CNS Neuroscience & Therapeutics最新文献

{"title":"A Drug Delivery to Improve Prognosis of Traumatic Brain Injury Mice Through Mouse-Derived Nerve Growth Factor Coated by a Nanoparticle","authors":"Ruichen Zhao,&nbsp;Shiying Dong,&nbsp;Di Wu,&nbsp;Yu Tian,&nbsp;Jiangyuan Yuan,&nbsp;Liang Mi,&nbsp;Chenrui Wu,&nbsp;Shiao Tong,&nbsp;Rongcai Jiang","doi":"10.1111/cns.70603","DOIUrl":"10.1111/cns.70603","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The large molecular weight and limited permeability of mouse-derived nerve growth factor (mNGF) across the blood–brain barrier (BBB) have restricted its therapeutic use after brain injury. We therefore hypothesized that encapsulating mNGF in nanoparticles would facilitate BBB transit, increase delivery to the brain parenchyma, and consequently improve the treatment of traumatic brain injury (TBI).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Nanoparticles were used to encapsulate the high-molecular-weight protein mNGF to improve its delivery. Traumatic brain injury (TBI) was induced in mice, which were then allocated to four groups, including a sham group. Intramuscular injections of mNGF—either free or nanoparticle-encapsulated—were administered. To elucidate the mechanism of action, the aquaporin-4 inhibitor 2-nicotinamide-1,3,4-thiadiazole (TGN-020) was additionally given to the nanoparticle group. Glymphatic function (cerebrospinal fluid influx and efflux) was quantified by immunofluorescence. Blood–brain barrier integrity, peri-lesional parenchymal structure, and axonal repair were examined using Evans blue extravasation, immunofluorescence, and Western blotting. Neuronal apoptosis and focal neurological damage were measured with TUNEL staining and Western blot analysis. Functional outcomes were assessed with the modified Neurological Severity Score, rotarod performance, and the Morris water maze.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Nanoparticle encapsulation markedly increased the amount of mNGF that reached the brain parenchyma relative to conventional administration. Enhanced delivery enabled substantially more exogenous mNGF to traverse the BBB in TBI mice than did uncoated mNGF. The treatment attenuated TBI-induced neuronal apoptosis, up-regulated genes involved in neurogenesis and myelinogenesis, restored glymphatic inflow and outflow, repaired BBB structure and function, and mitigated cognitive deficits. These benefits were abolished by the aquaporin-4 inhibitor TGN-020, indicating that mNGF improves TBI outcome by correcting AQP4 dysfunction. To our knowledge, this is the first demonstration that nanocrystallized mNGF can cross the BBB efficiently after TBI and thereby foster neural repair and functional recovery.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 10","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70603","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211228","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":"Serum Vitamin D Levels Were Not Associated With the Risk of Aneurysmal Subarachnoid Hemorrhage: A Large Cohort Study With Propensity Score Matching and Mendelian Randomization Analysis","authors":"Haoran Qiu,&nbsp;Kai Chen,&nbsp;Yang Yu,&nbsp;Ziyin Song,&nbsp;Jingzheng Liu,&nbsp;Lvyin Luo,&nbsp;Xinlong Ma,&nbsp;Zhaoyang Yuan,&nbsp;Maogui Li,&nbsp;Jianfeng Zhuang,&nbsp;Mingxiang Zhang,&nbsp;Wandong Su,&nbsp;Yunyan Wang,&nbsp;Donghai Wang,&nbsp;Weiying Zhong","doi":"10.1111/cns.70617","DOIUrl":"10.1111/cns.70617","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Vitamin D (VitD) may protect arterial health, but its link to cerebral aneurysm rupture remains unclear. This study aims to investigate the correlation between serum VitD levels and the risk of aneurysmal subarachnoid hemorrhage (aSAH).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective study included patients with ruptured or unruptured aneurysms treated between 2018 and 2021. Univariate and multivariate analyses were conducted. Propensity score matching (PSM) analysis was conducted to balance confounding factors. Furthermore, the causal relationship between VitD and aSAH was investigated using a two-sample Mendelian randomization (MR) analysis. Summary-level data for the exposure (VitD) and outcome (aSAH) were obtained from public genome-wide association study datasets. Multiple MR methods, including inverse variance weighted, MR-Egger, weighted median, simple mode, and weighted mode, were utilized to assess causality. Sensitivity analyses were conducted to evaluate the robustness and reliability of the causal estimates.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 499 patients with 619 intracranial aneurysms were included. Among them, 337 (68%) were female, 184 cases (36.9%) had ruptured aneurysms, and 105 (21.0%) had multiple aneurysms. VitD levels and VitD deficiency showed no association with aSAH in univariate or multivariate analysis before PSM (<i>p</i> &gt; 0.05). After PSM (112 matched aSAH patients), VitD levels and VitD deficiency remained unassociated with the risk of aSAH (<i>p</i> = 0.947). MR analysis, including inverse variance weighted methods, found no causal link between VitD levels and aSAH (OR: 1.00; 95% CI: 0.82–1.23; <i>p</i> = 0.966).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study found that serum VitD levels are neither associated with nor causally linked to aSAH. The inverse associations observed in previous studies may be attributed to confounding factors or reverse causation. A prospective, large-scale study with long-term follow-up is warranted to validate these findings.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 10","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70617","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145190540","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":"EEG-Based Deep Learning Model for Hyper-Acute Large Vessel Occlusion Stroke Detection in Mice","authors":"Tan Zhang,&nbsp;Xiaolin Li,&nbsp;Xinxin Hu,&nbsp;Zhiyong Zhou,&nbsp;Qingchun Mu,&nbsp;Xiaoke Chai,&nbsp;Qing Lan,&nbsp;Jizong Zhao","doi":"10.1111/cns.70592","DOIUrl":"https://doi.org/10.1111/cns.70592","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aims to develop a deep learning model for the early and accurate detection of hyper-acute large vessel occlusion (LVO) stroke using EEG data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A pMCAO mouse model was used to simulate LVO stroke, with high-resolution EEG data collected during the hyper-acute phase. <i>EEGNet</i>, a specialized deep learning architecture, was employed to develop a model based on EEG signals for the detection of hyper-acute LVO strokes. Seven-fold cross-validation was conducted to evaluate the model's performance across multiple metrics, including accuracy, AUC, precision, recall, and F1 score.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The model achieved an overall accuracy of 97.9% and an AUC of 0.977, demonstrating excellent diagnostic performance across the hyper-acute phase. Stroke detection was reliable within 1.5 h post-onset, with classification accuracies exceeding 95% in all five time intervals segmented by hour. t-SNE analysis confirmed effective feature extraction, and comparisons with sham-operated mice validated the model's specificity for stroke-related EEG changes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The EEG-based deep learning model showed robust performance in hyper-acute LVO stroke detection, achieving high accuracy and specificity. These results highlight its potential as a biomarker for early stroke diagnosis and as a foundation for real-time, non-invasive monitoring in clinical and prehospital settings.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70592","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145146628","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":"Congenital Hypothyroidism Dysregulates TRPC6 to Mediate Abnormal Dendritic Spine Growth of Hippocampal Neurons","authors":"Tianci Li,&nbsp;Feifei Shen,&nbsp;Lingling Li,&nbsp;Peng Chen,&nbsp;Zhiwen Zhu,&nbsp;Yuqin Zheng,&nbsp;Haiying Li,&nbsp;Guihai Suo,&nbsp;Yongjun Wang,&nbsp;Jinlong Shi,&nbsp;Youjia Wu","doi":"10.1111/cns.70618","DOIUrl":"10.1111/cns.70618","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Congenital hypothyroidism (CH) may lead to irreversible neurological dysfunction of offspring by affecting hippocampal morphogenesis. The dentate gyrus (DG) is primarily the affected tissue by the CH, in which the dendritic spine density of gyrus granule cells (DGCs) is significantly reduced, thereby resulting in the cognitive impairment. The CaMKIV/CREB signaling pathway has been shown to mediate the deficient growth of DGCs dendritic spines, but the mechanism of CH in modulating the Ca²⁺-dependent CaMKIV is still elusive.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>CH model of rat pups was prepared by the supply of 0.02% methimazole in the drinking water of pregnant dams from the 9th day of gestation. The dendritic spine density of hippocampal DGCs was detected by Golgi staining before or after administration of drugs. Additionally, the expression of CH-mediated effectors in the hippocampus or primary neurons was determined by Western blot or RT-PCR, and the immunofluorescence or subcellular fractionation was used to examine the distribution of these factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the present study, the calcium influx-related channel TRPC6 was identified under the regulation of T3, which was significantly downregulated in the DGCs of CH pups. TRPC6 deficiency has been revealed to decrease the dendritic spine density by affecting intracellular calcium transients and the CaMKIV/CREB signaling pathway. Pharmacological activation of TRPC6 with hyperforin was shown to be efficient in the rescue of DGCs dendritic spines and in improving the cognitive function of CH pups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>CH of the neonates leads to downregulation of TRPC6 in hippocampal dentate gyrus neurons, which affects calcium influx and decreases activation of CaMKIV and downstream signaling, thereby causing abnormal growth of DGCs' dendritic spines and impaired cognitive function in the offspring. This study provides a new target for CH-mediated developmental abnormality of the hippocampus in the offspring.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70618","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145135958","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":"Network Pharmacology-Based and Experimental Validation Elucidate the Target Mechanism of Vinorine in Ameliorating Secondary Brain Injury After Intracerebral Hemorrhage","authors":"Jia-Wei Wu,&nbsp;Yi-Ting Zhou,&nbsp;Bing-Xin Wang,&nbsp;Peng Wang,&nbsp;Xu-Qi Zhang,&nbsp;Shi-Qing Du,&nbsp;Xiao-Jie Lu,&nbsp;Zeng-Li Miao,&nbsp;Xu-Dong Zhao","doi":"10.1111/cns.70609","DOIUrl":"10.1111/cns.70609","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intracerebral hemorrhage (ICH) is a severe stroke subtype associated with high mortality and long-term disability, for which no effective treatment currently exists. Vinorine (Vin), a monoterpene indole alkaloid derived from <i>Rauvolfia reflexa</i>, has been traditionally used for age-related neurological disorders, yet its therapeutic potential and mechanisms in ICH remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>An ICH mouse model was established via intracranial collagenase injection. Vin was administered intraperitoneally at varying doses, and its effects on motor function, sensory deficits, and neural regeneration were evaluated. Network pharmacology was employed to predict potential targets and pathways, followed by validation through molecular docking, in vivo experiments, and in vitro assays.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Network pharmacology identified four core targets and 35 related pathways, with JAK2 as a central node. In vivo, Vin significantly improved motor deficits, reduced cerebral edema, preserved blood–brain barrier integrity, and promoted hematoma resolution. These effects were mediated through modulation of the CXCR2–JAK–STAT axis and suppression of JAK2 phosphorylation. In vitro, Vin inhibited JAK–STAT activation in microglia, downregulated MMP expression, and facilitated the transition from M1 to M2 phenotypic polarization. Additionally, Vin enhanced the expression of neuronal markers (NF200, PSD95, GAP43) and reduced neuronal apoptosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Vin attenuates neurological deficits after ICH likely by inhibiting MMP expression in microglia via regulation of the CXCR2–JAK–STAT pathway. These findings highlight the therapeutic potential of Vin and provide mechanistic support for its further development as a treatment for ICH.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70609","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145135951","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":"Elucidating the Mechanism of Emodin in Treating Post-Stroke Depression Through Network Pharmacology and Animal Experiments","authors":"Xiaoju Liu,&nbsp;Jie Gao,&nbsp;Kai Yang,&nbsp;Weiming Zhu,&nbsp;Ming Su,&nbsp;Zichun Liu,&nbsp;Yaxin Yuan,&nbsp;Linya Cao,&nbsp;Tong Wu,&nbsp;Wei Liu","doi":"10.1111/cns.70581","DOIUrl":"10.1111/cns.70581","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Evaluate the mechanism of Emodin therapy for Post-stroke depression (PSD) using network pharmacology and animal experiments.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Firstly, the effectiveness of Em in treating PSD was confirmed by constructing a PSD rat model. Then, network pharmacology and molecular docking techniques were used to analyze the potential signaling pathways and targets of Em therapy for PSD. Further exploration and validation were conducted using the PSD rat model. Finally, the expressions of tissue plasminogen activator (tPA), matrix metallopeptidase-9 (MMP9), furin, and proprotein convertases (PC) in the hippocampus and medial prefrontal cortex (mPFC) were further detected.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Em exhibited significant neuroprotective and antidepressant effects on PSD. Network pharmacology analysis revealed that Em may exert pharmacological effects on PSD through 47 core targets. These targets were involved in multiple signaling pathways. Molecular docking studies demonstrated that Em had a strong binding affinity for core targets. Animal experiments further indicated that Em could regulate the expression of precursor brain-derived neurotrophic factor (proBDNF) and mature BDNF (mBDNF) in the hippocampus and mPFC, ameliorating apoptosis. In addition, Em could upregulate the expression of tPA gene and protein in the hippocampus and mPFC, as well as upregulate the expression of Furin gene and protein in the mPFC. This confirmed that the balance regulation of proBDNF/mBDNF depends on tPA and Furin.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The therapeutic effects of Em on PSD are multi-targets and multi-pathways. Em may exert therapeutic effects on PSD by binding to the core target, BDNF. The mechanism may be to regulate the balance proBDNF/mBDNF via tPA and Furin, improving apoptosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70581","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145135953","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":"Adiponectin Receptor Agonist Ameliorates Synaptic Dysfunction in 3xTg Alzheimer's Disease Mouse Model by Activation of AMPK","authors":"Jenna Bloemer,&nbsp;Priyanka D. Pinky,&nbsp;Vishnu Suppiramaniam,&nbsp;Miranda N. Reed","doi":"10.1111/cns.70616","DOIUrl":"https://doi.org/10.1111/cns.70616","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>The hormone adiponectin impacts various facets of brain function, including neurogenesis, energy homeostasis, and synaptic processes. The use of adiponectin or adiponectin receptor agonists may protect against Alzheimer's disease (AD) and reduce AD pathology. Here, we investigated the ability of the adiponectin receptor agonist, AdipoRon, to restore synaptic function in an AD mouse model and the underlying mechanism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Acute hippocampal slices from 3xTg-AD mice and age-matched controls were used to evaluate the ability of AdipoRon to rescue synaptic deficits in an AD model. Slices were incubated in AdipoRon or other pharmacological agents, followed by electrophysiological field recordings to evaluate synaptic function and plasticity. Signaling pathway alterations were evaluated by Western blot, with a focus on AMP-activated protein kinase (AMPK) signaling.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Incubation of hippocampal slices with AdipoRon ameliorated long-term potentiation (LTP) and basal synaptic transmission deficits in 3xTg-AD mice. AdipoRon was unable to restore these parameters in the presence of the AMPK inhibitor, Compound C. AdipoRon altered presynaptic parameters by a mechanism that did not appear to be solely dependent on AMPK. AdipoRon slice incubation was associated with activation of AMPK, inhibition of GSK3β, and altered glutamatergic receptor subunit phosphorylation based on Western blot analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Activation of adiponectin receptors restores synaptic function in an AD model in part through AMPK signaling. These results warrant further investigation into adiponectin receptor agonists as a novel approach for AD prevention or treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70616","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic Modification of Mesenchymal Stem Cell to Overexpress CXCR4 Enhances Treatment Efficacy for Brain Injury After Cardiopulmonary Resuscitation","authors":"Yongfei Liu,&nbsp;Li Zhang,&nbsp;Jingxiang Wang,&nbsp;Yuan Qin,&nbsp;Liang Zhang,&nbsp;Anlin Yue,&nbsp;Zhongting Wang,&nbsp;Xiao Xiao,&nbsp;Shuang Wang,&nbsp;Lu Huang,&nbsp;Changjun Gao","doi":"10.1111/cns.70621","DOIUrl":"https://doi.org/10.1111/cns.70621","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To investigate whether genetically modifying human umbilical cord-derived mesenchymal stem cells (MSC) to overexpress the CXCR4 receptor can enhance their therapeutic efficacy for treating brain injury following cardiac arrest (CA).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>MSC were engineered to overexpress CXCR4 (CXCR4-MSC) via lentiviral transduction. The migration capacity of these cells was tested using in vitro chemotaxis assays. In a rat model of CA/CPR, the homing ability of CXCR4-MSC to the brain was tracked in vivo, and their therapeutic effects on neuronal death and neurological recovery were assessed. The role of exosomes and their impact on key proteins (NLRP3, ASC, GSDMD) in the pyroptosis pathway was also investigated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Result</h3>\u0000 \u0000 <p>CXCR4 overexpression significantly enhanced the migration of MSC in vitro and their homing to injured brain tissue in vivo. Treatment with CXCR4-MSC markedly reduced neuronal death and improved neurological recovery in resuscitated rats. This was accompanied by decreased expression of NLRP3. Furthermore, exosomes derived from CXCR4-MSC were found to suppress pyroptosis-related proteins (NLRP3/ASC/GSDMD) in post-CPR neurons, an effect that was reversed upon exosome inhibition.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Genetic modification to overexpress CXCR4 enhances the therapeutic efficacy of MSC for CA-induced brain injury by promoting their migration to the brain via the CXCL12/CXCR4 axis. A key mechanism of this protection is exosome-mediated inhibition of neuronal pyroptosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70621","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111347","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":"Artificial Intelligence-Driven Hemodynamic Monitoring of Simulated Bruxism Using Functional Near-Infrared Spectroscopy: A Preliminary Study","authors":"Noor Fatima,&nbsp;Zia Mohy Ud Din,&nbsp;Abdullah Al Aishan,&nbsp;Jahan Zeb Gul","doi":"10.1111/cns.70619","DOIUrl":"https://doi.org/10.1111/cns.70619","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Sleep-related and neuromuscular conditions affect the daily lives of individuals as they impact physical and cognitive well-being. While not classified as a disorder, bruxism has emerged as a prevalent condition characterized by involuntary teeth grinding and jaw clenching, occurring either during sleep or wakefulness. Often left unnoticed, this unconscious behavior can contribute to severe dental damage, facial muscle fatigue, and temporomandibular joint disorders. These consequences require early detection and intervention to prevent long-term complications. Traditionally, polysomnography (PSG) is widely used for bruxism assessments as it gives insights into the multimodal physiological data, but it lacks direct spatial mapping of neural regions involved in rhythmic masticatory muscular activity (RMMA) associated with bruxism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methodology</h3>\u0000 \u0000 <p>This research introduces functional Near Infrared Spectroscopy (fNIRS) as a neuroimaging tool to monitor cortical activity associated with RMMA, distinguishing bruxism from other masticatory activities. The data were acquired in a controlled simulated paradigm setup from 10 subjects in three trials via a 20-channeled optode setup of fNIRS placed over the motor cortex region. A total of 12 temporal and frequency domain features were optimized by employing techniques of feature selection, feature importance, and feature reduction. Furthermore, synthetic data augmentation techniques of Synthetic Minority Oversampling Technique (SMOTE), Synthetic Minority Oversampling Technique for Nominal features (SMOTEN), and Adaptive Synthetic sampling (ADASYN) were compared to five machine learning classifiers including k-Nearest Neighbors (kNN), Logistic Regression (LR), Naive Bayes (NB), Decision Tree (DT), and Random Forest (RF).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The kNN outperformed in detecting simulated bruxism among other mandible joint movements with an accuracy of 92%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The findings highlight the potential of fNIRS as a tool for identifying and distinguishing bruxism-like motor activities from other jaw movements, contributing to the timely management and detection of bruxism in future studies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70619","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111072","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":"Proanthocyanidin B2 Alleviates Cuprizone-Induced Demyelination by Regulating the Astrocytic xCT/GSH/GPX4 Axis","authors":"Jian Liu,&nbsp;Yan-Xia Hou,&nbsp;Ying Chen,&nbsp;Ya-Jie Liang,&nbsp;Meng Pu,&nbsp;Lu-Lu Zheng,&nbsp;Zi-Wei Zhang,&nbsp;Ying Xiao,&nbsp;Zhen Mao,&nbsp;Cun-Gen Ma,&nbsp;Qing Wang","doi":"10.1111/cns.70598","DOIUrl":"10.1111/cns.70598","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Multiple sclerosis (MS) is marked by inflammatory demyelination in the central nervous system (CNS), involving diverse glial populations. This pathological process is associated with inflammation and oxidative stress. Proanthocyanidin B2 (PCB2), with its potent antioxidant properties, has been shown to alleviate demyelination in the cuprizone (CPZ) mouse model. It attenuates neuroinflammation and oxidative stress in both the cerebral microenvironment and astrocytes (AS). The xCT/GSH/GPX4 axis is a key regulatory pathway for oxidative stress. Therefore, we hypothesize that PCB2 can alleviate CPZ-induced demyelination by regulating the xCT/GSH/GPX4 axis in AS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The study utilized forty C57BL/6 mice, randomly allocated into four groups of ten: a control group, a control group supplemented with PCB2 (60 mg/kg/day), a CPZ-exposed group, and a CPZ-exposed group supplemented with PCB2 (60 mg/kg/day). The control groups received a standard diet, whereas the CPZ groups were given the same diet supplemented with 0.2% CPZ for 6 weeks. From the fifth week onwards, the control and CPZ groups were administered physiological saline via intraperitoneal injection, whereas the PCB2-supplemented groups received PCB2 for 2 weeks. Immunofluorescence staining, Western blot, and ELISA elucidated the cellular/molecular mechanisms of PCB2 targeting the xCT/GSH/GPX4 axis in AS to alleviate demyelination in vivo and in vitro.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In this study, PCB2 markedly regulated the xCT/GSH/GPX4 axis in AS, ameliorated the behavioral performance in CPZ mice, reduced inflammation, oxidative stress, lipid peroxidation, and the damage to oligodendrocytes (OLs), and inhibited demyelination.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>PCB2 can regulate the entire xCT/GSH/GPX4 axis of AS to reduce CPZ-induced OL injury and demyelination, which may be a potentially effective drug for the treatment of multiple sclerosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70598","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145084538","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}