CNS Neuroscience & Therapeutics最新文献

{"title":"High-Frequency rTMS Improves Visual Working Memory in Patients With aMCI: A Cognitive Neural Mechanism Study","authors":"Meng Liu, Ren Ren-Li, Jin Nan Sun, Janelle S. Y. Yeo, Jing Ma, Jia-Xin Yan,  BuMaYiLaMu-XueKeEr, Zhao-Xi Tu, Yun-Xia Li","doi":"10.1111/cns.70301","DOIUrl":"https://doi.org/10.1111/cns.70301","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Visual working memory (VWM), which is an essential component of higher cognitive processes, declines with age and is associated with the progression from amnestic mild cognitive impairment (aMCI) to Alzheimer's disease (AD). Cognitive impairment, particularly in VWM, is prominent in aMCI and may indicate disease progression. This study investigates the cognitive neural mechanisms responsible for VWM impairment in aMCI, with a focus on identifying the VWM processing stages affected. The study targets the dorsolateral prefrontal cortex (DLPFC) for repetitive transcranial magnetic stimulation (rTMS) to investigate its influence on VWM in aMCI patients. The role of the DLPFC in the top-down control of VWM processing is central to understanding rTMS effects on the stages of information processing in aMCI-related VWM impairments.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A 7-day rTMS intervention was performed in 25 aMCI patients and 15 healthy elderly controls to investigate its effects on VWM and cognitive functions. Tasks included VWM change detection, digital symbol transformation, and the Stroop task for attention and executive functions. EEG analyses consisting of ERP, ERSP, and functional connectivity (wPLI) were integrated. The first part of the study addressed the cognitive neural mechanism of VWM impairment in aMCI and differentiated the processing stages using EEG. The second part investigated the effects of rTMS on EEG processing at different VWM stages and revealed cognitive neural mechanisms that improve visual working memory in aMCI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The results indicated a significant deterioration of VWM tasks in aMCI, especially in accuracy and memory capacity, with prolonged reaction time and increased duration of the Stroop task. In the VWM memory encoding phase, N2pc amplitude, α-oscillation in the parieto-occipital region, and θ-band synchronization in the frontoparietal connectivity decreased. Conversely, rTMS improved N2pc amplitude, α-oscillation, and θ-band synchronization, which correlated with improved frontoparietal connectivity, parieto-occipital α-oscillation, and attentional capacity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Patients with aMCI experience significant deterioration in VWM function, particularly during the encoding phase. This deterioration manifests in reduced accuracy and capacity of memory performance, accompanied by a significant decrease in N2pc amplitude, alpha oscillations, and theta-band connectivity in frontoparietal an","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70301","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690105","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":"A Novel Compound QO-83 Alleviates Acute and Chronic Epileptic Seizures in Rodents by Modulating KV7 Channel Activity","authors":"Xiangyu Wang,&nbsp;Yang Zhang,&nbsp;Hui Liu,&nbsp;Jiahao Wang,&nbsp;Boxuan Zhang,&nbsp;Tenghui He,&nbsp;Huiran Zhang,&nbsp;Zhumei Xiong,&nbsp;Xingang Liu,&nbsp;Jincan Li,&nbsp;Weidong Zhao,&nbsp;Xiao Liu,&nbsp;Wei Zhang,&nbsp;Le Yang,&nbsp;Qian Li,&nbsp;Hailin Zhang,&nbsp;Jinlong Qi,&nbsp;Qingzhong Jia","doi":"10.1111/cns.70334","DOIUrl":"https://doi.org/10.1111/cns.70334","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>K_V7 channels are promising targets for antiepileptic therapy. However, the classic K_V7 channel opener retigabine has been withdrawn due to severe adverse reactions. We developed a novel K_V7 channel opener, QO-83, with good chemical stability and blood–brain barrier penetration, and sought to evaluate its K_V7-opening activity, antiepileptic effects, and mechanisms of action.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used patch-clamp electrophysiology, electroencephalogram recordings, dynamic simulations, and various epilepsy models to investigate the mechanisms and antiepileptic activity of QO-83.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compound QO-83 exhibits greater potency at K_V7.2/7.3 channels compared to K_V7.4 or K_V7.5 channels. It shows superior efficacy for K_V7.2 with voltage-dependent opening than retigabine, with W236 identified as the key binding site for the K_V7.2 channel. QO-83 significantly inhibited epileptiform discharge and influenced hippocampal sEPSC and sIPSC amplitudes. QO-83 has a more effective dose of 1 mg/kg in acute and chronic epilepsy models smaller than that of retigabine (10 mg/kg). The higher potency of QO-83 may be attributed to its greater stability at the K_V7.2 binding pocket compared to retigabine.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>QO-83, as a newly developed Kv7.2 opener, has the advantages of stable properties, strong affinity, and high activity compared with retigabine, and is expected to become a new antiepileptic drug.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70334","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690106","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":"Aloe-Emodin Improves Mitophagy in Alzheimer's Disease via Activating the AMPK/PGC-1α/SIRT3 Signaling Pathway","authors":"Yulu Wang,&nbsp;Yunzhi Ge,&nbsp;Siyu Hua,&nbsp;Chenrui Shen,&nbsp;Biao Cai,&nbsp;Han Zhao","doi":"10.1111/cns.70346","DOIUrl":"https://doi.org/10.1111/cns.70346","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Impaired mitophagy results in the accumulation of defective mitochondria that are unable to be cleared effectively in Alzheimer's disease (AD). Aloe-emodin (AE), a key component of the traditional Chinese medicine Rhubarb, exhibits neuroprotective effects against Alzheimer's disease, though the underlying mechanism remains unclear. Studying aloe-emodin's role in enhancing mitophagy is vital for improving cognitive function and reducing neuronal damage in Alzheimer's disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The APP/PS1 double transgenic mice were adopted as models for AD to assess the effects of aloe-emodin upon cognitive function and its neuroprotective impact on hippocampal neurons. Additionally, we investigated the regulatory mechanisms of proteins within the aforementioned pathway, and the morphological characteristics of mitophagy-related proteins. An AD hippocampal neuron model was developed using Aβ25-35 to evaluate the mitochondrial function, the protein expression of such a pathway and the mitophagy. This approach aims to elucidate the effects and underlying mechanisms of aloe-emodin in relation to AD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>AE activates mitophagy in neurons, improves cognitive dysfunction, reduces hippocampal damage, and alleviates AD symptoms in model mice. AE activates the expression of AMPK, PGC-1α and SIRT3. Increased expression of SIRT3 in mitochondria promotes mitophagy and regulates the function of mitochondrial proteins. When mitochondrial autophagy is enhanced, the expression of Beclin1, LC3, P62, Parkin, and PINK1-related proteins changes. Further in vitro experiments showed that AE can enhance mitochondrial function in Alzheimer's disease cell models. The mitochondrial membrane potential, GSH, ROS and Ca2+ levels gradually recover, alleviating the pathological manifestations of AD. Knocking down SIRT3 leads to increased mitochondrial damage and a reduction in mitophagy in HT22 cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Experimental results show that AE can activate mitophagy through AMPK/PGC-1α/SIRT3 pathway, alleviate cognitive dysfunction in AD, and reduce damage to hippocampal neurons.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70346","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690107","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":"Gastrodin Alleviates Tau Pathology by Targeting the Alzheimer's Risk Gene FERMT2, Reversing the Reduction in Brain Viscoelasticity","authors":"Li Wang,&nbsp;Bo Li,&nbsp;Zhi Tang,&nbsp;Yang Wang,&nbsp;Yaqian Peng,&nbsp;Ting Sun,&nbsp;Anni Zhang,&nbsp;Xiaolan Qi","doi":"10.1111/cns.70283","DOIUrl":"10.1111/cns.70283","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;The pathogenesis of Alzheimer's disease (AD) remains incompletely elucidated, and there is a notable deficiency in effective and safe therapeutic interventions. The influence of brain matrix viscoelasticity on the progression of AD has frequently been underestimated. It is imperative to elucidate these overlooked pathogenic factors and to innovate novel therapeutic strategies for AD. Gastrodin, a bioactive constituent derived from the traditional Chinese medicinal herb Gastrodia elata, exhibits a range of pharmacological properties, notably in the enhancement of neural function. Nevertheless, the underlying mechanisms of its action remain insufficiently elucidated. Consequently, this study seeks to examine the therapeutic effects and underlying mechanisms of gastrodin in the context of AD, with particular emphasis on its potential influence on the viscoelastic properties of the brain matrix.&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;This study employs a range of methodologies, including the Morris water maze test, Y-maze spontaneous alternation test, atomic force microscopy (AFM), immunofluorescence, transmission electron microscopy, molecular docking, and Cellular Thermal Shift Assay (CETSA), to demonstrate that gastrodin mitigates tau pathology by modulating FERMT2, thereby reversing the deterioration of mechanical viscoelasticity in the brain.&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;Gastrodin administration via gavage has been demonstrated to mitigate cognitive decline associated with AD, attenuate the hyperphosphorylation of tau protein in the hippocampus and cortex, and ameliorate synaptic damage. Additionally, gastrodin was observed to counteract the reduction in brain matrix viscoelasticity in 3xTg-AD mice, as evidenced by the upregulation of extracellular matrix components pertinent to viscoelasticity, notably collagen types I and IV. Furthermore, molecular docking and CETSA revealed a strong binding affinity between gastrodin and FERMT2. Gastrodin treatment resulted in a reduction of FERMT2 fluorescence intensity, which is selectively expressed in astrocytes. Additionally, gastrodin contributed to the restoration of the blood–brain barrier (BBB) and modulated the expression levels of inflammatory mediators interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and matrix metallopeptidase 8 (MMP8).&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;Gastrodin treatment has the potential to mitigate tau pathology, thereby enhancing learning and memory in AD mouse models. This effect may be m","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70283","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676639","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":"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}