Experimental Neurology最新文献

{"title":"Lactate exacerbates neuroinflammation in sepsis-associated encephalopathy via promoting neutrophil migration from skull bone marrow to the meninge","authors":"Yutao Du ,&nbsp;Yicheng Li ,&nbsp;Fanfan Ye ,&nbsp;Hanxiao Cai ,&nbsp;Wenmian Huang ,&nbsp;Tao Liu ,&nbsp;Xiaochang Xue ,&nbsp;Guodong Feng","doi":"10.1016/j.expneurol.2025.115318","DOIUrl":"10.1016/j.expneurol.2025.115318","url":null,"abstract":"<div><div>Sepsis-associated encephalopathy (SAE) is one of the most common and severe complications of sepsis. Although lactate and neutrophils play pivotal roles in SAE, the mechanisms linking lactate, neutrophils, and neuroinflammation in SAE remain largely unclear.</div><div>In this study, SAE model was induced in C57BL/6 J mice via intraperitoneal lipopolysaccharide (LPS) injection, with lactate production inhibited by administering the lactate dehydrogenase inhibitor FX-11. Neutrophils were visualized by immunofluorescence, and immune cell subsets were quantified via flow cytometry. Our findings revealed that lactate levels in the skull bone marrow (SBM) were significantly elevated in SAE mice, accompanied by decreased SBM neutrophils and increased neutrophil extravasation into the meninges. These effects were reproduced in exogenous lactate-administered normal mice. Further studies identified that a CD31⁺ channel between the SBM and meninges facilitates neutrophil mobilization and migration. Notably, FX-11 injection significantly alleviated SAE in mice, as indicated by reduced SBM lactate production, inhibited neutrophil mobilization, decreased meningeal neutrophil extravasation, suppressed microglial activation and reduced hippocampal inflammatory cytokines as well.</div><div>In summary, our results show that elevated lactate levels in the SBM promote neutrophil migration between the skull and meninges and hence exacerbate SAE neuroinflammation, which can be potently improved in the presence of the lactate inhibitor FX-11. The migration of neutrophils influenced by lactate in the skull–meninges–brain axis could be a potential therapeutic target for the treatment of SAE.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"391 ","pages":"Article 115318"},"PeriodicalIF":4.6,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Salvianolic acid B exerts cerebroprotective effects after traumatic brain injury via Nrf2-dependent antioxidant and anti-inflammatory cascades","authors":"Dacheng Wang ,&nbsp;Yanxia Geng ,&nbsp;Fengming Gu ,&nbsp;Yan Zhuang ,&nbsp;Hai Lv ,&nbsp;Xue He ,&nbsp;Haicheng Yang ,&nbsp;Jun Lu","doi":"10.1016/j.expneurol.2025.115305","DOIUrl":"10.1016/j.expneurol.2025.115305","url":null,"abstract":"<div><h3>Background</h3><div>Oxidative stress and inflammatory responses play crucial roles in the development of secondary brain injury following traumatic brain injury (TBI). Thus, this study aimed to investigate the potential cerebroprotective effects of salvianolic acid B (SalB) in mitigating oxidative stress and inflammatory responses post-TBI through the activation of Nrf2.</div></div><div><h3>Purpose</h3><div>This study aims to investigate the potential cerebroprotective effects of SalB in ameliorating oxidative stress and inflammatory responses following TBI by activating Nrf2, thereby laying a foundation for TBI treatment.</div></div><div><h3>Study design</h3><div>Controlled cortical impact and hydrogen peroxide were employed to replicate TBI in animal and cellular models, respectively.Behavioral studies predict neural function, Western Blot (WB) predicts oxidative stress, immunofluorescence and ELISA predict inflammatory response.The Nrf2 inhibitor ML385 was employed to investigate the involvement of the Nrf2 pathway in mediating the protective effects of SalB.</div></div><div><h3>Methods</h3><div>SalB was delivered via intraperitoneal injection 1 h after TBI induction, with its neuroprotective efficacy evaluated across a range of concentrations. In the cellular assay, SalB was used to incubate cells simultaneously with H₂O₂. WB analysis was employed to quantify protein levels, while malondialdehyde, glutathione, superoxide intensity, and reactive oxygen radical probes were utilized to evaluate oxidative stress. Immunofluorescence and ELISA techniques were used to characterize microglia phenotype and inflammatory response. Behavioral assays were also conducted to evaluate neurological function. The Nrf2 inhibitor ML385 was employed to investigate the involvement of the Nrf2 pathway in mediating the protective effects of SalB.</div></div><div><h3>Results</h3><div>Animal and cellular experiments indicate that SalB can mitigate oxidative stress through the Nrf2/Peroxiredoxin 2 pathway, and reduce inflammatory response via the Nrf2/Toll-like receptor 4/Myeloid differentiation primary response protein 88 pathway in a dose-dependent manner. Consequently, SalB demonstrates efficacy in enhancing neurological function following TBI. Conversely, the inhibitory effects of ML385 counteract the antioxidant and anti-inflammatory properties of SalB.</div></div><div><h3>Conclusions</h3><div>SalB exerts its beneficial effects post-TBI through Nrf2-dependent antioxidants and as anti-inflammatory responses.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"391 ","pages":"Article 115305"},"PeriodicalIF":4.6,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering the NLRP3 inflammasome in diabetic encephalopathy: Molecular insights and emerging therapeutic targets","authors":"Xinyi Zeng ,&nbsp;Yi Yuan ,&nbsp;Yujia Li ,&nbsp;Ziyan Hu ,&nbsp;Shan Hu","doi":"10.1016/j.expneurol.2025.115304","DOIUrl":"10.1016/j.expneurol.2025.115304","url":null,"abstract":"<div><div>Diabetic encephalopathy (DE) is a neurological complication characterized by neuroinflammation, cognitive impairment, and memory decline, with its pathogenesis closely linked to the activation of the NLRP3 inflammasome. As a central regulator of the innate immune system, the NLRP3 inflammasome plays a pivotal role in DE progression by mediating neuroinflammation, pyroptosis, mitochondrial dysfunction, oxidative stress, endoplasmic reticulum (ER) stress, and microglial polarization. This review systematically explores the molecular mechanisms by which the NLRP3 inflammasome contributes to DE, focusing on its role in neuroinflammatory cascades and neuronal damage, as well as the diabetes-associated physiological changes that exacerbate DE pathogenesis. Furthermore, we summarize emerging therapeutic strategies targeting the NLRP3 inflammasome, including small-molecule inhibitors and bioactive compounds derived from traditional herbal medicine, highlighting their potential for DE treatment. These findings not only advance our understanding of DE but also provide a foundation for developing NLRP3-targeted pharmacological interventions.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"391 ","pages":"Article 115304"},"PeriodicalIF":4.6,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144083932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-Nogo-A antibody treatment six months post-stroke results in neuroplasticity and improved functional outcome","authors":"Shih-Yen Tsai ,&nbsp;Son T. Ton ,&nbsp;Timothy E. O'Brien ,&nbsp;Douglas G. Wallace ,&nbsp;Russ P. Nockels ,&nbsp;Gwendolyn L. Kartje","doi":"10.1016/j.expneurol.2025.115306","DOIUrl":"10.1016/j.expneurol.2025.115306","url":null,"abstract":"<div><div>We have reported that anti-Nogo-A antibody therapy is effective in enhancing neuroplasticity and improving functional recovery when given up to two months post-stroke. Here we assessed whether this therapy would be effective at a much later time point post-stroke. Rats underwent middle cerebral artery occlusion to permanently impair their preferred forelimb and six months later were given either anti-Nogo-A antibody, control antibody or no antibody. Rats receiving anti-Nogo-A antibody showed significant behavioral improvement that correlated with cortico-rubral plasticity, indicating that anti-Nogo-A antibody is effective even long after the injury has occurred, opening the treatment window for many stroke survivors.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"391 ","pages":"Article 115306"},"PeriodicalIF":4.6,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Remote ischemic conditioning–induced shift from a vulnerable to a tolerant penumbra: A proteomic perspective","authors":"Petra Bonová ,&nbsp;Jana Končeková ,&nbsp;Miroslava Némethová ,&nbsp;Marko Morávek ,&nbsp;Peter Baráth ,&nbsp;Maksym Danchenko ,&nbsp;Martin Bona","doi":"10.1016/j.expneurol.2025.115307","DOIUrl":"10.1016/j.expneurol.2025.115307","url":null,"abstract":"<div><div>The concept of the ischaemic penumbra – stroke tissue with the potential to survive – has opened the door to a wide range of experimental strategies that could benefit the recovery of patients after a stroke. In this study, we used proteomic analysis to examine how remote ischaemic postconditioning (RIPC) mediates a shift from a vulnerable to a tolerant penumbra. We identified 450 differentially abundant proteins between the control group and the groups subjected to ischaemia via middle cerebral artery occlusion with or without RIPC during infarct expansion. The majority of proteins were downregulated following RIPC. Based on Gene Ontology enrichment analysis, we uncovered 24 gene sets significantly influenced during the reprogramming from a vulnerable to a tolerant penumbra. RIPC treatment positively impacted the synthesis of proteins enriched in the cytosol (GO:0005829) but inhibited the abundance of proteins belonging to the cytoskeleton (GO:0005874 microtubule) and the glutamatergic synapse (GO:0098978). The shift to a tolerant phenotype involved overexpression of aminopeptidases (GO:0004177) related to proteolysis (GO:0006508). RIPC also downregulated proteins involved in the tricarboxylic acid cycle (GO:0006099), adenosine triphosphate (ATP) binding (GO:0005524), and ATP hydrolysis (GO:0016887). We validated our proteomic findings by selecting two candidate genes (Map2 and Tubb3) for immunofluorescence. We identified the low-molecular-weight Map2 isoform as a potential marker of the shift from a vulnerable to a tolerant penumbra. In summary, our findings have revealed novel avenues for multimodal investigation of reprogramming the penumbra as part of recovery from stroke.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"391 ","pages":"Article 115307"},"PeriodicalIF":4.6,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The overexpression of miR-146a in hippocampal microglia via IRAK1/TRAF6/NF-κB pathway improves cognitive function in diabetic mice","authors":"Jingyu Zhang ,&nbsp;Xiaoyun Lin ,&nbsp;Qing Huang ,&nbsp;Zhang Fu ,&nbsp;Yihuan Huang ,&nbsp;Zhiqing Chen ,&nbsp;Ningning Li ,&nbsp;Xiahong Lin","doi":"10.1016/j.expneurol.2025.115291","DOIUrl":"10.1016/j.expneurol.2025.115291","url":null,"abstract":"<div><h3>Background and objective</h3><div>Diabetic encephalopathy (DEP), a central nervous system complication of diabetes, is primarily characterized by cognitive dysfunction. Despite its high prevalence and significant risks, the pathogenesis remains poorly understood. This study investigates the effects and mechanisms of miR-146a on cognitive function in DEP mice.</div></div><div><h3>Methods</h3><div>Type 2 diabetic mice models were established by feeding a high-fat diet and administering a low-dose of streptozotocin. And the Morris water maze test was conducted to assess the learning and memory. The adeno-associated virus was delivered into hippocampus by stereotactic injection to overexpress miR-146a in microglia. The mRNA and protein expression levels were determined by quantitative real-time polymerase chain reaction, immunofluorescence, Western blot, and enzyme-linked immunosorbent assay.</div></div><div><h3>Results</h3><div>DEP mice exhibited significantly reduced miR-146a expression in hippocampal microglia. This reduction was associated with elevated IRAK1, TRAF6, and NF-κB expression, increased markers of pro-inflammatory microglial phenotypes (CD86 and iNOS), and decreased markers of anti-inflammatory phenotypes (Arg-1 and CD206). Pro-inflammatory cytokines TNF-α and IL-6 were elevated, while anti-inflammatory IL-10 was reduced. Eventually, neuronal apoptosis and cognitive dysfunction were evident. Overexpression of miR-146a in hippocampal microglia reversed these molecular and phenotypic abnormalities, decreased neuronal apoptosis, and significantly improved cognitive performance in diabetic mice.</div></div><div><h3>Conclusion</h3><div>Downregulation of miR-146a in hippocampal microglia disrupts immune homeostasis through the IRAK1/TRAF6/NF-κB pathway, contributing to DEP. Targeted overexpression of miR-146a restores immune homeostasis, reduces neuronal apoptosis, and ameliorates cognitive impairment.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"391 ","pages":"Article 115291"},"PeriodicalIF":4.6,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Icariin attenuates oxidative stress via SIRT1/PGC-1α pathway in SAH mice","authors":"Xingwei Lei,&nbsp;Daochen Wen,&nbsp;Zichao Huang,&nbsp;Xiaoguo Li,&nbsp;Liuyang Tang,&nbsp;Yajun Zhu,&nbsp;Zongduo Guo","doi":"10.1016/j.expneurol.2025.115303","DOIUrl":"10.1016/j.expneurol.2025.115303","url":null,"abstract":"<div><div>Oxidative stress plays a pivotal role in the pathological response of subarachnoid hemorrhage (SAH). Icariin (ICA), with its potent antioxidant properties, exerts neuroprotective effects in stroke. This study investigated the beneficial effects of ICA on SAH-induced oxidative damage and its possible molecular mechanisms. The results indicated that ICA treatment improved both short-term and long-term neurobehavioral functions in mice with SAH. ICA significantly inhibited SAH-induced reactive oxygen species (ROS) generation and lipid peroxidation. Simultaneously, ICA restored the activity of the endogenous antioxidant enzyme system. Furthermore, ICA mitigated mitochondrial damage, improved mitochondrial morphology, further reduced neuronal apoptosis, and decreased brain edema following SAH. Mechanistically, ICA suppressed oxidative stress after SAH by activating Sirtuin 1 (SIRT1), subsequently upregulating the expression of PGC-1α. The SIRT1 inhibitor EX527 significantly inhibited ICA-induced SIRT1 activation and abolished the antioxidant and neuroprotective effects of ICA. In cellular experiments, ICA also inhibited ROS production and enhanced cell viability. These effects were associated with SIRT1 activation and were reversed by EX527 treatment. In conclusion, this study explored the protective effects of ICA against SAH-induced oxidative damage, suggesting that ICA could be a potential therapeutic agent for SAH.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"390 ","pages":"Article 115303"},"PeriodicalIF":4.6,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143931541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of Plxdc2 exacerbates microglia-mediated neuroinflammation and ischemic brain injury","authors":"Lixuan Yang ,&nbsp;Yang Geng ,&nbsp;Yi Qian ,&nbsp;Ningning Zong ,&nbsp;Shengnan Xia ,&nbsp;Haiyan Yang ,&nbsp;Xinyu Bao ,&nbsp;Jian Chen ,&nbsp;Yun Xu","doi":"10.1016/j.expneurol.2025.115302","DOIUrl":"10.1016/j.expneurol.2025.115302","url":null,"abstract":"<div><div>Microglia are the supervisors maintaining intracerebral homeostasis, which function importantly in determining the outcome of ischemic stroke. Plxdc2 is a single-transmembrane protein and mainly studied in the development of central nervous system and cancers, whereas its role in the function of microglia remains elusive. In this study, based on our previous scRNA-seq of ischemic brain and transcriptomic analysis of microglia isolated from the ischemic brain, we found that Plxdc2 was abundantly expressed in microglia and remarkably downregulated after stroke. Further, with adeno-associated virus (AAV) overexpressing or lentivirus interfering Plxdc2 in microglia in vivo, Plxdc2 was proved to protect against ischemic brain injury. Plxdc2 helps maintain microglial homeostatic state both in vitro and in vivo, and downregulation of Plxdc2 exacerbated microglial inflammatory response. In addition, we found that Plxdc2 participated in regulating the activation of NF-κB p65 signaling, and also modulated microglial lipid metabolism. Moreover, Plxdc2 was found to facilitate the activation of PPARγ, which might account for its impact on NF-κB p65 signaling and lipid metabolism in microglia. Overall, our results illustrated a vital role of Plxdc2 in modulating post-stroke microglial activation, which holds potential to be a novel target for immunomodulation in ischemic stroke.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"391 ","pages":"Article 115302"},"PeriodicalIF":4.6,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynein-regulated brain transduction of AAV.CAP-B10 via cerebral lateral ventricle enhances hippocampal function after traumatic brain injury through Ngf gene delivery in mice","authors":"Jiang-Chang Wang ,&nbsp;Sheng-Hao Ding ,&nbsp;Zheng-Hui He ,&nbsp;Jia-lin Huang ,&nbsp;Wei-Ji Weng ,&nbsp;Ying-Wei Gao ,&nbsp;Ji-Yao Jiang ,&nbsp;Yong Lin ,&nbsp;Jun-Feng Feng","doi":"10.1016/j.expneurol.2025.115285","DOIUrl":"10.1016/j.expneurol.2025.115285","url":null,"abstract":"<div><div>The blood-brain barrier (BBB) poses a significant challenge for the intravenous delivery of drugs targeting central nervous system (CNS) diseases. Recently, a novel adeno-associated virus (AAV)-9 variant, AAV.CAP-B10, has shown promise due to its high BBB-crossing efficiency and low liver toxicity. However, its strain dependency, ability to transduce the brain following cerebral lateral ventricle (CLV) injection, and underlying mechanisms remain unclear. In this study, we intravenously administered AAV.CAP-B10 to C57BL/6 and BALB/c mice to evaluate its ability to cross the BBB. We also injected AAV.CAP-B10 into the CLV of both mouse strains to assess brain transduction and explored its mechanisms using ciliobrevin D, a dynein inhibitor. Additionally, we tested whether AAV.CAP-B10 could deliver the nerve growth factor (<em>Ngf</em>) gene to treat traumatic brain injury (TBI) in mice. Our results showed that intravenous AAV.CAP-B10 effectively crossed the BBB in C57BL/6 mice but not in BALB/c mice. Brain transduction via CLV was significantly reduced in ciliobrevin D-treated mice, implicating dynein in this process. Furthermore, AAV.CAP-B10-mediated <em>Ngf</em> gene expression improved hippocampal function in TBI mice. These findings highlight the strain-dependent BBB penetration of AAV.CAP-B10, its dynein-associated hippocampal transduction via CLV, and its potential as a therapeutic gene vector for TBI treatment.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"391 ","pages":"Article 115285"},"PeriodicalIF":4.6,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143937406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Npas4 as a biomarker for CICI by transcriptomics combined with bioinformatics and machine learning approaches","authors":"Zhenyu He ,&nbsp;Huanhuan Ma ,&nbsp;Yu Zhang ,&nbsp;Liping Chen ,&nbsp;Yueling Pang ,&nbsp;Xiaoshan Ding ,&nbsp;Yanan Wang ,&nbsp;Yongqi Liu ,&nbsp;Ling Li ,&nbsp;Jiawei Li","doi":"10.1016/j.expneurol.2025.115290","DOIUrl":"10.1016/j.expneurol.2025.115290","url":null,"abstract":"<div><div>Chemotherapy is one of the most successful strategies for treating cancer. Unfortunately, up to 70 % of cancer survivors develop cognitive impairment during or after chemotherapy, which severely affects their quality of life. We first established a mouse model of CICI and combined bioinformatics, machine learning, and transcriptome sequencing to screen diagnostic genes associated with CICI. Relevant DEGs were screened by differential analysis, and potential biological functions of DEGs were explored by GO and KEGG analysis. WGCNA analysis was then used to find the most relevant modules for CICI. The diagnostic gene Npas4 was screened by combining the three machine learning methods; its diagnostic value was proved by ROC analysis, GSEA analyzed its potential biological function, and then we preliminarily explored the chemicals associated with Npas4. Our study found that Npas4 can be used as an early diagnostic gene for CICI, which provides a theoretical basis for further research.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"391 ","pages":"Article 115290"},"PeriodicalIF":4.6,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144004971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}