小胶质细胞在中枢神经系统和胶质瘤中的免疫学作用及其相关研究进展

血脑屏障在正常情况下能够保证脑的内环境的高度稳定性,以利于中枢神经系统的机能活动.中枢神经系统内缺乏各种常见的抗原递呈细胞,但小胶质细胞可作为潜在的抗原递呈细胞将MHC分子结合的抗原肽与T细胞受体结合介导相应的免疫反应.而在胶质瘤组织中高度浸润的小胶质细胞可通过对肿瘤微环境的免疫抑制而促进肿瘤生长.一旦小胶质细胞被激活就能成为强大的免疫效应细胞,在中枢神经系统损伤和疾病中发挥多种生物学功能.     

小胶质细胞在创伤性脑损伤中作用的研究进展

小胶质细胞(MG)是人体中枢神经系统(CNS)固有的免疫细胞成分,正常情况下处于静止状态,缺乏吞噬功能,仅具有一定的迁移能力和吞饮功能。但作为CNS的第一道防线,可在CNS病变时被激活发挥类似于巨噬细胞的吞噬保护功能;当功能发生紊乱时又会加重病变的发生发展,从而具有修复和损伤的"双刃剑"作用。创伤性脑损伤(TBI)是一个影响社会的重大健康和社会经济问题,包括突然加速或减速的间接损伤、冲击或撞击引起的脑挫伤和爆炸伤等。TBI发生时会激活MG,使其增生与聚集,同时常伴有免疫表型、细胞形态与功能等一系列的变化。本文旨在针对MG参与TBI病理生理过程进行综述。     

小胶质细胞引起和促进阿尔茨海默病的研究进展

小胶质细胞是神经系统免疫细胞,具有双重特性,既可以通过免疫反应增强吞噬能力、释放抗炎因子维持脑组织的稳态和保护神经元,又可以增加炎性反应、降低有害蛋白清除能力损伤神经元.受衰老的影响,在基因表达方面,小胶质细胞CD33表达增加而髓系细胞触发受体2(TREM2)表达减少;在活化表型方面,衰老环境下的小胶质细胞更倾向活化为...     

小胶质细胞及其相关炎性信号通路

小胶质细胞作为中枢系统重要的免疫效应细胞,在中枢神经系统损伤及疾病处理中发挥着不可忽视的作用。本文从小胶质细胞的生物学特性及其相关的炎性信号通路（Notch信号通路、Toll样信号通路、AMPK信号通路、NF-κB信号通路）两大方面探讨,以期为临床抗炎药物的开发提供新思路。     

小胶质细胞在中枢神经系统介导的免疫损伤与保护作用的研究进展

20世纪初,人们对小胶质细胞进行了较为详细的观察,由此开始了对这一重要免疫细胞的深入研究。小胶质细胞作为中枢神经系统(CNS)的一种组织巨噬细胞,在成熟大脑稳定状态、组织发生过程以及损伤、疾病、修复等病理状态具有不同的形态和功能,并具有不同的免疫活性。其在CNS的功能和疾病介导作用,是深入研究的热点。     

小胶质细胞在自杀中的作用及其机制

自杀的发生率日益提高,但是其发生机制尚不清楚。近年来的研究表明神经生物学因素与自杀有着密切的关系。作为中枢神经系统的重要组成部分,小胶质细胞对神经递质代谢、免疫调节和神经炎症等都有较大影响,过度激活的小胶质细胞被认为在自杀中发挥了重要作用。本文将对小胶质细胞状态与自杀的关系,以及小胶质细胞介导的神经炎症、神经免疫、应激反应过程影响自杀行为的相关机制进行综述,以期为自杀的神经机制研究提供思路,为自杀预防策略的制定提供理论依据。     

小胶质细胞在神经系统病变中的作用

小胶质细胞(micro-glia,MG)是广泛分布于哺乳动物中枢神经系统的一种具有运动活性的细胞[1]。1891年Nissl首次描述MG后,MG一直以来都很受人们的重视。1919年,西班牙学者Del Rion-Horte-ga用碳酸银染色法将MG与其它细胞区分开来,并证明它是中枢神经系统最具代表性的免疫细胞。在     

小胶质细胞与脑缺血

自从1891年Nissl首次描述小胶质细胞以来,它一直受到人们的重视,学术争论不断,现在人们注意到小胶质细胞作为中枢神经系统固有的免疫效应细胞参与其免疫反应和病理过程。研究发现小胶质细胞在脑缺血后异常活跃,脑缺血所激发的小胶质细胞反应极为复杂,现将小胶质细胞在脑缺血病理过程中形态变化和保护作用等作一综述。     

星形胶质细胞在中枢神经系统炎性疾病中作用的研究进展

星形胶质细胞应对多种中枢神经系统(CNS)损伤并活化为反应性星形胶质细胞,通过神经保护或神经毒性作用影响CNS的组织修复和神经炎性疾病的发生和发展.反应性星形胶质细胞的发生机制主要与其表型转化及下游炎性通路的激活相关.探索反应性星形胶质细胞的特征及其对CNS炎性疾病的调控机制可能为CNS炎性疾病的发病机制提供新见解和潜在干预靶点.     

小胶质细胞对坐骨神经损伤后的反应

目的 探讨对小细胞对周围神经损伤的反应。方法 用Thymosin β4抗体标汜小胶质细胞,在大鼠坐骨神经切断后1、2、3、4、6、8、10、12、14、18、20d,检测其脊髓及脑干内小胶质细胞、并对有变化者用电镜观察。结果 发现在坐骨神经损伤后第1天开始至第20天,在相应脊髓节段同侧灰质及脑干的薄束核内见到许多体积增大、数量增多的Thymosin β4标记阳性细胞即激活的小胶质细胞。激活的小胶质细胞数量在损伤后第3天达到高峰,然后逐渐下降,至第20天后才消失;与相应脊髓节段相比较,薄束核内激活的小胶质细胞数量要少些。电镜观察发现,这些激活的小胶质细胞多位于神经元胞体的周围并与神经元有密切的接触。结论 周围神经损伤,可引起相应中枢部位的小胶质细胞激活与增殖．其作用可能与保护受损的神经元、维护神经元的周围环境有关。     

Rare case of a primary non-dural central nervous system low grade B-cell lymphoma and literature review

We present a case of a 70-year-old HIV negative man with a five-year history of progressive dysnomia and new onset right extremity numbness, dysarthria, and blurry vision. On magnetic resonance imaging (MRI), an infiltrative enhancing tumor was noted. Follow up brain biopsy results revealed a small lymphocytic infiltrate with scattered plasma cells in a predominantly perivascular growth pattern. Flow-cytometric findings revealed a lambda monotypic B-cell population. The morphology and the flow cytometric findings were consistent with involvement by a low grade B-cell lymphoma. Subsequent positron emission tomography (PET) studies along with bone marrow biopsy and serum protein electrophoresis showed no evidence of systemic disease. The above findings are consistent with involvement by a non-dural extranodal marginal zone B-cell lymphoma (MZBCL) primary to the central nervous system (CNS). This is the first reported case of a primary CNS MZBCL with flow cytometric analysis. A review of literature on this rare entity is also included.     

Early pathological changes in the central nervous system of acutely feline-immunodeficiency-virus-infected cats

The animal model of feline immunodeficiency virus (FIV) infection of cats was used to dissect the pathogenic role of microglia within the first 6 months of infection. Applying real-time PCR, microglia-associated FIV replication was first detectable at 14 days past inoculation (dpi) and remained at elevated levels throughout the whole observation period. In contrast, FIV RNA levels within paired serum samples declined again after an initial peak between 14 dpi and 28 dpi. Concomitant with the onset of viral reproduction, microglia transiently upregulated expression of MHC class I and class II molecules. Virus-induced microglial activation was followed by a mild infiltration of peripheral leukocytes into the CNS parenchyma. The presented data suggest that microglia is infected by FIV very early after peripheral entry of the virus. Virus replicating microglia withstands eradication by brain-infiltrating leukocytes resulting in formation of a brain-resident virus reservoir, which probably cannot be cleared by peripheral chemotherapy.     

Factors influencing the response to high dose methotrexate-based vincristine and procarbazine combination chemotherapy for primary central nervous system lymphoma

The authors investigated objective response rate to high dose methotrexate (HDMTX)-based combination chemotherapy in primary central nervous system lymphoma (PCNSL), and sought to identify factors that influence response to HDMTX-based combination therapy. Prospective observational analysis was performed on 52 PCNSL patients. All patients received HDMTX (3.5 g/m(2)) and vincristine (1.4 mg/m(2)/day) for one day during weeks 1, 3, 5, 7, and 9, and procarbazine (100 mg/m(2)/day) for one week during weeks 1, 5, and 9. Forty-one patients (78.8%) achieved complete or partial remission. Higher objective response rates were observed for patients with: 1) age < 60 yr; 2) Eastern Cooperative Oncology Group (ECOG) performance score of < 2; 3) low risk status as defined by the International Extranodal Lymphoma Study Group; 4) p53 positivity; 5) XBP-1 negativity; 6) MUM-1 negativity; and 7) homogenous gadolinium enhancement in MR images. Multivariate analysis showed that ECOG performance score of < 2, low risk, negativity for XBP-1, homogenous gadolinium enhancement by MRI, and response to chemotherapy were associated with longer overall survival. In particular, it is interesting to note that patients with a PCNSL that is homogeneously enhanced by gadolinium have a higher objective response rate, and a longer progression-free survival and overall survival.     

Bridges between nervous and immune systems: their disconnection and clinical consequences

Nervous and immune systems are connected by several mutual links, thus constituting a diffuse functional network in the body. In particular, neurohormones, neuropeptides, and cytokines represent the major mediators of the so-called psychoneuroendocrinoimmune axis. In this review, special emphasis is placed on certain pathologies characterized by a disconnection of the existing bridges between nervous and immune systems. For instance, spinal cord injury (SCI) is a clinical condition in which loss of neurons and very poor axon growth represent the main features. The role played by infiltrating and resident immunocompetent cells is still debated in SCI. However, to enhance axon growth in SCI, current therapeutic attempts are based on the stimulation of the immune response within the central nervous system, thus triggering either cell-mediated or humoral immune responsiveness.     

Tandem high-dose chemotherapy and autologous stem cell transplantation in young children with atypical teratoid/rhabdoid tumor of the central nervous system

The feasibility and effectiveness of tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT) were evaluated in children younger than 3 yr of age with atypical teratoid/rhabdoid tumors (ATRT). Tandem HDCT/autoSCT was administered following six cycles of induction chemotherapy. Radiotherapy (RT) was administered if the tumor relapsed or progressed, otherwise, it was administered after 3 yr of age. Tumors relapsed or progressed during induction chemotherapy in 5 of 9 patients enrolled; 3 of these 5 received tandem HDCT/autoSCT as a salvage treatment. One patient died from sepsis during induction chemotherapy. The remaining 3 patients proceeded to tandem HDCT/autoSCT; however, 2 of these patients showed tumor relapse/progression after tandem HDCT/autoSCT. All 7 relapses/progressions occurred at primary sites even in patients with leptomeningeal seeding. Toxicities during tandem HDCT/autoSCT were manageable. A total of 5 patients were alive with a median follow-up of 20 (range 16-70) months from diagnosis. Four of 5 patients who received RT after relapse/progression are alive. The probability of overall survival at 3 yr from diagnosis was 53.3% ± 17.3%. Our tandem HDCT/autoSCT is feasible; however, early administration of RT prior to tandem HDCT/autoSCT should be considered to improve the outcome after tandem HDCT/autoSCT.     

对中枢与外周运动性疲劳的再认识

背景：在运动性疲劳的研究工作中,不少学者多采用力竭的动物模型,混淆了筋疲力尽与运动性疲劳。 目的：正确的认识运动性疲劳,了解其发生机制,掌握合理有效的防治措施从而消除疲劳对增进大众健康、提高运动成绩、预防运动伤病的发生,对运动性疲劳的概念、研究现状以及存在问题进行综合分析。 方法：以“运动性疲劳、外周疲劳;中枢疲劳、exercise-induced fatigue”为检索词,计算机检索Medline、EMbase、中国生物医学文献数据库、中国期刊全文数据库1966至-2014年与运动性疲劳或与运动疲劳密切相关的文献,对其中49篇进行归纳总结。 结果与结论：运动性疲劳研究的标准和条件控制存在需要再认识的问题,关于中枢疲劳和外周疲劳发生部位、原因与物质变化依旧存在很大的争议。外周疲劳发生在神经肌肉接头、横管系统、肌浆网、线粒体及肌细胞膜等部位,并引起相应的物质变化。运动性中枢疲劳时中枢神经系统产生的神经递质、调质、神经激素会发生相应的变化,这些改变与运动性中枢疲劳的产生有密切关系。 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

Role of microglia in central nervous system infections

The nature of microglia fascinated many prominent researchers in the 19th and early 20th centuries, and in a classic treatise in 1932, Pio del Rio-Hortega formulated a number of concepts regarding the function of these resident macrophages of the brain parenchyma that remain relevant to this day. However, a renaissance of interest in microglia occurred toward the end of the 20th century, fueled by the recognition of their role in neuropathogenesis of infectious agents, such as human immunodeficiency virus type 1, and by what appears to be their participation in other neurodegenerative and neuroinflammatory disorders. During the same period, insights into the physiological and pathological properties of microglia were gained from in vivo and in vitro studies of neurotropic viruses, bacteria, fungi, parasites, and prions, which are reviewed in this article. New concepts that have emerged from these studies include the importance of cytokines and chemokines produced by activated microglia in neurodegenerative and neuroprotective processes and the elegant but astonishingly complex interactions between microglia, astrocytes, lymphocytes, and neurons that underlie these processes. It is proposed that an enhanced understanding of microglia will yield improved therapies of central nervous system infections, since such therapies are, by and large, sorely needed.     

Copolymer effects on microglia and T cells in the central nervous system of humanized mice

The random amino acid copolymers FYAK and VWAK ameliorate EAE in a humanized mouse model expressing both a human transgenic myelin basic protein (MBP)85-99-specific T cell receptor and HLA-DR2. Here we show that microglia isolated from the central nervous system (CNS) of humanized mice with EAE induced by MBP85-99 and treated with these copolymers had reduced expression of HLA-DR, and thus reduced capacity to present MBP85-99 and activate transgenic T cells. In vitro microglia up-regulated empty HLA-DR2 upon activation with GM-CSF with or without LPS or IFN-gamma, but not with IL-4 or IL-10. Correspondingly, gene chip arrays showed that the CNS of untreated and YFAK-treated mice differentially expressed pro- and anti-inflammatory molecules during MBP85-99-induced EAE. Interestingly, microglia expressed the full-length gammabeta and alphabeta subunits of the tetrameric adaptor protein complexes AP-1 and AP-2 respectively, but after treatment with GM-CSF these complexes were cleaved, as had been found in immature dendritic cells derived from bone marrow. Strikingly, in vivo the perivascular lymphocyte infiltration seen in untreated mice immunized with MBP85-99 was composed of equal numbers of hVbeta2+ MPB85-99-specific transgenic and hVbeta2- endogenous T cells, while the much smaller infiltration seen after treatment with YFAK was composed predominantly of hVbeta2- endogenous T cells.