CNS Neuroscience & Therapeutics最新文献

{"title":"Cognitive Remediation in Patients With Bipolar Disorder: A Randomized Trial by Sequential tDCS and Navigated rTMS Targeting the Primary Visual Cortex","authors":"Hetong Zhou, Minmin Wang, Ting Xu, Xiaomei Zhang, Xudong Zhao, Lili Tang, Pengfei Zhao, Dandan Wang, Jianbo Lai, Fei Wang, Shaomin Zhang, Shaohua Hu","doi":"10.1111/cns.70179","DOIUrl":"10.1111/cns.70179","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Non-invasive brain stimulation (NIBS), such as transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS), has emerged as a promising alternative in the precise treatment of clinical symptoms, such as the cognitive impairment of bipolar disorder (BD). Optimizing the neurocognitive effects by combining tDCS and rTMS to strengthen the clinical outcome is a challenging research issue.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>In this randomized, controlled trial, we first combined tDCS and neuronavigated rTMS targeting the V1 region to explore the efficacy on neurocognitive function in BD patients with depressive episodes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Eligible individuals (<i>n</i> = 105) were assigned into three groups, Group A (active tDCS-active rTMS), Group B (sham tDCS-active rTMS), and Group C (active tDCS-sham rTMS). All participants received 3-week treatment in which every participant received 15 sessions of stimulation through the study, 5 sessions every week, with tDCS treatment followed by neuronavigated rTMS every session. We evaluated the cognitive, emotional, and safety outcomes at week-0 (w0, baseline), week-3 (w3, immediately post-treatment), and week-8 (w8, follow-up period). The THINC-integrated tool (THINC-it), 17-item Hamilton Depression Rating Scale, and Young Mania Rating Scale were applied for evaluating the cognitive function and emotional state, respectively. Data were analyzed by repeated measure ANOVA and paired <i>t</i>-test.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Eventually, 32 patients in Group A, 27 in Group B, and 23 in Group C completed the entire treatment. Compared to Groups B and C, Group A showed greater improvement in Symbol Check items (Time and Accuracy) at W3 and Symbol Check Accuracy at W8 (<i>p</i> < 0.01). The W0-W3 analysis indicated a significant improvement in depressive symptoms in both Group A and Group B (<i>p</i> < 0.01). Additionally, neuroimaging data revealed increased activity in the calcarine sulcus in Group A, suggesting potential neuroplastic changes in the visual cortex following the electromagnetic stimulation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings provide preliminary evidence that the combination of navigated rTMS with tDCS targeting V1 region may serve as a potential treatment strategy for improving cognitive impairment and depressive symptoms in","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 12","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70179","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862642","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":"Causal Relationships Between Epilepsy, Anti-Epileptic Drugs, and Serum Vitamin D and Vitamin D Binding Protein: A Bidirectional and Drug Target Mendelian Randomization Study","authors":"Zizhang Cheng,&nbsp;Jinyi Zuo,&nbsp;Xintao Peng,&nbsp;Haoran Zhang,&nbsp;Wenlong Su,&nbsp;Guoming Luan,&nbsp;Yuguang Guan","doi":"10.1111/cns.70183","DOIUrl":"10.1111/cns.70183","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Previous studies suggest potential associations between epilepsy, anti-epileptic drugs (AEDs), and levels of vitamin D and vitamin D-binding protein (VDBP). This study aims to investigate the causal relationships among these variables using Mendelian Randomization (MR) methods.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using summary data from genome-wide association studies on serum 25-hydroxyvitamin D [25(OH)D] levels (<i>N</i> = 417,580), VDBP concentrations (<i>N</i> = 65,589), and various types of epilepsy (Ncases = 27,559), MR analyses were conducted to determine bidirectional causal relationships among these variables. Additionally, eQTL data from eQTLGen (<i>N</i> = 31,684) were employed to model the effects of AEDs and evaluate their causal impact on both biomarkers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>No causal relationships were found between serum 25(OH)D or VDBP levels and epilepsy. Although genetically predicted focal epilepsy risk was potentially associated with increased serum 25(OH)D levels (OR 1.031, 95% CI: 1.006–1.058, <i>p</i> = 0.017), and a higher genetic risk of juvenile myoclonic epilepsy was linked to lower VDBP levels (OR 0.977, 95% CI: 0.961–0.993, <i>p</i> = 0.004), both associations lost significance after multiple correction. Furthermore, significant associations were observed between serum 25(OH)D levels and AED target genes SCN4A, GABBR1, CA13, ALDH5A1, and CA8. No significant associations were found between AED target genes and VDBP levels after correction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>No causal relationships were found between genetically determined serum 25(OH)D levels, VDBP, and epilepsy or its subtypes. Furthermore, the use of AEDs, such as Carbamazepine, Oxcarbazepine, Progabide, and Valproic Acid, reduces serum 25(OH)D levels, while not affect VDBP levels.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 12","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70183","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862638","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":"Theta Rhythm-Based Attention Switch Training Effectively Modified Negative Attentional Bias","authors":"Guo Li,&nbsp;Xueli Cai,&nbsp;Yifeng Wang","doi":"10.1111/cns.70157","DOIUrl":"10.1111/cns.70157","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Attentional bias modification training (ABMT) is commonly employed to regulate negative attentional bias (NAB) and, in turn, to prevent or alleviate depressive symptoms. Recent advancements in attention switch theory have facilitated the development of a novel training paradigm that may enhance the efficacy of such interventions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of fifty-seven college students were assigned to two groups: one exhibiting NAB and the other without. Both groups underwent training with a novel paradigm integrating theta rhythm with the traditional dot-probe task (DPT). The DPT was also administered as a pre- and post-test measure.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>For individuals with NAB, rhythmic DPT effectively alleviates their NAB. Additionally, within the training procedure's DPT, flashing negative stimuli elicits faster responses when the probe appears at the positive stimulus' location. Baseline attention scores can negatively predict changes in subsequent corresponding attentional performance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study presents a novel training paradigm—the theta rhythm-based DPT—that effectively modifies NAB. The mechanism underlying this intervention may be driven by positive salient stimuli at the critical trough, facilitating the switch of attention from negative to positive stimuli.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 12","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70157","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862645","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":"STING Activation in Macrophages and Microglia Drives Poststroke Inflammation: Implications for Neuroinflammatory Mechanisms and Therapeutic Interventions","authors":"Zhiruo Liu,&nbsp;Qin Qin,&nbsp;Shisi Wang,&nbsp;Xinmei Kang,&nbsp;Yuxin Liu,&nbsp;Lei Wei,&nbsp;Zhengqi Lu,&nbsp;Wei Cai,&nbsp;Mengyan Hu","doi":"10.1111/cns.70106","DOIUrl":"10.1111/cns.70106","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Monocyte-derived macrophages and microglia initially adopt an anti-inflammatory phenotype following stroke but later transition to a pro-inflammatory state. The mechanisms underlying this phenotypic shift remain unclear. This study investigates the activation dynamics of molecular signaling pathways in macrophages and microglia after stroke.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We utilized publicly available single-cell RNA sequencing datasets to examine the activation dynamics of molecular signaling pathways alongside the pro-inflammatory phenotype of macrophages and microglia. Male C57BL/6 mice underwent transient middle cerebral artery occlusion (tMCAO), with the STING inhibitor H151 administered to tMCAO mice. Neurobehavioral performance was assessed using rotarod, foot fault, novel object recognition, and water maze tests at 5-, 7-, 10-, and 14-days post-stroke. Primary microglia and bone marrow-derived macrophages were cultured for in vitro experiments.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Single-cell sequencing data indicated that the activation of STING and subsequent type I interferon signaling drove the phenotypic shift of microglia and macrophages toward a pro-inflammatory state in the stroke lesion. Immunostaining demonstrated that the emergence of pro-inflammatory microglia and macrophages aligned with the activation time course of STING and type I interferon signaling. Continuous phagocytosis by macrophages and microglia led to STING activation, which triggered type I interferon signaling and promoted the phenotypic shift. Inhibition of STING signaling prevented this transition, reduced neuroinflammation, and conferred protection against ischemic stroke.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings elucidated the critical role of STING-mediated type I interferon signaling in driving post-stroke neuroinflammation and underscored the potential of STING inhibition as a therapeutic strategy for alleviating neuroinflammatory responses following stroke.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 12","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70106","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142851793","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":"STING Driving Synaptic Phagocytosis of Hippocampal Microglia/Macrophages Contributes to Cognitive Impairment in Sepsis-Associated Encephalopathy in Mice","authors":"Xin Lv,&nbsp;Min Jia,&nbsp;Xiao Feng,&nbsp;Jia-xiong Jian,&nbsp;Jian-jun Yang,&nbsp;Da-qing Ma,&nbsp;Mu-huo Ji,&nbsp;Yu-gang Diao,&nbsp;Jin-chun Shen","doi":"10.1111/cns.70166","DOIUrl":"10.1111/cns.70166","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Sepsis-associated encephalopathy (SAE) is a serious neurologic complication in septic patients with poor prognoses. There is increasing evidence that stimulator of interferon genes (STING) plays a crucial role in neuroinflammation and cognitive impairment. However, whether sepsis associated with STING changes contributes to cognitive impairment is unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Male adult mice received lipopolysaccharide (LPS) injection (a single dose of 4 mg/kg; i.p. injection) and 30 min later, they were injected with STING inhibitor C-176 (a single dose of 30 mg/kg, i.p. injection). Behavioral assessments, biochemical measurements, in vivo and ex vivo electrophysiology techniques were conducted to investigate the association between LPS-induced STING overexpression and cognitive function.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Cognitive impairment was associated with STING overexpression and activation of microglia/macrophages. Phagocytosis of microglia/macrophages as well as complement C1q release were increased after LPS injection, leading to abnormal pruning synapses, synaptic transmission reduction, long-term potentiation (LTP) impairment, as well as abnormal theta oscillation in the hippocampus. Notably, STING inhibitor C-176 significantly reversed these changes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Sepsis-induced STING overexpression in microglia/macrophages may lead to synaptic loss, abnormal theta oscillation and LTP impairment through microglia/macrophages activation and complement C1q modulation, ultimately resulting in cognitive impairment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 12","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70166","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142851794","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":"Interleukin-3 Modulates Macrophage Phagocytic Activity and Promotes Spinal Cord Injury Repair","authors":"Jianjian Li,&nbsp;Meige Zheng,&nbsp;Fangru Ouyang,&nbsp;Jianan Ye,&nbsp;Jinxin Huang,&nbsp;Yuanzhe Zhao,&nbsp;Jingwen Wang,&nbsp;Fangli Shan,&nbsp;Ziyu Li,&nbsp;Shuishen Yu,&nbsp;Fei Yao,&nbsp;Dasheng Tian,&nbsp;Li Cheng,&nbsp;Juehua Jing","doi":"10.1111/cns.70181","DOIUrl":"10.1111/cns.70181","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Effective clearance of lipid-rich debris by macrophages is critical for neural repair and regeneration after spinal cord injury (SCI). Interleukin-3 (IL-3) has been implicated in programming microglia to cluster and clear pathological aggregates in neurodegenerative disease. Yet, the influence of IL-3 on lipid debris clearance post-SCI is not well characterized.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We established a mouse model of spinal cord compression injury to investigate the role of IL-3. Blockage of IL-3 was achieved through intrathecal delivery of an IL-3-neutralizing antibody, while IL-3 activation was augmented via in situ injection of recombinant IL-3 into the lesion site immediately post-SCI. Immunofluorescence staining was performed to determine IL-3 and IL-3Rα sources and distribution, lipid droplet accumulation, neuron preservation, and axon regeneration after SCI. The Basso Mouse Scale (BMS) and footprint analysis were employed to evaluate locomotor function recovery.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that IL-3 expression was significantly upregulated post-SCI, peaking at 14 days post-injury (dpi) and persisting until 28 dpi. Notably, IL-3 was primarily secreted by astrocytes surrounding the lesion epicenter. Correspondingly, IL-3Rα was predominantly observed in macrophages within the injury core, also elevating at 14 dpi. Neutralization of IL-3 led to increased lipid droplet accumulation, along with markedly widespread of macrophages and decreased neuronal survival, resulting in severe motor deficits compared to controls. Conversely, in situ injection of IL-3 reduced lipid droplet accumulation in macrophages, preserved neurons, promoted axon regeneration, and ultimately contributed to the recovery of motor function after SCI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings shed light on the role of IL-3 in modulating macrophage phagocytic activity and suggest that the IL-3/IL-3Rα pathway may be a potential therapeutic target for enhancing neural repair and functional recovery after SCI.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 12","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70181","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142851792","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":"Potential and Challenges of Transcranial Photobiomodulation for the Treatment of Stroke","authors":"Siyue Li,&nbsp;Thomson W. L. Wong,&nbsp;Shamay S. M. Ng","doi":"10.1111/cns.70142","DOIUrl":"10.1111/cns.70142","url":null,"abstract":"<p>Photobiomodulation (PBM), also known as low-level laser therapy, employs red or near-infrared light emitted from a laser or light-emitting diode for the treatment of various conditions. Transcranial PBM (tPBM) is a form of PBM that is delivered to the head to improve brain health, as tPBM enhances mitochondrial function, improves antioxidant responses, reduces inflammation, offers protection from apoptosis, improves blood flow, increases cellular energy production, and promotes neurogenesis and neuroplasticity. As such, tPBM holds promise as a treatment for stroke. This review summarizes recent findings on tPBM as a treatment for stroke, presenting evidence from both animal studies and clinical trials that demonstrate its efficacy. Additionally, it discusses the potential and challenges encountered in the translation process. Furthermore, it proposes new technologies and directions for the development of light-delivery methods and emphasizes the need for extensive studies to validate and widen the application of tPBM in future treatments for stroke.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 12","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70142","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845409","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":"Esketamine Provides Neuroprotection After Intracerebral Hemorrhage in Mice via the NTF3/PI3K/AKT Pathway","authors":"Xiaoyu Niu,&nbsp;Yuanyuan Zheng,&nbsp;Wang Wang,&nbsp;Liwei Zhang,&nbsp;Shaoshuai Wang,&nbsp;Xihua Lu,&nbsp;Junyang Wang,&nbsp;Gaiqing Yang,&nbsp;Ting Zhao,&nbsp;Qiang Li,&nbsp;Nan Li,&nbsp;Junmin Wang,&nbsp;Jian Wang,&nbsp;Changsheng Li","doi":"10.1111/cns.70145","DOIUrl":"10.1111/cns.70145","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Esketamine (ESK), a noncompetitive antagonist of N-methyl-D-aspartate (NMDA) receptors, modulates neurotransmitter signaling in the central nervous system. However, the specific mechanisms and therapeutic potential of ESK for intracerebral hemorrhage (ICH) remain unclear. This study aimed to investigate whether ESK promotes nerve repair and improves neurological outcomes in an experimental model of ICH.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>ICH was induced in mice via collagenase injection into the striatum. Body weight, neurological impairment, and behavioral changes were assessed. ESK administration significantly improved several indicators of ICH. Comprehensive RNA transcriptome sequencing and network pharmacology analyses identified neurotrophin-3 (NTF3) and the PI3K/AKT signaling pathway as targets for ESK treatment. Western blotting and immunofluorescence detected the protein expression levels and cellular localization of NTF3.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>After 28 days of adeno-associated virus infection in the mouse striatum, ESK treatment significantly enhanced neuroprotection, indicating the crucial role of NTF3 in ESK-mediated neuroprotection in ICH mice. Inhibition of the PI3K/AKT pathway using the PI3K-specific inhibitor LY294002 significantly attenuated the therapeutic effects of ESK, suggesting that this pathway is involved in ESK-mediated neurorepair in ICH mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>ESK treatment significantly improved functional outcomes and demonstrated neuroprotective effects in animal models of ICH. NTF3/PI3K/AKT pathway activation by ESK indicates its therapeutic potential in the treatment of ICH.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 12","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70145","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845354","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":"Altered Hippocampal Subfields Functional Connectivity in Benign Paroxysmal Positional Vertigo Patients With Residual Dizziness: A Resting-State fMRI Study","authors":"Zhengwei Chen,&nbsp;Lijie Xiao,&nbsp;Yueji Liu,&nbsp;Xiue Wei,&nbsp;Zhuo Wang,&nbsp;Xingyi Cao,&nbsp;Haiyan Liu,&nbsp;Yujia Zhai,&nbsp;Liangqun Rong","doi":"10.1111/cns.70175","DOIUrl":"10.1111/cns.70175","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To explore alterations in functional connectivity (FC) focusing on hippocampal subfields in benign paroxysmal positional vertigo (BPPV) patients with residual dizziness (RD) after successful canalith repositioning procedure (CRP).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted resting-state functional magnetic resonance imaging (fMRI) on 95 BPPV patients, comprising 50 patients with RD and 45 without. Seed-to-voxel and seed-to-seed analyses were employed to examine changes in FC between the two groups. The hippocampal subfields, including the bilateral dentate gyrus (DG), cornu ammonis (CA), entorhinal cortex (EC), subiculum, and hippocampal amygdalar transition area (HATA) were selected as seeds. Additionally, we assessed the relationship between abnormal FC and clinical symptoms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Seed-to-voxel analysis indicated that, compared to non-RD patients, those with RD exhibited decreased FC between the right DG and right parietal operculum cortex, right HATA and right precuneus, left HATA and left precuneus, left EC and cerebellar vermis 8/−crus 1, and between the left subiculum and left angular gyrus. Conversely, we observed increased FC between the left CA and left lingual gyrus, as well as between the right CA and right fusiform gyrus in RD patients. Furthermore, these variations in FC were significantly correlated with clinical features including the duration of RD and scores on the Hamilton Anxiety Scale and Dizziness Handicap Inventory.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>BPPV patients with RD exhibited altered FC between hippocampal subfields and brain regions associated with spatial orientation and navigation, vestibular and visual processing, and emotional regulation. These findings offer novel insights into the pathophysiological mechanisms in BPPV patients with RD following successful CRP.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 12","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70175","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845351","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":"Integrating Neutrophil-To-Albumin Ratio and Triglycerides: A Novel Indicator for Predicting Spontaneous Hemorrhagic Transformation in Acute Ischemic Stroke Patients","authors":"Jiajia Bao,&nbsp;Mengmeng Ma,&nbsp;Kongyuan Wu,&nbsp;Jian Wang,&nbsp;Muke Zhou,&nbsp;Jian Guo,&nbsp;Ning Chen,&nbsp;Jinghuan Fang,&nbsp;Li He","doi":"10.1111/cns.70133","DOIUrl":"10.1111/cns.70133","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;Hemorrhagic transformation (HT) is a tragic complication of acute ischemic stroke (AIS), with spontaneous HT (sHT) occurring even without reperfusion therapies. Despite evidence suggesting that several inflammation biomarkers are closely related to HT, its utility in sHT risk stratification remains unclear. This study aimed to identify and integrate effective inflammatory biomarkers associated with sHT and to develop a novel nomogram model for the early detection of sHT.&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;We conducted a retrospective observational cohort study of AIS patients receiving conventional medical treatment solely from March 2022 to March 2023, using a prospectively maintained database. All patients underwent CT follow-up within 7 days after admission, with sHT occurrence within this period as the outcome. Data on demographics, clinical information, laboratory results, and imaging were collected. The cohort was divided into training and validation sets (7:3). Least absolute shrinkage and selection operator (LASSO) regression selected inflammatory biomarkers for a novel index. Univariable and multivariable logistic regressions were conducted to identify independent sHT risk factors. Receiver operating characteristic (ROC) analysis determined optimal cut-off values for continuous factors. A nomogram was developed and validated internally and externally. Predictive accuracy was assessed using the area under the ROC curve (AUC) and calibration plots. Decision curve analysis (DCA) evaluated clinical usefulness.&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;Of 803 AIS patients, 325 were included in the final analysis. sHT was found in 9.5% (31 patients). Training (&lt;i&gt;n&lt;/i&gt; = 228) and validation (&lt;i&gt;n&lt;/i&gt; = 97) cohorts showed no significant demographic or clinical differences. LASSO regression integrated neutrophil-to-albumin ratio (NAR) and triglycerides (TGs) into a novel index—NATG. Independent sHT risk factors included baseline National Institute of Health Stroke Scale (NIHSS) (OR = 1.09, 95% CI (1.02, 1.16), &lt;i&gt;p&lt;/i&gt; = 0.0095), NATG (OR = 1534.87, 95% CI (5.02, 469638.44), &lt;i&gt;p&lt;/i&gt; = 0.0120), D-dimer (DD) (OR = 1.12, 95% CI (1.01, 1.25), &lt;i&gt;p&lt;/i&gt; = 0.0249), and total cholesterol (TC) (OR = 1.01, 95% CI (1.00, 1.01), &lt;i&gt;p&lt;/i&gt; = 0.0280), with their respective optimal cut-off values being 13, 0.059, 0.86, and 3.6. These factors were used to develop the nomogram in the training cohort, which achieved an AUC of 0.804 (95% CI, 0.643–0.918) in the training cohort and 0.713 (95% CI, 0.499–0.868) in the validation cohort, demonstrating consistent calibration. DCA confirmed the nomogram's clinical app","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 12","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70133","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845383","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}