CNS Neuroscience & Therapeutics最新文献

{"title":"Dual Roles of Autophagy in Radiation-Induced Brain Injury: Mechanistic Insights and Therapeutic Implications","authors":"Jiayu Tian,&nbsp;Yanna Mao,&nbsp;Dandan Liu,&nbsp;Tao Li,&nbsp;Lihuan Shi,&nbsp;Yafeng Wang,&nbsp;Changlian Zhu","doi":"10.1111/cns.70464","DOIUrl":"https://doi.org/10.1111/cns.70464","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cranial radiotherapy, while essential for treating brain tumors, often leads to radiation-induced brain injury, a debilitating condition marked by cognitive decline and neuronal damage. Autophagy, a key cellular process for recycling damaged organelles and proteins, has emerged as both a protective and detrimental player in radiation-induced brain injury.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This review systematically explores the dualistic role of autophagy in radiation-induced brain injury, synthesizing insights on its interplay with apoptosis, ferroptosis, neuroinflammation, oxidative stress, the blood–brain barrier, mitophagy, endoplasmic reticulum stress, and mitochondrial biogenesis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>While autophagy supports neuronal resilience by mitigating oxidative and inflammatory stress, excessive or dysregulated autophagy can lead to autophagic cell death and exacerbate injury. Pharmacological modulators such as mTOR inhibitors, AMP-activated protein kinase activators, demonstrate therapeutic potential in preclinical settings.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>By elucidating the mechanistic underpinnings of autophagy in radiation-induced brain injury, this review underscores its dual roles and therapeutic relevance, offering a foundation for targeted interventions that optimize autophagic balance to protect brain function postradiotherapy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70464","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144245010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Excitatory Glutamate Receptors for Morphine Tolerance: A Narrative Review","authors":"Min Huang,&nbsp;Limin Luo,&nbsp;Wenying Wang,&nbsp;Hao Xu,&nbsp;Moxi Chen,&nbsp;Xiaqing Ma,&nbsp;Tao Xu","doi":"10.1111/cns.70468","DOIUrl":"https://doi.org/10.1111/cns.70468","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Opioids remain a primary treatment for moderate-to-severe chronic pain, but prolonged use frequently induces analgesic tolerance. Excitatory glutamate receptors, ubiquitous in the central and peripheral nervous systems, are pivotal in physiological and pathological processes and are now recognized as significant contributors to opioid tolerance development.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We comprehensively analyzed experimental data from our team's intensive investigations over the past 10 years, alongside relevant peer-reviewed studies on glutamate receptor mechanisms in opioid tolerance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Excitatory glutamate receptors (including NMDA, AMPA, and metabotropic subtypes) fundamentally regulate neuroadaptations underlying morphine tolerance. Our work and others' demonstrate their involvement in synaptic plasticity, neuroinflammation, and downstream signaling pathways that drive tolerance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Targeting excitatory glutamate receptors presents a promising therapeutic strategy for mitigating opioid tolerance. Future research should prioritize elucidating receptor-specific mechanisms, peripheral-central nervous system crosstalk, and translating preclinical findings into clinically viable.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70468","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144244374","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":"Pharmacological Inhibition of Mitochondrial Division Attenuates Simulated High-Altitude Exposure-Induced Memory Impairment in Mice: Involvement of Inhibition of Microglia-Mediated Synapse Elimination","authors":"Panpan Chang,&nbsp;Mengqing Xu,&nbsp;Jiawei Zhu,&nbsp;Jiangpei Bian,&nbsp;Yapeng Lu,&nbsp;Qianqian Luo,&nbsp;Dan Wang,&nbsp;Li Zhu","doi":"10.1111/cns.70473","DOIUrl":"https://doi.org/10.1111/cns.70473","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To examine the protective effect of mitochondrial division inhibitor-1 (Mdivi-1) against high-altitude-induced memory impairment in mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>C57BL/6J male mice were administered Mdivi-1 before exposure to a simulated high-altitude hypoxia environment. The novel object recognition test and Morris water maze were used to test cognitive function. Golgi staining was used to visualize dendritic spines. PCR, Western blot, and immunofluorescence were performed to detect microglial activation and synaptic phagocytosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Mice exposed to short-term or long-term simulated high-altitude conditions experienced memory deficits. However, these deficits were significantly mitigated by pre-treatment with Mdivi-1. Simulated high-altitude exposure caused a reduction in synapses (dendritic spines) and the activation of microglia. Following Mdivi-1 injection, synapse density was significantly increased, and microglial activation was attenuated. Under hypoxic conditions, primary cultured microglia exhibited significantly enhanced phagocytic activity towards TRITC-Dextran or synaptosomes, which was abolished by Mdivi-1. Additionally, Mdivi-1 inhibited the HIF-1 signaling pathway and restricted the hypoxia-induced glycolytic activity in microglia. Specific inhibition of glycolysis effectively weakened the phagocytic capacity of microglia under hypoxia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Mdivi-1 dramatically mitigated memory impairment in mice induced by simulated high-altitude exposure. Mdivi-1 reduced microglial glycolysis in hypoxic conditions, thereby limiting microglial activation and preventing excessive synaptic phagocytosis. Consequently, it effectively protected memory.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70473","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144244373","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":"Surgical Treatment Could Improve Long-Term Functional Outcomes in Intracerebral Hemorrhage Patients With NIHSS ≥ 10","authors":"Guangshuo Li,&nbsp;Kaijiang Kang,&nbsp;Yi Ju,&nbsp;Yang Du,&nbsp;Anxin Wang,&nbsp;Xiaoli Zhang,&nbsp;Yunyun Xiong,&nbsp;Xingquan Zhao,&nbsp;Wenjuan Wang","doi":"10.1111/cns.70458","DOIUrl":"https://doi.org/10.1111/cns.70458","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Purpose</h3>\u0000 \u0000 <p>Surgical treatment has been shown to decrease mortality in patients with intracerebral hemorrhage (ICH) but has not consistently improved functional outcomes. This study aimed to investigate whether surgical treatment could enhance functional outcomes in ICH patients with a National Institutes of Health Stroke Scale (NIHSS) score of 10 or higher.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This multicenter study included patients from a registry cohort in China with supratentorial ICH, NIHSS scores of 10 or higher, and hematoma sizes of 25 mL or more. Patients were divided into surgical and medical treatment groups. The primary outcome was a modified Rankin Scale (mRS) score of 0–3 at 1 year.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 429 patients were analyzed. The median NIHSS score at admission was 22 [15–29], and the ICH volume was 50 [35.28–72.9] ml. The surgical group had a higher proportion of mRS scores of 0–3 at 1 year compared to the medical group (49.68% vs. 38.32%, <i>p</i> = 0.022). Both craniotomy and minimally invasive surgery improved functional outcomes at 1 year (mRS 0–3, craniotomy: OR 2.324, 95% CI 1.266–4.267, <i>p</i> = 0.007; minimally invasive surgery: OR 4.884, 95% CI 1.914–12.445, <i>p</i> = 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>For patients with supratentorial ICH, NIHSS scores of 10 or higher, and hematoma sizes of 25 mL or more, surgical treatment improved functional outcomes at 1 year compared to medical treatment. The specific subgroup of ICH patients that could benefit from surgical intervention remains controversial.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70458","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144244376","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":"DeSUMOylation of IGF2BP2 Promotes Neuronal Differentiation of OM-MSCs by Stabilizing SOX11 to Ameliorate Brain Injury After Intracerebral Hemorrhage","authors":"Jun He,&nbsp;Yuhan Luo,&nbsp;Chuang Wang,&nbsp;Chonghua Jiang,&nbsp;Jian Wang,&nbsp;Ying Xia","doi":"10.1111/cns.70463","DOIUrl":"https://doi.org/10.1111/cns.70463","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Our previous study demonstrated that olfactory mucosa mesenchymal stem cell (OM-MSC) neuronal differentiation can reduce neural damage following intracerebral hemorrhage (ICH). However, the mechanisms that regulate OM-MSC neuronal differentiation to mitigate ICH-induced brain injury remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The ICH model was established through autologous blood injection to evaluate the impact of OM-MSCs on brain injury, using the mNSS method, TUNEL, and Nissl staining, as well as the Western blot assay. qPCR, Western blotting, flow cytometry, and immunofluorescence assays were employed to assess the neuronal differentiation of OM-MSCs. The SUMOylation assay was conducted to investigate the relationship between IGF2BP2 and SENP1. RIP, RNA pull-down, and mRNA stability assays were performed to analyze the molecular interaction network involving SENP1, IGF2BP2, and SOX11.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>IGF2BP2 enhanced the protective effects of OM-MSCs against ICH-induced brain injury, as demonstrated by a significant reduction in brain edema, mNSS scores, and apoptosis, along with improved neuronal survival. Furthermore, the overexpression of IGF2BP2 increased the expression of Tuj-1, MAP2, NF200, and NeuN, while decreasing GFAP and ALDH1L1 levels, suggesting the stimulatory effects of IGF2BP2 on the neuronal differentiation of OM-MSCs. Mechanistically, SENP1 enhanced IGF2BP2 expression through SUMO1-induced IGF2BP2 SUMOylation. Additionally, IGF2BP2 functioned as an RNA-binding protein for SOX11, thereby increasing SOX11 levels. The depletion of IGF2BP2 negated the SENP1-induced neuronal differentiation of OM-MSCs. The overexpression of SOX11 mitigated the inhibitory effects of IGF2BP2 silencing on OM-MSC neuronal differentiation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The SENP1/IGF2BP2/SOX11 axis played a crucial role in the neuronal differentiation of OM-MSCs and ameliorated brain damage caused by ICH.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70463","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144244378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting HDAC3 Suppresses Ferroptosis and Demyelination in White Matter Injury by Restoring PDK4-Mediated Iron Homeostasis","authors":"Ting Xu,&nbsp;Lisha Ye,&nbsp;Wenfeng Li,&nbsp;Fangming Liu,&nbsp;Tianjiao Wei,&nbsp;Wenhui Gu,&nbsp;Lihua Xu,&nbsp;Mingde Fang,&nbsp;Qianqian Luo,&nbsp;Chuanjie Wu,&nbsp;Guohua Wang","doi":"10.1111/cns.70471","DOIUrl":"https://doi.org/10.1111/cns.70471","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>White matter injury (WMI), characterized by white matter degeneration and iron deposition, contributes to neurological dysfunction. Histone deacetylase 3 (HDAC3) is implicated in neurodegenerative processes, yet its role in WMI-associated ferroptosis remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Clinical assessments in WMI patients revealed correlations between serum iron, α-synuclein, and antioxidant levels and MRI-confirmed white matter degeneration. In a cuprizone-induced demyelination mouse model, white matter integrity, oligodendrocyte dysfunction, iron accumulation, and lipid peroxidation were evaluated through behavioral testing, histological staining, and biochemical analyses. To identify potential molecular targets of HDAC3-mediated ferroptosis, CUT&amp;Tag sequencing was performed. The involvement of this pathway was further validated in vitro using iron overload assays and in vivo through HDAC3 overexpression via AAV vectors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the present study, HDAC3 expression was elevated following demyelination and was suppressed by RGFP966 treatment. Brain MRI findings from clinical patients and histological analyses in CPZ-treated mice revealed disrupted iron metabolism following white matter injury, likely driven by increased iron deposition and lipid peroxidation in the affected regions. HDAC3 inhibition alleviated oligodendrocyte lineage dysfunction, preserved myelin integrity, and mitigated cognitive and motor deficits induced by demyelination. CUT&amp;Tag sequencing suggested that the therapeutic effects of RGFP966 are mediated through HDAC3-dependent regulation of ferroptosis. The reliability of these findings was further supported by in vivo validation of ferroptosis-related gene expression, indicating that the HDAC3–pyruvate dehydrogenase kinase 4 (PDK4) axis plays a critical role in the epigenetic regulation of ferroptosis-related pathways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>HDAC3 drives ferroptosis in WMI via iron metabolism and lipid peroxidation, highlighting the HDAC3-PDK4 axis as a therapeutic target.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70471","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144244375","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":"Optimized Stereo-Electroencephalography-Guided Three-Dimensional Radiofrequency Thermocoagulation for Hypothalamic Hamartomas-Related Epilepsy: A Single-Center Experience in 69 Patients","authors":"Yang Dai,&nbsp;Yihe Wang,&nbsp;Zesheng Li,&nbsp;Xiaotong Fan,&nbsp;Liankun Ren,&nbsp;Josemir W. Sander,&nbsp;Penghu Wei,&nbsp;Yongzhi Shan,&nbsp;Guoguang Zhao","doi":"10.1111/cns.70462","DOIUrl":"https://doi.org/10.1111/cns.70462","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The high risk of resection surgery for hypothalamic hamartoma (HH) epilepsy drives interest in minimally invasive treatment. Stereo-electroencephalography-guided three-dimensional radiofrequency thermocoagulation (SEEG-3D RFTC) offers an alternative option. We investigated this technology's efficacy, safety, and prognostic risk factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients with HH who underwent SEEG-3D RFTC were retrospectively analyzed. A high-density focal stereo-array electrode implantation was adopted. SEEG-3D RFTC was performed between two contiguous contacts of the same electrode or adjacent contacts of different electrodes. Outcomes were separately evaluated for clinical seizures, gelastic seizures (GS), and non-gelastic seizures (nGS). Kaplan–Meier survival analysis was used to assess treatment effectiveness. Risk factors were analyzed using log-rank tests and Cox regression analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Sixty-nine patients were enrolled. The mean follow-up was 41.00 ± 18.19 months. Seizure freedom was obtained by 48/69 (69.57%) patients for clinical seizures, 50/62 (80.65%) patients for GS, and 41/54 (75.93%) patients for nGS. Surgical procedures were well tolerated. In this study, the proportion of patients experiencing long-term complications was 10.14%. The percentages of HH ablation (<i>p</i> = 0.003; hazard ratio 0.956, 95% confidence interval 0.928–0.985) and HH attachment ablation (<i>p</i> = 0.001; hazard ratio 0.931, 95% confidence interval 0.892–0.970) were significantly associated with seizure outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Optimized SEEG-3D RFTC is an effective and safe option for HH-related epilepsy and is especially suitable for use where laser interstitial thermal therapy is unavailable. Complete ablation of the HH and attachment site is essential for good outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70462","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144232361","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":"Associations of Estimated Glucose Disposal Rate With Stroke Risk and Poststroke Adverse Outcomes: A Prospective Cohort Study","authors":"Xiaxuan Huang,&nbsp;Peina Dong,&nbsp;Yixian Xu,&nbsp;Yitong Ling,&nbsp;Shanyuan Tan,&nbsp;Zihong Bai,&nbsp;Si Shen,&nbsp;Jun Lyu,&nbsp;Hao Wang","doi":"10.1111/cns.70420","DOIUrl":"https://doi.org/10.1111/cns.70420","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study investigated the relationship between estimated glucose disposal rate (eGDR), a validated marker of insulin resistance, and stroke subtypes and poststroke outcomes. Despite eGDR's established role in predicting cardiovascular outcomes, its impact on stroke risk and prognosis has not been fully explored.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study included 462,550 participants from the UK Biobank with eGDR assessments, and participants were stratified into three categories based on tertiles of eGDR. The primary outcomes were stroke and its subtypes (ischemic and hemorrhagic stroke). Cox proportional hazard models and restricted cubic spline regression were used to analyze associations between eGDR and outcomes. Secondary analyses investigated poststroke adverse events (depression, disability, epilepsy, and delirium). Mediation analyses were conducted to explore the underlying mechanisms driven by inflammatory markers, eGDR, and stroke.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>During a median follow-up of 13.9 years, 12,325 stroke cases were recorded. Compared to the lowest eGDR tertile (&lt; 6.525 mg/kg/min), individuals in the highest tertile (&gt; 8.494 mg/kg/min) demonstrated a significantly reduced risk of stroke (HR = 0.53, 95% CI: 0.50–0.56), particularly ischemic stroke (HR = 0.53, 95% CI: 0.50–0.57). Higher eGDR levels were also associated with a decreased risk of poststroke adverse outcomes (HR = 0.83, 95% CI: 0.73–0.94), with similar risk estimates observed for depression, disability, epilepsy, and delirium. Furthermore, inflammatory markers partially mediated the relationship between eGDR and stroke risk.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Elevated eGDR levels were associated with decreased risks of stroke and poststroke adverse outcomes. These findings suggest improving insulin sensitivity, as reflected by higher eGDR, maybe a potential therapeutic target for stroke prevention or stroke rehabilitation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70420","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144220158","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":"Whole Brain Monosynaptic Input of Distinct Neurons in the Globus Pallidus Externa","authors":"Ming-feng Ma,&nbsp;Jie Hu,&nbsp;Ya-xin Hao,&nbsp;Kai-ying Zhang,&nbsp;Xiang Zhang,&nbsp;Meng-chu Zhu,&nbsp;Zong-lei Zhou,&nbsp;Xiang-shan Yuan,&nbsp;Fang Yuan","doi":"10.1111/cns.70459","DOIUrl":"https://doi.org/10.1111/cns.70459","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The globus pallidus externa (GPe) is involved in mediating physiological functions and contains two types of neurons: Forkhead box protein P2-expressing (GPe^FoxP2) neurons which inhibit motor, and parvalbumin-expressing (GPe^PV) neurons which improve motor. The functional complexity of the GPe, directly linked to its neuronal heterogeneity, necessitates exploring the neuroanatomical circuits of its distinct neuron types as a foundation for functional research.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, we employed specific, modified rabies viruses and adeno-associated viruses to investigate the monosynaptic inputs of GPe^FoxP2 and GPe^PV neurons.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that the input projections to both types of neurons are widespread, including the cortex, subcortical structures, amygdala, thalamus, hypothalamus, and brainstem. These inputs exhibit significant similarity, with 49 nuclei simultaneously innervating both types of neurons. However, GPe^PV neurons receive a lower proportion of inputs from the cortex and a higher proportion of inputs from the thalamus, compared to GPe^FoxP2 neurons. Clustering analysis indicates that GPe^FoxP2 neurons receive extensive afferent inputs from four nuclear clusters in the brain, whereas GPe^PV neurons receive afferent inputs from only three clusters, suggesting GPe^FoxP2 neurons may be involved in more diverse functional regulations than GPe^PV.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Collectively, our results reveal the similarities and differences in the input projections to the two types of neurons in the GPe and lay the neuroanatomic groundwork for further studies to explore the critical physiological functions of GPe.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70459","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144206345","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 Oxytocin Neurons in the Paraventricular Nucleus Are Essential for Chronic Sleep Deprivation-Mediated Anxiety-Related Behaviors","authors":"Yuxin Wang,&nbsp;Yifei Zhang,&nbsp;Yanchao Liu,&nbsp;Zhendong Xu,&nbsp;Jiyan Zhang,&nbsp;Like Wang,&nbsp;Yufeng Cang,&nbsp;Junbin Xin,&nbsp;Fuyu Han,&nbsp;Zhouhua Li,&nbsp;Chuanwei Hu,&nbsp;Xiangjie Kong,&nbsp;Yuchen Deng,&nbsp;Li Zhang,&nbsp;Hairong Wang,&nbsp;Haibo Xu,&nbsp;Ming Chen,&nbsp;Linlin Bi","doi":"10.1111/cns.70465","DOIUrl":"https://doi.org/10.1111/cns.70465","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Sleep disorders increase the risk of anxiety disorders. The underlying mechanisms and potential targets remain poorly understood. Our research aimed to discover the essential role of oxytocin neurons in the paraventricular nucleus (PVN^OXT neurons) in regulating anxiety-related behaviors following chronic sleep deprivation (cSD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In vivo optogenetic stimulation was used to regulate the activity of PVN^OXT neurons, and meanwhile, anxiety-related behavioral tests were performed. Electrophysiological analysis was used to test neuronal synaptic transmission. In vivo fiber photometry was used to assess OXT release.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Through c-Fos staining of the whole brain, we found that cSD decreased c-Fos expression in the PVN and increased c-Fos expression in the medial prefrontal cortex (mPFC). cSD promoted anxiety-related behaviors mainly through inhibiting AMPAR-mediated postsynaptic excitability of PVN^OXT neurons. Instant optogenetic activation of PVN^OXT neurons decreased anxiety-like behaviors and promoted fear memory extinction by promoting oxytocin release into the mPFC. Similar to cSD, optogenetic long-term low-frequency (LTF) stimulation of PVN^OXT neurons promoted a prolonged inhibition of PVN^OXT neurons and increased anxiety-like behaviors. Interestingly, short-term high-frequency stimulation (HFS) of PVN^OXT neurons displayed a long-term potentiation of AMPAR-mediated synaptic transmission of PVN^OXT neurons and could reverse cSD-induced anxiety by promoting the OXT-mediated inhibitory transmission of the mPFC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings provide key mechanisms and promising deep brain stimulation strategies associated with synaptic plasticity for cSD-induced obsessive anxiety.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70465","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214007","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}