Regulatory T cells in the central nervous system

Regulatory T cells (Tregs) are critical to the human immune system, providing appropriately scaled immune responses and mediating peripheral tolerance. A central role for forkhead box protein 3 (FoxP3)(+) Tregs has been shown in the pathogenesis of mechanistically diverse central nervous system (CNS) diseases from autoimmune diseases such as multiple sclerosis to glioblastomas. Understanding how tumors induce Treg function to escape immune surveillance in marked contrast to autoimmune diseases, where there is loss of Treg function, will provide valuable lessons regarding Treg biology and potential therapeutic targets for CNS diseases.     

原发性中枢神经系统淋巴瘤临床病理及病因学分析

目的 探讨原发性中枢神经系统淋巴瘤(primary central nervous system lymphoma, PCNSL)的临床病理特征、预后指标及病因学.方法 复习39例PCNSL患者的临床资料,同时进行免疫组化、原位杂交检测EBER及PCR检测bcl-2/JH基因重排,并对临床资料、免疫标志物与预后的关系进行分析.结果 34例PCNSL患者的3年生存率为46.4%,5年生存率为27.1%,年龄≥60岁及病变部位深对预后不利(P=0.009和P=0.027),bcl-6阳性表达者的生存率高于阴性表达者(P=0.044),但多因素Cox回归分析显示,进入回归方程的为年龄因素.CD10/bcl-6/MUM-1/CD138分型和治疗方法对预后的判断无显著性差异(P＞0.05).39例患者EBER原位杂交均为阴性,bcl-2/JH基因重排5例阳性(12.8%),其中3例为CD10阳性病例.结论 PCNSL是一种少见的高侵袭性结外非霍奇金淋巴瘤,年龄因素是判断预后的独立性指标,CD10/bcl-6/MUM-1/CD138分型未发现有预后意义,但显示PCNSL的同质性较高,可能是弥漫性大B细胞淋巴瘤的一种亚型.EB病毒感染与PCNSL的病因无相关性.     

中枢神经系统非典型畸胎瘤样/横纹肌样瘤临床病理特点

目的探讨中枢神经系统非典型畸胎瘤样／横纹肌样瘤(atypical teratoid／rhabdoid tumor，AT／RT)的临床病理特征、组织发生及预后。方法应用光镜、特殊染色及免疫组化染色观察1例2岁儿童大脑AT／RT的病理组织学特点，结合国内外文献进行讨论。结果肿瘤含有横纹肌样细胞、原始神经外胚层、上皮及间叶多向分化成分。肿瘤中网状纤维丰．富。免疫组化染色Vim、EMA、CKpan、GFAP、Syn及CgA均呈阳性表达，PLAP、CD117、SMA及：NF?呈阴性反应。结论AT／RT为发生在儿童中枢神经系统罕见的高度恶性肿瘤，多数患者1年内死亡。肿瘤极易误诊为髓母细胞瘤、原始神经外胚叶肿瘤(PNET)、脉络丛乳头状癌及生殖细胞肿瘤。免疫组化染色对确诊AT／RT十分重要。本瘤的组织发生仍不清楚。     

Double immunolabeling of central nervous system atypical teratoid/rhabdoid tumors.

The central nervous system atypical teratoid/rhabdoid tumor (ATRT) is a highly malignant tumor with a heterogeneous immunohistochemical profile and with some morphologic similarity to central nervous system primitive neuroectodermal tumors (PNET). Although several studies have investigated double immunolabeling in PNET, we are aware of no studies of double labeling of ATRT. A total of 10 ATRT from surgical and consultation materials at the Children's Hospital of Philadelphia were selected and stained for a variety of antigens using indirect immunofluorescence to detect single and double labeling. Most tumor cells showed only single labeling; rare cells showed double labeling as follows: 70% of tumors coexpressed (VIM) and glial fibrillary acidic protein (GFAP), 30% smooth muscle actin and GFAP, 20% epithelial membrane antigen (EMA) and VIM, 20% EMA/GFAP, and 20% EMA/SMA. These results are discussed in view of current debates over the histogenesis of CNS PNET and ATRT, and in reference to the classification of rhabdoid tumors as an entity or phenotype.     

Endogenous colony formation in mice with experimental pathology of the central nervous system

Models of endo- and exogenous clone formation were used to study colony formation in (CBA X C57B1)F1 mice in different periods after damage to the hypothalamic structures. The following dynamics of colony formation was revealed in the animals with hypothalamic damage in endogenous clone formation: intensified colony formation occurring 24 hours after injury to the brain structures was replaced by a tendency to decrease in 4 days, which was followed by marked inhibition of colony formation 8 days after injury to the hypothalamic structures. The effect of inhibition of colony formation was encountered in animals with damage to the posterior hypothalamic field. No essential changes were revealed in colony formation 4 and 8 hours after hypothalamic injury in exogenous clone formation. Comparison of the results of endo- and exogenous clone formation suggests that the inhibition of colony formation in late-term periods after injury to the posterior hypothalamic field may be due to inhibition of the migration of hematopoietic stem cells from the bone marrow.     

The role of astrocytes in the physiology and pathology of the central nervous system

Astrocytes are the main class of neuroglia, serving a wide range of adaptive functions in the mammalian nervous system. They interact with neurons, providing structural, metabolic and trophic support for them. In pathological circumstances, astrocytes have the potential to induce neuronal dysfunction, but they can also play a neuroprotective role, releasing neuronal growth factors. Here we review recent findings regarding the role of astrocytes in the biology of the brain in physiological conditions, as well as their reaction following the onset of neurodegenerative disorders.     

A new approach to understanding adaptive visual-vestibular interactions in the central nervous system

Recent neurophysiological findings, cited in previous publications imply that some vestibular commissural pathways may form positive feedback loops across the midline. It has already been shown theoretically that such feedback coupling of the vestibular nuclei could play an important role in the realization of the central integrator in the vestibuloocular reflex (VOR). In addition, it was found that known commissural plasticity during vestibular compensation, if placed at the level of such cross-midline loops, could reconcile findings after labyrinthine lesions. This paper examines theoretically the role such commissural feedback loops could play in the adaptation of the dynamics of the VOR in normal behaving animals. A simple static example is used to illustrate that changes in synaptic efficacy along cross-midline feedback loops could serve to adjust both balance and gain in vestibular reflexes. A bilateral model of the VOR and its interactions with vision is used to explore analytically the consequences of parametric changes along cerebellar and/or commissural pathways in three protocols: VOR in the dark, visual pursuit, and visual VOR suppression. Model predictions are systematically related to published findings after short- and long-term adaptation of the VOR. Conclusions arising from the theoretical results point to specific strategies that can be used in experiments on intact alert animals, in the further study of vestibular adaptation, and in the diagnosis of possible sites of plasticity. This should be relevant to arguments on cerebellar versus brain stem sites for vestibular adaptation, currently a highly controversial issue. For example, it is found that observations of responses in the adapted VOR in the dark are not sufficient to distinguish between a brain stem or cerebellar site for VOR plasticity. Also, the analysis shows that, in the model, changes in the VOR gain would often be associated with parallel changes in VOR dynamics; this has often been reported, but previously left unexplained. Model predictions of response changes in the adapted VOR, during VOR suppression, do provide a means of distinguishing between brain stem or cerebellar sites of plasticity; only the brain stem site, postulated here in the commissural loops, would produce cerebellar response changes compatible with the observations of Miles and Lisberger, during long-term adaptation of the VOR. A cerebellar site for VOR adaptation in the model would produce changes in cerebellar responses that would only be compatible with observations to date during rapid, or short-term (hours), modification of the VOR, as reported by Ito and his group.(ABSTRACT TRUNCATED AT 400 WORDS)     

A new hypothesis for electrical transmission in the mammalian central nervous system.

It has been previously shown that the anatomical synapse does not exist in the living central nervous system, and that receptors are unlikely to be unique molecules sited on particular locations in or on the cell membrane. These conclusions and the rapidity of action of intravenously administered substances necessitated the adumbration of a new electrical hypothesis for the mechanism whereby signals pass from one part of the brain and spinal cord to another. The hypothesis proposed implies some testable predictions.     

中枢神经系统非典型畸胎样/横纹肌样瘤临床病理及免疫表型特征

目的 探讨中枢神经系统非典型畸胎样／横纹肌样瘤的临床病理特征、诊断及鉴别诊断。方法 对2例非典型畸胎样／横纹肌样瘤应用光镜行HE、网状纤维染色及免疫组织化学染色观察,并结合文献复习。结果 非典型畸胎样／横纹肌样瘤具有特征性的横纹肌样细胞,伴有不同程度的原始神经外胚叶、上皮和间质分化。肿瘤组织富于网状纤维,免疫组织化学标记示波形蛋白、CD99、上皮细胞膜抗原、细胞角蛋白、胶质纤维酸性蛋白、S-100蛋白、神经微丝蛋白、结蛋白、平滑肌肌动蛋白阳性,突触素、肌调节蛋白、胎盘碱性磷酸酶和HMB45阴性。结论 非典型畸胎样／横纹肌样瘤是中枢神经系统一种罕见的高度恶性肿瘤,好发于儿童,偶见于成人,呈异源性组织学和免疫组织化学表型。其诊断需与脑内其他多形性肿瘤鉴别。     

Pathogenetic and morphological characteristics of acute inflammation of the central nervous system

Virus, bacteria, mycoplasma, protozoa can be the causes of acute neuroinfections. The agents can penetrate into the brain by blood, nerve, lymphatic vessels, from the sinuses directly. Peculiarities of manifestations of acute neuroinfections depend on the agent tropism to receptors of nervous cell and specificity of brain immunoreactivity. The brain injuries can be induced by microorganism action or through immunopathologic processes. Dynamics of morphological changes in acute neuroinfections of different etiology are summarized. Histological, cytological, bacteriological, serological, immunofluorescent, histochemical methods are evaluated. Acute neuroinfection pathogenesis has many unresolved problems.     

State of the small intestine and its intramural nervous system after interruption of all nervous connections with the central nervous system

Central denervation of the small intestine causes sharply defined and prolonged disturbances of its structure and function. Reinnervation reduces the severity of these disturbances and hastens the return to a normal state of the intestine.Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Kovanov.Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 70, No. 12, pp. 101–105, December, 1970. Original article submitted August 18, 1969.     

Glutathione: new candidate neuropeptide in the central nervous system.

The physiological significance of glutathione in the mammalian central nervous system is still uncertain, although some evidence indicates that it may be an important regulatory peptide. In the present study, the distribution and characteristics of glutathione binding sites in the brain have been studied. Biotinyl-glutathione was synthesized as a probe to detect glutathione binding sites in the CNS. Specific glutathione binding sites in the brain were largely localized to the white matter, suggesting the presence of glutathione receptors on neuroglial cells. The colloidal gold technique and immunofluorescence double staining allowed the visualization of the receptor at the cellular level and thus demonstrated that there are glutathione receptors on cultured astrocytes. Glutathione applied to cultured astrocytes elicited increased levels of intracellular inositol-1,4,5-trisphosphate, suggesting that glutathione receptors were coupled to phospholipase C. The localization of glutathione receptors on astrocytes and the activation of a second messenger system by glutathione suggest that glutathione may be a neuropeptide in the central nervous system.     

The role of electron microscopy in the diagnosis of surgical pathology in the central nervous system

Electron microscopy has played an important role in the diagnosis of surgical pathology and the establishment of new tumor entities and variants in the central nervous system. However, the use of ultrastructural analysis of brain tumors has decreased with the advent of immunohistochemistry. I present here my personal experiences and perspective on the role of electron microscopy in surgical neuropathology.