CNS Neuroscience & Therapeutics最新文献

Development and Validation of Multiple Machine Learning Models Integrating Neutrophil-Lymphocyte Ratio for Prediction of Hemorrhagic Transformation After Intravenous Thrombolysis in Acute Ischemic Stroke 利用中性粒细胞-淋巴细胞比值预测急性缺血性卒中静脉溶栓后出血转化的多机器学习模型的开发与验证。

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2025-12-12 DOI: 10.1111/cns.70667

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.

背景：出血性转化（HT）是急性缺血性卒中（AIS）静脉溶栓（IVT）的一个重要并发症。本研究开发并验证了整合炎症生物标志物和临床指标的机器学习（ML）模型，以预测ivt后的HT。方法：在1272例ivt治疗的AIS患者中，最小绝对收缩和选择算子（LASSO）回归从17个变量中识别出5个预测因子，随后用于构建8个ML模型。对模型进行训练（70%数据）和测试（30%数据）。此外，在独立队列上进行的外部验证证实了最优模型的泛化性。SHapley加性解释（SHAP）方法解释了特征的重要性。结果：LASSO筛选了五个重要的预测指标：中性粒细胞与淋巴细胞比率（NLR）、入院时美国国立卫生研究院卒中量表（NIHSS）评分、阿尔伯塔卒中计划早期CT评分（ASPECTS）、血糖和心房颤动。Logistic回归（LR）达到最佳效果，内部AUC为0.833，外部AUC为0.842。SHAP分析优先考虑NIHSS是最大的贡献者，而nomogram则阐明了HT风险的变异性。结论：将NLR与脑卒中严重程度和神经影像学生物标志物相结合可提高HT预测的准确性。基于lr的nomographic为个性化IVT决策提供了实用工具，强调了系统性炎症在AIS管理中的预后价值。

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引用次数: 0

Activation and Long-Term Maintenance of Adaptive Immunity in the Central Nervous System: A Double-Edged Sword? 中枢神经系统适应性免疫的激活和长期维持：一把双刃剑？

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2025-12-12 DOI: 10.1002/cns.70697

Luojinyun Wang, Feng Zhang, Jiehong Wu, Sibo Yang, Daqiang Zhou, Xiaodi Sun, Bohao Chang, Bo Hu, Yifan Zhou

Background

For a long time, the brain was considered an organ with “immune privilege”, where microglial cells played a phagocytic role, maintaining immune self-sufficiency. However, recent studies have revealed the presence of immune-related structures and immune cell infiltration in the brain, which participates in adaptive immunity.

Aim of Review

This review aims to synthesize recent findings on the activation and long-term maintenance of adaptive immunity in the central nervous system (CNS), exploring how adaptive immune responses function in pathogen clearance, tumor defense, and CNS inflammation. It highlights both the protective and detrimental roles of adaptive immunity in these contexts.

Key Scientific Concepts

Antigen-presenting cells (APCs) present antigen information to naive T cells, initiating adaptive immunity in the CNS. Activated T cells can differentiate into effector T cells to perform immediate immune functions or into tissue-resident memory T cells (TRMs) that persist in the CNS, providing long-term immune surveillance. Over the past 15 years, studies have shown that adaptive immunity is activated and maintained during intracranial pathogen infections, brain tumors, and CNS inflammation. While adaptive immunity can clear pathogens, eliminate tumor cells, and protect the brain, it can also lead to CNS inflammation under certain conditions, resulting in undesirable outcomes.

背景：长期以来，大脑被认为是具有“免疫特权”的器官，其中小胶质细胞发挥吞噬作用，维持免疫自给自足。然而，最近的研究表明，大脑中存在免疫相关结构和免疫细胞浸润，参与适应性免疫。综述目的：本文综述了近年来在中枢神经系统（CNS）适应性免疫的激活和长期维持方面的研究进展，探讨了适应性免疫反应在病原体清除、肿瘤防御和中枢神经系统炎症中的作用。它强调了适应性免疫在这些情况下的保护和有害作用。关键科学概念：抗原呈递细胞（APCs）向幼稚T细胞呈递抗原信息，启动中枢神经系统的适应性免疫。激活的T细胞可以分化为效应T细胞，执行即时免疫功能，也可以分化为组织驻留记忆T细胞（TRMs），持续存在于中枢神经系统中，提供长期免疫监视。在过去的15年里，研究表明适应性免疫在颅内病原体感染、脑肿瘤和中枢神经系统炎症期间被激活和维持。虽然适应性免疫可以清除病原体，消除肿瘤细胞，保护大脑，但在某些情况下，它也会导致中枢神经系统炎症，导致不良后果。

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引用次数: 0

Mechanism of Hypoxia-Induced HMGB1 Regulating NLRP3 Inflammasome/Caspase-1 Pathway-Mediated Pyroptosis in Myocardial Ischemia Reperfusion Injury Through the Nrf2/HO-1 Pathway 缺氧诱导HMGB1通过Nrf2/HO-1途径调控NLRP3炎性体/Caspase-1途径介导的心肌缺血再灌注损伤中的焦亡机制

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2025-12-11 DOI: 10.1111/cns.70661

Fuzhen Zheng, Licheng Yan, Fei Ren, Wenlong Cai, Yongrong Lan, Hong Chen, Qian Chen, Guoxing Weng

Objective

Myocardial ischemia–reperfusion injury (MIRI) represents an inevitable risk event for acute myocardial infarction. We explored the mechanism of hypoxia-induced high-mobility group box 1 (HMGB1) promoting MIRI by modulating the NLRP3 inflammasome/Caspase-1 pathway-mediated pyroptosis via the Nrf2/HO-1 pathway.

Methods

In vitro cultured mouse cardiomyocytes were exposed to hypoxia/reoxygenation (H/R) to establish an MIRI cell model, then treated with short hairpin-HMGB1, a NLRP3 agonist (Nigericin), and a Nrf2 inhibitor (ML385). Cell viability and injury were assessed via MTT and LDH assays. HMGB1 (nuclear/cytoplasm), Nrf2 (nuclear/cytoplasm), HO-1, NLRP3, ASC, cleaved Caspase-1, and GSDMD-N protein levels, and IL-1β and IL-18 levels in cell supernatants were determined by western blot and ELISA. HMGB1 and Nrf2 distribution were analyzed by immunofluorescence, with their interaction verified by co-immunoprecipitation. An MIRI mouse model was developed and treated with HMGB1 Box A for in vivo verification.

Results

H/R induction declined the nuclear HMGB1 protein level and cell viability, and intensified the cytoplasmic HMGB1 protein level, cell damage, and pyroptosis-related protein and inflammatory cytokine levels, which were averted by HMGB1 knockdown. NLRP3 activation partially reversed HMGB1 knockdown's effect on improving cardiomyocyte pyroptosis. Hypoxia-induced HMGB1 inhibited Nrf2/HO-1 activation by interacting with Nrf2. Nrf2/HO-1 suppression partly counteracted HMGB1 knockdown's suppressive effects on NLRP3 inflammasome activation and pyroptosis. HMGB1 suppressed the Nrf2/HO-1 axis to enhance NLRP3 inflammasome/Caspase-1 pathway-mediated pyroptosis, thereby exacerbating MIRI in vivo.

Conclusion

Hypoxia induces HMGB1's nucleus-to-cytoplasm translocation, which binds to Nrf2 to repress Nrf2 nuclear translocation to suppress Nrf2/HO-1 activation to promote NLRP3 inflammasome/Caspase-1-mediated pyroptosis, thereby exacerbating MIRI.

目的：心肌缺血再灌注损伤（MIRI）是急性心肌梗死不可避免的危险事件。我们通过Nrf2/HO-1通路调节NLRP3炎性体/Caspase-1通路介导的焦亡，探讨缺氧诱导的高迁移率组盒1 （HMGB1）促进MIRI的机制。方法：体外培养的小鼠心肌细胞缺氧/再氧化（H/R）建立MIRI细胞模型，然后用短发夹- hmgb1、NLRP3激动剂（Nigericin）和Nrf2抑制剂（ML385）处理。通过MTT和LDH测定细胞活力和损伤程度。western blot和ELISA法检测细胞上清液中HMGB1（核/胞质）、Nrf2（核/胞质）、HO-1、NLRP3、ASC、cleaved Caspase-1、GSDMD-N蛋白水平和IL-1β、IL-18水平。通过免疫荧光分析HMGB1和Nrf2的分布，并通过共免疫沉淀验证它们的相互作用。建立MIRI小鼠模型，用HMGB1 Box A处理进行体内验证。结果：H/R诱导使细胞核HMGB1蛋白水平下降，细胞活力下降，胞质HMGB1蛋白水平升高，细胞损伤、热释相关蛋白和炎症因子水平升高，而这些均可通过HMGB1敲除而避免。NLRP3激活部分逆转HMGB1敲低对心肌细胞焦亡的改善作用。缺氧诱导的HMGB1通过与Nrf2相互作用抑制Nrf2/HO-1的激活。Nrf2/HO-1抑制部分抵消了HMGB1敲低对NLRP3炎性小体激活和焦亡的抑制作用。HMGB1抑制Nrf2/HO-1轴，增强NLRP3炎性体/Caspase-1途径介导的焦亡，从而在体内加重MIRI。结论：缺氧诱导HMGB1核-胞质易位，与Nrf2结合抑制Nrf2核易位，抑制Nrf2/HO-1活化，促进NLRP3炎性小体/ caspase -1介导的焦亡，从而加重MIRI。

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引用次数: 0

Dl-3-n-Butylphthalide Promotes Cortical Angiogenesis via Akt/GSK-3β Signaling in Ischemic Stroke Mice dl -3-n-丁苯酞通过Akt/GSK-3β信号通路促进缺血性脑卒中小鼠皮质血管生成

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2025-12-10 DOI: 10.1002/cns.70698

Lan Zhang, Shanshan Wei, Jian Zhang, Rong Chen, Jiangyong Miao, Lina Wang, Peipei Zhang, Wenyan Shang, Renhao Xu, Xiangjian Zhang, Cong Zhang

Aims

Dl-3-n-butylphthalide (NBP) is a novel agent for acute ischemic stroke. This study aimed to investigate its effects on cortical angiogenesis and vasodilation during stroke recovery.

Methods

Mice underwent distal middle cerebral artery occlusion (dMCAO) and subsequently received NBP treatment. Therapeutic efficacy was measured by neurological deficits and infarct size. Angiogenesis was assessed by immunofluorescent staining. Laser speckle and two-photon microscopy imaging were employed to evaluate dynamic changes in cortical cerebral blood flow and vascular structure in vivo. The modulation of the Akt/GSK-3β signaling pathway was detected by western blotting.

Results

NBP administration promoted neurological recovery and reduced infarct size in the subacute phase. It facilitated cerebral blood flow and vasodilation, enhanced angiogenesis as evidenced by increased BrdU⁺/CD31⁺ cells and improved astrocyte/pericyte coverage around microvessels. Moreover, the pro-angiogenesis effect of NBP depends on the activation of the Akt/GSK-3β pathway, and this effect is blocked by LY294002.

Conclusion

In conclusion, NBP enhances recovery after ischemic stroke by promoting cortical angiogenesis and vasodilation through activation of the Akt/GSK-3β pathway. These findings highlight its therapeutic potential for delayed intervention in ischemic stroke.

目的：dl -3-正丁苯酞（NBP）是一种治疗急性缺血性脑卒中的新型药物。本研究旨在探讨其对脑卒中恢复期皮质血管生成和血管舒张的影响。方法：小鼠大脑中远端动脉闭塞（dMCAO）后给予NBP治疗。治疗效果通过神经功能缺损和梗死面积来衡量。免疫荧光染色评价血管生成。采用激光散斑成像和双光子显微成像技术观察脑皮质血流和血管结构的动态变化。western blotting检测Akt/GSK-3β信号通路的调节。结果：NBP可促进亚急性期神经功能恢复，减少梗死面积。它促进脑血流和血管舒张，促进血管生成，BrdU+/CD31+细胞增加，微血管周围星形胶质细胞/周细胞覆盖率提高。此外，NBP的促血管生成作用依赖于Akt/GSK-3β通路的激活，而这一作用被LY294002阻断。结论：NBP通过激活Akt/GSK-3β通路促进皮质血管生成和血管舒张，从而促进缺血性脑卒中后的恢复。这些发现突出了其在缺血性卒中延迟干预治疗中的潜力。

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引用次数: 0

Recent Advances in Repetitive Transcranial Magnetic Stimulation for the Treatment of Post-Stroke Cognitive Impairment 重复经颅磁刺激治疗脑卒中后认知功能障碍的最新进展。

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2025-12-10 DOI: 10.1002/cns.70702

Yu Liu, Yansong Li, Ding Ding, Aiguo Xie, Jiaran Yan, Xiaojin Xu, Zihan Zhao, Jing Wu, Jing Wang, Mingfeng Qian

Background

Post-stroke cognitive impairment (PSCI) is a prevalent and disabling condition with limited effective treatment options. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a potential non-invasive neuromodulation therapy. This review synthesizes recent advances in rTMS for PSCI, focusing on its mechanisms, therapeutic effects across cognitive domains, and safety profile.

Methods

We summarize evidence indicating that rTMS exerts its effects by modulating cortical excitability, promoting neuroplasticity via BDNF signaling, and regulating dysfunctional brain networks, particularly the central executive and default mode networks.

Results

Clinical studies demonstrate that high-frequency stimulation, primarily targeting the dorsolateral prefrontal cortex (DLPFC), can significantly improve memory, executive function, attention, and activities of daily living (ADLs) in patients with PSCI. A favorable safety profile is reported, with mild and transient adverse effects being most common. However, significant heterogeneity in stimulation parameters (e.g., frequency, intensity, pulses) exists across studies. Current evidence suggests that ensuring a sufficient number of stimulation pulses and duration may be necessary.

Conclusion

rTMS represents a promising therapeutic tool for PSCI, demonstrating benefits in key cognitive and functional domains. Future research must prioritize large-scale, standardized randomized controlled trials to optimize stimulation protocols, confirm long-term efficacy, and explore synergistic combinations with other rehabilitation strategies.

背景：脑卒中后认知障碍（PSCI）是一种普遍的致残性疾病，有效的治疗方案有限。重复经颅磁刺激（rTMS）已成为一种潜在的无创神经调节疗法。本文综述了rTMS治疗PSCI的最新进展，重点介绍了rTMS治疗PSCI的机制、跨认知领域的治疗效果和安全性。方法：我们总结了rTMS通过调节皮质兴奋性，通过BDNF信号传导促进神经可塑性，调节功能失调的大脑网络，特别是中央执行网络和默认模式网络来发挥其作用的证据。结果：临床研究表明，主要针对背外侧前额叶皮质（DLPFC）的高频刺激可以显著改善PSCI患者的记忆、执行功能、注意力和日常生活活动（ADLs）。报告了良好的安全性，最常见的是轻微和短暂的不良反应。然而，在不同的研究中，刺激参数（如频率、强度、脉冲）存在显著的异质性。目前的证据表明，确保足够数量的刺激脉冲和持续时间可能是必要的。结论：rTMS是一种很有前景的治疗PSCI的工具，在关键的认知和功能领域显示出益处。未来的研究必须优先考虑大规模、标准化的随机对照试验，以优化刺激方案，确认长期疗效，并探索与其他康复策略的协同组合。

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引用次数: 0

Joint Effects of Anticholinergic Burden and Neurofilament Light on Dementia Risk: The Shanghai Aging Study 抗胆碱能负荷和神经丝光在痴呆风险中的联合作用：上海衰老研究。

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2025-12-10 DOI: 10.1002/cns.70691

Danyi Chi, Xiaoniu Liang, Zhenxu Xiao, Xiaowen Zhou, Qianhua Zhao, Bin Wang, Ding Ding

Aims

Anticholinergic drugs (ACDs) and the neurodegeneration biomarker neurofilament light chain (NfL) are associated with dementia; however, the interplay between anticholinergic drug exposure and neurodegeneration in dementia risk remains underexplored.

Methods

This prospective cohort study analyzed 1529 dementia-free adults (median follow-up 5.2 years) from the Shanghai Aging Study. Cumulative anticholinergic burden was quantified using the anticholinergic cognitive burden (ACB) scale and total standardized daily dose (TSDD) over 1 year pre-baseline. Neurofilament light chain (NfL) levels were assayed via single-molecule array (Simoa).

Results

Elevated NfL (adjusted HR 1.77, 95% CI, 1.07–2.92) and TSDD exposure (HR 1.55, 1.08–2.24) were independently associated with incident dementia risk. Participants with both TSDD exposure and high NfL levels showed substantially greater cumulative dementia incidence versus those with no TSDD/low NfL (log-rank p < 0.0001; adjusted HR 2.24, 1.20–4.20). Individuals with both high TSDD and high NfL demonstrated a significantly higher dementia risk (HR 6.34, 95% CI, 1.90–21.20) compared to low-burden counterparts.

Conclusions

These findings identify plasma NfL as a critical modifier of anticholinergic-related cognitive vulnerability, providing mechanistic insights for risk stratification and supporting biomarker-guided deprescribing strategies in older adults exposed to ACDs.

目的：抗胆碱能药物（ACDs）和神经退行性生物标志物神经丝轻链（NfL）与痴呆相关；然而，抗胆碱能药物暴露与痴呆风险神经退行性变之间的相互作用仍未得到充分探讨。方法：本前瞻性队列研究分析了来自上海老龄化研究的1529名无痴呆成年人（中位随访5.2年）。使用抗胆碱能认知负担（ACB）量表和总标准化日剂量（TSDD）对基线前1年的累积抗胆碱能负担进行量化。通过单分子阵列（Simoa）检测神经丝轻链（NfL）水平。结果：NfL升高（调整后危险度1.77,95% CI, 1.07-2.92）和TSDD暴露（危险度1.55,1.08-2.24）与痴呆发生风险独立相关。结论：这些发现确定血浆NfL是抗胆碱能相关认知易感性的关键调节剂，为风险分层提供了机制见解，并支持暴露于ACDs的老年人的生物标志物指导的处方策略。

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引用次数: 0

Da-Bu-Yin-Wan and Qian-Zheng-San Alleviate Parkinson's Disease by Activating the Keap1/Nrf2/HO-1 Pathway to Positively Regulate Oxidative Stress 大补银丸、千正散通过激活Keap1/Nrf2/HO-1通路正向调节氧化应激缓解帕金森病。

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2025-12-09 DOI: 10.1002/cns.70681

Huimin Zhu, Zijian Liu, Jing Feng, Die Hu, Xia Li, Zhenyu Guo, Xueying Zhu, Cong Gai

<div> <section> <h3> Background</h3> <p>Parkinson's disease (PD) is a neurodegenerative disorder that worsens progressively. Different pathological mechanisms are involved in the progression of PD, including the loss of dopaminergic (DA) neurons and exacerbated oxidative damage in the nigrostriatal path. Da-Bu-Yin-Wan combined with Qian-Zheng-San is called Bu-Yin-Qian-Zheng Formula (BYQZF), which is a prescription for PD used in traditional Chinese medicine, but its neuroprotective effects and mechanisms are not well understood.</p> </section> <section> <h3> Purpose</h3> <p>The purpose of this study was to explore how BYQZF can activate the Keap1/Nrf2/HO-1 pathway to effectively lessen oxidative damage, providing insights into its potential anti-PD effects.</p> </section> <section> <h3> Methods</h3> <p>The chemical constituents and pharmacokinetics of BYQZF were analyzed by ultraperformance liquid chromatography in tandem with mass spectrometry (UPLC-MS/MS). Then, we evaluated the toxicity and safety of BYQZF treatment. After establishing MPTP-induced PD mouse models and the administration of BYQZF treatment, PD-like behaviors were assessed through the pole test, rotarod test and open field experiment. DA neuron loss and apoptosis in the nigrostriatal path were detected via immunofluorescence and western blotting analysis. Oxidative stress levels and the dissociation state of Keap1-Nrf2 in these brain areas were assessed by ELISA, immunofluorescence Co-IP, RT-qPCR, and western blot analysis. We constructed Nrf2-knockdown PD cell models. The transcriptional and Nrf2 protein expression levels were determined using both real-time quantitative PCR and western blot analysis. We further assessed cellular viability, intracellular ATP content, apoptotic cell ratio, as well as the expression levels of CAT and GSH following MPP<sup>+</sup>, and BYQZF exposure.</p> </section> <section> <h3> Results</h3> <p>The chemical constituents of BYQZF were systematically characterized using UPLC-MS/MS technology. The results of pharmacokinetic evaluation suggested that the pathological conditions of PD significantly affected the pharmacokinetic behavior of BYQZF in vivo. BYQZF treatment ultimately improved the movement disorders in MPTP-induced PD mice, by alleviating the damage of dopaminergic neurons within the nigrostriatal path. In addition, BYQZF reduced the damage caused by oxidative stress by decreasing the 8-OHdG level and increasing the CAT, GSH/GSSG, HO-1, NQO1, and GCLM levels. Further, BYQZF treatment advanced the dissociation of Keap1 and Nrf2 and the nucle

背景：帕金森病（PD）是一种进行性恶化的神经退行性疾病。PD的进展涉及不同的病理机制，包括多巴胺能（DA）神经元的丢失和黑质纹状体通路氧化损伤的加剧。大补阴丸与乾正散合用称为补阴乾正方（BYQZF），是一种治疗帕金森病的中药方剂，但其神经保护作用及其机制尚不清楚。目的：本研究旨在探讨BYQZF如何激活Keap1/Nrf2/HO-1通路，有效减轻氧化损伤，从而揭示其潜在的抗pd作用。方法：采用超高效液相色谱-质谱联用技术（UPLC-MS/MS）对BYQZF的化学成分和药代动力学进行分析。然后，我们对BYQZF治疗的毒性和安全性进行了评价。建立mptp诱导的PD小鼠模型并给予BYQZF处理后，通过极试验、旋转杆试验和空地实验评估PD样行为。免疫荧光和western blot检测大鼠黑质纹状体通路DA神经元的丢失和凋亡情况。通过ELISA、免疫荧光Co-IP、RT-qPCR和western blot分析，评估这些脑区氧化应激水平和Keap1-Nrf2解离状态。构建nrf2敲低PD细胞模型。采用实时定量PCR和western blot检测转录和Nrf2蛋白表达水平。我们进一步评估了MPP+和BYQZF暴露后的细胞活力、细胞内ATP含量、凋亡细胞比例以及CAT和GSH的表达水平。结果：采用超高效液相色谱-质谱联用技术系统表征了BYQZF的化学成分。药动学评价结果表明，PD的病理状态显著影响BYQZF在体内的药动学行为。BYQZF治疗通过减轻黑质纹状体通路内多巴胺能神经元的损伤，最终改善了mptp诱导的PD小鼠的运动障碍。此外，BYQZF通过降低8-OHdG水平，提高CAT、GSH/GSSG、HO-1、NQO1和GCLM水平，减轻氧化应激造成的损伤。此外，BYQZF处理促进了Keap1和Nrf2的解离和Nrf2的核易位。最后，通过Nrf2敲低PD细胞模型的功能实验表明，BYQZF的神经保护作用依赖于Nrf2的完整性，Nrf2缺失显著削弱了其抗氧化和抗凋亡作用。结论：本研究阐明BYQZF通过Keap1/Nrf2/HO-1信号通路改善PD，减轻氧化应激，有助于启发PD药物开发新策略。

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引用次数: 0

Electroacupuncture Prevents Against AD-Like Phenotypes in APP/PS1 Mice: Investigation of the Mechanisms From Cerebral Microangiopathy 电针预防APP/PS1小鼠ad样表型：脑微血管病机制的研究

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2025-12-09 DOI: 10.1002/cns.70696

Chen Yang, Baobao Li, Shaojie Yang, Xuncui Wang, Guoqi Zhu, Jingji wang

Background

Electroacupuncture (EA) has been widely used in Alzheimer's disease (AD) treatment. However, its underlying mechanisms remain poorly elucidated.

Purpose

This study aimed to investigate the effects of EA on AD-like phenotypes and explore the mechanisms.

Methods

We first evaluated AD-like behaviors and cerebral blood flow (CBF) changes in APP_swe/PS1dE9 (APP/PS1) mice at different ages. Subsequently, the therapeutic effects of EA at acupoints Baihui (GV20), Guanyuan (CV4), and Zusanli (ST36), as well as sunitinib, a PDGFRβ-specific inhibitor, on AD-like phenotypes in APP/PS1 mice were investigated. CBF was monitored by laser speckle imaging, and hippocampal synaptic ultrastructure and microvascular morphology were examined by transmission electron microscopy (TEM). Western blot was performed to measure related protein expression. Finally, functional ultrasound (fUS) imaging was used to assess changes in brain-wide functional connectivity.

Results

Compared with age-matched wild-type (WT) mice, 6- and 9-month-old APP/PS1 mice exhibited significant cognitive decline, while all age groups (3-, 6-, and 9-month-old) of APP/PS1 mice showed significantly reduced CBF. APP/PS1 mice showed elevated expression of microvascular markers in both the hippocampus and cortex. EA significantly ameliorated AD-like behaviors and prevented CBF reduction as well as microvascular deformation in 6-month-old APP/PS1 mice compared with non-treatment group. TEM and western blot analysis revealed damaged synaptic structure and reduced synaptic proteins in APP/PS1 mice, all of which were markedly alleviated by EA treatment. In addition, EA treatment downregulated the aberrantly elevated expression of PDGFRβ and CD31, enhanced the levels of tight junction proteins (Occludin, Claudin-5, and ZO-1) and glucose transporter 1 (GLUT1), and suppressed the expression of inflammatory proteins. Of note, intervention with sunitinib also improved AD-like behaviors in APP/PS1 mice. Remarkably, fUS imaging results showed that EA enhanced the functional connection between hippocampal regions of APP/PS1 mice.

Conclusion

Our data demonstrates that EA ameliorates AD-like phenotypes, potentially through preventing microangiopathy.

背景：电针（EA）在阿尔茨海默病（AD）治疗中得到广泛应用。然而，其潜在机制仍不清楚。目的：研究EA对ad样表型的影响并探讨其作用机制。方法：首先对APP/ PS1dE9 （APP/PS1）小鼠不同年龄ad样行为和脑血流量（CBF）变化进行评价。随后，研究了EA穴位百会（GV20）、官园（CV4）、足三里（ST36）以及pdgfr β特异性抑制剂舒尼替尼对APP/PS1小鼠ad样表型的治疗作用。采用激光散斑成像监测脑血流，透射电镜观察海马突触超微结构和微血管形态。Western blot检测相关蛋白表达。最后，使用功能超声（fUS）成像评估全脑功能连通性的变化。结果：与年龄匹配的野生型（WT）小鼠相比，6月龄和9月龄APP/PS1小鼠表现出明显的认知能力下降，而APP/PS1小鼠的所有年龄组（3月龄、6月龄和9月龄）均表现出显著的CBF减少。APP/PS1小鼠海马和皮质微血管标志物表达均升高。与未治疗组相比，EA可显著改善6月龄APP/PS1小鼠的ad样行为，防止CBF减少和微血管变形。透射电镜和western blot分析显示APP/PS1小鼠突触结构受损，突触蛋白减少，EA治疗后明显减轻。此外，EA治疗下调PDGFRβ和CD31的异常升高表达，提高紧密连接蛋白（Occludin， Claudin-5和ZO-1）和葡萄糖转运蛋白1 （GLUT1）的水平，抑制炎症蛋白的表达。值得注意的是，舒尼替尼干预也改善了APP/PS1小鼠的ad样行为。fUS显像结果显示，EA增强了APP/PS1小鼠海马区域之间的功能连接。结论：我们的数据表明，EA可能通过预防微血管病变来改善ad样表型。

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引用次数: 0

Decoding the Therapeutic Effects of Acupuncture in Hemorrhagic Stroke Using Single-Cell RNA Sequencing 利用单细胞RNA测序解码针刺对出血性中风的治疗效果。

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2025-12-09 DOI: 10.1002/cns.70689

Chen Ruan, Jia Du, Wentao Zhang, Jiacheng Song, Peipei Feng, Jiajun Shi, Kelang Lou, Yuqiang Lu, Xinwei Li, Zhongwei Guo, Hao Liu

Background

Acupuncture has been proposed as a therapeutic intervention for stroke recovery, yet the underlying molecular mechanisms remain poorly understood.

Method

In this study, we used a mouse model of hemorrhagic stroke induced by autologous blood injection to investigate the effects of acupuncture on post-stroke recovery at the cellular and molecular levels, utilizing single-cell RNA sequencing.

Results

Our findings revealed that acupuncture modulates the gene expression of microglia, astrocytes, and oligodendrocytes, three major glial cell types, which may contribute to the improvement of stroke-induced phenotypes. Notably, we identified a potential role of the APOE-TREM2 signaling axis, with ligand-binding interactions enhancing microglia activation and promoting their neuroprotective functions. These findings also suggested that acupuncture may promote microglia–astrocyte interactions, leading to enhanced neuroinflammation resolution and tissue repair.

Conclusions

Our study provided new insights into the cellular mechanisms underlying acupuncture's therapeutic effects in stroke recovery and highlighted the potential of targeting glial cell-mediated pathways, including APOE-TREM2, as a strategy for improving post-stroke rehabilitation.

背景：针灸已被提出作为中风恢复的一种治疗干预措施，但其潜在的分子机制仍然知之甚少。方法：利用单细胞RNA测序技术，利用自体血液注射致出血性脑卒中小鼠模型，从细胞和分子水平研究针刺对脑卒中后恢复的影响。结果：我们的研究结果表明，针刺可调节小胶质细胞、星形胶质细胞和少突胶质细胞这三种主要胶质细胞的基因表达，这可能有助于改善中风诱导的表型。值得注意的是，我们确定了APOE-TREM2信号轴的潜在作用，配体结合相互作用增强了小胶质细胞的激活并促进了它们的神经保护功能。这些发现还表明，针灸可能促进小胶质细胞与星形胶质细胞的相互作用，从而增强神经炎症的消退和组织修复。结论：我们的研究为针刺在脑卒中恢复中的治疗作用提供了新的细胞机制，并强调了靶向胶质细胞介导的途径，包括APOE-TREM2，作为改善脑卒中后康复的策略的潜力。

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引用次数: 0

Cellular Communication Networks Mediated by Microglia in Ischemic Stroke 缺血性卒中中小胶质细胞介导的细胞通讯网络。

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2025-12-09 DOI: 10.1002/cns.70687

Feiyu Ma, Yi Bai, Na Li, Xiangyu Cai, Ruicong Xu, Xiang Cao

Introduction

Microglia, the resident immune cells of the central nervous system, rapidly activate after ischemic stroke and actively communicate with neurons, astrocytes, endothelial cells, and infiltrating peripheral immune cells. As ischemic stroke remains a major cause of death and long-term disability worldwide, growing evidence highlights that microglia-driven communication—through direct cell–cell contact, soluble factors, and extracellular vesicles—plays a central role in regulating neuroinflammation and shaping disease progression. A clearer understanding of these communication networks may help identify new therapeutic strategies targeting glial function.

Methods

This review summarizes recent advances in understanding microglial states after ischemic stroke and their communication with neural and peripheral immune cells. Literature was collected from PubMed and Web of Science, with attention to mechanisms involving direct cell–cell interaction, cytokine and chemokine signaling, extracellular vesicle communication, and newly described tunneling structures. Key regulatory processes at different pathological stages are compared.

Results

Experimental and clinical evidence shows that microglia display dynamic and heterogeneous activation patterns after ischemic stroke. Through diverse communication pathways, they influence neuronal survival, synaptic remodeling, inflammatory responses, and blood–brain barrier integrity. Soluble mediators—including cytokines, chemokines, and damage-associated molecular patterns—shape both local and systemic immune reactions, while extracellular vesicles regulate neuroinflammation and tissue repair by transferring bioactive molecules. Recently reported microglial tunneling structures further increase the complexity of intercellular communication. Together, these pathways determine the progression of ischemic injury and recovery.

Conclusions

Microglia act as central coordinators of communication among neurons, glial cells, and immune cells during ischemic stroke, thereby influencing disease severity and functional outcome. Clarifying microglia-mediated communication mechanisms may help guide the development of targeted immunomodulatory treatments. Continued research will be important for advancing these findings toward clinical translation.

小胶质细胞是中枢神经系统的常驻免疫细胞，在缺血性卒中后迅速激活，并积极与神经元、星形胶质细胞、内皮细胞和浸润性外周免疫细胞进行交流。缺血性中风仍然是世界范围内死亡和长期残疾的主要原因，越来越多的证据表明，小胶质细胞驱动的通讯——通过直接的细胞-细胞接触、可溶性因子和细胞外囊泡——在调节神经炎症和塑造疾病进展中起着核心作用。更清楚地了解这些通讯网络可能有助于确定针对胶质细胞功能的新治疗策略。方法：本文综述了缺血性脑卒中后小胶质细胞状态及其与神经和外周免疫细胞的联系的最新进展。文献收集自PubMed和Web of Science，重点关注细胞间直接相互作用、细胞因子和趋化因子信号传导、细胞外囊泡通讯以及新近描述的隧道结构等机制。比较不同病理阶段的关键调控过程。结果：实验和临床证据表明，缺血性脑卒中后小胶质细胞表现出动态和异质性的激活模式。通过不同的通讯途径，它们影响神经元存活、突触重塑、炎症反应和血脑屏障完整性。可溶性介质——包括细胞因子、趋化因子和损伤相关的分子模式——塑造局部和全身免疫反应，而细胞外囊泡通过转移生物活性分子来调节神经炎症和组织修复。最近报道的小胶质隧道结构进一步增加了细胞间通讯的复杂性。总之，这些途径决定了缺血性损伤的进展和恢复。结论：缺血性卒中时，小胶质细胞作为神经元、胶质细胞和免疫细胞之间通讯的中枢协调者，从而影响疾病的严重程度和功能结局。阐明小胶质细胞介导的通讯机制可能有助于指导靶向免疫调节治疗的发展。持续的研究对于将这些发现推向临床翻译将是重要的。

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引用次数: 0