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Fasudil Alleviates Postoperative Neurocognitive Disorders in Mice by Downregulating the Surface Expression of α5GABAAR in Hippocampus 法舒地尔通过下调海马中α5GABAAR的表面表达缓解小鼠术后神经认知障碍
IF 4.8 1区 医学 Q1 NEUROSCIENCES Pub Date : 2024-11-03 DOI: 10.1111/cns.70098
Jinpeng Dong, Zhun Wang, Lixuan Li, Mengxue Zhang, Sixuan Wang, Yuan Luo, Ying Dong, Xiaokun Wang, Yongan Wang, Kaiyuan Wang, Yiqing Yin

Aim

Postoperative neurocognitive disorder (PND) refers to the cognitive impairment experienced by patients after surgery. As a target of sevoflurane, a kind of inhalation anesthetic, the balance of the GABAergic system can be disrupted during the perioperative period. In this study, we explored the promoting effect of abnormal elevation of the α5 subtype of γ-aminobutyric acid type A (GABAA) receptors caused by sevoflurane and surgical trauma on PND, as well as the therapeutic effect of fasudil on PND.

Methods

Eight-week-old mice were pretreated with fasudil, and after 10 days, sevoflurane-induced femoral fracture surgery was performed to establish an animal model of PND. The Morris water maze and fear conditioning tests were used to evaluate PND induced by this model. Biochemical and electrophysiological analyses were conducted to assess the protective effect of fasudil on the GABAergic system.

Results

Following artificial fracture, the hippocampus-dependent memory was damaged in these mice. Fasudil pretreatment, however, ameliorated cognitive function impairment in mice induced by sevoflurane and surgery. Mechanistically, fasudil was found to restore the increased hippocampus expression and function of α5GABAARs in mice with PND. In addition, pretreatment with Fasudil inhibited the enhancement in the calcium ion concentration and phosphorylation of Camk2, as well as the activation of the Radixin pathway which led to increased phosphorylation of the ERM family in the hippocampal CA1 region of the PND model.

Conclusion

Preadministration of fasudil improved postoperative cognitive function in PND mice by inhibiting the activation of Camk2 and Radixin pathways and finally downregulating the surface expression of α5GABAAR in hippocampus neurons.

目的:术后神经认知障碍(PND)是指患者在手术后出现的认知障碍。七氟醚是一种吸入麻醉剂,作为七氟醚的作用靶点,GABA能系统的平衡在围手术期会被打破。本研究探讨了七氟烷和手术创伤引起的γ-氨基丁酸A型(GABAA)受体α5亚型异常升高对PND的促进作用,以及法舒地尔对PND的治疗作用:方法:用法舒地尔预处理8周龄小鼠,10天后进行七氟醚诱导的股骨骨折手术,建立PND动物模型。采用莫里斯水迷宫和恐惧条件反射试验评估该模型诱导的PND。生化和电生理分析评估了法舒地尔对GABA能系统的保护作用:结果:人工骨折后,这些小鼠的海马依赖性记忆受损。然而,法舒地尔预处理可改善七氟醚和手术引起的小鼠认知功能损伤。从机理上讲,法舒地尔可恢复PND小鼠海马中增加的α5GABAARs表达和功能。此外,法舒地尔还能抑制钙离子浓度的升高和Camk2的磷酸化,以及Radixin通路的激活,从而导致PND模型海马CA1区ERM家族磷酸化的增加:结论:法舒地尔通过抑制Camk2和Radixin通路的激活,最终下调海马神经元中α5GABAAR的表面表达,改善了PND小鼠的术后认知功能。
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引用次数: 0
Ginsenoside Rg1 Regulates the Activation of Astrocytes Through lncRNA-Malat1/miR-124-3p/Lamc1 Axis Driving PI3K/AKT Signaling Pathway, Promoting the Repair of Spinal Cord Injury 人参皂苷Rg1通过lncRNA-Malat1/miR-124-3p/Lamc1轴驱动PI3K/AKT信号通路调控星形胶质细胞的激活,促进脊髓损伤的修复
IF 4.8 1区 医学 Q1 NEUROSCIENCES Pub Date : 2024-11-03 DOI: 10.1111/cns.70103
Yin Zhu, Wenjun Zou, Baihan Sun, Kelv Shen, Feiyun Xia, Hao Wang, Fengxian Jiang, Zhengfeng Lu

Aim

To investigate the regulation of ginsenoside Rg1 on the PI3K/AKT pathway through the lncRNA-Malat1/miR-124-3p/ Laminin gamma1 (Lamc1) axis, activating astrocytes (As) to promote the repair of spinal cord injury (SCI).

Methods

Bioinformatics analysis was used to predict miRNA targeting Lamc1 and lncRNA targeting miR-124-3p, which were then validated through a dual-luciferase assay. Following transfection, the relationships between Malat1, miR-124-3p, and Lamc1 expression levels were assessed by qRT-PCR and Western blot (WB). Immunofluorescence staining and immunohistochemistry were utilized to measure Lamc1 expression, while changes in cavity area were observed through hematoxylin–eosin (HE) staining. Basso-Beattie-Bresnahan (BBB) scale and footprint analysis were used to evaluate functional recovery. WB was performed to assess the expression of PI3K/AKT pathway-related protein.

Results

Rg1 was found to upregulate Malat1 expression, which in turn modulated the Malat1/miR-124-3p/Lamc1 axis. Furthermore, Rg1 activated the PI3K/Akt signaling pathway, significantly reducing the SCI cavity area and improving hind limb motor function. However, knockout of Malat1 hindered these effects, and inhibition of miR-124-3p reversed the silencing effects of Malat1.

Conclusions

Rg1 can induce Malat1 expression to activate the Lamc1/PI3K/AKT signaling pathway by sponging with miR-124-3p, thereby regulating As activity to repair SCI.

目的:研究人参皂苷Rg1通过lncRNA-Malat1/miR-124-3p/ Laminin gamma1(Lamc1)轴调控PI3K/AKT通路,激活星形胶质细胞(As)促进脊髓损伤(SCI)修复:方法:利用生物信息学分析预测靶向Lamc1的miRNA和靶向miR-124-3p的lncRNA,然后通过双荧光素酶试验进行验证。转染后,通过 qRT-PCR 和 Western 印迹(WB)评估 Malat1、miR-124-3p 和 Lamc1 表达水平之间的关系。免疫荧光染色和免疫组化被用来测量Lamc1的表达,而空腔面积的变化则通过苏木精-伊红(HE)染色来观察。巴索-巴蒂-布雷斯纳汉(BBB)量表和足迹分析用于评估功能恢复情况。进行WB检测以评估PI3K/AKT通路相关蛋白的表达:结果:研究发现,Rg1能上调Malat1的表达,进而调节Malat1/miR-124-3p/Lamc1轴。此外,Rg1还能激活PI3K/Akt信号通路,显著减少SCI腔面积并改善后肢运动功能。然而,Malat1的敲除阻碍了这些效应,而miR-124-3p的抑制则逆转了Malat1的沉默效应:结论:Rg1能诱导Malat1的表达,通过与miR-124-3p的海绵作用激活Lamc1/PI3K/AKT信号通路,从而调节As的活性以修复SCI。
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引用次数: 0
The early diagnosis of Alzheimer's disease: Blood-based panel biomarker discovery by proteomics and metabolomics. 阿尔茨海默病的早期诊断:通过蛋白质组学和代谢组学发现基于血液的生物标记物。
IF 4.8 1区 医学 Q1 NEUROSCIENCES Pub Date : 2024-11-01 DOI: 10.1111/cns.70060
Yun Dong, Xun Song, Xiao Wang, Shaoxiang Wang, Zhendan He

Diagnosis and prediction of Alzheimer's disease (AD) are increasingly pressing in the early stage of the disease because the biomarker-targeted therapies may be most effective. Diagnosis of AD largely depends on the clinical symptoms of AD. Currently, cerebrospinal fluid biomarkers and neuroimaging techniques are considered for clinical detection and diagnosis. However, these clinical diagnosis results could provide indications of the middle and/or late stages of AD rather than the early stage, and another limitation is the complexity attached to limited access, cost, and perceived invasiveness. Therefore, the prediction of AD still poses immense challenges, and the development of novel biomarkers is needed for early diagnosis and urgent intervention before the onset of obvious phenotypes of AD. Blood-based biomarkers may enable earlier diagnose and aid detection and prognosis for AD because various substances in the blood are vulnerable to AD pathophysiology. The application of a systematic biological paradigm based on high-throughput techniques has demonstrated accurate alterations of molecular levels during AD onset processes, such as protein levels and metabolite levels, which may facilitate the identification of AD at an early stage. Notably, proteomics and metabolomics have been used to identify candidate biomarkers in blood for AD diagnosis. This review summarizes data on potential blood-based biomarkers identified by proteomics and metabolomics that are closest to clinical implementation and discusses the current challenges and the future work of blood-based candidates to achieve the aim of early screening for AD. We also provide an overview of early diagnosis, drug target discovery and even promising therapeutic approaches for AD.

阿尔茨海默病(AD)的诊断和预测在疾病的早期阶段越来越紧迫,因为生物标志物靶向疗法可能最有效。阿尔茨海默病的诊断主要取决于阿尔茨海默病的临床症状。目前,脑脊液生物标志物和神经影像技术被认为是临床检测和诊断的方法。然而,这些临床诊断结果只能提供 AD 中期和/或晚期的指征,而不能提供早期的指征。因此,预测渐冻人症仍面临巨大挑战,需要开发新型生物标志物,以便在渐冻人症出现明显表型之前进行早期诊断和紧急干预。由于血液中的各种物质易受AD病理生理学的影响,因此基于血液的生物标志物可帮助早期诊断AD,并帮助检测和预后AD。基于高通量技术的系统生物学范式的应用已证明,在 AD 发病过程中,分子水平(如蛋白质水平和代谢物水平)会发生准确的变化,这可能有助于在早期阶段识别 AD。值得注意的是,蛋白质组学和代谢组学已被用于确定血液中用于诊断AD的候选生物标志物。本综述总结了通过蛋白质组学和代谢组学鉴定出的最接近临床应用的潜在血液生物标记物的数据,并讨论了为实现早期筛查AD的目标,基于血液的候选生物标记物目前所面临的挑战和未来的工作。我们还概述了 AD 的早期诊断、药物靶点发现甚至是有前景的治疗方法。
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引用次数: 0
Magnetic Resonance-Guided Laser Interstitial Thermal Therapy Using Dual-Wavelength Dual-Output Laser Within Two Probe Trajectories for Treatment of Drug-Resistant Epilepsy. 磁共振引导下的激光间质热疗,在两个探头轨迹内使用双波长双输出激光治疗耐药性癫痫。
IF 4.8 1区 医学 Q1 NEUROSCIENCES Pub Date : 2024-11-01 DOI: 10.1111/cns.70118
Jingquan Lin, Wei Gao, Yuqi Ying, Ahmed Abdulsalam Ali Bakrbaldawi, Zhoule Zhu, Chengwei Cai, Xinxia Guo, Jianmin Zhang, Junming Zhu

Objective: Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) is a novel tool and a minimally invasive treatment to drug-resistant epilepsy (DRE). The focus of this research was to evaluate the effectiveness and safety of the newly developed dual-wavelength dual-output MRgLITT system LaserRO within two probe trajectories in treating DRE patients.

Methods: This is a retrospective analysis conducted at a single center, examining patients with DRE who received treatment with the LaserRO MRgLITT system. The system utilizes a sophisticated laser technology that can be configured as conventional single output for single wavelength or innovative dual outputs for dual wavelengths. The study involved a comprehensive review of patient information, encompassing demographics, seizure history, details related to the surgical parameters, and the subsequent clinical results. Primary outcome was post-operation seizure outcome defined as Engel Scale Class at the end of follow-up time.

Results: This study included a total of eight DRE patients received MRgLITT surgery between August 2022 and October 2023. Out of these, there were four mesial temporal lobe epilepsy (MTLE), three focal cortical dysplasia (FCD), and one cavernous malformation (CM) patients. Within the two probe trajectories, seven patients had single wavelength (980 or 1064 nm) laser treatment and one patient had dual-wavelength (980 and 1064 nm) laser treatment. The median age of the patients was 27 (22-31) years, with a median follow-up period of 9.7 (8.4-12.1) months. The mean BMI was recorded at 20.24 ± 2.95 kg/m2, and epilepsy history was 13 ± 6 years. The median intraoperative blood loss was 5 (5-9) mL, operation time was 231 (169-254) minutes, and length of stay (LOS) was 3 (3-5) days. The mean ablation volume ratio was 96.52% ± 3.67%. In terms of outcomes, over a median follow-up time of 9.7 (range 8.4-12.1) months, there were two patients got Engel I, five patients got seizure-free, and one patient decreased 75% seizure. Importantly, no serious complications following the procedures occurred.

Conclusions: The preliminary results indicate that the MRgLITT procedure, which operates dual-output laser with single or dual wavelengths (980/1064 nm) within the two trajectories, is both effective and safe as a minimally invasive approach for different types of DRE patients.

目的:磁共振引导激光间质热疗(MRgLITT)是治疗耐药性癫痫(DRE)的一种新型工具和微创疗法。本研究的重点是评估新开发的双波长双输出 MRgLITT 系统 LaserRO 在两个探头轨迹内治疗 DRE 患者的有效性和安全性:这是一项在单一中心进行的回顾性分析,研究对象是接受 LaserRO MRgLITT 系统治疗的 DRE 患者。该系统采用先进的激光技术,可配置为传统的单波长单输出或创新的双波长双输出。该研究涉及对患者信息的全面审查,包括人口统计学、癫痫发作史、手术参数相关细节以及随后的临床结果。主要结果是手术后的癫痫发作结果,即随访结束时的恩格尔量表分级:本研究共纳入了 8 名在 2022 年 8 月至 2023 年 10 月期间接受 MRgLITT 手术的 DRE 患者。其中,颞叶中叶癫痫(MTLE)患者4例,局灶性皮质发育不良(FCD)患者3例,海绵畸形(CM)患者1例。在两个探头轨迹中,七名患者接受了单波长(980 或 1064 纳米)激光治疗,一名患者接受了双波长(980 和 1064 纳米)激光治疗。患者的中位年龄为 27(22-31)岁,中位随访时间为 9.7(8.4-12.1)个月。平均体重指数为 20.24 ± 2.95 kg/m2,癫痫病史为 13 ± 6 年。术中出血量中位数为5(5-9)毫升,手术时间为231(169-254)分钟,住院时间为3(3-5)天。平均消融体积比为 96.52% ± 3.67%。就结果而言,在中位随访时间 9.7 个月(8.4-12.1 个月)期间,有 2 名患者获得恩格尔 I 型,5 名患者无癫痫发作,1 名患者癫痫发作减少 75%。重要的是,手术后未出现严重并发症:初步结果表明,MRgLITT 手术在两个轨迹内使用单波长或双波长(980/1064 nm)的双输出激光,作为一种微创方法,对不同类型的 DRE 患者既有效又安全。
{"title":"Magnetic Resonance-Guided Laser Interstitial Thermal Therapy Using Dual-Wavelength Dual-Output Laser Within Two Probe Trajectories for Treatment of Drug-Resistant Epilepsy.","authors":"Jingquan Lin, Wei Gao, Yuqi Ying, Ahmed Abdulsalam Ali Bakrbaldawi, Zhoule Zhu, Chengwei Cai, Xinxia Guo, Jianmin Zhang, Junming Zhu","doi":"10.1111/cns.70118","DOIUrl":"https://doi.org/10.1111/cns.70118","url":null,"abstract":"<p><strong>Objective: </strong>Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) is a novel tool and a minimally invasive treatment to drug-resistant epilepsy (DRE). The focus of this research was to evaluate the effectiveness and safety of the newly developed dual-wavelength dual-output MRgLITT system LaserRO within two probe trajectories in treating DRE patients.</p><p><strong>Methods: </strong>This is a retrospective analysis conducted at a single center, examining patients with DRE who received treatment with the LaserRO MRgLITT system. The system utilizes a sophisticated laser technology that can be configured as conventional single output for single wavelength or innovative dual outputs for dual wavelengths. The study involved a comprehensive review of patient information, encompassing demographics, seizure history, details related to the surgical parameters, and the subsequent clinical results. Primary outcome was post-operation seizure outcome defined as Engel Scale Class at the end of follow-up time.</p><p><strong>Results: </strong>This study included a total of eight DRE patients received MRgLITT surgery between August 2022 and October 2023. Out of these, there were four mesial temporal lobe epilepsy (MTLE), three focal cortical dysplasia (FCD), and one cavernous malformation (CM) patients. Within the two probe trajectories, seven patients had single wavelength (980 or 1064 nm) laser treatment and one patient had dual-wavelength (980 and 1064 nm) laser treatment. The median age of the patients was 27 (22-31) years, with a median follow-up period of 9.7 (8.4-12.1) months. The mean BMI was recorded at 20.24 ± 2.95 kg/m<sup>2</sup>, and epilepsy history was 13 ± 6 years. The median intraoperative blood loss was 5 (5-9) mL, operation time was 231 (169-254) minutes, and length of stay (LOS) was 3 (3-5) days. The mean ablation volume ratio was 96.52% ± 3.67%. In terms of outcomes, over a median follow-up time of 9.7 (range 8.4-12.1) months, there were two patients got Engel I, five patients got seizure-free, and one patient decreased 75% seizure. Importantly, no serious complications following the procedures occurred.</p><p><strong>Conclusions: </strong>The preliminary results indicate that the MRgLITT procedure, which operates dual-output laser with single or dual wavelengths (980/1064 nm) within the two trajectories, is both effective and safe as a minimally invasive approach for different types of DRE patients.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 11","pages":"e70118"},"PeriodicalIF":4.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Neural Influences on Tumor Progression Within the Central Nervous System 中枢神经系统内肿瘤进展的神经影响因素
IF 4.8 1区 医学 Q1 NEUROSCIENCES Pub Date : 2024-10-29 DOI: 10.1111/cns.70097
Wenhao Lv, Yongjie Wang

For decades, researchers have studied how brain tumors, the immune system, and drugs interact. With the advances in cancer neuroscience, which centers on defining and therapeutically targeting nervous system-cancer interactions, both within the local tumor microenvironment (TME) and on a systemic level, the subtle relationship between neurons and tumors in the central nervous system (CNS) has been deeply studied. Neurons, as the executors of brain functional activities, have been shown to significantly influence the emergence and development of brain tumors, including both primary and metastatic tumors. They engage with tumor cells via chemical or electrical synapses, directly regulating tumors or via intricate coupling networks, and also contribute to the TME through paracrine signaling, secreting proteins that exert regulatory effects. For instance, in a study involving a mouse model of glioblastoma, the authors observed a 42% increase in tumor volume when neuronal activity was stimulated, compared to controls (p < 0.01), indicating a direct correlation between neural activity and tumor growth. These thought-provoking results offer promising new strategies for brain tumor therapies, highlighting the potential of neuronal modulation to curb tumor progression. Future strategies may focus on developing drugs to inhibit or neutralize proteins and other bioactive substances secreted by neurons, break synaptic connections and interactions between infiltrating cells and tumor cells, as well as disrupt electrical coupling within glioma cell networks. By harnessing the insights gained from this research, we aspire to usher in a new era of brain tumor therapies that are both more potent and precise.

几十年来,研究人员一直在研究脑肿瘤、免疫系统和药物之间是如何相互作用的。癌症神经科学的研究重点是在局部肿瘤微环境(TME)和全身范围内定义神经系统与癌症之间的相互作用并以此为治疗目标,随着癌症神经科学的发展,人们对中枢神经系统(CNS)中神经元与肿瘤之间的微妙关系进行了深入研究。神经元作为大脑功能活动的执行者,已被证明对脑肿瘤(包括原发性和转移性肿瘤)的出现和发展有重大影响。它们通过化学或电突触与肿瘤细胞接触,直接或通过错综复杂的耦合网络对肿瘤进行调控,还通过旁分泌信号,分泌能发挥调控作用的蛋白质,为 TME 做出贡献。例如,在一项涉及胶质母细胞瘤小鼠模型的研究中,作者观察到与对照组相比,当神经元活动受到刺激时,肿瘤体积增加了 42%(P<0.05)。
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引用次数: 0
Probiotics by Modulating Gut–Brain Axis Together With Brivaracetam Mitigate Seizure Progression, Behavioral Incongruities, and Prevented Neurodegeneration in Pentylenetetrazole-Kindled Mice 益生菌通过调节肠脑轴与布利瓦西坦减轻戊四唑诱导小鼠的癫痫进展、行为不协调并防止神经退行性变
IF 4.8 1区 医学 Q1 NEUROSCIENCES Pub Date : 2024-10-29 DOI: 10.1111/cns.70078
Muhammad Usman Shakoor, Fashwa Khan Tareen, Zohabia Rehman, Khaled Ahmed Saghir, Waseem Ashraf, Syed Muhammad Muneeb Anjum, Tanveer Ahmad, Faleh Alqahtani, Imran Imran

Background

The microbiota–gut–brain axis (MGBA) is a central nexus that integrates higher cognitive and emotional centers of the central nervous system (CNS) within the intricate functioning of the intestine. Accumulating evidence suggests that dysbiosis in the taxonomic diversity of gut flora plays a salient role in the progression of epilepsy and comorbid secondary complications.

Methods

In the current study, we investigated the impact of long-term oral bacteriotherapy (probiotics; 10 mL/kg; 109 colony-forming unit/ml) as an adjunctive treatment intervention with brivaracetam (BRV; 10 mg/kg) over 21 days on pentylenetetrazole (PTZ) induced augmented epileptic response and associated electrographical and behavioral perturbations in mice. Moreover, we also unveiled antioxidant capacity and histopathologic changes in treated versus non-treated animals.

Results

Results revealed combination increases seizure threshold and prevented high ictal spiking. Additionally, it alleviated PTZ-induced neuropsychiatric disturbances such as anxiety and depressive-like phenotype along with cognitive deficits. Furthermore, dual therapy prompted physiological oxidant/antioxidant balance as evidenced by increased activity of antioxidant enzymes (SOD and catalase) and reduced levels of oxidative stressor (MDA). This therapeutic intervention with commensal species suppressed network-driven neuroinflammation and preserved normal cytoarchitecture with intact morphology in the pyramidal layers of cornu ammonis (CA1 and CA3).

Conclusion

Our study provides supporting evidence for the use of probiotics as adjunctive therapy with anti-seizure medications to modulate epileptogenic processes and related multimorbidities, particularly in individuals with drug-resistant seizures.

背景:微生物群-肠-脑轴(MGBA)是将中枢神经系统(CNS)的高级认知和情感中枢与肠道的复杂功能结合在一起的中心环节。越来越多的证据表明,肠道菌群分类多样性的失调在癫痫的进展和合并继发性并发症中起着突出的作用:在当前的研究中,我们调查了长期口服细菌疗法(益生菌;10 mL/kg; 109 菌落总数形成单位/ml)作为布利瓦西坦(BRV;10 mg/kg)的辅助治疗干预21天对戊四唑(PTZ)诱导的癫痫反应增强及相关电图和行为紊乱的影响。此外,我们还揭示了治疗与未治疗动物的抗氧化能力和组织病理学变化:结果:研究结果表明,联合用药能提高癫痫发作阈值,防止高发作尖峰。此外,它还缓解了 PTZ 引起的神经精神障碍,如焦虑和抑郁样表型以及认知障碍。此外,双重疗法还能促进生理氧化/抗氧化平衡,这体现在抗氧化酶(SOD和过氧化氢酶)活性的提高和氧化应激因子(MDA)水平的降低。共生物种的这种治疗干预抑制了网络驱动的神经炎症,并保留了正常的细胞结构和粟粒体锥体层(CA1 和 CA3)的完整形态:我们的研究为使用益生菌作为抗癫痫药物的辅助疗法提供了支持性证据,以调节致痫过程和相关的多发病,尤其是对耐药癫痫患者。
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引用次数: 0
Role of Hippocampal Glutamatergic Synaptic Alterations in Sevoflurane-Induced Cognitive Dysfunction in Aged Mice 海马谷氨酸能突触改变在七氟醚诱导的老年小鼠认知功能障碍中的作用
IF 4.8 1区 医学 Q1 NEUROSCIENCES Pub Date : 2024-10-28 DOI: 10.1111/cns.70093
Yixuan Niu, Guoying Liao, Zhengjie Miao, Jinnan Xu, Yanyong Cheng, Fan Wang, Chuanyu Qi, Tiannan Chen, Yi Gao, Lei Zhang, Hong Jiang, Jia Yan

Aims

Perioperative neurocognitive disorders (PND), including postoperative delirium (POD) and postoperative cognitive dysfunction (POCD), are common following anesthesia and surgery in older patients and significantly increase morbidity and mortality. However, the underlying mechanism of PND is unclear. Our study aims to analyze the differentially expressed genes (DEGs) in excitatory neurons and investigate the role of hippocampal glutamatergic synaptic alterations in sevoflurane-induced cognitive dysfunction in aged mice.

Methods

We performed single-nucleus RNA sequencing (snRNA-seq) technology to examine the alterations of excitatory neurons in hippocampus induced by sevoflurane in aged mice. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of DEGs were performed in excitatory neurons. At last, immunofluorescence staining was used to validate sevoflurane-induced alternation of glutamatergic synapses in the hippocampus of aged mice.

Results

This study demonstrates that DEGs in excitatory neurons are associated with reduction of glutamatergic synapses and cognitive dysfunction. After immunofluorescence staining validation, we also confirmed that sevoflurane anesthesia decreased the density of glutamatergic synapses in the hippocampus of aged mice.

Conclusions

Our findings demonstrated a key role of hippocampal glutamatergic synaptic alterations in sevoflurane-induced cognitive dysfunction in aged mice.

目的:围手术期神经认知障碍(PND),包括术后谵妄(POD)和术后认知功能障碍(POCD),是老年患者麻醉和手术后的常见病,会显著增加发病率和死亡率。然而,PND 的内在机制尚不清楚。我们的研究旨在分析兴奋性神经元中的差异表达基因(DEGs),并探讨海马谷氨酸能突触改变在七氟醚诱导的老年小鼠认知功能障碍中的作用:我们采用单核RNA测序(snRNA-seq)技术研究了七氟烷诱导的老年小鼠海马兴奋性神经元的改变。对兴奋性神经元的基因本体(GO)和京都基因组百科全书(KEGG)进行了DEGs分析。最后,免疫荧光染色验证了七氟烷诱导的老龄小鼠海马谷氨酸能突触的交替:结果:这项研究表明,兴奋性神经元中的 DEGs 与谷氨酸能突触的减少和认知功能障碍有关。经过免疫荧光染色验证,我们还证实七氟醚麻醉降低了老年小鼠海马中谷氨酸能突触的密度:我们的研究结果表明,海马谷氨酸能突触的改变在七氟醚诱导的老年小鼠认知功能障碍中起着关键作用。
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引用次数: 0
Comparative Side-Effects of Neurosurgical Treatment of Treatment-Resistant Depression 神经外科治疗难治性抑郁症的副作用比较。
IF 4.8 1区 医学 Q1 NEUROSCIENCES Pub Date : 2024-10-28 DOI: 10.1111/cns.70090
Alexandre Lim Eng Keat, Keith Tan Jian Li, Teo Chuin Hau, Tomoko Soga

Introduction

Treatment-resistant depression (TRD) is a condition in which patients suffering from depression no longer respond to common methods of treatment, such as anti-depressant medication. Neurosurgical procedures such as ablative surgery, deep brain stimulation, and vagus nerve stimulation have been used in efforts to overcome TRD.

Objectives

This review aims to provide an overview of the side effects of neurosurgery performed in clinical studies related to depression.

Methods

A literature search was conducted through PubMed, MEDLINE, EMBASE, Ovid, and ClinicalTrials.gov databases.

Results

This review selected 10 studies for ablative surgery, 12 for deep brain stimulation, and 10 for vagus nerve stimulation, analyzing their side effect profiles of neurosurgery for TRD. The major side effects of each type of neurosurgery were identified, such as incontinence and confusion for ablative surgery, headaches and increased suicide ideation for deep brain stimulation, and voice hoarseness and dyspnea for vagus nerve stimulation.

Conclusion

The review discusses the merits and demerits of neurosurgery as a treatment option for TRD. It also suggests new insights into decreasing the burden of these neurosurgical side effects so that they can be a viable, high-efficacy treatment method for TRD.

导言:抗药性抑郁症(TRD)是指抑郁症患者对抗抑郁药物等普通治疗方法不再产生反应。神经外科手术,如消融手术、脑深部刺激和迷走神经刺激,已被用于克服 TRD:本综述旨在概述抑郁症相关临床研究中进行的神经外科手术的副作用:方法:通过PubMed、MEDLINE、EMBASE、Ovid和ClinicalTrials.gov数据库进行文献检索:本综述选取了10项消融手术研究、12项脑深部刺激研究和10项迷走神经刺激研究,分析了神经外科手术治疗TRD的副作用。确定了每种神经外科手术的主要副作用,如消融手术的尿失禁和精神错乱,深部脑刺激的头痛和自杀意念增强,迷走神经刺激的声音嘶哑和呼吸困难:本综述讨论了神经外科手术作为 TRD 治疗选择的优缺点。结论:这篇综述讨论了神经外科手术作为 TRD 治疗方法的优缺点,并就如何减轻这些神经外科副作用的负担提出了新的见解,从而使神经外科手术成为 TRD 的一种可行、高效的治疗方法。
{"title":"Comparative Side-Effects of Neurosurgical Treatment of Treatment-Resistant Depression","authors":"Alexandre Lim Eng Keat,&nbsp;Keith Tan Jian Li,&nbsp;Teo Chuin Hau,&nbsp;Tomoko Soga","doi":"10.1111/cns.70090","DOIUrl":"10.1111/cns.70090","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Treatment-resistant depression (TRD) is a condition in which patients suffering from depression no longer respond to common methods of treatment, such as anti-depressant medication. Neurosurgical procedures such as ablative surgery, deep brain stimulation, and vagus nerve stimulation have been used in efforts to overcome TRD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>This review aims to provide an overview of the side effects of neurosurgery performed in clinical studies related to depression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A literature search was conducted through PubMed, MEDLINE, EMBASE, Ovid, and ClinicalTrials.gov databases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>This review selected 10 studies for ablative surgery, 12 for deep brain stimulation, and 10 for vagus nerve stimulation, analyzing their side effect profiles of neurosurgery for TRD. The major side effects of each type of neurosurgery were identified, such as incontinence and confusion for ablative surgery, headaches and increased suicide ideation for deep brain stimulation, and voice hoarseness and dyspnea for vagus nerve stimulation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The review discusses the merits and demerits of neurosurgery as a treatment option for TRD. It also suggests new insights into decreasing the burden of these neurosurgical side effects so that they can be a viable, high-efficacy treatment method for TRD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 10","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70090","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520505","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
The Dopamine Transporter Is a New Target for Ischemic Stroke 多巴胺转运体是缺血性中风的新靶点
IF 4.8 1区 医学 Q1 NEUROSCIENCES Pub Date : 2024-10-28 DOI: 10.1111/cns.70092
Yan-Qiong Cheng, Ruo-Xi Zhang, Xing-Yuan Li, Xiao-Ting Zhou, Ming Chen, Ai-Jun Liu

Aims

Dopamine transporter (DAT) can regulate DA homeostasis and has been implicated in many nervous system diseases. Whether DAT is involved in the protection against ischemic stroke is unclear.

Methods

In vivo microdialysis measurements of DA were recorded in the ischemic penumbral area of mice with middle cerebral artery occlusion (MCAO). DAT coding gene, Slc6a3 mutation, and DAT overexpression animals were performed MCAO. Madopar (compound formulation of levodopa) and nomifensine (DA reuptake inhibitor) were administered in MCAO animals. Brain slices were prepared in Slc6a3 mutation or wild-type (WT) animals with MCAO to record miniature excitatory postsynaptic currents (mEPSCs) and miniature inhibitory postsynaptic currents (mIPSCs). The effects of DA and its dopamine-1 receptor (D1R) antagonists (SCH-23390) on mEPSCs, mIPSCs, and neurons protection were recorded.

Results

MCAO caused a prominent increase in DA. Slc6a3 mutation significantly attenuated the ischemic injury, whereas DAT overexpression aggravated this injury. Both nomifensine and madopar protected against brain injury. Slc6a3 mutation and DA restored the disturbance of mEPSCs and mIPSC, and protected against neuron death, which was abolished by SCH-23390.

Conclusion

DAT inhibition might be explored as a strategy for ischemic stroke prevention. DA and D1R involve in the restoration of synaptic dysfunction and neuron protection.

目的:多巴胺转运体(DAT)可调节DA稳态,与多种神经系统疾病有关。DAT是否参与缺血性中风的保护尚不清楚:方法:对大脑中动脉闭塞(MCAO)小鼠缺血半月区的DA进行体内微透析测量。对DAT编码基因、Slc6a3突变和DAT过表达动物进行了MCAO。给 MCAO 动物注射 Madopar(左旋多巴复方制剂)和 nomifensine(DA 再摄取抑制剂)。制备Slc6a3突变或野生型(WT)MCAO动物的脑片,记录微型兴奋性突触后电流(mEPSCs)和微型抑制性突触后电流(mIPSCs)。记录了DA及其多巴胺-1受体(D1R)拮抗剂(SCH-23390)对mEPSCs、mIPSCs和神经元保护的影响:结果:MCAO导致DA显著增加。结果:MCAO导致DA显著增加,Slc6a3突变明显减轻了缺血损伤,而DAT过表达则加重了缺血损伤。诺米芬新和马多帕对脑损伤均有保护作用。Slc6a3突变和DA可恢复mEPSCs和mIPSC的紊乱,并防止神经元死亡,而SCH-23390可消除神经元死亡:结论:抑制DAT可作为预防缺血性脑卒中的一种策略。DA和D1R参与了突触功能障碍的恢复和神经元的保护。
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引用次数: 0
The Gut Microbiota Modulates Neuroinflammation in Alzheimer's Disease: Elucidating Crucial Factors and Mechanistic Underpinnings 肠道微生物群调节阿尔茨海默病的神经炎症:阐明关键因素和机制基础
IF 4.8 1区 医学 Q1 NEUROSCIENCES Pub Date : 2024-10-26 DOI: 10.1111/cns.70091
Jianshe Yang, Junyi Liang, Niyuan Hu, Ningjuan He, Bin Liu, Guoliang Liu, Ying Qin

Background and Purpose

Alzheimer's disease (AD) is characterized by progressive cognitive decline and neuronal loss, commonly linked to amyloid-β plaques, neurofibrillary tangles, and neuroinflammation. Recent research highlights the gut microbiota as a key player in modulating neuroinflammation, a critical pathological feature of AD. Understanding the role of the gut microbiota in this process is essential for uncovering new therapeutic avenues and gaining deeper insights into AD pathogenesis.

Methods

This review provides a comprehensive analysis of how gut microbiota influences neuroinflammation and glial cell function in AD. A systematic literature search was conducted, covering studies from 2014 to 2024, including reviews, clinical trials, and animal studies. Keywords such as “gut microbiota,” “Alzheimer's disease,” “neuroinflammation,” and “blood–brain barrier” were used.

Results

Dysbiosis, or the imbalance in gut microbiota composition, has been implicated in the modulation of key AD-related mechanisms, including neuroinflammation, blood–brain barrier integrity, and neurotransmitter regulation. These disruptions may accelerate the onset and progression of AD. Additionally, therapeutic strategies targeting gut microbiota, such as probiotics, prebiotics, and fecal microbiota transplantation, show promise in modulating AD pathology.

Conclusions

The gut microbiota is a pivotal factor in AD pathogenesis, influencing neuroinflammation and disease progression. Understanding the role of gut microbiota in AD opens avenues for innovative diagnostic, preventive, and therapeutic strategies.

背景和目的:阿尔茨海默病(AD)的特征是进行性认知能力下降和神经元丧失,通常与淀粉样β斑块、神经纤维缠结和神经炎症有关。最近的研究强调,肠道微生物群是调节神经炎症的关键因素,而神经炎症是注意力缺失症的一个重要病理特征。了解肠道微生物群在这一过程中的作用对于发现新的治疗途径和深入了解 AD 的发病机制至关重要:本综述全面分析了肠道微生物群如何影响 AD 的神经炎症和神经胶质细胞功能。本综述全面分析了肠道微生物群如何影响AD的神经炎症和神经胶质细胞功能。我们进行了系统的文献检索,涵盖2014年至2024年的研究,包括综述、临床试验和动物实验。关键词包括 "肠道微生物群"、"阿尔茨海默病"、"神经炎症 "和 "血脑屏障":结果:肠道微生物菌群失调或肠道微生物菌群组成失衡已被认为与调节与阿尔茨海默病相关的关键机制有关,包括神经炎症、血脑屏障完整性和神经递质调节。这些干扰可能会加速 AD 的发病和进展。此外,针对肠道微生物群的治疗策略,如益生菌、益生元和粪便微生物群移植,在调节AD病理学方面也显示出前景:结论:肠道微生物群是影响神经炎症和疾病进展的AD发病机制的关键因素。了解肠道微生物群在 AD 中的作用为创新诊断、预防和治疗策略开辟了道路。
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引用次数: 0
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CNS Neuroscience & Therapeutics
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