;Zhisheng Hong,&nbsp;Xian Zhang,&nbsp;Songtao Qi,&nbsp;Yaomin Li","doi":"10.1111/cns.70333","DOIUrl":"https://doi.org/10.1111/cns.70333","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Glioblastoma (GBM) is one of the most aggressive primary brain tumors in adults. Over 95% of GBM patients experience recurrence in the peritumoral brain tissue or distant regions, indicating the presence of critical factors in these areas that drive tumor recurrence. Current clinical treatments primarily focus on tumor cells from the tumor core (TC), while the role of neoplastic cells beyond the TC has been largely neglected.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a comprehensive review of existing literature and studies on GBM, focusing on the identification and characterization of questionable cells (Q cells). Advanced imaging techniques, such as diffusion tensor imaging (DTI), magnetic resonance spectroscopy (MRS), and positron emission tomography (PET), were utilized to identify Q cells beyond the tumor core. We also analyzed the functional properties, cellular microenvironment, and physical characteristics of Q cells, as well as their implications for surgical resection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our review revealed that Q cells exhibit unique functional attributes, including enhanced invasiveness, metabolic adaptations, and resistance mechanisms. These cells reside in a distinct cellular microenvironment and are influenced by physical properties such as solid stress and stiffness. Advanced imaging techniques have improved the identification of Q cells, enabling more precise surgical resection. Targeting Q cells in therapeutic strategies could significantly reduce the risk of GBM recurrence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The presence of Q cells in the peritumoral brain zone (PBZ) and beyond is a critical factor in GBM recurrence. Current treatments, which primarily target tumor cells in the TC, are insufficient to prevent recurrence due to the neglect of Q cells. Future research should focus on understanding the mechanisms influencing Q cells and developing targeted therapies to improve patient outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70333","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143645719","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":"Acute Restraint Stress Induces Long-Lasting Synaptic Enhancement by Inhibiting AMPK Activation in AD Model Mice","authors":"Ming Wang,&nbsp;Baoyuan Jin,&nbsp;Jihoon Jo","doi":"10.1111/cns.70335","DOIUrl":"https://doi.org/10.1111/cns.70335","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Alzheimer's disease (AD) is characterized by a gradual synaptic loss. The progression of AD severely affects late-phase long-term potentiation (L-LTP), which is essential for long-term memory consolidation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>We have previously demonstrated the beneficial effects of acute restraint stress (ARS) on hippocampal LTP in AD mouse models. This study aimed to verify the effects and potential mechanisms of ARS on the maintenance of hippocampal L-LTP in two AD mouse models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>5xFAD and Tg2576 mice underwent a 30-min body immobilization protocol to induce ARS, followed by electrophysiological recordings of L-LTP (&gt; 3 h) in the CA1 region of thehippocampus.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The ARS-exposed group exhibited significantly enhanced L-LTP compared to the control group. Maintenance of L-LTP requires new protein synthesis and signaling via the mammalian target of rapamycin (mTOR) pathway. Our findings revealed that ARS increased hippocampal adenosine triphosphate (ATP) production and reduced AMPK activity. Inactivation of AMPK and subsequent activation of the mTOR pathway were strongly associated with the ARS-facilitated enhancement of L-LTP. Furthermore, our experiments using the mTOR inhibitor rapamycin demonstrated that it effectively prevented the enhancement of L-LTP following ARS, underscoring the pivotal role of mTOR in this process.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>ARS may significantly modify AMPK activation and mTOR regulation in L-LTP, potentially triggering the mechanisms of long-term memory consolidation in AD mouse model mice. Identifying these underlying mechanisms could help promote the development of novel pharmaceutical agents for the treatment of AD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70335","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646061","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":"Incidence, Characteristics, and Risk Factors of Post-Radiosurgery Headaches: A Prospective Observational Study","authors":"Shaobo Xiao,&nbsp;Jiayi Liu,&nbsp;Yunmo Liu,&nbsp;Guangshuang Lu,&nbsp;Yan Chang,&nbsp;Jinjing Zhao,&nbsp;Wenjie Su,&nbsp;Xinghao Guo,&nbsp;Nan Gao,&nbsp;Xiufen Zhang,&nbsp;Ke Liu,&nbsp;Zhen Zhang,&nbsp;Shengyuan Yu,&nbsp;Longsheng Pan,&nbsp;Ruozhuo Liu","doi":"10.1111/cns.70344","DOIUrl":"https://doi.org/10.1111/cns.70344","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This prospective observational study aimed to characterize the incidence, clinical features, and risk factors of headaches following CyberKnife radiosurgery (CKRS) in patients with intracranial pathologies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In a prospective observational study conducted from January 2022 to January 2023, we enrolled consecutive patients who underwent CKRS. Patients completed headache-related questionnaires developed based on the International Classification of Headache Disorders (ICHD-3) guidelines at 24 h, 1 week, and 3 months post-radiosurgery. The incidence of CKRS-related headaches was determined, and the link between risk factors and outcomes was analyzed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 153 patients (female 58.2%; mean age 47.7 ± 14.8 years), all completed a 3-month follow-up. Among 153 patients, 61 (39.9%) developed post-CKRS headaches, with 83.6% reporting peak intensity within 2 weeks post-procedure. Fifty (32.7%) developed headaches within 2 weeks, resolving within 3 months. A strong temporal association between headache onset and CKRS supports a causal relationship. Multivariate Cox regression analysis identified female sex (HR = 2.16, 95% CI = 1.14–4.11, <i>p</i> = 0.019), younger age (HR = 0.97 per year, <i>p</i> = 0.006), absence of prior craniocerebral surgery (HR = 0.55, <i>p</i> = 0.046), and multiple lesions (HR = 2.28, <i>p</i> = 0.047) as independent risk factors. Although headaches were more frequently observed following radiation targeting the basal ganglia and thalamus, this association lacked statistical significance (<i>p</i> &gt; 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Headaches attributed to brain radiosurgery constitute a significant yet overlooked clinical issue, warranting increased focus from surgical teams to deliver improved and tailored treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70344","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of TCD in Assessing Postoperative Collateral Development and Long-Term Clinical Outcome in Moyamoya Disease","authors":"Shuangfeng Huang,&nbsp;Songtao Pei,&nbsp;Yiqin Han,&nbsp;Jiali Xu,&nbsp;Lanjing Wang,&nbsp;Heguan Fu,&nbsp;Changhong Ren,&nbsp;Xunming Ji,&nbsp;Sijie Li,&nbsp;Cong Han","doi":"10.1111/cns.70245","DOIUrl":"https://doi.org/10.1111/cns.70245","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To explore the role of transcranial Doppler (TCD) parameters after encephaloduroarteriosynangiosis (EDAS) to identify collateral development in moyamoya disease (MMD) and assess the relationship between these collateral formations and long-term postoperative cerebrovascular events.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective analysis of 91 MMD patients who underwent EDAS. Patients were categorized into rich or poor collateral groups based on postoperative angiography. TCD was used to monitor changes in hemodynamic parameters pre-and post-surgery. The association between clinical outcome, TCD parameters, and the degree of collateral development was investigated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Outcomes</h3>\u0000 \u0000 <p>Ninety-one patients were assessed, with 45 (49.0%) exhibiting rich collaterals and 46 (51.0%) showing poor collaterals. Over 2 years, the rich collateral group experienced significantly fewer cerebrovascular events than the poor collateral group (<i>p</i> = 0.041). Postoperative evaluations demonstrated significant improvements in hemodynamic parameters within the rich collateral group, including increases in peak-systolic velocity (PSV), end-diastolic velocity (EDV), and mean velocity (MV), alongside decreases in resistance index (RI) and pulsatility index (PI) (<i>p</i> &lt; 0.05). An EDV cutoff of &gt; 16.62 cm/s in the superficial temporal artery (STA) effectively identified collateral development, yielding an area under the curve (AUC) of 0.907. Additionally, multivariate analysis revealed a strong association between preoperative MV of the STA and collateral formation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>TCD sonography is a non-invasive modality essential for assessing cerebral hemodynamics after revascularization in MMD. Collateral development shown on angiography corresponds to hemodynamic changes reflected in TCD. The postoperative EDV of the STA was a vital indicator of effective collaterals. Patients with well-developed collaterals were at a lower risk of long-term cerebrovascular events post-surgery.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70245","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646171","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":"Prevalence of Aspirin or Clopidogrel Pharmacological Resistance in Ischemic Stroke: A Step Toward Precision Medicine","authors":"Samantha Cencer,&nbsp;Laurel Packard,&nbsp;Alan Davis,&nbsp;Asad Ahrar,&nbsp;Malgorzata Miller,&nbsp;Nadeem Khan,&nbsp;Nabil Wees,&nbsp;Jiangyong Min","doi":"10.1111/cns.70343","DOIUrl":"https://doi.org/10.1111/cns.70343","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Objectives</h3>\u0000 \u0000 <p>Currently, there is not sufficient data regarding the prevalence of resistance or inadequate platelet function inhibition with the use of antiplatelet therapy in patients with noncardioembolic stroke. This study was designed to evaluate the prevalence of antiplatelet inactivity to aspirin and clopidogrel in the setting of chronic use and presentation with primary or recurrent stroke.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients who were taking aspirin, clopidogrel, or both at the time of presentation for stroke were selected in this study. Those with confirmed stroke on MRI or clinically determined TIA and age &gt; 18 years were included. A standard laboratory test, VerifyNow aspirin or P2Y12 assay, was utilized to assess the responsiveness to the platelet inhibitors. A total of 158 patients were identified, 52 presenting with primary stroke and 106 with recurrent stroke. Data were analyzed using chi-squared or Fisher's exact as well as <i>t</i>-test analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of the primary stroke population, 4% of patients demonstrated resistance to aspirin and 30% to clopidogrel. Of the patients presenting with recurrent stroke, 13% demonstrated resistance to aspirin and 38% to clopidogrel. The data also suggest increased resistance to aspirin and clopidogrel in Caucasians compared to minorities, with 11% versus 8% in regard to aspirin and 33% versus 17% to clopidogrel. Additionally, this study demonstrated 17% resistance to aspirin in males compared to 4% in females and 13% in males compared to 36% in females, respectively, regarding resistance to clopidogrel. No difference in inactivity to either aspirin or clopidogrel was detected between patients with stroke mechanisms of small or large vessel disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The present result demonstrated that a sizeable portion of the population has inefficacious activity in the setting of specific antiplatelet agents. Additionally, sex and ethnicity differences in responsiveness to aspirin or clopidogrel have been noted. Determining a patient's response to medications could provide opportunities to individualize treatment and better prevent future strokes. Further studies of a larger scale are indeed needed to apply this information to pursue individualized treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70343","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143638907","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":"Quantitative EEG Insights Into A Hundred Adult ADHD Patients: A Deep Dive Into Test of Variables of Attention (TOVA) Correlations and Attention Dynamics","authors":"Elvan Ciftci,&nbsp;Zeynep Betul Alp","doi":"10.1111/cns.70304","DOIUrl":"https://doi.org/10.1111/cns.70304","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This study aimed to enhance the diagnostic accuracy of attention-deficit/hyperactivity disorder (ADHD) by integrating quantitative electroencephalography (qEEG) power bands with the test of variables of attention (TOVA) and self-reported psychiatric symptoms. We examined the relationship between TOVA scores, qEEG findings—particularly the theta-beta ratio—and comorbid psychiatric conditions to assess their role in refining ADHD diagnoses according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V).&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;A total of 100 participants were assessed using TOVA, qEEG, and psychological scales, including the Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), Maudsley Obsessive-Compulsive Inventory (MOCI), and the Mood Disorder Questionnaire (MDQ). Participants were categorized into groups based on their Attention Comparison Scores (ACS) above or below the zero threshold. Mann–Whitney &lt;i&gt;U&lt;/i&gt;-tests, correlation analyses, and predictive modeling using automatic linear modeling (ALM) were conducted to evaluate group differences, age-related changes, and predictor variables for attention performance.&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;All participants met the diagnostic criteria for ADHD. Among them, 37% exhibited anxiety, 60% depression, 26% obsessive-compulsive, and 35% mood disorder symptoms. The group with ACS above zero was significantly older (&lt;i&gt;p&lt;/i&gt; = 0.034) and performed better on all Tests of Variables of Attention (TOVA) measures (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). Age negatively correlated with attention scores (&lt;i&gt;r&lt;/i&gt; = −0.371, &lt;i&gt;p&lt;/i&gt; &lt; 0.001), response time variability (&lt;i&gt;r&lt;/i&gt; = −0.241, &lt;i&gt;p&lt;/i&gt; = 0.016), and response time (&lt;i&gt;r&lt;/i&gt; = −0.311, &lt;i&gt;p&lt;/i&gt; = 0.002). qEEG showed significant age-related changes in theta-to-beta and delta-to-beta ratios (&lt;i&gt;p&lt;/i&gt; &lt; 0.005). TOVA and qEEG ratios, particularly beta and delta activity, predicted attention and response time variability, with adjusted &lt;i&gt;R&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; values between 71.5% and 87.1%.&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;The findings highlight that attention performance in ADHD is shaped by age, neuropsychological factors, and qEEG-measured brain activity. Higher attention scores correlate with better TOVA results, particularly in response time and error rates. Age-related declines in attention align with reductions in theta-to-beta and delta-to-beta ratios. Predictive modeling underscores the value of combining TOVA and qEEG to identify key pred","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70304","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of Repetitive Transcranial Magnetic Stimulation of the Dorsolateral Prefrontal Cortex on the Amyotrophic Lateral Sclerosis Patients With Cognitive Impairment: A Double-Blinded, Randomized, and Sham Control Trial","authors":"Wensi Zheng,&nbsp;Xiaojie Zhang,&nbsp;Jingjiong Chen,&nbsp;Xinghua Luan,&nbsp;Jijun Wang,&nbsp;Liren Zhang,&nbsp;Kun Liu,&nbsp;Yuwu Zhao,&nbsp;Zhouwei Xu","doi":"10.1111/cns.70316","DOIUrl":"https://doi.org/10.1111/cns.70316","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease. A large number of ALS patients have cognitive impairment. In this double-blinded, randomized, and sham-controlled study, we aimed to investigate the effect of repetitive transcranial magnetic stimulation (rTMS) on ALS patients with cognitive impairment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 90 ALS patients with cognitive impairment were recruited from two cohorts; 80 participants were randomly assigned in a 1:1 ratio to receive 10 Hz rTMS or sham treatment on the bilateral dorsolateral prefrontal cortices (DLPFC) for 4 consecutive weeks. The patients were assessed by ECAS and ALSFRS-R scales. The Zarit care burden scale was administered to caregivers of ALS patients. The primary outcome measured was the rate of decline in the total ECAS score between pretreatment, 6 months post-treatment, and 12 months post-treatment. Secondary outcomes included the group difference in the slope of the Zarit score, ALSFRS-R total score, and the neurofilament light chain plasma levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The ECAS total score in the intention-to-treat population significantly changed from 79.74 ± 6.39 to 81.98 ± 6.51 and 79.22 ± 6.50 with rTMS intervention at the 6-month and 12-month follow-ups, respectively (<i>p</i> = 0.031, <i>p</i> = 0.042). The Zarit score also significantly decreased from 57.65 ± 3.42 to 52.24 ± 3.34 and 56.42 ± 3.41 at the 3-month and 6-month post-treatment time points, respectively (<i>p</i> = 0.003, <i>p</i> = 0.014). No significant differences were observed between the groups for other secondary endpoints. However, there was a trend of decreasing NF-L level rates in the treatment group over the first 6 months' follow-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>rTMS could yield short-term positive effects on the ALS patients subgroup with cognitive impairment and alleviate caregivers' burden. No improvement was observed in the severity of ALS and ALS plasma biomarkers.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70316","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639118","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":"Intranasal Administration of a Novel ApoE-Mimetic Peptide-Coated Gold Nanoparticles as Therapy for Ischemic Stroke","authors":"Ming-Yan Yang,&nbsp;Ya-Wen Yu,&nbsp;Da-Lei Li,&nbsp;Teng Liu,&nbsp;Zhi-Xia Wang,&nbsp;Bai-Fang Gong,&nbsp;Xin-Xin Bai,&nbsp;Ya-Ping He,&nbsp;Hai-Yue Liang,&nbsp;Hua-Ying Fan","doi":"10.1111/cns.70263","DOIUrl":"https://doi.org/10.1111/cns.70263","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Discovering new drugs for ischemic stroke is an effective intervention that may address the significant unmet clinical need of stroke. There is increasing evidence indicating that apolipoprotein E (ApoE) can be a potential candidate for the treatment of ischemic stroke. A short ApoE peptide could maintain the anti-inflammation and neuroprotection of the intact protein. Herein, we synthetized a novel ApoE memetic peptide, referred to as CS15, and explored its efficacy and neuroprotection of its innovative formulation of gold nanoparticles (GNPs) in transient focal ischemia in rat.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We examined anti-inflammatory activities of CS15 using LPS-induced inflammatory response in BV2 cells and in mice. GNPs were prepared by citrate reduction method and surface modified with CS15 to generate CS15-coated GNPs (CS15-GNPs). The accumulation and distribution of CS15-GNPs in the brain were confirmed by detecting the gold amount and fluorescent intensity. The neuroprotection of CS15 and CS15-GNPs was evaluate using middle cerebral artery occlusion (MCAO) model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The results showed that CS15 exhibited more potent anti-inflammation than COG1410. GNPs are capable of transporting CS15 to the brain, expanding its duration of action. Intranasal administration of CS15-GNPs notably reduced infarct size and neuronal damage, improved neurological function and inhibited cerebral inflammation in transient focal ischemia in rat, which had much higher efficiency than free CS15.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>CS15-GNPs exhibited favorable neuroprotection and biosafety. This study develops an innovative ApoE-mimetic peptide-capped GNPs, which provides a potential strategy for the treatment of ischemic stroke.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70263","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646038","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}