CNS Neuroscience & Therapeutics最新文献

{"title":"AI-Driven Hemodynamic Detection of Self-Induced Daydreaming With EMG-Based Physiological Triggers During Pre- and Post-Prandial States Using fNIRS and EGG.","authors":"Anusha Ishtiaq, Zia Mohy-Ud-Din, Abdullah Al Aishan, Noman Naseer, Syed Ghufran Khalid, Jahan Zeb Gul","doi":"10.1002/cns.70899","DOIUrl":"https://doi.org/10.1002/cns.70899","url":null,"abstract":"<p><strong>Background: </strong>Daydreaming can be monitored either to avoid it while doing hands-on tasks or to enhance it to foster creativity. Although significant research has been conducted in Brain recordings and Machine learning, some problems have not received sufficient attention. One of them is the automated identification and classification of daydream states with emphasis on physiological signals and prandial states. Until now, researchers have been relying only on subjective questionnaire-based methods of daydream identification, neglecting neural hemodynamics.</p><p><strong>Methodology: </strong>In this study, EMG-based physiological triggers have been incorporated to detect self-induced daydream episodes in pre- and post-meal prandial states. For the AI-driven hemodynamic monitoring of the brain in relation to the analysis of the electrical activity of the stomach during self-induced daydreaming, fNIRS and EGG signals of 30 participants were recorded, preprocessed, and investigated simultaneously. Both the duration and frequency of the daydreaming episodes were analyzed using these two modalities, which were further subjected to a feature extraction and class label encoding process to facilitate a four-class classification of daydreaming and prandial state.</p><p><strong>Results and conclusion: </strong>Machine learning models were incorporated for classification and resulted in the highest testing accuracy of 90.77% for daydream detection and gave insights into the connection between meal consumption and daydreaming.</p><p><strong>Future work: </strong>In the future, this study could serve as the preliminary basis for multimodal monitoring systems used to assess the state of cognition in parallel with the analysis of meal intake patterns. This research can also lead to the development of person-specific treatments in the domain of mental and attentional health.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 5","pages":"e70899"},"PeriodicalIF":5.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809206","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":"Transcutaneous Auricular Vagus Nerve Stimulation Alleviates Oxidative Stress and Improves Neurological Outcomes After Traumatic Brain Injury in Mice.","authors":"Xiaoxuan Li, Yifan Fu, Minghao Xu, Xinyu Xu, Jiuyu Gao, Shilin Liu, Zhige Wang, Chuandong Cheng, Tao Jiang","doi":"10.1002/cns.70913","DOIUrl":"10.1002/cns.70913","url":null,"abstract":"<p><strong>Objective: </strong>Traumatic brain injury (TBI) can trigger secondary oxidative stress and exacerbate neurological dysfunction. This study investigated whether transcutaneous auricular vagus nerve stimulation (taVNS) attenuates oxidative stress and improves neurological recovery after TBI in mice.</p><p><strong>Methods: </strong>The TBI model was established using a controlled cortical impact (CCI) model. Seventy C57BL/6 mice were divided into the sham group, TBI group, taVNS group, MDHB (pathway agonist, administered alone) group, and ML385 (pathway inhibitor, administered 30 min before each taVNS session) group. Outcomes were assessed by Western blotting, ELISA, immunofluorescence, T2-weighted MRI-based volumetric quantification of edema, and behavioral tests.</p><p><strong>Results: </strong>TBI markedly increased oxidative stress and neurological impairment, as reflected by reduced serum glutathione (GSH) and superoxide dismutase (SOD) levels, increased lesion and edema burden on MRI, and worsened behavioral performance. TaVNS significantly alleviated these changes, increasing GSH and SOD levels, reducing edema burden, and improving mNSS and open-field performance. In addition, taVNS was associated with increased expression of antioxidant-related proteins, including Nrf-2 and HO-1, whereas pharmacological inhibition with ML385 attenuated these beneficial effects.</p><p><strong>Conclusion: </strong>These findings suggest that taVNS may alleviate oxidative stress and improve neurological outcomes after TBI in mice, with possible involvement of the Nrf-2/HO-1 pathway.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 5","pages":"e70913"},"PeriodicalIF":5.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13137120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147808820","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":"Non-Invasive Temporal Interference Electrical Stimulation Modulates Neurotransmitter Release and Improves Aberrant Neural Oscillations in Alzheimer's Disease.","authors":"Linyan Wu, Sinan Li, Liang Huang, Long Li, Ping Zhou, Zhiyuan Lu, Tian Liu, Jue Wang","doi":"10.1002/cns.70848","DOIUrl":"https://doi.org/10.1002/cns.70848","url":null,"abstract":"<p><strong>Background: </strong>Modulating brain oscillations has significant therapeutic promise. Traditional non-invasive neuromodulation techniques can alleviate clinical signs of Alzheimer's disease (AD) by restoring normal neural oscillatory activity in certain brain regions. As a novel non-invasive brain modulation technique, temporal interference (TI) has been demonstrated to precisely control hippocampus neural oscillations while minimizing its impact on cortical neural activity, but its exact mechanism of action is still unclear.</p><p><strong>Method: </strong>We simulated and experimentally measured the intracranial electric field under TI to determine the precision of TI intervention. Subsequently, TI stimulation was applied to the APP/PS1 transgenic AD mouse model, and the impact of TI stimulation on the stimulated brain region was compared from the perspectives of behavior, electrophysiology, and cell biology.</p><p><strong>Results: </strong>This work showed that in the APP/PS1 Alzheimer's disease mice model, TI stimulation significantly increased GABA levels and decreased NMDA receptor activation at the targeted region. Following neurotransmitter regulation, the rhythm of the gamma oscillations they associate also changed. This, in turn, influenced other memory-related neural oscillation frequencies and brain regions through cross-frequency coupling and brain connectivity, ultimately improving the behavioral performance of AD model mice.</p><p><strong>Conclusions: </strong>The results of our work demonstrated how TI stimulation alters brain oscillations to enhance memory in mice with Alzheimer's disease, offering a possible theoretical foundation for TI's clinical application.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 5","pages":"e70848"},"PeriodicalIF":5.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13141679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147831191","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":"HBO-PC Reprograms Neuroimmune Metabolism Through Disruption of the LRG1-HIF-1α-IL-6-STAT3 Amplification Loop Attenuates Pyroptosis and Ischemia-Reperfusion Injury.","authors":"Wenying Lv, Junzhe Lv, Kexin Xiong, Shunshun Yuan, Jingyao Yang, Dazhi Guo","doi":"10.1002/cns.70907","DOIUrl":"10.1002/cns.70907","url":null,"abstract":"<p><strong>Background: </strong>Neuroinflammation and pyroptosis driven by excessive microglial activation play key roles in cerebral ischemia-reperfusion injury (CIRI). Hyperbaric oxygen preconditioning (HBO-PC) exhibits neuroprotective effects, but its mechanisms remain unclear. Leucine-rich α-2-glycoprotein 1 (LRG1) is implicated in CIRI pathology, yet whether HBO-PC modulates neuroinflammation and pyroptosis via LRG1 is unknown.</p><p><strong>Methods: </strong>A mouse CIRI model was generated by middle cerebral artery occlusion. HBO-PC and LRG1 siRNA knockdown were applied. Neurological function and molecular changes were evaluated.</p><p><strong>Results: </strong>HBO-PC reduced infarct volume and improved neurological outcomes, while downregulating LRG1 in neurons and microglia. LRG1 promoted HIF-1α accumulation by inhibiting prolyl hydroxylase activity, leading to caspase-3-dependent GSDME cleavage and pyroptosis. Released IL-6 activated STAT3, which further transcriptionally upregulated LRG1, forming a self-amplifying HIF-1α/GSDME/IL-6/STAT3 loop. HBO-PC disrupted this circuit and shifted microglia toward an anti-inflammatory phenotype.</p><p><strong>Conclusion: </strong>HBO-PC protects against CIRI by breaking the LRG1-HIF-1α-IL-6-STAT3 feedback loop, thereby attenuating pyroptosis and neuroinflammation while promoting anti-inflammatory microglial polarization. LRG1 represents a promising therapeutic target in ischemic brain injury.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 5","pages":"e70907"},"PeriodicalIF":5.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13127231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758278","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":"Antithrombotic Therapy After Intracerebral Hemorrhage: Real-World Evidence for In-Hospital Resumption.","authors":"Shengde Li, Tian Qu, Xiang Zhou, Qi Miao, Jun Ni, Bin Peng","doi":"10.1002/cns.70883","DOIUrl":"10.1002/cns.70883","url":null,"abstract":"<p><strong>Background and purpose: </strong>Patients with intracerebral hemorrhage (ICH) who require antithrombotic therapy (AT) face competing risks of recurrent bleeding and ischemic events. Optimal timing of AT resumption during hospitalization remains uncertain. We evaluated whether restarting AT in hospitalized patients with acute spontaneous ICH reduces ischemic complications without increasing hemorrhagic risk.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study at Peking Union Medical College Hospital (2014-2022) including adults (≥ 18 years) admitted with spontaneous ICH within 6 months of onset. Patients were categorized as: Group 1, no AT indication; Group 2, AT indicated but not treated; Group 3, AT indicated and treated. Primary endpoints were ischemic events (ischemic stroke, transient ischemic attack, myocardial infarction, pulmonary embolism, deep venous thrombosis) and hemorrhagic events (new ICH or hematoma expansion ≥ 12.5 mL or ≥ 33%). Outcomes were assessed from onset to discharge.</p><p><strong>Results: </strong>Among 601 patients (median age 58 years; 40.3% female), 256 (42.6%) were in Group 1, 247 (41.1%) in Group 2, and 98 (16.3%) in Group 3. Median time to AT resumption was 19 days (IQR 8-36). Restarting AT (Group 3) significantly reduced ischemic events (14.3% vs. 28.7%; adjusted HR 0.34, 95% CI 0.18-0.65) without increasing hemorrhagic events (5.1% vs. 6.3%; adjusted HR 0.67, 95% CI 0.20-2.19). Competing-risk models and sensitivity analysis confirmed these findings.</p><p><strong>Conclusions: </strong>In-hospital resumption of AT after acute spontaneous ICH significantly decreased ischemic events without excess hemorrhagic risk, supporting its potential benefit in carefully selected patients.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 5","pages":"e70883"},"PeriodicalIF":5.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13125426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758315","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":"Novel Insights Into the Association Between Parkinson's Disease and Constipation: Role of SHMT2 as a Promising Biomarker.","authors":"Jiehua Su, Kaixun Huang, Xiuna Jing, Xiaohuan Liu, Cheng Wen, Rulin Geng, Zhuoying Lai, Zhijia Ruan, Yiqiang Zhan, Danyu Lin, Enxiang Tao","doi":"10.1002/cns.70912","DOIUrl":"10.1002/cns.70912","url":null,"abstract":"<p><strong>Aims: </strong>We aimed to investigate the shared molecular pathways between Parkinson's disease (PD) and constipation using bioinformatics analysis.</p><p><strong>Methods: </strong>Differentially expressed genes (DEGs) were identified via the R limma package, and Weighted Gene Co-Expression Network Analysis (WGCNA) was conducted to identify hub modules. Biological enrichment analysis clarified the biological processes involved. A gene-gene interaction (GGI) network was constructed to identify shared hub biomarkers. Validation of these biomarkers was done in vitro with α-synuclein (α-syn)-treated SH-SY5Y cells and in vivo through α-syn-induced PD mouse models, A53T transgenic mice, and loperamide-induced constipation models.</p><p><strong>Results: </strong>Numerous DEGs were identified in both conditions, with 14 shared DEGs found through the intersection of core modules and upregulated DEGs. These DEGs are primarily involved in energy metabolism, protein modification, and mitochondrial function. Five key hub genes were identified using the GGI network and gene topological analysis. Notably, Serine hydroxymethyltransferase 2 (SHMT2) expression was significantly upregulated after α-syn treatment in vitro. Immunohistochemical and immunofluorescence analyses revealed elevated SHMT2 expression in brain and colon tissues in PD mouse models (p < 0.001), whereas in constipation models, SHMT2 was only elevated in the colon wall with no significant expression in the enteric nervous system.</p><p><strong>Conclusion: </strong>Our findings offer new views on the molecular link between PD and constipation, suggesting SHMT2 as a possible biomarker and therapeutic target for PD symptoms.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 5","pages":"e70912"},"PeriodicalIF":5.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13136694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147808675","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":"Myelin Oligodendrocyte Glycoprotein Antibody-Associated Cerebral Cortical Encephalitis: A Comparative Study With Antibody-Negative and Non-MOG Antibody-Positive Cortical Encephalitis in Chinese Adults.","authors":"Qing Yin, Binhong Han, Kai Su, Weiqi Dai, Jing Wu, Li Yang, Yuwei Dai, Dan Wang","doi":"10.1002/cns.70915","DOIUrl":"10.1002/cns.70915","url":null,"abstract":"<p><strong>Aims: </strong>To investigate the clinical, radiological, and prognostic characteristics of autoimmune cortical encephalitis associated with different autoantibodies in Chinese adults, and to compare the features of myelin oligodendrocyte glycoprotein antibody-associated cerebral cortical encephalitis (MOG-CCE) with antibody-negative and non-MOG antibody-positive autoimmune cortical encephalitis.</p><p><strong>Methods: </strong>A retrospective study was conducted on 120 adult patients diagnosed with autoimmune cortical encephalitis at the Second Xiangya Hospital, Central South University, from 2014 to 2024. Patients were divided into three subgroups: the antibody-negative group, the non-MOG antibody-positive group, and the MOG-CCE group. Clinical, radiological, and therapeutic characteristics were analyzed, and logistic regression was performed to identify predictors of poor prognosis.</p><p><strong>Results: </strong>MOG-CCE accounted for 18.3% of all autoimmune cortical encephalitis cases. Compared with other subtypes, MOG-CCE was characterized by seizure-dominant clinical presentation and unilateral cortical MRI lesions. Patients with MOG-CCE responded favorably to immunotherapy and exhibited lower recurrence and disability rates. In contrast, antibody-negative and non-MOG antibody-positive autoimmune cortical encephalitis showed more severe neuropsychiatric symptoms and poorer outcomes. A higher peak mRS score was the strongest independent predictor of long-term disability.</p><p><strong>Conclusions: </strong>MOG-CCE represents a distinct clinical phenotype within autoimmune cortical encephalitis, with favorable immunotherapy responsiveness and prognosis. Antibody profiling aids in disease classification and prognostic evaluation. Prospective multicenter studies are warranted to elucidate underlying mechanisms and refine individualized therapeutic strategies.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 5","pages":"e70915"},"PeriodicalIF":5.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13148144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147830964","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":"Luteolin Protects Against Noise-Induced Hearing Loss via Mitigating Oxidative Stress and Apoptosis, With Potential Regulation of the EGR1/SPRY4 Axis.","authors":"Jia-Ning Guo, Hong-Kai Mei, Rui Liang, Peng-Wei Ma, Wei-Long Wang, Jia-Wei Chen, Zi Wang, Hao Yuan, Yu-Qiang Lun, Wei Gao, Lian-Jun Lu","doi":"10.1002/cns.70906","DOIUrl":"https://doi.org/10.1002/cns.70906","url":null,"abstract":"<p><strong>Aims: </strong>Noise-induced hearing loss (NIHL) is a globally prevalent disorder caused by oxidative stress-mediated hair cell death, with no effective clinical treatments. This study explored the protective effect of luteolin (LL), a natural antioxidant flavonoid, against NIHL and its underlying molecular mechanism.</p><p><strong>Methods: </strong>In vivo, mice received intratympanic LL injections around noise exposure, followed by ABR testing and cochlear immunofluorescence staining. In vitro, cochlear explants and HEI-OC1 cells were pretreated with LL, followed by the induction of oxidative stress using tert-butyl hydroperoxide (TBHP). Cellular viability, oxidative stress, and apoptosis were assessed. CRISPR/Cas9 technique was used to establish an Early growth response 1 (EGR1) knockout cell line. ChIP-PCR and dual-luciferase reporter assays clarified molecular mechanisms.</p><p><strong>Results: </strong>Intratympanic LL significantly attenuated noise-induced auditory threshold elevation and outer hair cell loss in mice without affecting normal hearing. In vitro, LL dose-dependently mitigated TBHP-induced damage via regulating oxidative stress and apoptotic pathways, reversed TBHP-induced EGR1 upregulation, EGR1 knockout enhanced oxidative stress resistance, and EGR1 directly regulated sprouty RTK signaling antagonist 4 (SPRY4) transcription, while LL inhibited TBHP-induced SPRY4 upregulation.</p><p><strong>Conclusion: </strong>Luteolin protects against NIHL by alleviating oxidative stress and suppressing apoptosis, with potential involvement of the EGR1/SPRY4 signaling axis, representing a promising candidate for NIHL prevention.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 5","pages":"e70906"},"PeriodicalIF":5.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809177","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":"Sestrin2 Mitigates Neuronal Ferroptosis Following Subarachnoid Hemorrhage via Orchestration of the AMPK/PGC1α/Nrf2 Signaling Axis.","authors":"Yi Zhang, Xichen Wan, Hongyan Zhang, Zhaoyan Chen, Shining Xiao, Wansong Wang, Jun Wang, Renli Zheng, Xiuping Chen, Youqing Yang","doi":"10.1002/cns.70908","DOIUrl":"10.1002/cns.70908","url":null,"abstract":"<p><strong>Background: </strong>Early brain injury after subarachnoid hemorrhage (SAH) involves oxidative stress and ferroptosis. Sestrin2 (SESN2) regulates redox homeostasis, but its role in SAH-induced ferroptosis remains unclear.</p><p><strong>Methods: </strong>SAH was induced by internal carotid puncture; HT22 cells were hemin-treated. We assessed neurological deficits, brain edema, BBB integrity, iron levels, mitochondrial ultrastructure, and ferroptosis and signaling proteins by Western blot and immunofluorescence. SESN2 function was probed using knockdown, recombinant human SESN2 (rh-SESN2), and pathway inhibitors.</p><p><strong>Results: </strong>rh-SESN2 improved neurological outcomes, attenuated iron accumulation, and preserved mitochondrial morphology after SAH. In HT22 cells, rh-SESN2 increased viability, decreased ROS and MDA, and partially restored SOD activity. rh-SESN2 upregulated GPX4, SLC7A11, and Nrf2 and its nuclear translocation, whereas SESN2 knockdown exacerbated ferroptosis and reduced these proteins. Mechanistically, SESN2 activated AMPK and upregulated PGC1α, facilitating Nrf2 nuclear translocation and inducing antiferroptotic proteins. Pathway inhibition established an AMPK/PGC1α/Nrf2 hierarchy: AMPK inhibition suppressed PGC1α and Nrf2 activation, PGC1α inhibition reduced Nrf2 translocation, and ML385 abrogated SESN2's protective effects.</p><p><strong>Conclusion: </strong>SESN2 activates AMPK, which in turn upregulates PGC1α and promotes Nrf2 nuclear translocation, ultimately inhibiting neuronal ferroptosis after SAH. Targeting this AMPK/PGC1α/Nrf2 axis may provide a novel therapeutic approach for post-SAH neuroprotection.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 5","pages":"e70908"},"PeriodicalIF":5.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13131070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758291","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 Small Molecule Compound Eupalinolide B Ameliorates Depressive Behaviors and Neuropathic Pain in Mice With Spared Nerve Injury: Integrating Network Pharmacology, Molecular Docking, Bioinformatics, Molecular Dynamics Simulation and Experimental Verification","authors":"Xuesong Yang,&nbsp;Fan Jiang,&nbsp;Yanqiong Wu,&nbsp;Kun Chen,&nbsp;Hongbing Xiang","doi":"10.1002/cns.70872","DOIUrl":"10.1002/cns.70872","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Neuropathic pain (NP) frequently co-occurs with depression (DP), exhibiting complex pathogenesis and limited clinical treatment options. This study aims to investigate the efficacy of Eupalinolide B (EB) in alleviating NP co-occurring with DP and its potential molecular mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Combining network pharmacology, molecular docking, and molecular dynamics simulations to screen potential targets for EB, validated through transcriptomic data. Using a sciatic nerve branch-preserving injury (SNI) mouse model, we assessed pain and depression-like behaviors through von Frey testing, hot plate testing, tail suspension testing, forced swimming testing, and open field testing. Concurrently, Western blotting, immunofluorescence, and Nissl staining were employed to analyze relevant molecules and neuropathological alterations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Network pharmacology and bioinformatics analysis identified EGFR, PTGS2, and JUN as the key targets for EB in treating NP combined with DP. Behavioral studies showed that 20 mg/kg of EB significantly alleviated pain in SNI mice and improved depressive-like behaviors. Mechanism research indicated that EB downregulated the expression of EGFR and PTGS2, inhibited the activation of microglia and astrocytes, and reduced neuronal damage. Additionally, EB could upregulate the expression of synaptic proteins (PSD95, SYN1, and BDNF) in the hippocampus.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>EB alleviates neuroinflammation by reducing EGFR and PTGS2 protein expression, modulates synaptic plasticity, and improves pain-depression comorbidity. EB may represent a promising therapeutic approach for pain-related depression.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 4","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13067920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147643407","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}