Sadegh Ghaderi, Sana Mohammadi, Ali Fathi Jouzdani, Amir Mahmoud Ahmadzadeh
Objective
To evaluate glymphatic dysfunction in mild cognitive impairment (MCI) using the diffusion tensor imaging along the perivascular space (DTI-ALPS) index.
Methods
Using PRISMA 2020, we searched PubMed, Web of Science, Scopus, and Embase (until May 10, 2025) for studies comparing the ALPS index in MCI patients versus healthy controls.
Results
The pooled meta-analysis of 18 studies (1133 MCI patients, mean age 69.3 years; 1275 HCs) revealed a significantly lower ALPS index in MCI patients than in HCs (Cohen's d = −0.70; 95% CI: −1.10, −0.29; p < 0.001), with high heterogeneity (I2 = 95.3%). Sensitivity analyses confirmed the robustness of the effect and a cumulative meta-analysis showed a consistent negative trend from 2021 to 2025. Subgroup analyses showed trends toward larger effect sizes in older patients (> 68 years, d = −0.83) and in studies using ≥ 64 diffusion directions (d = −0.99), although formal tests for subgroup differences were not statistically significant. Small-study effects were found (Egger's p = 0.004; Begg's p = 0.019), but the studies had high methodological quality. Trim-and-fill analysis added six studies, adjusting pooled Cohen's d from −0.70 to −0.98, indicating potential overestimation from publication bias.
Conclusions
These findings support the utility of the ALPS index as a noninvasive biomarker for early glymphatic dysfunction in cognitive decline.
目的：应用沿血管周围间隙弥散张量成像（DTI-ALPS）指数评价轻度认知障碍（MCI）患者的淋巴功能障碍。方法：使用PRISMA 2020，我们检索了PubMed、Web of Science、Scopus和Embase（截至2025年5月10日），以比较MCI患者与健康对照组的ALPS指数。结果：18项研究（1133例MCI患者，平均年龄69.3岁；1275例hcc）的汇总荟萃分析显示，MCI患者的ALPS指数明显低于hcc患者（Cohen’s d = -0.70; 95% CI: -1.10, -0.29; p 2 = 95.3%）。敏感性分析证实了该效应的稳健性，累积荟萃分析显示，从2021年到2025年，该效应呈一致的负趋势。亚组分析显示，在老年患者（bb0 ~ 68岁，d = -0.83）和使用≥64个扩散方向的研究中（d = -0.99），效应量趋势更大，尽管亚组差异的正式检验没有统计学意义。小研究效应被发现（Egger’s p = 0.004; Begg’s p = 0.019），但这些研究具有较高的方法学质量。trim -fill分析增加了6项研究，将Cohen’s d从-0.70调整到-0.98，表明发表偏倚可能导致高估。结论：这些发现支持了ALPS指数作为认知衰退中早期淋巴功能障碍的无创生物标志物的实用性。
{"title":"Glymphatic Pathway Dysfunction in Mild Cognitive Impairment: A Systematic Review and Meta-Analysis Using Diffusion Tensor Imaging Along the Perivascular Space","authors":"Sadegh Ghaderi, Sana Mohammadi, Ali Fathi Jouzdani, Amir Mahmoud Ahmadzadeh","doi":"10.1002/cns.70695","DOIUrl":"10.1002/cns.70695","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To evaluate glymphatic dysfunction in mild cognitive impairment (MCI) using the diffusion tensor imaging along the perivascular space (DTI-ALPS) index.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using PRISMA 2020, we searched PubMed, Web of Science, Scopus, and Embase (until May 10, 2025) for studies comparing the ALPS index in MCI patients versus healthy controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The pooled meta-analysis of 18 studies (1133 MCI patients, mean age 69.3 years; 1275 HCs) revealed a significantly lower ALPS index in MCI patients than in HCs (Cohen's <i>d</i> = −0.70; 95% CI: −1.10, −0.29; <i>p</i> < 0.001), with high heterogeneity (<i>I</i><sup>2</sup> = 95.3%). Sensitivity analyses confirmed the robustness of the effect and a cumulative meta-analysis showed a consistent negative trend from 2021 to 2025. Subgroup analyses showed trends toward larger effect sizes in older patients (> 68 years, <i>d</i> = −0.83) and in studies using ≥ 64 diffusion directions (<i>d</i> = −0.99), although formal tests for subgroup differences were not statistically significant. Small-study effects were found (Egger's <i>p</i> = 0.004; Begg's <i>p</i> = 0.019), but the studies had high methodological quality. Trim-and-fill analysis added six studies, adjusting pooled Cohen's <i>d</i> from −0.70 to −0.98, indicating potential overestimation from publication bias.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings support the utility of the ALPS index as a noninvasive biomarker for early glymphatic dysfunction in cognitive decline.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 12","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12715781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145792831","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}
Q. Jiang, C. Wang, Q. Gao, et al., “Multiple Sevoflurane Exposures During Mid-Trimester Induce Neurotoxicity in the Developing Brain Initiated by 15LO2-Mediated Ferroptosis,” CNS Neuroscience & Therapeutics 29, no. 10(2023): 2972–2985. https://doi.org/10.1111/cns.14236.
In the original version of this article, there was an error in Figure 2G and Figure 4G. Specifically, the immunohistochemical image of NeuN for the Sev+F group in Figure 2G and Nissl's staining image for the “Ctrl” group in Figure 4G were incorrect. Additionally, in Figure 5G, it showed the wrong Nissl's staining image in “Ctrl+K” group. The correct images are provided below. The corrections do not change the results or conclusions of this paper.
{"title":"Correction to “Multiple Sevoflurane Exposures During Mid-Trimester Induce Neurotoxicity in the Developing Brain Initiated by 15LO2-Mediated Ferroptosis”","authors":"","doi":"10.1002/cns.70685","DOIUrl":"10.1002/cns.70685","url":null,"abstract":"<p>Q. Jiang, C. Wang, Q. Gao, et al., “Multiple Sevoflurane Exposures During Mid-Trimester Induce Neurotoxicity in the Developing Brain Initiated by 15LO2-Mediated Ferroptosis,” <i>CNS Neuroscience & Therapeutics</i> 29, no. 10(2023): 2972–2985. https://doi.org/10.1111/cns.14236.</p><p>In the original version of this article, there was an error in Figure 2G and Figure 4G. Specifically, the immunohistochemical image of NeuN for the Sev+F group in Figure 2G and Nissl's staining image for the “Ctrl” group in Figure 4G were incorrect. Additionally, in Figure 5G, it showed the wrong Nissl's staining image in “Ctrl+K” group. The correct images are provided below. The corrections do not change the results or conclusions of this paper.</p><p>We apologize for this error.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 12","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12715775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145792771","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}
Yajie An, Ying Wu, Xiangyong Li, Taihe Zhou, Heming Liu, Yao Xiao, Wenyu Lai, Yuxin Qiu, Xuhong Wei
<div> <section> <h3> Background</h3> <p>Neuropathic pain is frequently accompanied by cognitive deficits, but the neural circuits and molecular mechanisms linking nociceptive hypersensitivity to cognitive dysfunction remain incompletely understood. The hippocampal dentate gyrus (DG), a critical hub for adult neurogenesis and memory encoding, is emerging as a key substrate integrating pain processing and cognitive impairment, but how peripheral nerve injury disrupts DG homeostasis remains unclear.</p> </section> <section> <h3> Methods</h3> <p>In this study, we used the spared nerve injury (SNI) mouse model to investigate the cellular and molecular mechanisms underlying comorbid neuropathic pain and cognitive deficits. Behavioral assessments, stereotaxic viral/drug delivery, Western blot, immunofluorescence staining, whole-cell patch-clamp recordings, ELISA, and primary astrocyte culture were employed to characterize phenotypic changes and regulatory pathways in the dorsal DG.</p> </section> <section> <h3> Results</h3> <p>We found that SNI induced persistent mechanical hypersensitivity and cognitive impairment in mice, which was associated with reduced neurogenesis (decreased nestin<sup>+</sup> radial glial-like cells, DCX<sup>+</sup> immature neurons, and NeuroD1 expression) and diminished intrinsic excitability of dorsal DG granule cells. Mechanistically, SNI triggered a “double hit” to dorsal DG homeostasis: (1) neuron-specific insulin-like growth factor-1 (IGF-1) resistance, characterized by increased serine phosphorylation of insulin receptor substrate-1 (IRS1) at S612 in mature granule cells, reduced IGF-1 levels, and impaired PI3K/AKT signaling; (2) downregulation of astrocyte-derived WNT3, a key neurogenic regulator, which was mediated by proinflammatory cytokine TNF-<i>α</i>. Therapeutically, local supplementation of IGF-1 into the dorsal DG reversed SNI-induced nociceptive and cognitive deficits via IGF-1R/AKT-dependent restoration of neurogenesis and granule cell excitability. Similarly, chemogenetic activation of dorsal DG astrocytes alleviated comorbid symptoms by enhancing WNT3 secretion, while chronic inhibition of these astrocytes mimicked SNI-induced pain hypersensitivity, cognitive impairment, and disrupted neurogenesis. Exogenous administration of WNT3a recapitulated the therapeutic effects by activating AKT, independent of IGF-1R signaling.</p> </section> <section> <h3> Conclusion</h3> <p>Our findings identify that decreased WNT3 secretion from astrocytes in dorsal DG integrates nociceptive and cognitive dysfunction after nerve in
{"title":"Impaired WNT3/IGF-1 Signaling in Dorsal Dentate Gyrus Contributes to Chronic Pain-Related Cognitive Impairment","authors":"Yajie An, Ying Wu, Xiangyong Li, Taihe Zhou, Heming Liu, Yao Xiao, Wenyu Lai, Yuxin Qiu, Xuhong Wei","doi":"10.1002/cns.70714","DOIUrl":"10.1002/cns.70714","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Neuropathic pain is frequently accompanied by cognitive deficits, but the neural circuits and molecular mechanisms linking nociceptive hypersensitivity to cognitive dysfunction remain incompletely understood. The hippocampal dentate gyrus (DG), a critical hub for adult neurogenesis and memory encoding, is emerging as a key substrate integrating pain processing and cognitive impairment, but how peripheral nerve injury disrupts DG homeostasis remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, we used the spared nerve injury (SNI) mouse model to investigate the cellular and molecular mechanisms underlying comorbid neuropathic pain and cognitive deficits. Behavioral assessments, stereotaxic viral/drug delivery, Western blot, immunofluorescence staining, whole-cell patch-clamp recordings, ELISA, and primary astrocyte culture were employed to characterize phenotypic changes and regulatory pathways in the dorsal DG.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that SNI induced persistent mechanical hypersensitivity and cognitive impairment in mice, which was associated with reduced neurogenesis (decreased nestin<sup>+</sup> radial glial-like cells, DCX<sup>+</sup> immature neurons, and NeuroD1 expression) and diminished intrinsic excitability of dorsal DG granule cells. Mechanistically, SNI triggered a “double hit” to dorsal DG homeostasis: (1) neuron-specific insulin-like growth factor-1 (IGF-1) resistance, characterized by increased serine phosphorylation of insulin receptor substrate-1 (IRS1) at S612 in mature granule cells, reduced IGF-1 levels, and impaired PI3K/AKT signaling; (2) downregulation of astrocyte-derived WNT3, a key neurogenic regulator, which was mediated by proinflammatory cytokine TNF-<i>α</i>. Therapeutically, local supplementation of IGF-1 into the dorsal DG reversed SNI-induced nociceptive and cognitive deficits via IGF-1R/AKT-dependent restoration of neurogenesis and granule cell excitability. Similarly, chemogenetic activation of dorsal DG astrocytes alleviated comorbid symptoms by enhancing WNT3 secretion, while chronic inhibition of these astrocytes mimicked SNI-induced pain hypersensitivity, cognitive impairment, and disrupted neurogenesis. Exogenous administration of WNT3a recapitulated the therapeutic effects by activating AKT, independent of IGF-1R signaling.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings identify that decreased WNT3 secretion from astrocytes in dorsal DG integrates nociceptive and cognitive dysfunction after nerve in","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 12","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12715354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145779788","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}
While multi-site noninvasive brain stimulation demonstrates enhanced cognitive benefits in mild cognitive impairment (MCI), the efficacy of transcranial alternating current stimulation (tACS) in this paradigm remains unestablished. The study aims were to investigate the therapeutic effects of multi-site tACS on MCI patients and its underlying neural mechanism.
Methods
A parallel, sham-controlled trial was conducted with 60 MCI participants assigned to multi-site tACS (prefrontal gyrus and precuneus), single-site tACS (precuneus), or sham groups. All participants underwent 20 days of 7 Hz tACS concurrent with working memory training. Cognitive assessments and fMRI examinations were performed pre- and post- intervention. Local and remote functional connectivity changes were evaluated using regional homogeneity (Reho) and resting-state network (RSN) analyses, respectively.
Results
Multi-site tACS demonstrated superior cognitive improvements, particularly in verbal fluency (p = 0.006) and recognition memory (p = 0.025), compared to sham stimulation. Significant ReHo changes were observed in the superior frontal gyrus (SFG) and superior temporal gyrus (STG) exclusively in the multi-site group (p < 0.05). Additionally, multi-site tACS induced broader functional connectivity alterations in the default mode network (DMN), executive control network (ECN), and left frontoparietal network (FPN). Correlations were found between the Reho changes in SFG and STG and the score changes of immediate memory (r = 0.367, p = 0.039) and language naming (r = 0.371, p = 0.037), respectively. Functional connectivity changes in the right inferior parietal lobe were also significantly correlated with the score changes of language naming (r = −0.374, p = 0.035). Moreover, more functional connectivity changes between the prefrontal gyrus stimulation site and the salience network and DMN were also detected in the multi-site group relative to the single-site group.
Conclusions
Multi-site tACS is more effective than single-site tACS in enhancing cognitive functions and modulating cognition-related brain networks in MCI patients. These superior neuromodulatory effects of multi-site tACS may be attributed to its capacity to modulate functional networks across the prefrontal gyrus more extensively.
{"title":"Multi-Site Theta-tACS Improves Memory and Language Performance and Associated Local and Remote Functional Connectivity in Mild Cognitive Impairment","authors":"Zhiwei Guo, Yi Jiang, Jiayuan He, Ning Jiang","doi":"10.1002/cns.70707","DOIUrl":"10.1002/cns.70707","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>While multi-site noninvasive brain stimulation demonstrates enhanced cognitive benefits in mild cognitive impairment (MCI), the efficacy of transcranial alternating current stimulation (tACS) in this paradigm remains unestablished. The study aims were to investigate the therapeutic effects of multi-site tACS on MCI patients and its underlying neural mechanism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A parallel, sham-controlled trial was conducted with 60 MCI participants assigned to multi-site tACS (prefrontal gyrus and precuneus), single-site tACS (precuneus), or sham groups. All participants underwent 20 days of 7 Hz tACS concurrent with working memory training. Cognitive assessments and fMRI examinations were performed pre- and post- intervention. Local and remote functional connectivity changes were evaluated using regional homogeneity (Reho) and resting-state network (RSN) analyses, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Multi-site tACS demonstrated superior cognitive improvements, particularly in verbal fluency (<i>p</i> = 0.006) and recognition memory (<i>p</i> = 0.025), compared to sham stimulation. Significant ReHo changes were observed in the superior frontal gyrus (SFG) and superior temporal gyrus (STG) exclusively in the multi-site group (<i>p</i> < 0.05). Additionally, multi-site tACS induced broader functional connectivity alterations in the default mode network (DMN), executive control network (ECN), and left frontoparietal network (FPN). Correlations were found between the Reho changes in SFG and STG and the score changes of immediate memory (<i>r</i> = 0.367, <i>p</i> = 0.039) and language naming (<i>r</i> = 0.371, <i>p</i> = 0.037), respectively. Functional connectivity changes in the right inferior parietal lobe were also significantly correlated with the score changes of language naming (<i>r</i> = −0.374, <i>p</i> = 0.035). Moreover, more functional connectivity changes between the prefrontal gyrus stimulation site and the salience network and DMN were also detected in the multi-site group relative to the single-site group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Multi-site tACS is more effective than single-site tACS in enhancing cognitive functions and modulating cognition-related brain networks in MCI patients. These superior neuromodulatory effects of multi-site tACS may be attributed to its capacity to modulate functional networks across the prefrontal gyrus more extensively.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 12","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12715273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145779756","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}
Yi Zhang, Hui-Fen Huang, Juan-Juan Xie, Wang Ni, Hao Yu, Zhi-Ying Wu
Aim
This study aims to expand the clinical and genetic spectrum of Krabbe disease (KD) in Chinese adult patients and to improve diagnosis and understanding of its phenotypic diversity.
Methods
Patients clinically suspected of leukodystrophy were recruited between 2015 and 2025. Clinical features were collected, and whole-exome sequencing (WES) was performed to identify potential variants. The pathogenicity of detected variants was classified according to the American College of Medical Genetics and Genomics (ACMG) standards and guidelines. Functional assays assessing protein expression, processing, secretion, subcellular localization, and enzymatic activity were conducted to further validate variant pathogenicity.
Results
Fourteen unrelated patients were genetically diagnosed with KD, and their genetic and clinical features were summarized. Eleven variants in GALC were identified, including a novel missense variant c.1019C>T (p.P340L) which is not reported in the Human Gene Mutation Database (HGMD). Unlike most adult patients who typically present with spastic paraplegia, the patient carrying this variant exhibited initial symptoms of peripheral neuropathy. Functional experiments demonstrated that the variant led to impaired protein processing and localization, as well as reduced GALC enzymatic activity. Other variants including p.D56H, p.L377X, p.L441X, and p.L634S also affected GALC functions to varying degrees.
Conclusion
This study enhances the genotypic and phenotypic characterization of KD in China, aiding in differential diagnosis and genetic counseling. Functional data reinforce the pathogenicity of identified variants.
{"title":"Genetic and Clinical Characteristics of Chinese Adult Patients With Krabbe Disease","authors":"Yi Zhang, Hui-Fen Huang, Juan-Juan Xie, Wang Ni, Hao Yu, Zhi-Ying Wu","doi":"10.1002/cns.70708","DOIUrl":"10.1002/cns.70708","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>This study aims to expand the clinical and genetic spectrum of Krabbe disease (KD) in Chinese adult patients and to improve diagnosis and understanding of its phenotypic diversity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients clinically suspected of leukodystrophy were recruited between 2015 and 2025. Clinical features were collected, and whole-exome sequencing (WES) was performed to identify potential variants. The pathogenicity of detected variants was classified according to the American College of Medical Genetics and Genomics (ACMG) standards and guidelines. Functional assays assessing protein expression, processing, secretion, subcellular localization, and enzymatic activity were conducted to further validate variant pathogenicity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Fourteen unrelated patients were genetically diagnosed with KD, and their genetic and clinical features were summarized. Eleven variants in <i>GALC</i> were identified, including a novel missense variant c.1019C>T (p.P340L) which is not reported in the Human Gene Mutation Database (HGMD). Unlike most adult patients who typically present with spastic paraplegia, the patient carrying this variant exhibited initial symptoms of peripheral neuropathy. Functional experiments demonstrated that the variant led to impaired protein processing and localization, as well as reduced GALC enzymatic activity. Other variants including p.D56H, p.L377X, p.L441X, and p.L634S also affected GALC functions to varying degrees.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study enhances the genotypic and phenotypic characterization of KD in China, aiding in differential diagnosis and genetic counseling. Functional data reinforce the pathogenicity of identified variants.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 12","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12715268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145779783","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}
Alzheimer's disease (AD) is a global health event with progressive cognitive decline affecting millions of elderly people worldwide. Emerging evidence indicates that sevoflurane may be associated with AD progression. However, the underlying mechanism remains poorly understood. Herein, we explored the potential role of sevoflurane exposure in cognitive ability and the possible mechanisms of action in the early stage of Tg4510 (P301L tau) transgenic mice.
Methods
Using the novel object recognition test and Y-maze test, we assessed the change in cognitive abilities in 3-month-old male WT mice and Tg4510 mice with or without 3% sevoflurane exposure. By histological analysis and western blot, we determined the effect of sevoflurane exposure on tau pathology, synaptic function, and neuroinflammatory response. TMT-labeled proteomics technique coupled with bioinformatics analysis was performed to identify the potential key pathways or proteins involved in sevoflurane-induced cognitive deterioration.
Results
Behavioral test showed that sevoflurane exposure exacerbated cognitive impairment of young Tg4510 mice. Pathologically, immunofluorescence demonstrated that sevoflurane exposure increased tau phosphorylation, synaptic defects, and neuroinflammatory response, which were further supported by the result of immunoblotting in Tg4510 mice exposed to sevoflurane. Proteomic analysis revealed an obvious decrease in autophagy-related proteins including Sort1, Vps28, and Atg3 in the hippocampus of sevoflurane-exposed Tg4510 mice compared to the nonexposed group. As an upstream signaling of autophagy, the AKT/mTOR pathway was found to be inhibited in sevoflurane-exposed Tg4510 mice. Moreover, our data also validated an inhibition of autophagy signaling associated with sevoflurane exposure in the context of tau pathology, as indicated by the upregulated expression of p62 and the downregulated expression of Sort1, Vps28, and Atg3.
Conclusion
These findings suggest that autophagy signaling appears to be a promising target for intervention in sevoflurane-induced cognitive impairment in the early tau pathology, which lays the foundation for further study of the underlying mechanisms.
{"title":"Sevoflurane Exposure Exacerbates Memory Impairment and Pathological Manifestation by Inhibiting AKT/mTOR-Mediated Autophagy in P301L Tau Transgenic Mice","authors":"Kaiwu He, Zhijing Zhang, Youzhi Li, Wei Xiong, Yanmei Xing, Wenli Gao, Wei Kong, Lixin Chen, Xifei Yang, Zhongliang Dai","doi":"10.1002/cns.70694","DOIUrl":"10.1002/cns.70694","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Alzheimer's disease (AD) is a global health event with progressive cognitive decline affecting millions of elderly people worldwide. Emerging evidence indicates that sevoflurane may be associated with AD progression. However, the underlying mechanism remains poorly understood. Herein, we explored the potential role of sevoflurane exposure in cognitive ability and the possible mechanisms of action in the early stage of Tg4510 (P301L tau) transgenic mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using the novel object recognition test and Y-maze test, we assessed the change in cognitive abilities in 3-month-old male WT mice and Tg4510 mice with or without 3% sevoflurane exposure. By histological analysis and western blot, we determined the effect of sevoflurane exposure on tau pathology, synaptic function, and neuroinflammatory response. TMT-labeled proteomics technique coupled with bioinformatics analysis was performed to identify the potential key pathways or proteins involved in sevoflurane-induced cognitive deterioration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Behavioral test showed that sevoflurane exposure exacerbated cognitive impairment of young Tg4510 mice. Pathologically, immunofluorescence demonstrated that sevoflurane exposure increased tau phosphorylation, synaptic defects, and neuroinflammatory response, which were further supported by the result of immunoblotting in Tg4510 mice exposed to sevoflurane. Proteomic analysis revealed an obvious decrease in autophagy-related proteins including Sort1, Vps28, and Atg3 in the hippocampus of sevoflurane-exposed Tg4510 mice compared to the nonexposed group. As an upstream signaling of autophagy, the AKT/mTOR pathway was found to be inhibited in sevoflurane-exposed Tg4510 mice. Moreover, our data also validated an inhibition of autophagy signaling associated with sevoflurane exposure in the context of tau pathology, as indicated by the upregulated expression of p62 and the downregulated expression of Sort1, Vps28, and Atg3.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings suggest that autophagy signaling appears to be a promising target for intervention in sevoflurane-induced cognitive impairment in the early tau pathology, which lays the foundation for further study of the underlying mechanisms.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 12","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12710523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145766700","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}
The pathogenesis of ischemic stroke is multifaceted, and growing evidence highlights that mixed etiologies should be considered. This prospective cohort study investigated the relationship between plasma levels of trimethylamine N-oxide (TMAO), a cardiovascular disease risk factor, and etiologic stroke subtypes.
Methods
Plasma TMAO levels were compared in 223 patients, including 95, 73, and 55 patients with large artery atherosclerosis (LAA), cardioembolism (CE), and cardioembolism with culprit artery stenosis (CES), respectively, admitted with acute ischemic stroke complicated by large vessel occlusion and treated with endovascular therapy. At-admission clinical data and blood samples obtained during intervention were collected.
Results
After adjusting for covariates, including age, sex, hypertension, diabetes mellitus, estimated glomerular filtration rate(eGFR), smoking, and alcohol consumption, plasma TMAO levels were highest in the CES group (1.583 μmol/L), followed by the LAA and CE groups (1.064 and 0.583 μmol/L, respectively), with significant differences among the three groups detected (Wald χ2 = 22.877, p < 0.001). By binary logistic regression analysis after adjusting for the same covariates, plasma TMAO level was an independent predictor for distinguishing the CES subtype from the CE subtype (95% CI, 2.062–8.183; p < 0.001), with an area under the curve of 0.778.
Conclusion
Plasma TMAO levels, which were highest in patients with stroke due to CES, followed by those with stroke due to LAA and CE, may serve as an independent predictor for distinguishing CE from CES as the stroke etiology.
{"title":"Trimethylamine N-Oxide Linking Gut Microbiota to Cardiocerebral Disease Is a Novel Biomarker for Stroke Subtypes With Mixed Etiology: A Prospective Cohort Study","authors":"Yukun Wang, Yeju Hu, Ruoyu Qin, Wei Li, Chu Zhou, Rongrong Liu, Qiyang Yuan, Ruicheng Zhang, Guiyun Cui, Shiguang Zhu","doi":"10.1002/cns.70704","DOIUrl":"10.1002/cns.70704","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The pathogenesis of ischemic stroke is multifaceted, and growing evidence highlights that mixed etiologies should be considered. This prospective cohort study investigated the relationship between plasma levels of trimethylamine N-oxide (TMAO), a cardiovascular disease risk factor, and etiologic stroke subtypes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Plasma TMAO levels were compared in 223 patients, including 95, 73, and 55 patients with large artery atherosclerosis (LAA), cardioembolism (CE), and cardioembolism with culprit artery stenosis (CES), respectively, admitted with acute ischemic stroke complicated by large vessel occlusion and treated with endovascular therapy. At-admission clinical data and blood samples obtained during intervention were collected.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>After adjusting for covariates, including age, sex, hypertension, diabetes mellitus, estimated glomerular filtration rate(eGFR), smoking, and alcohol consumption, plasma TMAO levels were highest in the CES group (1.583 μmol/L), followed by the LAA and CE groups (1.064 and 0.583 μmol/L, respectively), with significant differences among the three groups detected (Wald χ<sup>2</sup> = 22.877, <i>p</i> < 0.001). By binary logistic regression analysis after adjusting for the same covariates, plasma TMAO level was an independent predictor for distinguishing the CES subtype from the CE subtype (95% CI, 2.062–8.183; <i>p</i> < 0.001), with an area under the curve of 0.778.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Plasma TMAO levels, which were highest in patients with stroke due to CES, followed by those with stroke due to LAA and CE, may serve as an independent predictor for distinguishing CE from CES as the stroke etiology.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 12","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12706172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145761629","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}
Daji Guo, Mengjiao Cai, Yanmin Xian, Yinyin Chen, Yujun Feng, Chun Hu, Lizhang Zeng, Lei Shi, Shiqing Zhang
Background
Transient receptor potential (TRP) ion channels, a ubiquitous family of nonselective cation channels, are extensively expressed across the nervous system, immune system, and peripheral tissues. These channels serve as critical sensors for detecting temperature, mechanical forces, and chemical stimuli, thereby regulating numerous physiological and pathological processes. Over the past decade, their pivotal role in neuroimmune crosstalk and inflammatory signaling has emerged as a key focus within neuroscience research.
Methods
A comprehensive literature review was conducted in PubMed using key terms “TRP channel,” “neuroinflammation,” and each of the following neurological disorders: neuropathic pain, migraine, stroke, multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease (PD), autism spectrum disorder (ASD), epilepsy, and psychiatric disorders.
Results
This review synthesizes the current evidence to elucidate the dual-edged contributions of TRP channels as mediators of inflammation in neuropathic pain, migraine, stroke, MS, AD, PD, ASD, epilepsy, and psychiatric disorders. Furthermore, we also evaluate emerging therapeutic strategies targeting TRP channels, encompassing both nonpharmacological approaches and pharmacological interventions.
Conclusions
By integrating mechanistic insights with translational perspectives, this review highlights TRP channels as promising targets for precision medicine and underscores their potential in the development of novel, mechanism-based therapies for complex neurological disorders, thereby advancing a new era of targeted neuroimmunomodulation.
{"title":"Transient Receptor Potential Channels as Key Regulators of Neuroinflammation in Neurological Disorders: Mechanistic Insights, Therapeutic Potentials, and Future Directions","authors":"Daji Guo, Mengjiao Cai, Yanmin Xian, Yinyin Chen, Yujun Feng, Chun Hu, Lizhang Zeng, Lei Shi, Shiqing Zhang","doi":"10.1002/cns.70700","DOIUrl":"10.1002/cns.70700","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Transient receptor potential (TRP) ion channels, a ubiquitous family of nonselective cation channels, are extensively expressed across the nervous system, immune system, and peripheral tissues. These channels serve as critical sensors for detecting temperature, mechanical forces, and chemical stimuli, thereby regulating numerous physiological and pathological processes. Over the past decade, their pivotal role in neuroimmune crosstalk and inflammatory signaling has emerged as a key focus within neuroscience research.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A comprehensive literature review was conducted in PubMed using key terms “TRP channel,” “neuroinflammation,” and each of the following neurological disorders: neuropathic pain, migraine, stroke, multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease (PD), autism spectrum disorder (ASD), epilepsy, and psychiatric disorders.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>This review synthesizes the current evidence to elucidate the dual-edged contributions of TRP channels as mediators of inflammation in neuropathic pain, migraine, stroke, MS, AD, PD, ASD, epilepsy, and psychiatric disorders. Furthermore, we also evaluate emerging therapeutic strategies targeting TRP channels, encompassing both nonpharmacological approaches and pharmacological interventions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>By integrating mechanistic insights with translational perspectives, this review highlights TRP channels as promising targets for precision medicine and underscores their potential in the development of novel, mechanism-based therapies for complex neurological disorders, thereby advancing a new era of targeted neuroimmunomodulation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 12","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12706177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145761704","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}
While both gut–brain axis dysfunction and blood–brain barrier (BBB) breakdown are documented in Alzheimer's disease (AD), current research treats these as separate phenomena. However, emerging evidence suggests that the BBB may function as an active integration interface that processes microbiota-derived metabolites and thereby potentially modulates how peripheral signals influence cognitive health.
Objective
This review synthesizes current evidence on microbiota metabolites as modulators of BBB integration capacity, discussing how such mechanisms may contribute to variability in cognitive outcomes despite similar gut microbiome profiles by demonstrating how BBB signal-integration mechanisms determine gut–brain communication effectiveness in AD.
Methods
We analyzed peer-reviewed literature from 2010 to 2025, focusing on BBB dynamic properties, microbiota metabolite effects on BBB function, and their integration patterns, emphasizing functional evidence supporting the BBB's active signal processing capabilities.
Results
Current evidence suggests that the BBB exhibits integration properties, including dynamic permeability regulation, context-dependent metabolite processing, and coordinated responses to complex signal streams. Short-chain fatty acids enhance integration capacity through HDAC inhibition and coordinated receptor activation, while lipopolysaccharides and trimethylamine N-oxide may overwhelm integration processes through TLR4-mediated disruption. BBB dysfunction precedes classical AD pathology and correlates with altered metabolite processing capacity. Individual variations in BBB integration capacity may help account for why individuals with similar gut microbiome profiles show different cognitive outcomes.
Conclusion
Viewing the BBB as an active integration interface offers a useful perspective for organizing current evidence on gut–brain interactions in AD. This conceptual perspective suggests that therapeutic strategies might benefit from supporting BBB integration capacity and optimizing metabolite-processing mechanisms alongside improving gut health.
{"title":"The Blood–Brain Barrier as an Integration Hub in Alzheimer's Disease: How Microbiota Metabolites Modulate Central Signal Processing","authors":"O. Giangiulio, R. Maccarone","doi":"10.1002/cns.70703","DOIUrl":"10.1002/cns.70703","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>While both gut–brain axis dysfunction and blood–brain barrier (BBB) breakdown are documented in Alzheimer's disease (AD), current research treats these as separate phenomena. However, emerging evidence suggests that the BBB may function as an active integration interface that processes microbiota-derived metabolites and thereby potentially modulates how peripheral signals influence cognitive health.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This review synthesizes current evidence on microbiota metabolites as modulators of BBB integration capacity, discussing how such mechanisms may contribute to variability in cognitive outcomes despite similar gut microbiome profiles by demonstrating how BBB signal-integration mechanisms determine gut–brain communication effectiveness in AD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed peer-reviewed literature from 2010 to 2025, focusing on BBB dynamic properties, microbiota metabolite effects on BBB function, and their integration patterns, emphasizing functional evidence supporting the BBB's active signal processing capabilities.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Current evidence suggests that the BBB exhibits integration properties, including dynamic permeability regulation, context-dependent metabolite processing, and coordinated responses to complex signal streams. Short-chain fatty acids enhance integration capacity through HDAC inhibition and coordinated receptor activation, while lipopolysaccharides and trimethylamine N-oxide may overwhelm integration processes through TLR4-mediated disruption. BBB dysfunction precedes classical AD pathology and correlates with altered metabolite processing capacity. Individual variations in BBB integration capacity may help account for why individuals with similar gut microbiome profiles show different cognitive outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Viewing the BBB as an active integration interface offers a useful perspective for organizing current evidence on gut–brain interactions in AD. This conceptual perspective suggests that therapeutic strategies might benefit from supporting BBB integration capacity and optimizing metabolite-processing mechanisms alongside improving gut health.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 12","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12703014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145754926","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}
Fanhai Bu, Runlu Cai, Ying Hu, Xiaohong Tang, Wei Zhang, Xinxin Yang
Background
Hemorrhagic transformation (HT) is a critical complication of intravenous thrombolysis (IVT) in acute ischemic stroke (AIS). This study developed and validated machine learning (ML) models integrating inflammatory biomarkers with clinical indicators to predict post-IVT HT.
Methods
In 1272 IVT-treated AIS patients, the least absolute shrinkage and selection operator (LASSO) regression identified five predictors from 17 variables, which were subsequently utilized to construct eight ML models. The models were trained (70% data) and tested (30% data). Furthermore, external validation conducted on an independent cohort substantiated the generalizability of the optimal model. The SHapley Additive exPlanations (SHAP) method explained feature importance.
Results
LASSO screened five significant predictors: the neutrophil-to-lymphocyte ratio (NLR), admission National Institutes of Health Stroke Scale (NIHSS) score, the Alberta Stroke Program Early CT Score (ASPECTS), blood glucose, and atrial fibrillation. Logistic regression (LR) achieved optimal performance with an AUC of 0.833 internally and 0.842 externally. SHAP analysis prioritized NIHSS as the top contributor, while the nomogram elucidated the variability in HT risk.
Conclusion
Integrating NLR with stroke severity and neuroimaging biomarkers enhances the accuracy of HT predictions. The LR-based nomogram provided a practical tool for personalized IVT decisions, emphasizing the prognostic value of systemic inflammation in AIS management.
{"title":"Development and Validation of Multiple Machine Learning Models Integrating Neutrophil-Lymphocyte Ratio for Prediction of Hemorrhagic Transformation After Intravenous Thrombolysis in Acute Ischemic Stroke","authors":"Fanhai Bu, Runlu Cai, Ying Hu, Xiaohong Tang, Wei Zhang, Xinxin Yang","doi":"10.1111/cns.70667","DOIUrl":"10.1111/cns.70667","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hemorrhagic transformation (HT) is a critical complication of intravenous thrombolysis (IVT) in acute ischemic stroke (AIS). This study developed and validated machine learning (ML) models integrating inflammatory biomarkers with clinical indicators to predict post-IVT HT.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In 1272 IVT-treated AIS patients, the least absolute shrinkage and selection operator (LASSO) regression identified five predictors from 17 variables, which were subsequently utilized to construct eight ML models. The models were trained (70% data) and tested (30% data). Furthermore, external validation conducted on an independent cohort substantiated the generalizability of the optimal model. The SHapley Additive exPlanations (SHAP) method explained feature importance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>LASSO screened five significant predictors: the neutrophil-to-lymphocyte ratio (NLR), admission National Institutes of Health Stroke Scale (NIHSS) score, the Alberta Stroke Program Early CT Score (ASPECTS), blood glucose, and atrial fibrillation. Logistic regression (LR) achieved optimal performance with an AUC of 0.833 internally and 0.842 externally. SHAP analysis prioritized NIHSS as the top contributor, while the nomogram elucidated the variability in HT risk.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Integrating NLR with stroke severity and neuroimaging biomarkers enhances the accuracy of HT predictions. The LR-based nomogram provided a practical tool for personalized IVT decisions, emphasizing the prognostic value of systemic inflammation in AIS management.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 12","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70667","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145740244","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}
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