CNS Neuroscience & Therapeutics最新文献_第5页

Coagulation Pathways as Determinants of Acute Subdural Hematoma Resolution: Genetic Evidence From Human Data 凝血途径作为急性硬膜下血肿消退的决定因素：来自人类数据的遗传证据。

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2026-01-07 DOI: 10.1002/cns.70741

Qizhong Wu, Tingting Xu, Bo Tan

Background

Acute subdural hematoma (ASDH) is a severe complication of traumatic brain injury, with high mortality and disability. Spontaneous hematoma resolution is an important determinant of functional recovery, but the biological mechanisms underlying this process remain poorly understood. Coagulopathy, common in ASDH, may influence hematoma dynamics, but its causal role remains uncertain.

Methods

We conducted a two-sample Mendelian randomization (MR) study to investigate the causal effects of coagulation traits on hematoma resolution. Genetic instruments for fibrinogen isoforms, coagulation factors VIII, XI, V, VII, natural anticoagulants, and platelet traits were obtained from large genome-wide association studies. Due to the absence of ASDH-specific GWAS data, we used genetic susceptibility to intracerebral hemorrhage (ICH) and poststroke functional outcome as indirect proxies for hematoma persistence and clearance. We acknowledge that these proxies cannot fully capture the unique pathophysiology of ASDH, but they represent pragmatic, biologically relevant surrogates. Causal estimates were obtained using inverse-variance weighted MR with robust sensitivity analyses.

Results

Genetically higher fibrinogen γ' levels were associated with increased odds of hematoma resolution (OR 1.25, 95% CI 1.10–1.42). Higher factor VIII and XI levels were associated with reduced odds of Resolution (OR 0.82, 95% CI 0.72–0.94; OR 0.88, 95% CI 0.78–1.00). Secondary analyses using poststroke functional outcome yielded similar patterns but did not reach statistical significance (OR ~1.10, p = 0.15).

Conclusions

Our findings provide genetic evidence suggesting coagulation pathways, particularly fibrinogen γ' and factors VIII and XI, may influence hematoma resolution in ASDH. However, due to the indirect nature of the proxies used, these results should be considered hypothesis-generating and require further validation in ASDH-specific cohorts.

背景：急性硬膜下血肿（ASDH）是外伤性脑损伤的严重并发症，死亡率和致残率高。自发性血肿消退是功能恢复的重要决定因素，但这一过程背后的生物学机制尚不清楚。凝血功能障碍，常见于ASDH，可能影响血肿动力学，但其因果作用仍不确定。方法：我们进行了一项双样本孟德尔随机化（MR）研究，以调查凝血特性对血肿消退的因果关系。纤维蛋白原异构体、凝血因子VIII、XI、V、VII、天然抗凝剂和血小板性状的遗传仪器均来自大型全基因组关联研究。由于缺乏asdh特异性GWAS数据，我们使用脑出血（ICH）的遗传易感性和脑卒中后功能结局作为血肿持续和清除的间接指标。我们承认，这些替代方法不能完全捕捉ASDH独特的病理生理学，但它们代表了实用的、生物学相关的替代方法。因果估计使用反方差加权MR与稳健敏感性分析。结果：遗传上较高的纤维蛋白原γ水平与血肿消退的几率增加相关（OR 1.25, 95% CI 1.10-1.42）。较高的因子VIII和XI水平与分辨率降低相关（OR 0.82, 95% CI 0.72-0.94; OR 0.88, 95% CI 0.78-1.00）。卒中后功能结果的二次分析也得出了类似的结果，但没有统计学意义（OR ~1.10, p = 0.15）。结论：我们的研究结果提供了遗传证据，表明凝血途径，特别是纤维蛋白原γ′和因子VIII和XI，可能影响ASDH的血肿消退。然而，由于所使用的代理的间接性质，这些结果应该被认为是假设产生的，需要在asdh特定队列中进一步验证。

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引用次数: 0

Pitolisant Inhibits Alcohol Drinking and Improves Withdrawal Negative Affect Through Lateral Habenula Histaminergic Signaling in Mice Pitolisant通过小鼠侧缰组胺能信号抑制饮酒并改善戒断负面影响。

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2026-01-06 DOI: 10.1002/cns.70732

Yan Zhao, Yixin Fu, Tianhao Liu, Zanhao Yang, Zhengzhong Yang, Bingqing Chen, Lipeng Zhou, Juntao Yang, Duo Chen, Xiaojiao Han, Ying Tang, Jiang-Hong Ye, Chao-Yu Miao, Rao Fu

Background

Alcohol use disorder (AUD) is a chronic condition marked by compulsive drinking and withdrawal-related negative affect. Histamine (HA) signaling, particularly via the histamine H3 receptor (H3R), may modulate alcohol-related behaviors. We investigated the effects of pitolisant, an FDA-approved H3R antagonist, on ethanol (EtOH)-related behaviors in mice.

Method

Adult male C57BL/6J mice underwent acute or chronic (2 or > 8 weeks) intermittent alcohol exposure. Pitolisant pretreatment was administered, and then pharmacological behavior, histologic, and molecular assays were conducted.

Result

Pitolisant administration reduced acute EtOH-induced locomotor activation, conditioned place preference, and sedative effects, and also curtailed EtOH intake. It alleviated anxiety and depression-like behavior during 24-h withdrawal (Post-EtOH). Mechanistically, the Post-EtOH condition was featured by complicated brain cFos expression mapping, including elevated cFos, [HA] and [glutamine]/[glutamate] ratio in the lateral habenula (LHb). However, systemic pitolisant treatment significantly increased [norepinephrine]/[normetanephrine] ratio, and restored the diminished phosphorylated CREB and BDNF levels in the LHb. Intra-LHb H2R antagonist cimetidine infusion partly blocked the pitolisant therapeutic effect on alcohol-related behavior.

Conclusion

These findings highlight the HAergic system as a critical regulator of alcohol-related behaviors. The LHb HA signaling and norepinephrine neurotransmission might underlie pitolisant's potential novel therapeutic strategy for AUD.

背景：酒精使用障碍（AUD）是一种以强迫性饮酒和戒断相关的负面影响为特征的慢性疾病。组胺（HA）信号，特别是通过组胺H3受体（H3R），可能调节与酒精相关的行为。我们研究了经fda批准的H3R拮抗剂pitolisant对小鼠乙醇（EtOH）相关行为的影响。方法：成年雄性C57BL/6J小鼠急性或慢性（2周或8周）间歇性酒精暴露。给予抗松剂预处理，然后进行药理学行为、组织学和分子分析。结果：顽固性给药可降低乙酰胆碱诱导的急性运动激活、条件性位置偏好和镇静作用，并可减少乙酰胆碱的摄入。它减轻了24小时戒断期间（etoh后）的焦虑和抑郁样行为。机制上，etoh后表现为复杂的脑cFos表达图谱，包括cFos、[HA]和外侧habenula (LHb)[谷氨酰胺]/[谷氨酸]比值升高。然而，全身性抗压治疗显著增加了[去甲肾上腺素]/[去甲肾上腺素]比值，并恢复了LHb中磷酸化的CREB和BDNF水平。lhb H2R拮抗剂西咪替丁输注部分阻断了对酒精相关行为的抗醇治疗作用。结论：这些发现强调了HAergic系统是酒精相关行为的关键调节器。LHb HA信号和去甲肾上腺素神经传递可能是pitolisant治疗AUD的潜在新策略的基础。

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引用次数: 0

Tumor Electric Field Therapy Inhibits TGF-β/C1R Signaling Axis-Driven Epithelial-Mesenchymal Transition in Glioblastoma 肿瘤电场治疗抑制胶质母细胞瘤中TGF-β/C1R信号轴驱动的上皮-间质转化。

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2026-01-05 DOI: 10.1002/cns.70738

Junyi Chen, Yuyang Liu, Qi Liu, Hongyu Liu, Cheng Sun, Xu Chen, Xinchen Zhao, Jinxin Lan, Yaping Feng, Lilin Qin, Jialin Liu, Ze Li, Ling Chen

Background

Glioblastoma (GBM) is one of the most aggressive and treatment-resistant primary brain tumors, with the mesenchymal subtype exhibiting particularly poor prognosis. Tumor electric field therapy (TEFT) has emerged as a promising adjunctive treatment, but its underlying molecular mechanisms remain incompletely understood.

Methods

GBM functional states were analyzed using CancerSEA datasets. GBM cell lines were treated with 200 kHz TEFT at 2.2 V/m for 72 h. C1R was knocked down using siRNA and shRNA. Cell morphology, migration, invasion, proliferation, and signaling pathways were assessed through various assays. Findings were validated in animal models and clinical specimens.

Results

C1R was identified at the intersection of TEFT-downregulated genes, poor prognosis markers, and functional state genes. C1R was significantly upregulated in mesenchymal GBM and strongly correlated with epithelial-mesenchymal transition (EMT). Single-cell RNA sequencing revealed C1R was predominantly expressed in MES-like malignant cells with high EMT signature scores. TEFT treatment induced morphological changes from elongated spindle-shaped to rounded epithelial-like morphology, increased E-cadherin expression, and decreased mesenchymal markers (N-cadherin, Vimentin, YKL-40). Mechanistically, TEFT suppressed the TGF-β/SMAD2/3/STAT3 signaling pathway, downregulating C1R expression. C1R knockdown significantly reduced tumor growth in vivo, while exogenous TGF-β restored C1R expression and reversed the mesenchymal phenotype in a dose- and time-dependent manner.

Conclusion

TEFT inhibits GBM progression by suppressing the TGF-β/SMAD2/3/STAT3/C1R axis, thereby attenuating EMT and reducing tumor aggressiveness. These findings uncover a novel mechanism of TEFT and identify C1R as a potential biomarker and therapeutic target for GBM.

背景：胶质母细胞瘤（GBM）是最具侵袭性和治疗抵抗性的原发性脑肿瘤之一，其中间充质亚型表现出特别差的预后。肿瘤电场治疗（TEFT）已成为一种很有前景的辅助治疗方法，但其潜在的分子机制尚不完全清楚。方法：使用CancerSEA数据集对GBM功能状态进行分析。用200 kHz TEFT （2.2 V/m）处理GBM细胞株72 h。C1R被siRNA和shRNA敲低。通过各种检测评估细胞形态、迁移、侵袭、增殖和信号通路。研究结果在动物模型和临床标本中得到了验证。结果：C1R在teft下调基因、不良预后标志物和功能状态基因的交汇处被发现。C1R在间充质GBM中显著上调，并与上皮-间充质转化（EMT）密切相关。单细胞RNA测序显示，C1R主要表达于具有高EMT特征评分的mes样恶性细胞中。TEFT处理诱导细胞形态学改变，从细长纺锤形变为圆形上皮样形态，E-cadherin表达增加，间质标志物（N-cadherin, Vimentin, YKL-40）降低。在机制上，TEFT抑制TGF-β/SMAD2/3/STAT3信号通路，下调C1R表达。体内C1R敲低显著降低肿瘤生长，而外源性TGF-β恢复C1R表达并以剂量和时间依赖的方式逆转间质表型。结论：TEFT通过抑制TGF-β/SMAD2/3/STAT3/C1R轴抑制GBM进展，从而减弱EMT，降低肿瘤侵袭性。这些发现揭示了TEFT的新机制，并确定C1R是GBM的潜在生物标志物和治疗靶点。

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引用次数: 0

Multidimensional Assessment of Neurological Adverse Reactions Related to PD-1 Inhibitors: A Real-World Pharmacovigilance Study 与PD-1抑制剂相关的神经系统不良反应的多维评估：一项现实世界药物警戒研究。

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2026-01-05 DOI: 10.1002/cns.70734

Xiaofeng Hu, Xiaoli Wang, Bufu Tang, Dehuan Zhang, Rongbing Cai, Hui Jiang, Yaling Lin, Yiheng Song, Yiou Wang, Hairuo Huang, Dandan Guo, Xubin Sun, Hongjie Fan

Background

PD-1 inhibitors have revolutionized cancer immunotherapy but present significant neurological safety concerns. While clinical trials have documented neurological adverse events (nAEs), a comprehensive understanding of their patterns and risk factors remains limited. This study systematically analyzed a decade of FAERS data to investigate PD-1 inhibitor–associated neurotoxicities.

Methods

Using FAERS data (2014–2024), we conducted disproportionality analyses (ROR, IC, PRR) to assess PD-1 inhibitor–nAE associations. Risk factors were evaluated using logistic regression; timing analyses used log-rank and Mann–Whitney U tests, while group comparisons used Chi-square tests.

Results

Among 115,000 PD-1 inhibitor–associated adverse events, 7968 (6.93%) involved nAEs, showing an increasing trend from 4.96% (Q4 2014) to 7.67% (Q1-Q2 2024). PD-1 inhibitors showed significant nAE signals (ROR: 1.21, 95% CI: 1.18–1.23), with cemiplimab showing the strongest association (ROR: 1.38, 95% CI: 1.18–1.62). The most common nAEs were dizziness (N = 942, 10.3%), encephalitis (N = 435, 4.8%), and cerebrovascular accident (N = 451, 4.9%). Risk factors included age > 65 years (OR: 1.10), female sex (OR: 1.04), skin cancer (OR: 1.36), and nervous system cancers (OR: 1.44). The median onset time was 34 days (IQR: 12–104), with 63.8% occurring within 2 months and 59% resulting in severe outcomes.

Conclusion

This study reveals a spectrum of PD-1 inhibitor–related neurological toxicities, mainly involving central nervous system dysfunction, providing important insights into risk patterns and timing characteristics. These findings support improved clinical monitoring practices and inform the development of personalized patient care strategies.

背景：PD-1抑制剂已经彻底改变了癌症免疫治疗，但存在显著的神经安全性问题。虽然临床试验已经记录了神经系统不良事件（nAEs），但对其模式和风险因素的全面了解仍然有限。本研究系统分析了十年FAERS数据，以研究PD-1抑制剂相关的神经毒性。方法：使用FAERS数据（2014-2024），我们进行歧化分析（ROR， IC， PRR）来评估PD-1抑制剂与nae的关联。采用logistic回归评价危险因素；时间分析采用log-rank检验和Mann-Whitney U检验，而组间比较采用卡方检验。结果：在11.5万例PD-1抑制剂相关不良事件中，7968例（6.93%）涉及nAEs，呈上升趋势，从2014年第四季度的4.96%上升至2024年第二季度的7.67%。PD-1抑制剂表现出显著的nAE信号（ROR: 1.21, 95% CI: 1.18-1.23），其中塞米单抗表现出最强的相关性（ROR: 1.38, 95% CI: 1.18-1.62）。最常见的nAEs是头晕（N = 942, 10.3%）、脑炎（N = 435, 4.8%）和脑血管意外（N = 451, 4.9%）。危险因素包括年龄0 ~ 65岁（OR: 1.10）、女性（OR: 1.04）、皮肤癌（OR: 1.36）和神经系统癌症（OR: 1.44）。中位发病时间为34天（IQR: 12-104）， 63.8%发生在2个月内，59%发生严重后果。结论：本研究揭示了PD-1抑制剂相关的神经毒性谱，主要涉及中枢神经系统功能障碍，为风险模式和时间特征提供了重要见解。这些发现支持改进临床监测实践，并为个性化患者护理策略的发展提供信息。

{"title":"Multidimensional Assessment of Neurological Adverse Reactions Related to PD-1 Inhibitors: A Real-World Pharmacovigilance Study","authors":"Xiaofeng Hu, Xiaoli Wang, Bufu Tang, Dehuan Zhang, Rongbing Cai, Hui Jiang, Yaling Lin, Yiheng Song, Yiou Wang, Hairuo Huang, Dandan Guo, Xubin Sun, Hongjie Fan","doi":"10.1002/cns.70734","DOIUrl":"10.1002/cns.70734","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>PD-1 inhibitors have revolutionized cancer immunotherapy but present significant neurological safety concerns. While clinical trials have documented neurological adverse events (nAEs), a comprehensive understanding of their patterns and risk factors remains limited. This study systematically analyzed a decade of FAERS data to investigate PD-1 inhibitor–associated neurotoxicities.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using FAERS data (2014–2024), we conducted disproportionality analyses (ROR, IC, PRR) to assess PD-1 inhibitor–nAE associations. Risk factors were evaluated using logistic regression; timing analyses used log-rank and Mann–Whitney <i>U</i> tests, while group comparisons used Chi-square tests.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 115,000 PD-1 inhibitor–associated adverse events, 7968 (6.93%) involved nAEs, showing an increasing trend from 4.96% (Q4 2014) to 7.67% (Q1-Q2 2024). PD-1 inhibitors showed significant nAE signals (ROR: 1.21, 95% CI: 1.18–1.23), with cemiplimab showing the strongest association (ROR: 1.38, 95% CI: 1.18–1.62). The most common nAEs were dizziness (<i>N</i> = 942, 10.3%), encephalitis (<i>N</i> = 435, 4.8%), and cerebrovascular accident (<i>N</i> = 451, 4.9%). Risk factors included age > 65 years (OR: 1.10), female sex (OR: 1.04), skin cancer (OR: 1.36), and nervous system cancers (OR: 1.44). The median onset time was 34 days (IQR: 12–104), with 63.8% occurring within 2 months and 59% resulting in severe outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study reveals a spectrum of PD-1 inhibitor–related neurological toxicities, mainly involving central nervous system dysfunction, providing important insights into risk patterns and timing characteristics. These findings support improved clinical monitoring practices and inform the development of personalized patient care strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12767002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145898863","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}

引用次数: 0

Elevated CHI3L1 as a Potential Biomarker of Cognitive Dysfunction in Anti-NMDAR Encephalitis: Evidence From Clinical Results and Mice Model 升高的CHI3L1作为抗nmdar脑炎认知功能障碍的潜在生物标志物：来自临床结果和小鼠模型的证据

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2026-01-05 DOI: 10.1002/cns.70739

Yuhang Li, Ran Ding, Jiaxin Yang, Xiaoyue Yang, Ziyao Han, Xue Li, Jie Liu, Yan Jiang, Li Cheng, Jiannan Ma, Hanyu Luo, Li Jiang

Background

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is frequently associated with long-term cognitive impairment. However, the underlying mechanisms remain poorly understood, and reliable biomarkers for predicting cognitive outcomes are lacking.

Methods

We established an active immunization mouse model of anti-NMDAR encephalitis by immunizing with the GluN1_356-385 peptide. Hippocampal proteomic profiling was performed, followed by molecular and histological validation. Behavioral tests were used to assess cognitive function. In parallel, serum and cerebrospinal fluid (CSF) samples were analyzed from a clinical cohort of children with anti-NMDAR encephalitis to evaluate expression of the targeted biomarker and its association with clinical outcomes.

Results

Proteomic analysis and subsequent validation revealed significant upregulation of chitinase-3-like protein 1 (CHI3L1) in the hippocampus of model mice, primarily derived from astrocytes. Elevated CHI3L1 levels were observed in parallel with impaired hippocampal neurogenesis, reflected by decreased DCX⁺ immature neurons and increased SOX2⁺ neural progenitors. These changes were accompanied by cognitive deficits in behavioral tests. In parallel, we analyzed a pediatric cohort of 83 children with anti-NMDAR encephalitis. CHI3L1 levels in both serum and CSF were significantly elevated compared to controls. While CHI3L1 levels showed no association with modified Rankin Scale scores at one-year follow-up, higher CHI3L1 levels in serum and CSF were significantly correlated with persistent cognitive impairment.

Conclusions

Our findings provide preliminary evidence that astrocyte-derived CHI3L1 may contribute to disrupted hippocampal neurogenesis and cognitive dysfunction in anti-NMDAR encephalitis. CHI3L1 may serve as a potential biomarker for cognitive prognosis and a therapeutic target for reducing long-term neurological sequelae.

背景：抗n -甲基- d -天冬氨酸受体（NMDAR）脑炎通常与长期认知障碍有关。然而，潜在的机制仍然知之甚少，并且缺乏预测认知结果的可靠生物标志物。方法：采用GluN1356-385肽免疫建立抗nmdar脑炎小鼠主动免疫模型。进行海马蛋白质组学分析，然后进行分子和组织学验证。行为测试用于评估认知功能。同时，对抗nmdar脑炎儿童临床队列的血清和脑脊液（CSF）样本进行分析，以评估靶向生物标志物的表达及其与临床结果的关系。结果：蛋白质组学分析和随后的验证显示，模型小鼠海马中主要来源于星形胶质细胞的几丁质酶-3样蛋白1 （CHI3L1）显著上调。CHI3L1水平升高与海马神经发生受损同时发生，表现为DCX+未成熟神经元减少，SOX2+神经祖细胞增加。这些变化伴随着行为测试中的认知缺陷。同时，我们分析了83名患有抗nmdar脑炎的儿童队列。与对照组相比，血清和脑脊液中CHI3L1水平均显著升高。在一年的随访中，CHI3L1水平与修改后的Rankin量表评分没有关联，但血清和脑脊液中较高的CHI3L1水平与持续性认知障碍显著相关。结论：我们的研究结果提供了初步证据，星形胶质细胞来源的CHI3L1可能导致抗nmdar脑炎海马神经发生中断和认知功能障碍。CHI3L1可能作为认知预后的潜在生物标志物和减少长期神经系统后遗症的治疗靶点。

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引用次数: 0

Differences in the Efficacy of Cognitive Function Treatment Related to Functional Patterns in the Frontal-Limbic Network in Patients With Bipolar Disorder 双相情感障碍患者额边缘网络功能模式相关认知功能治疗的疗效差异。

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2026-01-05 DOI: 10.1002/cns.70730

Sujuan Li, Yangpan Ou, Haiping Liu, Qianyu Dong, Yan Qiu, Ziwei Teng, Hui Tang, Hui Xiang, Guowei Wu, Jindong Chen, Bolun Wang, Lutao Jiang, Haishan Wu

Background

This study aimed to identify neurobiomarkers that predict the efficacy of treatment of cognition in patients with bipolar disorder (BD).

Methods

Regional homogeneity (ReHo) and degree centrality (DC) values, which are two functional magnetic resonance imaging indicators, were analyzed to compare differences in brain activities between patients with BD and healthy controls (HC).

Results

BD patients (N = 92) exhibited increased activity in the right hippocampus or right parahippocampal gyrus compared to HC, while their ReHo and DC values in the left middle frontal gyrus decreased in the resting state. The delayed memory scores were predicted by using connectome-based predictive modeling in patients with BD at baseline. After 12 weeks of treatment, the patients with BD, whose cognitive function improved (n = 24), showed activity in the right superior temporal gyrus (STG) and left anterior cingulate cortex (ACC) at baseline. The improvement in cognitive function of patients with BD is distinguished by abnormal activities using support vector machine analysis.

Conclusions

The abnormal frontal-limbic network plays a critical role in the underlying neuropathological mechanism of cognitive impairment in patients with BD. The right STG and left ACC hold the potential to serve as neurobiomarkers for predicting the clinical efficacy of cognitive function treatment. These regions provide additional target options for future physical treatments of cognitive impairment in patients with BD.

背景：本研究旨在确定预测双相情感障碍（BD）患者认知治疗效果的神经生物标志物。方法：分析功能磁共振成像指标区域均匀性（ReHo）和度中心性（DC）值，比较BD患者与健康对照组（HC）脑活动的差异。结果：与HC相比，BD患者（N = 92）在静息状态下右侧海马或右侧海马旁回活动增加，左侧额叶中回ReHo和DC值下降。在基线时，使用基于连接体的预测模型预测双相障碍患者的延迟记忆评分。治疗12周后，认知功能改善的BD患者（n = 24）在基线时显示右侧颞上回（STG）和左侧前扣带皮层（ACC）活动。采用支持向量机分析方法对BD患者认知功能的改善进行区分。结论：额边缘网络异常在BD患者认知功能障碍的潜在神经病理机制中起关键作用，右侧STG和左侧ACC有可能作为预测认知功能治疗临床疗效的神经生物标志物。这些区域为未来双相障碍患者认知功能障碍的物理治疗提供了额外的靶点选择。

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引用次数: 0

Effect of Anticholinergic Drug Burden on Postoperative Delirium in Elderly Patients: A Nested Case–Control Study 抗胆碱能药物负担对老年患者术后谵妄的影响：一项巢式病例对照研究。

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2026-01-04 DOI: 10.1002/cns.70731

Ting Zhang, Tianqi Shen, Ningxin Li, Xiaoying Zhang, Kai Zhang, Chang Liu, Bingbing Meng, Shaohua Zhang, Guangyu Tang, Ziyi Zhang, Qiang Fu, Yanhong Liu, Jingsheng Lou, Jiangbei Cao, Weidong Mi, Hao Li

Background

Postoperative delirium (POD) is a common complication in elderly patients. This study aimed to investigate the association between preoperative anticholinergic drug burden and POD in elderly patients.

Methods

This nested case–control study included patients aged ≥ 65 years who underwent general anesthesia between April 2020 and April 2022 at multiple hospitals in China. POD occurring within 7 days postoperatively was assessed using the 3-Minute Diagnostic Interview for Confusion Assessment Method. Preoperative anticholinergic drug burden was quantified using the Anticholinergic Cognitive Burden (ACB) scale. Univariate and multivariate logistic regression models with random effects were used to determine the association between ACB scores and POD occurrence. Kaplan–Meier survival analysis with log-rank tests was plotted to compare the cumulative POD incidence across groups. Subgroup analyses were performed to explore the relationship between ACB scores and POD occurrence within specific populations.

Results

Among 10,296 patients, 1131 (11.0%) developed POD. The study employed a 5:1 matched case–control design and included 1125 cases and 5296 matched controls. Univariate (odds ratio [OR]: 1.230; 95% confidence interval [CI]: 1.119–1.353, p < 0.001) and multivariate (adjusted OR: 1.118; 95% CI: 1.006–1.243, p = 0.037) analyses demonstrated a significant association between higher anticholinergic drug burden and increased POD risk. When analyzed categorically (ACB score 0 as reference), adjusted ORs were 1.100 (95% CI: 0.919–1.317; p = 0.296) for ACB = 1, 1.213 (95% CI: 0.831–1.771; p = 0.318) for ACB = 2, and 1.963 (95% CI: 1.253–3.076; p = 0.003) for ACB ≥ 3. Kaplan–Meier analysis demonstrated a significantly higher cumulative incidence of POD in the ACB ≥ 3 group (log-rank p < 0.001), with divergence starting on postoperative day 3.

Conclusion

A higher preoperative anticholinergic drug burden is associated with an increased risk of POD in elderly patients, particularly when the ACB scores are ≥ 3.

背景：术后谵妄（POD）是老年患者常见的并发症。本研究旨在探讨老年患者术前抗胆碱能药物负担与POD的关系。方法：本套式病例对照研究纳入了2020年4月至2022年4月在中国多家医院接受全身麻醉的年龄≥65岁的患者。术后7天内发生的POD采用3分钟诊断访谈法进行评估。术前采用抗胆碱能认知负担量表（ACB）量化抗胆碱能药物负担。采用随机效应的单因素和多因素logistic回归模型来确定ACB评分与POD发生之间的关系。Kaplan-Meier生存分析采用log-rank检验，比较各组间POD的累计发病率。进行亚组分析，探讨特定人群中ACB评分与POD发生之间的关系。结果：10296例患者中，1131例（11.0%）发生POD。该研究采用5:1匹配病例-对照设计，包括1125例病例和5296例匹配对照。单因素（比值比[OR]: 1.230； 95%可信区间[CI]: 1.119-1.353, p）结论：老年患者术前抗胆碱能药物负担加重与POD风险增加相关，特别是当ACB评分≥3分时。

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引用次数: 0

Lineage-Biased Neural Stem Cell Grafting Promotes Neuronal Differentiation and Vascular Repair in the Chronic Phase of Stroke 谱系偏向性神经干细胞移植促进脑卒中慢性期神经元分化和血管修复。

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2026-01-04 DOI: 10.1002/cns.70701

Tingting Zhang, Da Li, Qibiao Guan, Bin An, Yun Sun, Qiang Wang, Yukai Wang, Baoyang Hu

Aims

Ischemic stroke (IS) is a harmful neurological disorder, yet current therapies fail to achieve effective functional neural and vascular restoration. Neural stem cell (NSC) transplantation offers high potential for neuronal replenishment and vascular reconstruction. However, its clinical application is limited by inconsistent in vivo cell fate, unclear therapeutic mechanisms, and variability in differentiation protocols. To address these limitations, we aimed to identify a neural lineage-biased NSC suitable for neuronal and vascular recovery after IS.

Methods

We assessed two strategies for deriving transplantable NSCs: one involving embryoid body (EB) formation, and the other employing a direct differentiation protocol bypassing EB formation. We compared the cell fate of NSCs derived via both protocols in vitro and following transplantation into mice subjected to IS induced by transient middle cerebral artery occlusion (tMCAO). RNA sequencing and immunofluorescence were used to assess cell fate. Cerebral blood flow (CBF) and behavioral tests were conducted to evaluate functional recovery.

Results

Comparative analyses demonstrated that nEB-NSCs exhibit elevated neural stemness marker expression, improved neuronal differentiation with reduced astrocytic commitment, and accelerated neurovascular repair kinetics, contributing to considerable motor recovery.

Conclusions

nEB-NSCs represent a promising cell source for enhancing neurovascular repair and functional recovery following IS.

目的：缺血性脑卒中（IS）是一种有害的神经系统疾病，但目前的治疗方法无法实现有效的神经和血管功能恢复。神经干细胞移植在神经元补充和血管重建方面具有很高的潜力。然而，其临床应用受到体内细胞命运不一致，治疗机制不明确以及分化方案的可变性的限制。为了解决这些局限性，我们的目标是确定一种神经谱系偏向的NSC，适合于IS后的神经元和血管恢复。方法：我们评估了两种获得可移植NSCs的策略：一种涉及胚状体（EB）形成，另一种采用直接分化方案绕过EB形成。我们比较了两种方法获得的NSCs在体外和移植后的细胞命运，这些NSCs移植到由短暂性大脑中动脉闭塞（tMCAO）诱导的IS小鼠体内。采用RNA测序和免疫荧光法评估细胞命运。脑血流量（CBF）和行为测试评估功能恢复。结果：比较分析表明，nEB-NSCs表现出神经干标记物表达升高，神经元分化改善，星形细胞承诺减少，神经血管修复动力学加速，有助于相当程度的运动恢复。结论：nEB-NSCs是促进IS后神经血管修复和功能恢复的有希望的细胞来源。

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引用次数: 0

Four Distinct Dynamic Intracranial Pressure Trajectories and Their Prognostic Implications in Acute Brain Injury: A Multicenter Cohort Study 急性脑损伤的四种不同动态颅内压轨迹及其预后意义：一项多中心队列研究。

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2026-01-03 DOI: 10.1002/cns.70735

Juan Wang, Haibo Li, Manman Xu, Wen-Juan Li, Longyang Cheng, Shaoya Li, Chun-Hua Hang, Penglai Zhao

Background

Acute brain injury (ABI) often elevates intracranial pressure (ICP), yet static measurements miss dynamic risk. We evaluated the prognostic value of early ICP trajectories.

Methods

We formed a multicenter ICU cohort from MIMIC-IV (2008–2022), eICU (2014–2015), and NSICU (2024–2025). Latent class growth modeling identified ICP trajectories over the first 120 h. Associations with in-hospital mortality were tested with Cox models, and incremental value beyond baseline clinical variables was quantified by AUC, integrated discrimination improvement (IDI), and net reclassification improvement (NRI). Sensitivity analyses were performed across datasets and age groups.

Results

Among 1700 patients with ABI, four trajectories emerged—Severe Progressive, Stabilized Elevated, Mildly Elevated Stable, and Normal. Versus Normal, mortality risk was highest for Severe Progressive (HR 13.54; 95% CI 9.35–19.59), followed by Stabilized Elevated (HR 2.53; 1.83–3.49) and Mildly Elevated Stable (HR 1.48; 1.16–1.91). In patients aged ≥ 55 years, risk with Stabilized Elevated was amplified (HR 2.87; 1.97–4.20). Adding trajectories improved risk stratification (IDI +0.065; NRI +0.201) with modest AUC gains.

Conclusions

Early ICP trajectories define reproducible phenotypes with distinct mortality risk. Incorporating trajectories—particularly the stabilized-elevated pattern in older adults—adds prognostic value beyond clinical variables and supports prospective validation.

背景：急性脑损伤（ABI）经常升高颅内压（ICP），但静态测量错过了动态风险。我们评估早期ICP轨迹的预后价值。方法：我们从MIMIC-IV（2008-2022）、eICU（2014-2015）和NSICU（2024-2025）组成了一个多中心ICU队列。潜在类别增长模型确定了前120小时内的ICP轨迹。采用Cox模型检验与院内死亡率的相关性，并通过AUC、综合判别改善（IDI）和净重分类改善（NRI）量化超出基线临床变量的增量值。对数据集和年龄组进行敏感性分析。结果：在1700例ABI患者中，出现了四种轨迹：严重进行性、稳定升高、轻度升高稳定和正常。与正常患者相比，严重进展患者的死亡风险最高（HR 13.54; 95% CI 9.35-19.59），其次是稳定升高患者（HR 2.53; 1.83-3.49）和轻度升高患者（HR 1.48; 1.16-1.91）。在年龄≥55岁的患者中，稳定升高的风险被放大（HR 2.87; 1.97-4.20）。增加轨迹改善了风险分层（IDI +0.065; NRI +0.201）， AUC增加适度。结论：早期ICP轨迹定义了具有明显死亡风险的可复制表型。结合轨迹-特别是老年人的稳定升高模式-增加了临床变量之外的预后价值，并支持前瞻性验证。

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引用次数: 0

Association of Original and Revised Pooled Cohort Equations With Cardiovascular and Cerebrovascular Mortality 原始和修订的合并队列方程与心脑血管死亡率的关联。

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2026-01-03 DOI: 10.1002/cns.70737

Chuanhao Lu, Min Li, Deyu Sun, Hongchen Zhang, Liang Li, Yang Yu, Juan Wang, Lele Cao, Zhen Hu, Xia Li

Background

Cardiovascular (CVD) and cerebrovascular diseases (CeVD) are leading causes of mortality. The Pooled Cohort Equations (PCE) are widely used for ASCVD risk prediction, but face calibration concerns, particularly in diverse populations. The Revised Pooled Cohort Equations (RPCE) were developed to address these limitations. While prior research has evaluated these models for ASCVD, less is known about their performance for CVD and CeVD mortality outcomes.

Objective

This study aimed to comprehensively compare the association of PCE and RPCE with CVD mortality and combined CVD and CeVD mortality, including subgroup analyses by race and gender, within a nationally representative US adult population.

Methods

We analyzed 16,584 primary prevention participants (aged 40–79 years) from National Health and Nutrition Examination Survey (1999–2018), linked to National Death Index mortality data. We calculated 10-year ASCVD risk using both PCE and RPCE. Bland–Altman plots assessed score agreement. Cox proportional hazards models evaluated the association of standardized PCE and RPCE scores with CVD and combined CVD and CeVD mortality, adjusting for confounders and stratifying by race and gender.

Results

Both PCE and RPCE were significantly associated with CVD mortality (adjusted hazard ratio (HR) for PCE: 1.91 [95% CI: 1.82–2.01]; RPCE: 1.65 [95% CI: 1.59–1.72]) and combined CVD and CeVD mortality (adjusted HR for PCE: 1.91 [95% CI: 1.82–2.00]; RPCE: 1.65 [95% CI: 1.60–1.72]). Bland–Altman analyses revealed PCE consistently overestimated risk compared to RPCE, with differences increasing at higher risk levels. RPCE demonstrated improved calibration, especially in racially diverse populations, where PCE overestimation was more pronounced.

Conclusion

Both PCE and RPCE are robust prognostic tools for vascular mortality. However, RPCE offers improved calibration, particularly in racially diverse populations, by providing more conservative yet comparably predictive risk estimates. These findings highlight the importance of selecting risk models tailored to target populations to optimize prevention and avoid potential overtreatment.

背景：心血管（CVD）和脑血管疾病（CeVD）是导致死亡的主要原因。汇集队列方程（PCE）广泛用于ASCVD风险预测，但面临校准问题，特别是在不同人群中。修订的合并队列方程（RPCE）是为了解决这些局限性而开发的。虽然先前的研究已经评估了这些ASCVD模型，但对它们在CVD和CeVD死亡率结果方面的表现知之甚少。目的：本研究旨在全面比较PCE和RPCE与CVD死亡率以及CVD和CeVD合并死亡率的关系，包括在具有全国代表性的美国成年人中按种族和性别进行亚组分析。方法：我们分析了1999-2018年国家健康与营养调查（National Health and Nutrition Examination Survey）的16584名一级预防参与者（40-79岁），并与国家死亡指数（National Death Index）死亡率数据相关联。我们使用PCE和RPCE计算10年ASCVD风险。Bland-Altman地块评估得分一致性。Cox比例风险模型评估了标准化PCE和RPCE评分与CVD以及CVD和CeVD合并死亡率的关系，调整了混杂因素并按种族和性别分层。结果：PCE和RPCE均与CVD死亡率显著相关(PCE的校正危险比（HR）： 1.91 [95% CI: 1.82-2.01]；RPCE: 1.65 [95% CI: 1.59-1.72])和CVD和CeVD合并死亡率（PCE的校正HR: 1.91 [95% CI: 1.82-2.00]; RPCE: 1.65 [95% CI: 1.60-1.72]）。Bland-Altman分析显示，与RPCE相比，PCE始终高估了风险，风险水平越高，差异越大。RPCE证明了改进的校准，特别是在种族多样化的人群中，其中PCE高估更为明显。结论：PCE和RPCE都是血管死亡率的可靠预后工具。然而，RPCE提供了改进的校准，特别是在种族多样化的人群中，通过提供更保守但可比较预测的风险估计。这些发现强调了选择适合目标人群的风险模型以优化预防和避免潜在的过度治疗的重要性。

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引用次数: 0