Brain disorders (Amsterdam, Netherlands)最新文献_第7页

Treatment outcome and risk factors of ischemic stroke among adult patients in two selected hospital in Addis Ababa, Ethiopia 埃塞俄比亚亚的斯亚贝巴两家选定医院成年患者缺血性卒中的治疗结果和危险因素

Brain disorders (Amsterdam, Netherlands)

Pub Date : 2025-05-29 DOI: 10.1016/j.dscb.2025.100242

Selemon Gebrezgabiher Asgedom , Dejen Tekiea Gebrewahd , Milion Gebrewold Abdi , Yoseph Abebe Wondie , Berhanu Abebaw Mekonnen , Kefyalew Taye Belete

Background

Ischemic stroke remains a major cause of morbidity and mortality worldwide, with a growing burden in low- and middle-income countries such as Ethiopia. Identifying risk factors, clinical profiles, and outcomes is crucial for improving stroke prevention strategies.

Methods

A retrospective cohort study was conducted from September 2023 to December 2024 at two public hospitals in Addis Ababa. Data was collected from 219 adult ischemic stroke patients through structured interviews and detailed chart reviews. Sociodemographic characteristics, comorbidities, and outcomes were analyzed. Multivariable logistic regression analysis was used to identify predictors of poor functional outcomes, defined as a mRS score of 3–6.

Results

The mean age of patients was 61.7 years, with 61.19 % aged 60 years or older. Hypertension (61.19 %), dyslipidemia (49 %), and diabetes mellitus (46.12 %) were the most common comorbidities. A significant proportion (94.06 %) arrived at the hospital after 4.5 h of symptom onset, and none received thrombolytic therapy due to unavailability. Poor outcomes (mRS 3–6) were significantly associated with age ≥60 years (AOR = 4.8, 95 % CI:2.67–8.32, p < 0.001), delayed hospital arrival (AOR = 2.92, CI:1.41–4.38, p = 0.03), and Glasgow Coma Scale score ≤8 (AOR = 4.5, CI:2.2–9.2, p = 0.001), prior stroke history (AOR = 1.88, CI:1.1–3.28, p = 0.03), and prolonged hospital stay over seven days (AOR = 2.1, CI:1.1–4.12, p = 0.02). The overall in-hospital mortality rate was 20.55 %.

Conclusion

Advanced age, delayed hospital presentation, low GCS at presentation, prior stroke history, and prolonged hospital stay were independent predictors of poor outcomes among ischemic stroke patients. Strengthening early detection programs, ensuring timely hospital access, expanding thrombolytic therapy availability, and targeting modifiable risk factors are critical strategies to improve stroke outcomes in Ethiopia.

缺血性脑卒中仍然是世界范围内发病和死亡的主要原因，在埃塞俄比亚等低收入和中等收入国家造成的负担越来越重。确定风险因素、临床概况和结果对于改善卒中预防策略至关重要。方法于2023年9月至2024年12月在亚的斯亚贝巴两所公立医院进行回顾性队列研究。通过结构化访谈和详细的图表回顾，收集了219例成年缺血性脑卒中患者的数据。分析社会人口学特征、合并症和结果。多变量逻辑回归分析用于识别功能不良预后的预测因素，定义为mRS评分为3-6。结果患者平均年龄61.7岁，60岁及以上年龄占61.19%。高血压（61.19%）、血脂异常（49%）和糖尿病（46.12%）是最常见的合并症。显著比例（94.06%）在症状出现4.5小时后到达医院，由于无法获得溶栓治疗，没有人接受溶栓治疗。不良预后（mRS 3-6）与年龄≥60岁显著相关(AOR = 4.8, 95% CI: 2.67-8.32, p <；延迟到院（AOR = 2.92, CI:1.41 ~ 4.38, p = 0.03）、格拉斯哥昏迷量表评分≤8 （AOR = 4.5, CI:2.2 ~ 9.2, p = 0.001）、既往卒中史（AOR = 1.88, CI:1.1 ~ 3.28, p = 0.03）、住院时间超过7天（AOR = 2.1, CI:1.1 ~ 4.12, p = 0.02）。住院总死亡率为20.55%。结论高龄、就诊时间延迟、就诊时GCS低、既往卒中史和住院时间延长是缺血性卒中患者预后不良的独立预测因素。加强早期检测项目，确保及时就医，扩大溶栓治疗的可用性，并针对可改变的风险因素，是改善埃塞俄比亚中风结果的关键策略。

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引用次数: 0

Comparing the impact of low frequency vs high frequency deep brain stimulation in Patient’s with Parkinson’s disease: A systematic review 比较低频与高频脑深部刺激对帕金森病患者的影响：一项系统综述

Brain disorders (Amsterdam, Netherlands)

Pub Date : 2025-05-29 DOI: 10.1016/j.dscb.2025.100239

Govind Singh Mann , Binay K. Panjiyar , MD Parbej Allam , Fnu Asifa , Ahsan Ullah , Shivangi Jha

Aim

Deep brain stimulation (DBS) involves implanting electrodes in specific brain areas. High-frequency Stimulation (HFS) and low-frequency Stimulation (LFS) target motor and non-motor symptoms differently. DBS is crucial in Parkinson's disease (PD) treatment for managing medication-resistant symptoms and improving quality of life. This review aims to evaluate the differential impact of high-frequency and low-frequency DBS on motor symptoms in PD patients. This systematic review adheres to PRISMA guidelines and focuses on clinical studies involving human subjects.

Methods

Systematic search in electronic databases (PubMed, Google Scholar, Science Direct, Cochrane Collaboration Database of Randomized Trials) was performed to identify randomized controlled trials (RCTs) up to 13th July 2024.

Results

Among 126 pooled patients from 8 RCTs, it was found that LFS significantly improved gait stability, swallowing, and verbal fluency with minimal adverse effects. Conversely, HFS was effective in reducing rigidity and tremor but was associated with potential side effects such as gait and speech impairment.

Conclusion

This review underscores the frequency dependent effects of Subthalamic Nucleus DBS (STN-DBS) in PD. High-frequency stimulation (>100 Hz) remains effective for controlling tremor and rigidity but is often associated with adverse effects. In contrast, low-frequency stimulation (≤100 Hz) shows a lower risk of these adverse effects, though it may be less effective for core motor symptoms. An optimal therapeutic window between 80 and 130 Hz may balance efficacy and tolerability. These findings support the need for individualized DBS programming and future research on adaptive stimulation technologies to optimize patient-specific outcomes.

脑深部电刺激（DBS）包括在大脑的特定区域植入电极。高频刺激（HFS）和低频刺激（LFS）针对运动和非运动症状不同。DBS在帕金森病（PD）治疗中对于控制耐药症状和改善生活质量至关重要。本综述旨在评估高频和低频DBS对PD患者运动症状的不同影响。本系统综述遵循PRISMA指南，重点关注涉及人类受试者的临床研究。方法系统检索PubMed、b谷歌Scholar、Science Direct、Cochrane Collaboration Database of random Trials等电子数据库，检索截止到2024年7月13日的随机对照试验（rct）。结果在8项随机对照试验的126例患者中，发现LFS显著改善了步态稳定性、吞咽和语言流畅性，不良反应最小。相反，HFS在减少僵硬和震颤方面有效，但与潜在的副作用有关，如步态和语言障碍。结论本综述强调了丘脑下核DBS （STN-DBS）在PD中的频率依赖性作用。高频刺激（100赫兹）对控制震颤和强直仍然有效，但通常伴有不良反应。相比之下，低频刺激（≤100 Hz）显示出这些不良反应的风险较低，尽管它对核心运动症状可能效果较差。最佳的治疗窗在80和130赫兹之间，可以平衡疗效和耐受性。这些发现支持了个性化DBS规划和未来适应性刺激技术研究的必要性，以优化患者特异性结果。

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引用次数: 0

Unlocking the potential of Shilajit in Vascular Dementia behind pathology and management - A concise review 揭示Shilajit在血管性痴呆病理和治疗背后的潜力-简要回顾

Brain disorders (Amsterdam, Netherlands)

Pub Date : 2025-05-28 DOI: 10.1016/j.dscb.2025.100244

Kousik Maparu, Shamsher Singh

Vascular dementia (VaD), the second most common type of dementia after Alzheimer's disease, is distinguished by cognitive decline caused by cerebrovascular problems such as cerebral infarctions and white matter abnormalities, by various factors including sedentary lifestyle, smoking, alcohol, various gene mutations such as APP, PSEN, BACE, CADASIL, CARASIL APOE. Risk factors cause the generation of oxidative stress and ROS production leads to apoptosis, impaired autophagy, and neuroinflammation are important variables that cause neuronal loss and cognitive decline. Various inflammatory markers, including TNF, IL, NF-κβ, NLR, and MAPK, cause neurodegeneration and vascular damage, leading to Vascular dementia. Vascular homeostasis depends on nitric oxide, and a lack of it is associated with advancing vascular disease. There are existing therapy alternatives, and a new study suggests that targeting the nitric oxide-cAMP pathway may open new treatment possibilities. Shilajit, a traditional herbomineral Ayurvedic ingredient, has several health benefits, including anemia, digestive difficulties, and neurological illnesses. It has a high mineral content, humic substances, fatty acid content, and bioactive substances that have anti-inflammatory, antioxidant, and memory-enhancing properties. Fulvic acid adds to Shilajit’s anti-aging and neuroprotective qualities, also lowers inflammation, and enhances cardiovascular health. It may be used as a dietary supplement to prevent vascular dementia.

血管性痴呆（VaD）是仅次于阿尔茨海默病的第二大常见痴呆类型，其特点是脑梗死和白质异常等脑血管问题引起的认知能力下降，受久坐生活方式、吸烟、饮酒、APP、PSEN、BACE、CADASIL、CARASIL APOE等各种基因突变等多种因素影响。危险因素导致氧化应激的产生，ROS的产生导致细胞凋亡、自噬受损和神经炎症是导致神经元丢失和认知能力下降的重要变量。TNF、IL、NF-κβ、NLR、MAPK等多种炎症标志物可引起神经变性和血管损伤，导致血管性痴呆。血管内稳态依赖于一氧化氮，缺乏一氧化氮与血管疾病的进展有关。有现有的治疗方案，一项新的研究表明，针对一氧化氮- camp途径可能开辟新的治疗可能性。Shilajit是一种传统的草药成分，对健康有很多好处，包括贫血、消化困难和神经系统疾病。它具有高矿物质含量、腐殖质、脂肪酸含量和生物活性物质，具有抗炎、抗氧化和增强记忆的特性。黄腐酸增加了Shilajit的抗衰老和神经保护特性，也降低炎症，增强心血管健康。它可以作为一种膳食补充剂来预防血管性痴呆。

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引用次数: 0

Analysis of anti-IgLON5 antibody-associated encephalopathy after trauma 创伤后抗iglon5抗体相关脑病分析

Brain disorders (Amsterdam, Netherlands)

Pub Date : 2025-05-27 DOI: 10.1016/j.dscb.2025.100240

Mai Hailing , Zhang Jia , Zhu Rui , Liang Panpan , Jin Lijuan

Materials and Methods

This study aims to elucidate the pathogenic factors, early diagnosis, and treatment of anti-IgLON5 antibody-associated encephalopathy by examining the clinical characteristics and management of a patient following a traumatic injury and reviewing relevant literature. We analyzed the clinical data and treatment process of a patient diagnosed with anti-IgLON5 antibody-associated encephalopathy after an injury at the People's Hospital of Ningxia Hui Autonomous Region on September 21, 2020. Clinical characteristics and the diagnostic and therapeutic approaches for this condition were summarized.

Results

The patient was a 68-year-old male who was admitted after sustaining multiple injuries from a car accident eight days prior and presenting with fever for two days. His medical history included clear trauma from the accident, with CT imaging revealing multiple cerebral contusions. Upon admission, his consciousness fluctuated from sleepiness to lethargy, accompanied by high fever and seizures. Follow-up CT scans showed no significant changes. We actively sought the cause of the fever and investigated potential infections while administering antiepileptic drugs, glucocorticoids, and immunosuppressants, yielding acceptable results. Immunological analysis of the cerebrospinal fluid (CSF) revealed positive anti-IgLON5 antibodies.

Conclusion 1

Confirm the established clinical and diagnostic features while emphasizing the therapeutic value of early immunotherapy. 2. Link mechanical injury to autoimmune activation and suggest trauma as a new triggering factor. 3. Highlight hippocampal MRI abnormalities as potential diagnostic clues and urge the expansion of neuroimaging protocols in suspected cases.

材料与方法本研究旨在通过分析1例外伤性脑病患者的临床特点和处理方法，并复习相关文献，探讨抗iglon5抗体相关脑病的发病因素、早期诊断和治疗。我们分析了2020年9月21日在宁夏回族自治区人民医院诊断为抗iglon5抗体相关脑病的患者的临床资料和治疗过程。本文总结了该病的临床特点及诊治方法。结果患者为68岁男性，8天前因车祸多处受伤，发热2天后入院。他的病史包括明显的事故创伤，CT成像显示多发脑挫伤。入院时，他的意识由嗜睡到昏睡，并伴有高烧和癫痫发作。后续CT扫描未见明显变化。在给予抗癫痫药物、糖皮质激素和免疫抑制剂的同时，我们积极寻找发烧的原因并调查潜在的感染，结果可以接受。脑脊液免疫学分析显示抗iglon5抗体阳性。结论1在强调早期免疫治疗的治疗价值的同时，确认已有的临床和诊断特征。2. 将机械损伤与自身免疫激活联系起来，提示创伤是新的触发因素。3. 强调海马MRI异常作为潜在的诊断线索，并敦促扩大疑似病例的神经影像学方案。

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引用次数: 0

A systematic review of diffusion microstructure imaging (DMI): Current and future applications in neurology research 弥散微结构成像（DMI）在神经学研究中的应用现状与未来综述

Brain disorders (Amsterdam, Netherlands)

Pub Date : 2025-05-22 DOI: 10.1016/j.dscb.2025.100238

Sadegh Ghaderi , Sana Mohammadi , Farzad Fatehi

Diffusion Microstructure Imaging (DMI) has emerged as a transformative neuroimaging technique that offers unprecedented insights into brain tissue microstructure by disentangling contributions from the volumes of the intra-axonal (V-intra), extra-axonal (V-extra), and free-fluid (V-CSF) compartments. We aimed to systematically review the current applications and future directions of the DMI for neurology research. Following the PRISMA 2020 guidelines, PubMed, Scopus, Web of Science, and Embase were searched for articles published up to May 2025. Our review synthesized narratively, DMI’s applications in neurology, and evaluated its diagnostic and prognostic potential across neurological disorders. Twenty-one studies were included. Across various studies on tumors, neurodegeneration, stroke, aging, hydrocephalus, epilepsy, and pain, DMI consistently identified microstructural alterations that could not be detected by conventional diffusion tensor imaging and diffusion kurtosis imaging. In brain tumors, the DMI demonstrated high diagnostic accuracy by distinguishing lymphoma from glioblastoma and characterizing peritumoral infiltration in glioblastoma compared to metastases. In Parkinsonian syndromes, elevated free-water fractions in the basal ganglia and cerebellopontine tracts were strongly correlated with clinical severity and enabled subtype differentiation. In cases of acute stroke and COVID-19, DMI metrics provided more sensitive mapping of cytotoxic and vasogenic edema than the Apparent Diffusion Coefficient. Normative aging studies revealed distinct patterns of tract-specific maturation and senescence. Furthermore, applications in idiopathic normal pressure hydrocephalus, epilepsy, and migraine showed DMI’s capability to detect fluid accumulation, axonal loss, and the integrity of nociceptive pathways, respectively. This review underscores that DMI demonstrates superior sensitivity compared to conventional diffusion techniques.

扩散微结构成像（DMI）是一种革命性的神经成像技术，通过分离轴突内（V-intra）、轴突外（V-extra）和自由流体（V-CSF）区室的体积，提供了前所未有的脑组织微结构洞察。我们旨在系统地综述DMI在神经学研究中的应用现状和未来发展方向。根据PRISMA 2020指南，检索了PubMed、Scopus、Web of Science和Embase，检索了截至2025年5月发表的文章。本文综述了DMI在神经病学中的应用，并评估了其在神经系统疾病中的诊断和预后潜力。纳入了21项研究。在对肿瘤、神经退行性变、中风、衰老、脑积水、癫痫和疼痛的各种研究中，DMI一致地发现了传统弥散张量成像和弥散峰度成像无法检测到的微结构改变。在脑肿瘤中，DMI在区分淋巴瘤和胶质母细胞瘤以及胶质母细胞瘤与转移瘤的肿瘤周围浸润特征方面表现出很高的诊断准确性。在帕金森综合征中，基底神经节和桥小脑束中游离水含量的升高与临床严重程度和亚型分化密切相关。在急性卒中和COVID-19病例中，DMI指标提供了比表观弥散系数更敏感的细胞毒性和血管源性水肿制图。规范的衰老研究揭示了不同的模式的管道特异性成熟和衰老。此外，在特发性常压脑积水、癫痫和偏头痛中的应用表明，DMI能够分别检测液体积聚、轴突损失和伤害性通路的完整性。本综述强调，与传统的扩散技术相比，DMI具有更高的灵敏度。

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引用次数: 0

Progestogens reduce tau phosphorylation via ERK 1/2 in a tau overexpression cell model 在tau过表达细胞模型中，孕激素通过ERK 1/2降低tau磷酸化

Brain disorders (Amsterdam, Netherlands)

Pub Date : 2025-05-17 DOI: 10.1016/j.dscb.2025.100236

Taysa Bervian Bassani , Rafaela Brito Oliveira , Giulia Ventura Portella , Michelle Sayuri Nishino , Angelica Jardim Costa , Rodrigo Portes Ureshino

Several studies have suggested the neuroprotective effects of progestogens in neurodegenerative diseases. Among the most common neurodegenerative diseases are tauopathies. Tauopathies are characterized by the formation of neurofibrillary tangles within neurons, resulting from the aggregation of hyperphosphorylated tau protein, cytoskeleton impairment and, ultimately, cell death. However, the effect of progestogens on those processes needs to be further explored. Thus, this work aims to investigate the effect of progesterone and allopregnanolone on tau hyperphosphorylation in a cellular model of tau overexpression. We used a neuronal cellular model overexpressing the human tau protein (isoform 0N4R) fused with EGFP. The data showed that progesterone effectively decreased the accumulation of overexpressed EGFP-tau. In addition, both compounds reduced tau phosphorylation in different sites, as progesterone reduced at the AT8 and allopregnanolone at AT180 site. The attenuation of its phosphorylation appears to be related to inhibiting the kinase activity of enzymes involved in tau phosphorylation, such as ERK 1/2. Thus, the progestogens tested showed promising neuroprotective potential for the treatment of tauopathies, especially by attenuating hyperphosphorylated forms that give rise to paired helical filaments and neurofibrillary tangles, probably due to modulation of intracellular pathways.

一些研究表明，孕激素在神经退行性疾病中具有神经保护作用。最常见的神经退行性疾病是牛头病。tau病的特点是神经元内形成神经原纤维缠结，由过度磷酸化的tau蛋白聚集引起，细胞骨架受损，最终导致细胞死亡。然而，孕激素对这些过程的影响需要进一步探讨。因此，本研究旨在探讨在tau过表达的细胞模型中，黄体酮和异孕酮对tau过度磷酸化的影响。我们使用过表达人tau蛋白（同种异构体0N4R）与EGFP融合的神经元细胞模型。数据显示，黄体酮可有效降低过表达EGFP-tau的积累。此外，这两种化合物都减少了不同位点的tau磷酸化，如黄体酮在AT8位点和异孕酮在AT180位点的磷酸化。其磷酸化的衰减似乎与抑制参与tau磷酸化的酶（如erk1 /2）的激酶活性有关。因此，孕激素测试显示出治疗牛头病的有希望的神经保护潜力，特别是通过减弱可能由于调节细胞内通路而产生成对螺旋细丝和神经原纤维缠结的过度磷酸化形式。

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引用次数: 0

Plasma macrophage migration inhibitory factor and matrix metalloproteinase-9 levels, and their related factors in Alzheimer’s disease 阿尔茨海默病血浆巨噬细胞迁移抑制因子和基质金属蛋白酶-9水平及其相关因素

Brain disorders (Amsterdam, Netherlands)

Pub Date : 2025-05-16 DOI: 10.1016/j.dscb.2025.100237

Zhengchuang Fu , Min Wang , Ming Yu, Quanfeng Zhu, Yali Zheng

Previous studies have shown that the levels of macrophage migration inhibitory factor (MIF) and matrix metalloproteinase-9 (MMP-9) in its downstream signaling pathway are related to the occurrence and development of Alzheimer’s disease (AD); some studies have suggested that plasma levels of MIF and MMP-9 could be used as potential biomarkers for AD. This study aimed to explore the changes in MIF and MMP-9 levels in the plasma of patients with AD and whether they were correlated with other clinical indicators and cognitive function. Altogether, 43 patients with AD and 40 healthy controls (HCs) were enrolled in this study. Socio-demographic information of the subjects was collected, and their cognitive function was assessed using Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Further, the biochemical indicators and plasma MIF and MMP-9 levels were detected. Our study found that plasma MIF levels were not significantly altered in patients with AD compared to HCs, while MMP-9 levels were significantly increased, and prolactin levels had significant effects on MMP-9 levels. In addition, plasma levels of MIF and MMP-9 in patients with AD had no significant correlation with cognitive function. In summary, plasma levels of MIF and MMP-9 in AD patients may be influenced by multiple factors and could vary significantly across different disease stages. Further studies are needed to elucidate their roles and underlying mechanisms in AD.

既往研究表明，巨噬细胞迁移抑制因子（MIF）及其下游信号通路中基质金属蛋白酶-9 （MMP-9）水平与阿尔茨海默病（AD）的发生发展有关；一些研究表明，血浆中MIF和MMP-9的水平可以作为AD的潜在生物标志物。本研究旨在探讨AD患者血浆中MIF和MMP-9水平的变化及其与其他临床指标和认知功能的相关性。总共有43名AD患者和40名健康对照者（hc）参加了这项研究。收集被试的社会人口学信息，采用迷你精神状态检查（MMSE）和蒙特利尔认知评估（MoCA）对被试的认知功能进行评估。进一步检测生化指标及血浆MIF、MMP-9水平。我们的研究发现，与hc相比，AD患者血浆MIF水平没有显著改变，而MMP-9水平显著升高，泌乳素水平对MMP-9水平有显著影响。此外，AD患者血浆中MIF和MMP-9水平与认知功能无显著相关性。综上所述，AD患者血浆中MIF和MMP-9水平可能受到多种因素的影响，并且在不同的疾病阶段可能存在显著差异。需要进一步的研究来阐明它们在AD中的作用和潜在机制。

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引用次数: 0

Hemihypomimia and lingual tremor in Parkinson’s disease: A case report 帕金森氏病的半贫血和舌颤1例报告

Brain disorders (Amsterdam, Netherlands)

Pub Date : 2025-05-15 DOI: 10.1016/j.dscb.2025.100234

Anita Senthinathan, Sharon Tudorovsky

Parkinson's disease is a progressive nervous system disorder that can cause many other non-motor and motor symptoms in addition to tremors and stiffness (Emamzadeh et al., 2018). Hemihypomimia and lingual abnormalities are rare occurrences in Parkinson’s disease (PD). The following report describes a unique case of this dual symptomology in a case of short disease duration and early onset PD. In addition, prior case reports have shown a predominantly right-sided effect (Panichelli & Spitz, 2021; Ozekmekçi et al., 2007; Zingler et al., 2005). Hemihypomimia (HH) can persist for several years and is consistent with normal asymmetrical involvement of the limbs (Ozekmekçi et al., 2007). HH mostly appears in the lower portion of the right side of the face (Bologna et al., 2016). Lingual tremor and strength deficits are a rare phenomenon in PD, and the implications for speech and swallowing are important for QOL considerations.

帕金森病是一种进行性神经系统疾病，除了震颤和僵硬外，还会引起许多其他非运动和运动症状（Emamzadeh et al., 2018）。在帕金森氏症（PD）中，低贫血症和舌部异常是罕见的。以下报告描述了一个独特的病例，这种双重症状的情况下，疾病持续时间短，早发性帕金森病。此外，先前的病例报告显示主要是右侧效应(Panichelli &；施皮茨,2021;ozekmeki et al., 2007；Zingler et al., 2005)。半低血症（HH）可持续数年，与正常的四肢不对称受累是一致的（ozekmeki et al., 2007）。HH主要出现在右侧面部的下半部（Bologna et al., 2016）。舌颤和力量缺陷在PD中是罕见的现象，言语和吞咽的影响对生活质量的考虑是重要的。

引用次数: 0

Navigating multiple sclerosis: From clinical categories to clinical management 导航多发性硬化症：从临床分类到临床管理

Brain disorders (Amsterdam, Netherlands)

Pub Date : 2025-05-12 DOI: 10.1016/j.dscb.2025.100235

Isra Omar , Ahmed Alakhras , Samahir Mutwali , Moiz Bakhiet

Multiple sclerosis (MS) is a chronic, immune-mediated neurological disorder that continues to challenge both researchers and clinicians. While advances in understanding its pathophysiology have led to improved disease-modifying therapies, these treatments primarily focus on immunosuppression and relapse prevention, leaving progressive forms of MS with limited options. Neurodegeneration, myelin loss, and long-term disability remain major hurdles, underscoring the urgent need for therapies that go beyond symptom management to actively repair damage and alter disease progression. With emerging breakthroughs in regenerative medicine, including stem cell-based therapies and novel immune-targeting treatments, we are entering a new era of MS research that prioritizes neuroprotection and repair. This review explores the latest insights into MS classification, pathogenesis, and treatment approaches, with a particular focus on cutting-edge therapies that hold the potential to shift MS care from disease suppression to long-term recovery. By bridging research and clinical application, this study aims to highlight the most promising avenues for future innovation and improved patient outcomes.

多发性硬化症（MS）是一种慢性、免疫介导的神经系统疾病，一直是研究人员和临床医生面临的挑战。虽然对其病理生理学的理解取得了进步，导致了疾病修饰疗法的改进，但这些治疗主要集中在免疫抑制和复发预防上，这使得进展型MS的选择有限。神经退行性变、髓磷脂丢失和长期残疾仍然是主要障碍，强调迫切需要超越症状管理的治疗方法，积极修复损伤并改变疾病进展。随着再生医学的新突破，包括基于干细胞的疗法和新的免疫靶向治疗，我们正在进入一个优先考虑神经保护和修复的MS研究的新时代。这篇综述探讨了MS的分类、发病机制和治疗方法的最新见解，特别侧重于将MS护理从疾病抑制转变为长期康复的前沿疗法。通过衔接研究和临床应用，本研究旨在突出未来创新和改善患者预后的最有希望的途径。

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引用次数: 0

Computational discovery of plant-derived flavonoids as potential amyloid-β fibril disaggregating agents for alzheimer’s disease 植物衍生类黄酮作为阿尔茨海默病潜在淀粉样蛋白-β纤维分解剂的计算发现

Brain disorders (Amsterdam, Netherlands)

Pub Date : 2025-05-12 DOI: 10.1016/j.dscb.2025.100233

Uthirapathi Logeswari Rakesh , Golla Anil Kumar , Theivendren Panneerselvam , Parasuraman Pavadai , Suganthan Veerachamy , Ponnusamy Palanisamy , SunilKumar Bandral , Selvaraj Kunjiappan

The neurological hallmark of Alzheimer's disease (AD) is a pathogenic deposition of amyloid-β peptide in the brain. Amyloid-β aggregation is neurotoxic and ultimately results in dysfunction of the nervous system. The present study aims to find potential amyloid-β fibrils disaggregating molecules from plant sources through molecular modeling techniques, which seems to be a promising and attractive therapeutic approach. Here, 500 flavonoids from various plants were considered, initially undergoing ADME studies to screen molecules that could cross the blood-brain barrier. Later, potential Amyloid-β-disaggregating molecules were predicted by molecular docking and molecular dynamics studies. Five molecules, prenylmethoxy flavonol (-7.3 kcal × mol^-1), isopentenyl flavonol (-7.3 kcal × mol^-1), 7,3′-Dihydroxyflavone (-7.2 kcal × mol^-1), 7-Hydroxy-5-methyl-4′-methoxyflavone (-7.2 kcal × mol^-1), 8‑hydroxy-7-methoxyflavone (-7 kcal × mol^-1) exhibited top binding score against Alzheimer's Aβ (1–42) fibrils, and these are very close to the standard drug (Donepezil) (-7.90 kcal × mol^-1). Further, the MD simulation studies confirmed the stability of the five selected ligands-Amyloid-β oligomer protein complex. Based on these findings, the selected five compounds might be used as potential Amyloid-β fibril disaggregating agents, and in vitro and in vivo studies are necessary to confirm the promising therapeutic capability.

阿尔茨海默病（AD）的神经学特征是大脑中淀粉样蛋白-β肽的致病性沉积。淀粉样蛋白-β聚集具有神经毒性，最终导致神经系统功能障碍。本研究旨在通过分子建模技术寻找潜在的植物源淀粉样蛋白-β原纤维分解分子，这似乎是一种有前途和有吸引力的治疗方法。这里考虑了来自不同植物的500种黄酮类化合物，最初进行ADME研究以筛选可以穿过血脑屏障的分子。随后，通过分子对接和分子动力学研究预测了潜在的淀粉样蛋白β分解分子。戊烯基甲氧基黄酮醇（-7.3 kcal × mol-1）、异戊烯基黄酮醇（-7.3 kcal × mol-1）、7,3 ' -二羟基黄酮（-7.2 kcal × mol-1）、7-羟基-5-甲基-4 ' -甲氧基黄酮（-7.2 kcal × mol-1）、8 -羟基-7-甲氧基黄酮（-7 kcal × mol-1）对阿尔茨海默病Aβ(1-42)原纤维的结合评分最高，与标准药物多奈哌齐（-7.90 kcal × mol-1）非常接近。此外，MD模拟研究证实了所选择的五种配体-淀粉样蛋白-β寡聚物蛋白复合物的稳定性。基于这些发现，所选择的5种化合物可能作为潜在的淀粉样蛋白-β纤维分解剂，并且有必要进行体外和体内研究以证实其具有良好的治疗能力。

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