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Neuroscience and Neuroimmunology Solutions for Osteoarthritis Pain: Biological Drugs, Growth Factors, Peptides and Monoclonal Antibodies Targeting Peripheral Nerves 骨关节炎疼痛的神经科学和神经免疫学解决方案:生物药物、生长因子、多肽和靶向周围神经的单克隆抗体
Q3 CLINICAL NEUROLOGY Pub Date : 2020-12-31 DOI: 10.20944/preprints202012.0823.v1
A. Mobasheri
Neuroscience is a vast discipline that deals with the anatomy, biochemistry, molecular biology, physiology and pathophysiology of central and peripheral nerves. Advances made through basic, translational, and clinical research in the field of neuroscience have great potential for long-lasting and beneficial impacts on human and animal health. The emerging field of biological therapy is intersecting with the disciplines of neuroscience, orthopaedics and rheumatology, creating new horizons for interdisciplinary and applied research. Biological drugs, growth factors, therapeutic peptides and monoclonal antibodies are being developed and tested for the treatment of painful arthritic and rheumatic diseases. This concise communication focuses on the solutions provided by the fields of neuroscience and neuroimmunology for real-world clinical problems in the field of orthopaedics and rheumatology, focusing on synovial joint pain and the emerging biological treatments that specifically target pathways implicated in osteoarthritis pain in peripheral nerves.
神经科学是一门涉及中枢神经和周围神经的解剖学、生物化学、分子生物学、生理学和病理生理学的广泛学科。神经科学领域的基础研究、转化研究和临床研究取得的进展对人类和动物健康具有巨大的长期和有益的影响潜力。生物治疗这一新兴领域正在与神经科学、骨科和风湿病学等学科交叉,为跨学科和应用研究创造新的视野。生物药物、生长因子、治疗性多肽和单克隆抗体正在开发和试验,用于治疗痛苦的关节炎和风湿病。这篇简短的交流主要集中在神经科学和神经免疫学领域为骨科和风湿病学领域的现实临床问题提供的解决方案,重点是滑膜关节疼痛和新兴的生物治疗,特别是针对周围神经中涉及骨关节炎疼痛的通路。
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引用次数: 0
Post-Mortem 7.0-Tesla Magnetic Resonance Imaging of the Hippocampus in Progressive Supranuclear Palsy with and without Cerebral Amyloid Angiopathy 伴和不伴脑淀粉样血管病的进行性核上性麻痹海马死后7.0-Tesla磁共振成像
Q3 CLINICAL NEUROLOGY Pub Date : 2020-12-21 DOI: 10.3390/neurosci1020011
J. Reuck, F. Auger, N. Durieux, C. Maurage, V. Deramecourt, C. Cordonnier, F. Pasquier, D. Leys, R. Bordet
Introduction and Purpose: Cerebral amyloid angiopathy (CAA) can be observed in patients with progressive supranuclear palsy (PSP), though to a lesser degree than in Alzheimer’s disease. The present post-mortem 7.0-tesla magnetic resonance imaging (MRI) evaluates whether CAA has an influence on the degree of hippocampal atrophy (HA) and on the incidence of associated micro-infarcts (HMIs) and cortical micro-bleeds (HMBs). Material and Methods: Eight brains with PSP-CAA were compared to 20 PSP brains without CAA. In addition to the neuropathological examination, the hippocampus was evaluated on the most representative coronal section with T2 and T2*-weighted MRI sequences. The average degree of HA was determined in both groups. The incidence of HMIs and HMBs was also compared as well as the frequency of cortical micro-infarcts (CoMIs) and cortical micro-bleeds (CoMBs) in the hemispheric neocortex. Results: The neuropathological examination showed a higher incidence of lacunar infarcts in the PSP-CAA brains compared to the PSP ones. With magnetic resonance imaging (MRI), the severity of HA and the incidence of HMIs and HMBs was similar between both groups. Additionally, the frequency of CoMIs and CoMBs in the neocortex was comparable. Conclusions: The association of CAA in PSP brains has no influence on the degree of HA and on the incidence of the small cerebrovascular lesions in the hippocampus as well as in the neocortex.
简介和目的:进行性核上性麻痹(PSP)患者可观察到脑淀粉样血管病(CAA),但其程度低于阿尔茨海默病。目前的死后7.0特斯拉磁共振成像(MRI)评估CAA是否对海马萎缩(HA)程度以及相关微梗死(hmi)和皮质微出血(HMBs)的发生率有影响。材料与方法:将8个PSP-CAA脑与20个不含CAA的PSP脑进行比较。除神经病理检查外,采用最具代表性的冠状面T2和T2加权MRI序列对海马进行评估。测定两组患者HA的平均程度。我们还比较了hmi和HMBs的发生率以及半球新皮层皮层微梗死(CoMIs)和皮层微出血(CoMBs)的频率。结果:神经病理学检查显示PSP- caa脑腔隙性梗死发生率高于PSP。磁共振成像(MRI)显示,两组患者HA的严重程度、hmi和hmb的发生率相似。此外,comi和CoMBs在新皮层的频率是相似的。结论:PSP脑内CAA的关联对HA程度和海马及新皮层小脑血管病变发生率无影响。
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引用次数: 0
Subjective Socioeconomic Status and Children's Amygdala Volume: Minorities' Diminish Returns. 主观社会经济地位与儿童杏仁核体积:少数群体的递减收益。
Q3 CLINICAL NEUROLOGY Pub Date : 2020-12-01 DOI: 10.3390/neurosci1020006
Shervin Assari, Shanika Boyce, Mohsen Bazargan

Considerable research has suggested that low socioeconomic status (SES) negatively influences brain structure, including but not limited to decreased amygdala volume. Considering race and ethnicity as sociological rather than biological constructs, this study was built on minorities' diminished returns (MDRs) to test if the effects of family SES on the total amygdala volume is weaker for black and Latino children than white and non-Latino children. We borrowed data from the Adolescent Brain Cognitive Development (ABCD) study, a national multi-center brain imaging investigation of childhood brain development in the US. The total sample was 9380 9-10-year-old children. The independent variables were subjective family SES and parental education. The primary outcome was total amygdala volume. High subjective SES and parental education were independently associated with larger total amygdala size. The association between high subjective SES and larger total amygdala volume was less pronounced for black and Latino children than white and non-Latino children. For American children, family SES has unequal effects on amygdala size and function, a pattern that is consistent with MDRs. This result suggests that SES loses some of its expected effects for racial and ethnic minority families.

大量研究表明,低社会经济地位(SES)会对大脑结构产生负面影响,包括但不限于杏仁核体积的减少。考虑到种族和民族是社会学而非生物学结构,本研究基于少数族裔的减少收益(mdr)来测试家庭经济地位对黑人和拉丁裔儿童的杏仁核总体积的影响是否比白人和非拉丁裔儿童弱。我们借用了青少年大脑认知发展(ABCD)研究的数据,这是一项美国儿童大脑发育的国家多中心脑成像研究。总样本为9380名9-10岁儿童。自变量为主观家庭经济地位和父母教育程度。主要观察指标为杏仁核总体积。主观社会经济地位高和父母受教育程度高与杏仁核总大小较大独立相关。与白人和非拉丁裔儿童相比,黑人和拉丁裔儿童主观经济地位高与杏仁核总体积较大之间的关联不那么明显。对于美国儿童来说,家庭经济地位对杏仁核大小和功能的影响是不相等的,这种模式与mdr是一致的。这一结果表明,社会经济地位对少数民族家庭失去了一些预期的影响。
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引用次数: 24
An Improved Method for Physical Separation of Cerebral Vasculature and Parenchyma Enables Detection of Blood-Brain-Barrier Dysfunction 一种改进的物理分离脑血管和脑实质的方法可以检测血脑屏障功能障碍
Q3 CLINICAL NEUROLOGY Pub Date : 2020-11-16 DOI: 10.20944/preprints202011.0404.v1
F. Matthes, Hana Matušková, Kajsa Arkelius, S. Ansar, I. Lundgaard, A. Meissner
The neurovascular niche is crucial for constant blood supply and blood-brain barrier (BBB) function and is altered in a number of different neurological conditions, making this an intensely active field of research. Brain vasculature is unique for its tight association of endothelial cells with astrocytic endfeet processes. Separation of the vascular compartment by centrifugation-based methods confirmed enrichment of astrocytic endfeet processes, making it possible to study the entire vascular niche with such methods. Several centrifugation-based separation protocols are found in the literature; however, with some constraints which limit their applicability and the scope of the studies. Here, we describe and validate a protocol for physically separating the neurovascular niche from the parenchyma, which is optimized for smaller tissue quantities. Using endothelial, neuronal, and astrocyte markers, we show that quantitative Western blot-based target detection can be performed of both the vessel-enriched and parenchymal fractions using as little as a single mouse brain hemisphere. Validation of our protocol in rodent stroke models by detecting changes in tight junction protein expression, serum albumin signals and astrocyte activation, i.e., increased glial fibrillary acidic protein expression, between the ipsilateral and the lesion-free contralateral hemisphere demonstrates this protocol as a new way of detecting BBB breakdown and astrogliosis, respectively.
神经血管生态位对于维持血液供应和血脑屏障(BBB)功能至关重要,并在许多不同的神经系统疾病中发生改变,使其成为一个非常活跃的研究领域。脑血管系统是独特的,其紧密关联的内皮细胞与星形细胞终足突。基于离心的方法分离血管室证实了星形细胞终足突的富集,使得用这种方法研究整个血管生态位成为可能。在文献中发现了几种基于离心的分离方案;然而,有一些限制,限制了它们的适用性和研究的范围。在这里,我们描述并验证了一种物理分离神经血管生态位与薄壁组织的方案,该方案针对较小的组织量进行了优化。利用内皮细胞、神经元和星形胶质细胞标记物,我们证明了基于Western blot的定量靶检测可以在血管富集和实质部分进行,只需使用单个小鼠大脑半球。我们的方案在啮齿类动物中风模型中通过检测同侧和无病变的对侧半球之间紧密连接蛋白表达、血清白蛋白信号和星形胶质细胞激活的变化(即胶质纤维酸性蛋白表达增加)来验证,表明该方案分别是检测血脑屏障破坏和星形胶质细胞形成的新方法。
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引用次数: 7
Systems Biology in Neuroscience: the Paramount Importance of Data Sharing and Citation 神经科学中的系统生物学:数据共享和引用的最高重要性
Q3 CLINICAL NEUROLOGY Pub Date : 2020-11-09 DOI: 10.3390/neurosci1020009
Xavier Gallart‐Palau
The emergence and maturation, in the last decade, of high powerful technologies in the fields of neurogenomics, neurometabolomics, and neuroproteomics has opened exciting novel possibilities of research [...]
在过去的十年中,神经基因组学、神经代谢组学和神经蛋白质组学领域的强大技术的出现和成熟,为研究提供了令人兴奋的新可能性[…]
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引用次数: 0
Statistical Properties in Jazz Improvisation Underline Individuality of Musical Representation 爵士乐即兴演奏的统计特性强调音乐表现的个性
Q3 CLINICAL NEUROLOGY Pub Date : 2020-09-21 DOI: 10.3390/NEUROSCI1010004
T. Daikoku
Statistical learning is an innate function in the brain and considered to be essential for producing and comprehending structured information such as music. Within the framework of statistical learning the brain has an ability to calculate the transitional probabilities of sequences such as speech and music, and to predict a future state using learned statistics. This paper computationally examines whether and how statistical learning and knowledge partially contributes to musical representation in jazz improvisation. The results represent the time-course variations in a musician’s statistical knowledge. Furthermore, the findings show that improvisational musical representation might be susceptible to higher- but not lower-order statistical knowledge (i.e., knowledge of higher-order transitional probability). The evidence also demonstrates the individuality of improvisation for each improviser, which in part depends on statistical knowledge. Thus, this study suggests that statistical properties in jazz improvisation underline individuality of musical representation.
统计学习是大脑的一种先天功能,对于产生和理解结构化信息(如音乐)至关重要。在统计学习的框架内,大脑有能力计算语音和音乐等序列的过渡概率,并利用所学的统计预测未来的状态。本文通过计算检验统计学习和知识是否以及如何部分地促进爵士乐即兴创作中的音乐表现。结果代表了音乐家统计知识的时间过程变化。此外,研究结果表明,即兴音乐表现可能容易受到高阶统计知识(即高阶过渡概率知识)的影响,但不受低阶统计知识的影响。证据还显示了每个即兴表演者的个性,这在一定程度上取决于统计知识。因此,本研究表明,爵士乐即兴演奏的统计特性强调了音乐表现的个性。
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引用次数: 0
Hematological Alterations Related to Treatment with Teriflunomide and Dimethyl Fumarate in Multiple Sclerosis 特立氟米特和富马酸二甲酯治疗多发性硬化症的血液学改变
Q3 CLINICAL NEUROLOGY Pub Date : 2020-09-21 DOI: 10.3390/NEUROSCI1010003
D. García-Estévez
The exact mechanism of action of different modifying treatments in the evolutionary course of multiple sclerosis (MS) remains unknown, but it is assumed that they act upon the cells involved in acquired immunity. One effect of these treatments is the development of lymphopenia, which carries inherent safety risks. This study was conducted to understand the alterations that teriflunomide (TERI) and dimethyl fumarate (DMF) exert upon white blood cells in a series of patients with MS. This study included a total of 99 patients; 44 treated with DMF and 55 patients treated with TERI. Blood counts were evaluated at baseline and every 6 months in order to track the absolute leukocyte, lymphocyte, and neutrophil counts. Twelve months after starting treatment, we observed a significant decrease in leukocytes (21.1%), lymphocytes (39.1%), and neutrophils (10%) in the DMF group. In the TERI group, leukocytes decreased by 11.1%, lymphocytes by 8.1%, and neutrophils by 15.7%. Both TERI and DMF produced a significant decrease in leukocytes during the first year of treatment and this was mainly related with a decrease in neutrophils in the TERI group and a decrease in lymphocytes in the DMF group.
不同修饰治疗在多发性硬化(MS)进化过程中的确切作用机制尚不清楚,但假设它们作用于参与获得性免疫的细胞。这些治疗的一个影响是淋巴细胞减少症的发展,这带有固有的安全风险。本研究旨在了解特立氟米特(teri氟米特,TERI)和富马酸二甲酯(DMF)对一系列多发性硬化症患者白细胞的影响。44例采用DMF治疗,55例采用TERI治疗。在基线和每6个月评估一次血细胞计数,以跟踪绝对白细胞、淋巴细胞和中性粒细胞计数。开始治疗12个月后,我们观察到DMF组白细胞(21.1%)、淋巴细胞(39.1%)和中性粒细胞(10%)显著下降。在TERI组,白细胞减少11.1%,淋巴细胞减少8.1%,中性粒细胞减少15.7%。在治疗的第一年,TERI和DMF都产生了白细胞的显著减少,这主要与TERI组中性粒细胞的减少和DMF组淋巴细胞的减少有关。
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引用次数: 3
Motivational and Control Mechanisms Underlying Adolescent versus Adult Alcohol Use 青少年与成人酒精使用的动机和控制机制
Q3 CLINICAL NEUROLOGY Pub Date : 2020-09-05 DOI: 10.20944/preprints202009.0131.v1
J. Cousijn, Kayla H. Green, M. Labots, L. Vanderschuren, J. Kenemans, H. Lesscher
Increased motivation towards alcohol use and suboptimal behavioral control are suggested to predispose adolescents to alcohol use disorders (AUDs). Paradoxically however, most adolescent AUDs resolve over time without any formal intervention, suggesting adolescent resilience to AUDs. Importantly, studies directly comparing adolescent and adult alcohol use are largely missing. We therefore aimed to unravel the moderating role of age in the relation between alcohol use and motivational and control-related cognitive processes in 45 adolescent drinkers compared to 45 adults. We found that enhancement drinking motives and impulsivity related positively to alcohol use. Although enhancement drinking motives and impulsivity were higher in adolescents, the strength of the relation between these measures and alcohol use did not differ between age groups. None of the alcohol use-related motivational measures (i.e., craving, attentional bias, and approach bias) and behavioral control measures (i.e., interference control, risky decision making, and working-memory) were associated with alcohol use or differed between age groups. These findings support the role of impulsivity and affective sensitivity in adolescent drinking but question the moderating role of age therein. The current study contributes towards understanding the role of age in the relation between alcohol use and cognition.
酒精使用动机增加和次优行为控制被认为是青少年酒精使用障碍(AUDs)的易感因素。然而,矛盾的是,大多数青少年aud在没有任何正式干预的情况下随着时间的推移而消退,这表明青少年对aud的适应能力。重要的是,直接比较青少年和成人饮酒的研究在很大程度上是缺失的。因此,我们旨在揭示年龄在45名青少年饮酒者与45名成年人的酒精使用与动机和控制相关认知过程之间的关系中的调节作用。我们发现增强饮酒动机和冲动性与酒精使用呈正相关。虽然增强饮酒动机和冲动性在青少年中较高,但这些措施与酒精使用之间的关系强度在年龄组之间没有差异。与酒精使用相关的动机测量(如渴望、注意偏差和方法偏差)和行为控制测量(如干扰控制、风险决策和工作记忆)与酒精使用无关,也没有年龄组之间的差异。这些发现支持冲动和情感敏感性在青少年饮酒中的作用,但质疑年龄在其中的调节作用。目前的研究有助于理解年龄在酒精使用和认知之间的关系中的作用。
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引用次数: 2
The Rotenone Models Reproducing Central and Peripheral Features of Parkinson’s Disease 再现帕金森病中枢和外周特征的鱼藤酮模型
Q3 CLINICAL NEUROLOGY Pub Date : 2020-08-05 DOI: 10.3390/neurosci1010001
I. Miyazaki, M. Asanuma
Parkinson’s disease (PD) is a complex, multi-system, neurodegenerative disorder; PD patients exhibit motor symptoms (such as akinesia/bradykinesia, tremor, rigidity, and postural instability) due to a loss of nigrostriatal dopaminergic neurons, and non-motor symptoms such as hyposmia, autonomic disturbance, depression, and REM sleep behavior disorder (RBD), which precedes motor symptoms. Pathologically, α-synuclein deposition is observed in the central and peripheral nervous system of sporadic PD patients. To clarify the mechanism of neurodegeneration in PD and to develop treatment to slow or stop PD progression, there is a great need for experimental models which reproduce neurological features of PD. Animal models exposed to rotenone, a commonly used pesticide, have received most attention since Greenamyre and his colleagues reported that chronic exposure to rotenone could reproduce the anatomical, neurochemical, behavioral, and neuropathological features of PD. In addition, recent studies demonstrated that rotenone induced neuropathological change not only in the central nervous system but also in the peripheral nervous system in animals. In this article, we review rotenone models especially focused on reproducibility of central and peripheral multiple features of PD. This review also highlights utility of rotenone models for investigation of PD pathogenesis and development of disease-modifying drugs for PD in future.
帕金森病(PD)是一种复杂的多系统神经退行性疾病;由于黑质纹状体多巴胺能神经元的缺失,PD患者表现出运动症状(如运动障碍/运动迟缓、震颤、强直和姿势不稳定),以及非运动症状,如低体温、自主神经障碍、抑郁和快速眼动睡眠行为障碍(RBD),这些症状发生在运动症状之前。病理上,散发性PD患者的中枢和周围神经系统可见α-突触核蛋白沉积。为了阐明帕金森病神经退行性变的机制,开发减缓或阻止帕金森病进展的治疗方法,迫切需要能够再现帕金森病神经学特征的实验模型。自从Greenamyre和他的同事报道长期暴露于鱼藤酮(一种常用的农药)可以重现PD的解剖、神经化学、行为和神经病理特征以来,暴露于鱼藤酮的动物模型受到了极大的关注。此外,近年来的研究表明,鱼藤酮不仅能引起动物中枢神经系统的神经病理改变,还能引起周围神经系统的神经病理改变。在本文中,我们回顾了鱼藤酮模型,特别是关注PD的中心和周围多重特征的再现性。本文综述了鱼藤酮模型在帕金森病发病机制研究和帕金森病治疗药物开发中的应用。
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引用次数: 10
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