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Sample records for human central nervous

  1. Detection of BMAA in the human central nervous system.

    PubMed

    Berntzon, L; Ronnevi, L O; Bergman, B; Eriksson, J

    2015-04-30

    Amyotrophic lateral sclerosis (ALS) is an extremely devastating neurodegenerative disease with an obscure etiology. The amino acid β-N-methylamino-l-alanine (BMAA) produced by globally widespread phytoplankton has been implicated in the etiology of human motor neuron diseases [corrected]. BMAA was recently proven to be present in Baltic Sea food webs, ranging from plankton to larger Baltic Sea organisms, some serving as important food items (fish) for humans. To test whether exposure to BMAA in a Baltic Sea setting is reflected in humans, blood and cerebrospinal fluid (CSF) from individuals suffering from ALS were analyzed, together with sex- and age-matched individuals not inflicted with ALS. Ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) and multiple reaction monitoring (MRM), in conjunction with diagnostic transitions revealed BMAA in three (12%) of the totally 25 Swedish individuals tested, with no preference for those suffering from ALS. The three BMAA-positive samples were all retrieved from the CSF, while BMAA was not detected in the blood. The data show that BMAA, potentially originating from Baltic Sea phytoplankton, may reach the human central nervous system, but does not lend support to the notion that BMAA is resident specifically in ALS-patients. However, while dietary exposure to BMAA may be intermittent and, if so, difficult to detect, our data provide the first demonstration of BMAA in the central nervous system of human individuals ante mortem quantified with UHPLC-MS/MS, and therefore calls for extended research efforts. PMID:25725357

  2. D-serine in the developing human central nervous system.

    PubMed

    Fuchs, Sabine A; Dorland, Lambertus; de Sain-van der Velden, Monique G; Hendriks, Margriet; Klomp, Leo W J; Berger, Ruud; de Koning, Tom J

    2006-10-01

    To elucidate the role of D-serine in human central nervous system, we analyzed D-serine, L-serine, and glycine concentrations in cerebrospinal fluid of healthy children and children with a defective L-serine biosynthesis (3-phosphoglycerate dehydrogenase deficiency). Healthy children showed high D-serine concentrations immediately after birth, both absolutely and relative to glycine and L-serine, declining to low values at infancy. D-Serine concentrations were almost undetectable in untreated 3-phosphoglycerate dehydrogenase-deficient patients. In one patient treated prenatally, D-serine concentration was nearly normal at birth and the clinical phenotype was normal. These observations suggest a pivotal role for D-serine in normal and aberrant human brain development. PMID:17068790

  3. Is schizophrenia the price of human central nervous system complexity?

    PubMed

    Dean, Brian

    2009-01-01

    The purpose of the present study was to determine if there is evidence to support the hypothesis that schizophrenia is a human-specific disorder associated with the need for highly complex central nervous system (CNS) development. A review was therefore undertaken of published literature relevant to the identification of human-specific CNS development. There was no clear evidence found at the macroscopic, microscopic or molecular level that suggests unique changes have occurred in the evolution of the human CNS. Rather, highly significant changes in the size of the frontal lobe, increases in numbers of specific cell types, changes in gene expression and changes in genome sequence all seem to be involved in the evolution of the human CNS. Human-specific changes in CNS development are wide ranging. The modification in CNS structure and function that has resulted from these changes affects many pathways and behaviours that appear to be also affected in subjects with schizophrenia. Therefore there is evidence to support the hypothesis that schizophrenia is a disease that develops because of derangements to human-specific CNS functions that have emerged since our species diverged from non-human primates. PMID:19085524

  4. Human neural progenitor cells in central nervous system lesions.

    PubMed

    Åkesson, Elisabet; Sundström, Erik

    2016-02-01

    Various immature cells can be isolated from human embryonic and fetal central nervous system (CNS) residual tissue and potentially be used in cell therapy for a number of neurological diseases and CNS insults. Transplantation of neural stem and progenitor cells is essential for replacing lost cells, particularly in the CNS with very limited endogenous regenerative capacity. However, while dopamine released from transplanted cells can substitute the lost dopamine neurons in the experimental models of Parkinson's disease, stem and progenitor cells primarily have a neuroprotective effect, probably through the release of trophic factors. Understanding the therapeutic effects of transplanted cells is crucial to determine the design of clinical trials. During the last few years, a number of clinical trials for CNS diseases and insults such as amyotrophic lateral sclerosis (ALS), stroke, and spinal cord trauma using neural progenitor cells have been initiated. Data from these early studies will provide vital information on the safety of transplanting these cells, which still is a major concern. That the beneficial results observed in experimental models also can be repeated in the clinical setting is highly hoped for. PMID:26803559

  5. Intranasal treatment of central nervous system dysfunction in humans.

    PubMed

    Chapman, Colin D; Frey, William H; Craft, Suzanne; Danielyan, Lusine; Hallschmid, Manfred; Schiöth, Helgi B; Benedict, Christian

    2013-10-01

    One of the most challenging problems facing modern medicine is how to deliver a given drug to a specific target at the exclusion of other regions. For example, a variety of compounds have beneficial effects within the central nervous system (CNS), but unwanted side effects in the periphery. For such compounds, traditional oral or intravenous drug delivery fails to provide benefit without cost. However, intranasal delivery is emerging as a noninvasive option for delivering drugs to the CNS with minimal peripheral exposure. Additionally, this method facilitates the delivery of large and/or charged therapeutics, which fail to effectively cross the blood-brain barrier (BBB). Thus, for a variety of growth factors, hormones, neuropeptides and therapeutics including insulin, oxytocin, orexin, and even stem cells, intranasal delivery is emerging as an efficient method of administration, and represents a promising therapeutic strategy for the treatment of diseases with CNS involvement, such as obesity, Alzheimer's disease, Parkinson's disease, Huntington's disease, depression, anxiety, autism spectrum disorders, seizures, drug addiction, eating disorders, and stroke. PMID:23135822

  6. Central nervous system control of the laryngeal muscles in humans

    PubMed Central

    Ludlow, Christy L.

    2005-01-01

    Laryngeal muscle control may vary for different functions such as: voice for speech communication, emotional expression during laughter and cry, breathing, swallowing, and cough. This review discusses the control of the human laryngeal muscles for some of these different functions. Sensori-motor aspects of laryngeal control have been studied by eliciting various laryngeal reflexes. The role of audition in learning and monitoring ongoing voice production for speech is well known; while the role of somatosensory feedback is less well understood. Reflexive control systems involving central pattern generators may contribute to swallowing, breathing and cough with greater cortical control during volitional tasks such as voice production for speech. Volitional control is much less well understood for each of these functions and likely involves the integration of cortical and subcortical circuits. The new frontier is the study of the central control of the laryngeal musculature for voice, swallowing and breathing and how volitional and reflexive control systems may interact in humans. PMID:15927543

  7. Central nervous system

    MedlinePlus

    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.

  8. Glial biomarkers in human central nervous system disease.

    PubMed

    Garden, Gwenn A; Campbell, Brian M

    2016-10-01

    There is a growing understanding that aberrant GLIA function is an underlying factor in psychiatric and neurological disorders. As drug discovery efforts begin to focus on glia-related targets, a key gap in knowledge includes the availability of validated biomarkers to help determine which patients suffer from dysfunction of glial cells or who may best respond by targeting glia-related drug mechanisms. Biomarkers are biological variables with a significant relationship to parameters of disease states and can be used as surrogate markers of disease pathology, progression, and/or responses to drug treatment. For example, imaging studies of the CNS enable localization and characterization of anatomical lesions without the need to isolate tissue for biopsy. Many biomarkers of disease pathology in the CNS involve assays of glial cell function and/or response to injury. Each major glia subtype (oligodendroglia, astroglia and microglia) are connected to a number of important and useful biomarkers. Here, we describe current and emerging glial based biomarker approaches for acute CNS injury and the major categories of chronic nervous system dysfunction including neurodegenerative, neuropsychiatric, neoplastic, and autoimmune disorders of the CNS. These descriptions are highlighted in the context of how biomarkers are employed to better understand the role of glia in human CNS disease and in the development of novel therapeutic treatments. GLIA 2016;64:1755-1771. PMID:27228454

  9. Human central nervous system myelin inhibits neurite outgrowth.

    PubMed

    Ng, W P; Cartel, N; Roder, J; Roach, A; Lozano, A

    1996-05-13

    In vitro and animal studies have identified molecules in mammalian CNS myelin which inhibit neuritic extension and which may be responsible, at least in part, for the lack of axonal regeneration after injury in the injured brain, optic nerve and spinal cord. To determine whether such inhibitory activity may be present in human CNS myelin, we used a bioassay to characterize neurite outgrowth on this substrate. Human CNS myelin strongly inhibited neuritic outgrowth from newborn rat dorsal root ganglion neurons and NG-108-15 cells, a neuroblastoma-glioma hybrid cell line. Similar but less potent inhibitory activity was identified in human gray matter. The CNS myelin inhibition of neuritic outgrowth appeared to be dependent on direct contact between the myelin substrate and neurites. The inhibitory activity in human CNS myelin closely resembled that described in adult rodents. Inhibition of neurite growth by human CNS myelin in this in vitro bioassay mirrors the lack of regeneration in vivo and can be used as a model to develop strategies designed to enhance axonal regeneration and neural recovery. PMID:8782892

  10. L-3,4-dihydroxyphenylalanine (levodopa) lowers central nervous system S-adenosylmethionine concentrations in humans.

    PubMed Central

    Surtees, R; Hyland, K

    1990-01-01

    To determine whether levodopa reduces the levels of S-adenosylmethionine in the human central nervous system, cerebrospinal fluid (CSF) concentrations of S-adenosylmethionine, methionine, 3-methoxytyrosine, levodopa and 5-methyltetrahydrofolate were measured in six children with dopamine deficiency before and after treatment. In four, the lack of dopamine was secondary to a reduction in concentration of levodopa and these were treated with levodopa together with a peripheral dopa-decarboxylase inhibitor. In the other two, levodopa in the central nervous system naturally accumulated due to a congenital deficiency of aromatic-L-amino acid decarboxylase and these were treated with pyridoxine (which in this condition lowers central levodopa concentrations). Raising levodopa concentrations in the central nervous system caused a fall in CSF S-adenosyl-methionine concentration and a rise in CSF 3-methoxytyrosine concentration. No change was observed in CSF methionine concentration and in all patients CSF 5-methyltetrahydrofolate concentration was normal. With one exclusion there was a linear relationship between CSF S-adenosylmethionine and 3-methoxytyrosine concentrations. This is the first demonstration of such effects in humans and the implications upon levodopa therapy are discussed. PMID:2391519

  11. Central nervous system regulation of eating: Insights from human brain imaging.

    PubMed

    Farr, Olivia M; Li, Chiang-Shan R; Mantzoros, Christos S

    2016-05-01

    Appetite and body weight regulation are controlled by the central nervous system (CNS) in a rather complicated manner. The human brain plays a central role in integrating internal and external inputs to modulate energy homeostasis. Although homeostatic control by the hypothalamus is currently considered to be primarily responsible for controlling appetite, most of the available evidence derives from experiments in rodents, and the role of this system in regulating appetite in states of hunger/starvation and in the pathogenesis of overeating/obesity remains to be fully elucidated in humans. Further, cognitive and affective processes have been implicated in the dysregulation of eating behavior in humans, but their exact relative contributions as well as the respective underlying mechanisms remain unclear. We briefly review each of these systems here and present the current state of research in an attempt to update clinicians and clinical researchers alike on the status and future directions of obesity research. PMID:27085777

  12. Astrocytes As the Main Players in Primary Degenerative Disorders of the Human Central Nervous System

    PubMed Central

    Capani, Francisco; Quarracino, Cecilia; Caccuri, Roberto; Sica, Roberto E. P.

    2016-01-01

    Along the last years it has been demonstrated that non-neural cells play a major role in the pathogenesis of the primary degenerative disorders (PDDs) of the human central nervous system. Among them, astrocytes coordinate and participate in many different and complex metabolic processes, in close interaction with neurons. Moreover, increasing experimental evidence hints an early astrocytic dysfunction in these diseases. In this mini review we summarize the astrocytic behavior in PDDs, with special consideration to the experimental observations where astrocytic pathology precedes the development of neuronal dysfunction. We also suggest a different approach that could be consider in human investigations in Alzheimer’s and Parkinson’s disease. We believe that the study of PDDs with human brain samples may hold the key of a paradigmatic physiopathological process in which astrocytes might be the main players. PMID:26973519

  13. Astrocytes As the Main Players in Primary Degenerative Disorders of the Human Central Nervous System.

    PubMed

    Capani, Francisco; Quarracino, Cecilia; Caccuri, Roberto; Sica, Roberto E P

    2016-01-01

    Along the last years it has been demonstrated that non-neural cells play a major role in the pathogenesis of the primary degenerative disorders (PDDs) of the human central nervous system. Among them, astrocytes coordinate and participate in many different and complex metabolic processes, in close interaction with neurons. Moreover, increasing experimental evidence hints an early astrocytic dysfunction in these diseases. In this mini review we summarize the astrocytic behavior in PDDs, with special consideration to the experimental observations where astrocytic pathology precedes the development of neuronal dysfunction. We also suggest a different approach that could be consider in human investigations in Alzheimer's and Parkinson's disease. We believe that the study of PDDs with human brain samples may hold the key of a paradigmatic physiopathological process in which astrocytes might be the main players. PMID:26973519

  14. Fighting the Monster: Applying the Host Damage Framework to Human Central Nervous System Infections

    PubMed Central

    Panackal, Anil A.; Williamson, Kim C.; van de Beek, Diederik; Boulware, David R.

    2016-01-01

    ABSTRACT The host damage-response framework states that microbial pathogenesis is a product of microbial virulence factors and collateral damage from host immune responses. Immune-mediated host damage is particularly important within the size-restricted central nervous system (CNS), where immune responses may exacerbate cerebral edema and neurological damage, leading to coma and death. In this review, we compare human host and therapeutic responses in representative nonviral generalized CNS infections that induce archetypal host damage responses: cryptococcal menigoencephalitis and tuberculous meningitis in HIV-infected and non-HIV-infected patients, pneumococcal meningitis, and cerebral malaria. Consideration of the underlying patterns of host responses provides critical insights into host damage and may suggest tailored adjunctive therapeutics to improve disease outcome. PMID:26814182

  15. Cell-Specific Survival Motor Neuron Gene Expression during Human Development of the Central Nervous System

    PubMed Central

    Tizzano, Eduardo F.; Cabot, Carmen; Baiget, Montserrat

    1998-01-01

    Spinal muscular atrophy is an autosomal recessive disorder characterized by the progressive loss or degeneration of the motor neurons. To investigate the expression of survival motor neuron (SMN), the spinal muscular atrophy-determining gene, and its relationship with the pathogenesis of the disease, we analyzed by means of in situ hybridization the location of SMN mRNA in fetal, newborn, infant, and adult human central nervous system tissues. The large motor neurons of the spinal cord are the main cells that express SMN together with the neurons of the medulla oblongata, the pyramidal cells of the cortex, and the Purkinje cells of the cerebellum. Some sensory neurons from the posterior horn and dorsal root ganglia express SMN to a lesser degree. Furthermore, strong SMN expression is detected in the ependymal cells of the central canal. The expression is present in the spinal cord at 8 weeks of fetal life throughout postnatal and adult life. The sharp expression of SMN in the motor neurons of the human spinal cord, the target cells in spinal muscular atrophy, suggests that this gene is implicated in neuronal development and in the pathogenesis of the disease. The location of the SMN gene expression in other neuronal structures not clearly or directly associated with clinical manifestations or pathological findings of spinal muscular atrophy may indicate a varying sensitivity to the absence or dysfunction of the SMN gene in motor neurons. PMID:9708795

  16. Central Nervous System Lipoproteins

    PubMed Central

    Mahley, Robert W.

    2016-01-01

    ApoE on high-density lipoproteins is primarily responsible for lipid transport and cholesterol homeostasis in the central nervous system (CNS). Normally produced mostly by astrocytes, apoE is also produced under neuropathologic conditions by neurons. ApoE on high-density lipoproteins is critical in redistributing cholesterol and phospholipids for membrane repair and remodeling. The 3 main structural isoforms differ in their effectiveness. Unlike apoE2 and apoE3, apoE4 has markedly altered CNS metabolism, is associated with Alzheimer disease and other neurodegenerative disorders, and is expressed at lower levels in brain and cerebrospinal fluid. ApoE4-expressing cultured astrocytes and neurons have reduced cholesterol and phospholipid secretion, decreased lipid-binding capacity, and increased intracellular degradation. Two structural features are responsible for apoE4 dysfunction: domain interaction, in which arginine-61 interacts ionically with glutamic acid-255, and a less stable conformation than apoE3 and apoE2. Blocking domain interaction by gene targeting (replacing arginine-61 with threonine) or by small-molecule structure correctors increases CNS apoE4 levels and lipid-binding capacity and decreases intracellular degradation. Small molecules (drugs) that disrupt domain interaction, so-called structure correctors, could prevent the apoE4-associated neuropathology by blocking the formation of neurotoxic fragments. Understanding how to modulate CNS cholesterol transport and metabolism is providing important insights into CNS health and disease. PMID:27174096

  17. Activity of D-amino acid oxidase is widespread in the human central nervous system

    PubMed Central

    Sasabe, Jumpei; Suzuki, Masataka; Imanishi, Nobuaki; Aiso, Sadakazu

    2014-01-01

    It has been proposed that D-amino acid oxidase (DAO) plays an essential role in degrading D-serine, an endogenous coagonist of N-methyl-D-aspartate (NMDA) glutamate receptors. DAO shows genetic association with amyotrophic lateral sclerosis (ALS) and schizophrenia, in whose pathophysiology aberrant metabolism of D-serine is implicated. Although the pathology of both essentially involves the forebrain, in rodents, enzymatic activity of DAO is hindbrain-shifted and absent in the region. Here, we show activity-based distribution of DAO in the central nervous system (CNS) of humans compared with that of mice. DAO activity in humans was generally higher than that in mice. In the human forebrain, DAO activity was distributed in the subcortical white matter and the posterior limb of internal capsule, while it was almost undetectable in those areas in mice. In the lower brain centers, DAO activity was detected in the gray and white matters in a coordinated fashion in both humans and mice. In humans, DAO activity was prominent along the corticospinal tract, rubrospinal tract, nigrostriatal system, ponto-/olivo-cerebellar fibers, and in the anterolateral system. In contrast, in mice, the reticulospinal tract and ponto-/olivo-cerebellar fibers were the major pathways showing strong DAO activity. In the human corticospinal tract, activity-based staining of DAO did not merge with a motoneuronal marker, but colocalized mostly with excitatory amino acid transporter 2 and in part with GFAP, suggesting that DAO activity-positive cells are astrocytes seen mainly in the motor pathway. These findings establish the distribution of DAO activity in cerebral white matter and the motor system in humans, providing evidence to support the involvement of DAO in schizophrenia and ALS. Our results raise further questions about the regulation of D-serine in DAO-rich regions as well as the physiological/pathological roles of DAO in white matter astrocytes. PMID:24959138

  18. Applications of human umbilical cord blood cells in central nervous system regeneration.

    PubMed

    Herranz, Antonio S; Gonzalo-Gobernado, Rafael; Reimers, Diana; Asensio, Maria J; Rodríguez-Serrano, Macarena; Bazán, Eulalia

    2010-03-01

    In recent decades, there has been considerable amount of information about embryonic stem cells (ES). The dilemma facing scientists interested in the development and use of human stem cells in replacement therapies is the source of these cells, i.e. the human embryo. There are many ethical and moral problems related to the use of these cells. Hematopoietic stem cells from umbilical cord blood have been proposed as an alternative source of embryonic stem cells. After exposure to different agents, these cells are able to express antigens of diverse cellular lineages, including the neural type. The In vitro manipulation of human umbilical cord blood (hUCB) cells has shown their stem capacity and plasticity. These cells are easily accessible, In vitro amplifiable, well tolerated by the host, and with more primitive molecular characteristics that give them great flexibility. Overall, these properties open a promising future for the use of hUCB in regenerative therapies for the Central Nervous System (CNS). This review will focus on the available literature concerning umbilical cord blood cells as a therapeutic tool for the treatment of neurodegenerative diseases. PMID:19807661

  19. Blast shockwaves propagate Ca2+ activity via purinergic astrocyte networks in human central nervous system cells

    PubMed Central

    Ravin, Rea; Blank, Paul S.; Busse, Brad; Ravin, Nitay; Vira, Shaleen; Bezrukov, Ludmila; Waters, Hang; Guerrero-Cazares, Hugo; Quinones-Hinojosa, Alfredo; Lee, Philip R.; Fields, R. Douglas; Bezrukov, Sergey M.; Zimmerberg, Joshua

    2016-01-01

    In a recent study of the pathophysiology of mild, blast-induced traumatic brain injury (bTBI) the exposure of dissociated, central nervous system (CNS) cells to simulated blast resulted in propagating waves of elevated intracellular Ca2+. Here we show, in dissociated human CNS cultures, that these calcium waves primarily propagate through astrocyte-dependent, purinergic signaling pathways that are blocked by P2 antagonists. Human, compared to rat, astrocytes had an increased calcium response and prolonged calcium wave propagation kinetics, suggesting that in our model system rat CNS cells are less responsive to simulated blast. Furthermore, in response to simulated blast, human CNS cells have increased expressions of a reactive astrocyte marker, glial fibrillary acidic protein (GFAP) and a protease, matrix metallopeptidase 9 (MMP-9). The conjoint increased expression of GFAP and MMP-9 and a purinergic ATP (P2) receptor antagonist reduction in calcium response identifies both potential mechanisms for sustained changes in brain function following primary bTBI and therapeutic strategies targeting abnormal astrocyte activity. PMID:27162174

  20. Blast shockwaves propagate Ca(2+) activity via purinergic astrocyte networks in human central nervous system cells.

    PubMed

    Ravin, Rea; Blank, Paul S; Busse, Brad; Ravin, Nitay; Vira, Shaleen; Bezrukov, Ludmila; Waters, Hang; Guerrero-Cazares, Hugo; Quinones-Hinojosa, Alfredo; Lee, Philip R; Fields, R Douglas; Bezrukov, Sergey M; Zimmerberg, Joshua

    2016-01-01

    In a recent study of the pathophysiology of mild, blast-induced traumatic brain injury (bTBI) the exposure of dissociated, central nervous system (CNS) cells to simulated blast resulted in propagating waves of elevated intracellular Ca(2+). Here we show, in dissociated human CNS cultures, that these calcium waves primarily propagate through astrocyte-dependent, purinergic signaling pathways that are blocked by P2 antagonists. Human, compared to rat, astrocytes had an increased calcium response and prolonged calcium wave propagation kinetics, suggesting that in our model system rat CNS cells are less responsive to simulated blast. Furthermore, in response to simulated blast, human CNS cells have increased expressions of a reactive astrocyte marker, glial fibrillary acidic protein (GFAP) and a protease, matrix metallopeptidase 9 (MMP-9). The conjoint increased expression of GFAP and MMP-9 and a purinergic ATP (P2) receptor antagonist reduction in calcium response identifies both potential mechanisms for sustained changes in brain function following primary bTBI and therapeutic strategies targeting abnormal astrocyte activity. PMID:27162174

  1. Application of synchrotron radiation for elemental microanalysis of human central nervous System tissue

    NASA Astrophysics Data System (ADS)

    Szczerbowska-Boruchowska, M.; Lankosz, M.; Ostachowicz, J.; Adamek, D.; Krygowska-Wajs, A.; Tomik, B.; Szczudlik, A.; Simionovici, A.; Bohic, S.

    2003-03-01

    The pathogenesis of two neurodegenerative diseases i.e. Parkinson's Disease (PD) and amyotrophic lateral sclerosis (ALS) are still not known. It is supposed that disturbance of metal ions homeostasis may promote degeneration and atrophy of neurones. As a preliminary study. the quantitative and topographic elemental analysis of selected parts of human brain and spinal cord was performed using synchrotron microbeam-X ray fluorescence (μ-SXRF) technique. The samples were taken during the autopsy from patients with PD, ALS and from patients died due to non-neurological conditions events. X-ray fluorescence imaging showed that increased concentration of selected elements are observed in neurons perikarial parts in compare with surrounding area. Moreover, comparable analysis showed significant differences in accumulation of selected elements between the pathological and control cases. The investigations indicate that micro-beam of synchrotron radiation can be satisfactory applied for analysis of central nervous System tissue providing useful information about distribution and contents of elements at the single cell level.

  2. Central nervous system cryptococcoma in a Ugandan patient with Human Immunodeficiency Virus

    PubMed Central

    Velamakanni, Sruti S.; Bahr, Nathan C.; Musubire, Abdu K.; Boulware, David R.; Rhein, Joshua; Nabeta, Henry W.

    2014-01-01

    Mortality due to AIDS-related Cryptococcal meningitis (CM) is often >50% in low-middle income countries. Dissemination of CM can result in intracranial mass lesions known as cryptococcoma. Patients who develop cryptococcomas often have worse outcomes when compared to patients with cryptococcosis without cryptococcoma. We describe a cryptococcoma in the central nervous system (CNS) in a Ugandan patient with AIDS, and review the diagnosis and management with special focus on difficulties encountered in low or middle-income countries. PMID:25379390

  3. Aluminum in the central nervous system (CNS): toxicity in humans and animals, vaccine adjuvants, and autoimmunity.

    PubMed

    Shaw, C A; Tomljenovic, L

    2013-07-01

    We have examined the neurotoxicity of aluminum in humans and animals under various conditions, following different routes of administration, and provide an overview of the various associated disease states. The literature demonstrates clearly negative impacts of aluminum on the nervous system across the age span. In adults, aluminum exposure can lead to apparently age-related neurological deficits resembling Alzheimer's and has been linked to this disease and to the Guamanian variant, ALS-PDC. Similar outcomes have been found in animal models. In addition, injection of aluminum adjuvants in an attempt to model Gulf War syndrome and associated neurological deficits leads to an ALS phenotype in young male mice. In young children, a highly significant correlation exists between the number of pediatric aluminum-adjuvanted vaccines administered and the rate of autism spectrum disorders. Many of the features of aluminum-induced neurotoxicity may arise, in part, from autoimmune reactions, as part of the ASIA syndrome. PMID:23609067

  4. [Isoforms of the human histamine H3 receptor: Generation, expression in the central nervous system and functional implications].

    PubMed

    García-Gálvez, Ana Maricela; Arias-Montaño, José Antonio

    2016-01-01

    Histamine plays a significant role as a neuromodulator in the human central nervous system. Histamine-releasing neurons are exclusively located in the tuberomammillary nucleus of the hypothalamus, project to all major areas of the brain, and participate in functions such as the regulation of sleep/wakefulness, locomotor activity, feeding and drinking, analgesia, learning, and memory. The functional effects of histamine are exerted through the activation of four G protein-coupled receptors (H1, H2, H3 and H4), and in the central nervous system the first three receptors are widely expressed. The H3 receptor (H3R) is found exclusively in neuronal cells, where it functions as auto- and hetero-receptor. One remarkable characteristic of the H3R is the existence of isoforms, generated by alternative splicing of the messenger RNA. For the human H3R, 20 isoforms have been reported; although a significant number lack those regions required for agonist binding or receptor signaling, at least five isoforms appear functional upon heterologous expression. In this work we review the evidence for the generation of human H3R isoforms, their expression, and the available information regarding the functionality of such receptors. PMID:26927649

  5. Epstein-Barr and human immunodeficiency viruses in acquired immunodeficiency syndrome-related primary central nervous system lymphoma.

    PubMed Central

    Morgello, S.

    1992-01-01

    The prevalence of Epstein-Barr virus (EBV) and human immunodeficiency virus (HIV) in acquired immunodeficiency syndrome (AIDS)-related primary central nervous system (CNS) lymphoma was examined. Deoxyribonucleic acid (DNA) extracted from 12 formalin-fixed, paraffin-embedded tumors was used as substrate for the polymerase chain reaction (PCR). Targets for amplification were the EBNA-1 region of EBV, the gag region of HIV, and a single copy cellular sequence as a control. The cases studied were autopsy and surgical specimens collected between the years 1985 and 1989. By the working formulation for non-Hodgkin's lymphomas, five had large cell, four had mixed large and small cleaved cell, two had small cleaved cell, and one had an unclassified histology. Epstein-Barr virus was detected in 6 of 12 tumors studied. Human immunodeficiency virus was not detected in any of the tumors. The presence of EBV was not correlated with any particular histologic tumor type. It is concluded that EBV, not HIV, can be detected in a large percentage (50%) of AIDS-related primary central nervous system (CNS) lymphomas. This viral association may be significant in light of the demonstrated ability of EBV to induce lymphoid tumors in experimental mammalian systems. Images Figure 1 Figure 2 PMID:1323221

  6. The Role of Gap Junction Channels During Physiologic and Pathologic Conditions of the Human Central Nervous System

    PubMed Central

    Basilio, Daniel; Sáez, Juan C.; Orellana, Juan A.; Raine, Cedric S.; Bukauskas, Feliksas; Bennett, Michael V. L.; Berman, Joan W.

    2013-01-01

    Gap junctions (GJs) are expressed in most cell types of the nervous system, including neuronal stem cells, neurons, astrocytes, oligodendrocytes, cells of the blood brain barrier (endothelial cells and astrocytes) and under inflammatory conditions in microglia/macrophages. GJs connect cells by the docking of two hemichannels, one from each cell with each hemichannel being formed by 6 proteins named connexins (Cx). Unapposed hemichannels (uHC) also can be open on the surface of the cells allowing the release of different intracellular factors to the extracellular space. GJs provide a mechanism of cell-to-cell communication between adjacent cells that enables the direct exchange of intracellular messengers, such as calcium, nucleotides, IP3, and diverse metabolites, as well as electrical signals that ultimately coordinate tissue homeostasis, proliferation, differentiation, metabolism, cell survival and death. Despite their essential functions in physiological conditions, relatively little is known about the role of GJs and uHC in human diseases, especially within the nervous system. The focus of this review is to summarize recent findings related to the role of GJs and uHC in physiologic and pathologic conditions of the central nervous system. PMID:22438035

  7. Sleep Deprivation Impairs the Human Central and Peripheral Nervous System Discrimination of Social Threat.

    PubMed

    Goldstein-Piekarski, Andrea N; Greer, Stephanie M; Saletin, Jared M; Walker, Matthew P

    2015-07-15

    Facial expressions represent one of the most salient cues in our environment. They communicate the affective state and intent of an individual and, if interpreted correctly, adaptively influence the behavior of others in return. Processing of such affective stimuli is known to require reciprocal signaling between central viscerosensory brain regions and peripheral-autonomic body systems, culminating in accurate emotion discrimination. Despite emerging links between sleep and affective regulation, the impact of sleep loss on the discrimination of complex social emotions within and between the CNS and PNS remains unknown. Here, we demonstrate in humans that sleep deprivation impairs both viscerosensory brain (anterior insula, anterior cingulate cortex, amygdala) and autonomic-cardiac discrimination of threatening from affiliative facial cues. Moreover, sleep deprivation significantly degrades the normally reciprocal associations between these central and peripheral emotion-signaling systems, most prominent at the level of cardiac-amygdala coupling. In addition, REM sleep physiology across the sleep-rested night significantly predicts the next-day success of emotional discrimination within this viscerosensory network across individuals, suggesting a role for REM sleep in affective brain recalibration. Together, these findings establish that sleep deprivation compromises the faithful signaling of, and the "embodied" reciprocity between, viscerosensory brain and peripheral autonomic body processing of complex social signals. Such impairments hold ecological relevance in professional contexts in which the need for accurate interpretation of social cues is paramount yet insufficient sleep is pervasive. PMID:26180190

  8. Sleep Deprivation Impairs the Human Central and Peripheral Nervous System Discrimination of Social Threat

    PubMed Central

    Goldstein-Piekarski, Andrea N.; Greer, Stephanie M.; Saletin, Jared M.

    2015-01-01

    Facial expressions represent one of the most salient cues in our environment. They communicate the affective state and intent of an individual and, if interpreted correctly, adaptively influence the behavior of others in return. Processing of such affective stimuli is known to require reciprocal signaling between central viscerosensory brain regions and peripheral-autonomic body systems, culminating in accurate emotion discrimination. Despite emerging links between sleep and affective regulation, the impact of sleep loss on the discrimination of complex social emotions within and between the CNS and PNS remains unknown. Here, we demonstrate in humans that sleep deprivation impairs both viscerosensory brain (anterior insula, anterior cingulate cortex, amygdala) and autonomic-cardiac discrimination of threatening from affiliative facial cues. Moreover, sleep deprivation significantly degrades the normally reciprocal associations between these central and peripheral emotion-signaling systems, most prominent at the level of cardiac-amygdala coupling. In addition, REM sleep physiology across the sleep-rested night significantly predicts the next-day success of emotional discrimination within this viscerosensory network across individuals, suggesting a role for REM sleep in affective brain recalibration. Together, these findings establish that sleep deprivation compromises the faithful signaling of, and the “embodied” reciprocity between, viscerosensory brain and peripheral autonomic body processing of complex social signals. Such impairments hold ecological relevance in professional contexts in which the need for accurate interpretation of social cues is paramount yet insufficient sleep is pervasive. PMID:26180190

  9. Human T-cell lymphotropic virus type III infection of the central nervous system: a preliminary in situ analysis

    SciTech Connect

    Stoler, M.H.; Eskin, T.A.; Benn, S.; Angerer, R.C.; Angerer, L.M.

    1986-11-07

    Patients with acquired immunodeficiency syndrome (AIDS) are subject to a spectrum of central nervous system (CNS) disorders. Recent evidence implicates the human T-cell lymphotropic virus type III (HTLV-III) in the pathogenesis of some of these illnesses, although the cells infected by the virus have yet to be identified. Using in situ hybridization, the authors examined brain tissue from two patients with AIDS encephalopathy for the presence of HTLV-III RNA. In both cases, viral RNA was detected and concentrated in, though not limited to, the white matter. The CNS cells most frequently infected included macrophages, pleomorphic microglia, and multinucleated giant cells. Less frequently, cells morphologically consistent with astrocytes, oligodendroglia, and rarely neurons were also infected. The findings strengthen the association of HTLV-III with the pathogenesis of AIDS encephalopathy. In situ hybridization can be applied to routinely prepared biopsy tissue in the diagnosis of HTLV-III infection of the CNS.

  10. [Primary central nervous system vasculitis].

    PubMed

    Schuster, S; Magnus, T

    2015-12-01

    Primary angiitis of the central nervous system (PACNS) is a rare disorder. However, it is often considered in the differential diagnosis of vascular or inflammatory CNS diseases. Diagnosis is challenging, as specific biomarkers are lacking and the clinical presentation can be variable. A definitive diagnosis can only be established by biopsy of the inflammatory changes in the vascular wall. Alternatively, the diagnosis of PACNS can also be based on the synopsis of clinical, radiological, and laboratory findings. Different subtypes of PACNS have been described in recent years, depending on the size of the affected vessels or histopathological patterns. Based on selective literature research in the database PubMed on the subject of CNS vasculitis, this article reviews the diagnostic characteristics and differential diagnosis of the condition. We suggest a diagnostic algorithm customized to the size of the affected vessels. Lastly, therapeutic options and the outcome of PACNS are briefly outlined. PMID:26589203

  11. Viral Diseases of the Central Nervous System

    PubMed Central

    Swanson, Phillip A.; McGavern, Dorian B.

    2015-01-01

    Virus-induced diseases of the central nervous system (CNS) represent a significant burden to human health worldwide. The complexity of these diseases is influenced by the sheer number of different neurotropic viruses, the diverse routes of CNS entry, viral tropism, and the immune system. Using a combination of human pathological data and experimental animal models, we have begun to uncover many of the mechanisms that viruses use to enter the CNS and cause disease. This review highlights a selection of neurotropic viruses that infect the CNS and explores the means by which they induce neurological diseases such as meningitis, encephalitis, and myelitis. PMID:25681709

  12. Central nervous pathways underlying synchronization of human motor unit firing studied during voluntary contractions.

    PubMed Central

    Datta, A K; Farmer, S F; Stephens, J A

    1991-01-01

    1. Motor unit firing has been studied during weak voluntary isometric contractions with pairs of needle electrodes in normal human subjects. 2. Pre- and post-stimulus time histograms of the firing time of firing of one event unit before and after the time of firing of another reference (stimulus) unit showed a clear central peak, indicative of synchronization. 3. Synchronization was seen in all the muscles studied. The mean strength of synchronization, expressed as the number of concomitant discharges of the two units as a proportion of the number of stimulus unit discharges, was 0.095 extra event unit spikes/reference unit spike (range 0.042-0.28) for first dorsal interosseous muscle, 0.016 extra event unit spikes per reference unit spike (range 0-0.043) for medial gastrocnemius and 0.056 extra event unit spikes per reference unit spike range 0.016-0.079) for tibialis anterior. 4. The mean duration of synchronization was 11.3 ms (range 5.0-21.0 ms) for first dorsal interosseous, 10.3 ms (range 3.5-21.7 ms) for medial gastrocnemious and 13.5 ms (range 3.0-25.0) for tibialis anterior. 5. Seven patients with radiographically and clinically identified central strokes were studied while they made weak voluntary isometric contractions. The duration of synchronization was significantly prolonged compared to that found in normal subjects. In these stroke patients the mean duration of synchronization on the affected side was longer than that seen in the normal subjects, and in first dorsal interosseous muscle was 35.4 ms (range 12.0-65.0 ms), in medial gastrocnemius was 21.3 ms (range 4.0-43.0 ms) and in tibialis anterior was 28.8 ms (range 14.0-49.0 ms). 6. The mean strength of synchronization of motor unit discharge was found to be greater in the stroke patients than that seen in the normal subjects for first dorsal interosseous muscle (0.161 extra event unit spikes per reference unit spike, range 0.017-0.391) and for medial gastrocnemius (0.030 extra event unit spikes

  13. A Comparison of the Anorexic Effects of Chicken, Porcine, Human and Bovine Insulin on the Central Nervous System of Chicks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The aim of the present study was to determine if some naturally-occurring substitutions of amino acid residues of insulin could act differentially within the central nervous system (CNS) of neonatal chicks to control ingestive behavior. Intracerebroventricular (ICV) administration of chicken insuli...

  14. Novel central nervous system drug delivery systems.

    PubMed

    Stockwell, Jocelyn; Abdi, Nabiha; Lu, Xiaofan; Maheshwari, Oshin; Taghibiglou, Changiz

    2014-05-01

    For decades, biomedical and pharmaceutical researchers have worked to devise new and more effective therapeutics to treat diseases affecting the central nervous system. The blood-brain barrier effectively protects the brain, but poses a profound challenge to drug delivery across this barrier. Many traditional drugs cannot cross the blood-brain barrier in appreciable concentrations, with less than 1% of most drugs reaching the central nervous system, leading to a lack of available treatments for many central nervous system diseases, such as stroke, neurodegenerative disorders, and brain tumors. Due to the ineffective nature of most treatments for central nervous system disorders, the development of novel drug delivery systems is an area of great interest and active research. Multiple novel strategies show promise for effective central nervous system drug delivery, giving potential for more effective and safer therapies in the future. This review outlines several novel drug delivery techniques, including intranasal drug delivery, nanoparticles, drug modifications, convection-enhanced infusion, and ultrasound-mediated drug delivery. It also assesses possible clinical applications, limitations, and examples of current clinical and preclinical research for each of these drug delivery approaches. Improved central nervous system drug delivery is extremely important and will allow for improved treatment of central nervous system diseases, causing improved therapies for those who are affected by central nervous system diseases. PMID:24325540

  15. Functional MRI localisation of central nervous system regions associated with volitional inspiration in humans

    PubMed Central

    Evans, Karleyton C; Shea, Steven A; Saykin, Andrew J

    1999-01-01

    Functional magnetic resonance imaging (fMRI) provides a means of studying neuronal circuits that control respiratory muscles in humans with better spatial and temporal resolution than in previous positron emission tomography (PET) studies. Whole brain blood oxygenation level-dependent (BOLD) changes determined by fMRI were used to identify areas of neuronal activation associated with volitional inspiration in five healthy men. Four series of scans of each subject were acquired during voluntary breathing (active task) and mechanical ventilation (passive task). Ventilation and end-tidal PCO2 were similar between tasks. Scan data were re-aligned to correct for movement artefacts and cross-referenced breath by breath to respiratory data for selective averaging of inspiratory and expiratory images. Group analysis identified significant increases in the fMRI signal with volitional inspiration in the superior motor cortex, premotor cortex and supplementary motor area at loci similar to those detected in earlier studies that used PET. Additional regions activated by volitional inspiration included inferolateral sensorimotor cortex, prefrontal cortex and striatum (these foci were only revealed by PET under significant inspiratory load). This study represents the first synchronised breath-by-breath analysis of respiratory-related neuronal activity with whole brain imaging in humans. Temporal resolution is sufficient to distinguish individual breaths at a normal breathing frequency. PMID:10523407

  16. Plants and the central nervous system.

    PubMed

    Carlini, E A

    2003-06-01

    This review article draws the attention to the many species of plants possessing activity on the central nervous system (CNS). In fact, they cover the whole spectrum of central activity such as psychoanaleptic, psycholeptic and psychodysleptic effects, and several of these plants are currently used in therapeutics to treat human ailments. Among the psychoanaleptic (stimulant) plants, those utilized by human beings to reduce body weight [Ephedra spp. (Ma Huang), Paullinia spp. (guaraná), Catha edulis Forssk. (khat)] and plants used to improve general health conditions (plant adaptogens) were scrutinized. Many species of hallucinogenic (psychodysleptic) plants are used by humans throughout the world to achieve states of mind distortions; among those, a few have been used for therapeutic purposes, such as Cannabis sativa L., Tabernanthe iboga Baill. and the mixture of Psychotria viridis Ruiz and Pav. and Banisteriopsis caapi (Spruce ex Griseb.) C.V. Morton. Plants showing central psycholeptic activities, such as analgesic or anxiolytic actions (Passiflora incarnata L., Valeriana spp. and Piper methysticum G. Forst.), were also analysed.Finally, the use of crude or semipurified extracts of such plants instead of the active substances seemingly responsible for their therapeutic effect is discussed. PMID:12895668

  17. Photoplethysmographic measurements from central nervous system tissue

    NASA Astrophysics Data System (ADS)

    Phillips, J. P.; Kyriacou, P. A.; Chang, S. H.; Maney, K.; George, K. J.; Langford, R. M.

    2007-10-01

    A new system for measuring the oxygen saturation of blood within tissue has been developed, for a number of potential patient monitoring applications. This proof of concept project aims to address the unmet need of real-time measurement of oxygen saturation in the central nervous system (CNS) for patients recovering from neurosurgery or trauma, by developing a fibre optic signal acquisition system for internal placement through small apertures. The development and testing of a two-wavelength optical fibre reflectance photoplethysmography (PPG) system is described together with measurements in rats and preliminary results from a clinical trial of the system in patients undergoing neurosurgery. It was found that good quality red and near-infrared PPG signals could be consistently obtained from the rat spinal cord (n=6) and human cerebral cortex (n=4) using the fibre optic probe. These findings justify further development and clinical evaluation of this fibre optic system.

  18. Central nervous system toxicity of metallic nanoparticles

    PubMed Central

    Feng, Xiaoli; Chen, Aijie; Zhang, Yanli; Wang, Jianfeng; Shao, Longquan; Wei, Limin

    2015-01-01

    Nanomaterials (NMs) are increasingly used for the therapy, diagnosis, and monitoring of disease- or drug-induced mechanisms in the human biological system. In view of their small size, after certain modifications, NMs have the capacity to bypass or cross the blood–brain barrier. Nanotechnology is particularly advantageous in the field of neurology. Examples may include the utilization of nanoparticle (NP)-based drug carriers to readily cross the blood–brain barrier to treat central nervous system (CNS) diseases, nanoscaffolds for axonal regeneration, nanoelectromechanical systems in neurological operations, and NPs in molecular imaging and CNS imaging. However, NPs can also be potentially hazardous to the CNS in terms of nano-neurotoxicity via several possible mechanisms, such as oxidative stress, autophagy, and lysosome dysfunction, and the activation of certain signaling pathways. In this review, we discuss the dual effect of NMs on the CNS and the mechanisms involved. The limitations of the current research are also discussed. PMID:26170667

  19. Emerging infections of the central nervous system.

    PubMed

    Lyons, Jennifer; McArthur, Justin

    2013-12-01

    Emerging infections affecting the central nervous system often present as encephalitis and can cause substantial morbidity and mortality. Diagnosis requires not only careful history taking, but also the application of newly developed diagnostic tests. These diseases frequently occur in outbreaks stemming from viruses that have mutated from an animal host and gained the ability to infect humans. With globalization, this can translate to the rapid emergence of infectious clusters or the establishment of endemicity in previously naïve locations. Since these infections are often vector borne and effective treatments are almost uniformly lacking, prevention is at least as important as prompt diagnosis and institution of supportive care. In this review, we focus on some of the recent literature addressing emerging and resurging viral encephalitides in the United States and around the world-specifically, West Nile virus, dengue, polio, and cycloviruses. We also discuss new, or "emerging," techniques for the precise and rapid diagnosis of encephalitides. PMID:24136412

  20. Central nervous system phenotypes in craniosynostosis

    PubMed Central

    Aldridge, Kristina; Marsh, Jeffrey L; Govier, Daniel; Richtsmeier, Joan T

    2002-01-01

    Though reduction in the number of cranial elements through loss of a suture is a recognized trend in vertebrate evolution, the premature closure of cranial sutures in humans, craniosynostosis, is considered a pathological condition. Previous research on craniosynostosis has focused primarily on the skeletal phenotype, but the intimate relationship between the developing central nervous system (CNS) and skull is well documented. We investigate the morphology of the CNS in patients with isolated craniosynostosis through an analysis of cortical and subcortical features using 3-D magnetic resonance images (MRI). Results show that a distinct CNS phenotype can be defined for specific diagnostic categories. Many differences in CNS morphology observed in the patient samples may be anticipated based on skeletal morphology, but others are not reflected in the skull. We propose a developmental approach to determining the cause of premature suture fusion, which includes investigation of the craniofacial complex as a system, rather than study of isolated tissues. PMID:12171474

  1. 75 FR 75681 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-06

    ... HUMAN SERVICES Food and Drug Administration Peripheral and Central Nervous System Drugs Advisory...). The meeting will be open to the public. Name of Committee: Peripheral and Central Nervous System Drugs... and circulation) of the central nervous system. The BBB is an area consisting of specialized...

  2. [Parasitic diseases of the central nervous system].

    PubMed

    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.). PMID:20111855

  3. Central nervous system manifestations of Angiostrongylus cantonensis infection.

    PubMed

    Martins, Yuri C; Tanowitz, Herbert B; Kazacos, Kevin R

    2015-01-01

    Over 20 species of Angiostrongylus have been described from around the world, but only Angiostrongylus cantonensis has been confirmed to cause central nervous system disease in humans. A neurotropic parasite that matures in the pulmonary arteries of rats, A. cantonensis is the most common cause of eosinophilic meningitis in southern Asia and the Pacific and Caribbean islands. The parasite can also cause encephalitis/encephalomyelitis and rarely ocular angiostrongyliasis. The present paper reviews the life cycle, epidemiology, pathogenesis, clinical features, diagnosis, treatment, prevention and prognosis of A. cantonesis infection. Emphasis is given on the spectrum of central nervous system manifestations and disease pathogenesis. PMID:25312338

  4. Central nervous system manifestations of Angiostrongylus cantonensis infection

    PubMed Central

    Martins, Yuri C.; Tanowitz, Herbert B.; Kazacos, Kevin R.

    2014-01-01

    Over 20 species of Angiostrongylus have been described from around the world, but only Angiostrongylus cantonensis has been confirmed to cause central nervous system disease in humans. A neurotropic parasite that matures in the pulmonary arteries of rats, A. cantonensis is the most common cause of eosinophilic meningitis in southern Asia and the Pacific and Caribbean islands. The parasite can also cause encephalitis/encephalomyelitis and rarely ocular angiostrongyliasis. The present paper reviews the life cycle, epidemiology, pathogenesis, clinical features, diagnosis, treatment, prevention and prognosis of A. cantonesis infection. Emphasis is given on the spectrum of central nervous system manifestations and disease pathogenesis. PMID:25312338

  5. Imaging the fetal central nervous system

    PubMed Central

    De Keersmaecker, B.; Claus, F.; De Catte, L.

    2011-01-01

    The low prevalence of fetal central nervous system anomalies results in a restricted level of exposure and limited experience for most of the obstetricians involved in prenatal ultrasound. Sonographic guidelines for screening the fetal brain in a systematic way will probably increase the detection rate and enhance a correct referral to a tertiary care center, offering the patient a multidisciplinary approach of the condition. This paper aims to elaborate on prenatal sonographic and magnetic resonance imaging (MRI) diagnosis and outcome of various central nervous system malformations. Detailed neurosonographic investigation has become available through high resolution vaginal ultrasound probes and the development of a variety of 3D ultrasound modalities e.g. ultrasound tomographic imaging. In addition, fetal MRI is particularly helpful in the detection of gyration and neurulation anomalies and disorders of the gray and white matter. PMID:24753859

  6. Computed tomography of the central nervous system

    SciTech Connect

    Bentson, J.R.

    1982-01-01

    The objective of this chapter is to review the most pertinent articles published during the past year on the subject of computed tomography of the central nervous system. The chapter contains sections on pediatric computed tomography, and on the diagnostic use of CT in white matter disease, in infectious disease, for intracranial aneurysms, trauma, and intracranial tumors. Metrizamide flow studies and contrast enhancement are also examined. (KRM)

  7. Gravitational Study of the Central Nervous System

    NASA Technical Reports Server (NTRS)

    Horowitz, J. M.

    1983-01-01

    A series of experiments conducted at 1G are discussed with reference to the role of calcium ions in information processing by the central nervous system. A technique is described which allows thin sections of a mammalian hippocampus to be isolated while maintaining neural activity. Two experiments carried out in hypergravic fields are also addressed; one investigating altered stimulation in the auditory system, the other determining temperature regulation responses in hypergravic fields.

  8. Zygomycotic invasion of the central nervous system.

    PubMed

    Sasaki, Tomoaki; Mineta, Masayuki; Kobayashi, Keigo; Ando, Masakatsu; Obata, Masahiko

    2010-06-01

    Zygomycosis is an opportunistic fungal infection that affects the central nervous system (CNS). In this report, we present three cases of zygomycosis with CNS involvement. In two patients zygomycosis developed after neurosurgery, and in the third patient zygomycosis developed after bone marrow transplantation for leukemia. All patients developed persistent fever and neurological deficits. They presented with progressive cerebral infarction accompanied by hemorrhage. Intraoperative findings and histopathological examinations revealed that zygomycotic hyphae caused mycotic aneurysm, vasculitis, and venous occlusion. PMID:20585927

  9. α-Synuclein in human cerebrospinal fluid is principally derived from neurons of the central nervous system.

    PubMed

    Mollenhauer, Brit; Trautmann, Ellen; Otte, Birgit; Ng, Juliana; Spreer, Annette; Lange, Peter; Sixel-Döring, Friederike; Hakimi, Mansoureh; Vonsattel, Jean-Paul; Nussbaum, Robert; Trenkwalder, Claudia; Schlossmacher, Michael G

    2012-07-01

    The source of Parkinson disease-linked α-synuclein (aSyn) in human cerebrospinal fluid (CSF) remains unknown. We decided to measure the concentration of aSyn and its gradient in human CSF specimens and compared it with serum to explore its origin. We correlated aSyn concentrations in CSF versus serum (Q(aSyn)) to the albumin quotient (Q(albumin)) to evaluate its relation to blood-CSF barrier function. We also compared aSyn with several other CSF constituents of either central or peripheral sources (or both) including albumin, neuron-specific enolase, β-trace protein and total protein content. Finally, we examined whether aSyn is present within the structures of the choroid plexus (CP). We observed that Q(aSyn) did not rise or fall with Q(albumin) values, a relative measure of blood-CSF barrier integrity. In our CSF gradient analyses, aSyn levels decreased slightly from rostral to caudal fractions, in parallel to the recorded changes for neuron-specific enolase; the opposite trend was recorded for total protein, albumin and β-trace protein. The latter showed higher concentrations in caudal CSF fractions due to the diffusion-mediated transfer of proteins from blood and leptomeninges into CSF in the lower regions of the spine. In postmortem sections of human brain, we detected highly variable aSyn reactivity within the epithelial cell layer of CP in patients diagnosed with a range of neurological diseases; however, in sections of mice that express only human SNCA alleles (and in those without any Snca gene expression), we detected no aSyn signal in the epithelial cells of the CP. We conclude from these complementary results that despite its higher levels in peripheral blood products, neurons of the brain and spinal cord represent the principal source of aSyn in human CSF. PMID:22426833

  10. Human nervous system function emulator.

    PubMed

    Frenger, P

    2000-01-01

    This paper describes a modular, extensible, open-systems design for a multiprocessor network which emulates the major functions of the human nervous system. Interchangeable hardware/software components, a socketed software bus with plug-and-play capability and self diagnostics are included. The computer hardware is based on IEEE P996.1 bus cards. Its operating system utilizes IEEE 1275 standard software. Object oriented design techniques and programming are featured. A machine-independent high level script-based command language was created for this project. Neural anatomical structures which were emulated include the cortex, brainstem, cerebellum, spinal cord, autonomic and peripheral nervous systems. Motor, sensory, autoregulatory, and higher cognitive artificial intelligence, behavioral and emotional functions are provided. The author discusses how he has interfaced this emulator to machine vision, speech recognition/speech synthesis, an artificial neural network and a dexterous hand to form an android robotic platform. PMID:10834247

  11. Vascularisation of the central nervous system

    PubMed Central

    Tata, Mathew; Ruhrberg, Christiana; Fantin, Alessandro

    2015-01-01

    The developing central nervous system (CNS) is vascularised through the angiogenic invasion of blood vessels from a perineural vascular plexus, followed by continued sprouting and remodelling until a hierarchical vascular network is formed. Remarkably, vascularisation occurs without perturbing the intricate architecture of the neurogenic niches or the emerging neural networks. We discuss the mouse hindbrain, forebrain and retina as widely used models to study developmental angiogenesis in the mammalian CNS and provide an overview of key cellular and molecular mechanisms regulating the vascularisation of these organs. PMID:26222953

  12. Catastrophic primary central nervous system vasculitis.

    PubMed

    Salvarani, Carlo; Brown, Robert D; Morris, Jonathan M; Huston, John; Hunder, Gene G

    2014-01-01

    Primary central nervous system vasculitis (PCNSV) is an uncommon condition that affects the brain and the spinal cord. It is heterogeneous in presenting characteristics and outcomes. We report a patient with a catastrophic rapidly progressive course refractory to intensive treatment with pulses of methylprednisolone and iv cyclophosphamide. The condition rapidly deteriorated and the patient died 6 weeks after presentation. Rapidly progressive PCNSV represents the worst end of the clinical spectrum of PCNSV. These patients are characterised by bilateral, multiple, large cerebral vessel lesions on angiograms and multiple bilateral cerebral infarctions. PMID:24854370

  13. Central Nervous System Complications of Oncologic Therapy.

    PubMed

    Hoeffner, Ellen G

    2016-08-01

    Traditional and newer agents used to treat cancer can cause significant toxicity to the central nervous system. MRI of the brain and spine is the imaging modality of choice for patients with cancer who develop neurologic symptoms. It is important to be aware of the agents that can cause neurotoxicity and their associated imaging findings so that patients are properly diagnosed and treated. In some instances conventional MRI may not be able to differentiate posttreatment effects from disease progression. In these instances advanced imaging techniques may be helpful, although further research is still needed. PMID:27444003

  14. Histoplasmosis of the central nervous system.

    PubMed Central

    Tan, V; Wilkins, P; Badve, S; Coppen, M; Lucas, S; Hay, R; Schon, F

    1992-01-01

    Histoplasma capsulatum infection of the central nervous system is extremely rare in the United Kingdom partly because the organism is not endemic. However, because the organism can remain quiescent in the lungs or the adrenal glands for over 40 years before dissemination, it increasingly needs to be considered in unexplained neurological disease particularly in people who lived in endemic areas as children. In this paper a rapidly progressive fatal myelopathy in an English man brought up in India was shown at necropsy to be due to histoplasmosis. The neurological features of this infection are reviewed. Images PMID:1640242

  15. Neuroimaging in Central Nervous System Lymphoma.

    PubMed

    Nabavizadeh, Seyed Ali; Vossough, Arastoo; Hajmomenian, Mehrdad; Assadsangabi, Reza; Mohan, Suyash

    2016-08-01

    Primary central nervous system lymphoma (PCNSL) is a rare aggressive high-grade type of extranodal lymphoma. PCNSL can have a variable imaging appearance and can mimic other brain disorders such as encephalitis, demyelination, and stroke. In addition to PCNSL, the CNS can be secondarily involved by systemic lymphoma. Computed tomography and conventional MRI are the initial imaging modalities to evaluate these lesions. Recently, however, advanced MRI techniques are more often used in an effort to narrow the differential diagnosis and potentially inform diagnostic and therapeutic decisions. PMID:27443998

  16. Mold Infections of the Central Nervous System

    PubMed Central

    McCarthy, Matthew; Rosengart, Axel; Schuetz, Audrey N.; Kontoyiannis, Dimitrios P.; Walsh, Thomas J.

    2016-01-01

    The recent outbreak of exserohilum rostratum meningitis linked to epidural injections of methylprednisolone acetate has brought renewed attention to mold infections of the central nervous system (CNS).1 Although uncommon, these infections are often devastating and difficult to treat. This focused review of the epidemiologic aspects, clinical characteristics, and treatment of mold infections of the CNS covers a group of common pathogens: aspergillus, fusarium, and scedosporium species, molds in the order Mucorales, and dematiaceous molds. Infections caused by these pathogen groups have distinctive epidemiologic profiles, clinical manifestations, microbiologic characteristics, and therapeutic implications, all of which clinicians should understand. PMID:25006721

  17. Activation of Latent Human Immunodeficiency Virus by the Histone Deacetylase Inhibitor Panobinostat: A Pilot Study to Assess Effects on the Central Nervous System

    PubMed Central

    Rasmussen, Thomas A.; Tolstrup, Martin; Møller, Holger Jon; Brinkmann, Christel R.; Olesen, Rikke; Erikstrup, Christian; Laursen, Alex L.; Østergaard, Lars; Søgaard, Ole S.

    2015-01-01

    In a substudy of a clinical trial, we assessed whether activation of latent human immunodeficiency virus (HIV) by the histone deacetylase inhibitor panobinostat had detrimental effects on the central nervous system (CNS). Adults infected with HIV received oral panobinostat 20 mg 3 times per week every other week for 8 weeks. In cerebrospinal fluid (CSF), we assayed panobinostat concentration, HIV RNA, and the level of neuroinflammatory or degenerative biomarkers in 11 individuals before and during study therapy. Neither panobinostat nor HIV RNA was detected in CSF. In addition, there was no change from baseline in CSF biomarkers. Thus, panobinostat administration was not associated with CNS adverse effects as assessed by CSF biomarkers. PMID:26034779

  18. The central nervous system of ascidian larvae.

    PubMed

    Hudson, Clare

    2016-09-01

    Ascidians are marine invertebrate chordates. Their tadpole larvae contain a dorsal tubular nervous system, resulting from the rolling up of a neural plate. Along the anterior-posterior (A-P) axis, the central nervous system (CNS) is organized into a sensory vesicle, neck, trunk ganglion, and tail nerve cord and consists of approximately only 330 cells, of which around 100 are thought to be neurons. The organization of distinct neuronal cell types and neurotransmitter gene expression within the CNS has been described. The unique developmental mode of ascidians, with a small number of cells and a fixed cell division pattern, allows individual cells to be traced throughout development. This feature has led to the complete documentation of the cell lineages of certain cell types in the CNS. Thus, a step-by-step understanding of nervous system development from the initial stages of neural induction to the neurogenesis of individual neurons is a feasible goal. The genetic control of neural fate induction and early neural plate patterning are now well understood. The molecular mechanisms specifying the cholinergic neurons of the trunk ganglion as well as the pigment cells of the sensory organs are also well elucidated. In addition, studies have begun on the morphogenetic processes of neurulation. Remaining challenges include building an embryonic atlas integrating gene expression patterns, cell lineage, and neuronal cell types as well as developing the gene regulatory networks of cell fate specification and integrating them with the genetic control of morphogenesis. WIREs Dev Biol 2016, 5:538-561. doi: 10.1002/wdev.239 For further resources related to this article, please visit the WIREs website. PMID:27328318

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

    NASA Astrophysics Data System (ADS)

    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.

  20. VIIP: Central Nervous System (CNS) Modeling

    NASA Technical Reports Server (NTRS)

    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.

  1. Advances in Primary Central Nervous System Lymphoma.

    PubMed

    Patrick, Lauren B; Mohile, Nimish A

    2015-12-01

    Primary central nervous system lymphoma (PCNSL) is a rare form of non-Hodgkin lymphoma that is limited to the CNS. Although novel imaging techniques aid in discriminating lymphoma from other brain tumors, definitive diagnosis requires brain biopsy, vitreoretinal biopsy, or cerebrospinal fluid analysis. Survival rates in clinical studies have improved over the past 20 years due to the addition of high-dose methotrexate-based chemotherapy regimens to whole-brain radiotherapy. Long-term survival, however, is complicated by clinically devastating delayed neurotoxicity. Newer regimens are attempting to reduce or eliminate radiotherapy from first-line treatment with chemotherapy dose intensification. Significant advances have also been made in the fields of pathobiology and treatment, with more targeted treatments on the horizon. The rarity of the disease makes conducting of prospective clinical trials challenging, requiring collaborative efforts between institutions. This review highlights recent advances in the biology, detection, and treatment of PCNSL in immunocompetent patients. PMID:26475775

  2. [Histopathology of central nervous system cavernomas].

    PubMed

    Mosnier, J-F; Brunon, J; Nuti, C

    2007-06-01

    Central nervous system cavernomas are vascular malformations, which occur in two circumstances: sporadic forms and familial autosomal dominant forms. The lesion consists of enlarged, closely packed vessels without interposition of brain parenchyma, surrounded by hemosiderin and gliosis, calcified in few cases. In 80% of sporadic forms the lesion is unique, multiple lesions are rare (median: 4). In familial forms the lesions are always multiple. Cavernomas are often associated with other vascular malformations, especially with venous developmental anomalies. The size of cavernomas is variable from 1 mm to several centimeters. About 70% of cases are supratentorial and 30% in the posterior fossa, particularly in the brain stem. Macroscopic and histopathological findings are typical and the diagnostic is generally easy. PMID:17498756

  3. Scaffolds for central nervous system tissue engineering

    NASA Astrophysics Data System (ADS)

    He, Jin; Wang, Xiu-Mei; Spector, Myron; Cui, Fu-Zhai

    2012-03-01

    Traumatic injuries to the brain and spinal cord of the central nervous system (CNS) lead to severe and permanent neurological deficits and to date there is no universally accepted treatment. Owing to the profound impact, extensive studies have been carried out aiming at reducing inflammatory responses and overcoming the inhibitory environment in the CNS after injury so as to enhance regeneration. Artificial scaffolds may provide a suitable environment for axonal regeneration and functional recovery, and are of particular importance in cases in which the injury has resulted in a cavitary defect. In this review we discuss development of scaffolds for CNS tissue engineering, focusing on mechanism of CNS injuries, various biomaterials that have been used in studies, and current strategies for designing and fabricating scaffolds.

  4. 78 FR 63481 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-24

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Peripheral and Central Nervous System Drugs Advisory...). The meeting will be open to the public. Name of Committee: Peripheral and Central Nervous System...

  5. 77 FR 20037 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-03

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Peripheral and Central Nervous System Drugs Advisory...). The meeting will be open to the public. Name of Committee: Peripheral and Central Nervous System...

  6. 78 FR 20328 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-04

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Peripheral and Central Nervous System Drugs Advisory...). The meeting will be open to the public. Name of Committee: Peripheral and Central Nervous System...

  7. 75 FR 36428 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-25

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Peripheral and Central Nervous System Drugs Advisory...). The meeting will be open to the public. Name of Committee: Peripheral and Central Nervous System...

  8. 75 FR 12768 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-17

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Peripheral and Central Nervous System Drugs Advisory...). The meeting will be open to the public. Name of Committee: Peripheral and Central Nervous System...

  9. 76 FR 3912 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-21

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Peripheral and Central Nervous System Drugs Advisory...). The meeting will be open to the public. Name of Committee: Peripheral and Central Nervous System...

  10. 75 FR 17417 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-06

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Peripheral and Central Nervous System Drugs Advisory...). The meeting will be open to the public. Name of Committee: Peripheral and Central Nervous System...

  11. 78 FR 63478 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-24

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Peripheral and Central Nervous System Drugs Advisory...). The meeting will be open to the public. Name of Committee: Peripheral and Central Nervous System...

  12. Neurotropic Enterovirus Infections in the Central Nervous System

    PubMed Central

    Huang, Hsing-I; Shih, Shin-Ru

    2015-01-01

    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. PMID:26610549

  13. Herpesvirus infections of the central nervous system in immunocompromised patients

    PubMed Central

    Strank, Cornelia

    2012-01-01

    Human herpesviruses may cause infections of the central nervous system during primary infection or following reactivation from a latent state. Especially in immunosuppressed patients the infection can take a life-threatening course, and therefore early diagnosis of herpesvirus-associated neurological diseases should have high priority. Clinical presentation in these patients is usually without typical features, making diagnosis even more challenging. Therefore general broad testing for different herpesviruses in cerebrospinal fluid samples is highly recommended. In addition, determination of the virus DNA level in the cerebrospinal fluid by quantitative assays seems to be of high importance to determine prognosis. Moreover, it might help to differentiate between specific virus-associated disease and unspecific presence of virus in the cerebrospinal fluid, especially in immunocompromised patients. Polymerase chain reaction analysis of cerebrospinal fluid has revolutionized the diagnosis of nervous system viral infections, particularly those caused by human herpesviruses. This review summarizes the role human herpesviruses play in central nervous system infections in immunocompromised patients, with a focus on the clinical manifestation of encephalitis. PMID:22973424

  14. The human myelin basic protein gene is included within a 179-kilobase transcription unit: Expression in the immune and central nervous systems

    SciTech Connect

    Pribyl, T.M.; Campagnoni, C.W.; Kampf, K.; Kashima, T.; Handley, V.W.; Campagnoni, A.T. ); McMahon, J. )

    1993-11-15

    Two human Golli (for gene expressed in the oligodendrocyte lineage)-MBP (for myelin basic protein) cDNAs have been isolated from a human oligodendroglioma cell line. Analysis of these cDNAs has enabled the authors to determine the entire structure of the human Golli-MBP gene. The Golli-MBP gene, which encompasses the MBP transcription unit, is [approx] 179 kb in length and consists of 10 exons, seven of which constitute the MBP gene. The human Golli-MBP gene contains two transcription start sites, each of which gives rise to a family of alternatively spliced transcipts. At least two Golli-MBP transcripts, containing the first three exons of the gene and one or more MBP exons, are produced from the first transcription start site. The second family of transcripts contains only MBP exons and produces the well-known MBPs. In humans, RNA blot analysis revealed that Golli-MBP transcripts were expressed in fetal thymus, spleen, and human B-cell and macrophage cell lines, as well as in fetal spinal cord. These findings clearly link the expression of exons encoding the autoimmunogen/encephalitogen MBP in the central nervous system to cells and tissues of the immune system through normal expression of the Golli-MBP gene. They also establish that this genetic locus, which includes the MBP gene, is conserved among species, providing further evidence that the MBP transcription unit is an integral part of the Golli transcription unit and suggest that this structural arrangement is important for the genetic function and/or regulation of these genes.

  15. Central nervous system adaptation to exercise training

    NASA Astrophysics Data System (ADS)

    Kaminski, Lois Anne

    Exercise training causes physiological changes in skeletal muscle that results in enhanced performance in humans and animals. Despite numerous studies on exercise effects on skeletal muscle, relatively little is known about adaptive changes in the central nervous system. This study investigated whether spinal pathways that mediate locomotor activity undergo functional adaptation after 28 days of exercise training. Ventral horn spinal cord expression of calcitonin gene-related peptide (CGRP), a trophic factor at the neuromuscular junction, choline acetyltransferase (Chat), the synthetic enzyme for acetylcholine, vesicular acetylcholine transporter (Vacht), a transporter of ACh into synaptic vesicles and calcineurin (CaN), a protein phosphatase that phosphorylates ion channels and exocytosis machinery were measured to determine if changes in expression occurred in response to physical activity. Expression of these proteins was determined by western blot and immunohistochemistry (IHC). Comparisons between sedentary controls and animals that underwent either endurance training or resistance training were made. Control rats received no exercise other than normal cage activity. Endurance-trained rats were exercised 6 days/wk at 31m/min on a treadmill (8% incline) for 100 minutes. Resistance-trained rats supported their weight plus an additional load (70--80% body weight) on a 60° incline (3 x 3 min, 5 days/wk). CGRP expression was measured by radioimmunoassay (RIA). CGRP expression in the spinal dorsal and ventral horn of exercise-trained animals was not significantly different than controls. Chat expression measured by Western blot and IHC was not significantly different between runners and controls but expression in resistance-trained animals assayed by IHC was significantly less than controls and runners. Vacht and CaN immunoreactivity in motor neurons of endurance-trained rats was significantly elevated relative to control and resistance-trained animals. Ventral

  16. West Nile Virus Infection in the Central Nervous System

    PubMed Central

    Winkelmann, Evandro R.; Luo, Huanle; Wang, Tian

    2016-01-01

    West Nile virus (WNV), a neurotropic single-stranded flavivirus has been the leading cause of arboviral encephalitis worldwide.  Up to 50% of WNV convalescent patients in the United States were reported to have long-term neurological sequelae.  Neither antiviral drugs nor vaccines are available for humans.  Animal models have been used to investigate WNV pathogenesis and host immune response in humans.  In this review, we will discuss recent findings from studies in animal models of WNV infection, and provide new insights on WNV pathogenesis and WNV-induced host immunity in the central nervous system. PMID:26918172

  17. Prenatal diagnosis of central nervous system abnormalities.

    PubMed

    Angtuaco, E E; Angtuaco, T L; Angtuaco, E J

    1994-01-01

    Fetal anomalies have been the subject of innumerable publications both in the prenatal and neonatal literature. This has significantly increased in the last 10 years, mainly because of the advent of high-resolution ultrasound equipment and improvement of scanning techniques. In addition, guidelines issued by professional organizations involved in prenatal diagnosis have encouraged a more universal approach to the imaging and documentation of prenatal findings. The fetal central nervous system is the most frequently investigated organ system, mainly because of its easy accessibility and prominence even in the early stages of embryologic development. The biparietal diameter was the first fetal measurement to be widely used in determining gestational age. As investigators gained more experience, the appearance of ultrasound images achieved the resolution that allows direct comparisons with gross specimens and more recent sophisticated techniques of computed tomography and magnetic resonance imaging. Now endovaginal ultrasound can document early first trimester development and compare it to known embryologic landmarks. Interest in demonstrating the ultrasound counterpart of central nervous system structures in the early stages of development has resulted in a plethora of articles proving the unique ability of ultrasound in imaging the developing fetus. In view of all these developments, the beginning ultrasound specialist is faced with the challenge and responsibility not only of being familiar with the literature but also of the mastery of scanning techniques that allow accurate prenatal diagnosis. It is therefore helpful to review key developmental milestones in embryologic life and correlate them with the corresponding prenatal ultrasound appearance. In addition, the changing appearance of the developing fetus has created a need for a systematic approach in the evaluation of structures so routine protocols can be established. This has been the subject of other

  18. Environmental effects on the central nervous system.

    PubMed Central

    Paulson, G W

    1977-01-01

    The central nervous system (CNS) is designed to respond to the environment and is peculiarly vulnerable to many of the influences found in the environment. Utilizing an anatomical classification (cortex, cerebellum, peripheral nerves) major toxins and stresses are reviewed with selections from recent references. Selective vulnerability of certain areas to particular toxins is apparent at all levels of the CNS, although the amount of damage produced by any noxious agent depends on the age and genetic substrate of the subject. It is apparent that the effects of certain well known and long respected environmental toxins such as lead, mercury, etc., deserve continued surveillance. In addition, the overwhelming impact on the CNS of social damages such as trauma, alcohol, and tobacco cannot be ignored by environmentalists. The effect of the hospital and therapeutic environment has become apparent in view of increased awareness of iatrogenic disorders. The need for particular laboratory tests, for example, examination of CSF and nerve conduction toxicity studies, is suggested. Epidemics such as the recent solvent neuropathies suggest a need for continued animal studies that are chronic, as well as acute evaluations when predicting the potential toxic effects of industrial compounds. PMID:202447

  19. Central Nervous System Immune Reconstitution Inflammatory Syndrome

    PubMed Central

    Boulware, David R.; Marais, Suzaan; Scriven, James; Wilkinson, Robert J.; Meintjes, Graeme

    2013-01-01

    Central nervous system immune reconstitution inflammatory syndrome (CNS-IRIS) develops in 9 %–47 % of persons with HIV infection and a CNS opportunistic infection who start antiretroviral therapy and is associated with a mortality rate of 13 %–75 %. These rates vary according to the causative pathogen. Common CNS-IRIS events occur in relation to Cryptococcus, tuberculosis (TB), and JC virus, but several other mycobacteria, fungi, and viruses have been associated with IRIS. IRIS symptoms often mimic the original infection, and diagnosis necessitates consideration of treatment failure, microbial resistance, and an additional neurological infection. These diagnostic challenges often delay IRIS diagnosis and treatment. Corticosteroids have been used to treat CNS-IRIS, with variable responses; the best supportive evidence exists for the treatment of TB-IRIS. Pathogenic mechanisms vary: Cryptococcal IRIS is characterized by a paucity of cerebrospinal inflammation prior to antiretroviral therapy, whereas higher levels of inflammatory markers at baseline predispose to TB meningitis IRIS. This review focuses on advances in the understanding of CNS-IRIS over the past 2 years. PMID:24173584

  20. Time Perception Mechanisms at Central Nervous System

    PubMed Central

    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

    2016-01-01

    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. PMID:27127597

  1. Time Perception Mechanisms at Central Nervous System.

    PubMed

    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. PMID:27127597

  2. Central nervous system stimulants and sport practice

    PubMed Central

    Avois, L; Robinson, N; Saudan, C; Baume, N; Mangin, P; Saugy, M

    2006-01-01

    Background and objectives Central nervous system (CNS) stimulants may be used to reduce tiredness and increase alertness, competitiveness, and aggression. They are more likely to be used in competition but may be used during training to increase the intensity of the training session. There are several potential dangers involving their misuse in contact sports. This paper reviews the three main CNS stimulants, ephedrine, amfetamine, and cocaine, in relation to misuse in sport. Methods Description of the pharmacology, actions, and side effects of amfetamine, cocaine, and ephedrine. Results CNS stimulants have psychotropic effects that may be perceived to be ergogenic. Some are prescription drugs, such as Ephedra alkaloids, and there are issues regarding their appropriate therapeutic use. Recently attention has been given to their widespread use by athletes, despite the lack of evidence regarding any ergogenic or real performance benefit, and their potentially serious side effects. Recreational drugs, some of which are illegal (cocaine, amfetamines), are commonly used by athletes and cause potential ergolytic effects. Overall, these drugs are important for their frequent use and mention in anti‐doping laboratories statistics and the media, and their potentially serious adverse effects. Conclusions Doping with CNS stimulants is a real public health problem and all sports authorities should participate in its prevention. Dissemination of information is essential to prevent doping in sport and to provide alternatives. Adequate training and education in this domain should be introduced. PMID:16799095

  3. [Diagnostic imaging of central nervous system vasculitis].

    PubMed

    Yokota, Hajime; Yamada, Kei

    2015-03-01

    Vasculitis involving the central nervous system presents with infarction and hemorrhage, which are often nonspecific findings. Laboratory examinations are essential for diagnosis of vasculitis in addition to comprehensive and systematic review of the clinical course. Although most findings tend to be nonspecific, enhancement and thickening of the vascular wall indicate vasculitis. Visualization of the vascular wall requires selection of the appropriate imaging modality and mode of image acquisition. Contrast-enhanced CT, MRI, and FDG-PET are useful for visualizing large vessel vasculitis, while CT, MRI, and angiography are effective for medium vessel vasculitis. The use of ultrasound is limited to evaluating vessels on the body surface. Although relatively thick vessels can be demonstrated by angiography, complete survey of small vessels is difficult. Here, we summarize the characteristics of each imaging modality and imaging findings of typical vasculitides-Takayasu arteritis, giant cell arteritis, ANCA-associated vasculitis, Behçet's disease, primary angiitis of the CNS, and vasculitis associated with systemic disease. Differential diagnoses are also shown, including infective endocarditis, tuberculous meningitis, Ehlers-Danlos syndrome, and reversible cerebral vasoconstriction syndrome. PMID:25846439

  4. Extracellular matrix-remodeling metalloproteinases and infection of the central nervous system with retrovirus human T-lymphotropic virus type I (HTLV-I).

    PubMed

    Giraudon, P; Buart, S; Bernard, A; Thomasset, N; Belin, M F

    1996-06-01

    Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) are involved in physiological processes and contribute to the phenotype of several pathological conditions associated with uncontrolled tissue degradation. In the central nervous system (CNS), MMPs are thought to play a role in cell migration and synaptic plasticity. We have investigated the expression, regulation and possible role of MMPs and TIMPs during infection of glial cells with human T-lymphotropic virus type I (HTLV-I), the causative agent of a progressive chronic myelopathy, TSP/HAM. The major alteration consists in a high increase in MMP-9 secretion and TIMP-2 mRNA expression. Cytokines TNF alpha and IL1 alpha, induced in glial cells during HTLV-I infection, promote the upregulation of MMP-9. In addition, cerebrospinal fluid from TSP/HAM patients contain high MMP-9 level. The exact role of dysregulated MMPs/TIMPs in the pathogenesis of TSP/HAM is not known; however, functions of these proteases in physiological processes should provide valuable clues. MMPs can affect the blood-brain barrier and the intercellular connectivity by degrading the extracellular matrix of endothelial and neural cells. They can be involved in autoimmunity by generating preformed specific peptides from myelin components. Finally, they can direct and prolong TNF activity in the CNS by converting its inactive precursor into active molecules. PMID:8844825

  5. Human immunodeficiency virus type 1 expression in the central nervous system correlates directly with extent of disease

    SciTech Connect

    Weiser, B.; La Neve, D.; Eilbott, D.J.; Burger, H.; Seidman, R. ); Peress, N. Veterans Administration Medical Center, Northport, NY )

    1990-05-01

    To investigate human immunodeficiency virus type 1 (HIV-1) pathogenesis in infected individuals and examine the correlation of HIV-1 expression with extent of clinical and pathologic disease, the authors studied spinal cords from acquired immunodeficiency syndrome patients with a wide range of spinal cord pathology. By performing in situ hybridization with HIV-1-specific riboprobes, they detected HIV-1 RNA in all 10 cords from acquired immunodeficiency syndrome patients with a common, characteristic pathologic entity called vacuolar myelopathy but not in 10 control cords from HIV-1-infected and uninfected patients. In the cords from individuals with vacuolar myelopathy, the level of HIV-1 RNA expression correlated directly with extent of spinal cord pathology and clinical findings. These data support a role for HIV-1 int he pathogenesis of tissue damage and related clinical disease in infected individuals.

  6. Cleavage of a Neuroinvasive Human Respiratory Virus Spike Glycoprotein by Proprotein Convertases Modulates Neurovirulence and Virus Spread within the Central Nervous System

    PubMed Central

    Meessen-Pinard, Mathieu; Dubé, Mathieu; Day, Robert; Seidah, Nabil G.; Talbot, Pierre J.

    2015-01-01

    Human coronaviruses (HCoV) are respiratory pathogens that may be associated with the development of neurological diseases, in view of their neuroinvasive and neurotropic properties. The viral spike (S) glycoprotein is a major virulence factor for several coronavirus species, including the OC43 strain of HCoV (HCoV-OC43). In an attempt to study the role of this protein in virus spread within the central nervous system (CNS) and neurovirulence, as well as to identify amino acid residues important for such functions, we compared the sequence of the S gene found in the laboratory reference strain HCoV-OC43 ATCC VR-759 to S sequences of viruses detected in clinical isolates from the human respiratory tract. We identified one predominant mutation at amino acid 758 (from RRSR↓ G758 to RRSR↓R758), which introduces a putative furin-like cleavage (↓) site. Using a molecular cDNA infectious clone to generate a corresponding recombinant virus, we show for the first time that such point mutation in the HCoV-OC43 S glycoprotein creates a functional cleavage site between the S1 and S2 portions of the S protein. While the corresponding recombinant virus retained its neuroinvasive properties, this mutation led to decreased neurovirulence while potentially modifying the mode of virus spread, likely leading to a limited dissemination within the CNS. Taken together, these results are consistent with the adaptation of HCoV-OC43 to the CNS environment, resulting from the selection of quasi-species harboring mutations that lead to amino acid changes in viral genes, like the S gene in HCoV-OC43, which may contribute to a more efficient establishment of a less pathogenic but persistent CNS infection. This adaptative mechanism could potentially be associated with human encephalitis or other neurological degenerative pathologies. PMID:26545254

  7. Human CLP1 mutations alter tRNA biogenesis affecting both peripheral and central nervous system function

    PubMed Central

    Karaca, Ender; Weitzer, Stefan; Pehlivan, Davut; Shiraishi, Hiroshi; Gogakos, Tasos; Hanada, Toshikatsu; Jhangiani, Shalini N.; Wiszniewski, Wojciech; Withers, Marjorie; Campbell, Ian M.; Erdin, Serkan; Isikay, Sedat; Franco, Luis M.; Gonzaga-Jauregui, Claudia; Gambin, Tomasz; Gelowani, Violet; Hunter, Jill V.; Yesil, Gozde; Koparir, Erkan; Yilmaz, Sarenur; Brown, Miguel; Briskin, Daniel; Hafner, Markus; Morozov, Pavel; Farazi, Thalia A.; Bernreuther, Christian; Glatzel, Markus; Trattnig, Siegfried; Friske, Joachim; Kronnerwetter, Claudia; Bainbridge, Matthew N.; Gezdirici, Alper; Seven, Mehmet; Muzny, Donna M.; Boerwinkle, Eric; Ozen, Mustafa; Clausen, Tim; Tuschl, Thomas; Yuksel, Adnan; Hess, Andreas; Gibbs, Richard A.; Martinez, Javier; Penninger, Josef M.; Lupski, James R.

    2014-01-01

    CLP1 is a RNA kinase involved in tRNA splicing. Recently, CLP1 kinase-dead mice were shown to display a neuromuscular disorder with loss of motor neurons and muscle paralysis. Human genome analyses now identified a CLP1 homozygous missense mutation (p.R140H) in five unrelated families, leading to a loss of CLP1 interaction with the tRNA splicing endonuclease (TSEN) complex, largely reduced pre-tRNA cleavage activity, and accumulation of linear tRNA introns. The affected individuals develop severe motor-sensory defects, cortical dysgenesis and microcephaly. Mice carrying kinase-dead CLP1 also displayed microcephaly and reduced cortical brain volume due to the enhanced cell death of neuronal progenitors that is associated with reduced numbers of cortical neurons. Our data elucidate a novel neurological syndrome defined by CLP1 mutations that impair tRNA splicing. Reduction of a founder mutation to homozygosity illustrates the importance of rare variations in disease and supports the clan genomics hypothesis. PMID:24766809

  8. Gut Commensalism, Cytokines, and Central Nervous System Demyelination

    PubMed Central

    Ochoa-Repáraz, Javier; Kasper, Lloyd H.

    2014-01-01

    There is increasing support for the importance of risk factors such as genetic makeup, obesity, smoking, vitamin D insufficiency, and antibiotic exposure contributing to the development of autoimmune diseases, including human multiple sclerosis (MS). Perhaps the greatest environmental risk factor associated with the development of immune-mediated conditions is the gut microbiome. Microbial and helminthic agents are active participants in shaping the immune systems of their hosts. This concept is continually reinforced by studies in the burgeoning area of commensal-mediated immunomodulation. The clinical importance of these findings for MS is suggested by both their participation in disease and, perhaps of greater clinical importance, attenuation of disease severity. Observations made in murine models of central nervous system demyelinating disease and a limited number of small studies in human MS suggest that immune homeostasis within the gut microbiome may be of paramount importance in maintaining a disease-free state. This review describes three immunological factors associated with the gut microbiome that are central to cytokine network activities in MS pathogenesis: T helper cell polarization, T regulatory cell function, and B cell activity. Comparisons are drawn between the regulatory mechanisms attributed to first-line therapies and those described in commensal-mediated amelioration of central nervous system demyelination. PMID:25084177

  9. Gut commensalism, cytokines, and central nervous system demyelination.

    PubMed

    Telesford, Kiel; Ochoa-Repáraz, Javier; Kasper, Lloyd H

    2014-08-01

    There is increasing support for the importance of risk factors such as genetic makeup, obesity, smoking, vitamin D insufficiency, and antibiotic exposure contributing to the development of autoimmune diseases, including human multiple sclerosis (MS). Perhaps the greatest environmental risk factor associated with the development of immune-mediated conditions is the gut microbiome. Microbial and helminthic agents are active participants in shaping the immune systems of their hosts. This concept is continually reinforced by studies in the burgeoning area of commensal-mediated immunomodulation. The clinical importance of these findings for MS is suggested by both their participation in disease and, perhaps of greater clinical importance, attenuation of disease severity. Observations made in murine models of central nervous system demyelinating disease and a limited number of small studies in human MS suggest that immune homeostasis within the gut microbiome may be of paramount importance in maintaining a disease-free state. This review describes three immunological factors associated with the gut microbiome that are central to cytokine network activities in MS pathogenesis: T helper cell polarization, T regulatory cell function, and B cell activity. Comparisons are drawn between the regulatory mechanisms attributed to first-line therapies and those described in commensal-mediated amelioration of central nervous system demyelination. PMID:25084177

  10. Melatonin Metabolism in the Central Nervous System

    PubMed Central

    Hardeland, Rüdiger

    2010-01-01

    The metabolism of melatonin in the central nervous system is of interest for several reasons. Melatonin enters the brain either via the pineal recess or by uptake from the blood. It has been assumed to be also formed in some brain areas. Neuroprotection by melatonin has been demonstrated in numerous model systems, and various attempts have been undertaken to counteract neurodegeneration by melatonin treatment. Several concurrent pathways lead to different products. Cytochrome P450 subforms have been demonstrated in the brain. They either demethylate melatonin to N-acetylserotonin, or produce 6-hydroxymelatonin, which is mostly sulfated already in the CNS. Melatonin is deacetylated, at least in pineal gland and retina, to 5-methoxytryptamine. N1-acetyl-N2-formyl-5-methoxykynuramine is formed by pyrrole-ring cleavage, by myeloperoxidase, indoleamine 2,3-dioxygenase and various non-enzymatic oxidants. Its product, N1-acetyl-5-methoxykynuramine, is of interest as a scavenger of reactive oxygen and nitrogen species, mitochondrial modulator, downregulator of cyclooxygenase-2, inhibitor of cyclooxygenase, neuronal and inducible NO synthases. Contrary to other nitrosated aromates, the nitrosated kynuramine metabolite, 3-acetamidomethyl-6-methoxycinnolinone, does not re-donate NO. Various other products are formed from melatonin and its metabolites by interaction with reactive oxygen and nitrogen species. The relative contribution of the various pathways to melatonin catabolism seems to be influenced by microglia activation, oxidative stress and brain levels of melatonin, which may be strongly changed in experiments on neuroprotection. Many of the melatonin metabolites, which may appear in elevated concentrations after melatonin administration, possess biological or pharmacological properties, including N-acetylserotonin, 5-methoxytryptamine and some of its derivatives, and especially the 5-methoxylated kynuramines. PMID:21358968

  11. Radiation response of the central nervous system

    SciTech Connect

    Schultheiss, T.E.; Kun, L.E.; Stephens, L.C.

    1995-03-30

    This report reviews the anatomical, pathophysiological, and clinical aspects of radiation injury to the central nervous system (CNS). Despite the lack of pathoGyomonic characteristics for CNS radiation lesions, demyelination and malacia are consistently the dominant morphological features of radiation myelopathy. In addition, cerebral atrophy is commonly observed in patients with neurological deficits related to chemotherapy and radiation, and neurocognitive deficits are associated with diffuse white matter changes. Clinical and experimental dose-response information have been evaluated and summarized into specific recommendations for the spinal cord and brain. The common spinal cord dose limit of 45 Gn in 22 to 25 fractions is conservative and can be relaxed if respecting this limit materially reduces the probability of tumor control. It is suggested that the 5% incidence of radiation myelopathy probably lies between 57 and 61 Gy to the spinal cord in the absence of dose modifying chemotherapy. A clinically detectable length effect for the spinal cord has not been observed. The effects of chemotherapy and altered fractionation are also discussed. Brain necrosis in adults is rarely noted below 60 Gy in conventional fractionation, with imaging and clinical changes being observed generally only above 50 Gy. However, neurocognitive effects are observed at lower doses, especially in children. A more pronounced volume effect is believed to exist in the brain than in the spinal cord. Tumor progression may be hard to distinguish from radiation and chemotherapy effects. Diffuse white matter injury can be attributed to radiation and associated with neurological deficits, but leukoencephalopathy is rarely observed in the absence of chemotherapy. Subjective, objective, management, and analytic (SOMA) parameters related to radiation spinal cord and brain injury have been developed and presented on ordinal scales. 140 refs., 3 figs., 6 tabs.

  12. Strategies for Enhanced Drug Delivery to the Central Nervous System

    PubMed Central

    Dwibhashyam, V. S. N. M.; Nagappa, A. N.

    2008-01-01

    Treating central nervous system diseases is very challenging because of the presence of a variety of formidable obstacles that impede drug delivery. Physiological barriers like the blood-brain barrier and blood-cerebrospinal fluid barrier as well as various efflux transporter proteins make the entry of drugs into the central nervous system very difficult. The present review provides a brief account of the blood brain barrier, the P-glycoprotein efflux and various strategies for enhancing drug delivery to the central nervous system. PMID:20046703

  13. A Rare Case of Central Nervous System Tuberculosis

    PubMed Central

    Haftka, Alexis; Porter, Ashleigh

    2014-01-01

    Intracranial abscess is an extremely rare form of central nervous system (CNS) tuberculosis (TB). We describe a case of central nervous system tuberculous abscess in absence of human immunodeficiency virus (HIV) infection. A 82-year-old Middle Eastern male from Yemen was initially brought to the emergency room due to altered mental status and acute renal failure. Cross-sectional imaging revealed multiple ring enhancing lesions located in the left cerebellum and in bilateral frontal lobe as well as in the inferior parietal lobe on the left. The patient was placed on an empiric antibiotic regimen. Preliminary testing for infectious causes was negative. Chest radiography and CT of chest showed no positive findings. He was not on any immunosuppressive medications and human immunodeficiency virus (HIV) enzyme immunoassay (EIA) test was negative. A subsequent MRI one month later showed profound worsening of the lesions with increasing vasogenic edema and newly found mass effect impinging on the fourth ventricle. Brain biopsy showed focal exudative cerebellitis and inflamed granulation tissue consistent with formation of abscesses. The diagnosis of CNS TB was finally confirmed by positive acid-fast bacilli (AFB) cultures. The patient was started on standard tuberculosis therapy but expired due to renal failure and cardiac arrest. PMID:25478256

  14. Human T cell leukemia virus type I and neurologic disease: events in bone marrow, peripheral blood, and central nervous system during normal immune surveillance and neuroinflammation.

    PubMed

    Grant, Christian; Barmak, Kate; Alefantis, Timothy; Yao, Jing; Jacobson, Steven; Wigdahl, Brian

    2002-02-01

    Human T cell lymphotropic/leukemia virus type I (HTLV-I) has been identified as the causative agent of both adult T cell leukemia (ATL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Although the exact sequence of events that occur during the early stages of infection are not known in detail, the initial route of infection may predetermine, along with host, environmental, and viral factors, the subset of target cells and/or the primary immune response encountered by HTLV-I, and whether an HTLV-I-infected individual will remain asymptomatic, develop ATL, or progress to the neuroinflammatory disease, HAM/TSP. Although a large number of studies have indicated that CD4(+) T cells represent an important target for HTLV-I infection in the peripheral blood (PB), additional evidence has accumulated over the past several years demonstrating that HTLV-I can infect several additional cellular compartments in vivo, including CD8(+) T lymphocytes, PB monocytes, dendritic cells, B lymphocytes, and resident central nervous system (CNS) astrocytes. More importantly, extensive latent viral infection of the bone marrow, including cells likely to be hematopoietic progenitor cells, has been observed in individuals with HAM/TSP as well as some asymptomatic carriers, but to a much lesser extent in individuals with ATL. Furthermore, HTLV-I(+) CD34(+) hematopoietic progenitor cells can maintain the intact proviral genome and initiate viral gene expression during the differentiation process. Introduction of HTLV-I-infected bone marrow progenitor cells into the PB, followed by genomic activation and low level viral gene expression may lead to an increase in proviral DNA load in the PB, resulting in a progressive state of immune dysregulation including the generation of a detrimental cytotoxic Tax-specific CD8(+) T cell population, anti-HTLV-I antibodies, and neurotoxic cytokines involved in disruption of myelin-producing cells and neuronal degradation

  15. Central Nervous System Control of Voice and Swallowing

    PubMed Central

    Ludlow, Christy L.

    2015-01-01

    This review of the central nervous control systems for voice and swallowing has suggested that the traditional concepts of a separation between cortical and limbic and brain stem control should be refined and more integrative. For voice production, a separation of the non-human vocalization system from the human learned voice production system has been posited based primarily on studies of non-human primates. However, recent humans studies of emotionally based vocalizations and human volitional voice production has shown more integration between these two systems than previously proposed. Recent human studies have shown that reflexive vocalization as well as learned voice production not involving speech, involve a common integrative system. On the other hand, recent studies of non-human primates have provided evidence of some cortical activity during vocalization and cortical changes with training during vocal behavior. For swallowing, evidence from the macaque and functional brain imaging in humans indicates that the control for the pharyngeal phase of swallowing is not primarily under brain stem mechanisms as previously proposed. Studies suggest that the initiation and patterning of swallowing for the pharyngeal phase is also under active cortical control for both spontaneous as well as volitional swallowing in awake humans and non-human primates. PMID:26241238

  16. Pathogen-inspired drug delivery to the central nervous system

    PubMed Central

    McCall, Rebecca L; Cacaccio, Joseph; Wrabel, Eileen; Schwartz, Mary E; Coleman, Timothy P; Sirianni, Rachael W

    2014-01-01

    For as long as the human blood-brain barrier (BBB) has been evolving to exclude bloodborne agents from the central nervous system (CNS), pathogens have adopted a multitude of strategies to bypass it. Some pathogens, notably viruses and certain bacteria, enter the CNS in whole form, achieving direct physical passage through endothelial or neuronal cells to infect the brain. Other pathogens, including bacteria and multicellular eukaryotic organisms, secrete toxins that preferentially interact with specific cell types to exert a broad range of biological effects on peripheral and central neurons. In this review, we will discuss the directed mechanisms that viruses, bacteria, and the toxins secreted by higher order organisms use to enter the CNS. Our goal is to identify ligand-mediated strategies that could be used to improve the brain-specific delivery of engineered nanocarriers, including polymers, lipids, biologically sourced materials, and imaging agents. PMID:25610755

  17. General Information about Childhood Central Nervous System Embryonal Tumors

    MedlinePlus

    ... System Embryonal Tumors Treatment (PDQ®)–Patient Version General Information About Childhood Central Nervous System Embryonal Tumors Go ... in patients with a high-risk tumor. The information from tests and procedures done to detect (find) ...

  18. Are astrocytes executive cells within the central nervous system?

    PubMed

    Sica, Roberto E; Caccuri, Roberto; Quarracino, Cecilia; Capani, Francisco

    2016-08-01

    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. PMID:27556379

  19. Review: Glial lineages and myelination in the central nervous system

    PubMed Central

    COMPSTON, ALASTAIR; ZAJICEK, JOHN; SUSSMAN, JON; WEBB, ANNA; HALL, GILLIAN; MUIR, DAVID; SHAW, CHRISTOPHER; WOOD, ANDREW; SCOLDING, NEIL

    1997-01-01

    Oligodendrocytes, derived from stem cell precursors which arise in subventricular zones of the developing central nervous system, have as their specialist role the synthesis and maintenance of myelin. Astrocytes contribute to the cellular architecture of the central nervous system and act as a source of growth factors and cytokines; microglia are bone-marrow derived macrophages which function as primary immunocompetent cells in the central nervous system. Myelination depends on the establishment of stable relationships between each differentiated oligodendrocyte and short segments of several neighbouring axons. There is growing evidence, especially from studies of glial cell implantation, that oligodendrocyte precursors persist in the adult nervous system and provide a limited capacity for the restoration of structure and function in myelinated pathways damaged by injury or disease. PMID:9061442

  20. Morphologic features of human chorionic gonadotropin- or alpha-fetoprotein-producing germ cell tumors of the central nervous system: histological heterogeneity and surgical meaning.

    PubMed

    Sugiyama, K; Arita, K; Tominaga, A; Hanaya, R; Taniguchi, E; Okamura, T; Itoh, Y; Yamasaki, F; Kurisu, K

    2001-01-01

    Our study of germ cell tumors (GCT) of the central nervous system (CNS) investigated the relationship between tumor histology and patient serum titers of human chorionic gonadotropin (HGC) and alpha-fetoprotein (AFP). Thirty-five patients were enrolled. Their serum titers of HCG (mlU/ml) and/or AFP (ng/ml) before initial treatment were available, as were tumor specimens obtained before the administration of adjuvant therapy. They were divided into three groups, depending on whether HCG alone (group H), AFP alone (group A), or both HCG and AFP (group HA) were detected. Each group was subdivided into three groups: patients in group I had H, A, and/or HA titers below 9.9; patients in group II/III had titers from 10.0 to 999; and those in group IV had titers of 1000 or more. Serial sections of tissue specimens were repeatedly stained, mainly with hematoxylin and eosin (H-E) stain, HCG immunostain, and AFP immunostain. There were seven patients in the H-I group and five in H-II/III. Of these 12 patients, 11 had germinomas (G) and one had an embryonal carcinoma (EC). Five patients were included in group A: one was classified as A-II/III and had a germinoma, and the remaining four patients were in A-IV and had yolk sac tumors (YST) or mixed GCT consisting mainly of YST or EC (MXGCT-YST, EC). The HA group consisted of 18 patients. Three were classified as HA-I and had germinomas; nine HA-II/III patients had T or MXGCT-T; and six HA-IV patients had choriocarcinoma (CC), YST, MXGCT-CC, or MXGCT-YST. Throughout the study, the situations for the elevated serum titers could be elucidated in only four cases (three in group A-IV and one in group HA-IV). These results led to the conclusion that serologic evaluation is superior to morphologic evaluation in diagnosing marker-producing GCTs. From a diagnostic perspective, the role of surgery is to verify the HCG- and AFP-immunonegative tissue in patients with G, T, and EC. PMID:11908867

  1. Fungal Infections of the Central Nervous System: A Pictorial Review

    PubMed Central

    Gavito-Higuera, Jose; Mullins, Carola Birgit; Ramos-Duran, Luis; Olivas Chacon, Cristina Ivette; Hakim, Nawar; Palacios, Enrique

    2016-01-01

    Fungal infections of the central nervous system (CNS) pose a threat to especially immunocompromised patients and their development is primarily determined by the immune status of the host. With an increasing number of organ transplants, chemotherapy, and human immunodeficiency virus infections, the number of immunocompromised patients as susceptible hosts is growing and fungal infections of the CNS are more frequently encountered. They may result in meningitis, cerebritis, abscess formation, cryptococcoma, and meningeal vasculitis with rapid disease progression and often overlapping symptoms. Although radiological characteristics are often nonspecific, unique imaging patterns can be identified through computer tomography as a first imaging modality and further refined by magnetic resonance imaging. A rapid diagnosis and the institution of the appropriate therapy are crucial in helping prevent an often fatal outcome. PMID:27403402

  2. Emerging Viral Infections of the Central Nervous System

    PubMed Central

    Tyler, Kenneth L.

    2010-01-01

    The first part of this review ended with a discussion of new niches for known viruses as illustrated by viral central nervous system (CNS) disease associated with organ transplant and the syndrome of human herpesvirus 6–associated posttransplant acute limbic encephalitis. In this part, we begin with a continuation of this theme, reviewing the association of JC virus–associated progressive multifocal leukoencephalopathy (PML) with novel immunomodulatory agents. This part then continues with emerging viral infections associated with importation of infected animals (monkeypox virus), then spread of vectors and enhanced vector competence (chikungunya virus [CHIK]), and novel viruses causing CNS infections including Nipah and Hendra viruses and bat lyssaviruses (BLV). PMID:19752295

  3. Development-Inspired Reprogramming of the Mammalian Central Nervous System

    PubMed Central

    Amamoto, Ryoji; Arlotta, Paola

    2014-01-01

    In 2012, John Gurdon and Shinya Yamanaka shared the Nobel Prize for the exciting demonstration that the identity of differentiated cells is not irreversibly determined but can be changed back to a pluripotent state under appropriate instructive signals. The principle that differentiated cells can revert to an embryonic state and even be converted directly from one cell-type into another not only turns fundamental principles of development on their head but also has profound implications for regenerative medicine. Replacement of diseased tissue with newly reprogrammed cells and modeling of human disease are concrete opportunities. Here, we focus on the central nervous system to consider whether and how reprogramming of cell identity may impact regeneration and modeling of a system historically considered immutable and hardwired. PMID:24482482

  4. Interferons, Signal Transduction Pathways, and the Central Nervous System

    PubMed Central

    Nallar, Shreeram C.

    2014-01-01

    The interferon (IFN) family of cytokines participates in the development of innate and acquired immune defenses against various pathogens and pathogenic stimuli. Discovered originally as a proteinaceous substance secreted from virus-infected cells that afforded immunity to neighboring cells from virus infection, these cytokines are now implicated in various human pathologies, including control of tumor development, cell differentiation, and autoimmunity. It is now believed that the IFN system (IFN genes and the genes induced by them, and the factors that regulate these processes) is a generalized alarm of cellular stress, including DNA damage. IFNs exert both beneficial and deleterious effects on the central nervous system (CNS). Our knowledge of the IFN-regulated processes in the CNS is far from being clear. In this article, we reviewed the current understanding of IFN signal transduction pathways and gene products that might have potential relevance to diseases of the CNS. PMID:25084173

  5. Evolving character of chronic central nervous system HIV infection.

    PubMed

    Price, Richard W; Spudich, Serena S; Peterson, Julia; Joseph, Sarah; Fuchs, Dietmar; Zetterberg, Henrik; Gisslén, Magnus; Swanstrom, Ronald

    2014-02-01

    Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous system (CNS) begins early in systemic infection and continues throughout its untreated course. Despite a common cerebrospinal fluid inflammatory response, it is usually neurologically asymptomatic for much of this course, but can evolve in some individuals to HIV-associated dementia (HAD), a severe encephalopathy with characteristic cognitive and motor dysfunction. While widespread use of combination antiretroviral therapy (ART) has led to a marked decline in both the CNS infection and its neurologic severe consequence, HAD continues to afflict individuals presenting with advanced systemic infection in the developed world and a larger number in resource-poor settings where ART is more restricted. Additionally, milder CNS injury and dysfunction have broader prevalence, including in those treated with ART. Here we review the history and evolving nomenclature of HAD, its viral pathogenesis, clinical presentation and diagnosis, and treatment. PMID:24715483

  6. Central Nervous System and its Disease Models on a Chip.

    PubMed

    Yi, YoonYoung; Park, JiSoo; Lim, Jaeho; Lee, C Justin; Lee, Sang-Hoon

    2015-12-01

    Technologies for microfluidics and biological microelectromechanical systems have been rapidly progressing over the past decade, enabling the development of unique microplatforms for in vitro human central nervous system (CNS) and related disease models. Most fundamental techniques include manipulation of axons, synapses, and neuronal networks, and different culture conditions are possible, such as compartmental, co-culturing, and 3D. Various CNS disease models, such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), epilepsy, N-methyl-D-aspartate receptor (NMDAR) encephalitis, migraine, diffuse axonal injury, and neuronal migration disorders, have been successfully established on microplatforms. In this review, we summarize fundamental technologies and current existing CNS disease models on microplatforms. We also discuss possible future directions, including application of these methods to pathological studies, drug screening, and personalized medicine, with 3D and personalized disease models that could generate more realistic CNS disease models. PMID:26497426

  7. Fungal Infections of the Central Nervous System: A Pictorial Review.

    PubMed

    Gavito-Higuera, Jose; Mullins, Carola Birgit; Ramos-Duran, Luis; Olivas Chacon, Cristina Ivette; Hakim, Nawar; Palacios, Enrique

    2016-01-01

    Fungal infections of the central nervous system (CNS) pose a threat to especially immunocompromised patients and their development is primarily determined by the immune status of the host. With an increasing number of organ transplants, chemotherapy, and human immunodeficiency virus infections, the number of immunocompromised patients as susceptible hosts is growing and fungal infections of the CNS are more frequently encountered. They may result in meningitis, cerebritis, abscess formation, cryptococcoma, and meningeal vasculitis with rapid disease progression and often overlapping symptoms. Although radiological characteristics are often nonspecific, unique imaging patterns can be identified through computer tomography as a first imaging modality and further refined by magnetic resonance imaging. A rapid diagnosis and the institution of the appropriate therapy are crucial in helping prevent an often fatal outcome. PMID:27403402

  8. Autophagy in the central nervous system: implications for neurodegenerative disorders.

    PubMed

    Xilouri, Maria; Stefanis, Leonidas

    2010-12-01

    The autophagy-lysosomal pathway is a major proteolytic pathway that in mammalian systems mainly comprises of macroautophagy and chaperone-mediated autophagy. The former is relatively non-selective and involves bulk degradation of proteins and organelles, whereas the latter is selective for certain cytosolic proteins. These autophagy pathways are important in development, differentiation, cellular remodeling and survival during nutrient starvation. Autophagy is crucial for neuronal homeostasis and acts as a local housekeeping process, since neurons are post-mitotic cells and require effective protein degradation to prevent accumulation of toxic aggregates. A growing body of evidence now suggests that dysfunction of autophagy causes accumulation of abnormal proteins and/or damaged organelles. Such accumulation has been linked to synaptic dysfunction, cellular stress and neuronal death. Abnormal autophagy may be involved in the pathology of both chronic nervous system disorders, such as proteinopathies (Alzheimer's, Parkinson's, Huntington's disease) and acute brain injuries. Although autophagy is generally beneficial, its aberrant activation may also exert a detrimental role in neurological diseases depending on the environment and the insult, leading to autophagic neuronal death. In this review we summarize the current knowledge regarding the role of autophagy-lysosomal pathway in the central nervous system and discuss the implication of autophagy dysregulation in human neurological diseases and animal models. PMID:20942791

  9. Structural and functional features of central nervous system lymphatic vessels.

    PubMed

    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. PMID:26030524

  10. Central Nervous System Cancers, Version 2.2014

    PubMed Central

    Nabors, Louis Burt; Portnow, Jana; Ammirati, Mario; Brem, Henry; Brown, Paul; Butowski, Nicholas; Chamberlain, Marc C.; DeAngelis, Lisa M.; Fenstermaker, Robert A.; Friedman, Allan; Gilbert, Mark R.; Hattangadi-Gluth, Jona; Hesser, Deneen; Holdhoff, Matthias; Junck, Larry; Lawson, Ronald; Loeffler, Jay S.; Moots, Paul L.; Mrugala, Maciej M.; Newton, Herbert B.; Raizer, Jeffrey J.; Recht, Lawrence; Shonka, Nicole; Shrieve, Dennis C.; Sills, Allen K.; Swinnen, Lode J.; Tran, David; Tran, Nam; Vrionis, Frank D.; Wen, Patrick Yung; McMillian, Nicole R.; Ho, Maria

    2015-01-01

    The NCCN Guidelines for Central Nervous System Cancers provide multidisciplinary recommendations for the clinical management of patients with cancers of the central nervous system. These NCCN Guidelines Insights highlight recent updates regarding the management of metastatic brain tumors using radiation therapy. Use of stereotactic radiosurgery (SRS) is no longer limited to patients with 3 or fewer lesions, because data suggest that total disease burden, rather than number of lesions, is predictive of survival benefits associated with the technique. SRS is increasingly becoming an integral part of management of patients with controlled, low-volume brain metastases. PMID:25361798

  11. Cryptococcosis of the central nervous system

    PubMed Central

    Edwards, V. E.; Sutherland, J. M.; Tyrer, J. H.

    1970-01-01

    (1) A survey of cryptococcal infections of the nervous system in Queensland, Australia, revealed the nine year prevalence rate for the Australian aboriginal to be some 17 times greater than that of the white population. Uncommon in the first decade of life, the disease was developed by 79% of 29 patients between 20 and 59 years, males being affected twice as commonly as females. (2) Cryptococcosis appears to be more common in Australia than in the United Kingdom, and in Queensland the nine year incidence of neurological cryptococcosis was 4·7 per 100,000 in the tropical north compared with 1·8 per 100,000 in the southern parts of the State. Because of this, and since 20 of the 29 patients were regarded as having outdoor occupations, it is suggested that a high environmental exposure to the fungus may be associated with an animal reservoir and with dry, dusty conditions. It is also possible that geographical and occupational factors rather than racial predisposition account for the high incidence of the disease in the Australian aborigine. However, individual resistance and susceptibility are probably also important factors, since the clinical disease appears to be positively correlated with certain other diseases, or with steroid therapy, which would impair the immune responses of the body. (3) Headache is the outstanding symptom of neurological cryptococcosis and fever or evidence of meningeal reaction, though often present, may be absent. An awareness of the possibility of neurological cryptococcosis in the differential diagnosis of various intracranial disorders should lead to identification of the encapsulated C. neoformans in the cerebrospinal fluid. Although in eight of 26 patients the lumbar cerebrospinal fluid was sterile on repeated examination, in five cases C. neoformans was found on direct examination of cerebrospinal fluid obtained by ventricular puncture. The remaining three died before further investigations could be performed. (4) Before the

  12. The Role of Central Nervous System Plasticity in Tinnitus

    ERIC Educational Resources Information Center

    Saunders, James C.

    2007-01-01

    Tinnitus is a vexing disorder of hearing characterized by sound sensations originating in the head without any external stimulation. The specific etiology of these sensations is uncertain but frequently associated with hearing loss. The "neurophysiogical" model of tinnitus has enhanced appreciation of central nervous system (CNS) contributions.…

  13. School Reentry for Children with Acquired Central Nervous Systems Injuries

    ERIC Educational Resources Information Center

    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…

  14. Parasitic Central Nervous System Infections in Immunocompromised Hosts

    PubMed Central

    Walker, Melanie; Zunt, Joseph R.

    2009-01-01

    Immunosuppression due to therapy after transplantation or associated with HIV infection increases susceptibility to various central nervous system (CNS) infections. This article discusses how immunosuppression modifies the presentation, diagnosis, and treatment of selected parasitic CNS infections, with a focus on toxoplasmosis, Chagas disease, neurocysticercosis, schistosomiasis, and strongyloidiasis. PMID:15824993

  15. Evolution of flatworm central nervous systems: Insights from polyclads.

    PubMed

    Quiroga, Sigmer Y; Carolina Bonilla, E; Marcela Bolaños, D; Carbayo, Fernando; Litvaitis, Marian K; Brown, Federico D

    2015-01-01

    The nervous systems of flatworms have diversified extensively as a consequence of the broad range of adaptations in the group. Here we examined the central nervous system (CNS) of 12 species of polyclad flatworms belonging to 11 different families by morphological and histological studies. These comparisons revealed that the overall organization and architecture of polyclad central nervous systems can be classified into three categories (I, II, and III) based on the presence of globuli cell masses -ganglion cells of granular appearance-, the cross-sectional shape of the main nerve cords, and the tissue type surrounding the nerve cords. In addition, four different cell types were identified in polyclad brains based on location and size. We also characterize the serotonergic and FMRFamidergic nervous systems in the cotylean Boninia divae by immunocytochemistry. Although both neurotransmitters were broadly expressed, expression of serotonin was particularly strong in the sucker, whereas FMRFamide was particularly strong in the pharynx. Finally, we test some of the major hypothesized trends during the evolution of the CNS in the phylum by a character state reconstruction based on current understanding of the nervous system across different species of Platyhelminthes and on up-to-date molecular phylogenies. PMID:26500427

  16. Evolution of flatworm central nervous systems: Insights from polyclads

    PubMed Central

    Quiroga, Sigmer Y.; Carolina Bonilla, E.; Marcela Bolaños, D.; Carbayo, Fernando; Litvaitis, Marian K.; Brown, Federico D.

    2015-01-01

    The nervous systems of flatworms have diversified extensively as a consequence of the broad range of adaptations in the group. Here we examined the central nervous system (CNS) of 12 species of polyclad flatworms belonging to 11 different families by morphological and histological studies. These comparisons revealed that the overall organization and architecture of polyclad central nervous systems can be classified into three categories (I, II, and III) based on the presence of globuli cell masses -ganglion cells of granular appearance-, the cross-sectional shape of the main nerve cords, and the tissue type surrounding the nerve cords. In addition, four different cell types were identified in polyclad brains based on location and size. We also characterize the serotonergic and FMRFamidergic nervous systems in the cotylean Boninia divae by immunocytochemistry. Although both neurotransmitters were broadly expressed, expression of serotonin was particularly strong in the sucker, whereas FMRFamide was particularly strong in the pharynx. Finally, we test some of the major hypothesized trends during the evolution of the CNS in the phylum by a character state reconstruction based on current understanding of the nervous system across different species of Platyhelminthes and on up-to-date molecular phylogenies. PMID:26500427

  17. Targeting Human Central Nervous System Protein Kinases: An Isoform Selective p38αMAPK Inhibitor That Attenuates Disease Progression in Alzheimer’s Disease Mouse Models

    PubMed Central

    2015-01-01

    The first kinase inhibitor drug approval in 2001 initiated a remarkable decade of tyrosine kinase inhibitor drugs for oncology indications, but a void exists for serine/threonine protein kinase inhibitor drugs and central nervous system indications. Stress kinases are of special interest in neurological and neuropsychiatric disorders due to their involvement in synaptic dysfunction and complex disease susceptibility. Clinical and preclinical evidence implicates the stress related kinase p38αMAPK as a potential neurotherapeutic target, but isoform selective p38αMAPK inhibitor candidates are lacking and the mixed kinase inhibitor drugs that are promising in peripheral tissue disease indications have limitations for neurologic indications. Therefore, pursuit of the neurotherapeutic hypothesis requires kinase isoform selective inhibitors with appropriate neuropharmacology features. Synaptic dysfunction disorders offer a potential for enhanced pharmacological efficacy due to stress-induced activation of p38αMAPK in both neurons and glia, the interacting cellular components of the synaptic pathophysiological axis, to be modulated. We report a novel isoform selective p38αMAPK inhibitor, MW01-18-150SRM (=MW150), that is efficacious in suppression of hippocampal-dependent associative and spatial memory deficits in two distinct synaptic dysfunction mouse models. A synthetic scheme for biocompatible product and positive outcomes from pharmacological screens are presented. The high-resolution crystallographic structure of the p38αMAPK/MW150 complex documents active site binding, reveals a potential low energy conformation of the bound inhibitor, and suggests a structural explanation for MW150’s exquisite target selectivity. As far as we are aware, MW150 is without precedent as an isoform selective p38MAPK inhibitor or as a kinase inhibitor capable of modulating in vivo stress related behavior. PMID:25676389

  18. Alcoholism and its effects on the central nervous system.

    PubMed

    Mukherjee, Sukhes

    2013-08-01

    Alcohol abuse is a major health problem worldwide, resulting to extensive admissions in many general hospitals. The overall economic cost of alcohol abuse is enormous worldwide. As a small molecule, alcohol can easily cross membrane barriers and reach different parts of the body very quickly. Attainment of its equilibrium concentration in different cellular compartments depends on the respective water content. Alcohol can affect several parts of the brain, but, in general, contracts brain tissues, destroys brain cells, as well as depresses the central nervous system. Excessive drinking over a prolonged period of time can cause serious problems with cognition and memory. Alcohol interacts with the brain receptors, interfering with the communication between nerve cells, and suppressing excitatory nerve pathway activity. Neuro-cognitive deficits, neuronal injury, and neurodegeneration are well documented in alcoholics, yet the underlying mechanisms remain elusive. The effect can be both direct and/ or indirect. In this review we highlighted the role of alcoholism on the CNS and its impact on human health. PMID:23713737

  19. Post-streptococcal autoimmune disorders of the central nervous system.

    PubMed

    Dale, Russell C

    2005-11-01

    Group A Streptococcus can induce autoimmune disease in humans with particular involvement of the heart, joints, and brain. The spectrum of post-streptococcal disease of the central nervous system (CNS) has been widened recently and includes movement disorders (chorea, tics, dystonia, and Parkinsonism), psychiatric disorders (particularly emotional disorders), and associated sleep disorders. Neuroimaging and pathological studies indicate that the most vulnerable brain region is the basal ganglia. The immunopathogenesis of the disease is incompletely defined, and although there is some support for autoantibody-mediated disease, several conflicting studies cast doubt on the autoantibody hypothesis. It has been speculated that post-streptococcal autoimmunity has a role in common neuropsychiatric disease but the evidence is conflicting and routine screening of patients with Tourette syndrome and obsessive-compulsive disorder for post-streptococcal autoimmune abnormalities is not be recommended at present. However, post-streptococcal disorders of the CNS remain a useful model of neuropsychiatric disease, which may improve our understanding of abnormal movements and behaviours in children. PMID:16225745

  20. Multiple Sclerosis and the Blood-Central Nervous System Barrier

    PubMed Central

    Palmer, Alan M.

    2013-01-01

    The central nervous system (CNS) is isolated from the blood system by a physical barrier that contains efflux transporters and catabolic enzymes. This blood-CNS barrier (BCNSB) plays a pivotal role in the pathophysiology of multiple sclerosis (MS). It binds and anchors activated leukocytes to permit their movement across the BCNSB and into the CNS. Once there, these immune cells target particular self-epitopes and initiate a cascade of neuroinflammation, which leads to the breakdown of the BCNSB and the formation of perivascular plaques, one of the hallmarks of MS. Immunomodulatory drugs for MS are either biologics or small molecules, with only the latter having the capacity to cross the BCNSB and thus have a propensity to cause CNS side effects. However, BCNSB penetration is a desirable feature of MS drugs that have molecular targets within the CNS. These are nabiximols and dalfampridine, which target cannabinoid receptors and potassium channels, respectively. Vascular cell adhesion molecule-1, present on endothelial cells of the BCNSB, also serves as a drug discovery target since it interacts with α4-β1-integrin on leucocytes. The MS drug natalizumab, a humanized monoclonal antibody against α4-β1-integrin, blocks this interaction and thus reduces the movement of immune cells into the CNS. This paper further elaborates on the role of the BCNSB in the pathophysiology and pharmacotherapy of MS. PMID:23401746

  1. [Dementia in Patients with Central Nervous System Mycosis].

    PubMed

    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. PMID:27056851

  2. Emerging viral infections of the central nervous system: part 1.

    PubMed

    Tyler, Kenneth L

    2009-08-01

    In this 2-part review, I will focus on emerging virus infections of the central nervous system (CNS). Part 1 will introduce the basic features of emerging infections, including their definition, epidemiology, and the frequency of CNS involvement. Important mechanisms of emergence will be reviewed, including viruses spreading into new host ranges as exemplified by West Nile virus (WNV), Japanese encephalitis (JE) virus, Toscana virus, and enterovirus 71 (EV71). Emerging infections also result from opportunistic spread of viruses into known niches, often resulting from attenuated host resistance to infection. This process is exemplified by transplant-associated cases of viral CNS infection caused by WNV, rabies virus, lymphocytic choriomeningitis, and lymphocytic choriomeningitis-like viruses and by the syndrome of human herpesvirus 6 (HHV6)-associated posttransplantation acute limbic encephalitis. The second part of this review begins with a discussion of JC virus and the occurrence of progressive multifocal leukoencephalopathy in association with novel immunomodulatory therapies and then continues with an overview of the risk of infection introduced by imported animals (eg, monkeypox virus) and examples of emerging diseases caused by enhanced competence of viruses for vectors and the spread of vectors (eg, chikungunya virus) and then concludes with examples of novel viruses causing CNS infection as exemplified by Nipah and Hendra viruses and bat lyssaviruses. PMID:19667214

  3. 3D in vitro modeling of the central nervous system

    PubMed Central

    Hopkins, Amy M.; DeSimone, Elise; Chwalek, Karolina; Kaplan, David L.

    2015-01-01

    There are currently more than 600 diseases characterized as affecting the central nervous system (CNS) which inflict neural damage. Unfortunately, few of these conditions have effective treatments available. Although significant efforts have been put into developing new therapeutics, drugs which were promising in the developmental phase have high attrition rates in late stage clinical trials. These failures could be circumvented if current 2D in vitro and in vivo models were improved. 3D, tissue-engineered in vitro systems can address this need and enhance clinical translation through two approaches: (1) bottom-up, and (2) top-down (developmental/regenerative) strategies to reproduce the structure and function of human tissues. Critical challenges remain including biomaterials capable of matching the mechanical properties and extracellular matrix (ECM) composition of neural tissues, compartmentalized scaffolds that support heterogeneous tissue architectures reflective of brain organization and structure, and robust functional assays for in vitro tissue validation. The unique design parameters defined by the complex physiology of the CNS for construction and validation of 3D in vitro neural systems are reviewed here. PMID:25461688

  4. Central Nervous System Multiparameter Optimization Desirability: Application in Drug Discovery.

    PubMed

    Wager, Travis T; Hou, Xinjun; Verhoest, Patrick R; Villalobos, Anabella

    2016-06-15

    Significant progress has been made in prospectively designing molecules using the central nervous system multiparameter optimization (CNS MPO) desirability tool, as evidenced by the analysis reported herein of a second wave of drug candidates that originated after the development and implementation of this tool. This simple-to-use design algorithm has expanded design space for CNS candidates and has further demonstrated the advantages of utilizing a flexible, multiparameter approach in drug discovery rather than individual parameters and hard cutoffs of physicochemical properties. The CNS MPO tool has helped to increase the percentage of compounds nominated for clinical development that exhibit alignment of ADME attributes, cross the blood-brain barrier, and reside in lower-risk safety space (low ClogP and high TPSA). The use of this tool has played a role in reducing the number of compounds submitted to exploratory toxicity studies and increasing the survival of our drug candidates through regulatory toxicology into First in Human studies. Overall, the CNS MPO algorithm has helped to improve the prioritization of design ideas and the quality of the compounds nominated for clinical development. PMID:26991242

  5. Emerging Viral Infections of the Central Nervous System

    PubMed Central

    Tyler, Kenneth L.

    2010-01-01

    In this 2-part review, I will focus on emerging virus infections of the central nervous system (CNS). Part 1 will introduce the basic features of emerging infections, including their definition, epidemiology, and the frequency of CNS involvement. Important mechanisms of emergence will be reviewed, including viruses spreading into new host ranges as exemplified by West Nile virus (WNV), Japanese encephalitis (JE) virus, Toscana virus, and enterovirus 71 (EV71). Emerging infections also result from opportunistic spread of viruses into known niches, often resulting from attenuated host resistance to infection. This process is exemplified by transplant-associated cases of viral CNS infection caused by WNV, rabies virus, lymphocytic choriomeningitis, and lymphocytic choriomeningitis–like viruses and by the syndrome of human herpesvirus 6 (HHV6)–associated posttransplantation acute limbic encephalitis. The second part of this review begins with a discussion of JC virus and the occurrence of progressive multifocal leukoencephalopathy in association with novel immunomodulatory therapies and then continues with an overview of the risk of infection introduced by imported animals (eg, monkeypox virus) and examples of emerging diseases caused by enhanced competence of viruses for vectors and the spread of vectors (eg, chikungunya virus) and then concludes with examples of novel viruses causing CNS infection as exemplified by Nipah and Hendra viruses and bat lyssaviruses. PMID:19667214

  6. Invasion of the Central Nervous System by Intracellular Bacteria

    PubMed Central

    Drevets, Douglas A.; Leenen, Pieter J. M.; Greenfield, Ronald A.

    2004-01-01

    Infection of the central nervous system (CNS) is a severe and frequently fatal event during the course of many diseases caused by microbes with predominantly intracellular life cycles. Examples of these include the facultative intracellular bacteria Listeria monocytogenes, Mycobacterium tuberculosis, and Brucella and Salmonella spp. and obligate intracellular microbes of the Rickettsiaceae family and Tropheryma whipplei. Unfortunately, the mechanisms used by intracellular bacterial pathogens to enter the CNS are less well known than those used by bacterial pathogens with an extracellular life cycle. The goal of this review is to elaborate on the means by which intracellular bacterial pathogens establish infection within the CNS. This review encompasses the clinical and pathological findings that pertain to the CNS infection in humans and includes experimental data from animal models that illuminate how these microbes enter the CNS. Recent experimental data showing that L. monocytogenes can invade the CNS by more than one mechanism make it a useful model for discussing the various routes for neuroinvasion used by intracellular bacterial pathogens. PMID:15084504

  7. Monoclonal antibodies to a rat nestin fusion protein recognize a 220-kDa polypeptide in subsets of fetal and adult human central nervous system neurons and in primitive neuroectodermal tumor cells.

    PubMed Central

    Tohyama, T.; Lee, V. M.; Rorke, L. B.; Marvin, M.; McKay, R. D.; Trojanowski, J. Q.

    1993-01-01

    Nestin is the major intermediate filament protein of embryonic central nervous system (CNS) progenitor cells. To identify proteins involved in early stages of lineage commitment in the developing human CNS we generated monoclonal antibodies to a TrpE-rat nestin fusion protein. This resulted in a monoclonal antibody (designated NST11) that did not recognize authentic human nestin, but did recognize a novel neuron-specific human polypeptide expressed in a subset of embryonic and adult CNS neurons as well as in medulloblastomas. NST11 immunoreactivity was abundant in developing spinal cord motor neurons, but was extinguished in these neurons by 17 weeks gestation. NST11 also labeled Purkinje cells at 17 weeks gestation, but Purkinje cells continued to express the NST11 antigen throughout gestation as well as in the adult cerebellum, and NST11 immunoreactivity was more abundant in Purkinje cells than in any other human CNS neurons. No NST11 immunoreactivity was detected in cells of the adult human peripheral nervous system or in a variety of adult non-neural human tissues. Further, NST11 almost exclusively stained cerebellar medulloblastomas. In Western blots of immature and mature human cerebral and cerebellar extracts, NST11 did not bind human nestin, but did detect an immunoband with a molecular weight of 220 kd. A similar immunoband was detected in medulloblastoma-derived cell lines with a neuron-like phenotype. These findings suggest that the NST11 monoclonal antibody recognizes a novel protein expressed by a subpopulation of immature and mature human CNS neurons, medulloblastomas, and medulloblastoma-derived cell lines. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:7686344

  8. Hemichorea in a patient with HIV-associated central nervous system histoplasmosis.

    PubMed

    Estrada-Bellmann, Ingrid; Camara-Lemarroy, Carlos R; Flores-Cantu, Hazael; Calderon-Hernandez, Hector J; Villareal-Velazquez, Hector J

    2016-01-01

    Central nervous system histoplasmosis is a rare opportunistic infection with a heterogeneous clinical presentation. We describe the first case of human immunodeficiency virus-associated cerebral histoplasmosis presenting with hemichorea. The patient recovered after treatment with conventional amphotericin B and itraconazole. PMID:25505048

  9. 21 CFR 882.5550 - Central nervous system fluid shunt and components.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Central nervous system fluid shunt and components. 882.5550 Section 882.5550 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... shunt is a device or combination of devices used to divert fluid from the brain or other part of...

  10. 21 CFR 882.5550 - Central nervous system fluid shunt and components.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Central nervous system fluid shunt and components. 882.5550 Section 882.5550 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... shunt is a device or combination of devices used to divert fluid from the brain or other part of...

  11. 21 CFR 882.5550 - Central nervous system fluid shunt and components.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Central nervous system fluid shunt and components. 882.5550 Section 882.5550 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... shunt is a device or combination of devices used to divert fluid from the brain or other part of...

  12. 21 CFR 882.5550 - Central nervous system fluid shunt and components.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Central nervous system fluid shunt and components. 882.5550 Section 882.5550 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... shunt is a device or combination of devices used to divert fluid from the brain or other part of...

  13. 21 CFR 882.5550 - Central nervous system fluid shunt and components.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Central nervous system fluid shunt and components. 882.5550 Section 882.5550 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... shunt is a device or combination of devices used to divert fluid from the brain or other part of...

  14. Central nervous system infection in the pediatric population

    PubMed Central

    Sahu, Rabi Narayan; Kumar, Raj; Mahapatra, A. K.

    2009-01-01

    Infection of the central nervous system is a life-threatening condition in the pediatric population. Almost all agents can cause infection within the central nervous system and the extent of infection ranges from diffuse involvement of the meninges, brain, or the spinal cord to localized involvement presenting as a space-occupying lesion. Modern imaging techniques define the anatomic region infected, the evolution of the disease, and help in better management of these patients. Acute bacterial meningitis remains a major cause of mortality and long-term neurological disability. Fortunately, the incidence of infection after clean craniotomy is < 5%, but it leads to significant morbidity as well as fiscal loss. The most significant causative factor in postcraniotomy infections is postoperative CSF leak. Cerebral abscess related to organic congenital heart disease is one of the leading causes of morbidity and mortality in the pediatric population. The administration of prophylactic antibiotics is indicated for contaminated and clean-contaminated wounds. PMID:21887170

  15. [VARICELLA ZOSTER VIRUS AND DISEASES OF CENTRAL NERVOUS SYSTEM VESSELS].

    PubMed

    Kazanova, A S; Lavrov, V F; Zverev, V V

    2015-01-01

    Systemized data on epidemiology, pathogenesis, clinical manifestation, diagnostics and therapy of VZV-vasculopathy--a disease, occurring due to damage of arteries of the central nervous system by Varicella Zoster virus, are presented in the review. A special attention in the paper is given to the effect of vaccine prophylaxis of chicken pox and herpes zoster on the frequency of development and course of VZV-vasculopathy. PMID:26259280

  16. The role of leptin in central nervous system diseases

    PubMed Central

    Li, Xiao-Mei; Yan, Hai-Jing; Guo, Yi-Shan

    2016-01-01

    Leptin is a peptide hormone produced by adipose tissue and acts in brain centers to control critical physiological functions. Leptin receptors are especially abundant in the hypothalamus and trigger specific neuronal subpopulations, and activate several intracellular signaling events, including the JAK/STAT, MAPK, PI3K, and mTOR pathway. Although most studies focus on its role in energy intake and expenditure, leptin also plays a critical role in many central nervous system diseases. PMID:26885866

  17. The central nervous system in childhood chronic kidney disease.

    PubMed

    Gipson, Debbie S; Duquette, Peter J; Icard, Phil F; Hooper, Stephen R

    2007-10-01

    Neurodevelopmental deficits in pediatric and adult survivors of childhood onset chronic kidney disease (CKD) have been documented for many years. This paper reviews the available literature on central nervous system involvement incurred in childhood CKD. The studies reviewed include recent work in neuroimaging, electrophysiology, and neuropsychology, along with commentary on school functioning and long-term outcomes. The paper concludes with suggestions for monitoring the neurodevelopmental status and pursuing appropriate early interventions for children with CKD. PMID:17072652

  18. Space radiation risks to the central nervous system

    NASA Astrophysics Data System (ADS)

    Cucinotta, Francis A.; Alp, Murat; Sulzman, Frank M.; Wang, Minli

    2014-07-01

    Central nervous system (CNS) risks which include during space missions and lifetime risks due to space radiation exposure are of concern for long-term exploration missions to Mars or other destinations. Possible CNS risks during a mission are altered cognitive function, including detriments in short-term memory, reduced motor function, and behavioral changes, which may affect performance and human health. The late CNS risks are possible neurological disorders such as premature aging, and Alzheimer's disease (AD) or other dementia. Radiation safety requirements are intended to prevent all clinically significant acute risks. However the definition of clinically significant CNS risks and their dependences on dose, dose-rate and radiation quality is poorly understood at this time. For late CNS effects such as increased risk of AD, the occurrence of the disease is fatal with mean time from diagnosis of early stage AD to death about 8 years. Therefore if AD risk or other late CNS risks from space radiation occur at mission relevant doses, they would naturally be included in the overall acceptable risk of exposure induced death (REID) probability for space missions. Important progress has been made in understanding CNS risks due to space radiation exposure, however in general the doses used in experimental studies have been much higher than the annual galactic cosmic ray (GCR) dose (∼0.1 Gy/y at solar maximum and ∼0.2 Gy/y at solar minimum with less than 50% from HZE particles). In this report we summarize recent space radiobiology studies of CNS effects from particle accelerators simulating space radiation using experimental models, and make a critical assessment of their relevance relative to doses and dose-rates to be incurred on a Mars mission. Prospects for understanding dose, dose-rate and radiation quality dependencies of CNS effects and extrapolation to human risk assessments are described.

  19. Central- and autonomic nervous system coupling in schizophrenia.

    PubMed

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

    2016-05-13

    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

  20. Centralization of the deuterostome nervous system predates chordates.

    PubMed

    Nomaksteinsky, Marc; Röttinger, Eric; Dufour, Héloïse D; Chettouh, Zoubida; Lowe, Chris J; Martindale, Mark Q; Brunet, Jean-François

    2009-08-11

    The origin of the chordate central nervous system (CNS) is unknown. One theory is that a CNS was present in the first bilaterian and that it gave rise to both the ventral cord of protostomes and the dorsal cord of deuterostomes. Another theory proposes that the chordate CNS arose by a dramatic process of dorsalization and internalization from a diffuse nerve net coextensive with the skin of the animal, such as enteropneust worms (Hemichordata, Ambulacraria) are supposed to have. We show here that juvenile and adult enteropneust worms in fact have a bona fide CNS, i.e., dense agglomerations of neurons associated with a neuropil, forming two cords, ventral and dorsal. The latter is internalized in the collar as a chordate-like neural tube. Contrary to previous assumptions, the greater part of the adult enteropneust skin is nonneural, although elements of the peripheral nervous system (PNS) are found there. We use molecular markers to show that several neuronal types are anatomically segregated in the CNS and PNS. These neuroanatomical features, whatever their homologies with the chordate CNS, imply that nervous system centralization predates the evolutionary separation of chordate and hemichordate lineages. PMID:19559615

  1. Effect of Artificial Gravity: Central Nervous System Neurochemical Studies

    NASA Technical Reports Server (NTRS)

    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.

  2. The pleiotropic effects of erythropoietin in the central nervous system.

    PubMed

    Buemi, M; Cavallaro, E; Floccari, F; Sturiale, A; Aloisi, C; Trimarchi, M; Corica, F; Frisina, N

    2003-03-01

    Erythropoietin (Epo) is a hydrophobic sialoglycoproteic hormone produced by the kidney and responsible for the proliferation, maturation, and differentiation of the precursors of the erythroid cell line. Human recombinant erythropoietin (rHuEpo) is used to treat different types of anemia, not only in uremic patients but also in newborns with anemia of prematurity, in patients with cancer-related anemia or myeloproliferative disease, thalassemias, bone marrow transplants, or those with chronic infectious diseases. The pleiotropic functions of Epo are well known. It has been shown that this hormone can modulate the inflammatory and immune response, has direct hemodynamic and vasoactive effects, could be considered a proangiogenic factor because of its interaction with vascular endothelial growth factor, and its ability to stimulate mitosis and motility of endothelial cells. The multifunctional role of Epo has further been confirmed by the discovery in the central nervous system of a specific Epo/Epo receptor (EpoR) system. Both Epo and EpoR are expressed by astrocytes and neurons and Epo is present in the cerebrospinal fluid (CSF). Therefore, novel functions of Epo, tissue-specific regulation, and the mechanisms of action have been investigated. In this review we have tried to summarize the current data on the role of Epo on brain function. We discuss the different sites of cerebral expression and mechanisms of regulation of Epo and its receptor and its role in the development and maturation of the brain. Second, we discuss the neurotrophic and neuroprotective function of Epo in different conditions of neuronal damage, such as hypoxia, cerebral ischemia, and subarachnoid hemorrhage, and the consequent possibility that rHuEpo therapy could soon be used in clinical practice to limit neuronal damage induced by these diseases. PMID:12638727

  3. Central Nervous System Effects of Ginkgo Biloba, a Plant Extract.

    PubMed

    Itil, Turan M.; Eralp, Emin; Tsambis, Elias; Itil, Kurt Z.; Stein, Ulrich

    1996-01-01

    Extracts of Ginkgo biloba (EGb) are among the most prescribed drugs in France and Germany. EGb is claimed to be effective in peripheral arterial disorders and in "cerebral insufficiency." The mechanism of action is not yet well understood. Three of the ingredients of the extract have been isolated and found to be pharmacologically active, but which one alone or in combination is responsible for clinical effects is unknown. The recommended daily dose (3 x 40 mg extract) is based more on empirical data than on clinical dose-findings studies. However, despite these, according to double-blind, placebo-controlled clinical trials, EGb has therapeutic effects, at least, on the diagnostic entity of "cerebral insufficiency," which is used in Europe as synonymous with early dementia. To determine whether EGb has significant pharmacological effects on the human brain, a pharmacodynamic study was conducted using the Quantitative Pharmacoelectroencephalogram (QPEEG(R)) method. It was established that the pharmacological effects (based on a predetermined 7.5--13.0-Hz alpha frequency band in a computer-analyzed electroencephalogram = CEEG(R)) of EGb on the central nervous system (CNS) are significantly different than placebo, and the high and low doses could be discriminated from each other. The 120-mg, but particularly the 240-mg, single doses showed the most consistent CNS effects with an earlier onset (1 h) and longer duration (7 h). Furthermore, it was established that the electrophysiological effects of EGb in CNS are similar to those of well-known cognitive activators such as "nootropics" as well as tacrine, the only marketed "antidementia" drug currently available in the United States. PMID:11856998

  4. The Central Nervous Connections Involved in the Vomiting Reflex

    NASA Technical Reports Server (NTRS)

    Brizzee, K. R.; Mehler, W. R.

    1986-01-01

    The vomiting reflex may be elicited by a number of different types or classes of stimuli involving many varieties of receptor structures and considerable diversity in afferent pathways and central connections. Central relay or mediating structures thus may vary widely according to the type of initial emetic stimulus. The emetic circuits which have been most completely delineated to date are probably those in which the Chemoreceptor Trigger Zone (CTZ) in the Area Postrema (AP) functions as a key mediating structure. Even in this system, however, there are large gaps in our knowledge of the nerve tracts and central nervous connections involved. Knowledge of most other emetic circuits subserving the emetic reflex resulting from many diverse types of stimuli such, for example, as emotional stress (e.g. psychogenic vomiting, Wruble et al. 1982), pain (e.g. testicular trauma), and chemical or mechanical irritation of the gastrointestinal tract or urinary tract is quite incomplete at this time, thus precluding any very adequate description of their central connections at present. One physiological system, however, which has received considerable attention recently in relation to the vomiting reflex elicited by motion stimuli is the vestibular system. Due to the paucity of data on central nervous connections of several or the non-vestibular types of emetic stimuli cited above, we will devote most of our attention in this brief review to the central connections of the vestibular system which seem likely to be involved in the vomiting response to motion stimuli. However, the latter part of the review will be concerned with the concept of the reticular vomiting centre in relation to the ParviCellular Reticular Formation (PCRF), and will thus probably pertain to all of the many classes of emetic stimuli since it will address the question of the final common emetic pathway.

  5. [Molecular Approaches for the Diagnosis of Central Nervous System Infections].

    PubMed

    Ohkusu, Kiyofumi

    2015-07-01

    In recent years, molecular microbiology techniques have proven to be a useful supplement to conventional assays not only in identification of strains from culture, but also in direct detection of pathogens from clinical specimens. This review explores the application of molecular diagnostic techniques for infectious diseases in certain clinical contexts. It aims to assess how these molecular techniques can be integrated to enhance diagnostic capabilities for infectious diseases of the central nervous system. Finally, it emphasizes the need for close collaboration between physicians and clinical microbiologists when considering molecular diagnostics from unusual specimens/cases, because assays must be customized according to the clinical settings. PMID:26160810

  6. Near misdiagnosis of glioblastoma as primary central nervous system lymphoma.

    PubMed

    Bhatt, Vijaya Raj; Shrestha, Rajesh; Shonka, Nicole; Bociek, R Gregory

    2014-08-01

    Primary central nervous system (CNS) lymphoma, most frequently a diffuse large B-cell lymphoma, is a rare aggressive lymphoma confined to the CNS, thus requiring differentiation from other brain malignancies such as glioblastoma. Although stereotactic biopsy can confirm the diagnosis, this is invasive, not always feasible and can be inconclusive after steroid use. Hence, cranial magnetic resonance imaging (MRI) with contrast and cerebrospinal fluid analysis are frequently used to make a prompt diagnosis. We report a case of a woman with two brain masses who presented unique diagnostic challenge. PMID:24883157

  7. Near Misdiagnosis of Glioblastoma as Primary Central Nervous System Lymphoma

    PubMed Central

    Bhatt, Vijaya Raj; Shrestha, Rajesh; Shonka, Nicole; Bociek, R. Gregory

    2014-01-01

    Primary central nervous system (CNS) lymphoma, most frequently a diffuse large B-cell lymphoma, is a rare aggressive lymphoma confined to the CNS, thus requiring differentiation from other brain malignancies such as glioblastoma. Although stereotactic biopsy can confirm the diagnosis, this is invasive, not always feasible and can be inconclusive after steroid use. Hence, cranial magnetic resonance imaging (MRI) with contrast and cerebrospinal fluid analysis are frequently used to make a prompt diagnosis. We report a case of a woman with two brain masses who presented unique diagnostic challenge. PMID:24883157

  8. School reentry for children with acquired central nervous systems injuries.

    PubMed

    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 education is not necessarily a special classroom, but an individualized set of educational needs, determined by a multidisciplinary school team, to promote educational success. The purpose of this article is to inform those pediatricians and pediatric allied health professionals treating children with CNS injury of the systems in place to support successful school reentry and their role in contributing to developing an appropriate educational plan. PMID:19489086

  9. Fulminant Demyelinating Diseases of the Central Nervous System.

    PubMed

    Bevan, Carolyn J; Cree, Bruce A

    2015-12-01

    Fulminant demyelinating diseases of the central nervous system include acute disseminated encephalomyelitis, the related acute hemorrhagic leukoencephalitis, multiple sclerosis variants, neuromyelitis optica spectrum disorders, and idiopathic transverse myelitis. These syndromes are often managed with similar acute treatments including high-dose corticosteroids and plasmapheresis; however, long-term management varies. Although the prognosis of fulminant demyelinating disease was historically poor, outcomes today may be improved due to earlier diagnosis, rapid implementation of anti-inflammatory therapies such as high-dose corticosteroids and plasmapheresis, and improved supportive care. PMID:26595866

  10. Gemella morbillorum: an underestimated aetiology of central nervous system infection?

    PubMed

    Benedetti, Paolo; Rassu, Mario; Branscombe, Michele; Sefton, Armine; Pellizzer, Giampietro

    2009-12-01

    A case is reported of cerebellar abscess and diffuse cerebritis due to Gemella morbillorum. The clinical course was 'biphasic', developing with an acute meningeal infection followed shortly afterwards by suppuration in the cerebellar and cerebral parenchyma; this pattern seemed to suggest a latent survival of the aetiological agent, probably within the central nervous system (CNS), despite systemic antibiotic therapy. Based upon a review of cases so far described, infections of the CNS caused by G. morbillorum appear to be an emerging reality. PMID:19713361

  11. Neuroplasticity. Key to recovery after central nervous system injury.

    PubMed Central

    Dobkin, B H

    1993-01-01

    After an injury to the central nervous system, physical and cognitive impairments and disabilities often abate. These gains may be partly mediated by mechanisms that allow reorganizing of the structure and function within gray and white matter. The potential to enhance neurologic recovery by manipulating the brain and spinal cord must now be considered in clinical practice. Today's rehabilitation routines may not encourage maximum recovery. Indeed, some commonly used physical and pharmacologic methods could inhibit the restoration of motor activities such as walking. On the other hand, therapies that use our expanding knowledge of neuroplasticity could lead to better results for patients. PMID:8351906

  12. Effects of snake venom polypeptides on central nervous system.

    PubMed

    Osipov, Alexey; Utkin, Yuri

    2012-12-01

    The nervous system is a primary target for animal venoms as the impairment of its function results in the fast and efficient immobilization or death of a prey. There are numerous evidences about effects of crude snake venoms or isolated toxins on peripheral nervous system. However, the data on their interactions with the central nervous system (CNS) are not abundant, as the blood-brain barrier (BBB) impedes penetration of these compounds into brain. This updated review presents the data about interaction of snake venom polypeptides with CNS. Such data will be described according to three main modes of interactions: - Direct in vivo interaction of CNS with venom polypeptides either capable to penetrate BBB or injected into the brain. - In vitro interactions of cell or sub-cellular fractions of CNS with crude venoms or purified toxins. - Indirect effects of snake venoms or their components on functioning of CNS under different conditions. Although the venom components penetrating BBB are not numerous, they seem to be the most suitable candidates for the leads in drug design. The compounds with other modes of action are more abundant and better studied, but the lack of the data about their ability to penetrate BBB may substantially aggravate the potentials for their medical perspectives. Nevertheless, many such compounds are used for research of CNS in vitro. These investigations may give invaluable information for understanding the molecular basis of CNS diseases and thus lay the basis for targeted drug design. This aspect also will be outlined in the review. PMID:23270323

  13. Genomic characterization of primary central nervous system lymphoma.

    PubMed

    Fukumura, Kazutaka; Kawazu, Masahito; Kojima, Shinya; Ueno, Toshihide; Sai, Eirin; Soda, Manabu; Ueda, Hiroki; Yasuda, Takahiko; Yamaguchi, Hiroyuki; Lee, Jeunghun; Shishido-Hara, Yukiko; Sasaki, Atsushi; Shirahata, Mitsuaki; Mishima, Kazuhiko; Ichimura, Koichi; Mukasa, Akitake; Narita, Yoshitaka; Saito, Nobuhito; Aburatani, Hiroyuki; Nishikawa, Ryo; Nagane, Motoo; Mano, Hiroyuki

    2016-06-01

    Primary central nervous system lymphoma (PCNSL) is a rare malignancy confined to the central nervous system (CNS), and majority of PCNSL is pathologically classified as diffuse large B-cell lymphoma (DLBCL). We have now performed whole-exome sequencing for 41 tumor tissues of DLBCL-type PCNSL and paired normal specimens and also RNA-sequencing for 30 tumors, revealing a very high frequency of nonsynonymous somatic mutations in PIM1 (100 %), BTG2 (92.7 %), and MYD88 (85.4 %). Many genes in the NF-κB pathway are concurrently mutated within the same tumors. Further, focal deletion or somatic mutations in the HLA genes are associated with poor prognosis. Copy number amplification and overexpression of genes at chromosome 7q35 were both found to predict short progression-free survival as well. Oncogenic mutations in GRB2 were also detected, the effects of which in cultured cells were attenuated by inhibitors of the downstream kinases MAP2K1 and MAP2K2. Individuals with tumors positive for MYD88 mutations also harbored the same mutations at a low frequency in peripheral blood mononuclear cells, suggesting that MYD88 mutation-positive precancerous cells originate outside of the CNS and develop into lymphoma after additional genetic hits that confer adaptation to the CNS environment. PMID:26757737

  14. [Central Nervous Involvement in Patients with Fukuyama Congenital Muscular Dystrophy].

    PubMed

    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. PMID:26873231

  15. Engineering Biomaterial Properties for Central Nervous System Applications

    NASA Astrophysics Data System (ADS)

    Rivet, Christopher John

    Biomaterials offer unique properties that are intrinsic to the chemistry of the material itself or occur as a result of the fabrication process; iron oxide nanoparticles are superparamagnetic, which enables controlled heating in the presence of an alternating magnetic field, and a hydrogel and electrospun fiber hybrid material provides minimally invasive placement of a fibrous, artificial extracellular matrix for tissue regeneration. Utilization of these unique properties towards central nervous system disease and dysfunction requires a thorough definition of the properties in concert with full biological assessment. This enables development of material-specific features to elicit unique cellular responses. Iron oxide nanoparticles are first investigated for material-dependent, cortical neuron cytotoxicity in vitro and subsequently evaluated for alternating magnetic field stimulation induced hyperthermia, emulating the clinical application for enhanced chemotherapy efficacy in glioblastoma treatment. A hydrogel and electrospun fiber hybrid material is first applied to a rat brain to evaluate biomaterial interface astrocyte accumulation as a function of hybrid material composition. The hybrid material is then utilized towards increasing functional engraftment of dopaminergic progenitor neural stem cells in a mouse model of Parkinson's disease. Taken together, these two scenarios display the role of material property characterization in development of biomaterial strategies for central nervous system repair and regeneration.

  16. Astrocyte scar formation aids central nervous system axon regeneration.

    PubMed

    Anderson, Mark A; Burda, Joshua E; Ren, Yilong; Ao, Yan; O'Shea, Timothy M; Kawaguchi, Riki; Coppola, Giovanni; Khakh, Baljit S; Deming, Timothy J; Sofroniew, Michael V

    2016-04-14

    Transected axons fail to regrow in the mature central nervous system. Astrocytic scars are widely regarded as causal in this failure. Here, using three genetically targeted loss-of-function manipulations in adult mice, we show that preventing astrocyte scar formation, attenuating scar-forming astrocytes, or ablating chronic astrocytic scars all failed to result in spontaneous regrowth of transected corticospinal, sensory or serotonergic axons through severe spinal cord injury (SCI) lesions. By contrast, sustained local delivery via hydrogel depots of required axon-specific growth factors not present in SCI lesions, plus growth-activating priming injuries, stimulated robust, laminin-dependent sensory axon regrowth past scar-forming astrocytes and inhibitory molecules in SCI lesions. Preventing astrocytic scar formation significantly reduced this stimulated axon regrowth. RNA sequencing revealed that astrocytes and non-astrocyte cells in SCI lesions express multiple axon-growth-supporting molecules. Our findings show that contrary to the prevailing dogma, astrocyte scar formation aids rather than prevents central nervous system axon regeneration. PMID:27027288

  17. [Primary central nervous system post-transplant lymphoproliferative disorders].

    PubMed

    Honda, Masaya; Koga, Michiaki; Kanda, Takashi

    2014-08-01

    The post-transplant lymphoproliferative disorders (PTLD) are a heterogeneous disease entity of lymphoid and plasmacytic proliferations that can occur after solid organ and bone marrow/stem cell transplantation. PTLD sometimes involves the central nervous system (CNS), but primary occurrence in central nervous system (PCNS-PTLD) is rare. The Epstein-Barr virus (EBV) plays a causative role, and up to 90% of the tumors are associated with this virus. Diagnosing PCNS-PTLD is often challenging based solely on computed tomography, magnetic resonance imaging, and physical findings; therefore, direct biopsy of the lesion is usually necessary to make a definitive diagnosis. The optimal therapy for PCNS-PTLD remains unknown. Dose reduction or discontinuation of immunosuppressive agents is effective for approximately half of PTLD patients, but not for most patients with PCNS-PTLD. It has been noted that CNS involvement is a poor prognostic factor, but early diagnosis and initiation of chemotherapy or radiotherapy seem critical for maximizing the likelihood of a favorable outcome. PMID:25082316

  18. Applications of Nanotechnology to the Central Nervous System

    NASA Astrophysics Data System (ADS)

    Blumling, James P., II

    Nanotechnology and nanomaterials, in general, have become prominent areas of academic research. The ability to engineer at the nano scale is critical to the advancement of the physical and medical sciences. In the realm of physical sciences, the applications are clear: smaller circuitry, more powerful computers, higher resolution intruments. However, the potential impact in the fields of biology and medicine are perhaps even grander. The implementation of novel nanodevices is of paramount importance to the advancement of drug delivery, molecular detection, and cellular manipulation. The work presented in this thesis focuses on the development of nanotechnology for applications in neuroscience. The nervous system provides unique challenges and opportunities for nanoscale research. This thesis discusses some background in nanotechnological applications to the central nervous system and details: (1) The development of a novel calcium nanosenser for use in neurons and astrocytes. We implemented the calcium responsive component of Dr. Roger Tsien's Cameleon sensor, a calmodulin-M13 fusion, in the first quantum dot-based calcium sensor. (2) The exploration of cell-penetrating peptides as a delivery mechanism for nanoparticles to cells of the nervous system. We investigated the application of polyarginine sequences to rat primary cortical astrocytes in order to assess their efficacy in a terminally differentiated neural cell line. (3) The development of a cheap, biocompatible alternative to quantum dots for nanosensor and imaging applications. We utilized a positively charged co-matrix to promote the encapsulation of free sulforhodamine B in silica nanoparticles, a departure from conventional reactive dye coupling to silica matrices. While other methods have been invoked to trap dye not directly coupled to silica, they rely on positively charged dyes that typically have a low quantum yield and are not extensively tested biologically, or they implement reactive dyes bound

  19. Systemic delivery to central nervous system by engineered PLGA nanoparticles.

    PubMed

    Cai, Qiang; Wang, Long; Deng, Gang; Liu, Junhui; Chen, Qianxue; Chen, Zhibiao

    2016-01-01

    Neurological disorders are an important global public health problem, but pharmaceutical treatments are limited due to drug access to the central nervous system being restricted by the blood-brain barrier (BBB). Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) are one of the most promising drug and gene delivery systems for crossing the BBB. While these systems offer great promise, PLGA NPs also have some intrinsic drawbacks and require further engineering for clinical and research applications. Multiple strategies have been developed for using PLGA NPs to deliver compounds across the BBB. We classify these strategies into three categories according to the adaptations made to the PLGA NPs (1) to facilitate travel from the injection site (pre-transcytosis strategies); (2) to enhance passage across the brain endothelial cells (BBB transcytosis strategies) and (3) to achieve targeting of the impaired nervous system cells (post-transcytosis strategies). PLGA NPs modified according to these three strategies are denoted first, second, and third generation NPs, respectively. We believe that fusing these three strategies to engineer multifunctional PLGA NPs is the only way to achieve translational applications. PMID:27158367

  20. Systemic delivery to central nervous system by engineered PLGA nanoparticles

    PubMed Central

    Cai, Qiang; Wang, Long; Deng, Gang; Liu, Junhui; Chen, Qianxue; Chen, Zhibiao

    2016-01-01

    Neurological disorders are an important global public health problem, but pharmaceutical treatments are limited due to drug access to the central nervous system being restricted by the blood-brain barrier (BBB). Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) are one of the most promising drug and gene delivery systems for crossing the BBB. While these systems offer great promise, PLGA NPs also have some intrinsic drawbacks and require further engineering for clinical and research applications. Multiple strategies have been developed for using PLGA NPs to deliver compounds across the BBB. We classify these strategies into three categories according to the adaptations made to the PLGA NPs (1) to facilitate travel from the injection site (pre-transcytosis strategies); (2) to enhance passage across the brain endothelial cells (BBB transcytosis strategies) and (3) to achieve targeting of the impaired nervous system cells (post-transcytosis strategies). PLGA NPs modified according to these three strategies are denoted first, second, and third generation NPs, respectively. We believe that fusing these three strategies to engineer multifunctional PLGA NPs is the only way to achieve translational applications. PMID:27158367

  1. Ion Channels as Drug Targets in Central Nervous System Disorders

    PubMed Central

    Waszkielewicz, A.M; Gunia, A; Szkaradek, N; Słoczyńska, K; Krupińska, S; Marona, H

    2013-01-01

    Ion channel targeted drugs have always been related with either the central nervous system (CNS), the peripheral nervous system, or the cardiovascular system. Within the CNS, basic indications of drugs are: sleep disorders, anxiety, epilepsy, pain, etc. However, traditional channel blockers have multiple adverse events, mainly due to low specificity of mechanism of action. Lately, novel ion channel subtypes have been discovered, which gives premises to drug discovery process led towards specific channel subtypes. An example is Na+ channels, whose subtypes 1.3 and 1.7-1.9 are responsible for pain, and 1.1 and 1.2 – for epilepsy. Moreover, new drug candidates have been recognized. This review is focusing on ion channels subtypes, which play a significant role in current drug discovery and development process. The knowledge on channel subtypes has developed rapidly, giving new nomenclatures of ion channels. For example, Ca2+ channels are not any more divided to T, L, N, P/Q, and R, but they are described as Cav1.1-Cav3.3, with even newer nomenclature α1A-α1I and α1S. Moreover, new channels such as P2X1-P2X7, as well as TRPA1-TRPV1 have been discovered, giving premises for new types of analgesic drugs. PMID:23409712

  2. Fine structure of synaptogenesis in the vertebrate central nervous system.

    PubMed

    Vaughn, J E

    1989-01-01

    This article reviews studies of the formation of synaptic junctions in the vertebrate central nervous system. It is focused on electron microscopic investigations of synaptogenesis, although insights from other disciplines are interwoven where appropriate, as are findings from developing peripheral and invertebrate nervous systems. The first part of the review is concerned with the morphological maturation of synapses as described from both qualitative and quantitative perspectives. Next, epigenetic influences on synaptogenesis are examined, and later in the article the concept of epigenesis is integrated with that of hierarchy. It is suggested that the formation of synaptic junctions may take place as an ordered progression of epigenetically modulated events wherein each level of cellular affinity becomes subordinate to the one that follows. The ultimate determination of whether a synapse is maintained, modified or dissolved would be made by the changing molecular fabric of its junctional membranes. In closing, a hypothetical model of synaptogenesis is proposed, and an hierarchial order of events is associated with a speculative synaptogenic sequence. Key elements of this hypothesis are 1) epigenetic factors that facilitate generally appropriate interactions between neurites; 2) independent expression of surface specializations that contain sufficient information for establishing threshold recognition between interacting neurites; 3) exchange of molecular information that biases the course of subsequent junctional differentiation and ultimately results in 4) the stabilization of synaptic junctions into functional connectivity patterns. PMID:2655146

  3. [Role of drug transporters in the central nervous system].

    PubMed

    Erdő, Franciska; Temesszentandrási-Ambrus, Csilla; Beéry, Erzsébet

    2016-03-01

    Although the presence of blood-brain barrier in the mammalian organisms was discovered in the early 1900s, its precise structure and the drug transporter proteins localized in the blood-brain barrier were identified only in the last decades. Beside the ATP-binding cassette transporter proteins responsible for the protection of the brain, the Solute Carrier transporters play also an important role in the function of the central nervous system by its feeding, energy supply and cleaning function during the metabolism. This review provides an overview on the main types of transporters located in the brain, on their localization in different cell types and the main techniques for their investigation. In the second part of this article various neurodegenerative disorders and the pathology-related transporter proteins are presented. In the light of recent experimental results new therapeutic strategies may come into the focus of research for the treatment of disorders currently without effective therapy. PMID:26920327

  4. Outcomes of persons with blastomycosis involving the central nervous system.

    PubMed

    Bush, Jonathan W; Wuerz, Terry; Embil, John M; Del Bigio, Marc R; McDonald, Patrick J; Krawitz, Sherry

    2013-06-01

    Blastomyces dermatitidis is a dimorphic fungus which is potentially life-threatening if central nervous system (CNS) dissemination occurs. Sixteen patients with proven or probable CNS blastomycosis are presented. Median duration of symptoms was 90 days; headache and focal neurologic deficit were the most common presenting symptoms. Magnetic resonance imaging (MRI) consistently demonstrated an abnormality, compared to 58% of computed tomography scans. Tissue culture yielded the pathogen in 71% of histology-confirmed cases. All patients who completed treatment of an amphotericin B formulation and extended azole-based therapy did not relapse. Initial nonspecific symptoms lead to delayed diagnosis of CNS blastomycosis. A high index of suspicion is necessary if there is history of contact with an area where B. dermatitidis is endemic. Diagnostic tests should include MRI followed by biopsy for tissue culture and pathology. Optimal treatment utilizes a lipid-based amphotericin B preparation with an extended course of voriconazole. PMID:23566338

  5. Regenerative Therapies for Central Nervous System Diseases: a Biomaterials Approach

    PubMed Central

    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

  6. Magnetic resonance imaging in central nervous system tuberculosis

    PubMed Central

    Trivedi, Richa; Saksena, Sona; Gupta, Rakesh K

    2009-01-01

    Tuberculosis (TB) in any form is a devastating disease, which in its most severe form involves the central nervous system (CNS), with a high mortality and morbidity. Early diagnosis of CNS TB is necessary for appropriate treatment to reduce this morbidity and mortality. Routine diagnostic techniques involve culture and immunological tests of the tissue and biofluids, which are time-consuming and may delay definitive management. Noninvasive imaging modalities such as computed tomography (CT) scan and magnetic resonance imaging (MRI) are routinely used in the diagnosis of neurotuberculosis, with MRI offering greater inherent sensitivity and specificity than CT scan. In addition to conventional MRI imaging, magnetization transfer imaging, diffusion imaging, and proton magnetic resonance spectroscopy techniques are also being evaluated for better tissue characterization in CNS TB. The current article reviews the role of various MRI techniques in the diagnosis and management of CNS TB. PMID:19881100

  7. Cell fate control in the developing central nervous system

    SciTech Connect

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

    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.

  8. Enterovirus Infections of the Central Nervous System Review

    PubMed Central

    Rhoades, Ross E.; Tabor-Godwin, Jenna M.; Tsueng, Ginger; Feuer, Ralph

    2011-01-01

    Enteroviruses (EV) frequently infect the central nervous system (CNS) and induce neurological diseases. Although the CNS is composed of many different cell types, the spectrum of tropism for each EV is considerable. These viruses have the ability to completely shut down host translational machinery and are considered highly cytolytic, thereby causing cytopathic effects. Hence, CNS dysfunction following EV infection of neuronal or glial cells might be expected. Perhaps unexpectedly given their cytolytic nature, EVs may establish a persistent infection within the CNS, and the lasting effects on the host might be significant with unanticipated consequences. This review will describe the clinical aspects of EV-mediated disease, mechanisms of disease, determinants of tropism, immune activation within the CNS, and potential treatment regimes. PMID:21251690

  9. Excitability tuning of axons in the central nervous system.

    PubMed

    Ohura, Shunsuke; Kamiya, Haruyuki

    2016-05-01

    The axon is a long neuronal process that originates from the soma and extends towards the presynaptic terminals. The pioneering studies on the squid giant axon or the spinal cord motoneuron established that the axon conducts action potentials faithfully to the presynaptic terminals with self-regenerative processes of membrane excitation. Recent studies challenged the notion that the fundamental understandings obtained from the study of squid giant axons are readily applicable to the axons in the mammalian central nervous system (CNS). These studies revealed that the functional and structural properties of the CNS axons are much more variable than previously thought. In this review article, we summarize the recent understandings of axon physiology in the mammalian CNS due to progress in the subcellular recording techniques which allow direct recordings from the axonal membranes, with emphasis on the hippocampal mossy fibers as a representative en passant axons typical for cortical axons. PMID:26493201

  10. Targeting protein kinases in central nervous system disorders

    PubMed Central

    Chico, Laura K.; Van Eldik, Linda J.; Watterson, D. Martin

    2010-01-01

    Protein kinases are a growing drug target class in disorders in peripheral tissues, but the development of kinase-targeted therapies for central nervous system (CNS) diseases remains a challenge, largely owing to issues associated specifically with CNS drug discovery. However, several candidate therapeutics that target CNS protein kinases are now in various stages of preclinical and clinical development. We review candidate compounds and discuss selected CNS protein kinases that are emerging as important therapeutic targets. In addition, we analyse trends in small-molecule properties that correlate with key challenges in CNS drug discovery, such as blood–brain barrier penetrance and cytochrome P450-mediated metabolism, and discuss the potential of future approaches that will integrate molecular-fragment expansion with pharmacoinformatics to address these challenges. PMID:19876042

  11. Electrical stimuli in the central nervous system microenvironment.

    PubMed

    Thompson, Deanna M; Koppes, Abigail N; Hardy, John G; Schmidt, Christine E

    2014-07-11

    Electrical stimulation to manipulate the central nervous system (CNS) has been applied as early as the 1750s to produce visual sensations of light. Deep brain stimulation (DBS), cochlear implants, visual prosthetics, and functional electrical stimulation (FES) are being applied in the clinic to treat a wide array of neurological diseases, disorders, and injuries. This review describes the history of electrical stimulation of the CNS microenvironment; recent advances in electrical stimulation of the CNS, including DBS to treat essential tremor, Parkinson's disease, and depression; FES for the treatment of spinal cord injuries; and alternative electrical devices to restore vision and hearing via neuroprosthetics (retinal and cochlear implants). It also discusses the role of electrical cues during development and following injury and, importantly, manipulation of these endogenous cues to support regeneration of neural tissue. PMID:25014787

  12. Magnetic resonance imaging of the central nervous system

    SciTech Connect

    Not Available

    1988-02-26

    This report reviews the current applications of magnetic resonance imaging of the central nervous system. Since its introduction into the clinical environment in the early 1980's, this technology has had a major impact on the practice of neurology. It has proved to be superior to computed tomography for imaging many diseases of the brain and spine. In some instances it has clearly replaced computed tomography. It is likely that it will replace myelography for the assessment of cervicomedullary junction and spinal regions. The magnetic field strengths currently used appear to be entirely safe for clinical application in neurology except in patients with cardiac pacemakers or vascular metallic clips. Some shortcomings of magnetic resonance imaging include its expense, the time required for scanning, and poor visualization of cortical bone.

  13. Role of radiology in central nervous system stimulation

    PubMed Central

    Pereira, E A C; Young, V E L; Hogarth, K M; Quaghebeur, G

    2015-01-01

    Central nervous system (CNS) stimulation is becoming increasingly prevalent. Deep brain stimulation (DBS) has been proven to be an invaluable treatment for movement disorders and is also useful in many other neurological conditions refractory to medical treatment, such as chronic pain and epilepsy. Neuroimaging plays an important role in operative planning, target localization and post-operative follow-up. The use of imaging in determining the underlying mechanisms of DBS is increasing, and the dependence on imaging is likely to expand as deep brain targeting becomes more refined. This article will address the expanding role of radiology and highlight issues, including MRI safety concerns, that radiologists may encounter when confronted with a patient with CNS stimulation equipment in situ. PMID:25715044

  14. Optimized optical clearing method for imaging central nervous system

    NASA Astrophysics Data System (ADS)

    Yu, Tingting; Qi, Yisong; Gong, Hui; Luo, Qingming; Zhu, Dan

    2015-03-01

    The development of various optical clearing methods provides a great potential for imaging entire central nervous system by combining with multiple-labelling and microscopic imaging techniques. These methods had made certain clearing contributions with respective weaknesses, including tissue deformation, fluorescence quenching, execution complexity and antibody penetration limitation that makes immunostaining of tissue blocks difficult. The passive clarity technique (PACT) bypasses those problems and clears the samples with simple implementation, excellent transparency with fine fluorescence retention, but the passive tissue clearing method needs too long time. In this study, we not only accelerate the clearing speed of brain blocks but also preserve GFP fluorescence well by screening an optimal clearing temperature. The selection of proper temperature will make PACT more applicable, which evidently broaden the application range of this method.

  15. [Neurocognitive Disorders Caused by Central Nervous System Lupus Erythematosus].

    PubMed

    Nishimura, Katsuji

    2016-04-01

    Systemic lupus erythematosus (SLE) is a chronic autoimmune disease involving multiple biological systems that has primary and secondary effects on the central nervous system. Neuropsychiatric manifestations of SLE (NPSLE) are common and are associated with a worse prognosis, more cumulative organ damage, and decreased quality of life. The neurocognitive disorders of NPSLE include an acute confusional state and cognitive dysfunction. The pathogenic mechanisms underlying NPSLE are likely to be multifactorial and may involve vasculopathy of predominantly small intracranial blood vessels, autoantibody production, and intrathecal production of proinflammatory cytokines. No disease-specific diagnostic markers or diagnostic gold standard is known for NPSLE. Thus, the first step of the diagnostic work-up is to exclude non-SLE-related conditions. The correct diagnosis is derived from careful analysis of the clinical, laboratory, and imaging data on a case-by-case basis. This article reviews the current literature, especially on the neurocognitive disorders of NPSLE. PMID:27056854

  16. Studies on central nervous system serotonin receptors in mood disorders.

    PubMed

    Young, A; Goodwin, G M

    1991-01-01

    The evidence from studies of central nervous system serotonin (5-HT) receptors is reviewed and the role of these in the pathogenesis of mood disorders is discussed. Clinical evidence indicates that 5-HT function is abnormal in mood disorders. 5-HT precursors and selective inhibitors of 5-HT uptake are effective antidepressives and inhibition of 5-HT synthesis can block the action of antidepressives. Studies of 5-HT in experimental animals after chronic administration of antidepressive treatments suggest that intact 5-HT neurons are necessary for the action of these treatments. Multiple 5-HT receptor subtypes have recently been identified and the effects of chronic antidepressive treatment on some receptor subtypes function in experimental animals have been established. The increasing availability of powerful new in vivo imaging techniques like single photon emission tomography (SPET), and positron emission tomography (PET) may make possible a more direct examination of 5-HT receptor function in patients suffering from mood disorders. PMID:2029163

  17. Zinc in the central nervous system: From molecules to behavior

    PubMed Central

    Gower-Winter, Shannon D.; Levenson, Cathy W.

    2012-01-01

    The trace metal zinc is a biofactor that plays essential roles in the central nervous system across the lifespan from early neonatal brain development through the maintenance of brain function in adults. At the molecular level, zinc regulates gene expression through transcription factor activity and is responsible for the activity of dozens of key enzymes in neuronal metabolism. At the cellular level, zinc is a modulator of synaptic activity and neuronal plasticity in both development and adulthood. Given these key roles, it is not surprising that alterations in brain zinc status have been implicated in a wide array of neurological disorders including impaired brain development, neurodegenerative disorders such as Alzheimer’s disease, and mood disorders including depression. Zinc has also been implicated in neuronal damage associated with traumatic brain injury, stroke, and seizure. Understanding the mechanisms that control brain zinc homeostasis is thus critical to the development of preventive and treatment strategies for these and other neurological disorders. PMID:22473811

  18. Recovery from central nervous system changes following volatile substance misuse.

    PubMed

    Dingwall, Kylie M; Cairney, Sheree

    2011-01-01

    This review examines cognitive, neurological, and neuroanatomical recovery associated with abstinence from volatile substance misuse (VSM). Articles describing functional or structural brain changes longitudinally or cross-sectional reports comparing current and abstinent users were identified and reviewed. A significant lack of empirical studies investigating central nervous system recovery following VSM was noted. The few case reports and group studies identified indicated that cognitive and neurological impairments appear to follow a progression of decline and progression of recovery model, with the severity of impairment related to the duration and severity of misuse, blood lead levels among leaded petrol misusers, and the duration of abstinence for recovery. By contrast, severe neurological impairment known as lead encephalopathy from sniffing leaded petrol occurred as more catastrophic or abrupt damage to cerebellar processes that may never fully recover. Neuroanatomical damage may not recover even with prolonged abstinence. PMID:21609150

  19. Cysticercosis of the central nervous system: clinical and therapeutic considerations.

    PubMed Central

    Torrealba, G; Del Villar, S; Tagle, P; Arriagada, P; Kase, C S

    1984-01-01

    In a group of forty cases of cysticercosis of the central nervous system, 59% presented with intracranial hypertension due to obstructive hydrocephalus. Ventricular or cisternal cysts, and chronic cysticercus meningitis were the most common causes of hydrocephalus. Seizures occurred in 40% of the patients, in one-half of them in association with CT-detected parenchymatous cysts. In 20% of the cases progressive mental deterioration was the main clinical feature, at times associated with hydrocephalus. CT scan provided the highest diagnostic yield, being abnormal in 90% of cases. Long term prognosis was poor, with a mortality rate of 38% over a 40-month follow-up period. The most common cause of death (60%) was meningitis. CSF shunting is the treatment of choice for hydrocephalus, irrespective of its mechanism. Surgical resection is indicated in some cases with a single superficial (cortical) or posterior fossa cyst. Supratentorial cysts carry a relatively benign prognosis. Images PMID:6470720

  20. Methods for Gene Transfer to the Central Nervous System

    PubMed Central

    Kantor, Boris; Bailey, Rachel M.; Wimberly, Keon; Kalburgi, Sahana N.; Gray, Steven J.

    2015-01-01

    Gene transfer is an increasingly utilized approach for research and clinical applications involving the central nervous system (CNS). Vectors for gene transfer can be as simple as an unmodified plasmid, but more commonly involve complex modifications to viruses to make them suitable gene delivery vehicles. This chapter will explain how tools for CNS gene transfer have been derived from naturally occurring viruses. The current capabilities of plasmid, retroviral, adeno-associated virus, adenovirus, and herpes simplex virus vectors for CNS gene delivery will be described. These include both focal and global CNS gene transfer strategies, with short- or long-term gene expression. As is described in this chapter, an important aspect of any vector is the cis-acting regulatory elements incorporated into the vector genome that control when, where, and how the transgene is expressed. PMID:25311922

  1. Breast Cancer Metastasis to the Central Nervous System

    PubMed Central

    Weil, Robert J.; Palmieri, Diane C.; Bronder, Julie L.; Stark, Andreas M.; Steeg, Patricia S.

    2005-01-01

    Clinically symptomatic metastases to the central nervous system (CNS) occur in ∼10 to 15% of patients with metastatic beast cancer. CNS metastases are traditionally viewed as a late complication of systemic disease, for which few effective treatment options exist. Recently, patients with Her-2-positive breast tumors who were treated with trastuzumab have been reported to develop CNS metastases at higher rates, often while responding favorably to treatment. The blood:brain barrier and the unique brain microenvironment are hypothesized to promote distinct molecular features in CNS metastases that may require tailored therapeutic approaches. New research approaches using cell lines that reliably and preferentially metastasize in vivo to the brain have been reported. Using such model systems, as well as in vitro analogs of blood-brain barrier penetration and tissue-based studies, new molecular leads into this disease are unfolding. PMID:16192626

  2. Breast cancer metastasis to the central nervous system.

    PubMed

    Weil, Robert J; Palmieri, Diane C; Bronder, Julie L; Stark, Andreas M; Steeg, Patricia S

    2005-10-01

    Clinically symptomatic metastases to the central nervous system (CNS) occur in approximately 10 to 15% of patients with metastatic beast cancer. CNS metastases are traditionally viewed as a late complication of systemic disease, for which few effective treatment options exist. Recently, patients with Her-2-positive breast tumors who were treated with trastuzumab have been reported to develop CNS metastases at higher rates, often while responding favorably to treatment. The blood:brain barrier and the unique brain microenvironment are hypothesized to promote distinct molecular features in CNS metastases that may require tailored therapeutic approaches. New research approaches using cell lines that reliably and preferentially metastasize in vivo to the brain have been reported. Using such model systems, as well as in vitro analogs of blood-brain barrier penetration and tissue-based studies, new molecular leads into this disease are unfolding. PMID:16192626

  3. Rosai-Dorfman Disease of the Central Nervous System

    PubMed Central

    Sandoval-Sus, Jose D.; Sandoval-Leon, Ana C.; Chapman, Jennifer R.; Velazquez-Vega, Jose; Borja, Maria J.; Rosenberg, Shai; Lossos, Alexander; Lossos, Izidore S.

    2014-01-01

    Abstract Rosai-Dorfman disease (RDD), also known as sinus histiocytosis with massive lymphadenopathy (SHML), is an uncommon benign idiopathic lymphoproliferative disorder. The histologic hallmark of RDD is the finding of emperipolesis displayed by lesional histiocytes. While RDD most commonly affects lymph nodes, extranodal involvement of multiple organs has been reported, including the central nervous system (CNS). However, CNS involvement in RDD is rare and is not well characterized. As a result, therapeutic approaches to CNS involvement in RDD are not well established. Herein we report 6 cases of RDD with isolated CNS involvement and review the literature on RDD with CNS involvement. One of the presented cases exhibited intramedullary involvement of the spinal cord—a very rare form of RDD with CNS involvement. PMID:24797172

  4. Central Nervous System Cancers, Version 1.2015.

    PubMed

    Nabors, Louis Burt; Portnow, Jana; Ammirati, Mario; Baehring, Joachim; Brem, Henry; Brown, Paul; Butowski, Nicholas; Chamberlain, Marc C; Fenstermaker, Robert A; Friedman, Allan; Gilbert, Mark R; Hattangadi-Gluth, Jona; Holdhoff, Matthias; Junck, Larry; Kaley, Thomas; Lawson, Ronald; Loeffler, Jay S; Lovely, Mary P; Moots, Paul L; Mrugala, Maciej M; Newton, Herbert B; Parney, Ian; Raizer, Jeffrey J; Recht, Lawrence; Shonka, Nicole; Shrieve, Dennis C; Sills, Allen K; Swinnen, Lode J; Tran, David; Tran, Nam; Vrionis, Frank D; Weiss, Stephanie; Wen, Patrick Yung; McMillian, Nicole; Engh, Anita M

    2015-10-01

    The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Central Nervous System (CNS) Cancers provide interdisciplinary recommendations for managing adult CNS cancers. Primary and metastatic brain tumors are a heterogeneous group of neoplasms with varied outcomes and management strategies. These NCCN Guidelines Insights summarize the NCCN CNS Cancers Panel's discussion and highlight notable changes in the 2015 update. This article outlines the data and provides insight into panel decisions regarding adjuvant radiation and chemotherapy treatment options for high-risk newly diagnosed low-grade gliomas and glioblastomas. Additionally, it describes the panel's assessment of new data and the ongoing debate regarding the use of alternating electric field therapy for high-grade gliomas. PMID:26483059

  5. Primary Central Nervous System Vasculitis With Optic Nerve Involvement.

    PubMed

    Benson, Christy E; Knezevic, Alexander; Lynch, Shannon C

    2016-06-01

    A 20-year-old woman presented with headache, decreased vision, eye pain, and urinary retention. During her clinical course, visual acuity declined to 20/800, right eye, and 20/50, left eye, associated with bilateral optic disc edema. Brain magnetic resonance imaging revealed enhancement of the leptomeninges, right optic nerve, and right side of the optic chiasm. Extensive evaluation of the central nervous system (CNS) for an infectious cause was negative. Brain biopsy showed a pattern consistent with vasculitis. The patient was treated with prednisone and cyclophosphamide, resulting in improvement of her vision and systemic symptoms. Primary CNS vasculitis is a rare condition that may affect the anterior visual pathways. PMID:26693942

  6. Tuberculous Panophthalmitis with Lymphadenitis and Central Nervous System Tuberculoma

    PubMed Central

    Srichatrapimuk, Sirawat; Wattanatranon, Duangkamon

    2016-01-01

    Tuberculosis (TB) is a serious infectious disease that spreads globally. The ocular manifestations of TB are uncommon and diverse. TB panophthalmitis has been rarely reported. Here, we described a 38-year-old Thai man presenting with panophthalmitis of the right eye. Further investigation showed that he had concurrent TB lymphadenitis and central nervous system (CNS) tuberculoma, as well as HIV infection, with a CD4 cell count of 153 cells/mm3. Despite the initial response to antituberculous agents, the disease had subsequently progressed and enucleation was required. The pathological examination revealed acute suppurative granulomatous panophthalmitis with retinal detachment. Further staining demonstrated acid-fast bacilli in the tissue. Colonies of Mycobacterium tuberculosis were obtained from tissue culture. He was treated with antiretroviral agents for HIV infection and 12 months of antituberculous agents. Clinicians should be aware of the possibility of TB in the differential diagnosis of endophthalmitis and panophthalmitis, especially in regions where TB is endemic. PMID:27051539

  7. Multifaceted interactions between adaptive immunity and the central nervous system.

    PubMed

    Kipnis, Jonathan

    2016-08-19

    Neuroimmunologists seek to understand the interactions between the central nervous system (CNS) and the immune system, both under homeostatic conditions and in diseases. Unanswered questions include those relating to the diversity and specificity of the meningeal T cell repertoire; the routes taken by immune cells that patrol the meninges under healthy conditions and invade the parenchyma during pathology; the opposing effects (beneficial or detrimental) of these cells on CNS function; the role of immune cells after CNS injury; and the evolutionary link between the two systems, resulting in their tight interaction and interdependence. This Review summarizes the current standing of and challenging questions related to interactions between adaptive immunity and the CNS and considers the possible directions in which these aspects of neuroimmunology will be heading over the next decade. PMID:27540163

  8. Central nervous system infections caused by varicella-zoster virus.

    PubMed

    Chamizo, Francisco J; Gilarranz, Raúl; Hernández, Melisa; Ramos, Diana; Pena, María José

    2016-08-01

    We carried out a clinical and epidemiological study of adult patients with varicella-zoster virus central nervous system infection diagnosed by PCR in cerebrospinal fluid. Twenty-six patients were included. Twelve (46.2 %) patients were diagnosed with meningitis and fourteen (53.8 %) with meningoencephalitis. Twelve (46.2 %) had cranial nerves involvement (mainly the facial (VII) and vestibulocochlear (VIII) nerves), six (23.1 %) had cerebellar involvement, fourteen (53.8 %) had rash, and four (15.4 %) developed Ramsay Hunt syndrome. Three (11.5 %) patients had sequelae. Length of stay was significantly lower in patients diagnosed with meningitis and treatment with acyclovir was more frequent in patients diagnosed with meningoencephalitis. We believe routine detection of varicella-zoster virus, regardless of the presence of rash, is important because the patient may benefit from a different clinical management. PMID:26769041

  9. Central nervous system hypoxia in children due to near drowning

    SciTech Connect

    Fitch, S.J.; Gerald, B.; Magill, H.L.; Tonkin, I.L.D.

    1985-09-01

    Fourteen children who experienced acute, profound central nervous system hypoxia secondary to near drowning, aspiration, or respiratory arrest underwent CT examination. During the first week after the episode, the most frequent finding was a loss of gray-white matter differentiation. Other findings included effacement of sulci and cisterns, focal areas of edema in the cerebral cortex or basal ganglia, and hemorrhagic infarctions of the basal ganglia. Subsequent CT scans obtained from two weeks to five months after the hypoxic episode showed progression of cerebral loss from cortical infarction with gyral hemorrhage and enhancement to global parenchymal atrophy. The prognosis is poor in these patients: seven children experienced severe neurologic deficits and seven died.

  10. Neuroinvasion and Inflammation in Viral Central Nervous System Infections

    PubMed Central

    Schroten, Horst

    2016-01-01

    Neurotropic viruses can cause devastating central nervous system (CNS) infections, especially in young children and the elderly. The blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB) have been described as relevant sites of entry for specific viruses as well as for leukocytes, which are recruited during the proinflammatory response in the course of CNS infection. In this review, we illustrate examples of established brain barrier models, in which the specific reaction patterns of different viral families can be analyzed. Furthermore, we highlight the pathogen specific array of cytokines and chemokines involved in immunological responses in viral CNS infections. We discuss in detail the link between specific cytokines and chemokines and leukocyte migration profiles. The thorough understanding of the complex and interrelated inflammatory mechanisms as well as identifying universal mediators promoting CNS inflammation is essential for the development of new diagnostic and treatment strategies. PMID:27313404

  11. Optimizing Central Nervous System Drug Development Using Molecular Imaging.

    PubMed

    Hargreaves, R J; Hoppin, J; Sevigny, J; Patel, S; Chiao, P; Klimas, M; Verma, A

    2015-07-01

    Advances in multimodality fusion imaging technologies promise to accelerate the understanding of the systems biology of disease and help in the development of new therapeutics. The use of molecular imaging biomarkers has been proven to shorten cycle times for central nervous system (CNS) drug development and thereby increase the efficiency and return on investment from research. Imaging biomarkers can be used to help select the molecules, doses, and patients most likely to test therapeutic hypotheses by stopping those that have little chance of success and accelerating those with potential to achieve beneficial clinical outcomes. CNS imaging biomarkers have the potential to drive new medical care practices for patients in the latent phases of progressive neurodegenerative disorders by enabling the detection, preventative treatment, and tracking of disease in a paradigm shift from today's approaches that have to see the overt symptoms of disease before treating it. PMID:25869938

  12. Control of cutaneous blood flow by central nervous system.

    PubMed

    Ootsuka, Youichirou; Tanaka, Mutsumi

    2015-01-01

    Hairless skin acts as a heat exchanger between body and environment, and thus greatly contributes to body temperature regulation by changing blood flow to the skin (cutaneous) vascular bed during physiological responses such as cold- or warm-defense and fever. Cutaneous blood flow is also affected by alerting state; we 'go pale with fright'. The rabbit ear pinna and the rat tail have hairless skin, and thus provide animal models for investigating central pathway regulating blood flow to cutaneous vascular beds. Cutaneous blood flow is controlled by the centrally regulated sympathetic nervous system. Sympathetic premotor neurons in the medullary raphé in the lower brain stem are labeled at early stage after injection of trans-synaptic viral tracer into skin wall of the rat tail. Inactivation of these neurons abolishes cutaneous vasomotor changes evoked as part of thermoregulatory, febrile or psychological responses, indicating that the medullary raphé is a common final pathway to cutaneous sympathetic outflow, receiving neural inputs from upstream nuclei such as the preoptic area, hypothalamic nuclei and the midbrain. Summarizing evidences from rats and rabbits studies in the last 2 decades, we will review our current understanding of the central pathways mediating cutaneous vasomotor control. PMID:27227053

  13. Control of cutaneous blood flow by central nervous system

    PubMed Central

    Ootsuka, Youichirou; Tanaka, Mutsumi

    2015-01-01

    Hairless skin acts as a heat exchanger between body and environment, and thus greatly contributes to body temperature regulation by changing blood flow to the skin (cutaneous) vascular bed during physiological responses such as cold- or warm-defense and fever. Cutaneous blood flow is also affected by alerting state; we ‘go pale with fright’. The rabbit ear pinna and the rat tail have hairless skin, and thus provide animal models for investigating central pathway regulating blood flow to cutaneous vascular beds. Cutaneous blood flow is controlled by the centrally regulated sympathetic nervous system. Sympathetic premotor neurons in the medullary raphé in the lower brain stem are labeled at early stage after injection of trans-synaptic viral tracer into skin wall of the rat tail. Inactivation of these neurons abolishes cutaneous vasomotor changes evoked as part of thermoregulatory, febrile or psychological responses, indicating that the medullary raphé is a common final pathway to cutaneous sympathetic outflow, receiving neural inputs from upstream nuclei such as the preoptic area, hypothalamic nuclei and the midbrain. Summarizing evidences from rats and rabbits studies in the last 2 decades, we will review our current understanding of the central pathways mediating cutaneous vasomotor control. PMID:27227053

  14. Metabolic Profiling and Phenotyping of Central Nervous System Diseases: Metabolites Bring Insights into Brain Dysfunctions.

    PubMed

    Dumas, Marc-Emmanuel; Davidovic, Laetitia

    2015-09-01

    Metabolic phenotyping corresponds to the large-scale quantitative and qualitative analysis of the metabolome i.e., the low-molecular weight <1 KDa fraction in biological samples, and provides a key opportunity to advance neurosciences. Proton nuclear magnetic resonance and mass spectrometry are the main analytical platforms used for metabolic profiling, enabling detection and quantitation of a wide range of compounds of particular neuro-pharmacological and physiological relevance, including neurotransmitters, secondary messengers, structural lipids, as well as their precursors, intermediates and degradation products. Metabolic profiling is therefore particularly indicated for the study of central nervous system by probing metabolic and neurochemical profiles of the healthy or diseased brain, in preclinical models or in human samples. In this review, we introduce the analytical and statistical requirements for metabolic profiling. Then, we focus on key studies in the field of metabolic profiling applied to the characterization of animal models and human samples of central nervous system disorders. We highlight the potential of metabolic profiling for pharmacological and physiological evaluation, diagnosis and drug therapy monitoring of patients affected by brain disorders. Finally, we discuss the current challenges in the field, including the development of systems biology and pharmacology strategies improving our understanding of metabolic signatures and mechanisms of central nervous system diseases. PMID:25616565

  15. Severe and fatal central nervous system disease in humans caused by Baylisascaris procyonis, the common roundworm of raccoons: a review of current literature.

    PubMed

    Wise, Matthew E; Sorvillo, Frank J; Shafir, Shira C; Ash, Lawrence R; Berlin, O George

    2005-02-01

    Baylisascaris procyonis, a parasitic infection of raccoons, causes severe neurologic disease in humans when infective eggs from raccoon feces are ingested. Definitive diagnosis is challenging, but can be made by isolation of larvae in brain biopsy or exclusion of other potential causes of eosinophilic meningoencephalitis. Prevention efforts are critical due to the lack of effective treatment. PMID:15715975

  16. Do the Images of Neuronal Pathways in the Human Central Nervous System Show Feed-back? A Comparative Study in Fifteen Countries.

    ERIC Educational Resources Information Center

    Clement, Pierre; Mouelhi, Lassaad; Kochkar, Momahed; Valanides, Nicos; Nisiforou, Olia; Thiaw, Seyni Mame; Ndiaye, Valdiodio; Jeanbart, Paula; Horvath, Daniel; Ferreira, Claudia; Carvalho, Graca S.

    2010-01-01

    In the human brain, the neuronal pathways are networks which support our learning, memory and thought, and which work with permanent feedback. However, only 19% of illustrations of these neuronal pathways, in the 55 analysed school textbooks coming from 15 countries, were showing feedbacks. The neuronal pathways related to movements were generally…

  17. Surinabant, a selective cannabinoid receptor type 1 antagonist, inhibits Δ9-tetrahydrocannabinol-induced central nervous system and heart rate effects in humans

    PubMed Central

    Klumpers, Linda E; Roy, Christine; Ferron, Geraldine; Turpault, Sandrine; Poitiers, Franck; Pinquier, Jean-Louis; van Hasselt, Johan G C; Zuurman, Lineke; Erwich, Frank A S; van Gerven, Joop M A

    2013-01-01

    Aim Cannabinoid receptor type 1 (CB1) antagonists have been developed for the treatment of obesity and associated risk factors. Surinabant is a high affinity CB1 antagonist in vitro. The aim of this study was to assess the magnitude of inhibition by surinabant of CNS effects and heart rate induced by Δ9-tetrahydrocannabinol (THC) in humans. Methods This was a double-blind, placebo-controlled, randomized, four period six sequence crossover study. Thirty healthy young male occasional cannabis users (<1 per week) were included. A single oral dose of surinabant (5, 20 or 60 mg) or placebo was administered followed 1.5 h later by four intrapulmonary THC doses (2, 4, 6 and 6 mg) or vehicle, administered at 1 h intervals. The wash-out period was 14–21 days. Subjective and objective pharmacodynamic (PD) measurements were performed. A population PK–PD model for THC and surinabant quantified PK and PD effects. Results Surinabant 20 and 60 mg inhibited all THC-induced PD effects in a similar range for both doses with inhibition ratios ranging from 68.3% (95% CI = 32.5, 104.2; heart rate) to 91.1% (95% CI = 30.3, 151.8; body sway). IC50 ranged from 22.0 ng ml−1 [relative standard error (RSE) = 45.2%; body sway] to 58.8 ng ml−1 (RSE = 44.2%; internal perception). Surinabant 5 mg demonstrated no significant effects. Conclusions The dose-related inhibition by surinabant, without any effect of its own, suggests that this compound behaves as a CB1 receptor antagonist in humans at these concentrations. A single surinabant dose between 5 to 20 mg and above was able to antagonize THC-induced effects in humans. PMID:23278647

  18. The role of microbiome in central nervous system disorders.

    PubMed

    Wang, Yan; Kasper, Lloyd H

    2014-05-01

    Mammals live in a co-evolutionary association with the plethora of microorganisms that reside at a variety of tissue microenvironments. The microbiome represents the collective genomes of these co-existing microorganisms, which is shaped by host factors such as genetics and nutrients but in turn is able to influence host biology in health and disease. Niche-specific microbiome, prominently the gut microbiome, has the capacity to effect both local and distal sites within the host. The gut microbiome has played a crucial role in the bidirectional gut-brain axis that integrates the gut and central nervous system (CNS) activities, and thus the concept of microbiome-gut-brain axis is emerging. Studies are revealing how diverse forms of neuro-immune and neuro-psychiatric disorders are correlated with or modulated by variations of microbiome, microbiota-derived products and exogenous antibiotics and probiotics. The microbiome poises the peripheral immune homeostasis and predisposes host susceptibility to CNS autoimmune diseases such as multiple sclerosis. Neural, endocrine and metabolic mechanisms are also critical mediators of the microbiome-CNS signaling, which are more involved in neuro-psychiatric disorders such as autism, depression, anxiety, stress. Research on the role of microbiome in CNS disorders deepens our academic knowledge about host-microbiome commensalism in central regulation and in practicality, holds conceivable promise for developing novel prognostic and therapeutic avenues for CNS disorders. PMID:24370461

  19. Connexin32 expression in central and peripheral nervous systems

    SciTech Connect

    Deschenes, S.M.; Scherer, S.S.; Fischbeck, K.H.

    1994-09-01

    Mutations have been identified in the gap junction gene, connexin32 (Cx32), in patients affected with the X-linked form of the demyelinating neuropathy, Charcot-Marie-Tooth disease (CMTX). Gap junctions composed of Cx32 are present and developmentally regulated in a wide variety of tissues. In peripheral nerve, our immunohistochemical analysis localized Cx32 to the noncompacted myelin of the paranodal regions and the Schmidt-Lantermann incisures, where previous studies describe gap junctions. In contrast to the location of Cx32 in peripheral nerve and the usual restriction of clinical manifestations to the peripheral nervous system (PNS) (abstract by Paulson describes an exception), preliminary studies show that Cx32 is present in the compacted myelin of the central nervous system (CNS), as demonstrated by radial staining through the myelin sheath of oligodendrocytes in rat spinal cord. Analysis of Cx32 expression in various regions of rat CNS during development shows that the amount of Cx32 mRNA and protein increases as myelination increases, a pattern observed for other myelin genes. Studies in the PNS provide additional evidence that Cx32 and myelin genes are coordinately regulated at the transcriptional level; Cx32 and peripheral myelin gene PMP-22 mRNAs are expressed in parallel following transient or permanent nerve injury. Differences in post-translational regulation of Cx32 in the CNS and PNS may be indicated by the presence of a faster migrating form of Cs32 in cerebrum versus peripheral nerve. Studies are currently underway to determine the unique role of Cx32 in peripheral nerve.

  20. Detection of human herpesvirus-6 in adult central nervous system tumors: predominance of early and late viral antigens in glial tumors.

    PubMed

    Crawford, John R; Santi, Maria Rita; Cornelison, Robbie; Sallinen, Satu-Leena; Haapasalo, Hannu; MacDonald, Tobey J

    2009-10-01

    The purpose is to determine the incidence of active and latent human herpesvirus-6 (HHV-6) infection in a large cohort of adult primary and recurrent CNS tumors. We screened a tissue microarray (TMA) containing more than 200 adult primary and recurrent CNS tumors with known clinical information for the presence of HHV-6 DNA by in situ hybridization (ISH) and protein by immunohistochemistry (IHC). One hundred six of 224 (47%) CNS tumors were positive for HHV-6 U57 Major Capsid Protein (MCP) gene by ISH compared to 0/25 non tumor control brain (P = 0.001). Fourteen of 30 (47%) tumors were HHV-6 MCP positive by nested PCR compared to 0/25 non-tumor brain controls (P = 0.001), revealing HHV-6 Variant A in 6 of 14 samples. HHV-6A/B early (p41) and late (gp116/64/54) antigens were detected by IHC in 66 of 277 (24%) (P = 0.003) and 84 of 282 (35%) (P = 0.002) tumors, respectively, suggesting active infection. HHV-6 p41 (P = 0.645) and gp116/64/54 (P = 0.198) antigen detection was independent of recurrent disease. Glial tumors were 3 times more positive by IHC compared to non glial tumors for both HHV-6 gp116/64/54 (P = 0.0002) and HHV-6 p41 (P = 0.004). Kaplan Meier survival analysis showed no effect of HHV-6 gp116/64/54 (P = 0.852) or HHV-6 p41 (P = 0.817) antigen detection on survival. HHV-6 early and late antigens are detected in adult primary and recurrent CNS tumors more frequently in glial tumors. We hypothesize that the glial-tropic features of HHV-6 may play an important modifying role in tumor biology that warrants further investigation. PMID:19424665

  1. Detection frequency of human herpesviruses-6A, -6B, and -7 genomic sequences in central nervous system DNA samples from post-mortem individuals with unspecified encephalopathy.

    PubMed

    Chapenko, Svetlana; Roga, Silvija; Skuja, Sandra; Rasa, Santa; Cistjakovs, Maksims; Svirskis, Simons; Zaserska, Zane; Groma, Valerija; Murovska, Modra

    2016-08-01

    In this autopsy-based study, human herpesvirus-6 (HHV-6) and -7 (HHV-7) genomic sequence frequency, HHV-6 variants, HHV-6 load and the expression of HHV-6 antigens in brain samples from the individuals, with and without unspecified encephalopathy (controls), using nested and real-time polymerase chain reactions, restriction endonuclease, and immunohistochemical analysis were examined. GraphPad Prism 6.0 Mann-Whitney nonparametric and chi-square test and Fisher's exact test were used for statistical analysis. The encephalopathy diagnoses were shown by magnetic resonance imaging made during their lifetime and macro- and microscopically studied autopsy tissue materials. Widespread HHV-6 and/or HHV-7 positivity was detected in the brain tissue of various individuals with encephalopathy, as well as in controls (51/57, 89.4 % and 35/51, 68.6 %, respectively; p = 0.009). Significantly higher detection frequency of single HHV-6 and concurrent HHV-6 + HHV-7 DNA was found in pia mater meninges, frontal lobe, temporal lobe, and olfactory tract DNAs in individuals with encephalopathy compared to the control group. HHV-6 load and higher frequency of the viral load >10 copies/10(6) cells significantly differed in samples from individuals with and without encephalopathy. The expression of HHV-6 antigens was revealed in different neural cell types with strong predominance in the encephalopathy group. In all HHV-6-positive autopsy samples of individuals with and without encephalopathy, HHV-6B was revealed. Significantly higher detection frequency of beta-herpesvirus DNA, more often detected HHV-6 load >10 copies/10(6) cells, as well as the expression of HHV-6 antigens in different brain tissue samples from individuals with encephalopathy in comparison with control group indicate on potential involvement of these viruses in encephalopathy development. PMID:26727906

  2. Evolution of bilaterian central nervous systems: a single origin?

    PubMed Central

    2013-01-01

    The question of whether the ancestral bilaterian had a central nervous system (CNS) or a diffuse ectodermal nervous system has been hotly debated. Considerable evidence supports the theory that a CNS evolved just once. However, an alternative view proposes that the chordate CNS evolved from the ectodermal nerve net of a hemichordate-like ancestral deuterostome, implying independent evolution of the CNS in chordates and protostomes. To specify morphological divisions along the anterior/posterior axis, this ancestor used gene networks homologous to those patterning three organizing centers in the vertebrate brain: the anterior neural ridge, the zona limitans intrathalamica and the isthmic organizer, and subsequent evolution of the vertebrate brain involved elaboration of these ancestral signaling centers; however, all or part of these signaling centers were lost from the CNS of invertebrate chordates. The present review analyzes the evidence for and against these theories. The bulk of the evidence indicates that a CNS evolved just once – in the ancestral bilaterian. Importantly, in both protostomes and deuterostomes, the CNS represents a portion of a generally neurogenic ectoderm that is internalized and receives and integrates inputs from sensory cells in the remainder of the ectoderm. The expression patterns of genes involved in medio/lateral (dorso/ventral) patterning of the CNS are similar in protostomes and chordates; however, these genes are not similarly expressed in the ectoderm outside the CNS. Thus, their expression is a better criterion for CNS homologs than the expression of anterior/posterior patterning genes, many of which (for example, Hox genes) are similarly expressed both in the CNS and in the remainder of the ectoderm in many bilaterians. The evidence leaves hemichordates in an ambiguous position – either CNS centralization was lost to some extent at the base of the hemichordates, or even earlier, at the base of the hemichordates

  3. Evolution of bilaterian central nervous systems: a single origin?

    PubMed

    Holland, Linda Z; Carvalho, João E; Escriva, Hector; Laudet, Vincent; Schubert, Michael; Shimeld, Sebastian M; Yu, Jr-Kai

    2013-01-01

    The question of whether the ancestral bilaterian had a central nervous system (CNS) or a diffuse ectodermal nervous system has been hotly debated. Considerable evidence supports the theory that a CNS evolved just once. However, an alternative view proposes that the chordate CNS evolved from the ectodermal nerve net of a hemichordate-like ancestral deuterostome, implying independent evolution of the CNS in chordates and protostomes. To specify morphological divisions along the anterior/posterior axis, this ancestor used gene networks homologous to those patterning three organizing centers in the vertebrate brain: the anterior neural ridge, the zona limitans intrathalamica and the isthmic organizer, and subsequent evolution of the vertebrate brain involved elaboration of these ancestral signaling centers; however, all or part of these signaling centers were lost from the CNS of invertebrate chordates. The present review analyzes the evidence for and against these theories. The bulk of the evidence indicates that a CNS evolved just once - in the ancestral bilaterian. Importantly, in both protostomes and deuterostomes, the CNS represents a portion of a generally neurogenic ectoderm that is internalized and receives and integrates inputs from sensory cells in the remainder of the ectoderm. The expression patterns of genes involved in medio/lateral (dorso/ventral) patterning of the CNS are similar in protostomes and chordates; however, these genes are not similarly expressed in the ectoderm outside the CNS. Thus, their expression is a better criterion for CNS homologs than the expression of anterior/posterior patterning genes, many of which (for example, Hox genes) are similarly expressed both in the CNS and in the remainder of the ectoderm in many bilaterians. The evidence leaves hemichordates in an ambiguous position - either CNS centralization was lost to some extent at the base of the hemichordates, or even earlier, at the base of the hemichordates

  4. New approaches in primary central nervous system lymphoma

    PubMed Central

    Fraser, Eleanor; Gruenberg, Katherine; Rubenstein, James L.

    2016-01-01

    Primary central nervous system lymphoma (PCNSL) has long been associated with an inferior prognosis compared to other aggressive non-Hodgkin’s lymphomas (NHLs). However, during the past 10 years an accumulation of clinical experience has demonstrated that long-term progression-free survival (PFS) can be attained in a major proportion of PCNSL patients who receive dose-intensive consolidation chemotherapy and avoid whole brain radiotherapy. One recent approach that has reproducibly demonstrated efficacy for newly diagnosed PCNSL patients is an immunochemotherapy combination regimen used during induction that consists of methotrexate, temozolomide, and rituximab followed by consolidative infusional etoposide plus high-dose cytarabine (EA), administered in first complete remission (CR). Other high-dose chemotherapy-based consolidative regimens have shown efficacy as well. Our goal in this review is to update principles of diagnosis and management as well as data regarding the molecular pathogenesis of PCNSL, information that may constitute a basis for development of more effective therapies required to make additional advances in this phenotype of aggressive NHL. PMID:25841718

  5. Whole-central nervous system functional imaging in larval Drosophila

    PubMed Central

    Lemon, William C.; Pulver, Stefan R.; Höckendorf, Burkhard; McDole, Katie; Branson, Kristin; Freeman, Jeremy; Keller, Philipp J.

    2015-01-01

    Understanding how the brain works in tight concert with the rest of the central nervous system (CNS) hinges upon knowledge of coordinated activity patterns across the whole CNS. We present a method for measuring activity in an entire, non-transparent CNS with high spatiotemporal resolution. We combine a light-sheet microscope capable of simultaneous multi-view imaging at volumetric speeds 25-fold faster than the state-of-the-art, a whole-CNS imaging assay for the isolated Drosophila larval CNS and a computational framework for analysing multi-view, whole-CNS calcium imaging data. We image both brain and ventral nerve cord, covering the entire CNS at 2 or 5 Hz with two- or one-photon excitation, respectively. By mapping network activity during fictive behaviours and quantitatively comparing high-resolution whole-CNS activity maps across individuals, we predict functional connections between CNS regions and reveal neurons in the brain that identify type and temporal state of motor programs executed in the ventral nerve cord. PMID:26263051

  6. Clinical Proton MR Spectroscopy in Central Nervous System Disorders

    PubMed Central

    Alger, Jeffry R.; Barker, Peter B.; Bartha, Robert; Bizzi, Alberto; Boesch, Chris; Bolan, Patrick J.; Brindle, Kevin M.; Cudalbu, Cristina; Dinçer, Alp; Dydak, Ulrike; Emir, Uzay E.; Frahm, Jens; González, Ramón Gilberto; Gruber, Stephan; Gruetter, Rolf; Gupta, Rakesh K.; Heerschap, Arend; Henning, Anke; Hetherington, Hoby P.; Howe, Franklyn A.; Hüppi, Petra S.; Hurd, Ralph E.; Kantarci, Kejal; Klomp, Dennis W. J.; Kreis, Roland; Kruiskamp, Marijn J.; Leach, Martin O.; Lin, Alexander P.; Luijten, Peter R.; Marjańska, Małgorzata; Maudsley, Andrew A.; Meyerhoff, Dieter J.; Mountford, Carolyn E.; Nelson, Sarah J.; Pamir, M. Necmettin; Pan, Jullie W.; Peet, Andrew C.; Poptani, Harish; Posse, Stefan; Pouwels, Petra J. W.; Ratai, Eva-Maria; Ross, Brian D.; Scheenen, Tom W. J.; Schuster, Christian; Smith, Ian C. P.; Soher, Brian J.; Tkáč, Ivan; Vigneron, Daniel B.; Kauppinen, Risto A.

    2014-01-01

    A large body of published work shows that proton (hydrogen 1 [1H]) magnetic resonance (MR) spectroscopy has evolved from a research tool into a clinical neuroimaging modality. Herein, the authors present a summary of brain disorders in which MR spectroscopy has an impact on patient management, together with a critical consideration of common data acquisition and processing procedures. The article documents the impact of 1H MR spectroscopy in the clinical evaluation of disorders of the central nervous system. The clinical usefulness of 1H MR spectroscopy has been established for brain neoplasms, neonatal and pediatric disorders (hypoxia-ischemia, inherited metabolic diseases, and traumatic brain injury), demyelinating disorders, and infectious brain lesions. The growing list of disorders for which 1H MR spectroscopy may contribute to patient management extends to neurodegenerative diseases, epilepsy, and stroke. To facilitate expanded clinical acceptance and standardization of MR spectroscopy methodology, guidelines are provided for data acquisition and analysis, quality assessment, and interpretation. Finally, the authors offer recommendations to expedite the use of robust MR spectroscopy methodology in the clinical setting, including incorporation of technical advances on clinical units. © RSNA, 2014 Online supplemental material is available for this article. PMID:24568703

  7. Headache and inflammatory disorders of the central nervous system.

    PubMed

    La Mantia, L; Erbetta, A

    2004-10-01

    The subcommittee of the International Headache Society for headache classification (ICHD-II) has recently recognised that secondary headaches may occur in patients affected by inflammatory diseases (ID) of the central nervous system (CNS), classifying them among the headaches attributed to non-vascular intracranial disorders. The aim of the study was to verify the association between headache and inflammatory non-infectious diseases of the CNS, by a review of the literature data on the topic, integrated by personal cases and data. Secondary headaches may occur in four main disorders: neurosarcoidosis (sec 7.3.1), aseptic (non-infectious) meningitis (7.3.2), other non-infectious ID (7.3.3) and lymphocytic hypophysitis (7.3.4). Headache and/or primary headaches are frequently reported in patients with neurosarcoidosis (30%), Behcet's syndrome (BS) (55%) and acute disseminated encephalomyelitis (45-58%). Recent data show a high incidence of headache also in multiple sclerosis (MS) (58%) (not mentioned in ICHD-II). The association between headache and inflammatory dysimmune diseases of the CNS, in particular BS and MS, might suggest a pathogenetic relationship. PMID:15549526

  8. Solitary Fibrous Tumor of Central Nervous System: A Case Report

    PubMed Central

    Kim, Jang Hoon; Yoon, Pyeong Ho; Kie, Jeong Hae

    2015-01-01

    Solitary fibrous tumor (SFT) is a rare neoplasm of mesenchymal origin, especially in the central nervous system (CNS). Reported herein is a case of SFT of CNS in a 63-year-old female patient who had confused mentality, without other neurological deficit. The brain MRI showed an ovoid mass in the right frontal lobe. The tumor was surgically removed grossly and totally, and the pathologic diagnosis was SFT. At 55 months after the surgery, the tumor recurred at the primary site and at an adjacent area. A second operation was thus done, and the tumor was again surgically removed grossly and totally. The pathologic diagnosis was the same as the previous, but the Ki-67 index was elevated. Ten months later, two small recurring tumors in the right frontal skull base were found in the follow-up MRI. It was decided that radiation therapy be done, and MRI was done again 3 months later. In the follow-up MRI, the size of the recurring mass was found to have decreased, and the patient did not manifest any significant symptom. Follow-up will again be done 18 months after the second surgery. PMID:26605270

  9. Chemotherapy in newly diagnosed primary central nervous system lymphoma

    PubMed Central

    Hashemi-Sadraei, Nooshin; Peereboom, David M.

    2010-01-01

    Primary central nervous system lymphoma (PCNSL) accounts for only 3% of brain tumors. It can involve the brain parenchyma, leptomeninges, eyes and the spinal cord. Unlike systemic lymphoma, durable remissions remain uncommon. Although phase III trials in this rare disease are difficult to perform, many phase II trials have attempted to define standards of care. Treatment modalities for patients with newly diagnosed PCNSL include radiation and/or chemotherapy. While the role of radiation therapy for initial management of PCNSL is controversial, clinical trials will attempt to improve the therapeutic index of this modality. Routes of chemotherapy administration include intravenous, intraocular, intraventricular or intra-arterial. Multiple trials have outlined different methotrexate-based chemotherapy regimens and have used local techniques to improve drug delivery. A major challenge in the management of patients with PCNSL remains the delivery of aggressive treatment with preservation of neurocognitive function. Because PCNSL is rare, it is important to perform multicenter clinical trials and to incorporate detailed measurements of long-term toxicities. In this review we focus on different chemotherapeutic approaches for immunocompetent patients with newly diagnosed PCNSL and discuss the role of local drug delivery in addition to systemic therapy. We also address the neurocognitive toxicity of treatment. PMID:21789140

  10. Comprehensive Craniospinal Radiation for Controlling Central Nervous System Leukemia

    SciTech Connect

    Walker, Gary V.; Shihadeh, Ferial; Kantarjian, Hagop; Allen, Pamela; Rondon, Gabriela; Kebriaei, Partow; O'Brien, Susan; Kedir, Aziza; Said, Mustefa; Grant, Jonathan D.; Thomas, Deborah A.; Gidley, Paul W.; Arzu, Isidora; Pinnix, Chelsea; Reed, Valerie; Dabaja, Bouthaina S.

    2014-12-01

    Purpose: To determine the benefit of radiation therapy (RT) in resolution of neurologic symptoms and deficits and whether the type of RT fields influences central nervous system (CNS) control in adults with CNS leukemia. Methods and Materials: A total of 163 adults from 1996 to 2012 were retrospectively analyzed. Potential associations between use of radiation and outcome were investigated by univariate and multivariate analysis. Results: The median survival time was 3.8 months after RT. Common presenting symptoms were headache in 79 patients (49%), cranial nerve VII deficit in 46 (28%), and cranial nerve II deficit in 44 (27%). RT was delivered to the base of skull in 48 patients (29%), to the whole brain (WB) in 67 (41%), and to the craniospinal axis (CS) in 48 (29%). Among 149 patients with a total of 233 deficits, resolution was observed in 34 deficits (15%), improvement in 126 deficits (54%), stability in 34 deficits (15%), and progression in 39 deficits (17%). The 12-month CNS progression-free survival was 77% among those receiving CS/WB and 51% among those receiving base of skull RT (P=.02). On multivariate analysis, patients who did not undergo stem cell transplantation after RT and base of skull RT were associated with worse CNS progression-free survival. Conclusions: Improvement or resolution of symptoms occurred in two thirds of deficits after RT. Comprehensive radiation to the WB or CS seems to offer a better outcome, especially in isolated CNS involvement.

  11. Current Management of Primary Central Nervous System Lymphoma

    SciTech Connect

    Schultz, Christopher J.; Bovi, Joseph

    2010-03-01

    Primary central nervous cell lymphoma (PCNSL) is an uncommon neoplasm of the brain, leptomeninges, and rarely the spinal cord. Initially thought to be characteristically associated with congenital, iatrogenic, or acquired immunosuppression, PCNSL is now recognized with increasing frequency in immunocompetent individuals. The role of surgery is limited to establishing diagnosis, as PCNSL is often multifocal with a propensity to involve the subarachnoid space. A whole-brain radiation volume has empirically been used to adequately address the multifocal tumor frequently encountered at the time of PCNSL diagnosis. Despite high rates of response after whole-brain radiotherapy (WBRT), rapid recurrence is common and long-term survival is the exception. Chemotherapy alone or in combination with WBRT has more recently become the treatment of choice. Most effective regimens contain high-dose methotrexate and or other agents that are capable of penetrating the blood-brain barrier. High response rates and improved survival with the use of chemotherapy has led to treatment strategies that defer or eliminate WBRT in hopes of lessening the risk of neurotoxicity attributed to WBRT. Unfortunately, elimination of WBRT is also associated with a higher rate of relapse. Combined chemotherapy and WBRT regimens are now being explored that use lower total doses of radiation and altered fractionation schedules with the aim of maintaining high rates of tumor control while minimizing neurotoxicity. Pretreatment, multifactor prognostic indices have recently been described that may allow selection of treatment regimens that strike an appropriate balance of risk and benefit for the individual PCNSL patient.

  12. Central nervous system vasculitis in adults and children.

    PubMed

    Twilt, Marinka; Benseler, Susanne M

    2016-01-01

    Primary angiitis of the central nervous system (PACNS) is an inflammatory brain disease targeting the cerebral blood vessels, leading to a wide spectrum of signs and symptoms, including neurologic deficits, cognitive dysfunction, and psychiatric symptoms. The inflammation could be reversible if diagnosed and treated early. The diagnosis requires the careful consideration and rapid evaluation of systemic underlying conditions and disease mimics. The differential diagnosis is distinctly different for angiography-positive and -negative PACNS subtypes and differs depending on age, so there is childhood PACNS or adult PACNS. Distinct disease subtypes have been described, with characteristic disease course, neuroimaging findings, and histopathologic features. Novel and traditional biomarkers, including von Willebrand factor antigen and cytokine levels, can help diagnose, and define subtype and disease activity. Treatment of PACNS should be tailored to the disease subtypes and clinical symptoms. Beyond immunosuppression it should include medications to control symptoms in order to support and enhance the child's or adult's ability to actively participate in rehabilitation. The mortality of PACNS has decreased; studies determining the morbidity and its determinants are urgently needed. PMID:27112683

  13. Early CT findings of global central nervous system hypoperfusion

    SciTech Connect

    Kjos, B.O.; Brant-Zawadzki, M.; Young, R.G.

    1983-12-01

    The early computed tomographic (CT) findings of acute global central nervous system hypoperfusion were studied in 10 patients. The findings could be characterized as: (1) diffuse mass effect with effacement of the cerebral sulci and of the brainstem cisterns (nine patients); (2) global decrease in the cortical gray-matter density from edema, causing loss of the normal gray-white matter differentiation (six patients); (3) low-density lesions of the basal ganglia bilaterally (five patients); and (4) decreased gray-matter density in watershed distributions bilaterally (two patients). Subsequent contrast-enhanced scans in three of the 10 patients demonstrated selective enhancement of the cerebral cortex or the basal ganglia or both. The CT findings seen in this study predicted a poor outcome; nine of the 10 patients died from the insult. The abnormal CT findings can be ascribed to increased vulnerability of the cerebral cortex and basal ganglia to hypotensive episodes. This vulnerability is due to the large metabolic demand of these regions and their characteristic local cerebral blood flow.

  14. Imaging of opioid receptors in the central nervous system

    PubMed Central

    Henriksen, Gjermund

    2008-01-01

    In vivo functional imaging by means of positron emission tomography (PET) is the sole method for providing a quantitative measurement of μ-, κ and δ-opioid receptor-mediated signalling in the central nervous system. During the last two decades, measurements of changes to the regional brain opioidergic neuronal activation—mediated by endogenously produced opioid peptides, or exogenously administered opioid drugs—have been conducted in numerous chronic pain conditions, in epilepsy, as well as by stimulant- and opioidergic drugs. Although several PET-tracers have been used clinically for depiction and quantification of the opioid receptors changes, the underlying mechanisms for regulation of changes to the availability of opioid receptors are still unclear. After a presentation of the general signalling mechanisms of the opioid receptor system relevant for PET, a critical survey of the pharmacological properties of some currently available PET-tracers is presented. Clinical studies performed with different PET ligands are also reviewed and the compound-dependent findings are summarized. An outlook is given concluding with the tailoring of tracer properties, in order to facilitate for a selective addressment of dynamic changes to the availability of a single subclass, in combination with an optimization of the quantification framework are essentials for further progress in the field of in vivo opioid receptor imaging. PMID:18048446

  15. Role of Wnt Signaling in Central Nervous System Injury.

    PubMed

    Lambert, Catherine; Cisternas, Pedro; Inestrosa, Nibaldo C

    2016-05-01

    The central nervous system (CNS) is highly sensitive to external mechanical damage, presenting a limited capacity for regeneration explained in part by its inability to restore either damaged neurons or the synaptic network. The CNS may suffer different types of external injuries affecting its function and/or structure, including stroke, spinal cord injury, and traumatic brain injury. These pathologies critically affect the quality of life of a large number of patients worldwide and are often fatal because available therapeutics are ineffective and produce limited results. Common effects of the mentioned pathologies involves the triggering of several cellular and metabolic responses against injury, including infiltration of blood cells, inflammation, glial activation, and neuronal death. Although some of the underlying molecular mechanisms of those responses have been elucidated, the mechanisms driving these processes are poorly understood in the context of CNS injury. In the last few years, it has been suggested that the activation of the Wnt signaling pathway could be important in the regenerative response after CNS injury, activating diverse protective mechanisms including the stimulation of neurogenesis, blood brain structure consolidation and the recovery of cognitive brain functions. Because Wnt signaling is involved in several physiological processes, the putative positive role of its activation after injury could be the basis for novel therapeutic approaches to CNS injury. PMID:25976365

  16. [Sensitivity of animals to central nervous system stimulants in hypokinesia].

    PubMed

    Kolemeeva, L Ia; Shashkov, V S; Egorov, B B

    1977-01-01

    The experiments were carried out on 1150 non-inbred white male rats weighing 200+/-50 g. The animals were housed in small cages for 1, 5, 10, 15, 30, 45 and 60 days. Control rats remained normally active. The experimental and control animals were given a typical diet. On the above days the rats were injected intraperitoneally with central nervous stimulants--caffeine, phenamine and strychnine. Changes in the animal sensitivity to the stimulants were measured with respect to the alterating of LD16, LD50 and LD54 in test animals as compared with the controls and in regards to the emergence and duration of behavioural reactions: adynamics (caffeine), stereotype behavior (phenamine) and convulsions (strychnine). The greatest changes in the animal sensitivity were noted in response to phenamine. A significant increase in the sensitivity to caffeine was found on the 5, 15 and 45th experimental days and to strychnine only on the 5 and 45th days. Convulsions in response to strychnine were recorded in experimental animals earlier than in the controls and their duration was dependent on the doses injected. Adynamics in response to caffeine developed in experimental rats later than in the controls (on the 15th day) and its duration changed cyclically. Stereotype behavior in response to phenamine showed cyclic pattern and its duration in experimental rats was shorter than in the controls. PMID:15162

  17. Evolution of centralized nervous systems: Two schools of evolutionary thought

    PubMed Central

    Northcutt, R. Glenn

    2012-01-01

    Understanding the evolution of centralized nervous systems requires an understanding of metazoan phylogenetic interrelationships, their fossil record, the variation in their cephalic neural characters, and the development of these characters. Each of these topics involves comparative approaches, and both cladistic and phenetic methodologies have been applied. Our understanding of metazoan phylogeny has increased greatly with the cladistic analysis of molecular data, and relaxed molecular clocks generally date the origin of bilaterians at 600–700 Mya (during the Ediacaran). Although the taxonomic affinities of the Ediacaran biota remain uncertain, a conservative interpretation suggests that a number of these taxa form clades that are closely related, if not stem clades of bilaterian crown clades. Analysis of brain–body complexity among extant bilaterians indicates that diffuse nerve nets and possibly, ganglionated cephalic neural systems existed in Ediacaran organisms. An outgroup analysis of cephalic neural characters among extant metazoans also indicates that the last common bilaterian ancestor possessed a diffuse nerve plexus and that brains evolved independently at least four times. In contrast, the hypothesis of a tripartite brain, based primarily on phenetic analysis of developmental genetic data, indicates that the brain arose in the last common bilaterian ancestor. Hopefully, this debate will be resolved by cladistic analysis of the genomes of additional taxa and an increased understanding of character identity genetic networks. PMID:22723354

  18. Molecular targets to promote central nervous system regeneration.

    PubMed

    Ferraro, Gino B; Alabed, Yazan Z; Fournier, Alyson E

    2004-01-01

    Trauma in the adult mammalian central nervous system (CNS) results in devastating clinical consequences due to the failure of injured axons to spontaneously regenerate. This regenerative failure can be attributed to both a lack of positive cues and to the presence of inhibitory cues that actively prevent regeneration. Substantial progress has been made in elucidating the molecular identity of negative cues present at the CNS injury site following injury. In the past several years, multiple myelin-associated inhibitors including Nogo, Myelin-associated glycoprotein and Oligodendrocyte-myelin glycoprotein have been characterized. Furthermore a neuronal receptor complex and several intracellular substrates leading to outgrowth inhibition have been identified. Rapid progress has also been made in identifying the role of neurotrophins and other positive cues in promoting axonal regrowth. The most recent advances in our understanding of positive stimuli for axon regeneration come from transplantation studies at the CNS lesion site. A number of artificial substrates, tissues, and cells including fetal cells, neural stem cells, Schwann cells and olfactory-ensheathing cells have been tested in animal models of CNS injury. Based on our expanded knowledge of inhibitory influences and on the positive characteristics of various transplants, a number of interventions have been tested to promote recovery in models of CNS trauma. These advances represent the first steps in developing a viable therapy to promote axon regeneration following CNS trauma. PMID:16181067

  19. Antiretroviral Therapy and Central Nervous System HIV-1 Infection

    PubMed Central

    Price, Richard W.; Spudich, Serena

    2008-01-01

    Central nervous system (CNS) HIV-1 infection begins during primary viremia and continues throughout the course of untreated systemic infection. While frequently accompanied by local inflammatory reactions detectable in cerebrospinal fluid (CSF), CNS HIV-1 infection is not usually clinically apparent. In a minority of patients, CNS HIV-1 infection evolves late in the course of systemic infection into encephalitis, which compromises brain function and presents clinically as AIDS dementia complex (ADC). Combination highly active antiretroviral therapy (HAART) has had a major impact on all aspects of HIV-1 CNS infection and disease. In those with asymptomatic infection, HAART usually effectively suppresses CSF HIV-1 and markedly reduces the incidence of symptomatic ADC. In those presenting with ADC, HAART characteristically prevents neurological progression and leads to variable, and at times substantial, recovery. Treatment has similarly reduced CNS opportunistic infections. With better control of these severe disorders, attention has turned to the possible consequences of chronic silent infection, and the issue of whether indolent, low-grade brain injury might require earlier treatment intervention. PMID:18447615

  20. The Role of Central Nervous System Plasticity in Tinnitus

    PubMed Central

    Saunders, James C.

    2007-01-01

    Tinnitus is a vexing disorder of hearing characterized by sound sensations originating in the head without any external stimulation. The specific etiology of these sensations is uncertain but frequently associated with hearing loss. The “neurophysiogical” model of tinnitus has enhanced appreciation of central nervous system (CNS) contributions. The model assumes that plastic changes in the primary and non-primary auditory pathways contribute to tinnitus with the former perhaps sustaining them, and the latter contributing to perceived severity and emotionality. These plastic changes are triggered by peripheral injury, which results in new patterns of brain activity due to anatomic alterations in the connectivity of CNS neurons. These alterations may change the balance between excitatory and inhibitory brain processes, perhaps producing cascades of new neural activity flowing between brainstem and cortex in a self-sustaining manner that produces persistent perceptions of tinnitus. The bases of this model are explored with an attempt to distinguish phenomenological from mechanistic explanations. Learning outcomes (1) Readers will learn that the variables associated with the behavioral experience of tinnitus are as complex as the biological variables. (2) Readers will understand what the concept of neuroplastic brain change means, and how it is associated with tinnitus. (3) Readers will learn that there may be no one brain location associated with tinnitus, and it may result from interactions between multiple brain areas. (4) Readers will learn how disinhibition, spontaneous activity, neural synchronization, and tonotopic reorganization may contribute to tinnitus. PMID:17418230

  1. [Malignant lymphoma in the central nervous system: overview].

    PubMed

    Namekawa, Michito

    2014-08-01

    Malignant lymphoma can affect the central nervous system (CNS) in three different ways: as a consequence (relapse or invasion) of systemic lymphoma, as a primary CNS lymphoma (PCNSL) without systemic involvement, and through intravascular lymphomatosis (IVL). It is essential to distinguish PCNSL from the others, since the therapeutic strategy for treating this disease differs. FDG-PET/CT fusion imagery is a powerful tool for detecting systemic lesions. If a marked elevation of lactate dehydrogenase and the soluble IL-2 receptor suggests IVL, a random skin biopsy can permit a differential diagnosis. It is not certain why PCNSL occurs solely in the CNS, where there is no lymphatic system. The special environment, so-called "sanctuary site", where is free from attack of the immune system and penetration of chemotherapeutic agents by blood-brain barrier is deeply related to malignant transformation. The prognoses for patients with CNS invasion of systemic lymphoma and those with PCNSL remain bleak in the post-rituximab era. Over half of the patients who received high-dose methotrexate will subsequently relapse. Therefore, novel therapeutic strategies are earnestly sought. PMID:25082313

  2. Central nervous system effects in acute thallium poisoning.

    PubMed

    Tsai, Yu-Tai; Huang, Chin-Chang; Kuo, Hung-Chou; Wang, Hsuan-Min; Shen, Wu-Shiun; Shih, Tung-Sheng; Chu, Nai-Shin

    2006-03-01

    We report the central nervous system manifestations, neuropsychological studies and brain magnetic resonance image (MRI) findings of two patients with acute thallium intoxication. Neurologically the patients suffered from confusion, disorientation, and hallucination in the acute stage, followed by anxiety, depression, lack of attention, and memory impairment, in addition to peripheral neuropathy. Neuropsychological tests revealed an impairment of memory function, including reversed digital span, memory registration, memory recall, memory recognition, similarity, proverb reasoning, and verbal fluency. High concentrations of thallium were found in the urine, blood, and drinking water of these two patients. Brain MRI showed lesions in the corpus striatum in one patient. During the follow-up periods, the clinical manifestations and neuropsychological studies showed a slowly progressive improvement, and a follow-up brain MRI 1.5 months later demonstrated a resolution of the lesions. We conclude that thallium intoxication might induce encephalopathy, and brain MRI studies demonstrated the acute-stage brain lesions in a severe intoxicated patient. In addition, neuropsychological tests also confirmed memory deficits, although the brain lesions in the corpus striatum might resolve. PMID:16337004

  3. Microparticles: A New Perspective in Central Nervous System Disorders

    PubMed Central

    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

  4. Growth Cone Biomechanics in Peripheral and Central Nervous System Neurons

    NASA Astrophysics Data System (ADS)

    Urbach, Jeffrey; Koch, Daniel; Rosoff, Will; Geller, Herbert

    2012-02-01

    The growth cone, a highly motile structure at the tip of an axon, integrates information about the local environment and modulates outgrowth and guidance, but little is known about effects of external mechanical cues and internal mechanical forces on growth-cone mediated guidance. We have investigated neurite outgrowth, traction forces and cytoskeletal substrate coupling on soft elastic substrates for dorsal root ganglion (DRG) neurons (from the peripheral nervous system) and hippocampal neurons (from the central) to see how the mechanics of the microenvironment affect different populations. We find that the biomechanics of DRG neurons are dramatically different from hippocampal, with DRG neurons displaying relatively large, steady traction forces and maximal outgrowth and forces on substrates of intermediate stiffness, while hippocampal neurons display weak, intermittent forces and limited dependence of outgrowth and forces on substrate stiffness. DRG growth cones have slower rates of retrograde actin flow and higher density of localized paxillin (a protein associated with substrate adhesion complexes) compared to hippocampal neurons, suggesting that the difference in force generation is due to stronger adhesions and therefore stronger substrate coupling in DRG growth cones.

  5. Microglia in central nervous system repair after injury.

    PubMed

    Jin, Xuemei; Yamashita, Toshihide

    2016-05-01

    Accumulating evidence suggests that immune cells perform crucial inflammation-related functions including clearing dead tissue and promoting wound healing. Thus, they provide a conducive environment for better neuronal regeneration and functional recovery after adult mammalian central nervous system (CNS) injury. However, activated immune cells can also induce secondary damage of intact tissue and inhibit post-injury CNS repair. The inflammation response is due to the microglial production of cytokines and chemokines for the recruitment of peripheral immune cell populations, such as monocytes, neutrophils, dendritic cells and T lymphocytes. Interestingly, microglia and T lymphocytes can be detected at the injured site in both the early and later stages after nerve injury, whereas other peripheral immune cells infiltrate the injured parenchyma of the brain and spinal cord only in the early post-injury phase, and subsequently disappear. This suggests that microglia and T cells may play crucial roles in the post-injury functional recovery of the CNS. In this review, we summarize the current studies on microglia that examined neuronal regeneration and the molecular signalling mechanisms in the injured CNS. Better understanding of the effects of microglia on neural regeneration will aid the development of therapy strategies to enhance CNS functional recovery after injury. PMID:26861995

  6. MRI in central nervous system infections: A simplified patterned approach.

    PubMed

    Rangarajan, Krithika; Das, Chandan J; Kumar, Atin; Gupta, Arun Kumar

    2014-09-28

    Recognition and characterization of central nervous system infections poses a formidable challenge to the neuro-radiologist. Imaging plays a vital role, the lesions typically being relatively inaccessible to tisue sampling. The results of an accurate diagnosis are endlessly rewarding, given the availability of excellent pharmacological regimen. The availability of numerous magnetic resonance (MR) sequences which provide functional and molecular information is a powerful tool in the hands of the radiologist. However, the plethora of sequences and the possibilities on each sequence is also intimidating, and often confusing as well as time consuming. While a large number of reviews have already described in detail the possible imaging findings in each infection, we intend to classify infections based on their imaging characteristics. In this review we describe an algorithm for first classifying the imaging findings into patterns based on basic MR sequences (T1, T2 and enhancement pattern with Gadolinium), and then sub-classify them based on more advanced molecular and functional sequences (Diffusion, Perfusion, Susceptibility imaging, MR Spectroscopy). This patterned approach is intended as a guide to radiologists in-training and in-practice for quickly narrowing their list of differentials when faced with a clinical challenge. The entire content of the article has also been summarised in the form of flow-charts for the purpose of quick reference. PMID:25276314

  7. Microglia in Infectious Diseases of the Central Nervous System

    PubMed Central

    Mariani, Monica M.; Kielian, Tammy

    2010-01-01

    Microglia are the resident macrophage population in the central nervous system (CNS) parenchyma and, as such, are poised to provide a first line of defense against invading pathogens. Microglia are endowed with a vast repertoire of pattern recognition receptors that include such family members as Toll-like receptors and phagocytic receptors, which collectively function to sense and eliminate microbes invading the CNS parenchyma. In addition, microglial activation elicits a broad range of pro-inflammatory cytokines and chemokines that are involved in the recruitment and subsequent activation of peripheral immune cells infiltrating the infected CNS. Studies from several laboratories have demonstrated the ability of microglia to sense and respond to a wide variety of pathogens capable of colonizing the CNS including bacterial, viral, and fungal species. This review will highlight the role of microglia in microbial recognition and the resultant antipathogen response that ensues in an attempt to clear these infections. Implications as to whether microglial activation is uniformly beneficial to the CNS or in some circumstances may exacerbate pathology will also be discussed. PMID:19728102

  8. Venous endothelial injury in central nervous system diseases

    PubMed Central

    2013-01-01

    The role of the venous system in the pathogenesis of inflammatory neurological/neurodegenerative diseases remains largely unknown and underinvestigated. Aside from cerebral venous infarcts, thromboembolic events, and cerebrovascular bleeding, several inflammatory central nervous system (CNS) diseases, such as multiple sclerosis (MS), acute disseminated encephalomyelitis (ADEM), and optic neuritis, appear to be associated with venous vascular dysfunction, and the neuropathologic hallmark of these diseases is a perivenous, rather than arterial, lesion. Such findings raise fundamental questions about the nature of these diseases, such as the reasons why their pathognomonic lesions do not develop around the arteries and what exactly are the roles of cerebral venous inflammation in their pathogenesis. Apart from this inflammatory-based view, a new hypothesis with more focus on the hemodynamic features of the cerebral and extracerebral venous system suggests that MS pathophysiology might be associated with the venous system that drains the CNS. Such a hypothesis, if proven correct, opens new therapeutic windows in MS and other neuroinflammatory diseases. Here, we present a comprehensive review of the pathophysiology of MS, ADEM, pseudotumor cerebri, and optic neuritis, with an emphasis on the roles of venous vascular system programming and dysfunction in their pathogenesis. We consider the fundamental differences between arterial and venous endothelium, their dissimilar responses to inflammation, and the potential theoretical contributions of venous insufficiency in the pathogenesis of neurovascular diseases. PMID:24228622

  9. Central nervous system effects of whole-body proton irradiation.

    PubMed

    Sweet, Tara Beth; Panda, Nirlipta; Hein, Amy M; Das, Shoshana L; Hurley, Sean D; Olschowka, John A; Williams, Jacqueline P; O'Banion, M Kerry

    2014-07-01

    Space missions beyond the protection of Earth's magnetosphere expose astronauts to an environment that contains ionizing proton radiation. The hazards that proton radiation pose to normal tissues, such as the central nervous system (CNS), are not fully understood, although it has been shown that proton radiation affects the neurogenic environment, killing neural precursors and altering behavior. To determine the time and dose-response characteristics of the CNS to whole-body proton irradiation, C57BL/6J mice were exposed to 1 GeV/n proton radiation at doses of 0-200 cGy and behavioral, physiological and immunohistochemical end points were analyzed over a range of time points (48 h-12 months) postirradiation. These experiments revealed that proton radiation exposure leads to: 1. an acute decrease in cell division within the dentate gyrus of the hippocampus, with significant differences detected at doses as low as 10 cGy; 2. a persistent effect on proliferation in the subgranular zone, at 1 month postirradiation; 3. a decrease in neurogenesis at doses as low as 50 cGy, at 3 months postirradiation; and 4. a decrease in hippocampal ICAM-1 immunoreactivity at doses as low as 10 cGy, at 1 month postirradiation. The data presented contribute to our understanding of biological responses to whole-body proton radiation and may help reduce uncertainty in the assessment of health risks to astronauts. These findings may also be relevant to clinical proton beam therapy. PMID:24937778

  10. Clinical epidemiology for childhood primary central nervous system tumors.

    PubMed

    Bauchet, Luc; Rigau, Valérie; Mathieu-Daudé, Hélène; Fabbro-Peray, Pascale; Palenzuela, Gilles; Figarella-Branger, Dominique; Moritz, Jorge; Puget, Stéphanie; Bauchet, Fabienne; Pallusseau, Lorelei; Duffau, Hugues; Coubes, Philippe; Trétarre, Brigitte; Labrousse, François; Dhellemmes, Patrick

    2009-03-01

    This work was conducted by the French Brain Tumor Data Bank (FBTDB) and aims to prospectively record all primary central nervous system tumors (PCNST), in France, for which histological diagnosis is available. Results concerning children are presented. This study analyzes the childhood cases (0-19 years) of newly diagnosed and histologically confirmed PCNST (during the years 2004-2006) which have been recorded by the FBTDB. All French neuropathology and neurosurgery departments participated in this program. Neurosurgeons and neuropathologists completed a data file containing socio-demographic, clinical, radiologic and anatomopathologic information. The Tumor Registry from Herault was authorized to compile the data files with personal identifiers. About 1,017 cases (533 boys and 484 girls) of newly diagnosed childhood PCNST have been recorded (gliomas: 52%, all other neuroepithelial tumors: 31%, craniopharyngioma: 5%, germ cell tumors, meningioma and neurinoma: approximately 3% each, all histological subtypes have been detailed). Tumor resections were performed in 83.3%, and biopsies in 16.7%. The distributions by histology, cryopreservation of the samples, age, sex, tumor site and surgery have been detailed. To our knowledge, this work is the first databank in Europe dedicated to PCNST that includes the collection of clinical, radiological and histological data (including cryopreservation of the specimen). The long term goals of the FBTDB are to create a national registry and a network to perform epidemiological studies, to implement clinical and basic research protocols, and to evaluate and harmonize the healthcare of children and adult patients affected by PCNST. PMID:19020806

  11. Challenges in diagnosis of isolated central nervous system vasculitis

    PubMed Central

    Amara, Amy W; Bashir, Khurram; Palmer, Cheryl A; Walker, Harrison C

    2011-01-01

    Isolated central nervous system (CNS) vasculitis is a rare and complicated disorder. Patients typically present with nonspecific neurologic symptoms such as headache and encephalopathy, and have variable progression and severity of the disease. Challenges to definitive diagnosis include the limitations of currently available diagnostic modalities with high likelihood of false-positive or false-negative findings. Imaging, serologic, and cerebrospinal fluid (CSF) evaluation, and even angiography can fail to establish the diagnosis. Often, brain biopsy is required. In order to illustrate these challenges, we report the case of a patient who presented with subacute cognitive decline and was ultimately diagnosed with isolated CNS eosinophilic vasculitis. Initial work-up included CSF and serologic analyses, magnetic resonance imaging (MRI), and cerebral angiography, but definitive diagnosis required brain biopsy. Immunosuppressive therapy resulted in clinical improvement and stabilization. To our knowledge, only one other case of isolated CNS eosinophilic vasculitis has been reported in the literature. We discuss the importance of a high index of clinical suspicion in cases of progressive nonspecific neurologic symptoms. PMID:22398982

  12. Pharmacokinetics and pharmacodynamics of antiretrovirals in the central nervous system.

    PubMed

    Calcagno, Andrea; Di Perri, Giovanni; Bonora, Stefano

    2014-10-01

    HIV-positive patients may be effectively treated with highly active antiretroviral therapy and such a strategy is associated with striking immune recovery and viral load reduction to very low levels. Despite undeniable results, the central nervous system (CNS) is commonly affected during the course of HIV infection, with neurocognitive disorders being as prevalent as 20-50 % of treated subjects. This review discusses the pathophysiology of CNS infection by HIV and the barriers to efficacious control of such a mechanism, including the available data on compartmental drug penetration and on pharmacokinetic/pharmacodynamic relationships. In the reviewed articles, a high variability in drug transfer to the CNS is highlighted with several mechanisms as well as methodological issues potentially influencing the observed results. Nevirapine and zidovudine showed the highest cerebrospinal fluid (CSF) to plasma ratios, although target concentrations are currently unknown for the CNS. The use of the composite CSF concentration effectiveness score has been associated with better virological outcomes (lower HIV RNA) but has been inconsistently associated with neurocognitive outcomes. These findings support the CNS effectiveness of commonly used highly antiretroviral therapies. The use of antiretroviral drugs with increased CSF penetration and/or effectiveness in treating or preventing neurocognitive disorders however needs to be assessed in well-designed prospective studies. PMID:25200312

  13. Comprehensive Craniospinal Radiation for Controlling Central Nervous System Leukemia

    PubMed Central

    Walker, Gary V.; Shihadeh, Ferial; Kantarjian, Hagop; Allen, Pamela; Rondon, Gabriela; Kebriaei, Partow; O’Brien, Susan; Kedir, Aziza; Said, Mustefa; Grant, Jonathan D.; Thomas, Deborah A.; Gidley, Paul W.; Arzu, Isidora; Pinnix, Chelsea; Reed, Valerie; Dabaja, Bouthaina S.

    2016-01-01

    Purpose To determine the benefit of radiation therapy (RT) in resolution of neurologic symptoms and deficits and whether the type of RT fields influences central nervous system (CNS) control in adults with CNS leukemia. Methods and Materials A total of 163 adults from 1996 to 2012 were retrospectively analyzed. Potential associations between use of radiation and outcome were investigated by univariate and multivariate analysis. Results The median survival time was 3.8 months after RT. Common presenting symptoms were headache in 79 patients (49%), cranial nerve VII deficit in 46 (28%), and cranial nerve II deficit in 44 (27%). RT was delivered to the base of skull in 48 patients (29%), to the whole brain (WB) in 67 (41%), and to the craniospinal axis (CS) in 48 (29%). Among 149 patients with a total of 233 deficits, resolution was observed in 34 deficits (15%), improvement in 126 deficits (54%), stability in 34 deficits (15%), and progression in 39 deficits (17%). The 12-month CNS progression-free survival was 77% among those receiving CS/WB and 51% among those receiving base of skull RT (P = .02). On multivariate analysis, patients who did not undergo stem cell transplantation after RT and base of skull RT were associated with worse CNS progression-free survival. Conclusions Improvement or resolution of symptoms occurred in two thirds of deficits after RT. Comprehensive radiation to the WB or CS seems to offer a better outcome, especially in isolated CNS involvement. PMID:25539370

  14. Database mining applied to central nervous system (CNS) activity.

    PubMed

    Pintore, M; Taboureau, O; Ros, F; Chrétien, J R

    2001-04-01

    A data set of 389 compounds, active in the central nervous system (CNS) and divided into eight classes according to the receptor type, was extracted from the RBI database and analyzed by Self-Organizing Maps (SOM), also known as Kohonen Artificial Neural Networks. This method gives a 2D representation of the distribution of the compounds in the hyperspace derived from their molecular descriptors. As SOM belongs to the category of unsupervised techniques, it has to be combined with another method in order to generate classification models with predictive ability. The fuzzy clustering (FC) approach seems to be particularly suitable to delineate clusters in a rational way from SOM and to get an automatic objective map interpretation. Maps derived by SOM showed specific regions associated with a unique receptor type and zones in which two or more activity classes are nested. Then, the modeling ability of the proposed SOM/FC Hybrid System tools applied simultaneously to eight activity classes was validated after dividing the 389 compounds into a training set and a test set, including 259 and 130 molecules, respectively. The proper experimental activity class, among the eight possible ones, was predicted simultaneously and correctly for 81% of the test set compounds. PMID:11461760

  15. Solitary Fibrous Tumor of Central Nervous System: A Case Report.

    PubMed

    Kim, Jang Hoon; Yang, Kook Hee; Yoon, Pyeong Ho; Kie, Jeong Hae

    2015-10-01

    Solitary fibrous tumor (SFT) is a rare neoplasm of mesenchymal origin, especially in the central nervous system (CNS). Reported herein is a case of SFT of CNS in a 63-year-old female patient who had confused mentality, without other neurological deficit. The brain MRI showed an ovoid mass in the right frontal lobe. The tumor was surgically removed grossly and totally, and the pathologic diagnosis was SFT. At 55 months after the surgery, the tumor recurred at the primary site and at an adjacent area. A second operation was thus done, and the tumor was again surgically removed grossly and totally. The pathologic diagnosis was the same as the previous, but the Ki-67 index was elevated. Ten months later, two small recurring tumors in the right frontal skull base were found in the follow-up MRI. It was decided that radiation therapy be done, and MRI was done again 3 months later. In the follow-up MRI, the size of the recurring mass was found to have decreased, and the patient did not manifest any significant symptom. Follow-up will again be done 18 months after the second surgery. PMID:26605270

  16. Mechanisms of magnetic stimulation of central nervous system neurons.

    PubMed

    Pashut, Tamar; Wolfus, Shuki; Friedman, Alex; Lavidor, Michal; Bar-Gad, Izhar; Yeshurun, Yosef; Korngreen, Alon

    2011-03-01

    Transcranial magnetic stimulation (TMS) is a stimulation method in which a magnetic coil generates a magnetic field in an area of interest in the brain. This magnetic field induces an electric field that modulates neuronal activity. The spatial distribution of the induced electric field is determined by the geometry and location of the coil relative to the brain. Although TMS has been used for several decades, the biophysical basis underlying the stimulation of neurons in the central nervous system (CNS) is still unknown. To address this problem we developed a numerical scheme enabling us to combine realistic magnetic stimulation (MS) with compartmental modeling of neurons with arbitrary morphology. The induced electric field for each location in space was combined with standard compartmental modeling software to calculate the membrane current generated by the electromagnetic field for each segment of the neuron. In agreement with previous studies, the simulations suggested that peripheral axons were excited by the spatial gradients of the induced electric field. In both peripheral and central neurons, MS amplitude required for action potential generation was inversely proportional to the square of the diameter of the stimulated compartment. Due to the importance of the fiber's diameter, magnetic stimulation of CNS neurons depolarized the soma followed by initiation of an action potential in the initial segment of the axon. Passive dendrites affect this process primarily as current sinks, not sources. The simulations predict that neurons with low current threshold are more susceptible to magnetic stimulation. Moreover, they suggest that MS does not directly trigger dendritic regenerative mechanisms. These insights into the mechanism of MS may be relevant for the design of multi-intensity TMS protocols, may facilitate the construction of magnetic stimulators, and may aid the interpretation of results of TMS of the CNS. PMID:21455288

  17. Effects of Petroleum Ether Extract of Amorphophallus paeoniifolius Tuber on Central Nervous System in Mice

    PubMed Central

    Das, S. S.; Sen, Malini; Dey, Y. N.; De, S.; Ghosh, A. K.

    2009-01-01

    The central nervous system activity of the petroleum ether extract of Amorphophallus paeoniifolius tuber was examined in mice, fed normal as well as healthy conditions. The petroleum ether extract of Amorphophallus paeoniifolius tuber at the doses of 100, 300 and 1000 mg/kg showed significant central nervous system activity in mice. PMID:20376218

  18. Central Nervous System Strongyloidiasis and Cryptococcosis in an HIV-Infected Patient Starting Antiretroviral Therapy

    PubMed Central

    Rodríguez, Mónica; Flores, Paúl; Ahumada, Víctor; Vázquez-Vázquez, Lorena; Alvarado-de la Barrera, Claudia; Reyes-Terán, Gustavo

    2012-01-01

    We report a case of Strongyloides stercoralis hyperinfection syndrome with central nervous system involvement, in a patient with late human immunodeficiency virus (HIV) infection starting antiretroviral therapy, in whom Strongyloides stercoralis larvae and Cryptococcus neoformans were isolated antemortem from cerebrospinal fluid. Our patient was not from an endemic region for the parasite, so strongyloidiasis was not originally suspected. For this reason, we conclude that Strongyloides stercoralis infection should be suspected in HIV-infected patients starting antiretroviral therapy in order to avoid potential fatal outcomes. PMID:22924046

  19. 75 FR 56548 - Joint Meeting of the Peripheral and Central Nervous System Drugs Advisory Committee and the Drug...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-16

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Joint Meeting of the Peripheral and Central Nervous System Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee; Notice of Meeting AGENCY: Food and Drug Administration,...

  20. Effect of insulin-induced hypoglycaemia on the central nervous system: evidence from experimental studies.

    PubMed

    Jensen, V F H; Bøgh, I B; Lykkesfeldt, J

    2014-03-01

    Insulin-induced hypoglycaemia (IIH) is a major acute complication in type 1 as well as in type 2 diabetes, particularly during intensive insulin therapy. The brain plays a central role in the counter-regulatory response by eliciting parasympathetic and sympathetic hormone responses to restore normoglycaemia. Brain glucose concentrations, being approximately 15-20% of the blood glucose concentration in humans, are rigorously maintained during hypoglycaemia through adaptions such as increased cerebral glucose transport, decreased cerebral glucose utilisation and, possibly, by using central nervous system glycogen as a glucose reserve. However, during sustained hypoglycaemia, the brain cannot maintain a sufficient glucose influx and, as the cerebral hypoglycaemia becomes severe, electroencephalogram changes, oxidative stress and regional neuronal death ensues. With particular focus on evidence from experimental studies on nondiabetic IIH, this review outlines the central mechanisms behind the counter-regulatory response to IIH, as well as cerebral adaption to avoid sequelae of cerebral neuroglycopaenia, including seizures and coma. PMID:24428753

  1. Expression of the receptor for complement C5a (CD88) is up-regulated on reactive astrocytes, microglia, and endothelial cells in the inflamed human central nervous system.

    PubMed Central

    Gasque, P.; Singhrao, S. K.; Neal, J. W.; Götze, O.; Morgan, B. P.

    1997-01-01

    C5a receptor (C5aR, CD88) is a receptor originally described on neutrophils and monocyte-macrophages but recently found on hepatocytes, epithelial cells, endothelial cells, and tissue mast cells. We recently reported that human fetal astrocytes expressed a functional C5aR in vitro. Here we examine C5aR expression in adult brain cultures by immunostaining with six different anti-C5aRs and show that C5aR is expressed constitutively by astrocytes, microglia, and fibroblast-like cells but not by oligodendrocytes. In fetal brain cultures we confirmed that astrocytes constitutively expressed C5aR and demonstrated that fetal microglia and fibroblast-like cells but not oligodendrocytes and neurones expressed C5aR. Incubation with inflammatory cytokines (interferon gamma, interleukin-1, and tumor necrosis factor alpha) or phorbol ester failed to induce or up-regulate C5aR expression on fetal or adult brain cells. Immunohistochemistry was performed to determine the expression and distribution of C5aR in the normal and inflamed brain. In the normal brain C5aR was minimally expressed, whereas in inflamed brains from a variety of pathologies, C5aR expression was greatly up-regulated on reactive astrocytes and microglia and to a lesser extent on endothelial cells. We propose that expression of C5aR is a marker of central nervous system inflammation, and that C5aR expression on brain cells in inflammation plays an important role in cell activation and recruitment (gliosis). Images Figure 1 Figure 2 Figure 3 PMID:9006319

  2. Biology and Treatment of Primary Central Nervous System Lymphoma

    PubMed Central

    Algazi, Alain P.; Kadoch, Cigall; Rubenstein, James L.

    2016-01-01

    Summary Primary central nervous system lymphoma (PCNSL) is a rare variant of extranodal non-Hodgkin lymphoma that is restricted in distribution to the brain, leptomeninges, spinal cord and intraocular compartments. While PCNSL shares overlapping features of systemic lymphoma, recent studies also reveal a unique pattern of gene and protein expression in PCNSL. These findings have yielded new insights into the pathophysiology of the disease as well as the identification of novel prognostic biomarkers. Immune system compromise such as that seen in the acquired immune deficiency syndrome is the best established known risk factor for PCNSL. Like other lesions of the brain, meninges, and eye, the presenting symptoms associated with PCNSL typically include focal neurological deficits related to the site of disease or more global consequences of increased intracranial pressure. Diagnosis of PCNSL typically includes gadolinium-enhanced magnetic resonance imaging and pathological tissue analysis as well as additional studies aimed at excluding concurrent systemic disease. PCNSL is typically associated with a worse overall prognosis than systemic lymphoma. High dose chemotherapy, particularly with methotrexate-based regimens, is the backbone of therapy for most patients and chemotherapy is associated with much lower rates of treatment-related morbidity and mortality than whole brain irradiation. Autologous stem cell transplantation is an emerging treatment modality, particularly in younger patients with relapsed disease, but high rates of treatment related mortality are observed in older patients. Immunotherapy, including treatment with intrathecal rituximab, is another area of active research that may have promise in refractory or relapsed disease. Treatment options for intraocular lymphoma parallel those for PCNSL elsewhere in the brain and they included systemic chemotherapy, radiation, and local delivery of cytotoxic and immunologically-active agents such as anti-CD20

  3. Central nervous system regeneration: from leech to opossum.

    PubMed

    Mladinic, M; Muller, K J; Nicholls, J G

    2009-06-15

    A major problem of neurobiology concerns the failure of injured mammalian spinal cord to repair itself. This review summarizes work done on two preparations in which regeneration can occur: the central nervous system of an invertebrate, the leech, and the spinal cord of an immature mammal, the opossum. The aim is to understand cellular and molecular mechanisms that promote and prevent regeneration. In the leech, an individual axon regrows successfully to re-establish connections with its synaptic target, while avoiding other neurons. Functions that were lost are thereby restored. Moreover, pairs of identified neurons become re-connected with appropriate synapses in culture. It has been shown that microglial cells and nitric oxide play key roles in leech CNS regeneration. In the opossum, the neonatal brain and spinal cord are so tiny that they survive well in culture. Fibres grow across spinal cord lesions in neonatal animals and in vitro, but axon regeneration stops abruptly between postnatal days 9 and 12. A comprehensive search has been made in spinal cords that can and cannot regenerate to identify genes and establish their locations. At 9 days, growth-promoting genes, their receptors and key transcription molecules are up-regulated. By contrast at 12 days, growth-inhibitory molecules associated with myelin are prominent. The complete sequence of the opossum genome and new methods for transfecting genes offer ways to determine which molecules promote and which inhibit spinal cord regeneration. These results lead to questions about how basic research on mechanisms of regeneration could be 'translated' into effective therapies for patients with spinal cord injuries. PMID:19525562

  4. New Insights on NOX Enzymes in the Central Nervous System

    PubMed Central

    Nayernia, Zeynab; Jaquet, Vincent

    2014-01-01

    Abstract Significance: There is increasing evidence that the generation of reactive oxygen species (ROS) in the central nervous system (CNS) involves the NOX family of nicotinamide adenine dinucleotide phosphate oxidases. Controlled ROS generation appears necessary for optimal functioning of the CNS through fine-tuning of redox-sensitive signaling pathways, while overshooting ROS generation will lead to oxidative stress and CNS disease. Recent Advances: NOX enzymes are not only restricted to microglia (i.e. brain phagocytes) but also expressed in neurons, astrocytes, and the neurovascular system. NOX enzymes are involved in CNS development, neural stem cell biology, and the function of mature neurons. While NOX2 appears to be a major source of pathological oxidative stress in the CNS, other NOX isoforms might also be of importance, for example, NOX4 in stroke. Globally speaking, there is now convincing evidence for a role of NOX enzymes in various neurodegenerative diseases, cerebrovascular diseases, and psychosis-related disorders. Critical Issues: The relative importance of specific ROS sources (e.g., NOX enzymes vs. mitochondria; NOX2 vs. NOX4) in different pathological processes needs further investigation. The absence of specific inhibitors limits the possibility to investigate specific therapeutic strategies. The uncritical use of non-specific inhibitors (e.g., apocynin, diphenylene iodonium) and poorly validated antibodies may lead to misleading conclusions. Future Directions: Physiological and pathophysiological studies with cell-type-specific knock-out mice will be necessary to delineate the precise functions of NOX enzymes and their implications in pathomechanisms. The development of CNS-permeant, specific NOX inhibitors will be necessary to advance toward therapeutic applications. Antioxid. Redox Signal. 20: 2815–2837. PMID:24206089

  5. Paraneoplastic and Other Autoimmune Disorders of the Central Nervous System

    PubMed Central

    McKeon, Andrew

    2013-01-01

    As a result of the burgeoning growth of disease-specific neural autoantibody markers available for diagnostic patient evaluation, there has been increasing awareness of autoimmune central nervous system (CNS) disorders in hospital practice. Hospital-based neurologists have also taken great interest in these disorders since many occur in the setting of an occult systemic cancer which can be detected and treated at an early stage, and many affected patients are responsive to immunotherapy. Associated neurological disorders are typically subacute in onset, some are common or classic (eg, limbic encephalitis, cerebellar degeneration), but others have atypical or multifocal presentations. For patients with a suspected paraneoplastic disorder, many and costly oncological evaluations may be required for diagnosis. Comprehensive serological and cerebrospinal fluid (CSF) evaluation for neural autoantibodies may permit a focused cancer evaluation (eg, antineuronal nuclear antibody type 1 [ANNA-1] is associated with small cell lung carcinoma), and in some circumstances may indicate the likelihood of a good response to therapy (eg, voltage-gated potassium channel complex antibody) or poor neurological prognosis (eg, purkinje cell cytoplasmic antibody type 1 [antiYo]). Positron-emission tomography–computed tomography (PET-CT) imaging of trunk may increase the diagnostic yield for certain cancers where other modalities have been negative. For some patients, rapid treatment with immunotherapy may facilitate marked improvement, or full recovery; multiple sequential trials of one or more of steroids, intravenous immunoglobulin or plasma exchange, or combination therapy are often required. For patients with N-methyl-d-aspartate receptor antibody encephalitis, early treatment with immunosuppressants and weeks or months of supportive intensive care may additionally be required. One or more of clinical examination, electroencephalogram (including video telemetry), and imaging provide

  6. Control of the Cutaneous Circulation by the Central Nervous System.

    PubMed

    Blessing, William; McAllen, Robin; McKinley, Michael

    2016-01-01

    The central nervous system (CNS), via its control of sympathetic outflow, regulates blood flow to the acral cutaneous beds (containing arteriovenous anastomoses) as part of the homeostatic thermoregulatory process, as part of the febrile response, and as part of cognitive-emotional processes associated with purposeful interactions with the external environment, including those initiated by salient or threatening events (we go pale with fright). Inputs to the CNS for the thermoregulatory process include cutaneous sensory neurons, and neurons in the preoptic area sensitive to the temperature of the blood in the internal carotid artery. Inputs for cognitive-emotional control from the exteroceptive sense organs (touch, vision, sound, smell, etc.) are integrated in forebrain centers including the amygdala. Psychoactive drugs have major effects on the acral cutaneous circulation. Interoceptors, chemoreceptors more than baroreceptors, also influence cutaneous sympathetic outflow. A major advance has been the discovery of a lower brainstem control center in the rostral medullary raphé, regulating outflow to both brown adipose tissue (BAT) and to the acral cutaneous beds. Neurons in the medullary raphé, via their descending axonal projections, increase the discharge of spinal sympathetic preganglionic neurons controlling the cutaneous vasculature, utilizing glutamate, and serotonin as neurotransmitters. Present evidence suggests that both thermoregulatory and cognitive-emotional control of the cutaneous beds from preoptic, hypothalamic, and forebrain centers is channeled via the medullary raphé. Future studies will no doubt further unravel the details of neurotransmitter pathways connecting these rostral control centers with the medullary raphé, and those operative within the raphé itself. © 2016 American Physiological Society. Compr Physiol 6:1161-1197, 2016. PMID:27347889

  7. Central nervous insulin administration does not potentiate the acute glucoregulatory impact of concurrent mild hyperinsulinemia.

    PubMed

    Ott, Volker; Lehnert, Hendrik; Staub, Josefine; Wönne, Kathrin; Born, Jan; Hallschmid, Manfred

    2015-03-01

    Experiments in rodents suggest that hypothalamic insulin signaling essentially contributes to the acute control of peripheral glucose homeostasis. Against this background, we investigated in healthy humans whether intranasal (IN) insulin, which is known to effectively reach the brain compartment, impacts systemic glucose metabolism. Twenty overnight-fasted healthy, normal-weight men were IN administered 210 and 420 international units [IU] (10 and 20 IU every 15 min) of the insulin analog aspart (ins-asp) and placebo, respectively, during experimental sessions lasting 6 h. The use of ins-asp rather than human insulin enabled us to disentangle exogenous and endogenous insulin kinetics. IN insulin dose-dependently decreased plasma glucose concentrations while reducing C-peptide and attenuating endogenous insulin levels. However, we also observed a slight dose-dependent permeation of ins-asp into the circulation. In control experiments mimicking the systemic but not the central nervous uptake of the IN 210 IU dose via intravenous infusion of ins-asp at a dose of 0.12 IU/kg/24 h (n = 10), we obtained essentially identical effects on fasting plasma glucose concentrations. This pattern indicates that sustained IN insulin administration to the human brain to enhance central nervous insulin signaling does not acutely alter systemic glucose homeostasis beyond effects accounted for by concurrent mild hyperinsulinemia. PMID:25277390

  8. Systematic Review of Central Post Stroke Pain: What Is Happening in the Central Nervous System?

    PubMed

    Akyuz, Gulseren; Kuru, Pinar

    2016-08-01

    Central poststroke pain (CPSP) is one of the most common central neuropathic pain syndromes seen after stroke. It is mainly related with vascular damage at certain brain territory and pain related to corresponding body areas. In the past, it was described as one of the definitive symptoms of thalamic lesion. However, recent findings suggest that it is not only seen after thalamic lesions but also seen after vascular lesions in any part of the central nervous system. Although there are certain hypotheses to explain physiopathologic mechanisms of CPSP, further evidence is needed. The majority of the cases are intractable and unresponsive to analgesic treatment. Electrical stimulation such as deep brain stimulation and repetitive transcranial magnetic stimulation seems to be effective in certain cases. In this systematic review, recent advancements related to CPSP mechanisms have been evaluated. Further investigations are needed in order to reveal the mystery of the pathophysiologic mechanisms of CPSP. PMID:27175563

  9. Pharmacokinetics and central nervous system effects of the novel dopamine D2 receptor antagonist JNJ-37822681.

    PubMed

    te Beek, Erik T; Moerland, Matthijs; de Boer, Peter; van Nueten, Luc; de Kam, Marieke L; Burggraaf, Jacobus; Cohen, Adam F; van Gerven, Joop M A

    2012-08-01

    Using the rate of dissociation from the D(2) receptor as a means to screen novel compounds for antipsychotic drug candidates, the centrally acting and fast-dissociating selective dopamine D(2) receptor antagonist JNJ-37822681 was developed. In a blinded, placebo-controlled, randomized first-in-human study, JNJ-37822681 was administered orally to 27 healthy male volunteers at doses of 0.5, 2, 5, 10, 15 and 20 mg. Safety, pharmacokinetics and central nervous system effects were evaluated by measuring prolactin levels, eye movements, adaptive tracking, visual analogue scales, body sway, finger tapping and electroencephalography. JNJ-37822681 was well tolerated and somnolence was the most frequently reported adverse effect. Peak plasma concentrations increased more than proportional to dose, but increases in the area under curve (AUC) were dose-proportional. Prolactin elevations started at doses of 5 mg, whereas small decreases in adaptive tracking were demonstrated at 10 mg doses. At higher doses, JNJ-37822681 caused a small decrease in saccadic peak velocity, smooth pursuit, alertness, finger tapping and electroencephalography activity, and an increase in body sway. This effect profile is likely to be the result of the selectivity of JNJ-37822681 for the D(2) receptor, leading to strong D(2) receptor-mediated elevations in serum prolactin, but fewer effects on more complex central nervous system functions, which are likely to involve multiple neurotransmitters. PMID:21890591

  10. Mechanisms of spreading depolarization in vertebrate and insect central nervous systems.

    PubMed

    Spong, Kristin E; Andrew, R David; Robertson, R Meldrum

    2016-09-01

    Spreading depolarization (SD) is generated in the central nervous systems of both vertebrates and invertebrates. SD manifests as a propagating wave of electrical depression caused by a massive redistribution of ions. Mammalian SD underlies a continuum of human pathologies from migraine to stroke damage, whereas insect SD is associated with environmental stress-induced neural shutdown. The general cellular mechanisms underlying SD seem to be evolutionarily conserved throughout the animal kingdom. In particular, SD in the central nervous system of Locusta migratoria and Drosophila melanogaster has all the hallmarks of mammalian SD. Locust SD is easily induced and monitored within the metathoracic ganglion (MTG) and can be modulated both pharmacologically and by preconditioning treatments. The finding that the fly brain supports repetitive waves of SD is relatively recent but noteworthy, since it provides a genetically tractable model system. Due to the human suffering caused by SD manifestations, elucidating control mechanisms that could ultimately attenuate brain susceptibility is essential. Here we review mechanisms of SD focusing on the similarities between mammalian and insect systems. Additionally we discuss advantages of using invertebrate model systems and propose insect SD as a valuable model for providing new insights to mammalian SD. PMID:27334953

  11. The effects of Aconitum alkaloids on the central nervous system.

    PubMed

    Ameri, A

    1998-10-01

    Preparations of Aconitum roots are employed in Chinese and Japanese medicine for analgesic, antirheumatic and neurological indications. The recent surge in use of phytomedicine derived from traditional Chinese medicine as well as increasing concerns about possible toxic effects of these compounds have inspired a great deal of research into the mechanisms by which certain Aconitum alkaloids may act on the central nervous system. The pharmacological effects of preparations of Aconitum roots are attributed to several diterpenoid alkaloids. The main alkaloid of these plants is aconitine, a highly toxic diterpenoid alkaloid which is known to suppress the inactivation of voltage-dependent Na+ channels by binding to neurotoxin binding site 2 of the alpha-subunit of the channel protein. In this article the pharmacology of several structurally related Aconitum alkaloids is highlighted and their therapeutic vs toxic potential is discussed. Neurochemical and neurophysiological studies will be reviewed with emphasis on the effects of the alkaloids in regions of the brain that have been implicated in pain transmission and generation of epileptic activity. Considering the chemical structure of the Aconitum alkaloids as well as their mechanism of action, a subdivision in three groups becomes obvious: the first group comprises such alkaloids which possess high toxicity due to two ester boundings at the diterpene skeleton. The members of this group activate voltage-dependent sodium channels already at resting potential and inhibit noradrenaline reuptake. Activation of sodium channels and in consequence excessive depolarization with final inexcitability and suppression of pain transmission account for their antinociceptive properties. The second group comprises less toxic monoesters which have been shown to possess strong antinociceptive, antiarrhythmic and antiepileptiform properties due to a blockade of the voltage-dependent sodium channel. Electrophysiological studies have

  12. Synaptic Targets of Δ9-Tetrahydrocannabinol in the Central Nervous System

    PubMed Central

    Hoffman, Alexander F.; Lupica, Carl R.

    2013-01-01

    The availability of potent synthetic agonists for cannabinoid receptors has facilitated our understanding of cannabinoid actions on synaptic transmission in the central nervous system. Moreover, the ability of these compounds to inhibit neurotransmitter release at many central synapses is thought to underlie most of the behavioral effects of cannabinoid agonists. However, despite the widespread use and misuse of marijuana, and recognition of its potential adverse psychological effects in humans, comparatively few studies have examined the actions of its primary psychoactive constituent, Δ9-tetrahydrocannabinol (THC), at well-defined synaptic pathways. Here we examine the recent literature describing the effects of acute and repeated THC exposure on synaptic function in several brain regions and explore the importance of these neurobiological actions of THC in drug addiction. PMID:23209160

  13. General Information about Childhood Central Nervous System Atypical Teratoid/Rhabdoid Tumor

    MedlinePlus

    ... Teratoid/Rhabdoid Tumor Treatment (PDQ®)–Patient Version General Information About Childhood Central Nervous System (CNS) Atypical Teratoid/ ... the PDQ Pediatric Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  14. Cerebral angiography as a guide for therapy in isolated central nervous system vasculitis

    SciTech Connect

    Stein, R.L.; Martino, C.R.; Weinert, D.M.; Hueftle, M.; Kammer, G.M.

    1987-04-24

    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.

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

    ERIC Educational Resources Information Center

    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)

  16. New model to determine the central nervous system reaction to peripheral trauma

    SciTech Connect

    Sjoelund, B.H.W.; Wallstedt, L.

    1988-01-01

    Monitoring the activity of the central nervous system with the /sup 14/C-2-deoxyglucose method of Sokoloff was utilized to explore the possibility to develop a model for the study of central nervous system reaction to peripheral trauma. Preliminary evidence indicates that the activation caused by tactile stimuli to one hindlimb nerve is that expected from earlier physiologic studies. However, an increase of stimulation intensity to recruit nociceptive (pain) fibers seems to abolish the changes, indicating that inhibitory systems have been activated.

  17. Superficial Siderosis of the Central Nervous System Originating from the Thoracic Spine: A Case Report

    PubMed Central

    Ryu, Sung Mo; Kim, Seung-Kook; Lee, Sun-Ho; Eoh, Whan

    2016-01-01

    Superficial siderosis of the central nervous system(SSCNS) is a rare disease characterized by hemosiderin deposition on the surface of the central nervous system. We report a case of SSCNS originating from the thoracic spine, presenting with neurological deficits including, sensorineuronal hearing loss, ataxia, and corticospinal and dorsal column tract signs. The patient underwent dural repair with an artificial dural patch. Clinical findings were elicited by neurological examination, imaging studies, and intraoperative findings, and these were addressed through literature review. PMID:27437021

  18. Magnetic Resonance Imaging of the Central Nervous System—An Update

    PubMed Central

    Brant-Zawadzki, Michael; Norman, David; Newton, T. Hans; Kucharczyk, Walter

    1985-01-01

    Magnetic resonance imaging has developed rapidly and now has superior ability to detect and to characterize disease in the central nervous system without any significant biologic hazard. It is becoming the screening method of choice in the diagnosis of neoplasm, ischemia, hemorrhage, infection and degenerative and demyelinating diseases involving the central nervous system. ImagesFigure 1.Figure 2.Figure 3.Figure 4.Figure 5.Figure 6.Figure 7.Figure 8.Figure 9. PMID:3976220

  19. Superficial Siderosis of the Central Nervous System Originating from the Thoracic Spine: A Case Report.

    PubMed

    Ryu, Sung Mo; Kim, Eun-Sang; Kim, Seung-Kook; Lee, Sun-Ho; Eoh, Whan

    2016-06-01

    Superficial siderosis of the central nervous system(SSCNS) is a rare disease characterized by hemosiderin deposition on the surface of the central nervous system. We report a case of SSCNS originating from the thoracic spine, presenting with neurological deficits including, sensorineuronal hearing loss, ataxia, and corticospinal and dorsal column tract signs. The patient underwent dural repair with an artificial dural patch. Clinical findings were elicited by neurological examination, imaging studies, and intraoperative findings, and these were addressed through literature review. PMID:27437021

  20. [The functional state of the cardiovascular and central nervous system in patients with occupational deafness].

    PubMed

    Tin'kov, A N; Raĭtselis, I V

    2009-01-01

    The workers of the Orenburg gas-processing plant have been found to be at high risk for concomitant diseases of the cardiovascular, central nervous, and other systems in the presence of occupational sensorineural deafness. Among the comorbidities in deaf patients, cardiovascular disease heads the list (63%), of them autonomic vascular dystonia is most common (22%); diseases of the central nervous system and lung rank second (13%) and third (11%), respectively. PMID:19802944

  1. An illustrative case of primary angiitis of the central nervous system

    PubMed Central

    Zagami, Alessandro S

    2014-01-01

    Primary angiitis of the central nervous system is a rare idiopathic vasculitis affecting small- and medium-sized vessels, isolated to the brain, leptomeninges and spinal cord. We report a case of biopsy-proven primary angiitis of the central nervous system, displaying some atypical features. This case highlights several key diagnostic and management issues of the disorder as well as its potential heterogeneity. PMID:27489666

  2. ADDME – Avoiding Drug Development Mistakes Early: central nervous system drug discovery perspective

    PubMed Central

    Tsaioun, Katya; Bottlaender, Michel; Mabondzo, Aloise

    2009-01-01

    The advent of early absorption, distribution, metabolism, excretion, and toxicity (ADMET) screening has increased the attrition rate of weak drug candidates early in the drug-discovery process, and decreased the proportion of compounds failing in clinical trials for ADMET reasons. This paper reviews the history of ADMET screening and its place in pharmaceutical development, and central nervous system drug discovery in particular. Assays that have been developed in response to specific needs and improvements in technology that result in higher throughput and greater accuracy of prediction of human mechanisms of absorption and toxicity are discussed. The paper concludes with the authors' forecast of new models that will better predict human efficacy and toxicity. PMID:19534730

  3. In Vivo Imaging of Histone Deacetylases (HDACs) in the Central Nervous System and Major Peripheral Organs

    PubMed Central

    2015-01-01

    Epigenetic enzymes are now targeted to treat the underlying gene expression dysregulation that contribute to disease pathogenesis. Histone deacetylases (HDACs) have shown broad potential in treatments against cancer and emerging data supports their targeting in the context of cardiovascular disease and central nervous system dysfunction. Development of a molecular agent for non-invasive imaging to elucidate the distribution and functional roles of HDACs in humans will accelerate medical research and drug discovery in this domain. Herein, we describe the synthesis and validation of an HDAC imaging agent, [11C]6. Our imaging results demonstrate that this probe has high specificity, good selectivity, and appropriate kinetics and distribution for imaging HDACs in the brain, heart, kidney, pancreas, and spleen. Our findings support the translational potential for [11C]6 for human epigenetic imaging. PMID:25203558

  4. Astrocytic TYMP and VEGFA drive blood-brain barrier opening in inflammatory central nervous system lesions.

    PubMed

    Chapouly, Candice; Tadesse Argaw, Azeb; Horng, Sam; Castro, Kamilah; Zhang, Jingya; Asp, Linnea; Loo, Hannah; Laitman, Benjamin M; Mariani, John N; Straus Farber, Rebecca; Zaslavsky, Elena; Nudelman, German; Raine, Cedric S; John, Gareth R

    2015-06-01

    In inflammatory central nervous system conditions such as multiple sclerosis, breakdown of the blood-brain barrier is a key event in lesion pathogenesis, predisposing to oedema, excitotoxicity, and ingress of plasma proteins and inflammatory cells. Recently, we showed that reactive astrocytes drive blood-brain barrier opening, via production of vascular endothelial growth factor A (VEGFA). Here, we now identify thymidine phosphorylase (TYMP; previously known as endothelial cell growth factor 1, ECGF1) as a second key astrocyte-derived permeability factor, which interacts with VEGFA to induce blood-brain barrier disruption. The two are co-induced NFκB1-dependently in human astrocytes by the cytokine interleukin 1 beta (IL1B), and inactivation of Vegfa in vivo potentiates TYMP induction. In human central nervous system microvascular endothelial cells, VEGFA and the TYMP product 2-deoxy-d-ribose cooperatively repress tight junction proteins, driving permeability. Notably, this response represents part of a wider pattern of endothelial plasticity: 2-deoxy-d-ribose and VEGFA produce transcriptional programs encompassing angiogenic and permeability genes, and together regulate a third unique cohort. Functionally, each promotes proliferation and viability, and they cooperatively drive motility and angiogenesis. Importantly, introduction of either into mouse cortex promotes blood-brain barrier breakdown, and together they induce severe barrier disruption. In the multiple sclerosis model experimental autoimmune encephalitis, TYMP and VEGFA co-localize to reactive astrocytes, and correlate with blood-brain barrier permeability. Critically, blockade of either reduces neurologic deficit, blood-brain barrier disruption and pathology, and inhibiting both in combination enhances tissue preservation. Suggesting importance in human disease, TYMP and VEGFA both localize to reactive astrocytes in multiple sclerosis lesion samples. Collectively, these data identify TYMP as an

  5. Astrocytic TYMP and VEGFA drive blood–brain barrier opening in inflammatory central nervous system lesions

    PubMed Central

    Chapouly, Candice; Tadesse Argaw, Azeb; Horng, Sam; Castro, Kamilah; Zhang, Jingya; Asp, Linnea; Loo, Hannah; Laitman, Benjamin M.; Mariani, John N.; Straus Farber, Rebecca; Zaslavsky, Elena; Nudelman, German; Raine, Cedric S.

    2015-01-01

    In inflammatory central nervous system conditions such as multiple sclerosis, breakdown of the blood–brain barrier is a key event in lesion pathogenesis, predisposing to oedema, excitotoxicity, and ingress of plasma proteins and inflammatory cells. Recently, we showed that reactive astrocytes drive blood–brain barrier opening, via production of vascular endothelial growth factor A (VEGFA). Here, we now identify thymidine phosphorylase (TYMP; previously known as endothelial cell growth factor 1, ECGF1) as a second key astrocyte-derived permeability factor, which interacts with VEGFA to induce blood–brain barrier disruption. The two are co-induced NFκB1-dependently in human astrocytes by the cytokine interleukin 1 beta (IL1B), and inactivation of Vegfa in vivo potentiates TYMP induction. In human central nervous system microvascular endothelial cells, VEGFA and the TYMP product 2-deoxy-d-ribose cooperatively repress tight junction proteins, driving permeability. Notably, this response represents part of a wider pattern of endothelial plasticity: 2-deoxy-d-ribose and VEGFA produce transcriptional programs encompassing angiogenic and permeability genes, and together regulate a third unique cohort. Functionally, each promotes proliferation and viability, and they cooperatively drive motility and angiogenesis. Importantly, introduction of either into mouse cortex promotes blood–brain barrier breakdown, and together they induce severe barrier disruption. In the multiple sclerosis model experimental autoimmune encephalitis, TYMP and VEGFA co-localize to reactive astrocytes, and correlate with blood–brain barrier permeability. Critically, blockade of either reduces neurologic deficit, blood–brain barrier disruption and pathology, and inhibiting both in combination enhances tissue preservation. Suggesting importance in human disease, TYMP and VEGFA both localize to reactive astrocytes in multiple sclerosis lesion samples. Collectively, these data identify TYMP

  6. [Metastasis tumors of the central nervous system: molecular biology].

    PubMed

    Bello, M Josefa; González-Gómez, P; Rey, J A

    2004-12-01

    Metastases in the nervous system represent an important and growing problem in the clinical practice, being the cause of a great mortality in the developed countries. This article reviews the few data available on the molecular mechanisms involved in the pathogenesis of these tumours, leading to oncogene activation, inactivation of tumour suppressor genes, not only by the classical mechanisms, but also by the tumour cell epigenetic balance alteration. We conclude that all this knowledge will lead in the future to a better diagnosis, treatment and clinic evolution of these patients. PMID:15632995

  7. REVIEW ARTICLE: In vivo magnetic resonance imaging: insights into structure and function of the central nervous system

    NASA Astrophysics Data System (ADS)

    Natt, Oliver; Frahm, Jens

    2005-04-01

    Spatially resolved nuclear magnetic resonance (NMR) techniques provide structural, metabolic and functional insights into the central nervous system and allow for repetitive in vivo studies of both humans and animals. Complementing its prominent role in diagnostic imaging, magnetic resonance imaging (MRI) has evolved into an indispensable research tool in system-oriented neurobiology where contributions to functional genomics and translational medicine bridge the gap from molecular biology to animal models and clinical applications. This review presents an overview on some of the most relevant advances in MRI. An introduction covering the basic principles is followed by a discussion of technological improvements in instrumentation and imaging sequences including recent developments in parallel acquisition techniques. Because MRI is noninvasive in contrast to most other imaging modalities, examples focus on in vivo studies of the central nervous system in a variety of species ranging from humans to mice and insects.

  8. The sympathetic nervous system alterations in human hypertension.

    PubMed

    Grassi, Guido; Mark, Allyn; Esler, Murray

    2015-03-13

    Several articles have dealt with the importance and mechanisms of the sympathetic nervous system alterations in experimental animal models of hypertension. This review addresses the role of the sympathetic nervous system in the pathophysiology and therapy of human hypertension. We first discuss the strengths and limitations of various techniques for assessing the sympathetic nervous system in humans, with a focus on heart rate, plasma norepinephrine, microneurographic recording of sympathetic nerve traffic, and measurements of radiolabeled norepinephrine spillover. We then examine the evidence supporting the importance of neuroadrenergic factors as promoters and amplifiers of human hypertension. We expand on the role of the sympathetic nervous system in 2 increasingly common forms of secondary hypertension, namely hypertension associated with obesity and with renal disease. With this background, we examine interventions of sympathetic deactivation as a mode of antihypertensive treatment. Particular emphasis is given to the background and results of recent therapeutic approaches based on carotid baroreceptor stimulation and radiofrequency ablation of the renal nerves. PMID:25767284

  9. THE SYMPATHETIC NERVOUS SYSTEM ALTERATIONS IN HUMAN HYPERTENSION

    PubMed Central

    Grassi, Guido; Mark, Allyn; Esler, Murray

    2015-01-01

    A number of articles have dealt with the importance and mechanisms of the sympathetic nervous system alterations in experimental animal models of hypertension. This review addresses the role of the sympathetic nervous system in the pathophysiology and therapy of human hypertension. We first discuss the strengths and limitations of various techniques for assessing the sympathetic nervous system in humans, with a focus on heart rate, plasma norepinephrine, microneurographic recording of sympathetic nerve traffic, and measurements of radiolabeled norepinephrine spillover. We then examine the evidence supporting the importance of neuroadrenergic factors as “promoters” and “amplifiers” of human hypertension. We expand on the role of the sympathetic nervous system in two increasingly common forms of secondary hypertension, namely hypertension associated with obesity and with renal disease. With this background, we examine interventions of sympathetic deactivation as a mode of antihypertensive treatment. Particular emphasis is given to the background and results of recent therapeutic approaches based on carotid baroreceptor stimulation and radiofrequency ablation of the renal nerves. PMID:25767284

  10. Current Proteomic Methods to Investigate the Dynamics of Histone Turnover in the Central Nervous System.

    PubMed

    Farrelly, L A; Dill, B D; Molina, H; Birtwistle, M R; Maze, I

    2016-01-01

    Characterizing the dynamic behavior of nucleosomes in the central nervous system is vital to our understanding of brain-specific chromatin-templated processes and their roles in transcriptional plasticity. Histone turnover-the complete loss of old, and replacement by new, nucleosomal histones-is one such phenomenon that has recently been shown to be critical for cell-type-specific transcription in brain, synaptic plasticity, and cognition. Such revelations that histones, long believed to static proteins in postmitotic cells, are highly dynamic in neurons were only possible owing to significant advances in analytical chemistry-based techniques, which now provide a platform for investigations of histone dynamics in both healthy and diseased tissues. Here, we discuss both past and present proteomic methods (eg, mass spectrometry, human "bomb pulse labeling") for investigating histone turnover in brain with the hope that such information may stimulate future investigations of both adaptive and aberrant forms of "neuroepigenetic" plasticity. PMID:27423867

  11. Blood to brain transport of interleukin links the immune and central nervous systems

    SciTech Connect

    Banks, W.A.; Kastin, A.J. Tulane Univ. School of Medicine, New Orleans, LA )

    1991-01-01

    Interleukins (IL) are naturally occurring proteins that regulate, and thus link, both the immune system and the central nervous system (CNS). Since proteins are assumed not to be able to cross the blood-brain barrier (BBB), it is controversial how this linkage could occur. The authors show here that after iv injection of {sup 125}I-hIL-1{alpha}, radioactivity in the brain eluted on HPLC in the position of the labeled cytokine. In addition, entry was inhibited by unlabeled hIL-1{alpha}. The authors demonstration of a saturable, carrier-mediated system that transports recombinant human IL-1{alpha} in intact form from the blood into the CNS indicates a direct immune-CNS connection.

  12. Glycosaminoglycan binding facilitates entry of a bacterial pathogen into central nervous systems.

    PubMed

    Chang, Yung-Chi; Wang, Zhipeng; Flax, Lindsay A; Xu, Ding; Esko, Jeffrey D; Nizet, Victor; Baron, Miriam J

    2011-06-01

    Certain microbes invade brain microvascular endothelial cells (BMECs) to breach the blood-brain barrier (BBB) and establish central nervous system (CNS) infection. Here we use the leading meningitis pathogen group B Streptococcus (GBS) together with insect and mammalian infection models to probe a potential role of glycosaminoglycan (GAG) interactions in the pathogenesis of CNS entry. Site-directed mutagenesis of a GAG-binding domain of the surface GBS alpha C protein impeded GBS penetration of the Drosophila BBB in vivo and diminished GBS adherence to and invasion of human BMECs in vitro. Conversely, genetic impairment of GAG expression in flies or mice reduced GBS dissemination into the brain. These complementary approaches identify a role for bacterial-GAG interactions in the pathogenesis of CNS infection. Our results also highlight how the simpler yet genetically conserved Drosophila GAG pathways can provide a model organism to screen candidate molecules that can interrupt pathogen-GAG interactions for future therapeutic applications. PMID:21731486

  13. Glycosaminoglycan Binding Facilitates Entry of a Bacterial Pathogen into Central Nervous Systems

    PubMed Central

    Chang, Yung-Chi; Wang, Zhipeng; Flax, Lindsay A.; Xu, Ding; Esko, Jeffrey D.; Nizet, Victor; Baron, Miriam J.

    2011-01-01

    Certain microbes invade brain microvascular endothelial cells (BMECs) to breach the blood-brain barrier (BBB) and establish central nervous system (CNS) infection. Here we use the leading meningitis pathogen group B Streptococcus (GBS) together with insect and mammalian infection models to probe a potential role of glycosaminoglycan (GAG) interactions in the pathogenesis of CNS entry. Site-directed mutagenesis of a GAG-binding domain of the surface GBS alpha C protein impeded GBS penetration of the Drosophila BBB in vivo and diminished GBS adherence to and invasion of human BMECs in vitro. Conversely, genetic impairment of GAG expression in flies or mice reduced GBS dissemination into the brain. These complementary approaches identify a role for bacterial-GAG interactions in the pathogenesis of CNS infection. Our results also highlight how the simpler yet genetically conserved Drosophila GAG pathways can provide a model organism to screen candidate molecules that can interrupt pathogen-GAG interactions for future therapeutic applications. PMID:21731486

  14. Current Proteomic Methods to Investigate the Dynamics of Histone Turnover in the Central Nervous System

    PubMed Central

    Farrelly, L.A.; Dill, B.D.; Molina, H.; Birtwistle, M.R.; Maze, I.

    2016-01-01

    Characterizing the dynamic behavior of nucleosomes in the central nervous system is vital to our understanding of brain-specific chromatin-templated processes and their roles in transcriptional plasticity. Histone turnover—the complete loss of old, and replacement by new, nucleosomal histones—is one such phenomenon that has recently been shown to be critical for cell-type-specific transcription in brain, synaptic plasticity, and cognition. Such revelations that histones, long believed to static proteins in postmitotic cells, are highly dynamic in neurons were only possible owing to significant advances in analytical chemistry-based techniques, which now provide a platform for investigations of histone dynamics in both healthy and diseased tissues. Here, we discuss both past and present proteomic methods (eg, mass spectrometry, human “bomb pulse labeling”) for investigating histone turnover in brain with the hope that such information may stimulate future investigations of both adaptive and aberrant forms of “neuroepigenetic” plasticity. PMID:27423867

  15. The pathogenesis of murine coronavirus infection of the central nervous system

    PubMed Central

    Hosking, Martin P.; Lane, Thomas E.

    2009-01-01

    Mouse hepatitis virus (MHV) is a positive strand RNA virus that causes an acute encephalomyelitis which later resolves into a chronic fulminating demyelinating disease. Cytokine production, chemokine secretion, and immune cell infiltration into the central nervous system are critical to control viral replication during acute infection. Despite potent anti – viral T lymphocyte activity, sterile immunity is not achieved, and MHV chronically persists within oligodendrocytes. Continued infiltration and activation of the immune system, a result of the lingering viral antigen and RNA within oligodendrocytes, lead directly to the development of an immune – mediated demyelination that bears remarkable similarities, both clinically and histologically, to the human demyelinating disease multiple sclerosis. MHV offers a unique model system for studying host defense during acute viral infection and immune – mediated demyelination during chronic infection. PMID:20370625

  16. Cannabis, Cannabinoids, and Cerebral Metabolism: Potential Applications in Stroke and Disorders of the Central Nervous System.

    PubMed

    Latorre, Julius Gene S; Schmidt, Elena B

    2015-09-01

    No compound has generated more attention in both the scientific and recently in the political arena as much as cannabinoids. These diverse groups of compounds referred collectively as cannabinoids have both been vilified due to its dramatic and potentially harmful psychotropic effects and glorified due to its equally dramatic and potential application in a number of acute and chronic neurological conditions. Previously illegal to possess, cannabis, the plant where natural form of cannabinoids are derived, is now accepted in a growing number of states for medicinal purpose, and some even for recreational use, increasing opportunities for more scientific experimentation. The purpose of this review is to summarize the growing body of literature on cannabinoids and to present an overview of our current state of knowledge of the human endocannabinoid system in the hope of defining the future of cannabinoids and its potential applications in disorders of the central nervous system, focusing on stroke. PMID:26238742

  17. Role of Nuclear Receptors in Central Nervous System Development and Associated Diseases.

    PubMed

    Olivares, Ana Maria; Moreno-Ramos, Oscar Andrés; Haider, Neena B

    2015-01-01

    The nuclear hormone receptor (NHR) superfamily is composed of a wide range of receptors involved in a myriad of important biological processes, including development, growth, metabolism, and maintenance. Regulation of such wide variety of functions requires a complex system of gene regulation that includes interaction with transcription factors, chromatin-modifying complex, and the proper recognition of ligands. NHRs are able to coordinate the expression of genes in numerous pathways simultaneously. This review focuses on the role of nuclear receptors in the central nervous system and, in particular, their role in regulating the proper development and function of the brain and the eye. In addition, the review highlights the impact of mutations in NHRs on a spectrum of human diseases from autism to retinal degeneration. PMID:27168725

  18. Role of Nuclear Receptors in Central Nervous System Development and Associated Diseases

    PubMed Central

    Olivares, Ana Maria; Moreno-Ramos, Oscar Andrés; Haider, Neena B.

    2015-01-01

    The nuclear hormone receptor (NHR) superfamily is composed of a wide range of receptors involved in a myriad of important biological processes, including development, growth, metabolism, and maintenance. Regulation of such wide variety of functions requires a complex system of gene regulation that includes interaction with transcription factors, chromatin-modifying complex, and the proper recognition of ligands. NHRs are able to coordinate the expression of genes in numerous pathways simultaneously. This review focuses on the role of nuclear receptors in the central nervous system and, in particular, their role in regulating the proper development and function of the brain and the eye. In addition, the review highlights the impact of mutations in NHRs on a spectrum of human diseases from autism to retinal degeneration. PMID:27168725

  19. Thioredoxin System Regulation in the Central Nervous System: Experimental Models and Clinical Evidence

    PubMed Central

    Silva-Adaya, Daniela; Gonsebatt, María E.; Guevara, Jorge

    2014-01-01

    The reactive oxygen species produced continuously during oxidative metabolism are generated at very high rates in the brain. Therefore, defending against oxidative stress is an essential task within the brain. An important cellular system against oxidative stress is the thioredoxin system (TS). TS is composed of thioredoxin, thioredoxin reductase, and NADPH. This review focuses on the evidence gathered in recent investigations into the central nervous system, specifically the different brain regions in which the TS is expressed. Furthermore, we address the conditions that modulate the thioredoxin system in both, animal models and the postmortem brains of human patients associated with the most common neurodegenerative disorders, in which the thioredoxin system could play an important part. PMID:24723994

  20. Programmed cell death acts at different stages of Drosophila neurodevelopment to shape the central nervous system.

    PubMed

    Pinto-Teixeira, Filipe; Konstantinides, Nikolaos; Desplan, Claude

    2016-08-01

    Nervous system development is a process that integrates cell proliferation, differentiation, and programmed cell death (PCD). PCD is an evolutionary conserved mechanism and a fundamental developmental process by which the final cell number in a nervous system is established. In vertebrates and invertebrates, PCD can be determined intrinsically by cell lineage and age, as well as extrinsically by nutritional, metabolic, and hormonal states. Drosophila has been an instrumental model for understanding how this mechanism is regulated. We review the role of PCD in Drosophila central nervous system development from neural progenitors to neurons, its molecular mechanism and function, how it is regulated and implemented, and how it ultimately shapes the fly central nervous system from the embryo to the adult. Finally, we discuss ideas that emerged while integrating this information. PMID:27404003

  1. The role of repulsive guidance molecules in the embryonic and adult vertebrate central nervous system

    PubMed Central

    Mueller, Bernhard K; Yamashita, Toshihide; Schaffar, Gregor; Mueller, Reinhold

    2006-01-01

    During the development of the nervous system, outgrowing axons often have to travel long distances to reach their target neurons. In this process, outgrowing neurites tipped with motile growth cones rely on guidance cues present in their local environment. These cues are detected by specific receptors expressed on growth cones and neurites and influence the trajectory of the growing fibres. Neurite growth, guidance, target innervation and synapse formation and maturation are the processes that occur predominantly but not exclusively during embryonic or early post-natal development in vertebrates. As a result, a functional neural network is established, which is usually remarkably stable. However, the stability of the neural network in higher vertebrates comes at an expensive price, i.e. the loss of any significant ability to regenerate injured or damaged neuronal connections in their central nervous system (CNS). Most importantly, neurite growth inhibitors prevent any regenerative growth of injured nerve fibres. Some of these inhibitors are associated with CNS myelin, others are found at the lesion site and in the scar tissue. Traumatic injuries in brain and spinal cord of mammals induce upregulation of embryonic inhibitory or repulsive guidance cues and their receptors on the neurites. An example for embryonic repulsive directional cues re-expressed at lesion sites in both the rat and human CNS is provided with repulsive guidance molecules, a new family of directional guidance cues. PMID:16939972

  2. Evidence Report: Risk of Acute and Late Central Nervous System Effects from Radiation Exposure

    NASA Technical Reports Server (NTRS)

    Nelson, Gregory A.; Simonsen, Lisa; Huff, Janice L.

    2016-01-01

    Possible acute and late risks to the central nervous system (CNS) from galactic cosmic rays (GCR) and solar particle events (SPE) are concerns for human exploration of space. Acute CNS risks may include: altered cognitive function, reduced motor function, and behavioral changes, all of which may affect performance and human health. Late CNS risks may include neurological disorders such as Alzheimer's disease (AD), dementia and premature aging. Although detrimental CNS changes are observed in humans treated with high-dose radiation (e.g., gamma rays and 9 protons) for cancer and are supported by experimental evidence showing neurocognitive and behavioral effects in animal models, the significance of these results on the morbidity to astronauts has not been elucidated. There is a lack of human epidemiology data on which to base CNS risk estimates; therefore, risk projection based on scaling to human data, as done for cancer risk, is not possible for CNS risks. Research specific to the spaceflight environment using animal and cell models must be compiled to quantify the magnitude of CNS changes in order to estimate this risk and to establish validity of the current permissible exposure limits (PELs). In addition, the impact of radiation exposure in combination with individual sensitivity or other space flight factors, as well as assessment of the need for biological/pharmaceutical countermeasures, will be considered after further definition of CNS risk occurs.

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

    SciTech Connect

    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.

  4. Interleukin-6, a Major Cytokine in the Central Nervous System

    PubMed Central

    Erta, María; Quintana, Albert; Hidalgo, Juan

    2012-01-01

    Interleukin-6 (IL-6) is a cytokine originally identified almost 30 years ago as a B-cell differentiation factor, capable of inducing the maturation of B cells into antibody-producing cells. As with many other cytokines, it was soon realized that IL-6 was not a factor only involved in the immune response, but with many critical roles in major physiological systems including the nervous system. IL-6 is now known to participate in neurogenesis (influencing both neurons and glial cells), and in the response of mature neurons and glial cells in normal conditions and following a wide arrange of injury models. In many respects, IL-6 behaves in a neurotrophin-like fashion, and seemingly makes understandable why the cytokine family that it belongs to is known as neuropoietins. Its expression is affected in several of the main brain diseases, and animal models strongly suggest that IL-6 could have a role in the observed neuropathology and that therefore it is a clear target of strategic therapies. PMID:23136554

  5. CARD9-Dependent Neutrophil Recruitment Protects against Fungal Invasion of the Central Nervous System

    PubMed Central

    Swamydas, Muthulekha; Rodriguez, Carlos A.; Lim, Jean K.; Mendez, Laura M.; Fink, Danielle L.; Hsu, Amy P.; Zhai, Bing; Karauzum, Hatice; Mikelis, Constantinos M.; Rose, Stacey R.; Ferre, Elise M. N.; Yockey, Lynne; Lemberg, Kimberly; Kuehn, Hye Sun; Rosenzweig, Sergio D.; Lin, Xin; Chittiboina, Prashant; Datta, Sandip K.; Belhorn, Thomas H.; Weimer, Eric T.; Hernandez, Michelle L.; Hohl, Tobias M.; Kuhns, Douglas B.; Lionakis, Michail S.

    2015-01-01

    Candida is the most common human fungal pathogen and causes systemic infections that require neutrophils for effective host defense. Humans deficient in the C-type lectin pathway adaptor protein CARD9 develop spontaneous fungal disease that targets the central nervous system (CNS). However, how CARD9 promotes protective antifungal immunity in the CNS remains unclear. Here, we show that a patient with CARD9 deficiency had impaired neutrophil accumulation and induction of neutrophil-recruiting CXC chemokines in the cerebrospinal fluid despite uncontrolled CNS Candida infection. We phenocopied the human susceptibility in Card9-/- mice, which develop uncontrolled brain candidiasis with diminished neutrophil accumulation. The induction of neutrophil-recruiting CXC chemokines is significantly impaired in infected Card9-/- brains, from both myeloid and resident glial cellular sources, whereas cell-intrinsic neutrophil chemotaxis is Card9-independent. Taken together, our data highlight the critical role of CARD9-dependent neutrophil trafficking into the CNS and provide novel insight into the CNS fungal susceptibility of CARD9-deficient humans. PMID:26679537

  6. CARD9-Dependent Neutrophil Recruitment Protects against Fungal Invasion of the Central Nervous System.

    PubMed

    Drummond, Rebecca A; Collar, Amanda L; Swamydas, Muthulekha; Rodriguez, Carlos A; Lim, Jean K; Mendez, Laura M; Fink, Danielle L; Hsu, Amy P; Zhai, Bing; Karauzum, Hatice; Mikelis, Constantinos M; Rose, Stacey R; Ferre, Elise M N; Yockey, Lynne; Lemberg, Kimberly; Kuehn, Hye Sun; Rosenzweig, Sergio D; Lin, Xin; Chittiboina, Prashant; Datta, Sandip K; Belhorn, Thomas H; Weimer, Eric T; Hernandez, Michelle L; Hohl, Tobias M; Kuhns, Douglas B; Lionakis, Michail S

    2015-12-01

    Candida is the most common human fungal pathogen and causes systemic infections that require neutrophils for effective host defense. Humans deficient in the C-type lectin pathway adaptor protein CARD9 develop spontaneous fungal disease that targets the central nervous system (CNS). However, how CARD9 promotes protective antifungal immunity in the CNS remains unclear. Here, we show that a patient with CARD9 deficiency had impaired neutrophil accumulation and induction of neutrophil-recruiting CXC chemokines in the cerebrospinal fluid despite uncontrolled CNS Candida infection. We phenocopied the human susceptibility in Card9-/- mice, which develop uncontrolled brain candidiasis with diminished neutrophil accumulation. The induction of neutrophil-recruiting CXC chemokines is significantly impaired in infected Card9-/- brains, from both myeloid and resident glial cellular sources, whereas cell-intrinsic neutrophil chemotaxis is Card9-independent. Taken together, our data highlight the critical role of CARD9-dependent neutrophil trafficking into the CNS and provide novel insight into the CNS fungal susceptibility of CARD9-deficient humans. PMID:26679537

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

    ERIC Educational Resources Information Center

    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…

  8. Blocking Neurogenic Inflammation for the Treatment of Acute Disorders of the Central Nervous System

    PubMed Central

    Lewis, Kate Marie; Turner, Renée Jade

    2013-01-01

    Classical inflammation is a well-characterized secondary response to many acute disorders of the central nervous system. However, in recent years, the role of neurogenic inflammation in the pathogenesis of neurological diseases has gained increasing attention, with a particular focus on its effects on modulation of the blood-brain barrier BBB. The neuropeptide substance P has been shown to increase blood-brain barrier permeability following acute injury to the brain and is associated with marked cerebral edema. Its release has also been shown to modulate classical inflammation. Accordingly, blocking substance P NK1 receptors may provide a novel alternative treatment to ameliorate the deleterious effects of neurogenic inflammation in the central nervous system. The purpose of this paper is to provide an overview of the role of substance P and neurogenic inflammation in acute injury to the central nervous system following traumatic brain injury, spinal cord injury, stroke, and meningitis. PMID:23819099

  9. Endothelial cells are a replicative niche for entry of Toxoplasma gondii to the central nervous system.

    PubMed

    Konradt, Christoph; Ueno, Norikiyo; Christian, David A; Delong, Jonathan H; Pritchard, Gretchen Harms; Herz, Jasmin; Bzik, David J; Koshy, Anita A; McGavern, Dorian B; Lodoen, Melissa B; Hunter, Christopher A

    2016-01-01

    An important function of the blood-brain barrier is to exclude pathogens from the central nervous system, but some microorganisms benefit from the ability to enter this site. It has been proposed that Toxoplasma gondii can cross biological barriers as a motile extracellular form that uses transcellular or paracellular migration, or by infecting a host cell that then crosses the blood-brain barrier. Unexpectedly, analysis of acutely infected mice revealed significant numbers of free parasites in the blood and the presence of infected endothelial cells in the brain vasculature. The use of diverse transgenic parasites combined with reporter mice and intravital imaging demonstrated that replication in and lysis of endothelial cells precedes invasion of the central nervous system, and highlight a novel mechanism for parasite entry to the central nervous system. PMID:27572166

  10. The Central Nervous System Sites Mediating the Orexigenic Actions of Ghrelin

    PubMed Central

    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

  11. The central nervous system sites mediating the orexigenic actions of ghrelin.

    PubMed

    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

  12. Endothelial cells are a replicative niche for entry of Toxoplasma gondii to the central nervous system

    PubMed Central

    Konradt, Christoph; Ueno, Norikiyo; Christian, David A.; Delong, Jonathan H.; Pritchard, Gretchen Harms; Herz, Jasmin; Bzik, David J.; Koshy, Anita A.; McGavern, Dorian B.; Lodoen, Melissa B.; Hunter, Christopher A.

    2016-01-01

    An important function of the blood–brain barrier is to exclude pathogens from the central nervous system, but some microorganisms benefit from the ability to enter this site. It has been proposed that Toxoplasma gondii can cross biological barriers as a motile extracellular form that uses transcellular or paracellular migration, or by infecting a host cell that then crosses the blood–brain barrier. Unexpectedly, analysis of acutely infected mice revealed significant numbers of free parasites in the blood and the presence of infected endothelial cells in the brain vasculature. The use of diverse transgenic parasites combined with reporter mice and intravital imaging demonstrated that replication in and lysis of endothelial cells precedes invasion of the central nervous system, and highlight a novel mechanism for parasite entry to the central nervous system. PMID:27478622

  13. Local Nitric Oxide Production in Viral and Autoimmune Diseases of the Central Nervous System

    NASA Astrophysics Data System (ADS)

    Hooper, D. Craig; Tsuyoshi Ohnishi, S.; Kean, Rhonda; Numagami, Yoshihiro; Dietzschold, Bernhard; Koprowski, Hilary

    1995-06-01

    Because of the short half-life of NO, previous studies implicating NO in central nervous system pathology during infection had to rely on the demonstration of elevated levels of NO synthase mRNA or enzyme expression or NO metabolites such as nitrate and nitrite in the infected brain. To more definitively investigate the potential causative role of NO in lesions of the central nervous system in animals infected with neurotropic viruses or suffering from experimental allergic encephalitis, we have determined directly the levels of NO present in the central nervous system of such animals. Using spin trapping of NO and electron paramagnetic resonance spectroscopy, we confirm here that copious amounts of NO (up to 30-fold more than control) are elaborated in the brains of rats infected with rabies virus or borna disease virus, as well as in the spinal cords of rats that had received myelin basic protein-specific T cells.

  14. Functional structure and dynamics of the human nervous system

    NASA Technical Reports Server (NTRS)

    Lawrence, J. A.

    1981-01-01

    The status of an effort to define the directions needed to take in extending pilot models is reported. These models are needed to perform closed-loop (man-in-the-loop) feedback flight control system designs and to develop cockpit display requirements. The approach taken is to develop a hypothetical working model of the human nervous system by reviewing the current literature in neurology and psychology and to develop a computer model of this hypothetical working model.

  15. Central nervous system cancers, version 2.2014. Featured updates to the NCCN Guidelines.

    PubMed

    Nabors, Louis Burt; Portnow, Jana; Ammirati, Mario; Brem, Henry; Brown, Paul; Butowski, Nicholas; Chamberlain, Marc C; DeAngelis, Lisa M; Fenstermaker, Robert A; Friedman, Allan; Gilbert, Mark R; Hattangadi-Gluth, Jona; Hesser, Deneen; Holdhoff, Matthias; Junck, Larry; Lawson, Ronald; Loeffler, Jay S; Moots, Paul L; Mrugala, Maciej M; Newton, Herbert B; Raizer, Jeffrey J; Recht, Lawrence; Shonka, Nicole; Shrieve, Dennis C; Sills, Allen K; Swinnen, Lode J; Tran, David; Tran, Nam; Vrionis, Frank D; Wen, Patrick Yung; McMillian, Nicole R; Ho, Maria

    2014-11-01

    The NCCN Guidelines for Central Nervous System Cancers provide multidisciplinary recommendations for the clinical management of patients with cancers of the central nervous system. These NCCN Guidelines Insights highlight recent updates regarding the management of metastatic brain tumors using radiation therapy. Use of stereotactic radiosurgery (SRS) is no longer limited to patients with 3 or fewer lesions, because data suggest that total disease burden, rather than number of lesions, is predictive of survival benefits associated with the technique. SRS is increasingly becoming an integral part of management of patients with controlled, low-volume brain metastases. PMID:25361798

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

    NASA Astrophysics Data System (ADS)

    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.

  17. Peptides from regenerating central nervous system promote specific populations of macroglia.

    PubMed Central

    Giulian, D; Tomozawa, Y; Hindman, H; Allen, R L

    1985-01-01

    The regenerating central nervous system of goldfish contains peptides referred to as glia-promoting factors (GPFs) that stimulate the proliferation of mammalian macroglia. We find that, in vitro, GPF1 and GPF3 promote the appearance of oligodendroglia and GPF2 and GPF4 stimulate proliferation of astroglia. The activities of GPF1, GPF3, and GPF4 increase during regeneration of the goldfish visual system. These results suggest that brain peptides may play a role in the recovery of the injured central nervous system by regulating the growth and development of specific macroglial populations. Images PMID:3858882

  18. Exosome-mediated inflammasome signaling after central nervous system injury.

    PubMed

    de Rivero Vaccari, Juan Pablo; Brand, Frank; Adamczak, Stephanie; Lee, Stephanie W; Perez-Barcena, Jon; Wang, Michael Y; Bullock, M Ross; Dietrich, W Dalton; Keane, Robert W

    2016-01-01

    Neuroinflammation is a response against harmful effects of diverse stimuli and participates in the pathogenesis of brain and spinal cord injury (SCI). The innate immune response plays a role in neuroinflammation following CNS injury via activation of multiprotein complexes termed inflammasomes that regulate the activation of caspase 1 and the processing of the pro-inflammatory cytokines IL-1β and IL-18. We report here that the expression of components of the nucleotide-binding and oligomerization domain (NOD)-like receptor protein-1 (NLRP-1) inflammasome, apoptosis speck-like protein containing a caspase recruitment domain (ASC), and caspase 1 are significantly elevated in spinal cord motor neurons and cortical neurons after CNS trauma. Moreover, NLRP1 inflammasome proteins are present in exosomes derived from CSF of SCI and traumatic brain-injured patients following trauma. To investigate whether exosomes could be used to therapeutically block inflammasome activation in the CNS, exosomes were isolated from embryonic cortical neuronal cultures and loaded with short-interfering RNA (siRNA) against ASC and administered to spinal cord-injured animals. Neuronal-derived exosomes crossed the injured blood-spinal cord barrier, and delivered their cargo in vivo, resulting in knockdown of ASC protein levels by approximately 76% when compared to SCI rats treated with scrambled siRNA. Surprisingly, siRNA silencing of ASC also led to a significant decrease in caspase 1 activation and processing of IL-1β after SCI. These findings indicate that exosome-mediated siRNA delivery may be a strong candidate to block inflammasome activation following CNS injury. We propose the following signaling cascade for inflammasome activation in peripheral tissues after CNS injury: CNS trauma induces inflammasome activation in the nervous system and secretion of exosomes containing inflammasome protein cargo into cerebral spinal fluid. The inflammasome containing exosomes then fuse with target

  19. Involvement of central nervous system in diabetes mellitus.

    PubMed Central

    Verma, A; Bisht, M S; Ahuja, G K

    1984-01-01

    Brainstem auditory evoked responses were recorded in 22 diabetic patients with a variable duration of illness (mean 5.8 years) and 14 normal healthy controls of comparable age. The initial 10 millisecond components, found to be most consistent and reproducible, were analysed. Variations in the form of individual wave latency, interpeak latencies and V wave amplitude were compared in both the groups. No difference was found in any of the parameters. It was concluded that central neural pathways are not involved at least initially in diabetes mellitus. PMID:6726270

  20. The central nervous system and its operation in cardiovascular control.

    PubMed

    Korner, P I

    1981-01-01

    In the intact organism environmental disturbances affecting the circulation often result in simultaneous changes of several groups of peripheral afferents. These elicit characteristic patterns of autonomic activity with distinctive patterns of vagal activity, of regional sympathetic neural activity and of adrenal catecholamine secretion. During simultaneous changes in several groups of afferents the autonomic responses are often non-linear, with the response to one input markedly influenced by the level of the others. When these non-linear interactions involve the central arterial baroreflex pathways the properties of the body's blood pressure system can become greatly altered. With certain combinations of afferents these interactions make it possible for the organism to better withstand large perturbations than it could do through the normal properties of the arterial baroreceptor reflex. The different neuron groups contributing to the CNS autonomic pathways release many different transmitters including noradrenaline or serotonin and changes in reflex properties result from alterations in transmitter release in one or other of the pathways of the particular network. The peripheral arterial baroreceptors become rapidly reset during sustained alterations in blood pressure. Their 'memory' for any given absolute blood pressure is only a few minutes duration. Hence sustained changes in autonomic activity depend on the properties of the CNS either through signals arising from other groups of peripheral receptors, from central 'command' or owing to changes in transmitter release in a given pathway. PMID:7249873

  1. FTY720 (fingolimod) in Multiple Sclerosis: therapeutic effects in the immune and the central nervous system

    PubMed Central

    Brinkmann, Volker

    2009-01-01

    FTY720 (fingolimod) is a first-in-class sphingosine 1-phosphate (S1P) receptor modulator that was highly effective in Phase II clinical trials for Multiple Sclerosis (MS). FTY720 is phosphorylated in vivo by sphingosine kinase-2 to form the active moiety FTY720-phosphate that binds to four of the five G protein-coupled S1P receptor subtypes. Studies using conditional S1P1 receptor-deficient and sphingosine kinase-deficient mice showed that the egress of lymphocytes from lymph nodes requires signalling of lymphocytic S1P1 receptors by the endogenous ligand S1P. The S1P mimetic FTY720-phosphate causes internalization and degradation of cell membrane-expressed S1P1, thereby antagonizing S1P action at the receptor. In models of human MS and demyelinating polyneuropathies, functional antagonism of lymphocytic S1P1 slows S1P-driven egress of lymphocytes from lymph nodes, thereby reducing the numbers of autoaggressive TH17 cells that recirculate via lymph and blood to the central nervous system and the sciatic/ischiatic nerves. Based on its lipophilic nature, FTY720 crosses the blood–brain barrier, and ongoing experiments suggest that the drug also down-modulates S1P1 in neural cells/astrocytes to reduce astrogliosis, a phenomenon associated with neurodegeneration in MS. This may help restore gap-junctional communication of astrocytes with neurons and cells of the blood–brain barrier. Additional effects may result from (down-) modulation of S1P3 in astrocytes and of S1P1 and S1P5 in oligodendrocytes. In conclusion, FTY720 may act through immune-based and central mechanisms to reduce inflammation and support structural restoration of the central nervous system parenchyma. Beyond the autoimmune indications, very recent studies suggest that short-term, low-dose administration of FTY720 could help treat chronic (viral) infections. Differential effects of the drug on the trafficking of naïve, central memory and effector memory T cell subsets are discussed. PMID:19814729

  2. Central nervous system leukemia and lymphoma: computed tomographic manifestations

    SciTech Connect

    Pagani, J.J.; Libshitz, H.I.; Wallace, S.; Hayman, L.A.

    1981-12-01

    Computed tomographic (CT) abnormalities in the brain were identified in 31 of 405 patients with leukemia or lymphoma. Abnormalities included neoplastic masses (15), hemorrhage (nine), abscess (two), other brain tumors (four), and methotrexate leukoencephalopathy (one). CT was normal in 374 patients including 148 with meningeal disease diagnosed by cerebrospinal fluid cytologic examination. Prior to treatment, malignant masses were isodense or of greater density with varying amounts of edema. Increase in size or number of the masses indicated worsening. Response to radiation and chemotherapy was manifested by development of a central low density region with an enhancing rim. CT findings correlated with clinical and cerebrospinal fluid findings. The differential diagnosis of the various abnormalities is considered.

  3. Compartmentalized Histoplasma capsulatum Infection of the Central Nervous System

    PubMed Central

    Eid, Albert J.; Leever, John D.; Husmann, Kathrin

    2015-01-01

    Background. Histoplasmosis is a common fungal infection in the southeastern, mid-Atlantic, and central states; however, its presentation can be atypical. Case Presentation. We report a case of Histoplasma capsulatum infection presenting as slowly progressive weakness in the lower extremities, followed by the development of numbness below the midthoracic area, urinary incontinence, and slurred speech. Brain MRI showed leptomeningeal enhancement, predominantly linear, involving the basal cisterns, the brainstem, and spinal cord. Cerebrospinal fluid analysis showed lymphocytic pleocytosis. Discussion. CNS histoplasmosis is usually seen in patients with disseminated histoplasmosis. Isolated CNS histoplasmosis is rarely seen, especially in immunocompetent patients. Conclusions. Histoplasmosis should be considered in the differential diagnosis of patients experiencing slowly progressive neurological deficit. PMID:26199770

  4. Baroreflex failure in a patient with central nervous system lesions involving the nucleus tractus solitarii

    NASA Technical Reports Server (NTRS)

    Biaggioni, I.; Whetsell, W. O.; Jobe, J.; Nadeau, J. H.

    1994-01-01

    Animal studies have shown the importance of the nucleus tractus solitarii, a collection of neurons in the brain stem, in the acute regulation of blood pressure. Impulses arising from the carotid and aortic baroreceptors converge in this center, where the first synapse of the baroreflex is located. Stimulation of the nucleus tractus solitarii provides an inhibitory signal to other brain stem structures, particularly the rostral ventrolateral medulla, resulting in a reduction in sympathetic outflow and a decrease in blood pressure. Conversely, experimental lesions of the nucleus tractus solitarii lead to loss of baroreflex control of blood pressure, sympathetic activation, and severe hypertension in animals. In humans, baroreflex failure due to deafferentation of baroreceptors has been previously reported and is characterized by episodes of severe hypertension and tachycardia. We present a patient with an undetermined process of the central nervous system characterized pathologically by ubiquitous infarctions that were particularly prominent in the nucleus tractus solitarii bilaterally but spared the rostral ventrolateral medulla. Absence of a functioning baroreflex was evidenced by the lack of reflex tachycardia to the hypotensive effects of sodium nitroprusside, exaggerated pressor responses to handgrip and cold pressor test, and exaggerated depressor responses to meals and centrally acting alpha 2-agonists. This clinicopathological correlate suggests that the patient's baroreflex failure can be explained by the unique combination of the destruction of sympathetic inhibitory centers (ie, the nucleus tractus solitarii) and preservation of centers that exert a positive modulation on sympathetic tone (ie, the rostral ventrolateral medulla).

  5. Novel approaches and challenges to treatment of central nervous system viral infections.

    PubMed

    Nath, Avindra; Tyler, Kenneth L

    2013-09-01

    Existing and emerging viral central nervous system (CNS) infections are major sources of human morbidity and mortality. Treatments of proven efficacy are currently limited predominantly to herpesviruses and human immunodeficiency virus (HIV). Development of new therapies has been hampered by the lack of appropriate animal model systems for some important viruses and by the difficulty in conducting human clinical trials for diseases that may be rare, or in the case of arboviral infections, often have variable seasonal and geographic incidence. Nonetheless, many novel approaches to antiviral therapy are available, including candidate thiazolide and pyrazinecarboxamide derivatives with potential broad-spectrum antiviral efficacy. New herpesvirus drugs include viral helicase-primase and terminase inhibitors. The use of antisense oligonucleotides and other strategies to interfere with viral RNA translation has shown efficacy in experimental models of CNS viral disease. Identifying specific molecular targets within viral replication cycles has led to many existing antiviral agents and will undoubtedly continue to be the basis of future drug design. A promising new area of research involves therapies based on enhanced understanding of host antiviral immune responses. Toll-like receptor agonists and drugs that inhibit specific cytokines as well as interferon preparations have all shown potential therapeutic efficacy. Passive transfer of virus-specific cytotoxic T lymphocytes has been used in humans and may provide an effective therapy for some herpesvirus infections and potentially for progressive multifocal leukoencephalopathy. Humanized monoclonal antibodies directed against specific viral proteins have been developed and in several cases evaluated in humans in settings including West Nile virus and HIV infection and in pre-exposure prophylaxis for rabies. PMID:23913580

  6. The Equine Neonatal Central Nervous System: Development and Diseases.

    PubMed

    Tennent-Brown, Brett S; Morrice, Ashleigh V; Reed, Stephen

    2015-12-01

    Neonatal encephalopathy is the most common neurologic condition affecting newborn foals and shares similarities with perinatal asphyxia syndrome of human infants. In many cases of neonatal encephalopathy there is no obvious episode of acute or chronic hypoxia and other mechanisms likely play a role in the pathogenesis. Increased concentrations of neuroactive progestagens are found in affected foals; whether these molecules are protective, as has been suggested, or play a role in the pathogenesis is unknown. Neurologic diseases other than neonatal encephalopathy affect foals occasionally and should be considered when evaluating sick foals with clinical signs of neurologic dysfunction. PMID:26612749

  7. Central Nervous System Regulation of Brown Adipose Tissue

    PubMed Central

    Morrison, Shaun F.; Madden, Christopher J.

    2015-01-01

    Thermogenesis, the production of heat energy, in brown adipose tissue is a significant component of the homeostatic repertoire to maintain body temperature during the challenge of low environmental temperature in many species from mouse to man and plays a key role in elevating body temperature during the febrile response to infection. The sympathetic neural outflow determining brown adipose tissue (BAT) thermogenesis is regulated by neural networks in the CNS which increase BAT sympathetic nerve activity in response to cutaneous and deep body thermoreceptor signals. Many behavioral states, including wakefulness, immunologic responses, and stress, are characterized by elevations in core body temperature to which central command-driven BAT activation makes a significant contribution. Since energy consumption during BAT thermogenesis involves oxidation of lipid and glucose fuel molecules, the CNS network driving cold-defensive and behavioral state-related BAT activation is strongly influenced by signals reflecting the short and long-term availability of the fuel molecules essential for BAT metabolism and, in turn, the regulation of BAT thermogenesis in response to metabolic signals can contribute to energy balance, regulation of body adipose stores and glucose utilization. This review summarizes our understanding of the functional organization and neurochemical influences within the CNS networks that modulate the level of BAT sympathetic nerve activity to produce the thermoregulatory and metabolic alterations in BAT thermogenesis and BAT energy expenditure that contribute to overall energy homeostasis and the autonomic support of behavior. PMID:25428857

  8. Video Views and Reviews: Neurulation and the Fashioning of the Vertebrate Central Nervous System

    ERIC Educational Resources Information Center

    Watters, Christopher

    2006-01-01

    The central nervous system (CNS) is the first adult organ system to appear during vertebrate development, and the process of its emergence is commonly called neurulation. Such biological "urgency" is perhaps not surprising given the structural and functional complexity of the CNS and the importance of neural function to adaptive behavior and…

  9. A Comparative Study of Successful Central Nervous System Drugs Using Molecular Modeling

    ERIC Educational Resources Information Center

    Kim, Hyosub; Sulaimon, Segun; Menezes, Sandra; Son, Anne; Menezes, Warren J. C.

    2011-01-01

    Molecular modeling is a powerful tool used for three-dimensional visualization and for exploring electrostatic forces involved in drug transport. This tool enhances student understanding of structure-property relationships, as well as actively engaging them in class. Molecular modeling of several central nervous system (CNS) drugs is used to…

  10. T-cell-mediated clearance of mouse hepatitis virus strain JHM from the central nervous system.

    PubMed Central

    Sussman, M A; Shubin, R A; Kyuwa, S; Stohlman, S A

    1989-01-01

    Clearance of the neurotropic JHM strain of mouse hepatitis virus from the central nervous system was examined by the transfer of spleen cells from immunized donors. A T cell with the surface phenotype of Thy1.2+ CD4+ CD8- asialo-GM1+ Mac-1- was found to be necessary for viral clearance. The surface phenotype and adherence to nylon wool suggest that these cells are activated helper-inducer T cells. Adoptive transfer to congenic histocompatibility strains demonstrated the necessity for compatibility at the D locus of the major histocompatibility complex. The expression of the CD4 surface marker and the requirement for major histocompatibility complex class I were further studied by the transfer of cells to recipients treated with anti-CD4 or anti-CD8 monoclonal antibodies. Treatment of recipients with either the anti-CD8 or the anti-CD4 antibodies inhibited virus clearance from the central nervous system. This suggests that the CD4+ cell acts as a helper and that virus is cleared from the central nervous system. This suggests that the CD4+ cell acts as a helper and that virus is cleared from the central nervous system by CD8+ cells that recognize viral antigen in the context of the H-2Db gene product. PMID:2542613

  11. Serotonin-like immunoreactivity in the central nervous system of two Ixodid tick species

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Immunocytochemistry was used to detect the presence of serotonin-like immunoreactive (5HT-IR) neurons and neuronal processes in the central nervous system (CNS), the synganglion, of two Ixodid tick species; the winter tick, Dermacentor albipictus and the lone star tick, Amblyomma americanum. Seroto...

  12. National Training Course. Emergency Medical Technician. Paramedic. Instructor's Lesson Plans. Module VII. Central Nervous System.

    ERIC Educational Resources Information Center

    National Highway Traffic Safety Administration (DOT), Washington, DC.

    This instructor's lesson plan guide on the central nervous system is one of fifteen modules designed for use in the training of emergency medical technicians. Four units of study are presented: (1) anatomy and physiology; (2) assessment of patients with neurological problems; (3) pathophysiology and management of neurological problems; (4)…

  13. Assessment of Visual Acuity in Relation to Central Nervous System Activation in Children with Mental Retardation.

    ERIC Educational Resources Information Center

    Jacobsen, Karl; Grottland, Havar; Flaten, Magne Arve

    2001-01-01

    Assessment of visual acuity, using Teller Acuity Cards, was combined with observations of behavioral state to indicate central nervous system activation in 24 individuals with mental retardation. Results indicate that forced-choice preferential-looking technique can be used to test visual acuity in this population unless the participant is drowsy.…

  14. Analyzing cell fusion events within the central nervous system using bone marrow chimerism.

    PubMed

    Kemp, Kevin; Hares, Kelly

    2015-01-01

    It has emerged that cells which typically reside in the bone marrow have the capacity to cross the blood brain barrier and contribute genetic material to a range of neuronal cell types within the central nervous system. One such mechanism to account for this phenomenon is cellular fusion, occurring between migrating bone marrow-derived stem cells and neuronal cells in-situ. Biologically, the significance as to why cells from distinct lineages fuse with cells of the central nervous system is, as yet, unclear. Growing evidence however suggests that these cell fusion events could provide an efficient means of rescuing the highly complex and differentiated neuronal cell types that cannot be replaced in adulthood. To facilitate further understanding of cell fusion within the central nervous system, we describe here a technique to establish chimeric mice that are stably reconstituted with green fluorescent protein expressing sex-mismatched bone marrow. These chimeric mice are known to represent an excellent model for studying bone marrow cell migration and infiltration throughout the body, while in parallel, as will be described here, also provide a means to neatly analyze both bone marrow-derived cell fusion and trans-differentiation events within the central nervous system. PMID:25947664

  15. Maturation of the Central Nervous System as Related to Communication and Cognitive Development.

    ERIC Educational Resources Information Center

    Hallett, Terry; Proctor, Adele

    1996-01-01

    Major events in the maturation of the central nervous system (CNS) are reviewed relative to milestones for communication, speech, language, and cognition. Early insults to the CNS and their neuropsychological consequences are discussed. The role of patterns of myelination and dendritic branching to evolving stages of language and cognition are…

  16. Primary central nervous system T-cell lymphoma mimicking meningoencephalomyelitis in a cat

    PubMed Central

    Guil-Luna, Silvia; Carrasco, Librado; Gómez-Laguna, Jaime; Hilbe, Monika; Mínguez, Juan J.; Köhler, Kernt; de las Mulas, Juana Martín

    2013-01-01

    A cat was presented with right head tilt and circling. The lack of expression of virus antigens did not support the postmortem diagnosis of encephalomyelitis pointing to a diffuse primary central nervous system T-cell lymphoma on the basis of CD3 and CD45R co-expression with absence of CD79α staining. PMID:24155454

  17. Primary central nervous system T-cell lymphoma mimicking meningoencephalomyelitis in a cat.

    PubMed

    Guil-Luna, Silvia; Carrasco, Librado; Gómez-Laguna, Jaime; Hilbe, Monika; Mínguez, Juan J; Köhler, Kernt; de las Mulas, Juana Martín

    2013-06-01

    A cat was presented with right head tilt and circling. The lack of expression of virus antigens did not support the postmortem diagnosis of encephalomyelitis pointing to a diffuse primary central nervous system T-cell lymphoma on the basis of CD3 and CD45R co-expression with absence of CD79α staining. PMID:24155454

  18. The impact of nandrolone decanoate on the central nervous system.

    PubMed

    Busardò, Francesco P; Frati, Paola; Sanzo, Mariantonia Di; Napoletano, Simona; Pinchi, Enrica; Zaami, Simona; Fineschi, Vittorio

    2015-01-01

    Nandrolone is included in the class II of anabolic androgenic steroids (AAS) which is composed of 19-nor-testosterone-derivates. In general, AAS is a broad and rapidly increasing group of synthetic androgens used both clinically and illicitly. AAS in general and nandrolone decanoate (ND) in particular have been associated with several behavioral disorders. The purpose of this review is to summarize the literature concerning studies dealing with ND exposure on animal models, mostly rats that mimic human abuse systems (i.e. supraphysiological doses). We have focused in particular on researches that have investigated how ND alters the function and expression of neuronal signaling molecules that underlie behavior, anxiety, aggression, learning and memory, reproductive behaviors, locomotion and reward. PMID:26074747

  19. The Impact of Nandrolone Decanoate on the Central Nervous System

    PubMed Central

    Busardò, Francesco P.; Frati, Paola; Sanzo, Mariantonia Di; Napoletano, Simona; Pinchi, Enrica; Zaami, Simona; Fineschi, Vittorio

    2015-01-01

    Nandrolone is included in the class II of anabolic androgenic steroids (AAS) which is composed of 19-nor-testosterone-derivates. In general, AAS is a broad and rapidly increasing group of synthetic androgens used both clinically and illicitly. AAS in general and nandrolone decanoate (ND) in particular have been associated with several behavioral disorders. The purpose of this review is to summarize the literature concerning studies dealing with ND exposure on animal models, mostly rats that mimic human abuse systems (i.e. supraphysiological doses). We have focused in particular on researches that have investigated how ND alters the function and expression of neuronal signaling molecules that underlie behavior, anxiety, aggression, learning and memory, reproductive behaviors, locomotion and reward. PMID:26074747

  20. Medicinal chemical properties of successful central nervous system drugs.

    PubMed

    Pajouhesh, Hassan; Lenz, George R

    2005-10-01

    Fundamental physiochemical features of CNS drugs are related to their ability to penetrate the blood-brain barrier affinity and exhibit CNS activity. Factors relevant to the success of CNS drugs are reviewed. CNS drugs show values of molecular weight, lipophilicity, and hydrogen bond donor and acceptor that in general have a smaller range than general therapeutics. Pharmacokinetic properties can be manipulated by the medicinal chemist to a significant extent. The solubility, permeability, metabolic stability, protein binding, and human ether-ago-go-related gene inhibition of CNS compounds need to be optimized simultaneously with potency, selectivity, and other biological parameters. The balance between optimizing the physiochemical and pharmacokinetic properties to make the best compromises in properties is critical for designing new drugs likely to penetrate the blood brain barrier and affect relevant biological systems. This review is intended as a guide to designing CNS therapeutic agents with better drug-like properties. PMID:16489364

  1. Evaluation of the acute cardiac and central nervous system effects of the fluorocarbon trifluoromethane in baboons

    SciTech Connect

    Branch, C.A.; Goldberg, D.A.; Ewing, J.R.; Butt, S.S.; Gayner, J.; Fagan, S.C.

    1994-12-31

    The gaseous fluorocarbon trifluoromethane has recently been investigated for its potential as an in vivo gaseous indicator for nuclear magnetic resonance studies of brain perfusion. Trifluoromethane may also have significant value as a replacement for chlorofluorocarbon fire retardants. Because of possible species-specific cardiotoxic and anesthetic properties, the toxicological evaluation of trifluoromethane in primates (Papio anubis) is necessary prior to its evaluation in humans. We report the acute cardiac and central nervous system effects of trifluoromethane in eight anesthetized baboons. A dose-response effect was established for respiratory rate, electroencephalogram, and cardiac sinus rate, which exhibited a stepwise decrease from 10% trifluoromethane. No spontaneous arrhythmias were noted, and arterial blood pressure remained unchanged at any inspired level. Intravenous epinephrine infusions (1 {mu}g/kg) induced transient cardiac arrhythmia in 1 animal only at 70% FC-23 (v/v) trifluoromethane. Trifluoromethane appears to induce mild dose-related physiological changes at inspired levels of 30% or more, indicative of an anesthetic effect. These data suggest that trifluoromethane may be safe to use in humans, without significant adverse acute effects, at an inspired level of 30%. 23 refs., 3 figs., 3 tabs.

  2. Disseminated BK type polyomavirus infection in an AIDS patient associated with central nervous system disease.

    PubMed Central

    Vallbracht, A.; Löhler, J.; Gossmann, J.; Glück, T.; Petersen, D.; Gerth, H. J.; Gencic, M.; Dörries, K.

    1993-01-01

    A 27-year-old man with hemophilia type A and acquired immunodeficiency syndrome developed a subacute meningoencephalitis, associated with a normotensive internal hydrocephalus, 14 weeks before his death. From cerebrospinal fluid and brain autopsy material, a virus could be isolated and was classified by Southern blot analysis and restriction endonuclease reactions as the human polyomavirus BK. The postmortem findings of polyomavirus antigen and BK virus DNA in various cell types of the kidneys, lungs, and central nervous system strongly suggest that BK virus was the causative agent of a tubulointerstitial nephropathy, an interstitial desquamative pneumonitis, and a subacute meningoencephalitis with accentuation of the ventricular and meningeal surfaces of the brain. Besides distinctive cytopathic effects, the presence of intranuclear inclusions was a prominent histopathological feature. Therefore, the human polyomavirus BK should be regarded as a new candidate on the still growing list of opportunistic pathogens in acquired immunodeficiency syndrome. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 PMID:8391217

  3. Digesting the emerging role for the gut microbiome in central nervous system demyelination.

    PubMed

    Joscelyn, Jennifer; Kasper, Lloyd H

    2014-10-01

    The fields of microbiology, immunology, neurology and nutrition are rapidly converging, as advanced sequencing and genomics-based methodologies have enabled the mapping out of the microbial diversity of humans for the first time. Bugs, guts, brains and behavior were once believed to be separate domains of clinical practice and research; however, recent observations in our understanding of the microbiome indicate that the boundaries between domains are becoming permeable. This permeability is multidirectional: Biological systems are operating simultaneously in a vastly complex and interconnected web. Understanding the microbiome-gut-brain axis will entail fleshing out the mechanisms by which transduction across each domain occurs, allowing us ultimately to appreciate the role of commensal organisms in shaping and modulating host immunity. This article will highlight animal and human research to date, as well as highlight directions for future research. We speculate that the gut microbiome is potentially the premier environmental risk factor mediating inflammatory central nervous system demyelination, in particular multiple sclerosis. PMID:25070675

  4. Occupational exposure and defects of the central nervous system in offspring: review.

    PubMed Central

    Roeleveld, N; Zielhuis, G A; Gabreëls, F

    1990-01-01

    A study of published work was carried out in a search for evidence of a causal role for parental occupational exposure in the origin of structural and functional defects of the central nervous system (CNS) in children. Studies that consider this topic are scarce and mostly refer to broad categories of exposures and effects. Non-occupational studies referring to environmental exposure of humans and studies on experimental animals were also reviewed. The studies on animals provided straightforward evidence about morphological and behavioural abnormalities resulting from some agents used occupationally. The studies on humans yielded a scala of defects that could be ascribed to exposure to high doses of various agents in the environment. Evidence for a causal role of occupational exposure has not been found, but a highly probable influence on the developing CNS is hypothesised for lead, methyl mercury, and ionising radiation. Parental occupational exposure to cadmium, organic solvents, anaesthetics, and pesticides may also play a part in causing defects of the CNS. Well designed future research is needed to test the above hypotheses. PMID:2207028

  5. Potential role of CYP2D6 in the central nervous system

    PubMed Central

    Cheng, Jie; Zhen, Yueying; Miksys, Sharon; Beyoğlu, Diren; Krausz, Kristopher W.; Tyndale, Rachel F.; Yu, Aiming; Idle, Jeffrey R.; Gonzalez, Frank J.

    2013-01-01

    Cytochrome P450 2D6 (CYP2D6) is a pivotal enzyme responsible for a major human drug oxidation polymorphism in human populations. Distribution of CYP2D6 in brain and its role in serotonin metabolism suggest this CYP2D6 may have a function in central nervous system. To establish an efficient and accurate platform for the study of CYP2D6 in vivo, a transgenic human CYP2D6 (Tg-2D6) model was generated by transgenesis in wild-type C57BL/6 (WT) mice using a P1 phage artificial chromosome clone containing the complete human CYP2D locus, including CYP2D6 gene and 5’- and 3’- flanking sequences. Human CYP2D6 was expressed not only in the liver, but also in brain. The abundance of serotonin and 5-hydroxyindoleacetic acid in brain of Tg-2D6 is higher than in WT mice either basal levels or after harmaline induction. Metabolomics of brain homogenate and cerebrospinal fluid revealed a significant up-regulation of l-carnitine, acetyl-l-carnitine, pantothenic acid, dCDP, anandamide, N-acetylglucosaminylamine, and a down-regulation of stearoyl-l-carnitine in Tg-2D6 mice compared with WT mice. Anxiety tests indicate Tg-2D6 mice have a higher capability to adapt to anxiety. Overall, these findings indicate that the Tg-2D6 mouse model may serve as a valuable in vivo tool to determine CYP2D6-involved neurophysiological metabolism and function. PMID:23614566

  6. [Brain temperature in patients with central nervous system lesions].

    PubMed

    Mariak, Z; Lysoń, T; Piekarski, P; Lewko, J; Jadeszko, M; Szydlik, P

    2000-01-01

    The knowledge of human brain temperature is still very limited. In this report we investigated the relationship between brain and trunk temperature in neurosurgical patients during normothermia and fever. Another problem addressed was that of possible gradients of temperature within the brain. We carried out direct recordings of temperature in 63 operated, neurosurgical patients with a variety of intracranial pathologies. Flexible, teflon-coated thermocouples were placed intracranially during neurosurgical procedures. Oesophageal, rectal and tympanic temperatures were also monitored. An error of up to 1.3 degrees C is to be expected in single cases if brain temperature is deduced from the rectal or oesophageal temperature. Mean differences between brain temperature and core body temperature measured in the rectum or in the oesophagus, were between 0 to 0.3 degree C. Tympanic temperature (Tty) improved the approximation of brain temperature (Tbr) to within the mean difference between Tbr-Tty close to 0 degree C. Nevertheless Tty also differed from Tbr by as much as 1 degree C in single cases. Brain temperature was the highest body temperature measured, either in normothermia or in fever. Temperature gradients were proved to exist between the warmer brain interior and cooler surface, with maximal differences in temperature reaching 0.6 degree C. This temperature gradient tended to increase along with the rise in intracranial pressure and deterioration of the level of consciousness. Our results suggest that conclusions regarding brain temperature drawn on the basis of other core temperatures, may lead to significant errors, and intracranial temperature measurement is desirable in neurosurgical intensive care. Temperature gradients within the brain may exacerbate its biochemical injury during ischaemia and fever--a combination seen frequently in neurosurgical patients. This may be particularly so, since brain temperature in fever is the highest body temperature in a

  7. Enzyme replacement improves ataxic gait and central nervous system histopathology in a mouse model of metachromatic leukodystrophy.

    PubMed

    Matzner, Ulrich; Lüllmann-Rauch, Renate; Stroobants, Stijn; Andersson, Claes; Weigelt, Cecilia; Eistrup, Carl; Fogh, Jens; D'Hooge, Rudi; Gieselmann, Volkmar

    2009-04-01

    Inherited deficiencies of lysosomal hydrolases cause lysosomal storage diseases (LSDs) that are characterized by a progressive multisystemic pathology and premature death. Repeated intravenous injection of the active counterpart of the deficient enzyme, a treatment strategy called enzyme replacement therapy (ERT), evolved as a clinical option for several LSDs without central nervous system (CNS) involvement. To assess the efficacy of long-term ERT in metachromatic leukodystrophy (MLD), an LSD with prevailing nervous system disease, we treated immunotolerant arylsulfatase A (ASA) knockout mice with 52 doses of either 4 or 50 mg/kg recombinant human ASA (rhASA). ERT was tolerated without side effects and improved disease manifestations in a dose-dependent manner. Dosing of 4 mg/kg diminished sulfatide storage in kidney and peripheral nervous system (PNS) but not the CNS, whereas treatment with 50 mg/kg was also effective in the CNS in reducing storage in brain and spinal cord by 34 and 45%, respectively. Histological analyses revealed regional differences in sulfatide clearance. While 70% less storage profiles were detectable, for example, in the hippocampal fimbria, the histopathology of the brain stem was unchanged. Both enzyme doses normalized the ataxic gait of ASA knockout mice, demonstrating prevention of nervous system dysfunctions that dominate early stages of MLD. PMID:19174759

  8. Enzyme Replacement Improves Ataxic Gait and Central Nervous System Histopathology in a Mouse Model of Metachromatic Leukodystrophy

    PubMed Central

    Matzner, Ulrich; Lüllmann-Rauch, Renate; Stroobants, Stijn; Andersson, Claes; Weigelt, Cecilia; Eistrup, Carl; Fogh, Jens; D'Hooge, Rudi; Gieselmann, Volkmar

    2009-01-01

    Inherited deficiencies of lysosomal hydrolases cause lysosomal storage diseases (LSDs) that are characterized by a progressive multisystemic pathology and premature death. Repeated intravenous injection of the active counterpart of the deficient enzyme, a treatment strategy called enzyme replacement therapy (ERT), evolved as a clinical option for several LSDs without central nervous system (CNS) involvement. To assess the efficacy of long-term ERT in metachromatic leukodystrophy (MLD), an LSD with prevailing nervous system disease, we treated immunotolerant arylsulfatase A (ASA) knockout mice with 52 doses of either 4 or 50 mg/kg recombinant human ASA (rhASA). ERT was tolerated without side effects and improved disease manifestations in a dose-dependent manner. Dosing of 4 mg/kg diminished sulfatide storage in kidney and peripheral nervous system (PNS) but not the CNS, whereas treatment with 50 mg/kg was also effective in the CNS in reducing storage in brain and spinal cord by 34 and 45%, respectively. Histological analyses revealed regional differences in sulfatide clearance. While 70% less storage profiles were detectable, for example, in the hippocampal fimbria, the histopathology of the brain stem was unchanged. Both enzyme doses normalized the ataxic gait of ASA knockout mice, demonstrating prevention of nervous system dysfunctions that dominate early stages of MLD. PMID:19174759

  9. Remyelination of the central nervous system: a valuable contribution from the periphery.

    PubMed

    Zujovic, Violetta; Bachelin, Corinne; Baron-Van Evercooren, Anne

    2007-08-01

    The loss of myelin, a major element involved in the saltatory conduction of the electrical impulse of the nervous system, is a major target of current research. Serious long-term disabilities are observed in patients with demyelinating disease of the central nervous system, such as multiple sclerosis. New therapeutic strategies aimed at overcoming myelin damage and axonal loss focus on the repair potential of myelin-forming cells. This review examines the use of peripheral myelin-forming cells, the Schwann cells, to promote myelin repair. PMID:17644768

  10. [Molecular genetics of familial tumour syndromes of the central nervous system].

    PubMed

    Murnyák, Balázs; Szepesi, Rita; Hortobágyi, Tibor

    2015-02-01

    Although most of the central nervous system tumours are sporadic, rarely they are associated with familial tumour syndromes. These disorders usually present with an autosomal dominant inheritance and neoplasia develops at younger age than in sporadic cases. Most of these tumours are bilateral, multiplex or multifocal. The causative mutations occur in genes involved in cell cycle regulation, cell growth, differentiation and DNA repair. Studying these hereditary cancer predisposition syndromes associated with nervous system tumours can facilitate the deeper understanding of the molecular background of sporadic tumours and the development of novel therapeutic agents. This review is an update on hereditary tumour syndromes with nervous system involvement with emphasis on molecular genetic characteristics and their clinical implications. PMID:25618858

  11. Swift onset of central nervous system depression and asystole followingan overdose of Guaifenesin.

    PubMed

    Okic, Merisa; Johnson, Tom; Crifasi, Joseph A; Long, Christopher; Mitchell, Erik K

    2013-06-01

    Guaifenesin is an over-the-counter expectorant used for chest congestion and is available both in single-ingredient formulations and in combination with antihistamines, cough suppressants and decongestants. The documented side-effects of guaifenesin are generally mild. We present the case of a 23-year-old female who committed suicide by ingestion of guaifenesin along with small amounts of cetirizine, ethanol and sertraline. Approximately 2 h after ingestion, the patient experienced central nervous system depression followed by asystole. No anatomic cause of death could be determined at autopsy. The initial toxicology detected only ethanol, which was found at a concentration insufficient to cause death. Upon further analysis, guaifenesin was detected in femoral blood at 25.0 μg/mL, urine at >50.0 μg/mL, vitreous fluid at 9.2 μg/mL, brain at 17.0 μg/g and liver at 25.0 μg/g. This is the first reported human case that can be considered a death to which guaifenesin was the significant pharmacologic contributor. Guaifenesin is not detected by the primary screening methods employed by some labs and may be missed in toxicological analyses of overdoses unless specifically suspected. PMID:23580607

  12. Rapid Nipah virus entry into the central nervous system of hamsters via the olfactory route.

    PubMed

    Munster, Vincent J; Prescott, Joseph B; Bushmaker, Trenton; Long, Dan; Rosenke, Rebecca; Thomas, Tina; Scott, Dana; Fischer, Elizabeth R; Feldmann, Heinz; de Wit, Emmie

    2012-01-01

    Encephalitis is a hallmark of Nipah virus (NiV) infection in humans. The exact route of entry of NiV into the central nervous system (CNS) is unknown. Here, we performed a spatio-temporal analysis of NiV entry into the CNS of hamsters. NiV initially predominantly targeted the olfactory epithelium in the nasal turbinates. From there, NiV infected neurons were visible extending through the cribriform plate into the olfactory bulb, providing direct evidence of rapid CNS entry. Subsequently, NiV disseminated to the olfactory tubercle and throughout the ventral cortex. Transmission electron microscopy on brain tissue showed extravasation of plasma cells, neuronal degeneration and nucleocapsid inclusions in affected tissue and axons, providing further evidence for axonal transport of NiV. NiV entry into the CNS coincided with the occurrence of respiratory disease, suggesting that the initial entry of NiV into the CNS occurs simultaneously with, rather than as a result of, systemic virus replication. PMID:23071900

  13. Biomarkers of Central Nervous System Inflammation in Infantile and Juvenile Gangliosidoses

    PubMed Central

    Utz, Jeanine R.; Crutcher, Thomas; Schneider, Joseph; Sorgen, Patrick; Whitley, Chester B.

    2015-01-01

    Background The gangliosidoses (Tay-Sachs disease, Sandhoff disease and GM1-gangliosidosis) are progressive neurodegenerative diseases caused by lysosomal enzyme activity deficiencies and consequent accumulation of gangliosides in the central nervous system (CNS). The infantile forms are distinguished from the juvenile forms by age of onset, rate of disease progression and age of death. There are no approved treatments for the gangliosidoses. In search of potential biomarkers of disease, we quantified 188 analytes in CSF and serum from living human patients with longitudinal (serial) measurements. Notably, several associated with inflammation were elevated in the CSF of infantile gangliosidosis patients, and less so in more slowly progressing forms of juvenile gangliosidosis, but not in MPS disease. Thirteen CSF and two serum biomarker candidates were identified. Five candidate biomarkers were distinguished by persistent elevation in the CSF of patients with the severe infantile phenotype: ENA-78, MCP-1, MIP-1α, MIP-1β, TNFR2. Correspondence of abnormal elevation with other variables of disease --- i.e., severity of clinical phenotype, differentiation from changes in serum, and lack of abnormality in other neurodegenerative lysosomal diseases ---identifies these analytes as biomarkers of neuropathology specific to the gangliosidosis diseases. PMID:25557439

  14. Central Nervous Insulin Signaling in Sleep-Associated Memory Formation and Neuroendocrine Regulation

    PubMed Central

    Feld, Gordon B; Wilhem, Ines; Benedict, Christian; Rüdel, Benjamin; Klameth, Corinna; Born, Jan; Hallschmid, Manfred

    2016-01-01

    The neurochemical underpinnings of sleep's contribution to the establishment and maintenance of memory traces are largely unexplored. Considering that intranasal insulin administration to the CNS improves memory functions in healthy and memory-impaired humans, we tested whether brain insulin signaling and sleep interact to enhance memory consolidation in healthy participants. We investigated the effect of intranasal insulin on sleep-associated neurophysiological and neuroendocrine parameters and memory consolidation in 16 men and 16 women (aged 18–30 years), who learned a declarative word-pair task and a procedural finger sequence tapping task in the evening before intranasal insulin (160 IU) or placebo administration and 8 h of nocturnal sleep. On the subsequent evening, they learned interfering word-pairs and a new finger sequence before retrieving the original memories. Insulin increased growth hormone concentrations in the first night-half and EEG delta power during the second 90 min of non-rapid-eye-movement sleep. Insulin treatment impaired the acquisition of new contents in both the declarative and procedural memory systems on the next day, whereas retrieval of original memories was unchanged. Results indicate that sleep-associated memory consolidation is not a primary mediator of insulin's acute memory-improving effect, but that the peptide acts on mechanisms that diminish the subsequent encoding of novel information. Thus, by inhibiting processes of active forgetting during sleep, central nervous insulin might reduce the interfering influence of encoding new information. PMID:26448203

  15. Rapid Nipah virus entry into the central nervous system of hamsters via the olfactory route

    PubMed Central

    Munster, Vincent J.; Prescott, Joseph B.; Bushmaker, Trenton; Long, Dan; Rosenke, Rebecca; Thomas, Tina; Scott, Dana; Fischer, Elizabeth R.; Feldmann, Heinz; de Wit, Emmie

    2012-01-01

    Encephalitis is a hallmark of Nipah virus (NiV) infection in humans. The exact route of entry of NiV into the central nervous system (CNS) is unknown. Here, we performed a spatio-temporal analysis of NiV entry into the CNS of hamsters. NiV initially predominantly targeted the olfactory epithelium in the nasal turbinates. From there, NiV infected neurons were visible extending through the cribriform plate into the olfactory bulb, providing direct evidence of rapid CNS entry. Subsequently, NiV disseminated to the olfactory tubercle and throughout the ventral cortex. Transmission electron microscopy on brain tissue showed extravasation of plasma cells, neuronal degeneration and nucleocapsid inclusions in affected tissue and axons, providing further evidence for axonal transport of NiV. NiV entry into the CNS coincided with the occurrence of respiratory disease, suggesting that the initial entry of NiV into the CNS occurs simultaneously with, rather than as a result of, systemic virus replication. PMID:23071900

  16. Management of central nervous system germinoma: proposal for a modern strategy.

    PubMed

    Shibamoto, Yuta

    2009-01-01

    With the development of diagnostic, radiologic, and therapeutic modalities, strategies for management of central nervous system (CNS) germinoma are changing gradually. The author advocates that typical germinomas can be diagnosed based on their typical clinical and radiological findings, together with slight elevation of beta-human chorionic gonadotropin levels in the serum and/or cerebrospinal fluid (CSF) and quick response to radiation or chemotherapy. Radiation therapy has been the standard treatment for CNS germinoma until recently. Germinomas 4 cm or less in diameter can be cured with radiation doses of 40-45 Gy. Regarding the treatment volume, an individualized approach is recommended and a focal radiation field covering at least major parts of the ventricular system is recommended if no CSF dissemination is present and CSF cytology is negative. Such irradiation is best given by intensity-modulated radiation therapy. Systemic chemotherapy with reduced doses (24-30 Gy) of radiation has to some extent been successful, but longer follow-up periods are necessary to draw conclusions regarding the superiority of this treatment over standard-dose radiation therapy. CNS germinoma patients should be completely cured with minimum morbidity, probably by employing appropriate doses of chemotherapy and intensity-modulated radiation therapy in the future. PMID:19329866

  17. Selective and antigen-dependent effects of myelin degeneration on central nervous system inflammation.

    PubMed

    Aboul-Enein, Fahmy; Bauer, Jan; Klein, Matthias; Schubart, Anna; Flügel, Alexander; Ritter, Thomas; Kawakami, Naoto; Siedler, Frank; Linington, Christopher; Wekerle, Hartmut; Lassmann, Hans; Bradl, Monika

    2004-12-01

    Damage to myelin sheath or oligodendrocytes may precede or even provoke inflammation of the central nervous system (CNS), but the extent to which these degenerative changes affect inflammation remains largely undefined. To study these processes in more detail, we used CNS antigen-specific T cells in the presence or absence of anti-myelin antibodies to induce experimental autoimmune encephalomyelitis (EAE) in transgenic Lewis rats with low-grade subclinical myelin degeneration and associated microglia cell activation, and in wild-type Lewis rats with an intact CNS. We found that myelin degeneration affects the localization of inflammatory lesions, the numbers of T cells recruited to these lesions, and the severity of the resulting clinical disease. In addition, myelin degeneration and associated microglia cell activation jointly enhance the susceptibility of the CNS to the action of anti-myelin antibodies. Our data show that even subtle alterations of myelin and oligodendrocytes may massively amplify the extent of demyelination and tissue damage, involving different immune effector mechanisms. A similar causal relationship might also operate in human patients with multiple sclerosis, where T cell-mediated inflammation and antibody-mediated demyelination have been documented, and where genetic factors might determine the susceptibility of the target tissue for immune-mediated injury. PMID:15624765

  18. The innate immune response in the central nervous system and its role in glioma immune surveillance.

    PubMed

    Friese, M A; Steinle, A; Weller, M

    2004-10-01

    The innate immune system encompasses natural killer (NK) cells, macrophages and granulocytes, the complement system and antimicrobial peptides. Recognition pathways of the innate immune system include microbial non-self recognition, missing-self recognition and induced- self recognition. The central nervous system (CNS) participates in responses of the innate immune system. However, immune inhibitory and anti-inflammatory mechanisms physiologically outbalance and counteract immune activity and thereby limit immune-mediated tissue damage in the brain. Human gliomas appear to take advantage of this immunosuppressive milieu. Moreover, glioma cells themselves interfere with anti-tumor immune responses by expressing immune inhibitory cell surface molecules, such as HLA-G, or by releasing soluble immunosuppressants such as transforming growth factor (TGF)-beta. Yet, although glioma cells exhibit all cellular features of malignancy, these tumors very rarely metastasize outside the brain, raising the possibility of immune-mediated control of these cells outside, but not inside, the brain. Accordingly, activating the innate immune system by forcing glioma cells to express danger signals such as NKG2D ligands is a promising strategy of immunotherapy for these tumors. PMID:15585981

  19. Autoradiographic localization of thyrotropin releasing hormone (TRH) receptors in the central nervous system

    SciTech Connect

    Manaker, S.

    1985-01-01

    Quantitative autoradiography was used to examine the distribution of thyrotropin-releasing hormone (TRH) receptors in the rat and human central nervous system (CNS). The binding of (/sup 3/H)-3-methyl-histidine/sup 2/-TRH ((/sup 3/H)-MeTRH) to TRH receptors was saturable, of a high affinity (K/sub d/ = 5 nM), and specific for TRH analogs. Studies with neurotoxins ibotenic acid and 6-hydroxydopamine (6-OHDA) suggest that TRH receptors within the amygdala are predominantly located on cell bodies, and not nerve terminals. Finally, an examination was made of the concentrations of TRH receptors in spinal cords of patients with amyotrophic lateral sclerosis (ALS), a degenerative disease of the motor neurons located in Lamina IX. Large decreases in TRH receptors were noted in ALS spinal cords, when compared to non-neurological controls, probably reflecting the loss of motor neurons. In addition, decreases in the TRH receptor concentration of Lamina II were observed. This finding may reflect the sensitivity of neurons throughout the CNS to the pathophysiologic mechanisms of neuronal degeneration which cause ALS.

  20. AAV9-mediated central nervous system–targeted gene delivery via cisterna magna route in mice

    PubMed Central

    Lukashchuk, Vera; Lewis, Katherine E; Coldicott, Ian; Grierson, Andrew J; Azzouz, Mimoun

    2016-01-01

    Current barriers to the use of adeno-associated virus serotype 9 (AAV9) in clinical trials for treating neurological disorders are its high expression in many off-target tissues such as liver and heart, and lack of cell specificity within the central nervous system (CNS) when using ubiquitous promoters such as human cytomegalovirus (CMV) or chicken-β-actin hybrid (CAG). To enhance targeting the transgene expression in CNS cells, self-complementary (sc) AAV9 vectors, scAAV9-GFP vectors carrying neuronal Hb9 and synapsin 1, and nonspecific CMV and CAG promoters were constructed. We demonstrate that synapsin 1 and Hb9 promoters exclusively targeted neurons in vitro, although their strengths were up to 10-fold lower than that of CMV. In vivo analyses of mouse tissue after scAAV9-GFP vector delivery via the cisterna magna revealed a significant advantage of synapsin 1 promoter over both Hb9 variants in targeting neurons throughout the brain, since Hb9 promoters were driving gene expression mainly within the motor-related areas of the brain stem. In summary, this study demonstrates that cisterna magna administration is a safe alternative to intracranial or intracerebroventricular vector delivery route using scAAV9, and introduces a novel utility of the Hb9 promoter for the targeted gene expression for both in vivo and in vitro applications. PMID:26942208

  1. Quantitative autoradiography of TRH receptors and radioimmunoassay of TRH in the cat central nervous system

    SciTech Connect

    Bogin, R.M.; Kreider, M.S.; Caine, S.B.; Pack, A.I.; Winokur, A.

    1986-03-05

    In the cat, microinjection of Thyrotropin-Releasing Hormone (TRH) into certain areas of the central nervous system (CNS) changes ventilation and cardiovascular variables. To initiate a more systematic investigation of these effects, they undertook a study to determine the location of TRH and its receptors in the cat CNS. Using techniques previously described from the laboratory, quantitative autoradiograms for TRH receptors of the cat brain were produced; additional specimens were dissected, and radioimmunoassay for TRH was performed. Heterogeneous distribution of receptors was observed in the cat brain. In the forebrain, large quantities of TRH receptors were found in amygdala, hippocampus, claustrum, pyriform nucleus, and tuberculum olfactorium. In the brainstem, high concentrations were localized to the dorsal motor nucleus of the vagus, the hypoglossal nucleus, and the periaqueductal grey. The cerebellum contained few receptors. The largest quantities of the TRH tripeptide were noted in the hypothalamus and septum, with substantial amounts also obtained from the olfactory bulb, corpus striatum, and thalamus. The results demonstrate that the distribution of TRH and TRH receptors in the cat brain is very similar to that previously described in the rat and human brain. They provide a basis for exploring the physiological and pharmacological effects of TRH in cats.

  2. Jet Fuel, Noise, and the Central Auditory Nervous System: A Literature Review.

    PubMed

    Warner, Rachelle; Fuente, Adrian; Hickson, Louise

    2015-09-01

    Prompted by the continued prevalence of hearing related disabilities accepted as eligible for compensation and treatment under Australian Department of Veterans' Affairs legislation, a review of recent literature regarding possible causation mechanisms and thus, possible prevention strategies, is timely. The emerging thoughts on the effects of a combination of jet fuel and noise exposure on the central auditory nervous system (CANS) have relevance in the military aviation context because of the high exposures to solvents (including fuels) and unique noise hazards related to weapons systems and military aircraft. This literature review aimed to identify and analyze the current knowledge base of the effects of combined exposure to JP-8 jet fuel (or its aromatic solvent components) and noise on the CANS in human populations. We reviewed articles examining electrophysiological and behavioral measurement of the CANS following combined exposures to jet fuel (or its aromatic constituents) and noise. A total of 6 articles met the inclusion criteria for the review and their results are summarized. The articles considered in this review indicate that assessment of the CANS should be undertaken as part of a comprehensive test battery for military members exposed to both noise and solvents in the workplace. PMID:26327546

  3. Central Nervous Insulin Signaling in Sleep-Associated Memory Formation and Neuroendocrine Regulation.

    PubMed

    Feld, Gordon B; Wilhem, Ines; Benedict, Christian; Rüdel, Benjamin; Klameth, Corinna; Born, Jan; Hallschmid, Manfred

    2016-05-01

    The neurochemical underpinnings of sleep's contribution to the establishment and maintenance of memory traces are largely unexplored. Considering that intranasal insulin administration to the CNS improves memory functions in healthy and memory-impaired humans, we tested whether brain insulin signaling and sleep interact to enhance memory consolidation in healthy participants. We investigated the effect of intranasal insulin on sleep-associated neurophysiological and neuroendocrine parameters and memory consolidation in 16 men and 16 women (aged 18-30 years), who learned a declarative word-pair task and a procedural finger sequence tapping task in the evening before intranasal insulin (160 IU) or placebo administration and 8 h of nocturnal sleep. On the subsequent evening, they learned interfering word-pairs and a new finger sequence before retrieving the original memories. Insulin increased growth hormone concentrations in the first night-half and EEG delta power during the second 90 min of non-rapid-eye-movement sleep. Insulin treatment impaired the acquisition of new contents in both the declarative and procedural memory systems on the next day, whereas retrieval of original memories was unchanged. Results indicate that sleep-associated memory consolidation is not a primary mediator of insulin's acute memory-improving effect, but that the peptide acts on mechanisms that diminish the subsequent encoding of novel information. Thus, by inhibiting processes of active forgetting during sleep, central nervous insulin might reduce the interfering influence of encoding new information. PMID:26448203

  4. Current Understanding of Circulating Tumor Cells – Potential Value in Malignancies of the Central Nervous System

    PubMed Central

    Adamczyk, Lukasz A.; Williams, Hannah; Frankow, Aleksandra; Ellis, Hayley Patricia; Haynes, Harry R.; Perks, Claire; Holly, Jeff M. P.; Kurian, Kathreena M.

    2015-01-01

    Detection of circulating tumor cells (CTCs) in the blood via so-called “liquid biopsies” carries enormous clinical potential in malignancies of the central nervous system (CNS) because of the potential to follow disease evolution with a blood test, without the need for repeat neurosurgical procedures with their inherent risk of patient morbidity. To date, studies in non-CNS malignancies, particularly in breast cancer, show increasing reproducibility of detection methods for these rare tumor cells in the circulation. However, no method has yet received full recommendation to use in clinical practice, in part because of lack of a sufficient evidence base regarding clinical utility. In CNS malignancies, one of the main challenges is finding a suitable biomarker for identification of these cells, because automated systems, such as the widely used Cell Search system, are reliant on markers, such as the epithelial cell adhesion molecule, which are not present in CNS tumors. This review examines methods for CTC enrichment and detection, and reviews the progress in non-CNS tumors and the potential for using this technique in human brain tumors. PMID:26322014

  5. Maladaptive change of body representation in the brain after damage to central or peripheral nervous system.

    PubMed

    Oouchida, Yutaka; Sudo, Tamami; Inamura, Tetsunari; Tanaka, Naofumi; Ohki, Yukari; Izumi, Shin-Ichi

    2016-03-01

    Our brain has great flexibility to cope with various changes in the environment. Use-dependent plasticity, a kind of functional plasticity, plays the most important role in this ability to cope. For example, the functional recovery of paretic limb motor movement during post-stroke rehabilitation depends mainly on how much it is used. Patients with hemiparesis, however, tend to gradually disuse the paretic limb because of its motor impairment. Decreased use of the paretic hand then leads to further functional decline brought by use-dependent plasticity. To break this negative loop, body representation, which is the conscious and unconscious information regarding body state stored in the brain, is key for using the paretic limb because it plays an important role in selecting an effector while a motor program is generated. In an attempt to understand body representation in the brain, we reviewed animal and human literature mainly on the alterations of the sensory maps in the primary somatosensory cortex corresponding to the changes in limb usage caused by peripheral or central nervous system damage. PMID:26748075

  6. Antiviral Type I and Type III Interferon Responses in the Central Nervous System

    PubMed Central

    Sorgeloos, Frédéric; Kreit, Marguerite; Hermant, Pascale; Lardinois, Cécile; Michiels, Thomas

    2013-01-01

    The central nervous system (CNS) harbors highly differentiated cells, such as neurons that are essential to coordinate the functions of complex organisms. This organ is partly protected by the blood-brain barrier (BBB) from toxic substances and pathogens carried in the bloodstream. Yet, neurotropic viruses can reach the CNS either by crossing the BBB after viremia, or by exploiting motile infected cells as Trojan horses, or by using axonal transport. Type I and type III interferons (IFNs) are cytokines that are critical to control early steps of viral infections. Deficiencies in the IFN pathway have been associated with fatal viral encephalitis both in humans and mice. Therefore, the IFN system provides an essential protection of the CNS against viral infections. Yet, basal activity of the IFN system appears to be low within the CNS, likely owing to the toxicity of IFN to this organ. Moreover, after viral infection, neurons and oligodendrocytes were reported to be relatively poor IFN producers and appear to keep some susceptibility to neurotropic viruses, even in the presence of IFN. This review addresses some trends and recent developments concerning the role of type I and type III IFNs in: i) preventing neuroinvasion and infection of CNS cells; ii) the identity of IFN-producing cells in the CNS; iii) the antiviral activity of ISGs; and iv) the activity of viral proteins of neurotropic viruses that target the IFN pathway. PMID:23503326

  7. 3-Hydroxykynurenine: an intriguing molecule exerting dual actions in the central nervous system.

    PubMed

    Colín-González, Ana Laura; Maldonado, Perla D; Santamaría, Abel

    2013-01-01

    Kynurenine pathway is gaining attention due to the many metabolic processes in which it has been involved. The tryptophan conversion into several other metabolites through this pathway provides neuronal and redox modulators useful for maintenance of major functions in the brain. However, when physiopathological conditions prevail - i.e. oxidative stress, excitotoxicity, and inflammation - preferential formation and accumulation of toxic metabolites could trigger factors for degeneration in neurological disorders. 3-Hydroxykynurenine has been largely described as one of these toxic metabolites capable of inducing oxidative damage and cell death; consequently, this metabolite has been hypothesized to play a pivotal role in different neurological and psychiatric disorders. Supporting evidence has shown altered 3-hydroxykynurenine levels in samples of patients from several disorders. In contrast, some experimental studies have provided evidence of antioxidant and scavenging properties inherent to this molecule. In this review, we explored most of literature favoring one or the other concept, in order to provide an accurate vision on the real participation of this tryptophan metabolite in both experimental paradigms and human brain pathologies. Through this collected evidence, we provide an integrative hypothesis on how 3-hydroxykynurenine is exerting its dual actions in the central nervous system and what will be the course of investigations in this field for the next years. PMID:23219925

  8. Activity of T-DM1 in HER-2 positive central nervous system breast cancer metastases

    PubMed Central

    Torres, Sofia; Maralani, Pejman; Verma, Sunil

    2014-01-01

    A 55-year-old woman with metastatic human epidermal growth factor receptor 2 (HER-2) positive breast cancer (BC) to the lungs and bones was diagnosed with central nervous system (CNS) metastases in November 2011. The MRI showed a right parietal lobe mass with adjacent leptomeningeal disease and several small bilateral cerebellar metastases. She was treated with whole brain irradiation (WBI), followed by capecitabine and lapatinib (December 2011-March 2013) and trastuzumab and lapatinib (May 2013-August 2013). Then, the brain MRI showed progression. In the absence of significant neurological symptoms, we postponed WBI and closely monitored for the development of neurological symptoms. Systemic treatment with trastuzumab emtansine (T-DM1), an antibody-drug conjugate composed of the cytotoxic agent DM1 conjugated to trastuzumab, was initiated in September 2013 to control systemic disease. Unexpectedly, after two cycles of treatment the brain MRI showed a decrease in size of CNS metastases. This case report suggests possible activity of T-DM1 in HER-2 positive BC with CNS metastases. PMID:25123575

  9. Non-paraneoplastic limbic encephalitis and central nervous HHV-6B reactivation: Causality or coincidence?

    PubMed

    Niehusmann, Pitt; Widman, Guido; Eis-Hübinger, Anna M; Greschus, Susanne; Robens, Barbara K; Grote, Alexander; Becker, Albert J

    2016-08-01

    Autoantibody-related encephalopathies represent an important differential diagnosis in adult onset epilepsy. Here, we report the case of a 25-year-old patient with new-onset epilepsy and psychotic syndrome, who underwent biopsy resection for etiological classification. MRI analysis and neuropathological examination showed a T-lymphocytic dominated encephalitis with involvement of the limbic system. An indirect immunohistochemistry approach identified autoantibodies against glutamic acid decarboxylase (GAD) in cerebral spinal fluid and serum, which were confirmed by affinity purification / mass spectrometry analysis. Further examinations revealed evidence of chromosomally integrated human herpes virus type 6B (HHV-6B). However, astrocytic expression of HHV-6 lytic protein was detected by double immunofluorescence analysis. The cerebral expression of HHV-6 antigen, a clinical improvement under antiviral therapy as well as an initial finding of HHV-6 IgM antibodies strongly argue for an additional active HHV-6B infection. Review of the literature reveals singular reports of patients with GAD antibody-positive limbic encephalitis and central nervous system infections with HHV-6B. Since herpes simplex virus encephalitis has been recently reported as a trigger of N-methyl-D-aspartate receptor antibody encephalitis, it is tempting to speculate that HHV-6B infections may trigger a non-paraneoplastic form of limbic encephalitis in a parallel cascade. PMID:27431532

  10. Expression of a Drosophila melanogaster acetylcholine receptor-related gene in the central nervous system

    SciTech Connect

    Wadsworth, S.C.; Rosenthal, L.S.; Kammermeyer, K.L.; Potter, M.B.; Nelson, D.J.

    1988-02-01

    The authors isolated Drosophila melanogaster genomic sequences with nucleotide and amino acid sequence homology to subunits of vertebrate acetylcholine receptor by hybridization with a Torpedo acetylcholine receptor subunit cDNA probe. Five introns are present in the portion of the Drosophila gene encoding the unprocessed protein and are positionally conserved relative to the human acetylcholine receptor alpha-subunit gene. The Drosophila genomic clone hybridized to salivary gland polytene chromosome 3L within region 64B and was termed AChR64B. A 3-kilobasae poly(A)-containing transcript complementary to the AChR64B clone was readily detectable by RNA blot hybridizations during midembryogenesis, during metamorphosis, and in newly enclosed adults. AChR64B transcripts were localized to the cellular regions of the central nervous system during embryonic, larval, pupal, and adult stages of development. During metamorphosis, a temporal relationship between the morphogenesis of the optic lobe and expression of AChR64B transcripts was observed.

  11. Pulmonary, Gonadal, and Central Nervous System Status after Bone Marrow Transplantation for Sickle Cell Disease

    PubMed Central

    Walters, Mark C.; Hardy, Karen; Edwards, Sandie; Adamkiewicz, Thomas; Barkovich, James; Bernaudin, Francoise; Buchanan, George R.; Bunin, Nancy; Dickerhoff, Roswitha; Giller, Roger; Haut, Paul R.; Horan, John; Hsu, Lewis L.; Kamani, Naynesh; Levine, John E.; Margolis, David; Ohene-Frempong, Kwaku; Patience, Melinda; Redding-Lallinger, Rupa; Roberts, Irene A. G.; Rogers, Zora R.; Sanders, Jean E.; Scott, J. Paul; Sullivan, Keith M.

    2010-01-01

    We conducted a prospective, multicenter investigation of human-leukocyte antigen (HLA) identical sibling bone marrow transplantation (BMT) in children with severe sickle cell disease (SCD) between 1991 and 2000. To determine if children were protected from complications of SCD after successful BMT, we extended our initial study of BMT for SCD to conduct assessments of the central nervous system (CNS) and of pulmonary function 2 or more years after transplantation. In addition, the impact on gonadal function was studied. After BMT, patients with stroke who had stable engraftment of donor cells experienced no subsequent stroke events after BMT, and brain magnetic resonance imaging (MRI) exams demonstrated stable or improved appearance. However, 2 patients with graft rejection had a second stroke after BMT. After transplantation, most patients also had unchanged or improved pulmonary function. Among the 11 patients who had restrictive lung changes at baseline, 5 were improved and 6 had persistent restrictive disease after BMT. Of the 2 patients who had obstructive changes at baseline, 1 improved and 1 had worsened obstructive disease after BMT. There was, however, significant gonadal toxicity after BMT, particularly among female recipients. In summary, individuals who had stable donor engraftment did not experience sickle-related complications after BMT, and were protected from progressive CNS and pulmonary disease. PMID:19822218

  12. Opposing Roles of Interferon-Gamma on Cells of the Central Nervous System in Autoimmune Neuroinflammation

    PubMed Central

    Ottum, Payton A.; Arellano, Gabriel; Reyes, Lilian I.; Iruretagoyena, Mirentxu; Naves, Rodrigo

    2015-01-01

    Multiple sclerosis (MS) is the principal cause of autoimmune neuroinflammation in humans, and its animal model, experimental autoimmune encephalomyelitis (EAE), is widely used to gain insight about their immunopathological mechanisms for and the development of novel therapies for MS. Most studies on the role of interferon (IFN)-γ in the pathogenesis and progression of EAE have focused on peripheral immune cells, while its action on central nervous system (CNS)-resident cells has been less explored. In addition to the well-known proinflammatory and damaging effects of IFN-γ in the CNS, evidence has also endowed this cytokine both a protective and regulatory role in autoimmune neuroinflammation. Recent investigations performed in this research field have exposed the complex role of IFN-γ in the CNS uncovering unexpected mechanisms of action that underlie these opposing activities on different CNS-resident cell types. The mechanisms behind these two-faced effects of IFN-γ depend on dose, disease phase, and cell development stage. Here, we will review and discuss the dual role of IFN-γ on CNS-resident cells in EAE highlighting its protective functions and the mechanisms proposed. PMID:26579119

  13. Life threatening central nervous system manifestations and hypothermia due to maneb intoxication in a child: a case report.

    PubMed

    de Tollenaer, S M; Buysse, Cmp; van den Anker, J N; Touw, D J; de Hoog, M

    2006-12-01

    Maneb, manganese ethylene-bis-dithiocarbamate, is a fungicide pesticide used in the agriculture and bulb flower culture sector. Toxicological effects for humans have been reported in literature and are diverse. They vary from allergic reactions (dermatitis, conjunctivitis, and bronchitis), central nervous system effects (muscarinic, nicotinic, central and extrapyramidal) and renal toxicity (acute renal failure).A 7-year old girl was admitted to the pediatric intensive care unit because of status epilepticus. Physical examination showed respiratory insufficiency, convulsions, and severe hypothermia (32.5 degrees C). The patient was intubated and her convulsions were successfully treated with benzodiazepines. Except for a combined metabolic and respiratory acidosis and hyperglycemia, diagnostic investigations on admission (full blood count, electrolytes, liver and renal functions, cerebrospinal fluid investigation, toxicology screening of blood and urine for barbiturates and benzodiazepines, blood culture, herpes PCR, and a CT scan of the brain) were normal. Within 24 hours, there was a complete recovery of all neurological signs. Within 72 hours, the patient was discharged from the hospital. Liquid chromatography-mass spectrometric investigation of her blood showed amounts of maneb, which can explain all symptoms and signs. However, effects of this magnitude on the central nervous system have not previously been reported in humans. PMID:17164699

  14. Central Nervous System Parasitosis and Neuroinflammation Ameliorated by Systemic IL-10 Administration in Trypanosoma brucei-Infected Mice.

    PubMed

    Rodgers, Jean; Bradley, Barbara; Kennedy, Peter G E; Sternberg, Jeremy M

    2015-01-01

    Invasion of the central nervous system (CNS) by African trypanosomes represents a critical step in the development of human African trypanosomiasis. In both clinical cases and experimental mouse infections it has been demonstrated that predisposition to CNS invasion is associated with a type 1 systemic inflammatory response. Using the Trypanosoma brucei brucei GVR35 experimental infection model, we demonstrate that systemic delivery of the counter-inflammatory cytokine IL-10 lowers plasma IFN-γ and TNF-α concentrations, CNS parasitosis and ameliorates neuro-inflammatory pathology and clinical symptoms of disease. The results provide evidence that CNS invasion may be susceptible to immunological attenuation. PMID:26505761

  15. Comparative studies of a real time-PCR method and three enzyme-linked immunosorbent-assays for the detection of central nervous system tissues in meat products

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The removal of Central Nervous System (CNS) tissues as part of the Bovine Spongiform Encephalopathy (BSE) risk material from the food chain is one of the highest priority tasks to avoid contamination of the human food chain with BSE. The present study evaluated a recently developed real time-PCR ass...

  16. A fluorescence based method, exploiting lipofuscin, for the real-time detection of central nervous system (CNS) tissues on bovine carcasses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The removal of Central Nervous System (CNS) tissues as part of Bovine Spongiform Encephalopathy (BSE) risk material is one of the highest priority tasks to avoid contamination of the human food chain with BSE. No currently available method enables the real-time detection of possible CNS tissue conta...

  17. IL-10-dependent Tr1 cells attenuate astrocyte activation and ameliorate chronic central nervous system inflammation.

    PubMed

    Mayo, Lior; Cunha, Andre Pires Da; Madi, Asaf; Beynon, Vanessa; Yang, Zhiping; Alvarez, Jorge I; Prat, Alexandre; Sobel, Raymond A; Kobzik, Lester; Lassmann, Hans; Quintana, Francisco J; Weiner, Howard L

    2016-07-01

    SEE WINGER AND ZAMVIL DOI101093/BRAIN/AWW121 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: The innate immune system plays a central role in the chronic central nervous system inflammation that drives neurological disability in progressive forms of multiple sclerosis, for which there are no effective treatments. The mucosal immune system is a unique tolerogenic organ that provides a physiological approach for the induction of regulatory T cells. Here we report that nasal administration of CD3-specific antibody ameliorates disease in a progressive animal model of multiple sclerosis. This effect is IL-10-dependent and is mediated by the induction of regulatory T cells that share a similar transcriptional profile to Tr1 regulatory cells and that suppress the astrocyte inflammatory transcriptional program. Treatment results in an attenuated inflammatory milieu in the central nervous system, decreased microglia activation, reduced recruitment of peripheral monocytes, stabilization of the blood-brain barrier and less neurodegeneration. These findings suggest a new therapeutic approach for the treatment of progressive forms of multiple sclerosis and potentially other types of chronic central nervous system inflammation. PMID:27246324

  18. Does Acupuncture Alter Pain-related Functional Connectivity of the Central Nervous System? A Systematic Review.

    PubMed

    Villarreal Santiago, María; Tumilty, Steve; Mącznik, Aleksandra; Mani, Ramakrishnan

    2016-08-01

    Acupuncture has been studied for several decades to establish evidence-based clinical practice. This systematic review aims to evaluate evidence for the effectiveness of acupuncture in influencing the functional connectivity of the central nervous system in patients with musculoskeletal pain. A systematic search of the literature was conducted to identify studies in which the central response of acupuncture in patients with musculoskeletal pain was evaluated by neuroimaging techniques. Databases searched were AMED, CINAHL, Cochrane Library, EMBASE, MEDLINE, PEDro, Pubmed, SCOPUS, SPORTDiscuss, and Web of Science. Included studies were assessed by two independent reviewers for their methodological quality by using the Downs and Black questionnaire and for their levels of completeness and transparency in reporting acupuncture interventions by using Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) criteria. Seven studies met the inclusion criteria. Three studies were randomized controlled trials (RCTs) and four studies were nonrandomized controlled trials (NRCTs). The neuroimaging techniques used were functional magnetic resonance imaging (fMRI) and positron emission tomography (PET). Positive effects on the functional connectivity of the central nervous system more consistently occurred during long-term acupuncture treatment. The results were heterogeneous from a descriptive perspective; however, the key findings support acupuncture's ability to alter pain-related functional connectivity in the central nervous system in patients with musculoskeletal pain. PMID:27555221

  19. IL-10-dependent Tr1 cells attenuate astrocyte activation and ameliorate chronic central nervous system inflammation

    PubMed Central

    Mayo, Lior; Cunha, Andre Pires Da; Madi, Asaf; Beynon, Vanessa; Yang, Zhiping; Alvarez, Jorge I.; Prat, Alexandre; Sobel, Raymond A.; Kobzik, Lester; Lassmann, Hans; Quintana, Francisco J.

    2016-01-01

    See Winger and Zamvil (doi:10.1093/brain/aww121) for a scientific commentary on this article. The innate immune system plays a central role in the chronic central nervous system inflammation that drives neurological disability in progressive forms of multiple sclerosis, for which there are no effective treatments. The mucosal immune system is a unique tolerogenic organ that provides a physiological approach for the induction of regulatory T cells. Here we report that nasal administration of CD3-specific antibody ameliorates disease in a progressive animal model of multiple sclerosis. This effect is IL-10-dependent and is mediated by the induction of regulatory T cells that share a similar transcriptional profile to Tr1 regulatory cells and that suppress the astrocyte inflammatory transcriptional program. Treatment results in an attenuated inflammatory milieu in the central nervous system, decreased microglia activation, reduced recruitment of peripheral monocytes, stabilization of the blood–brain barrier and less neurodegeneration. These findings suggest a new therapeutic approach for the treatment of progressive forms of multiple sclerosis and potentially other types of chronic central nervous system inflammation. PMID:27246324

  20. Incontinence and psychological problems in children: a common central nervous pathway?

    PubMed

    Van Herzeele, Charlotte; Vande Walle, Johan

    2016-05-01

    Nocturnal enuresis is caused by a mismatch between the nocturnal bladder capacity and the nocturnal diuresis rate, in the presence of a deficient arousability in the majority of patients, according to the pediatric and urologic literature. Psychiatric and psychologic literature are still concentrating on the potential role of psychological factors and central nervous mechanisms in the pathogenesis, as is reflected in the DMS-5 criteria. However, research has clearly shown several important comorbidities between neuropsychological dysfunctions and nocturnal enuresis. Due to the increased comorbidity of (neuro)psychological problems, sleep problems, circadian rhythms, and enuresis, the question arises as to whether there is a possible common central pathway in the pathogenesis. It is likely that the coexistence of these problems can be attributed to a common central nervous system involvement. The specific role of the central nervous system remains unclear, but several pathways are possible. The high comorbidity between enuresis, sleep, and (neuro)psychological functioning is probably attributable to a common pathogenetic pathway, emphasizing the importance of a multidisciplinary focus in screening and treatment in children with nocturnal enuresis. PMID:26872485

  1. Central Nervous System Viral Invasion and Inflammation During Acute HIV Infection

    PubMed Central

    Valcour, Victor; Chalermchai, Thep; Sailasuta, Napapon; Marovich, Mary; Lerdlum, Sukalaya; Suttichom, Duanghathai; Suwanwela, Nijasri C.; Jagodzinski, Linda; Michael, Nelson; Spudich, Serena; van Griensven, Frits; de Souza, Mark; Kim, Jerome; Ananworanich, Jintanat

    2012-01-01

    Background. Understanding the earliest central nervous system (CNS) events during human immunodeficiency virus (HIV) infection is crucial to knowledge of neuropathogenesis, but these have not previously been described in humans. Methods. Twenty individuals who had acute HIV infection (Fiebig stages I-IV), with average 15 days after exposure, underwent clinical neurological, cerebrospinal fluid (CSF), magnetic resonance imaging, and magnetic resonance spectroscopy (MRS) characterization. Results. HIV RNA was detected in the CSF from 15 of 18 subjects as early as 8 days after estimated HIV transmission. Undetectable CSF levels of HIV (in 3 of 18) was noted during Fiebig stages I, II, and III, with plasma HIV RNA levels of 285 651, 2321, and 81 978 copies/mL, respectively. On average, the CSF HIV RNA level was 2.42 log10 copies/mL lower than that in plasma. There were no cases in which the CSF HIV RNA level exceeded that in plasma. Headache was common during the acute retroviral syndrome (in 11 of 20 subjects), but no other neurological signs or symptoms were seen. Intrathecal immune activation was identified in some subjects with elevated CSF neopterin, monocyte chemotactic protein/CCL2, and interferon γ–induced protein 10/CXCL-10 levels. Brain inflammation was suggested by MRS. Conclusions. CSF HIV RNA was detectable in humans as early as 8 days after exposure. CNS inflammation was apparent by CSF analysis and MRS in some individuals during acute HIV infection. PMID:22551810

  2. Defensive Perimeter in the Central Nervous System: Predominance of Astrocytes and Astrogliosis during Recovery from Varicella-Zoster Virus Encephalitis

    PubMed Central

    Carpenter, John E.; Clayton, Amy C.; Halling, Kevin C.; Bonthius, Daniel J.; Buckingham, Erin M.; Jackson, Wallen; Dotzler, Steven M.; Card, J. Patrick; Enquist, Lynn W.

    2015-01-01

    ABSTRACT Varicella-zoster virus (VZV) is a highly neurotropic virus that can cause infections in both the peripheral nervous system and the central nervous system. Several studies of VZV reactivation in the peripheral nervous system (herpes zoster) have been published, while exceedingly few investigations have been carried out in a human brain. Notably, there is no animal model for VZV infection of the central nervous system. In this report, we characterized the cellular environment in the temporal lobe of a human subject who recovered from focal VZV encephalitis. The approach included not only VZV DNA/RNA analyses but also a delineation of infected cell types (neurons, microglia, oligodendrocytes, and astrocytes). The average VZV genome copy number per cell was 5. Several VZV regulatory and structural gene transcripts and products were detected. When colocalization studies were performed to determine which cell types harbored the viral proteins, the majority of infected cells were astrocytes, including aggregates of astrocytes. Evidence of syncytium formation within the aggregates included the continuity of cytoplasm positive for the VZV glycoprotein H (gH) fusion-complex protein within a cellular profile with as many as 80 distinct nuclei. As with other causes of brain injury, these results suggested that astrocytes likely formed a defensive perimeter around foci of VZV infection (astrogliosis). Because of the rarity of brain samples from living humans with VZV encephalitis, we compared our VZV results with those found in a rat encephalitis model following infection with the closely related pseudorabies virus and observed similar perimeters of gliosis. IMPORTANCE Investigations of VZV-infected human brain from living immunocompetent human subjects are exceedingly rare. Therefore, much of our knowledge of VZV neuropathogenesis is gained from studies of VZV-infected brains obtained at autopsy from immunocompromised patients. These are not optimal samples with which

  3. Naeglaeria infection of the central nervous system, CT scan findings: a case series.

    PubMed

    Naqi, Rohana; Azeemuddin, Muhammad

    2013-03-01

    The imaging findings in four cases of a rare infection of the central nervous system caused by amoebae, Naeglaeria fowleri are presented. Naeglaeria fowleri are pathogenic free-living amoebae. They cause primary amoebic meningoencephalitis (PAM), a rapidly fatal disease of the central nervous system. The computed tomography brain findings in 3 (75%) of our cases of pan amoebic meningoencephalitis showed non-specific brain oedema; 2 (66%) of these cases also had moderate hydrocephalus and among that 1 (50%) case showed an old lacunar infarction in peri-ventricular region. In the remaining 1 (25%) case the scan was normal with no evidence of oedema or abnormal lesion. Out of three cases with diffuse brain oedema, postcontrast images showed abnormal meningeal enhancement throughout the brain parenchyma in 1 (33%) case. However, no definite focal enhancing lesion was noted. In the rest of the cases, no abnormal parenchymal or meningeal enhancement was seen on post-contrast images. PMID:23914650

  4. Molecular Mechanisms Underlying the Effects of Statins in the Central Nervous System

    PubMed Central

    McFarland, Amelia J.; Anoopkumar-Dukie, Shailendra; Arora, Devinder S.; Grant, Gary D.; McDermott, Catherine M.; Perkins, Anthony V.; Davey, Andrew K.

    2014-01-01

    3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, commonly referred to as statins, are widely used in the treatment of dyslipidaemia, in addition to providing primary and secondary prevention against cardiovascular disease and stroke. Statins’ effects on the central nervous system (CNS), particularly on cognition and neurological disorders such as stroke and multiple sclerosis, have received increasing attention in recent years, both within the scientific community and in the media. Current understanding of statins’ effects is limited by a lack of mechanism-based studies, as well as the assumption that all statins have the same pharmacological effect in the central nervous system. This review aims to provide an updated discussion on the molecular mechanisms contributing to statins’ possible effects on cognitive function, neurodegenerative disease, and various neurological disorders such as stroke, epilepsy, depression and CNS cancers. Additionally, the pharmacokinetic differences between statins and how these may result in statin-specific neurological effects are also discussed. PMID:25391045

  5. Intravascular Lymphomatosis Mimicking Primary Central Nervous System Lymphoma: A Case Report and Literature Review

    PubMed Central

    Oomura, Masahiro; Sakakibara, Noriyuki; Suzuki, Shugo; Wakita, Atsushi; Mori, Yuji; Kamimoto, Kaoru

    2014-01-01

    We herein report a 75-year-old female patient with intravascular lymphomatosis (IVL) who presented with fever of unknown origin. Examination, including contrast-enhanced CT and 67Ga scintigraphy, failed to show any lesions. Her blood levels of lactate dehydrogenase and soluble interleukin-2 receptors were high, suggesting a lymphomatous tumor. A bone marrow puncture was negative, and a random skin biopsy revealed a monoclonal proliferation of naked, large lymphocytes in the vascular space of the subcutaneous tissue, confirming the diagnosis of IVL. MRI, performed 7 weeks after admission, showed a brain mass mimicking primary central nervous system lymphoma. The mass was considered to be a collection of malignant lymphocyte cells invading from the vessels. Without the random skin biopsy, this case may have been misdiagnosed as primary central nervous system lymphoma. PMID:24761147

  6. Physiological, pathological, and engineered cell identity reprogramming in the central nervous system.

    PubMed

    Smith, Derek K; Wang, Lei-Lei; Zhang, Chun-Li

    2016-07-01

    Multipotent neural stem cells persist in restricted regions of the adult mammalian central nervous system. These proliferative cells differentiate into diverse neuron subtypes to maintain neural homeostasis. This endogenous process can be reprogrammed as a compensatory response to physiological cues, traumatic injury, and neurodegeneration. In addition to innate neurogenesis, recent research has demonstrated that new neurons can be engineered via cell identity reprogramming in non-neurogenic regions of the adult central nervous system. A comprehensive understanding of these reprogramming mechanisms will be essential to the development of therapeutic neural regeneration strategies that aim to improve functional recovery after injury and neurodegeneration. WIREs Dev Biol 2016, 5:499-517. doi: 10.1002/wdev.234 For further resources related to this article, please visit the WIREs website. PMID:27258392

  7. Ramsay Hunt Syndrome Associated with Central Nervous System Involvement in an Adult.

    PubMed

    Chan, Tommy L H; Cartagena, Ana M; Bombassaro, Anne Marie; Hosseini-Moghaddam, Seyed M

    2016-01-01

    Ramsay Hunt syndrome associated with varicella zoster virus reactivation affecting the central nervous system is rare. We describe a 55-year-old diabetic female who presented with gait ataxia, right peripheral facial palsy, and painful vesicular lesions involving her right ear. Later, she developed dysmetria, fluctuating diplopia, and dysarthria. Varicella zoster virus was detected in the cerebrospinal fluid by polymerase chain reaction. She was diagnosed with Ramsay Hunt syndrome associated with spread to the central nervous system. Her facial palsy completely resolved within 48 hours of treatment with intravenous acyclovir 10 mg/kg every 8 hours. However, cerebellar symptoms did not improve until a tapering course of steroid therapy was initiated. PMID:27366189

  8. A rare case of nonenhancing primary central nervous system lymphoma mimic multiple sclerosis

    PubMed Central

    Chen, Hai; Dong, Huiqing

    2015-01-01

    Primary central nervous system lymphoma (PCNSL) is reported to have increased in the last decades. Early diagnosis is crucial for proper management of this tumor. We report a case of a 48-year-old man who was initially diagnosed with multiple sclerosis. Magnetic resonance imaging of the brain revealed multiple lesions with hypersignals in the bilateral basal ganglia and brain stem in T2-weighted image and non-enhancement, while positron emission tomography showed a low uptake of 18F-fluorodeoxyglucose in the affected brain, indicative of demyelination. However, this individual was correctly diagnosed with PCNSL after biopsy and further histological analysis. Primary central nervous system lymphoma must be considered even when nonenhancing, diffuse lesions are seen on MRI. A visible tumor on imaging is essential to ensure an early brain biopsy and histological diagnosis. PMID:26492120

  9. Ramsay Hunt Syndrome Associated with Central Nervous System Involvement in an Adult

    PubMed Central

    Chan, Tommy L. H.; Cartagena, Ana M.; Bombassaro, Anne Marie; Hosseini-Moghaddam, Seyed M.

    2016-01-01

    Ramsay Hunt syndrome associated with varicella zoster virus reactivation affecting the central nervous system is rare. We describe a 55-year-old diabetic female who presented with gait ataxia, right peripheral facial palsy, and painful vesicular lesions involving her right ear. Later, she developed dysmetria, fluctuating diplopia, and dysarthria. Varicella zoster virus was detected in the cerebrospinal fluid by polymerase chain reaction. She was diagnosed with Ramsay Hunt syndrome associated with spread to the central nervous system. Her facial palsy completely resolved within 48 hours of treatment with intravenous acyclovir 10 mg/kg every 8 hours. However, cerebellar symptoms did not improve until a tapering course of steroid therapy was initiated. PMID:27366189

  10. Central nervous system disorders and possible brain type carnitine palmitoyltransferase II deficiency.

    PubMed

    Ohtani, Y; Tomoda, A; Miike, T; Matsukura, M; Miyatake, M; Narazaki, O

    1994-01-01

    We describe two male infants with central nervous system disorders, i.e. infantile spasms in one and athetotic quadriplegia in the other, and with recurrent attacks of high plasma creatine kinase levels induced by viral infections. Although carnitine palmitoyltransferase I (CPT I) activity in biopsied muscle was normal in both cases, that of carnitine palmitoyltransferase II (CPT II) was decreased to 37% and 25% of the control value, respectively. Meanwhile, to determine whether or not and how CPT exists in the central nervous system (CNS), we studied animal brain tissues. CPT activity was demonstrated in almost all regions, especially in the brainstem, cerebellum and spinal cord. Although CPT deficiency can be classified into hepatic (CPT I) and muscular (CPT II) presentations, these data suggest that another symptomatology of CPT II deficiency with CNS involvement (brain type?) might exist. PMID:8048703

  11. A Role of Ginseng and Its Constituents in the Treatment of Central Nervous System Disorders

    PubMed Central

    Rokot, Natasya Trivena; Kairupan, Timothy Sean; Cheng, Kai-Chun; Runtuwene, Joshua; Kapantow, Nova Hellen; Amitani, Marie; Morinaga, Akinori; Amitani, Haruka; Asakawa, Akihiro

    2016-01-01

    Ginseng, a perennial plant belonging to the Panax genus of the Araliaceae family, has been used in China, Korea, and Japan as a traditional herbal medicine for thousands of years. Ginseng is recorded to have exhibited a wide variety of beneficial pharmacological effects and has become a popular and worldwide known health supplement and drug. The protective effects of ginseng on central nervous system are discussed in this review. Ginseng species and ginsenosides and their intestinal metabolism and bioavailability are concisely introduced. The molecular mechanisms of the effects of ginseng on central nervous system, mainly focused on the neuroprotection properties of ginseng, memory, and learning enhanced properties, and the effects on neurodegenerative disorders are presented. Thus, ginseng and its constituents are of potential merits in the treatment of cerebral disorders.

  12. Central nervous system malformations in relation to two polyvinyl chloride production facilities

    SciTech Connect

    Rosenman, K.D.; Rizzo, J.E.; Conomos, M.G.; Halpin, G.J. )

    1989-09-01

    A modified case-control study was conducted for selected birth defects that occurred among residents who lived in areas that surrounded two vinyl chloride polymerization facilities in New Jersey. Odds ratios for central nervous system defects (ICD 9, 740-742) decreased as the distance the mothers' residences were located from the facilities increased. Higher odds ratios for central nervous system birth defects were found in the areas around the plant that had higher vinyl chloride emissions. None of the odds ratios, however, were statistically significant. The differences in concentrations of emissions from the different plants may contribute to the discrepancies reported in previous studies wherein the risk of environmental exposure to vinyl chloride was assessed.

  13. Modulation of steroid action in the central and peripheral nervous systems by nuclear receptor coactivators

    PubMed Central

    Tetel, Marc J.

    2009-01-01

    Steroid hormones act in the central and peripheral nervous systems to regulate a variety of functions, including development, cell proliferation, cognition and behavior. Many of these effects of steroid hormones are mediated by their respective receptors, which are members of the nuclear receptor superfamily of transcriptional activators. A variety of cell culture studies reveal that nuclear receptor coactivators are recruited to the steroid receptor complex and are critical in modulating steroid-dependent transcription. Thus, in addition to the availability of the hormone and its receptor, the expression of nuclear receptor coactivators is essential for modulating steroid receptor mediated transcription. This review will discuss the significance of nuclear receptor coactivators in modulating steroid-dependent gene expression in the central and peripheral nervous systems and the regulation of behavior. PMID:19541426

  14. Tumors of the Central Nervous System: Clinical Aspects, Molecular Mechanisms, Unanswered Questions, and Future Research Directions

    PubMed Central

    Babcock, Michael A.; Kostova, Felina V.; Fountain, Jane; Guha, Abhijit; Packer, Roger J.; Pollack, Ian F.; Maria, Bernard L.

    2013-01-01

    Central nervous system tumors are the most common solid tumors in children. Many histological subtypes and biological variants exist. The 2007 Neurobiology of Disease in Children Symposium, held in conjunction with the 36th annual meeting of the Child Neurology Society, aimed to define current knowledge in the field and to develop specific aims for future clinical, translational, and fundamental science. Because of advances in structural and metabolic imaging, surgical technique, and combination therapies, the life expectancy of children with some of the most common tumors, such as cerebellar astrocytomas and medulloblastomas, has improved. Other common tumor types, including diffuse pontine gliomas and malignant embryonal tumors, still have a dismal prognosis. As novel therapies are identified for pediatric central nervous system tumors, long-term survival may be associated with considerable disability. A cooperative effort is crucial to early diagnosis and to translating basic research findings into safe, effective new treatments. PMID:18952577

  15. Neonatal herpes simplex virus type-1 central nervous system disease with acute retinal necrosis.

    PubMed

    Fong, Choong Yi; Aye, Aye Mya Min; Peyman, Mohammadreza; Nor, Norazlin Kamal; Visvaraja, Subrayan; Tajunisah, Iqbal; Ong, Lai Choo

    2014-04-01

    We report a case of neonatal herpes simplex virus (HSV)-1 central nervous system disease with bilateral acute retinal necrosis (ARN). An infant was presented at 17 days of age with focal seizures. Cerebrospinal fluid polymerase chain reaction was positive for HSV-1 and brain magnetic resonance imaging showed cerebritis. While receiving intravenous acyclovir therapy, the infant developed ARN with vitreous fluid polymerase chain reaction positive for HSV-1 necessitating intravitreal foscarnet therapy. This is the first reported neonatal ARN secondary to HSV-1 and the first ARN case presenting without external ocular or cutaneous signs. Our report highlights that infants with neonatal HSV central nervous system disease should undergo a thorough ophthalmological evaluation to facilitate prompt diagnosis and immediate treatment of this rapidly progressive sight-threatening disease. PMID:24378951

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

    SciTech Connect

    Barani, Igor J.; Benedict, Stanley H.; Lin, Peck-Sun . E-mail: plin@vcu.edu

    2007-06-01

    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.

  17. A Diagnostic Dilemma: Similarity of Neuroradiological Findings in Central Nervous System Hemophagocytic Lymphohistiocytosis and Aspergillosis.

    PubMed

    Foley, Jessica M; Borders, Heather; Kurt, Beth A

    2016-07-01

    Central nervous system (CNS) involvement in the context of hemophagocytic lymphohistiocytosis (HLH) is not uncommon. Given the immunosuppressive nature of HLH therapy, infectious complications are also seen. We describe a 9-year-old male who developed acute neurological decline secondary to aspergillosis while undergoing HLH therapy. The significant overlap observed in CNS neuroimaging of HLH and aspergillosis and the subtleties that may help differentiate the two are discussed. The importance of obtaining tissue for definitive diagnosis is underscored. PMID:26970537

  18. Vessel wall enhancement in herpes simplex virus central nervous system vasculitis.

    PubMed

    Guerrero, Waldo R; Dababneh, Haitham; Hedna, Shushrutha; Johnson, James A; Peters, Keith; Waters, Michael F

    2013-09-01

    Infection is a well-known cause of cerebral vasculopathy and vasculitis. We report a 36-year-old woman with cerebral vasculitis and ischemic stroke secondary to herpes simplex virus (HSV). MRI studies revealed a pontine stroke with basilar artery stenosis and vessel wall gadolinium enhancement. This case demonstrates the ability of HSV to cause a focal brainstem vasculitis and the utility of enhanced MRI in the diagnosis of stroke related to HSV central nervous system vasculitis. PMID:23517674

  19. [Ultrasound imaging of normal fetal central nervous system at 8 to 12 weeks of gestation].

    PubMed

    Vojtech, J; Krofta, L; Urbánková, I; Dlouhá, K; Haaková, L; Feyereisl, J

    2011-12-01

    With ongoing evolution of advanced ultrasound diagnostic in prenatal care the trend is to detect potential fetal anomalies in the first trimester if possible. Complex knowledge of normal fetal anatomy, embryology and ultrasound anatomy is important to be able to identify subtle abnormalities. In this review we demonstrate the possibilities of ultrasound imaging of fetal brain at late first trimester and describe normal central nervous system development week by week. Original images are presented. PMID:22312839

  20. Enhancement of the white matter following prophylactic therapy of the central nervous system for leukemia

    SciTech Connect

    Shalen, P.R.; Ostrow; P.T.; Glass, P.J.

    1981-08-01

    A case of fatal necrotizing leukoencephalopathy following prophylactic therapy of the central nervous system for acute lymphoblastic leukemia is reported. The clinical, CT, and neuropathological findings are described. The CT scan demonstrated symmetrical white-matter enhancement. Histological analysis was consistent with the effects of irradiation and methotrexate. The differential diagnosis of the clinical and CT findings is discussed. Brain biopsy is the diagnostic procedure of choice.

  1. Everything to gain: Sir Hugh Cairns' treatment of central nervous system infection at Oxford and abroad.

    PubMed

    Chalif, Joshua I; Gillies, Martin J; Magdum, Shailendra A; Aziz, Tipu Z; Pereira, Erlick A C

    2013-02-01

    Antibiotics have revolutionized survival from central nervous system (CNS) infections. Sixty years after the death of Sir Hugh Cairns, we present archive material of historical interest from the Radcliffe Infirmary in Oxford from the time of his first trials of penicillin for CNS infection. We discuss Cairns' important wartime and subsequent contributions to antibiosis in CNS infection and include drawings by Audrey Arnott illustrating the surgical techniques used to treat abscesses at the time. PMID:23149954

  2. Group D Adenoviruses Infect Primary Central Nervous System Cells More Efficiently than Those from Group C

    PubMed Central

    Chillon, Miguel; Bosch, Assumpció; Zabner, Joseph; Law, Lane; Armentano, Donna; Welsh, Michael J.; Davidson, Beverly L.

    1999-01-01

    Group C adenovirus-mediated gene transfer to central nervous system cells is inefficient. We found that wild-type group D viruses, or recombinant adenovirus type 2 (Ad2) (group C) modified to contain Ad17 (group D) fiber, were more efficient in infecting primary cultures of neurons. Together with studies on primary vascular endothelial cells and tissue culture cell lines, our results indicate that there is not a universally applicable adenovirus serotype for use as a gene transfer vector. PMID:9971839

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

    PubMed

    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. PMID:26912633

  4. Lipomas of the central nervous system in the newborns – a report of eight cases

    PubMed Central

    Gradowska, Kinga; Czech-Kowalska, Justyna; Jurkiewicz, Elżbieta; Komornicka, Justyna; Dobrzańska, Anna

    2011-01-01

    Summary Background: Central nervous system lipomas are rare tumours. In most of the cases they are located in corpus callosum of the brain. The ultrasonographic image of lipomas tends to be quite characteristic. Final diagnosis is however done on a basis of brain resonance. The purpose of this work is to present proceeding in case of central nervous system lipomas with particular attention to diagnostic imaging. This work is based on own research. Case Report: There are eight patients with central nervous system lipomas described in this work. The ultrasonographic imaging performed upon patients’ birth revealed features of agenesis of corpus callosum with presence of hyperechoic structure in the area of median line within corpus callosum. This image correlated with Nuclear Magnetic Resonance examination results. Our research confirms that patients with central nervous system lipomas represent rare diagnostic and therapeutic cases. Due to characteristic results of ultrasonographic imaging of the brain, recognition of agenesis of corpus callosum would not cause difficulties. However the presence of hyperechoic structure without vascular flow which may suggest lipomas of corpus callosum would require final verification of the diagnosis and wider assessment of brain with NMR examination. We did not recognize any relation between corpus callosum pathology and neuroinfection of cytomegalovirus etiology. In all of the eight research cases there were malformations diagnostics conducted. There were genetic irregularities in case of two of the neonates only. Until today, all of the patients remain under neurological care. Their psychomotor development is regularly controlled. Conclusions: Taking into consideration that numerous malformations occur altogether with brain lipomas, it is recommended to conduct appropriate diagnostics, to inform parents on an essence of diagnosis and on necessity of observing child’s psychomotor development. Obviously, it is crucial to secure

  5. Nocardia farcinica Meningitis Masquerading as Central Nervous System Metastasis in a Child With Cerebellar Pilocytic Astrocytoma.

    PubMed

    Davis, Jennifer; Kreppel, Andrew J; Brady, Rebecca C; Jones, Blaise; Stevenson, Charles B; Fouladi, Maryam; Hummel, Trent R

    2015-08-01

    Juvenile pilocytic astrocytoma, the most common pediatric central nervous system (CNS) neoplasm, characteristically displays an indolent growth pattern and rarely demonstrates metastatic dissemination. Reports of infections mimicking CNS metastatic disease are also rare and can impact treatment. We report the youngest known case of a child with a CNS Nocardia farcinica infection who had a known cerebellar pilocytic astrocytoma, review other infections that may masquerade as CNS neoplasms, and discuss N. farcinica CNS infections. PMID:26181420

  6. [Polyneuropathy and central nervous system diseases before and after heart transplantation. Is cyclosporin neurotoxic?].

    PubMed

    Porschke, H; Strenge, H; Stauch, C

    1991-10-18

    In a cross-sectional study, 52 patients (44 men, 8 women, mean age 50.6 [19-68] years) were investigated clinically and electrophysiologically for evidence of peripheral and central nervous system damage before and after heart transplantation. 20 patients were investigated before heart transplantation (group 1), 16 at 7 days to 5 months after transplantation (early post-operative group; group 2) and 16 at 6 to 32 months after transplantation (late post-operative group; group 3). Nerve conduction studies (median, peroneal and sural nerves) revealed polyneuropathy in 14 out of 16 patients in group 2, significantly more than in group 1 (11 out of 19) and group 3 (9 out of 16). The mean blood cyclosporin concentration was 656 ng/ml in group 2 and 409 ng/ml in group 3 (P less than 0.001). Patients in group 3 with polyneuropathy had significantly higher cyclosporin concentrations than patients without polyneuropathy (505 vs 284 ng/ml; P less than 0.01). Among patients who had undergone operations, there were no noteworthy differences between the mean cyclosporin concentrations and clinical data in those with or without central nervous system lesions. There is preliminary evidence of a neurotoxic effect of cyclosporin on the peripheral but not the central nervous system. PMID:1935623

  7. Tachykinin-1 in the Central Nervous System Regulates Adiposity in Rodents

    PubMed Central

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

    2015-01-01

    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. PMID:25751638

  8. Caffeine and the central nervous system: mechanisms of action, biochemical, metabolic and psychostimulant effects.

    PubMed

    Nehlig, A; Daval, J L; Debry, G

    1992-01-01

    Caffeine is the most widely consumed central-nervous-system stimulant. Three main mechanisms of action of caffeine on the central nervous system have been described. Mobilization of intracellular calcium and inhibition of specific phosphodiesterases only occur at high non-physiological concentrations of caffeine. The only likely mechanism of action of the methylxanthine is the antagonism at the level of adenosine receptors. Caffeine increases energy metabolism throughout the brain but decreases at the same time cerebral blood flow, inducing a relative brain hypoperfusion. Caffeine activates noradrenaline neurons and seems to affect the local release of dopamine. Many of the alerting effects of caffeine may be related to the action of the methylxanthine on serotonin neurons. The methylxanthine induces dose-response increases in locomotor activity in animals. Its psychostimulant action on man is, however, often subtle and not very easy to detect. The effects of caffeine on learning, memory, performance and coordination are rather related to the methylxanthine action on arousal, vigilance and fatigue. Caffeine exerts obvious effects on anxiety and sleep which vary according to individual sensitivity to the methylxanthine. However, children in general do not appear more sensitive to methylxanthine effects than adults. The central nervous system does not seem to develop a great tolerance to the effects of caffeine although dependence and withdrawal symptoms are reported. PMID:1356551

  9. Translocation of Inhaled Ultrafine Manganese Oxide Particles to the Central Nervous System

    PubMed Central

    Elder, Alison; Gelein, Robert; Silva, Vanessa; Feikert, Tessa; Opanashuk, Lisa; Carter, Janet; Potter, Russell; Maynard, Andrew; Ito, Yasuo; Finkelstein, Jacob; Oberdörster, Günter

    2006-01-01

    Background Studies in monkeys with intranasally instilled gold ultrafine particles (UFPs; < 100 nm) and in rats with inhaled carbon UFPs suggested that solid UFPs deposited in the nose travel along the olfactory nerve to the olfactory bulb. Methods To determine if olfactory translocation occurs for other solid metal UFPs and assess potential health effects, we exposed groups of rats to manganese (Mn) oxide UFPs (30 nm; ~ 500 μg/m3) with either both nostrils patent or the right nostril occluded. We analyzed Mn in lung, liver, olfactory bulb, and other brain regions, and we performed gene and protein analyses. Results After 12 days of exposure with both nostrils patent, Mn concentrations in the olfactory bulb increased 3.5-fold, whereas lung Mn concentrations doubled; there were also increases in striatum, frontal cortex, and cerebellum. Lung lavage analysis showed no indications of lung inflammation, whereas increases in olfactory bulb tumor necrosis factor-α mRNA (~ 8-fold) and protein (~ 30-fold) were found after 11 days of exposure and, to a lesser degree, in other brain regions with increased Mn levels. Macrophage inflammatory protein-2, glial fibrillary acidic protein, and neuronal cell adhesion molecule mRNA were also increased in olfactory bulb. With the right nostril occluded for a 2-day exposure, Mn accumulated only in the left olfactory bulb. Solubilization of the Mn oxide UFPs was < 1.5% per day. Conclusions We conclude that the olfactory neuronal pathway is efficient for translocating inhaled Mn oxide as solid UFPs to the central nervous system and that this can result in inflammatory changes. We suggest that despite differences between human and rodent olfactory systems, this pathway is relevant in humans. PMID:16882521

  10. Vorinostat and Bortezomib in Treating Young Patients With Refractory or Recurrent Solid Tumors, Including Central Nervous System Tumors and Lymphoma

    ClinicalTrials.gov

    2013-07-01

    Childhood Burkitt Lymphoma; Childhood Central Nervous System Choriocarcinoma; Childhood Central Nervous System Germ Cell Tumor; Childhood Central Nervous System Germinoma; Childhood Central Nervous System Mixed Germ Cell Tumor; Childhood Central Nervous System Teratoma; Childhood Central Nervous System Yolk Sac Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Medulloepithelioma; Childhood Meningioma; Childhood Mixed Glioma; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Childhood Oligodendroglioma; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Central Nervous System Embryonal Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Unspecified Childhood Solid Tumor, Protocol Specific

  11. An altered form of pp60/sup c-src/ is expressed primarily in the central nervous system

    SciTech Connect

    Le Beau, J.M.; Wiestler, O.D.; Walter, G.

    1987-11-01

    The expression of two forms of pp60/sup c-scr/, pp60 and pp60/sup +/, was measured in the central nervous system (CNS) and the peripheral nervous system. Both forms were expressed in the CNS, whereas only pp60 was primarily detected in the peripheral nervous system. Our findings suggest that pp60/sup +/ may play a role in events important to the CNS.

  12. The role of the Rho/ROCK signaling pathway in inhibiting axonal regeneration in the central nervous system.

    PubMed

    Liu, Jing; Gao, Hong-Yan; Wang, Xiao-Feng

    2015-11-01

    The Rho/Rho-associated coiled-coil containing protein kinase (Rho/ROCK) pathway is a major signaling pathway in the central nervous system, transducing inhibitory signals to block regeneration. After central nervous system damage, the main cause of impaired regeneration is the presence of factors that strongly inhibit regeneration in the surrounding microenvironment. These factors signal through the Rho/ROCK signaling pathway to inhibit regeneration. Therefore, a thorough understanding of the Rho/ROCK signaling pathway is crucial for advancing studies on regeneration and repair of the injured central nervous system. PMID:26807132

  13. The role of the Rho/ROCK signaling pathway in inhibiting axonal regeneration in the central nervous system

    PubMed Central

    Liu, Jing; Gao, Hong-yan; Wang, Xiao-feng

    2015-01-01

    The Rho/Rho-associated coiled-coil containing protein kinase (Rho/ROCK) pathway is a major signaling pathway in the central nervous system, transducing inhibitory signals to block regeneration. After central nervous system damage, the main cause of impaired regeneration is the presence of factors that strongly inhibit regeneration in the surrounding microenvironment. These factors signal through the Rho/ROCK signaling pathway to inhibit regeneration. Therefore, a thorough understanding of the Rho/ROCK signaling pathway is crucial for advancing studies on regeneration and repair of the injured central nervous system. PMID:26807132

  14. Central Nervous System Control of Gastrointestinal Motility and Secretion and Modulation of Gastrointestinal Functions

    PubMed Central

    Browning, Kirsteen N.; Travagli, R. Alberto

    2016-01-01

    Although the gastrointestinal (GI) tract possesses intrinsic neural plexuses that allow a significant degree of autonomy over GI functions, the central nervous system (CNS) provides extrinsic neural inputs that regulate, modulate, and control these functions. While the intestines are capable of functioning in the absence of extrinsic inputs, the stomach and esophagus are much more dependent upon extrinsic neural inputs, particularly from parasympathetic and sympathetic pathways. The sympathetic nervous system exerts a predominantly inhibitory effect upon GI muscle and provides a tonic inhibitory influence over mucosal secretion while, at the same time, regulates GI blood flow via neurally mediated vasoconstriction. The parasympathetic nervous system, in contrast, exerts both excitatory and inhibitory control over gastric and intestinal tone and motility. Although GI functions are controlled by the autonomic nervous system and occur, by and large, independently of conscious perception, it is clear that the higher CNS centers influence homeostatic control as well as cognitive and behavioral functions. This review will describe the basic neural circuitry of extrinsic inputs to the GI tract as well as the major CNS nuclei that innervate and modulate the activity of these pathways. The role of CNS-centered reflexes in the regulation of GI functions will be discussed as will modulation of these reflexes under both physiological and pathophysiological conditions. Finally, future directions within the field will be discussed in terms of important questions that remain to be resolved and advances in technology that may help provide these answers. PMID:25428846

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

    PubMed Central

    Badhan, Raj K. Singh; Chenel, Marylore; Penny, Jeffrey I.

    2014-01-01

    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. PMID:24647103

  16. A biophysical study on molecular physiology of the uncoupling proteins of the central nervous system

    PubMed Central

    Hoang, Tuan; Kuljanin, Miljan; Smith, Matthew D.

    2015-01-01

    Mitochondrial inner membrane uncoupling proteins (UCPs) facilitate transmembrane (TM) proton flux and consequently reduce the membrane potential and ATP production. It has been proposed that the three neuronal human UCPs (UCP2, UCP4 and UCP5) in the central nervous system (CNS) play significant roles in reducing cellular oxidative stress. However, the structure and ion transport mechanism of these proteins remain relatively unexplored. Recently, we reported a novel expression system for obtaining functionally folded UCP1 in bacterial membranes and applied this system to obtain highly pure neuronal UCPs in high yields. In the present study, we report on the structure and function of the three neuronal UCP homologues. Reconstituted neuronal UCPs were dominantly helical in lipid membranes and transported protons in the presence of physiologically-relevant fatty acid (FA) activators. Under similar conditions, all neuronal UCPs also exhibited chloride transport activities that were partially inhibited by FAs. CD, fluorescence and MS measurements and semi-native gel electrophoresis collectively suggest that the reconstituted proteins self-associate in the lipid membranes. Based on SDS titration experiments and other evidence, a general molecular model for the monomeric, dimeric and tetrameric functional forms of UCPs in lipid membranes is proposed. In addition to their shared structural and ion transport features, neuronal UCPs differ in their conformations and proton transport activities (and possibly mechanism) in the presence of different FA activators. The differences in FA-activated UCP-mediated proton transport could serve as an essential factor in understanding and differentiating the physiological roles of UCP homologues in the CNS. PMID:26182433

  17. Risk of pneumonia in central nervous system injury with alcohol intake: a meta-analysis

    PubMed Central

    Sun, Chunming; Shen, Liang; Li, Xuetao; Liu, Chuanjin; Zhou, Youxin

    2015-01-01

    Objective: Central nervous system (CNS) injury can increased the risk of secondary mortality because of its late inflammatory complications. Alcohol intake increases the risk of damage and complications subsequent to a (CNS) injury. How about the risk of pneumonia after CNS injury under the effect of alcoholic drink? Though animal trails of material prosperity and studies for human have been investigated in recent decades, the outcome maintains poor understanding. Pneumonia is one of the serious complication at the time of hospitalization and it should be known as more as possible for steadying patient conditions in intensive care unit and shortening length of stay. Thus, we conducted a meta-analysis of published materials to assess the association between alcohol intake and pneumonia in CNS injury. Methods: Two authors searched the PUBMED, EMBASE, Cochrane Library, and web of science up to September, 2014 for published literatures without any limitations. Reference lists from identified studies were also screened carefully by us for additional data. The summary relative risks (RRs) and 95% confidence intervals (CI) were calculated by statistical analysis software (Stata 12.0) with fixed-effects models to estimate the risk. Result: The results indicated that a higher incidence of pneumonia was found in CNS injury under the influence of alcohol (RR = 1.32, 95% CI = 1.21-1.43), and the risk has no relation to blood alcohol concentration (BAC) (BAC ≥ 80 mg/dl vs < 80 mg/dl, BAC ≥ 100 mg/dl vs < 100 mg/dl). Conclusion: Traumatic brain injury (TBI) and spinal cord injury patients who are under the influence of alcoholic drink have a higher risk of pneumonia. PMID:26629070

  18. Inflammatory myofibroblastic tumor of the central nervous system and its relationship to inflammatory pseudotumor.

    PubMed

    Swain, Rebecca S; Tihan, Tarik; Horvai, Andrew E; Di Vizio, Dolores; Loda, Massimo; Burger, Peter C; Scheithauer, Bernd W; Kim, Grace E

    2008-03-01

    Inflammatory myofibroblastic tumor (IMT) is a distinctive spindle cell lesion and occurs primarily in soft tissue. Recent evidence suggests a neoplastic nature, although historically, both neoplastic and nonneoplastic processes were combined in this category. Originally described as a nonneoplastic process, the term inflammatory pseudotumor (IP) has been used synonymously with IMT. IMTs have been linked to ALK gene (2p23) rearrangements, and some have suggested an association with the human herpesvirus 8 (HHV-8). IMT in the central nervous system (CNS) is rare, its characteristics are poorly defined, and its relation to similar tumors at other sites is unclear. To better characterize IMT within the CNS, we studied clinicopathologic features of 6 IMTs and compared them with 18 nonneoplastic lesions originally classified as IP. The IMT group consisted of 2 male and 4 female patients with a median age of 29 years. Of the six IMTs, 5 occurred within the cerebral hemispheres, and one was in the posterior fossa. All tumors were composed of neoplastic spindle cells and a variable amount of inflammatory infiltrate. Eighteen IPs included in this study consisted of predominantly inflammatory masses occasionally seen in the setting of systemic diseases. Only 1 IMT and none of the IPs recurred during the follow-up period. Four IMTs had either ALK protein overexpression or 2p23 rearrangement, and 1 case demonstrated both. None of the IPs were positive for ALK. Neither IMT nor IP cases demonstrated HHV-8 expression. We suggest that IMT in the CNS is distinct from the nonneoplastic IP, and distinguishing IMT from nonneoplastic lesions should enable better decisions for patient management. PMID:18261625

  19. A review of nanoparticle functionality and toxicity on the central nervous system

    PubMed Central

    Yang, Z.; Liu, Z. W.; Allaker, R. P.; Reip, P.; Oxford, J.; Ahmad, Z.; Ren, G.

    2010-01-01

    Although nanoparticles have tremendous potential for a host of applications, their adverse effects on living cells have raised serious concerns recently for their use in the healthcare and consumer sectors. As regards the central nervous system (CNS), research data on nanoparticle interaction with neurons has provided evidence of both negative and positive effects. Maximal application dosage of nanoparticles in materials to provide applications such as antibacterial and antiviral functions is approximately 0.1–1.0 wt%. This concentration can be converted into a liquid phase release rate (leaching rate) depending upon the host or base materials used. For example, nanoparticulate silver (Ag) or copper oxide (CuO)-filled epoxy resin demonstrates much reduced release of the metal ions (Ag+ or Cu2+) into their surrounding environment unless they are mechanically removed or aggravated. Subsequent to leaching effects and entry into living systems, nanoparticles can also cross through many other barriers, such as skin and the blood–brain barrier (BBB), and may also reach bodily organs. In such cases, their concentration or dosage in body fluids is considered to be well below the maximum drug toxicity test limit (10−5 g ml−1) as determined in artificial cerebrospinal solution. As this is a rapidly evolving area and the use of such materials will continue to mature, so will their exposure to members of society. Hence, neurologists have equal interests in nanoparticle effects (positive functionality and negative toxicity) on human neuronal cells within the CNS, where the current research in this field will be highlighted and reviewed. PMID:20519209

  20. Female rats are more susceptible to central nervous system oxygen toxicity than male rats

    PubMed Central

    Held, Heather E.; Pilla, Raffaele; Ciarlone, Geoffrey E.; Landon, Carol S.; Dean, Jay B.

    2014-01-01

    Abstract Tonic–clonic seizures typify central nervous system oxygen toxicity (CNS‐OT) in humans and animals exposed to high levels of oxygen, as are encountered during scuba diving. We previously demonstrated that high doses of pseudoephedrine (PSE) decrease the latency to seizure (LS) for CNS‐OT in young male rats. This study investigated whether female rats respond similarly to PSE and hyperbaric oxygen (HBO). We implanted 60 virgin stock (VS) and 54 former breeder (FB) female rats with radio‐telemetry devices that measured brain electrical activity. One week later, rats were gavaged with saline or PSE in saline (40, 80, 120, 160, or 320 mg/kg) before diving to five atmospheres absolute in 100% oxygen. The time between reaching maximum pressure and exhibiting seizure was LS. Vaginal smears identified estrus cycle phase. PSE did not decrease LS for VS or FB, primarily because they exhibited low LS for all conditions tested. VS had shorter LS than males at 0, 40, and 80 mg/kg (−42, −49, and −57%, respectively). FB also had shorter LS than males at 0, 40, and 80 mg/kg (−60, −86, and −73%, respectively). FB were older than VS (286 ± 10 days vs. 128 ± 5 days) and weighed more than VS (299 ± 2.7 g vs. 272 ± 2.1 g). Males tested were younger (88 ± 2 days), heavier (340 ± 4.5 g), and gained more weight postoperatively (7.2 ± 1.6 g) than either VS (−0.4 ± 1.5 g) or FB (−1.6 ± 1.5 g); however, LS correlated poorly with age, body mass, change in body mass, and estrus cycle phase. We hypothesize that differences in sex hormones underlie females' higher susceptibility to CNS‐OT than males. PMID:24771690

  1. Docosahexaenoic acid (DHA) and the developing central nervous system (CNS) - Implications for dietary recommendations.

    PubMed

    Guesnet, Philippe; Alessandri, Jean-Marc

    2011-01-01

    The accretion of docosahexaenoic acid (DHA) in membranes of the central nervous system is required for the optimum development of retina and brain functions. DHA status is determined by the dietary intake of n-3 polyunsaturated fatty acids (PUFA), both the metabolic precursor α-linolenic acid (α-LNA) and DHA. Clinical studies have shown that feeding term or premature infants with formula low in total n-3 PUFA may alter the maturation of visual acuity. Moreover, feeding infants over the first 6 mon of life with formula containing adequate α-LNA, but no DHA, did not sustain the same cerebral accretion of DHA as that of breast-fed infants. Whether lower DHA accretion in brain of formula-fed term infants impairs neurophysiological performances is not clearly established. Contradictory data have been published, possibly owing to confounding factors such as maternal intakes and/or genetic variations in PUFA metabolism. Nevertheless, a large corpus of data is in favor of the recommendation of regular dietary intakes of DHA (during at least the first 6 mon of life) and suggest that DHA should be added in formulas at the level generally found in human milk (0.2-0.3 wt% of total fatty acids). The maternal intake of n-3 PUFA during pregnancy and lactation is also crucial, since the n-3 PUFA are provided during perinatal development through placental transfer and maternal milk, which determines the DHA status of the newborn and consequently impacts on post-natal development of brain and visual functions. Whether more clinical studies are needed to control and improve the impact of DHA maternal intakes on the progeny's neurodevelopment, several commissions recommended by precaution that DHA average intake for pregnant and lactating women should be of 200-300 mg/day. PMID:20478353

  2. A biophysical study on molecular physiology of the uncoupling proteins of the central nervous system.

    PubMed

    Hoang, Tuan; Kuljanin, Miljan; Smith, Matthew D; Jelokhani-Niaraki, Masoud

    2015-01-01

    Mitochondrial inner membrane uncoupling proteins (UCPs) facilitate transmembrane (TM) proton flux and consequently reduce the membrane potential and ATP production. It has been proposed that the three neuronal human UCPs (UCP2, UCP4 and UCP5) in the central nervous system (CNS) play significant roles in reducing cellular oxidative stress. However, the structure and ion transport mechanism of these proteins remain relatively unexplored. Recently, we reported a novel expression system for obtaining functionally folded UCP1 in bacterial membranes and applied this system to obtain highly pure neuronal UCPs in high yields. In the present study, we report on the structure and function of the three neuronal UCP homologues. Reconstituted neuronal UCPs were dominantly helical in lipid membranes and transported protons in the presence of physiologically-relevant fatty acid (FA) activators. Under similar conditions, all neuronal UCPs also exhibited chloride transport activities that were partially inhibited by FAs. CD, fluorescence and MS measurements and semi-native gel electrophoresis collectively suggest that the reconstituted proteins self-associate in the lipid membranes. Based on SDS titration experiments and other evidence, a general molecular model for the monomeric, dimeric and tetrameric functional forms of UCPs in lipid membranes is proposed. In addition to their shared structural and ion transport features, neuronal UCPs differ in their conformations and proton transport activities (and possibly mechanism) in the presence of different FA activators. The differences in FA-activated UCP-mediated proton transport could serve as an essential factor in understanding and differentiating the physiological roles of UCP homologues in the CNS. PMID:26182433

  3. Female rats are more susceptible to central nervous system oxygen toxicity than male rats.

    PubMed

    Held, Heather E; Pilla, Raffaele; Ciarlone, Geoffrey E; Landon, Carol S; Dean, Jay B

    2014-01-01

    Abstract Tonic-clonic seizures typify central nervous system oxygen toxicity (CNS-OT) in humans and animals exposed to high levels of oxygen, as are encountered during scuba diving. We previously demonstrated that high doses of pseudoephedrine (PSE) decrease the latency to seizure (LS) for CNS-OT in young male rats. This study investigated whether female rats respond similarly to PSE and hyperbaric oxygen (HBO). We implanted 60 virgin stock (VS) and 54 former breeder (FB) female rats with radio-telemetry devices that measured brain electrical activity. One week later, rats were gavaged with saline or PSE in saline (40, 80, 120, 160, or 320 mg/kg) before diving to five atmospheres absolute in 100% oxygen. The time between reaching maximum pressure and exhibiting seizure was LS. Vaginal smears identified estrus cycle phase. PSE did not decrease LS for VS or FB, primarily because they exhibited low LS for all conditions tested. VS had shorter LS than males at 0, 40, and 80 mg/kg (-42, -49, and -57%, respectively). FB also had shorter LS than males at 0, 40, and 80 mg/kg (-60, -86, and -73%, respectively). FB were older than VS (286 ± 10 days vs. 128 ± 5 days) and weighed more than VS (299 ± 2.7 g vs. 272 ± 2.1 g). Males tested were younger (88 ± 2 days), heavier (340 ± 4.5 g), and gained more weight postoperatively (7.2 ± 1.6 g) than either VS (-0.4 ± 1.5 g) or FB (-1.6 ± 1.5 g); however, LS correlated poorly with age, body mass, change in body mass, and estrus cycle phase. We hypothesize that differences in sex hormones underlie females' higher susceptibility to CNS-OT than males. PMID:24771690

  4. Trends in primary central nervous system lymphoma incidence and survival in the U.S.

    PubMed

    Shiels, Meredith S; Pfeiffer, Ruth M; Besson, Caroline; Clarke, Christina A; Morton, Lindsay M; Nogueira, Leticia; Pawlish, Karen; Yanik, Elizabeth L; Suneja, Gita; Engels, Eric A

    2016-08-01

    It is suspected that primary central nervous system lymphoma (PCNSL) rates are increasing among immunocompetent people. We estimated PCNSL trends in incidence and survival among immunocompetent persons by excluding cases among human immunodeficiency virus (HIV)-infected persons and transplant recipients. PCNSL data were derived from 10 Surveillance, Epidemiology and End Results (SEER) cancer registries (1992-2011). HIV-infected cases had reported HIV infection or death due to HIV. Transplant recipient cases were estimated from the Transplant Cancer Match Study. We estimated PCNSL trends overall and among immunocompetent individuals, and survival by HIV status. A total of 4158 PCNSLs were diagnosed (36% HIV-infected; 0·9% transplant recipients). HIV prevalence in PCNSL cases declined from 64·1% (1992-1996) to 12·7% (2007-2011), while the prevalence of transplant recipients remained low. General population PCNSL rates were strongly influenced by immunosuppressed cases, particularly in 20-39 year-old men. Among immunocompetent people, PCNSL rates in men and women aged 65+ years increased significantly (1·7% and 1·6%/year), but remained stable in other age groups. Five-year survival was poor, particularly among HIV-infected cases (9·0%). Among HIV-uninfected cases, 5-year survival increased from 19·1% (1992-1994) to 30·1% (2004-2006). In summary, PCNSL rates have increased among immunocompetent elderly adults, but not in younger individuals. Survival remains poor for both HIV-infected and HIV-uninfected PCNSL patients. PMID:27018254

  5. A comparative study of experimental mouse models of central nervous system demyelination.

    PubMed

    Dumitrascu, O M; Mott, K R; Ghiasi, H

    2014-06-01

    Several mouse models of multiple sclerosis (MS) are now available. We have established a mouse model, in which ocular infection with a recombinant HSV-1 that expresses murine interleukin (IL)-2 constitutively (HSV-IL-2) causes central nervous system demyelination in different strains of mice. This model differs from most other models, in which it represents a mixture of viral and immune triggers. In the present study, we directly compared MOG35-55, MBP35-47 and PLP190-209 models of experimental autoimmune encephalitis with our HSV-IL-2-induced MS model. Mice with HSV-IL-2- and myelin oligodendrocyte glycoprotein (MOG)-induced demyelinating diseases demonstrated a similar pattern and distribution of demyelination in their brain, spinal cord (SC) and optic nerves (ONs). In contrast, no demyelination was detected in the ONs of myelin basic protein (MBP)- and proteolipid protein (PLP)-injected mice. Interferon-β (IFN-β) injections significantly reduced demyelination in brains of all groups, in the SCs of the MOG and MBP groups, and completely blocked it in the SCs of the PLP and HSV-IL-2 groups as well as in ONs of MOG and HSV-IL-2 groups. In contrast to IFN-β treatment, IL-12p70 protected the HSV-IL-2 group from demyelination, whereas IL-4 was not effective at all in preventing demyelination. MOG-injected mice showed clinical signs of paralysis and disease-related mortality, whereas mice in the other treatment groups did not. Collectively, the results indicate that the HSV-IL-2 model and the MOG model complement each other and, together, provide unique insights into the heterogeneity of human MS. PMID:24718267

  6. Transglutaminase 6: a protein associated with central nervous system development and motor function.

    PubMed

    Thomas, Helen; Beck, Konrad; Adamczyk, Magdalena; Aeschlimann, Pascale; Langley, Martin; Oita, Radu C; Thiebach, Lars; Hils, Martin; Aeschlimann, Daniel

    2013-01-01

    Transglutaminases (TG) form a family of enzymes that catalyse various post-translational modifications of glutamine residues in proteins and peptides including intra- and intermolecular isopeptide bond formation, esterification and deamidation. We have characterized a novel member of the mammalian TG family, TG6, which is expressed in a human carcinoma cell line with neuronal characteristics and in mouse brain. Besides full-length protein, alternative splicing results in a short variant lacking the second β-barrel domain in man and a variant with truncated β-sandwich domain in mouse. Biochemical data show that TG6 is allosterically regulated by Ca(2+) and guanine nucleotides. Molecular modelling indicates that TG6 could have Ca(2+) and GDP-binding sites related to those of TG3 and TG2, respectively. Localization of mRNA and protein in the mouse identified abundant expression of TG6 in the central nervous system. Analysis of its temporal and spatial pattern of induction in mouse development indicates an association with neurogenesis. Neuronal expression of TG6 was confirmed by double-labelling of mouse forebrain cells with cell type-specific markers. Induction of differentiation in mouse Neuro 2a cells with NGF or dibutyryl cAMP is associated with an upregulation of TG6 expression. Familial ataxia has recently been linked to mutations in the TGM6 gene. Autoantibodies to TG6 were identified in immune-mediated ataxia in patients with gluten sensitivity. These findings suggest a critical role for TG6 in cortical and cerebellar neurons. PMID:21984379

  7. Invasion of the Central Nervous System by Cryptococcus neoformans Requires a Secreted Fungal Metalloprotease

    PubMed Central

    Vu, Kiem; Tham, Rick; Uhrig, John P.; Thompson, George R.; Na Pombejra, Sarisa; Jamklang, Mantana; Bautos, Jennifer M.

    2014-01-01

    ABSTRACT Cryptococcus spp. cause life-threatening fungal infection of the central nervous system (CNS), predominantly in patients with a compromised immune system. Why Cryptococcus neoformans has this remarkable tropism for the CNS is not clear. Recent research on cerebral pathogenesis of C. neoformans revealed a predominantly transcellular migration of cryptococci across the brain endothelium; however, the identities of key fungal virulence factors that function specifically to invade the CNS remain unresolved. Here we found that a novel, secreted metalloprotease (Mpr1) that we identified in the extracellular proteome of C. neoformans (CnMpr1) is required for establishing fungal disease in the CNS. Mpr1 belongs to a poorly characterized M36 class of fungalysins that are expressed in only some fungal species. A strain of C. neoformans lacking the gene encoding Mpr1 (mpr1Δ) failed to breach the endothelium in an in vitro model of the human blood-brain barrier (BBB). A mammalian host infected with the mpr1Δ null strain demonstrated significant improvement in survival due to a reduced brain fungal burden and lacked the brain pathology commonly associated with cryptococcal disease. The in vivo studies further indicate that Mpr1 is not required for fungal dissemination and Mpr1 likely targets the brain endothelium specifically. Remarkably, the sole expression of CnMPR1 in Saccharomyces cerevisiae resulted in a robust migration of yeast cells across the brain endothelium, demonstrating Mpr1’s specific activity in breaching the BBB and suggesting that Mpr1 may function independently of the hyaluronic acid-CD44 pathway. This distinct role for Mpr1 may develop into innovative treatment options and facilitate a brain-specific drug delivery platform. PMID:24895304

  8. Toll-6 and Toll-7 function as neurotrophin receptors in the Drosophila central nervous system

    PubMed Central

    McIlroy, Graham; Foldi, Istvan; Aurikko, Jukka; Wentzell, Jill S.; Lim, Mei Ann; Fenton, Janine C.; Gay, Nicholas J.; Hidalgo, Alicia

    2015-01-01

    Neurotrophin receptors corresponding to vertebrate Trk, p75NTR or Sortilin have not been identified in Drosophila, thus it is unknown how neurotrophism may be implemented in insects. Two Drosophila neurotrophins, DNT1 and DNT2, have nervous system functions, but their receptors are unknown. The Toll receptor superfamily has ancient evolutionary origins and a universal function in innate immunity. Here we show that Toll paralogues unrelated to the mammalian neurotrophin receptors function as neurotrophin receptors in fruit-flies. Toll-6 and Toll-7 are expressed in the central nervous system throughout development, and regulate locomotion, motoraxon targeting and neuronal survival. DNT1 and 2 interact genetically with Toll-6 and 7, bind to Toll-7 and 6 promiscuously, and are distributed in vivo in complementary or overlapping domains. We conclude that in fruit-flies, Tolls are not only involved in development and immunity but also in neurotrophism, revealing an unforeseen relationship between the neurotrophin and Toll protein families. PMID:23892553

  9. Leishmania amastigotes in the central nervous system of a naturally infected dog.

    PubMed

    Márquez, Merce; Pedregosa, José Raúl; López, Jesús; Marco-Salazar, Paola; Fondevila, Dolors; Pumarola, Martí

    2013-01-01

    A 4-year-old male Labrador Retriever dog was presented with a 10-day history of tetraplegia, depression, and absent postural reflexes. The cerebrospinal fluid was positive for Leishmania spp. DNA. At necropsy, a 2-cm long mass was observed adhered to C(7) and C(8) left spinal nerves. Microscopically, nerve fiber destruction together with mixed inflammatory infiltration was observed in the spinal nerves. Cervical spinal cord sections showed multifocal, diffuse granulomatous inflammation in the white matter. In the brain, perivascular infiltrates were observed in some areas together with subtle pallor of the parenchyma. Immunohistochemistry for Leishmania infantum confirmed the presence of amastigotes in the spinal nerves, spinal cord, brain parenchyma, and choroid plexuses. The current study describes the presence of Leishmania amastigotes in nervous tissue inciting radiculoneuritis, myelitis, and mild meningoencephalitis, suggesting a likely route by which L. infantum amastigotes reach and affect the central nervous system parenchyma. PMID:23166183

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

    PubMed Central

    El-Tahir, Heba M; Dietz, Frank; Dringen, Ralf; Schwabe, Kerstin; Strenge, Karen; Kelm, Sørge; Abouzied, Mekky M; Gieselmann, Volkmar; Franken, Sebastian

    2006-01-01

    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. PMID:16430771

  11. Integrating in Silico and in Vitro Approaches To Predict Drug Accessibility to the Central Nervous System.

    PubMed

    Zhang, Yan-Yan; Liu, Houfu; Summerfield, Scott G; Luscombe, Christopher N; Sahi, Jasminder

    2016-05-01

    Estimation of uptake across the blood-brain barrier (BBB) is key to designing central nervous system (CNS) therapeutics. In silico approaches ranging from physicochemical rules to quantitative structure-activity relationship (QSAR) models are utilized to predict potential for CNS penetration of new chemical entities. However, there are still gaps in our knowledge of (1) the relationship between marketed human drug derived CNS-accessible chemical space and preclinical neuropharmacokinetic (neuroPK) data, (2) interpretability of the selected physicochemical descriptors, and (3) correlation of the in vitro human P-glycoprotein (P-gp) efflux ratio (ER) and in vivo rodent unbound brain-to-blood ratio (Kp,uu), as these are assays routinely used to predict clinical CNS exposure, during drug discovery. To close these gaps, we explored the CNS druglike property boundaries of 920 market oral drugs (315 CNS and 605 non-CNS) and 846 compounds (54 CNS drugs and 792 proprietary GlaxoSmithKline compounds) with available rat Kp,uu data. The exact permeability coefficient (Pexact) and P-gp ER were determined for 176 compounds from the rat Kp,uu data set. Receiver operating characteristic curves were performed to evaluate the predictive power of human P-gp ER for rat Kp,uu. Our data demonstrates that simple physicochemical rules (most acidic pKa ≥ 9.5 and TPSA < 100) in combination with P-gp ER < 1.5 provide mechanistic insights for filtering BBB permeable compounds. For comparison, six classification modeling methods were investigated using multiple sets of in silico molecular descriptors. We present a random forest model with excellent predictive power (∼0.75 overall accuracy) using the rat neuroPK data set. We also observed good concordance between the structural interpretation results and physicochemical descriptor importance from the Kp,uu classification QSAR model. In summary, we propose a novel, hybrid in silico/in vitro approach and an in silico screening model for the

  12. Experimental treatment of Epstein-Barr virus-associated primary central nervous system lymphoma.

    PubMed

    Roychowdhury, Sameek; Peng, Ruoqi; Baiocchi, Robert A; Bhatt, Darshna; Vourganti, Srinivas; Grecula, John; Gupta, Nilendu; Eisenbeis, Charles F; Nuovo, Gerard J; Yang, Weilian; Schmalbrock, Petra; Ferketich, Amy; Moeschberger, Melvin; Porcu, Pierluigi; Barth, Rolf F; Caligiuri, Michael A

    2003-03-01

    Primary central nervous system lymphoma (PCNSL) that arises in immune-deficient patients is an aggressive B-cell neoplasm that is universally associated with the EBV. Patients with EBV(+) PCNSL face a particularly poor prognosis with median survival times of 2-12 months despite aggressive management with radiation therapy. We have developed a preclinical model of EBV(+) PCNSL to explore strategies that specifically target EBV-infected B lymphoblasts in vivo. Stereotactic implantation of EBV-transformed human lymphoblastoid B-cell lines into the caudate nucleus of the nude rat resulted in lethal CNS tumor burden manifested by the onset of focal neurological symptoms within 21 days. Histological evaluation at autopsy revealed a multifocal, perivascular human EBV(+) lymphoblastic B-cell infiltrate that displayed a latency type III EBV gene expression profile similar to PCNSL that develops in some immune-deficient patients. Radiation (1600 cGy) of lymphoblastoid B-cell lines resulted in up-regulation of the EBV thymidine kinase (EBV-TK) transcript and sensitization of these cells to drug-induced apoptosis using nucleoside analogs. Enhanced expression of EBV-TK mRNA in EBV(+) PCNSL tumors by radiation therapy occurred in a dose-dependent fashion. In vivo trials using the nude rat PCNSL model demonstrated significantly improved mean survival time (MST) with single fraction whole-brain radiotherapy (WBRT) and antiviral therapy consisting of zidovudine (AZT) and ganciclovir (GCV; MST 41.3 +/- 3.3 days; P = 0.05), compared with either antiviral therapy (MST 32.1 +/- 1.1 days) or WBRT alone (MST 22 +/- 0.8 days). We found constitutive and abundant EBV-TK mRNA expression in a stereotactic core biopsy specimen from a solid organ transplant patient with EBV(+) PCNSL. Withdrawal of immunosuppression did not result in disease regression. This patient achieved a complete response after therapy with high-dose AZT and GCV in the absence of WBRT, and remains in remission on oral

  13. The therapeutic potential of sigma (σ) receptors for the treatment of central nervous system diseases: evaluation of the evidence.

    PubMed

    Banister, Samuel D; Kassiou, Michael

    2012-01-01

    Since their proposal in 1976, sigma (σ) receptors have been increasingly implicated in the pathophysiology of virtually all major central nervous system (CNS) disorders, including anxiety, depression, schizophrenia, and drug addiction. Due to their involvement in motor function and higher cognitive function,σ receptors have also been implicated in movement disorders (such as Parkinson's disease) and memory deficits (including Alzheimer's disease). In most cases the precise mechanism(s) linking σ receptors to CNS disease are unknown or yet to be fully elucidated. However, many σ ligands have shown promise in pharmacological studies and animal models of the aforementioned diseases, and some have entered clinical trials. This review will assess the validity of receptors as a target for various CNS diseases based on evidence from animal models of human diseases, preclinical studies in humans, and full clinical trials. PMID:22288410

  14. Intracerebroventricular enzyme infusion corrects central nervous system pathology and dysfunction in a mouse model of metachromatic leukodystrophy.

    PubMed

    Stroobants, Stijn; Gerlach, Debora; Matthes, Frank; Hartmann, Dieter; Fogh, Jens; Gieselmann, Volkmar; D'Hooge, Rudi; Matzner, Ulrich

    2011-07-15

    Arylsulfatase A (ASA) catalyzes the desulfation of sulfatide, a major lipid component of myelin. Inherited functional deficiencies of ASA cause the lysosomal storage disease (LSD) metachromatic leukodystrophy (MLD), which is characterized by intralysosomal accumulation of sulfatide, progressive neurological symptoms and early death. Enzyme replacement therapy (ERT) using intravenous injection of active enzyme is a treatment option for many LSDs as exogenous lysosomal enzymes are delivered to lysosomes of patient's cells via receptor-mediated endocytosis. Efficient treatment of MLD and other LSDs with central nervous system (CNS) involvement is, however, hampered by the blood-brain barrier (BBB), which limits transfer of therapeutic enzymes from the circulation to the brain parenchyma. To bypass the BBB, we infused recombinant human ASA (rhASA) by implanted miniature pumps into the cerebrospinal fluid (CSF) of a conventional and a novel, genetically aggravated ASA knockout mouse model of MLD. rhASA continuously delivered to the lateral ventricle for 4 weeks penetrated the brain parenchyma and was targeted to the lysosomes of brain cells. Histological analysis revealed complete reversal of lysosomal storage in the infused hemisphere. rhASA concentrations and sulfatide clearance declined with increasing distance from the infusion site. Correction of the ataxic gait indicated reversal of central nervous system dysfunctions. The profound histopathological and functional improvements, the requirement of low enzyme doses and the absence of immunological side effects suggest intracerebroventricular ERT to be a promising treatment option for MLD and other LSDs with prevailing CNS disease. PMID:21515587

  15. The transcobalamin receptor knockout mouse: a model for vitamin B12 deficiency in the central nervous system

    PubMed Central

    Lai, Shao-Chiang; Nakayama, Yasumi; Sequeira, Jeffrey M.; Wlodarczyk, Bogdan J.; Cabrera, Robert M.; Finnell, Richard H.; Bottiglieri, Teodoro; Quadros, Edward V.

    2013-01-01

    The membrane receptor (TCblR/CD320) for transcobalamin (TC)-bound cobalamin (Cbl) facilitates the cellular uptake of Cbl. A genetically modified mouse model involving ablation of the CD320 gene was generated to study the effects on cobalamin homeostasis. The nonlethal nature of this knockout and the lack of systemic cobalamin deficiency point to other mechanisms for cellular Cbl uptake in the mouse. However, severe cobalamin depletion in the central nervous system (CNS) after birth (P<0.01) indicates that TCblR is the only receptor responsible for Cbl uptake in the CNS. Metabolic Cbl deficiency in the brain was evident from the increased methylmalonic acid (P<0.01–0.04), homocysteine (P<0.01), cystathionine (P<0.01), and the decreased S-adenosylmethionine/S-adenosyl homocysteine ratio (P<0.01). The CNS pathology of Cbl deficiency seen in humans may not manifest in this mouse model; however, it does provide a model with which to evaluate metabolic pathways and genes affected.—Lai, S.-C., Nakayama, Y., Sequeira, J. M., Wlodarczyk, B. J., Cabrera, R. M., Finnell, R. H., Bottiglieri, T., Quadros, E. V. The transcobalamin receptor knockout mouse: a model for vitamin B12 deficiency in the central nervous system. PMID:23430977

  16. Serotonin 5-HT7 receptor agents: structure-activity relationships and potential therapeutic applications in central nervous system disorders

    PubMed Central

    Leopoldo, Marcello; Lacivita, Enza; Berardi, Francesco; Perrone, Roberto; Hedlund, Peter B.

    2010-01-01

    Since its discovery in the 1940s in serum, the mammalian intestinal mucosa, and in the central nervous system, serotonin (5-HT) has been shown to be involved in virtually all cognitive and behavioral human functions, and alterations in its neurochemistry have been implicated in the etiology of a plethora of neuropsychiatric disorders. The cloning of 5-HT receptor subtypes has been of importance in enabling them to be classified as specific protein molecules encoded by specific genes. The 5-HT7 receptor is the most recently classified member of the serotonin receptor family. Since its identification, it has been the subject of intense research efforts driven by its presence in functionally relevant regions of the brain. The availability of some selective antagonists and agonists, in combination with genetically modified mice lacking the 5-HT7 receptor, has allowed for a better understanding of the pathophysiological role of this receptor. This paper reviews data on localization and pharmacological properties of the 5-HT7 receptor, and summarizes the results of structure-activity relationship studies aimed at the discovery of selective 5-HT7 receptor ligands. Additionally, an overview of the potential therapeutic applications of 5-HT7 receptor agonists and antagonists in central nervous system disorders is presented. PMID:20923682

  17. Self-assembling peptide nanofiber hydrogels for central nervous system regeneration

    NASA Astrophysics Data System (ADS)

    Liu, Xi; Pi, Bin; Wang, Hui; Wang, Xiu-Mei

    2015-03-01

    Central nervous system (CNS) presents a complex regeneration problem due to the inability of central neurons to regenerate correct axonal and dendritic connections. However, recent advances in developmental neurobiology, cell signaling, cell-matrix interaction, and biomaterials technologies have forced a reconsideration of CNS regeneration potentials from the viewpoint of tissue engineering and regenerative medicine. The applications of a novel tissue regeneration-inducing biomaterial and stem cells are thought to be critical for the mission. The use of peptide nanofiber hydrogels in cell therapy and tissue engineering offers promising perspectives for CNS regeneration. Self-assembling peptide undergo a rapid transformation from liquid to gel upon addition of counterions or pH adjustment, directly integrating with the host tissue. The peptide nanofiber hydrogels have mechanical properties that closely match the native central nervous extracellular matrix, which could enhance axonal growth. Such materials can provide an optimal three dimensional microenvironment for encapsulated cells. These materials can also be tailored with bioactive motifs to modulate the wound environment and enhance regeneration. This review intends to detail the recent status of self-assembling peptide nanofiber hydrogels for CNS regeneration.

  18. The ultrastructure of prosternal sensory hair afferents within the locust central nervous system.

    PubMed

    Watson, A H; Pflüger, H J

    1984-01-01

    The sensory neurones innervating long prosternal hairs of Locusta migratorioides were backfilled with horseradish peroxidase through their dendrites. The neurones' central projections in and around the medial ventral tract were examined with electron microscopy. Most synapses occur on axon collaterals which ramify through the neuropile around the tract where both input and output synapses were observed. Serial sectioning methods were used to determine the relative distribution of inputs and outputs which often lie in close proximity to one another on the axon terminals. The prosternal hair terminals contain agranular synaptic vesicles approximately 37 nm in diameter. Surrounding unidentified neuropilar profiles contain vesicles which are either statistically indistinguishable in size, or are larger, 45 nm diameter agranular vesicles. Neurones which are pre- or postsynaptic to labelled terminals generally contain vesicles of the second type. Input synapses onto the central terminals of primary afferent neurones can be recognised as a widespread phenomenon in the nervous systems of both invertebrates and vertebrates which will allow a fine degree of control of sensory inflow into the central nervous system. PMID:6709188

  19. Central nervous system complications of sickle cell disease in children: an overview.

    PubMed

    Wang, Winfred C

    2007-03-01

    Complications involving the central nervous system are among the most devastating manifestations of sickle cell disease. Although overt stroke occurs in 1 in 10 children with Hemoglobin SS, "silent cerebral infarcts" are even more frequent. Both are associated with significant neuropsychological deficits. The end result of these effects on the CNS often is diminished school performance. The use of transcranial Doppler ultrasonography screening allows the identification of patients at high risk for clinical stroke as well as stroke prevention by chronic transfusion. However, definitive prophylaxis and treatment for most CNS complications of sickle cell disease have yet to be determined. PMID:17364568

  20. Femoral-facial syndrome with malformations in the central nervous system.

    PubMed

    Leal, Evelia; Macías-Gómez, Nelly; Rodríguez, Lisa; Mercado, F Miguel; Barros-Núñez, Patricio

    2003-01-01

    The femoral hypoplasia-unusual facies syndrome (FFS) is a very rare association of femoral and facial abnormalities. Maternal diabetes mellitus has been mainly involved as the causal agent. We report the second case of FFS with anomalies in the central nervous system (CNS) including corticosubcortical atrophy, colpocephaly, partial agenesis of corpus callosum, hypoplasia of the falx cerebri and absent septum pellucidum. The psychomotor development has been normal. We propose that the CNS defects observed in these patients are part of the spectrum of abnormalities in the FFS. PMID:12504316

  1. Disrupted in schizophrenia 1 and synaptic function in the mammalian central nervous system

    PubMed Central

    Randall, Andrew D; Kurihara, Mai; Brandon, Nicholas J; Brown, Jon T

    2014-01-01

    The disrupted in schizophrenia 1 (DISC1) gene is found at the breakpoint of an inherited chromosomal translocation, and segregates with major mental illnesses. Its potential role in central nervous system (CNS) malfunction has triggered intensive investigation of the biological roles played by DISC1, with the hope that this may shed new light on the pathobiology of psychiatric disease. Such work has ranged from investigations of animal behavior to detailed molecular-level analysis of the assemblies that DISC1 forms with other proteins. Here, we discuss the evidence for a role of DISC1 in synaptic function in the mammalian CNS. PMID:24712987

  2. Disrupted in schizophrenia 1 and synaptic function in the mammalian central nervous system.

    PubMed

    Randall, Andrew D; Kurihara, Mai; Brandon, Nicholas J; Brown, Jon T

    2014-04-01

    The disrupted in schizophrenia 1 (DISC1) gene is found at the breakpoint of an inherited chromosomal translocation, and segregates with major mental illnesses. Its potential role in central nervous system (CNS) malfunction has triggered intensive investigation of the biological roles played by DISC1, with the hope that this may shed new light on the pathobiology of psychiatric disease. Such work has ranged from investigations of animal behavior to detailed molecular-level analysis of the assemblies that DISC1 forms with other proteins. Here, we discuss the evidence for a role of DISC1 in synaptic function in the mammalian CNS. PMID:24712987

  3. Single neuron electroporation in manipulating and measuring the central nervous system

    PubMed Central

    2010-01-01

    The development and application of single neuron electroporation largely advanced the use of traditional genetics in investigations of the central nervous system. This quick and accurate manipulation of the brain at individual neuron level allowed the gain and loss of functional analyses of different genes and/or proteins. This manuscript reviewed the development of the technique and discussed some technical aspects in practical manipulations. Then the manuscript summarized the potential applications with this technique. Last but not least, the technique showed prospective future when combined with other modern methods in neuroscience research. PMID:21054865

  4. A Coumarin-Based Fluorescent Probe as a Central Nervous System Disease Biomarker

    PubMed Central

    Yap, Ann-Chee; Mahamad, Ummi Affah; Lim, Shen-Yang; Kim, Hae-Jo; Choo, Yeun-Mun

    2014-01-01

    Homocysteine and methylmalonic acid are important biomarkers for diseases associated with an impaired central nervous system (CNS). A new chemoassay utilizing coumarin-based fluorescent probe 1 to detect the levels of homocysteine is successfully implemented using Parkinson's disease (PD) patients' blood serum. In addition, a rapid identification of homocysteine and methylmalonic acid levels in blood serum of PD patients was also performed using the liquid chromatography-mass spectrometry (LC-MS). The results obtained from both analyses were in agreement. The new chemoassay utilizing coumarin-based fluorescent probe 1 offers a cost- and time-effective method to identify the biomarkers in CNS patients. PMID:25390405

  5. Meeting report: primary central nervous system lymphoma: standards of care and future perspectives.

    PubMed

    Herrlinger, Ulrich; Korfel, Agnieszka; Hebart, Holger; Schlegel, Uwe; Plasswilm, Ludwig; Illerhaus, Gerald; Finke, Jürgen; Krüger, William; Montemurro, Michael; Wolf, Timo; Thiel, Eckhart; Bamberg, Michael; Weller, Michael; Kanz, Lothar

    2005-02-01

    A standard of care for patients with primary central nervous system lymphoma (PCNSL) has not been defined. Current controversies concern, amongst others, the role, dose and timing of radiotherapy, the role of intrathecal chemotherapy and the delineation of age-specific standards of care. Given the strong clinical trial activities for PCNSL in Germany, the PCNSL conference held in Tubingen aimed at comparing the diverging trial strategies in Germany and at exploring the options for joint activities of the various PCNSL study groups in the near future. PMID:15692223

  6. L-serine synthesis in the central nervous system: a review on serine deficiency disorders.

    PubMed

    Tabatabaie, L; Klomp, L W; Berger, R; de Koning, T J

    2010-03-01

    The de novo synthesis of the amino acid L-serine plays an essential role in the development and functioning of the central nervous system (CNS). L-serine displays many metabolic functions during different developmental stages; among its functions providing precursors for amino acids, protein synthesis, nucleotide synthesis, neurotransmitter synthesis and L-serine derived lipids. Patients with congenital defects in the L-serine synthesizing enzymes present with severe neurological abnormalities and underscore the importance of this synthetic pathway. In this review, we will discuss the cellular functions of the L-serine pathway, structure and enzymatic properties of the enzymes involved and genetic defects associated with this pathway. PMID:19963421

  7. Late Isolated Central Nervous System Relapse from Ovarian Serous Adenocarcinoma: A Case Report and Literature Review

    PubMed Central

    de Castria, Tiago Biachi; Rodrigues, Sylvia Regina Quintanilha; Diz, Maria del Pilar Estevez

    2014-01-01

    Central nervous system involvement by ovarian serous adenocarcinoma is rare. We report a case of a 60-year-old woman that developed brain metastasis as isolated site of relapse 4.5 years after a complete resection and adjuvant chemotherapy for a stage Ic disease. She proceeded to a craniotomy with resection of the lesion and, subsequently, to a whole brain radiotherapy. Nineteen months later, she developed carcinomatous meningitis as isolated site of recurrence. Patient was submitted to intrathecal chemotherapy with methotrexate; however, she died from progressive neurologic involvement disease few weeks later. PMID:25506007

  8. Primary central nervous system T-cell lymphoma in a common dolphin (Delphinus delphis).

    PubMed

    Arbelo, M; Espinosa de los Monteros, A; Herráez, P; Suárez-Bonnet, A; Andrada, M; Rivero, M; Grau-Bassas, E R; Fernández, A

    2014-01-01

    This report describes the pathological findings in an adult female short-beaked common dolphin (Delphinus delphis) stranded alive in the Canary Islands. Necropsy examination revealed the presence of a nodular neoplastic growth in the central nervous system (CNS) at the level of the thalamus. Microscopical examination revealed the mass to be a lymphoma and immunohistochemical labelling demonstrated a T-cell origin. No significant lesions were observed in other organs, including lymphoid organs. This is the first report of a primary T-cell lymphoma in the CNS in cetaceans. PMID:24650893

  9. A case of relapsing-remitting tumour-like inflammation of the central nervous system.

    PubMed

    Miante, Silvia; Perini, Paola; Rinaldi, Francesca; Gallo, Paolo

    2015-11-01

    The case of a 37-year-old woman suffering from a relapsing-remitting tumefactive inflammatory disease of the central nervous system (CNS) is described. The patient had four severe relapses over eight years, and was treated with steroids, immunosuppression and plasma-exchange with modest benefit. No magnetic resonance imaging or cerebrospinal spinal fluid findings suggestive of multiple sclerosis emerged during the eight-year follow-up. 'Relapsing-remitting tumefactive inflammation' seems to have the features of a distinct inflammatory CNS disease. PMID:26362889

  10. Osteodysplastic primordial dwarfism type II with normal intellect but delayed central nervous system myelination.

    PubMed

    Halder, A; Pahi, J; Sharma, A K; Bhatia, V L; Phadke, R V; Gujral, R; Agarwal, S S

    1998-10-30

    We describe a 7-year-boy with severe prenatal and postnatal growth retardation, skeletal changes, normal intellect, and unusual facial appearance. The skeletal changes are suggestive of osteodysplastic primordial dwarfism type II (OPD II). He is the first patient of this kind from the Indian subcontinent and the 18th to be reported, based on a literature search (MEDLINE; 1982 to April 1997). He also represents the first case of OPD-II with normal intellect but delayed central nervous system myelination. PMID:9800906

  11. Efficient reactivation of latent herpes simplex virus from mouse central nervous system tissues.

    PubMed

    Chen, Shih-Heng; Yao, Hui-Wen; Huang, Wen-Yen; Hsu, Kuei-Sen; Lei, Huan-Yao; Shiau, Ai-Li; Chen, Shun-Hua

    2006-12-01

    For decades, numerous ex vivo studies have documented that latent herpes simplex virus (HSV) reactivates efficiently from ganglia, but rarely from the central nervous systems (CNS), of mice when assayed by mincing tissues before explant culture, despite the presence of viral genomes in both sites. Here we show that 88% of mouse brain stems reactivated latent virus when they were dissociated into cell suspensions before ex vivo explant culture. The efficient reactivation of HSV from the mouse CNS was demonstrated with more than one viral strain, viral serotype, and mouse strain, further indicating that the CNS can be an authentic latency site for HSV with the potential to cause recurrent disease. PMID:17005636

  12. Making sense of central nervous system infections at the reference desk.

    PubMed

    Fikar, Charles R

    2004-01-01

    This paper discusses concepts and terminology of some aspects of infections of the central nervous system as it relates to medical reference work. Details of anatomic, biochemical, and pathologic processes are not discussed. Specific terminology involved in this area will be reviewed in order to help ensure a good approach to developing prudent strategies for database searching of the medical literature. MeSH thesauri terms are discussed and text word synonyms are presented that provide tools for thorough searching techniques. Commonly used medical jargon for this area is also explained. Examples of specific search strategies are illustrated. PMID:15364650

  13. Central Nervous System Tuberculosis: An Imaging-Focused Review of a Reemerging Disease

    PubMed Central

    Sanei Taheri, Morteza; Karimi, Mohammad Ali; Haghighatkhah, Hamidreza; Samadian, Mohammad; Delavar Kasmaei, Hosein

    2015-01-01

    Central nervous system (CNS) tuberculosis is a potentially life threatening condition which is curable if the correct diagnosis is made in the early stages. Its clinical and radiologic manifestations may mimic other infectious and noninfectious neurological conditions. Hence, familiarity with the imaging presentations of various forms of CNS tuberculosis is essential in timely diagnosis, and thereby reducing the morbidity and mortality of this disease. In this review, we describe the imaging characteristics of the different forms of CNS tuberculosis, including meningitis, tuberculoma, miliary tuberculosis, abscess, cerebritis, and encephalopathy. PMID:25653877

  14. Central nervous system tuberculosis: an imaging-focused review of a reemerging disease.

    PubMed

    Sanei Taheri, Morteza; Karimi, Mohammad Ali; Haghighatkhah, Hamidreza; Pourghorban, Ramin; Samadian, Mohammad; Delavar Kasmaei, Hosein

    2015-01-01

    Central nervous system (CNS) tuberculosis is a potentially life threatening condition which is curable if the correct diagnosis is made in the early stages. Its clinical and radiologic manifestations may mimic other infectious and noninfectious neurological conditions. Hence, familiarity with the imaging presentations of various forms of CNS tuberculosis is essential in timely diagnosis, and thereby reducing the morbidity and mortality of this disease. In this review, we describe the imaging characteristics of the different forms of CNS tuberculosis, including meningitis, tuberculoma, miliary tuberculosis, abscess, cerebritis, and encephalopathy. PMID:25653877

  15. Gene delivery systems for gene therapy in tissue engineering and central nervous system applications.

    PubMed

    Giordano, C; Causa, F; Bianco, F; Perale, G; Netti, P A; Ambrosio, L; Cigada, A

    2008-12-01

    The present review aims to describe the potential applications of gene delivery systems to tissue engineering and central nervous system diseases. Some key experimental work has been done with interesting results, but the subject is far from being fully explored. The combined approach of gene therapy and material science has a huge potential to improve the therapeutic approaches now available for a wide range of medical applications. Focus is given to this multidisciplinary strategy in neurodegenerative pathologies, where the use of polymeric matrices as gene carriers might make a crucial difference. PMID:19115193

  16. Immunotherapy for cancer in the central nervous system: Current and future directions

    PubMed Central

    Binder, David C.; Davis, Andrew A.; Wainwright, Derek A.

    2016-01-01

    ABSTRACT Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults and still remains incurable. Although immunotherapeutic vaccination against GBM has demonstrated immune-stimulating activity with some promising survival benefits, tumor relapse is common, highlighting the need for additional and/or combinatorial approaches. Recently, antibodies targeting immune checkpoints were demonstrated to generate impressive clinical responses against advanced melanoma and other malignancies, in addition to showing potential for enhancing vaccination and radiotherapy (RT). Here, we summarize the current knowledge of central nervous system (CNS) immunosuppression, evaluate past and current immunotherapeutic trials and discuss promising future immunotherapeutic directions to treat CNS-localized malignancies. PMID:27057463

  17. Acid-Sensing Ion Channels as Potential Pharmacological Targets in Peripheral and Central Nervous System Diseases.

    PubMed

    Radu, Beatrice Mihaela; Banciu, Adela; Banciu, Daniel Dumitru; Radu, Mihai

    2016-01-01

    Acid-sensing ion channels (ASICs) are widely expressed in the body and represent good sensors for detecting protons. The pH drop in the nervous system is equivalent to ischemia and acidosis, and ASICs are very good detectors in discriminating slight changes in acidity. ASICs are important pharmacological targets being involved in a variety of pathophysiological processes affecting both the peripheral nervous system (e.g., peripheral pain, diabetic neuropathy) and the central nervous system (e.g., stroke, epilepsy, migraine, anxiety, fear, depression, neurodegenerative diseases, etc.). This review discusses the role played by ASICs in different pathologies and the pharmacological agents acting on ASICs that might represent promising drugs. As the majority of above-mentioned pathologies involve not only neuronal dysfunctions but also microvascular alterations, in the next future, ASICs may be also considered as potential pharmacological targets at the vasculature level. Perspectives and limitations in the use of ASICs antagonists and modulators as pharmaceutical agents are also discussed. PMID:26920689

  18. Central nervous system of Rhipicephalus sanguineus ticks (Acari: Ixodidae): an ultrastructural study.

    PubMed

    Roma, Gislaine Cristina; Nunes, Pablo Henrique; de Oliveira, Patrícia Rosa; Remédio, Rafael Neodini; Bechara, Gervásio Henrique; Camargo-Mathias, Maria Izabel

    2012-09-01

    This study performed the ultrastructural description of the synganglion of Rhipicephalus sanguineus males and females, aiming to contribute to the understanding of the cellular organization of this organ. The results show that the central nervous system of these individuals consists of a mass of fused nerves, named synganglion, from where nerves emerge towards several parts of the body. It is surrounded by the neural lamella, a uniform and acellular layer, constituted by repeated layers of homogeneous and finely granular material. The perineurium is just below, composed of glial cells, which extensions invaginate throughout the nervous tissue. The synganglion is internally divided into an outer cortex, which contains the cellular bodies of the neural cells and an inner neuropile. The neural cells can be classified into two types according to cell size, cytoplasm-nucleus relation, and neurosecretory activity. Type I cells are oval or spherical and present a large nucleus occupying most part of the cytoplasm, which contains few organelles. Type 2 cells are polygonal, present a great cytoplasm volume, and their nuclei are located in the cell periphery. The cytoplasm of these cells contains a well-developed rough endoplasmic reticulum, Golgi regions, mitochondria, and several neurosecretory granules. The subperineurium and the tracheal ramifications are found between the cortex and the neuropile. The latter is formed mainly by neural fibers, tracheal elements, and glial cells. The results obtained show that R. sanguineus males' and females' nervous tissue present an ultrastructural organization similar to the one described in the literature for other tick species. PMID:22610445

  19. Voluntary activation of the sympathetic nervous system and attenuation of the innate immune response in humans.

    PubMed

    Kox, Matthijs; van Eijk, Lucas T; Zwaag, Jelle; van den Wildenberg, Joanne; Sweep, Fred C G J; van der Hoeven, Johannes G; Pickkers, Peter

    2014-05-20

    Excessive or persistent proinflammatory cytokine production plays a central role in autoimmune diseases. Acute activation of the sympathetic nervous system attenuates the innate immune response. However, both the autonomic nervous system and innate immune system are regarded as systems that cannot be voluntarily influenced. Herein, we evaluated the effects of a training program on the autonomic nervous system and innate immune response. Healthy volunteers were randomized to either the intervention (n = 12) or control group (n = 12). Subjects in the intervention group were trained for 10 d in meditation (third eye meditation), breathing techniques (i.a., cyclic hyperventilation followed by breath retention), and exposure to cold (i.a., immersions in ice cold water). The control group was not trained. Subsequently, all subjects underwent experimental endotoxemia (i.v. administration of 2 ng/kg Escherichia coli endotoxin). In the intervention group, practicing the learned techniques resulted in intermittent respiratory alkalosis and hypoxia resulting in profoundly increased plasma epinephrine levels. In the intervention group, plasma levels of the anti-inflammatory cytokine IL-10 increased more rapidly after endotoxin administration, correlated strongly with preceding epinephrine levels, and were higher. Levels of proinflammatory mediators TNF-α, IL-6, and IL-8 were lower in the intervention group and correlated negatively with IL-10 levels. Finally, flu-like symptoms were lower in the intervention group. In conclusion, we demonstrate that voluntary activation of the sympathetic nervous system results in epinephrine release and subsequent suppression of the innate immune response in humans in vivo. These results could have important implications for the treatment of conditions associated with excessive or persistent inflammation, such as autoimmune diseases. PMID:24799686

  20. The Isotropic Fractionator as a Tool for Quantitative Analysis in Central Nervous System Diseases.

    PubMed

    Repetto, Ivan E; Monti, Riccardo; Tropiano, Marta; Tomasi, Simone; Arbini, Alessia; Andrade-Moraes, Carlos-Humberto; Lent, Roberto; Vercelli, Alessandro

    2016-01-01

    One major aim in quantitative and translational neuroscience is to achieve a precise and fast neuronal counting method to work on high throughput scale to obtain reliable results. Here, we tested the isotropic fractionator (IF) method for evaluating neuronal and non-neuronal cell loss in different models of central nervous system (CNS) pathologies. Sprague-Dawley rats underwent: (i) ischemic brain damage; (ii) intraperitoneal injection with kainic acid (KA) to induce epileptic seizures; and (iii) monolateral striatal injection with quinolinic acid (QA) mimicking human Huntington's disease. All specimens were processed for IF method and cell loss assessed. Hippocampus from KA-treated rats and striatum from QA-treated rats were carefully dissected using a dissection microscope and a rat brain matrix. Ischemic rat brains slices were first processed for TTC staining and then for IF. In the ischemic group the cell loss corresponded to the neuronal loss suggesting that hypoxia primarily affects neurons. Combining IF with TTC staining we could correlate the volume of lesion to the neuronal loss; by IF, we could assess that neuronal loss also occurs contralaterally to the ischemic side. In the epileptic group we observed a reduction of neuronal cells in treated rats, but also evaluated the changes in the number of non-neuronal cells in response to the hippocampal damage. In the QA model, there was a robust reduction of neuronal cells on ipsilateral striatum. This neuronal cell loss was not related to a drastic change in the total number of cells, being overcome by the increase in non-neuronal cells, thus suggesting that excitotoxic damage in the striatum strongly activates inflammation and glial proliferation. We concluded that the IF method could represent a simple and reliable quantitative technique to evaluate the effects of experimental lesions mimicking human diseases, and to consider the neuroprotective/anti-inflammatory effects of different treatments in the whole

  1. The Isotropic Fractionator as a Tool for Quantitative Analysis in Central Nervous System Diseases

    PubMed Central

    Repetto, Ivan E.; Monti, Riccardo; Tropiano, Marta; Tomasi, Simone; Arbini, Alessia; Andrade-Moraes, Carlos-Humberto; Lent, Roberto; Vercelli, Alessandro

    2016-01-01

    One major aim in quantitative and translational neuroscience is to achieve a precise and fast neuronal counting method to work on high throughput scale to obtain reliable results. Here, we tested the isotropic fractionator (IF) method for evaluating neuronal and non-neuronal cell loss in different models of central nervous system (CNS) pathologies. Sprague-Dawley rats underwent: (i) ischemic brain damage; (ii) intraperitoneal injection with kainic acid (KA) to induce epileptic seizures; and (iii) monolateral striatal injection with quinolinic acid (QA) mimicking human Huntington’s disease. All specimens were processed for IF method and cell loss assessed. Hippocampus from KA-treated rats and striatum from QA-treated rats were carefully dissected using a dissection microscope and a rat brain matrix. Ischemic rat brains slices were first processed for TTC staining and then for IF. In the ischemic group the cell loss corresponded to the neuronal loss suggesting that hypoxia primarily affects neurons. Combining IF with TTC staining we could correlate the volume of lesion to the neuronal loss; by IF, we could assess that neuronal loss also occurs contralaterally to the ischemic side. In the epileptic group we observed a reduction of neuronal cells in treated rats, but also evaluated the changes in the number of non-neuronal cells in response to the hippocampal damage. In the QA model, there was a robust reduction of neuronal cells on ipsilateral striatum. This neuronal cell loss was not related to a drastic change in the total number of cells, being overcome by the increase in non-neuronal cells, thus suggesting that excitotoxic damage in the striatum strongly activates inflammation and glial proliferation. We concluded that the IF method could represent a simple and reliable quantitative technique to evaluate the effects of experimental lesions mimicking human diseases, and to consider the neuroprotective/anti-inflammatory effects of different treatments in the whole

  2. The Human Sympathetic Nervous System Response to Spaceflight

    NASA Technical Reports Server (NTRS)

    Ertl, Andrew C.; Diedrich, Andre; Paranjape, Sachin Y.; Biaggioni, Italo; Robertson, Rose Marie; Lane, Lynda D.; Shiavi, Richard; Robertson, David

    2003-01-01

    The sympathetic nervous system is an important part of the autonomic (or automatic) nervous system. When an individual stands up, the sympathetic nervous system speeds the heart and constricts blood vessels to prevent a drop in blood pressure. A significant number of astronauts experience a drop in blood pressure when standing for prolonged periods after they return from spaceflight. Difficulty maintaining blood pressure with standing is also a daily problem for many patients. Indirect evidence available before the Neurolab mission suggested the problem in astronauts while in space might be due partially to reduced sympathetic nervous system activity. The purpose of this experiment was to identify whether sympathetic activity was reduced during spaceflight. Sympathetic nervous system activity can be determined in part by measuring heart rate, nerve activity going to blood vessels, and the release of the hormone norepinephrine into the blood. Norepinephrine is a neurotransmitter discharged from active sympathetic nerve terminals, so its rate of release can serve as a marker of sympathetic nervous system action. In addition to standard cardiovascular measurements (heart rate, blood pressure), we determined sympathetic nerve activity as well as norepinephrine release and clearance on four crewmembers on the Neurolab mission. Contrary to our expectation, the results demonstrated that the astronauts had mildly elevated resting sympathetic nervous system activity in space. Sympathetic nervous system responses to stresses that simulated the cardiovascular effects of standing (lower body negative pressure) were brisk both during and after spaceflight. We concluded that, in the astronauts tested, the activity and response of the sympathetic nervous system to cardiovascular stresses appeared intact and mildly elevated both during and after spaceflight. These changes returned to normal within a few days.

  3. On the morphology of the central nervous system in larval stages of Carcinus maenas L. (Decapoda, Brachyura)

    NASA Astrophysics Data System (ADS)

    Harzsch, S.; Dawirs, R. R.

    1993-02-01

    We investigated the morphology of the central nervous system throughout the larval development of Carcinus maenas. For that purpose single larvae were reared in the laboratory from hatching through metamorphosis. Complete series of whole mout semithin sections were obtained from individuals of all successive larval stages and analysed with a light microscope. Morphological feature and spatial arrangement of discernable neural cell clusters, fibre tracts and neuropile are described and compared with the adult pattern. We found that most of the morphological features characterizing the adult nervous system are already present in the zoea-1. Nevertheless, there are marked differences with respect to the arrangement of nerve cell bodies, organization of cerebral neuropile, and disposition of ganglia in the ventral nerve cord. It appears that complexity of the central nervous neuropile is selectively altered during postmetamorphotic development, probably reflecting adaptive changes of sensory-motor integration in response to behavioural maturation. In contrast, during larval development there was little change in the overall structural organization of the central nervous system despite some considerable growth. However, the transition from zoea-4 to megalopa brings about multiple fundamental changes in larval morphology and behavioural pattern. Since central nervous integration should properly adapt to the altered behavioural repertoire of the megalopa, it seems necessary to ask in which respect synaptic rearrangement might characterize development of the central nervous system.

  4. Central nervous control of energy and glucose balance: Focus on the central melanocortin system

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Studies have suggested that manipulations of the central melanocortin circuitry by pharmacological agents produce robust effects on the regulation of body weight and glucose homeostasis. In this review, we discuss recent findings from genetic mouse models that have further established the physiologi...

  5. PBAN/pyrokinin peptides in the central nervous system of the fire ant, Solenopsis invicta.

    PubMed

    Choi, Man-Yeon; Raina, Ashok; Vander Meer, Robert K

    2009-02-01

    The pyrokinin/pheromone-biosynthesis-activating neuropeptide (PBAN) family of peptides found in insects is characterized by a 5-amino-acid C-terminal sequence, FXPRLamide. The pentapeptide is the active core required for diverse physiological functions, including the stimulation of pheromone biosynthesis in female moths, muscle contraction, induction of embryonic diapause, melanization, acceleration of puparium formation, and termination of pupal diapause. We have used immunocytochemical techniques to demonstrate the presence of pyrokinin/PBAN-like peptides in the central nervous system of the fire ant, Solenopsis invicta. Polyclonal antisera against the C-terminal end of PBAN have revealed the location of the peptide-producing cell bodies and axons in the central nervous system. Immunoreactive material is detectable in at least three groups of neurons in the subesophageal ganglion and corpora cardiaca of all adult sexual forms. The ventral nerve cord of adults consists of two segmented thoracic ganglia and four segmented abdominal ganglia. Two immunoreactive pairs of neurons are present in the thoracic ganglia, and three neuron pairs in each of the first three abdominal ganglia. The terminal abdominal ganglion has no immunoreactive neurons. PBAN immunoreactive material found in abdominal neurons appears to be projected to perisympathetic organs connected to the abdominal ganglia. These results indicate that the fire ant nervous system contains pyrokinin/PBAN-like peptides, and that these peptides are released into the hemolymph. In support of our immunocytochemical results, significant pheromonotropic activity is found in fire ant brain-subesophageal ganglion extracts from all adult fire ant forms (queens, female and male alates, and workers) when extracts are injected into decapitated females of Helicoverpa zea. This is the first demonstration of the presence of pyrokinin/PBAN-like peptides and pheromonotropic activity in an ant species. PMID:19002499

  6. Yeast central nervous system infection in a critically ill patient: a case report

    PubMed Central

    2014-01-01

    Introduction Invasive fungal infections are alarmingly common in intensive care unit patients; invasive fungal infections are associated with increased morbidity and mortality. Risk factors are the increased use of indwelling central venous catheters, the use of broad spectrum antibiotics, parenteral nutrition, renal replacement therapy and immunosuppression. Diagnosis of these infections might be complicated, requiring tissue cultures. In addition, therapy of invasive fungal infections might be difficult, given the rising resistance of fungi to antifungal agents. Case presentation We describe the case of a 28-year-old Greek man with yeast central nervous system infection. Conclusions Difficult-to-treat fungal infections may complicate the clinical course of critically ill patients and render their prognosis unfavorable. This report presents a case that was rare and difficult to treat, along with a thorough review of the investigation and treatment of these kinds of fungal infections in critically ill patients. PMID:25026870

  7. Novel Indications for Benzodiazepine Antagonist Flumazenil in GABA Mediated Pathological Conditions of the Central Nervous System.

    PubMed

    Hulse, Gary; Kelty, Erin; Hood, Sean; Norman, Amanda; Basso, Maria Rita; Reece, Albert Stuart

    2015-01-01

    This review paper discusses the central role of gamma-aminobutyric acid (GABA) in diverse physiological systems and functions and the therapeutic potential of the benzodiazepine antagonist flumazenil (Ro 15- 1788) for a wide range of disorders of the central nervous system (CNS). Our group and others have studied the potential of flumazenil as a treatment for benzodiazepine dependence. A small but growing body of research has indicated that flumazenil may also have clinical application in CNS disorders such as Parkinson's disease, idiopathic hypersomnia and amyotrophic lateral sclerosis. Despite this body of research the therapeutic potential of flumazenil remains poorly understood and largely unrealized. The purpose of this paper is not to provide an exhaustive review of all possible therapeutic applications for flumazenil but rather to stimulate research interest, and discussion of the exciting therapeutic potential of this drug for a range of chronic debilitating conditions. PMID:26088116

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

    NASA Astrophysics Data System (ADS)

    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.

  9. Retinal Electrophysiology Is a Viable Preclinical Biomarker for Drug Penetrance into the Central Nervous System

    PubMed Central

    Charng, Jason; He, Zheng; Vingrys, Algis J.; Fish, Rebecca L.; Gurrell, Rachel; Bui, Bang V.; Nguyen, Christine T.

    2016-01-01

    Objective. To examine whether retinal electrophysiology is a useful surrogate marker of drug penetrance into the central nervous system (CNS). Materials and Methods. Brain and retinal electrophysiology were assessed with full-field visually evoked potentials and electroretinograms in conscious and anaesthetised rats following systemic or local administrations of centrally penetrant (muscimol) or nonpenetrant (isoguvacine) compounds. Results. Local injections into the eye/brain bypassed the blood neural barriers and produced changes in retinal/brain responses for both drugs. In conscious animals, systemic administration of muscimol resulted in retinal and brain biopotential changes, whereas systemic delivery of isoguvacine did not. General anaesthesia confounded these outcomes. Conclusions. Retinal electrophysiology, when recorded in conscious animals, shows promise as a viable biomarker of drug penetration into the CNS. In contrast, when conducted under anaesthetised conditions confounds can be induced in both cortical and retinal electrophysiological recordings. PMID:27239335

  10. The role of myelin in Theiler's virus persistence in the central nervous system.

    PubMed

    Roussarie, Jean-Pierre; Ruffié, Claude; Brahic, Michel

    2007-02-01

    Theiler's virus, a picornavirus, persists for life in the central nervous system of mouse and causes a demyelinating disease that is a model for multiple sclerosis. The virus infects neurons first but persists in white matter glial cells, mainly oligodendrocytes and macrophages. The mechanism, by which the virus traffics from neurons to glial cells, and the respective roles of oligodendrocytes and macrophages in persistence are poorly understood. We took advantage of our previous finding that the shiverer mouse, a mutant with a deletion in the myelin basic protein gene (Mbp), is resistant to persistent infection to examine the role of myelin in persistence. Using immune chimeras, we show that resistance is not mediated by immune responses or by an efficient recruitment of inflammatory cells into the central nervous system. With both in vivo and in vitro experiments, we show that the mutation does not impair the permissiveness of neurons, oligodendrocytes, and macrophages to the virus. We demonstrate that viral antigens are present in cytoplasmic channels of myelin during persistent infection of wild-type mice. Using the optic nerve as a model, we show that the virus traffics from the axons of retinal ganglion cells to the cytoplasmic channels of myelin, and that this traffic is impaired by the shiverer mutation. These results uncover an unsuspected axon to myelin traffic of Theiler's virus and the essential role played by the infection of myelin/oligodendrocyte in persistence. PMID:17305428

  11. Neonatal head ultrasound: systematic approach to congenital Central Nervous System anomalies. A pictorial essay.

    PubMed

    Yoon, Hye-Kyung; Cho, Seong Whi

    2016-09-01

    Brain ultrasound is widely used for the screening of prematurely born babies. Although the best imaging modality for the central nervous system anomaly is brain MRI, the first imaging study in the post-natal period is brain ultrasonography in most cases. Anomalies could be found incidentally on screening ultrasound, or in those cases already suspected on prenatal ultrasound. In order not to miss congenital structural abnormalities of the brain on screening ultrasound, systematic approaches would be very helpful. The ventricles and sylvian fissures are very important structures to suspect central nervous system anomalies: they are symmetric structures so we should look for any asymmetry or maldevelopment. And then, on sagittal images, the midline structures including the corpus callosum and cerebellar vermis should be observed carefully. Finally, we should look for any abnormality in gyration or cortical development. Skull defect with herniation of intracranial contents, a spectrum of encephalo-meningocele, could be also identified on ultrasound. Congenital infections such as cytomegalovirus infection may show ventriculomegaly and malformation of the cortical development on imaging studies. PMID:27622417

  12. Beneficial effects of x-irradiation on recovery of lesioned mammalian central nervous tissue

    SciTech Connect

    Kalderon, N.; Alfieri, A.A.; Fuks, Z. )

    1990-12-01

    We examined the potential of x-irradiation, at clinical dose levels, to manipulate the cellular constituents and thereby change the consequences of transection injury to adult mammalian central nervous tissue (rat olfactory bulb). Irradiation resulted in reduction or elimination of reactive astrocytes at the site of incision provided that it was delivered within a defined time window postinjury. Under conditions optimal for the elimination of gliosis (15-18 days postinjury), irradiation of severed olfactory bulbs averted some of the degenerative consequences of lesion. We observed that irradiation was accompanied by prevention of tissue degeneration around the site of lesion, structural healing with maintenance of the typical cell lamination, and rescue of some axotomized mitral cells (principal bulb neurons). Thus radiation resulted in partial preservation of normal tissue morphology. It is postulated that intrusive cell populations are generated in response to injury and reactive astrocytes are one such group. Our results suggest that selective elimination of these cells by irradiation enabled some of the regenerative processes that are necessary for full recovery to maintain their courses. The cellular targets of these cells, their modes of intervention in recovery, and the potential role of irradiation as a therapeutic modality for injured central nervous system are discussed.

  13. Central nervous system tumours in children in Ibadan, Nigeria: a histopathologic study

    PubMed Central

    Ogun, Gabriel Olabiyi; Adeleye, Amos Olufemi; Babatunde, Taiwo Olabimpe; Ogun, Olufunmilola Abimbola; Salami, Ayodeji; Brown, Biobele Jotham; Akang, Effiong

    2016-01-01

    Introduction Contrary to some earlier teachings that central nervous system (CNS) tumours are uncommon in black children, these neoplasms are the fourth most common paediatric tumours in Ibadan. Our centre is the major referral centre for CNS tumours in Nigeria. The last major study of paediatric CNS neoplasms from Ibadan was in 1985. An update of the data on paediatric CNS neoplasms at our centre is presented. Methods A retrospective review of all histologically diagnosed CNS tumours in children (0-14 years) from January 2001 to December 2010 from the database of the Department of Pathology, University College Hospital, Ibadan, Nigeria was done. The cases were classified using the 2007 WHO Classification of Tumours of the Central Nervous System and were also based on their supratentorial and infratentorial locations. Results Seventy-seven tumours, 44 in males, were included in the study. Astrocytic tumour comprised 20 cases, embryonal tumours 15, ependymal tumours 15, germ cell tumours 6, sellar tumours (all craniopharyngiomas) 9 and other histological types- 12 cases. Thirty-seven were WHO Grade 1, eleven Grade 2, ten Grade 3 and nineteen Grade 4 neoplasms. Thirty-six cases were supratentorial and thirty-eight were infratentorial in location. The most common tumours in this series were pilocytic astrocytomas, medulloblastomas, craniopharyngiomas and ependymomas in that order. Conclusion Childhood CNS tumours are being increasingly diagnosed in our centre. This is largely explained by the recent expansion of the available neurosurgical services. PMID:27583098

  14. Application value of magnetic resonance imaging in diagnosing central nervous system lymphoma

    PubMed Central

    Zhang, Shanhua; Li, Hongjun; Zhu, Rongguang; Zhang, Mingming

    2016-01-01

    Objective: To describe the magnetic resonance imaging (MRI) appearance of central nervous system lymphoma. Methods: We retrospectively reviewed MRI images of 40 patients who had pathologically proven primary central nervous system lymphoma (PCNSL) and received treatment in Binzhou People’s Hospital, Shandong, China from January to December in 2014. Location, size and form of tumor was observed and relevant data were recorded for analysis. Results: Foci of 40 cases of PCNSL all located in brain, among which. 18 cases were single (45.0%) and 22 cases were multiple (55.5%). Of 96 Foci, 84 were supratentorial, 12 were subtentorial. Enhanced MRI scanning showed that, most Foci had significant homogenous enhancement, shaping as multiple nodular or lumpy, and few had ring-enhancement. MRI suggested that, T1 signal of most Foci concentrated on low signal segment and T2 signal gathered on high signal segment, suggesting a significant homogeneous enhancement; moreover, mild and medium edema surrounded the tumor. They were pathologically confirmed as B cell derived non-hodgkin lymphoma. Except one case of Burkitt lymphoma, the others were all diffuse large B cell lymphoma which was observed with diffuse distribution of cancer cells (little cytoplasm, large nucleus, rough perichromatin granule) in same size. Fifteen cases were observed with sleeve-like infiltration of cancer cells around blood vessels. No case was found with hemorrhage, necrosis or calcification. Conclusion: Pathological foundation of PCNSL determines its characteristic MRI performance. Typical case of PCNSL can be diagnosed accurately by MRI. PMID:27182246

  15. Distribution of NMDA receptor subunit NR1 in Arctic ground squirrel central nervous system

    PubMed Central

    Zhao, Huiwen W.; Christian, Sherri L.; Castillo, Marina R.; Bult-Ito, Abel; Drew, Kelly L.

    2013-01-01

    Hibernation is a natural model of neuroprotection and adult synaptic plasticity. NMDA receptors (NMDAR), which play key roles in excitotoxicity and synaptic plasticity, have not been characterized in a hibernating species. Tolerance to excitotoxicity and cognitive enhancement in Arctic ground squirrels (AGS, Spermophilus parryii) suggests that NMDAR expression may decrease in hibernation and increase upon arousal. NMDAR consist of at least one NMDAR1 (NR1) subunit, which is required for receptor function. Localization of NR1 reflects localization of the majority, if not all, NMDAR complexes. The purpose of this study, therefore, was to characterize the distribution of NR1 subunits in AGS central nervous system using immunohistochemistry. In addition, we compare NR1 expression in hippocampus of hibernating AGS (hAGS) and inter-bout euthermic AGS (ibeAGS) and assess changes in cell somata size using NR1 stained sections in three hippocampal sub-regions (CA1, CA3, and dentate gyrus). For the first time, we report that immunoreactivity of anti-NR1 is widely distributed throughout the central nervous system in AGS and is similar to other species. No differences exist in the expression and distribution of NR1 in hAGS and ibeAGS. However, we report a significant decrease in size of hippocampal CA1 and dentate gyrus NR1-expressing neuronal somata during hibernation torpor. PMID:17097266

  16. Central nervous system transplantation benefited by low-level laser irradiation

    NASA Astrophysics Data System (ADS)

    Rochkind, S.; Lubart, Rachel; Wollman, Yoram; Simantov, Rabi; Nissan, Moshe; Barr-Nea, Lilian

    1990-06-01

    Effect of low-level laser irradiation on the central nervous system transplantation is reported. Ernbryonal brain allografts were transplanted into the brain of 20 adult rats and peripheral nerve graft transplanted into the severely injured spinal cord of 16 dogs. The operated wound of 10 rats and 8 dogs were exposed daily for 21 days to lowpower laser irradiation CW HeNe laser (35 mW, 632.8 run, energy density of 30 J/cm2 at each point for rats and 70 J/cm2 at each point for dogs). This study shows that (i) the low-level laser irradiation prevents extensive glial scar formation (a limiting factor in CNS regeneration) between embryonal transplants and host brain; (ii) Dogs made paraplegic by spinal cord injury were able to walk 3-6 months later. Recovery of these dogs was effected by the implantation of a fragment of autologous sciatic nerve at the site of injury and subsequently exposing the dogs to low-level laser irradiation. The effect of laser irradiation on the embryonal nerve cells grown in tissue culture was also observed. We found that low-level laser irradiation induced intensive migration of neurites outward of the aggregates 15-22 The results of the present study and our previous investigations suggest that low-level laser irradiation is a novel tool for treatment of peripheral and central nervous system injuries.

  17. Antinociceptive activity of crotoxin in the central nervous system: a functional Magnetic Resonance Imaging study.

    PubMed

    Wolz-Richter, S; Esser, K-H; Hess, A

    2013-11-01

    Crotoxin, the main neurotoxic component of the venom of South American rattlesnake (Crotalus durissus terrificus), is reported to have potent antinociceptive activity. Several authors have shown mainly in behavioral pain models that crotoxin induces antinociceptive effects, supposed to be mediated by actions on the central nervous system. The antinociceptive effects of crotoxin (45 μg/kg ip) in rats were verified in this study by increased response latencies in a Hargreaves test and tail flick test. In addition, it was demonstrated that crotoxin does not lead to motor impairments during a rotarod test and open field test. The main objective, carried out by blood oxygen level dependent functional Magnetic Resonance Imaging (BOLD fMRI) in anesthetized rats, was to determine which specific brain structures are involved in these antinociceptive effects. Moreover, potential antihyperalgesic effects were investigated by inducing a local hyperalgesia on the left hind paw. Therefore, antinociceptive effects (right paw) and antihyperalgesic effects (left paw) of crotoxin were able to be differentiated. As a result, crotoxin exhibited dominant antihyperalgesic but also antinociceptive effects during pain stimulation. Reductions of BOLD signal already occurred in brain input structures but were most prominent in primary and secondary somatosensory cortices. In conclusion, BOLD fMRI in anesthetized rats proved to be a helpful tool in toxinology, particularly in unraveled mechanisms of modulating nociception in the central nervous system by (potential) analgesics like crotoxin. PMID:23916599

  18. Chondroitin sulphate proteoglycans in the central nervous system: changes and synthesis after injury.

    PubMed

    Properzi, F; Asher, R A; Fawcett, J W

    2003-04-01

    Chondroitin sulphate proteoglycans (CSPGs) are up-regulated in the central nervous system after injury, specifically around the lesion site where the glial scar forms. This structure contains astrocytes, oligodendrocyte precursor cells, microglia and meningeal cells, and forms an inhibitory substrate for axon re-growth. CSPGs have been shown to be closely involved in this neuronal growth inhibition, specifically through their sugar chains. These chains are composed of repeats of the same disaccharide unit carrying sulphate groups in different positions. The sulphation pattern directly influences the CSPG binding properties and function; the specific sulphation pattern required for the inhibitory activity of these molecules on axon growth is unknown at present. The expression of the chondroitin sulphotransferases, which sulphate the disaccharide residues of CSPGs and thus are responsible for the structural diversity of the chondroitin sulphate sugar chains, is regulated differently in central nervous system during development and after injury, suggesting the implication of a specific sulphation pattern in the inhibitory activity of CSPGs. PMID:12653631

  19. Neural Stem Cell Therapy and Rehabilitation in the Central Nervous System: Emerging Partnerships.

    PubMed

    Ross, Heather H; Ambrosio, Fabrisia; Trumbower, Randy D; Reier, Paul J; Behrman, Andrea L; Wolf, Steven L

    2016-05-01

    The goal of regenerative medicine is to restore function through therapy at levels such as the gene, cell, tissue, or organ. For many disorders, however, regenerative medicine approaches in isolation may not be optimally effective. Rehabilitation is a promising adjunct therapy given the beneficial impact that physical activity and other training modalities can offer. Accordingly, "regenerative rehabilitation" is an emerging concentration of study, with the specific goal of improving positive functional outcomes by enhancing tissue restoration following injury. This article focuses on one emerging example of regenerative rehabilitation-namely, the integration of clinically based protocols with stem cell technologies following central nervous system injury. For the purposes of this review, the state of stem cell technologies for the central nervous system is summarized, and a rationale for a synergistic benefit of carefully orchestrated rehabilitation protocols in conjunction with cellular therapies is provided. An overview of practical steps to increase the involvement of physical therapy in regenerative rehabilitation research also is provided. PMID:26847015

  20. Quantitative autoradiographic distribution of L-(3H)glutamate-binding sites in rat central nervous system

    SciTech Connect

    Greenamyre, J.T.; Young, A.B.; Penney, J.B.

    1984-08-01

    Quantitative autoradiography was used to determine the distribution of L-(3H)glutamate-binding sites in the rat central nervous system. Autoradiography was carried out in the presence of Cl- and Ca2+ ions. Scatchard plots and Hill coefficients of glutamate binding suggested that glutamate was interacting with a single population of sites having a K-D of about 300 nM and a capacity of 14.5 pmol/mg of protein. In displacement studies, ibotenate also appeared to bind to a single class of non-interacting sites with a KI of 28 microM. However, quisqualate displacement of (3H)glutamate binding revealed two well-resolved sites with KIS of 12 nM and 114 microM in striatum. These sites were unevenly distributed, representing different proportions of specific glutamate binding in different brain regions. The distribution of glutamate-binding sites correlated very well with the projection areas of putative glutamatergic pathways. This technique provides an extremely sensitive assay which can be used to gather detailed pharmacological and anatomical information about L-(3H)glutamate binding in the central nervous system.

  1. The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems

    PubMed Central

    Carabotti, Marilia; Scirocco, Annunziata; Maselli, Maria Antonietta; Severi, Carola

    2015-01-01

    The gut-brain axis (GBA) consists of bidirectional communication between the central and the enteric nervous system, linking emotional and cognitive centers of the brain with peripheral intestinal functions. Recent advances in research have described the importance of gut microbiota in influencing these interactions. This interaction between microbiota and GBA appears to be bidirectional, namely through signaling from gut-microbiota to brain and from brain to gut-microbiota by means of neural, endocrine, immune, and humoral links. In this review we summarize the available evidence supporting the existence of these interactions, as well as the possible pathophysiological mechanisms involved. Most of the data have been acquired using technical strategies consisting in germ-free animal models, probiotics, antibiotics, and infection studies. In clinical practice, evidence of microbiota-GBA interactions comes from the association of dysbiosis with central nervous disorders (i.e. autism, anxiety-depressive behaviors) and functional gastrointestinal disorders. In particular, irritable bowel syndrome can be considered an example of the disruption of these complex relationships, and a better understanding of these alterations might provide new targeted therapies. PMID:25830558

  2. Early exposure of rotating magnetic fields promotes central nervous regeneration in planarian Girardia sinensis.

    PubMed

    Chen, Qiang; Lin, Gui-Miao; Wu, Nan; Tang, Sheng-Wei; Zheng, Zhi-Jia; Lin, Marie Chia-Mi; Xu, Gai-Xia; Liu, Hao; Deng, Yue-Yue; Zhang, Xiao-Yun; Chen, Si-Ping; Wang, Xiao-Mei; Niu, Han-Ben

    2016-05-01

    Magnetic field exposure is an accepted safe and effective modality for nerve injury. However, it is clinically used only as a supplement or salvage therapy at the later stage of treatment. Here, we used a planarian Girardia sinensis decapitated model to investigate beneficial effects of early rotary non-uniform magnetic fields (RMFs) exposure on central nervous regeneration. Our results clearly indicated that magnetic stimulation induced from early RMFs exposure significantly promoted neural regeneration of planarians. This stimulating effect is frequency and intensity dependent. Optimum effects were obtained when decapitated planarians were cultured at 20 °C, starved for 3 days before head-cutting, and treated with 6 Hz 0.02 T RMFs. At early regeneration stage, RMFs exposure eliminated edema around the wound and facilitated subsequent formation of blastema. It also accelerated cell proliferation and recovery of neuron functionality. Early RMFs exposure up-regulated expression of neural regeneration related proteins, EGR4 and Netrin 2, and mature nerve cell marker proteins, NSE and NPY. These results suggest that RMFs therapy produced early and significant benefit in central nervous regeneration, and should be clinically used at the early stage of neural regeneration, with appropriate optimal frequency and intensity. Bioelectromagnetics. Bioelectromagnetics. 37:244-255, 2016. © 2016 Wiley Periodicals, Inc. PMID:27061713

  3. Diffuse large B-cell lymphoma involving the central nervous system.

    PubMed

    Gualco, Gabriela; Weiss, Lawrence M; Barber, Glen N; Bacchi, Carlos E

    2011-02-01

    Lymphomas involving the central nervous system are recognized increasingly in immunocompetent as well as immunosuppressed individuals, and the majority of the cases are diffuse large B-cell lymphoma (DLBCL). The aim of this study was to compare the immunophenotype, clinicopathological features, and association with Epstein-Barr virus (EBV) of DLBCL of the central nervous system (CNS) in 3 different clinical situations: primary, in immunocompetent patients; "primary," in immunosuppressed patients; and in patients with secondary involvement by systemic lymphoma. The authors reviewed the clinicopathological features, morphology, immunophenotype (according to germinal-center B-cell-like and nongerminal B-cell-like subtypes), and association with EBV in 36 cases of DLBCL of the CNS, including 25 primary cases, 5 associated with immunosuppression, and 6 cases with secondary involvement. Survival was evaluated in 15 cases of primary CNS lymphomas. Of the 36 patients, 19 were male and 18 female. Only 2 cases of lymphomas were EBV-positive; both occurred in immunosuppressed patients. Separation into germinal-center and non-germinal center subtypes by an immunohistochemistry panel showed that 68% of primary, 80% of secondary, and 83% of the cases associated with immunosuppression were of non-germinal-center subtype, respectively. Patients with non-germinal-center immunophenotype showed significantly worse survival than those with CNS lymphomas of the germinal-center subtype. PMID:21087986

  4. Recommendations regarding imaging of the central nervous system in fetuses and neonates.

    PubMed

    Helwich, Ewa; Bekiesińska-Figatowska, Monika; Bokiniec, Renata

    2014-06-01

    An abnormal presentation of the central nervous system in a fetus during a screening examination is an indication for extended diagnosis, the aim of which is to explain the character of such an anomaly (a congenital defect, destructive effect of intrauterine infection or abnormality with reasons that are difficult to explain). Knowledge of normal development sequence of the fetal brain, which is discussed in this paper, is the basis for correct interpretation of imaging findings. Together with the increase in survival of preterm neonates, a high risk of early brain damage is still a problem in this extremely immature population. Therefore, imaging examinations become necessary. The paper presents intrauterine and postnatal risk factors of early brain damage as well as classification of such lesions, of hemorrhagic and hypoxic-ischemic etiology. The diagnosis of the cerebellum damage, which is currently believed to be a significant cause of autism, is emphasized. The evolution of lesions over time is also presented. Moreover, the elements of diagnosis important for prognosis are stressed. The standards of imaging examinations of the central nervous system include the schedule of ultrasound examinations and provide indications for extended diagnosis with the use of magnetic resonance imaging. PMID:26672743

  5. Central nervous system gene expression changes in a transgenic mouse model for bovine spongiform encephalopathy

    PubMed Central

    2011-01-01

    Gene expression analysis has proven to be a very useful tool to gain knowledge of the factors involved in the pathogenesis of diseases, particularly in the initial or preclinical stages. With the aim of finding new data on the events occurring in the Central Nervous System in animals affected with Bovine Spongiform Encephalopathy, a comprehensive genome wide gene expression study was conducted at different time points of the disease on mice genetically modified to model the bovine species brain in terms of cellular prion protein. An accurate analysis of the information generated by microarray technique was the key point to assess the biological relevance of the data obtained in terms of Transmissible Spongiform Encephalopathy pathogenesis. Validation of the microarray technique was achieved by RT-PCR confirming the RNA change and immunohistochemistry techniques that verified that expression changes were translated into variable levels of protein for selected genes. Our study reveals changes in the expression of genes, some of them not previously associated with prion diseases, at early stages of the disease previous to the detection of the pathological prion protein, that might have a role in neuronal degeneration and several transcriptional changes showing an important imbalance in the Central Nervous System homeostasis in advanced stages of the disease. Genes whose expression is altered at early stages of the disease should be considered as possible therapeutic targets and potential disease markers in preclinical diagnostic tool development. Genes non-previously related to prion diseases should be taken into consideration for further investigations. PMID:22035425

  6. Proposal for research and education: joint lectures and practicals on central nervous system anatomy and physiology.

    PubMed

    Kageyama, Ikuo; Yoshimura, Ken; Satoh, Yoshihide; Nanayakkara, Chinthani D; Pallegama, Ranjith W; Iwasaki, Shin-Ichi

    2016-07-01

    We coordinated anatomy and physiology lectures and practicals to facilitate an integrated understanding of morphology and function in a basic medical science program for dental students and to reduce the time spent on basic science education. This method is a means to provide the essential information and skills in less time. The overall impression was that the practice of joint central nervous system lectures and practicals was an efficient method for students, which suggests that joint lectures might also be useful for clinical subjects. About two-thirds of students felt that the joint anatomy and physiology lecture on the central nervous system was useful and necessary in understanding the relationship between morphology and function, at least for this subject. One-third of students were neutral on the effectiveness of this method. However, the survey results suggest that improvements are needed in the method and timing of joint lectures and practicals. The present teaching approach can be further improved by conducting combined lectures in which the form and function of anatomic structures are presented by the relevant departments during the same lecture. Finally, joint lecturers and practicals offer an opportunity to increase student understanding of the importance of new research findings by the present authors and other researchers. PMID:26621026

  7. [Pharmacological study of mequitazine (LM-209) (III). Action on the central nervous system (author's transl)].

    PubMed

    Fujimura, H; Tsurumi, K; Yanagihara, M; Hiramatsu, Y; Tamura, Y; Shimizu, Y; Hojo, M; Yoshida, Y; Serizawa, I

    1981-10-01

    The action of an anti-histaminic agent, Mequitazine (LM-209) on the central nervous system was investigated. We found that LM-209 did not affect the spontaneous and co-operative movement in mice, did not induce muscle relaxation, analgesic effects or anti-convulsant effect in micr or hypothermic effects in rats. The anti-oxotremorine effect of LM-209 in mice was about 10 times more potent than clemastine fumarate (CL) and the same as promethazine. The activity and duration of the action were also superior to diethazine and orphenadrine used as an anti-Parkinson drug. LM-209 prolonged by 50% the hypnotic time induced by hexobarbital at 50 mg/kg (p.o.) in mice, while CL prolonged 50 and 100% it at 25 and 50 mg/kg (p.o.) respectively. In the EEG of rabbits, LM-209 produced a resting pattern, inhibited the arousal responses and recruiting responses and the effect was the same as CL and less potent than promethazine. From these results, the activity of LM-209 on the central nervous system (except for the anti-oxotremorine effect) seems to be the same as or somewhat less potent than CL. Therefore LM-209 should be an effective and anti-histaminic agent for clinical application. PMID:6120125

  8. In the presence of danger: the extracellular matrix defensive response to central nervous system injury

    PubMed Central

    Jakeman, Lyn B.; Williams, Kent E.; Brautigam, Bryan

    2014-01-01

    Glial cells in the central nervous system (CNS) contribute to formation of the extracellular matrix, which provides adhesive sites, signaling molecules, and a diffusion barrier to enhance efficient neurotransmission and axon potential propagation. In the normal adult CNS, the extracellular matrix (ECM) is relatively stable except in selected regions characterized by dynamic remodeling. However, after trauma such as a spinal cord injury or cortical contusion, the lesion epicenter becomes a focus of acute neuroinflammation. The activation of the surrounding glial cells leads to a dramatic change in the composition of the ECM at the edges of the lesion, creating a perilesion environment dominated by growth inhibitory molecules and restoration of the peripheral/central nervous system border. An advantage of this response is to limit the invasion of damaging cells and diffusion of toxic molecules into the spared tissue regions, but this occurs at the cost of inhibiting migration of endogenous repair cells and preventing axonal regrowth. The following review was prepared by reading and discussing over 200 research articles in the field published in PubMed and selecting those with significant impact and/or controversial points. This article highlights structural and functional features of the normal adult CNS ECM and then focuses on the reactions of glial cells and changes in the perilesion border that occur following spinal cord or contusive brain injury. Current research strategies directed at modifying the inhibitory perilesion microenvironment without eliminating the protective functions of glial cell activation are discussed. PMID:24999352

  9. Structure of the central nervous system of a juvenile acoel, Symsagittifera roscoffensis.

    PubMed

    Bery, Amandine; Cardona, Albert; Martinez, Pedro; Hartenstein, Volker

    2010-09-01

    The neuroarchitecture of Acoela has been at the center of morphological debates. Some authors, using immunochemical tools, suggest that the nervous system in Acoela is organized as a commissural brain that bears little resemblance to the central, ganglionic type brain of other flatworms, and bilaterians in general. Others, who used histological staining on paraffin sections, conclude that it is a compact structure (an endonal brain; e.g., Raikova 2004; von Graff 1891; Delage Arch Zool Exp Gén 4:109-144, 1886). To address this question with modern tools, we have obtained images from serial transmission electron microscopic sections of the entire hatchling of Symsagittifera roscoffensis. In addition, we obtained data from wholemounts of hatchlings labeled with markers for serotonin and tyrosinated tubulin. Our data show that the central nervous system of a juvenile S. roscoffensis consists of an anterior compact brain, formed by a dense, bilobed mass of neuronal cell bodies surrounding a central neuropile. The neuropile flanks the median statocyst and contains several types of neurites, classified according to their types of synaptic vesicles. The neuropile issues three pairs of nerve cords that run at different dorso-ventral positions along the whole length of the body. Neuronal cell bodies flank the cords, and neuromuscular synapses are abundant. The TEM analysis also reveals different classes of peripheral sensory neurons and provides valuable information about the spatial relationships between neurites and other cell types within the brain and nerve cords. We conclude that the acoel S. roscoffensis has a central brain that is comparable in size and architecture to the brain of other (rhabditophoran) flatworms. PMID:20549514

  10. Structure of the central nervous system of a juvenile acoel, Symsagittifera roscoffensis

    PubMed Central

    Cardona, Albert; Martinez, Pedro

    2010-01-01

    The neuroarchitecture of Acoela has been at the center of morphological debates. Some authors, using immunochemical tools, suggest that the nervous system in Acoela is organized as a commissural brain that bears little resemblance to the central, ganglionic type brain of other flatworms, and bilaterians in general. Others, who used histological staining on paraffin sections, conclude that it is a compact structure (an endonal brain; e.g., Raikova 2004; von Graff 1891; Delage Arch Zool Exp Gén 4:109-144, 1886). To address this question with modern tools, we have obtained images from serial transmission electron microscopic sections of the entire hatchling of Symsagittifera roscoffensis. In addition, we obtained data from wholemounts of hatchlings labeled with markers for serotonin and tyrosinated tubulin. Our data show that the central nervous system of a juvenile S. roscoffensis consists of an anterior compact brain, formed by a dense, bilobed mass of neuronal cell bodies surrounding a central neuropile. The neuropile flanks the median statocyst and contains several types of neurites, classified according to their types of synaptic vesicles. The neuropile issues three pairs of nerve cords that run at different dorso-ventral positions along the whole length of the body. Neuronal cell bodies flank the cords, and neuromuscular synapses are abundant. The TEM analysis also reveals different classes of peripheral sensory neurons and provides valuable information about the spatial relationships between neurites and other cell types within the brain and nerve cords. We conclude that the acoel S. roscoffensis has a central brain that is comparable in size and architecture to the brain of other (rhabditophoran) flatworms. PMID:20549514

  11. Differences in the central nervous system distribution and pharmacology of the mouse 5-hydroxytryptamine-6 receptor compared with rat and human receptors investigated by radioligand binding, site-directed mutagenesis, and molecular modeling.

    PubMed

    Hirst, Warren D; Abrahamsen, Bjarke; Blaney, Frank E; Calver, Andrew R; Aloj, Lucia; Price, Gary W; Medhurst, Andrew D

    2003-12-01

    There is increasing evidence for a role of 5-hydroxytrypta-mine-6 (5-HT6) receptors in cognitive function. In the rat and human brain, 5-HT6 receptors are widely expressed and highly enriched in the basal ganglia. However, in the mouse brain, only very low levels of 5-HT6 receptor mRNA and receptor protein, measured by TaqMan reverse transcriptase-polymerase chain reaction and selective radioligand binding, could be detected, with no evidence of enrichment in the basal ganglia. The mouse receptor was cloned and transiently expressed in human embryonic kidney 293 cells to characterize its pharmacological profile. Despite significant sequence homology between human, rat, and mouse 5-HT6 receptors, the pharmacological profile of the mouse receptor was significantly different from the rat and human receptors. Four amino acid residues, conserved in rat and human and divergent in mouse receptors, were identified, and various mutant receptors were generated and their pharmacologies studied. Residues 188 (tyrosine in mouse, phenylalanine in rat and human) in transmembrane region 5 and 290 (serine in mouse, asparagine in rat and human) in transmembrane region 6 were identified as key amino acids responsible for the different pharmacological profiles. Molecular modeling of the receptor and docking of selective and nonselective compounds was undertaken to elucidate the ligand receptor interactions. The binding pocket was predicted to be different in the mouse compared with rat and human 5-HT6 receptors, and the models were in excellent agreement with the observed mutation results and have been used extensively in the design of further selective 5-HT6 antagonists. PMID:14645659

  12. Space physiology II: adaptation of the central nervous system to space flight--past, current, and future studies.

    PubMed

    Clément, Gilles; Ngo-Anh, Jennifer Thu

    2013-07-01

    Experiments performed in orbit on the central nervous system have focused on the control of posture, eye movements, spatial orientation, as well as cognitive processes, such as three-dimensional visual perception and mental representation of space. Brain activity has also been recorded during and immediately after space flight for evaluating the changes in brain structure activation during tasks involving perception, attention, memory, decision, and action. Recent ground-based studies brought evidence that the inputs from the neurovestibular system also participate in orthostatic intolerance. It is, therefore, important to revisit the flight data of neuroscience studies in the light of new models of integrative physiology. The outcomes of this exercise will increase our knowledge on the adaptation of body functions to changing gravitational environment, vestibular disorders, aging, and our approach towards more effective countermeasures during human space flight and planetary exploration. PMID:23053128

  13. An Integrated Model of the Cardiovascular and Central Nervous Systems for Analysis of Microgravity Induced Fluid Redistribution

    NASA Technical Reports Server (NTRS)

    Price, R.; Gady, S.; Heinemann, K.; Nelson, E. S.; Mulugeta, L.; Ethier, C. R.; Samuels, B. C.; Feola, A.; Vera, J.; Myers, J. G.

    2015-01-01

    A recognized side effect of prolonged microgravity exposure is visual impairment and intracranial pressure (VIIP) syndrome. The medical understanding of this phenomenon is at present preliminary, although it is hypothesized that the headward shift of bodily fluids in microgravity may be a contributor. Computational models can be used to provide insight into the origins of VIIP. In order to further investigate this phenomenon, NASAs Digital Astronaut Project (DAP) is developing an integrated computational model of the human body which is divided into the eye, the cerebrovascular system, and the cardiovascular system. This presentation will focus on the development and testing of the computational model of an integrated model of the cardiovascular system (CVS) and central nervous system (CNS) that simulates the behavior of pressures, volumes, and flows within these two physiological systems.

  14. Ultrasound-mediated blood-brain barrier disruption for targeted drug delivery in the central nervous system

    PubMed Central

    Aryal, Muna; Arvanitis, Costas D.; Alexander, Phillip M.; McDannold, Nathan

    2014-01-01

    The physiology of the vasculature in the central nervous system (CNS), which includes the blood-brain barrier (BBB) and other factors, complicates the delivery of most drugs to the brain. Different methods have been used to bypass the BBB, but they have limitations such as being invasive, non-targeted or requiring the formulation of new drugs. Focused ultrasound (FUS), when combined with circulating microbubbles, is a noninvasive method to locally and transiently disrupt the BBB at discrete targets. This review provides insight on the current status of this unique drug delivery technique, experience in preclinical models, and potential for clinical translation. If translated to humans, this method would offer a flexible means to target therapeutics to desired points or volumes in the brain, and enable the whole arsenal of drugs in the CNS that are currently prevented by the BBB. PMID:24462453

  15. Histamine Immunoreactive Elements in the Central and Peripheral Nervous Systems of the Snail, Biomphalaria spp., Intermediate Host for Schistosoma mansoni

    PubMed Central

    Habib, Mohamed R.; Mohamed, Azza H.; Osman, Gamalat Y.; Sharaf El-Din, Ahmed T.; Mossalem, Hanan S.; Delgado, Nadia; Torres, Grace; Rolón-Martínez, Solymar; Miller, Mark W.; Croll, Roger P.

    2015-01-01

    Histamine appears to be an important transmitter throughout the Animal Kingdom. Gastropods, in particular, have been used in numerous studies establishing potential roles for this biogenic amine in the nervous system and showing its involvement in the generation of diverse behaviours. And yet, the distribution of histamine has only previously been described in a small number of molluscan species. The present study examined the localization of histamine-like immunoreactivity in the central and peripheral nervous systems of pulmonate snails of the genus Biomphalaria. This investigation demonstrates immunoreactive cells throughout the buccal, cerebral, pedal, left parietal and visceral ganglia, indicative of diverse regulatory functions in Biomphalaria. Immunoreactivity was also present in statocyst hair cells, supporting a role for histamine in graviception. In the periphery, dense innervation by immunoreactive fibers was observed in the anterior foot, perioral zone, and other regions of the body wall. This study thus shows that histamine is an abundant transmitter in these snails and its distribution suggest involvement in numerous neural circuits. In addition to providing novel subjects for comparative studies of histaminegic neurons in gastropods, Biomphalaria is also the major intermediate host for the digenetic trematode parasite, which causes human schistosomiasis. The study therefore provides a foundation for understanding potential roles for histamine in interactions between the snail hosts and their trematode parasites. PMID:26086611

  16. Comparative mapping of GABA-immunoreactive neurons in the central nervous systems of nudibranch molluscs.

    PubMed

    Gunaratne, Charuni A; Sakurai, Akira; Katz, Paul S

    2014-03-01

    The relative simplicity of certain invertebrate nervous systems, such as those of gastropod molluscs, allows behaviors to be dissected at the level of small neural circuits composed of individually identifiable neurons. Elucidating the neurotransmitter phenotype of neurons in neural circuits is important for understanding how those neural circuits function. In this study, we examined the distribution of γ-aminobutyric-acid;-immunoreactive (GABA-ir) neurons in four species of sea slugs (Mollusca, Gastropoda, Opisthobranchia, Nudibranchia): Tritonia diomedea, Melibe leonina, Dendronotus iris, and Hermissenda crassicornis. We found consistent patterns of GABA immunoreactivity in the pedal and cerebral-pleural ganglia across species. In particular, there were bilateral clusters in the lateral and medial regions of the dorsal surface of the cerebral ganglia as well as a cluster on the ventral surface of the pedal ganglia. There were also individual GABA-ir neurons that were recognizable across species. The invariant presence of these individual neurons and clusters suggests that they are homologous, although there were interspecies differences in the numbers of neurons in the clusters. The GABAergic system was largely restricted to the central nervous system, with the majority of axons confined to ganglionic connectives and commissures, suggesting a central, integrative role for GABA. GABA was a candidate inhibitory neurotransmitter for neurons in central pattern generator (CPG) circuits underlying swimming behaviors in these species, however none of the known swim CPG neurons were GABA-ir. Although the functions of these GABA-ir neurons are not known, it is clear that their presence has been strongly conserved across nudibranchs. PMID:24638845

  17. Design of Drug Delivery Methods for the Brain and Central Nervous System

    NASA Astrophysics Data System (ADS)

    Lueshen, Eric

    Due to the impermeability of the blood-brain barrier (BBB) to macromolecules delivered systemically, drug delivery to the brain and central nervous system (CNS) is quite difficult and has become an area of intense research. Techniques such as convection-enhanced intraparenchymal delivery and intrathecal magnetic drug targeting offer a means of circumventing the blood-brain barrier for targeted delivery of therapeutics. This dissertation focuses on three aspects of drug delivery: pharmacokinetics, convection-enhanced delivery, and intrathecal magnetic drug targeting. Classical pharmacokinetics mainly uses black-box curve fitting techniques without biochemical or biological basis. This dissertation advances the state-of-the-art of pharmacokinetics and pharmacodynamics by incorporating first principles and biochemical/biotransport mechanisms in the prediction of drug fate in vivo. A whole body physiologically-based pharmacokinetics (PBPK) modeling framework is engineered which creates multiscale mathematical models for entire organisms composed of organs, tissues, and a detailed vasculature network to predict drug bioaccumulation and to rigorously determine kinetic parameters. These models can be specialized to account for species, weight, gender, age, and pathology. Systematic individual therapy design using the proposed mechanistic PBPK modeling framework is also a possibility. Biochemical, anatomical, and physiological scaling laws are also developed to accurately project drug kinetics in humans from small animal experiments. Our promising results demonstrate that the whole-body mechanistic PBPK modeling approach not only elucidates drug mechanisms from a biochemical standpoint, but offers better scaling precision. Better models can substantially accelerate the introduction of drug leads to clinical trials and eventually to the market by offering more understanding of the drug mechanisms, aiding in therapy design, and serving as an accurate dosing tool. Convection

  18. Phase I Trial Using Patupilone (Epothilone B) and Concurrent Radiotherapy for Central Nervous System Malignancies

    SciTech Connect

    Fogh, Shannon; Machtay, Mitchell; Werner-Wasik, Maria; Curran, Walter J.; Bonanni, Roseann; Axelrod, Rita; Andrews, David; Dicker, Adam P.

    2010-07-15

    Purpose: Based on preclinical data indicating the radiosensitizing potential of epothilone B, the present study was designed to evaluate the toxicity and response rate of patupilone, an epothilone B, with concurrent radiotherapy (RT) for the treatment of central nervous system malignancies. Methods and Materials: The present Phase I study evaluated the toxicities associated with patupilone combined with RT to establish the maximal tolerated dose. Eligible patients had recurrent gliomas (n = 10) primary (n = 5) or metastatic (n = 17) brain tumors. Dose escalation occurred if no dose-limiting toxicities, defined as any Grade 4-5 toxicity or Grade 3 toxicity requiring hospitalization, occurred during treatment. Results: Of 14 patients, 5 were treated with weekly patupilone at 1.5 mg/m{sup 2}, 4 at 2.0 mg/m{sup 2}, 4 at 2.5 mg/m{sup 2}, and 1 at 4 mg/m{sup 2}. Of 18 patients, 7 were treated in the 6-mg/m{sup 2} group, 6 in the 8-mg/m{sup 2} group, and 5 in the 10-mg/m{sup 2} group. Primary central nervous system malignancies received RT to a median dose of 60 Gy. Central nervous system metastases received whole brain RT to a median dose of 37.4 Gy, and patients with recurrent gliomas underwent stereotactic RT to a median dose of 37.5 Gy. One dose-limiting toxicity (pneumonia) was observed in group receiving 8-mg/m{sup 2} every 3 weeks. At the subsequent dose level (10 mg/m{sup 2}), two Grade 4 dose-limiting toxicities occurred (renal failure and pulmonary hemorrhage); thus, 8 mg/m{sup 2} every 3 weeks was the maximal tolerated dose and the recommended Phase II dose. Conclusion: Combined with a variety of radiation doses and fractionation schedules, concurrent patupilone was well tolerated and safe, with a maximal tolerated dose of 8 mg/m{sup 2} every 3 weeks.

  19. Infrared neural stimulation: a new stimulation tool for central nervous system applications

    PubMed Central

    Chernov, Mykyta; Roe, Anna Wang

    2014-01-01

    Abstract. The traditional approach to modulating brain function (in both clinical and basic science applications) is to tap into the neural circuitry using electrical currents applied via implanted electrodes. However, it suffers from a number of problems, including the risk of tissue trauma, poor spatial specificity, and the inability to selectively stimulate neuronal subtypes. About a decade ago, optical alternatives to electrical stimulation started to emerge in order to address the shortcomings of electrical stimulation. We describe the use of one optical stimulation technique, infrared neural stimulation (INS), during which short (of the order of a millisecond) pulses of infrared light are delivered to the neural tissue. Very focal stimulation is achieved via a thermal mechanism and stimulation location can be quickly adjusted by redirecting the light. After describing some of the work done in the peripheral nervous system, we focus on the use of INS in the central nervous system to investigate functional connectivity in the visual and somatosensory areas, target specific functional domains, and influence behavior of an awake nonhuman primate. We conclude with a positive outlook for INS as a tool for safe and precise targeted brain stimulation. PMID:26157967

  20. Kynurenines and Multiple Sclerosis: The Dialogue between the Immune System and the Central Nervous System

    PubMed Central

    Rajda, Cecilia; Majláth, Zsófia; Pukoli, Dániel; Vécsei, László

    2015-01-01

    Multiple sclerosis is an inflammatory disease of the central nervous system, in which axonal transection takes place in parallel with acute inflammation to various, individual extents. The importance of the kynurenine pathway in the physiological functions and pathological processes of the nervous system has been extensively investigated, but it has additionally been implicated as having a regulatory function in the immune system. Alterations in the kynurenine pathway have been described in both preclinical and clinical investigations of multiple sclerosis. These observations led to the identification of potential therapeutic targets in multiple sclerosis, such as synthetic tryptophan analogs, endogenous tryptophan metabolites (e.g., cinnabarinic acid), structural analogs (laquinimod, teriflunomid, leflunomid and tranilast), indoleamine-2,3-dioxygenase inhibitors (1MT and berberine) and kynurenine-3-monooxygenase inhibitors (nicotinylalanine and Ro 61-8048). The kynurenine pathway is a promising novel target via which to influence the immune system and to achieve neuroprotection, and further research is therefore needed with the aim of developing novel drugs for the treatment of multiple sclerosis and other autoimmune diseases. PMID:26287161

  1. Conservation of neural nicotinic acetylcholine receptors from Drosophila to vertebrate central nervous systems.

    PubMed Central

    Bossy, B; Ballivet, M; Spierer, P

    1988-01-01

    Nicotinic acetylcholine receptors (nAChR) are found both in vertebrate and insect central nervous systems. We have isolated a Drosophila gene by crosshybridization with a vertebrate probe. Structural conservation of domains of the deduced protein and of intron/exon boundaries indicate that the Drosophila gene encodes an nAChR alpha-like subunit (ALS). That the Drosophila gene product most resembles the neuronal set of vertebrate nAChRs alpha-subunits is also indicated by the failure of an ALS-beta-galactosidase fusion protein to bind alpha-bungarotoxin on blots in contrast to vertebrate endplate alpha-subunit constructions. The ALS encoding gene exceeds 54 kb in length and the transcript has a very long and unusual 5' leader. As we found previously for a gene whose product is also involved in cholinergic synapses, acetylcholinesterase, the leader encodes short open reading frames, which might be involved in translation control. We also note the presence of opa repeats in the gene, as has been found for various Drosophila genes expressed in the nervous system. Images PMID:2840281

  2. Inflammation on the Mind: Visualizing Immunity in the Central Nervous System

    PubMed Central

    Kang, Silvia S.

    2016-01-01

    The central nervous system (CNS) is a remarkably complex structure that utilizes electrochemical signaling to coordinate activities throughout the entire body. Because the nervous system contains nonreplicative cells, it is postulated that, through evolutionary pressures, this compartment has acquired specialized mechanisms to limit damage. One potential source of damage comes from our immune system, which has the capacity to survey the CNS and periphery for the presence of foreign material. The immune system is equipped with numerous effector mechanisms and can greatly alter the homeostasis and function of the CNS. Degeneration, autoimmunity, and pathogen infection can all result in acute, and sometimes chronic, inflammation within the CNS. Understanding the specialized functionality of innate and adaptive immune cells within the CNS is critical to the design of more efficacious treatments to mitigate CNS inflammatory conditions. Much of our knowledge of CNS-immune interactions stems from seminal studies that have used static and dynamic imaging approaches to visualize inflammatory cells responding to different CNS conditions. This review will focus on how imaging techniques have elevated our understanding of CNS inflammation as well as the exciting prospects that lie ahead as we begin to pursue investigation of the inflamed CNS in real time. PMID:19521688

  3. Growth Arrest Specific 1 (GAS1) Is Abundantly Expressed in the Adult Mouse Central Nervous System

    PubMed Central

    Zarco, Natanael; Bautista, Elizabeth; Cuéllar, Manola; Vergara, Paula; Flores-Rodriguez, Paola; Aguilar-Roblero, Raúl

    2013-01-01

    Growth arrest specific 1 (GAS1) is a pleiotropic protein that induces apoptosis and cell arrest in different tumors, but it is also involved in the development of the nervous system and other tissues and organs. This dual ability is likely caused by its capacity to interact both by inhibiting the intracellular signaling cascade induced by glial cell-line derived neurotrophic factor and by facilitating the activity of the sonic hedgehog pathway. The presence of GAS1 mRNA has been described in adult mouse brain, and here we corroborated this observation. We then proceeded to determine the distribution of the protein in the adult central nervous system (CNS). We detected, by western blot analysis, expression of GAS1 in olfactory bulb, caudate-putamen, cerebral cortex, hippocampus, mesencephalon, medulla oblongata, cerebellum, and cervical spinal cord. To more carefully map the expression of GAS1, we performed double-label immunohistochemistry and noticed expression of GAS1 in neurons in all brain areas examined. We also observed expression of GAS1 in astroglial cells, albeit the pattern of expression was more restricted than that seen in neurons. Briefly, in the present article, we report the widespread distribution and cellular localization of the GAS1 native protein in adult mammalian CNS. PMID:23813868

  4. The 2007 WHO classification of tumours of the central nervous system.

    PubMed

    Louis, David N; Ohgaki, Hiroko; Wiestler, Otmar D; Cavenee, Webster K; Burger, Peter C; Jouvet, Anne; Scheithauer, Bernd W; Kleihues, Paul

    2007-08-01

    The fourth edition of the World Health Organization (WHO) classification of tumours of the central nervous system, published in 2007, lists several new entities, including angiocentric glioma, papillary glioneuronal tumour, rosette-forming glioneuronal tumour of the fourth ventricle, papillary tumour of the pineal region, pituicytoma and spindle cell oncocytoma of the adenohypophysis. Histological variants were added if there was evidence of a different age distribution, location, genetic profile or clinical behaviour; these included pilomyxoid astrocytoma, anaplastic medulloblastoma and medulloblastoma with extensive nodularity. The WHO grading scheme and the sections on genetic profiles were updated and the rhabdoid tumour predisposition syndrome was added to the list of familial tumour syndromes typically involving the nervous system. As in the previous, 2000 edition of the WHO 'Blue Book', the classification is accompanied by a concise commentary on clinico-pathological characteristics of each tumour type. The 2007 WHO classification is based on the consensus of an international Working Group of 25 pathologists and geneticists, as well as contributions from more than 70 international experts overall, and is presented as the standard for the definition of brain tumours to the clinical oncology and cancer research communities world-wide. PMID:17618441

  5. Quantitative autoradiographic characterization of GA-BA sub B receptors in mammalian central nervous system

    SciTech Connect

    Chu, D.Chin-Mei.

    1989-01-01

    The inhibitory effects of the amino acid neurotransmitter {gamma}-aminobutyric acid (GABA) within the nervous system appear to be mediated through two distinct classes of receptors: GABA{sub A} and GABA{sub B} receptors. A quantitative autoradiographic method with {sup 3}H-GABA was developed to examine the hypotheses that GABA{sub A} and GABA{sub B} sites have distinct anatomical distributions, pharmacologic properties, and synaptic localizations within the rodent nervous system. The method was also applied to a comparative study of these receptors in postmortem human brain from individuals afflicted with Alzheimer's disease and those without neurologic disease. The results indicated that GABA{sub B} receptors occur in fewer numbers and have a lower affinity for GABA than GABA{sub A} receptors in both rodent and human brain. Within rodent brain, the distribution of these two receptor populations were clearly distinct. GABA{sub B} receptors were enriched in the medial habenula, interpeduncular nucleus, cerebellar molecular layer and olfactory glomerular layer. After selective lesions of postsynaptic neurons of the corticostriatal and perforant pathway, both GABA{sub B} and GABA{sub A} receptors were significantly decreased in number. Lesions of the presynaptic limbs of the perforant but not the corticostriatal pathway resulted in upregulation of both GABA receptors in the area of innervation. GABA{sub B} receptors were also upregulated in CA3 dendritic regions after destruction of dentate granule neurons.

  6. Cellular immune surveillance of central nervous system bypasses blood-brain barrier and blood-cerebrospinal-fluid barrier: revealed with the New Marburg cerebrospinal-fluid model in healthy humans.

    PubMed

    Kleine, Tilmann O

    2015-03-01

    In healthy human brain/spinal cord, blood capillaries and venules are locked differently with junctions and basement membrane (blood-brain barrier, blood-venule barrier). In choroid plexus, epithelial tight junctions and basement membrane lock blood-cerebrospinal-fluid (CSF) barrier. Lymphocytic cell data, quantified with multicolour flow-cytometry or immuno-cytochemical methods in sample pairs of lumbar CSF, ventrictricular CSF and peripheral venous blood, are taken from references; similarly, data of thoracic duct chyle and blood sample pairs. Through three circumventricular organs (median eminence, organum vasculosum lamina terminalis, area postrema), 15-30 μl blood are pressed by blood pressure through fenestrated capillaries, matrix/basement membrane spaces and ependyma cell lacks into ventricular/suboccipital CSF to generate CD3(+) , CD4(+) , CD8(+) , CD3(+) HLA-DR(+) , CD16(+) 56(+) 3(-) NK, CD19(+) 3(-) B subsets; some B, few NK cells adhere in circumventricular organs. Into lumbar CSF, 10-15 μl thoracic chyle with five lymphocyte subsets (without CD3(+) HLA-DR(+) cells) reflux, when CSF drains out with to-and-fro movements of chyle/CSF along nerve roots. Lymphocytes in lumbar CSF represent a mixture of blood and lymph lymphocytic cells with similar HLA-DR(+) CD3(+) cell counts in ventricular and lumbar CSF, higher CD3(+) , CD4(+) , CD8(+) subsets in lumbar CSF, and few NK and B cells due to absorption in circumventricular organs. The Marburg CSF Model reflects origin and turnover of lymphatic cells in CSF realistically; the model differs from ligand-multistep processes of activated lymphocytes through blood-brain-, blood-venule-, and blood-CSF-barriers; because transfer of inactivated native lymphocytes through the barriers is not found with healthy humans, although described so in literature. PMID:25641944

  7. Pathogens Penetrating the Central Nervous System: Infection Pathways and the Cellular and Molecular Mechanisms of Invasion

    PubMed Central

    Dando, Samantha J.; Mackay-Sim, Alan; Norton, Robert; Currie, Bart J.; St. John, James A.; Ekberg, Jenny A. K.; Batzloff, Michael

    2014-01-01

    SUMMARY The brain is well protected against microbial invasion by cellular barriers, such as the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB). In addition, cells within the central nervous system (CNS) are capable of producing an immune response against invading pathogens. Nonetheless, a range of pathogenic microbes make their way to the CNS, and the resulting infections can cause significant morbidity and mortality. Bacteria, amoebae, fungi, and viruses are capable of CNS invasion, with the latter using axonal transport as a common route of infection. In this review, we compare the mechanisms by which bacterial pathogens reach the CNS and infect the brain. In particular, we focus on recent data regarding mechanisms of bacterial translocation from the nasal mucosa to the brain, which represents a little explored pathway of bacterial invasion but has been proposed as being particularly important in explaining how infection with Burkholderia pseudomallei can result in melioidosis encephalomyelitis. PMID:25278572

  8. [The therapeutic effect of central nervous stimulants in edema disease of swine].

    PubMed

    Orban, P; Bilkei Papp, G; Bölcskei, A

    1993-12-01

    During a natural outbreak of edema disease in different farms 160 weaned piglets showing the clinical symptoms of palpebral edema, mental discomfort and apathy were selected and divided into three groups. The groups were treated as follows: Group 1 (51 piglets) received twice daily one i. m. dose of Gentamycin (11 mg/kg body weight), Prednisolone (1 mg/kg body weight), Melperone (4 mg/kg body weight) for 3 days. Group 2 (55 piglets) received twice daily one i. m. dose of Amphetaminum Phosphoricum 1 mg/kg body weight for 3 days. Group 3 (54 piglets) untreated control. The result showed that group 2 treated with stimulant of the central nervous system gave the best results concerning survival. It ist the authors opinion that concerning clinical symptoms and therapy further classification is necessary. PMID:7907469

  9. Hazard effects of nanoparticles in central nervous system: Searching for biocompatible nanomaterials for drug delivery.

    PubMed

    Leite, Paulo Emílio Corrêa; Pereira, Mariana Rodrigues; Granjeiro, José Mauro

    2015-10-01

    Nanostructured materials are widely used in many applications of industry and biomedical fields. Nanoparticles emerges as potential pharmacological carriers that can be applied in the regenerative medicine, diagnosis and drug delivery. Different types of nanoparticles exhibit ability to cross the brain blood barrier (BBB) and accumulate in several brain areas. Then, efforts have been done to develop safer nanocarrier systems to treat disorders of central nervous system (CNS). However, several in vitro and in vivo studies demonstrated that nanoparticles of different materials exhibit a wide range of neurotoxic effects inducing neuroinflammation and cognitive impairment. For this reason, polymeric nanoparticles arise as a promisor alternative due to their biocompatible and biodegradable properties. After an overview of CNS location and neurotoxic effects of translocated nanoparticles, this review addresses the use of polymeric nanoparticles to the treatment of neuroinfectious diseases, as acquired immunodeficiency syndrome (AIDS) and meningitis. PMID:26116398

  10. Molecular Analysis of Central Nervous System Disease Spectrum in Childhood Acute Lymphoblastic Leukemia

    PubMed Central

    Hicks, Chindo; Sitthi-Amorn, Jitsuda; Douglas, Jessica; Ramani, Ritika; Miele, Lucio; Vijayakumar, Vani; Karlson, Cynthia; Chipeta, James; Megason, Gail

    2016-01-01

    Treatment of the central nervous system (CNS) is an essential therapeutic component in childhood acute lymphoblastic leukemia (ALL). The goal of this study was to identify molecular signatures distinguishing patients with CNS disease from those without the disease in pediatric patients with ALL. We analyzed gene expression data from 207 pediatric patients with ALL. Patients without CNS were classified as CNS1, while those with mild and advanced CNS disease were classified as CNS2 and CNS3, respectively. We compared gene expression levels among the three disease classes. We identified gene signatures distinguishing the three disease classes. Pathway analysis revealed molecular networks and biological pathways dysregulated in response to CNS disease involvement. The identified pathways included the ILK, WNT, B-cell receptor, AMPK, ERK5, and JAK signaling pathways. The results demonstrate that transcription profiling could be used to stratify patients to guide therapeutic decision-making in pediatric ALL. PMID:26997880

  11. Parasitic diseases of the central nervous system: lessons for clinicians and policy makers.

    PubMed

    Carpio, Arturo; Romo, Matthew L; Parkhouse, R M E; Short, Brooke; Dua, Tarun

    2016-04-01

    Parasitic diseases of the central nervous system are associated with high mortality and morbidity, especially in resource-limited settings. The burden of these diseases is amplified as survivors are often left with neurologic sequelae affecting mobility, sensory organs, and cognitive functions, as well as seizures/epilepsy. These diseases inflict suffering by causing lifelong disabilities, reducing economic productivity, and causing social stigma. The complexity of parasitic life cycles and geographic specificities, as well as overlapping clinical manifestations in the host reflecting the diverse pathogenesis of parasites, can present diagnostic challenges. We herein provide an overview of these parasitic diseases and summarize clinical aspects, diagnosis, therapeutic strategies and recent milestones, and aspects related to prevention and control. PMID:26894629

  12. The Continuing Value of Ultrastructural Observation in Central Nervous System Neoplasms in Children

    PubMed Central

    Kim, Na Rae; Park, Sung-Hye

    2015-01-01

    Central nervous system (CNS) neoplasms are the second most common childhood malignancy after leukemia and the most common solid organ neoplasm in children. Diagnostic dilemmas with small specimens from CNS neoplasms are often the result of multifactorial etiologies such as frozen or fixation artifact, biopsy size, or lack of knowledge about rare or unfamiliar entities. Since the late 1950s, ultrastructural examination has been used in the diagnosis of CNS neoplasms, though it has largely been replaced by immunohistochemical and molecular cytogenetic studies. Nowadays, pathologic diagnosis of CNS neoplasms is achieved through intraoperative cytology, light microscopy, immunohistochemistry, and molecular cytogenetic results. However, the utility of electron microscopy (EM) in the final diagnosis of CNS neoplasms and investigation of its pathogenetic origin remains critical. Here, we reviewed the distinguishing ultrastructural features of pediatric CNS neoplasms and emphasize the continuing value of EM in the diagnosis of CNS neoplasms. PMID:26459406

  13. Acute and prolonged complement activation in the central nervous system during herpes simplex encephalitis.

    PubMed

    Eriksson, Charlotta E; Studahl, Marie; Bergström, Tomas

    2016-06-15

    Herpes simplex encephalitis (HSE) is characterized by a pronounced inflammatory activity in the central nervous system (CNS). Here, we investigated the acute and prolonged complement system activity in HSE patients, by using enzyme-linked immunosorbent assays (ELISAs) for numerous complement components (C). We found increased cerebrospinal fluid concentrations of C3a, C3b, C5 and C5a in HSE patients compared with healthy controls. C3a and C5a concentrations remained increased also compared with patient controls. Our results conclude that the complement system is activated in CNS during HSE in the acute phase, and interestingly also in later stages supporting previous reports of prolonged inflammation. PMID:27235358

  14. How appropriate are cerebrospinal fluid polymerase chain reaction requests for suspected central nervous system infections?

    PubMed

    Mamoojee, Yaasir; Chadwick, David

    2011-12-01

    Cerebrospinal fluid (CSF) polymerase chain reaction (PCR) assays have become the main diagnostic tests for central nervous system viral infections in recent years. Previous studies have suggested algorithms based on CSF leukocyte count and total protein levels to determine when CSF PCR assays are indicated. Based on these criteria, 1,469 CSF PCR tests requested over a two-year period were reviewed. A proportion of positive PCR results were found in children with normal CSF, unlike in adults where such occurrences were extremely rare. The results suggest that applying a strategy of screening CSF specimens using leukocyte count, glucose and protein, at least in adults, may have avoided more than half of CSF PCR requests with little detriment to patient care and considerable cost savings. Larger prospective studies are needed to determine whether algorithms using standard CSF parameters and clinical information can optimise the use of CSF PCR assays in clinical practice. PMID:22268308

  15. Neuropsychological evaluation for detecting alterations in the central nervous system after chemical exposure.

    PubMed

    Bolla, K I

    1996-08-01

    Individuals with multiple chemical sensitivity (MCS) report decreased attention/concentration, memory loss, disorientation, confusion, fatigue, depression, irritability, decreased libido, sleep disturbances, headaches, and weakness. These neurobehavioral symptoms represent possible alterations in the central nervous system (CNS). The evaluation of neurobehavioral functioning using neuropsychological techniques provides an indirect method for determining the integrity of the CNS. However, caution must be used in interpreting neuropsychological test results, since this technique is extremely sensitive but is not specific. Clinically significant aberrant test performance may be noted after chemical exposure as well as with other diseases of the CNS. In addition, neuropsychiatric conditions such as anxiety and depression are often manifested as cognitive difficulties that are similar in pattern to the cognitive dysfunction caused by toxic chemicals. Herein, limitations and cautions in the interpretations of neuropsychological test results are discussed. PMID:8921555

  16. ssiRNA Induced Gene Silencing is Transmitted Between Cells From the Mammalian Central Nervous System

    PubMed Central

    Zhao, Tian-Yong; Zou, Shi-Ping; Alimova, Yelena V.; Wang, Guoying; Hauser, Kurt F.; Ghandour, M. Said; Knapp, Pamela E.

    2014-01-01

    Although siRNA induced gene silencing can be transmitted between cells in plants and in C. elegans, this phenomenon has been barely studied in mammalian cells. Both immortalized oligodendrocytes and SNB-19 glioblastoma cells were transfected with siRNA constructs for PTEN (phosphatase and tensin homolog deleted on chromosome 10) or Akt (Akt/protein kinase B). Co-cultures were established between silenced cells and non-silenced cells which were hygromycin resistant and/or expressed green fluorescent protein (GFP). After fluorescence sorting or hygromycin selection to remove the silenced cells, the expression of PTEN or Akt genes in the originally unsilenced cells was in all cases significantly decreased. Importantly, silencing did not occur in transwell culture studies, suggesting that transmission of the silencing signal requires a close association between cells. These results provide the first direct demonstration that an siRNA induced silencing signal can be transmitted between mammalian central nervous system (CNS) cells. PMID:16923165

  17. Origin, fate and dynamics of macrophages at central nervous system interfaces.

    PubMed

    Goldmann, Tobias; Wieghofer, Peter; Jordão, Marta Joana Costa; Prutek, Fabiola; Hagemeyer, Nora; Frenzel, Kathrin; Amann, Lukas; Staszewski, Ori; Kierdorf, Katrin; Krueger, Martin; Locatelli, Giuseppe; Hochgerner, Hannah; Zeiser, Robert; Epelman, Slava; Geissmann, Frederic; Priller, Josef; Rossi, Fabio M V; Bechmann, Ingo; Kerschensteiner, Martin; Linnarsson, Sten; Jung, Steffen; Prinz, Marco

    2016-07-01

    Perivascular, subdural meningeal and choroid plexus macrophages are non-parenchymal macrophages that mediate immune responses at brain boundaries. Although the origin of parenchymal microglia has recently been elucidated, much less is known about the precursors, the underlying transcriptional program and the dynamics of the other macrophages in the central nervous system (CNS). It was assumed that they have a high turnover from blood-borne monocytes. However, using parabiosis and fate-mapping approaches in mice, we found that CNS macrophages arose from hematopoietic precursors during embryonic development and established stable populations, with the notable exception of choroid plexus macrophages, which had dual origins and a shorter life span. The generation of CNS macrophages relied on the transcription factor PU.1, whereas the MYB, BATF3 and NR4A1 transcription factors were not required. PMID:27135602

  18. Pharmacological studies of the aqueous extract of Sapindus trifoliatus on central nervous system: possible antimigraine mechanisms.

    PubMed

    Arulmozhi, D K; Veeranjaneyulu, A; Bodhankar, S L; Arora, S K

    2005-03-21

    The aqueous extract of pericarp of fruits of Sapindus trifoliatus (ST) Linn., family Sapindaceae was evaluated for its potential effects on central nervous system in mice. The extract at doses 20 and 100 mg/kg, i.p. significantly (p < 0.001) reduced the spontaneous locomotor activity and at 100 mg/kg, increased the thiopental-induced sleeping time. In rota-rod motor co-ordination test, ST at 100 mg/kg, i.p. significantly (p < 0.05-0.01) reduced the endurance time. Further ST exhibited no protection against maximal electroshock (MES)- and pentylenetetrazole (PTZ)-induced convulsions in mice. In receptor radioligand binding studies, ST exhibited affinity towards dopaminergic, alpha-adrenergic and muscarnic receptors. The findings suggest that, ST may possess principles with potential neuroleptic properties. PMID:15740885

  19. The spectrum of primary blastomycotic meningitis: a review of central nervous system blastomycosis.

    PubMed

    Gonyea, E F

    1978-01-01

    Three cases of meningitis with initial and exclusive neurological involvement prompted a review of the clinical, cerebrospinal fluid, and pathological findings in an additional 78 patients with central nervous system blastomycosis. The first patient of the 3 had progressive cerebellar dysfunction as the result of chronic basilar meningitis. The second had a C8-T1 radiculopathy without other evidence of superior sulcus syndrome, and subsequent acute fatal meningitis. The third had aseptic, benign, self-limited meningitis followed by clinically obvious systemic blastomycosis. Diagnosis is difficult, and it is likely that other cases have been presumptively treated for tuberculous meningitis. A more aggressive approach to diagnosis is proposed that takes into account the condition of the patient, the likelihood of dissemination at necropsy, and the frequent meningeal infections that are negative on culture of lumbar CSF. PMID:655652

  20. Lipoprotein Receptor LRP1 Regulates Leptin Signaling and Energy Homeostasis in the Adult Central Nervous System

    PubMed Central

    Liu, Qiang; Zhang, Juan; Zerbinatti, Celina; Zhan, Yan; Kolber, Benedict J.; Herz, Joachim; Muglia, Louis J.; Bu, Guojun

    2011-01-01

    Obesity is a growing epidemic characterized by excess fat storage in adipocytes. Although lipoprotein receptors play important roles in lipid uptake, their role in controlling food intake and obesity is not known. Here we show that the lipoprotein receptor LRP1 regulates leptin signaling and energy homeostasis. Conditional deletion of the Lrp1 gene in the brain resulted in an obese phenotype characterized by increased food intake, decreased energy consumption, and decreased leptin signaling. LRP1 directly binds to leptin and the leptin receptor complex and is required for leptin receptor phosphorylation and Stat3 activation. We further showed that deletion of the Lrp1 gene specifically in the hypothalamus by Cre lentivirus injection is sufficient to trigger accelerated weight gain. Together, our results demonstrate that the lipoprotein receptor LRP1, which is critical in lipid metabolism, also regulates food intake and energy homeostasis in the adult central nervous system. PMID:21264353