Phenotype of Antigen Unexperienced TH Cells in the Inflamed Central Nervous System in Experimental Autoimmune Encephalomyelitis.

Science.gov (United States)

Franck, Sophia; Paterka, Magdalena; Birkenstock, Jerome; Zipp, Frauke; Siffrin, Volker; Witsch, Esther

2017-06-01

Multiple sclerosis is a chronic, disseminated inflammation of the central nervous system which is thought to be driven by autoimmune T cells. Genetic association studies in multiple sclerosis and a large number of studies in the animal model of the disease support a role for effector/memory T helper cells. However, the mechanisms underlying relapses, remission and chronic progression in multiple sclerosis or the animal model experimental autoimmune encephalomyelitis, are not clear. In particular, there is only scarce information on the role of central nervous system-invading naive T helper cells in these processes. By applying two-photon laser scanning microscopy we could show in vivo that antigen unexperienced T helper cells migrated into the deep parenchyma of the inflamed central nervous system in experimental autoimmune encephalomyelitis, independent of their antigen specificity. Using flow cytometric analyses of central nervous system-derived lymphocytes we found that only antigen-specific, formerly naive T helper cells became activated during inflammation of the central nervous system encountering their corresponding antigen.

Early and late endocrine effects in pediatric central nervous system diseases.

Science.gov (United States)

Aslan, Ivy R; Cheung, Clement C

2014-01-01

Endocrinopathies are frequently linked to central nervous system disease, both as early effects prior to the disease diagnosis and/or late effects after the disease has been treated. In particular, tumors and infiltrative diseases of the brain and pituitary, such as craniopharyngioma, optic pathway and hypothalamic gliomas, intracranial germ cell tumor, and Langerhans cell histiocytosis, can present with abnormal endocrine manifestations that precede the development of neurological symptoms. Early endocrine effects include diabetes insipidus, growth failure, obesity, and precocious or delayed puberty. With improving prognosis and treatment of childhood brain tumors, many survivors experience late endocrine effects related to medical and surgical interventions. Chemotherapeutic agents and radiation therapy can affect the hypothalamic-pituitary axes governing growth, thyroid, gonadal, and adrenal function. In addition, obesity and metabolic alterations are frequent late manifestations. Diagnosing and treating both early and late endocrine manifestations can dramatically improve the growth, well-being, and quality of life of patients with childhood central nervous system diseases.

Neuronal chemokines : Versatile messengers in central nervous system cell interaction

NARCIS (Netherlands)

de Haas, A. H.; van Weering, H. R. J.; de Jong, E. K.; Boddeke, H. W. G. M.; Biber, K. P. H.

2007-01-01

Whereas chemokines are well known for their ability to induce cell migration, only recently it became evident that chemokines also control a variety of other cell functions and are versatile messengers in the interaction between a diversity of cell types. In the central nervous system (CNS),

Lactate overrides central nervous but not beta-cell glucose sensing in humans.

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Schmid, Sebastian M; Jauch-Chara, Kamila; Hallschmid, Manfred; Oltmanns, Kerstin M; Peters, Achim; Born, Jan; Schultes, Bernd

2008-12-01

Lactate has been shown to serve as an alternative energy substrate in the central nervous system and to interact with hypothalamic glucose sensors. On the background of marked similarities between central nervous and beta-cell glucose sensing, we examined whether lactate also interacts with pancreatic glucose-sensing mechanisms in vivo. The effects of intravenously infused lactate vs placebo (saline) on central nervous and pancreatic glucose sensing were assessed during euglycemic and hypoglycemic clamp experiments in 10 healthy men. The release of neuroendocrine counterregulatory hormones during hypoglycemia was considered to reflect central nervous glucose sensing, whereas endogenous insulin secretion as assessed by serum C-peptide levels served as an indicator of pancreatic beta-cell glucose sensing. Lactate infusion blunted the counterregulatory hormonal responses to hypoglycemia, in particular, the release of epinephrine (P = .007) and growth hormone (P = .004), so that higher glucose infusion rates (P = .012) were required to maintain the target blood glucose levels. In contrast, the decrease in C-peptide concentrations during the hypoglycemic clamp remained completely unaffected by lactate (P = .60). During euglycemic clamp conditions, lactate infusion did not affect the concentrations of C-peptide and of counterregulatory hormones, with the exception of norepinephrine levels that were lower during lactate than saline infusion (P = .049) independently of the glycemic condition. Data indicate that glucose sensing of beta-cells is specific to glucose, whereas glucose sensing at the central nervous level can be overridden by lactate, reflecting the brain's ability to rely on lactate as an alternative major energy source.

Peripheral dendritic cells are essential for both the innate and adaptive antiviral immune responses in the central nervous system

International Nuclear Information System (INIS)

Steel, Christina D.; Hahto, Suzanne M.; Ciavarra, Richard P.

2009-01-01

Intranasal application of vesicular stomatitis virus (VSV) causes acute infection of the central nervous system (CNS). However, VSV encephalitis is not invariably fatal, suggesting that the CNS may contain a professional antigen-presenting cell (APC) capable of inducing or propagating a protective antiviral immune response. To examine this possibility, we first characterized the cellular elements that infiltrate the brain as well as the activation status of resident microglia in the brains of normal and transgenic mice acutely ablated of peripheral dendritic cells (DCs) in vivo. VSV encephalitis was characterized by a pronounced infiltrate of myeloid cells (CD45 high CD11b + ) and CD8 + T cells containing a subset that was specific for the immunodominant VSV nuclear protein epitope. This T cell response correlated temporally with a rapid and sustained upregulation of MHC class I expression on microglia, whereas class II expression was markedly delayed. Ablation of peripheral DCs profoundly inhibited the inflammatory response as well as infiltration of virus-specific CD8 + T cells. Unexpectedly, the VSV-induced interferon-gamma (IFN-γ) response in the CNS remained intact in DC-deficient mice. Thus, both the inflammatory and certain components of the adaptive primary antiviral immune response in the CNS are dependent on peripheral DCs in vivo.

A pediatric renal lymphoma case presenting with central nervous system findings.

Science.gov (United States)

Baran, Ahmet; Küpeli, Serhan; Doğru, Omer

2013-06-01

In pediatric patients renal lymphoma frequently presents in the form of multiple, bilateral mass lesions, infrequently as a single or retroperitoneal mass, and rarely as diffuse infiltrative lesions. In patients with apparent central nervous system involvement close attention to other physical and laboratory findings are essential for preventing a delay in the final diagnosis. Herein we present a pediatric patient with renal lymphoma that presented with central nervous system findings that caused a delay in diagnosis. None declared.

Central nervous system in leukemia

Energy Technology Data Exchange (ETDEWEB)

Phair, J P; Anderson, R E; Namiki, Hideo

1964-03-12

The present report summarizes the pertinent clinical and pathologic findings in 165 cases of leukemia in atomic bomb exposed victims autopsied during the period 1949 to 1962 at ABCC in Hiroshima and Nagasaki, Japan. Significant parenchymal hemorrhage occurred most often in acute myelogenous leukemia and was markedly increased in patients dying with high terminal white blood cell counts. Possible mechanisms involved in the pathogenesis of cerebral hemorrhage in leukemia are discussed. Subarachnoid hemorrhage and subdural hematoma were not related to leukocytosis but appeared to be influenced by marked thrombocytopenia. Leukemic infiltrates of a diffuse nature involving the meninges were paradoxically increased in patients receiving adequate chemotherapy. Meningeal tumors did not show this peculiar relationship to therapy and were not found in association with lymphatic leukemia. Infections involving the central nervous system were confined to patients receiving chemotherapy including steroids. 39 references, 3 figures, 4 tables.

Selective chemokine receptor usage by central nervous system myeloid cells in CCR2-red fluorescent protein knock-in mice.

Directory of Open Access Journals (Sweden)

Noah Saederup

2010-10-01

Full Text Available Monocyte subpopulations distinguished by differential expression of chemokine receptors CCR2 and CX3CR1 are difficult to track in vivo, partly due to lack of CCR2 reagents.We created CCR2-red fluorescent protein (RFP knock-in mice and crossed them with CX3CR1-GFP mice to investigate monocyte subset trafficking. In mice with experimental autoimmune encephalomyelitis, CCR2 was critical for efficient intrathecal accumulation and localization of Ly6C(hi/CCR2(hi monocytes. Surprisingly, neutrophils, not Ly6C(lo monocytes, largely replaced Ly6C(hi cells in the central nervous system of these mice. CCR2-RFP expression allowed the first unequivocal distinction between infiltrating monocytes/macrophages from resident microglia.These results refine the concept of monocyte subsets, provide mechanistic insight about monocyte entry into the central nervous system, and present a novel model for imaging and quantifying inflammatory myeloid populations.

Biological restoration of central nervous system architecture and function: part 3-stem cell- and cell-based applications and realities in the biological management of central nervous system disorders: traumatic, vascular, and epilepsy disorders.

Science.gov (United States)

Farin, Azadeh; Liu, Charles Y; Langmoen, Iver A; Apuzzo, Michael L J

2009-11-01

STEM CELL THERAPY has emerged as a promising novel therapeutic endeavor for traumatic brain injury, spinal cord injury, stroke, and epilepsy in experimental studies. A few preliminary clinical trials have further supported its safety and early efficacy after transplantation into humans. Although not yet clinically available for central nervous system disorders, stem cell technology is expected to evolve into one of the most powerful tools in the biological management of complex central nervous system disorders, many of which currently have limited treatment modalities. The identification of stem cells, discovery of neurogenesis, and application of stem cells to treat central nervous system disorders represent a dramatic evolution and expansion of the neurosurgeon's capabilities into the neurorestoration and neuroregeneration realms. In Part 3 of a 5-part series on stem cells, we discuss the theory, experimental evidence, and clinical data pertaining to the use of stem cells for the treatment of traumatic, vascular, and epileptic disorders.

Pathologic and Protective Roles for Microglial Subsets and Bone Marrow- and Blood-Derived Myeloid Cells in Central Nervous System Inflammation

DEFF Research Database (Denmark)

Wlodarczyk, Agnieszka; Cédile, Oriane; Jensen, Kirstine Nolling

2015-01-01

Inflammation is a series of processes designed for eventual clearance of pathogens and repair of damaged tissue. In the context of autoimmune recognition, inflammatory processes are usually considered to be pathological. This is also true for inflammatory responses in the central nervous system...... (CNS). However, as in other tissues, neuroinflammation can have beneficial as well as pathological outcomes. The complex role of encephalitogenic T cells in multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE) may derive from heterogeneity of the myeloid cells...... with which these T cells interact within the CNS. Myeloid cells, including resident microglia and infiltrating bone marrow-derived cells, such as dendritic cells (DC) and monocytes/macrophages [bone marrow-derived macrophages (BMDM)], are highly heterogeneous populations that may be involved in neurotoxicity...

White-matter abnormalities in unirradiated patients cured of primary central nervous system lymphoma

International Nuclear Information System (INIS)

Kim, L.; Hochberg, F.H.; Shaeffer, P.

2000-01-01

On MRI, primary brain tumors are commonly seen as contrast-enhancing masses surrounded by areas of abnormal signal on T2-weighted images. Following successful treatment tumors may no longer show contrast enhancement. The residual abnormalities are assumed to be represent ''edema'' and infiltrating tumor cells. We report nine patients with primary lymphoma of the central nervous system who had complete responses to intravenous methotrexate, but did not receive intrathecal chemotherapy or cranial irradiation. After complete resolution of contrast-enhancing lesions, persistent abnormalities on T2-weighted images in the region of prior tumor were initially assumed to reflect residual viable tumor. As they remained unchanged for years, however, this may not hold true in the cases in which primary central nervous system lymphoma responds to chemotherapy alone. (orig.)

Modulation of Tumor Tolerance in Primary Central Nervous System Malignancies

Directory of Open Access Journals (Sweden)

Theodore S. Johnson

2012-01-01

Full Text Available Central nervous system tumors take advantage of the unique immunology of the CNS and develop exquisitely complex stromal networks that promote growth despite the presence of antigen-presenting cells and tumor-infiltrating lymphocytes. It is precisely this immunological paradox that is essential to the survival of the tumor. We review the evidence for functional CNS immune privilege and the impact it has on tumor tolerance. In this paper, we place an emphasis on the role of tumor-infiltrating myeloid cells in maintaining stromal and vascular quiescence, and we underscore the importance of indoleamine 2,3-dioxygenase activity as a myeloid-driven tumor tolerance mechanism. Much remains to be discovered regarding the tolerogenic mechanisms by which CNS tumors avoid immune clearance. Thus, it is an open question whether tumor tolerance in the brain is fundamentally different from that of peripheral sites of tumorigenesis or whether it simply stands as a particularly strong example of such tolerance.

The central nervous system environment controls effector CD4+ T cell cytokine profile in experimental allergic encephalomyelitis

DEFF Research Database (Denmark)

Krakowski, M L; Owens, T

1997-01-01

In experimental allergic encephalomyelitis (EAE), CD4+ T cells infiltrate the central nervous system (CNS). We derived CD4+ T cell lines from SJL/J mice that were specific for encephalitogenic myelin basic protein (MBP) peptides and produced both Th1 and Th2 cytokines. These lines transferred EAE...... to naive mice. Peptide-specific cells re-isolated from the CNS only produced Th1 cytokines, whereas T cells in the lymph nodes produced both Th1 and Th2 cytokines. Mononuclear cells isolated from the CNS, the majority of which were microglia, presented antigen to and stimulated MBP-specific T cell lines...... in vitro. Although CNS antigen-presenting cells (APC) supported increased production of interferon (IFN)-gamma mRNA by these T cells, there was no increase in the interleukin (IL)-4 signal, whereas splenic APC induced increases in both IFN-gamma and IL-4. mRNA for IL-12 (p40 subunit) was up...

Immunosenescence of microglia and macrophages: impact on the ageing central nervous system.

Science.gov (United States)

Rawji, Khalil S; Mishra, Manoj K; Michaels, Nathan J; Rivest, Serge; Stys, Peter K; Yong, V Wee

2016-03-01

Ageing of the central nervous system results in a loss of both grey and white matter, leading to cognitive decline. Additional injury to both the grey and white matter is documented in many neurological disorders with ageing, including Alzheimer's disease, traumatic brain and spinal cord injury, stroke, and multiple sclerosis. Accompanying neuronal and glial damage is an inflammatory response consisting of activated macrophages and microglia, innate immune cells demonstrated to be both beneficial and detrimental in neurological repair. This article will propose the following: (i) infiltrating macrophages age differently from central nervous system-intrinsic microglia; (ii) several mechanisms underlie the differential ageing process of these two distinct cell types; and (iii) therapeutic strategies that selectively target these diverse mechanisms may rejuvenate macrophages and microglia for repair in the ageing central nervous system. Most responses of macrophages are diminished with senescence, but activated microglia increase their expression of pro-inflammatory cytokines while diminishing chemotactic and phagocytic activities. The senescence of macrophages and microglia has a negative impact on several neurological diseases, and the mechanisms underlying their age-dependent phenotypic changes vary from extrinsic microenvironmental changes to intrinsic changes in genomic integrity. We discuss the negative effects of age on neurological diseases, examine the response of senescent macrophages and microglia in these conditions, and propose a theoretical framework of therapeutic strategies that target the different mechanisms contributing to the ageing phenotype in these two distinct cell types. Rejuvenation of ageing macrophage/microglia may preserve neurological integrity and promote regeneration in the ageing central nervous system. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions

Checkpoints to the Brain: Directing Myeloid Cell Migration to the Central Nervous System

Directory of Open Access Journals (Sweden)

Meredith Harrison-Brown

2016-12-01

Full Text Available Myeloid cells are a unique subset of leukocytes with a diverse array of functions within the central nervous system during health and disease. Advances in understanding of the unique properties of these cells have inspired interest in their use as delivery vehicles for therapeutic genes, proteins, and drugs, or as “assistants” in the clean-up of aggregated proteins and other molecules when existing drainage systems are no longer adequate. The trafficking of myeloid cells from the periphery to the central nervous system is subject to complex cellular and molecular controls with several ‘checkpoints’ from the blood to their destination in the brain parenchyma. As important components of the neurovascular unit, the functional state changes associated with lineage heterogeneity of myeloid cells are increasingly recognized as important for disease progression. In this review, we discuss some of the cellular elements associated with formation and function of the neurovascular unit, and present an update on the impact of myeloid cells on central nervous system (CNS diseases in the laboratory and the clinic. We then discuss emerging strategies for harnessing the potential of site-directed myeloid cell homing to the CNS, and identify promising avenues for future research, with particular emphasis on the importance of untangling the functional heterogeneity within existing myeloid subsets.

Central Nervous System Vasculitis

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... of Vasculitis / Central Nervous System (CNS) Vasculitis Central Nervous System (CNS) Vasculitis Swap out your current Facebook Profile ... Facebook personal page. Replace with this image. Central nervous system (CNS) vasculitis is inflammation of blood vessel walls ...

Comparison of microglia and infiltrating CD11c+ cells as antigen presenting cells for T cell proliferation and cytokine response

DEFF Research Database (Denmark)

Wlodarczyk, Agnieszka; Løbner, Morten; Cédile, Oriane

2014-01-01

BACKGROUND: Tissue-resident antigen-presenting cells (APC) exert a major influence on the local immune environment. Microglia are resident myeloid cells in the central nervous system (CNS), deriving from early post-embryonic precursors, distinct from adult hematopoietic lineages. Dendritic cells...... (DC) and macrophages infiltrate the CNS during experimental autoimmune encephalomyelitis (EAE). Microglia are not considered to be as effective APC as DC or macrophages. METHODS: In this work we compared the antigen presenting capacity of CD11c+ and CD11c- microglia subsets with infiltrating CD11c......+ APC, which include DC. The microglial subpopulations (CD11c- CD45dim CD11b+ and CD11c+ CD45dim CD11b+) as well as infiltrating CD11c+ CD45high cells were sorted from CNS of C57BL/6 mice with EAE. Sorted cells were characterised by flow cytometry for surface phenotype and by quantitative real-time PCR...

Childhood Central Nervous System Germ Cell Tumors Treatment (PDQ®)—Patient Version

Science.gov (United States)

Childhood central nervous system (CNS) germ cell tumors form from germ cells (a type of cell that forms as a fetus develops and later becomes sperm in the testicles or eggs in the ovaries). Learn about the signs, tests to diagnose, and treatment of pediatric germ cell tumors in the brain in this expert-reviewed summary.

Structural and functional features of central nervous system lymphatic vessels.

Science.gov (United States)

Louveau, Antoine; Smirnov, Igor; Keyes, Timothy J; Eccles, Jacob D; Rouhani, Sherin J; Peske, J David; Derecki, Noel C; Castle, David; Mandell, James W; Lee, Kevin S; Harris, Tajie H; Kipnis, Jonathan

2015-07-16

One of the characteristics of the central nervous system is the lack of a classical lymphatic drainage system. Although it is now accepted that the central nervous system undergoes constant immune surveillance that takes place within the meningeal compartment, the mechanisms governing the entrance and exit of immune cells from the central nervous system remain poorly understood. In searching for T-cell gateways into and out of the meninges, we discovered functional lymphatic vessels lining the dural sinuses. These structures express all of the molecular hallmarks of lymphatic endothelial cells, are able to carry both fluid and immune cells from the cerebrospinal fluid, and are connected to the deep cervical lymph nodes. The unique location of these vessels may have impeded their discovery to date, thereby contributing to the long-held concept of the absence of lymphatic vasculature in the central nervous system. The discovery of the central nervous system lymphatic system may call for a reassessment of basic assumptions in neuroimmunology and sheds new light on the aetiology of neuroinflammatory and neurodegenerative diseases associated with immune system dysfunction.

Central and peripheral nervous systems: master controllers in cancer metastasis.

Science.gov (United States)

Shi, Ming; Liu, Dan; Yang, Zhengyan; Guo, Ning

2013-12-01

Central and sympathetic nervous systems govern functional activities of many organs. Solid tumors like organs are also innervated by sympathetic nerve fibers. Neurotransmitters released from sympathetic nerve fibers can modulate biological behaviors of tumor cells. Multiple physiologic processes of tumor development may be dominated by central and sympathetic nervous systems as well. Recent studies suggest that dysfunction of central and sympathetic nervous systems and disorder of the hormone network induced by psychological stress may influence malignant progression of cancer by inhibiting the functions of immune system, regulating metabolic reprogramming of tumor cells, and inducing interactions between tumor and stromal cells. Over-release of inflammatory cytokines by tumors may aggravate emotional disorder, triggering the vicious cycles in tumor microenvironment and host macroenvironment. It is reasonable to hypothesize that cancer progression may be controlled by central and sympathetic nervous systems. In this review, we will focus on the recent information about the impacts of central and sympathetic nervous systems on tumor invasion and metastasis.

Neural Stem Cells: Implications for the Conventional Radiotherapy of Central Nervous System Malignancies

International Nuclear Information System (INIS)

Barani, Igor J.; Benedict, Stanley H.; Lin, Peck-Sun

2007-01-01

Advances in basic neuroscience related to neural stem cells and their malignant counterparts are challenging traditional models of central nervous system tumorigenesis and intrinsic brain repair. Neurogenesis persists into adulthood predominantly in two neurogenic centers: subventricular zone and subgranular zone. Subventricular zone is situated adjacent to lateral ventricles and subgranular zone is confined to the dentate gyrus of the hippocampus. Neural stem cells not only self-renew and differentiate along multiple lineages in these regions, but also contribute to intrinsic brain plasticity and repair. Ionizing radiation can depopulate these exquisitely sensitive regions directly or impair in situ neurogenesis by indirect, dose-dependent and inflammation-mediated mechanisms, even at doses <2 Gy. This review discusses the fundamental neural stem cell concepts within the framework of cumulative clinical experience with the treatment of central nervous system malignancies using conventional radiotherapy

In vivo imaging in autoimmune diseases in the central nervous system.

Science.gov (United States)

Kawakami, Naoto

2016-07-01

Intravital imaging is becoming more popular and is being used to visualize cellular motility and functions. In contrast to in vitro analysis, which resembles in vivo analysis, intravital imaging can be used to observe and analyze cells directly in vivo. In this review, I will summarize recent imaging studies of autoreactive T cell infiltration into the central nervous system (CNS) and provide technical background. During their in vivo journey, autoreactive T cells interact with many different cells. At first, autoreactive T cells interact with endothelial cells in the airways of the lung or with splenocytes, where they acquire a migratory phenotype to infiltrate into the CNS. After arriving at the CNS, they interact with endothelial cells of the leptomeningeal vessels or the choroid plexus before passing through the blood-brain barrier. CNS-infiltrating T cells become activated by recognizing endogenous autoantigens presented by local antigen-presenting cells (APCs). This activation was visualized in vivo by using protein-based sensors. One such sensor detects changes in intracellular calcium concentration as an early marker of T cell activation. Another sensor detects translocation of Nuclear factor of activated T-cells (NFAT) from cytosol to nucleus as a definitive sign of T cell activation. Importantly, intravital imaging is not just used to visualize cellular behavior. Together with precise analysis, intravital imaging deepens our knowledge of cellular functions in living organs and also provides a platform for developing therapeutic treatments. Copyright © 2016 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

Experimental study on central nervous toxicity of 'misonidazole' a hypoxic cell radiosensitizer

International Nuclear Information System (INIS)

Takahashi, Iku

1981-01-01

'Misonidazole', a radiosensitizer for hypoxic cells is expected to be applied to the treatment of malignant tumors, but its side effect becomes a subject of study, because its effective dose is close to its lethal dose. The auther performed experiments with mice on the central nervous toxicity, which is the most lethal of the side effects of Misonidazole, with the following results; 1. The abrupt death seen after the administration of a large dose of Misonidazole was attributable to the central nervous toxicity. LD 50 for d.d. strain mouse was 1.55 mg per body weight g. 2. The used mice always developed convulsion before death. But the administration of anticonvulsant failed to free them from death. 3. Autopsy findings were such abnormal ones as the degeneration and exfoliation of nerve cells and diapedetic focus. After sacrifice, however, no findings indicative of disturbance of central nerve could be detected. 4. Misonidazole, even in a small divided dose, left intracerebral retention, though slightly, indicating that its accumulation in the brain would be increased with increase in the dose. 5. The disturbance of central nerve was not exacerbated by the whole brain irradiation with Misonidazole. (author)

Programmed Cell Death Ligand 1 Expression in Primary Central Nervous System Lymphomas: A Clinicopathological Study.

Science.gov (United States)

Hayano, Azusa; Komohara, Yoshihiro; Takashima, Yasuo; Takeya, Hiroto; Homma, Jumpei; Fukai, Junya; Iwadate, Yasuo; Kajiwara, Koji; Ishizawa, Shin; Hondoh, Hiroaki; Yamanaka, Ryuya

2017-10-01

Programmed cell death ligand 1 (PD-L1)/programmed cell death 1 (PD-1) have been shown to predict response to PD-L1/PD-1-targeted therapy. We analyzed PD-L1 expression in primary central nervous system lymphomas (PCNSLs). PD-L1 protein and mRNA expression were evaluated in 64 PCNSL tissue samples. IFN-γ, IL-10, CD4, and CD8 mRNA expression was also evaluated. PD-L1 protein was detected in tumor cells in 2 (4.1%) cases and in tumor microenvironments in 25 (52%) cases. PD-L1 mRNA positively correlated with IFN-γ (p=0.0024) and CD4 (p=0.0005) mRNA expression. IFN-γ mRNA positively correlated with CD8 mRNA expression (p=0.0001). Furthermore, tumor cell PD-L1 expression correlated positively with overall survival (p=0.0177), whereas microenvironmental PD-L1 expression exhibited an insignificant negative trend with overall survival (p=0.188). PD-L1 was expressed on both tumor and/or tumor-infiltrating immune cells in PCNSL. The biological roles of this marker warrant further investigation. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Unusual location of central nervous system langerhans cell histiocytosis: case report

International Nuclear Information System (INIS)

Kim, E. Yup; Lee, Jae Kyu; Kim, Chan Kyo; Lee, Chang Hyun; Kang, Chang Ho; Chung, Phil Wook

2003-01-01

Langerhans cell histiocytosis of the central nervous system (CNS) usually involves the hypothalamic-pituitary axis, and T1-weighted MR images normally demonstrate infundibular thickening and/or a mass lesion in the hypothalamus and the absence of a posterior pituitary 'bright spot'. We recently encountered a case of CNS langerhans cell histiocytosis with no posterior pituitary 'bright spot' and with lesions involving the cerebellum and basal ganglia but not the hypothalamic-pituitary axis

Cell fate control in the developing central nervous system

Energy Technology Data Exchange (ETDEWEB)

Guérout, Nicolas; Li, Xiaofei; Barnabé-Heider, Fanie, E-mail: Fanie.Barnabe-Heider@ki.se

2014-02-01

The principal neural cell types forming the mature central nervous system (CNS) are now understood to be diverse. This cellular subtype diversity originates to a large extent from the specification of the earlier proliferating progenitor populations during development. Here, we review the processes governing the differentiation of a common neuroepithelial cell progenitor pool into mature neurons, astrocytes, oligodendrocytes, ependymal cells and adult stem cells. We focus on studies performed in mice and involving two distinct CNS structures: the spinal cord and the cerebral cortex. Understanding the origin, specification and developmental regulators of neural cells will ultimately impact comprehension and treatments of neurological disorders and diseases. - Highlights: • Similar mechanisms regulate cell fate in different CNS cell types and structures. • Cell fate regulators operate in a spatial–temporal manner. • Different neural cell types rely on the generation of a diversity of progenitor cells. • Cell fate decision is dictated by the integration of intrinsic and extrinsic signals.

Cell fate control in the developing central nervous system

International Nuclear Information System (INIS)

Guérout, Nicolas; Li, Xiaofei; Barnabé-Heider, Fanie

2014-01-01

The principal neural cell types forming the mature central nervous system (CNS) are now understood to be diverse. This cellular subtype diversity originates to a large extent from the specification of the earlier proliferating progenitor populations during development. Here, we review the processes governing the differentiation of a common neuroepithelial cell progenitor pool into mature neurons, astrocytes, oligodendrocytes, ependymal cells and adult stem cells. We focus on studies performed in mice and involving two distinct CNS structures: the spinal cord and the cerebral cortex. Understanding the origin, specification and developmental regulators of neural cells will ultimately impact comprehension and treatments of neurological disorders and diseases. - Highlights: • Similar mechanisms regulate cell fate in different CNS cell types and structures. • Cell fate regulators operate in a spatial–temporal manner. • Different neural cell types rely on the generation of a diversity of progenitor cells. • Cell fate decision is dictated by the integration of intrinsic and extrinsic signals

Unusual location of central nervous system langerhans cell histiocytosis: case report

Energy Technology Data Exchange (ETDEWEB)

Kim, E. Yup; Lee, Jae Kyu; Kim, Chan Kyo; Lee, Chang Hyun; Kang, Chang Ho; Chung, Phil Wook [Armed Forces Capital Hospital, Seongnam (Korea, Republic of)

2003-03-01

Langerhans cell histiocytosis of the central nervous system (CNS) usually involves the hypothalamic-pituitary axis, and T1-weighted MR images normally demonstrate infundibular thickening and/or a mass lesion in the hypothalamus and the absence of a posterior pituitary 'bright spot'. We recently encountered a case of CNS langerhans cell histiocytosis with no posterior pituitary 'bright spot' and with lesions involving the cerebellum and basal ganglia but not the hypothalamic-pituitary axis.

Downregulation of membrane type-matrix metalloproteinases in the inflamed or injured central nervous system

DEFF Research Database (Denmark)

Toft-Hansen, Henrik; Babcock, Alicia A; Millward, Jason M

2007-01-01

BACKGROUND: Matrix metalloproteinases (MMPs) are thought to mediate cellular infiltration in central nervous system (CNS) inflammation by cleaving extracellular matrix proteins associated with the blood-brain barrier. The family of MMPs includes 23 proteinases, including six membrane type-MMPs (M...

The Central Nervous System of Box Jellyfish

DEFF Research Database (Denmark)

Garm, Anders Lydik; Ekström, Peter

2008-01-01

of behaviors in the box jellyfish such as obstacle avoidance and navigation. The need to process the visual information and turn it into the appropriate behavior puts strong demands on the nervous system of box jellyfish, which appears more elaborate than in other cnidarians. Here, the central part...... of this nervous system is described. Each rhopalium holds a separate part of the CNS with 1,000 nerve cells and a large amount of neuropil. The rhopalial nervous system has several subsystems defined by the anatomy, location, and immunocytochemistry of the cells. Most of the subsystems connect to one or more...... of the eye types, and it is likely that the rhopalial nervous system accounts for most of the visual processing. The major part of the CNS is made up of a ring nerve encircling the bell shaped body. The ring nerve holds around 10,000 cells and is directly connected to all four rhopalial nervous systems...

Statin therapy inhibits remyelination in the central nervous system

DEFF Research Database (Denmark)

Miron, Veronique E; Zehntner, Simone P; Kuhlmann, Tanja

2009-01-01

Remyelination of lesions in the central nervous system contributes to neural repair following clinical relapses in multiple sclerosis. Remyelination is initiated by recruitment and differentiation of oligodendrocyte progenitor cells (OPCs) into myelinating oligodendrocytes. Simvastatin, a blood...... that OPCs were maintained in an immature state (Olig2(strong)/Nkx2.2(weak)). NogoA+ oligodendrocyte numbers were decreased during all simvastatin treatment regimens. Our findings suggest that simvastatin inhibits central nervous system remyelination by blocking progenitor differentiation, indicating...... the need to monitor effects of systemic immunotherapies that can access the central nervous system on brain tissue-repair processes....

Hydrogels for central nervous system therapeutic strategies.

Science.gov (United States)

Russo, Teresa; Tunesi, Marta; Giordano, Carmen; Gloria, Antonio; Ambrosio, Luigi

2015-12-01

The central nervous system shows a limited regenerative capacity, and injuries or diseases, such as those in the spinal, brain and retina, are a great problem since current therapies seem to be unable to achieve good results in terms of significant functional recovery. Different promising therapies have been suggested, the aim being to restore at least some of the lost functions. The current review deals with the use of hydrogels in developing advanced devices for central nervous system therapeutic strategies. Several approaches, involving cell-based therapy, delivery of bioactive molecules and nanoparticle-based drug delivery, will be first reviewed. Finally, some examples of injectable hydrogels for the delivery of bioactive molecules in central nervous system will be reported, and the key features as well as the basic principles in designing multifunctional devices will be described. © IMechE 2015.

Central nervous system

Science.gov (United States)

The central nervous system is composed of the brain and spinal cord. Your brain and spinal cord serve as the main "processing center" for your entire nervous system. They control all the workings of your body.

Bioengineered Hydrogel to Inhibit Post-Traumatic Central Nervous System Scarring

Science.gov (United States)

2016-10-01

AWARD NUMBER: W81XWH-14-1-0586 TITLE: Bioengineered Hydrogel to Inhibit Post-Traumatic Central Nervous System Scarring PRINCIPAL...Hydrogel to Inhibit Post-Traumatic Central Nervous System Scarring 5a. CONTRACT NUMBER W81XWH-14-1-0586 5b. GRANT NUMBER W81XWH- 14-1-0586 5c...barriers that prevent the optimal delivery of biologics and cells to the injured nervous system . A significant problem is the formation of scar tissue

Risk Factors for Subsequent Central Nervous System Tumors in Pediatric Allogeneic Hematopoietic Cell Transplant

DEFF Research Database (Denmark)

Gabriel, Melissa; Shaw, Bronwen E; Brazauskas, Ruta

2017-01-01

Survivors of hematopoietic cell transplantation (HCT) are at risk of subsequent solid tumors, including central nervous system (CNS) tumors. The risk of CNS tumors after HCT in pediatric HCT recipients is not known. We evaluated the incidence and risk factors for CNS tumors in pediatric recipients...

Prevalence and characteristics of central nervous system involvement by chronic lymphocytic leukemia.

Science.gov (United States)

Strati, Paolo; Uhm, Joon H; Kaufmann, Timothy J; Nabhan, Chadi; Parikh, Sameer A; Hanson, Curtis A; Chaffee, Kari G; Call, Timothy G; Shanafelt, Tait D

2016-04-01

Abroad array of conditions can lead to neurological symptoms in chronic lymphocytic leukemia patients and distinguishing between clinically significant involvement of the central nervous system by chronic lymphocytic leukemia and symptoms due to other etiologies can be challenging. Between January 1999 and November 2014, 172 (4%) of the 4174 patients with chronic lymphocytic leukemia followed at our center had a magnetic resonance imaging of the central nervous system and/or a lumbar puncture to evaluate neurological symptoms. After comprehensive evaluation, the etiology of neurological symptoms was: central nervous system chronic lymphocytic leukemia in 18 patients (10% evaluated by imaging and/or lumbar puncture, 0.4% overall cohort); central nervous system Richter Syndrome in 15 (9% evaluated, 0.3% overall); infection in 40 (23% evaluated, 1% overall); autoimmune/inflammatory conditions in 28 (16% evaluated, 0.7% overall); other cancer in 8 (5% evaluated, 0.2% overall); and another etiology in 63 (37% evaluated, 1.5% overall). Although the sensitivity of cerebrospinal fluid analysis to detect central nervous system disease was 89%, the specificity was only 42% due to the frequent presence of leukemic cells in the cerebrospinal fluid in other conditions. No parameter on cerebrospinal fluid analysis (e.g. total nucleated cells, total lymphocyte count, chronic lymphocytic leukemia cell percentage) were able to offer a reliable discrimination between patients whose neurological symptoms were due to clinically significant central nervous system involvement by chronic lymphocytic leukemia and another etiology. Median overall survival among patients with clinically significant central nervous system chronic lymphocytic leukemia and Richter syndrome was 12 and 11 months, respectively. In conclusion, clinically significant central nervous system involvement by chronic lymphocytic leukemia is a rare condition, and neurological symptoms in patients with chronic lymphocytic

The central nervous system

International Nuclear Information System (INIS)

Holmes, R.A.

1984-01-01

The first section presents a comprehensive evaluation of radionuclide imaging of the central nervous system and provides a comparison of the detection accuracies of radionuclide imaging (RNI) and XCT in certain lesions, realizing that the XCT results may vary when radiocontrast or newer generation XCT scanners are used. Although conventional radionuclide imaging of the central nervous system has experienced no significant changes over the last 7 years except for mild refinements, a new section has been added on positron emission tomography (PET). Most positron radiopharmaceuticals passively cross the intact blood-brain barrier, and their localization has catalyzed renewed interest in our ability to metabolically study and obtain images of the central nervous system. The section on radionuclide cisternography has been rewritten to reflect present day practice and the wider application of XCT in describing conditions affecting the ventricular system

CNS infiltration of peripheral immune cells: D-Day for neurodegenerative disease?

Science.gov (United States)

Rezai-Zadeh, Kavon; Gate, David; Town, Terrence

2009-12-01

While the central nervous system (CNS) was once thought to be excluded from surveillance by immune cells, a concept known as "immune privilege," it is now clear that immune responses do occur in the CNS-giving rise to the field of neuroimmunology. These CNS immune responses can be driven by endogenous (glial) and/or exogenous (peripheral leukocyte) sources and can serve either productive or pathological roles. Recent evidence from mouse models supports the notion that infiltration of peripheral monocytes/macrophages limits progression of Alzheimer's disease pathology and militates against West Nile virus encephalitis. In addition, infiltrating T lymphocytes may help spare neuronal loss in models of amyotrophic lateral sclerosis. On the other hand, CNS leukocyte penetration drives experimental autoimmune encephalomyelitis (a mouse model for the human demyelinating disease multiple sclerosis) and may also be pathological in both Parkinson's disease and human immunodeficiency virus encephalitis. A critical understanding of the cellular and molecular mechanisms responsible for trafficking of immune cells from the periphery into the diseased CNS will be key to target these cells for therapeutic intervention in neurodegenerative diseases, thereby allowing neuroregenerative processes to ensue.

Neurotropic Enterovirus Infections in the Central Nervous System.

Science.gov (United States)

Huang, Hsing-I; Shih, Shin-Ru

2015-11-24

Enteroviruses are a group of positive-sense single stranded viruses that belong to the Picornaviridae family. Most enteroviruses infect humans from the gastrointestinal tract and cause mild symptoms. However, several enteroviruses can invade the central nervous system (CNS) and result in various neurological symptoms that are correlated to mortality associated with enteroviral infections. In recent years, large outbreaks of enteroviruses occurred worldwide. Therefore, these neurotropic enteroviruses have been deemed as re-emerging pathogens. Although these viruses are becoming large threats to public health, our understanding of these viruses, especially for non-polio enteroviruses, is limited. In this article, we review recent advances in the trafficking of these pathogens from the peripheral to the central nervous system, compare their cell tropism, and discuss the effects of viral infections in their host neuronal cells.

Neurotropic Enterovirus Infections in the Central Nervous System

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Hsing-I Huang

2015-11-01

Full Text Available Enteroviruses are a group of positive-sense single stranded viruses that belong to the Picornaviridae family. Most enteroviruses infect humans from the gastrointestinal tract and cause mild symptoms. However, several enteroviruses can invade the central nervous system (CNS and result in various neurological symptoms that are correlated to mortality associated with enteroviral infections. In recent years, large outbreaks of enteroviruses occurred worldwide. Therefore, these neurotropic enteroviruses have been deemed as re-emerging pathogens. Although these viruses are becoming large threats to public health, our understanding of these viruses, especially for non-polio enteroviruses, is limited. In this article, we review recent advances in the trafficking of these pathogens from the peripheral to the central nervous system, compare their cell tropism, and discuss the effects of viral infections in their host neuronal cells.

Primary central nervous system diffuse large B-cell lymphoma shows an activated B-cell-like phenotype with co-expression of C-MYC, BCL-2, and BCL-6.

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Li, Xiaomei; Huang, Ying; Bi, Chengfeng; Yuan, Ji; He, Hong; Zhang, Hong; Yu, QiuBo; Fu, Kai; Li, Dan

2017-06-01

Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma, whose main prognostic factor is closely related to germinal center B-cell-like subtype (GCB- DLBCL) or activated B-cell-like type (non-GCB-DLBCL). The most common type of primary central nervous system lymphoma is diffuse large B-cell type with poor prognosis and the reason is unclear. This study aims to stratify primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL) according to the cell-of-origin (COO) and to investigate the multiple proteins expression of C-MYC, BCL-6, BCL-2, TP53, further to elucidate the reason why primary central nervous system diffuse large B-cell lymphoma possesses a poor clinical outcome as well. Nineteen cases of primary central nervous system DLBCL were stratified according to immunostaining algorithms of Hans, Choi and Meyer (Tally) and we investigated the multiple proteins expression of C-MYC, BCL-6, BCL-2, TP53. The Epstein-Barr virus and Borna disease virus infection were also detected. Among nineteen cases, most (15-17 cases) were assigned to the activated B-cell-like subtype, highly expression of C-MYC (15 cases, 78.9%), BCL-2 (10 cases, 52.6%), BCL-6 (15 cases, 78.9%). Unfortunately, two cases were positive for PD-L1 while PD-L2 was not expressed in any case. Two cases infected with BDV but no one infected with EBV. In conclusion, most primary central nervous system DLBCLs show an activated B-cell-like subtype characteristic and have multiple expressions of C-MYC, BCL-2, BCL-6 protein, these features might be significant factor to predict the outcome and guide treatment of PCNS-DLBCLs. Copyright © 2017 Elsevier GmbH. All rights reserved.

Infundibulo-hypophysitis-like radiological image in a patient with pituitary infiltration of a diffuse large B-cell non-Hodgkin lymphoma

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A León-Suárez

2016-12-01

Full Text Available Non-Hodgkin lymphoma (NHL is a hematological tumor caused by abnormal lymphoid proliferation. NHL can arise in any part of the body, including central nervous system (CNS. However, pituitary involvement is a quite rare presentation. The diffuse large B-cell lymphoma (DLBCL is the most common subtype when pituitary is infiltrated. Here, we report a case of pituitary infiltration of NHL DLBCL type in a woman with hypopituitarism and an infundibulum-hypophysitis-like image on magnetic resonance imaging (MRI. A female aged 64 years, complained of dyspepsia, fatigue, weight loss and urine volume increment with thirst. Endoscopy and gastric biopsy confirmed diffuse large B-cell lymphoma. Treatment with chemotherapy using R-CHOP was initiated. During her hospitalization, hypotension and polyuria were confirmed. Hormonal evaluation was compatible with central diabetes insipidus and hypopituitarism. Simple T1 sequence of MRI showed thickening of the infundibular stalk with homogeneous enhancement. After lumbar puncture analysis, CNS infiltration was confirmed showing positive atypical lymphocytes. Pituitary and infundibular stalk size normalized after R-CHOP chemotherapy treatment. In conclusion, pituitary infiltration of NHL with infundibular-hypophysitis-like image on MRI is a rare finding. Clinical picture included hypopituitarism and central diabetes insipidus. Diagnosis should be suspected after biochemical analysis and MRI results. Treatment consists of chemotherapy against NHL and hormonal replacement for pituitary dysfunction.

Localization of Reversion-Induced LIM Protein (RIL) in the Rat Central Nervous System

International Nuclear Information System (INIS)

Iida, Yuko; Matsuzaki, Toshiyuki; Morishima, Tetsuro; Sasano, Hiroshi; Asai, Kiyofumi; Sobue, Kazuya; Takata, Kuniaki

2009-01-01

Reversion-induced LIM protein (RIL) is a member of the ALP (actinin-associated LIM protein) subfamily of the PDZ/LIM protein family. RIL serves as an adaptor protein and seems to regulate cytoskeletons. Immunoblotting suggested that RIL is concentrated in the astrocytes in the central nervous system. We then examined the expression and localization of RIL in the rat central nervous system and compared it with that of water channel aquaporin 4 (AQP4). RIL was concentrated in the cells of ependyma lining the ventricles in the brain and the central canal in the spinal cord. In most parts of the central nervous system, RIL was expressed in the astrocytes that expressed AQP4. Double-labeling studies showed that RIL was concentrated in the cytoplasm of astrocytes where glial fibrillary acidic protein was enriched as well as in the AQP4-enriched regions such as the endfeet or glia limitans. RIL was also present in some neurons such as Purkinje cells in the cerebellum and some neurons in the brain stem. Differential expression of RIL suggests that it may be involved in the regulation of the central nervous system

Central nervous system mesenchymal chondrosarcoma

Energy Technology Data Exchange (ETDEWEB)

Salvati, M.; Frati, A.; Piccirilli, M.; Agrillo, A.; Brogna, C.; Occhiogrosso, G.; Giangaspero, F. [INM Neuromed IRCCS, Pozzilli (Italy). Dept. of Neurosurgery; Caroli, E. [Policlinico S. Andrea, Rome (Italy). Dept. of Neurological Sciences, Neurosurgery

2005-06-15

Central nervous system mesenchymal chondrosarcomas are rare malignant tumors that constitute a separate entity from the classical chondrosarcoma and myxoid variant. Clinical behaviour of central nervous system chondrosarcomas is still unknown. We describe two rare examples of intracranial mesenchymal chondrosarcoma with a review of the literature, in an attempt to clarify the clinical characteristics, prognosis and treatment of choice of these unusual tumors. Among the 55 reported cases, 23 had postoperative radiotherapy. Although there is no statistical significance according to the Log-Rank test (p=0.7), the patients treated with radiation therapy seem to have a better chance of survival. Patients who had adjuvant chemotherapy (only 5) showed survival times similar to those patients who had none. Although clinical behaviour of central nervous system chondrosarcomas remains to be defined, data from our series as well as literature show that radical removal is the best therapeutic choice. In addition, patients treated with postoperative radiotherapy seem to show a trend toward increased survival.

Central nervous system mesenchymal chondrosarcoma

International Nuclear Information System (INIS)

Salvati, M.; Frati, A.; Piccirilli, M.; Agrillo, A.; Brogna, C.; Occhiogrosso, G.; Giangaspero, F.; Caroli, E.

2005-01-01

Central nervous system mesenchymal chondrosarcomas are rare malignant tumors that constitute a separate entity from the classical chondrosarcoma and myxoid variant. Clinical behaviour of central nervous system chondrosarcomas is still unknown. We describe two rare examples of intracranial mesenchymal chondrosarcoma with a review of the literature, in an attempt to clarify the clinical characteristics, prognosis and treatment of choice of these unusual tumors. Among the 55 reported cases, 23 had postoperative radiotherapy. Although there is no statistical significance according to the Log-Rank test (p=0.7), the patients treated with radiation therapy seem to have a better chance of survival. Patients who had adjuvant chemotherapy (only 5) showed survival times similar to those patients who had none. Although clinical behaviour of central nervous system chondrosarcomas remains to be defined, data from our series as well as literature show that radical removal is the best therapeutic choice. In addition, patients treated with postoperative radiotherapy seem to show a trend toward increased survival

In situ immune response and mechanisms of cell damage in central nervous system of fatal cases microcephaly by Zika virus.

Science.gov (United States)

Azevedo, Raimunda S S; de Sousa, Jorge R; Araujo, Marialva T F; Martins Filho, Arnaldo J; de Alcantara, Bianca N; Araujo, Fernanda M C; Queiroz, Maria G L; Cruz, Ana C R; Vasconcelos, Beatriz H Baldez; Chiang, Jannifer O; Martins, Lívia C; Casseb, Livia M N; da Silva, Eliana V; Carvalho, Valéria L; Vasconcelos, Barbara C Baldez; Rodrigues, Sueli G; Oliveira, Consuelo S; Quaresma, Juarez A S; Vasconcelos, Pedro F C

2018-01-08

Zika virus (ZIKV) has recently caused a pandemic disease, and many cases of ZIKV infection in pregnant women resulted in abortion, stillbirth, deaths and congenital defects including microcephaly, which now has been proposed as ZIKV congenital syndrome. This study aimed to investigate the in situ immune response profile and mechanisms of neuronal cell damage in fatal Zika microcephaly cases. Brain tissue samples were collected from 15 cases, including 10 microcephalic ZIKV-positive neonates with fatal outcome and five neonatal control flavivirus-negative neonates that died due to other causes, but with preserved central nervous system (CNS) architecture. In microcephaly cases, the histopathological features of the tissue samples were characterized in three CNS areas (meninges, perivascular space, and parenchyma). The changes found were mainly calcification, necrosis, neuronophagy, gliosis, microglial nodules, and inflammatory infiltration of mononuclear cells. The in situ immune response against ZIKV in the CNS of newborns is complex. Despite the predominant expression of Th2 cytokines, other cytokines such as Th1, Th17, Treg, Th9, and Th22 are involved to a lesser extent, but are still likely to participate in the immunopathogenic mechanisms of neural disease in fatal cases of microcephaly caused by ZIKV.

Nerve Regeneration in the Peripheral Nervous System versus the Central Nervous System and the Relevance to Speech and Hearing after Nerve Injuries

Science.gov (United States)

Gordon, Tessa; Gordon, Karen

2010-01-01

Schwann cells normally form myelin sheaths around axons in the peripheral nervous system (PNS) and support nerve regeneration after nerve injury. In contrast, nerve regeneration in the central nervous system (CNS) is not supported by the myelinating cells known as oligodendrocytes. We have found that: 1) low frequency electrical stimulation can be…

Is Ghrelin Synthesized in the Central Nervous System?

Science.gov (United States)

Cabral, Agustina; López Soto, Eduardo J; Epelbaum, Jacques; Perelló, Mario

2017-03-15

Ghrelin is an octanoylated peptide that acts via its specific receptor, the growth hormone secretagogue receptor type 1a (GHSR-1a), and regulates a vast variety of physiological functions. It is well established that ghrelin is predominantly synthesized by a distinct population of endocrine cells located within the gastric oxyntic mucosa. In addition, some studies have reported that ghrelin could also be synthesized in some brain regions, such as the hypothalamus. However, evidences of neuronal production of ghrelin have been inconsistent and, as a consequence, it is still as a matter of debate if ghrelin can be centrally produced. Here, we provide a comprehensive review and discussion of the data supporting, or not, the notion that the mammalian central nervous system can synthetize ghrelin. We conclude that no irrefutable and reproducible evidence exists supporting the notion that ghrelin is synthetized, at physiologically relevant levels, in the central nervous system of adult mammals.

Is Ghrelin Synthesized in the Central Nervous System?

Directory of Open Access Journals (Sweden)

Agustina Cabral

2017-03-01

Full Text Available Ghrelin is an octanoylated peptide that acts via its specific receptor, the growth hormone secretagogue receptor type 1a (GHSR-1a, and regulates a vast variety of physiological functions. It is well established that ghrelin is predominantly synthesized by a distinct population of endocrine cells located within the gastric oxyntic mucosa. In addition, some studies have reported that ghrelin could also be synthesized in some brain regions, such as the hypothalamus. However, evidences of neuronal production of ghrelin have been inconsistent and, as a consequence, it is still as a matter of debate if ghrelin can be centrally produced. Here, we provide a comprehensive review and discussion of the data supporting, or not, the notion that the mammalian central nervous system can synthetize ghrelin. We conclude that no irrefutable and reproducible evidence exists supporting the notion that ghrelin is synthetized, at physiologically relevant levels, in the central nervous system of adult mammals.

Related B cell clones populate the meninges and parenchyma of patients with multiple sclerosis.

Science.gov (United States)

Lovato, Laura; Willis, Simon N; Rodig, Scott J; Caron, Tyler; Almendinger, Stefany E; Howell, Owain W; Reynolds, Richard; O'Connor, Kevin C; Hafler, David A

2011-02-01

In the central nervous system of patients with multiple sclerosis, B cell aggregates populate the meninges, raising the central question as to whether these structures relate to the B cell infiltrates found in parenchymal lesions or instead, represent a separate central nervous system immune compartment. We characterized the repertoires derived from meningeal B cell aggregates and the corresponding parenchymal infiltrates from brain tissue derived primarily from patients with progressive multiple sclerosis. The majority of expanded antigen-experienced B cell clones derived from meningeal aggregates were also present in the parenchyma. We extended this investigation to include 20 grey matter specimens containing meninges, 26 inflammatory plaques, 19 areas of normal appearing white matter and cerebral spinal fluid. Analysis of 1833 B cell receptor heavy chain variable region sequences demonstrated that antigen-experienced clones were consistently shared among these distinct compartments. This study establishes a relationship between extraparenchymal lymphoid tissue and parenchymal infiltrates and defines the arrangement of B cell clones that populate the central nervous system of patients with multiple sclerosis.

Central nervous system depressant activityof Leonurus sibiricus ...

African Journals Online (AJOL)

The methanol extract of aerial parts of Leonurus sibiricus was shown to possess central nervous system depressant action by significantly decreased the time of onset of sleep and potentiated the pentobarbital induced sleeping time in mice. Keywords: Leonurus sibiricus, labiatae, central nervous depressant, sedation

Central nervous system involvement in mantle cell lymphoma : clinical features, prognostic factors and outcomes from the European Mantle Cell Lymphoma Network

NARCIS (Netherlands)

Cheah, C. Y.; George, A.; Gine, E.; Chiappella, A.; Kluin-Nelemans, H. C.; Jurczak, W.; Krawczyk, K.; Mocikova, H.; Klener, P.; Salek, D.; Walewski, J.; Szymczyk, M.; Smolej, L.; Auer, R. L.; Ritchie, D. S.; Arcaini, L.; Williams, M. E.; Dreyling, M.; Seymour, J. F.

Central nervous system (CNS) involvement in mantle cell lymphoma (MCL) is uncommon, and the manifestations and natural history are not well described. We present the data on 57 patients with MCL who developed CNS involvement, from a database of 1396 consecutively treated patients at 14 institutions.

Are astrocytes executive cells within the central nervous system?

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Roberto E. Sica

2016-08-01

Full Text Available ABSTRACT Experimental evidence suggests that astrocytes play a crucial role in the physiology of the central nervous system (CNS by modulating synaptic activity and plasticity. Based on what is currently known we postulate that astrocytes are fundamental, along with neurons, for the information processing that takes place within the CNS. On the other hand, experimental findings and human observations signal that some of the primary degenerative diseases of the CNS, like frontotemporal dementia, Parkinson’s disease, Alzheimer’s dementia, Huntington’s dementia, primary cerebellar ataxias and amyotrophic lateral sclerosis, all of which affect the human species exclusively, may be due to astroglial dysfunction. This hypothesis is supported by observations that demonstrated that the killing of neurons by non-neural cells plays a major role in the pathogenesis of those diseases, at both their onset and their progression. Furthermore, recent findings suggest that astrocytes might be involved in the pathogenesis of some psychiatric disorders as well.

Vitamin D and the central nervous system.

Science.gov (United States)

Wrzosek, Małgorzata; Łukaszkiewicz, Jacek; Wrzosek, Michał; Jakubczyk, Andrzej; Matsumoto, Halina; Piątkiewicz, Paweł; Radziwoń-Zaleska, Maria; Wojnar, Marcin; Nowicka, Grażyna

2013-01-01

Vitamin D is formed in human epithelial cells via photochemical synthesis and is also acquired from dietary sources. The so-called classical effect of this vitamin involves the regulation of calcium homeostasis and bone metabolism. Apart from this, non-classical effects of vitamin D have recently gained renewed attention. One important yet little known of the numerous functions of vitamin D is the regulation of nervous system development and function. The neuroprotective effect of vitamin D is associated with its influence on neurotrophin production and release, neuromediator synthesis, intracellular calcium homeostasis, and prevention of oxidative damage to nervous tissue. Clinical studies suggest that vitamin D deficiency may lead to an increased risk of disease of the central nervous system (CNS), particularly schizophrenia and multiple sclerosis. Adequate intake of vitamin D during pregnancy and the neonatal period seems to be crucial in terms of prevention of these diseases.

Immunohistochemical analysis of MMP-9, MMP-2 and TIMP-1, TIMP-2 expression in the central nervous system following infection with viral and bacterial meningitis.

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Lech Chyczewski

2009-01-01

Full Text Available Matrix metalloproteinases (MMPs are capable of degrading components of the basal lamina of cerebral vessels, thereby disrupting the blood-brain barrier and inducing leukocyte recruitment. This study provides comprehensive information regarding the cell specificity of matrix metalloproteinases (MMP-2, MMP-9 and their binding tissue inhibitors (TIMP-1, TIMP-2 in the central nervous system during viral and bacterial meningitis. Specifically, we evaluated the immunoreactivity of MMPs and TIMPs in various cell types in brain parenchyma and meninges obtained from autopsy tissues. We found that a higher proportion of endothelial cells were positive for MMP-9 during meningitis when compared to controls. In addition, the immunoreactivity of MMP-9 decreased and the immunoreactivity of TIMP-1 increased in astrocytes upon infection. Furthermore, the results of this study revealed that mononuclear cells were highly immunoreactive for TIMP-1, TIMP-2 and MMP-9 during viral meningitis and that the expression of TIMPs in polymorphonuclear cells was even higher during bacterial meningitis. Taken together the results of this study indicated that the central nervous system resident cells and inflammatory infiltrates contribute to MMPs activity and that the expression patterns vary between cell types and in response to viral and bacterial meningitis.

Chapter 1. Central nervous system

International Nuclear Information System (INIS)

Planiol, T.; Veyre, A.; Plagne, R.

1975-01-01

The present situation with regard to explorations of the central nervous system by radioactive compounds is reviewed. For the sake of clarity the brain and cerebrospinal fluid examinations are described separately, with emphasis nevertheless on their complementarity. The tracers used in each of these examinations are listed, together with the criteria governing their choice. The different techniques employed are described. Scintigraphy is presented apart from gamma-angio-encephalography since it is not possible with rectilinear scintigraphs to observe the circulatory phase. The results are interpreted by an analysis of normal and pathological aspects of the different stages of the central nervous system [fr

Central nervous system tumors

International Nuclear Information System (INIS)

Curran, W.J. Jr.

1991-01-01

Intrinsic tumors of the central nervous system (CNS) pose a particularly challenging problem to practicing oncologists. These tumors rarely metastasize outside the CNS, yet even histologically benign tumors can be life-threatening due to their local invasiveness and strategic location. The surrounding normal tissues of the nervous system is often incapable of full functional regeneration, therefore prohibiting aggressive attempts to use either complete surgical resection or high doses of irradiation. Despite these limitations, notable achievements have recently been recorded in the management of these tumors

The central nervous system of sea cucumbers (Echinodermata: Holothuroidea shows positive immunostaining for a chordate glial secretion

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Grondona Jesus M

2009-06-01

Full Text Available Abstract Background Echinoderms and chordates belong to the same monophyletic taxon, the Deuterostomia. In spite of significant differences in body plan organization, the two phyla may share more common traits than was thought previously. Of particular interest are the common features in the organization of the central nervous system. The present study employs two polyclonal antisera raised against bovine Reissner's substance (RS, a secretory product produced by glial cells of the subcomissural organ, to study RS-like immunoreactivity in the central nervous system of sea cucumbers. Results In the ectoneural division of the nervous system, both antisera recognize the content of secretory vacuoles in the apical cytoplasm of the radial glia-like cells of the neuroepithelium and in the flattened glial cells of the non-neural epineural roof epithelium. The secreted immunopositive material seems to form a thin layer covering the cell apices. There is no accumulation of the immunoreactive material on the apical surface of the hyponeural neuroepithelium or the hyponeural roof epithelium. Besides labelling the supporting cells and flattened glial cells of the epineural roof epithelium, both anti-RS antisera reveal a previously unknown putative glial cell type within the neural parenchyma of the holothurian nervous system. Conclusion Our results show that: a the glial cells of the holothurian tubular nervous system produce a material similar to Reissner's substance known to be synthesized by secretory glial cells in all chordates studied so far; b the nervous system of sea cucumbers shows a previously unrealized complexity of glial organization. Our findings also provide significant clues for interpretation of the evolution of the nervous system in the Deuterostomia. It is suggested that echinoderms and chordates might have inherited the RS-producing radial glial cell type from the central nervous system of their common ancestor, i.e., the last common

21 CFR 882.5550 - Central nervous system fluid shunt and components.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Central nervous system fluid shunt and components... Central nervous system fluid shunt and components. (a) Identification. A central nervous system fluid... central nervous system to an internal delivery site or an external receptacle for the purpose of relieving...

Childhood Central Nervous System Embryonal Tumors Treatment (PDQ®)—Patient Version

Science.gov (United States)

Childhood central nervous system embryonal tumors and pineal tumors are treated with surgery, radiation therapy, chemotherapy, high-dose chemotherapy with stem cell rescue and targeted therapy. Learn more in this expert-reviewed summary.

Central nervous system complications after liver transplantation.

Science.gov (United States)

Kim, Jeong-Min; Jung, Keun-Hwa; Lee, Soon-Tae; Chu, Kon; Roh, Jae-Kyu

2015-08-01

We investigated the diversity of central nervous system complications after liver transplantation in terms of clinical manifestations and temporal course. Liver transplantation is a lifesaving option for end stage liver disease patients but post-transplantation neurologic complications can hamper recovery. Between 1 January 2001 and 31 December 2010, patients who had undergone liver transplantation at a single tertiary university hospital were included. We reviewed their medical records and brain imaging data and classified central nervous system complications into four categories including vascular, metabolic, infectious and neoplastic. The onset of central nervous system complications was grouped into five post-transplantation intervals including acute (within 1 month), early subacute (1-3 months), late subacute (3-12 months), chronic (1-3 years), and long-term (after 3 years). During follow-up, 65 of 791 patients (8.2%) experienced central nervous system complications, with 30 occurring within 1 month after transplantation. Vascular etiology was the most common (27 patients; 41.5%), followed by metabolic (23; 35.4%), infectious (nine patients; 13.8%), and neoplastic (six patients). Metabolic encephalopathy with altered consciousness was the most common etiology during the acute period, followed by vascular disorders. An initial focal neurologic deficit was detected in vascular and neoplastic complications, whereas metabolic and infectious etiologies presented with non-focal symptoms. Our study shows that the etiology of central nervous system complications after liver transplantation changes over time, and initial symptoms can help to predict etiology. Copyright © 2015 Elsevier Ltd. All rights reserved.

Potential of stem cell based therapy and tissue engineering in the regeneration of the central nervous system

International Nuclear Information System (INIS)

An Yihua; Tsang, Kent K S; Zhang Han

2006-01-01

The insufficiency of self-repair and regeneration of the central nervous system (CNS) leads to difficulty of rehabilitation of the injured brain. In the past few decades, the significant progress in cell therapy and tissue engineering has contributed to the functional recovery of the CNS to a great extent. The present review focuses on the potential role of stem cell based therapy and tissue engineering in the regeneration of the CNS. (topical review)

Axonal Elongation into Peripheral Nervous System ``Bridges'' after Central Nervous System Injury in Adult Rats

Science.gov (United States)

David, Samuel; Aguayo, Albert J.

1981-11-01

The origin, termination, and length of axonal growth after focal central nervous system injury was examined in adult rats by means of a new experimental model. When peripheral nerve segments were used as ``bridges'' between the medulla and spinal cord, axons from neurons at both these levels grew approximately 30 millimeters. The regenerative potential of these central neurons seems to be expressed when the central nervous system glial environment is changed to that of the peripheral nervous system.

Neuro-Coagulopathy: Blood Coagulation Factors in Central Nervous System Diseases.

Science.gov (United States)

De Luca, Ciro; Virtuoso, Assunta; Maggio, Nicola; Papa, Michele

2017-10-12

Blood coagulation factors and other proteins, with modulatory effects or modulated by the coagulation cascade have been reported to affect the pathophysiology of the central nervous system (CNS). The protease-activated receptors (PARs) pathway can be considered the central hub of this regulatory network, mainly through thrombin or activated protein C (aPC). These proteins, in fact, showed peculiar properties, being able to interfere with synaptic homeostasis other than coagulation itself. These specific functions modulate neuronal networks, acting both on resident (neurons, astrocytes, and microglia) as well as circulating immune system cells and the extracellular matrix. The pleiotropy of these effects is produced through different receptors, expressed in various cell types, in a dose- and time-dependent pattern. We reviewed how these pathways may be involved in neurodegenerative diseases (amyotrophic lateral sclerosis, Alzheimer's and Parkinson's diseases), multiple sclerosis, ischemic stroke and post-ischemic epilepsy, CNS cancer, addiction, and mental health. These data open up a new path for the potential therapeutic use of the agonist/antagonist of these proteins in the management of several central nervous system diseases.

Central nervous system resuscitation

DEFF Research Database (Denmark)

McIntosh, T K; Garde, E; Saatman, K E

1997-01-01

Traumatic injury to the central nervous system induces delayed neuronal death, which may be mediated by acute and chronic neurochemical changes. Experimental identification of these injury mechanisms and elucidation of the neurochemical cascade following trauma may provide enhanced opportunities...

Bioengineered Hydrogel to Inhibit Post-Traumatic Central Nervous System Scarring

Science.gov (United States)

2016-10-01

necessary to unlock the full therapeutic value of stem cell -based regenerative therapies. The present proposal takes advantage of a long- standing, cross...the Journal of Controlled Release (J Control Release. 2015 Jun 28;208:76-84). 15. SUBJECT TERMS prevalence, trauma, hydrogel, stem cell therapy...cavitations that are not spontaneously repaired. Early after injury, blood enters the central nervous system (CNS) and directly kills brain cells but also

Effect of Artificial Gravity: Central Nervous System Neurochemical Studies

Science.gov (United States)

Fox, Robert A.; D'Amelio, Fernando; Eng, Lawrence F.

1997-01-01

The major objective of this project was to assess chemical and morphological modifications occurring in muscle receptors and the central nervous system of animals subjected to altered gravity (2 x Earth gravity produced by centrifugation and simulated micro gravity produced by hindlimb suspension). The underlying hypothesis for the studies was that afferent (sensory) information sent to the central nervous system by muscle receptors would be changed in conditions of altered gravity and that these changes, in turn, would instigate a process of adaptation involving altered chemical activity of neurons and glial cells of the projection areas of the cerebral cortex that are related to inputs from those muscle receptors (e.g., cells in the limb projection areas). The central objective of this research was to expand understanding of how chronic exposure to altered gravity, through effects on the vestibular system, influences neuromuscular systems that control posture and gait. The project used an approach in which molecular changes in the neuromuscular system were related to the development of effective motor control by characterizing neurochemical changes in sensory and motor systems and relating those changes to motor behavior as animals adapted to altered gravity. Thus, the objective was to identify changes in central and peripheral neuromuscular mechanisms that are associated with the re-establishment of motor control which is disrupted by chronic exposure to altered gravity.

Central nervous system affecting drugs and road traffic accidents ...

African Journals Online (AJOL)

Central nervous system affecting drugs and road traffic accidents among commercial motorcyclists. ... including driving under the influence of drugs that affect the central nervous system (CNS). ... Keywords: Brain, influence, riders, substances ...

Primary angiitis of the central nervous system with diffuse cerebral mass effect and giant cells.

LENUS (Irish Health Repository)

Kinsella, J A

2012-02-01

Primary angiitis of the central nervous system (PACNS), also called primary CNS vasculitis, is an idiopathic inflammatory condition affecting only intracranial and spinal cord vessels, particularly medium-sized and smaller arteries and arterioles. Angiography and histopathology typically do not reveal evidence of systemic vasculitis.(1,2) Histopathology usually reveals granulomatous inflammation affecting arterioles and small arteries of the parenchyma and\\/or leptomeninges, similar to that seen in Takayasu\\'s or giant cell arteritis.(1-3) We report a patient with biopsy-proven PACNS with giant cells and cerebral mass effect on MRI. Magnetic resonance angiography and cerebral angiography appeared normal and there was no evidence of extracranial vasculitis.

High-fat diet feeding differentially affects the development of inflammation in the central nervous system.

Science.gov (United States)

Guillemot-Legris, Owein; Masquelier, Julien; Everard, Amandine; Cani, Patrice D; Alhouayek, Mireille; Muccioli, Giulio G

2016-08-26

Obesity and its associated disorders are becoming a major health issue in many countries. The resulting low-grade inflammation not only affects the periphery but also the central nervous system. We set out to study, in a time-dependent manner, the effects of a high-fat diet on different regions of the central nervous system with regard to the inflammatory tone. We used a diet-induced obesity model and compared at several time-points (1, 2, 4, 6, 8, and 16 weeks) a group of mice fed a high-fat diet with its respective control group fed a standard diet. We also performed a large-scale analysis of lipids in the central nervous system using HPLC-MS, and we then tested the lipids of interest on a primary co-culture of astrocytes and microglial cells. We measured an increase in the inflammatory tone in the cerebellum at the different time-points. However, at week 16, we evidenced that the inflammatory tone displayed significant differences in two different regions of the central nervous system, specifically an increase in the cerebellum and no modification in the cortex for high-fat diet mice when compared with chow-fed mice. Our results clearly suggest region-dependent as well as time-dependent adaptations of the central nervous system to the high-fat diet. The differences in inflammatory tone between the two regions considered seem to involve astrocytes but not microglial cells. Furthermore, a large-scale lipid screening coupled to ex vivo testing enabled us to identify three classes of lipids-phosphatidylinositols, phosphatidylethanolamines, and lysophosphatidylcholines-as well as palmitoylethanolamide, as potentially responsible for the difference in inflammatory tone. This study demonstrates that the inflammatory tone induced by a high-fat diet does not similarly affect distinct regions of the central nervous system. Moreover, the lipids identified and tested ex vivo showed interesting anti-inflammatory properties and could be further studied to better characterize

Connexin: a potential novel target for protecting the central nervous system?

Directory of Open Access Journals (Sweden)

Hong-yan Xie

2015-01-01

Full Text Available Connexin subunits are proteins that form gap junction channels, and play an important role in communication between adjacent cells. This review article discusses the function of connexins/hemichannels/gap junctions under physiological conditions, and summarizes the findings regarding the role of connexins/hemichannels/gap junctions in the physiological and pathological mechanisms underlying central nervous system diseases such as brain ischemia, traumatic brain and spinal cord injury, epilepsy, brain and spinal cord tumor, migraine, neuroautoimmune disease, Alzheimer′s disease, Parkinson′s disease, X-linked Charcot-Marie-Tooth disease, Pelizaeus-Merzbacher-like disease, spastic paraplegia and maxillofacial dysplasia. Connexins are considered to be a potential novel target for protecting the central nervous system.

Focal lesions in the central nervous system

International Nuclear Information System (INIS)

Fabrikant, J.I.; Budinger, T.F.; Tobias, C.A.; Born, J.L.

1980-01-01

This report reviews the animal and human studies currently in progress at LBL with heavy-ion beams to induce focal lesions in the central nervous system, and discusses the potential future prospects of fundamental and applied brain research with heavy-ion beams. Methods are being developed for producing discrete focal lesions in the central nervous system using the Bragg ionization peak to investigate nerve pathways and neuroendocrine responses, and for treating pathological disorders of the brain

Smart electromechanical systems the central nervous system

CERN Document Server

Kurbanov, Vugar

2017-01-01

This book describes approaches to solving the problems of developing the central nervous system of robots (CNSR) based on smart electromechanical systems (SEMS) modules, principles of construction of the various modules of the central nervous system and variants of mathematical software CNSR in control systems for intelligent robots. It presents the latest advances in theory and practice at the Russian Academy of Sciences. Developers of intelligent robots to solve modern problems in robotics are increasingly addressing the use of the bionic approach to create robots that mimic the complexity and adaptability of biological systems. These have smart electromechanical system (SEMS), which are used in various cyber-physical systems (CPhS), and allow the functions of calculation, control, communications, information storage, monitoring, measurement and control of parameters and environmental parameters to be integrated. The behavior of such systems is based on the information received from the central nervous syst...

Childhood Central Nervous System Atypical Teratoid/Rhabdoid Tumor Treatment

Science.gov (United States)

... teratoid/rhabdoid tumor. There is no standard staging system for central nervous system atypical teratoid/rhabdoid tumor. The extent or spread ... different types of treatment for patients with central nervous system atypical teratoid/rhabdoid tumor. Different types of treatment ...

The twitcher mouse. Central nervous system pathology after bone marrow transplantation

NARCIS (Netherlands)

Suzuki, K.; Hoogerbrugge, P. M.; Poorthuis, B. J.; Bekkum, D. W.

1988-01-01

Effects of bone marrow transplantation (BMT) on the pathology of the central nervous system were evaluated, at light and electron microscope levels, in the homozygous twitcher mouse (twi/twi), an authentic murine model of globoid cell leukodystrophy (GLD, Krabbe disease) in humans. In the twitcher

Treatment Sequencing in a Chronic Lymphocytic Leukemia Patient with Central Nervous System Involvement

Directory of Open Access Journals (Sweden)

Filipa Mousinho

2018-01-01

Full Text Available Early-stage chronic lymphocytic leukemia (CLL with neurologic involvement is a rare condition and should require a careful follow-up. Although no standard protocol exists for this condition, intrathecal chemotherapy, combined with systemic chemoimmunotherapy, has been used previously. This case describes the treatment of a patient with CLL and symptomatic compromise of the central nervous system. Our results suggest that a combination of chemotherapy, radiotherapy, and ibrutinib, administered sequentially over a 2-year period, led to a near-complete resolution of the cerebral spinal fluid neoplastic infiltration. Importantly, this response has been maintained with ibrutinib monotherapy for more than 12 months.

Primary Central Nervous System Lymphoma: Incorporating MRI in the Planning of Treatment Strategies

International Nuclear Information System (INIS)

Eloraby, A.; Zaki, I.

2001-01-01

Primary lymphoma of the central nervous system is becoming increasingly encountered secondary to the acquired immune-deficiency disorders. MRI is rapidly evolving diagnostic tool in the management of the lymphomatous CNS primary infiltrates. Methods and materials: 40 patients of the National Cancer Institute of Cairo University were studied by medium and high power MRI machines before and after intra-venous contrast enhancement. Results: The cerebral lesions exhibited specific diagnostic criteria regarding the anatomical configuration, signal pattern, peri-focal oedema and response to steroids, such manifestations made. Conclusion: MRI a highly reliable tool in the management of the disease. The work proved that spinal cord primary lymphoma is a rare entity

Central Nervous System Infections in Denmark

Science.gov (United States)

2018-02-04

Central Nervous System Infections; Bacterial Meningitis; Viral Meningitis; Aseptic Meningitis; Encephalitis; Brain Abscess; Neuroborreliosis; Neurosyphilis; Lyme Disease; Tertiary Syphilis; Cerebral Abscess; Meningitis

Expanding Role of T Cells in Human Autoimmune Diseases of the Central Nervous System

Directory of Open Access Journals (Sweden)

Deepti Pilli

2017-06-01

Full Text Available It is being increasingly recognized that a dysregulation of the immune system plays a vital role in neurological disorders and shapes the treatment of the disease. Aberrant T cell responses, in particular, are key in driving autoimmunity and have been traditionally associated with multiple sclerosis. Yet, it is evident that there are other neurological diseases in which autoreactive T cells have an active role in pathogenesis. In this review, we report on the recent progress in profiling and assessing the functionality of autoreactive T cells in central nervous system (CNS autoimmune disorders that are currently postulated to be primarily T cell driven. We also explore the autoreactive T cell response in a recently emerging group of syndromes characterized by autoantibodies against neuronal cell-surface proteins. Common methodology implemented in T cell biology is further considered as it is an important determinant in their detection and characterization. An improved understanding of the contribution of autoreactive T cells expands our knowledge of the autoimmune response in CNS disorders and can offer novel methods of therapeutic intervention.

Pomalidomide and Dexamethasone in Treating Patients With Relapsed or Refractory Primary Central Nervous System Lymphoma or Newly Diagnosed or Relapsed or Refractory Intraocular Lymphoma

Science.gov (United States)

2017-08-28

B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma; Central Nervous System Lymphoma; Intraocular Lymphoma; Primary Diffuse Large B-Cell Lymphoma of the Central Nervous System; Recurrent Adult Diffuse Large Cell Lymphoma; Retinal Lymphoma

[Parasitic diseases of the central nervous system].

Science.gov (United States)

Schmutzhard, E

2010-02-01

Central nervous system infections and infestations by protozoa and helminths constitute a problem of increasing importance throughout all of central European and northern/western countries. This is partially due to the globalisation of our society, tourists and business people being more frequently exposed to parasitic infection/infestation in tropical countries than in moderate climate countries. On top of that, migrants may import chronic infestations and infections with parasitic pathogens, eventually also--sometimes exclusively--involving the nervous system. Knowledge of epidemiology, initial clinical signs and symptoms, diagnostic procedures as well as specific chemotherapeutic therapies and adjunctive therapeutic strategies is of utmost important in all of these infections and infestations of the nervous systems, be it by protozoa or helminths. This review lists, mainly in the form of tables, all possible infections and infestations of the nervous systems by protozoa and by helminths. Besides differentiating parasitic diseases of the nervous system seen in migrants, tourists etc., it is very important to have in mind that disease-related (e.g. HIV) or iatrogenic immunosuppression has led to the increased occurrence of a wide variety of parasitic infections and infestations of the nervous system (e. g. babesiosis, Chagas disease, Strongyloides stercoralis infestation, toxoplasmosis, etc.).

Neuroprotective Effects of Lipoxin A4 in Central Nervous System Pathologies

Directory of Open Access Journals (Sweden)

Alessandra Cadete Martini

2014-01-01

Full Text Available Many diseases of the central nervous system are characterized and sometimes worsened by an intense inflammatory response in the affected tissue. It is now accepted that resolution of inflammation is an active process mediated by a group of mediators that can act in synchrony to switch the phenotype of cells, from a proinflammatory one to another that favors the return to homeostasis. This new genus of proresolving mediators includes resolvins, protectins, maresins, and lipoxins, the first to be discovered. In this short review we provide an overview of current knowledge into the cellular and molecular interactions of lipoxins in diseases of the central nervous system in which they appear to facilitate the resolution of inflammation, thus exerting a neuroprotective action.

Central nervous system tissue heterotopia of the nose: case report and review of the literature

Science.gov (United States)

Altissimi, G; Ascani, S; Falcetti, S; Cazzato, C; Bravi, I

2009-01-01

Summary The Authors present a case of heterotopic central nervous system tissue observed in an 81-year-old male in the form of an ethmoidal polyp. A review of the literature indicates that this is a rare condition characterised by a connective tissue lesion with astrocytic and oligodendrocytic glial cells, which may be located outside the nasal pyramid in some cases and inside the nasal cavity in others. The most important diagnostic aspect involves differentiating these from meningoencephalocele, which maintains an anatomical connection with central nervous system tissue. Contrast-enhanced imaging is essential for diagnosis, as in cases of heterotopic central nervous system tissue, it will demonstrate that there are no connections with intra-cranial tissue. Endoscopic excision is the treatment of choice. PMID:20161881

Neutrophils that infiltrate the central nervous system regulate T cell responses

DEFF Research Database (Denmark)

Zehntner, Simone P; Brickman, Cristina; Bourbonnière, Lyne

2005-01-01

Regulation of inflammatory responses is critical to progression of organ-specific autoimmune disease. Although many candidate cell types have been identified, immunoregulatory activity has rarely been directly assayed and never from the CNS. We have analyzed the regulatory capability of Gr-1high ...

[Late sequelae of central nervous system prophylaxis in children with acute lymphoblastic leukemia: high doses of intravenous methotrexate versus radiotherapy of the central nervous system--review of literature].

Science.gov (United States)

Zając-Spychała, Olga; Wachowiak, Jacek

2012-01-01

Acute lymphoblastic leukemia is the most common malignancy in children. All current therapy regimens used in the treatment of childhood acute lymphoblastic leukemia include prophylaxis of the central nervous system. Initially it was thought that the best way of central nervous system prophylaxis is radiotherapy. But despite its effectiveness this method, may cause late sequelae and complications. In the programme currently used in Poland to treat acute lymphoblastic leukemia, prophylactic radiotherapy has been reduced by 50% (12 Gy) and is used only in patients stratified into the high risk group and in patients diagnosed as T-cell ALL (T-ALL). Complementary to radiotherapy, intrathecal methotrexate is given alone or in combination with cytarabine and hydrocortisone is given, as well as systemic chemotherapy with intravenous methotrexate is administered in high or medium doses (depending on risk groups and leukemia immunophenotype). Recent studies have shown that high dose irradiation of the central nervous system impairs cognitive development causing memory loss, visuomotor coordination impairment, attention disorders and reduction in the intelligence quotient. It has been proved that the degree of cognitive impairment depends on the radiation dose directed to the medial temporal lobe structures, particularly in the hippocampus and the surrounding cortex. Also, methotrexate used intravenously in high doses, interferes with the metabolism of folic acid which is necessary for normal development and the optimal functioning of neurons in the central nervous system. It has been proved that patients who have been treated with high doses of methotrexate are characterized by reduced memory skills and a lower intelligence quotient. The literature data concerning long term neuroanatomical abnormalities and neuropsychological deficits are ambiguous, and there is still no data concerning current methods of central nervous system prophylaxis with low doses of irradiation in

Cell and biomolecule delivery for tissue repair and regeneration in the central nervous system.

Science.gov (United States)

Elliott Donaghue, Irja; Tam, Roger; Sefton, Michael V; Shoichet, Molly S

2014-09-28

Tissue engineering frequently involves cells and scaffolds to replace damaged or diseased tissue. It originated, in part, as a means of effecting the delivery of biomolecules such as insulin or neurotrophic factors, given that cells are constitutive producers of such therapeutic agents. Thus cell delivery is intrinsic to tissue engineering. Controlled release of biomolecules is also an important tool for enabling cell delivery since the biomolecules can enable cell engraftment, modulate inflammatory response or otherwise benefit the behavior of the delivered cells. We describe advances in cell and biomolecule delivery for tissue regeneration, with emphasis on the central nervous system (CNS). In the first section, the focus is on encapsulated cell therapy. In the second section, the focus is on biomolecule delivery in polymeric nano/microspheres and hydrogels for the nerve regeneration and endogenous cell stimulation. In the third section, the focus is on combination strategies of neural stem/progenitor cell or mesenchymal stem cell and biomolecule delivery for tissue regeneration and repair. In each section, the challenges and potential solutions associated with delivery to the CNS are highlighted. Copyright © 2014 Elsevier B.V. All rights reserved.

Type, Frequency, and Spatial Distribution of Immune Cell Infiltrates in CNS Germinomas: Evidence for Inflammatory and Immunosuppressive Mechanisms.

Science.gov (United States)

Zapka, Pia; Dörner, Evelyn; Dreschmann, Verena; Sakamato, Noriaki; Kristiansen, Glen; Calaminus, Gabriele; Vokuhl, Christian; Leuschner, Ivo; Pietsch, Torsten

2018-02-01

Central nervous system germinomas are characterized by a massive immune cell infiltrate. We systematically characterized these immune cells in 28 germinomas by immunophenotyping and image analysis. mRNA expression was analyzed by Nanostring technology and in situ RNA hybridization. Tumor infiltrating lymphocytes (TILs) were composed of 61.8% ± 3.1% (mean ± SE) CD3-positive T cells, including 45.2% ± 3.5% of CD4-positive T-helper cells, 23.4% ± 1.5% of CD8-positive cytotoxic T cells, 5.5% ± 0.9% of FoxP3-positive regulatory T cells, and 11.9% ±1.3% PD-1-positive TILs. B cells accounted for 35.8% ± 2.9% of TILs and plasma cells for 9.3% ± 1.6%. Tumor-associated macrophages consisted of clusters of activated PD-L1-positive macrophages and interspersed anti-inflammatory macrophages expressing CD163. Germinoma cells did not express PD-L1. Expression of genes encoding immune cell markers and cytokines was high and comparable to mRNA levels in lymph node tissue. IFNG and IL10 mRNA was detected in subfractions of TILs and in PD-L1-positive macrophages. Taken together, the strong immune reaction observed in germinomas involves inflammatory as well as various suppressive mechanisms. Expression of PD-1 and PD-L1 and infiltration of cytotoxic T cells are biomarkers predictive of response to anti-PD-1/PD-L1 therapies, constituting a rationale for possible novel treatment approaches. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

CT diagnosis of congenital anomalies of the central nervous system

International Nuclear Information System (INIS)

Mori, Koreaki

1980-01-01

In the diagnosis of central nervous system congenital anomalies, understanding of embryology of the central nervous system and pathophysiology of each anomaly are essential. It is important for clinical approach to central nervous system congenital anomalies to evaluate the size of the head and tention of the anterior fontanelle. Accurate diagnosis of congenital anomalies depends on a correlation of CT findings to clinical pictures. Clinical diagnosis of congenital anomalies should include prediction of treatability and prognosis, in addition to recognition of a disease. (author)

The Emerging Roles for Telomerase in the Central Nervous System

Directory of Open Access Journals (Sweden)

Meng-Ying Liu

2018-05-01

Full Text Available Telomerase, a specialized ribonucleoprotein enzyme complex, maintains telomere length at the 3′ end of chromosomes, and functions importantly in stem cells, cancer and aging. Telomerase exists in neural stem cells (NSCs and neural progenitor cells (NPCs, at a high level in the developing and adult brains of humans and rodents. Increasing studies have demonstrated that telomerase in NSCs/NPCs plays important roles in cell proliferation, neuronal differentiation, neuronal survival and neuritogenesis. In addition, recent works have shown that telomerase reverse transcriptase (TERT can protect newborn neurons from apoptosis and excitotoxicity. However, to date, the link between telomerase and diseases in the central nervous system (CNS is not well reviewed. Here, we analyze the evidence and summarize the important roles of telomerase in the CNS. Understanding the roles of telomerase in the nervous system is not only important to gain further insight into the process of the neural cell life cycle but would also provide novel therapeutic applications in CNS diseases such as neurodegenerative condition, mood disorders, aging and other ailments.

Endothelial β-Catenin Signaling Is Required for Maintaining Adult Blood-Brain Barrier Integrity and Central Nervous System Homeostasis.

Science.gov (United States)

Tran, Khiem A; Zhang, Xianming; Predescu, Dan; Huang, Xiaojia; Machado, Roberto F; Göthert, Joachim R; Malik, Asrar B; Valyi-Nagy, Tibor; Zhao, You-Yang

2016-01-12

The blood-brain barrier (BBB) formed by brain endothelial cells interconnected by tight junctions is essential for the homeostasis of the central nervous system. Although studies have shown the importance of various signaling molecules in BBB formation during development, little is known about the molecular basis regulating the integrity of the adult BBB. Using a mouse model with tamoxifen-inducible endothelial cell-restricted disruption of ctnnb1 (iCKO), we show here that endothelial β-catenin signaling is essential for maintaining BBB integrity and central nervous system homeostasis in adult mice. The iCKO mice developed severe seizures accompanied by neuronal injury, multiple brain petechial hemorrhages, and central nervous system inflammation, and all had postictal death. Disruption of endothelial β-catenin induced BBB breakdown and downregulation of the specific tight junction proteins claudin-1 and -3 in adult brain endothelial cells. The clinical relevance of the data is indicated by the observation of decreased expression of claudin-1 and nuclear β-catenin in brain endothelial cells of hemorrhagic lesions of hemorrhagic stroke patients. These results demonstrate the prerequisite role of endothelial β-catenin in maintaining the integrity of adult BBB. The results suggest that BBB dysfunction secondary to defective β-catenin transcription activity is a key pathogenic factor in hemorrhagic stroke, seizure activity, and central nervous system inflammation. © 2015 American Heart Association, Inc.

Central nervous system prophylaxis in diffuse large B-cell lymphoma.

Science.gov (United States)

Zahid, Mohammad Faizan; Khan, Nadia; Hashmi, Shahrukh K; Kizilbash, Sani Haider; Barta, Stefan K

2016-08-01

Central nervous system (CNS) involvement with diffuse large B-cell lymphoma (DLBCL) is a relatively uncommon manifestation; with most cases of CNS involvement occuring during relapse after primary therapy. CNS dissemination typically occurs early in the disease course and is most likely present subclinically at the time of diagnosis in many patients who later relapse in the CNS. CNS relapse in these patients is associated with poor outcomes. Based on a CNS relapse rate of 5% in DLBCL and weighing the benefits against the toxicities, universal application of CNS prophylaxis is not justified. The introduction of rituximab has significantly reduced the incidence of CNS relapse in DLBCL. Different studies have employed other agents for CNS prophylaxis, such as intrathecal chemotherapy and high-dose systemic agents with sufficient CNS penetration. If CNS prophylaxis is to be given, it should be preferably administered during primary chemotherapy. However, there is no strong evidence that supports any single approach for CNS prophylaxis. In this review, we outline different strategies of administering CNS prophylaxis in DLBCL patients reported in literature and discuss their advantages and drawbacks. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Central nervous system infection following allogeneic hematopoietic stem cell transplantation.

Science.gov (United States)

Hanajiri, Ryo; Kobayashi, Takeshi; Yoshioka, Kosuke; Watanabe, Daisuke; Watakabe, Kyoko; Murata, Yutaka; Hagino, Takeshi; Seno, Yasushi; Najima, Yuho; Igarashi, Aiko; Doki, Noriko; Kakihana, Kazuhiko; Sakamaki, Hisashi; Ohashi, Kazuteru

2017-03-01

Here, we described the clinical characteristics and outcomes of central nervous system (CNS) infections occurring after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in a single institution over the previous 6 years. Charts of 353 consecutive allogeneic transplant recipients were retrospectively reviewed for CNS infection. A total of 17 cases of CNS infection were identified at a median of 38 days (range, 10-1028 days) after allo-HSCT. Causative pathogens were human herpesvirus-6 (n=6), enterococcus (n=2), staphylococcus (n=2), streptococcus (n=2), varicella zoster virus (n=1), cytomegalovirus (n=1), John Cunningham virus (n=1), adenovirus (n=1), and Toxoplasma gondii (n=1). The cumulative incidence of CNS infection was 4.1% at 1 year and 5.5% at 5 years. Multivariate analysis revealed that high-risk disease status was a risk factor for developing CNS infection (p=.02), and that overall survival at 3 years after allo-HSCT was 33% in patients with CNS infection and 53% in those without CNS infection (p=.04). Copyright © 2016 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved.

[Central nervous system involvement in systemic lupus erythematosus - diagnosis and therapy].

Science.gov (United States)

Szmyrka, Magdalena

Nervous system involvement in lupus belongs to its severe complications and significantly impacts its prognosis. Neuropsychiatric lupus includes 19 disease manifestations concerning both central and peripheral nervous system. This paper presents clinical aspects of central nervous system involvement in lupus. It reviews its epidemiology, risk factors and principles of diagnosis and therapy.

DNA methylation-based classification of central nervous system tumours

DEFF Research Database (Denmark)

Capper, David; Jones, David T.W.; Sill, Martin

2018-01-01

Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging - with substantial inter-observer variabil......Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging - with substantial inter......-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show...

Pharmacotherapy for Adults with Tumors of the Central Nervous System

OpenAIRE

Schor, Nina F.

2008-01-01

Tumors of the adult central nervous system are among the most common and most chemoresistant neoplasms. Malignant tumors of the brain and spinal cord collectively account for approximately 1.3% of all cancers and 2.2% of all cancer-related deaths. Novel pharmacological approaches to nervous system tumors are urgently needed. This review presents the current approaches and challenges to successful pharmacotherapy of adults with malignant tumors of the central nervous system and discusses novel...

Immune response induction in the central nervous system

DEFF Research Database (Denmark)

Owens, Trevor; Babcock, Alicia

2002-01-01

The primary function of the immune response is protection of the host against infection with pathogens, including viruses. Since viruses can infect any tissue of the body, including the central nervous system (CNS), it is logical that cells of the immune system should equally have access to all...... tissues. Nevertheless, the brain and spinal cord are noted for their lack of immune presence. Relative to other organ systems, the CNS appears immunologically privileged. Furthermore, when immune responses do occur in the CNS, they are frequently associated with deleterious effects such as inflammatory...

Characteristics of experimental Candida albicans infection of the central nervous system in rabbits.

Science.gov (United States)

Jafari, H S; Sáez-Llorens, X; Grimprel, E; Argyle, J C; Olsen, K D; McCracken, G H

1991-08-01

Different concentrations (10(7), 10(5), 10(3) cfu/ml) of Candida albicans were injected intracisternally in rabbits. The highest inoculum was fatal within 14 h in all animals. In recipients of 10(5) and 10(3) cfu/ml inocula, the mean +/- SD peak cerebrospinal fluid (CSF) tumor necrosis factor-alpha (TNF alpha) concentrations were 1.6 +/- 2.42 and 0.3 +/- 0.59 ng/ml, respectively, at 6 h; the mean +/- SD CSF leukocyte and protein concentrations were 6291 +/- 6515 and 453 +/- 674 cells/mm3 (at 24 h) and 118 +/- 90 and 109 +/- 122 mg/dl (at 12 and 24 h), respectively. At 6-10 days after inoculation, a second peak of TNF alpha activity was accompanied by increased CSF inflammation. Mortality in the 10(5) and 10(3) cfu/ml inoculum groups was 56% and 22%, respectively. Fatal infection was associated with higher second CSF peak TNF alpha and leukocyte concentrations and a larger proportion of culture-positive CSF samples. Histopathology revealed hyphal invasion, vasculitis, abscesses, and acute and chronic inflammatory infiltration of meninges and brain parenchyma. This model can be useful for evaluation of the pathogenesis and therapy of central nervous system fungal infections.

[Primary central nervous system lymphoma mimicking ventriculitis].

Science.gov (United States)

Yamamoto, Shiro; Nagano, Seiji; Shibata, Sumiya; Kunieda, Takeharu; Imai, Yukihiro; Kohara, Nobuo

2013-01-01

A 66-year-old man presented with deteriorated bradykinesia, gait disturbance, disorientation, and urinary incontinence for three weeks. Magnetic resonance imaging (MRI) showed dilatation of the ventricles. Cerebrospinal fluid (CSF) examination demonstrated lymphocytic pleocytosis, elevation of protein levels, and decreased of glucose levels. A gadolinium-enhanced MRI revealed lesions in the ventricular wall and choroid plexus, mimicking ventriculitis. No evidence of bacterial, fungal, mycobacterial, or viral infections were observed in the CSF. Flow cytometry of CSF showed predominance of CD20+, λ+ cells. PCR examination of CSF revealed positive IgH gene rearrangement, suggesting B cell lymphoma. Endoscopic brain biopsy showed diffuse large B cell lymphoma. As the patient had no evidence of lymphoma in the other organs, we made a diagnosed of primary central nervous system lymphoma (PCNSL). A limited intraventricular spread of PCNSL is rare but important as one of differential diagnosis of ventriculitis.

Radiation therapy of tumours of the central nervous system

International Nuclear Information System (INIS)

Skolyszewski, J.

1980-01-01

The aim of this work is to present the principles of radiation therapy of tumours of the central nervous system, according to the experience of the Institute of Oncology in Krakow. The text was designed primarily for the radiotherapists involved in the treatment of tumours of the central nervous system, and may be used as an auxiliary textbook for those preparing for the examination in radiotherapy. (author)

In Acute Experimental Autoimmune Encephalomyelitis, Infiltrating Macrophages Are Immune Activated, Whereas Microglia Remain Immune Suppressed

NARCIS (Netherlands)

Vainchtein, I. D.; Vinet, J.; Brouwer, N.; Brendecke, S.; Biagini, G.; Biber, K.; Boddeke, H. W. G. M.; Eggen, B. J. L.

2014-01-01

Multiple sclerosis (MS) is an autoimmune demyelinating disorder of the central nervous system (CNS) characterized by loss of myelin accompanied by infiltration of T-lymphocytes and monocytes. Although it has been shown that these infiltrates are important for the progression of MS, the role of

Iron Oxide Magnetic Nanoparticles Highlight Early Involvement of the Choroid Plexus in Central Nervous System Inflammation

Directory of Open Access Journals (Sweden)

Jason M. Millward

2013-03-01

Full Text Available Neuroinflammation during multiple sclerosis involves immune cell infiltration and disruption of the BBB (blood–brain barrier. Both processes can be visualized by MRI (magnetic resonance imaging, in multiple sclerosis patients and in the animal model EAE (experimental autoimmune encephalomyelitis. We previously showed that VSOPs (very small superparamagnetic iron oxide particles reveal CNS (central nervous system lesions in EAE which are not detectable by conventional contrast agents in MRI. We hypothesized that VSOP may help detect early, subtle inflammatory events that would otherwise remain imperceptible. To investigate the capacity of VSOP to reveal early events in CNS inflammation, we induced EAE in SJL mice using encephalitogenic T-cells, and administered VSOP prior to onset of clinical symptoms. In parallel, we administered VSOP to mice at peak disease, and to unmanipulated controls. We examined the distribution of VSOP in the CNS by MRI and histology. Prior to disease onset, in asymptomatic mice, VSOP accumulated in the choroid plexus and in spinal cord meninges in the absence of overt inflammation. However, VSOP was undetectable in the CNS of non-immunized control mice. At peak disease, VSOP was broadly distributed; we observed particles in perivascular inflammatory lesions with apparently preserved glia limitans. Moreover, at peak disease, VSOP was prominent in the choroid plexus and was seen in elongated endothelial structures, co-localized with phagocytes, and diffusely disseminated in the parenchyma, suggesting multiple entry mechanisms of VSOP into the CNS. Thus, using VSOP we were able to discriminate between inflammatory events occurring in established EAE and, importantly, we identified CNS alterations that appear to precede immune cell infiltration and clinical onset.

Central nervous insulin resistance: a promising target in the treatment of metabolic and cognitive disorders?

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Hallschmid, M; Schultes, B

2009-11-01

Research on functions and signalling pathways of insulin has traditionally focused on peripheral tissues such as muscle, fat and liver, while the brain was commonly believed to be insensitive to the effects of this hormone secreted by pancreatic beta cells. However, since the discovery some 30 years ago that insulin receptors are ubiquitously found in the central nervous system, an ever-growing research effort has conclusively shown that circulating insulin accesses the brain, which itself does not synthesise insulin, and exerts pivotal functions in central nervous networks. As an adiposity signal reflecting the amount of body fat, insulin provides direct negative feedback to hypothalamic nuclei that control whole-body energy and glucose homeostasis. Moreover, insulin affects distinct cognitive processes, e.g. by triggering the formation of psychological memory contents. Accordingly, metabolic and cognitive disorders such as obesity, type 2 diabetes mellitus and Alzheimer's disease are associated with resistance of central nervous structures to the effects of insulin, which may derive from genetic polymorphisms as well as from long-term exposure to excess amounts of circulating insulin due to peripheral insulin resistance. Thus, overcoming central nervous insulin resistance, e.g. by pharmacological interventions, appears to be an attractive strategy in the treatment and prevention of these disorders. Enhancement of central nervous insulin signalling by administration of intranasal insulin, insulin analogues and insulin sensitisers in basic research approaches has yielded encouraging results that bode well for the successful translation of these effects into future clinical practice.

Sjogrens Syndrome Presenting with Central Nervous System Involvement

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Tülay Terzi

2012-01-01

Full Text Available Sjogren’s syndrome is a slowly progressive autoimmune disease. Neurological involvement occurs in approximately 20-25% cases in Sjogren’s syndrome. 87% of the neurological involvement is peripheral nervous system, almost 13% in the form of central nervous system involvement. Affected central nervous system may show similar clinical and radiological findings as in multiple sclerosis (MS. In this paper, a 43-year-old patient is discussed who was referred with the complaint of dizziness, there was MS- like lesions in brain imaging studies and was diagnosed with Sjogren’s syndrome. MS- like clinical and radiologic tables can be seen, albeit rarely in Sjogren’s syndrome. In these cases, early diagnosis and early treatment for the sjögren has a great importance for the prognosis of the disease.

The Choroid Plexus Functions as a Niche for T-Cell Stimulation Within the Central Nervous System

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Itai Strominger

2018-05-01

Full Text Available The choroid plexus (CP compartment in the ventricles of the brain comprises fenestrated vasculature and, therefore, it is permeable to blood-borne mediators of inflammation. Here, we explored whether T-cell activation in the CP plays a role in regulating central nervous system (CNS inflammation. We show that CD4 T cells injected into the lateral ventricles adhere to the CP, transmigrate across its epithelium, and undergo antigen-specific activation and proliferation. This process is enhanced following peripheral immune stimulation and significantly impacts the immune signaling induced by the CP. Ex vivo studies demonstrate that T-cell harboring the CP through its apical surface is a chemokine- and adhesion molecule-dependent process. We suggest that, within the CNS, the CP serves an immunological niche, which rapidly responds to peripheral inflammation and, thereby, promotes two-way T-cell trafficking that impact adaptive immunity in the CNS.

Interferons in the central nervous system

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Owens, Trevor; Khorooshi, Reza M. H.; Wlodarczyk, Agnieszka

2014-01-01

Interferons (IFNs) are implicated as an important component of the innate immune system influencing viral infections, inflammation, and immune surveillance. We review here the complex biological activity of IFNs in the central nervous system (CNS) and associated glial–immune interactions...

Neural stem/progenitor cells as a promising candidate for regenerative therapy of the central nervous system

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Virginie eBonnamain

2012-04-01

Full Text Available Neural transplantation is a promising therapeutic strategy for neurodegenerative diseases and other affections of the central nervous system (CNS like Parkinson and Huntington diseases, multiple sclerosis or stroke. If cell replacement therapy already went through clinical trials for some of these diseases using fetal human neuroblasts, several important limitations led to the search for alternative cell sources that would be more suitable for intracerebral transplantation. Taking into account logistical and ethical issues linked to the use of tissue derived from human fetuses, and the immunologically special status of the CNS allowing the occurrence of deleterious immune reactions, Neural Stem/Progenitor Cells (NSPCs appear as an interesting cell source candidate. In addition to their ability for replacing cell populations lost during the pathological events, NSPCs also display surprising therapeutic effects of neuroprotection and immunomodulation. A better knowledge of the mechanisms involved in these specific characteristics will hopefully lead in the future to a successful use of NSPCs in regenerative medicine for CNS affections.

Localization of rem2 in the central nervous system of the adult rainbow trout (Oncorhynchus mykiss).

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Downs, Anna G; Scholles, Katie R; Hollis, David M

2016-12-01

Rem2 is member of the RGK (Rem, Rad, and Gem/Kir) subfamily of the Ras superfamily of GTP binding proteins known to influence Ca 2+ entry into the cell. In addition, Rem2, which is found at high levels in the vertebrate brain, is also implicated in cell proliferation and synapse formation. Though the specific, regional localization of Rem2 in the adult mammalian central nervous system has been well-described, such information is lacking in other vertebrates. Rem2 is involved in neuronal processes where the capacities between adults of different vertebrate classes vary. Thus, we sought to localize the rem2 gene in the central nervous system of an adult anamniotic vertebrate, the rainbow trout (Oncorhynchus mykiss). In situ hybridization using a digoxigenin (DIG)-labeled RNA probe was used to identify the regional distribution of rem2 expression throughout the trout central nervous system, while real-time polymerase chain reaction (rtPCR) further supported these findings. Based on in situ hybridization, the regional distribution of rem2 occurred within each major subdivision of the brain and included large populations of rem2 expressing cells in the dorsal telencephalon of the cerebrum, the internal cellular layer of the olfactory bulb, and the optic tectum of the midbrain. In contrast, no rem2 expressing cells were resolved within the cerebellum. These results were corroborated by rtPCR, where differential rem2 expression occurred between the major subdivisions assayed with the highest levels being found in the cerebrum, while it was nearly absent in the cerebellum. These data indicate that rem2 gene expression is broadly distributed and likely influences diverse functions in the adult fish central nervous system. Copyright © 2016 Elsevier B.V. All rights reserved.

MicroRNA expression in the adult mouse central nervous system

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Bak, Mads; Silahtaroglu, Asli; Møller, Morten

2008-01-01

distinct areas of the adult mouse central nervous system (CNS). Microarray profiling in combination with real-time RT-PCR and LNA (locked nucleic acid)-based in situ hybridization uncovered 44 miRNAs displaying more than threefold enrichment in the spinal cord, cerebellum, medulla oblongata, pons......RNA-related gene regulatory networks in the mammalian central nervous system. Udgivelsesdato: 2008-Mar...

Calcium signal communication in the central nervous system.

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Braet, Katleen; Cabooter, Liesbet; Paemeleire, Koen; Leybaert, Luc

2004-02-01

The communication of calcium signals between cells is known to be operative between neurons where these signals integrate intimately with electrical and chemical signal communication at synapses. Recently, it has become clear that glial cells also exchange calcium signals between each other in cultures and in brain slices. This communication pathway has received utmost attention since it is known that astrocytic calcium signals can be induced by neuronal stimulation and can be communicated back to the neurons to modulate synaptic transmission. In addition to this, cells that are generally not considered as brain cells become progressively incorporated in the picture, as astrocytic calcium signals are reported to be communicated to endothelial cells of the vessel wall and can affect smooth muscle cell tone to influence the vessel diameter and thus blood flow. We review the available evidence for calcium signal communication in the central nervous system, taking into account a basic functional unit -the brain cell tripartite- consisting of neurons, glial cells and vascular cells and with emphasis on glial-vascular calcium signaling aspects.

Effects of Brazilian scorpion venoms on the central nervous system.

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Nencioni, Ana Leonor Abrahão; Neto, Emidio Beraldo; de Freitas, Lucas Alves; Dorce, Valquiria Abrão Coronado

2018-01-01

In Brazil, the scorpion species responsible for most severe incidents belong to the Tityus genus and, among this group, T. serrulatus , T. bahiensis , T. stigmurus and T. obscurus are the most dangerous ones. Other species such as T. metuendus , T. silvestres, T. brazilae , T. confluens , T. costatus , T. fasciolatus and T. neglectus are also found in the country, but the incidence and severity of accidents caused by them are lower. The main effects caused by scorpion venoms - such as myocardial damage, cardiac arrhythmias, pulmonary edema and shock - are mainly due to the release of mediators from the autonomic nervous system. On the other hand, some evidence show the participation of the central nervous system and inflammatory response in the process. The participation of the central nervous system in envenoming has always been questioned. Some authors claim that the central effects would be a consequence of peripheral stimulation and would be the result, not the cause, of the envenoming process. Because, they say, at least in adult individuals, the venom would be unable to cross the blood-brain barrier. In contrast, there is some evidence showing the direct participation of the central nervous system in the envenoming process. This review summarizes the major findings on the effects of Brazilian scorpion venoms on the central nervous system, both clinically and experimentally. Most of the studies have been performed with T. serrulatus and T. bahiensis . Little information is available regarding the other Brazilian Tityus species.

Effects of heavy particle irradiation on central nervous system

International Nuclear Information System (INIS)

Nojima, Kumie; Nakadai, Taeko; Khono, Yukio

2006-01-01

Effects of low dose heavy particle radiation to central nervous system were studied using human embryonal carcinoma (Ntera2=NT2) and Human neuroblastoma cell (NB1). They exposed to heavy ions and X ray 80% confluent cells in culture bottles. The cells were different type about growth and differentiation in the neuron. The apoptosis profile was measured by AnnexinV-EGFP, PI stained and fluorescence-activated cell sorter (FACS). Memory and learning function of adult mice were studied using water maze test after carbon- or iron-ion irradiation. Memory functions were rapidly decreased after irradiation both ions. Iron -ion group were recovered 20 weeks after irradiation C-ion group were recovered 25 weeks after irradiation. Tier memory were still keep at over 100 weeks after irradiation. (author)

Herpesvirus-associated central nervous system diseases after allogeneic hematopoietic stem cell transplantation.

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Wu, Meiqing; Huang, Fen; Jiang, Xinmiao; Fan, Zhiping; Zhou, Hongsheng; Liu, Can; Jiang, Qianli; Zhang, Yu; Zhao, Ke; Xuan, Li; Zhai, Xiao; Zhang, Fuhua; Yin, Changxin; Sun, Jing; Feng, Ru; Liu, Qifa

2013-01-01

Herpesvirus infections of the central nervous system (CNS) are associated with encephalitis/myelitis and lymphoproliferative diseases in immunocompromised individuals. As of now, data of herpesvirus-associated CNS diseases in transplant recipients is limited. Hence, in this prospective study, we investigated the incidence of herpesvirus-associated CNS diseases and explored the diagnosis of these diseases in 281 allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Herpesvirus-DNA and cerebrospinal fluid (CSF) cells were sampled from 58 recipients with herpesvirus-associated diseases or with unexplainable CNS manifestations. Results showed that 23 patients were diagnosed as herpesvirus-associated CNS diseases, including 15 Epstein-Barr virus (EBV)-associated diseases (4 encephalitis and 11 lymphoproliferative diseases), 5 herpes simplex virus type 1 encephalitis, 2 cytomegalovirus encephalitis/myelitis and 1 varicella zoster virus encephalitis. The median time of diseases onset was 65 (range 22-542) days post-transplantation. The 3-year cumulative incidence of herpesvirus-associated encephalitis/myelitis and post-transplant lymphoproliferative disorder (PTLD) was 6.3% ± 1.9% and 4.1% ± 1.2%, respectively. Of the evaluable cases, CSF cells mainly consisted of CD19(+)CD20(+) B cells (7/11) and had clonal rearrangement of immunoglobulin genes (3/11) in patients with CNS-PTLD. On the contrary, in patients with encephalitis/myelitis, CSF cells were comprised of different cell populations and none of the gene rearrangement was detected. Herpesvirus-associated CNS diseases are common in the early stages of allo-HSCT, wherein EBV is the most frequent causative virus. The immunophenotypic and clonal analysis of CSF cells might be helpful in the differential diagnosis between encephalitis and lymphoproliferative diseases.

CT findings of central nervous system in congenital syphilis infant

International Nuclear Information System (INIS)

Yang Cheng; Yang Xinghui; Wang Man

2005-01-01

Objective: To investigate the CT features of the central nervous system in congenital syphilis infant. Methods: CT findings of central nervous system in 11 infants with clinically proved congenital syphilis were analyzed retrospectively. Results: CT findings in 10 syphilis neonates were diffuse hypodense lesions in the white matter, with subarachnoid and intra-encephalic hemorrhage in 3 and 1 cases, respectively. One 2-month-old syphilis infant case and 5 cases of follow-up after 45 days to 6 months of treatment demonstrated bilateral widened sulci and cistern with enlarged ventricles in 3 of them. Conclusion: CT findings of the central nervous system in congenital syphilis infant are similar to those of hypoxic-ischemic encephalopathy in neonates, and extra-encephalic hydrocephalus or brain hypogenesis ensues later on. (authors)

[Central nervous system control of energy homeostasis].

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Machleidt, F; Lehnert, H

2011-03-01

The brain is continuously supplied with information about the distribution and amount of energy stores from the body periphery. Endocrine, autonomic and cognitive-hedonic signals are centrally integrated and exert effects on the whole organism via anabolic and catabolic pathways. The adiposity signals insulin and leptin reflect the amount of body fat and are part of a negative feedback mechanism between the periphery and the central nervous system. The hypothalamic arcuate nucleus is the most important central nervous structure, which integrates this information. Furthermore, the CNS is able to directly measure and to respond to changes in the concentration of certain nutrients. In order to develop effective therapies for the treatment of disorders of energy balance the further elucidation of these neuro-biological processes is of crucial importance. This article provides an overview of the CNS regulation of metabolism and its underlying molecular mechanisms. © Georg Thieme Verlag KG Stuttgart · New York.

Microglia - insights into immune system structure, function, and reactivity in the central nervous system

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Wirenfeldt, Martin; Babcock, Alicia A; Vinters, Harry V

2011-01-01

Microglia are essential cellular components of a well-functioning central nervous system (CNS). The development and establishment of the microglial population differs from the other major cell populations in the CNS i.e. neurons and macroglia (astrocytes and oligodendrocytes). This different onto...

Patients with primary diffuse large B-cell lymphoma of female genital tract have high risk of central nervous system relapse.

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Cao, Xin-xin; Li, Jian; Zhang, Wei; Duan, Ming-hui; Shen, Ti; Zhou, Dao-bin

2014-06-01

The objective of this study was to evaluate retrospectively the clinical characteristics, treatments, and outcomes of patients with primary diffuse large B-cell lymphoma (DLBCL) of the female genital tract. The basic characteristics, treatments, and outcomes of six patients diagnosed with primary DLBCL of the female genital tract, including the ovary, uterine cervix, and vagina, treated in our hospital between 2000 and 2012, were analyzed retrospectively. Seven of 323 (2.2 %) newly diagnosed DLBCLs were diagnosed as primary female genital tract DLBCL. Six patients with complete medical data were included in the analysis. The median age at diagnosis was 52.5 years (range 20-65). The presenting symptoms included abnormal vaginal bleeding, increased vaginal discharge, abdominal fullness, and abdominal pain. Two patients had stage IE disease and four patients had stage IIE disease. Treatment included chemotherapy only in five patients, and combined chemotherapy and localized radiation in one patient. After a median follow-up of 58 months, four patients showed relapse in the central nervous system and two had died from progressive disease. The median progression-free survival was 27 months and the median overall survival for this group has not been reached. Patients with primary female genital tract DLBCL may have poor outcomes and a high risk of central nervous system relapse. Central nervous system prophylaxis might be considered in addition to systemic chemotherapy for DLBCL of the female genital tract.

Thiophene Scaffold as Prospective Central Nervous System Agent: A Review.

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Deep, Aakash; Narasimhan, Balasubramanian; Aggarwal, Swati; Kaushik, Dhirender; Sharma, Arun K

2016-01-01

Heterocyclic compounds are extensively dispersed in nature and are vital for life. Various investigational approaches towards Structural Activity Relationship that focus upon the exploration of optimized candidates have become vastly important. Literature studies tell that for a series of compounds that are imperative in industrial and medicinal chemistry, thiophene acts as parent. Among various classes of heterocyclic compounds that have potential central nervous system activity, thiophene is the most important one. In the largely escalating chemical world of heterocyclic compounds showing potential pharmacological character, thiophene nucleus has been recognized as the budding entity. Seventeen Papers were included in this review article to define the central nervous system potential of thiophene. This review article enlightens the rationalized use and scope of thiophene scaffold as novel central nervous system activity such as anticonvulsant, acetylcholinesterase inhibitor, cyclin-dependent kinase 5 (cdk5/p25) inhibitors, CNS depressant, capability to block norepinephrine, serotonin and dopamine reuptake by their respective transporters etc. The Finding of this review confirm the importance of thiophene scaffold as potential central nervous system agents. From this outcome, ideas for future molecular modifications leading to the novel derivatives with better constructive pharmacological potential may be derived.

75 FR 75681 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

Science.gov (United States)

2010-12-06

...] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee: To provide...) and/or abnormal vascularity (abnormal blood supply and circulation) of the central nervous system. The...

Expression of Hepatoma-derived growth factor family members in the adult central nervous system

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Abouzied Mekky M

2006-01-01

Full Text Available Abstract Background Hepatoma-derived growth factor (HDGF belongs to a polypeptide family containing five additional members called HDGF related proteins 1–4 (HRP-1 to -4 and Lens epithelial derived growth factor. Whereas some family members such as HDGF and HRP-2 are expressed in a wide range of tissues, the expression of others is very restricted. HRP-1 and -4 are only expressed in testis, HRP-3 only in the nervous system. Here we investigated the expression of HDGF, HRP-2 and HRP-3 in the central nervous system of adult mice on the cellular level by immunohistochemistry. In addition we performed Western blot analysis of various brain regions as well as neuronal and glial cell cultures. Results HDGF was rather evenly expressed throughout all brain regions tested with the lowest expression in the substantia nigra. HRP-2 was strongly expressed in the thalamus, prefrontal and parietal cortex, neurohypophysis, and the cerebellum, HRP-3 in the bulbus olfactorius, piriform cortex and amygdala complex. HDGF and HRP-2 were found to be expressed by neurons, astrocytes and oligodendrocytes. In contrast, strong expression of HRP-3 in the adult nervous system is restricted to neurons, except for very weak expression in oligodendrocytes in the brain stem. Although the majority of neurons are HRP-3 positive, some like cerebellar granule cells are negative. Conclusion The coexpression of HDGF and HRP-2 in glia and neurons as well as the coexpression of all three proteins in many neurons suggests different functions of members of the HDGF protein family in cells of the central nervous system that might include proliferation as well as cell survival. In addition the restricted expression of HRP-3 point to a special function of this family member for neuronal cells.

Differential effects of interleukin-17 receptor signaling on innate and adaptive immunity during central nervous system bacterial infection

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Vidlak Debbie

2012-06-01

Full Text Available Abstract Although IL-17A (commonly referred to as IL-17 has been implicated in the pathogenesis of central nervous system (CNS autoimmune disease, its role during CNS bacterial infections remains unclear. To evaluate the broader impact of IL-17 family members in the context of CNS infection, we utilized IL-17 receptor (IL-17R knockout (KO mice that lack the ability to respond to IL-17, IL-17F and IL-17E (IL-25. In this article, we demonstrate that IL-17R signaling regulates bacterial clearance as well as natural killer T (NKT cell and gamma-delta (γδ T cell infiltrates during Staphylococcus aureus-induced brain abscess formation. Specifically, when compared with wild-type (WT animals, IL-17R KO mice exhibited elevated bacterial burdens at days 7 and 14 following S. aureus infection. Additionally, IL-17R KO animals displayed elevated neutrophil chemokine production, revealing the ability to compensate for the lack of IL-17R activity. Despite these differences, innate immune cell recruitment into brain abscesses was similar in IL-17R KO and WT mice, whereas IL-17R signaling exerted a greater influence on adaptive immune cell recruitment. In particular, γδ T cell influx was increased in IL-17R KO mice at day 7 post-infection. In addition, NK1.1high infiltrates were absent in brain abscesses of IL-17R KO animals and, surprisingly, were rarely detected in the livers of uninfected IL-17R KO mice. Although IL-17 is a key regulator of neutrophils in other infection models, our data implicate an important role for IL-17R signaling in regulating adaptive immunity during CNS bacterial infection.

Magnetic resonance imaging of blood brain/nerve barrier dysfunction and leukocyte infiltration: closely related or discordant?

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Gesa eWeise

2012-12-01

Full Text Available Unlike other organs the nervous system is secluded from the rest of the organism by the blood brain (BBB or blood nerve barrier (BNB preventing passive influx of fluids from the circulation. Similarly, leukocyte entry to the nervous system is tightly controlled. Breakdown of these barriers and cellular inflammation are hallmarks of inflammatory as well as ischemic neurological diseases and thus represent potential therapeutic targets. The spatiotemporal relationship between BBB/BNB disruption and leukocyte infiltration has been a matter of debate. We here review contrast-enhanced magnetic resonance imaging (MRI as a non-invasive tool to depict barrier dysfunction and its relation to macrophage infiltration in the central and peripheral nervous system under pathological conditions. Novel experimental contrast agents like Gadofluorine M (Gf allow more sensitive assessment of BBB dysfunction than conventional Gadolinium (Gd-DTPA-enhanced MRI. In addition, Gf facilitates visualization of functional and transient alterations of the BBB remote from lesions. Cellular contrast agents such as superparamagnetic iron oxide particles (SPIO and perfluorocarbons (PFC enable assessment of leukocyte (mainly macrophage infiltration by MR technology. Combined use of these MR contrast agents disclosed that leukocytes can enter the nervous system independent from a disturbance of the BBB, and vice versa, a dysfunctional BBB/BNB by itself is not sufficient to attract inflammatory cells from the circulation. We will illustrate these basic imaging findings in animal models of multiple sclerosis (MS, cerebral ischemia and traumatic nerve injury and review corresponding findings in patients.

Pazopanib efficacy in recurrent central nervous system hemangiopericytomas.

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Apra, Caroline; Alentorn, Agusti; Mokhtari, Karima; Kalamarides, Michel; Sanson, Marc

2018-04-26

There is currently no treatment for solitary fibrous tumors/hemangiopericytomas (SFT/H) of the central nervous system recurring after multiple surgeries and radiotherapies. The NAB2-STAT6 gene fusion is the hallmark of these tumors, and upregulates Early Growth Factor, activating several growth pathways. We treated two patients presenting pluri-recurrent meningeal SFT/H with Pazopanib, a broad-spectrum tyrosine kinase inhibitor. We analyzed the exome and RNA sequencing data of one of them and, in addition to another meningeal SFT/H, compared it to the transcriptomic profiling of 5 systemic SFT/H. A dramatic clinical and radiological response was observed in both cases, respectively 84 and 43% decrease after 3 months. As a comparison, Pazopanib has only a stabilizing effect in systemic SFT/H. Indeed, central nervous system SFT/H show overexpression of different tyrosine kinases targeted by Pazopanib. Two consecutive patients with untreatable central nervous system SFT/H showed a spectacular partial response to Pazopanib, an unprecedented result in SFT/H. This result could be explained by differences in expression profiles and calls for a confirmation in a larger cohort of patients.

Immunocytochemical distribution of glial fibrillary acidic protein in the central nervous system of the Japanese quail (Coturnix coturnix japonica).

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Cameron-Curry, P; Aste, N; Viglietti-Panzica, C; Panzica, G C

1991-01-01

In the present study we detailed the distribution of GFAP-immunopositive structures within the central nervous system of the Japanese quail. Different fixation and embedding procedures were applied. The best results were obtained on frozen cryostatic sections from freshly dissected brains subsequently fixed by a short immersion in cold acetone. Immunopositive structures were observed both with immunofluorescence, and with immunoperoxidase methods. Immunoreactive cell bodies and processes were observed within the whole central nervous system, and different cell types can be identified on the basis of their topographical location and morphology. A first class of astrocytes is composed of intensely stained unipolar cells lining the inner surface of the pia mater and the large blood vessels. A second type is represented by multipolar astrocytes of variable size, provided with an irregular cell body. The last type is represented by similar elements, showing an immunonegative cell body, that can be identified only by the presence of converging processes. These three types of cells, and several isolated processes, show a differential distribution within the quail central nervous system, both in the grey and in the white matter. Present results suggest that GFAP may represent a good marker for at least part of the astroglial population in quail.

Role of T cell – glial cell interactions in creating and amplifying Central Nervous System inflammation and Multiple Sclerosis disease symptoms

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Eric S. Huseby

2015-08-01

Full Text Available Multiple Sclerosis (MS is an inflammatory disease of the Central Nervous System (CNS that causes the demyelination of nerve cells and destroys oligodendrocytes, neurons and axons. Historically, MS has been thought of as a T cell-mediated autoimmune disease of CNS white matter. However, recent studies have identified gray matter lesions in MS patients, suggesting that CNS antigens other than myelin proteins may be involved during the MS disease process. We have recently found that T cells targeting astrocyte-specific antigens can drive unique aspects of inflammatory CNS autoimmunity, including the targeting of gray matter and white matter of the brain and inducing heterogeneous clinical disease courses. In addition to being a target of T cells, astrocytes play a critical role in propagating the inflammatory response within the CNS through cytokine induced NF-ΚB signaling. Here, we will discuss the pathophysiology of CNS inflammation mediated by T cell – glial cell interactions and its contributions to CNS autoimmunity.

Stimulation of adult oligodendrogenesis by myelin-specific T cells

DEFF Research Database (Denmark)

Hvilsted Nielsen, Helle; Toft-Hansen, Henrik; Lambertsen, Kate Lykke

2011-01-01

of calretinergic associational/commissural fibers within the dentate gyrus. These results have implications for the perception of MS pathogenesis because they show that infiltrating myelin-specific T cells can stimulate oligodendrogenesis in the adult central nervous system....

Experimental alkylmercurial poisoning in swine. Lesions in the peripheral and central nervous systems

Energy Technology Data Exchange (ETDEWEB)

Charlton, K M

1974-01-01

The effects of alkylmercurial poisoning were studied in 16 pigs poisoned with daily oral doses of a fungicide containing methylmercury 2, 3-dihydroxy propyl mercaptide and methylmercury acetate. Clinical signs included weakness, wobbling gait, blindness, recumbency and death. Microscopic studies of the peripheral nervous system revealed Wallerian degeneration in sensory fibers and neuronal degeneration in dorsal root ganglia. In the central nervous system, there were neuronal degeneration of ischemic type, glial degeneration, gliosis and necrosis of the media of meningeal arterioles. The last mentioned lesion was not extensive. The sequential development of lesions and the absence of segmental demyelination suggest that the primary lesion in the peripheral nervous system was neuronal-axonal degeneration rather than degeneration of the Schwann cell and myelin sheath. 25 references.

One Patient, Two Uncommon B-Cell Neoplasms: Solitary Plasmacytoma following Complete Remission from Intravascular Large B-Cell Lymphoma Involving Central Nervous System

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Joycelyn Lee

2014-01-01

Full Text Available Second lymphoid neoplasms are an uncommon but recognized feature of non-Hodgkin’s lymphomas, putatively arising secondary to common genetic or environmental risk factors. Previous limited evaluations of clonal relatedness between successive mature B-cell malignancies have yielded mixed results. We describe the case of a man with intravascular large B-cell lymphoma involving the central nervous system who went into clinical remission following immunochemotherapy and brain radiation, only to relapse 2 years later with a plasmacytoma of bone causing cauda equina syndrome. The plasmacytoma stained strongly for the cell cycle regulator cyclin D1 on immunohistochemistry, while the original intravascular large cell lymphoma was negative, a disparity providing no support for clonal identity between the 2 neoplasms. Continued efforts atcataloging and evaluating unique associations of B-cell malignancies are critical to improving understanding of overarching disease biology in B-cell malignancies.

Microbiota-gut-brain axis and the central nervous system

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Zhu, Xiqun; Han, Yong; Du, Jing; Liu, Renzhong; Jin, Ketao; Yi, Wei

2017-01-01

The gut and brain form the gut-brain axis through bidirectional nervous, endocrine, and immune communications. Changes in one of the organs will affect the other organs. Disorders in the composition and quantity of gut microorganisms can affect both the enteric nervous system and the central nervous system (CNS), thereby indicating the existence of a microbiota-gut-brain axis. Due to the intricate interactions between the gut and the brain, gut symbiotic microorganisms are closely associated ...

Treatment of initial parenchymal central nervous system involvement in systemic aggressive B-cell lymphoma.

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Nijland, Marcel; Jansen, Anne; Doorduijn, Jeanette K; Enting, Roelien H; Bromberg, Jacoline E C; Kluin-Nelemans, Hanneke C

2017-09-01

Central nervous system (CNS) involvement in systemic B-cell non-Hodgkin lymphoma (B-NHL) at diagnosis (sysCNS) is rare. We investigated the outcome of 21 patients with sysCNS, most commonly diffuse large B-cell lymphoma, treated with high dose methotrexate (HD-MTX) and R-CHOP. The median number of cycles of HD-MTX and R-CHOP was 4 (range 1-8) and 6 (range 0-8), respectively. Consolidative whole brain radiotherapy (WBRT) was given to 33% (7/21) patients. With a median follow-up of 44 months the 3-year progression free survival (PFS) and overall survival (OS) were 45% (95%CI 34-56%) and 49% (95%CI 38-60%), respectively. Over 90% of patients had an unfavorable international prognostic index score, reflected by treatment-related mortality of 19% (4/21) and relapse-related mortality of 28% (6/21). The outcome of these patients was, however, unexpectedly good when compared to secondary CNS relapses. Prospective studies are needed to define the optimal treatment for patients with sysCNS, but its rarity might be challenging.

Rat bone marrow progenitor cells transduced in situ by rSV40 vectors differentiate into multiple central nervous system cell lineages.

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Louboutin, Jean-Pierre; Liu, Bianling; Reyes, Beverly A S; Van Bockstaele, Elisabeth J; Strayer, David S

2006-12-01

Using bone marrow-directed gene transfer, we tested whether bone marrow-derived cells may function as progenitors of central nervous system (CNS) cells in adult animals. SV40-derived gene delivery vectors were injected directly into femoral bone marrow, and we examined transgene expression in blood and brain for 0-16 months thereafter by immunostaining for FLAG epitope marker. An average of 5% of peripheral blood cells and 25% of femoral marrow cells were FLAG(+) throughout the study. CNS FLAG-expressing cells were mainly detected in the dentate gyrus (DG) and periventricular subependymal zone (PSZ). Although absent before 1 month and rare at 4 months, DG and PSZ FLAG(+) cells were abundant 16 months after bone marrow injection. Approximately 5% of DG cells expressed FLAG, including neurons (48.6%) and microglia (49.7%), and occasional astrocytes (1.6%), as determined by double immunostaining for FLAG and lineage markers. These data suggest that one or more populations of cells resident within adult bone marrow can migrate to the brain and differentiate into CNS-specific cells.

Magnetic resonance imaging of central nervous system haemorrhage

International Nuclear Information System (INIS)

Silberstein, M.; Hennessy, O.

1993-01-01

The variable magnetic resonance imaging appearances of central nervous system haemorrhage, both intra- and extra-axial, are described. These will vary with the type of image contrast (T1 or T2 weighting), the nature of the imaging sequence (spin-echo or gradient-echo) and the time from onset of haemorrhage. Magnetic resonance imaging is a useful technique for imaging haemorrhage in the central nervous system as it yields temporal information about haematoma development, and it is the only non-invasive means of imaging intraspinal haemorrhage. However, in the imaging of haematomas within 24 h of onset and in subarachnoid haemorrhage computed tomography is the investigation of choice. 13 refs., 6 figs

Central Nervous System Vasculitis: Still More Questions than Answers

Science.gov (United States)

Alba, Marco A; Espígol-Frigolé, Georgina; Prieto-González, Sergio; Tavera-Bahillo, Itziar; García-Martínez, Ana; Butjosa, Montserrat; Hernández-Rodríguez, José; Cid, Maria C

2011-01-01

The central nervous system (CNS) may be involved by a variety of inflammatory diseases of blood vessels. These include primary angiitis of the central nervous system (PACNS), a rare disorder specifically targeting the CNS vasculature, and the systemic vasculitides which may affect the CNS among other organs and systems. Both situations are severe and convey a guarded prognosis. PACNS usually presents with headache and cognitive impairment. Focal symptoms are infrequent at disease onset but are common in more advanced stages. The diagnosis of PACNS is difficult because, although magnetic resonance imaging is almost invariably abnormal, findings are non specific. Angiography has limited sensitivity and specificity. Brain and leptomeningeal biopsy may provide a definitive diagnosis when disclosing blood vessel inflammation and are also useful to exclude other conditions presenting with similar findings. However, since lesions are segmental, a normal biopsy does not completely exclude PACNS. Secondary CNS involvement by systemic vasculitis occurs in less than one fifth of patients but may be devastating. A prompt recognition and aggressive treatment is crucial to avoid permanent damage and dysfunction. Glucocorticoids and cyclophosphamide are recommended for patients with PACNS and for patients with secondary CNS involvement by small-medium-sized systemic vasculitis. CNS involvement in large-vessel vasculitis is usually managed with high-dose glucocorticoids (giant-cell arteritis) or glucocorticoids and immunosuppressive agents (Takayasu’s disease). However, in large vessel vasculitis, where CNS symptoms are usually due to involvement of extracranial arteries (Takayasu’s disease) or proximal portions of intracranial arteries (giant-cell arteritis), revascularization procedures may also have an important role. PMID:22379458

STAT3 activation is associated with cerebrospinal fluid interleukin-10 (IL-10) in primary central nervous system diffuse large B cell lymphoma.

Science.gov (United States)

Mizowaki, Takashi; Sasayama, Takashi; Tanaka, Kazuhiro; Mizukawa, Katsu; Takata, Kumi; Nakamizo, Satoshi; Tanaka, Hirotomo; Nagashima, Hiroaki; Nishihara, Masamitsu; Hirose, Takanori; Itoh, Tomoo; Kohmura, Eiji

2015-09-01

Signal transducers and activators of transcription 3 (STAT3) are activated by various cytokines and oncogenes; however, the activity and pathogenesis of STAT3 in diffuse large B cell lymphoma of the central nervous system have not been thoroughly elucidated. We investigated the phosphorylation levels of STAT3 in 40 specimens of primary central nervous system diffuse large B-cell lymphoma (PCNS DLBCL) and analyzed the association between phsopho-STAT3 (pSTAT3) expression and cerebrospinal fluid (CSF) concentration of interleukin-10 (IL-10) or IL-6. Immunohistochemistry and Western blot analysis revealed that most of the specimens in PCNS DLBCL expressed pSTST3 protein, and a strong phosphorylation levels of STAT3 was statistically associated with high CSF IL-10 levels, but not with CSF IL-6 levels. Next, we demonstrated that recombinant IL-10 and CSF containing IL-10 induced the phosphorylation of STAT3 in PCNS DLBCL cells. Furthermore, molecular subtype classified by Hans' algorithm was correlated with pSTAT3 expression levels and CSF IL-10 levels. These results suggest that the STAT3 activity is correlated with CSF IL-10 level, which is a useful marker for STAT3 activity in PCNS DLBCLs.

Magnetic resonance imaging characteristics in four dogs with central nervous system neosporosis.

Science.gov (United States)

Parzefall, Birgit; Driver, Colin J; Benigni, Livia; Davies, Emma

2014-01-01

Neosporosis is a polysystemic disease that can affect dogs of any age and can cause inflammation of the central nervous system. Antemortem diagnosis can be challenging, as clinical and conventional laboratory test findings are often nonspecific. A previous report described cerebellar lesions in brain MRI studies of seven dogs and proposed that these may be characteristic for central nervous system Neosporosis. The purpose of this retrospective study was to describe MRI characteristics in another group of dogs with confirmed central nervous system neosporosis and compare them with the previous report. The hospital's database was searched for dogs with confirmed central nervous system neosporosis and four observers recorded findings from each dog's MRI studies. A total of four dogs met inclusion criteria. Neurologic examination was indicative of a forebrain and cerebellar lesion in dog 2 and multifocal central nervous system disease in dogs 1, 3, and 4. Magnetic resonance imaging showed mild bilateral and symmetrical cerebellar atrophy in three of four dogs (dogs 2, 3, 4), intramedullary spinal cord changes in two dogs (dogs 3, 4) and a mesencephalic and metencephalic lesion in one dog (dog 2). Multifocal brain lesions were recognized in two dogs (dogs 1, 4) and were present in the thalamus, lentiform nucleus, centrum semiovale, internal capsule, brainstem and cortical gray matter of the frontal, parietal or temporal lobe. Findings indicated that central nervous system neosporosis may be characterized by multifocal MRI lesions as well as cerebellar involvement in dogs. © 2014 American College of Veterinary Radiology.

Primary central nervous system lymphoma: is absence of intratumoral hemorrhage a characteristic finding on MRI?

Science.gov (United States)

Sakata, Akihiko; Okada, Tomohisa; Yamamoto, Akira; Kanagaki, Mitsunori; Fushimi, Yasutaka; Dodo, Toshiki; Arakawa, Yoshiki; Takahashi, Jun C; Miyamoto, Susumu; Togashi, Kaori

2015-06-01

Previous studies have shown that intratumoral hemorrhage is a common finding in glioblastoma multi-forme, but is rarely observed in primary central nervous system lymphoma. Our aim was to reevaluate whether intratumoral hemorrhage observed on T2-weighted imaging (T2WI) as gross intratumoral hemorrhage and on susceptibility-weighted imaging as intratumoral susceptibility signal can differentiate primary central nervous system lymphoma from glioblastoma multiforme. A retrospective cohort of brain tumors from August 2008 to March 2013 was searched, and 58 patients (19 with primary central nervous system lymphoma, 39 with glioblastoma multiforme) satisfied the inclusion criteria. Absence of gross intratumoral hemorrhage was examined on T2WI, and an intratumoral susceptibility signal was graded using a 3-point scale on susceptibility-weighted imaging. Results were compared between primary central nervous system lymphoma and glioblastoma multiforme, and values of P central nervous system lymphoma and 23 patients (59%) with glioblastoma multiforme. Absence of gross intratumoral hemorrhage could not differentiate between the two disorders (P = 0.20). However, intratumoral susceptibility signal grade 1 or 2 was diagnostic of primary central nervous system lymphoma with 78.9% sensitivity and 66.7% specificity (P central nervous system lymphoma from glioblastoma multiforme. However, specificity in this study was relatively low, and primary central nervous system lymphoma cannot be excluded based solely on the presence of an intratumoral susceptibility signal.

Biopsy-proven case of Epstein-Barr virus (EBV)-associated vasculitis of the central nervous system.

Science.gov (United States)

Kano, Kohei; Katayama, Takayuki; Takeguchi, Shiori; Asanome, Asuka; Takahashi, Kae; Saito, Tsukasa; Sawada, Jun; Saito, Masato; Anei, Ryogo; Kamada, Kyousuke; Miyokawa, Naoyuki; Nishihara, Hiroshi; Hasebe, Naoyuki

2017-06-01

A 75-year-old woman was admitted to our hospital with rapidly deteriorating consciousness disturbance. She had a 7-year history of rheumatoid arthritis (RA), which had been treated with methotrexate (MTX) and prednisolone. Brain T2-weighted MRI showed diffuse high-intensity lesions in the cerebral subcortical and deep white matter, bilateral basal ganglia and thalamus. A cerebrospinal fluid examination revealed elevated protein levels and positive Epstein-Barr virus (EBV) DNA. Human immunodeficiency virus was negative. Brain biopsy showed perivascular lymphocytic infiltration in the parenchyma and meninx with EBV-encoded small RNA (EBER). Since this case did not fulfill the criteria for chronic active EBV infection (CAEBV), she was diagnosed with Epstein-Barr virus (EBV)-associated vasculitis of the central nervous system. High-dose methylprednisolone, acyclovir, ganciclovir and foscarnet were not effective. Although EBV is a causative agent of infectious mononucleosis (IM), lymphomas and nasopharyngeal carcinomas, vasculitic pathology of the central nervous system with EBV reactivation in the elderly is rare. Immunosuppressive drugs such as steroids and MTX are widely used to treat autoimmune disorders, but may exacerbate the reactivation of EBV. This is the first case of biopsy-proven EBV-positive/HIV-negative vasculitis during the treatment of RA with MTX and steroids. This case indicates that EBV-associated vasculitis needs to be considered as a differential diagnosis of CNS vasculitis. © 2016 Japanese Society of Neuropathology.

Non-viral Nucleic Acid Delivery Strategies to the Central Nervous System

Directory of Open Access Journals (Sweden)

James-Kevin Tan

2016-11-01

Full Text Available With an increased prevalence and understanding of central nervous system injuries and neurological disorders, nucleic acid therapies are gaining promise as a way to regenerate lost neurons or halt disease progression. While more viral vectors have been used clinically as tools for gene delivery, non-viral vectors are gaining interest due to lower safety concerns and the ability to deliver all types of nucleic acids. Nevertheless, there are still a number of barriers to nucleic acid delivery. In this focused review, we explore the in vivo challenges hindering non-viral nucleic acid delivery to the central nervous system and the strategies and vehicles used to overcome them. Advantages and disadvantages of different routes of administration including: systemic injection, cerebrospinal fluid injection, intraparenchymal injection, and peripheral administration are discussed. Non-viral vehicles and treatment strategies that have overcome delivery barriers and demonstrated in vivo gene transfer to the central nervous system are presented. These approaches can be used as guidelines in developing synthetic gene delivery vectors for central nervous system applications and will ultimately bring non-viral vectors closer to clinical application.

[Primary lymphoma of the central nervous system: 20 years' experience in a referral hospital].

Science.gov (United States)

Calderón-Garcidueñas, A L; Pacheco-Calleros, J; Castelán-Maldonado, E; Nocedal-Rustrián, F C

Primary central nervous system lymphomas (PCNSL) are rare neoplasms. AIM. To study the clinical aspects and the immuno-phenotype of all cases of PCNSL in a 20 years lapse in a referral hospital in Northeastern Mexico. From January 1986 to December 2005 all PCNSL histologically confirmed were studied. The primary lymphomas were 1% of malignant central nervous system neoplasms. 21 cases were studied (ages from 9-70 years) with male predominance (2:1). 24% patients had immuno-suppression. The more frequent clinical data were: papilledema (71%), headache (62%), paresis (48%) and seizures (33%). 33% of patients died during the first six months after diagnosis. The T lymphomas were 19% of cases and corresponded to small cell type. PCNSL are still a diagnostic challenge. Multicenter studies are required in order to determine the best treatment protocol.

Imaging of the fetal central nervous system

NARCIS (Netherlands)

Pistorius, L.R.

2008-01-01

Introduction : Ultrasound and MR imaging of the fetal central nervous system (CNS) develop at an ever-increasing rate. Theoretically, the two modalities should be synergistic, but a literature review revealed the difficulties of determining the merit of either technique and revealed gaps in our

Central nervous system tumors

International Nuclear Information System (INIS)

Gavin, P.R.; Fike, J.R.; Hoopes, P.J.

1995-01-01

Central nervous system (CNS) tumors are relatively common in veterinary medicine, with most diagnoses occurring in the canine and feline species. Numerous tumor types from various cells or origins have been identified with the most common tumors being meningiomas and glial cell tumors. Radiation therapy is often used as an aid to control the clinical signs associated with these neoplasms. In general, these tumors have a very low metastatic potential, such that local control offers substantial benefit. Experience in veterinary radiation oncology would indicate that many patients benefit from radiation treatment. Current practice indicates the need for computed tomography or magnetic resonance imaging studies. These highly beneficial studies are used for diagnosis, treatment planning, and to monitor treatment response. Improvements in treatment planning and radiation delivered to the tumor, while sparing the normal tissues, should improve local control and decrease potential radiation related problems to the CNS. When possible, multiple fractions of 3 Gy or less should be used. The tolerance dose to the normal tissue with this fractionation schedule is 50 to 55 Gy. The most common and serious complications of radiation for CNS tumors is delayed radiation myelopathy and necrosis. Medical management of the patient during radiation therapy requires careful attention to anesthetic protocols, and medications to reduce intracranial pressure that is often elevated in these patients. Canine brain tumors have served as an experimental model to test numerous new treatments. Increased availability of advanced imaging modalities has spawned increased detection of these neoplasms. Early detection of these tumors with appropriate aggressive therapy should prove beneficial to many patients

Primary T cell central nervous system lymphoblastic lymphoma in a child: case report and literature review.

Science.gov (United States)

Mazur, Marcus D; Ravindra, Vijay M; Alashari, Mouied; Raetz, Elizabeth; Poppe, Matthew M; Bollo, Robert J

2015-06-01

Primary central nervous system lymphoma (PCNSL) of T cell origin is rare in pediatric patients. We report a case of T cell PCNSL in a 12-year-old boy and review the literature to highlight the importance of brain biopsy to definitively establish the diagnosis when PCNSL is suspected. A 12-year-old boy presented with worsening left-sided weakness, nausea, vomiting, headache, blurred vision, and diplopia. Magnetic resonance imaging revealed right parietal gyral thickening with faint meningeal contrast enhancement. No clear diagnosis was identified after serum testing, cerebrospinal fluid analysis, and cerebral angiography. To establish the diagnosis definitively, a right craniotomy and open, frameless stereotactic biopsy were performed, which yielded the diagnosis of lymphoblastic T cell lymphoma. PCNSL of T cell origin in children remains poorly studied, with only 18 detailed cases reported over the last three decades, including this case. Establishing a definitive diagnosis of PCNSL is challenging, and a brain biopsy is often required to obtain enough tissue for pathological analysis. Increasing awareness and identification of children diagnosed with T cell PCNSL is needed to better understand the molecular biology of this disease and develop more standardized treatment regimens.

Immune and Inflammatory Responses in the Central Nervous System: Modulation by Astrocytes

DEFF Research Database (Denmark)

Penkowa, Milena; hidalgo, juan; aschner, michael

2008-01-01

Beyond their long-recognized support functions, astrocytes are active partners of neurons in processing information, synaptic integration, and production of trophic factors, just to name a few. Both microglia and astrocytes produce and secrete a number of cytokines, modulating and integrating...... the communication between hematogenous cells and resident cells of the central nervous system (CNS). This review will address (1) the functions of astrocytes in the normal brain and (2) their role in surveying noxious stimuli within the brain, with particular emphasis on astrocytic responses to damage or disease...

Acute Central Nervous System Complications in Pediatric Acute Lymphoblastic Leukemia.

Science.gov (United States)

Baytan, Birol; Evim, Melike Sezgin; Güler, Salih; Güneş, Adalet Meral; Okan, Mehmet

2015-10-01

The outcome of childhood acute lymphoblastic leukemia has improved because of intensive chemotherapy and supportive care. The frequency of adverse events has also increased, but the data related to acute central nervous system complications during acute lymphoblastic leukemia treatment are sparse. The purpose of this study is to evaluate these complications and to determine their long term outcome. We retrospectively analyzed the hospital reports of 323 children with de novo acute lymphoblastic leukemia from a 13-year period for acute neurological complications. The central nervous system complications of leukemic involvement, peripheral neuropathy, and post-treatment late-onset encephalopathy, and neurocognitive defects were excluded. Twenty-three of 323 children (7.1%) suffered from central nervous system complications during acute lymphoblastic leukemia treatment. The majority of these complications (n = 13/23; 56.5%) developed during the induction period. The complications included posterior reversible encephalopathy (n = 6), fungal abscess (n = 5), cerebrovascular lesions (n = 5), syndrome of inappropriate secretion of antidiuretic hormone (n = 4), and methotrexate encephalopathy (n = 3). Three of these 23 children (13%) died of central nervous system complications, one from an intracranial fungal abscess and the others from intracranial thrombosis. Seven of the survivors (n = 7/20; 35%) became epileptic and three of them had also developed mental and motor retardation. Acute central neurological complications are varied and require an urgent approach for proper diagnosis and treatment. Collaboration among the hematologist, radiologist, neurologist, microbiologist, and neurosurgeon is essential to prevent fatal outcome and serious morbidity. Copyright © 2015 Elsevier Inc. All rights reserved.

Advances toward regenerative medicine in the central nervous system: challenges in making stem cell therapy a viable clinical strategy.

Science.gov (United States)

Stoll, Elizabeth A

2014-01-01

Over recent years, there has been a great deal of interest in the prospects of stem cell-based therapies for the treatment of nervous system disorders. The eagerness of scientists, clinicians, and spin-out companies to develop new therapies led to premature clinical trials in human patients, and now the initial excitement has largely turned to skepticism. Rather than embracing a defeatist attitude or pressing blindly ahead, I argue it is time to evaluate the challenges encountered by regenerative medicine in the central nervous system and the progress that is being made to solve these problems. In the twenty years since the adult brain was discovered to have an endogenous regenerative capacity, much basic research has been done to elucidate mechanisms controlling proliferation and cellular identity; how stem cells may be directed into neuronal lineages; genetic, pharmacological, and behavioral interventions that modulate neurogenic activity; and the exact nature of limitations to regeneration in the adult, aged, diseased and injured CNS. These findings should prove valuable in designing realistic clinical strategies to improve the prospects of stem cell-based therapies. In this review, I discuss how basic research continues to play a critical role in identifying both barriers and potential routes to regenerative therapy in the CNS.

Central nervous system tuberculomata presenting as internuclear ...

African Journals Online (AJOL)

Central nervous system (CNS) tuberculoma can have variable presentation depending upon the site and number of tuberculomata. We are reporting a rare case of a 15 years old girl who presented to our hospital with binocular diplopia on right gaze. Clinical examination revealed left sided internuclear ophthalmoplegia ...

Multiple sclerosis: a study of CXCL10 and CXCR3 co-localization in the inflamed central nervous system

DEFF Research Database (Denmark)

Sørensen, Torben Lykke; Trebst, Corinna; Kivisäkk, Pia

2002-01-01

T-cell accumulation in the central nervous system (CNS) is considered crucial to the pathogenesis of multiple sclerosis (MS). We found that the majority of T cells within the cerebrospinal fluid (CSF) compartment expressed the CXC chemokine receptor 3 (CXCR), independent of CNS inflammation...

The Central Nervous System and Bone Metabolism: An Evolving Story.

Science.gov (United States)

Dimitri, Paul; Rosen, Cliff

2017-05-01

Our understanding of the control of skeletal metabolism has undergone a dynamic shift in the last two decades, primarily driven by our understanding of energy metabolism. Evidence demonstrating that leptin not only influences bone cells directly, but that it also plays a pivotal role in controlling bone mass centrally, opened up an investigative process that has changed the way in which skeletal metabolism is now perceived. Other central regulators of bone metabolism have since been identified including neuropeptide Y (NPY), serotonin, endocannabinoids, cocaine- and amphetamine-regulated transcript (CART), adiponectin, melatonin and neuromedin U, controlling osteoblast and osteoclast differentiation, proliferation and function. The sympathetic nervous system was originally identified as the predominant efferent pathway mediating central signalling to control skeleton metabolism, in part regulated through circadian genes. More recent evidence points to a role of the parasympathetic nervous system in the control of skeletal metabolism either through muscarinic influence of sympathetic nerves in the brain or directly via nicotinic receptors on osteoclasts, thus providing evidence for broader autonomic skeletal regulation. Sensory innervation of bone has also received focus again widening our understanding of the complex neuronal regulation of bone mass. Whilst scientific advance in this field of bone metabolism has been rapid, progress is still required to understand how these model systems work in relation to the multiple confounders influencing skeletal metabolism, and the relative balance in these neuronal systems required for skeletal growth and development in childhood and maintaining skeletal integrity in adulthood.

Harnessing the capacity of cell-penetrating peptides for drug delivery to the central nervous system.

Science.gov (United States)

Kang, Ting; Gao, Xiaoling; Chen, Jun

2014-01-01

The existence of blood-brain barrier (BBB) represents the most formidable challenge for drug delivery to the central nervous system (CNS). Modern breakthrough in biology offers multiple choices for overcoming this barrier but yields modest outcomes for clinical application due to various problems such as safety concerns, insufficient delivery efficiency and poor penetration. Cell penetrating peptides (CPPs) possessing powerful transmembrane capacity have been shown to be effective transport vectors for bioactive molecules and an attractive alternative to traditional active targeting approaches. However, the non-specificity of CPPs has hindered them from targeting a desired site of action. Promisingly, design of novel CPP-mediated nanoparticulate delivery systems with specific targeting property may extricate CPPs from the dilemma. In this review, both the traditional and novel applications of CPPs-based strategies for CNS drug delivery will be discussed.

Expression of specific chemokines and chemokine receptors in the central nervous system of multiple sclerosis patients

DEFF Research Database (Denmark)

Sørensen, Torben Lykke; Tani, M; Jensen, J

1999-01-01

Chemokines direct tissue invasion by specific leukocyte populations. Thus, chemokines may play a role in multiple sclerosis (MS), an idiopathic disorder in which the central nervous system (CNS) inflammatory reaction is largely restricted to mononuclear phagocytes and T cells. We asked whether...

The Central Nervous System Sites Mediating the Orexigenic Actions of Ghrelin

Science.gov (United States)

Mason, B.L.; Wang, Q.; Zigman, J.M.

2014-01-01

The peptide hormone ghrelin is important for both homeostatic and hedonic eating behaviors, and its orexigenic actions occur mainly via binding to the only known ghrelin receptor, the growth hormone secretagogue receptor (GHSR). GHSRs are located in several distinct regions of the central nervous system. This review discusses those central nervous system sites that have been found to play critical roles in the orexigenic actions of ghrelin, including hypothalamic nuclei, the hippocampus, the amygdala, the caudal brain stem, and midbrain dopaminergic neurons. Hopefully, this review can be used as a stepping stone for the reader wanting to gain a clearer understanding of the central nervous system sites of direct ghrelin action on feeding behavior, and as inspiration for future studies to provide an even-more-detailed map of the neurocircuitry controlling eating and body weight. PMID:24111557

Central nervous system infections in heart transplant recipients

NARCIS (Netherlands)

van de Beek, Diederik; Patel, Robin; Daly, Richard C.; McGregor, Christopher G. A.; Wijdicks, Eelco F. M.

2007-01-01

OBJECTIVE: To study central nervous system infections after heart transplantations. DESIGN: Retrospective cohort study. SETTING: Cardiac Transplant Program at Mayo Clinic, Rochester, Minnesota. Patients Three hundred fifteen consecutive patients who underwent heart transplantation from January 1988

TNF-alpha expression by resident microglia and infiltrating leukocytes in the central nervous system of mice with experimental allergic encephalomyelitis

DEFF Research Database (Denmark)

Renno, T; Krakowski, M; Piccirillo, C

1995-01-01

in the pathology of multiple sclerosis and its animal model experimental allergic encephalomyelitis (EAE). We used reverse transcriptase (RT)-PCR to study the kinetics, cellular source, and regulation of cytokine gene expression in the central nervous system (CNS) of SJL/J mice with myelin basic protein......, the majority of which were identified as microglia and macrophages by their Mac-1 phenotype. Microglia could be discriminated by their low expression of CD45. Incubation of freshly derived, adult microglia from normal, uninfiltrated, CNS with activated Th1 supernatant induced the production of TNF-alpha m...

Eosinophilic Esophagitis: Relevance of Mast Cell Infiltration.

Science.gov (United States)

Strasser, Daniel S; Seger, Shanon; Bussmann, Christian; Pierlot, Gabin M; Groenen, Peter M A; Stalder, Anna K; Straumann, Alex

2018-05-17

Eosinophilic esophagitis (EoE) is a chronic-inflammatory disease characterized clinically by symptoms of esophageal dysfunction and histopathologically by a prominent eosinophilic inflammation. Despite eosinophils having histologically a pre-dominant position, their role in the immunopathogenesis of the disease is still questionable. Several other inflammatory cells are involved and may play a critical role as well. The purpose of this study was to characterize the mast cell infiltration, and to correlate it with clinical state of EoE. Using immunohistochemistry and quantitative morphometry, we extensively investigated eosinophils and mast cells in esophageal biopsies from patients with active EoE and from patients with EoE in remission, and compared the findings with healthy individuals. In EoE, epithelium and lamina propria were similarly infiltrated with eosinophils. In contrast, mast cells infiltration was limited to the epithelium, displaying a localized immune response. Interestingly, whereas epithelial mast cells and eosinophils were high in active EoE, some patients in remission e.g. normalized epithelial eosinophils, showed remaining high numbers of mast cells. Patient clustering supported 2 groups of patients in clinical remission, differentiating based on presence or absence of epithelial mast cells. Active EoE is characterized - in addition to the well-known tissue eosinophilia by a marked epithelium-restricted mast cell infiltration. Of interest, in a subgroup of patients, mast cell infiltration persisted despite clinical remission. To elucidate the clinical consequence of persistent epithelial mast cells infiltration further studies are required following patients in clinical remission longitudinally. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Central nervous system tuberculosis | Cherian | African Health ...

African Journals Online (AJOL)

Central nervous system (CNS) involvement, one of the most devastating clinical manifestations of tuberculosis (TB) is noted in 5 to 10% of extrapulmonary TB cases, and accounts for approximately 1% of all TB cases. Definitive diagnosis of tuberculous meningitis (TBM) depends upon the detection of the tubercle bacilli in ...

Histologic examination of the rat central nervous system after intrathecal administration of human beta-endorphin

DEFF Research Database (Denmark)

Hée, P.; Klinken, Leif; Ballegaard, Martin

1992-01-01

Neuropathology, analgesics - intrathecal, central nervous system, histology, human beta-endorphin, toxicity......Neuropathology, analgesics - intrathecal, central nervous system, histology, human beta-endorphin, toxicity...

MRI findings in central nervous system of neurofibromatosis-II

International Nuclear Information System (INIS)

Chen Maoen; Huang Suiqiao; Shen Jun; Hong Guobin; Wu Zhuo; Lin Xiaofeng

2007-01-01

Objective: To investigate the diagnostic value of MR imaging in central nervous system involvement of neurofibromatosis II. Methods: 7 patients with surgically and pathologically proved neurofibromatosis II were included. Their MR imaging findings and clinical features were retrospectively analyzed. Results: The main findings of 7 cases of neurofibraomaosis II on MR imaging included bilateral acoustic neurilemoma, multiple neurofibroma, meningioma and schwannoma. Among the 7 patients, Tl-weighted imaging after contrast enhancement displayed additional lesions which had been ignored on un-enhanced scan. Conclusion: MR imaging has advantages in the detection of central nervous sys- tem involvement of neurofibromatosis II with regard to its ability to show the lesions well, meanwhile displaying the size, morphology and signal features clearly. (authors)

Specific central nervous system recruitment of HLA-G(+) regulatory T cells in multiple sclerosis.

Science.gov (United States)

Huang, Yu-Hwa; Zozulya, Alla L; Weidenfeller, Christian; Metz, Imke; Buck, Dorothea; Toyka, Klaus V; Brück, Wolfgang; Wiendl, Heinz

2009-08-01

We have recently described a novel population of natural regulatory T cells (T(reg)) that are characterized by the expression of HLA-G and may be found at sites of tissue inflammation (HLA-G(pos) T(reg)). Here we studied the role of these cells in multiple sclerosis (MS), a prototypic autoimmune inflammatory disorder of the central nervous system (CNS). Sixty-four patients with different types of MS, 9 patients with other neurological diseases, and 20 healthy donors were included in this study. Inflamed brain lesions from 5 additional untreated MS patients were examined. HLA-G(pos) T(reg) were analyzed in the cerebrospinal fluid (CSF) by flow cytometry and in inflammatory demyelinating lesions of MS brain specimens by immunohistochemistry. Functional capacity was accessed and transmigration was determined using an in vitro model of the human blood-brain barrier (BBB). HLA-G(pos) T(reg) were found enriched in the inflamed CSF of MS patients and in inflammatory demyelinating lesions of MS brain specimens. HLA-G(pos) T(reg) showed a strong propensity to transmigrate across BBB, which was vigorously driven by inflammatory chemokines, and associated with a gain of suppressive capacity upon transmigration. CSF-derived HLA-G(pos) T(reg) of MS patients represented a population of activated central memory activated T cells with an upregulated expression of inflammatory chemokine receptors and exhibiting full suppressive capacity. Unlike natural FoxP3-expressing T(reg), HLA-G(pos) T(reg) derived from peripheral blood were functionally unimpaired in MS. In MS, HLA-G(pos) T(reg) may serve to control potentially destructive immune responses directly at the sites of CNS inflammation and to counterbalance inflammation once specifically recruited to the CNS.

A Case of Primary Central Nervous System Lymphoma Located at Brain Stem in a Child.

Science.gov (United States)

Kim, Jinho; Kim, Young Zoon

2016-10-01

Primary central nervous system lymphoma (PCNSL) is an extranodal Non-Hodgkin's lymphoma that is confined to the brain, eyes, and/or leptomeninges without evidence of a systemic primary tumor. Although the tumor can affect all age groups, it is rare in childhood; thus, its incidence and prognosis in children have not been well defined and the best treatment strategy remains unclear. A nine-year old presented at our department with complaints of diplopia, dizziness, dysarthria, and right side hemiparesis. Magnetic resonance image suggested a diffuse brain stem glioma with infiltration into the right cerebellar peduncle. The patient was surgically treated by craniotomy and frameless stereotactic-guided biopsy, and unexpectedly, the histopathology of the mass was consistent with diffuse large B cell lymphoma, and immunohistochemical staining revealed positivity for CD20 and CD79a. Accordingly, we performed a staging work-up for systemic lymphoma, but no evidence of lymphoma elsewhere in the body was obtained. In addition, she had a negative serologic finding for human immunodeficient virus, which confirmed the histopathological diagnosis of PCNSL. She was treated by radiosurgery at 12 Gy and subsequent adjuvant combination chemotherapy based on high dose methotrexate. Unfortunately, 10 months after the tissue-based diagnosis, she succumbed due to an acute hydrocephalic crisis.

Radon exposure and tumors of the central nervous system.

Science.gov (United States)

Ruano-Ravina, Alberto; Dacosta-Urbieta, Ana; Barros-Dios, Juan Miguel; Kelsey, Karl T

2017-03-15

To review the published evidence of links between radon exposure and central nervous system tumors through a systematic review of the scientific literature. We performed a thorough bibliographic search in Medline (PubMed) and EMBASE. We combined MeSH (Medical Subject Heading) terms and free text. We developed a purpose-designed scale to assess the quality of the included manuscripts. We have included 18 studies, 8 performed on miners, 3 on the general population and 7 on children, and the results have been structured using this classification. The results are inconclusive. An association between radon exposure and central nervous system tumors has been observed in some studies on miners, but not in others. The results observed in the general adult population and in children are also mixed, with some research evincing a statistically significant association and others showing no effect. We cannot conclude that there is a relationship between radon exposure and central nervous system tumors. The available studies are extremely heterogeneous in terms of design and populations studied. Further research is needed in this topic, particularly in the general population residing in areas with high levels of radon. Copyright © 2017 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

[The Role of Imaging in Central Nervous System Infections].

Science.gov (United States)

Yokota, Hajime; Tazoe, Jun; Yamada, Kei

2015-07-01

Many infections invade the central nervous system. Magnetic resonance imaging (MRI) is the main tool that is used to evaluate infectious lesions of the central nervous system. The useful sequences on MRI are dependent on the locations, such as intra-axial, extra-axial, and spinal cord. For intra-axial lesions, besides the fundamental sequences, including T1-weighted images, T2-weighted images, and fluid-attenuated inversion recovery (FLAIR) images, advanced sequences, such as diffusion-weighted imaging, diffusion tensor imaging, susceptibility-weighted imaging, and MR spectroscopy, can be applied. They are occasionally used as determinants for quick and correct diagnosis. For extra-axial lesions, understanding the differences among 2D-conventional T1-weighted images, 2D-fat-saturated T1-weighted images, 3D-Spin echo sequences, and 3D-Gradient echo sequence after the administration of gadolinium is required to avoid wrong interpretations. FLAIR plus gadolinium is a useful tool for revealing abnormal enhancement on the brain surface. For the spinal cord, the sequences are limited. Evaluating the distribution and time course of the spinal cord are essential for correct diagnoses. We summarize the role of imaging in central nervous system infections and show the pitfalls, key points, and latest information in them on clinical practices.

Regenerative Therapies for Central Nervous System Diseases: a Biomaterials Approach

Science.gov (United States)

Tam, Roger Y; Fuehrmann, Tobias; Mitrousis, Nikolaos; Shoichet, Molly S

2014-01-01

The central nervous system (CNS) has a limited capacity to spontaneously regenerate following traumatic injury or disease, requiring innovative strategies to promote tissue and functional repair. Tissue regeneration strategies, such as cell and/or drug delivery, have demonstrated promising results in experimental animal models, but have been difficult to translate clinically. The efficacy of cell therapy, which involves stem cell transplantation into the CNS to replace damaged tissue, has been limited due to low cell survival and integration upon transplantation, while delivery of therapeutic molecules to the CNS using conventional methods, such as oral and intravenous administration, have been limited by diffusion across the blood–brain/spinal cord-barrier. The use of biomaterials to promote graft survival and integration as well as localized and sustained delivery of biologics to CNS injury sites is actively being pursued. This review will highlight recent advances using biomaterials as cell- and drug-delivery vehicles for CNS repair. PMID:24002187

[Primary malignant melanoma of the central nervous system: A diagnostic challenge].

Science.gov (United States)

Quillo-Olvera, Javier; Uribe-Olalde, Juan Salvador; Alcántara-Gómez, Leopoldo Alberto; Rejón-Pérez, Jorge Dax; Palomera-Gómez, Héctor Guillermo

2015-01-01

The rare incidence of primary malignant melanoma of the central nervous system and its ability to mimic other melanocytic tumors on images makes it a diagnostic challenge for the neurosurgeon. A 51-year-old patient, with a tumor located in the right forniceal callosum area. Total surgical excision was performed. Histopathological result was consistent with the diagnosis of primary malignant melanoma of the central nervous system, after ruling out extra cranial and extra spinal melanocytic lesions. The primary malignant melanoma of the central nervous system is extremely rare. There are features in magnetic resonance imaging that increase the diagnostic suspicion; nevertheless there are other tumors with more prevalence that share some of these features through image. Since there is not an established therapeutic standard its prognosis is discouraging. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

Development of a Physiologically-Based Pharmacokinetic Model of the Rat Central Nervous System

Directory of Open Access Journals (Sweden)

Raj K. Singh Badhan

2014-03-01

Full Text Available Central nervous system (CNS drug disposition is dictated by a drug’s physicochemical properties and its ability to permeate physiological barriers. The blood–brain barrier (BBB, blood-cerebrospinal fluid barrier and centrally located drug transporter proteins influence drug disposition within the central nervous system. Attainment of adequate brain-to-plasma and cerebrospinal fluid-to-plasma partitioning is important in determining the efficacy of centrally acting therapeutics. We have developed a physiologically-based pharmacokinetic model of the rat CNS which incorporates brain interstitial fluid (ISF, choroidal epithelial and total cerebrospinal fluid (CSF compartments and accurately predicts CNS pharmacokinetics. The model yielded reasonable predictions of unbound brain-to-plasma partition ratio (Kpuu,brain and CSF:plasma ratio (CSF:Plasmau using a series of in vitro permeability and unbound fraction parameters. When using in vitro permeability data obtained from L-mdr1a cells to estimate rat in vivo permeability, the model successfully predicted, to within 4-fold, Kpuu,brain and CSF:Plasmau for 81.5% of compounds simulated. The model presented allows for simultaneous simulation and analysis of both brain biophase and CSF to accurately predict CNS pharmacokinetics from preclinical drug parameters routinely available during discovery and development pathways.

Diverse roles of neurotensin agonists in the central nervous system

Directory of Open Access Journals (Sweden)

Mona eBoules

2013-03-01

Full Text Available NT is a tridecapeptide that is found in the central nervous system and the gastrointestinal tract. NT behaves as a neurotransmitter in the brain and as a hormone in the gut. Additionally, NT acts as a neuromodulator to several neurotransmitter systems including dopaminergic, sertonergic, GABAergic, glutamatergic and cholinergic systems. Due to its association with such a wide variety of neurotransmitters, NT has been implicated in the pathophysiology of several central nervous system (CNS disorders such as schizophrenia, drug abuse, Parkinson’s disease, pain, central control of blood pressure, eating disorders, as well as, cancer and inflammation. The present review will focus on the role that NT and its analogs play in schizophrenia, endocrine function, pain, psychostimulant abuse, and Parkinson’s disease.

CT and MRI analysis of central nervous system Rosai-Dorfman disease

International Nuclear Information System (INIS)

Zhang Jiatang; Lang Senyang; Pu Chuanqiang; Zhu Ruyuan; Wang Dianjun

2008-01-01

Objective: To study the CT and MRI imaging features of central nervous system Rosai-Dorfman disease and to enhance knowledge and differential diagnostic ability for central nervous system Rosai-Doffman disease. Methods: The CT and MRI imaging appearances in 4 cases of pathologically proven Rosai-Dorfman disease were retrospectively evaluated and the literature of central nervous system Rosai- Dorfman disease were reviewed. Results: Two cases had cranial CT scans, 4 cases had cranial MRI scans. On CT scans, cerebral edema was demonstrated in one case and the other case was normal. MRI scans showed the lesions were solitary in saddle area in 3 cases, and multiple in anterior cranial fossa in 1 case. The lesions exhibited iso- to hypointensity on both T 1 WI and T 2 WI images. Following intravenous injection of contrast medium, ring-like enhancement was seen in 2 cases and homogeneous enhancement in 1 case. Nodular enhancement was seen in the case of multiple lesions in the anterior cranial fossa. All lesions were dural-based. Conclusions: In patients with fever, headache, elevation of the erythrocyte sedimentation rate (ESR) and a polyclonal increase in γ-globulins, the possibility of central nervous system Rosai-Dorfman disease should be considered when single or multiple dural-based mass lesions, especially in sellar region, were identified by CT and MRI. (authors)

Microbiota-gut-brain axis and the central nervous system.

Science.gov (United States)

Zhu, Xiqun; Han, Yong; Du, Jing; Liu, Renzhong; Jin, Ketao; Yi, Wei

2017-08-08

The gut and brain form the gut-brain axis through bidirectional nervous, endocrine, and immune communications. Changes in one of the organs will affect the other organs. Disorders in the composition and quantity of gut microorganisms can affect both the enteric nervous system and the central nervous system (CNS), thereby indicating the existence of a microbiota-gut-brain axis. Due to the intricate interactions between the gut and the brain, gut symbiotic microorganisms are closely associated with various CNS diseases, such as Parkinson's disease, Alzheimer's disease, schizophrenia, and multiple sclerosis. In this paper, we will review the latest advances of studies on the correlation between gut microorganisms and CNS functions & diseases.

Hydatid disease of the Central Nervous System: imaging characteristics and general features

International Nuclear Information System (INIS)

Abbassioun, K.; Amirjamshidi, A.; Sabouri Deylamie, M.

2003-01-01

Background: Hydatid disease primarily affects the liver and typically demonstrates characteristic imaging findings. Secondary involvement due to hematogenous dissemination may be seen in almost any locations, e.g., lung, kidney, spleen, bone and central nervous system. Objectives: To review the different aspects of hydatidosis of the central nervous system briefly and discuss the pathognomonic features and rare varieties of radiological findings useful in preoperative diagnosis of the disease in the human central nervous system. Materials and Methods: In a retrospective study, the records of almost 100 cases of central nervous system hydatidosis were analyzed . The available images were reviewed by independent observers, either a radiologist or a neurosurgeon, and reported separately. Results: In skull x-ray films, nonspecific changes denoted increased intracranial pressure, skull asymmetry and curvilinear calcification in rare instances. Computed tomography and magnetic resonance imaging demonstrated the round or oval, well-defined cystic mass with an attenuation or signal intensity similar to that of cerebrospinal fluid, with no associated perifocal edema, and no contrast enhancement as the pathognomonic findings of brain hydatidosis. Similar findings were detected in hydatid cysts involving the orbit, spinal column and spinal cord with some variations. Such findings as mild perifocal edema, non homogenous contrast enhancement, non-uniform shapes, calcification and multiplicity or septations have been the atypical radiological findings. Conclusion: In endemic areas, familiarity with typical and atypical radiological manifestations of hydatid disease of the central nervous system, will be helpful in making prompt and correct preoperative diagnosis leading to a better surgical outcome

Ultra-sensitive molecular MRI of cerebrovascular cell activation enables early detection of chronic central nervous system disorders

International Nuclear Information System (INIS)

Montagne, Axel; Gauberti, Maxime; Jullienne, Amandine; Briens, Aurelien; Docagne, Fabian; Vivien, Denis; Maubert, Eric; Macrez, Richard; Defer, Gilles; Raynaud, Jean-Sebastien; Louin, Gaelle; Buisson, Alain; Haelewyn, Benoit

2012-01-01

Since endothelial cells can be targeted by large contrast-carrying particles, molecular imaging of cerebrovascular cell activation is highly promising to evaluate the underlying inflammation of the central nervous system (CNS). In this study, we aimed to demonstrate that molecular magnetic resonance imaging (MRI) of cerebrovascular cell activation can reveal CNS disorders in the absence of visible lesions and symptoms. To this aim, we optimized contrast carrying particles targeting vascular cell adhesion molecule-1 and MRI protocols through both in vitro and in vivo experiments. Although, pre-contrast MRI images failed to reveal the ongoing pathology, contrast-enhanced MRI revealed hypoperfusion-triggered CNS injury in vascular dementia, unmasked amyloid-induced cerebrovascular activation in Alzheimer's disease and allowed monitoring of disease activity during experimental autoimmune encephalomyelitis. Moreover, contrast-enhanced MRI revealed the cerebrovascular cell activation associated with known risk factors of CNS disorders such as peripheral inflammation, ethanol consumption, hyperglycemia and aging. By providing a dramatically higher sensitivity than previously reported methods and molecular contrast agents, the technology described in the present study opens new avenues of investigation in the field of neuro-inflammation. (authors)

Lipomas of the central nervous system in childhood. Apropos of 3 cases

International Nuclear Information System (INIS)

Delucchi Bottato, M.; Scavone Mauro, C.; Delfino Albornoz, A.

2004-01-01

Lipomas of the central nervous system occur as a phenomenon consequences developmental malformations of the central nervous system (CNS) and are not considered neoplasms . It is often associated with other congenital malformations. Representing 0.5 percent of intracranial tumors. Imaging studies are central CT or MRI for diagnosis. They are generally associated with other malformations of the CNS. The surgical treatment is always discussed by the high morbidity associated with it. We present three cases of children with lipomas of different topography. (author) [es

Central- and autonomic nervous system coupling in schizophrenia

Science.gov (United States)

Schulz, Steffen; Bolz, Mathias; Bär, Karl-Jürgen

2016-01-01

The autonomic nervous system (ANS) dysfunction has been well described in schizophrenia (SZ), a severe mental disorder. Nevertheless, the coupling between the ANS and central brain activity has been not addressed until now in SZ. The interactions between the central nervous system (CNS) and ANS need to be considered as a feedback–feed-forward system that supports flexible and adaptive responses to specific demands. For the first time, to the best of our knowledge, this study investigates central–autonomic couplings (CAC) studying heart rate, blood pressure and electroencephalogram in paranoid schizophrenic patients, comparing them with age–gender-matched healthy subjects (CO). The emphasis is to determine how these couplings are composed by the different regulatory aspects of the CNS–ANS. We found that CAC were bidirectional, and that the causal influence of central activity towards systolic blood pressure was more strongly pronounced than such causal influence towards heart rate in paranoid schizophrenic patients when compared with CO. In paranoid schizophrenic patients, the central activity was a much stronger variable, being more random and having fewer rhythmic oscillatory components. This study provides a more in-depth understanding of the interplay of neuronal and autonomic regulatory processes in SZ and most likely greater insights into the complex relationship between psychotic stages and autonomic activity. PMID:27044986

Brief electrical stimulation accelerates axon regeneration in the peripheral nervous system and promotes sensory axon regeneration in the central nervous system.

Science.gov (United States)

Gordon, Tessa; Udina, Esther; Verge, Valerie M K; de Chaves, Elena I Posse

2009-10-01

Injured peripheral but not central nerves regenerate their axons but functional recovery is often poor. We demonstrate that prolonged periods of axon separation from targets and Schwann cell denervation eliminate regenerative capacity in the peripheral nervous system (PNS). A substantial delay of 4 weeks for all regenerating axons to cross a site of repair of sectioned nerve contributes to the long period of separation. Findings that 1h 20Hz bipolar electrical stimulation accelerates axon outgrowth across the repair site and the downstream reinnervation of denervated muscles in rats and human patients, provides a new and exciting method to improve functional recovery after nerve injuries. Drugs that elevate neuronal cAMP and activate PKA promote axon outgrowth in vivo and in vitro, mimicking the electrical stimulation effect. Rapid expression of neurotrophic factors and their receptors and then of growth associated proteins thereafter via cAMP, is the likely mechanism by which electrical stimulation accelerates axon outgrowth from the site of injury in both peripheral and central nervous systems.

Progress in study on central nervous system injuries caused by obstructive sleep apnea syndrome

Directory of Open Access Journals (Sweden)

ZHAO Xiang-xiang

2013-05-01

Full Text Available Chronic and repetitive intermittent hypoxia and dysfunction of sleep architecture mainly contribute to obstructive sleep apnea syndrome (OSAS. More and more evidences demonstrate it is a systemic disease, which is common encountered in clinic and strongly related to the systemic lesion of central nervous system. The central nervous system complications comprise cognitive impairment, brain atrophy and the growing risk of stroke and so on. Early treatment for OSAS has a positive significance on complications of central nervous system, and even the damage can be completely reversed.

[The blood-brain barrier and drug delivery in the central nervous system].

Science.gov (United States)

Loch-Neckel, Gecioni; Koepp, Janice

2010-08-01

To provide an updated view of the difficulties due to barriers and strategies used to allow the release of drugs in the central nervous system. The difficulty for the treatment of many diseases of the central nervous system, through the use of intra-venous drugs, is due to the presence of barriers that prevent the release of the same: the blood-brain barrier, blood-cerebro-spinal fluid barrier and the blood-arachnoid barrier. The blood-brain barrier is the main barrier for the transport of drugs in the brain that also acts as a immunologic and metabolic barrier. The endothelial cells of the blood-brain barrier are connected to a junction complex through the interaction of transmembrane proteins that protrude from de inside to the outside, forming a connection between the endothelial cells. The transport of substances to the brain depends on the mechanisms of transport present in the barrier and the diffusion of these compounds also depends on the physicochemical characteristics of the molecule. Some diseases alter the permeability of the blood-brain barrier and thus the passage of drugs. Strategies such as the use of methods for drug delivery in the brain have been investigated. Further details regarding the mechanisms of transport across the blood-brain barrier and the changes in neuropathology would provide important information about the etiology of diseases and lead to better therapeutic strategies.

Injectable hydrogels for central nervous system therapy

International Nuclear Information System (INIS)

Pakulska, Malgosia M; Shoichet, Molly S; Ballios, Brian G

2012-01-01

Diseases and injuries of the central nervous system (CNS) including those in the brain, spinal cord and retina are devastating because the CNS has limited intrinsic regenerative capacity and currently available therapies are unable to provide significant functional recovery. Several promising therapies have been identified with the goal of restoring at least some of this lost function and include neuroprotective agents to stop or slow cellular degeneration, neurotrophic factors to stimulate cellular growth, neutralizing molecules to overcome the inhibitory environment at the site of injury, and stem cell transplant strategies to replace lost tissue. The delivery of these therapies to the CNS is a challenge because the blood–brain barrier limits the diffusion of molecules into the brain by traditional oral or intravenous routes. Injectable hydrogels have the capacity to overcome the challenges associated with drug delivery to the CNS, by providing a minimally invasive, localized, void-filling platform for therapeutic use. Small molecule or protein drugs can be distributed throughout the hydrogel which then acts as a depot for their sustained release at the injury site. For cell delivery, the hydrogel can reduce cell aggregation and provide an adhesive matrix for improved cell survival and integration. Additionally, by choosing a biodegradable or bioresorbable hydrogel material, the system will eventually be eliminated from the body. This review discusses both natural and synthetic injectable hydrogel materials that have been used for drug or cell delivery to the CNS including hyaluronan, methylcellulose, chitosan, poly(N-isopropylacrylamide) and Matrigel. (paper)

Glial Cells: The Other Cells of the Nervous System

Indian Academy of Sciences (India)

nervous system. The present .... In the vertebrate nervous system, special types of cells called radial glia .... As men- tioned earlier, astrocytes extend a 'foot process' (Figure 3) that ... capillaries that for a long time it was thought that these cells.

Radiation induced effects in the developing central nervous system

International Nuclear Information System (INIS)

Gisone, P.; Dubner, D.; Michelin, S.C.; Perez, M.R. Del

1997-01-01

The embryo and the human foetus are particularly sensitive to ionizing radiation and this sensitivity presents various qualitative and quantitative functional changes during intra-uterine development. Apart from radiation induced carcinogenesis, the most serious consequence of prenatal exposure in human beings is severe mental retardation. The principal data on radiation effects on human beings in the development of the central nervous system come form epidemiological studies carried out in individuals exposed in utero during the atomic explosion at Hiroshima and Nagasaki. These observations demonstrate the existence of a time of maximum radiosensitivity between the weeks 8 and 15 of the gestational period, a period in which the proliferation and neuronal migration takes place. Determination of the characteristics of dose-response relationship and the possible existence of a threshold dose of radiation effects on the development of the central nervous system is relevant to radiation protection against low dose radiation and the establishment of dose limits for occupational exposure and the public. Studies were conducted on the generation of nitrous-oxide and its relation with the production of active species of oxygen in brains of exposed rats in utero exposed to doses of up to 1 Gy during their maximum radiosensitivity. The possible role of the mechanism of radiation induced damage in the development of the central nervous system is discussed

Gene Mutation Profiles in Primary Diffuse Large B Cell Lymphoma of Central Nervous System: Next Generation Sequencing Analyses

Science.gov (United States)

Todorovic Balint, Milena; Jelicic, Jelena; Mihaljevic, Biljana; Kostic, Jelena; Stanic, Bojana; Balint, Bela; Pejanovic, Nadja; Lucic, Bojana; Tosic, Natasa; Marjanovic, Irena; Stojiljkovic, Maja; Karan-Djurasevic, Teodora; Perisic, Ognjen; Rakocevic, Goran; Popovic, Milos; Raicevic, Sava; Bila, Jelena; Antic, Darko; Andjelic, Bosko; Pavlovic, Sonja

2016-01-01

The existence of a potential primary central nervous system lymphoma-specific genomic signature that differs from the systemic form of diffuse large B cell lymphoma (DLBCL) has been suggested, but is still controversial. We investigated 19 patients with primary DLBCL of central nervous system (DLBCL CNS) using the TruSeq Amplicon Cancer Panel (TSACP) for 48 cancer-related genes. Next generation sequencing (NGS) analyses have revealed that over 80% of potentially protein-changing mutations were located in eight genes (CTNNB1, PIK3CA, PTEN, ATM, KRAS, PTPN11, TP53 and JAK3), pointing to the potential role of these genes in lymphomagenesis. TP53 was the only gene harboring mutations in all 19 patients. In addition, the presence of mutated TP53 and ATM genes correlated with a higher total number of mutations in other analyzed genes. Furthermore, the presence of mutated ATM correlated with poorer event-free survival (EFS) (p = 0.036). The presence of the mutated SMO gene correlated with earlier disease relapse (p = 0.023), inferior event-free survival (p = 0.011) and overall survival (OS) (p = 0.017), while mutations in the PTEN gene were associated with inferior OS (p = 0.048). Our findings suggest that the TP53 and ATM genes could be involved in the molecular pathophysiology of primary DLBCL CNS, whereas mutations in the PTEN and SMO genes could affect survival regardless of the initial treatment approach. PMID:27164089

Central nervous system stimulants and drugs that suppress appetite

DEFF Research Database (Denmark)

Aagaard, Lise

2014-01-01

of the January 2012 to June 2013 publications on central nervous system stimulants and drugs that suppress appetite covers amphetamines (including metamfetamine, paramethoxyamfetamine and paramethoxymetamfetamine), fenfluramine and benfluorex, atomoxetine, methylphenidate, modafinil and armodafinil...

76 FR 44595 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

Science.gov (United States)

2011-07-26

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug... Committee: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee...

Phenylketonuria: central nervous system and microbiome interaction

Directory of Open Access Journals (Sweden)

Demian Arturo Herrera Morban

2017-06-01

Full Text Available Phenylketonuria (PKU is an autosomal recessive inborn error of metabolism characterized by increased phenylalanine (Phe levels causing an inadequate neurodevelopment; the treatment of PKU is a Phe-restricting diet, and as such it can modulate the intestinal microbiome of the individual, generating central nervous system secondary disturbances that, added to the baseline disturbance, can influence the outcome of the disease.

Intraventricular Delivery of siRNA Nanoparticles to the Central Nervous System

Directory of Open Access Journals (Sweden)

Rishab Shyam

2015-01-01

Full Text Available Alzheimer's disease (AD is a progressive neurodegenerative disease currently lacking effective treatment. Efficient delivery of siRNA via nanoparticles may emerge as a viable therapeutic approach to treat AD and other central nervous system disorders. We report here the use of a linear polyethyleneimine (LPEI-g-polyethylene glycol (PEG copolymer-based micellar nanoparticle system to deliver siRNA targeting BACE1 and APP, two therapeutic targets of AD. Using LPEI-siRNA nanoparticles against either BACE1 or APP in cultured mouse neuroblastoma (N2a cells, we observe selective knockdown, respectively, of BACE1 or APP. The encapsulation of siRNA by LPEI-g-PEG carriers, with different grafting degrees of PEG, leads to the formation of micellar nanoparticles with distinct morphologies, including worm-like, rod-like, or spherical nanoparticles. By infusing these shaped nanoparticles into mouse lateral ventricles, we show that rod-shaped nanoparticles achieved the most efficient knockdown of BACE1 in the brain. Furthermore, such knockdown is evident in spinal cords of these treated mice. Taken together, our findings indicate that the shape of siRNA-encapsulated nanoparticles is an important determinant for their delivery and gene knockdown efficiency in the central nervous system.

75 FR 12768 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

Science.gov (United States)

2010-03-17

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee: To provide...

78 FR 20328 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

Science.gov (United States)

2013-04-04

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee: To provide...

78 FR 63478 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

Science.gov (United States)

2013-10-24

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee: To provide...

75 FR 36428 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

Science.gov (United States)

2010-06-25

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee: To provide...

77 FR 20037 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

Science.gov (United States)

2012-04-03

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0001] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee: To provide...

76 FR 3912 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

Science.gov (United States)

2011-01-21

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee: To provide...

75 FR 17417 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

Science.gov (United States)

2010-04-06

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee: To provide...

78 FR 63481 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

Science.gov (United States)

2013-10-24

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001] Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Peripheral and Central Nervous System Drugs Advisory Committee. General Function of the Committee: To provide...

Peri-optic nerve infiltration during leukaemic relapse: MRI diagnosis

Energy Technology Data Exchange (ETDEWEB)

Madani, A.; Christophe, C. [Department of Imaging, Hopital Universitaire des Enfants Reine Fabiola, Brussels (Belgium); Ferster, A.; Dan, B. [Department of Paediatrics, Hopital Universitaire des Enfants Reine Fabiola, Brussels (Belgium)

2000-01-01

Background. A 10-year-old boy with a history of acute lymphoblastic leukaemia (ALL), but without previous evidence of central nervous system involvement, presented with seizures 3 years after complete remission. Materials and methods. MRI showed bilateral enlargement of the optic nerves despite normal ophthalmological examination. Results. Only the third cerebrospinal fluid examination showed 2 % blasts without concomitant bone-marrow infiltration. Enlargement of the optic nerves was consistent with bilateral leukaemic peri-optic nerve infiltration. The appearances returned to normal after chemotherapy. Conclusion. The optic nerves are a potential site of relapse in patients with systemic and meningeal ALL, even in the absence of ophthalmological signs. (orig.)

Mild hypothermia as a treatment for central nervous system injuries: Positive or negative effects.

Science.gov (United States)

Darwazeh, Rami; Yan, Yi

2013-10-05

Besides local neuronal damage caused by the primary insult, central nervous system injuries may secondarily cause a progressive cascade of related events including brain edema, ischemia, oxida-tive stress, excitotoxicity, and dysregulation of calcium homeostasis. Hypothermia is a beneficial strategy in a variety of acute central nervous system injuries. Mild hypothermia can treat high intra-cranial pressure following traumatic brain injuries in adults. It is a new treatment that increases sur-vival and quality of life for patients suffering from ischemic insults such as cardiac arrest, stroke, and neurogenic fever following brain trauma. Therapeutic hypothermia decreases free radical produc-tion, inflammation, excitotoxicity and intracranial pressure, and improves cerebral metabolism after traumatic brain injury and cerebral ischemia, thus protecting against central nervous system dam-age. Although a series of pathological and physiological changes as well as potential side effects are observed during hypothermia treatment, it remains a potential therapeutic strategy for central nervous system injuries and deserves further study.

Similar chemokine receptor profiles in lymphomas with central nervous system involvement - possible biomarkers for patient selection for central nervous system prophylaxis, a retrospective study.

Science.gov (United States)

Lemma, Siria A; Pasanen, Anna Kaisa; Haapasaari, Kirsi-Maria; Sippola, Antti; Sormunen, Raija; Soini, Ylermi; Jantunen, Esa; Koivunen, Petri; Salokorpi, Niina; Bloigu, Risto; Turpeenniemi-Hujanen, Taina; Kuittinen, Outi

2016-05-01

Central nervous system (CNS) relapse occurs in around 5% of diffuse large B-cell lymphoma (DLBCL) cases. No biomarkers to identify high-risk patients have been discovered. We evaluated the expression of lymphocyte-guiding chemokine receptors in systemic and CNS lymphomas. Immunohistochemical staining for CXCR4, CXCR5, CCR7, CXCL12, and CXCL13 was performed on 89 tissue samples, including cases of primary central nervous system lymphoma (PCNSL), secondary CNS lymphoma (sCNSL), and systemic DLBCL. Also, 10 reactive lymph node samples were included. Immunoelectron microscopy was performed on two PCNSLs, one sCNSL, one systemic DLBCL, and one reactive lymph node samples, and staining was performed for CXCR4, CXCR5, CXCL12, and CXCL13. Chi-square test was used to determine correlations between clinical parameters, diagnostic groups, and chemokine receptor expression. Strong nuclear CXCR4 positivity correlated with systemic DLBCL, whereas strong cytoplasmic CXCR5 positivity correlated with CNS involvement (P = 0.003 and P = 0.039). Immunoelectron microscopy revealed a nuclear CXCR4 staining in reactive lymph node, compared with cytoplasmic and membranous localization seen in CNS lymphomas. We found that CNS lymphoma presented a chemokine receptor profile different from systemic disease. Our findings give new information on the CNS tropism of DLBCL and, if confirmed, may contribute to more effective targeting of CNS prophylaxis among patients with DLBCL. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

GABA-ergic neurons in the leach central nervous system

International Nuclear Information System (INIS)

Cline, H.T.

1985-01-01

GABA is a candidate for an inhibitory neurotransmitter in the leech central nervous system because of the well-documented inhibitory action of GABA in other invertebrates. To demonstrate that GABA meets the criteria used to identify a substance as a neurotransmitter, the author examined GABA metabolism and synaptic interactions of inhibitory motor neurons in two leech species, Hirudo medicinalis and Haementeria ghilianii. Segmental ganglia of the leech ventral nerve cord and identified inhibitors have the capacity to synthesize GABA when incubated in the presence of the precursor glutamate. Application of GABA to cell bodies of excitatory motor neurons or muscle fibers innervated by the inhibitors hyperpolarizes the membrane potential of the target cell and activates a chloride ion conductance channel, similar to the inhibitory membrane response following intracellular stimulation of the inhibitor. Bicuculline methiodide (5 x 10 -5 M), GABA receptor antagonist, blocks reversibly the response to applied GABA and the inhibitory synaptic inputs onto the postsynaptic neurons or muscle fibers without interfering with their excitatory inputs. Furthermore, the inhibitors are included among approximately 25 neurons per segmental ganglion that take up GABA by a high affinity uptake system, as revealed by 3 H-GABA-autoradiography. The development of the capacities to synthesize and to take up GABA were examined in leech embryos. The embryos are able to synthesize GABA at early stages of the development of the nervous system, before any neurons have extended neutrites

Eosinophilic infiltration in Korea: idiopathic?

Energy Technology Data Exchange (ETDEWEB)

Lim, Jae Hoon; Lee, Kyung Soo [Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

2006-03-15

Eosinophilia is defined as the presence of more than 500 eosinophils/{mu}L in the peripheral blood, and may be accompanied by eosinophil infiltration in tissues. Focal eosinophilic infiltration in the lungs and liver is relatively common and is often associated with a parasitic infection, drug hypersensitivity, allergic diseases, collagen vascular diseased, and internal malignancies such as Hodgkin's disease, as well as cancer of the lung, stomach, pancreas or ovary. An eosinophilic abscess refers to a lesion of massive eosinophil infiltration and associated destroyed tissue, and an eosinophilic granuloma refers to a lesion consisting of central necrosis and mixed inflammatory cell infiltrates with numerous eosinophils, a number of neutrophils and lymphocytes, and a palisade of epithelioid histiocytes and/or giant cells.

Eosinophilic infiltration in Korea: idiopathic?

International Nuclear Information System (INIS)

Lim, Jae Hoon; Lee, Kyung Soo

2006-01-01

Eosinophilia is defined as the presence of more than 500 eosinophils/μL in the peripheral blood, and may be accompanied by eosinophil infiltration in tissues. Focal eosinophilic infiltration in the lungs and liver is relatively common and is often associated with a parasitic infection, drug hypersensitivity, allergic diseases, collagen vascular diseased, and internal malignancies such as Hodgkin's disease, as well as cancer of the lung, stomach, pancreas or ovary. An eosinophilic abscess refers to a lesion of massive eosinophil infiltration and associated destroyed tissue, and an eosinophilic granuloma refers to a lesion consisting of central necrosis and mixed inflammatory cell infiltrates with numerous eosinophils, a number of neutrophils and lymphocytes, and a palisade of epithelioid histiocytes and/or giant cells

Constitutive expression of a costimulatory ligand on antigen-presenting cells in the nervous system drives demyelinating disease

DEFF Research Database (Denmark)

Zehntner, Simone P; Brisebois, Marcel; Tran, Elise

2003-01-01

that transgenic mice constitutively expressing the costimulatory ligand B7.2/CD86 on microglia in the central nervous system (CNS) and on related cells in the proximal peripheral nervous tissue spontaneously develop autoimmune demyelinating disease. Disease-affected nervous tissue in transgenic mice showed...... recipients but not into non-transgenic recipients. These data provide evidence that B7/CD28 interactions within the nervous tissue are critical determinants of disease development. Our findings have important implications for understanding the etiology of nervous system autoimmune diseases such as multiple...

Neuromyelitis optica (NMO) - an autoimmune disease of the central nervous system (CNS)

DEFF Research Database (Denmark)

Asgari, N; Owens, T; Frøkiaer, J

2010-01-01

Asgari N, Owens T, Frøkiaer J, Stenager E, Lillevang ST, Kyvik KO. Neuromyelitis optica (NMO) - an autoimmune disease of the central nervous system (CNS).
Acta Neurol Scand: DOI: 10.1111/j.1600-0404.2010.01416.x.
© 2010 John Wiley & Sons A/S. In the past 10 years, neuromyelitis optica (NMO) has...... or by intrathecal administration to naive mice. NMO may be characterized as a channelopathy of the central nervous system with autoimmune characteristics....

Targeting choroid plexus epithelia and ventricular ependyma for drug delivery to the central nervous system

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Stopa Edward G

2011-01-01

Full Text Available Abstract Background Because the choroid plexus (CP is uniquely suited to control the composition of cerebrospinal fluid (CSF, there may be therapeutic benefits to increasing the levels of biologically active proteins in CSF to modulate central nervous system (CNS functions. To this end, we sought to identify peptides capable of ligand-mediated targeting to CP epithelial cells reasoning that they could be exploited to deliver drugs, biotherapeutics and genes to the CNS. Methods A peptide library displayed on M13 bacteriophage was screened for ligands capable of internalizing into CP epithelial cells by incubating phage with CP explants for 2 hours at 37C and recovering particles with targeting capacity. Results Three peptides, identified after four rounds of screening, were analyzed for specific and dose dependant binding and internalization. Binding was deemed specific because internalization was prevented by co-incubation with cognate synthetic peptides. Furthermore, after i.c.v. injection into rat brains, each peptide was found to target phage to epithelial cells in CP and to ependyma lining the ventricles. Conclusion These data demonstrate that ligand-mediated targeting can be used as a strategy for drug delivery to the central nervous system and opens the possibility of using the choroid plexus as a portal of entry into the brain.

Evaluation of IgG4+ Plasma Cell Infiltration in Patients with Systemic Plasmacytosis and Other Plasma Cell-infiltrating Skin Diseases

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Shintaro Takeoka

2018-02-01

Full Text Available Systemic plasmacytosis is a rare skin disorder characterized by marked infiltration of plasma cells in the dermis. IgG4-related disease is pathologically characterized by lymphoplasmacytic infiltration rich in IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis, accompanied by elevated levels of serum IgG4. Reports of cases of systemic plasmacytosis with abundant infiltration of IgG4+ plasma cells has led to discussion about the relationship between systemic plasmacytosis and IgG4-related disease. This study examined IgG4+/IgG+ plasma cell ratios in 4 patients with systemic plasmacytosis and 12 patients with other skin diseases that show marked infiltration of plasma cells. Furthermore, we examined whether these cases met one of the pathological diagnostic criteria for IgG4-related disease (i.e. IgG4+/IgG plasma cells ratio of over 40%. Only one out of 4 patients with systemic plasmacytosis met the criterion. These results suggest that systemic plasmacytosis and IgG4-related disease are distinct diseases.

The contribution of oligodendrocytes and oligodendrocyte progenitor cells to central nervous system repair in multiple sclerosis: perspectives for remyelination therapeutic strategies

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Adriana Octaviana Dulamea

2017-01-01

Full Text Available Oligodencrocytes (OLs are the main glial cells of the central nervous system involved in myelination of axons. In multiple sclerosis (MS, there is an imbalance between demyelination and remyelination processes, the last one performed by oligodendrocyte progenitor cells (OPCs and OLs, resulting into a permanent demyelination, axonal damage and neuronal loss. In MS lesions, astrocytes and microglias play an important part in permeabilization of blood-brain barrier and initiation of OPCs proliferation. Migration and differentiation of OPCs are influenced by various factors and the process is finalized by insufficient acummulation of OLs into the MS lesion. In relation to all these processes, the author will discuss the potential targets for remyelination strategies.

Longitudinal analysis of hearing loss in a case of hemosiderosis of the central nervous system

NARCIS (Netherlands)

Weekamp, H H; Huygen, P L M; Merx, J L; Kremer, H P H; Cremers, Cor W R J; Longridge, Neil S

OBJECTIVE: To describe cochleovestibular aspects of superficial hemosiderosis of the central nervous system. BACKGROUND: Superficial hemosiderosis of the central nervous system is a rare disease in which cochleovestibular impairment, cerebellar ataxia, and myelopathy are the most frequent signs.

Longitudinal analysis of hearing loss in a case of hemosiderosis of the central nervous system.

NARCIS (Netherlands)

Weekamp, H.; Huygen, P.L.M.; Merx, J.L.; Kremer, H.P.H.; Cremers, C.W.R.J.; Longridge, N.S.

2003-01-01

OBJECTIVE: To describe cochleovestibular aspects of superficial hemosiderosis of the central nervous system. BACKGROUND: Superficial hemosiderosis of the central nervous system is a rare disease in which cochleovestibular impairment, cerebellar ataxia, and myelopathy are the most frequent signs.

Tertiary Lymphoid Organs in Central Nervous System Autoimmunity

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Meike Mitsdoerffer

2016-10-01

Full Text Available Multiple sclerosis (MS is an autoimmune disease characterized by chronic inflammation in the central nervous system (CNS, which results in permanent neuronal damage and substantial disability in patients. Autoreactive T cells are important drivers of the disease, however, the efficacy of B cell depleting therapies uncovered an essential role for B cells in disease pathogenesis. They can contribute to inflammatory processes via presentation of autoantigen, secretion of pro-inflammatory cytokines and production of pathogenic antibodies. Recently, B cell aggregates reminiscent of tertiary lymphoid organs (TLOs were discovered in the meninges of MS patients, leading to the hypothesis that differentiation and maturation of autopathogenic B and T cells may partly occur inside the CNS. Since these structures were associated with a more severe disease course, it is extremely important to gain insight into the mechanism of induction, their precise function and clinical significance. Mechanistic studies in patiens are limited. However, a few studies in the MS animal model experimental autoimmune encephalomyelitis (EAE recapitulate TLO formation in the CNS and provide new insight into CNS TLO features, formation and function. This review summarizes what we know so far about CNS TLOs in MS and what we have learned about them from EAE models. It also highlights the areas that are in need of further experimental work, as we are just beginning to understand and evaluate the phenomenon of CNS TLOs.

Validation of tumor markers in central nervous system germ cell tumors by real-time reverse transcriptase polymerase chain reaction using formalin-fixed paraffin-embedded tissues.

Science.gov (United States)

Kim, Dowhan; Lee, Da Hye; Choi, Junjeong; Shim, Kyu Won; Kim, Se Hoon

2013-01-01

The therapeutic protocols for treatment of germinomas and non-germinomatous germ cell tumors (NGGCTs) are completely different, so it is important to distinguish pure germinomas from NGGCTs. As it can be difficult to diagnose by morphology alone, immunohisto-chemistry (IHC) has been widely used as an ancillary test to improve diagnostic accuracy. However, IHC has limitations due to the misinterpretation of results or the aberrant loss of immunoreactivity. However, real-time RT-PCR has certain advantages over IHC, including its quantitative nature. The aim of our study was to evaluate the usefulness of real-time RT-PCR on formalin-fixed paraffin-embedded (FFPE) tissue blocks for the diagnosis of germ cell tumors of the central nervous system. We selected eight markers of germ cell tumors using a literature search, and validated them using real-time RT-PCR. Among them, POU5F1, NANOG and TGFB2 were statistically significant (P=0.05) in multiple comparisons (MANOVA) of three groups (pure germinomas, mature teratomas and malignant germ cell tumors). Two-group (pure germinomas and NGGCTs) discriminant analysis achieved a 70.0% success rate in cross-validation. We concluded that real-time RT-PCR using FFPE tissue has adequate validating power comparable to IHC in the diagnosis of central nervous system germ cell tumors; therefore, when IHC is not available, not conclusive or not informative, RT-PCR is a potential alternative to a repeat biopsy.

[Central nervous system relapse in diffuse large B cell lymphoma: Risk factors].

Science.gov (United States)

Sancho, Juan-Manuel; Ribera, Josep-Maria

2016-01-15

Central nervous system (CNS) involvement by lymphoma is a complication associated, almost invariably, with a poor prognosis. The knowledge of the risk factors for CNS relapse is important to determine which patients could benefit from prophylaxis. Thus, patients with very aggressive lymphomas (such as lymphoblastic lymphoma or Burkitt's lymphoma) must systematically receive CNS prophylaxis due to a high CNS relapse rate (25-30%), while in patients with indolent lymphoma (such as follicular lymphoma or marginal lymphoma) prophylaxis is unnecessary. However, the question about CNS prophylaxis in patients with diffuse large B-cell lymphoma (DLBCL), the most common type of lymphoma, remains controversial. The information available is extensive, mainly based on retrospective and heterogeneous studies. There seems that immunochemotherapy based on rituximab reduces the CNS relapse rate. On the other hand, patients with increased serum lactate dehydrogenase plus more than one extranodal involvement seem to have a higher risk of CNS relapse, but a prophylaxis strategy based only on the presence of these 2 factors does not prevent all CNS relapses. Patients with involvement of testes or breast have high risk of CNS relapse and prophylaxis is mandatory. Finally, CNS prophylaxis could be considered in patients with DLBCL and renal or epidural space involvement, as well as in those cases with MYC rearrangements, although additional studies are necessary. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Review of dextromethorphan administration in 18 patients with subacute methotrexate central nervous system toxicity.

Science.gov (United States)

Afshar, Maryam; Birnbaum, Daniel; Golden, Carla

2014-06-01

The pathogenesis of methotrexate central nervous system toxicity is multifactorial, but it is likely related to central nervous system folate homeostasis. The use of folinate rescue has been described to decrease toxicity in patients who had received intrathecal methotrexate. It has also been described in previous studies that there is an elevated level of homocysteine in plasma and cerebrospinal fluid of patients who had received intrathecal methotrexate. Homocysteine is an N-methyl-D-aspartate receptor agonist. The use of dextromethorphan, noncompetitive N-methyl-D-aspartate receptor receptor antagonist, has been used in the treatment of sudden onset of neurological dysfunction associated with methotrexate toxicity. It remains unclear whether the dextromethorphan impacted the speed of recovery, and its use remains controversial. This study reviews the use of dextromethorphan in the setting of subacute methotrexate central nervous system toxicity. Charts of 18 patients who had sudden onset of neurological impairments after receiving methotrexate and were treated with dextromethorphan were reviewed. The use of dextromethorphan in most of our patients resulted in symptomatic improvement. In this patient population, earlier administration of dextromethorphan resulted in faster improvement of impairments and led to prevention of recurrence of seizure activity induced by methotrexate central nervous system toxicity. Our study provides support for the use of dextromethorphan in patients with subacute methotrexate central nervous system toxicity. Copyright © 2014 Elsevier Inc. All rights reserved.

Sino-orbital aspergillosis with central nervous system complication ...

African Journals Online (AJOL)

A central nervous system (CNS) complication (cerebral abscess) was diagnosed following seizures in the patient. The patient died a few days later. Conclusion: The diagnosis of aspergillosis of the orbit was only made from fungal culture after the patient's death. It requires a high index of suspicion to make a diagnosis of ...

Diverse roles of extracellular calcium-sensing receptor in the central nervous system

DEFF Research Database (Denmark)

Bandyopadhyay, Sanghamitra; Tfelt-Hansen, Jacob; Chattopadhyay, Naibedya

2010-01-01

The G-protein-coupled calcium-sensing receptor (CaSR), upon activation by Ca(2+) or other physiologically relevant polycationic molecules, performs diverse functions in the brain. The CaSR is widely expressed in the central nervous system (CNS) and is characterized by a robust increase in its...... to astrocytic or neuronal lineages. In adult CNS, CaSR has broad relevance in maintaining local ionic homeostasis. CaSR shares an evolutionary relationship with the metabotropic glutamate receptor and forms heteromeric complexes with the type B-aminobutyric acid receptor subunits that affects its cell surface...

Central Auditory Nervous System Dysfunction in Echolalic Autistic Individuals.

Science.gov (United States)

Wetherby, Amy Miller; And Others

1981-01-01

The results showed that all the Ss had normal hearing on the monaural speech tests; however, there was indication of central auditory nervous system dysfunction in the language dominant hemisphere, inferred from the dichotic tests, for those Ss displaying echolalia. (Author)

Invasive central nervous system aspergillosis in bone marrow transplantation recipients: an overview

International Nuclear Information System (INIS)

Guermazi, Ali; Gluckman, Eliane; Tabti, Bachir; Miaux, Yves

2003-01-01

Invasive central nervous system aspergillosis is being seen with an increased frequency, particularly due to the increased number of immunosuppressed patients. The major cause of invasive central nervous system aspergillosis is bone marrow transplantation. In most cases, aspergillosis develops in the paranasal sinuses and in the lungs, and secondarily spreads to the brain. Imaging of cerebral aspergillosis may present different patterns depending on the lesion's age and the immunologic status of the patient. Lesions of the spinal cord are far less common but has been encountered in our series. In this article we review the clinical and radiologic features of aspergillosis affecting the central nervous system in patients who underwent bone marrow transplantation. Different CT and MR patterns are presented, including pertinent clinical and pathologic material. Significant morbidity and mortality can be associated with this fungal infection, and it is therefore incumbent upon the radiologist to identify intracranial aspergillosis as early as possible so that appropriate therapy can be administered. (orig.)

Poliovirus trafficking toward central nervous system via human poliovirus receptor-dependent and -independent pathway.

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Seii eOHKA

2012-04-01

Full Text Available In humans, paralytic poliomyelitis results from the invasion of the central nervous system by circulating poliovirus (PV via the blood-brain barrier (BBB. After the virus enters the central nervous system (CNS, it replicates in neurons, especially in motor neurons (MNs, inducing the cell death that causes paralytic poliomyelitis. Along with this route of dissemination, neural pathway has been reported in humans, monkeys, and PV-sensitive human PV receptor (hPVR/CD155-transgenic (Tg mice. We demonstrated that a fast retrograde axonal transport process is required for PV dissemination through the sciatic nerve of hPVR-Tg mice and that intramuscularly inoculated PV causes paralysis in a hPVR-dependent manner. We also showed that hPVR-independent axonal transport of PV exists in hPVR-Tg and non-Tg mice, indicating that several different pathways for PV axonal transport exist in these mice. Circulating PV after intravenous inoculation in mice cross the BBB at a high rate in a hPVR-independent manner. Recently, we identified transferrin receptor 1 (TfR1 of mouse brain capillary endothelial cells as a binding protein to PV, implicating that TfR1 is a possible receptor for PV to permeate the BBB.

Risk of central nervous system defects in offspring of women with and without mental illness.

Science.gov (United States)

Ayoub, Aimina; Fraser, William D; Low, Nancy; Arbour, Laura; Healy-Profitós, Jessica; Auger, Nathalie

2018-02-22

We sought to determine the relationship between maternal mental illness and the risk of having an infant with a central nervous system defect. We analyzed a cohort of 654,882 women aged less than 20 years between 1989 and 2013 who later delivered a live born infant in any hospital in Quebec, Canada. The primary exposure was mental illness during pregnancy or hospitalization for mental illness before pregnancy. The outcomes were neural and non-neural tube defects of the central nervous system in any offspring. We computed risk ratios (RR) and 95% confidence intervals (CI) for the association between mental disorders and risk of central nervous system defects in log-binomial regression models adjusted for age at delivery, total parity, comorbidity, socioeconomic deprivation, place of residence, and time period. Maternal mental illness was associated with an increased risk of nervous system defects in offspring (RR 1.76, 95% CI 1.64-1.89). Hospitalization for any mental disorder was more strongly associated with non-neural tube (RR 1.84, 95% CI 1.71-1.99) than neural tube defects (RR 1.31, 95% CI 1.08-1.59). Women at greater risk of nervous system defects in offspring tended to be diagnosed with multiple mental disorders, have more than one hospitalization for mental disease, or be 17 or older at first hospitalization. A history of mental illness is associated with central nervous system defects in offspring. Women hospitalized for mental illness may merit counseling at first symptoms to prevent central nervous system defects at pregnancy.

Mer tyrosine kinase promotes the survival of t(1;19)-positive acute lymphoblastic leukemia (ALL) in the central nervous system (CNS).

Science.gov (United States)

Krause, Sarah; Pfeiffer, Christian; Strube, Susanne; Alsadeq, Ameera; Fedders, Henning; Vokuhl, Christian; Loges, Sonja; Waizenegger, Jonas; Ben-Batalla, Isabel; Cario, Gunnar; Möricke, Anja; Stanulla, Martin; Schrappe, Martin; Schewe, Denis M

2015-01-29

Patients with t(1;19)-positive acute lymphoblastic leukemia (ALL) are prone to central nervous system (CNS) relapses, and expression of the TAM (Tyro3, Axl, and Mer) receptor Mer is upregulated in these leukemias. We examined the functional role of Mer in the CNS in preclinical models and performed correlative studies in 64 t(1;19)-positive and 93 control pediatric ALL patients. ALL cells were analyzed in coculture with human glioma cells and normal rat astrocytes: CNS coculture caused quiescence and protection from methotrexate toxicity in Mer(high) ALL cell lines, which was antagonized by short hairpin RNA-mediated knockdown of Mer. Mer expression was upregulated, prosurvival Akt and mitogen-activated protein kinase signaling were activated, and secretion of the Mer ligand Galectin-3 was stimulated. Mer(high) t(1;19) primary cells caused CNS involvement to a larger extent in murine xenografts than in their Mer(low) counterparts. Leukemic cells from Mer(high) xenografts showed enhanced survival in coculture. Treatment of Mer(high) patient cells with the Mer-specific inhibitor UNC-569 in vivo delayed leukemia onset, reduced CNS infiltration, and prolonged survival of mice. Finally, a correlation between high Mer expression and CNS positivity upon initial diagnosis was observed in t(1;19) patients. Our data provide evidence that Mer is associated with survival in the CNS in t(1;19)-positive ALL, suggesting a role as a diagnostic marker and therapeutic target. © 2015 by The American Society of Hematology.

Mosaic serine proteases in the mammalian central nervous system.

Science.gov (United States)

Mitsui, Shinichi; Watanabe, Yoshihisa; Yamaguchi, Tatsuyuki; Yamaguchi, Nozomi

2008-01-01

We review the structure and function of three kinds of mosaic serine proteases expressed in the mammalian central nervous system (CNS). Mosaic serine proteases have several domains in the proenzyme fragment, which modulate proteolytic function, and a protease domain at the C-terminus. Spinesin/TMPRSS5 is a transmembrane serine protease whose presynaptic distribution on motor neurons in the spinal cord suggests that it is significant for neuronal plasticity. Cell type-specific alternative splicing gives this protease diverse functions by modulating its intracellular localization. Motopsin/PRSS12 is a mosaic protease, and loss of its function causes mental retardation. Recent reports indicate the significance of this protease for cognitive function. We mention the fibrinolytic protease, tissue plasminogen activator (tPA), which has physiological and pathological functions in the CNS.

Tumor-Infiltrating Immune Cells Promoting Tumor Invasion and Metastasis: Existing Theories

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Yan-gao Man, Alexander Stojadinovic, Jeffrey Mason, Itzhak Avital, Anton Bilchik, Bjoern Bruecher, Mladjan Protic, Aviram Nissan, Mina Izadjoo, Xichen Zhang, Anahid Jewett

2013-01-01

Full Text Available It is a commonly held belief that infiltration of immune cells into tumor tissues and direct physical contact between tumor cells and infiltrated immune cells is associated with physical destructions of the tumor cells, reduction of the tumor burden, and improved clinical prognosis. An increasing number of studies, however, have suggested that aberrant infiltration of immune cells into tumor or normal tissues may promote tumor progression, invasion, and metastasis. Neither the primary reason for these contradictory observations, nor the mechanism for the reported diverse impact of tumor-infiltrating immune cells has been elucidated, making it difficult to judge the clinical implications of infiltration of immune cells within tumor tissues. This mini-review presents several existing hypotheses and models that favor the promoting impact of tumor-infiltrating immune cells on tumor invasion and metastasis, and also analyzes their strength and weakness.

Some Central Nervous System Activities of Nerium Oleander Linn ...

African Journals Online (AJOL)

Erah

Nerium oleander Linn. on the central nervous system (CNS) of mice. Methods: The effect of the 50 % hydroalcohol extract of N. oleander flowers at dosage levels of 100 and 200 mg/kg ..... in the brain and inhibition of neuronal output could be ...

Microparticles: A New Perspective in Central Nervous System Disorders

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Stephanie M. Schindler

2014-01-01

Full Text Available Microparticles (MPs are a heterogeneous population of small cell-derived vesicles, ranging in size from 0.1 to 1 μm. They contain a variety of bioactive molecules, including proteins, biolipids, and nucleic acids, which can be transferred between cells without direct cell-to-cell contact. Consequently, MPs represent a novel form of intercellular communication, which could play a role in both physiological and pathological processes. Growing evidence indicates that circulating MPs contribute to the development of cancer, inflammation, and autoimmune and cardiovascular diseases. Most cell types of the central nervous system (CNS have also been shown to release MPs, which could be important for neurodevelopment, CNS maintenance, and pathologies. In disease, levels of certain MPs appear elevated; therefore, they may serve as biomarkers allowing for the development of new diagnostic tools for detecting the early stages of CNS pathologies. Quantification and characterization of MPs could also provide useful information for making decisions on treatment options and for monitoring success of therapies, particularly for such difficult-to-treat diseases as cerebral malaria, multiple sclerosis, and Alzheimer’s disease. Overall, studies on MPs in the CNS represent a novel area of research, which promises to expand the knowledge on the mechanisms governing some of the physiological and pathophysiological processes of the CNS.

Microparticles: A New Perspective in Central Nervous System Disorders

Science.gov (United States)

Schindler, Stephanie M.; Little, Jonathan P.

2014-01-01

Microparticles (MPs) are a heterogeneous population of small cell-derived vesicles, ranging in size from 0.1 to 1 μm. They contain a variety of bioactive molecules, including proteins, biolipids, and nucleic acids, which can be transferred between cells without direct cell-to-cell contact. Consequently, MPs represent a novel form of intercellular communication, which could play a role in both physiological and pathological processes. Growing evidence indicates that circulating MPs contribute to the development of cancer, inflammation, and autoimmune and cardiovascular diseases. Most cell types of the central nervous system (CNS) have also been shown to release MPs, which could be important for neurodevelopment, CNS maintenance, and pathologies. In disease, levels of certain MPs appear elevated; therefore, they may serve as biomarkers allowing for the development of new diagnostic tools for detecting the early stages of CNS pathologies. Quantification and characterization of MPs could also provide useful information for making decisions on treatment options and for monitoring success of therapies, particularly for such difficult-to-treat diseases as cerebral malaria, multiple sclerosis, and Alzheimer's disease. Overall, studies on MPs in the CNS represent a novel area of research, which promises to expand the knowledge on the mechanisms governing some of the physiological and pathophysiological processes of the CNS. PMID:24860829

Fanconi anemia: correlating central nervous system malformations and genetic complementation groups.

Science.gov (United States)

Johnson-Tesch, Benjamin A; Gawande, Rakhee S; Zhang, Lei; MacMillan, Margaret L; Nascene, David R

2017-06-01

Congenital central nervous system abnormalities in children with Fanconi anemia are poorly characterized, especially with regard to specific genetic complementation groups. To characterize the impact of genetic complementation groups on central nervous system anatomy. Through chart review we identified 36 patients with Fanconi anemia with available brain MRIs at the University of Minnesota (average age, 11.3 years; range, 1-43 years; M:F=19:17), which we reviewed and compared to 19 age- and sex-matched controls (average age, 7.9 years; range, 2-18 years; M:F=9:10). Genotypic information was available for 27 patients (15 FA-A, 2 FA-C, 3 FA-G, and 7 FA-D1 [biallelic mutations in BRCA2 gene]). Of the 36 patients, 61% had at least one congenital central nervous system or skull base abnormality. These included hypoplastic clivus (n=12), hypoplastic adenohypophysis (n=11), platybasia (n=8), pontocerebellar hypoplasia (n=7), isolated pontine hypoplasia (n=4), isolated vermis hypoplasia (n=3), and ectopic neurohypophysis (n=6). Average pituitary volume was significantly less in patients with Fanconi anemia (PFanconi anemia patients (P=0.006), but the basal angle of those with FA-D1 was not significantly different from controls (P=0.239). Clivus length was less in the Fanconi anemia group (P=0.002), but significance was only observed in the FA-D1 subgroup (PFanconi anemia have higher incidences of ectopic neurohypophysis, adenohypophysis hypoplasia, platybasia and other midline central nervous system skull base posterior fossa abnormalities than age- and sex-matched controls. Patients with posterior fossa abnormalities, including pontocerebellar hypoplasia, are more likely to have biallelic BRCA2 mutations.

An immmunohistochemical study of infiltrating cells in squamous cell carcinomas appeared on chronic radiodermatitis

International Nuclear Information System (INIS)

Terao, Hiroshi; Nakayama, Juichiro; Urabe, Atsumichi; Hori, Yoshiaki; Moon Doo-Chan.

1990-01-01

We investigated the infiltrating cells to chronic radiodermatitis (RD) and squamous cell carcinoma (SCC) appearing on RD by the Avidin-Biotin-Peroxidase Complex method using four monoclonal antibodies. About 50% of the infiltrating cells in RD were T-cells and the population of T-cells infiltrated in SCC was smaller than that in RD (in two of three cases). Natural Killer (NK) cells (Leu-7 positive cells) were found to be infiltrated into the tumor nests of SCC but were not in the radio-damaged epidermis in RD. In the case of RD, frozen sections stained with monoclonal antibodies showed that suppressor/cytotoxic T-cells were more predominant than helper/inducer T-cells in number. (author)

Aberrant nerve fibres within the central nervous system.

Science.gov (United States)

Moffie, D

1992-01-01

Three cases of aberrant nerve fibres in the spinal cord and medulla oblongata are described. The literature on these fibres is discussed and their possible role in regeneration. Different views on the possibility of regeneration or functional recovery of the central nervous system are mentioned in the light of recent publications, which are more optimistic than before.

Progress of radionuclide diagnostic methods in central nervous system diseases

International Nuclear Information System (INIS)

Badmaev, K.N.; Zen'kovich, S.G.

1982-01-01

A summarry on modern radionuclide diagnosis achivements of central nervous system diseases is presented. Most optimal tumorotropic preparations and compounds in the view of decreasing irradiation does and optimazing image are given

Downregulation of membrane type-matrix metalloproteinases in the inflamed or injured central nervous system

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Millward Jason M

2007-09-01

Full Text Available Abstract Background Matrix metalloproteinases (MMPs are thought to mediate cellular infiltration in central nervous system (CNS inflammation by cleaving extracellular matrix proteins associated with the blood-brain barrier. The family of MMPs includes 23 proteinases, including six membrane type-MMPs (MT-MMPs. Leukocyte infiltration is an integral part of the pathogenesis of autoimmune inflammation in the CNS, as occurs in multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE, as well as in the response to brain trauma and injury. We have previously shown that gene expression of the majority of MMPs was upregulated in the spinal cord of SJL mice with severe EAE induced by adoptive transfer of myelin basic protein-reactive T cells, whereas four of the six MT-MMPs (MMP-15, 16, 17 and 24 were downregulated. The two remaining MT-MMPs (MMP-14 and 25 were upregulated in whole tissue. Methods We used in vivo models of CNS inflammation and injury to study expression of MT-MMP and cytokine mRNA by real-time RT-PCR. Expression was also assessed in microglia sorted from CNS by flow cytometry, and in primary microglia cultures following treatment with IFNγ. Results We now confirm the expression pattern of MT-MMPs in the B6 mouse, independent of effects of adjuvant. We further show expression of all the MT-MMPs, except MMP-24, in microglia. Microglia isolated from mice with severe EAE showed statistically significant downregulation of MMP-15, 17 and 25 and lack of increase in levels of other MT-MMPs. Downregulation of MT-MMPs was also apparent following CNS injury. The pattern of regulation of MT-MMPs in neuroinflammation showed no association with expression of the proinflammatory cytokines TNFα, IL-1β, or IFNγ. Conclusion CNS inflammation and injury leads to downregulation in expression of the majority of MT-MMPs. Microglia in EAE showed a general downregulation of MT-MMPs, and our findings suggest that MT-MMP levels may

Radioautography of the central nervous system and pituitary after 3H steroid hormones injection into different mammals

International Nuclear Information System (INIS)

Warembourg, M.

1977-01-01

The central nervous system and pituitary of various mammals were examined by radioautography after injection of different tritiated steroid hormones. After injection of 3 H estradiol into ovariectomized mice, radioautograms revealed a significant labelling in cells of the amygdala, the bed nucleus of the stria terminalis, the nucleus preopticus medialis, the nuclei arcuatus and ventro-medialis. After injection of 3 H testosterone into castrated rats, the central nervous system and the anterior pituitary contained labelled cells. In the hypothalamus, the distribution pattern of androgen-neurons appears to be similar from the estrogen-neuron areas. After injection of 3 H progesterone into castrated estrogen-primed guinea-pigs, labelled neurons have been in the regions of nucleus arcuatus and nucleus preopticus suprachiasmaticus. After injection of 3 H corticosterone into adrenalectomized male rats, radioactivity was found to be selectively concentrated in neurons of septum, hippocampal complex indusium griseum, amygdala and in certain areas of the cortex. Most of the silver grains were localized in the nuclei of labelled cells. On the other hand, after injection of 3 H dexamethasone radioactivity concentration was high in the medial basal hypothalamus, in the anterior pituitary and in the pineal gland. Differences appear to exist in the topographic distribution of dexamethasone and corticosterone-concentrating cells [fr

Simultaneous Infiltration of Polyfunctional Effector and Suppressor T Cells into Renal Cell Carcinomas

NARCIS (Netherlands)

Attig, Sebastian; Hennenlotter, Jörg; Pawelec, Graham; Klein, Gerd; Koch, Sven D.; Pircher, Hanspeter; Feyerabend, Susan; Wernet, Dorothee; Stenzl, Arnulf; Rammensee, Hans-Georg; Gouttefangeas, Cécile

2009-01-01

Renal cell carcinoma is frequently infiltrated by cells of the immune system. This makes it important to understand interactions between cancer cells and immune cells so they can be manipulated to bring clinical benefit. Here, we analyze subsets and functions of T lymphocytes infiltrating renal cell

Human Immune System Mice for the Study of Human Immunodeficiency Virus-Type 1 Infection of the Central Nervous System

Science.gov (United States)

Evering, Teresa H.; Tsuji, Moriya

2018-01-01

Immunodeficient mice transplanted with human cell populations or tissues, also known as human immune system (HIS) mice, have emerged as an important and versatile tool for the in vivo study of human immunodeficiency virus-type 1 (HIV-1) pathogenesis, treatment, and persistence in various biological compartments. Recent work in HIS mice has demonstrated their ability to recapitulate critical aspects of human immune responses to HIV-1 infection, and such studies have informed our knowledge of HIV-1 persistence and latency in the context of combination antiretroviral therapy. The central nervous system (CNS) is a unique, immunologically privileged compartment susceptible to HIV-1 infection, replication, and immune-mediated damage. The unique, neural, and glia-rich cellular composition of this compartment, as well as the important role of infiltrating cells of the myeloid lineage in HIV-1 seeding and replication makes its study of paramount importance, particularly in the context of HIV-1 cure research. Current work on the replication and persistence of HIV-1 in the CNS, as well as cells of the myeloid lineage thought to be important in HIV-1 infection of this compartment, has been aided by the expanded use of these HIS mouse models. In this review, we describe the major HIS mouse models currently in use for the study of HIV-1 neuropathogenesis, recent insights from the field, limitations of the available models, and promising advances in HIS mouse model development. PMID:29670623

Improved infiltration of stem cells on electrospun nanofibers

International Nuclear Information System (INIS)

Shabani, Iman; Haddadi-Asl, Vahid; Seyedjafari, Ehsan; Babaeijandaghi, Farshad; Soleimani, Masoud

2009-01-01

Nanofibrous scaffolds have been recently used in the field of tissue engineering because of their nano-size structure which promotes cell attachment, function, proliferation and infiltration. In this study, nanofibrous polyethersulfone (PES) scaffolds was prepared via electrospinning. The scaffolds were surface modified by plasma treatment and collagen grafting. The surface changes then investigated by contact angle measurements and FTIR-ATR. The results proved grafting of the collagen on nanofibers surface and increased hydrophilicity after plasma treatment and collagen grafting. The cell interaction study was done using stem cells because of their ability to differentiate to different kinds of cell lines. The cells had normal morphology on nanofibers and showed very high infiltration through collagen grafted PES nanofibers. This infiltration capability is very useful and needed to make 3D scaffolds in tissue engineering.

Prenatal irradiation: radioinduced apoptosis in developing central nervous system

International Nuclear Information System (INIS)

Gisone, P.; Dubner, D.; Michelin, S.; Perez, M.R.; Barboza, M.

1998-01-01

Severe mental retardation (SMR) is the most significant effect of prenatal irradiation. The high radiosensitivity of developing brain is related with the chronology of morpho genetic phenomena regarding neuroblast proliferation, neuronal differentiation and migration, synaptogenesis and dendritic arborization. Programmed cell death (apoptosis) normally occurs during development in central nervous system (CNS). Apoptosis is a direct result of the expression of specific genes with a final common pathway leading to a characteristic DNA fragmentation pattern. A wide variety of situations and toxic agents have been reported to result in apoptotic death in developing CNS. The aim of this work was the characterization and quantification of apoptosis using an in vitro model of prenatal irradiation. Primary cell cultures from rat brain cortex of 17 days g.a. were irradiated with a gamma source, with doses between 0.2 Gy to 2 Gy. Apoptosis was evaluated 4 hours and 20 hours after irradiation by hematoxylin/eosin, fluorescent microscopy, flow cytometry and DNA electrophoresis. It was also evaluated the neuro protective effect of L-NAME, SOD and glutathion. A dose-dependent increase in apoptotic cell fraction was observed. A protector effect related with the presence of glutathion was observed. (author) [es

MRI changes in the central nervous system in a child with lupus erythematosus

International Nuclear Information System (INIS)

Gieron, M.A.; Khoromi, S.; Campos, A.

1995-01-01

We report on a 10-year-old girl with systemic lupus erythematosus who presented in status epilepticus as the only manifestation of central nervous system involvement. MRI of the brain showed diffuse gray and white matter lesions which almost completely resolved after treatment with methylprednisolone. MRI findings in this child are similar to those in adults with diffuse clinical manifestations. The study is essential in the initial evaluation of patients suspected of central nervous system lupus. (orig.)

MRI changes in the central nervous system in a child with lupus erythematosus

Energy Technology Data Exchange (ETDEWEB)

Gieron, M A [Dept. of Pediatrics, Univ. of South Florida, Coll. of Medicine, Tampa, FL (United States); Khoromi, S [Dept. of Neurology, Univ. of South Florida, Coll. of Medicine, Tampa, FL (United States); Campos, A [Dept. of Pediatrics, Univ. of South Florida, Coll. of Medicine, Tampa, FL (United States)

1995-05-01

We report on a 10-year-old girl with systemic lupus erythematosus who presented in status epilepticus as the only manifestation of central nervous system involvement. MRI of the brain showed diffuse gray and white matter lesions which almost completely resolved after treatment with methylprednisolone. MRI findings in this child are similar to those in adults with diffuse clinical manifestations. The study is essential in the initial evaluation of patients suspected of central nervous system lupus. (orig.)

Squamous cell carcinoma following radiation therapy for the infiltrative thymoma

International Nuclear Information System (INIS)

Ozawa, Shinji; Kitao, Takeshi

1992-01-01

This report represents one case of infiltrative thymoma followed by squamous cell carcinoma of the lungs. A 69-year-old man suffered from infiltrative thymoma which reduced by the radiation therapy. Seven years later its replase and the onset of squamous cell carcinoma were found simultaneously. Infiltrative thymoma metastasized not only to the mediastinum but also to the liver and bronchus. Squamous cell carcinoma developed in the right upper lobe. In spite of chemotherapy against them, the patient died. There are many cases in which infiltrative thymoma is accompanied by squamous cell carcinoma of the lung simultaneously; however, secondary onset of squamous cell carcinoma after the radiation therapy of infiltrative thymoma is rare. Secondary carcinogenesis of this case was considered to be closely related with immunological abnormalities caused by thymoma, effects of radiation, smoking and so on. (author)

DNA methylation-based classification of central nervous system tumours.

Science.gov (United States)

Capper, David; Jones, David T W; Sill, Martin; Hovestadt, Volker; Schrimpf, Daniel; Sturm, Dominik; Koelsche, Christian; Sahm, Felix; Chavez, Lukas; Reuss, David E; Kratz, Annekathrin; Wefers, Annika K; Huang, Kristin; Pajtler, Kristian W; Schweizer, Leonille; Stichel, Damian; Olar, Adriana; Engel, Nils W; Lindenberg, Kerstin; Harter, Patrick N; Braczynski, Anne K; Plate, Karl H; Dohmen, Hildegard; Garvalov, Boyan K; Coras, Roland; Hölsken, Annett; Hewer, Ekkehard; Bewerunge-Hudler, Melanie; Schick, Matthias; Fischer, Roger; Beschorner, Rudi; Schittenhelm, Jens; Staszewski, Ori; Wani, Khalida; Varlet, Pascale; Pages, Melanie; Temming, Petra; Lohmann, Dietmar; Selt, Florian; Witt, Hendrik; Milde, Till; Witt, Olaf; Aronica, Eleonora; Giangaspero, Felice; Rushing, Elisabeth; Scheurlen, Wolfram; Geisenberger, Christoph; Rodriguez, Fausto J; Becker, Albert; Preusser, Matthias; Haberler, Christine; Bjerkvig, Rolf; Cryan, Jane; Farrell, Michael; Deckert, Martina; Hench, Jürgen; Frank, Stephan; Serrano, Jonathan; Kannan, Kasthuri; Tsirigos, Aristotelis; Brück, Wolfgang; Hofer, Silvia; Brehmer, Stefanie; Seiz-Rosenhagen, Marcel; Hänggi, Daniel; Hans, Volkmar; Rozsnoki, Stephanie; Hansford, Jordan R; Kohlhof, Patricia; Kristensen, Bjarne W; Lechner, Matt; Lopes, Beatriz; Mawrin, Christian; Ketter, Ralf; Kulozik, Andreas; Khatib, Ziad; Heppner, Frank; Koch, Arend; Jouvet, Anne; Keohane, Catherine; Mühleisen, Helmut; Mueller, Wolf; Pohl, Ute; Prinz, Marco; Benner, Axel; Zapatka, Marc; Gottardo, Nicholas G; Driever, Pablo Hernáiz; Kramm, Christof M; Müller, Hermann L; Rutkowski, Stefan; von Hoff, Katja; Frühwald, Michael C; Gnekow, Astrid; Fleischhack, Gudrun; Tippelt, Stephan; Calaminus, Gabriele; Monoranu, Camelia-Maria; Perry, Arie; Jones, Chris; Jacques, Thomas S; Radlwimmer, Bernhard; Gessi, Marco; Pietsch, Torsten; Schramm, Johannes; Schackert, Gabriele; Westphal, Manfred; Reifenberger, Guido; Wesseling, Pieter; Weller, Michael; Collins, Vincent Peter; Blümcke, Ingmar; Bendszus, Martin; Debus, Jürgen; Huang, Annie; Jabado, Nada; Northcott, Paul A; Paulus, Werner; Gajjar, Amar; Robinson, Giles W; Taylor, Michael D; Jaunmuktane, Zane; Ryzhova, Marina; Platten, Michael; Unterberg, Andreas; Wick, Wolfgang; Karajannis, Matthias A; Mittelbronn, Michel; Acker, Till; Hartmann, Christian; Aldape, Kenneth; Schüller, Ulrich; Buslei, Rolf; Lichter, Peter; Kool, Marcel; Herold-Mende, Christel; Ellison, David W; Hasselblatt, Martin; Snuderl, Matija; Brandner, Sebastian; Korshunov, Andrey; von Deimling, Andreas; Pfister, Stefan M

2018-03-22

Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging-with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology.

Effect of immunomodulation on the fate of tumor cells in the central nervous system and systemic organs of mice. Distribution of [125I]5-iodo-2'-deoxyuridine-labeled KHT tumor cells after left intracardial injection

International Nuclear Information System (INIS)

Conley, F.K.

1982-01-01

The effect of systemic immunomodulation on tumor cell arrest and retention in the central nervous system was studied by following radioactively labeled tumor cells. KHT mouse sarcoma tumor cells were labeled in vitro with [ 125 I]IdUrd, and 1x10 5 tumor cells were injected into the left side of the hearts of syngeneic C3H mice. Experimental groups consisted of untreated normal mice, mice pretreated iv with Corynebacterium parvum, and mice chronically infected with Toxoplasma gondii; in this model both groups of immunomodulated mice are protected from developing systemic metastatic tumor, but only Toxoplasma-infected mice have protection against metastatic brain tumor. At time intervals from 1 to 96 hours, groups of mice from each experimental group were killed, and the brain and other organs were monitored for radioactivity to determine the number of viable tumor cells that had been present at the time of death. Normal mice demonstrated significant retention of tumor cells in the brain and kidneys plus adrenals at 96 hours. By contrast, in both groups of immunomodulated mice tumor cells were rapidly eliminated from systemic organs, but tumor cells were significantly retained in the central nervous system even at 96 hours after tumor cell injections. The results indicated that generalized immunomodulation had more effect in elimination of tumor cells from systemic organs than from the brain and that the elimination of tumor cells from the brain in Toxoplasma-infected mice was a delayed phenomenon

Adult central nervous system

International Nuclear Information System (INIS)

Sutton, M.L.

1985-01-01

Historically, the adult central nervous system (CNS) was regarded as relatively immune to the effects of ionising radiation, and the recognition of the CNS as a radio-vulnerable structure occurred later than was the case for many other tissues. Increasingly precise knowledge of the time-dose-volume relationships for CNS tolerance has had two important consequences: (1) it has permitted the avoidance of catastrophic and usually lethal late effects in the brain and spinal cord when these tissues are unavoidably irradiated during the treatment of adjacent non-CNS tumours, and (2) it has encouraged referral for irradiation of certain technically benign lesions which, although compatible with prolonged survival, represent a continuing threat to the patient - for example arteriovenous malformations, pituitary adenomas, and some meningiomas. Many of these can now be controlled for very long periods following radiation doses consistent with the long-term functional integrity of the CNS

Diffuse damage to central nervous system in progressive rheumatoid arthritis complicated by cerebral hermorrhage after radioisotope cisternography

International Nuclear Information System (INIS)

Tarnowska-Dziduszko, E.; Lazarowicz, J.

1980-01-01

Presented case reveals unusual reaction of central nervous system in the course of progressive rheumatoid arthritis and cerebral hemorrhage as a rare complication after radioisotope investigation of cerebro-spinal fluid spaces. Female, 58 years old which was treated for 22 years for progressive rheumatoid arthritis developed during last 3 years of life a psychoorganic syndrome with temporal epilepsy and slight left sided hemiparesis. After radioisotope cisternography appeared decerebration followed by death. On autopsy the hemorrhagic foci were found in left cerebral hemisphere and in the brain stem. Histological finding was generalized severe damage to interstitial vessels diagnosed as fibrinotic, necrotizing degeneration of capillary and arteriolar wall, significant proliferation of microglia in the white matter and brain stem. Chronic inflammatory infiltrates were present in leptomeninges. Pathogenesis of findings in connection with progressive rheumatoid arthritis and complications due to cisternography is discussed. (author)

Primary granulomatous angeitis of the central nervous system

International Nuclear Information System (INIS)

Barrena, R.; Sevilla, G.; Olivan, M.; Gutierrez, P.; Guelbenzo, S.; Ayuso, T.

1995-01-01

A case of a young man with primary granulomatous angeitis of the central nervous system manifesting as a seizure is presented. The patient did not show previous pathology. Laboratory tests, computed tomography and magnetic resonance imaging were performed, but the definitive diagnosis was made only by means of brain biopsy. Administration of steroids showed and improvement in symptoms. 8 refs

Central nervous system imaging in childhood Langerhans cell histiocytosis – a reference center analysis

International Nuclear Information System (INIS)

Porto, Luciana; Schöning, Stefan; Hattingen, Elke; Sörensen, Jan; Jurcoane, Alina; Lehrnbecher, Thomas

2015-01-01

The aim of our study was (1) to describe central nervous system (CNS) manifestations in children with Langerhans cell histiocytosis (LCH) based on images sent to a reference center and meeting minimum requirements and (2) to assess the inter-rater agreement of CNS-MRI results, which represents the overall reproducibility of this investigation. We retrospectively reviewed brain MRI examinations in children with LCH, for which MRI minimum requirements were met. Abnormalities were rated by two experienced neuroradiologists, and the inter-rater agreement was assessed. Out of a total of 94 imaging studies, only 31 MRIs met the minimum criteria, which included T2w, FLAIR, T1w images before/after contrast in at least two different section planes, and thin post contrast sagittal slices T1w through the sella. The most common changes were osseous abnormalities, followed by solid enlargement of the pineal gland, thickened enhancing stalk and signal changes of the dentate nucleus. Whereas inter-rater agreement in assessing most of the CNS lesions was relatively high (κ > 0.61), the application of minimum criteria often did not allow to evaluate the posterior pituitary. The diversity of radiological protocols from different institutions leads to difficulties in the diagnosis of CNS abnormalities in children with LCH. Although the inter-rater agreement between neuroradiologists was high, not all the LCH manifestations could be completely ruled out when using the minimum criteria. Brain MRIs should therefore follow LCH guideline protocols and include T1 pre-gadolinium sagittal images, and be centrally reviewed in order to improve the comparison of clinical trials

Fanconi anemia: correlating central nervous system malformations and genetic complementation groups

International Nuclear Information System (INIS)

Johnson-Tesch, Benjamin A.; Gawande, Rakhee S.; Nascene, David R.; Zhang, Lei; MacMillan, Margaret L.

2017-01-01

Congenital central nervous system abnormalities in children with Fanconi anemia are poorly characterized, especially with regard to specific genetic complementation groups. To characterize the impact of genetic complementation groups on central nervous system anatomy. Through chart review we identified 36 patients with Fanconi anemia with available brain MRIs at the University of Minnesota (average age, 11.3 years; range, 1-43 years; M:F=19:17), which we reviewed and compared to 19 age- and sex-matched controls (average age, 7.9 years; range, 2-18 years; M:F=9:10). Genotypic information was available for 27 patients (15 FA-A, 2 FA-C, 3 FA-G, and 7 FA-D1 [biallelic mutations in BRCA2 gene]). Of the 36 patients, 61% had at least one congenital central nervous system or skull base abnormality. These included hypoplastic clivus (n=12), hypoplastic adenohypophysis (n=11), platybasia (n=8), pontocerebellar hypoplasia (n=7), isolated pontine hypoplasia (n=4), isolated vermis hypoplasia (n=3), and ectopic neurohypophysis (n=6). Average pituitary volume was significantly less in patients with Fanconi anemia (P<0.0001) than in controls. Basal angle was significantly greater in Fanconi anemia patients (P=0.006), but the basal angle of those with FA-D1 was not significantly different from controls (P=0.239). Clivus length was less in the Fanconi anemia group (P=0.002), but significance was only observed in the FA-D1 subgroup (P<0.0001). Of the seven patients meeting criteria for pontocerebellar hypoplasia, six belonged to the FA-D1 group. Patients with Fanconi anemia have higher incidences of ectopic neurohypophysis, adenohypophysis hypoplasia, platybasia and other midline central nervous system skull base posterior fossa abnormalities than age- and sex-matched controls. Patients with posterior fossa abnormalities, including pontocerebellar hypoplasia, are more likely to have biallelic BRCA2 mutations. (orig.)

Fanconi anemia: correlating central nervous system malformations and genetic complementation groups

Energy Technology Data Exchange (ETDEWEB)

Johnson-Tesch, Benjamin A. [University of Minnesota, Department of Radiology, Minneapolis, MN (United States); Gawande, Rakhee S.; Nascene, David R. [University of Minnesota, Department of Radiology, Neuroradiology Section, Minneapolis, MN (United States); Zhang, Lei [University of Minnesota, Biostatistical Design and Analysis Centre, Minneapolis, MN (United States); MacMillan, Margaret L. [University of Minnesota, Blood and Marrow Transplant Program, Department of Pediatrics, Minneapolis, MN (United States)

2017-06-15

Congenital central nervous system abnormalities in children with Fanconi anemia are poorly characterized, especially with regard to specific genetic complementation groups. To characterize the impact of genetic complementation groups on central nervous system anatomy. Through chart review we identified 36 patients with Fanconi anemia with available brain MRIs at the University of Minnesota (average age, 11.3 years; range, 1-43 years; M:F=19:17), which we reviewed and compared to 19 age- and sex-matched controls (average age, 7.9 years; range, 2-18 years; M:F=9:10). Genotypic information was available for 27 patients (15 FA-A, 2 FA-C, 3 FA-G, and 7 FA-D1 [biallelic mutations in BRCA2 gene]). Of the 36 patients, 61% had at least one congenital central nervous system or skull base abnormality. These included hypoplastic clivus (n=12), hypoplastic adenohypophysis (n=11), platybasia (n=8), pontocerebellar hypoplasia (n=7), isolated pontine hypoplasia (n=4), isolated vermis hypoplasia (n=3), and ectopic neurohypophysis (n=6). Average pituitary volume was significantly less in patients with Fanconi anemia (P<0.0001) than in controls. Basal angle was significantly greater in Fanconi anemia patients (P=0.006), but the basal angle of those with FA-D1 was not significantly different from controls (P=0.239). Clivus length was less in the Fanconi anemia group (P=0.002), but significance was only observed in the FA-D1 subgroup (P<0.0001). Of the seven patients meeting criteria for pontocerebellar hypoplasia, six belonged to the FA-D1 group. Patients with Fanconi anemia have higher incidences of ectopic neurohypophysis, adenohypophysis hypoplasia, platybasia and other midline central nervous system skull base posterior fossa abnormalities than age- and sex-matched controls. Patients with posterior fossa abnormalities, including pontocerebellar hypoplasia, are more likely to have biallelic BRCA2 mutations. (orig.)

Atypical Teratoid Rhabdoid Tumor in a Teenager with Unusual Infiltration Into the Jugular Foramen.

Science.gov (United States)

Udaka, Yoko T; Yoon, Janet M; Malicki, Denise M; Khanna, Paritosh C; Levy, Michael L; Crawford, John R

2015-12-01

Atypical teratoid rhabdoid tumor is a rare malignant neoplasm that represents 1%-2% of all pediatric central nervous system tumors. Immunohistochemistry plays an important role in establishing the diagnosis with a loss of INI-1 staining in tumor cells. In this case report, we describe a teenager with an unusual presentation and pattern of infiltration of the tumor. A 13-year-old boy presented with a history over several months of progressive nausea, weight loss, and hoarseness of voice associated with multiple lower cranial nerve palsies on neurologic examination. Magnetic resonance imaging revealed a large heterogeneously enhancing extra-axial neoplasm with extension and bony expansion of the jugular foramen. After near total resection, neuropathology demonstrated the absence of INI-1 expression consistent with a diagnosis of atypical teratoid rhabdoid tumor. This case highlights the diverse clinical presentation and infiltrative potential of atypical teratoid rhabdoid tumors, thus expanding the differential diagnosis of extra-axial tumors invading the jugular foramen. Copyright © 2015 Elsevier Inc. All rights reserved.

Adult Central Nervous System Tumors Treatment (PDQ®)—Patient Version

Science.gov (United States)

Adult central nervous system tumor treatment may include surgery, radiosurgery, radiation therapy, chemotherapy, surveillance, and targeted therapy. Treatment depends on the tumor type. Learn more about brain and spinal tumor treatment in this expert-reviewed summary.

T-bet-dependent NKp46+ innate lymphoid cells regulate the onset of TH17-induced neuroinflammation. | Center for Cancer Research

Science.gov (United States)

The process by which self-reactive CD4+ T cells infiltrate the central nervous system (CNS) and trigger neuroinflammation is not fully understood. Lazarevic and colleagues show that NKp46+innate lymphoid cells dependent on the transcription factor T-bet are critical mediators in facilitating the entry of autoreactive CD4+ cells of the TH17 subset of helper T cells into the

Involvement of central nervous system in the schistosomiasis

Directory of Open Access Journals (Sweden)

Teresa Cristina de Abreu Ferrari

2004-08-01

Full Text Available The involvement of the central nervous system (CNS by schistosomes may or may not determine clinical manifestations. When symptomatic, neuroschistosomiasis (NS is one of the most severe presentations of schistosomal infection. Considering the symptomatic form, cerebral involvement is almost always due to Schistosoma japonicum and the spinal cord disease, caused by S. mansoni or S. haematobium. Available evidence suggests that NS depends basically on the presence of parasite eggs in the nervous tissue and on the host immune response. The patients with cerebral NS usually have the clinical manifestations of increased intracranial pressure associated with focal neurological signs; and those with schistosomal myeloradiculopathy (SMR present rapidly progressing symptoms of myelitis involving the lower cord, usually in association with the involvement of the cauda esquina roots. The diagnosis of cerebral NS is established by biopsy of the nervous tissue and SMR is usually diagnosed according to a clinical criterion. Antischistosomal drugs, corticosteroids and surgery are the resourses available for treating NS. The outcome is variable and is better in cerebral disease.

Central nervous system radiation injury in small animal models

International Nuclear Information System (INIS)

Kogel, A.J. van der

1991-01-01

Experimental studies on radiation injury in the central nervous system have been carried out in many species ranging from mouse to monkey. This review is restricted to studies in rodents irradiated with low linear energy transfer (LET) radiation. In this paper, the various rodent models of brain and spinal cord injury are described with particular emphasis on the pathology of different types of lesions and theories of their pathogenesis. Many of the initial studies were limited to relatively high single doses, but in later work more clinically relevant fractionated irradiation schemes were employed. This has led to the recognition of various types of early and late delayed injury that are analogous to the syndromes observed in humans. Two main pathways have been suggested for the pathogenesis, one involving predominantly the progressive loss of glial cells and the other involving vascular injury. The relative importance of both mechanisms will be discussed with respect to treatment conditions and to dose level in particular. An hypothesis is presented concerning the possible role of different cell types in the development of specific syndromes

Central nervous system medications and falls risk in men aged 60-75 years

DEFF Research Database (Denmark)

Masud, Tahir; Frost, Morten; Ryg, Jesper

2013-01-01

Introduction: drugs acting on the central nervous system (CNS) increase falls risk. Most data on CNS drugs and falls are in women/mixed-sex populations. This study assessed the relationship between CNS drugs and falls in men aged 60-75 years.......Introduction: drugs acting on the central nervous system (CNS) increase falls risk. Most data on CNS drugs and falls are in women/mixed-sex populations. This study assessed the relationship between CNS drugs and falls in men aged 60-75 years....

Tachykinin-1 in the central nervous system regulates adiposity in rodents.

Science.gov (United States)

Trivedi, Chitrang; Shan, Xiaoye; Tung, Yi-Chun Loraine; Kabra, Dhiraj; Holland, Jenna; Amburgy, Sarah; Heppner, Kristy; Kirchner, Henriette; Yeo, Giles S H; Perez-Tilve, Diego

2015-05-01

Ghrelin is a circulating hormone that targets the central nervous system to regulate feeding and adiposity. The best-characterized neural system that mediates the effects of ghrelin on energy balance involves the activation of neuropeptide Y/agouti-related peptide neurons, expressed exclusively in the arcuate nucleus of the hypothalamus. However, ghrelin receptors are expressed in other neuronal populations involved in the control of energy balance. We combined laser capture microdissection of several nuclei of the central nervous system expressing the ghrelin receptor (GH secretagoge receptor) with microarray gene expression analysis to identify additional neuronal systems involved in the control of central nervous system-ghrelin action. We identified tachykinin-1 (Tac1) as a gene negatively regulated by ghrelin in the hypothalamus. Furthermore, we identified neuropeptide k as the TAC1-derived peptide with more prominent activity, inducing negative energy balance when delivered directly into the brain. Conversely, loss of Tac1 expression enhances the effectiveness of ghrelin promoting fat mass gain both in male and in female mice and increases the susceptibility to diet-induced obesity in ovariectomized mice. Taken together, our data demonstrate a role TAC1 in the control energy balance by regulating the levels of adiposity in response to ghrelin administration and to changes in the status of the gonadal function.

X-ray microbeams: Tumor therapy and central nervous system research

International Nuclear Information System (INIS)

Dilmanian, F.A.; Qu, Y.; Liu, S.; Cool, C.D.; Gilbert, J.; Hainfeld, J.F.; Kruse, C.A.; Laterra, J.; Lenihan, D.; Nawrocky, M.M.; Pappas, G.; Sze, C.-I.; Yuasa, T.; Zhong, N.; Zhong, Z.; McDonald, J.W.

2005-01-01

Irradiation with parallel arrays of thin, planar slices of X-ray beams (microplanar beams, or microbeams) spares normal tissue, including the central nervous system (CNS), and preferentially damages tumors. The effects are mediated, at least in part, by the tissue's microvasculature that seems to effectively repair itself in normal tissue but fails to do so in tumors. Consequently, the therapeutic index of single-fraction unidirectional microbeam irradiations has been shown to be larger than that of single-fraction unidirectional unsegmented beams in treating the intracranial rat 9L gliosarcoma tumor model (9LGS) and the subcutaneous murine mammary carcinoma EMT-6. This paper presents results demonstrating that individual microbeams, or arrays of parallel ones, can also be used for targeted, selective cell ablation in the CNS, and also to induce demyelination. The results highlight the value of the method as a powerful tool for studying the CNS through selective cell ablation, besides its potential as a treatment modality in clinical oncology

Ibrutinib Treatment of Mantle Cell Lymphoma Relapsing at Central Nervous System: A Case Report and Literature Review

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Donato Mannina

2017-01-01

Full Text Available Mantle cell lymphoma (MCL accounts for about 5% of all lymphomas. Its clinical and histological features are heterogeneous. After a frequently good initial response, the disease generally and repeatedly relapses and finally the outcome is poor. Particularly severe is the prognosis of the rare occurrence of CNSi (Central Nervous System involvement. Ibrutinib, an oral inhibitor of Bruton tyrosine kinase (BTK, has shown strong activity in relapsing patients with Chronic Lymphocytic Leukemia (CLL and MCL. Few reports are available about treatment with ibrutinib of patients presenting CNSi by lymphoproliferative diseases (LPD. In all of them, ibrutinib, at the dosage between 420 and 560 mg/day, showed an impressive effectiveness. Here we describe a case of MCL with CNS relapse showing an excellent response to ibrutinib administered at the unusual dose of 280 mg/day because of concomitant treatment of cardiological disease.

Emergency Department Visits Involving Nonmedical Use of Central Nervous System Stimulants among Adults Aged 18 to 34 ...

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... Emergency Department Visits Involving Nonmedical Use of Central Nervous System Stimulants among Adults Aged 18 to 34 Increased between 2005 and 2011 Central nervous system (CNS) stimulants include prescription drugs, like those used ...

A Central Nervous System-Dependent Intron-Embedded Gene Encodes a Novel Murine Fyn Binding Protein.

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Ben Khalaf, Noureddine; Taha, Safa; Bakhiet, Moiz; Fathallah, M Dahmani

2016-01-01

The interplay between the nervous and immune systems is gradually being unraveled. We previously reported in the mouse the novel soluble immune system factor ISRAA, whose activation in the spleen is central nervous system-dependent. We also showed that ISRAA plays a role in modulating anti-infection immunity. Herein, we report the genomic description of the israa locus, along with some insights into the structure-function relationship of the protein. Our findings revealed that israa is nested within intron 6 of the mouse zmiz1 gene. Protein sequence analysis revealed a typical SH2 binding motif (Y102TEV), with Fyn being the most likely binding partner. Docking simulation showed a favorable conformation for the ISRAA-Fyn complex, with a specific binding mode for the binding of the YTEV motif to the SH2 domain. Experimental studies showed that in vitro, recombinant ISRAA is phosphorylated by Fyn at tyrosine 102. Cell transfection and pull-down experiments revealed Fyn as a binding partner of ISRAA in the EL4 mouse T-cell line. Indeed, we demonstrated that ISRAA downregulates T-cell activation and the phosphorylation of an activation tyrosine (Y416) of Src-family kinases in mouse splenocytes. Our observations highlight ISRAA as a novel Fyn binding protein that is likely to be involved in a signaling pathway driven by the nervous system.

A Central Nervous System-Dependent Intron-Embedded Gene Encodes a Novel Murine Fyn Binding Protein.

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Noureddine Ben Khalaf

Full Text Available The interplay between the nervous and immune systems is gradually being unraveled. We previously reported in the mouse the novel soluble immune system factor ISRAA, whose activation in the spleen is central nervous system-dependent. We also showed that ISRAA plays a role in modulating anti-infection immunity. Herein, we report the genomic description of the israa locus, along with some insights into the structure-function relationship of the protein. Our findings revealed that israa is nested within intron 6 of the mouse zmiz1 gene. Protein sequence analysis revealed a typical SH2 binding motif (Y102TEV, with Fyn being the most likely binding partner. Docking simulation showed a favorable conformation for the ISRAA-Fyn complex, with a specific binding mode for the binding of the YTEV motif to the SH2 domain. Experimental studies showed that in vitro, recombinant ISRAA is phosphorylated by Fyn at tyrosine 102. Cell transfection and pull-down experiments revealed Fyn as a binding partner of ISRAA in the EL4 mouse T-cell line. Indeed, we demonstrated that ISRAA downregulates T-cell activation and the phosphorylation of an activation tyrosine (Y416 of Src-family kinases in mouse splenocytes. Our observations highlight ISRAA as a novel Fyn binding protein that is likely to be involved in a signaling pathway driven by the nervous system.

The leech nervous system: a valuable model to study the microglia involvement in regenerative processes.

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Le Marrec-Croq, Françoise; Drago, Francesco; Vizioli, Jacopo; Sautière, Pierre-Eric; Lefebvre, Christophe

2013-01-01

Microglia are intrinsic components of the central nervous system (CNS). During pathologies in mammals, inflammatory processes implicate the resident microglia and the infiltration of blood cells including macrophages. Functions of microglia appear to be complex as they exhibit both neuroprotective and neurotoxic effects during neuropathological conditions in vivo and in vitro. The medicinal leech Hirudo medicinalis is a well-known model in neurobiology due to its ability to naturally repair its CNS following injury. Considering the low infiltration of blood cells in this process, the leech CNS is studied to specify the activation mechanisms of only resident microglial cells. The microglia recruitment is known to be essential for the usual sprouting of injured axons and does not require any other glial cells. The present review will describe the questions which are addressed to understand the nerve repair. They will discuss the implication of leech factors in the microglial accumulation, the identification of nerve cells producing these molecules, and the study of different microglial subsets. Those questions aim to better understand the mechanisms of microglial cell recruitment and their crosstalk with damaged neurons. The study of this dialog is necessary to elucidate the balance of the inflammation leading to the leech CNS repair.

The Leech Nervous System: A Valuable Model to Study the Microglia Involvement in Regenerative Processes

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Françoise Le Marrec-Croq

2013-01-01

Full Text Available Microglia are intrinsic components of the central nervous system (CNS. During pathologies in mammals, inflammatory processes implicate the resident microglia and the infiltration of blood cells including macrophages. Functions of microglia appear to be complex as they exhibit both neuroprotective and neurotoxic effects during neuropathological conditions in vivo and in vitro. The medicinal leech Hirudo medicinalis is a well-known model in neurobiology due to its ability to naturally repair its CNS following injury. Considering the low infiltration of blood cells in this process, the leech CNS is studied to specify the activation mechanisms of only resident microglial cells. The microglia recruitment is known to be essential for the usual sprouting of injured axons and does not require any other glial cells. The present review will describe the questions which are addressed to understand the nerve repair. They will discuss the implication of leech factors in the microglial accumulation, the identification of nerve cells producing these molecules, and the study of different microglial subsets. Those questions aim to better understand the mechanisms of microglial cell recruitment and their crosstalk with damaged neurons. The study of this dialog is necessary to elucidate the balance of the inflammation leading to the leech CNS repair.

Magnetic Resonance Spectroscopy in evaluation of central nervous system

International Nuclear Information System (INIS)

Krolicki, L.; Bak, M.; Grieb, P.

1996-01-01

The article presents the current results of MR spectroscopy in evaluation of central nervous system. This method is useful in examination of brain ischemia, brain tumors, epilepsy; white matter disorders and degeneration diseases. MR spectroscopy is unique technique for in vivo examination of the brain in physiological and pathophysiological states. (author)

Adverse effects of radiotherapy on the central nervous system

International Nuclear Information System (INIS)

Mocquard, Y.; Marion, J.L.; Goas, J.Y.

1985-01-01

Adverse effects of radiotherapy on the central nervous system are increasingly met with. Both the brain and spinal cord may be involved. Whereas some forms have a favorable outcome, many run a relentlessly progressive course, failing to respond to treatment. Improvement of radiation protocols should achieve a lower complication rate [fr

The role of surgery in primary central nervous system lymphomas

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Juan Francisco Villalonga

Full Text Available ABSTRACT Background Primary central nervous system lymphomas (PCNSL are infrequent. The traditional treatment of choice is chemotherapy. Complete resections have generally not been recommended, because of the risk of permanent central nervous system deficits with no proven improvement in survival. The aim of the current study was to compare survival among patients with PCNSL who underwent biopsy versus surgical resection. Methods A retrospective study was conducted on 50 patients with a confirmed diagnosis of PCNSL treated at our center from January 1994 to July 2015. Results Patients in the resection group exhibited significantly longer median survival time, relative to the biopsy group, surviving a median 31 months versus 14.5 months; p = 0.016. Conclusions In our series, patients who had surgical resection of their tumor survived a median 16.5 months longer than patients who underwent biopsy alone.

Diversity of imaging and pathological features at different stages of primary central nervous system lymphoma

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Jing LIU

2018-01-01

Full Text Available Objective The clinical, imaging and pathological manifestations of one patient at different stages of primary central nervous system lymphoma (PCNSL have been analyzed to disclose its pathogenesis. Methods and Results A 29-year-old female patient showed recurrent onsets. On the first onset, the main clinical manifestation was blurred vision and visual field defect. Cranial MRI showed a patchy lesion in the right parietal and occipital lobes without obvious occupying sign. T1WI showed slight low-intensity sign, T2WI and FLAIR showed high-intensity signs. Enhanced scanning showed heterogeneous punctate enhancement. The lesion disappeared gradually after glucocorticoid impact therapy. Headache, vomiting and left limb paralysis were the main clinical manifestations on the second onset, and MRI showed a lesion in the right frontal and parietal lobes with obvious occupying sign and solid enhancement, low-intensity on T1WI, high-intensity on T2WI and FLAIR. The tumor was totally removed under microscope. Histological findings showed large tumor cells, rich cytoplasm, nuclei with various sizes and shapes, conspicuous mitosis, patchy necrosis, and interstitial small vessel hyperplasia. Immunohistochemical staining showed that membrane of tumor cells was positive for CD20, and nuclei were positive for paired box gene 5 (PAX5 and multiple myeloma oncogene 1 (MUM1. In a few tumor cells, membrane was positive for CD10 and CD30, and nuclei were positive for cyclin D1. Besides, tumor cells were negative for CD3, anaplastic lymphoma kinase (ALK and glial fibrillary acidic protein (GFAP. Ki?67 labeling index was about 80%. EBER in situ hybridization (ISH assay showed that mRNA coded by Epstein?Barr (EB virus was negative. The tumor showed angiotropic characteristics, and the walls of involved blood vessels were wrapped and destructed. The final diagnosis was confirmed as diffuse large B cell lymphoma. Conclusions PCNSL has various imaging features, revealing as

Isolated Richter's syndrome in central nervous system: case report Sindrome de Richter isolada em sistema nervoso central: relato de caso

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Lucilene S.R. Resende

2005-06-01

Full Text Available Diffuse large cell non Hodgkin's lymphoma associated with chronic lymphoid leukemia (CLL, or Richter's syndrome, is a rare and serious complication. Isolated Richter's syndrome in the central nervous system is very rare; only 12 cases have been reported. We describe a 74-year-old patient with diffuse large cell non Hodgkin's lymphoma in the right frontal region with the appearance of multiform glioblastoma.Linfoma não Hodgkin difuso de grandes células em paciente portador de leucemia linfóide crônica (LLC, ou síndrome de Richter, é complicação rara e grave nesta leucemia. Síndrome de Richter isolada no sistema nervoso central é muito rara, tendo sido encontrados apenas 12 casos descritos. Descrevemos paciente de 74 anos, que apresentou linfoma não Hodgkin difuso de grandes células em região frontal direita, simulando glioblastoma multiforme.

The Diagnostic Value of Brain Scanning in the Diseases of the Central Nervous System

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Kim, Kwang Won; Lee, Myung Chul; Koh, Chang Soon; Lee, Mun Ho; Chang, Kee Hyun; Han, Man Chung; Choi, Kil Su; Son, Hyo Chung; Cho, Byung Kyu [Seoul National University College of Medicine, Seoul (Korea, Republic of)

1974-03-15

The purpose of this study is to evaluate the diagnostic value of the brain scanning and compare the diagnostic accuracy between the scan and carotid angiography. 109 cases which are proved by specific method to each disease, are analyzed to evaluate the diagnostic value of the brain scanning. The 70 cases among the proven 109 case are performed both the scanning and the arteriography and analyzed to compare the accuracy between the scanning and the arteriography. The results are as follows; 1) The diagnostic accuracy of the brain scanning in the diseases of the central nervous system is 64.2%. 2) The diagnostic accuracy of the brain scanning in the brain tumor is 88%, especially brain abscess, glioma, glioblastoma multiforme, meningioma and metastic tumor show high positive rate. 3) The diagnostic accuracy in the disease of the brain vessels is 54%. The comparison of the diagnostic value between the scanning and the arteriography is as follows;1) The diagnostic value in all diseases of the central nervous system is nearly equal. 2) The diagnostic accuracy in the intracranial tumor is slightly higher in the brain scanning (90. 9%) than in the arteriography (81.8%). 3) The diagnostic accuracy in the disease of the brain vessel is higher in the arteriography (77.3%) than in the scanning (54.5%). 5) The diagnostic value when combining the scanning and the arteriography, is 83% in the all central nervous system-lesions, 97% in the cranial tumor and 81.8% in the disease of the central nervous system-vessel. The brain scanning is simple and safe procedure, and moreover has excellent diagnostic value in the diagnosis of the central nervous system lesion.

The Diagnostic Value of Brain Scanning in the Diseases of the Central Nervous System

International Nuclear Information System (INIS)

Kim, Kwang Won; Lee, Myung Chul; Koh, Chang Soon; Lee, Mun Ho; Chang, Kee Hyun; Han, Man Chung; Choi, Kil Su; Son, Hyo Chung; Cho, Byung Kyu

1974-01-01

The purpose of this study is to evaluate the diagnostic value of the brain scanning and compare the diagnostic accuracy between the scan and carotid angiography. 109 cases which are proved by specific method to each disease, are analyzed to evaluate the diagnostic value of the brain scanning. The 70 cases among the proven 109 case are performed both the scanning and the arteriography and analyzed to compare the accuracy between the scanning and the arteriography. The results are as follows; 1) The diagnostic accuracy of the brain scanning in the diseases of the central nervous system is 64.2%. 2) The diagnostic accuracy of the brain scanning in the brain tumor is 88%, especially brain abscess, glioma, glioblastoma multiforme, meningioma and metastic tumor show high positive rate. 3) The diagnostic accuracy in the disease of the brain vessels is 54%. The comparison of the diagnostic value between the scanning and the arteriography is as follows;1) The diagnostic value in all diseases of the central nervous system is nearly equal. 2) The diagnostic accuracy in the intracranial tumor is slightly higher in the brain scanning (90. 9%) than in the arteriography (81.8%). 3) The diagnostic accuracy in the disease of the brain vessel is higher in the arteriography (77.3%) than in the scanning (54.5%). 5) The diagnostic value when combining the scanning and the arteriography, is 83% in the all central nervous system-lesions, 97% in the cranial tumor and 81.8% in the disease of the central nervous system-vessel. The brain scanning is simple and safe procedure, and moreover has excellent diagnostic value in the diagnosis of the central nervous system lesion.

Enriched Environment Increases PCNA and PARP1 Levels in Octopus vulgaris Central Nervous System: First Evidence of Adult Neurogenesis in Lophotrochozoa.

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Bertapelle, Carla; Polese, Gianluca; Di Cosmo, Anna

2017-06-01

Organisms showing a complex and centralized nervous system, such as teleosts, amphibians, reptiles, birds and mammals, and among invertebrates, crustaceans and insects, can adjust their behavior according to the environmental challenges. Proliferation, differentiation, migration, and axonal and dendritic development of newborn neurons take place in brain areas where structural plasticity, involved in learning, memory, and sensory stimuli integration, occurs. Octopus vulgaris has a complex and centralized nervous system, located between the eyes, with a hierarchical organization. It is considered the most "intelligent" invertebrate for its advanced cognitive capabilities, as learning and memory, and its sophisticated behaviors. The experimental data obtained by immunohistochemistry and western blot assay using proliferating cell nuclear antigen and poli (ADP-ribose) polymerase 1 as marker of cell proliferation and synaptogenesis, respectively, reviled cell proliferation in areas of brain involved in learning, memory, and sensory stimuli integration. Furthermore, we showed how enriched environmental conditions affect adult neurogenesis. © 2017 Wiley Periodicals, Inc.

Incidence and risk factors for central nervous system relapse in children and adolescents with acute lymphoblastic leukemia

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Cancela, Camila Silva Peres; Murao, Mitiko; Viana, Marcos Borato; de Oliveira, Benigna Maria

2012-01-01

Background Despite all the advances in the treatment of childhood acute lymphoblastic leukemia, central nervous system relapse remains an important obstacle to curing these patients. This study analyzed the incidence of central nervous system relapse and the risk factors for its occurrence in children and adolescents with acute lymphoblastic leukemia. Methods This study has a retrospective cohort design. The studied population comprised 199 children and adolescents with a diagnosis of acute lymphoblastic leukemia followed up at Hospital das Clinicas, Universidade Federal de Minas Gerais (HC-UFMG) between March 2001 and August 2009 and submitted to the Grupo Brasileiro de Tratamento de Leucemia da Infância - acute lymphoblastic leukemia (GBTLI-LLA-99) treatment protocol. Results The estimated probabilities of overall survival and event free survival at 5 years were 69.5% (± 3.6%) and 58.8% (± 4.0%), respectively. The cumulative incidence of central nervous system (isolated or combined) relapse was 11.0% at 8 years. The estimated rate of isolated central nervous system relapse at 8 years was 6.8%. In patients with a blood leukocyte count at diagnosis ≥ 50 x 109/L, the estimated rate of isolated or combined central nervous system relapse was higher than in the group with a count 50 x 109/L at diagnosis seems to be a significant prognostic factor for a higher incidence of central nervous system relapse in childhood acute lymphoblastic leukemia. PMID:23323068

Gross anatomy of central nervous system in firefly, Pteroptyx tener (Coleoptera: Lampyridae)

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Hudawiyah, Nur; Wahida, O. Nurul; Norela, S.

2015-09-01

This paper describes for the first time the organization and fine structure of the central nervous system (CNS) in the fireflies, Pteroptyx tener (Coleoptera: Lampyridae). The morphology of the CNS was examined by using Carl Zeiss AxioScope A1 photomicroscope with iSolution Lite software. Some specific structural features such as the localization of protocerebrum, deutocerebrum and tritocerebrum in the brain region were analyzed. Other than that, the nerve cord and its peripheral structure were also analyzed. This study suggests that, there is a very obvious difference between male and female central nervous system which illustrates that they may differ in function in controlling physiological and behavioral activities.

Advanced in study of cellular and molecular mechanisms of radiation effects on central nervous system

International Nuclear Information System (INIS)

Zhang Wei; Tu Yu; Wang Lili

2008-01-01

Along with radiation treatment extensively applied, radiation injury also is valued gradually. The effect of radiation to the cellular and molecular of central nervous system (CNS) is a complicated and moderately advanced process and the mechanism is remains incompletely clear yet. Inquiring into the possible mechanism of the CNS including the injury and the restoration of neuron, neuroglia cells, endotheliocyte cell and blood-brain barrier and the molecular level of change induced by radiation, so as to provide beneficial thought for preventing and curing radiation injury clinically. Some neuroprotective strategies are also addressed in the review. (authors)

Primary cerebral angitis of the central nervous | Das | East African ...

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Various medications like intravenous immunoglobulin, antibiotics, acyclovir, methyl prednisolone and management for raised intracranial pressure were instituted. She rapidly deteroriated and died on tenth hospital day. Only at autopsy was the diagnosis of primary angitis of central nervous system established. East African ...

Intraventricular ciprofloxacin usage in treatment of multidrug-resistant central nervous system infections: report of four cases

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Ayse Karaaslan

2014-12-01

Full Text Available In recent years, multidrug-resistant microorganisms appear as important nosocomial pathogens which treatment is quite difficult. As sufficient drug levels could not be achieved in cerebrospinal fluid during intravenous antibiotic therapy for central nervous system infections and due to multidrug-resistance treatment alternatives are limited. In this study, four cases of central nervous system infections due to multidrug-resistant microorganisms who were successfully treated with removal of the devices and intraventricular ciprofloxacin are presented. In conclusion, intraventricular ciprofloxacin can be used for treatment of central nervous system infections if the causative microorganism is sensitive to the drug and no other alternative therapy is available.

Time Perception Mechanisms at Central Nervous System.

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Fontes, Rhailana; Ribeiro, Jéssica; Gupta, Daya S; Machado, Dionis; Lopes-Júnior, Fernando; Magalhães, Francisco; Bastos, Victor Hugo; Rocha, Kaline; Marinho, Victor; Lima, Gildário; Velasques, Bruna; Ribeiro, Pedro; Orsini, Marco; Pessoa, Bruno; Leite, Marco Antonio Araujo; Teixeira, Silmar

2016-04-01

The five senses have specific ways to receive environmental information and lead to central nervous system. The perception of time is the sum of stimuli associated with cognitive processes and environmental changes. Thus, the perception of time requires a complex neural mechanism and may be changed by emotional state, level of attention, memory and diseases. Despite this knowledge, the neural mechanisms of time perception are not yet fully understood. The objective is to relate the mechanisms involved the neurofunctional aspects, theories, executive functions and pathologies that contribute the understanding of temporal perception. Articles form 1980 to 2015 were searched by using the key themes: neuroanatomy, neurophysiology, theories, time cells, memory, schizophrenia, depression, attention-deficit hyperactivity disorder and Parkinson's disease combined with the term perception of time. We evaluated 158 articles within the inclusion criteria for the purpose of the study. We conclude that research about the holdings of the frontal cortex, parietal, basal ganglia, cerebellum and hippocampus have provided advances in the understanding of the regions related to the perception of time. In neurological and psychiatric disorders, the understanding of time depends on the severity of the diseases and the type of tasks.

Time perception mechanisms at central nervous system

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Rhailana Fontes

2016-04-01

Full Text Available The five senses have specific ways to receive environmental information and lead to central nervous system. The perception of time is the sum of stimuli associated with cognitive processes and environmental changes. Thus, the perception of time requires a complex neural mechanism and may be changed by emotional state, level of attention, memory and diseases. Despite this knowledge, the neural mechanisms of time perception are not yet fully understood. The objective is to relate the mechanisms involved the neurofunctional aspects, theories, executive functions and pathologies that contribute the understanding of temporal perception. Articles form 1980 to 2015 were searched by using the key themes: neuroanatomy, neurophysiology, theories, time cells, memory, schizophrenia, depression, attention-deficit hyperactivity disorder and Parkinson’s disease combined with the term perception of time. We evaluated 158 articles within the inclusion criteria for the purpose of the study. We conclude that research about the holdings of the frontal cortex, parietal, basal ganglia, cerebellum and hippocampus have provided advances in the understanding of the regions related to the perception of time. In neurological and psychiatric disorders, the understanding of time depends on the severity of the diseases and the type of tasks.

Effects of heavy particle irradiation on central nervous system

International Nuclear Information System (INIS)

Nojima, Kumie; Liu Cuihua; Nagaoka, Shunji

2003-01-01

Effects of low dose heavy particle radiation to central nervous system were studied using mouse neonatal brain cells in culture exposed to heavy ions and X ray at fifth days of the culture. The subsequent biological effects were evaluated by an induction of apoptosis and the survivability of neurons focusing on the dependencies of the animal strains with different genetic types, and linear energy transfer (LET) of the different nucleons. Of the three mouse strains tested, severe combined immunodeficiency (SCID), B6 and C3H, used for brain cell culture, SCID was the most sensitive and C3H the least sensitive to both X-ray and carbon ion (290 MeV/n) when compared by 10% apoptotic induction. The LET dependency was compared with using SCID cells exposing to different ions, (X, C, Si, Ar, and Fe). Although no detectable LET dependency was observed at higher dose than 1 Gy, an enhancement was observed in the high LET region and at lower dose than 0.5 Gy. The survivability profiles of the neurons were different in the mouse strains and ions. Memory and learning function of adult mice were studied using water maze test after localized carbon- or iron-ion irradiation to hippocampus area. (author)

Metastatic neoplasms of the central nervous system

International Nuclear Information System (INIS)

Fenner, W.R.

1990-01-01

Metastatic neoplasms to the central nervous system are often encountered in the practice of surgical neuropathology. It is not uncommon for patients with systemic malignancies to present to medical attention because of symptoms from a brain metastasis and for the tissue samples procured from these lesions to represent the first tissue available to study a malignancy from an unknown primary. In general surgical pathology, the evaluation of a metastatic neoplasm of unknown primary is a very complicated process, requiring knowledge of numerous different tumor types, reagents, and staining patterns. The past few years, however, have seen a remarkable refinement in the immunohistochemical tools at our disposal that now empower neuropathologists to take an active role in defining the relatively limited subset of neoplasms that commonly metastasize to the central nervous system. This information can direct imaging studies to find the primary tumor in a patient with an unknown primary, clarify the likely primary site of origin in patients who have small tumors in multiple sites without an obvious primary lesion, or establish lesions as late metastases of remote malignancies. Furthermore, specific treatments can begin and additional invasive procedures may be prevented if the neuropathologic evaluation of metastatic neoplasms provides information beyond the traditional diagnosis of ''metastatic neoplasm.'' In this review, differential cytokeratins, adjuvant markers, and organ-specific antibodies are described and the immunohistochemical signatures of metastatic neoplasms that are commonly seen by neuropathologists are discussed

Conventional external beam radiotherapy for central nervous system malignancies

International Nuclear Information System (INIS)

Halperin, E.C.; Burger, P.C.

1985-01-01

Fractionated external beam photon radiotherapy is an important component of the clinical management of malignant disease of the central nervous system. The practicing neurologist or neurosurgeon frequently relies on the consultative and treatment skills of a radiotherapist. This article provides a review for the nonradiotherapist of the place of conventional external beam radiotherapy in neuro-oncology. 23 references

Some Central Nervous System Activities of Nerium Oleander Linn ...

African Journals Online (AJOL)

Purpose: The purpose of the study was to evaluate the activity of 50 % hydroalcohol flower extract of Nerium oleander Linn. on the central nervous system (CNS) of mice. Methods: The effect of the 50 % hydroalcohol extract of N. oleander flowers at dosage levels of 100 and 200 mg/kg p.o. on the locomotor activity of mice ...

Radiotherapy of the central nervous system in acute leukemia

International Nuclear Information System (INIS)

Novak, L.J.

1989-01-01

The central nervous system (CNS) is a site of occult and overt involvement with acute lymphoblastic leukemia (ALL) in children. Prophylactic treatment of the cranial and spinal meninges can significantly reduce the incidence of CNS relapse. This review addresses the issues associated with the role of radiation therapy in the treatment of the CNS in ALL.20 references

Nuclear magnetic resonance imaging of the central nervous system

International Nuclear Information System (INIS)

Knaap, M.S. van der; Valk, J.

1989-01-01

In this article a review is given of the use of magnetic resonance imaging for the central nervous system. An example of the screening of the population for multiple scelerosis is given. A good preliminary examination and the supply of relevant information to the person which performs the imaging is necessary. (R.B.). 9 figs.; 4 tabs

Computed tomography of the central nervous system in small animals

International Nuclear Information System (INIS)

Tipold, A.; Tipold, E.

1991-01-01

With computed tomography in 44 small animals some well defined anatomical structures and pathological processes of the central nervous system are described. Computed tomography is not only necessary for the diagnosis of tumors; malformations, inflammatory, degenerative and vascular diseases and traumas are also visible

School Reentry for Children with Acquired Central Nervous Systems Injuries

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Carney, Joan; Porter, Patricia

2009-01-01

Onset of acquired central nervous system (CNS) injury during the normal developmental process of childhood can have impact on cognitive, behavioral, and motor function. This alteration of function often necessitates special education programming, modifications, and accommodations in the education setting for successful school reentry. Special…

Neurogenesis in Aplysia californica resembles nervous system formation in vertebrates

International Nuclear Information System (INIS)

Jacob, M.H.

1984-01-01

The pattern of neurogenesis of the central nervous system of Aplysia californica was investigated by [ 3 H]thymidine autoradiography. Large numbers of animals at a series of early developmental stages were labeled with [ 3 H]thymidine for 24 or 48 hr and were subsequently sampled at specific intervals throughout the life cycle. I found that proliferative zones, consisting of columnar and placodal ectodermal cells, are established in regions of the body wall adjacent to underlying mesodermal cells. Mitosis in the proliferative zones generates a population of cells which leave the surface and migrate inward to join the nearby forming ganglia. Tracing specific [ 3 H]thymidine-labeled cells from the body wall to a particular ganglion and within the ganglion over time suggests that the final genomic replication of the neuronal precursors occurs before the cells join the ganglion while glial cell precursors and differentiating glial cells continue to divide within the ganglion for some time. Ultrastructural examination of the morphological features of the few mitosing cells observed within the Aplysia central nervous system supports this interpretation. The pattern of neurogenesis in the Aplysia central nervous system resembles the proliferation of cells in the neural tube and the migration of neural crest and ectodermal placode cells in the vertebrate nervous system but differs from the pattern described for other invertebrates

Expression of extracellular matrix components and their receptors in the central nervous system during experimental Toxoplasma gondii and Trypanosoma cruzi infection

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Silva A.A.

1999-01-01

Full Text Available Alterations in extracellular matrix (ECM expression in the central nervous system (CNS usually associated with inflammatory lesions have been described in several pathological situations including neuroblastoma and demyelinating diseases. The participation of fibronectin (FN and its receptor, the VLA-4 molecule, in the migration of inflammatory cells into the CNS has been proposed. In Trypanosoma cruzi infection encephalitis occurs during the acute phase, whereas in Toxoplasma infection encephalitis is a chronic persisting process. In immunocompromised individuals such as AIDS patients, T. cruzi or T. gondii infection can lead to severe CNS damage. At the moment, there are no data available regarding the molecules involved in the entrance of inflammatory cells into the CNS during parasitic encephalitis. Herein, we characterized the expression of the ECM components FN and laminin (LN and their receptors in the CNS of T. gondii- and T. cruzi-infected mice. An increased expression of FN and LN was detected in the meninges, leptomeninges, choroid plexus and basal lamina of blood vessels. A fine FN network was observed involving T. gondii-free and T. gondii-containing inflammatory infiltrates. Moreover, perivascular spaces presenting a FN-containing filamentous network filled with a4+ and a5+ cells were observed. Although an increased expression of LN was detected in the basal lamina of blood vessels, the CNS inflammatory cells were a6-negative. Taken together, our results suggest that FN and its receptors VLA-4 and VLA-5 might be involved in the entrance, migration and retention of inflammatory cells into the CNS during parasitic infections.

Central nervous system tumors and related intracranial pathologies in radium dial workers

International Nuclear Information System (INIS)

Stebbings, J.H.; Semkiw, W.

1988-01-01

Among the female radiation workers in the radium dial industry there is no overall excess of brain or central nervous system tumors. A significant excess did appear, however, in one of three major cohorts; the excess was not due to an excess of gliomas and cannot be ascribed with certainty to radium or external radiation. A significant proportional excess of tumors outside the brain was observed, and is consistent with irradiation of nervous system tissue from adjacent bone. Early deaths from brain abscess or mastoiditis, which are coded as diseases of the nervous system and sense organs, were observed. 12 refs., 11 tabs

A novel three-dimensional system to study interactions between endothelial cells and neural cells of the developing central nervous system

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Milner Richard

2007-01-01

Full Text Available Abstract Background During angiogenesis in the developing central nervous system (CNS, endothelial cells (EC detach from blood vessels growing on the brain surface, and migrate into the expanding brain parenchyma. Brain angiogenesis is regulated by growth factors and extracellular matrix (ECM proteins secreted by cells of the developing CNS. In addition, recent evidence suggests that EC play an important role in establishing the neural stem cell (NSC niche. Therefore, two-way communication between EC and neural cells is of fundamental importance in the developing CNS. To study the interactions between brain EC and neural cells of the developing CNS, a novel three-dimensional (3-D murine co-culture system was developed. Fluorescent-labelled brain EC were seeded onto neurospheres; floating cellular aggregates that contain NSC/neural precursor cells (NPC and smaller numbers of differentiated cells. Using this system, brain EC attachment, survival and migration into neurospheres was evaluated and the role of integrins in mediating the early adhesive events addressed. Results Brain EC attached, survived and migrated deep into neurospheres over a 5-day period. Neurospheres express the ECM proteins fibronectin and laminin, and brain EC adhesion to neurospheres was inhibited by RGD peptides and antibodies specific for the β1, but not the α6 integrin subunit. Conclusion A novel 3-D co-culture system for analysing the interactions between EC and neural cells of the developing CNS is presented. This system could be used to investigate the reciprocal influence of EC and NSC/NPC; to examine how NSC/NPC influence cerebral angiogenesis, and conversely, to examine how EC regulate the maintenance and differentiation of NSC/NPC. Using this system it is demonstrated that EC attachment to neurospheres is mediated by the fibronectin receptor, α5β1 integrin.

Xeroderma pigmentosum: Carcinome spinocellulaire infiltrant et délabrant du visage, chez une fillette de 3 ans et demi [Xeroderma pigmentosum: Squamous cell carcinoma infiltrating and disfiguring facial, in a girl of 3 years and a half

Directory of Open Access Journals (Sweden)

Laouali Salissou

2017-11-01

Full Text Available Most of serious complications observed during the development of Xeroderma pigmentosum (XP are cancerous. These include skin, eyes, tongue, nervous system, etc. We report the case of a 3 1/2-year-old girl with squamous cell carcinoma infiltrating and disfiguring the face with rapid onset of death. RÉSUMÉ La plupart des complications graves observées au cours de l’évolution du Xeroderma pigmentosum (XP sont de nature cancéreuse. Celles-ci concernent notamment la peau, mais également les yeux, la langue, le système nerveux, etc. Nous rapportons le cas d’une fillette âgée de 3 ans et demie ayant présenté un carcinome épidermoïde infiltrant et délabrant du visage avec la survenue rapide de décès.

The central nervous system phenotype of X-linked Charcot-Marie-Tooth disease: a transient disorder of children and young adults.

Science.gov (United States)

Al-Mateen, Majeed; Craig, Alexa Kanwit; Chance, Phillip F

2014-03-01

We describe 2 patients with X-linked Charcot-Marie-Tooth disease, type 1 (CMTX1) disease and central nervous system manifestations and review 19 cases from the literature. Our first case had not been previously diagnosed with Charcot-Marie-Tooth disease, and the second case, although known to have Charcot-Marie-Tooth disease, was suspected of having CMTX1 after presentation with central nervous system manifestations. The most common central nervous system manifestations were transient and included dysarthria, ataxia, hemiparesis, and tetraparesis resembling periodic paralysis. Of the 21 patients, 19 presented at 21 years of age or younger, implicating CMTX1 with transient central nervous system manifestations as a disorder that predominantly affects children and adolescents. CMTX1 should be included in the differential diagnosis of patients who present with transient central nervous system phenomena, including stroke-like episodes, tetraparesis suggestive of periodic paralysis, dysarthria, ataxia, or combinations of these deficits. Reversible, bilateral, nonenhancing white matter lesions and restricted diffusion on magnetic resonance imaging are characteristic features of the central nervous system phenotype of CMTX1.

Contraindications to Athletic Participation. Cardiac, Respiratory, and Central Nervous System Conditions.

Science.gov (United States)

Moeller, James L.

1996-01-01

Discusses contraindications to athletic participation, examining the cardiac, respiratory, and central nervous system conditions that warrant activity disqualification. Provides guidelines about when it is safe for individuals to participate, and discusses the physician's responsibility. (SM)

Distribution of transplanted human mesenchymal stem cells from Wharton’s Jelly in the central nervous systems of the EAE rats

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Kovalchuk M. V.

2015-10-01

Full Text Available Human Wharton’s Jelly MSCs (hWJ-MSCs have a considerable advantage and potential in treating the central nervous system diseases and can be a new alternative treatment of Multiple Sclerosis (MS. Aim. To study the persistence and distribution of hWJ-MSCs along the neuraxis following transplantation in central nervous system of rats with experimental autoimmune encephalomyelitis (EAE, the animal model of MS. Methods. Isolation and cultivation of hWJ-MSCs in vitro. Immunological phenotyping by flow cytometry. EAE induction. Intrathecal (suboccipital injection of MSCs into CNS of SCH-induced EAE rats. Persistence of hWJ-MSCs in the CNS of hWJ-MSCs -treated rats was detected through detection of the human alpha-satellite DNA in the tissue sections and the cerebrospinal fluid (CSF by PCR at days 2, 3, 4 and 5 Results. PCR-assays for alpha-satellite sequences revealed that Human DNA was detected during 5 days following intrathecal injection at the peak of disease in the treated rats. It has been demonstrated that the human DNA was traced in CSF and various segments of a spinal cord. Conclusions. The data obtained suggest that intrathecally delivered hWJ-MSCs, with time, can migrate through the CSF from the injection site to various segments of CNS and persist therein during the first week of post transplantation, which was performed at the EAE disease peak in the xenogeneic setting without immunosuppression. hWJ-MSCs may be considered as a delivery cell source of therapeutic molecules for CNS inflammatory diseases.

Radiotherapy applied to tumours of the intracranial central nervous systems in the dog

International Nuclear Information System (INIS)

Tortereau, Antonin

2009-01-01

As domestic animals such as dogs are living older because of a better life quality and better cares, they may more frequently develop tumours in their intracranial central nervous system. In this research thesis, the author addresses this specific topic. He first recalls fundamental physical and biological aspects for the understanding of radiotherapy action mechanisms, and the modalities of such a treatment. He addresses the general study of intracranial central nervous system tumours in dogs: brief recall on anatomic and histological aspects, presentation of their classification and their prevalence, and precise descriptions of their characteristics. In the third part, the author reports clinical and para-clinical data which allow the diagnosis of an intracranial nervous tissue tumour. The last part presents different available therapeutic modalities, more particularly addresses the interest of radiotherapy in neuro-oncology, and compares published results [fr

Central nervous system manifestations in pediatric patients with influenza A H1N1 infection during the 2009 pandemic.

Science.gov (United States)

Wilking, Ashley N; Elliott, Elizabeth; Garcia, Melissa N; Murray, Kristy O; Munoz, Flor M

2014-09-01

A novel H1N1 influenza A virus (A(H1N1)pdm09) particularly affected individuals central nervous system complications associated with pandemic influenza in the pediatric population. Retrospective review of patients with laboratory-confirmed influenza A(H1N1)pdm09 infection and central nervous system manifestations at Texas Children's Hospital between April 2009 and June 2010. Among 365 patients with influenza A(H1N1)pdm09, 32 (8.8%) had central nervous system manifestations at a median age of 4 years. Eight (25.0%) were previously healthy, and 12 (37.5%) had neurological pre-existing conditions. Of the 32 cases of influenza with neurological complications, seizure (n = 17; 53.1%) was the most common central nervous system manifestation, followed by encephalitis (n = 4; 12.5%), meningitis (n = 4; 12.5%), encephalopathy (n = 3; 9.4%), meningismus (n = 3; 9.4%), focal hemorrhagic brain lesions (n = 2; 6.3%), brain infarction (n = 1; 3.1%), and sensorineural hearing loss (n = 1; 3.1%). Two patients demonstrated two or more types of central nervous system complications. One patient had abnormal cerebrospinal fluid with pleocytosis. Almost two thirds of the children with central nervous system manifestations required intensive care unit admission and nearly half required mechanical ventilation. There were no deaths. Patients with pre-existing neurological conditions were at greater risk for central nervous system manifestations during pandemic influenza infection. Patients with central nervous system manifestations were more likely to experience severe illness, characterized by intensive care unit admission and mechanical ventilation, although overall outcomes were good. Influenza prevention in patients with underlying medical conditions, particularly those with neurological conditions, is important. Copyright © 2014 Elsevier Inc. All rights reserved.

Inhalation of Hydrocarbon Jet Fuel Suppress Central Auditory Nervous System Function.

Science.gov (United States)

Guthrie, O'neil W; Wong, Brian A; McInturf, Shawn M; Reboulet, James E; Ortiz, Pedro A; Mattie, David R

2015-01-01

More than 800 million L/d of hydrocarbon fuels is used to power cars, boats, and jet airplanes. The weekly consumption of these fuels necessarily puts the public at risk for repeated inhalation exposure. Recent studies showed that exposure to hydrocarbon jet fuel produces lethality in presynaptic sensory cells, leading to hearing loss, especially in the presence of noise. However, the effects of hydrocarbon jet fuel on the central auditory nervous system (CANS) have not received much attention. It is important to investigate the effects of hydrocarbons on the CANS in order to complete current knowledge regarding the ototoxic profile of such exposures. The objective of the current study was to determine whether inhalation exposure to hydrocarbon jet fuel might affect the functions of the CANS. Male Fischer 344 rats were randomly divided into four groups (control, noise, fuel, and fuel + noise). The structural and functional integrity of presynaptic sensory cells was determined in each group. Neurotransmission in both peripheral and central auditory pathways was simultaneously evaluated in order to identify and differentiate between peripheral and central dysfunctions. There were no detectable effects on pre- and postsynaptic peripheral functions. However, the responsiveness of the brain was significantly depressed and neural transmission time was markedly delayed. The development of CANS dysfunctions in the general public and the military due to cumulative exposure to hydrocarbon fuels may represent a significant but currently unrecognized public health issue.

Turning sex inside-out: Peripheral contributions to sexual differentiation of the central nervous system

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Swift-Gallant Ashlyn

2012-05-01

Full Text Available Abstract Sexual differentiation of the nervous system occurs via the interplay of genetics, endocrinology and social experience through development. Much of the research into mechanisms of sexual differentiation has been driven by an implicit theoretical framework in which these causal factors act primarily and directly on sexually dimorphic neural populations within the central nervous system. This review will examine an alternative explanation by describing what is known about the role of peripheral structures and mechanisms (both neural and non-neural in producing sex differences in the central nervous system. The focus of the review will be on experimental evidence obtained from studies of androgenic masculinization of the spinal nucleus of the bulbocavernosus, but other systems will also be considered.

Evaluation of the Fitness of Glass-Infiltrated Zirconia Core in Maxillary Central Incisor.

Science.gov (United States)

Kim, Ji-Won; Oh, Gye-Jeong; Lim, Hyun-Pil; Yun, Kwi-Dug; Park, Chan; Lee, Kyung-Ku; Ban, Jae-Sam; Park, Sang-Won; Yim, Eun-Kyung

2018-02-01

The purpose of this study was to evaluate the fitness of zirconia cores according to the amount and treated surface of glass infiltration. A maxillary right central incisor customized abutment was milled to have a 6° slope and a 1 mm deep chamfer margin and was manufactured in an intaglio mold using silicone impression material. Fifty-six stone dies were produced by injecting high strength dental stone into a mold and then zirconia cores were milled with CAD/CAM systems. The control group (Control) used non glass-infiltrated zirconia, and the experiment group was divided by one with the glass and distilled water ratio of 1:300 and the other with the ratio of 1:100. Each group was divided into subgroups by glasstreated surface: external surface infiltration, internal surface infiltration, and both surface infiltration. The zirconia cores sintered after glass infiltration were attached to the stone dies and then cut. Afterwards, the absolute marginal discrepancies and internal gaps of the buccal and lingual sides were measured. The buccal absolute marginal discrepancies and lingual internal gaps were influenced by the glass infiltration amount (p 0.05). As a result of the above experiments, the glass-infiltrated zirconia cores showed a clinically acceptable fitness, which is within 120 μm. This means that glass infiltration can be clinically used.

Obesity induced by a high-fat diet is associated with increased immune cell entry into the central nervous system.

Science.gov (United States)

Buckman, Laura B; Hasty, Alyssa H; Flaherty, David K; Buckman, Christopher T; Thompson, Misty M; Matlock, Brittany K; Weller, Kevin; Ellacott, Kate L J

2014-01-01

Obesity is associated with chronic low-grade inflammation in peripheral tissues caused, in part, by the recruitment of inflammatory monocytes into adipose tissue. Studies in rodent models have also shown increased inflammation in the central nervous system (CNS) during obesity. The goal of this study was to determine whether obesity is associated with recruitment of peripheral immune cells into the CNS. To do this we used a bone marrow chimerism model to track the entry of green-fluorescent protein (GFP) labeled peripheral immune cells into the CNS. Flow cytometry was used to quantify the number of GFP(+) immune cells recruited into the CNS of mice fed a high-fat diet compared to standard chow fed controls. High-fat feeding resulted in obesity associated with a 30% increase in the number of GFP(+) cells in the CNS compared to control mice. Greater than 80% of the GFP(+) cells recruited to the CNS were also CD45(+) CD11b(+) indicating that the GFP(+) cells displayed characteristics of microglia/macrophages. Immunohistochemistry further confirmed the increase in GFP(+) cells in the CNS of the high-fat fed group and also indicated that 93% of the recruited cells were found in the parenchyma and had a stellate morphology. These findings indicate that peripheral immune cells can be recruited to the CNS in obesity and may contribute to the inflammatory response. Copyright © 2013 Elsevier Inc. All rights reserved.

Cholesterol: Its Regulation and Role in Central Nervous System Disorders

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Matthias Orth

2012-01-01

Full Text Available Cholesterol is a major constituent of the human brain, and the brain is the most cholesterol-rich organ. Numerous lipoprotein receptors and apolipoproteins are expressed in the brain. Cholesterol is tightly regulated between the major brain cells and is essential for normal brain development. The metabolism of brain cholesterol differs markedly from that of other tissues. Brain cholesterol is primarily derived by de novo synthesis and the blood brain barrier prevents the uptake of lipoprotein cholesterol from the circulation. Defects in cholesterol metabolism lead to structural and functional central nervous system diseases such as Smith-Lemli-Opitz syndrome, Niemann-Pick type C disease, and Alzheimer’s disease. These diseases affect different metabolic pathways (cholesterol biosynthesis, lipid transport and lipoprotein assembly, apolipoproteins, lipoprotein receptors, and signaling molecules. We review the metabolic pathways of cholesterol in the CNS and its cell-specific and microdomain-specific interaction with other pathways such as the amyloid precursor protein and discuss potential treatment strategies as well as the effects of the widespread use of LDL cholesterol-lowering drugs on brain functions.

Imaging in the infectious diseases of the central nervous system

International Nuclear Information System (INIS)

Brunet, F.; Gandon, Y.; Heautot, J.F.; Montagne, C.; Michelet, C.; Carsin, M.

1989-01-01

The basic signs of the major bacterial, viral, parasitic or mycotic infections of the central nervous system with CT and MRI are described. The problems arising from the presence of the HIV virus are emphasized and the attitude required according to the findings of imaging, is defined [fr

Sodium nitrite induces acute central nervous system toxicity in guinea pigs exposed to systemic cell-free hemoglobin

International Nuclear Information System (INIS)

Buehler, Paul W.; Butt, Omer I.; D'Agnillo, Felice

2011-01-01

Highlights: → Toxicological implications associated with the use of NaNO 2 therapy to treat systemic cell-free Hb exposure are not well-defined. → Systemic Hb exposure followed by NaNO 2 infusion induces acute CNS toxicities in guinea pigs. → These CNS effects were not reproduced by the infusion of cell-free Hb or NaNO 2 alone. → NaNO 2 -mediated oxidation of cell-free Hb may play a causative role in the observed CNS changes. -- Abstract: Systemic cell-free hemoglobin (Hb) released via hemolysis disrupts vascular homeostasis, in part, through the scavenging of nitric oxide (NO). Sodium nitrite (NaNO 2 ) therapy can attenuate the hypertensive effects of Hb. However, the chemical reactivity of NaNO 2 with Hb may enhance heme- or iron-mediated toxicities. Here, we investigate the effect of NaNO 2 on the central nervous system (CNS) in guinea pigs exposed to systemic cell-free Hb. Intravascular infusion of NaNO 2 , at doses sufficient to alleviate Hb-mediated blood pressure changes, reduced the expression of occludin, but not zona occludens-1 (ZO-1) or claudin-5, in cerebral tight junctions 4 h after Hb infusion. This was accompanied by increased perivascular heme oxygenase-1 expression, neuronal iron deposition, increased astrocyte and microglial activation, and reduced expression of neuron-specific nuclear protein (NeuN). These CNS changes were not observed in animals treated with Hb or NaNO 2 alone. Taken together, these findings suggest that the use of nitrite salts to treat systemic Hb exposure may promote acute CNS toxicity.

Concurrent central nervous system infective pathology in a severely immunocompromised patient

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Thein Swe

2016-01-01

Full Text Available To our knowledge and literature search, concurrent cryptococcal meningitis and neurosyphilis in a patient have rarely been reported. Here, we report a 37-year-old male with HIV infection presented with headache and dizziness for 5 days along with memory difficulty and personality changes for about 1 week. During the hospital stay, cryptococcal meningitis was confirmed with positive cerebral spinal fluid (CSF cryptococcal antigen titer (1:320 and positive CSF culture. Diagnosis of neurosyphilis was made based upon CSF white blood cell count of 85 cells/mL, with CSF total protein of 87 mg/dL, reactive CSF treponemal antibody, and fluorescent treponemal antibody. The patient was treated with amphotericin B, flucytosine, fluconazole, and benzathine penicillin G, and the patient was recovered and discharged. HIV patients are at high risk of developing severe infections of the central nervous system. Awareness should be made not only to single infection but also for dual pathology for a better and life-saving management.

Adult Central Nervous System Tumors Treatment (PDQ®)—Health Professional Version

Science.gov (United States)

Adult central nervous system tumor treatment options include surgery, radiosurgery, radiation therapy, chemotherapy, surveillance, and supportive care. Get detailed information about the types and treatment of newly diagnosed and recurrent brain and spinal tumors in this clinician summary.

A rare case of anasarca caused by infiltration of the pituitary gland by diffuse large B-cell lymphoma

OpenAIRE

Kumabe, Ayako; Kenzaka, Tsuneaki; Nishimura, Yoshioki; Aikawa, Masaki; Mori, Masaki; Matsumura, Masami

2015-01-01

Background Anasarca in patients with lymphoma is a rare symptom. We report a patient with DLBCL associated with pituitary gland infiltration that was diagnosed based on significant anasarca. Case presentation A 72-year-old woman with a 10-year history of hypertension visited a local hospital presenting with anasarca and 15-kg weight gain in the past 3?months. we clinically diagnosed central hypothyroidism caused by pituitary gland infiltration of diffuse large B-cell lymphoma (DLBCL) (clinica...

Central nervous system tumours and related intracranial pathologies in radium dial workers

International Nuclear Information System (INIS)

Stebbings, J.H.; Semkiw, W.

1989-01-01

Among female radiation workers in the radium dial industry there is no overall excess of fatal brain or central nervous system tumours. A significant excess did appear, in one of three major cohorts; the excess was not due to an excess of gliomas and cannot be ascribed with certainty to radium or external radiation. A significant proportional excess of tumours outside of the brain was observed, consistent with irradiation of nervous system tissue from adjacent bone. Excess tumours of the eye, pituitary or pineal did not occur. Early deaths from brain abscess or mastoiditis, coded as diseases of the nervous system and sense organs, were observed. (author)

Cell Fusion along the Anterior-Posterior Neuroaxis in Mice with Experimental Autoimmune Encephalomyelitis.

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Sreenivasa R Sankavaram

Full Text Available It is well documented that bone marrow-derived cells can fuse with a diverse range of cells, including brain cells, under normal or pathological conditions. Inflammation leads to robust fusion of bone marrow-derived cells with Purkinje cells and the formation of binucleate heterokaryons in the cerebellum. Heterokaryons form through the fusion of two developmentally differential cells and as a result contain two distinct nuclei without subsequent nuclear or chromosome loss.In the brain, fusion of bone marrow-derived cells appears to be restricted to the complex and large Purkinje cells, raising the question whether the size of the recipient cell is important for cell fusion in the central nervous system. Purkinje cells are among the largest neurons in the central nervous system and accordingly can harbor two nuclei.Using a well-characterized model for heterokaryon formation in the cerebellum (experimental autoimmune encephalomyelitis - a mouse model of multiple sclerosis, we report for the first time that green fluorescent protein-labeled bone marrow-derived cells can fuse and form heterokaryons with spinal cord motor neurons. These spinal cord heterokaryons are predominantly located in or adjacent to an active or previously active inflammation site, demonstrating that inflammation and infiltration of immune cells are key for cell fusion in the central nervous system. While some motor neurons were found to contain two nuclei, co-expressing green fluorescent protein and the neuronal marker, neuron-specific nuclear protein, a number of small interneurons also co-expressed green fluorescent protein and the neuronal marker, neuron-specific nuclear protein. These small heterokaryons were scattered in the gray matter of the spinal cord.This novel finding expands the repertoire of neurons that can form heterokaryons with bone marrow-derived cells in the central nervous system, albeit in low numbers, possibly leading to a novel therapy for spinal cord

PICK1 expression in the Drosophila central nervous system primarily occurs in the neuroendocrine system

DEFF Research Database (Denmark)

Jansen, Anna M; Nässel, Dick R; Madsen, Kenneth L

2009-01-01

in the adult and larval Drosophila central nervous system. PICK1 was found in cell bodies in the subesophageal ganglion, the antennal lobe, the protocerebrum, and the neuroendocrine center pars intercerebralis. The cell types that express PICK1 were identified using GAL4 enhancer trap lines. The PICK1...... (AMPA) receptor subunit GluR2 and the dopamine transporter. PICK1 is strongly implicated in GluR2 trafficking and synaptic plasticity. In mammals, PICK1 has been characterized extensively in cell culture studies. To study PICK1 in an intact system, we characterized PICK1 expression immunohistochemically...... neurons in the neuroendocrine system, which express the transcription factor DIMM and the amidating enzyme peptidylglycine-alpha-hydroxylating monooxygenase (PHM). The PICK1-positive cells include neurosecretory cells that produce the insulin-like peptide dILP2. PICK1 expression in insulin-producing cells...

Single-Cell RNA-Seq Analysis of Infiltrating Neoplastic Cells at the Migrating Front of Human Glioblastoma

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Spyros Darmanis

2017-10-01

Full Text Available Summary: Glioblastoma (GBM is the most common primary brain cancer in adults and is notoriously difficult to treat because of its diffuse nature. We performed single-cell RNA sequencing (RNA-seq on 3,589 cells in a cohort of four patients. We obtained cells from the tumor core as well as surrounding peripheral tissue. Our analysis revealed cellular variation in the tumor’s genome and transcriptome. We were also able to identify infiltrating neoplastic cells in regions peripheral to the core lesions. Despite the existence of significant heterogeneity among neoplastic cells, we found that infiltrating GBM cells share a consistent gene signature between patients, suggesting a common mechanism of infiltration. Additionally, in investigating the immunological response to the tumors, we found transcriptionally distinct myeloid cell populations residing in the tumor core and the surrounding peritumoral space. Our data provide a detailed dissection of GBM cell types, revealing an abundance of information about tumor formation and migration. : Darmanis et al. perform single-cell transcriptomic analyses of neoplastic and stromal cells within and proximal to primary glioblastomas. The authors describe a population of neoplastic-infiltrating glioblastoma cells as well as a putative role of tumor-infiltrating immune cells in supporting tumor growth. Keywords: single cell, RNA-seq, glioma, glioblastoma, GBM, brain, heterogeneity, infiltrating, diffuse, checkpoint

Clonal expansion of renal cell carcinoma-infiltrating T lymphocytes

DEFF Research Database (Denmark)

Sittig, Simone; Køllgaard, Tania; Grønbæk, Kirsten

2013-01-01

T lymphocytes can mediate the destruction of cancer cells by virtue of their ability to recognize tumor-derived antigenic peptides that are presented on the cell surface in complex with HLA molecules and expand. Thus, the presence of clonally expanded T cells within neoplastic lesions is an indic......T lymphocytes can mediate the destruction of cancer cells by virtue of their ability to recognize tumor-derived antigenic peptides that are presented on the cell surface in complex with HLA molecules and expand. Thus, the presence of clonally expanded T cells within neoplastic lesions...... is an indication of ongoing HLA-restricted T cell-mediated immune responses. Multiple tumors, including renal cell carcinomas (RCCs), are often infiltrated by significant amounts of T cells, the so-called tumor-infiltrating lymphocytes (TILs). In the present study, we analyzed RCC lesions (n = 13) for the presence...... of expanded T-cell clonotypes using T-cell receptor clonotype mapping. Surprisingly, we found that RCCs comprise relatively low numbers of distinct expanded T-cell clonotypes as compared with melanoma lesions. The numbers of different T-cell clonotypes detected among RCC-infiltrating lymphocytes were...

Comparative morphology of serotonergic-like immunoreactive elements in the central nervous system of kinorhynchs (Kinorhyncha, Cyclorhagida).

Science.gov (United States)

Herranz, María; Pardos, Fernando; Boyle, Michael J

2013-03-01

Cycloneuralian taxa exhibit similar organ system architectures, providing informative characters of metazoan evolution, yet very few modern comparative descriptions of cellular and molecular homologies within and among those taxa are available. We immunolabeled and characterized elements of the serotonergic nervous system in the kinorhynchs Echinoderes spinifurca, Antygomonas paulae, and Zelinkaderes brightae using confocal laser scanning microscopy. Fluorescent markers targeting DNA were combined with observations of auto-fluorescent structures to guide interpretations of the internal and external anatomy in each species. Results show a common pattern of the central nervous system with a circumenteric brain divided into ring-shaped anterior and posterior neuronal somata and a central neuropil connected to a multi-stringed, longitudinal ventral nerve cord. Structural similarities and differences in the nervous systems of these species were observed and described, stressing the incomplete ring nature of the anterior region of the kinorhynch brain, the functional relationship between the brain and the movable introvert, and the number and arrangement of nerve strings and somata of the ventral nerve cord. The ventral cord ends in two ventrolateral cell bodies in E. spinifurca, and forms a terminal loop associated with a midterminal spine in A. paulae and Z. brightae. The possible functional and phylogenetic significance of these features and arrangements are discussed. Copyright © 2012 Wiley Periodicals, Inc.

Effects of the Autonomic Nervous System, Central Nervous System ...

African Journals Online (AJOL)

The gastrointestinal tract is chiefly involved in the digestion of ingested food, facilitation of absorption process and expulsion of the undigested food material through motility process. Motility is influenced by neurohormonal system which is associated with the enteric nervous system , autonomic nervous system and the ...

Conductive polymers for controlled release and treatment of central nervous system injury

Science.gov (United States)

Saigal, Rajiv

As one of the most devastating forms of neurotrauma, spinal cord injury remains a challenging clinical problem. The difficulties in treatment could potentially be resolved by better technologies for therapeutic delivery. In order to develop new approaches to treating central nervous system injury, this dissertation focused on using electrically-conductive polymers, controlled drug release, and stem cell transplantation. We first sought to enhance the therapeutic potential of neural stem cells by electrically increasing their production of neurotrophic factors (NTFs), important molecules for neuronal cell survival, differentiation, synaptic development, plasticity, and growth. We fabricated a new cell culture device for growing neural stem cells on a biocompatible, conductive polymer. Electrical stimulation via the polymer led to upregulation of NTF production by neural stem cells. This approach has the potential to enhance stem cell function while avoiding the pitfalls of genetic manipulation, possibly making stem cells more viable as a clinical therapy. Seeing the therapeutic potential of conductive polymers, we extended our studies to an in vivo model of spinal cord injury (SCI). Using a novel fabrication and extraction technique, a conductive polymer was fabricated to fit to the characteristic pathology that follows contusive SCI. Assessed via quantitative analysis of MR images, the conductive polymer significantly reduced compression of the injured spinal cord. Further characterizing astroglial and neuronal response of injured host tissue, we found significant neuronal sparing as a result of this treatment. The in vivo studies also demonstrated improved locomotor recovery mediated by a conductive polymer scaffold over a non-conductive control. We next sought to take advantage of conductive polymers for local, electronically-controlled release of drugs. Seeking to overcome reported limitations in drug delivery via polypyrrole, we first embedded drugs in poly

Central Gi(2) proteins, sympathetic nervous system and blood pressure regulation

Czech Academy of Sciences Publication Activity Database

Zicha, Josef

2016-01-01

Roč. 216, č. 3 (2016), s. 258-259 ISSN 1748-1708 Institutional support: RVO:67985823 Keywords : inhibitory G proteins * sympathetic nervous system * central blood pressure control Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 4.867, year: 2016

Gamma Delta T-Cells Regulate Inflammatory Cell Infiltration of the Lung after Trauma-Hemorrhage

Science.gov (United States)

2015-06-01

suggesting a role for this T- cell subset in both innate and acquired immunity (7, 8). Studies have shown that +% T cells are required for both controlled...increased infiltration of both lymphoid and myeloid cells in WT mice after TH-induced ALI. In parallel to +% T cells , myeloid cells (i.e., monocytes...GAMMA DELTA T CELLS REGULATE INFLAMMATORY CELL INFILTRATION OF THE LUNG AFTER TRAUMA-HEMORRHAGE Meenakshi Rani,* Qiong Zhang,* Richard F. Oppeltz

The Gut Microbiome as Therapeutic Target in Central Nervous System Diseases: Implications for Stroke.

Science.gov (United States)

Winek, Katarzyna; Dirnagl, Ulrich; Meisel, Andreas

2016-10-01

Research on commensal microbiota and its contribution to health and disease is a new and very dynamically developing field of biology and medicine. Recent experimental and clinical investigations underscore the importance of gut microbiota in the pathogenesis and course of stroke. Importantly, microbiota may influence the outcome of cerebral ischemia by modulating central nervous system antigen-specific immune responses. In this review we summarize studies linking gut microbiota with physiological function and disorders of the central nervous system. Based on these insights we speculate about targeting the gut microbiome in order to treat stroke.

Glial Cells: The Other Cells of the Nervous System

Indian Academy of Sciences (India)

Home; Journals; Resonance – Journal of Science Education; Volume 7; Issue 1. Glial Cells: The Other Cells of the Nervous System - An Introduction to Glial Cells. Medha S Rajadhyaksha Yasmin Khan. Series Article Volume 7 Issue 1 January 2002 pp 4-10 ...

Effects of heavy particle irradiation on central nervous system

International Nuclear Information System (INIS)

Nojima, Kumie; Nakadai, Taeko; Khono, Yukio; Nagaoka, Shunji

2004-01-01

Effects of low dose heavy particle radiation to central nervous system were studied using mouse neonatal brain cells in culture exposed to heavy ions and X ray at fifth days of the culture. The subsequent biological effects were evaluated by an induction of apoptosis and the survivability of neurons focusing on the dependencies of the animal strains with different genetic types, and linear energy transfer (LET) of the different nucleons. Of the three mouse strains tested, SCID, B6, B6C3F1 and C3H, used for brain cell culture, SCID was the most sensitive. Radiation sensitivity of these cells ware SCID>B6>B6C3F1>C3H to both X-ray and carbon ion (290 MeV/n) when compared by 10% apoptotic induction. The LET dependency was compared with using SCID cells exposing to different ions, (X, C, Si, Ar, and Fe). Although no detectable LET dependency was observed at higher dose than 1 Gy, an enhancement was observed in the high LET region and at lower dose than 0.5 Gy. The survivability profiles of the neurons were different in the mouse strains and ions. Memory and learning function of adult mice were studied using water maze test after localized carbon- or iron-ion irradiation to hippocampus area. Memory function were rapidly decrease after irradiation both ions. C-ion group were recovered 20 weeks after irradiation, but Iron group were different. (author)

Prions spread via the autonomic nervous system from the gut to the central nervous system in cattle incubating bovine spongiform encephalopathy.

Science.gov (United States)

Hoffmann, Christine; Ziegler, Ute; Buschmann, Anne; Weber, Artur; Kupfer, Leila; Oelschlegel, Anja; Hammerschmidt, Baerbel; Groschup, Martin H

2007-03-01

To elucidate the still-unknown pathogenesis of bovine spongiform encephalopathy (BSE), an oral BSE challenge and sequential kill study was carried out on 56 calves. Relevant tissues belonging to the peripheral and central nervous system, as well as to the lymphoreticular tract, from necropsied animals were analysed by highly sensitive immunohistochemistry and immunoblotting techniques to reveal the presence of BSE-associated pathological prion protein (PrPSc) depositions. Our results demonstrate two routes involving the autonomic nervous system through which BSE prions spread by anterograde pathways from the gastrointestinal tract (GIT) to the central nervous system (CNS): (i) via the coeliac and mesenteric ganglion complex, splanchnic nerves and the lumbal/caudal thoracic spinal cord (representing the sympathetic GIT innervation); and (ii) via the Nervus vagus (parasympathetic GIT innervation). The dorsal root ganglia seem to be subsequently affected, so it is likely that BSE prion invasion of the non-autonomic peripheral nervous system (e.g. sciatic nerve) is a secondary retrograde event following prion replication in the CNS. Moreover, BSE-associated PrPSc was already detected in the brainstem of an animal 24 months post-infection, which is 8 months earlier than reported previously. These findings are important for the understanding of BSE pathogenesis and for the development of new diagnostic strategies for this infectious disease.

CD8+ T cells in inflammatory demyelinating disease

DEFF Research Database (Denmark)

Weiss, Hanne A; Millward, Jason M; Owens, Trevor

2007-01-01

We review the contribution made by CD8+ T cells to inflammation in the central nervous system (CNS) in Multiple Sclerosis (MS), and discuss their role in the animal model Experimental Autoimmune Encephalomyelitis (EAE). We show that the inflammatory cytokines interferon-gamma and interleukin-17...... are differentially regulated in CNS-infiltrating CD4+ and CD8+ T cells in EAE, and that CD8+ T cells regulate disease. In MS, CD8+ T cells appear to play a role in promotion of disease, so cytokine regulation is likely different in CD8+ T cells in MS and EAE...

Differentiation of Enhancing Glioma and Primary Central Nervous System Lymphoma by Texture-Based Machine Learning.

Science.gov (United States)

Alcaide-Leon, P; Dufort, P; Geraldo, A F; Alshafai, L; Maralani, P J; Spears, J; Bharatha, A

2017-06-01

Accurate preoperative differentiation of primary central nervous system lymphoma and enhancing glioma is essential to avoid unnecessary neurosurgical resection in patients with primary central nervous system lymphoma. The purpose of the study was to evaluate the diagnostic performance of a machine-learning algorithm by using texture analysis of contrast-enhanced T1-weighted images for differentiation of primary central nervous system lymphoma and enhancing glioma. Seventy-one adult patients with enhancing gliomas and 35 adult patients with primary central nervous system lymphomas were included. The tumors were manually contoured on contrast-enhanced T1WI, and the resulting volumes of interest were mined for textural features and subjected to a support vector machine-based machine-learning protocol. Three readers classified the tumors independently on contrast-enhanced T1WI. Areas under the receiver operating characteristic curves were estimated for each reader and for the support vector machine classifier. A noninferiority test for diagnostic accuracy based on paired areas under the receiver operating characteristic curve was performed with a noninferiority margin of 0.15. The mean areas under the receiver operating characteristic curve were 0.877 (95% CI, 0.798-0.955) for the support vector machine classifier; 0.878 (95% CI, 0.807-0.949) for reader 1; 0.899 (95% CI, 0.833-0.966) for reader 2; and 0.845 (95% CI, 0.757-0.933) for reader 3. The mean area under the receiver operating characteristic curve of the support vector machine classifier was significantly noninferior to the mean area under the curve of reader 1 ( P = .021), reader 2 ( P = .035), and reader 3 ( P = .007). Support vector machine classification based on textural features of contrast-enhanced T1WI is noninferior to expert human evaluation in the differentiation of primary central nervous system lymphoma and enhancing glioma. © 2017 by American Journal of Neuroradiology.

Metallothionein expression in the central nervous system of multiple sclerosis patients

DEFF Research Database (Denmark)

Penkowa, M; Espejo, C; Ortega-Aznar, A

2003-01-01

Multiple sclerosis (MS) is a major chronic demyelinating and inflammatory disease of the central nervous system (CNS) in which oxidative stress likely plays a pathogenic role in the development of myelin and neuronal damage. Metallothioneins (MTs) are antioxidant proteins induced in the CNS...

Cerebrospinal fluid pleocytosis in infectious and noninfectious central nervous system disease

DEFF Research Database (Denmark)

Baunbæk Egelund, Gertrud; Ertner, Gideon; Langholz Kristensen, Kristina

2017-01-01

Cerebrospinal fluid (CSF) analysis is the most important tool for assessing central nervous system (CNS) disease. An elevated CSF leukocyte count rarely provides the final diagnosis, but is almost always an indicator of inflammation within the CNS.The present study investigated the variety...

The burden and epidemiology of community-acquired central nervous system infections

DEFF Research Database (Denmark)

Erdem, H; Inan, A; Guven, E

2017-01-01

Risk assessment of central nervous system (CNS) infection patients is of key importance in predicting likely pathogens. However, data are lacking on the epidemiology globally. We performed a multicenter study to understand the burden of community-acquired CNS (CA-CNS) infections between 2012...

Central nervous system involvement of leukemia and systemic lymphoma in children. CT and MR findings

International Nuclear Information System (INIS)

Tomura, Noriaki; Hirano, Hiroko; Kato, Kohki; Sashi, Ryuji; Hashimoto, Manabu; Watarai, Jiro; Watanabe, Arata

1997-01-01

The purpose of this paper is to retrospectively evaluate CT and MR findings of central nervous system (CNS) involvement of leukemia and systemic lymphoma in children. Over a 12-year period, sixty-five patients with leukemia and fifteen patients with systemic lymphoma underwent cerebral CT and/or MR imaging. Nine patients were diagnosed as CNS involvement of leukemia and lymphoma. The CT and MR abnormalities in these patients were correlated with the findings of histology, cerebrospinal fluid cytology, and/or treatment. The age of the patients ranged from 0 to 15 years old. They consisted of 6 boys and 3 girls. The CT examinations were performed before and after contrast administration. MR examinations were performed on a 1.5-T unit, and T1-weighted, T2-weighted, and proton density-weighted images were obtained using spin-echo or fast spin-echo sequences. Tumor masses were present in seven with leukemia, and in two with malignant lymphoma. On the CT scan, tumor masses were hyperdense with contrast enhancement. On the MR images, their signals were variable. In all of nine patients, tumor masses were contiguous with a meningeal surface. Postcontrast T1-weighted images were valuable in demonstrating meningeal infiltration. Tumoral hemorrhage was found in two patients. In a patient with tumor at the superior sagittal sinus, venous infarct was observed. CNS leukemic and lymphomatous masses are almost hyperdense on the CT and they are characteristically contiguous with a meningeal surface. MR imaging was valuable in demonstrating meningeal infiltration. (K.H.)

Preferential lentiviral targeting of astrocytes in the central nervous system.

Directory of Open Access Journals (Sweden)

Michael Fassler

Full Text Available The ability to visualize and genetically manipulate specific cell populations of the central nervous system (CNS is fundamental to a better understanding of brain functions at the cellular and molecular levels. Tools to selectively target cells of the CNS include molecular genetics, imaging, and use of transgenic animals. However, these approaches are technically challenging, time consuming, and difficult to control. Viral-mediated targeting of cells in the CNS can be highly beneficial for studying and treating neurodegenerative diseases. Yet, despite specific marking of numerous cell types in the CNS, in vivo selective targeting of astrocytes has not been optimized. In this study, preferential targeting of astrocytes in the CNS was demonstrated using engineered lentiviruses that were pseudotyped with a modified Sindbis envelope and displayed anti-GLAST IgG on their surfaces as an attachment moiety. Viral tropism for astrocytes was initially verified in vitro in primary mixed glia cultures. When injected into the brains of mice, lentiviruses that displayed GLAST IgG on their surface, exhibited preferential astrocyte targeting, compared to pseudotyped lentiviruses that did not incorporate any IgG or that expressed a control isotype IgG. Overall, this approach is highly flexible and can be exploited to selectively target astrocytes or other cell types of the CNS. As such, it can open a window to visualize and genetically manipulate astrocytes or other cells of the CNS as means of research and treatment.

Characteristic radionuclide appearance of certain pediatric central nervous system neoplasms

International Nuclear Information System (INIS)

Conway, J.J.

1974-01-01

The results of 5 years experience in the localization of brain neoplasms in children are summarized. The radiopharmaceutical of choice was /sup 99m/Tc-labeled pertechnetate administered in a dosage of 100μ Ci/lb. The appearance of the most common neoplasms of the central nervous system in childhood is characterized. (U.S.)

Regulation of Neurotransmitter Responses in the Central Nervous System.

Science.gov (United States)

1987-05-01

and identify by block number) FIELD GROUP SUB-GROUP J’-aminobutyric acid; yclic AM’P; neuromodulation ; brain 1ABTAT(Continue on reverse if necessary and...crucial enzyme for regulating neuromodulation in brain. Given the ultimate goal of developing novel pharmacological agents for N! manipulating...central nervous system function, the discovery of a biochemical response to a neuromodulator can be considered a major step in that direction. Thus, up to

Managing Atypical and Typical herpetic central nervous system infections

DEFF Research Database (Denmark)

Cag, Yasemin; Erdem, Hakan; Leib, Stephen

2016-01-01

There have been many studies pertaining to the management of herpetic meningoencephalitis (HME), but the majority of them have focussed on virologically unconfirmed cases or included only small sample sizes. We have conducted a multicentre study aimed at providing management strategies for HME. O...... the subtle nature of HME, CSF HSV PCR, EEG and MRI data should be collected for all patients with a central nervous system infection....

Implications of infiltrating immune cells within bone marrow of patients with diffuse large B-cell lymphoma.

Science.gov (United States)

Jeong, Juhyeon; Oh, Eun Ji; Yang, Woo Ick; Kim, Soo Jeong; Yoon, Sun Och

2017-06-01

The implications of infiltrating immune cells, especially T cells and macrophages, in the bone marrow (BM) microenvironment of patients with diffuse large B-cell lymphoma (DLBCL) have rarely been studied. We aimed to investigate the significance of infiltrating immune cells in the BM microenvironment as a prognostic factor for DLBCL patients. Using the initial pretreatment BM biopsy obtained from 198 DLBCL patients, we semiquantitatively evaluated CD3+ T cells, CD8+ T cells, and CD163+ macrophages that infiltrate into the paratrabecular and interstitial areas of BM by immunohistochemistry and analyzed their clinicopathological and prognostic implications. Levels of infiltrating CD3+ T cells, CD8+ T cells, and CD163+ macrophages were significantly higher in BM with DLBCL involvement (BMI-positive group) than in that without DLBCL involvement (BMI-negative group). Infiltration of CD8+ T cells significantly increased in cases with advanced Ann Arbor stage, elevated lactate dehydrogenase level, extranodal site involvement ≥2 sites, higher Eastern Cooperative Oncology Group performance status, and higher International Prognostic Index (IPI) risk. High levels of CD3+ T cells were significantly associated with age ≤60, and high levels of CD163+ macrophages were associated with advanced Ann Arbor stage and higher IPI risk. High infiltration of CD8+ T cells was significantly related to inferior overall and recurrence-free survival rate, even in the BMI-negative group. High infiltration of CD8+ T cells within the pretreatment BM was related to poor prognosis, and might be a useful prognostic factor of DLBCL patients. Therefore, evaluation of CD8+ T cells is helpful for predicting prognosis in initial pretreatment BM biopsy of DLBCL patients. Copyright © 2017 Elsevier Inc. All rights reserved.

75 FR 56548 - Joint Meeting of the Peripheral and Central Nervous System Drugs Advisory Committee and the Drug...

Science.gov (United States)

2010-09-16

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Joint Meeting of the Peripheral and Central Nervous System Drugs Advisory Committee and the Drug Safety... and Central Nervous System Drugs Advisory Committee and the Drug Safety and Risk Management Advisory...

Sodium nitrite induces acute central nervous system toxicity in guinea pigs exposed to systemic cell-free hemoglobin

Energy Technology Data Exchange (ETDEWEB)

Buehler, Paul W.; Butt, Omer I. [Laboratory of Biochemistry and Vascular Biology, Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD (United States); D' Agnillo, Felice, E-mail: felice.dagnillo@fda.hhs.gov [Laboratory of Biochemistry and Vascular Biology, Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD (United States)

2011-06-10

Highlights: {yields} Toxicological implications associated with the use of NaNO{sub 2} therapy to treat systemic cell-free Hb exposure are not well-defined. {yields} Systemic Hb exposure followed by NaNO{sub 2} infusion induces acute CNS toxicities in guinea pigs. {yields} These CNS effects were not reproduced by the infusion of cell-free Hb or NaNO{sub 2} alone. {yields} NaNO{sub 2}-mediated oxidation of cell-free Hb may play a causative role in the observed CNS changes. -- Abstract: Systemic cell-free hemoglobin (Hb) released via hemolysis disrupts vascular homeostasis, in part, through the scavenging of nitric oxide (NO). Sodium nitrite (NaNO{sub 2}) therapy can attenuate the hypertensive effects of Hb. However, the chemical reactivity of NaNO{sub 2} with Hb may enhance heme- or iron-mediated toxicities. Here, we investigate the effect of NaNO{sub 2} on the central nervous system (CNS) in guinea pigs exposed to systemic cell-free Hb. Intravascular infusion of NaNO{sub 2}, at doses sufficient to alleviate Hb-mediated blood pressure changes, reduced the expression of occludin, but not zona occludens-1 (ZO-1) or claudin-5, in cerebral tight junctions 4 h after Hb infusion. This was accompanied by increased perivascular heme oxygenase-1 expression, neuronal iron deposition, increased astrocyte and microglial activation, and reduced expression of neuron-specific nuclear protein (NeuN). These CNS changes were not observed in animals treated with Hb or NaNO{sub 2} alone. Taken together, these findings suggest that the use of nitrite salts to treat systemic Hb exposure may promote acute CNS toxicity.

Primary angiitis of the central nervous system presenting with subacute and fatal course of disease: a case report

Directory of Open Access Journals (Sweden)

Börnke Christian

2005-09-01

Full Text Available Abstract Background Primary angiitis of the central nervous system is an idiopathic disorder characterized by vasculitis within the dural confines. The clinical presentation shows a wide variation and the course and the duration of disease are heterogeneous. This rare but treatable disease provides a diagnostic challenge owing to the lack of pathognomonic tests and the necessity of a histological confirmation. Case presentation A 28-year-old patient presenting with headache and fluctuating signs of encephalopathy was treated on the assumption of viral meningoencephalitis. The course of the disease led to his death 10 days after hospital admission. Postmortem examination revealed primary angiitis of the central nervous system. Conclusion Primary angiitis of the central nervous system should always be taken into consideration when suspected infectious inflammation of the central nervous system does not respond to treatment adequately. In order to confirm the diagnosis with the consequence of a modified therapy angiography and combined leptomeningeal and brain biopsy should be considered immediately.

Chemokine receptor expression by inflammatory T cells in EAE

DEFF Research Database (Denmark)

Mony, Jyothi Thyagabhavan; Khorooshi, Reza; Owens, Trevor

2014-01-01

Chemokines direct cellular infiltration to tissues, and their receptors and signaling pathways represent targets for therapy in diseases such as multiple sclerosis (MS). The chemokine CCL20 is expressed in choroid plexus, a site of entry of T cells to the central nervous system (CNS). The CCL20...... receptor CCR6 has been reported to be selectively expressed by CD4(+) T cells that produce the cytokine IL-17 (Th17 cells). Th17 cells and interferon-gamma (IFNγ)-producing Th1 cells are implicated in induction of MS and its animal model experimental autoimmune encephalomyelitis (EAE). We have assessed...... whether CCR6 identifies specific inflammatory T cell subsets in EAE. Our approach was to induce EAE, and then examine chemokine receptor expression by cytokine-producing T cells sorted from CNS at peak disease. About 7% of CNS-infiltrating CD4(+) T cells produced IFNγ in flow cytometric cytokine assays...

Late effects of ionising radiation on the central nervous system of the rat

International Nuclear Information System (INIS)

Hubbard, B.M.

1977-01-01

This thesis investigated the role of neuroglial cells in the pathogenesis of delayed radionecrosis of the rat central nervous system (CNS) for up to one year after irradiation. The observed radiation induced changes in the cell kinetics of the subependymal plate of the brain were considered to be important in the development of white matter necrosis. White matter necrosis was apparent in the dorsal, ventral and lateral columns of the cervical cord but in the lumbar cord necrosis was only observed in the nerve bundles of the nerve roots. The glial cell population of the cervical cord was not static and a loss of oligodendrocytes appeared to be important in the development of white matter necrosis. Schwann cells also appeared to be involved in the development of nerve root necrosis of the lumbar cord. It is concluded that a gradual loss of radiation damaged, slowly turning-over supporting cells is the mechanism resulting in the development of late radiation necrosis in the mammalian CNS. The applications of these findings are considered. (UK)

Radiation induced effects in the developing central nervous system; Effectos radioinducidos sobre el sistema nervioso central en desarrollo

Energy Technology Data Exchange (ETDEWEB)

Gisone, P; Dubner, D; Michelin, S C; Perez, M.R. Del [Autoridad Regulatoria Nuclear, Gerencia de Apoyo Cientifico, Buenos Aires (Argentina)

1997-11-01

The embryo and the human foetus are particularly sensitive to ionizing radiation and this sensitivity presents various qualitative and quantitative functional changes during intra-uterine development. Apart from radiation induced carcinogenesis, the most serious consequence of prenatal exposure in human beings is severe mental retardation. The principal data on radiation effects on human beings in the development of the central nervous system come form epidemiological studies carried out in individuals exposed in utero during the atomic explosion at Hiroshima and Nagasaki. These observations demonstrate the existence of a time of maximum radiosensitivity between the weeks 8 and 15 of the gestational period, a period in which the proliferation and neuronal migration takes place. Determination of the characteristics of dose-response relationship and the possible existence of a threshold dose of radiation effects on the development of the central nervous system is relevant to radiation protection against low dose radiation and the establishment of dose limits for occupational exposure and the public. Studies were conducted on the generation of nitrous-oxide and its relation with the production of active species of oxygen in brains of exposed rats in utero exposed to doses of up to 1 Gy during their maximum radiosensitivity. The possible role of the mechanism of radiation induced damage in the development of the central nervous system is discussed. 8 refs.

Central nervous system tuberculosis: MRI

Energy Technology Data Exchange (ETDEWEB)

Kioumehr, F.; Dadsetan, M.R.; Rooholamini, S.A.; Au, A.

1994-02-01

The MRI findings of 18 proven cases of central nervous system (CNS) tuberculosis were reviewed; 10 patients were seropositive for HIV. All had medical, laboratory, or surgical proof of CNS tuberculosis. Eleven patients had meningitis, of whom two also had arachnoiditis. Five patients had focal intra-axial tuberculomas: four brain masses and one an intramedullary spinal lesion. Two patients had focal extra-axial tuberculomas: one in the pontine cistern, and one in the spine. In all 11 patients with meningitis MRI showed diffuse, thick, meningeal enhancement. All intraparenchymal tuberculomas showed low signal intensity on T2-weighted images and ring or nodular enhancement. The extra-axial tuberculomas had areas isointense or hypointense relative to normal brain and spinal cord on T2-weighted images. Although tuberculous meningitis cannot be differentiated from other meningitides on the basis of MR findings, intraparenchymal tuberculomas show characteristic T2 shortening, not found in most other space-occupying lesions. In the appropriate clinical setting, tuberculoma should be considered. (orig.)

Effects of Gentiana lutea ssp. symphyandra on the central nervous system in mice.

Science.gov (United States)

Oztürk, Nilgün; Başer, K Hüsnü Can; Aydin, Süleyman; Oztürk, Yusuf; Caliş, Ihsan

2002-11-01

A methanolic extact of Gentiana lutea ssp. symphyandra roots has been investigated for its possible effects on the central nervous system of mice. At doses of 250 and 500 mg/kg (i.p.), the methanol extract of Gentiana roots caused a significant increase in the swimming endurance test and exhibited slight analgesic activity, but no lethality in mice suggesting some activity on the central nervous system. However, there was no indication of sedation or muscular fatigue at the doses employed. HPLC analysis showed that three secoiridoid compounds, gentiopicroside, swertiamarine and sweroside were present and may have been responsible for the CNS effects of the methanol extract of Gentiana lutea ssp. symphyandra roots. Copyright 2002 John Wiley & Sons, Ltd.

Glial Cells: The Other Cells of the Nervous System

Indian Academy of Sciences (India)

nervous system and that glial cells were a mere glue holding neurons in place, Schleich ... fact that these cells did not show any electrical activity like neurons or muscles ... membrane potential higher than that of the surrounding neu- rons.

Involvement of the central nervous system in myotonic dystrophy

International Nuclear Information System (INIS)

Fukui, Ritsuko; Tobimatsu, Shozo; Kuroiwa, Yoshigoro; Iwashita, Hiroshi; Kato, Motohiro.

1985-01-01

In order to evaluate the central nervous system involvement in myotonic dystrophy, intelligence quotient (IQ), brain CT scan, EEG and pattern-reversal visual evoked potential (VEP) were analyzed in 10 patients with myotonic dystrophy. Impaired intelligence was observed in 9 out of 10 patients, abnormal brain CT in 7, and EEG abnormality in 7. The brain CT showed a diffuse cortical atrophy, a dilatation of the ventricles, and a periventricular lucency, mainly around the anterior horn of the lateral ventricle. The EEG findings showed a tendency toward generalized slowing of the background activity. These abnormal findings were well related to the clinical severity of MD, indicating that there is a diffuse cerebral involvement in the majority of the MD patients. VEP showed a prolonged P100 latency in 5 out of 10 patints, or 7 out of 19 eyes examined. These prolonged latency of the P100 component was considered to be due to dysfunctions of the visual pathway in the cerebral hemisphere, rather than due to cataracts and retinal dysfunctions because it was observed only in moderate and severe cases. These severe and moderate cases showed abnormalities in all four examinations. It was concluded that combination of different parameters might be useful to evaluate the central nervous system involvement in patients with MD. (author)

An optimised procedure for prenatal ethanol exposure with determination of its effects on central nervous system connections.

Science.gov (United States)

Sbriccoli, A; Carretta, D; Santarelli, M; Granato, A; Minciacchi, D

1999-01-01

We describe the protocol set-up to investigate an experimental model of foetal alcohol syndrome in the rat. The protocol has been devised to expose specific cell populations of the central nervous system to ethanol during their neurogenesis and has been applied to the study of diencephalo-telencephalic connections. We were able to demonstrate specific permanent changes of the adult thalamo-cortical circuitry. Our protocol can be applied to study other aspects of central nervous system-ethanol interactions, such as neurotransmitter and receptor patterns. It can also represent a useful tool to test the effects of different diets to prevent nutritional deficiencies and the efficacy of drug treatments to prevent foetal alcohol syndrome. We have shown in fact that ethanol-induced thalamo-cortical alterations are partially prevented by concurrent administration of acetyl-L-carnitine. Finally, the present protocol can be used to investigate the effects of ethanol exposure on the development of different brain structures. To this purpose, the gestational period for ethanol exposure must be chosen according to the peak of neurogenesis for the investigated structure.

Some Central Nervous System Effects of the aqueous Extract of the ...

African Journals Online (AJOL)

The leaves of Phyllanthus amarus is used in Southern Nigeria to treat variety of diseases including epilepsy. The aqueous extract of the leaves of Phyllanthus amarus was investigated for some central nervous system effects. Two animals models (maximal electroshock and pentylenetetrazol-induced convulsion), were used ...

A case of acute lymphoblastic leukemia with abnormal brain CT scan after cranial irradiation for central nervous system leukemia

International Nuclear Information System (INIS)

Sato, Junko; Abe, Takanori; Watanabe, Tsutomu

1988-01-01

A 21-year-old woman with acute lymphoblastic leukemia presented with central neurologic symptoms immediately after the second irradiation (20 Gy to the brain and 10 Gy to the spinal cord) for central nervous system (CNS)-leukemia 3 years and 2 months after the first cranial irradiation with 20 Gy. White matter was depicted as diffusely high density area on CT; histology revealed necrosis of leukemic cells. In the present patient with repeated recurrent CNS-leukemia, leukemic cells seemed to have been damaged simultaneously after irradiation because of parenchymal widespread involvement of leukemic cells, resulting in brain edema, an increased intracranial pressure and parenchymal disturbance. This finding may have an important implication for the risk of cranial irradiation in the case of widespread involvement of leukemic cells. Re-evaluation of cranial irradiation in such cases is suggested. (Namekawa, K.)

High-fat diet feeding differentially affects the development of inflammation in the central nervous system

OpenAIRE

Guillemot-Legris, Owein; Masquelier, Julien; Everard, Amandine; Cani, Patrice D.; Al Houayek, Mireille; Muccioli, Giulio

2016-01-01

Background Obesity and its associated disorders are becoming a major health issue in many countries. The resulting low-grade inflammation not only affects the periphery but also the central nervous system. We set out to study, in a time-dependent manner, the effects of a high-fat diet on different regions of the central nervous system with regard to the inflammatory tone. Methods We used a diet-induced obesity model and compared at several time-points (1, 2, 4, 6, 8, and 16?weeks) a group of ...

Primary cerebral non-Langerhans cell histiocytosis: MRI and differential diagnosis

Energy Technology Data Exchange (ETDEWEB)

Ernemann, U.; Skalej, M.; Voigt, K. [Department of Neuroradiology, University Hospital Tuebingen, Hoppe-Seyler-Strasse 3, 72076 Tuebingen (Germany); Hermisson, M.; Platten, M. [Department of Neurology, University Hospital Tuebingen, Hoppe-Seyler-Strasse 3, 72076 Tuebingen (Germany); Jaffe, R. [Pathology Department, Children' s Hospital of Pittsburgh, 3705 Fifth Avenue, Pittsburgh, PA 15213 (United States)

2002-09-01

We report a young woman with primary cerebral non-Langerhans cell histiocytosis of the juvenile xanthogranuloma family. The clinical course was complicated by extensive infiltration of cranial nerves and meninges and epi- and intramedullary spinal dissemination. Whereas the cutaneous form of juvenile xanthogranuloma is usually benign and self-limited, central nervous system involvement is associated with high morbidity and mortality and might therefore be considered a separate clinical entity. (orig.)

Ultrastructural changes of central nervous system irradiated with ionizing radiation

Energy Technology Data Exchange (ETDEWEB)

Kimura, Y [Keio Univ., Tokyo (Japan). School of Medicine

1975-12-01

Morphological changes of the central nervous tissues (cerebral and cerebellar cortices) of mice which were irradiated by a massive dose (5,000-80,000 rad) of Linac x-ray were observed with the lapse of time by electron microscopy, and changes in their ultrastructure were investigated. Capillaries and the processes of astrocytes surrounding them, when irradiated with 5,000-40,000 rad, showed swelling of endothelial cells, nuclear atrophy, destruction of basement membrane, and swelling and edematous changes of astrocytic processes. Morphological changes of the nerve cells, granule cells of cerebellum, and astrocytes increased depending on the dose of irradiation, and their injuries appeared in the early stage, showing pyknosis, chromatokinesis, and turbid swelling, transparent swelling of mitochondria, and disappearance of Nissl's bodies as cytoplasmic changes. Destruction of cell membrane was observed in the cerebellar granule cells and astrocytes; particularly in the cerebellar granule cells, pyknosis and prominent degeneration of cytoplasm appeared very early, compared with other cells. Although no definite change nor severance was observed in the marrow sheath of medullated nerve fibers within the dose range of this study, an image of degeneration was observed in the mitochondria in the axon; splitting of marrow sheath and deformity of axon membrane were more prominent in the 40,000 rad-irradiated group than in the other groups. Synaptic vesicles tended to increase and scatter when irradiated with 5,000 rad and 10,000 rad. However, by the irradiation with 40,000 rad, the synaptic vesicles tended to enlarge and decrease on the contrary, disappearing with the lapse of time.

Infiltrating blood-derived macrophages are vital cells playing an anti-inflammatory role in recovery from spinal cord injury in mice.

Science.gov (United States)

Shechter, Ravid; London, Anat; Varol, Chen; Raposo, Catarina; Cusimano, Melania; Yovel, Gili; Rolls, Asya; Mack, Matthias; Pluchino, Stefano; Martino, Gianvito; Jung, Steffen; Schwartz, Michal

2009-07-01

Although macrophages (MPhi) are known as essential players in wound healing, their contribution to recovery from spinal cord injury (SCI) is a subject of debate. The difficulties in distinguishing between different MPhi subpopulations at the lesion site have further contributed to the controversy and led to the common view of MPhi as functionally homogenous. Given the massive accumulation in the injured spinal cord of activated resident microglia, which are the native immune occupants of the central nervous system (CNS), the recruitment of additional infiltrating monocytes from the peripheral blood seems puzzling. A key question that remains is whether the infiltrating monocyte-derived MPhi contribute to repair, or represent an unavoidable detrimental response. The hypothesis of the current study is that a specific population of infiltrating monocyte-derived MPhi is functionally distinct from the inflammatory resident microglia and is essential for recovery from SCI. We inflicted SCI in adult mice, and tested the effect of infiltrating monocyte-derived MPhi on the recovery process. Adoptive transfer experiments and bone marrow chimeras were used to functionally distinguish between the resident microglia and the infiltrating monocyte-derived MPhi. We followed the infiltration of the monocyte-derived MPhi to the injured site and characterized their spatial distribution and phenotype. Increasing the naïve monocyte pool by either adoptive transfer or CNS-specific vaccination resulted in a higher number of spontaneously recruited cells and improved recovery. Selective ablation of infiltrating monocyte-derived MPhi following SCI while sparing the resident microglia, using either antibody-mediated depletion or conditional ablation by diphtheria toxin, impaired recovery. Reconstitution of the peripheral blood with monocytes resistant to ablation restored the lost motor functions. Importantly, the infiltrating monocyte-derived MPhi displayed a local anti

[Tumors of the central nervous system].

Science.gov (United States)

Alegría-Loyola, Marco Antonio; Galnares-Olalde, Javier Andrés; Mercado, Moisés

2017-01-01

Central nervous system (CNS) tumors constitute a heterogeneous group of neoplasms that share a considerable morbidity and mortality rate. Recent advances in the underlying oncogenic mechanisms of these tumors have led to new classification systems, which, in turn, allow for a better diagnostic approach and therapeutic planning. Most of these neoplasms occur sporadically and several risk factors have been found to be associated with their development, such as exposure to ionizing radiation or electromagnetic fields and the concomitant presence of conditions like diabetes, hypertension and Parkinson's disease. A relatively minor proportion of primary CNS tumors occur in the context of hereditary syndromes. The purpose of this review is to analyze the etiopathogenesis, clinical presentation, diagnosis and therapy of CNS tumors with particular emphasis in the putative risk factors mentioned above.

ESHAP chemotherapy is efficient in refractory/relapsed primary central nervous system lymphoma: report of four cases

Directory of Open Access Journals (Sweden)

Ungur R

2015-10-01

Full Text Available Rodica Ungur,1,2 Adrian Tempescul,3 Christian Berthou,3 Cristina Bagacean,1,2 Doinel Radeanu,1 Adriana Muresan,1 Mihnea Zdrenghea1,21Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy Cluj, 2Department of Hematology, Ion Chiricuta Oncology Institute, Cluj-Napoca, Romania; 3Department of Clinical Hematology, Institute of Cancerology and Hematology, Brest Teaching Hospital, Brest, FranceAbstract: Primary central nervous system non-Hodgkin’s lymphoma is a rare presentation, almost always of diffuse large B-cell type. Although there is no consensus regarding therapy for this condition, induction regimens are based on high-dose methotrexate and consolidation whole-brain radiotherapy, or, more preferred recently, blood–brain barrier penetrating drugs such as etoposide, cytarabine, and alkylating agents like temozolomide, ifosfamide, and lomustine. We present here four cases of relapsed/refractory primary central nervous system lymphoma treated with ESHAP (etoposide, solumedrol, high-dose cytarabine, and platinum chemotherapy to complete remission, with the eligible patients proceeding to autologous transplantation. We want to draw attention to this interesting, relatively well tolerated, underused therapeutic option, in a setting where treatment options are scarce and evidence-based recommendations are lacking.Keywords: cerebral lymphoma, PCNSL, refractory, relapsed, platinum

Diseases of the nervous system associated with calcium channelopathies

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Todorov, Boyan Bogdanov

2010-01-01

The aim of the studies described in this thesis was to investigate how abnormal CaV2.1 channel function can cause disease, in particular motor coordination dysfunction. The chapters illustrate how various neuronal cell types in the periphery (peripheral nervous system) and the central nervous system

Some central nervous system and blood pressure lowering effects of ...

African Journals Online (AJOL)

The methanol extract of the leaves of Spondias mombin (SP) was evaluated for some central nervous system and blood pressure lowering effect in albino wistar rats and mice. The extract was administered to pre-weighed mice (20-35 g), divided into five groups of five mice each at the doses of 50, 100 and 200 mg/kg for the ...

Neurophysiological changes in the central and peripheral nervous system of streptozotocin-diabetic rats. Course of development and effects of insulin treatment

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Gispen, W.H.; Biessels, G.J.; Cristino, N.A.; Rutten, G.J.; Hamers, F.P.; Erkelens, D.W.

1999-01-01

Diabetes mellitus can affect both the peripheral and the central nervous system. However, central deficits are documented less well than peripheral deficits. We therefore compared the course of development of neurophysiological changes in the central and peripheral nervous systems in

Value of computed tomography and magnetic resonance imaging in diagnosis of central nervous system

International Nuclear Information System (INIS)

Walecka, I.; Sicinska, J.; Szymanska, E.; Rudnicka, L.; Furmanek, M.; Walecki, J.; Olszewska, M.; Rudnicka, L.; Walecki, J.

2006-01-01

Systemic sclerosis is an autoimmune connective tissue disease characterized by vascular abnormalities and fibrotic changes in skin and internal organs. The aim of the study was to investigate involvement of the central nervous system in systemic sclerosis and the value of computed tomography (CT) and magnetic resonance imaging (MRI) in evaluation of central nervous system involvement in systemic sclerosis. 26 patients with neuropsychiatric symptoms in the course of systemic sclerosis were investigated for central nervous system abnormalities by computed tomography (CT) and magnetic resonance imaging (MRI). Among these 26 symptomatic patients lesions in brain MRI and CT examinations were present in 54% and in 50% patients respectively. Most common findings (in 46% of all patients), were symptoms of cortical and subcortical atrophy, seen in both, MRI and CT. Single and multiple focal lesions, predominantly in the white matter, were detected by MRI significantly more frequently as compared to CT (62% and 15% patients respectively). These data indicate that brain involvement is common in patients with severe systemic sclerosis. MRI shows significantly higher than CT sensitivity in detection focal brain lesions in these patients. (author)

The Intrinsic Electrophysiological Properties of Mammalian Neurons: Insights into Central Nervous System Function

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Llinas, Rodolfo R.

1988-12-01

This article reviews the electroresponsive properties of single neurons in the mammalian central nervous system (CNS). In some of these cells the ionic conductances responsible for their excitability also endow them with autorhythmic electrical oscillatory properties. Chemical or electrical synaptic contacts between these neurons often result in network oscillations. In such networks, autorhytmic neurons may act as true oscillators (as pacemakers) or as resonators (responding preferentially to certain firing frequencies). Oscillations and resonance in the CNS are proposed to have diverse functional roles, such as (i) determining global functional states (for example, sleep-wakefulness or attention), (ii) timing in motor coordination, and (iii) specifying connectivity during development. Also, oscillation, especially in the thalamo-cortical circuits, may be related to certain neurological and psychiatric disorders. This review proposes that the autorhythmic electrical properties of central neurons and their connectivity form the basis for an intrinsic functional coordinate system that provides internal context to sensory input.

Adult DRG Stem/Progenitor Cells Generate Pericytes in the Presence of Central Nervous System (CNS) Developmental Cues, and Schwann Cells in Response to CNS Demyelination.

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Vidal, Marie; Maniglier, Madlyne; Deboux, Cyrille; Bachelin, Corinne; Zujovic, Violetta; Baron-Van Evercooren, Anne

2015-06-01

It has been proposed that the adult dorsal root ganglia (DRG) harbor neural stem/progenitor cells (NPCs) derived from the neural crest. However, the thorough characterization of their stemness and differentiation plasticity was not addressed. In this study, we investigated adult DRG-NPC stem cell properties overtime, and their fate when ectopically grafted in the central nervous system. We compared them in vitro and in vivo to the well-characterized adult spinal cord-NPCs derived from the same donors. Using micro-dissection and neurosphere cultures, we demonstrate that adult DRG-NPCs have quasi unlimited self-expansion capacities without compromising their tissue specific molecular signature. Moreover, they differentiate into multiple peripheral lineages in vitro. After transplantation, adult DRG-NPCs generate pericytes in the developing forebrain but remyelinating Schwann cells in response to spinal cord demyelination. In addition, we show that axonal and endothelial/astrocytic factors as well astrocytes regulate the fate of adult DRG-NPCs in culture. Although the adult DRG-NPC multipotency is restricted to the neural crest lineage, their dual responsiveness to developmental and lesion cues highlights their impressive adaptive and repair potentials making them valuable targets for regenerative medicine. © 2015 AlphaMed Press.

Experimental concepts for toxicity prevention and tissue restoration after central nervous system irradiation

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Astner Sabrina T

2007-06-01

Full Text Available Abstract Several experimental strategies of radiation-induced central nervous system toxicity prevention have recently resulted in encouraging data. The present review summarizes the background for this research and the treatment results. It extends to the perspectives of tissue regeneration strategies, based for example on stem and progenitor cells. Preliminary data suggest a scenario with individually tailored strategies where patients with certain types of comorbidity, resulting in impaired regeneration reserve capacity, might be considered for toxicity prevention, while others might be "salvaged" by delayed interventions that circumvent the problem of normal tissue specificity. Given the complexity of radiation-induced changes, single target interventions might not suffice. Future interventions might vary with patient age, elapsed time from radiotherapy and toxicity type. Potential components include several drugs that interact with neurodegeneration, cell transplantation (into the CNS itself, the blood stream, or both and creation of reparative signals and a permissive microenvironment, e.g., for cell homing. Without manipulation of the stem cell niche either by cell transfection or addition of appropriate chemokines and growth factors and by providing normal perfusion of the affected region, durable success of such cell-based approaches is hard to imagine.

Vascular, glial, and lymphatic immune gateways of the central nervous system

NARCIS (Netherlands)

Engelhardt, Britta; Carare, Roxana O.; Bechmann, Ingo; Fluegel, Alexander; Laman, Jon D.; Weller, Roy O.

Immune privilege of the central nervous system (CNS) has been ascribed to the presence of a blood-brain barrier and the lack of lymphatic vessels within the CNS parenchyma. However, immune reactions occur within the CNS and it is clear that the CNS has a unique relationship with the immune system.

An Injury Paradigm to Investigate Central Nervous System Repair in Drosophila

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Kato, Kentaro; Hidalgo, Alicia

2013-01-01

An experimental method has been developed to investigate the cellular responses to central nervous system (CNS) injury using the fruit-fly Drosophila. Understanding repair and regeneration in animals is a key question in biology. The damaged human CNS does not regenerate, and understanding how to promote the regeneration is one of main goals of medical neuroscience. The powerful genetic toolkit of Drosophila can be used to tackle the problem of CNS regeneration. A lesion to the CNS ventral nerve cord (VNC, equivalent to the vertebrate spinal cord) is applied manually with a tungsten needle. The VNC can subsequently be filmed in time-lapse using laser scanning confocal microscopy for up to 24 hr to follow the development of the lesion over time. Alternatively, it can be cultured, then fixed and stained using immunofluorescence to visualize neuron and glial cells with confocal microscopy. Using appropriate markers, changes in cell morphology and cell state as a result of injury can be visualized. With ImageJ and purposely developed plug-ins, quantitative and statistical analyses can be carried out to measure changes in wound size over time and the effects of injury in cell proliferation and cell death. These methods allow the analysis of large sample sizes. They can be combined with the powerful genetics of Drosophila to investigate the molecular mechanisms underlying CNS regeneration and repair. PMID:23567253

Congenital Amegakaryocytic Thrombocytopenia Type II Presenting with Multiple Central Nervous System Anomalies

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Eshuis-Peters, Ellis; Versluys, Anne Brigitta; Stokman, Marijn Fijke; van der Crabben, Saskia Nanette; Nij Bijvank, Sebastiaan W A; van Wezel-Meijler, Gerda

Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare autosomal recessive bone marrow failure, caused by MPL gene mutations. The combination of CAMT and central nervous system abnormalities is uncommon. We describe a case with a homozygous missense MPL gene mutation and polymicrogyria,

The effect of central nervous system involvement and irradiation in childhood acute lymphoblastic leukemia

DEFF Research Database (Denmark)

Taskinen, Mervi; Oskarsson, Trausti; Levinsen, Mette

2017-01-01

BACKGROUND: Central nervous system irradiation (CNS-RT) has played a central role in the cure of acute lymphoblastic leukemia (ALL), but due to the risk of long-term toxicity, it is now considered a less-favorable method of CNS-directed therapy. PROCEDURES: Retrospectively, we estimated the effect...

Protein A from orange-spotted nervous necrosis virus triggers type I interferon production in fish cell.

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Huang, Runqing; Zhou, Qiong; Shi, Yan; Zhang, Jing; He, Jianguo; Xie, Junfeng

2018-05-04

Family Nodaviridae consists of two genera: Alphanodavirus and Betanodavirus, and the latter is classified into four genotypes, including red-spotted grouper nervous necrosis virus, tiger puffer nervous necrosis virus, striped jack nervous necrosis virus, and barfin flounder nervous necrosis virus. Type I interferons (IFNs) play a central role in the innate immune system and antiviral responses, and the interactions between IFN and NNV have been investigated in this study. We have found that the RNA-dependent RNA polymerase (RdRp) from orange-spotted nervous necrosis virus (OGNNV), named protein A, was capable of activating IFN promoter in fathead minnow (FHM) cells. Transient expression of protein A was found to induce IFN expression and secretion, endowing FHM cells with anti-tiger frog virus ability. Protein A from SJNNV can also induce IFN expression in FHM cells but that from Flock House virus (FHV), a well-studied representative species of genus Alphanodavirus, cannot. RdRp activity and mitochondrial localization were shown to be required for protein A to induce IFN expression by means of activating IRF3 but not NFκB. Furthermore, DsRNA synthesized in vitro transcription and poly I:C activated IFN promoter activity when transfected into FHM cells, and dsRNA were also detected in NNV-infected cells. We postulated that dsRNA, a PAMP, was produced by protein A, leading to activation of innate immune response. These results suggest that protein As from NNV are the agonists of innate immune response. This is the first work to demonstrate the interaction between NNV protein A and innate immune system, and may help to understand pathogenesis of NNV. Copyright © 2018. Published by Elsevier Ltd.

Multiple Myeloma of the Central Nervous System: 13 Cases and Review of the Literature

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Gergely Varga

2018-01-01

Full Text Available Central nervous system involvement is a rare complication of multiple myeloma with extremely poor prognosis as it usually fails to respond to therapy. We present 13 cases diagnosed at two centers in Budapest and review the current literature. The majority of our cases presented with high-risk features initially; two had plasma cell leukemia. Repeated genetic tests showed clonal evolution in 3 cases. Treatments varied according to the era, and efficacy was poor as generally reported in the literature. Only one patient is currently alive, with 3-month follow-up, and the patient responded to daratumumab-based treatment. Recent case reports show promising effectivity of pomalidomide and marizomib.

CD8+ Tumor-Infiltrating T Cells Are Trapped in the Tumor-Dendritic Cell Network

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Alexandre Boissonnas

2013-01-01

Full Text Available Chemotherapy enhances the antitumor adaptive immune T cell response, but the immunosuppressive tumor environment often dominates, resulting in cancer relapse. Antigen-presenting cells such as tumor-associated macrophages (TAMs and tumor dendritic cells (TuDCs are the main protagonists of tumor-infiltrating lymphocyte (TIL immuno-suppression. TAMs have been widely investigated and are associated with poor prognosis, but the immuno-suppressive activity of TuDCs is less well understood. We performed two-photon imaging of the tumor tissue to examine the spatiotemporal interactions between TILs and TuDCs after chemotherapy. In a strongly immuno-suppressive murine tumor model, cyclophosphamide-mediated chemotherapy transiently enhanced the antitumor activity of adoptively transferred ovalbumin-specific CD8+ T cell receptor transgenic T cells (OTI but barely affected TuDC compartment within the tumor. Time lapse imaging of living tumor tissue showed that TuDCs are organized as a mesh with dynamic interconnections. Once infiltrated into the tumor parenchyma, OTI T cells make antigen-specific and long-lasting contacts with TuDCs. Extensive analysis of TIL infiltration on histologic section revealed that after chemotherapy the majority of OTI T cells interact with TuDCs and that infiltration is restricted to TuDC-rich areas. We propose that the TuDC network exerts antigen-dependent unproductive retention that trap T cells and limit their antitumor effectiveness.

MRT of the central nervous system. 2. rev. and enl. ed.; MRT des Zentralnervensystems

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Forsting, Michael [Universitaetsklinikum Essen (Germany). Inst. fuer Diagnostische und Interventionelle Radiologie und Neuroradiologie; Jansen, Olav (ed.) [Universitaetsklinikum Schleswig-Holstein, Kiel (Germany). Klinik fuer Radiologie und Neuroradiologie

2014-11-01

The book on MRT of the central nervous system includes the following chapters: anatomy, vascular diseases, brain tumors, craniocerebral injuries, infectious diseases, multiple sclerosis and related diseases, metabolic diseases, degenerative diseases, malformations and developmental disorders, hydrocephalus and intracranial hypertension, spinal marrow, degenerative caused spinal and foraminal stenosis, traumata, tumors and tumor-like neoplasm, vascular diseases, inflammations, infections and related diseases, diseases of the peripheral nervous system.

Central nervous system involvement by multiple myeloma

DEFF Research Database (Denmark)

Jurczyszyn, Artur; Grzasko, Norbert; Gozzetti, Alessandro

2016-01-01

The multicenter retrospective study conducted in 38 centers from 20 countries including 172 adult patients with CNS MM aimed to describe the clinical and pathological characteristics and outcomes of patients with multiple myeloma (MM) involving the central nervous system (CNS). Univariate......, 97% patients received initial therapy for CNS disease, of which 76% received systemic therapy, 36% radiotherapy and 32% intrathecal therapy. After a median follow-up of 3.5 years, the median overall survival (OS) from the onset of CNS involvement for the entire group was 7 months. Untreated...... untreated patients and patients with favorable cytogenetic profile might be prolonged due to systemic treatment and/or radiotherapy. This article is protected by copyright. All rights reserved....

The Regulation of GluN2A by Endogenous and Exogenous Regulators in the Central Nervous System.

Science.gov (United States)

Sun, Yongjun; Zhan, Liying; Cheng, Xiaokun; Zhang, Linan; Hu, Jie; Gao, Zibin

2017-04-01

The NMDA receptor is the most widely studied ionotropic glutamate receptor, and it is central to many physiological and pathophysiological processes in the central nervous system. GluN2A is one of the two main types of GluN2 NMDA receptor subunits in the forebrain. The proper activity of GluN2A is important to brain function, as the abnormal regulation of GluN2A may induce some neuropsychiatric disorders. This review will examine the regulation of GluN2A by endogenous and exogenous regulators in the central nervous system.

Leptin and the central nervous system control of glucose metabolism.

Science.gov (United States)

Morton, Gregory J; Schwartz, Michael W

2011-04-01

The regulation of body fat stores and blood glucose levels is critical for survival. This review highlights growing evidence that leptin action in the central nervous system plays a key role in both processes. Investigation into underlying mechanisms has begun to clarify the physiological role of leptin in the control of glucose metabolism and raises interesting new possibilities for the treatment of diabetes and related disorders.

Cardiac biopotentials influence on central nervous system functioning: first steps in hypothesis verification

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Kondal'skaya Yu.O.

2012-12-01

Full Text Available The research goal is to verify the hypothesis on influence of cardiac biopotentials on central nervous system. Materials: 20 healthy individuals aged 18-26 years old have been participated in the investigations. Two groups composed of 10 patients each have been formed. Double increase in heart biopotentials by means of artificial impulse insertion between natural cardiac contractions has been modeled. Artificial impulses have been similar to unaffected ones, produced in a normal heart work. Additional impulses have been generated using external pacemaker and have been linked up with electrodes on the chest. They have been synchronized with the heart rhythm and located in-between R waves. The duration of those impulses has been fully matched to ventricular complex. Their amplitude has been adjusted individually depending on the height of R wave. Nervous system mobility has been used as the indicator reflecting the central nervous system functioning. Degree of mobility has been defined on the basis of tapping test results. The test has been repeated at specific intervals. Groups have been exposed to two adverse testing modes. Additional impulses have been conducted to the patients of group I within an hour over a period of the first and the third 15-minute intervals and to the patients of group II over a period of the second and the fourth 15-minute intervals. In the middle and in the end of each time interval tapping test has been carried out. After preliminary analysis two other modes of stimulation have been tested. The stimulation has been performed within the 40-minute course: over a period of the first 20-minute interval and vice versa. Results: Detailed evaluation has revealed that short-time increase of nervous processes has been checked in combination with decrease in their stability. Conclusion: The data obtained have shown that there is possible influence on central nervous system functioning. The article ends with prospects of further

Epstein-Barr virus and human herpesvirus type 8 infections of the central nervous system.

Science.gov (United States)

Volpi, Antonio

2004-06-01

In developing guidelines for the improved management of herpesvirus infections of the central nervous system (CNS), the International Herpes Management Forum (IHMF) has studied Epstein-Barr virus (EBV) and human herpesvirus type 8 (HHV-8)- related diseases. EBV has been associated with numerous CNS diseases including meningitis, encephalitis and post transplant lymphoproliferative disorder (PTLD). The pathogenesis of EBV-associated CNS disorders is not completely understood but may be due to direct virus invasion of the CNS. Alternatively, damage may be immunologically mediated by infiltration of cytotoxic CD8+ lymphocytes into neural tissue or deposition of antibody-antigen complexes. The IHMF recommends that diagnosis of EBV infections of the CNS may involve polymerase chain reaction (PCR) of cerebrospinal fluid (CSF) for EBV DNA but the sensitivity and specificity of the technique remains to be determined. Furthermore, the value of PCR in this context may be limited as EBV DNA is often detected in patients without neurological symptoms. Antiviral therapy has not demonstrated clinical efficacy in the treatment of EBV-related CNS disorders. CNS complications of HHV-8 infection are rare, but the virus has been associated with AIDS-dementia complex, amyotrophic lateral sclerosis (ALS) and primary CNS lymphoma; however these links remain to be proven.

In acute experimental autoimmune encephalomyelitis, infiltrating macrophages are immune activated, whereas microglia remain immune suppressed.

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Vainchtein, I D; Vinet, J; Brouwer, N; Brendecke, S; Biagini, G; Biber, K; Boddeke, H W G M; Eggen, B J L

2014-10-01

Multiple sclerosis (MS) is an autoimmune demyelinating disorder of the central nervous system (CNS) characterized by loss of myelin accompanied by infiltration of T-lymphocytes and monocytes. Although it has been shown that these infiltrates are important for the progression of MS, the role of microglia, the resident macrophages of the CNS, remains ambiguous. Therefore, we have compared the phenotypes of microglia and macrophages in a mouse model for MS, experimental autoimmune encephalomyelitis (EAE). In order to properly discriminate between these two cell types, microglia were defined as CD11b(pos) CD45(int) Ly-6C(neg) , and infiltrated macrophages as CD11b(pos) CD45(high) Ly-6C(pos) . During clinical EAE, microglia displayed a weakly immune-activated phenotype, based on the expression of MHCII, co-stimulatory molecules (CD80, CD86, and CD40) and proinflammatory genes [interleukin-1β (IL-1β) and tumour necrosis factor- α (TNF-α)]. In contrast, CD11b(pos) CD45(high) Ly-6C(pos) infiltrated macrophages were strongly activated and could be divided into two populations Ly-6C(int) and Ly-6C(high) , respectively. Ly-6C(high) macrophages contained less myelin than Ly-6C(int) macrophages and expression levels of the proinflammatory cytokines IL-1β and TNF-α were higher in Ly-6C(int) macrophages. Together, our data show that during clinical EAE, microglia are only weakly activated whereas infiltrated macrophages are highly immune reactive. © 2014 Wiley Periodicals, Inc.

Contemporary conceptions of etiology, pathogenesis, management and treatment of primary diffuse large b-cell central nervous system lymphoma

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S. V. Voloshin

2013-01-01

Full Text Available In this article we present the most up-to-date information about etiology, pathogenesis, diagnostic and treatment principles of primary central nervous system diffuse large B-cell lymphoma. We propose algorithm of diagnosis and treatment based on literature review and own experience. The main methods for diagnosis verification are magneto-resonance tomography and stereotactic biopsy of mass with subsequent histological examination including immune staining. The common first-line therapy regimen is high-dose methotrexate therapy. However long-term prognosis still remains poor. Adverse prognostic factors for therapy response are age > 60 years, multifocal lesions, neurologic symptoms,previous treated disease. Considerable part of patient have contraindications or high-risk of adverse events for high-dose chemotherapy treatment. Anti-CD20 monoclonal antibody has no neurological toxicity with intravenous and intrathecal administrations. Combination therapy with reduced dose methotrexate and monoclonal antibody can be a reasonable treatment alternative for old and disable persons. The further survival improvement would be achieved by patient stratification and using of risk-adapted treatment algorithm. 

Contemporary conceptions of etiology, pathogenesis, management and treatment of primary diffuse large b-cell central nervous system lymphoma

Directory of Open Access Journals (Sweden)

S. V. Voloshin

2014-07-01

Full Text Available In this article we present the most up-to-date information about etiology, pathogenesis, diagnostic and treatment principles of primary central nervous system diffuse large B-cell lymphoma. We propose algorithm of diagnosis and treatment based on literature review and own experience. The main methods for diagnosis verification are magneto-resonance tomography and stereotactic biopsy of mass with subsequent histological examination including immune staining. The common first-line therapy regimen is high-dose methotrexate therapy. However long-term prognosis still remains poor. Adverse prognostic factors for therapy response are age > 60 years, multifocal lesions, neurologic symptoms,previous treated disease. Considerable part of patient have contraindications or high-risk of adverse events for high-dose chemotherapy treatment. Anti-CD20 monoclonal antibody has no neurological toxicity with intravenous and intrathecal administrations. Combination therapy with reduced dose methotrexate and monoclonal antibody can be a reasonable treatment alternative for old and disable persons. The further survival improvement would be achieved by patient stratification and using of risk-adapted treatment algorithm. 

Xenograft transplantation of human malignant astrocytoma cells into immunodeficient rats: an experimental model of glioblastoma.

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Miura, Flávio Key; Alves, Maria Jose Ferreira; Rocha, Mussya Cisotto; da Silva, Roseli; Oba-Shinjo, Sueli Mieko; Marie, Suely Kazue Nagahashi

2010-03-01

Astrocytic gliomas are the most common intracranial central nervous system neoplasias, accounting for about 60% of all primary central nervous system tumors. Despite advances in the treatment of gliomas, no effective therapeutic approach is yet available; hence, the search for a more realistic model to generate more effective therapies is essential. To develop an experimental malignant astrocytoma model with the characteristics of the human tumor. Primary cells from subcutaneous xenograft tumors produced with malignant astrocytoma U87MG cells were inoculated intracerebrally by stereotaxis into immunosuppressed (athymic) Rowett rats. All four injected animals developed non-infiltrative tumors, although other glioblastoma characteristics, such as necrosis, pseudopalisading cells and intense mitotic activity, were observed. A malignant astrocytoma intracerebral xenograft model with poorly invasive behavior was achieved in athymic Rowett rats. Tumor invasiveness in an experimental animal model may depend on a combination of several factors, including the cell line used to induce tumor formation, the rat strains and the status of the animal's immune system.

Bilastine and the central nervous system.

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Montoro, J; Mullol, J; Dávila, I; Ferrer, M; Sastre, J; Bartra, J; Jáuregui, I; del Cuvillo, A; Valero, A

2011-01-01

Antihistamines have been classifed as first or second generation drugs, according to their pharmacokinetic properties, chemical structure and adverse effects. The adverse effects of antihistamines upon the central nervous system (CNS) depend upon their capacity to cross the blood-brain barrier (BBB) and bind to the central H1 receptors (RH1). This in turn depends on the lipophilicity of the drug molecule, its molecular weight (MW), and affinity for P-glycoprotein (P-gp) (CNS xenobiotic substances extractor protein). First generation antihistamines show scant affinity for P-gp, unlike the second generation molecules which are regarded as P-gp substrates. Histamine in the brain is implicated in many functions (waking-sleep cycle, attention, memory and learning, and the regulation of appetite), with numerous and complex interactions with different types of receptors in different brain areas. Bilastine is a new H1 antihistamine that proves to be effective in treating allergic rhinoconjunctivitis (seasonal and perennial) and urticaria. The imaging studies made, as well as the objective psychomotor tests and subjective assessment of drowsiness, indicate the absence of bilastine action upon the CNS. This fact, and the lack of interaction with benzodiazepines and alcohol, define bilastine as a clinically promising drug with a good safety profile as regards adverse effects upon the CNS.

Bone mineral density in subjects using central nervous system-active medications.

Science.gov (United States)

Kinjo, Mitsuyo; Setoguchi, Soko; Schneeweiss, Sebastian; Solomon, Daniel H

2005-12-01

Decreased bone mineral density defines osteoporosis according to the World Health Organization and is an important predictor of future fractures. The use of several types of central nervous system-active drugs, including benzodiazepines, anticonvulsants, antidepressants, and opioids, have all been associated with increased risk of fracture. However, it is unclear whether such an increase in risk is related to an effect of bone mineral density or to other factors, such as increased risk of falls. We sought to examine the relationship between bone mineral density and the use of benzodiazepines, anticonvulsants, antidepressants, and opioids in a representative US population-based sample. We analyzed data on adults aged 17 years and older from the Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994). Total femoral bone mineral density of 7114 male and 7532 female participants was measured by dual-energy x-ray absorptiometry. Multivariable linear regression models were used to quantify the relation between central nervous system medication exposure and total femoral bone mineral density. Models controlled for relevant covariates, including age, sex, and body mass index. In linear regression models, significantly reduced bone mineral density was found in subjects taking anticonvulsants (0.92 g/cm2; 95% confidence interval [CI]: 0.89 to 0.94) and opioids (0.92 g/cm2; 95% CI: 0.88 to 0.95) compared with nonusers (0.95 g/cm2; 95% CI: 0.95 to 0.95) after adjusting for several potential confounders. The other central nervous system-active drugs--benzodiazepines or antidepressants--were not associated with significantly reduced bone mineral density. In cross-sectional analysis of NHANES III, anticonvulsants and opioids (but not benzodiazepines or antidepressants) were associated with significantly reduced bone mineral density. These findings have implications for fracture-prevention strategies.

Echography of congenital malformations of the central nervous system

International Nuclear Information System (INIS)

Toirac Romani, Carlos Andres; Salmon Cruzata, Acelia; Musle Acosta, Mirelvis; Rosales Fargie, Yamile; Dosouto Infante, Vivian

2010-01-01

A descriptive and prospective study was conducted in 173 pregnant women attended at the Provincial Department of Clinical Genetics of Santiago de Cuba, from January, 2000 to December, 2004, to identify congenital malformations of the central nervous system detected by means of echography. The most frequent malformation was the hydrocephaly, followed by the fusion defects of the spine, associated with the hydrocephaly and the absence of cranial cavity. There was a prevalence of altered alpha fetoprotein and of elevated amniotic fluid

Central nervous system manifestations of HIV infection in children

International Nuclear Information System (INIS)

George, Reena; Andronikou, Savvas; Plessis, Jaco du; Plessis, Anne-Marie du; Maydell, Arthur; Toorn, Ronald van

2009-01-01

Vertically transmitted HIV infection is a major problem in the developing world due to the poor availability of antiretroviral agents to pregnant women. HIV is a neurotrophic virus and causes devastating neurological insults to the immature brain. The effects of the virus are further compounded by the opportunistic infections and neoplasms that occur as a result of the associated immune suppression. This review focuses on the imaging features of HIV infection and its complications in the central nervous system. (orig.)

Central nervous system manifestations of HIV infection in children

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George, Reena; Andronikou, Savvas; Plessis, Jaco du; Plessis, Anne-Marie du; Maydell, Arthur [University of Stellenbosch, Department of Radiology, Tygerberg Academic Hospital, Cape Town (South Africa); Toorn, Ronald van [University of Stellenbosch, Department of Paediatrics and Child Health, Tygerberg Academic Hospital, Cape Town (South Africa)

2009-06-15

Vertically transmitted HIV infection is a major problem in the developing world due to the poor availability of antiretroviral agents to pregnant women. HIV is a neurotrophic virus and causes devastating neurological insults to the immature brain. The effects of the virus are further compounded by the opportunistic infections and neoplasms that occur as a result of the associated immune suppression. This review focuses on the imaging features of HIV infection and its complications in the central nervous system. (orig.)

Epigenetics, Nervous System Tumors, and Cancer Stem Cells

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Qureshi, Irfan A. [Rosyln and Leslie Goldstein Laboratory for Stem Cell Biology and Regenerative Medicine, Albert Einstein College of Medicine, Bronx, New York, NY 10461 (United States); Institute for Brain Disorders and Neural Regeneration, Albert Einstein College of Medicine, Bronx, New York, NY 10461 (United States); Department of Neurology, Albert Einstein College of Medicine, Bronx, New York, NY 10461 (United States); Rose F. Kennedy Center for Research on Intellectual and Developmental Disabilities, Albert Einstein College of Medicine, Bronx, New York, NY 10461 (United States); Mehler, Mark F., E-mail: mark.mehler@einstein.yu.edu [Rosyln and Leslie Goldstein Laboratory for Stem Cell Biology and Regenerative Medicine, Albert Einstein College of Medicine, Bronx, New York, NY 10461 (United States); Institute for Brain Disorders and Neural Regeneration, Albert Einstein College of Medicine, Bronx, New York, NY 10461 (United States); Department of Neurology, Albert Einstein College of Medicine, Bronx, New York, NY 10461 (United States); Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York, NY 10461 (United States); Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Bronx, New York, NY 10461 (United States); Rose F. Kennedy Center for Research on Intellectual and Developmental Disabilities, Albert Einstein College of Medicine, Bronx, New York, NY 10461 (United States)

2011-09-13

Recent advances have begun to elucidate how epigenetic regulatory mechanisms are responsible for establishing and maintaining cell identity during development and adult life and how the disruption of these processes is, not surprisingly, one of the hallmarks of cancer. In this review, we describe the major epigenetic mechanisms (i.e., DNA methylation, histone and chromatin modification, non-coding RNA deployment, RNA editing, and nuclear reorganization) and discuss the broad spectrum of epigenetic alterations that have been uncovered in pediatric and adult nervous system tumors. We also highlight emerging evidence that suggests epigenetic deregulation is a characteristic feature of so-called cancer stem cells (CSCs), which are thought to be present in a range of nervous system tumors and responsible for tumor maintenance, progression, treatment resistance, and recurrence. We believe that better understanding how epigenetic mechanisms operate in neural cells and identifying the etiologies and consequences of epigenetic deregulation in tumor cells and CSCs, in particular, are likely to promote the development of enhanced molecular diagnostics and more targeted and effective therapeutic agents for treating recalcitrant nervous system tumors.

Epigenetics, Nervous System Tumors, and Cancer Stem Cells

International Nuclear Information System (INIS)

Qureshi, Irfan A.; Mehler, Mark F.

2011-01-01

Recent advances have begun to elucidate how epigenetic regulatory mechanisms are responsible for establishing and maintaining cell identity during development and adult life and how the disruption of these processes is, not surprisingly, one of the hallmarks of cancer. In this review, we describe the major epigenetic mechanisms (i.e., DNA methylation, histone and chromatin modification, non-coding RNA deployment, RNA editing, and nuclear reorganization) and discuss the broad spectrum of epigenetic alterations that have been uncovered in pediatric and adult nervous system tumors. We also highlight emerging evidence that suggests epigenetic deregulation is a characteristic feature of so-called cancer stem cells (CSCs), which are thought to be present in a range of nervous system tumors and responsible for tumor maintenance, progression, treatment resistance, and recurrence. We believe that better understanding how epigenetic mechanisms operate in neural cells and identifying the etiologies and consequences of epigenetic deregulation in tumor cells and CSCs, in particular, are likely to promote the development of enhanced molecular diagnostics and more targeted and effective therapeutic agents for treating recalcitrant nervous system tumors

Unusual presentation Of Sjögren-associated neuropathy with plasma cell-rich infiltrate.

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Naddaf, Elie; Berini, Sarah E; B Dyck, P James; Laughlin, Ruple S

2017-04-01

Sjögren syndrome is thought to be a lymphocyte-driven process. Peripheral nervous system involvement occurs in about 20%-25% of patients. A sensory-predominant, large-fiber peripheral neuropathy is most common, and it is usually associated with a subacute to chronic presentation. We report a rare case of an acute Sjögren-associated, sensory predominant, length-dependent peripheral neuropathy mimicking Guillain-Barré syndrome. The patient presented with sensory ataxia preceded by fever and polyarthralgia. She gave a history of years of dry eyes and dry mouth. She had a positive Shirmer test, abnormal salivary gland scan, and positive SS-A and SS-B antibodies. A sural nerve biopsy showed an unusual, dense, non-IgG4, polyclonal, plasma-cell perivascular infiltrate. The patient responded to treatment with weekly pulse intravenous methylprednisolone. Sjögren syndrome can present with acute-onset, sensory predominant peripheral neuropathy. The role of plasma cells in Sjögren syndrome is unexplored and deserves further study. Muscle Nerve 55: 605-608, 2017. © 2016 Wiley Periodicals, Inc.

Primary angiitis of the central nervous system: an ante-mortem diagnosis.

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Singh S

2000-10-01

Full Text Available A rare case of primary angiitis of the central nervous system (PACNS is reported with its clinical and magnetic resonance imaging (MRI features. A 20-year-old girl presented with headache, projectile vomiting, unsteadiness of gait and urgency of micturition. She had left seventh nerve upper motor neuron type paresis, increased tone in all four limbs, exaggerated deep tendon reflexes, cerebellar signs, and papilloedema. Cerebrospinal fluid showed lymphocytosis with elevated protein and normal glucose level. Cerebral computerised tomographic scan and MRI showed bilateral diffuse asymmetric supra- and infra-tentorial lesions (predominantly in the supratentorial and left cerebrum. On MRI, the lesions were hyperintense on T2, and proton density-weighted images and hypointense on T1-weighted images. Based on the clinical findings of raised intracranial tension and MRI features, initial diagnoses of gliomatosis cerebrii, tuberculous meningitis, primary central nervous system lymphoma and chronic viral encephalitis were considered. PACNS was not included in the initial differentials and, an open brain biopsy was advised which established the definitive diagnosis.

A rare case of anasarca caused by infiltration of the pituitary gland by diffuse large B-cell lymphoma.

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Kumabe, Ayako; Kenzaka, Tsuneaki; Nishimura, Yoshioki; Aikawa, Masaki; Mori, Masaki; Matsumura, Masami

2015-03-25

Anasarca in patients with lymphoma is a rare symptom. We report a patient with DLBCL associated with pituitary gland infiltration that was diagnosed based on significant anasarca. A 72-year-old woman with a 10-year history of hypertension visited a local hospital presenting with anasarca and 15-kg weight gain in the past 3 months. we clinically diagnosed central hypothyroidism caused by pituitary gland infiltration of diffuse large B-cell lymphoma (DLBCL) (clinical stage IV in the Ann Arbor staging classification). The first course of chemotherapy improved anasarca remarkably and the patient's body weight returned to what it was 3 months before. We experienced a patient with remarkable anasarca caused by DLBCL infiltration of the pituitary gland. A pituitary gland lesion with central hypothyroidism should be considered as one of the differential diagnoses of edema. This case was very valuable because we could assess it by following the time course of symptoms (edema and delayed relaxation time of the Achilles tendon reflex), laboratory data, and imaging findings (swelling anterior pituitary lobe).

[Dementia in Patients with Central Nervous System Mycosis].

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Morita, Akihiko; Ishihara, Masaki; Konno, Michiko

2016-04-01

Central nervous system (CNS) mycosis is a potentially life-threatening but treatable neurological emergency. CNS mycoses progress slowly and are sometimes difficult to distinguish from dementia. Though most patients with CNS mycosis have an underlying disease, such as human immunodeficiency virus (HIV) infection, cancer, diabetes mellitus, and/or use of immunosuppressants, cryptococcosis can occur in non-immunosuppressed persons. One of the major difficulties in accurate diagnosis is to detect the pathogen in patients' cerebrospinal fluid (CSF) cultures. Thus, the clinical diagnosis is often made by combining circumstantial evidence, including mononuclear cell-dominant pleocytosis with low glucose and protein elevation in the CSF, as well as positive results from an antigen-based assay and a (1-3)-beta-D-glucan assay using plasma and/or CSF. Polymerase chain reaction (PCR)-based diagnostics, which are not performed as routine examinations and are mostly performed as part of academic research in Japan, are sensitive tools for the early diagnosis of CNS mycosis. Mognetic resonance imaging (MRI) is useful to assess the complications of fungal meningitis, such as abscess, infarction, and hydrocephalus. Clinicians should realize the advantages and disadvantages of these diagnostic tools. Early and accurate diagnosis, including identification of the particular fungal species, enables optimal antifungal treatment that produces good outcomes in patients with CNS mycosis.

The effects of prophylactic treatment of the central nervous system on the intellectual functioning of children with acute lymphocytic leukemia

International Nuclear Information System (INIS)

Moss, H.A.; Nannis, E.D.; Poplack, D.G.

1981-01-01

The effect of central nervous system prophylaxis (cranial radiation and intrathecal chemotherapy) on intellectual function was studied in 24 children with acute lymphocytic leukemia. The Wechsler Intelligence tests were administered to these children and to a sample of their healthy siblings, who served as a comparison group. The mean Full Scale lQ was 98.6 for the patients and 112.5 for the sibling controls (p less than 0.001 level). Those patients who received central nervous system preventive treatment at a young age exhibited a greater decrement in intellectual abilities than did patients who were older when they received this treatment. In contrast, leukemia patients who had not received central nervous system prophylaxis had IQs that did not differ statistically from those of their siblings. These data suggest that central nervous system prophylaxis may have an adverse effect on the intellectual capability of children with acute lymphocytic leukemia

Evaluation of two stormwater infiltration trenches in central Copenhagen after 15 years of operation

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Bergman, Maria Kerstin; Hedegaard, Mathilde Jørgensen; Petersen, Mette Fjendbo

2011-01-01

to see whether the reduction in performance has continued and to determine how the system performs today. Water levels in the trenches were monitored for almost 4 months, and from this period seven events were selected to analyse the infiltration rate. A comparison with similar analyses on storm......Two stormwater infiltration trenches were installed in 1993 in an area in central Copenhagen. The system was monitored continuously for almost three years after establishment, and a small reduction in performance over that time, possibly due to clogging, was noted. A new study was conducted in 2009...... sequences from the first 3 years of operation shows that the infiltration has decreased since the establishment of the system 15 years ago. The decrease is statistically significant (p

Changes in the relative risk and sites of central nervous system metastasis with effective combined chemotherapy and radiation therapy for small cell carcinoma of the lung

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Komaki, R.; Cox, J.D.; Holoye, P.Y.; Byhardt, R.W.

1983-01-01

Prolongation of survival of patients with small cell carcinoma of the lung with current effective systemic therapy has been accompanied by a marked increase in the frequency of relapse in the central nervous system (CNS). Prophylactic cranial irradiation (PCI) was shown to reduce the frequency of brain metastasis, but there was no increased short-term survival. Therefore, the necessity for PCI early in the course of treatment has been questioned, especially for patients with extensive disease. From January 1974 through March 1982, 205 patients with small cell carcinoma of the lung were treated at the Medical College of Wisconsin Affiliated Hospitals. None had clinical, radioisotopic, or computed tomographic evidence of brain metastasis. Eighty-two patients received radiotherapy and chemotherapy, but no PCI; 123 patients received combination chemotherapy and radiation therapy with PCI. The cumulative probability of brain metastasis without PCI was 36% at 12 months and 47% at 24 months; the probabilities were 6 and 10%, respectively with PCI. The 24-month probability of brain metastasis in patients with limited disease and no PCI was 45%; for those with extensive disease, it was 47%. No patient presented with extracranial central nervous system (ECNS) metastasis and no one without PCI developed it. Twelve patients who received PCI developed ECNS metastasis; the cumulative probabilities rose to 14% at 12 months and 22% at 24 months. The increased frequency of ECNS involvement has led to a phase I trial of PCI followed by six cycles of combination chemotherapy, without maintenance chemotherapy, followed by irradiation of the chest and spinal cord for patients with complete response

Single cell cultures of Drosophila neuroectodermal and mesectodermal central nervous system progenitors reveal different degrees of developmental autonomy.

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Lüer, Karin; Technau, Gerhard M

2009-08-03

The Drosophila embryonic central nervous system (CNS) develops from two sets of progenitor cells, neuroblasts and ventral midline progenitors, which behave differently in many respects. Neuroblasts derive from the neurogenic region of the ectoderm and form the lateral parts of the CNS. Ventral midline precursors are formed by two rows of mesectodermal cells and build the CNS midline. There is plenty of evidence that individual identities are conferred to precursor cells by positional information in the ectoderm. It is unclear, however, how far the precursors can maintain their identities and developmental properties in the absence of normal external signals. To separate the respective contributions of autonomous properties versus extrinsic signals during their further development, we isolated individual midline precursors and neuroectodermal precursors at the pre-mitotic gastrula stage, traced their development in vitro, and analyzed the characteristics of their lineages in comparison with those described for the embryo. Although individually cultured mesectodermal cells exhibit basic characteristics of CNS midline progenitors, the clones produced by these progenitors differ from their in situ counterparts with regard to cell numbers, expression of molecular markers, and the separation of neuronal and glial fate. In contrast, clones derived from individually cultured precursors taken from specific dorsoventral zones of the neuroectoderm develop striking similarities to the lineages of neuroblasts that normally delaminate from these zones and develop in situ. This in vitro analysis allows for the first time a comparison of the developmental capacities in situ and in vitro of individual neural precursors of defined spatial and temporal origin. The data reveal that cells isolated at the pre-mitotic and pre-delamination stage express characteristics of the progenitor type appropriate to their site of origin in the embryo. However, presumptive neuroblasts, once

Radiologic studies in two outbreaks of isolated vasculitis in the central nervous system

International Nuclear Information System (INIS)

Robertson, H.J.; Perez, M.; Tilton, A.H.; Garcia, C.; McGarry, P.

1989-01-01

Cerebral vasculitis is only occasionally diagnosed with angiography. Two outbreaks of isolated central nervous system vasculitis permitted a comparison of the accuracy of diagnostic radiologic studies. Two new radiologic features and methods of diagnosis are discussed

Cerebral angiography as a guide for therapy in isolated central nervous system vasculitis

International Nuclear Information System (INIS)

Stein, R.L.; Martino, C.R.; Weinert, D.M.; Hueftle, M.; Kammer, G.M.

1987-01-01

The authors present a case of isolated central nervous system vasculitis documented by cerebral arteriography in which remission, using a treatment regimen of prednisone and cyclophosphamide, was guided by serial arteriography during a 15-month period

Phenotypic and Functional Properties of Tumor-Infiltrating Regulatory T Cells

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Gap Ryol Lee

2017-01-01

Full Text Available Regulatory T (Treg cells maintain immune homeostasis by suppressing excessive immune responses. Treg cells induce tolerance against self- and foreign antigens, thus preventing autoimmunity, allergy, graft rejection, and fetus rejection during pregnancy. However, Treg cells also infiltrate into tumors and inhibit antitumor immune responses, thus inhibiting anticancer therapy. Depleting whole Treg cell populations in the body to enhance anticancer treatments will produce deleterious autoimmune diseases. Therefore, understanding the precise nature of tumor-infiltrating Treg cells is essential for effectively targeting Treg cells in tumors. This review summarizes recent results relating to Treg cells in the tumor microenvironment, with particular emphasis on their accumulation, phenotypic, and functional properties, and targeting to enhance the efficacy of anticancer treatment.

VIIP: Central Nervous System (CNS) Modeling

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Vera, Jerry; Mulugeta, Lealem; Nelson, Emily; Raykin, Julia; Feola, Andrew; Gleason, Rudy; Samuels, Brian; Ethier, C. Ross; Myers, Jerry

2015-01-01

Current long-duration missions to the International Space Station and future exploration-class missions beyond low-Earth orbit expose astronauts to increased risk of Visual Impairment and Intracranial Pressure (VIIP) syndrome. It has been hypothesized that the headward shift of cerebrospinal fluid (CSF) and blood in microgravity may cause significant elevation of intracranial pressure (ICP), which in turn may then induce VIIP syndrome through interaction with various biomechanical pathways. However, there is insufficient evidence to confirm this hypothesis. In this light, we are developing lumped-parameter models of fluid transport in the central nervous system (CNS) as a means to simulate the influence of microgravity on ICP. The CNS models will also be used in concert with the lumped parameter and finite element models of the eye described in the related IWS works submitted by Nelson et al., Feola et al. and Ethier et al.

Central nervous system frontiers for the use of erythropoietin

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Olsen, Niels Vidiendal

2003-01-01

Recombinant human erythropoietin (r-HuEPO; epoetin alfa) is well established as safe and effective for the treatment of anemia. In addition to the erythropoietic effects of endogenous erythropoietin (EPO), recent evidence suggests that it may elicit a neuroprotective effect in the central nervous...... system (CNS). Preclinical studies have demonstrated the presence of EPO receptors in the brain that are up-regulated under hypoxic or ischemic conditions. Intracerebral and systemic administration of epoetin alfa have been demonstrated to elicit marked neuroprotective effects in multiple preclinical...

[Central Nervous Involvement in Patients with Fukuyama Congenital Muscular Dystrophy].

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Ishigaki, Keiko

2016-02-01

Fukuyama congenital muscular dystrophy (FCMD), the second most common muscular dystrophy in the Japanese population, is an autosomal recessive disorder caused by mutations in the fukutin (FKTN) gene. The main features of FCMD are a combination of infantile-onset hypotonia, generalized muscle weakness, eye abnormalities and central nervous system involvement with mental retardation and seizures associated with cortical migration defects. The FKTN gene product is thought to be necessary for maintaining migrating neurons in an immature state during migration, and for supporting migration via α-dystroglycan in the central nervous system. Typical magnetic resonance imaging findings in FCMD patients are cobblestone lissencephaly and cerebellar cystic lesions. White matter abnormalities with hyperintensity on T(2)-weighted images are seen especially in younger patients and those with severe phenotypes. Most FCMD patients are mentally retarded and the level is moderate to severe, with IQs ranging from 30 to 50. In our recent study, 62% of patients developed seizures. Among them, 71% had only febrile seizures, 6% had afebrile seizures from the onset, and 22% developed afebrile seizures following febrile seizures. Most patients had seizures that were controllable with just 1 type of antiepileptic drug, but 18% had intractable seizures that must be treated with 3 medications.

A Case Of Primary Central Nervous System Vasculitis Who Presented With Status Epilepticus

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Sırma Geyik

2014-12-01

Full Text Available Primary central nervous system vasculitis (PCNV is limited with central nervous system and rare vasculitis that mostly seen in middle-aged men. PCNV vasculitis is usually presented that headache, dementia, stroke and multifocal common neurological symptoms. PCNV especially involves small medium-sized leptomeningeal and cortical arteries. 43 years old male patient who have been progressive forgetfulness and headache for 3 years. He applied with recurrent that before starting right focal and than sprawling whole body which generalized tonic-clonic seizures to us. During management that he was transfered to the intensive care unit due to status epilepticus (SE. Later than we found right hemiparesis, motor aphasia and right babinski positivity in neurologic examination. Diffusion restriction was revealed in left MCA territory in diffusion magnetic resonance imaging(MRI. EEG showed two types abnormality that a slow background ritm and epileptiform activity. Biochemistry of blood, complete blood count, blood sedimentation rate, CRP and markers of vasculitis were found in the normal range. Cerebral anjiography revealed that irregularities in the distal vascular areas and fusiform aneurysm at the top of basilar artery. He was consulted with rheumatology and diagnosed central nervous system vasculitis with the existing findings. Biopsy couldn't be taken from the brain to verify the diagnosis. Finally, we applied treatment that pulse steroid and cyclophosphamide to patient. This case has been presented due to emphasize that PCNV rarely may play a role in the etiology of recurrent stroke and status epilepticus.

Candida infection of the central nervous system following neurosurgery: a 12-year review.

LENUS (Irish Health Repository)

O'Brien, Deirdre

2011-06-01

Candida infection of the central nervous system (CNS) following neurosurgery is relatively unusual but is associated with significant morbidity and mortality. We present our experience with this infection in adults and discuss clinical characteristics, treatment options, and outcome.

Central nervous system medication use in older adults with intellectual disability: Results from the successful ageing in intellectual disability study.

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Chitty, Kate M; Evans, Elizabeth; Torr, Jennifer J; Iacono, Teresa; Brodaty, Henry; Sachdev, Perminder; Trollor, Julian N

2016-04-01

Information on the rates and predictors of polypharmacy of central nervous system medication in older people with intellectual disability is limited, despite the increased life expectancy of this group. This study examined central nervous system medication use in an older sample of people with intellectual disability. Data regarding demographics, psychiatric diagnoses and current medications were collected as part of a larger survey completed by carers of people with intellectual disability over the age of 40 years. Recruitment occurred predominantly via disability services across different urban and rural locations in New South Wales and Victoria. Medications were coded according to the Monthly Index of Medical Specialties central nervous system medication categories, including sedatives/hypnotics, anti-anxiety agents, antipsychotics, antidepressants, central nervous system stimulants, movement disorder medications and anticonvulsants. The Developmental Behaviour Checklist for Adults was used to assess behaviour. Data were available for 114 people with intellectual disability. In all, 62.3% of the sample was prescribed a central nervous system medication, with 47.4% taking more than one. Of those who were medicated, 46.5% had a neurological diagnosis (a seizure disorder or Parkinson's disease) and 45.1% had a psychiatric diagnosis (an affective or psychotic disorder). Linear regression revealed that polypharmacy was predicted by the presence of neurological and psychiatric diagnosis, higher Developmental Behaviour Checklist for Adults scores and male gender. This study is the first to focus on central nervous system medication in an older sample with intellectual disability. The findings are in line with the wider literature in younger people, showing a high degree of prescription and polypharmacy. Within the sample, there seems to be adequate rationale for central nervous system medication prescription. Although these data do not indicate non-adherence to