Neuroprotection最新文献

{"title":"Chronic high-altitude exposure and intracerebral hemorrhage: A novel perspective from the vascular-immune-neuronal network.","authors":"Rongsu Huang, Linjie Wei, Mingxi Li, Bo Wu, Rongjian Ouyang, Gang Zhu, Yujie Chen","doi":"10.1002/nep3.70059","DOIUrl":"https://doi.org/10.1002/nep3.70059","url":null,"abstract":"<p><p>Intracerebral hemorrhage (ICH) under chronic high-altitude exposure exhibits distinct epidemiological characteristics: higher incidence, younger age at onset, more severe perihematomal edema, and worse clinical outcomes. However, the specific mechanisms underlying its pathogenesis and progression remain incompletely understood. In this review, we demonstrate that immigrant populations subjected to chronic high-altitude exposure are at increased risk of ICH relative to indigenous populations (Tibetans, Andeans), primarily due to the lack of adaptive genetic variations such as endothelial PAS domain protein 1 and small ubiquitin-like modifier-specific peptidase 1. Additionally, high-altitude polycythemia, high-altitude hypertension, and hyperuricemia have been identified as critical risk factors for high-altitude ICH. Further mechanistic exploration reveals that chronic high-altitude exposure-induced brain injury is structurally underpinned by vascular-immune-neuronal network dysfunction, which entails the interactive crosstalk of \"vascular injury-immune infiltration-neurodegeneration\" and thereby creates a unique pathological niche for high-altitude ICH. At the molecular level, the core driving mechanism is the reciprocal activation of the hypoxia-inducible factor pathway, oxidative stress, and neuroinflammation. This review represents a comprehensive synthesis of chronic high-altitude exposure-related brain injury and the subsequent exacerbation of ICH, providing a valuable reference for future research on high-altitude encephalopathy.</p>","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149119679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness and safety of efgartigimod in patients with anti-NMDAR or anti-LGI1 encephalitis and its ¹⁸F-DPA714 PET imaging evaluation: A multicenter, single-arm, prospective, observational real-world study.","authors":"Huanyu Meng, Siqi Tu, Yifan Zhou, Ruinan Shen, Xiaoyu Chen, Zhaozhao Cheng, Limei Wang, Yan Wu, Jie Lu, Shengjun Wang, Yan Xu, Wanhui Lin, Sheng Chen","doi":"10.1002/nep3.70063","DOIUrl":"10.1002/nep3.70063","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Efgartigimod disrupts the recycling of pathogenic IgG autoantibodies and may represent a candidate therapy for autoimmune encephalitis. This real-world study evaluated the clinical efficacy, safety, and impact of efgartigimod on brain inflammation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This multicenter, single-arm, prospective, observational real-world study enrolled 18 patients, including 10 with anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis and 8 with anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis. Participants received intravenous efgartigimod at a dose of 10 mg/kg weekly for a total of two to four doses, with or without concomitant immunosuppressive therapy. Anti-NMDAR-IgG/LGI1-IgG antibody titers, modified Rankin scale (mRS), Clinical Assessment Scale in Autoimmune Encephalitis (CASE), Montreal Cognitive Assessment, Mini-Mental State Examination, and Glasgow Coma Scale scores were assessed at baseline and at 1, 2, 3, 8, and 12 weeks after treatment. &lt;sup&gt;18&lt;/sup&gt;F-DPA714 positron emission tomography/magnetic resonance imaging was used to monitor brain inflammation in a subset of patients. Analyses were performed using SPSS 26.0 and Prism 10.0. Non-parametric tests, including Wilcoxon signed-rank, Mann-Whitney &lt;i&gt;U&lt;/i&gt;, and Friedman tests with Bonferroni post hoc correction, were applied. Two-tailed &lt;i&gt;p&lt;/i&gt; &lt; 0.05 indicated statistical significance; corrected &lt;i&gt;p&lt;/i&gt; &lt; 0.01 was applied for five longitudinal pairwise comparisons.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;At the final follow-up, median mRS scores in patients with anti-NMDAR encephalitis decreased significantly from 3 (range, 1-5) before treatment to 1 (range, 0-3) after treatment (&lt;i&gt;Z&lt;/i&gt; = -2.588, &lt;i&gt;p&lt;/i&gt; = 0.007). Median CASE scores decreased from 7.5 (range, 1-27) to 1.5 (range, 1-7) post-treatment (&lt;i&gt;Z&lt;/i&gt; = -2.714, &lt;i&gt;p&lt;/i&gt; = 0.005). In patients with anti-LGI1 encephalitis, CASE scores decreased markedly from 3 (range, 1-7) to 1.5 (range, 0-2) at the last visit (&lt;i&gt;Z&lt;/i&gt; = -2.154, &lt;i&gt;p&lt;/i&gt; = 0.046). All 18 patients underwent baseline imaging, and 7 patients underwent follow-up PET/MRI examinations. A subset of patients (&lt;i&gt;n&lt;/i&gt; = 4; three with anti-NMDAR encephalitis and one with anti-LGI1 encephalitis) showed reduced uptake in specific brain regions accompanied by symptom improvement. Both initial and follow-up imaging results were negative for the remaining three patients. Comparative analysis of efgartigimod monotherapy versus combination therapy with glucocorticoids and immunosuppressants revealed no significant differences in key outcomes, indicating that the therapeutic effect was independent of concomitant medication use. Efgartigimod was well tolerated. One patient (1/18) developed mild pneumonia, but no other serious adverse events were reported.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Efgartigimod may represent a novel therapeutic option for anti-NMDAR and anti-LGI1 encephalitis, potentially improving clinical outcomes in af","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13572831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148972788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repurposing antimicrobial agents for neuroprotection: Mechanisms, clinical potential, and challenges.","authors":"Mohammad Amin Manavi, Mohammadreza Salehi, Razieh Mohammad Jafari, Ramin Goudarzi, Saman Khosravi, Ahmad Reza Dehpour","doi":"10.1002/nep3.70042","DOIUrl":"10.1002/nep3.70042","url":null,"abstract":"<p><p>Antimicrobial agents, originally developed for infectious diseases, have become attractive candidates for repurposing in neurodegenerative and neuroinflammatory diseases owing to their anti-inflammatory, antioxidant, immunomodulatory, and neuroprotective activities. In this review, we critically examine the therapeutic potential of selected antimicrobial classes, including tetracyclines (e.g., minocycline), macrolides (e.g., azithromycin), antimalarial agents (e.g., chloroquine/hydroxychloroquine), sulfones (e.g., dapsone), and antiparasitic agents (e.g., ivermectin), in non-infectious neurological diseases. We performed a narrative review of pre-clinical and clinical studies to investigate the effects of these agents on the main neuropathological mechanisms, such as neuroinflammation, oxidative stress, mitochondrial dysfunction, impaired autophagy, and gut-brain axis dysregulation. The available evidence suggests that many of the antimicrobial agents have beneficial effects in a number of neurological disorders, including Alzheimer's disease, Parkinson's disease, epilepsy, stroke, and traumatic brain injury. These agents have been shown to modulate microglia activation, to inhibit production of pro-inflammatory cytokines, and to alter intracellular signaling pathways, including nuclear factor kappa-light-chain-enhancer of activated B cells. Furthermore, by reshaping the gut microbiota, antimicrobials modulate immune signaling, alter neurotransmitter levels, and compromise blood-brain barrier integrity-thereby positioning the gut-brain axis as central to their mechanism of action. Repurposing antimicrobial agents is a pragmatic and novel approach to treat complex neurological disorders with available approved drugs. Despite the encouraging evidence, we must carefully manage challenges such as antimicrobial resistance, off-target effects, and regulatory considerations. Further well-designed clinical trials are essential to validate their long-term safety and efficacy in neurodegenerative and neuroinflammatory diseases.</p>","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13564292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148957082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Noninvasive or minimally invasive neuromodulation in animal models of acute ischemic stroke: A systematic review and meta-analysis.","authors":"Igor Caitano Salles, Mateus Paquesse Pellegrino, Jessica Borges Kroth, Clara Lucato Dos Santos, Luca Schiliro Tristao, Jullyanna Sabrysna Morais Shinosaki, Wanderley Marques Bernardo, Adriana Bastos Conforto","doi":"10.1002/nep3.70056","DOIUrl":"10.1002/nep3.70056","url":null,"abstract":"<p><strong>Background: </strong>Neuromodulation therapy has emerged as a potential brain cytoprotective strategy in the hyperacute phase of ischemic stroke (IS). This systematic review aimed to evaluate the cytoprotective effects of neuromodulation in animal models of IS.</p><p><strong>Methods: </strong>A systematic search of the MEDLINE, Embase, and LILACS databases was conducted to identify in vivo preclinical studies that investigated noninvasive or minimally invasive neuromodulation therapy administered within 24 h of arterial occlusion and included a control group. The primary outcome was infarct volume, and the secondary outcomes included assessments of neurological function using validated behavioral scales. Random-effects meta-analyses were performed for all outcomes using the Cochrane Review Manager software (version 5.4.1). The protocol was prospectively registered in the International Prospective Register of Systematic Reviews database (No. CRD42020165347).</p><p><strong>Results: </strong>Thirty studies were included in the qualitative synthesis (2347 reported animals), and 25 studies were eligible for meta-analysis. Most studies employed middle cerebral artery occlusion models. Neuromodulation techniques included electroacupuncture, repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and vagus nerve stimulation. Pooled analyses demonstrated that neuromodulation significantly reduced infarct volume both in absolute (standardized mean difference [SMD]: -0.80; <i>p</i> < 0.001) and relative terms (SMD: -2.01; <i>p</i> < 0.001) and improved neurological outcomes (SMD: -1.53; <i>p</i> = 0.006). However, considerable heterogeneity was observed across studies and interventions.</p><p><strong>Conclusion: </strong>Neuromodulation confers brain cytoprotective effects in experimental IS models; however, the high heterogeneity in stimulation parameters and outcomes limits its translational potential. Standardization of experimental protocols and reporting is required to improve reproducibility.</p>","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13551444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148914637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesenchymal stem cells as cellular factories for targeted P2X7 blockade after traumatic brain injury.","authors":"Lucia Fadon-Padilla, Chengyan Chu, Lorissa McDougall, Yajie Liang, Chinmoy Sarkar, Marta Lipinski, Tim Magnus, Miroslaw Janowski, Piotr Walczak","doi":"10.1002/nep3.70055","DOIUrl":"10.1002/nep3.70055","url":null,"abstract":"<p><strong>Background: </strong>Traumatic brain injury (TBI) causes long-term disability, with inflammation contributing to both primary and secondary brain damage. Extracellular adenosine triphosphate (ATP) and its receptor purinergic receptor X7 (P2X7) drive neuroinflammation and represent promising therapeutic targets. Therefore, we developed a strategy to mitigate acute post-TBI inflammation using mesenchymal stem cells (MSCs) engineered to deliver a P2X7-blocking nanobody (P2X7nb).</p><p><strong>Methods: </strong>Primary MSCs were transfected in vitro with bicistronic messenger RNA (mRNA) encoding P2X7nb and a haloalkane dehalogenase Tag reporter, with nanobody secretion confirmed by enzyme-linked immunosorbent assay (ELISA). In vivo, TBI was induced in mice using the closed-head injury model. Twenty-4 hours post-TBI, MSCs labeled with iron oxide nanoparticles were administered via intra-arterial injection into the internal carotid artery. Dynamic 9.4 T magnetic resonance imaging (MRI) using susceptibility-weighted imaging (SWI) allowed real-time monitoring of cellular accumulation. Behavioral performance was assessed using the beam walk test, while mice were euthanized on Day 4 post-TBI for immunofluorescence analysis of cell localization. Data were analyzed using either an unpaired <i>t</i>-test or Mann-Whitney <i>U</i> test, depending on data distribution, with statistical significance set at <i>p</i> < 0.05.</p><p><strong>Results: </strong>Transfection (38.9% efficiency) and release of P2X7nb were confirmed, with a peak secretion of 17.29 ± 1.84 ng/mL. SWI MRI revealed accumulation of labeled MSCs in the brain post-injection, with a persistent hypointense signal ranging from 2.45% ± 2.93% to 0.77% ± 0.88% of cell area (% of right hemisphere) over 3 days. Behavioral assessment using the beam walk test revealed no cell transplantation-related motor impairment, while histology confirmed the presence of transfected MSCs in injured brain tissue.</p><p><strong>Conclusion: </strong>MSCs expressing a P2X7nb are detectable in the injured brain following intra-arterial delivery for at least 3 days, without producing adverse effects. These findings provide insights into cell-based immunomodulatory therapies targeting neuroinflammation in TBI and highlight the utility of noninvasive MRI to monitor therapeutic cell biodistribution and persistence.</p>","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13539514/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148889696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Burden of ischemic stroke in China from 1990 to 2050: A systematic review and analysis of Global Burden of Disease Study 2021.","authors":"Yijun Zhang, Jinqiao Zhu, Xue Xia, Meng Gao, Yunyi Hao, Anxin Wang","doi":"10.1002/nep3.70060","DOIUrl":"10.1002/nep3.70060","url":null,"abstract":"<p><strong>Background: </strong>Comprehensive understanding of the ischemic stroke (IS) burden in China is critical for policy and medical resource allocation. We aimed to identify the most up-to-date IS burden by age- and sex-specific temporal trends in China and forecast to 2050.</p><p><strong>Methods: </strong>Based on the Global Burden of Disease, Injuries, and Risk Factors Study (GBD) 2021, we investigated the IS burden in China from 1990 to 2021. IS incidence and mortality data were extracted by age and sex. Temporal trends were assessed using joinpoint regression to calculate average annual percentage changes (AAPCs). The Auto-regressive Integrated Moving Average (ARIMA) models, incorporating Socio-demographic Index and proportion of population aged >65 years as external predictors, were used to forecast the IS burden in China from 2022 to 2050. Decomposition analysis was performed to quantify the contributions of population growth, aging, and epidemiological changes to the observed and projected burden shifts.</p><p><strong>Results: </strong>From 1990 to 2021, the age-standardized incidence rate (ASIR) of IS increased (AAPC: 0.97%, 95% confidence interval [CI] 0.93-1.00); whereas the age-standardized mortality rate (ASMR) decreased (AAPC: -0.49%, 95% CI -0.75 to -0.23). The ASIR increased faster (AAPC: 1.13% vs. 0.72%) and ASMR decreased slower in males than in females (AAPC: -0.14% vs. -0.89%) between 1990 and 2021. From 2021 to 2050, the ASIR will increase slower (AAPC: 0.77%; 95% CI 0.75-0.79) and the ASMR will decrease faster (AAPC: -1.53%; 95% CI -1.56 to -1.51). The ASIR will increase more pronounced in females (AAPC: 1.04%, 95% CI 1.02-1.07) than in males (AAPC: 0.56%, 95% CI 0.56-0.57) between 2021 and 2050. By 2050, those over 85 years old will have the highest incidence and mortality, the number of IS incident cases and deaths will reach 3.68 million (95% uncertainty interval [UI] 3.05-4.40) and 1.50 million (95% UI 1.27-1.76). The predominant factor leading to the growth of IS incident cases (54.04%) and deaths (73.2%) between 2021 and 2050 will be shifted to aging.</p><p><strong>Conclusions: </strong>The IS burden is expected to continue increasing through 2050 albeit at a slower rate. Notably, the ASIR of IS will increase faster in females than in males from 2021 to 2050. Technological innovation, effective policies, and more health spending are needed to curb this increase.</p>","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13531434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148876956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding neurodegeneration and regeneration in the CNS: New concepts, clinical investigations, and an unsung hero of neuroscience.","authors":"Piotr Walczak, Shen Li, Xunming Ji, Johannes Boltze","doi":"10.1002/nep3.70058","DOIUrl":"10.1002/nep3.70058","url":null,"abstract":"","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":" ","pages":"191-194"},"PeriodicalIF":4.1,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13483558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148802645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current status and future perspectives of platelet function-guided precision antiplatelet therapy for patients with cerebral infarction.","authors":"Guoliang Zhu, Xiaoling Chen, Xinyi Huang, Quandan Tan, Qing Cao, Yali Yang, Yapeng Lin, Jie Yang","doi":"10.1002/nep3.70057","DOIUrl":"10.1002/nep3.70057","url":null,"abstract":"<p><p>Current evidence indicates that antiplatelet therapy as a cornerstone for secondary prevention of cerebral infarction. However, ischemic or bleeding events arising from antiplatelet drug resistance or excessive platelet inhibition can diminish its clinical benefit. These challenges have laid the foundation for individualized antiplatelet treatment. Although cytochrome P450 family 2 subfamily C member 19 (<i>CYP2C19</i>) genetic polymorphisms have partially addressed the issue of drug resistance in these patients, they remain insufficient to resolve the high incidence of both ischemic and bleeding events. Platelet function testing (PFT)-guided antiplatelet therapy has been proven beneficial in patients after percutaneous coronary intervention, yet its efficacy in patients with cerebral infarction remains controversial. Platelet function provides a direct and comprehensive reflection of antiplatelet effects, offering potential not only to overcome drug resistance but also to guide de-escalation strategies, thereby mitigating the frequent occurrence of both ischemic and bleeding events in cerebral infarction. Overall, the current application of PFT to guide personalized antiplatelet regimens in patients with cerebral infarction is characterized by considerable variability. In light of recent advances in this field, we herein review the current landscape of PFT-guided individualized antiplatelet therapy in cerebral infarction, with the aim of summarizing existing evidence and offering suggestions for future research.</p>","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13464319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148726663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum elemental profile-based machine learning models for Alzheimer's disease identification and cognitive score prediction.","authors":"Haotian Liu, Xinnan Liu, Yashuang Chen, Meng Pan, Ying Fu, Chao Ma, Wei Ge","doi":"10.1002/nep3.70054","DOIUrl":"10.1002/nep3.70054","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Current diagnostic approaches for Alzheimer's disease (AD) largely rely on cerebrospinal fluid biomarkers and neuroimaging, which may be invasive, costly, and not readily accessible in routine clinical settings. We investigated whether serum elemental profiling combined with machine learning could provide complementary information for AD identification and exploratory cognitive score prediction.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This retrospective cross-sectional study included 874 participants enrolled between 2017 and 2023 from the Brain Aging National Cohort-Peking Union Medical College cohort, comprising 427 cognitively normal controls (NCs) and 447 patients with clinically defined AD. Serum concentrations of 20 elements were quantified by inductively coupled plasma mass spectrometry. Associations between serum element concentrations and AD status were evaluated using age- and sex-adjusted logistic regression models with false discovery rate (FDR) correction. Associations with Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores were assessed using linear regression models with FDR correction. Machine learning classification models were developed for AD identification, whereas regression models were developed for exploratory MMSE and MoCA score prediction. Model performance was evaluated in an internal hold-out test set.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Age did not differ significantly between NC and AD participants (66.4 ± 9.9 vs. 67.1 ± 9.0 years; &lt;i&gt;t&lt;/i&gt;(872) = -1.13, &lt;i&gt;p&lt;/i&gt; = 0.260), whereas the proportion of women was higher in the AD group than in the NC group (255/447 [57.0%] vs. 211/427 [49.4%]; &lt;i&gt;χ&lt;/i&gt; &lt;sup&gt;2&lt;/sup&gt;(1) = 5.11, &lt;i&gt;p&lt;/i&gt; = 0.024). MMSE scores were significantly lower in patients with AD than in NC participants (AD: &lt;i&gt;n&lt;/i&gt; = 277, median [interquartile range (IQR)] = 24 [19-27]; NC: &lt;i&gt;n&lt;/i&gt; = 427, median [IQR] = 30 [30-30]; Mann-Whitney &lt;i&gt;U&lt;/i&gt; = 3043.5, &lt;i&gt;p&lt;/i&gt; &lt; 0.001), as were MoCA scores (AD: &lt;i&gt;n&lt;/i&gt; = 240, median [IQR] = 18.00 [14.00-20.25]; NC: &lt;i&gt;n&lt;/i&gt; = 427, median [IQR] = 30 [30.00-30.00]; Mann-Whitney &lt;i&gt;U&lt;/i&gt; = 13.5, &lt;i&gt;p&lt;/i&gt; &lt; 0.001). After adjustment for age and sex, higher serum lead (Pb) and tin (Sn) levels were associated with increased odds of AD (Pb: odds ratio [OR] = 4.95, 95% confidence interval [CI]: 3.42-7.37; Sn: OR = 1.45, 95% CI: 1.20-1.78), whereas higher serum antimony, nickel, manganese, cobalt, selenium, and calcium levels were associated with lower odds of AD (OR range: 0.50-0.81; all FDR-adjusted &lt;i&gt;p&lt;/i&gt;-values &lt; 0.05). Among the eight classification models evaluated in the internal hold-out test set, the random forest model showed the highest apparent performance for distinguishing AD from NC, achieving an accuracy of 88% and an area under the receiver operating (AUC) (acharacteristic curv of 0.94. Among the three regression models evaluated, the random forest regression showed the highest apparent performance for cogni","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13443228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148686836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global trends in epilepsy and the Chinese experience: Epidemiological transitions, underlying mechanisms, and integrated strategies (1990-2021).","authors":"Ting Chen, Mengqiao He, Sijia Basang, Hongyu Ren, Yutong Fu, Yu Li, Xin Shi, Lei Chen","doi":"10.1002/nep3.70053","DOIUrl":"10.1002/nep3.70053","url":null,"abstract":"<p><p>Epilepsy represents a global public health challenge, with its burden distribution profoundly illuminating patterns of health inequality. Based on the Global Burden of Disease Study 2021 (GBD 2021) data, this review constructs a three-dimensional analytical framework encompassing biological determinants, health system performance, and social determinants of health. Over the past three decades, although the absolute number of individuals with epilepsy worldwide has continued to increase, age-standardized mortality rates have declined substantially. However, 87.9% of the associated disability-adjusted life years (DALYs) are concentrated in low- and lower-middle-income countries (LMICs). China, with approximately 9-10 million people living with epilepsy, confronts a triple disparity encompassing regional disparities, urban-rural gaps, and health system hierarchy barriers: mortality rates in western provinces are approximately nine times higher than those in eastern regions; the treatment gap in rural areas reaches 60%-90%; and primary care capacity deficits within the tiered diagnosis and treatment system create bottlenecks in case identification and referral. Concurrently, the disease spectrum is undergoing a profound transition, with an increasing burden of post-stroke epilepsy in older adults, while special populations, including children and women, continue to face persistent challenges. Despite China's notable achievements in reducing mortality and establishing a tertiary epilepsy center network, multiple interacting factors perpetuate a vicious cycle of poverty, disease, and stigma among affected individuals. Future efforts require alignment with the World Health Organization Intersectoral Global Action Plan on Epilepsy and Other Neurological Disorders 2022-2031 (IGAP) to develop precision prevention and control strategies, thereby contributing the Chinese experience to global epilepsy governance.</p>","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":" ","pages":"199-212"},"PeriodicalIF":4.1,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13402926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148610915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}