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Sample records for affect central nervous

  1. Autoimmune disorders affecting both the central and peripheral nervous system.

    PubMed

    Kamm, Christoph; Zettl, Uwe K

    2012-01-01

    Various case series of patients with autoimmune demyelinating disease affecting both the central and peripheral nervous system (CNS and PNS), either sequentially or simultaneously, have been reported for decades, but their frequency is considerably lower than that of the "classical" neurological autoimmune diseases affecting only either CNS or PNS, such as multiple sclerosis (MS), chronic inflammatory demyelinating polyneuropathy (CIDP) or Guillain-Barré-Syndrome (GBS), and attempts to define or even recognize the former as a clinical entity have remained elusive. Frequently, demyelination started with CNS involvement with subsequent PNS pathology, in some cases with a relapsing-remitting course. Three potential mechanisms for the autoimmune etiology of these conditions can be discussed: (I) They could be caused by a common autoimmunological reactivity against myelin antigens or epitopes present in both the central and peripheral nervous system; (II) They could be due to a higher general susceptibility to autoimmune disease, which in some cases may have been caused or exacerbated by immunomodulatory treatment, e.g. b-interferon; (III) Their co-occurrence might be coincidental. Another example of an autoimmune disease variably involving the central or peripheral nervous system or both is the overlapping and continuous clinical spectrum of Fisher syndrome (FS), as a variant of GBS, and Bickerstaff brainstem encephalitis (BBE). Recent data from larger patient cohorts with demonstration of common autoantibodies, antecedent infections, and results of detailed clinical, neuroimaging and neurophysiological investigations suggest that these three conditions are not separate disorders, but rather form a continuous spectrum with variable central and peripheral nervous system involvement. We herein review clinical and paraclinical data and therapeutic options of these disorders and discuss potential underlying common vs. divergent immunopathogenic mechanisms.

  2. 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.

  3. 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.

  4. Vocational identity, positive affect, and career thoughts in a group of young adult central nervous system cancer survivors.

    PubMed

    Lange, Dustin D; Wong, Alex W K; Strauser, David R; Wagner, Stacia

    2014-12-01

    The aims of this study were as follows: (a) to compare levels of career thoughts and vocational identity between young adult childhood central nervous system (CNS) cancer survivors and noncancer peers and (b) to investigate the contribution of vocational identity and affect on career thoughts among cancer survivors. Participants included 45 young adult CNS cancer survivors and a comparison sample of 60 college students. Participants completed Career Thoughts Inventory, My Vocational Situation, and the Positive and Negative Affect Schedule. Multivariate analysis of variance and multiple regression analysis were used to analyze the data in this study. CNS cancer survivors had a higher level of decision-making confusion than the college students. Multiple regression analysis indicated that vocational identity and positive affect significantly predicted the career thoughts of CNS survivors. The differences in decision-making confusion suggest that young adult CNS survivors would benefit from interventions that focus on providing knowledge of how to make decisions, while increasing vocational identity and positive affect for this specific population could also be beneficial.

  5. GJB1-associated X-linked Charcot-Marie-Tooth disease, a disorder affecting the central and peripheral nervous systems.

    PubMed

    Abrams, Charles K; Freidin, Mona

    2015-06-01

    Charcot-Marie-Tooth disease (CMT) is a group of inherited diseases characterized by exclusive or predominant involvement of the peripheral nervous system. Mutations in GJB1, the gene encoding Connexin 32 (Cx32), a gap-junction channel forming protein, cause the most common X-linked form of CMT, CMT1X. Cx32 is expressed in Schwann cells and oligodendrocytes, the myelinating glia of the peripheral and central nervous systems, respectively. Thus, patients with CMT1X have both central and peripheral nervous system manifestations. Study of the genetics of CMT1X and the phenotypes of patients with this disorder suggest that the peripheral manifestations of CMT1X are likely to be due to loss of function, while in the CNS gain of function may contribute. Mice with targeted ablation of Gjb1 develop a peripheral neuropathy similar to that seen in patients with CMT1X, supporting loss of function as a mechanism for the peripheral manifestations of this disorder. Possible roles for Cx32 include the establishment of a reflexive gap junction pathway in the peripheral and central nervous system and of a panglial syncitium in the central nervous system.

  6. Poisonous plants affecting the central nervous system of horses in Brazil

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Poisoning by Indigofera pascuori was recently reported in horses in the state of Roraima. It causes chronic signs of sleepiness, unsteady gait, severe ataxia, and progressive weight loss. Some animals are blind. Young horses are more affected than adults. After the end of plant consumption the anima...

  7. Pathogenesis of the immune reconstitution inflammatory syndrome affecting the central nervous system in patients infected with HIV.

    PubMed

    Martin-Blondel, Guillaume; Delobel, Pierre; Blancher, Antoine; Massip, Patrice; Marchou, Bruno; Liblau, Roland S; Mars, Lennart T

    2011-04-01

    Anti-retroviral therapy partially restores the immune function of patients infected with human immunodeficiency virus, thereby drastically reducing morbidity and mortality. However, the clinical condition of a subset of patients on anti-retroviral therapy secondarily deteriorates due to an inflammatory process termed immune reconstitution inflammatory syndrome. This condition results from the restoration of the immune system that upon activation can be detrimental to the host. Among the various clinical manifestations, central nervous system involvement is associated with greater morbidity and mortality. This review covers the pathogenesis of this novel neuroinflammatory disease, including the nature of the provoking pathogens and the composition and specificity of the evoked immune responses. Our current perception of this neuroinflammatory disease supports therapeutic strategies aimed at modulating immune aggression without dampening the life-saving restoration of the immune response.

  8. [Central nervous system malformations: neurosurgery correlates].

    PubMed

    Jiménez-León, Juan C; Betancourt-Fursow, Yaline M; Jiménez-Betancourt, Cristina S

    2013-09-06

    Congenital malformations of the central nervous system are related to alterations in neural tube formation, including most of the neurosurgical management entities, dysraphism and craniosynostosis; alterations of neuronal proliferation; megalencefaly and microcephaly; abnormal neuronal migration, lissencephaly, pachygyria, schizencephaly, agenesis of the corpus callosum, heterotopia and cortical dysplasia, spinal malformations and spinal dysraphism. We expose the classification of different central nervous system malformations that can be corrected by surgery in the shortest possible time and involving genesis mechanisms of these injuries getting better studied from neurogenic and neuroembryological fields, this involves connecting innovative knowledge areas where alteration mechanisms in dorsal induction (neural tube) and ventral induction (telencephalization) with the current way of correction, as well as the anomalies of cell proliferation and differentiation of neuronal migration and finally the complex malformations affecting the posterior fossa and current possibilities of correcting them.

  9. Uropharmacology: X. Central nervous system stimulants and depressants.

    PubMed

    Bissada, N K; Finkbeiner, A E; Welch, L T

    1979-04-01

    Several drugs that are utilized primarily for their effects on the central nervous system also affect lower urinary tract function. Most of these effects are produced by the action of these drugs on adrenergic and cholinergic receptors or by direct action of lower urinary tract musculature. Central nervous system stimulants and depressants which are known to affect the storage or evacuation role of the lower urinary tract are discussed.

  10. Cellular Mechanisms of Central Nervous Modulation.

    DTIC Science & Technology

    1983-06-30

    achieve selective disruption of the neuroglia in the central nervous system 4 of our experimental animal, the cockroach (Periplaneta americana). Such...RD-A147 878 CELLULAR MECHANISMIS OF CENTRAL NERVOUS MODULATION(U) i/i I CAMBRIDGE UNIV (ENGLAND) DEPT OF ZOOLOGY J E TRENERNE 30 JUN 83 DHJA37-8i-C...BOOBI UNCLASSFE F/G 6/16 NL bi L& 2. MICROCOPY RESOLUTION TEST CHART NATIONA BUJREAUJ OF STANDOW-S1963-A [.1 PI CELLULAR MECHANISMIS OF CENTRAL NERVOUS

  11. Cellular Mechanisms of Central Nervous Modulation.

    DTIC Science & Technology

    1981-12-31

    Schofield, P.K. (1981) Mechanism of ionic homeostasis in the central nervous system of an insect. J. exp. Biol., 95, 61-73. Treherne, J.E., Schofield...P.K. & Lane, N.J. (1982) Physiological and ultra- structural evidence for an extracellular anion matrix in the central nervous system of an insect...AD-R147 875 CELLULAR MECHANISM1S OF CENTRAL NERVOUS tODULATION(U) I/i CAMBRIDGE UNIV (ENGLAND) DEPT OF ZOOLOGY J E TREHERNE 31 DEC 81 DAJA37-Si-C

  12. [Functional anatomy of the central nervous system].

    PubMed

    Krainik, A; Feydy, A; Colombani, J M; Hélias, A; Menu, Y

    2003-03-01

    The central nervous system (CNS) has a particular regional functional anatomy. The morphological support of cognitive functions can now be depicted using functional imaging. Lesions of the central nervous system may be responsible of specific symptoms based on their location. Current neuroimaging techniques are able to show and locate precisely macroscopic lesions. Therefore, the knowledge of functional anatomy of the central nervous system is useful to link clinical disorders to symptomatic lesions. Using radio-clinical cases, we present the functional neuro-anatomy related to common cognitive impairments.

  13. Massive myeloid sarcoma affecting the central nervous system, mediastinum, retroperitoneum, liver, and rectum associated with acute myeloblastic leukaemia: a case report

    PubMed Central

    Best-Aguilera, C R; Vazquez-Del Mercado, M; Muñoz-Valle, J F; Herrera-Zarate, L; Navarro-Hernandez, R E; Martin-Marquez, B T; Oregon-Romero, E; Ruiz-Quezada, S; Bonilla, G M; Lomeli-Guerrero, A

    2005-01-01

    Myeloid sarcomas are extramedullary tumours with granulocytic precursors. When associated with acute myelogenous leukaemia (AML), these tumours usually affect no more than two different extramedullary regions. This report describes a myeloid sarcoma associated with AML with tumour formation at five anatomical sites. The patient was a 37 year old man admitted in September 1999 with a two month history of weight loss, symptoms of anaemia, rectal bleeding, and left facial nerve palsy. The anatomical sites affected were: the rectum, the right lobe of the liver, the mediastinum, the retroperitoneum, and the central nervous system. A bone marrow smear was compatible with AML M2. Flow cytometry showed that the peripheral blood was positive for CD4, CD11, CD13, CD14, CD33, CD45, and HLA-DR. A karyotypic study of the bone marrow revealed an 8;21 translocation. The presence of multiple solid tumours in AML is a rare event. Enhanced expression of cell adhesion molecules may be the reason why some patients develop myeloid sarcomas. PMID:15735171

  14. Neuroactive steroids and central nervous system disorders.

    PubMed

    Wang, M; Bäckström, T; Sundström, I; Wahlström, G; Olsson, T; Zhu, D; Johansson, I M; Björn, I; Bixo, M

    2001-01-01

    Steroid hormones are vital for the cell life and affect a number of neuroendocrine and behavioral functions. In contrast to their endocrine actions, certain steroids have been shown to rapidly alter brain excitability and to produce behavioral effects within seconds to minutes. In this article we direct attention to this issue of neuroactive steroids by outlining several aspects of current interest in the field of steroid research. Recent advances in the neurobiology of neuroactive are described along with the impact of advances on drug design for central nervous system (CNS) disorders provoked by neuroactive steriods. The theme was selected in association with the clinical aspects and therapeutical potentials of the neuroactive steroids in CNS disorders. A wide range of topics relating to the neuroactive steroids are outlined, including steroid concentrations in the brain, premenstrual syndrome, estrogen and Alzheimer's disease, side effects of oral contraceptives, mental disorder in menopause, hormone replacement therapy, Catamenial epilepsy, and neuractive steroids in epilepsy treatment.

  15. [Idiopathic hypersomnia of the central nervous system].

    PubMed

    Bové-Ribé, A

    Idiopathic hypersomnia of the central nervous system is a cause of excessive diurnal somnolence which affects 5-10% of the patients who attend sleep clinics for this reason. We describe three male patients who consulted for excessive diurnal somnolence. Nocturnal polysomnographic studies followed by tests for multiple latencies of sleep were done. In all cases there was confirmation of lengthening of the time of nocturnal sleep with normal phases of sleep and an increase in the number of sleep spindles in phase II. Similarly there was an average latency of sleep of less than 10 minutes and fewer than two phases of REM in the multiple latencies test. All patients improved with drugs stimulating vigil, two of them with centramine and the third with methilphenidate. We consider the clinical data the polysomnographic criteria which help to establish the diagnosis.

  16. Central nervous system complications after liver transplantation.

    PubMed

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

    2015-08-01

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

  17. Comparison of detergent and protease enzyme combinations for the detection of scrapie-associated fibrils from the central nervous system of sheep naturally affected with scrapie.

    PubMed

    Stack, M J; Aldrich, A M; Davis, L A

    1997-02-01

    Standardized samples of tissue from the central nervous system of four sheep naturally affected with scrapie and from four healthy control sheep were subjected to a centrifugal extraction technique used to obtain scrapie-associated fibrils; the latter were then demonstrated by negative-contrast transmission electron microscopy. This regime was used to evaluate the fibril yield obtained from the 25 possible combinations of five different detergents and five different proteolytic enzymes. N-lauroylsarcosine detergent was found to be the most efficient detergent for all five enzymes, followed by sulphabetaine 3-14. Sodium dodecyl sulphate detergent was successful only in combination with a subtilisin Carlsberg enzyme. Octylglucoside and nonidet P40 detergents did not produce fibrils with any of the enzymes. Proteinase K was the least efficient of the five enzymes when used in combination with N-lauroylsarcosine; subtilisin Carlsberg, clostripain, pronase and trypsin enzymes all gave higher fibril yields. A combination of N-lauroylsarcosine detergent and subtilisin Carlsberg proteolytic enzyme gave the highest fibril yield.

  18. Hydrogels for central nervous system therapeutic strategies.

    PubMed

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

    2015-12-01

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

  19. [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.).

  20. CENTRAL NERVOUS MECHANISMS IN CIRCULATION REGULATION AND FUNCTIONAL DERANGEMENT (HYPERTENSION).

    DTIC Science & Technology

    BLOOD CIRCULATION, *CENTRAL NERVOUS SYSTEM, * HYPERTENSION , AUTONOMIC NERVOUS SYSTEM, ELECTROENCEPHALOGRAPHY, ELECTROPHYSIOLOGY, CHEMORECEPTORS...PERCEPTION, CARDIOVASCULAR SYSTEM, PATHOLOGY, REFLEXES, BEHAVIOR, BLOOD PRESSURE , ANOXIA, BRAIN, ITALY.

  1. Central nervous system tumors in Mexican children.

    PubMed

    De la Torre Mondragón, L; Ridaura Sanz, C; Reyes Mujica, M; Rueda Franco, F

    1993-08-01

    Five hundred and seventy primary central nervous system (CNS) tumors from the Department of Pathology at the National Institute of Pediatrics in Mexico City, collected from 1970 to 1989, were histologically reclassified in order to find out their relative incidence as well as their outstanding features. With this, we could establish a frame of reference for our local population, contributing to the epidemiological analysis of these entities. All the tumors were examined independently by two pathologists (C.R. and M.R.), using the classification of Rorke et al. Histological type, patient age and sex, and tumor location were analyzed. CNS tumors were the secondmost frequently encountered solid tumors, after lymphomas, and were increasing in incidence at a rate of 2.2 annually. Children in the age group 0-9 years were most often affected, and there was a predominance of male patients. Astrocytoma and medulloblastoma were the most common tumor types. The infratentorial region was the most frequent tumor location in the 2- to 9-year age group. By contrast, in the under 2-year-olds a supratentorial location was more frequent, and the incidence of germ cell tumors was proportionally high. In general, some histological types seemed to be associated with particular age groups. Although we found primitive neuroectodermal tumors to be the fifth most common at all ages (except for medulloblastoma), many other authors do not report a similar finding.

  2. 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.

  3. Tuberculoma of the central nervous system.

    PubMed

    DeLance, Arthur R; Safaee, Michael; Oh, Michael C; Clark, Aaron J; Kaur, Gurvinder; Sun, Matthew Z; Bollen, Andrew W; Phillips, Joanna J; Parsa, Andrew T

    2013-10-01

    Tuberculosis is among the oldest and most devastating infectious diseases worldwide. Nearly one third of the world's population has active or latent disease, resulting in 1.5 million deaths annually. Central nervous system involvement, while rare, is the most severe form of tuberculosis. Manifestations include tuberculoma and tuberculous meningitis, with the majority of cases occurring in children and immunocompromised patients. Despite advancements in imaging and laboratory diagnostics, tuberculomas of the central nervous system remain a diagnostic challenge due to their insidious nature and nonspecific findings. On imaging studies tuberculous meningitis is characterized by diffuse basal enhancement, but tuberculomas may be indistinguishable from neoplasms. Early diagnosis is imperative, since clinical outcomes are largely dependent on timely treatment. Stereotactic biopsy with histopathological analysis can provide a definitive diagnosis, but is only recommended when non-invasive methods are inconclusive. Standard medical treatment includes rifampicin, isoniazid, pyrazinamide, and streptomycin or ethambutol. In cases of drug resistance, revision of the treatment regimen with second-line agents is recommended over the addition of a single drug to the first-line regimen. Advances in genomics have identified virulent strains of tuberculosis and are improving our understanding of host susceptibility. Neurosurgical referral is advised for patients with elevated intracranial pressure, seizures, or brain or spinal cord compression. This review synthesizes pertinent findings in the literature surrounding central nervous system tuberculoma in an effort to highlight recent advances in pathophysiology, diagnosis, and treatment.

  4. Rhabdoid tumors of the central nervous system.

    PubMed

    Reinhardt, D; Behnke-Mursch, J; Weiss, E; Christen, H J; Kühl, J; Lakomek, M; Pekrun, A

    2000-04-01

    Rhabdoid tumors of the central nervous system are rare malignancies with a still almost uniformly fatal outcome. There is still no proven curative therapy available. We report our experience with nine patients with central nervous system rhabdoid tumors. Gross complete surgical removal of the tumor was achieved in six patients. Seven patients received intensive chemotherapy. Four of these were treated in addition with both neuroaxis radiotherapy and a local boost directed to the tumor region, while two patients received local radiotherapy only. The therapy was reasonably well tolerated in most cases. Despite the aggressive therapy, eight of the nine patients died from progressive tumor disease, and one patient died from hemorrhagic brain stem lesions of unknown etiology. The mean survival time was 10 months after diagnosis. Conventional treatment, although aggressive, cannot change the fatal prognosis of central nervous system rhabdoid tumors. As these neoplasms are so rare, a coordinated register would probably be a good idea, offering a means of learning more about the tumor's biology and possible strategies of treatment.

  5. Neuroinflammation of the central and peripheral nervous system: an update.

    PubMed

    Stüve, O; Zettl, U

    2014-03-01

    Inflammatory disorders of the peripheral nervous system (PNS) and central nervous system (CNS) are common, and contribute substantially to physical and emotional disability of affected individuals. Often, the afflicted are young and in their active years. In the past, physicians and scientists often had very little to offer in terms of diagnostic precision and therapeutic effectiveness. During the past two decades, both of these relative shortcomings have clearly improved. Some of the recent developments in clinical neuroimmunology are illustrated in this special edition of Clinical and Experimental Immunology.

  6. Neuroinflammation of the central and peripheral nervous system: an update

    PubMed Central

    Stüve, O; Zettl, U

    2014-01-01

    Inflammatory disorders of the peripheral nervous system (PNS) and central nervous system (CNS) are common, and contribute substantially to physical and emotional disability of affected individuals. Often, the afflicted are young and in their active years. In the past, physicians and scientists often had very little to offer in terms of diagnostic precision and therapeutic effectiveness. During the past two decades, both of these relative shortcomings have clearly improved. Some of the recent developments in clinical neuroimmunology are illustrated in this special edition of Clinical and Experimental Immunology. PMID:24384012

  7. Glycosaminoglycans of the porcine central nervous system†

    PubMed Central

    Liu, Zhenling; Masuko, Sayaka; Solakyildirim, Kemal; Pu, Dennis; Linhardt, Robert J.; Zhang, Fuming

    2010-01-01

    Glycosaminoglycans (GAG) are known to participate in central nervous system processes such as development, cell migration, and neurite outgrowth. In this paper, we report an initial glycomics study on GAGs from porcine central nervous system. GAGs of the porcine central nervous system, brain and spinal cord, were isolated and purified by defating, proteolysis, anion-exchange chromatography and methanol precipitation. The isolated GAG content in brain was 5-times higher than in spinal cord (0.35 mg/g, compared to 0.07 mg/g dry sample). In both tissues, chondroitin sulfate (CS) and heparan sulfate (HS) were the major and the minor GAG. The average molecular weight of CS from brain and spinal cord was 35.5 and 47.1 kDa, respectively, and HS from brain and spinal cord was 56.9 and 34 kDa, respectively. The disaccharide analysis showed that the composition of CS from brain and spinal cords are similar with uronic acid (1→3) 4-O-sulfo-N-acetylgalactosamine residue corresponding to the major disaccharide unit (CS type-A) along with five minor disaccharide units. The major disaccharides of both brain and spinal cord HS were uronic acid (1→4) N-acetylglucosamine and uronic acid (1→4) 6-O-sulfo-N-sulfoglucosamine but their composition of minor disaccharides differed. Analysis by 1H- and two-dimensional-NMR spectroscopy confirmed these disaccharide analyses and provided the glucuronic/iduronic acid ratio. Finally, both purified CS and HS were biotinylated and immobilized on BIAcore SA biochips. Interactions between these GAGs and fibroblast growth factors (FGF1 and FGF2) and sonic hedgehog (Shh) were investigated by surface plasmon resonance. PMID:20954748

  8. 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

  9. 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

  10. Central nervous system involvement of polyarteritis nodosa: a case report.

    PubMed

    Altinok, D; Yildiz, Y T; Ruşen, E; Eryilmaz, M; Tacal, T

    2001-01-01

    Polyarteritis nodosa (PAN) is a necrotizing vasculitis involving small and medium-sized arteries and it affects multiple organ systems in the body Central nervous system (CNS) involvement appears less frequently, and usually develops after the disease is established. Although aneurysms are common in visceral arteries in PAN, intracranial aneurysms are uncommon and have been documented rarely. This case is reported to raise awareness among radiologists as it has characteristic and rare, if not specific, imaging findings of CNS involvement of PAN.

  11. Metal toxicity in the central nervous system.

    PubMed Central

    Clarkson, T W

    1987-01-01

    The nervous system is the principal target for a number of metals. Inorganic compounds of aluminum, arsenic, lead, lithium, manganese, mercury, and thallium are well known for their neurological and behavioral effects in humans. The alkyl derivatives of certain metals--lead, mercury and tin--are specially neurotoxic. Concern over human exposure and in some cases, outbreaks of poisoning, have stimulated research into the toxic action of these metals. A number of interesting hypotheses have been proposed for the mechanism of lead toxicity on the nervous system. Lead is known to be a potent inhibitor of heme synthesis. A reduction in heme-containing enzymes could compromise energy metabolism. Lead may affect brain function by interference with neurotransmitters such as gamma-amino-isobutyric acid. There is mounting evidence that lead interferes with membrane transport and binding of calcium ions. Methylmercury produces focal damage to specific areas in the adult brain. One hypothesis proposes that certain cells are susceptible because they cannot repair the initial damage to the protein sythesis machinery. The developing nervous system is especially susceptible to damage by methylmercury. It has been discovered that microtubules are destroyed by this form of mercury and this effect may explain the inhibition of cell division and cell migration, processes that occur only in the developmental stages. These and other hypotheses will stimulate considerable experimental challenges in the future. PMID:3319566

  12. 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.

  13. Autonomic complications following central nervous system injury.

    PubMed

    Baguley, Ian J

    2008-11-01

    Severe sympathetic overactivity occurs in several conditions that are recognized as medical emergencies. Following central nervous system injury, a small proportion of individuals develop severe paroxysmal sympathetic and motor overactivity. These individuals have a high attendant risk of unnecessary secondary morbidity. Following acquired brain injury, the syndrome is known by a number of names including dysautonomia and sympathetic storm. Dysautonomia is currently a diagnosis of exclusion and often goes unrecognized. The evidence base for management is almost entirely anecdotal in nature; there has been little structured or prospective research. In contrast, the evidence base for autonomic dysreflexia following spinal cord injury is much stronger, with level 1 evidence for many treatment interventions. This review presents a current understanding of each condition and suggests simple management protocols. With the marked disparity in the literature for the two conditions, the main focus is on the literature for dysautonomia. The similarity between these two conditions and the other autonomic emergency conditions is discussed.

  14. 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.

  15. Gravity sensing in the central nervous system.

    PubMed

    Wiedemann, Meike; Hanke, Wolfgang

    2002-07-01

    For human based space research it is of high importance to understand the influence of gravity on the properties of the central nervous system (CNS). Until now it is not much known about how neuronal tissue can sense gravity. The aim of this study was to find out weather and how the CNS, as a complex system, can percept and react to changes in gravity. Neuronal tissue and especially the CNS fulfils all the requirements for excitable media. Consequently, self-organisation, pattern formation and propagating excitation waves as typical events of excitable media have been observed in such tissue. The spreading depression (SD), an excitation depression wave is the most obvious and best described of these phenomena in the CNS. In our experiments we showed that the properties of the SD and therefore the CNS in its properties as an excitable medium reacts very sensitive to changes in gravity.

  16. Central nervous system nocardiosis in Queensland

    PubMed Central

    Rafiei, Nastaran; Peri, Anna Maria; Righi, Elda; Harris, Patrick; Paterson, David L.

    2016-01-01

    Abstract Nocardia infection of the central nervous system (CNS) is an uncommon but clinically important disease, often occurring in immunocompromised individuals and carrying a high mortality rate. We present 20 cases of microbiologically proven CNS nocardiosis diagnosed in Queensland from 1997 to 2015 and review the literature from 1997 to 2016. Over 50% of cases occurred in immunocompromised individuals, with corticosteroid use posing a particularly significant risk factor. Nine (45%) patients were immunocompetent and 3 had no comorbidities at time of diagnosis. Nocardia farcinica was the most frequently isolated species (8/20) and resistance to trimethoprim–sulfamethoxazole (TMP-SMX) was found in 2 isolates. Overall, 35% of our patients died within 1 year, with the majority of deaths occurring in the first month following diagnosis. Interestingly, of the 7 deaths occurring at 1 year, 6 were attributed to N farcinica with the seventh isolate being unspeciated, suggesting the virulence of the N farcinica strain. PMID:27861348

  17. 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

  18. [Viral infections of human central nervous system].

    PubMed

    Agut, Henri

    2016-01-01

    The viruses that can infect the central nervous system of humans are numerous and form a heterogeneous group with respect to their structural, functional and epidemiological properties. The pathophysiological mechanisms leading to associated neurological diseases, mainly meningitis and encephalitis, also are complex and often intertwined. Overall, neurological clinical symptoms correspond either to acute viral diseases associated with primary infections or to acute, subacute or chronic diseases associated with persistent viral infections. The frequent severity of the clinical situation requires in all cases the practice of virological diagnosis for which the PCR techniques applied to cerebrospinal fluid samples occupy a prominent place. The severity of clinical manifestations justifies the use of prophylactic vaccination when available and antiviral treatment as soon as the causative virus is identified or suspected.

  19. 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.

  20. Behavioral effects and central nervous system levels of the broadly available κ-agonist hallucinogen salvinorin A are affected by P-glycoprotein modulation in vivo.

    PubMed

    Butelman, Eduardo R; Caspers, Michael; Lovell, Kimberly M; Kreek, Mary Jeanne; Prisinzano, Thomas E

    2012-06-01

    Active blood-brain barrier mechanisms, such as the major efflux transporter P-glycoprotein (mdr1), modulate the in vivo/central nervous system (CNS) effects of many pharmacological agents, whether they are used for nonmedical reasons or in pharmacotherapy. The powerful, widely available hallucinogen salvinorin A (from the plant Salvia divinorum) is a high-efficacy, selective κ-opioid agonist and displays fast-onset behavioral effects (e.g., within 1 min of administration) and relatively short duration of action. In vitro studies suggest that salvinorin A may be a P-glycoprotein substrate; thus, the functional status of P-glycoprotein may influence the behavioral effects of salvinorin A or its residence in CNS after parenteral administration. We therefore studied whether a competing P-glycoprotein substrate (the clinically available agent loperamide; 0.032-0.32 mg/kg) or a selective P-glycoprotein blocker, tariquidar (0.32-3.2 mg/kg) could enhance unconditioned behavioral effects (ptosis and facial relaxation, known to be caused by κ-agonists in nonhuman primates) of salvinorin A, as well as its entry and residence in the CNS, as measured by cerebrospinal fluid sampling. Pretreatment with either loperamide or tariquidar dose-dependently enhanced salvinorin A-induced ptosis, but not facial relaxation. In a control study, loperamide and tariquidar were inactive when given as a pretreatment to ((+)-(5α,7α,8β)-N-methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro[4.5]dec-8-yl]-benzeneacetamide (U69,593), a κ-agonist known to be a very poor P-glycoprotein substrate. Furthermore, pretreatment with tariquidar (3.2 mg/kg) also enhanced peak levels of salvinorin A in cerebrospinal fluid after intravenous administration. These are the first studies in vivo showing the sensitivity of salvinorin A effects to modulation by the P-glycoprotein transporter, a major functional component of the blood-brain barrier.

  1. 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

  2. Central nervous system manifestations of neonatal lupus: a systematic review.

    PubMed

    Chen, C C; Lin, K-L; Chen, C-L; Wong, A May-Kuen; Huang, J-L

    2013-12-01

    Neonatal lupus is a rare and acquired autoimmune disease. Central nervous system abnormalities are potential manifestations in neonatal lupus. Through a systematic literature review, we analyzed the clinical features of previously reported neonatal lupus cases where central nervous system abnormalities had been identified. Most reported neonatal lupus patients with central nervous system involvement were neuroimaging-determined and asymptomatic. Only seven neonatal lupus cases were identified as having a symptomatic central nervous system abnormality which caused physical disability or required neurosurgery. A high percentage of these neurosymptomatic neonatal lupus patients had experienced a transient cutaneous skin rash and had no maternal history of autoimmune disease before pregnancy.

  3. Bilastine and the central nervous system.

    PubMed

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

    2011-01-01

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

  4. Sequencing of Local Therapy Affects the Pattern of Treatment Failure and Survival in Children With Atypical Teratoid Rhabdoid Tumors of the Central Nervous System

    SciTech Connect

    Pai Panandiker, Atmaram S.; Merchant, Thomas E.; Beltran, Chris; Wu, Shengjie; Sharma, Shelly; Boop, Frederick A.; Jenkins, Jesse J.; Helton, Kathleen J.; Wright, Karen D.; Broniscer, Alberto; Kun, Larry E.; Gajjar, Amar

    2012-04-01

    Purpose: To assess the pattern of treatment failure associated with current therapeutic paradigms for childhood atypical teratoid rhabdoid tumors (AT/RT). Methods and Materials: Pediatric patients with AT/RT of the central nervous system treated at our institution between 1987 and 2007 were retrospectively evaluated. Overall survival (OS), progression-free survival, and cumulative incidence of local failure were correlated with age, sex, tumor location, extent of disease, and extent of surgical resection. Radiotherapy (RT) sequencing, chemotherapy, dose, timing, and volume administered after resection were also evaluated. Results: Thirty-one patients at a median age of 2.3 years at diagnosis (range, 0.45-16.87 years) were enrolled into protocols that included risk- and age-stratified RT. Craniospinal irradiation with focal tumor bed boost (median dose, 54 Gy) was administered to 18 patients. Gross total resection was achieved in 16. Ten patients presented with metastases at diagnosis. RT was delayed more than 3 months in 20 patients and between 1 and 3 months in 4; 7 patients received immediate postoperative irradiation preceding high-dose alkylator-based chemotherapy. At a median follow-up of 48 months, the cumulative incidence of local treatment failure was 37.5% {+-} 9%; progression-free survival was 33.2% {+-} 10%; and OS was 53.5% {+-} 10%. Children receiving delayed RT ({>=}1 month postoperatively) were more likely to experience local failure (hazard ratio [HR] 1.23, p = 0.007); the development of distant metastases before RT increased the risk of progression (HR 3.49, p = 0.006); and any evidence of disease progressionbefore RT decreased OS (HR 20.78, p = 0.004). Disease progression occurred in 52% (11/21) of children with initially localized tumors who underwent gross total resection, and the progression rate increased proportionally with increasing delay from surgery to RT. Conclusions: Delayed RT is associated with a higher rate of local and metastatic

  5. Behavioral Effects and Central Nervous System Levels of the Broadly Available κ-Agonist Hallucinogen Salvinorin A Are Affected by P-Glycoprotein Modulation In Vivo

    PubMed Central

    Caspers, Michael; Lovell, Kimberly M.; Kreek, Mary Jeanne; Prisinzano, Thomas E.

    2012-01-01

    Active blood-brain barrier mechanisms, such as the major efflux transporter P-glycoprotein (mdr1), modulate the in vivo/central nervous system (CNS) effects of many pharmacological agents, whether they are used for nonmedical reasons or in pharmacotherapy. The powerful, widely available hallucinogen salvinorin A (from the plant Salvia divinorum) is a high-efficacy, selective κ-opioid agonist and displays fast-onset behavioral effects (e.g., within 1 min of administration) and relatively short duration of action. In vitro studies suggest that salvinorin A may be a P-glycoprotein substrate; thus, the functional status of P-glycoprotein may influence the behavioral effects of salvinorin A or its residence in CNS after parenteral administration. We therefore studied whether a competing P-glycoprotein substrate (the clinically available agent loperamide; 0.032–0.32 mg/kg) or a selective P-glycoprotein blocker, tariquidar (0.32–3.2 mg/kg) could enhance unconditioned behavioral effects (ptosis and facial relaxation, known to be caused by κ-agonists in nonhuman primates) of salvinorin A, as well as its entry and residence in the CNS, as measured by cerebrospinal fluid sampling. Pretreatment with either loperamide or tariquidar dose-dependently enhanced salvinorin A-induced ptosis, but not facial relaxation. In a control study, loperamide and tariquidar were inactive when given as a pretreatment to ((+)-(5α,7α,8β)-N-methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro[4.5]dec-8-yl]-benzeneacetamide (U69,593), a κ-agonist known to be a very poor P-glycoprotein substrate. Furthermore, pretreatment with tariquidar (3.2 mg/kg) also enhanced peak levels of salvinorin A in cerebrospinal fluid after intravenous administration. These are the first studies in vivo showing the sensitivity of salvinorin A effects to modulation by the P-glycoprotein transporter, a major functional component of the blood-brain barrier. PMID:22434677

  6. 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

  7. 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

  8. [Microbiological diagnosis of central nervous system infections].

    PubMed

    Codina, María Gema; de Cueto, Marina; Vicente, Diego; Echevarría, Juan Emilio; Prats, Guillem

    2011-02-01

    The infections of the central nervous system are associated with high morbidity and mortality. Several agents including bacteria, viruses, fungi and protozoa can invade the CNS. They are different clinical presentations of these infections: meningitis, encephalitis, brain and epidural abscesses and cerebrospinal fluid shunt infections. The clinical course could be acute, subacute or chronic depending on the infecting agent and the location of the infection. The travelling entails a risk of infection by exotic agents of meningo-encephalitis such as robovirus and arbovirus, which require new diagnostic and therapeutic methods. Despite some progress in the treatment of the CNS infections, the mortality is usually high. Rapid diagnosis and emergent interventions are necessary to improve the outcome of those patients, and early and targeted antimicrobial treatment and support measures are of paramount importance for a favourable clinical patient outcome. The antigen detection techniques and particularly those of genetic diagnosis by amplification (PCR and others) have advanced, and improved the diagnostic of those diseases. In this paper the clinical signs and symptoms and diagnostic procedures of CNS infections are presented.

  9. Histology of the central nervous system.

    PubMed

    Garman, Robert H

    2011-01-01

    The intent of this article is to assist pathologists inexperienced in examining central nervous system (CNS) sections to recognize normal and abnormal cell types as well as some common artifacts. Dark neurons are the most common histologic artifact but, with experience, can readily be distinguished from degenerating (eosinophilic) neurons. Neuron degeneration stains can be useful in lowering the threshold for detecting neuron degeneration as well as for revealing degeneration within populations of neurons that are too small to show the associated eosinophilic cytoplasmic alteration within H&E-stained sections. Neuron degeneration may also be identified by the presence of associated macroglial and microglial reactions. Knowledge of the distribution of astrocyte cytoplasmic processes is helpful in determining that certain patterns of treatment-related neuropil vacuolation (as well as some artifacts) represent swelling of these processes. On the other hand, vacuoles with different distribution patterns may represent alterations of the myelin sheath. Because brains are typically undersampled for microscopic evaluation, many pathologists are unfamiliar with the circumventricuar organs (CVOs) that represent normal brain structures but are often mistaken for lesions. Therefore, the six CVOs found in the brain are also illustrated in this article.

  10. Primary central nervous system posttransplant lymphoproliferative disorders.

    PubMed

    Castellano-Sanchez, Amilcar A; Li, Shiyong; Qian, Jiang; Lagoo, Anand; Weir, Edward; Brat, Daniel J

    2004-02-01

    Posttransplant lymphoproliferative disorders (PTLDs) represent a spectrum ranging from Epstein-Barr virus (EBV)-driven polyclonal lymphoid proliferations to EBV+ or EBV- malignant lymphomas. Central nervous system (CNS) PTLDs have not been characterized fully. We reviewed the clinical, radiologic, and pathologic features of 12 primary CNS PTLDs to define them more precisely. Patients included 10 males and 2 females (median age, 43.4 years) who were recipients of kidney (n = 5), liver (n = 2), heart (n = 2), peripheral blood stem cells (n = 2), or bone marrow (n = 1). All received immunosuppressive therapy. CNS symptoms developed 3 to 131 months (mean, 31 months) after transplantation. By neuroimaging, most showed multiple (3 to 9) intra-axial, contrast-enhancing lesions. Histologic sections showed marked expansion of perivascular spaces by large, cytologically malignant lymphoid cells that were CD45+, CD20+, EBV+ and showed light chain restriction or immunoglobulin gene rearrangement. In distinction to PTLDs in other organ systems, CNS PTLDs were uniformly high-grade lymphomas that fulfilled the World Health Organization criteria for monomorphic PTLDs. Extremely short survival periods were noted for each CNS PTLD that followed peripheral blood stem cell transplantation. Survival of others with CNS PTLD varied; some lived more than 2 years.

  11. [Primary central nervous system lymphoma: report of one case].

    PubMed

    Zhao, Peng; Su, Rong-Gang

    2002-04-01

    One case of primary central nervous system lymphoma was reported. The patient received comprehensive therapy, mainly the surgical treatment, with the survival time 12 months, and local recurrence was considered as the major cause of death. The pathology, imagine examination, diagnosis and treatment of primary central nervous system lymphoma were discussed.

  12. [Necrotizing systemic sarcoidosis with pulmonary and central nervous system involvement].

    PubMed

    Ríos Fernández, R; Callejas-Rubio, J L; Guerrero Fernández, M; Serrano Falcón, M M; Ortego-Centeno, N

    2008-01-01

    Sarcoidosis is a multisystemic disease which diagnosis depends on the presence of nonnecrotizing granulomas in the biopsy. However there are variants such as necrotizing sarcoidal granulomas or nodular sarcoidosis which have atypical findings and make difficult the differential diagnosis with other infectious processes. We describe a case of a man who develops granulomas with extensive necrosis in a systemic sarcoidosis that affected the lung and the central nervous system. This finding made us to make the diagnosis of tuberculosis and delay the specific treatment.

  13. 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

  14. Aging, the Central Nervous System, and Mobility

    PubMed Central

    2013-01-01

    Background. Mobility limitations are common and hazardous in community-dwelling older adults but are largely understudied, particularly regarding the role of the central nervous system (CNS). This has limited development of clearly defined pathophysiology, clinical terminology, and effective treatments. Understanding how changes in the CNS contribute to mobility limitations has the potential to inform future intervention studies. Methods. A conference series was launched at the 2012 conference of the Gerontological Society of America in collaboration with the National Institute on Aging and the University of Pittsburgh. The overarching goal of the conference series is to facilitate the translation of research results into interventions that improve mobility for older adults. Results. Evidence from basic, clinical, and epidemiological studies supports the CNS as an important contributor to mobility limitations in older adults without overt neurologic disease. Three main goals for future work that emerged were as follows: (a) develop models of mobility limitations in older adults that differentiate aging from disease-related processes and that fully integrate CNS with musculoskeletal contributors; (b) quantify the contribution of the CNS to mobility loss in older adults in the absence of overt neurologic diseases; (c) promote cross-disciplinary collaboration to generate new ideas and address current methodological issues and barriers, including real-world mobility measures and life-course approaches. Conclusions. In addition to greater cross-disciplinary research, there is a need for new approaches to training clinicians and investigators, which integrate concepts and methodologies from individual disciplines, focus on emerging methodologies, and prepare investigators to assess complex, multisystem associations. PMID:23843270

  15. Congenital tumors of the central nervous system.

    PubMed

    Severino, Mariasavina; Schwartz, Erin S; Thurnher, Majda M; Rydland, Jana; Nikas, Ioannis; Rossi, Andrea

    2010-06-01

    Congenital tumors of the central nervous system (CNS) are often arbitrarily divided into "definitely congenital" (present or producing symptoms at birth), "probably congenital" (present or producing symptoms within the first week of life), and "possibly congenital" (present or producing symptoms within the first 6 months of life). They represent less than 2% of all childhood brain tumors. The clinical features of newborns include an enlarged head circumference, associated hydrocephalus, and asymmetric skull growth. At birth, a large head or a tense fontanel is the presenting sign in up to 85% of patients. Neurological symptoms as initial symptoms are comparatively rare. The prenatal diagnosis of congenital CNS tumors, while based on ultrasonography, has significantly benefited from the introduction of prenatal magnetic resonance imaging studies. Teratomas constitute about one third to one half of these tumors and are the most common neonatal brain tumor. They are often immature because of primitive neural elements and, rarely, a component of mixed malignant germ cell tumors. Other tumors include astrocytomas, choroid plexus papilloma, primitive neuroectodermal tumors, atypical teratoid/rhabdoid tumors, and medulloblastomas. Less common histologies include craniopharyngiomas and ependymomas. There is a strong predilection for supratentorial locations, different from tumors of infants and children. Differential diagnoses include spontaneous intracranial hemorrhage that can occur in the presence of coagulation factor deficiency or underlying vascular malformations, and congenital brain malformations, especially giant heterotopia. The prognosis for patients with congenital tumors is generally poor, usually because of the massive size of the tumor. However, tumors can be resected successfully if they are small and favorably located. The most favorable outcomes are achieved with choroid plexus tumors, where aggressive surgical treatment leads to disease-free survival.

  16. 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

  17. Disseminated encephalomyelitis-like central nervous system neoplasm in childhood.

    PubMed

    Zhao, Jianhui; Bao, Xinhua; Fu, Na; Ye, Jintang; Li, Ting; Yuan, Yun; Zhang, Chunyu; Zhang, Yao; Zhang, Yuehua; Qin, Jiong; Wu, Xiru

    2014-08-01

    A malignant neoplasm in the central nervous system with diffuse white matter changes on magnetic resonance imaging (MRI) is rare in children. It could be misdiagnosed as acute disseminated encephalomyelitis. This report presents our experience based on 4 patients (3 male, 1 female; aged 7-13 years) whose MRI showed diffuse lesions in white matter and who were initially diagnosed with acute disseminated encephalomyelitis. All of the patients received corticosteroid therapy. After brain biopsy, the patients were diagnosed with gliomatosis cerebri, primitive neuroectodermal tumor and central nervous system lymphoma. We also provide literature reviews and discuss the differentiation of central nervous system neoplasm from acute disseminated encephalomyelitis.

  18. Embryonic Development of the Central Nervous System.

    PubMed

    de Lahunta, Alexander; Glass, Eric N; Kent, Marc

    2016-03-01

    Ultimately, it is only with an understanding of normal embryologic development that there can be an understanding of why and how a specific malformation develops. Knowing from where and when a specific part of the nervous system develops and what morphogens are at play will enable us to identify undescribed malformation as well as better define causality. The following article reviews the normal embryologic development of the mammalian nervous system and is intended to serve as a foundation for the understanding of the various malformations presented in this issue.

  19. Vasculitis Syndromes of the Central and Peripheral Nervous Systems

    MedlinePlus

    ... the Central and Peripheral Nervous Systems Fact Sheet Table of Contents (click to jump to sections) What ... Information Page NINDS Epilepsy Information Page NINDS Familial Periodic Paralyses Information Page NINDS Farber's Disease Information Page ...

  20. [Microglial cells and development of the embryonic central nervous system].

    PubMed

    Legendre, Pascal; Le Corronc, Hervé

    2014-02-01

    Microglia cells are the macrophages of the central nervous system with a crucial function in the homeostasis of the adult brain. However, recent studies showed that microglial cells may also have important functions during early embryonic central nervous system development. In this review we summarize recent works on the extra embryonic origin of microglia, their progenitor niche, the pattern of their invasion of the embryonic central nervous system and on interactions between embryonic microglia and their local environment during invasion. We describe microglial functions during development of embryonic neuronal networks, including their roles in neurogenesis, in angiogenesis and developmental cell death. These recent discoveries open a new field of research on the functions of neural-microglial interactions during the development of the embryonic central nervous system.

  1. Central Nervous System Infections in Patients with Severe Burns

    DTIC Science & Technology

    2010-01-01

    both patients had bacteremia with identical microorganisms as isolated from CSF ( Acinetobacter baumannii and methicillin resistant Staphylococcus...multiresistant Acinetobacter baumannii central nervous system infections with intraventricular or intrathecal colistin: case series and literature review. J

  2. Role of metallothionein-III following central nervous system damage.

    PubMed

    Carrasco, Javier; Penkowa, Milena; Giralt, Mercedes; Camats, Jordi; Molinero, Amalia; Campbell, Iain L; Palmiter, Richard D; Hidalgo, Juan

    2003-06-01

    We evaluated the physiological relevance of metallothionein-III (MT-III) in the central nervous system following damage caused by a focal cryolesion onto the cortex by studying Mt3-null mice. In normal mice, dramatic astrogliosis and microgliosis and T-cell infiltration were observed in the area surrounding the lesioned tissue, along with signs of increased oxidative stress and apoptosis. There was also significant upregulation of cytokines/growth factors such as tumor necrosis factor-alpha, interleukin (IL)-1 alpha/beta, and IL-6 as measured by ribonuclease protection assay. Mt3-null mice did not differ from control mice in these responses, in sharp contrast to results obtained in Mt1- Mt2-null mice. In contrast, Mt3-null mice showed increased expression of several neurotrophins as well as of the neuronal sprouting factor GAP-43. Thus, unlike MT-I and MT-II, MT-III does not affect the inflammatory response elicited in the central nervous system by a cryoinjury, nor does it serve an important antioxidant role, but it may influence neuronal regeneration during the recovery process.

  3. Reorganization of the human central nervous system.

    PubMed

    Schalow, G; Zäch, G A

    2000-10-01

    The key strategies on which the discovery of the functional organization of the central nervous system (CNS) under physiologic and pathophysiologic conditions have been based included (1) our measurements of phase and frequency coordination between the firings of alpha- and gamma-motoneurons and secondary muscle spindle afferents in the human spinal cord, (2) knowledge on CNS reorganization derived upon the improvement of the functions of the lesioned CNS in our patients in the short-term memory and the long-term memory (reorganization), and (3) the dynamic pattern approach for re-learning rhythmic coordinated behavior. The theory of self-organization and pattern formation in nonequilibrium systems is explicitly related to our measurements of the natural firing patterns of sets of identified single neurons in the human spinal premotor network and re-learned coordinated movements following spinal cord and brain lesions. Therapy induced cell proliferation, and maybe, neurogenesis seem to contribute to the host of structural changes during the process of re-learning of the lesioned CNS. So far, coordinated functions like movements could substantially be improved in every of the more than 100 patients with a CNS lesion by applying coordination dynamic therapy. As suggested by the data of our patients on re-learning, the human CNS seems to have a second integrative strategy for learning, re-learning, storing and recalling, which makes an essential contribution of the functional plasticity following a CNS lesion. A method has been developed by us for the simultaneous recording with wire electrodes of extracellular action potentials from single human afferent and efferent nerve fibres of undamaged sacral nerve roots. A classification scheme of the nerve fibres in the human peripheral nervous system (PNS) could be set up in which the individual classes of nerve fibres are characterized by group conduction velocities and group nerve fibre diameters. Natural impulse patterns

  4. Central nervous system systemic lupus erythematosus mimicking progressive multifocal leucoencephalopathy.

    PubMed Central

    Kaye, B R; Neuwelt, C M; London, S S; DeArmond, S J

    1992-01-01

    The case is reported of a patient with central nervous system systemic lupus erythematosus (SLE) with features of progressive multifocal leucoencephalopathy (PML) seen clinically and by magnetic resonance imaging. A brain biopsy sample showed microinfarcts. The use of magnetic resonance imaging and IgG synthesis rates in evaluating central nervous system lupus, the co-occurrence of SLE and PML, and the differentiation of these entities by magnetic resonance imaging and by histology are considered. Images PMID:1444628

  5. Pharmacotherapy for Adults with Tumors of the Central Nervous System

    PubMed Central

    Schor, Nina F.

    2009-01-01

    Tumors of the adult central nervous system are among the most common and most chemoresistant neoplasms. Malignant tumors of the brain and spinal cord collectively account for approximately 1.3% of all cancers and 2.2% of all cancer-related deaths. Novel pharmacological approaches to nervous system tumors are urgently needed. This review presents the current approaches and challenges to successful pharmacotherapy of adults with malignant tumors of the central nervous system and discusses novel approaches aimed at overcoming these challenges. PMID:19091301

  6. 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

  7. Prolonged prenatal exposure to low-level ozone affects aggressive behaviour as well as NGF and BDNF levels in the central nervous system of CD-1 mice.

    PubMed

    Santucci, Daniela; Sorace, Alberto; Francia, Nadia; Aloe, Luigi; Alleva, Enrico

    2006-01-06

    The long-term effects on isolation-induced aggressive behaviour and central NGF and BDNF levels of gestational exposures to ozone (O(3)) were evaluated in adult CD-1 mice. Females were exposed to O(3), at the dose of 0.0, 0.3 or 0.6 ppm from 30 days prior the formation of breeding pairs until gestational day 17. Litters were fostered at birth to untreated dams and, at adulthood, male offspring underwent five successive daily encounters (15 min each) with a standard opponent of the same strain, sex, weight and age. The encounters on day 1, 3 and 5 were videotaped and agonistic and non-agonistic behavioural items finely scored. O(3)-exposed mice showed a significant increase in freezing and defensive postures, a decrease in nose-sniffing behaviour and reduced progressively the aggressive behavioural profile displayed on day 1. Reduced NGF levels in the hippocampus and increased BDNF in the striatum were also found upon O(3) exposure.

  8. Development-inspired reprogramming of the mammalian central nervous system.

    PubMed

    Amamoto, Ryoji; Arlotta, Paola

    2014-01-31

    In 2012, John Gurdon and Shinya Yamanaka shared the Nobel Prize for the 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 heads 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 affect regeneration and modeling of a system historically considered immutable and hardwired.

  9. 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.

  10. Calcium pumps in the central nervous system.

    PubMed

    Mata, Ana M; Sepúlveda, M Rosario

    2005-09-01

    Two families of Ca2+ transport ATPases are involved in the maintenance of Ca2+ homeostasis in the nervous system, the plasma membrane Ca2+-ATPase that pumps Ca2+ to the extracellular medium and the intracellular sarco/endoplasmic reticulum Ca2+-ATPase that transports Ca2+ from the cytosol to the endoplasmic reticulum. Both types of calcium pumps show precise regulatory properties and they are localized in specific subcellular regions. In this review, we describe the functional and regulatory properties of both families of calcium pumps, their distribution in nerve cells, and their involvement in neurological disorders. The functional characterization of neuronal calcium pumps is very important in order to understand the biochemical processes involved in the maintenance of intracellular calcium in synaptic terminals.

  11. Adenosine receptors and the central nervous system.

    PubMed

    Sebastião, Ana M; Ribeiro, Joaquim A

    2009-01-01

    The adenosine receptors (ARs) in the nervous system act as a kind of "go-between" to regulate the release of neurotransmitters (this includes all known neurotransmitters) and the action of neuromodulators (e.g., neuropeptides, neurotrophic factors). Receptor-receptor interactions and AR-transporter interplay occur as part of the adenosine's attempt to control synaptic transmission. A(2A)ARs are more abundant in the striatum and A(1)ARs in the hippocampus, but both receptors interfere with the efficiency and plasticity-regulated synaptic transmission in most brain areas. The omnipresence of adenosine and A(2A) and A(1) ARs in all nervous system cells (neurons and glia), together with the intensive release of adenosine following insults, makes adenosine a kind of "maestro" of the tripartite synapse in the homeostatic coordination of the brain function. Under physiological conditions, both A(2A) and A(1) ARs play an important role in sleep and arousal, cognition, memory and learning, whereas under pathological conditions (e.g., Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, stroke, epilepsy, drug addiction, pain, schizophrenia, depression), ARs operate a time/circumstance window where in some circumstances A(1)AR agonists may predominate as early neuroprotectors, and in other circumstances A(2A)AR antagonists may alter the outcomes of some of the pathological deficiencies. In some circumstances, and depending on the therapeutic window, the use of A(2A)AR agonists may be initially beneficial; however, at later time points, the use of A(2A)AR antagonists proved beneficial in several pathologies. Since selective ligands for A(1) and A(2A) ARs are now entering clinical trials, the time has come to determine the role of these receptors in neurological and psychiatric diseases and identify therapies that will alter the outcomes of these diseases, therefore providing a hopeful future for the patients who suffer from these diseases.

  12. 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

  13. 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.

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

    PubMed

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

    2014-01-01

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

  15. The renin-angiotensin system and the central nervous system.

    PubMed

    Ganong, W F

    1977-04-01

    One of several factors affecting the secretion of renin by the kidneys is the sympathetic nervous system. The sympathetic input is excitatory and is mediated by beta-adrenergic receptors, which are probably located on the membranes of the juxtaglomerular cells. Stimulation of sympathetic areas in the medulla, midbrain and hypothalamus raises blood pressure and increases renin secretion, whereas stimulation of other parts of the hypothalamus decreases blood pressure and renin output. The centrally active alpha-adrenergic agonist clonidine decreases renin secretion, lowers blood pressure, inhibits ACTH and vasopressin secretion, and increases growth hormone secretion in dogs. The effects on ACTH and growth hormone are abolished by administration of phenoxybenzamine into the third ventricle, whereas the effect on blood pressure is abolished by administration of phenoxybenzamine in the fourth ventricle without any effect on the ACTH and growth hormone responses. Fourth ventricular phenoxybenzamine decreases but does not abolish the inhibitory effect of clonidine on renin secretion. Circulating angiotensin II acts on the brain via the area postrema to raise blood pressure and via the subfornical organ to increase water intake. Its effect on vasopressin secretion is debated. The brain contains a renin-like enzyme, converting enzyme, renin substrate, and angiotensin. There is debate about the nature and physiological significance of the angiotensin II-generating enzyme in the brain, and about the nature of the angiotensin I and angiotensin II that have been reported to be present in the central nervous system. However, injection of angiotensin II into the cerebral ventricles produces drinking, increased secretion of vasopressin and ACTH, and increased blood pressure. The same responses are produced by intraventricular renin. Angiotensin II also facilitates sympathetic discharge in the periphery, and the possibility that it exerts a similar action on the adrenergic neurons

  16. Nongenomic Actions of Adrenal Steroids in the Central Nervous System

    PubMed Central

    Evanson, Nathan K.; Herman, James P.; Sakai, Randall R.; Krause, Eric G.

    2015-01-01

    Mineralocorticoids and glucocorticoids are steroid hormones that are released by the adrenal cortex in response to stress and hydromineral imbalance. Historically, adrenocorticosteroid actions are attributed to effects on gene transcription. More recently, however, it has become clear that genome-independent pathways represent an important facet of adrenal steroid actions. These hormones exert nongenomic effects throughout the body, but a significant portion of their actions are specific to the central nervous system. These actions are mediated by a variety of signalling pathways, and lead to physiologically meaningful events in vitro and in vivo. Here we review nongenomic effects of adrenal steroids in the central nervous system at the levels of behaviour, neural system activity, individual neurone activity, and subcellular signalling activity. A clearer understanding of adrenal steroid activity in the central nervous system will lead to a better ability both to treat human disease, and to reduce side-effects of steroid treatments already in use. PMID:20367759

  17. 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.

  18. 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.…

  19. Central Auditory Nervous System Dysfunction in Echolalic Autistic Individuals.

    ERIC Educational Resources Information Center

    Wetherby, Amy Miller; And Others

    1981-01-01

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

  20. 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…

  1. Aberrant nerve fibres within the central nervous system.

    PubMed

    Moffie, D

    1992-01-01

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

  2. 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

  3. Pediatric central nervous system infections and inflammatory white matter disease.

    PubMed

    Silvia, Mary T; Licht, Daniel J

    2005-08-01

    This article reviews the immunology of the central nervous system and the clinical presentation, diagnosis, and treatment of children with viral or parainfectious encephalitis. The emphasis is on the early recognition of treatable causes of viral encephalitis (herpes simplex virus), and the diagnosis and treatment of acute disseminated encephalomyelitis are described in detail. Laboratory and imaging findings in the two conditions also are described.

  4. 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.

  5. Heterotopic ossification after central nervous system trauma

    PubMed Central

    Sullivan, M. P.; Torres, S. J.; Mehta, S.; Ahn, J.

    2013-01-01

    Neurogenic heterotopic ossification (NHO) is a disorder of aberrant bone formation affecting one in five patients sustaining a spinal cord injury or traumatic brain injury. Ectopic bone forms around joints in characteristic patterns, causing pain and limiting movement especially around the hip and elbow. Clinical sequelae of neurogenic heterotopic ossification include urinary tract infection, pressure injuries, pneumonia and poor hygiene, making early diagnosis and treatment clinically compelling. However, diagnosis remains difficult with more investigation needed. Our pathophysiological understanding stems from mechanisms of basic bone formation enhanced by evidence of systemic influences from circulating humor factors and perhaps neurological ones. This increasing understanding guides our implementation of current prophylaxis and treatment including the use of non-steroidal anti-inflammatory drugs, bisphosphonates, radiation therapy and surgery and, importantly, should direct future, more effective ones. PMID:23610702

  6. Global research priorities for infections that affect the nervous system.

    PubMed

    John, Chandy C; Carabin, Hélène; Montano, Silvia M; Bangirana, Paul; Zunt, Joseph R; Peterson, Phillip K

    2015-11-19

    Infections that cause significant nervous system morbidity globally include viral (for example, HIV, rabies, Japanese encephalitis virus, herpes simplex virus, varicella zoster virus, cytomegalovirus, dengue virus and chikungunya virus), bacterial (for example, tuberculosis, syphilis, bacterial meningitis and sepsis), fungal (for example, cryptococcal meningitis) and parasitic (for example, malaria, neurocysticercosis, neuroschistosomiasis and soil-transmitted helminths) infections. The neurological, cognitive, behavioural or mental health problems caused by the infections probably affect millions of children and adults in low- and middle-income countries. However, precise estimates of morbidity are lacking for most infections, and there is limited information on the pathogenesis of nervous system injury in these infections. Key research priorities for infection-related nervous system morbidity include accurate estimates of disease burden; point-of-care assays for infection diagnosis; improved tools for the assessment of neurological, cognitive and mental health impairment; vaccines and other interventions for preventing infections; improved understanding of the pathogenesis of nervous system disease in these infections; more effective methods to treat and prevent nervous system sequelae; operations research to implement known effective interventions; and improved methods of rehabilitation. Research in these areas, accompanied by efforts to implement promising technologies and therapies, could substantially decrease the morbidity and mortality of infections affecting the nervous system in low- and middle-income countries.

  7. Global research priorities for infections that affect the nervous system

    PubMed Central

    John, Chandy C.; Carabin, Hélène; Montano, Silvia M.; Bangirana, Paul; Zunt, Joseph R.; Peterson, Phillip K.

    2015-01-01

    Infections that cause significant nervous system morbidity globally include viral (for example, HIV, rabies, Japanese encephalitis virus, herpes simplex virus, varicella zoster virus, cytomegalovirus, dengue virus and chikungunya virus), bacterial (for example, tuberculosis, syphilis, bacterial meningitis and sepsis), fungal (for example, cryptococcal meningitis) and parasitic (for example, malaria, neurocysticercosis, neuroschistosomiasis and soil-transmitted helminths) infections. The neurological, cognitive, behavioural or mental health problems caused by the infections probably affect millions of children and adults in low- and middle-income countries. However, precise estimates of morbidity are lacking for most infections, and there is limited information on the pathogenesis of nervous system injury in these infections. Key research priorities for infection-related nervous system morbidity include accurate estimates of disease burden; point-of-care assays for infection diagnosis; improved tools for the assessment of neurological, cognitive and mental health impairment; vaccines and other interventions for preventing infections; improved understanding of the pathogenesis of nervous system disease in these infections; more effective methods to treat and prevent nervous system sequelae; operations research to implement known effective interventions; and improved methods of rehabilitation. Research in these areas, accompanied by efforts to implement promising technologies and therapies, could substantially decrease the morbidity and mortality of infections affecting the nervous system in low- and middle-income countries. PMID:26580325

  8. 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

  9. Chaperone Proteins in the Central Nervous System and Peripheral Nervous System after Nerve Injury.

    PubMed

    Ousman, Shalina S; Frederick, Ariana; Lim, Erin-Mai F

    2017-01-01

    Injury to axons of the central nervous system (CNS) and the peripheral nervous system (PNS) is accompanied by the upregulation and downregulation of numerous molecules that are involved in mediating nerve repair, or in augmentation of the original damage. Promoting the functions of beneficial factors while reducing the properties of injurious agents determines whether regeneration and functional recovery ensues. A number of chaperone proteins display reduced or increased expression following CNS and PNS damage (crush, transection, contusion) where their roles have generally been found to be protective. For example, chaperones are involved in mediating survival of damaged neurons, promoting axon regeneration and remyelination and, improving behavioral outcomes. We review here the various chaperone proteins that are involved after nervous system axonal damage, the functions that they impact in the CNS and PNS, and the possible mechanisms by which they act.

  10. Chaperone Proteins in the Central Nervous System and Peripheral Nervous System after Nerve Injury

    PubMed Central

    Ousman, Shalina S.; Frederick, Ariana; Lim, Erin-Mai F.

    2017-01-01

    Injury to axons of the central nervous system (CNS) and the peripheral nervous system (PNS) is accompanied by the upregulation and downregulation of numerous molecules that are involved in mediating nerve repair, or in augmentation of the original damage. Promoting the functions of beneficial factors while reducing the properties of injurious agents determines whether regeneration and functional recovery ensues. A number of chaperone proteins display reduced or increased expression following CNS and PNS damage (crush, transection, contusion) where their roles have generally been found to be protective. For example, chaperones are involved in mediating survival of damaged neurons, promoting axon regeneration and remyelination and, improving behavioral outcomes. We review here the various chaperone proteins that are involved after nervous system axonal damage, the functions that they impact in the CNS and PNS, and the possible mechanisms by which they act. PMID:28270745

  11. Immunocytochemical Detection of Acetylcholine in the Rat Central Nervous System

    NASA Astrophysics Data System (ADS)

    Geffard, M.; McRae-Degueurce, A.; Souan, Marie Laure

    1985-07-01

    A specific antibody to acetylcholine was raised and used as a marker for cholinergic neurons in the rat central nervous system. The acetylcholine conjugate was obtained by a two-step immunogen synthesis procedure. An enzyme-linked immunosorbent assay was used to test the specificity and affinity of the antibody in vitro; the results indicated high affinity. A chemical perfusion mixture of allyl alcohol and glutaraldehyde was used to fix the acetylcholine in the nervous tissue. Peroxidase-antiperoxidase immunocytochemistry showed many acetylcholine-immunoreactive cells and fibers in sections from the medial septum region.

  12. Is Ghrelin Synthesized in the Central Nervous System?

    PubMed Central

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

    2017-01-01

    Ghrelin is an octanoylated peptide that acts via its specific receptor, the growth hormone secretagogue receptor type 1a (GHSR-1a), and regulates a vast variety of physiological functions. It is well established that ghrelin is predominantly synthesized by a distinct population of endocrine cells located within the gastric oxyntic mucosa. In addition, some studies have reported that ghrelin could also be synthesized in some brain regions, such as the hypothalamus. However, evidences of neuronal production of ghrelin have been inconsistent and, as a consequence, it is still as a matter of debate if ghrelin can be centrally produced. Here, we provide a comprehensive review and discussion of the data supporting, or not, the notion that the mammalian central nervous system can synthetize ghrelin. We conclude that no irrefutable and reproducible evidence exists supporting the notion that ghrelin is synthetized, at physiologically relevant levels, in the central nervous system of adult mammals. PMID:28294994

  13. Is Ghrelin Synthesized in the Central Nervous System?

    PubMed

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

    2017-03-15

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

  14. 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.

  15. 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.

  16. 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.

  17. Cholesterol: Its Regulation and Role in Central Nervous System Disorders

    PubMed Central

    Orth, Matthias; Bellosta, Stefano

    2012-01-01

    Cholesterol is a major constituent of the human brain, and the brain is the most cholesterol-rich organ. Numerous lipoprotein receptors and apolipoproteins are expressed in the brain. Cholesterol is tightly regulated between the major brain cells and is essential for normal brain development. The metabolism of brain cholesterol differs markedly from that of other tissues. Brain cholesterol is primarily derived by de novo synthesis and the blood brain barrier prevents the uptake of lipoprotein cholesterol from the circulation. Defects in cholesterol metabolism lead to structural and functional central nervous system diseases such as Smith-Lemli-Opitz syndrome, Niemann-Pick type C disease, and Alzheimer's disease. These diseases affect different metabolic pathways (cholesterol biosynthesis, lipid transport and lipoprotein assembly, apolipoproteins, lipoprotein receptors, and signaling molecules). We review the metabolic pathways of cholesterol in the CNS and its cell-specific and microdomain-specific interaction with other pathways such as the amyloid precursor protein and discuss potential treatment strategies as well as the effects of the widespread use of LDL cholesterol-lowering drugs on brain functions. PMID:23119149

  18. 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

  19. 3D in vitro modeling of the central nervous system.

    PubMed

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

    2015-02-01

    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.

  20. Neurogenesis during development of the vertebrate central nervous system

    PubMed Central

    Paridaen, Judith TML; Huttner, Wieland B

    2014-01-01

    During vertebrate development, a wide variety of cell types and tissues emerge from a single fertilized oocyte. One of these tissues, the central nervous system, contains many types of neurons and glial cells that were born during the period of embryonic and post-natal neuro- and gliogenesis. As to neurogenesis, neural progenitors initially divide symmetrically to expand their pool and switch to asymmetric neurogenic divisions at the onset of neurogenesis. This process involves various mechanisms involving intrinsic as well as extrinsic factors. Here, we discuss the recent advances and insights into regulation of neurogenesis in the developing vertebrate central nervous system. Topics include mechanisms of (a)symmetric cell division, transcriptional and epigenetic regulation, and signaling pathways, using mostly examples from the developing mammalian neocortex. PMID:24639559

  1. Central nervous system histoplasmosis in an immunocompetent pediatric patient.

    PubMed

    Esteban, Ignacio; Minces, Pablo; De Cristofano, Analía M; Negroni, Ricardo

    2016-06-01

    Neurohistoplasmosis is a rare disease, most prevalent in immunosuppressed patients, secondary to disseminated disease with a high mortality rate when diagnosis and treatment are delayed. We report a previously healthy 12 year old girl, from a bat infested region of Tucuman Province, Argentine Republic, who developed meningoencephalitis due to Histoplasma capsulatum. Eighteen months prior to admission the patient started with headaches and intermittent fever. The images of the central nervous system showed meningoencephalitis suggestive of tuberculosis. She received antibiotics and tuberculostatic medications without improvement. Liposomal amphotericin B was administered for six weeks. The patient's clinical status improved remarkably. Finally the culture of cerebral spinal fluid was positive for micelial form of Histoplasma capsulatum. The difficulties surrounding the diagnosis and treatment of neurohistoplasmosis in immunocompetent patients are discussed in this manuscript, as it also intends to alert to the presence of a strain of Histoplasma capsulatum with affinity for the central nervous system.

  2. 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

  3. Neurotropic Enterovirus Infections in the Central Nervous System.

    PubMed

    Huang, Hsing-I; Shih, Shin-Ru

    2015-11-24

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

  4. [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.

  5. Atypical presentation of pheochromocytoma: Central nervous system pseudovasculitis

    PubMed Central

    Rupala, Ketankumar; Mittal, Varun; Gupta, Rajiv; Yadav, Rajiv

    2017-01-01

    Pheochromocytoma has atypical presentation in 9%–10% of patients. Atypical presentations include myocardial infarction, renal failure, and rarely cerebrovascular events. Various etiologies for central nervous system (CNS) involvement in pheochromocytoma have been described in the literature. A rare association of CNS vasculitis-like features has been described with pheochromocytoma. We report a rare case of pheochromocytoma detected on evaluation for CNS vasculitis-like symptoms. PMID:28197038

  6. [Systemic lupus erythematosus and the central nervous system].

    PubMed

    Rojas, E; Orrea Solano, M

    1993-01-01

    The central nervous system (CNS) manifestations of the chronic autoimmune disease systemic lupus erythematous (SLE) are reviewed. SLE-CNS dysfunction is broadly divided into neurologic and psychiatric clinical categories. The distinct clinical entities within these broad categories are fully described. Diagnostic criteria employed to verify the presence of SLE-CNS dysfunction, including laboratory serum and cerebral spinal fluid analyses as well as radiologic and other multimodality diagnostic tools, are compared and contrasted with respect to sensitivity and specificity.

  7. TH1/TH2 cytokines in the central nervous system.

    PubMed

    Sredni-Kenigsbuch, Dvora

    2002-06-01

    For the past 20 years it has become increasingly evident that cytokines play an important role in both the normal development of the brain, acting as neurotrophic factors, and in brain injuries. Although cytokines and their receptors are synthesized and expressed in the brain (normally at low levels), increased cytokine production levels are now associated with various neurological disorders. T lymphocytes are the cells responsible for coordinating the immune response and a major source of cytokines. Different cytokines induce different subsets of T cells or have different effects on proliferation within a particular subset. Recent studies suggest that the immune response is in fact regulated by the balance between Th1 and Th2 cytokines. These two pathways are often mutually exclusive, the one resulting in protection and the other in progression of disease. Various studies describe the function and production of proinflammatory cytokines in the central nervous system (CNS) and their role in health and disease. Inflammation is upregulated following activation of Th1 cells, whereas Th2 cells may play a significant role in downregulating Th1 proinflammatory responses in those instances in which there is overproduction of Th2 cytokines. Although both Th1 and Th2 cytokines may influence CNS functioning, most studies have so far dealt with proinflammatory cytokines, probably because they directly affect CNS cells and are thought to be implicated in CNS pathology. It is of interest that endogenous glucocorticoids also control Th1-Th2 balance, favoring Th2 cell development. This review presents the evidence that cytokines have important functions in the CNS, both during development and as a part of brain pathology. In particular, the author highlighted recent work that supports a major role for the so-called inflammatory cytokines, Th1, and the anti-inflammatory Th2 cytokines.

  8. 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.

  9. Functional roles of neuropeptides in the insect central nervous system

    NASA Astrophysics Data System (ADS)

    Nässel, D. R.

    With the completion of the Drosophila genome sequencing project we can begin to appreciate the extent of the complexity in the components involved in signal transfer and modulation in the nervous system of an animal with reasonably complex behavior. Of all the different classes of signaling substances utilized by the nervous system, the neuropeptides are the most diverse structurally and functionally. Thus peptidergic mechanisms of action in the central nervous system need to be analyzed in the context of the neuronal circuits in which they act and generalized traits cannot be established. By taking advantage of Drosophila molecular genetics and the presence of identifiable neurons, it has been possible to interfere with peptidergic signaling in small populations of central neurons and monitor the consequences on behavior. These studies and experiments on other insects with large identifiable neurons, permitting cellular analysis of signaling mechanisms, have outlined important principles for temporal and spatial action of neuropeptides in outputs of the circadian clock and in orchestrating molting behavior. Considering the large number of neuropeptides available in each insect species and their diverse distribution patterns, it is to be expected that different neuropeptides play roles in most aspects of insect physiology and behavior.

  10. 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.

  11. [Pleasure, pain and affectivity in the nervous system].

    PubMed

    Houdart, R

    1999-01-01

    Affectivity plays an essential role in human life. It gives life its quality, and is responsible for what human beings have always considered to be main endeavor happiness. Still, looking for its description or organisation, in physiology or neurology, treatises is fruitless; there only one of its components is described pain, with no mention of pleasure. We wish to show, here, first, that pain and pleasure, depend of a same function, of which they are, of sorts, both extremities, and which in nothing but the most primitive function of the nervous system, and secondly, that this function in one of the components of an "affectivity center", which has its organisation in the limbic system. This center, integrating all the informations that arrives to the nervous system, triggers to each of them neuro-vegetative and neuro-hormonal informations that are "felt" by the organism, and thus transforms the information in a subjective feeling.

  12. 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.

  13. Vulnerable periods and processes during central nervous system development.

    PubMed Central

    Rodier, P M

    1994-01-01

    The developing central nervous system (CNS) is the organ system most frequently observed to exhibit congenital abnormalities. While the developing CNS lacks a blood brain barrier, the characteristics of known teratogens indicate that differential doses to the developing vs mature brain are not the major factor in differential sensitivity. Instead, most agents seem to act on processes that occur only during development. Thus, it appears that the susceptibility of the developing brain compared to the mature one depends to a great extent on the presence of processes sensitive to disruption. Yet cell proliferation, migration, and differentiation characterize many other developing organs, so the difference between CNS and other organs must depend on other properties of the developing CNS. The most important of these is probably the fact that nervous system development takes much longer than development of other organs, making it subject to injury over a longer period. PMID:7925182

  14. 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.

  15. 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.

  16. 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

  17. Magnetic resonance imaging of the central nervous system

    SciTech Connect

    Brant-Zawadzki, M.; Norman, D.

    1987-01-01

    This text provides an introduction to magnetic resonance imaging (MRI) of disorders of the central nervous system, spine, neck, and nasopharynx. The book offers guidance in performing and interpreting MRI studies for specific clinical problems. Included are more than 800 images showing pathologic findings for various disorders and demonstrating how abnormalities detected in MRI scans can aid both in differential diagnosis and in clinical staging. The book summarizes the basic principles of MRI and describes the major equipment components and contrast agents. A review of the principles and potential applications of magnetic resonance spectroscopy is also included.

  18. Language disorders in children with central nervous system injury

    PubMed Central

    Dennis, Maureen

    2011-01-01

    Children with injury to the central nervous system (CNS) exhibit a variety of language disorders that have been described by members of different disciplines, in different journals, using different descriptors and taxonomies. This paper is an overview of language deficits in children with CNS injury, whether congenital or acquired after a period of normal development. It first reviews the principal CNS conditions associated with language disorders in childhood. It then describes a functional taxonomy of language, with examples of the phenomenology and neurobiology of clinical deficits in children with CNS insults. Finally, it attempts to situate language in the broader realm of cognition and in current theoretical accounts of embodied cognition. PMID:20397297

  19. Area 51: How do Acanthamoeba invade the central nervous system?

    PubMed

    Siddiqui, Ruqaiyyah; Emes, Richard; Elsheikha, Hany; Khan, Naveed Ahmed

    2011-05-01

    Acanthamoeba granulomatous encephalitis generally develops as a result of haematogenous spread, but it is unclear how circulating amoebae enter the central nervous system (CNS) and cause inflammation. At present, the mechanisms which Acanthamoeba use to invade this incredibly well-protected area of the CNS and produce infection are not well understood. In this paper, we propose two key virulence factors: mannose-binding protein and extracellular serine proteases as key players in Acanthamoeba traversal of the blood-brain barrier leading to neuronal injury. Both molecules should provide excellent opportunities as potential targets in the rational development of therapeutic interventions against Acanthamoeba encephalitis.

  20. Vestigial expression in the Drosophila embryonic central nervous system.

    PubMed

    Guss, Kirsten A; Mistry, Hemlata; Skeath, James B

    2008-09-01

    The Drosophila central nervous system is an excellent model system in which to resolve the genetic and molecular control of neuronal differentiation. Here we show that the wing selector vestigial is expressed in discrete sets of neurons. We track the axonal trajectories of VESTIGIAL-expressing cells in the ventral nerve cord and show that these cells descend from neuroblasts 1-2, 5-1, and 5-6. In addition, along the midline, VESTIGIAL is expressed in ventral unpaired median motorneurons and cells that may descend from the median neuroblast. These studies form the requisite descriptive foundation for functional studies addressing the role of vestigial during interneuron differentiation.

  1. Inflammatory diseases of the central nervous system in dogs.

    PubMed

    Thomas, W B

    1998-08-01

    Inflammatory diseases of the central nervous system (CNS) are important causes of seizures in dogs. Specific diseases include canine distemper, rabies, cryptococcosis, coccidioidomycosis, toxoplasmosis, neosporosis, Rocky Mountain spotted fever, ehrlichiosis, granulomatous meningoencephalomyelitis, and pug dog encephalitis. Inflammatory disorders should be considered when a dog with seizures has persistent neurological deficits, suffers an onset of seizures at less than 1 or greater than 5 years of age, or exhibits signs of systemic illness. A thorough history, examination, and analysis of cerebrospinal fluid are important in the diagnosis of inflammatory diseases. However, even with extensive diagnostic testing, a specific etiology is identified in less than two thirds of dogs with inflammatory diseases of the CNS.

  2. [Extranuclear functions of protein sumoylation in the central nervous system].

    PubMed

    Martin, Stéphane

    2009-01-01

    Post-translational protein modifications play essential roles in many aspects of cellular functions and therefore in the maintenance of cell integrity. These protein modifications are involved at all stages of neuronal communication within the central nervous system. Sumoylation is a reversible post-translational protein modification that consists in the covalent labelling of a small protein called SUMO to lysine residues of selected target proteins. Sumoylation is a well characterized regulator of nuclear functions and has recently emerged as a key factor for numerous extranuclear processes. Furthermore, sumoylation has recently been shown to modulate synaptic transmission and is also implicated in a wide range of neurodegenerative diseases.

  3. [Primary central nervous system lymphoma: pathogenesis and histomorphology].

    PubMed

    Méhes, Gábor

    2017-03-08

    Lymphoproliferative diseases of the central nervous system are rare, diagnostics and treatment are accordingly challenging. Since the introduction of the 2008 WHO lymphoma classification, primary CNS DLBCL - also covering the associated primary ocular (vitreoretinal) lymphoma - is a separate entity. The special localization is related with a series of newly recognized genetic, genomic and immunologic features directing to the strong interaction between transformed lymphoma cells, neural tissue components and the local immune response. Histological differentiation is frequently disabled by the limited sampling opportunities and requires the application of all available hematopathologic technologies including immunohistochemistry, cytology, liquor serology, flow cytometry, fluorescence in situ hybridization and polymerase chain reaction with sequencing.

  4. Central nervous system tuberculosis: pathophysiology and imaging findings.

    PubMed

    Patkar, Deepak; Narang, Jayant; Yanamandala, Rama; Lawande, Malini; Shah, Gaurang V

    2012-11-01

    With the onset of the human immunodeficiency virus pandemic, the incidence of tuberculosis, including central nervous system (CNS) tuberculosis, has increased in developed countries. It is no longer a disease confined to underdeveloped and developing countries. The imaging appearance has become more complex with the onset of multidrug-resistant tuberculosis. Imaging plays an important role in the early diagnosis of CNS tuberculosis and may prevent unnecessary morbidity and mortality. This article presents an extensive review of typical and atypical imaging appearances of intracranial tuberculosis, and discusses pathogenesis, patterns of involvement, and advances in imaging of intracranial tuberculosis.

  5. 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.

  6. [Central nervous system vasculitis according to the 2012 revise international Chapel Hill consensus conference nomenclature of vasculitides].

    PubMed

    Koike, Haruki; Sobue, Gen

    2015-03-01

    Vasculitis can be primarily or secondarily to various underlying diseases. It frequently affects the nervous system, and neurological deficits may remain even after disease remission. Because the progression of vasculitides is usually acute to subacute, early initiation of treatment is important from the viewpoint of patients' functional status. However, early diagnosis may be difficult, particularly in patients with central nervous system vasculitis. Hence, it is important to understand the wide-ranging clinical manifestations of vasculitides. Here, we summarize the 2012 revised International Chapel Hill Consensus Conference nomenclature of vasculitides from the standpoint of central nervous system vasculitis.

  7. 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

  8. Diverse Roles of Neurotensin Agonists in the Central Nervous System

    PubMed Central

    Boules, Mona; Li, Zhimin; Smith, Kristin; Fredrickson, Paul; Richelson, Elliott

    2013-01-01

    Neurotensin (NT) is a tridecapeptide that is found in the central nervous system (CNS) and the gastrointestinal tract. NT behaves as a neurotransmitter in the brain and as a hormone in the gut. Additionally, NT acts as a neuromodulator to several neurotransmitter systems including dopaminergic, sertonergic, GABAergic, glutamatergic, and cholinergic systems. Due to its association with such a wide variety of neurotransmitters, NT has been implicated in the pathophysiology of several CNS disorders such as schizophrenia, drug abuse, Parkinson’s disease (PD), pain, central control of blood pressure, eating disorders, as well as, cancer and inflammation. The present review will focus on the role that NT and its analogs play in schizophrenia, endocrine function, pain, psychostimulant abuse, and PD. PMID:23526754

  9. 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.

  10. 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.

  11. Targeted Temperature Management in Pediatric Central Nervous System Disease

    PubMed Central

    Newmyer, Robert; Mendelson, Jenny; Pang, Diana; Fink, Ericka L.

    2015-01-01

    Opinion Statement Acute central nervous system conditions due to hypoxic-ischemic encephalopathy, traumatic brain injury (TBI), status epilepticus, and central nervous system infection/inflammation, are a leading cause of death and disability in childhood. There is a critical need for effective neuroprotective therapies to improve outcome targeting distinct disease pathology. Fever, defined as patient temperature > 38°C, has been clearly shown to exacerbate brain injury. Therapeutic hypothermia (HT) is an intervention using targeted temperature management that has multiple mechanisms of action and robust evidence of efficacy in multiple experimental models of brain injury. Prospective clinical evidence for its neuroprotective efficacy exists in narrowly-defined populations with hypoxic-ischemic injury outside of the pediatric age range while trials comparing hypothermia to normothermia after TBI have failed to demonstrate a benefit on outcome but consistently demonstrate potential use in decreasing refractory intracranial pressure. Data in children from prospective, randomized controlled trials using different strategies of targeted temperature management for various outcomes are few but a large study examining HT versus controlled normothermia to improve neurological outcome in cardiac arrest is underway. PMID:26042193

  12. HIV Immune Recovery Inflammatory Syndrome and Central Nervous System Paracoccidioidomycosis.

    PubMed

    de Almeida, Sérgio Monteiro; Roza, Thiago Henrique

    2017-04-01

    The immune reconstitution inflammatory syndrome (IRIS) is a deregulated inflammatory response to invading microorganisms. It is manifested when there is an abrupt change in host immunity from an anti-inflammatory and immunosuppressive state to a pro-inflammatory state as a result of rapid depletion or removal of factors that promote immune suppression or inhibition of inflammation. The aim of this paper is to discuss and re-interpret the possibility of association of paracoccidioidomycosis (PCM) with IRIS in the central nervous system (CNS) in a case from Brazil published by Silva-Vergara ML. et al. (Mycopathologia 177:137-141, 6). An AIDS patient who was not receiving medical care developed pulmonary PCM successfully treated with itraconazole. The patient developed central nervous system PCM (NPCM) after starting the ARV therapy with recovery of immunity and control of HIV viral load, although it was not interpreted as IRIS by the authors, it fulfills the criteria for CNS IRIS. This could be the first case of NPCM associated with IRIS described. Although not frequent, IRIS must be considered in PCM patients and HIV, from endemic areas or patients that traveled to endemic areas, receiving ARV treatment and with worsening symptoms.

  13. Interleukin-1β in Central Nervous System Injury and Repair

    PubMed Central

    Hewett, Sandra J.

    2015-01-01

    Summary Acute inflammation is a self-limiting, complex biological response mounted to combat pathogen invasion, to protect against tissue damage, and to promote tissue repair should it occur. However, unabated inflammation can be deleterious and contribute to injury and pathology. Interleukin-1β (IL-1β), a prototypical “pro-inflammatory” cytokine, is essential to cellular defense and tissue repair in nearly all tissues. With respect to brain, however, studies suggest that IL-1β has pleiotrophic effects. It acts as a neuromodulator in the healthy central nervous system (CNS), has been implicated in the pathogenic processes associated with a number of CNS maladies, but may also provide protection to the injured CNS. Here, we will review the physiological and pathophysiological functions of IL-1β in the central nervous system with regard to synaptic plasticity. With respect to disease, emphasis will be placed on stroke, epilepsy, Parkinson’s disease and Alzheimer’s disease where the ultimate injurious or reparative effects of IL-1β appear to depend on time, concentration and environmental milieu. PMID:26082912

  14. Mechanisms of immunological tolerance in central nervous system inflammatory demyelination.

    PubMed

    Mari, Elisabeth R; Moore, Jason N; Zhang, Guang-Xian; Rostami, Abdolmohamad

    2015-08-01

    Multiple sclerosis is a complex autoimmune disease of the central nervous system that results in a disruption of the balance between pro-inflammatory and anti-inflammatory signals in the immune system. Given that central nervous system inflammation can be suppressed by various immunological tolerance mechanisms, immune tolerance has become a focus of research in the attempt to induce long-lasting immune suppression of pathogenic T cells. Mechanisms underlying this tolerance induction include induction of regulatory T cell populations, anergy and the induction of tolerogenic antigen-presenting cells. The intravenous administration of encephalitogenic peptides has been shown to suppress experimental autoimmune encephalomyelitis and induce tolerance by promoting the generation of regulatory T cells and inducing apoptosis of pathogenic T cells. Safe and effective methods of inducing long-lasting immune tolerance are essential for the treatment of multiple sclerosis. By exploring tolerogenic mechanisms, new strategies can be devised to strengthen the regulatory, anti-inflammatory cell populations thereby weakening the pathogenic, pro-inflammatory cell populations.

  15. 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.

  16. 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

  17. Current approaches for drug delivery to central nervous system.

    PubMed

    Hossain, Sharif; Akaike, Toshihiro; Chowdhury, Ezharul Hoque

    2010-12-01

    Brain, the center of the nervous system in all vertebrate, plays the most vital role in every function of human body. However, many neurodegenerative diseases, cancer and infections of the brain become more prevalent as populations become older. In spite of the major advances in neuroscience, many potential therapeutics are still unable to reach the central nervous system (CNS) due to the blood-brain barrier (BBB) which is formed by the tight junctions within the capillary endothelium of the vertebrate brain. This results in the capillary wall behaving as a continuous lipid bilayer and preventing the passage of polar and lipid insoluble substances. Several approaches for delivering drugs to the CNS have been developed to enhance the capacity of therapeutic molecules to cross the BBB by modifying the drug itself, or by coupling it to a vector for receptor-mediated, carrier mediated or adsorption-mediated transcytosis. The current challenge is to develop drug delivery systems that ensure the safe and effective passage of drugs across the BBB. This review focuses on the strategies and approaches developed to enhance drug delivery to the CNS.

  18. 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

  19. Signaling Mechanisms Regulating Myelination in the Central Nervous System

    PubMed Central

    AHRENDSEN, Jared T.; MACKLIN, Wendy B.

    2014-01-01

    The precise and coordinated production of myelin is essential for proper development and function of the nervous system. Diseases that disrupt myelin, including multiple sclerosis (MS), cause significant functional disability. Current treatment aims to reduce the inflammatory component of the disease, thereby preventing damage resulting from demyelination. However, therapies are not yet available to improve natural repair processes after damage has already occurred. A thorough understanding of the signaling mechanisms that regulate myelin generation will improve our ability to enhance repair. In this review, we summarize the positive and negative regulators of myelination, focusing primarily on central nervous system myelination. Axon-derived signals, extracellular signals from both diffusible factors and the extracellular matrix, and intracellular signaling pathways within myelinating oligodendrocytes are discussed. Much more is known about the positive regulators that drive myelination, while less is known about the negative regulators that shift active myelination to myelin maintenance at the appropriate time. Therefore, we also provide new data on potential negative regulators of CNS myelination. PMID:23558589

  20. 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

  1. GABA-ergic neurons in the leach central nervous system

    SciTech Connect

    Cline, H.T.

    1985-01-01

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

  2. 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

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

    PubMed

    Aslan, Ivy R; Cheung, Clement C

    2014-01-01

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

  4. The central nervous system and its role in bowel and bladder control.

    PubMed

    Franco, Israel

    2011-04-01

    Bowel and bladder issues have been noted to be coexistent in children, and treatment of bladder symptoms without concomitant targeting of bowel issues generally leads to failure. This article explores the potential roots for this persistent connection between bowel and bladder and the role that the central nervous system plays in affecting both. An ever-increasing pool of knowledge drawn from multiple medical disciplines has provided us with a wealth of functional imaging information that is allowing us to map the areas of the brain better with regards to bowel and bladder function. We explore these new findings and attempt to connect the dots between the central nervous system bladder and bowel dysfunction.

  5. The influence of dietary factors in central nervous system plasticity and injury recovery.

    PubMed

    Gomez-Pinilla, Fernando; Gomez, Alexis G

    2011-06-01

    Although feeding is an essential component of life, it is only recently that the actions of foods on brain plasticity and function have been scrutinized. There is evidence that select dietary factors are important modifiers of brain plasticity and can have an impact on central nervous system health and disease. Results of new research indicate that dietary factors exert their effects by affecting molecular events related to the management of energy metabolism and synaptic plasticity. Recent study results show that select dietary factors have mechanisms similar to those of exercise, and that, in some cases, dietary factors can complement the action of exercise. Abundant research findings in animal models of central nervous system injury support the idea that nutrients can be taken in through whole foods and dietary supplements to reduce the consequences of neural damage. Therefore, exercise and dietary management appear as a noninvasive and effective strategy to help counteract neurologic and cognitive disorders.

  6. 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

  7. Infiltration of central nervous system in adult acute myeloid leukaemia.

    PubMed Central

    Pippard, M J; Callender, S T; Sheldon, P W

    1979-01-01

    Out of 64 consecutive unselected patients with acute myeloid leukaemia studied during 1973-6, five developed clinical evidence of spread to the central nervous system (CNS). Neuroradiological examination showed cerebral deposits in three, in whom rapid symptomatic relief was obtained with radiotherapy. In two of these patients who developed solid intracranial deposits haematological remission could be reinduced or maintained; they were still alive 86 and 134 weeks later. When patients presented with spread to the CNS complicating generalised uncontrolled leukaemia they had short survivals. CNS infiltration may respond dramatically to appropriate treatment provided that it is not associated with generalised uncontrolled leukaemia, which has a poor prognosis. In view of this, routine "prophylaxis" of the CNS in adult acute myeloid leukaemia does not seem justified at present. Images FIG 1 FIG 2 FIG 3 PMID:283873

  8. Neuronal Chemokines: Versatile Messengers In Central Nervous System Cell Interaction

    PubMed Central

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

    2007-01-01

    Whereas chemokines are well known for their ability to induce cell migration, only recently it became evident that chemokines also control a variety of other cell functions and are versatile messengers in the interaction between a diversity of cell types. In the central nervous system (CNS), chemokines are generally found under both physiological and pathological conditions. Whereas many reports describe chemokine expression in astrocytes and microglia and their role in the migration of leukocytes into the CNS, only few studies describe chemokine expression in neurons. Nevertheless, the expression of neuronal chemokines and the corresponding chemokine receptors in CNS cells under physiological and pathological conditions indicates that neuronal chemokines contribute to CNS cell interaction. In this study, we review recent studies describing neuronal chemokine expression and discuss potential roles of neuronal chemokines in neuron–astrocyte, neuron–microglia, and neuron–neuron interaction. PMID:17952658

  9. Noncongenital central nervous system infections in children: radiology review.

    PubMed

    Acosta, Jorge Humberto Davila; Rantes, Claudia Isabel Lazarte; Arbelaez, Andres; Restrepo, Feliza; Castillo, Mauricio

    2014-06-01

    Infections of the central nervous system (CNS) are a very common worldwide health problem in childhood with significant morbidity and mortality. In children, viruses are the most common cause of CNS infections, followed by bacterial etiology, and less frequent due to mycosis and other causes. Noncomplicated meningitis is easier to recognize clinically; however, complications of meningitis such as abscesses, infarcts, venous thrombosis, or extra-axial empyemas are difficult to recognize clinically, and imaging plays a very important role on this setting. In addition, it is important to keep in mind that infectious process adjacent to the CNS such as mastoiditis can develop by contiguity in an infectious process within the CNS. We display the most common causes of meningitis and their complications.

  10. Therapeutics targeting the inflammasome after central nervous system injury.

    PubMed

    de Rivero Vaccari, Juan Pablo; Dietrich, W Dalton; Keane, Robert W

    2016-01-01

    Innate immunity is part of the early response of the body to deal with tissue damage and infections. Because of the early nature of the innate immune inflammatory response, this inflammatory reaction represents an attractive option as a therapeutic target. The inflammasome is a component of the innate immune response involved in the activation of caspase 1 and the processing of pro-interleukin 1β. In this article, we discuss the therapeutic potential of the inflammasome after central nervous system (CNS) injury and stroke, as well as the basic knowledge we have gained so far regarding inflammasome activation in the CNS. In addition, we discuss some of the therapies available or under investigation for the treatment of brain injury, spinal cord injury, and stroke.

  11. MicroRNAs in central nervous system development.

    PubMed

    Díaz, Néstor F; Cruz-Reséndiz, Mónica S; Flores-Herrera, Héctor; García-López, Guadalupe; Molina-Hernández, Anayansi

    2014-01-01

    During early and late embryo neurodevelopment, a large number of molecules work together in a spatial and temporal manner to ensure the adequate formation of an organism. Diverse signals participate in embryo patterning and organization synchronized by time and space. Among the molecules that are expressed in a temporal and spatial manner, and that are considered essential in several developmental processes, are the microRNAs (miRNAs). In this review, we highlight some important aspects of the biogenesis and function of miRNAs as well as their participation in ectoderm commitment and their role in central nervous system (CNS) development. Instead of giving an extensive list of miRNAs involved in these processes, we only mention those miRNAs that are the most studied during the development of the CNS as well as the most likely mRNA targets for each miRNA and its protein functions.

  12. 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

  13. Therapeutic approaches of magnetic nanoparticles for the central nervous system.

    PubMed

    Dilnawaz, Fahima; Sahoo, Sanjeeb Kumar

    2015-10-01

    The diseases of the central nervous system (CNS) represent one of the fastest growing areas of concern requiring urgent medical attention. Treatment of CNS ailments is hindered owing to different physiological barriers including the blood-brain barrier (BBB), which limits the accessibility of potential drugs. With the assistance of a nanotechnology-based drug delivery strategy, the problems could be overcome. Recently, magnetic nanoparticles (MNPs) have proven immensely useful as drug carriers for site-specific delivery and as contrast agents owing to their magnetic susceptibility and biocompatibility. By utilizing MNPs, diagnosis and treatment of CNS diseases have progressed by overcoming the hurdles of the BBB. In this review, the therapeutic aspect and the future prospects related to the theranostic approach of MNPs are discussed.

  14. Implication of coumarins towards central nervous system disorders.

    PubMed

    Skalicka-Woźniak, Krystyna; Orhan, Ilkay Erdogan; Cordell, Geoffrey A; Nabavi, Seyed Mohammad; Budzyńska, Barbara

    2016-01-01

    Coumarins are widely distributed, plant-derived, 2H-1-benzopyran-2-one derivatives which have attracted intense interest in recent years as a result of their diverse and potent pharmacological properties. Particularly, their effects on the central nervous system (CNS) have been established. The present review discusses the most important pharmacological effects of natural and synthetic coumarins on the CNS, including their interactions with benzodiazepine receptors, their dopaminergic and serotonergic affinity, and their ability to inhibit cholinesterases and monoamine oxidases. The structure-activity relationships pertaining to these effects are also discussed. This review posits that natural or synthetic coumarins have the potential for development in the therapy of psychiatric and neurodegenerative disorders, including Alzheimer's and Parkinson's diseases, schizophrenia, anxiety, epilepsy, and depression.

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

    PubMed

    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.

  16. The expression of SEIPIN in the mouse central nervous system.

    PubMed

    Liu, Xiaoyun; Xie, Beibei; Qi, Yanfei; Du, Ximing; Wang, Shaoshi; Zhang, Yumei; Paxinos, George; Yang, Hongyuan; Liang, Huazheng

    2016-11-01

    Immunohistochemical staining was used to investigate the expression pattern of SEIPIN in the mouse central nervous system. SEIPIN was found to be present in a large number of areas, including the motor and somatosensory cortex, the thalamic nuclei, the hypothalamic nuclei, the mesencephalic nuclei, some cranial motor nuclei, the reticular formation of the brainstem, and the vestibular complex. Double labeling with NeuN antibody confirmed that SEIPIN-positive cells in some nuclei were neurons. Retrograde tracer injections into the spinal cord revealed that SEIPIN-positive neurons in the motor and somatosensory cortex and other movement related nuclei project to the mouse spinal cord. The present study found more nuclei positive for SEIPIN than shown using in situ hybridization and confirmed the presence of SEIPIN in neurons projecting to the spinal cord. The results of this study help to explain the clinical manifestations of patients with Berardinelli-Seip congenital lipodystrophy (Bscl2) gene mutations.

  17. Pyrimidine derivatives as potential agents acting on central nervous system.

    PubMed

    Kumar, Sanjiv; Deep, Aakash; Narasimhan, Balasubramanian

    2015-01-01

    Pyrimidine and its derivatives are present in many of the bioactive aromatic compounds that are of wide interest because of their diverse biological and clinical applications. The utility of pyrimidines as synthon for various biologically active compounds has given impetus to these studies. The review article aims to review the work reported on pharmacological activities of central nervous system (CNS) such as anticonvulsant and antidepressant, which created interest among researchers to synthesize variety of pyrimidine and their derivatives. The present study shows, objective of the work can be summarized as pyrimidine derivative constitute an important class of compounds for new drug development. These observations have been given novel idea for the development of new pyrimidine derivative that possess varied biological activities. This article aims to review the recent works on pyrimidine moiety together with the biological potential during the past year.

  18. Choroid plexus in the central nervous system: biology and physiopathology.

    PubMed

    Strazielle, N; Ghersi-Egea, J F

    2000-07-01

    Choroid plexuses (CPs) are localized in the ventricular system of the brain and form one of the interfaces between the blood and the central nervous system (CNS). They are composed of a tight epithelium responsible for cerebrospinal fluid secretion, which encloses a loose connective core containing permeable capillaries and cells of the lymphoid lineage. In accordance with its peculiar localization between 2 circulating fluid compartments, the CP epithelium is involved in numerous exchange processes that either supply the brain with nutrients and hormones, or clear deleterious compounds and metabolites from the brain. Choroid plexuses also participate in neurohumoral brain modulation and neuroimmune interactions, thereby contributing greatly in maintaining brain homeostasis. Besides these physiological functions, the implication of choroid plexuses in pathological processes is increasingly documented. In this review, we focus on some of the novel aspects of CP functions in relation to brain development, transfer of neuro-humoral information, brain/immune system interactions, brain aging, and cerebral pharmaco-toxicology.

  19. Chemokines and their receptors in central nervous system disease.

    PubMed

    Biber, Knut; de Jong, Eiko K; van Weering, Hilmar R J; Boddeke, Hendrikus W G M

    2006-01-01

    Almost a decade ago, it was discovered that the human deficiency virus (HIV) makes use of chemokine receptors to infect blood cells. This appreciation of the clinical relevance of specific chemokine receptors has initiated a considerable boost in the field of chemokine research. It is clear today that chemokine signaling orchestrates the immune system and is widely involved in both physiological and pathophysiological processes. Since the chemokine system offers various targets through which pathology could be influenced, most pharmaceutical companies have chosen this system as a therapeutic target for a variety of diseases. Here recent developments concerning the role of chemokines in diseases of the central nervous system (CNS) as well as their possible therapeutic relevance are discussed.

  20. 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

  1. 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.

  2. Therapeutics Targeting the Inflammasome After Central Nervous System Injury

    PubMed Central

    de Rivero Vaccari, Juan Pablo; Dietrich, W. Dalton; Keane, Robert W.

    2015-01-01

    Innate immunity is part of the early response of the body to deal with tissue damage and infections. Due to the early nature of the innate immune inflammatory response, this inflammatory reaction represents an attractive option as a therapeutic target. The inflammasome is a component of the innate immune response involved in the activation of caspase-1 and the processing of pro-interleukin-1β. In this article we discuss the therapeutic potential of the inflammasome after central nervous system (CNS) injury and stoke, as well as the basic knowledge we have gained so far regarding inflammasome activation in the CNS. In addition, we discuss some of the therapies available or under investigation for the treatment of brain injury, spinal cord injury and stroke. PMID:26024799

  3. 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

  4. 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

  5. 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.

  6. Primary large-cell lymphoma of the central nervous system

    SciTech Connect

    Amendola, B.E.; McClatchey, K.D.; Amendola, M.A.; Gebarski, S.S.

    1986-06-01

    Primary non-Hodgkin's lymphoma of the central nervous system (CNS) is a rare disease. Seven patients were seen and treated at the University of Michigan Medical Center between January 1969 and December 1983. All patients had histologically proven diagnoses of large cell lymphoma with clinical and radiologic evidence of involvement limited to the CNS. Five of seven patients received postoperative radiation therapy, two of whom have had apparent local control at 1- and 2-year follow-up. The two patients without postoperative radiation died of local recurrence 2 and 3 months following subtotal resection. These poor results suggest that adjuvant therapy may be required for improved control of this type of extranodal lymphoma.

  7. The logistics of myelin biogenesis in the central nervous system.

    PubMed

    Snaidero, Nicolas; Simons, Mikael

    2017-02-07

    Rapid nerve conduction depends on myelin, but not all axons in the central nervous system (CNS) are myelinated to the same extent. Here, we review our current understanding of the biology of myelin biogenesis in the CNS. We focus on how the different steps of myelination are interconnected and how distinct patterns of myelin are generated. Possibly, a "basal" mode of myelination is laying the groundwork in areas devoted to basic homeostasis early in development, whereas a "targeted" mode generates myelin in regions controlling more complex tasks throughout adulthood. Such mechanisms may explain why myelination progresses in some areas according to a typical chronological and topographic sequence, while in other regions it is regulated by environmental stimuli contributing to interindividual variability of myelin structure. GLIA 2017.

  8. Developmental and pathological angiogenesis in the central nervous system

    PubMed Central

    Vallon, Mario; Chang, Junlei; Zhang, Haijing

    2014-01-01

    Angiogenesis, the formation of new blood vessels from pre-existing vessels, in the central nervous system (CNS) is seen both as a normal physiological response as well as a pathological step in disease progression. Formation of the blood–brain barrier (BBB) is an essential step in physiological CNS angiogenesis. The BBB is regulated by a neurovascular unit (NVU) consisting of endothelial and perivascular cells as well as vascular astrocytes. The NVU plays a critical role in preventing entry of neurotoxic substances and regulation of blood flow in the CNS. In recent years, research on numerous acquired and hereditary disorders of the CNS has increasingly emphasized the role of angiogenesis in disease pathophysiology. Here, we discuss molecular mechanisms of CNS angiogenesis during embryogenesis as well as various pathological states including brain tumor formation, ischemic stroke, arteriovenous malformations, and neurodegenerative diseases. PMID:24760128

  9. [Imaging diagnosis of central nervous system malignant lymphoma].

    PubMed

    Kan, Shinichi

    2014-08-01

    With a typical case, imaging diagnosis of central nervous system malignant lymphoma is not difficult. High density on non contrast CT, periventricular location, homogenous contrast enhancement, iso- to hypointensity to gray matter on T(2) weighted MR imaging and high intensity on diffusion weighted MR imaging are characteristic findings. Hemorrhage is rare. When a patient is immunocompromised, irregular ring enhancement is noted on enhanced study. Intravascular lymphomatois is a rare type of lymphoma. A variety of imaging findings are reported. Differential diagnosis are many. Most difficult to distinguish is a tumefactive multiple sclerosis. Most of the reported cases of tumefactive multiple sclerosis are diagnosed by brain biopsy when the brain tumor, especially malignant lymphoma is suspected. CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) has been recently identified. However, there still remains whether CLIPPERS is an actual new disease entity or represents overlapping disease.

  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. 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.

  12. Intranasal delivery of biologics to the central nervous system.

    PubMed

    Lochhead, Jeffrey J; Thorne, Robert G

    2012-05-15

    Treatment of central nervous system (CNS) diseases is very difficult due to the blood-brain barrier's (BBB) ability to severely restrict entry of all but small, non-polar compounds. Intranasal administration is a non-invasive method of drug delivery which may bypass the BBB to allow therapeutic substances direct access to the CNS. Intranasal delivery of large molecular weight biologics such as proteins, gene vectors, and stem cells is a potentially useful strategy to treat a variety of diseases/disorders of the CNS including stroke, Parkinson's disease, multiple sclerosis, Alzheimer's disease, epilepsy, and psychiatric disorders. Here we give an overview of relevant nasal anatomy and physiology and discuss the pathways and mechanisms likely involved in drug transport from the nasal epithelium to the CNS. Finally we review both pre-clinical and clinical studies involving intranasal delivery of biologics to the CNS.

  13. 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.

  14. 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

  15. Leptin sustains spontaneous remyelination in the adult central nervous system

    PubMed Central

    Matoba, Ken; Muramatsu, Rieko; Yamashita, Toshihide

    2017-01-01

    Demyelination is a common feature of many central nervous system (CNS) diseases and is associated with neurological impairment. Demyelinated axons are spontaneously remyelinated depending on oligodendrocyte development, which mainly involves molecules expressed in the CNS environment. In this study, we found that leptin, a peripheral hormone secreted from adipocytes, promoted the proliferation of oligodendrocyte precursor cells (OPCs). Leptin increased the OPC proliferation via in vitro phosphorylation of extracellular signal regulated kinase (ERK); whereas leptin neutralization inhibited OPC proliferation and remyelination in a mouse model of toxin-induced demyelination. The OPC-specific leptin receptor long isoform (LepRb) deletion in mice inhibited both OPC proliferation and remyelination in the response to demyelination. Intrathecal leptin administration increased OPC proliferation. These results demonstrated a novel molecular mechanism by which leptin sustained OPC proliferation and remyelination in a pathological CNS. PMID:28091609

  16. [Histoplasmosis of the central nervous system in an immunocompetent patient].

    PubMed

    Osorio, Natalia; López, Yúrika; Jaramillo, Juan Camilo

    2014-01-01

    Histoplasmosis is a multifaceted condition caused by the dimorphic fungi Histoplasma capsulatum whose infective spores are inhaled and reach the lungs, the primary organ of infection. The meningeal form, considered one of the most serious manifestations of this mycosis, is usually seen in individuals with impaired cellular immunity such as patients with acquired immunodeficiency syndrome, systemic lupus erythematous or solid organ transplantation, and infants given their immunological immaturity. The most common presentation is self-limited and occurs in immunocompetent individuals who have been exposed to high concentrations of conidia and mycelia fragments of the fungi. In those people, the condition is manifested by pulmonary disorders and late dissemination to other organs and systems. We report a case of central nervous system histoplasmosis in an immunocompetent child.

  17. Central nervous system syndromes in solid organ transplant recipients.

    PubMed

    Wright, Alissa J; Fishman, Jay A

    2014-10-01

    Solid organ transplant recipients have a high incidence of central nervous system (CNS) complications, including both focal and diffuse neurologic deficits. In the immunocompromised host, the initial clinical evaluation must focus on both life-threatening CNS infections and vascular or anatomic lesions. The clinical signs and symptoms of CNS processes are modified by the immunosuppression required to prevent graft rejection. In this population, these etiologies often coexist with drug toxicities and metabolic abnormalities that complicate the development of a specific approach to clinical management. This review assesses the multiple risk factors for CNS processes in solid organ transplant recipients and establishes a timeline to assist in the evaluation and management of these complex patients.

  18. 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

  19. HIV and aging: effects on the central nervous system.

    PubMed

    Cañizares, Silvia; Cherner, Mariana; Ellis, Ronald J

    2014-02-01

    With the introduction of combination antiretroviral therapy, many human immunodeficiency virus-positive (HIV+) individuals are reaching advanced age. The proportion of people living with HIV older than 50 years already exceeds 50% in many communities, and is expected to reach this level nationally by 2015. HIV and aging are independently associated with neuropathological changes, but their concurrence may have a more deleterious effect on the central nervous system (CNS). Published data about neurocognitive and neuroimaging markers of HIV and aging are reviewed. Putative factors contributing to neurocognitive impairment and neuroimaging changes in the aging HIV+ brain, such as metabolic disturbances, cardiovascular risk factors, immune senescence, and neuroinflammation, are described. The possible relationship between HIV and some markers of Alzheimer's disease is presented. Current research findings emphasize multiple mechanisms related to HIV and combination antiretroviral therapy that compromise CNS structure and function with advancing age.

  20. HIV and Aging: Effects on the Central Nervous System

    PubMed Central

    Cañizares, Silvia; Cherner, Mariana; Ellis, Ronald J.

    2014-01-01

    With the introduction of combination antiretroviral therapy, many human immunodeficiency virus-positive (HIV+) individuals are reaching advanced age. The proportion of people living with HIV older than 50 years already exceeds 50% in many communities, and is expected to reach this level nationally by 2015. HIV and aging are independently associated with neuropathological changes, but their concurrence may have a more deleterious effect on the central nervous system (CNS). Published data about neurocognitive and neuroimaging markers of HIV and aging are reviewed. Putative factors contributing to neurocognitive impairment and neuroimaging changes in the aging HIV+ brain, such as metabolic disturbances, cardiovascular risk factors, immune senescence, and neuroinflammation, are described. The possible relationship between HIV and some markers of Alzheimer’s disease is presented. Current research findings emphasize multiple mechanisms related to HIV and combination antiretroviral therapy that compromise CNS structure and function with advancing age. PMID:24715486

  1. 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.

  2. 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

  3. 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

  4. Xenacoelomorpha: a case of independent nervous system centralization?

    PubMed Central

    Gavilán, Brenda; Perea-Atienza, Elena; Martínez, Pedro

    2016-01-01

    Centralized nervous systems (NSs) and complex brains are among the most important innovations in the history of life on our planet. In this context, two related questions have been formulated: How did complex NSs arise in evolution, and how many times did this occur? As a step towards finding an answer, we describe the NS of several representatives of the Xenacoelomorpha, a clade whose members show different degrees of NS complexity. This enigmatic clade is composed of three major taxa: acoels, nemertodermatids and xenoturbellids. Interestingly, while the xenoturbellids seem to have a rather ‘simple’ NS (a nerve net), members of the most derived group of acoel worms clearly have ganglionic brains. This interesting diversity of NS architectures (with different degrees of compaction) provides a unique system with which to address outstanding questions regarding the evolution of brains and centralized NSs. The recent sequencing of xenacoelomorph genomes gives us a privileged vantage point from which to analyse neural evolution, especially through the study of key gene families involved in neurogenesis and NS function, such as G protein-coupled receptors, helix-loop-helix transcription factors and Wnts. We finish our manuscript proposing an adaptive scenario for the origin of centralized NSs (brains). PMID:26598722

  5. Temozolomide and radiation for aggressive pediatric central nervous system malignancies.

    PubMed

    Loh, Kenneth C; Willert, Jennifer; Meltzer, Hal; Roberts, William; Kerlin, Bryce; Kadota, Richard; Levy, Michael; White, Greg; Geddis, Amy; Schiff, Deborah; Martin, Laura; Yu, Alice; Kung, Faith; Spear, Matthew A

    2005-05-01

    This study describes the outcomes of children treated with combinations of temozolomide and radiation therapy for various aggressive central nervous system malignancies. Their age at diagnosis ranged from 1 to 15 years. Patients with focal disease were treated with concomitant temozolomide (daily 75 mg/m) and three-dimensional conformal radiotherapy in a dose that ranged from 50 to 54 Gy, followed by temozolomide (200 mg/m/d x 5 days/month in three patients, 150 mg/m x 5 days/ month in one patient). Patients with disseminated disease were treated with craniospinal radiation (39.6 Gy) before conformal boost. One patient received temozolomide (200 mg/m x 5 days/month) before craniospinal radiation, and one patient received temozolomide (daily 95 mg/m) concomitant with craniospinal radiation and a radiosurgical boost, followed by temozolomide (200 mg/m x 5 days/month). Three patients achieved a partial response during treatment, with two of these patients dying of progressive disease after treatment. One patient has no evidence of disease. Three patients achieved stable disease, with one of these patients dying of progressive disease after treatment. Toxicities observed included low-grade neutropenia, thrombocytopenia, and lymphopenia. The combination of temozolomide and radiotherapy appears to be well tolerated in a variety of treatment schemas for aggressive pediatric central nervous system malignancies. This information is of particular use in designing future studies, given the recent positive results in a randomized study examining the use of temozolomide concomitant with radiation in the treatment of adult glioblastoma.

  6. 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.

  7. Fast food, central nervous system insulin resistance, and obesity.

    PubMed

    Isganaitis, Elvira; Lustig, Robert H

    2005-12-01

    Rates of obesity and insulin resistance have climbed sharply over the past 30 years. These epidemics are temporally related to a dramatic rise in consumption of fast food; until recently, it was not known whether the fast food was driving the obesity, or vice versa. We review the unique properties of fast food that make it the ideal obesigenic foodstuff, and elucidate the mechanisms by which fast food intake contributes to obesity, emphasizing its effects on energy metabolism and on the central regulation of appetite. After examining the epidemiology of fast food consumption, obesity, and insulin resistance, we review insulin's role in the central nervous system's (CNS) regulation of energy balance, and demonstrate the role of CNS insulin resistance as a cause of leptin resistance and in the promotion of the pleasurable or "hedonic" responses to food. Finally, we analyze the characteristics of fast food, including high-energy density, high fat, high fructose, low fiber, and low dairy intake, which favor the development of CNS insulin resistance and obesity.

  8. KCC3 axonopathy: neuropathological features in the central and peripheral nervous system.

    PubMed

    Auer, Roland N; Laganière, Janet L; Robitaille, Yves O; Richardson, John; Dion, Patrick A; Rouleau, Guy A; Shekarabi, Masoud

    2016-09-01

    Hereditary motor and sensory neuropathy associated with agenesis of the corpus callosum (HMSN/ACC) is an autosomal recessive disease of the central and peripheral nervous system that presents as early-onset polyneuropathy. Patients are hypotonic and areflexic from birth, with abnormal facial features and atrophic muscles. Progressive peripheral neuropathy eventually confines them to a wheelchair in the second decade of life, and death occurs by the fourth decade. We here define the neuropathologic features of the disease in autopsy tissues from eight cases. Both developmental and neurodegenerative features were found. Hypoplasia or absence of the major telencephalic commissures and a hypoplasia of corticospinal tracts to half the normal size, were the major neurodevelopmental defects we observed. Despite being a neurodegenerative disease, preservation of brain weight and a conspicuous absence of neuronal or glial cell death were signal features of this disease. Small tumor-like overgrowths of axons, termed axonomas, were found in the central and peripheral nervous system, indicating attempted axonal regeneration. We conclude that the neurodegenerative deficits in HMSN/ACC are primarily caused by an axonopathy superimposed upon abnormal development, affecting peripheral but also central nervous system axons, all ultimately because of a genetic defect in the axonal cotransporter KCC3.

  9. Peripheral nerve injury modulates neurotrophin signaling in the peripheral and central nervous system.

    PubMed

    Richner, Mette; Ulrichsen, Maj; Elmegaard, Siri Lander; Dieu, Ruthe; Pallesen, Lone Tjener; Vaegter, Christian Bjerggaard

    2014-12-01

    Peripheral nerve injury disrupts the normal functions of sensory and motor neurons by damaging the integrity of axons and Schwann cells. In contrast to the central nervous system, the peripheral nervous system possesses a considerable capacity for regrowth, but regeneration is far from complete and functional recovery rarely returns to pre-injury levels. During development, the peripheral nervous system strongly depends upon trophic stimulation for neuronal differentiation, growth and maturation. The perhaps most important group of trophic substances in this context is the neurotrophins (NGF, BDNF, NT-3 and NT-4/5), which signal in a complex spatial and timely manner via the two structurally unrelated p75(NTR) and tropomyosin receptor kinase (TrkA, Trk-B and Trk-C) receptors. Damage to the adult peripheral nerves induces cellular mechanisms resembling those active during development, resulting in a rapid and robust increase in the synthesis of neurotrophins in neurons and Schwann cells, guiding and supporting regeneration. Furthermore, the injury induces neurotrophin-mediated changes in the dorsal root ganglia and in the spinal cord, which affect the modulation of afferent sensory signaling and eventually may contribute to the development of neuropathic pain. The focus of this review is on the expression patterns of neurotrophins and their receptors in neurons and glial cells of the peripheral nervous system and the spinal cord. Furthermore, injury-induced changes of expression patterns and the functional consequences in relation to axonal growth and remyelination as well as to neuropathic pain development will be reviewed.

  10. 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.

  11. Neurological complications of chemotherapy to the central nervous system.

    PubMed

    Newton, Herbert B

    2012-01-01

    One of the most common complications of chemotherapeutic drugs is toxicity to the central nervous system (CNS). This toxicity can manifest in many ways, including encephalopathy syndromes and confusional states, seizure activity, headache, cerebrovascular complications and stroke, visual loss, cerebellar dysfunction, and spinal cord damage with myelopathy. For many drugs, the toxicity is related to route of administration and cumulative dose, and can vary from brief, transient episodes to more severe, chronic sequelae. However, the neurotoxicity can be idiosyncratic and unpredictable in some cases. Among the antimetabolite drugs, methotrexate, 5-fluorouracil, and cytosine arabinoside are most likely to cause CNS toxicity. Of the alkylating agent chemotherapeutic drugs, the nitrosoureas (e.g., BCNU) and cisplatin most frequently cause toxicity to the CNS, especially when given via the intra-arterial route. Ifosfamide is also likely to cause neurotoxicity at high intravenous doses. Other alkylating agents, such as busulfan, cyclophosphamide, procarbazine, and temozolomide, are better tolerated by the CNS at moderate doses. The retinoid drugs are known to cause severe headaches at high doses. l-Asparaginase can induce an encephalopathy syndrome, as well as cerebrovascular complications such as stroke.

  12. Occupational exposure and risk of central nervous system demyelination.

    PubMed

    Valery, P C; Lucas, R M; Williams, D B; Pender, M P; Chapman, C; Coulthard, A; Dear, K; Dwyer, T; Kilpatrick, T J; McMichael, A J; van der Mei, I; Taylor, B V; Ponsonby, A-L

    2013-05-01

    Inconsistent evidence exists regarding the association between work-related factors and risk of multiple sclerosis (MS). We examined the association between occupational exposures and risk of a first clinical diagnosis of central nervous system demyelination (FCD), which is strongly associated with progression to MS, in a matched case-control study of 276 FCD cases and 538 controls conducted in Australia (2003-2006). Using a personal residence and work calendar, information on occupational history and exposure to chemicals and animals was collected through face-to-face interviews. Few case-control differences were noted. Fewer cases had worked as professionals (≥6 years) than controls (adjusted odds ratio (AOR) = 0.60, 95% confidence interval (CI): 0.37, 0.96). After further adjustment for number of children, cases were more likely to have ever been exposed to livestock than controls (AOR = 1.54, 95% CI: 1.03, 2.29). Among women, there was an increase in FCD risk associated with 10 or more years of exposure to livestock (AOR = 2.78, 95% CI: 1.22, 6.33) or 6 or more years of farming (AOR = 2.00, 95% CI: 1.23, 3.25; also adjusted for number of children). Similar findings were not evident among men. Thus, farming and exposure to livestock may be important factors in the development of FCD among women, with this finding further revealed after the confounding effect of parity or number of children is considered.

  13. 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

  14. Pathway analysis of primary central nervous system lymphoma.

    PubMed

    Tun, Han W; Personett, David; Baskerville, Karen A; Menke, David M; Jaeckle, Kurt A; Kreinest, Pamela; Edenfield, Brandy; Zubair, Abba C; O'Neill, Brian P; Lai, Weil R; Park, Peter J; McKinney, Michael

    2008-03-15

    Primary central nervous system (CNS) lymphoma (PCNSL) is a diffuse large B-cell lymphoma (DLBCL) confined to the CNS. A genome-wide gene expression comparison between PCNSL and non-CNS DLBCL was performed, the latter consisting of both nodal and extranodal DLBCL (nDLBCL and enDLBCL), to identify a "CNS signature." Pathway analysis with the program SigPathway revealed that PCNSL is characterized notably by significant differential expression of multiple extracellular matrix (ECM) and adhesion-related pathways. The most significantly up-regulated gene is the ECM-related osteopontin (SPP1). Expression at the protein level of ECM-related SPP1 and CHI3L1 in PCNSL cells was demonstrated by immunohistochemistry. The alterations in gene expression can be interpreted within several biologic contexts with implications for PCNSL, including CNS tropism (ECM and adhesion-related pathways, SPP1, DDR1), B-cell migration (CXCL13, SPP1), activated B-cell subtype (MUM1), lymphoproliferation (SPP1, TCL1A, CHI3L1), aggressive clinical behavior (SPP1, CHI3L1, MUM1), and aggressive metastatic cancer phenotype (SPP1, CHI3L1). The gene expression signature discovered in our study may represent a true "CNS signature" because we contrasted PCNSL with wide-spectrum non-CNS DLBCL on a genomic scale and performed an in-depth bioinformatic analysis.

  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. Cerebrospinal fluid flow dynamics in the central nervous system.

    PubMed

    Sweetman, Brian; Linninger, Andreas A

    2011-01-01

    Cine-phase-contrast-MRI was used to measure the three-dimensional cerebrospinal fluid (CSF) flow field inside the central nervous system (CNS) of a healthy subject. Image reconstruction and grid generation tools were then used to develop a three-dimensional fluid-structure interaction model of the CSF flow inside the CNS. The CSF spaces were discretized using the finite-element method and the constitutive equations for fluid and solid motion solved in ADINA-FSI 8.6. Model predictions of CSF velocity magnitude and stroke volume were found to be in excellent agreement with the experimental data. CSF pressure gradients and amplitudes were computed in all regions of the CNS. The computed pressure gradients and amplitudes closely match values obtained clinically. The highest pressure amplitude of 77 Pa was predicted to occur in the lateral ventricles. The pressure gradient between the lateral ventricles and the lumbar region of the spinal canal did not exceed 132 Pa (~1 mmHg) at any time during the cardiac cycle. The pressure wave speed in the spinal canal was predicted and found to agree closely with values previously reported in the literature. Finally, the forward and backward motion of the CSF in the ventricles was visualized, revealing the complex mixing patterns in the CSF spaces. The mathematical model presented in this article is a prerequisite for developing a mechanistic understanding of the relationships among vasculature pulsations, CSF flow, and CSF pressure waves in the CNS.

  17. 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.

  18. 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

  19. Neuronal central nervous system syndromes probably mediated by autoantibodies

    PubMed Central

    Chefdeville, Aude; Honnorat, Jérôme; Hampe, Christiane S.; Desestret, Virginie

    2016-01-01

    In the last few years, a rapidly growing number of autoantibodies targeting neuronal cell-surface antigens have been identified in patients presenting with neurological symptoms. Targeted antigens include ionotropic receptors such as N-methyl-D-aspartate receptor or the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, metabotropic receptors such as mGluR1 and mGluR5, and other synaptic proteins, some of them belonging to the voltage-gated potassium channel complex. Importantly, the cell-surface location of these antigens makes them vulnerable to direct antibody-mediated modulation. Some of these autoantibodies, generally targeting ionotropic channels or their partner proteins, define clinical syndromes resembling models of pharmacological or genetic disruption of the corresponding antigen, suggesting a direct pathogenic role of the associated autoantibodies. Moreover, the associated neurological symptoms are usually immunotherapy-responsive, further arguing for a pathogenic effect of the antibodies. Some studies have shown that some patients’ antibodies may have structural and functional in vitro effects on the targeted antigens. Definite proof of the pathogenicity of these autoantibodies has been obtained for just a few through passive transfer experiments in animal models. In this review we present existing and converging evidence suggesting a pathogenic role of some autoantibodies directed against neuronal cell-surface antigens observed in patients with central nervous system disorders. We describe the main clinical symptoms characterizing the patients and discuss conflicting arguments regarding the pathogenicity of these antibodies. PMID:26918657

  20. 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.

  1. 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

  2. Central nervous system disease in Langerhans cell histiocytosis.

    PubMed Central

    Grois, N.; Tsunematsu, Y.; Barkovich, A. J.; Favara, B. E.

    1994-01-01

    Diabetes insipidus and anterior pituitary dysfunction, are familiar central nervous system (CNS) complications of Langerhans cell histiocytosis (LCH) but the pathophysiology and biological behaviour of other forms of CNS involvement in LCH are poorly understood. In an attempt to improve our understanding of these rare complications, we studied 23 patients with LCH in whom neuroradiological abnormalities, with or without neurological dysfunction other than diabetes insipidus, developed during the course of disease. Neuroradiological abnormalities were of three basic types (a) poorly-defined changes in white matter, (b) well-defined changes in white and grey matter and (c) extra-parenchymal "tumoural" masses. There was a profusion of associated neurological signs and symptoms in most cases but some patients were asymptomatic. The neuropathological features were complex but infiltration of the CNS by histiocytes with xanthomatous change, particularly prominent in mass lesions, was common in the 13 cases in which biopsies were done. Patients with lytic lesions of the skull and diabetes insipidus are evidently most at risk of developing these rare manifestations of LCH. Therapeutic questions could not be answered from this study because no standard treatment had been given and outcome varied widely. Images Figure 7 Figure 1 Figure 2 Figure 3 PMID:8075002

  3. Medulloblastomas and central nervous system primitive neuroectodermal tumors.

    PubMed

    McLean, Thomas W

    2003-12-01

    Significant advances in the treatment of medulloblastoma and primitive neuroectodermal tumors have been made in the past three decades. Maximal surgical resection is a mainstay of therapy. However, unlike many other central nervous system neoplasms, medulloblastoma and primitive neuroectodermal tumors are radiation and chemotherapy responsive. Despite this response, the prognosis for patients with these tumors remains variable and is relatively poor in infants and patients with metastatic disease. These tumors most commonly arise in children, thus most clinical trials emphasize the reduction of long-term sequelae, in addition to improving survival. All newly diagnosed patients who are eligible should be offered participation in a clinical trial. If a patient is ineligible or declines consent/assent for a clinical trial, the best current treatment approach is surgical resection, followed by radiation therapy (except for children younger than 3 years) with weekly vincristine. For high-risk patients, 36 Gy of craniospinal irradiation should be delivered plus a boost of 19.8 Gy to the posterior fossa/primary tumor bed and sites of bulk metastatic disease. For average-risk patients, the craniospinal irradiation dose may be lowered to 23.4 Gy plus 32.4 Gy to the posterior fossa/tumor bed. After radiation therapy, intensive multimodal chemotherapy should be used for all patients.

  4. 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

  5. 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.

  6. [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.

  7. Benzodiazepine Pharmacology and Central Nervous System–Mediated Effects

    PubMed Central

    Griffin, Charles E.; Kaye, Adam M.; Bueno, Franklin Rivera; Kaye, Alan D.

    2013-01-01

    Background Owing to the low therapeutic index of barbiturates, benzodiazepines (BZDs) became popular in this country and worldwide many decades ago for a wide range of conditions. Because of an increased understanding of pharmacology and physiology, the mechanisms of action of many BZDs are now largely understood, and BZDs of varying potency and duration of action have been developed and marketed. Although BZDs have many therapeutic roles and BZD-mediated effects are typically well tolerated in the general population, side effects and toxicity can result in morbidity and mortality for some patients. The elderly; certain subpopulations of patients with lung, liver, or kidney dysfunction; and patients on other classes of medication are especially prone to toxicity. Methods This review details the present knowledge about BZD mechanisms of action, drug profiles, clinical actions, and potential side effects. In addition, this review describes numerous types of BZD-mediated central nervous system effects. Conclusion For any patient taking a BZD, the prescribing physician must carefully evaluate the risks and benefits, and higher-risk patients require careful considerations. Clinically appropriate use of BZDs requires prudence and the understanding of pharmacology. PMID:23789008

  8. Palmitoylethanolamide in homeostatic and traumatic central nervous system injuries.

    PubMed

    Esposito, Emanuela; Cuzzocrea, Salvatore

    2013-02-01

    The role of palmitoylethanolamide (PEA) in the regulation of complex systems involved in the inflammatory response, pruritus, neurogenic and neuropathic pain is well understood. Growing evidence indicates that this Nacylethanolamine also exerts neuroprotective effects within the central nervous system (CNS), i.e. in spinal cord and traumatic brain injuries and in age-related pathological processes. PEA is abundant in the CNS, and is produced by glial cells. Several studies show that administering PEA during the first few hours after injury significantly limits CNS damage, reduces loss of neuronal tissue and improves functional recovery. PEA appears to exert its protective effect by decreasing the development of cerebral edema, down-regulating the inflammatory cascade, and limiting cellular necrosis and apoptosis. All these are plausible mechanisms of neuroprotection. This review provides an overview of current knowledge of PEA effect on glial functions in the brain and how targeting glial-specific pathways might ultimately impact the development of therapies for clinical management of neurodegenerative disorders. The diverse signaling mechanisms are also summarized.

  9. Excitation of central nervous system neurons by nonuniform electric fields.

    PubMed Central

    McIntyre, C C; Grill, W M

    1999-01-01

    The goal of this study was to determine which neural elements are excited by microstimulation of the central nervous system. A cable model of a neuron including an axon, initial segment, axon hillock, soma, and simplified dendritic tree was used to study excitation with an extracellular point source electrode. The model reproduced a wide range of experimentally documented extracellular excitation patterns. The site of action potential initiation (API) was a function of the electrode position, stimulus duration, and stimulus polarity. The axon or initial segment was always the site of API at threshold. When the electrode was positioned near the cell body, the site of excitation was dependent on the stimulus amplitude. With the electrode in close proximity to the neuron, short-duration cathodic pulses produced lower thresholds with the electrode positioned over the axon than over the cell body, and long-duration stimuli produced opposite relative thresholds. This result was robust to alterations in either the maximum conductances or the intracellular resistivities of the model. The site of maximum depolarization was not always an accurate predictor of the site of API, and the temporal evolution of the changes in membrane potential played a strong role in determining the site of excitation. PMID:9929489

  10. 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

  11. Liposomal Conjugates for Drug Delivery to the Central Nervous System

    PubMed Central

    Helm, Frieder; Fricker, Gert

    2015-01-01

    Treatments of central nervous system (CNS) diseases often fail due to the blood–brain barrier. Circumvention of this obstacle is crucial for any systemic treatment of such diseases to be effective. One approach to transfer drugs into the brain is the use of colloidal carrier systems—amongst others, liposomes. A prerequisite for successful drug delivery by colloidal carriers to the brain is the modification of their surface, making them invisible to the reticuloendothelial system (RES) and to target them to specific surface epitopes at the blood–brain barrier. This study characterizes liposomes conjugated with cationized bovine serum albumin (cBSA) as transport vectors in vitro in porcine brain capillary endothelial cells (PBCEC) and in vivo in rats using fluorescently labelled liposomes. Experiments with PBCEC showed that sterically stabilized (PEGylated) liposomes without protein as well as liposomes conjugated to native bovine serum albumin (BSA) were not taken up. In contrast, cBSA-liposomes were taken up and appeared to be concentrated in intracellular vesicles. Uptake occurred in a concentration and time dependent manner. Free BSA and free cBSA inhibited uptake. After intravenous application of cBSA-liposomes, confocal fluorescence microscopy of brain cryosections from male Wistar rats showed fluorescence associated with liposomes in brain capillary surrounding tissue after 3, 6 and 24 h, for liposomes with a diameter between 120 and 150 nm, suggesting successful brain delivery of cationized-albumin coupled liposomes. PMID:25835091

  12. Deoxyribozymes: New Therapeutics to Treat Central Nervous System Disorders

    PubMed Central

    Grimpe, Barbara

    2011-01-01

    This mini-review focuses on a knockdown technology called deoxyribozymes, which has rarely been utilized in the field of neurobiology/neuroscience. Deoxyribozymes are catalytic DNA molecules, which are also entitled DNA enzyme or DNAzyme. This mini-review presents a description of their development, structure, function, and therapeutic application. In addition, information on siRNA, ribozymes, and antisense are given. Further information on two deoxyribozymes against c-Jun and xylosyltransferase (XT) mRNA are summarized of which the first is important to influence many neurological disorders and the last potentially treats spinal cord injuries (SCIs). In particular, insults to the central nervous system (CNS) such as SCI generate an inhibitory environment (lesion scar) at the injury site that prevents the endogenous and therapy-induced axonal regeneration and thereby limits repair strategies. Presently, there are no treatments available. Hence, deoxyribozymes provide an opportunity for new therapeutics that alter the inhibitory nature of the lesion scar and thus promote axonal growth in the injured spinal cord. When used cautiously and within the limits of its ability the deoxyribozyme technology holds promise to become a major contributing factor in repair strategies of the CNS. PMID:21977013

  13. Two rare cases of central nervous system opportunistic mycoses.

    PubMed

    Mlinarić Missoni, Emilija; Baršić, Bruno

    2012-12-01

    This article presents two cases of opportunistic mycoses (OMs) of the central nervous system (CNS) caused by Cryptococcus neoformans and Aspergillus nidulans, respectively. The patients were hospitalised in local hospitals between 2009 and 2011 because of unspecific symptoms (fever, headache, and/or weight lost). Duration of symptoms varied from 4 days to over 2 weeks. The patients were treated with antibiotics and symptomatically. OM was not suspected in any of them. The patients became critically ill with symptoms of CNS involvement and were transferred to the Intensive Care Unit (ICU) of the University Hospital for Infectious diseases (UHID) in Zagreb. None of the patients belonged to the high-risk population for developing OMs. They were not HIV-infected, had no transplantation of bone marrow or solid organ, and were not on severe immunosuppressive chemotherapy. Fungi were isolated from cerebrospinal fluid (CSF) samples and, in one patient, from aspirate of cerebral abscess. Isolation and mycological identification of all fungal isolates and in vitro antifungal susceptibility testing of these isolates were done at the Reference Centre for Mycological Diagnostics of Systemic and Disseminated Infections (RCMDSDI) in Zagreb. The patient with cryptococcal meningitis was treated with amphotericin B and fluconazole and the patient with cerebral aspergilloma with voriconazole.

  14. Central nervous system imaging and congenital melanocytic naevi

    PubMed Central

    Kinsler, V; Aylett, S; Coley, S; Chong, W; Atherton, D

    2001-01-01

    AIM—To establish the prevalence of central nervous system (CNS) abnormalities on magnetic resonance imaging (MRI) in a population of children with congenital melanocytic naevi (CMN) over the head and/or spine, and to compare this with clinical findings.
METHODS—Forty three patients identified from outpatient clinics underwent MRI of the brain and/or spine. These were reported by a paediatric radiologist and findings compared with the clinical picture.
RESULTS—Nine patients had abnormal clinical neurology, seven had abnormal findings on MRI, and six had both abnormal clinical and radiological findings. Only three of the abnormal MRIs showed features of intracranial melanosis. Three others showed structural brain abnormalities: one choroid plexus papilloma, one cerebellar astrocytoma, and one posterior fossa arachnoid cyst; the first two of these have not previously been described in association with CMN. The last abnormal MRI showed equivocal changes requiring reimaging.
CONCLUSIONS—The prevalence of radiological CNS abnormality in this group of children was 7/43. Six of these developed abnormal clinical neurological signs within the first 18 months of life, but two did not do so until after the MRI. Two of the CNS lesions were operable; for this reason we support the routine use of early MRI in this group.

 PMID:11159293

  15. Nanotechnologies for the study of the central nervous system.

    PubMed

    Ajetunmobi, A; Prina-Mello, A; Volkov, Y; Corvin, A; Tropea, D

    2014-12-01

    The impact of central nervous system (CNS) disorders on the human population is significant, contributing almost €800 billion in annual European healthcare costs. These disorders not only have a disabling social impact but also a crippling economic drain on resources. Developing novel therapeutic strategies for these disorders requires a better understanding of events that underlie mechanisms of neural circuit physiology. Studying the relationship between genetic expression, synapse development and circuit physiology in CNS function is a challenging task, involving simultaneous analysis of multiple parameters and the convergence of several disciplines and technological approaches. However, current gold-standard techniques used to study the CNS have limitations that pose unique challenges to furthering our understanding of functional CNS development. The recent advancement in nanotechnologies for biomedical applications has seen the emergence of nanoscience as a key enabling technology for delivering a translational bridge between basic and clinical research. In particular, the development of neuroimaging and electrophysiology tools to identify the aetiology and progression of CNS disorders have led to new insights in our understanding of CNS physiology and the development of novel diagnostic modalities for therapeutic intervention. This review focuses on the latest applications of these nanotechnologies for investigating CNS function and the improved diagnosis of CNS disorders.

  16. Maternal drug histories and central nervous system anomalies.

    PubMed Central

    Winship, K A; Cahal, D A; Weber, J C; Griffin, J P

    1984-01-01

    Prescription data for the three months before the last menstrual period and for the first trimester of pregnancy were obtained for 764 mothers whose children had a defect of the central nervous system and for an equal number of mothers of control babies born from the same doctors' practices. There was a statistically significant difference overall between the numbers of mothers who were prescribed drugs in the study and control groups during the trimester before the last menstrual period but no such difference was found for the first pregnancy trimester, nor was there a significant difference for any specific group of drugs. For a composite group of non-steroid anti-inflammatory drugs, salicylates, and sulphasalazine there was a significant difference for the trimester before the last menstrual period. There are arguments against such an artificial grouping, however, and when the individual drugs were considered the comparisons were no longer significant. The odds ratios for all medicines containing folic acid taken in the trimester before the last menstrual period were considerably less than unity, in contrast with nearly all other comparisons. This supports a suggested protective effect against neural tube defects of folic acid supplements begun before the onset of pregnancy but the odds ratios of these comparisons were not statistically significant. PMID:6150687

  17. Primary Central Nervous System Anaplastic Large T-cell Lymphoma

    PubMed Central

    Splavski, Bruno; Muzevic, Dario; Ladenhauser-Palijan, Tatjana; Jr, Brano Splavski

    2016-01-01

    Introduction: Primary central nervous system lymphoma (PCNSL) of T-cell origin is an exceptionally rare, highly malignant intracranial neoplasm. Although such a tumor typically presents with a focal mass lesion. Case report: Past medical history of a 26-year-old male patient with a PCNS lymphoma of T-cell origin was not suggestive of intracranial pathology or any disorder of other organs and organic systems. To achieve a gross total tumor resection, surgery was performed via osteoplastic craniotomy using the left frontal transcortical transventricular approach. Histological and immunohistochemical analyses of the tissue removed described tumor as anaplastic large cell lymphoma of T-cells (T-ALCL). Postoperative and neurological recovery was complete, while control imaging of the brain showed no signs of residual tumor at a six-month follow-up. The patient, who did not appear immunocompromized, was referred to a hematologist and an oncologist where corticosteroids, the particular chemotherapeutic protocol and irradiation therapy were applied. Conclusion: Since PCNS lymphoma is a potentially curable brain tumor, we believe that proper selection of the management options, including early radical tumor resection for solitary PCNS lymphoma, may be proposed as a major treatment of such a tumor in selected patients, resulting in a satisfactory outcome. PMID:27703297

  18. 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

  19. ABNORMALITIES PRODUCED IN THE CENTRAL NERVOUS SYSTEM BY ELECTRICAL INJURIES.

    PubMed

    Langworthy, O R

    1930-05-31

    The alternating and continuous circuits produced different types of lesions in the central nervous system. Hemorrhages were common after alternating current shocks and few hemorrhages were observed in the continuous circuit group. With both types of circuits at 1000 and 500 volts potential, severe abnormalities in the nerve cells were observed. These were more marked in the continuous circuit group. A uniformly staining, shrunken, pyknotic nucleus was taken as a criterion of nerve cell death. The Purkinje cells of the cerebellum were most susceptible to the current. Injured cells were studied in the dorsal nucleus of the vagus, in the somatic motor group, among the primary sensory neurones and in the olives. Changes in the histological structure of the cells in reference to recovery have been discussed. Injury to the cerebral and cerebellar cortices occurred on the dorsal surface close to the head electrode. Small cavities were produced, particularly in the cerebral cortex, as the result of the circuit contact. With the continuous and alternating circuits at 110 and 220 volts potential less severe changes were observed in the nerve cells although hemorrhages were common in the alternating circuit group. It must be assumed in these cases that death was due to respiratory block rather than actual death of the cells.

  20. Scar-modulating treatments for central nervous system injury.

    PubMed

    Shen, Dingding; Wang, Xiaodong; Gu, Xiaosong

    2014-12-01

    Traumatic injury to the adult mammalian central nervous system (CNS) leads to complex cellular responses. Among them, the scar tissue formed is generally recognized as a major obstacle to CNS repair, both by the production of inhibitory molecules and by the physical impedance of axon regrowth. Therefore, scar-modulating treatments have become a leading therapeutic intervention for CNS injury. To date, a variety of biological and pharmaceutical treatments, targeting scar modulation, have been tested in animal models of CNS injury, and a few are likely to enter clinical trials. In this review, we summarize current knowledge of the scar-modulating treatments according to their specific aims: (1) inhibition of glial and fibrotic scar formation, and (2) blockade of the production of scar-associated inhibitory molecules. The removal of existing scar tissue is also discussed as a treatment of choice. It is believed that only a combinatorial strategy is likely to help eliminate the detrimental effects of scar tissue on CNS repair.

  1. Tertiary Lymphoid Organs in Central Nervous System Autoimmunity

    PubMed Central

    Mitsdoerffer, Meike; Peters, Anneli

    2016-01-01

    Multiple sclerosis (MS) is an autoimmune disease characterized by chronic inflammation in the central nervous system (CNS), which results in permanent neuronal damage and substantial disability in patients. Autoreactive T cells are important drivers of the disease; however, the efficacy of B cell depleting therapies uncovered an essential role for B cells in disease pathogenesis. They can contribute to inflammatory processes via presentation of autoantigen, secretion of pro-inflammatory cytokines, and production of pathogenic antibodies. Recently, B cell aggregates reminiscent of tertiary lymphoid organs (TLOs) were discovered in the meninges of MS patients, leading to the hypothesis that differentiation and maturation of autopathogenic B and T cells may partly occur inside the CNS. Since these structures were associated with a more severe disease course, it is extremely important to gain insight into the mechanism of induction, their precise function, and clinical significance. Mechanistic studies in patients are limited. However, a few studies in the MS animal model experimental autoimmune encephalomyelitis (EAE) recapitulate TLO formation in the CNS and provide new insight into CNS TLO features, formation, and function. This review summarizes what we know so far about CNS TLOs in MS and what we have learned about them from EAE models. It also highlights the areas that are in need of further experimental work, as we are just beginning to understand and evaluate the phenomenon of CNS TLOs. PMID:27826298

  2. Slice Culture Modeling of Central Nervous System (CNS) Viral Infection

    PubMed Central

    Dionne, Kalen R.; Tyler, Kenneth L.

    2016-01-01

    The complexity of the central nervous system (CNS) is not recapitulated in cell culture models. Thin slicing and subsequent culture of CNS tissue has become a valued means to study neuronal and glial biology within the context of the physiologically relevant tissue milieu. Modern membrane-interface slice culturing methodology allows straightforward access to both CNS tissue and feeding medium, enabling experimental manipulations and analyses that would otherwise be impossible in vivo. CNS slices can be successfully maintained in culture for up to several weeks for investigation of evolving pathology and long-term intervention in models of chronic neurologic disease. Herein, membrane-interface slice culture models for studying viral encephalitis and myelitis are detailed, with emphasis on the use of these models for investigation of pathogenesis and evaluation of novel treatment strategies. We describe techniques to (1) generate brain and spinal cord slices from rodent donors, (2) virally infect slices, (3) monitor viral replication, (4) assess virally induced injury/apoptosis, (5) characterize “CNS-specific” cytokine production, and (6) treat slices with cytokines/pharmaceuticals. Although our focus is on CNS viral infection, we anticipate that the described methods can be adapted to address a wide range of investigations within the fields of neuropathology, neuroimmunology, and neuropharmacology. PMID:23975824

  3. 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.

  4. HCV-related central and peripheral nervous system demyelinating disorders.

    PubMed

    Mariotto, Sara; Ferrari, Sergio; Monaco, Salvatore

    2014-01-01

    Chronic infection with hepatitis C virus (HCV) is associated with a large spectrum of extrahepatic manifestations (EHMs), mostly immunologic/rheumatologic in nature owing to B-cell proliferation and clonal expansion. Neurological complications are thought to be immune-mediated or secondary to invasion of neural tissues by HCV, as postulated in transverse myelitis and encephalopathic forms. Primarily axonal neuropathies, including sensorimotor polyneuropathy, large or small fiber sensory neuropathy, motor polyneuropathy, mononeuritis, mononeuritis multiplex, or overlapping syndrome, represent the most common neurological complications of chronic HCV infection. In addition, a number of peripheral demyelinating disorders are encountered, such as chronic inflammatory demyelinating polyneuropathy, the Lewis-Sumner syndrome, and cryoglobulin-associated polyneuropathy with demyelinating features. The spectrum of demyelinating forms also includes rare cases of iatrogenic central and peripheral nervous system disorders, occurring during treatment with pegylated interferon. Herein, we review HCV-related demyelinating conditions, and disclose the novel observation on the significantly increased frequency of chronic demyelinating neuropathy with anti-myelin-associated glycoprotein antibodies in a cohort of 59 consecutive patients recruited at our institution. We also report a second case of neuromyelitis optica with serum IgG autoantibody against the water channel aquaporin-4. The prompt recognition of these atypical and underestimated complications of HCV infection is of crucial importance in deciding which treatment option a patient should be offered.

  5. A case of disseminated central nervous system sparganosis

    PubMed Central

    Noiphithak, Raywat; Doungprasert, Gahn

    2016-01-01

    Background: Sparganosis is a very rare parasitic infection in various organs caused by the larvae of tapeworms called spargana. The larva usually lodges in the central nervous system (CNS) and the orbit. However, lumbar spinal canal involvement, as noted in the present case, is extremely rare. We report a rare case of disseminated CNS sparganosis involving the brain and spinal canal and review the literature. Case Description: A 54-year-old man presented with progressive low back pain and neurological deficit at the lumbosacral level for 2 months. Imaging indicated arachnoiditis and an abnormal lesion at the L4-5 vertebral level. The patient underwent laminectomy of the L4-5 with lesionectomy and lysis of adhesions between the nerve roots. Microscopic examination indicated sparganum infection. Further brain imaging revealed evidence of chronic inflammation in the left parieto-occipital area without evidence of live parasites. In addition, an ophthalmologist reported a nonactive lesion in the right conjunctiva. The patient recovered well after surgery, although he had residual back pain and bladder dysfunction probably due to severe adhesion of the lumbosacral nerve roots. Conclusion: CNS sparganosis can cause various neurological symptoms similar to those of other CNS infections. A preoperative enzyme-linked immunosorbent assay is helpful for diagnosis, especially in endemic areas. Surgical removal of the worm remains the treatment of choice. PMID:28031991

  6. 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

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

    PubMed

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

    2015-08-11

    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.

  8. Central nervous system-specific knockout of steroidogenic factor 1.

    PubMed

    Kim, Ki Woo; Zhao, Liping; Parker, Keith L

    2009-03-05

    Steroidogenic factor 1 (SF-1) is a nuclear receptor that plays important roles in the hypothalamus-pituitary-steroidogenic organ axis. Global knockout studies in mice revealed the essential in vivo roles of SF-1 in the ventromedial hypothalamic (VMH) nucleus, adrenal glands, and gonads. One limitation of global SF-1 knockout mice is their early postnatal death from adrenocortical insufficiency. To overcome limitations of the global knockout mice and to delineate the roles of SF-1 in the brain, we used Cre/loxP recombination technology to genetically ablate SF-1 specifically in the central nervous system (CNS). Mice with CNS-specific knockout of SF-1 mediated by nestin-Cre showed increased anxiety-like behavior, revealing a crucial role of SF-1 in a complex behavioral phenotype. Our studies with CNS-specific SF-1 KO mice also defined roles of SF-1 in regulating the VMH expression of target genes implicated in anxiety and energy homeostasis. Therefore, this review will focus on our recent studies defining the functional roles of SF-1 in the VMH linked to anxiety and energy homeostasis.

  9. Prolactin: Friend or Foe in Central Nervous System Autoimmune Inflammation?

    PubMed Central

    Costanza, Massimo; Pedotti, Rosetta

    2016-01-01

    The higher prevalence of multiple sclerosis (MS) in females, along with the modulation of disease activity observed during pregnancy and the post-partum period, has suggested a hormonal influence in MS. Even if prolactin (PRL) does not belong to the sex hormones family, its crucial role in female reproduction and lactation has prompted great efforts to understand if PRL could represent a gender factor in the pathogenesis of MS and experimental autoimmune encephalomyelitis (EAE), the animal model for this disease. Extensive literature has documented a remarkable immune-stimulating potential for this hormone, indicating PRL as a disease-promoting factor in MS and EAE. However, recent work has pointed out that PRL is endowed with important neuroprotective and remyelinating properties and has encouraged a reinterpretation of the involvement of this hormone in MS. In this review we summarize both the protective functions that PRL exerts in central nervous system tissue as well as the inflammatory activity of this hormone in the context of autoimmune responses against myelin. Last, we draw future lines of research that might help to better clarify the impact of PRL on MS pathology. PMID:27918427

  10. Role of Microglia in Central Nervous System Infections

    PubMed Central

    Rock, R. Bryan; Gekker, Genya; Hu, Shuxian; Sheng, Wen S.; Cheeran, Maxim; Lokensgard, James R.; Peterson, Phillip K.

    2004-01-01

    The nature of microglia fascinated many prominent researchers in the 19th and early 20th centuries, and in a classic treatise in 1932, Pio del Rio-Hortega formulated a number of concepts regarding the function of these resident macrophages of the brain parenchyma that remain relevant to this day. However, a renaissance of interest in microglia occurred toward the end of the 20th century, fueled by the recognition of their role in neuropathogenesis of infectious agents, such as human immunodeficiency virus type 1, and by what appears to be their participation in other neurodegenerative and neuroinflammatory disorders. During the same period, insights into the physiological and pathological properties of microglia were gained from in vivo and in vitro studies of neurotropic viruses, bacteria, fungi, parasites, and prions, which are reviewed in this article. New concepts that have emerged from these studies include the importance of cytokines and chemokines produced by activated microglia in neurodegenerative and neuroprotective processes and the elegant but astonishingly complex interactions between microglia, astrocytes, lymphocytes, and neurons that underlie these processes. It is proposed that an enhanced understanding of microglia will yield improved therapies of central nervous system infections, since such therapies are, by and large, sorely needed. PMID:15489356

  11. Superficial siderosis of the central nervous system: A case report

    PubMed Central

    GAO, JI-GUO; ZHOU, CHUN-KUI; LIU, JING-YAO

    2015-01-01

    Superficial siderosis of the central nervous system (SSCNS) is a rare syndrome resulting from hemosiderin deposits in neuronal tissues close to the cerebrospinal fluid. SSCNS is characterized by sensorineural deafness, cerebellar ataxia and signs of pyramidal tract dysfunction. The present study describes a patient with SSCNS that did not suffer from hearing loss, which is the most common symptom of SSCNS. The patient was a 48-year-old male, presenting with dizziness, ataxia and slurred speech. The patient’s ataxia was characterized by dizziness, nystagmus, dysarthria, abnormal finger-nose pointing and heel-knee-shin tests and a positive Chaddock sign. The patient had suffered from a pontine hemorrhage two years prior to the study. Audiometric tests showed normal hearing during the hospital stay and at the two-month follow-up examination. The diagnosis of SSCNS was made based on magnetic resonance images, which showed areas of linear hypointensity on the surface of the pons with mild cerebellar atrophy. However, a long-term follow-up is required to monitor the hearing of the patient. Improved understanding of SSCNS is important for clinicians to identify SSCNS patients who present without typical clinical symptoms. PMID:25780438

  12. HCV-Related Central and Peripheral Nervous System Demyelinating Disorders

    PubMed Central

    Mariotto, Sara; Ferrari, Sergio; Monaco, Salvatore

    2014-01-01

    Chronic infection with hepatitis C virus (HCV) is associated with a large spectrum of extrahepatic manifestations (EHMs), mostly immunologic/rheumatologic in nature owing to B-cell proliferation and clonal expansion. Neurological complications are thought to be immune-mediated or secondary to invasion of neural tissues by HCV, as postulated in transverse myelitis and encephalopathic forms. Primarily axonal neuropathies, including sensorimotor polyneuropathy, large or small fiber sensory neuropathy, motor polyneuropathy, mononeuritis, mononeuritis multiplex, or overlapping syndrome, represent the most common neurological complications of chronic HCV infection. In addition, a number of peripheral demyelinating disorders are encountered, such as chronic inflammatory demyelinating polyneuropathy, the Lewis-Sumner syndrome, and cryoglobulin-associated polyneuropathy with demyelinating features. The spectrum of demyelinating forms also includes rare cases of iatrogenic central and peripheral nervous system disorders, occurring during treatment with pegylated interferon. Herein, we review HCV-related demyelinating conditions, and disclose the novel observation on the significantly increased frequency of chronic demyelinating neuropathy with anti-myelin-associated glycoprotein antibodies in a cohort of 59 consecutive patients recruited at our institution. We also report a second case of neuromyelitis optica with serum IgG autoantibody against the water channel aquaporin-4. The prompt recognition of these atypical and underestimated complications of HCV infection is of crucial importance in deciding which treatment option a patient should be offered. PMID:25198705

  13. 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

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. Central nervous system granulomastous phlebitis with limited extracranial involvement of the heart and lungs: An autopsy case.

    PubMed

    Mlakar, Jernej; Zorman, Jerneja Videčnik; Matičič, Mojca; Vrabec, Matej; Alibegović, Armin; Popović, Mara

    2016-02-01

    Primary angiitis of the central nervous system is a rare condition, usually with an insidious onset. There is a wide variety of histological types (granulomatous, lymphocytic or necrotizing vasculitis) and types of vessel involved (arteries, veins or both). Most cases are idiopathic. We describe a first case of idiopathic granulomatous central nervous system phlebitis with additional limited involvement of the heart and lung, exclusively affecting small and medium sized veins in a 22-year-old woman, presenting as a sub acute headache. The reasons for this peculiar limitation of inflammation to the veins and the involvement of the heart and lungs are unknown.

  3. Modern imaging of tuberculosis in children: thoracic, central nervous system and abdominal tuberculosis.

    PubMed

    Andronikou, Savvas; Wieselthaler, Nicky

    2004-11-01

    Tuberculosis (TB) can affect any organ in the body. Children are a high-risk group for contracting the disease and pose a constant challenge to clinicians with regard to making a definitive diagnosis. Radiologists are playing a more active role in diagnosing TB, and armed with more accurate diagnostic investigations such as CT and MRI, they must face the cost implications as well as technical limitations. This review aims to guide the reader through the modern imaging techniques useful for diagnosing TB of the thorax, central nervous system and abdomen in children. The more specific features of each modality in the particular anatomical regions are highlighted.

  4. Toxocariasis of the central nervous system: With report of two cases.

    PubMed

    Abir, Bouthouri; Malek, Mansour; Ridha, Mrissa

    2017-03-01

    Toxocariasis is a parasitic infection caused by the roundworms Toxocara canis or Toxocara cati, mostly due to accidental ingestion of embryonated eggs. Clinical manifestations vary and are classified according to the organs affected. Central nervous system involvement is an unusual complication. Here, we report two cases with neurological manifestations, in which there was cerebrospinal fluid (CSF) eosinophilia with marked blood eosinophilia and a positive serology for Toxocara both in serum and CSF. Improvement of signs and symptoms after specific treatment was observed in the two cases.

  5. Novel, unifying mechanism for mescaline in the central nervous system

    PubMed Central

    Somanathan, Ratnasamy

    2009-01-01

    A unifying mechanism for abused drugs has been proposed previously from the standpoint of electron transfer. Mescaline can be accommodated within the theoretical framework based on redox cycling by the catechol metabolite with its quinone counterpart. Electron transfer may play a role in electrical effects involving the nervous system in the brain. This approach is in accord with structure activity relationships involving mescaline, abused drugs, catecholamines and etoposide. Inefficient demethylation is in keeping with the various drug properties, such as requirement for high dosage and slow acting. There is a discussion of receptor binding, electrical effects, cell signaling and other modes of action. Mescaline is a nonselective, seretonin receptor agonist. 5-HTP receptors are involved in the stimulus properties. Research addresses the aspect of stereochemical requirements. Receptor binding may involve the proposed quinone metabolite and/or the amino sidechain via protonation. Electroencephalographic studies were performed on the effects of mescaline on men. Spikes are elicited by stimulation of a cortical area. The potentials likely originate in nonsynaptic dendritic membranes. Receptor-mediated signaling pathways were examined which affect mescaline behavior. The hallucinogen belongs to the class of 2AR agonists which regulate pathways in cortical neurons. The research identifies neural and signaling mechanisms responsible for the biological effects. Recently, another hallucinogen, psilocybin, has been included within the unifying mechanistic framework. This mushroom constituent is hydrolyzed to the phenol psilocin, also active, which is subsequently oxidized to an ET o-quinone or iminoquinone. PMID:20716904

  6. Autoantibodies in traumatic brain injury and central nervous system trauma.

    PubMed

    Raad, M; Nohra, E; Chams, N; Itani, M; Talih, F; Mondello, S; Kobeissy, F

    2014-12-05

    Despite the debilitating consequences and the widespread prevalence of brain trauma insults including spinal cord injury (SCI) and traumatic brain injury (TBI), there are currently few effective therapies for most of brain trauma sequelae. As a consequence, there has been a major quest for identifying better diagnostic tools, predictive models, and directed neurotherapeutic strategies in assessing brain trauma. Among the hallmark features of brain injury pathology is the central nervous systems' (CNS) abnormal activation of the immune response post-injury. Of interest, is the occurrence of autoantibodies which are produced following CNS trauma-induced disruption of the blood-brain barrier (BBB) and released into peripheral circulation mounted against self-brain-specific proteins acting as autoantigens. Recently, autoantibodies have been proposed as the new generation class of biomarkers due to their long-term presence in serum compared to their counterpart antigens. The diagnostic and prognostic value of several existing autoantibodies is currently being actively studied. Furthermore, the degree of direct and latent contribution of autoantibodies to CNS insult is still not fully characterized. It is being suggested that there may be an analogy of CNS autoantibodies secretion with the pathophysiology of autoimmune diseases, in which case, understanding and defining the role of autoantibodies in brain injury paradigm (SCI and TBI) may provide a realistic prospect for the development of effective neurotherapy. In this work, we will discuss the accumulating evidence about the appearance of autoantibodies following brain injury insults. Furthermore, we will provide perspectives on their potential roles as pathological components and as candidate markers for detecting and assessing CNS injury.

  7. Craniospinal irradiation using helical tomotherapy for central nervous system tumors.

    PubMed

    Schiopu, Sanziana R I; Habl, Gregor; Häfner, Matthias; Katayama, Sonja; Herfarth, Klaus; Debus, Juergen; Sterzing, Florian

    2017-01-17

    The aim of this study was to describe early and late toxicity, survival and local control in 45 patients with primary brain tumors treated with helical tomotherapy craniospinal irradiation (HT-CSI). From 2006 to 2014, 45 patients with central nervous system malignancies were treated with HT-CSI. The most common tumors were medulloblastoma in 20 patients, ependymoma in 10 patients, intracranial germinoma (ICG) in 7 patients, and primitive neuroectodermal tumor in 4 patients. Hematological toxicity during treatment included leukopenia Grades 1-4 (6.7%, 33.3%, 37.8% and 17.8%, respectively), anemia Grades 1-4 (44.4%, 22.2%, 22.2% and 0%, respectively) and thrombocytopenia Grades 1-4 (51.1%, 15.6%, 15.6% and 6.7%, respectively). The most common acute toxicities were nausea, vomiting, fatigue, loss of appetite, alopecia and neurotoxicity. No Grade 3 or higher late toxicity occurred. The overall 3- and 5-year survival rates were 80% and 70%, respectively. Survival for the main tumor entities included 3- and 5-year survival rates of 80% and 70%, respectively, for patients with medulloblastoma, 70% for both in patients with ependymoma, and 100% for both in patients with ICG. Relapse occurred in 11 patients (24.4%): 10 with local and 1 with multifocal relapse. One patient experienced a secondary cancer. M-status and the results of the re-evaluation at the end of treatment were significantly related to survival. Survival after HT-CSI was in line with the existing literature, and acute treatment-induced toxicity resolved quickly. Compared with conventional radiotherapy, HT offers benefits such as avoiding gaps and junctions, sparing organs, and better and more homogeneous dose distribution and coverage of the target volume.

  8. 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.

  9. 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

  10. Persisting Rickettsia typhi Causes Fatal Central Nervous System Inflammation

    PubMed Central

    Papp, Stefanie; Moderzynski, Kristin; Kuehl, Svenja; Richardt, Ulricke; Fleischer, Bernhard

    2016-01-01

    Rickettsioses are emerging febrile diseases caused by obligate intracellular bacteria belonging to the family Rickettsiaceae. Rickettsia typhi belongs to the typhus group (TG) of this family and is the causative agent of endemic typhus, a disease that can be fatal. In the present study, we analyzed the course of R. typhi infection in C57BL/6 RAG1−/− mice. Although these mice lack adaptive immunity, they developed only mild and temporary symptoms of disease and survived R. typhi infection for a long period of time. To our surprise, 3 to 4 months after infection, C57BL/6 RAG1−/− mice suddenly developed lethal neurological disorders. Analysis of these mice at the time of death revealed high bacterial loads, predominantly in the brain. This was accompanied by a massive expansion of microglia and by neuronal cell death. Furthermore, high numbers of infiltrating CD11b+ macrophages were detectable in the brain. In contrast to the microglia, these cells harbored R. typhi and showed an inflammatory phenotype, as indicated by inducible nitric oxide synthase (iNOS) expression, which was not observed in the periphery. Having shown that R. typhi persists in immunocompromised mice, we finally asked whether the bacteria are also able to persist in resistant C57BL/6 and BALB/c wild-type mice. Indeed, R. typhi could be recultivated from lung, spleen, and brain tissues from both strains even up to 1 year after infection. This is the first report demonstrating persistence and reappearance of R. typhi, mainly restricted to the central nervous system in immunocompromised mice. PMID:26975992

  11. Central nervous system regeneration: from leech to opossum

    PubMed Central

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

    2009-01-01

    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

  12. 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.

  13. 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.

  14. Sex differences in the effects of androgens acting in the central nervous system on metabolism

    PubMed Central

    Morford, Jamie; Mauvais-Jarvis, Franck

    2016-01-01

    One of the most sexually dimorphic aspects of metabolic regulation is the bidirectional modulation of glucose and energy homeostasis by testosterone in males and females. Testosterone deficiency predisposes men to metabolic dysfunction, with excess adiposity, insulin resistance, and type 2 diabetes, whereas androgen excess predisposes women to insulin resistance, adiposity, and type 2 diabetes. This review discusses how testosterone acts in the central nervous system, and especially the hypothalamus, to promote metabolic homeostasis or dysfunction in a sexually dimorphic manner. We compare the organizational actions of testosterone, which program the hypothalamic control of metabolic homeostasis during development, and the activational actions of testosterone, which affect metabolic function after puberty. We also discuss how the metabolic effect of testosterone is centrally mediated via the androgen receptor. PMID:28179813

  15. Sex differences in the effects of androgens acting in the central nervous system on metabolism.

    PubMed

    Morford, Jamie; Mauvais-Jarvis, Franck

    2016-12-01

    One of the most sexually dimorphic aspects of metabolic regulation is the bidirectional modulation of glucose and energy homeostasis by testosterone in males and females. Testosterone deficiency predisposes men to metabolic dysfunction, with excess adiposity, insulin resistance, and type 2 diabetes, whereas androgen excess predisposes women to insulin resistance, adiposity, and type 2 diabetes. This review discusses how testosterone acts in the central nervous system, and especially the hypothalamus, to promote metabolic homeostasis or dysfunction in a sexually dimorphic manner. We compare the organizational actions of testosterone, which program the hypothalamic control of metabolic homeostasis during development, and the activational actions of testosterone, which affect metabolic function after puberty. We also discuss how the metabolic effect of testosterone is centrally mediated via the androgen receptor.

  16. Securing the future of drug discovery for central nervous system disorders.

    PubMed

    Andersen, Peter Høngaard; Moscicki, Richard; Sahakian, Barbara; Quirion, Rémi; Krishnan, Ranga; Race, Tim; Phillips, Anthony

    2014-12-01

    Innovative partnerships among researchers, patients, regulators, payors and industry are needed to reinvigorate drug discovery for central nervous system disorders. Here, we summarize plans of the Collegium Internationale Neuro-Psychopharmacologicum (CINP) to achieve this goal.

  17. 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.

  18. Sebaceous nevus syndrome, central nervous system malformations, aplasia cutis congenita, limbal dermoid, and pigmented nevus syndrome.

    PubMed

    Hsieh, Chih-Wei; Wu, Yu-Hung; Lin, Shuan-Pei; Peng, Chun-Chih; Ho, Che-Sheng

    2012-01-01

    SCALP syndrome is an acronym describing the coincidence of sebaceous nevus syndrome, central nervous system malformations, aplasia cutis congenita, limbal dermoid, and pigmented nevus (giant congenital melanocytic nevus). We present a fourth case of this syndrome.

  19. Central nervous system herpes simplex virus infection in afebrile children with seizures.

    PubMed

    Majumdar, Indrajit; Hartley-McAndrew, Michelle E; Weinstock, Arie L

    2012-04-01

    Central nervous system herpes simplex virus infection is suspected in patients presenting with acute-onset seizures and lethargy. The potential neurologic sequelae from untreated herpes infection can prompt empirical acyclovir therapy, even in afebrile subjects. The objectives of this study were to determine the frequency of central nervous system herpes simplex virus infection in children presenting with afebrile seizures and to assess the need for empirical acyclovir therapy. Clinical and laboratory data of children with acute-onset afebrile seizures and children with central nervous system herpes simplex virus infection were compared. Polymerase chain reaction and viral cultures of the cerebrospinal fluid for herpes simplex virus infection were negative in all subjects with afebrile seizures; 32.7% of these subjects were empirically treated with acyclovir. In conclusion, central nervous system herpes simplex virus infection is uncommon in children presenting with afebrile seizures, and acyclovir therapy is rarely necessary in subjects with normal neurologic examination and cerebrospinal fluid analysis.

  20. Central nervous system gene expression changes in a transgenic mouse model for bovine spongiform encephalopathy.

    PubMed

    Tortosa, Raül; Castells, Xavier; Vidal, Enric; Costa, Carme; Ruiz de Villa, María del Carmen; Sánchez, Alex; Barceló, Anna; Torres, Juan María; Pumarola, Martí; Ariño, Joaquín

    2011-10-28

    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.

  1. Vanadium (V)-induced neurotoxicity in the rat central nervous system: a histo-immunohistochemical study.

    PubMed

    Garcia, Graciela Beatriz; Biancardi, Maria Eugenia; Quiroga, Ariel Dario

    2005-01-01

    As vanadium was found to induce oxidative stress in the central nervous system, the morphological alterations of neurons and astroglial cells in adult rat central nervous system after vanadium exposure was studied, using histological markers of cellular injury. Animals were intraperitoneally injected with 3 mg/kg body weight of sodium metavanadate for 5 consecutive days. NADPH diaphorase histochemistry and heat shock protein (hsp) 70, glial fibrillary acidic protein (GFAP), and S-100 immunohistochemistry were performed in floating sections of several brain areas. NADPHd staining was higher in the molecular and granular layers of the cerebellar cortex, and small NADPHd-stained interneurons were observed in hippocampal sections in V(+5)-exposed animals. hsp 70 immunostaining showed the presence of reactive neurons in cerebellum of treated animals. GFAP and S-100 immunohistochemistry showed enlarged astrocytes in cerebellum and hippocampus in the V(+5)-exposed animals. The histological markers used showed that the main areas affected by vanadium-mediated free-radical generation were the hippocampus and the cerebellum.

  2. 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

  3. Neuropsychological sequelae of central nervous system prophylaxis in survivors of childhood acute lymphoblastic leukemia

    SciTech Connect

    Said, J.A.; Waters, B.G.; Cousens, P.; Stevens, M.M.

    1989-04-01

    We assessed neuropsychologically 106 children with acute lymphoblastic leukemia (ALL) who had all received cranial irradiation for the prevention of central nervous system (CNS) leukemia 1-13 years previously. Children were assessed for adverse late effects of their therapy, using age-appropriate Wechsler measures of overall intellectual ability and supplementary tests. Forty-five siblings near in age to the patients were tested as controls. The patients who had had the most intensive central nervous system (CNS) prophylaxis were found to have a WISC-R Full Scale IQ 17 points lower than the sibling control group. Performance IQ was more affected than verbal IQ. The patients were more easily distracted and less able to concentrate. The severity of the aftereffects was related to younger age at the time of CNS prophylaxis and to a higher dose of cranial irradiation but not to time since CNS prophylaxis. CNS prophylaxis using a combination of cranial irradiation and intrathecal methotrexate has lowered the incidence of CNS relapse in childhood ALL but is associated with considerable long-term morbidity in survivors.

  4. 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

  5. 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.

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

    PubMed

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

    2016-04-01

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

  7. 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

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

    PubMed Central

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

    2016-01-01

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

  9. Assessment of the peripheral, central, and autonomic nervous system function in styrene workers

    SciTech Connect

    Murata, K.; Araki, S.; Yokoyama, K. )

    1991-01-01

    To investigate the effects of styrene exposure on peripheral, central, and autonomic nervous system functions in man, we measured the distribution of nerve conduction velocities (DCV), short-latency somatosensory evoked potentials (SSEP), and variability in electrocardiographic R-R interval (CVRR) as well as conventional sensory and motor median nerve conduction velocities (SCV and MCV) in eleven styrene-exposed workers. The styrene workers' urinary phenylglyoxylic acid levels ranged from 31 to 419 (mean 169) mg/g creatinine at the end of the work shift on the examination day (estimated exposure to styrene of 22 ppm in air). Control subjects, matched to each styrene worker by sex and age, were selected from healthy adults without cardiovascular, neurologic and other potentially confounding disorders. In the styrene workers, we found that the V80 velocity of the DCV, below which 80% of active nerve fibers lie, and the SCV were both significantly slowed; the CVRR was also significantly reduced. There were no significant differences in SSEP latencies, MCV, or heart rate between the exposed workers and controls. These data, despite the small sample size, suggest that styrene affects the faster myelinated fibers of the peripheral sensory nerves, and that it also affects autonomic nervous activity.

  10. Central nervous system dysfunction in obesity-induced hypertension.

    PubMed

    Head, Geoffrey A; Lim, Kyungjoon; Barzel, Benjamin; Burke, Sandra L; Davern, Pamela J

    2014-09-01

    The activation of the sympathetic nervous system is a major mechanism underlying both human and experimental models of obesity-related hypertension. While insulin and the adipokine leptin have long been thought to contribute to obesity-related neurogenic mechanisms, the evidence is now very strong that they play a major role, shown particularly in animal studies using selective receptor antagonists. There is not just maintenance of leptin's sympatho-excitatory actions as previously suggested but considerable amplification particularly in renal sympathetic nervous activity. Importantly, these changes are not dependent on short-term elevation or reduction in plasma leptin or insulin, but require some weeks to develop indicating a slow "neural adaptivity" within hypothalamic signalling. These effects can be carried across generations even when offspring are raised on a normal diet. A better understanding of the underlying mechanism should be a high research priority given the prevalence of obesity not just in the current population but also for future generations.

  11. Central nervous system recurrence of systemic lymphoma in the era of stem cell transplantation--an International Primary Central Nervous System Lymphoma Study Group project.

    PubMed

    Bromberg, Jacoline E; Doorduijn, Jeanette K; Illerhaus, Gerald; Jahnke, Kristoph; Korfel, Agniezka; Fischer, Lars; Fritsch, Kristina; Kuittinen, Outti; Issa, Samar; van Montfort, Cees; van den Bent, Martin J

    2013-05-01

    Autologous stem cell transplantation has greatly improved the prognosis of systemic recurrent non-Hodgkin's lymphoma. However, no prospective data are available concerning the feasibility and efficacy of this strategy for systemic lymphoma relapsing in the central nervous system. We, therefore, we performed an international multicenter retrospective study of patients with a central nervous system recurrence of systemic lymphoma to assess the outcome of these patients in the era of stem cell transplantation. We collected clinical and treatment data on patients with a first central nervous system recurrence of systemic lymphoma treated between 2000 and 2010 in one of five centers in four countries. Patient- and treatment-related factors were analyzed and compared descriptively. Primary outcome measures were overall survival and percentage of patients transplanted. We identified 92 patients, with a median age of 59 years and a median Eastern Cooperative Oncology Group/World Health Organization performance status of 2, of whom 76% had diffuse large B-cell histology. The majority (79%) of these patients were treated with systemic chemotherapy with or without intravenous rituximab. Twenty-seven patients (29%) were transplanted; age and insufficient response to induction chemotherapy were the main reasons for not being transplanted in the remaining 65 patients. The median overall survival was 7 months (95% confidence interval 2.6-11.4), being 8 months (95% confidence interval 3.8-5.2) for patients ≤ 65 years old. The 1-year survival rate was 34.8%; of the 27 transplanted patients 62% survived more than 1 year. The Memorial Sloan Kettering Prognostic Index for primary central nervous system lymphoma was prognostic for both undergoing transplantation and survival. In conclusion, despite the availability of autologous stem cell transplantation for patients with central nervous system progression or relapse of systemic lymphoma, prognosis is still poor. Long-term survival

  12. Muscle fibers in the central nervous system of nemerteans: spatial organization and functional role.

    PubMed

    Petrov, A A; Zaitseva, O V

    2012-08-01

    The system of muscle fibers associated with the brain and lateral nerve cords is present in all major groups of enoplan nemerteans. Unfortunately, very little is known about the functional role and spatial arrangement of these muscles of the central nervous system. This article examines the architecture of the musculature of the central nervous system in two species of monostiliferous nemerteans (Emplectonema gracile and Tetrastemma cf. candidum) using phalloidin staining and confocal microscopy. The article also briefly discusses the body-wall musculature and the muscles of the cephalic region. In both species, the lateral nerve cords possess two pairs of cardinal muscles that run the length of the nerve cords and pass through the ventral cerebral ganglia. A system of peripheral muscles forms a meshwork around the lateral nerve cords in E. gracile. The actin-rich processes that ramify within the nerve cords in E. gracile (transverse fibers) might represent a separate population of glia-like cells or sarcoplasmic projections of the peripheral muscles of the central nervous system. The lateral nerve cords in T. cf. candidum lack peripheral muscles but have muscles similar in their position and orientation to the transverse fibers. The musculature of the central nervous system is hypothesized to function as a support system for the lateral nerve cords and brain, preventing rupturing and herniation of the nervous tissue during locomotion. The occurrence of muscles of the central nervous system in nemerteans and other groups and their possible relevance in taxonomy are discussed.

  13. T Cells in the Central Nervous System: The Delicate Balance between Viral Clearance and Disease

    PubMed Central

    McGavern, Dorian B.; Homann, Dirk; Oldstone, Michael B. A.

    2017-01-01

    The central nervous system (CNS) is considered an “immunoprivileged” site with restricted access and a unique microenvironment that profoundly affects the capacity of T cells to exert their functions. The lymphocytic choriomeningitis virus model offers a unique system in which to evaluate the contrasting roles of specific T cells in causing lethal CNS disease or curing pervasive and life-long CNS infection. Specific T cell kinetics in the periphery is briefly discussed. The T cell–mediated mechanisms leading to fatal choriomeningitis are reviewed as are recent methodologic advances that will facilitate the study of antigen-specific T cells in disease pathogenesis. Understanding the specific constraints imposed by the CNS on local T cell activity has important consequences for the design of therapeutic strategies aimed at preventing or curing CNS infection. PMID:12424690

  14. 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

    2016-01-01

    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.

  15. Parasitic diseases of the central nervous system: lessons for clinicians and policy makers

    PubMed Central

    Carpio, Arturo; Romo, Matthew L.; Parkhouse, R. M. E.; Short, Brooke; Dua, Tarun

    2016-01-01

    ABSTRACT 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

  16. Toxic Effects of Mercury on the Cardiovascular and Central Nervous Systems

    PubMed Central

    Fernandes Azevedo, Bruna; Barros Furieri, Lorena; Peçanha, Franck Maciel; Wiggers, Giulia Alessandra; Frizera Vassallo, Paula; Ronacher Simões, Maylla; Fiorim, Jonaina; Rossi de Batista, Priscila; Fioresi, Mirian; Rossoni, Luciana; Stefanon, Ivanita; Alonso, María Jesus; Salaices, Mercedes; Valentim Vassallo, Dalton

    2012-01-01

    Environmental contamination has exposed humans to various metal agents, including mercury. This exposure is more common than expected, and the health consequences of such exposure remain unclear. For many years, mercury was used in a wide variety of human activities, and now, exposure to this metal from both natural and artificial sources is significantly increasing. Many studies show that high exposure to mercury induces changes in the central nervous system, potentially resulting in irritability, fatigue, behavioral changes, tremors, headaches, hearing and cognitive loss, dysarthria, incoordination, hallucinations, and death. In the cardiovascular system, mercury induces hypertension in humans and animals that has wide-ranging consequences, including alterations in endothelial function. The results described in this paper indicate that mercury exposure, even at low doses, affects endothelial and cardiovascular function. As a result, the reference values defining the limits for the absence of danger should be reduced. PMID:22811600

  17. Overview of the Effect and Epidemiology of Parasitic Central Nervous System Infections in African Children

    PubMed Central

    Mallewa, Macpherson; Wilmshurst, Jo M.

    2014-01-01

    Infections of the central nervous system are a significant cause of neurologic dysfunction in resource-limited countries, especially in Africa. The prevalence is not known and is most likely underestimated because of the lack of access to accurate diagnostic screens. For children, the legacy of subsequent neurodisability, which affects those who survive, is a major cause of the burden of disease in Africa. Of the parasitic infections with unique effect in Africa, cerebral malaria, neurocysticercosis, human African trypanosomiasis, toxoplasmosis, and schistosomiasis are largely preventable conditions, which are rarely seen in resource-equipped settings. This article reviews the current understandings of these parasitic and other rarer infections, highlighting the specific challenges in relation to prevention, diagnosis, treatment, and the complications of coinfection. PMID:24655400

  18. Ependymal and periventricular magnetic resonance imaging changes in four dogs with central nervous system blastomycosis.

    PubMed

    Bentley, R Timothy; Reese, Michael J; Heng, Hock Gan; Lin, Tsang Long; Shimonohara, Nozomi; Fauber, Amy

    2013-01-01

    Rapid detection of central nervous system (CNS) involvement is important for dogs with blastomycosis, as this can affect antifungal drug selection and has been associated with an increased risk of death. Previous reports describing magnetic resonance imaging (MRI) characteristics of canine CNS blastomycosis primarily identified mass lesions. The purpose of this retrospective study was to determine whether other MRI characteristics of CNS blastomycosis may also occur. Medical records of the Purdue University Veterinary Teaching Hospital were searched and four dogs met inclusion criteria. Magnetic resonance imaging characteristics included periventricular edema, periventricular and meningeal contrast enhancement, and ventriculomegaly. Periventricular lesions most commonly involved the rostral horn of the lateral ventricles and the third ventricle. Increased meningeal contrast enhancement involved the cerebrum, thalamus, sella turcica, and brainstem. Findings indicated that, in addition to mass lesions, MRI characteristics of periventricular hyperintensity, contrast enhancement, and ventriculomegaly may also occur in dogs with CNS blastomycosis.

  19. Effects of low-dose prenatal irradiation on the central nervous system

    SciTech Connect

    Not Available

    1992-04-01

    Scientists are in general agreement about the effects of prenatal irradiation, including those affecting the central nervous system (CNS). Differing concepts and research approaches have resulted in some uncertainties about some quantitative relationships, underlying interpretations, and conclusions. Examples of uncertainties include the existence of a threshold, the quantitative relationships between prenatal radiation doses and resulting physical and functional lesions, and processes by which lesions originate and develop. A workshop was convened in which scientists with varying backgrounds and viewpoints discussed these relationships and explored ways in which various disciplines could coordinate concepts and methodologies to suggest research directions for resolving uncertainties. This Workshop Report summarizes, in an extended fashion, salient features of the presentations on the current status of our knowledge about the radiobiology and neuroscience of prenatal irradiation and the relationships between them.

  20. Mutation of fibulin-1 causes a novel syndrome involving the central nervous system and connective tissues

    PubMed Central

    Bohlega, Saeed; Al-Ajlan, Huda; Al-Saif, Amr

    2014-01-01

    Fibulin-1 is an extracellular matrix protein that has an important role in the structure of elastic fibers and basement membranes of various tissues. Using homozygosity mapping and exome sequencing, we discovered a missense mutation, p.(Cys397Phe), in fibulin-1 in three patients from a consanguineous family presented with a novel syndrome of syndactyly, undescended testes, delayed motor milestones, mental retardation and signs of brain atrophy. The mutation discovered segregated with the phenotype and was not found in 374 population-matched alleles. The affected cysteine is highly conserved across vertebrates and its mutation is predicted to abolish a disulfide bond that defines the tertiary structure of fibulin-1. Our findings emphasize the crucial role fibulin-1 has in development of the central nervous system and various connective tissues. PMID:24084572

  1. Cdk2 loss accelerates precursor differentiation and remyelination in the adult central nervous system

    PubMed Central

    Caillava, Céline; Vandenbosch, Renaud; Jablonska, Beata; Deboux, Cyrille; Spigoni, Giulia; Gallo, Vittorio; Malgrange, Brigitte

    2011-01-01

    The specific functions of intrinsic regulators of oligodendrocyte progenitor cell (OPC) division are poorly understood. Type 2 cyclin-dependent kinase (Cdk2) controls cell cycle progression of OPCs, but whether it acts during myelination and repair of demyelinating lesions remains unexplored. Here, we took advantage of a viable Cdk2−/− mutant mouse to investigate the function of this cell cycle regulator in OPC proliferation and differentiation in normal and pathological conditions. During central nervous system (CNS) development, Cdk2 loss does not affect OPC cell cycle, oligodendrocyte cell numbers, or myelination. However, in response to CNS demyelination, it clearly alters adult OPC renewal, cell cycle exit, and differentiation. Importantly, Cdk2 loss accelerates CNS remyelination of demyelinated axons. Thus, Cdk2 is dispensable for myelination but is important for adult OPC renewal, and could be one of the underlying mechanisms that drive adult progenitors to differentiate and thus regenerate myelin. PMID:21502361

  2. The Cellular and Molecular Landscapes of the Developing Human Central Nervous System

    PubMed Central

    Silbereis, John C.; Pochareddy, Sirisha; Zhu, Ying; Li, Mingfeng; Sestan, Nenad

    2016-01-01

    Summary The human central nervous system follows a pattern of development typical of all mammals, but certain neurodevelopmental features are highly derived. Building the human CNS requires the precise orchestration and coordination of myriad molecular and cellular processes across a staggering array of cell types and over a long period of time. Dysregulation of these processes affects the structure and function of the CNS and can lead to neurological or psychiatric disorders. Recent technological advances and increased focus on human neurodevelopment have enabled a more comprehensive characterization of the human CNS and its development in both health and disease. The aim of this review is to highlight recent advancements in our understanding of the molecular and cellular landscapes of the developing human CNS, with focus on the cerebral neocortex, and the insights these findings provide into human neural evolution, function, and dysfunction. PMID:26796689

  3. [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.

  4. Antibody staining of the central nervous system in adult Drosophila.

    PubMed

    Sweeney, Sean T; Hidalgo, Alicia; de Belle, J Steven; Keshishian, Haig

    2012-02-01

    The Drosophila nervous system provides a valuable model for studying various aspects of brain development and function. The postembryonic Drosophila brain is especially useful, because specific neuron types derive from specific progenitors at specific times. Elucidating the means by which diverse neuron types derive from a limited number of progenitors can contribute significantly to our understanding of the genetic and molecular mechanisms involved in developmental neurobiology. Antibody-labeling techniques are particularly useful for examining the Drosophila brain. These methods generally use primary antibodies specific to a protein or a structure of interest and a fluorescently labeled or enzyme-coupled secondary antibody to detect the primary antibodies. Immunofluorescence methods allow for simultaneous probing for multiple antigens using different fluorophores, as well as high-resolution confocal examination of deep structures. This protocol describes general procedures for antibody labeling of neural tissue from Drosophila, as well as visualization techniques for fluorescent and enzyme-linked probes.

  5. Convection-enhanced delivery to the central nervous system.

    PubMed

    Lonser, Russell R; Sarntinoranont, Malisa; Morrison, Paul F; Oldfield, Edward H

    2015-03-01

    Convection-enhanced delivery (CED) is a bulk flow-driven process. Its properties permit direct, homogeneous, targeted perfusion of CNS regions with putative therapeutics while bypassing the blood-brain barrier. Development of surrogate imaging tracers that are co-infused during drug delivery now permit accurate, noninvasive real-time tracking of convective infusate flow in nervous system tissues. The potential advantages of CED in the CNS over other currently available drug delivery techniques, including systemic delivery, intrathecal and/or intraventricular distribution, and polymer implantation, have led to its application in research studies and clinical trials. The authors review the biophysical principles of convective flow and the technology, properties, and clinical applications of convective delivery in the CNS.

  6. Evolution and regeneration of the planarian central nervous system.

    PubMed

    Umesono, Yoshihiko; Agata, Kiyokazu

    2009-04-01

    More than 100 years ago, early workers realized that planarians offer an excellent system for regeneration studies. Another unique aspect of planarians is that they occupy an interesting phylogenetic position with respect to the nervous system in that they possess an evolutionarily primitive brain structure and can regenerate a functional brain from almost any tiny body fragment. Recent molecular studies have revisited planarian regeneration and revealed key information about the cellular and molecular mechanisms underlying brain regeneration in planarians. One of our great advances was identification of a gene, nou-darake, which directs the formation of a proper extrinsic environment for pluripotent stem cells to differentiate into brain cells in the planarian Dugesia japonica. Our recent findings have provided mechanistic insights into stem cell biology and also evolutionary biology.

  7. The role of ZAP70 kinase in acute lymphoblastic leukemia infiltration into the central nervous system.

    PubMed

    Alsadeq, Ameera; Fedders, Henning; Vokuhl, Christian; Belau, Nele M; Zimmermann, Martin; Wirbelauer, Tim; Spielberg, Steffi; Vossen-Gajcy, Michaela; Cario, Gunnar; Schrappe, Martin; Schewe, Denis M

    2017-02-01

    Central nervous system infiltration and relapse are poorly understood in childhood acute lymphoblastic leukemia. We examined the role of zeta-chain-associated protein kinase 70 in preclinical models of central nervous system leukemia and performed correlative studies in patients. Zeta-chain-associated protein kinase 70 expression in acute lymphoblastic leukemia cells was modulated using short hairpin ribonucleic acid-mediated knockdown or ectopic expression. We show that zeta-chain-associated protein kinase 70 regulates CCR7/CXCR4 via activation of extracellular signal-regulated kinases. High expression of zeta-chain-associated protein kinase 70 in acute lymphoblastic leukemia cells resulted in a higher proportion of central nervous system leukemia in xenografts as compared to zeta-chain-associated protein kinase 70 low expressing counterparts. High zeta-chain-associated protein kinase 70 also enhanced the migration potential towards CCL19/CXCL12 gradients in vitro CCR7 blockade almost abrogated homing of acute lymphoblastic leukemia cells to the central nervous system in xenografts. In 130 B-cell precursor acute lymphoblastic leukemia and 117 T-cell acute lymphoblastic leukemia patients, zeta-chain-associated protein kinase 70 and CCR7/CXCR4 expression levels were significantly correlated. Zeta-chain-associated protein kinase 70 expression correlated with central nervous system disease in B-cell precursor acute lymphoblastic leukemia, and CCR7/CXCR4 correlated with central nervous system involvement in T-cell acute lymphoblastic leukemia patients. In multivariate analysis, zeta-chain-associated protein kinase 70 expression levels in the upper third and fourth quartiles were associated with central nervous system involvement in B-cell precursor acute lymphoblastic leukemia (odds ratio=7.48, 95% confidence interval, 2.06-27.17; odds ratio=6.86, 95% confidence interval, 1.86-25.26, respectively). CCR7 expression in the upper fourth quartile correlated with central

  8. The role of ZAP70 kinase in acute lymphoblastic leukemia infiltration into the central nervous system

    PubMed Central

    Alsadeq, Ameera; Fedders, Henning; Vokuhl, Christian; Belau, Nele M.; Zimmermann, Martin; Wirbelauer, Tim; Spielberg, Steffi; Vossen-Gajcy, Michaela; Cario, Gunnar; Schrappe, Martin; Schewe, Denis M.

    2017-01-01

    Central nervous system infiltration and relapse are poorly understood in childhood acute lymphoblastic leukemia. We examined the role of zeta-chain-associated protein kinase 70 in preclinical models of central nervous system leukemia and performed correlative studies in patients. Zeta-chain-associated protein kinase 70 expression in acute lymphoblastic leukemia cells was modulated using short hairpin ribonucleic acid-mediated knockdown or ectopic expression. We show that zeta-chain-associated protein kinase 70 regulates CCR7/CXCR4 via activation of extracellular signal-regulated kinases. High expression of zeta-chain-associated protein kinase 70 in acute lymphoblastic leukemia cells resulted in a higher proportion of central nervous system leukemia in xenografts as compared to zeta-chain-associated protein kinase 70 low expressing counterparts. High zeta-chain-associated protein kinase 70 also enhanced the migration potential towards CCL19/CXCL12 gradients in vitro. CCR7 blockade almost abrogated homing of acute lymphoblastic leukemia cells to the central nervous system in xenografts. In 130 B-cell precursor acute lymphoblastic leukemia and 117 T-cell acute lymphoblastic leukemia patients, zeta-chain-associated protein kinase 70 and CCR7/CXCR4 expression levels were significantly correlated. Zeta-chain-associated protein kinase 70 expression correlated with central nervous system disease in B-cell precursor acute lymphoblastic leukemia, and CCR7/CXCR4 correlated with central nervous system involvement in T-cell acute lymphoblastic leukemia patients. In multivariate analysis, zeta-chain-associated protein kinase 70 expression levels in the upper third and fourth quartiles were associated with central nervous system involvement in B-cell precursor acute lymphoblastic leukemia (odds ratio=7.48, 95% confidence interval, 2.06–27.17; odds ratio=6.86, 95% confidence interval, 1.86–25.26, respectively). CCR7 expression in the upper fourth quartile correlated with

  9. Isolation and distribution of endomorphins in the central nervous system.

    PubMed

    Zadina, James E

    2002-07-01

    Endomorphin-1 (Tyr-Pro-Trp-Phe-NH2, EM-1) and endomorphin-2 (Tyr-Pro-Phe-Phe-NH2, EM-2) have the highest affinity and selectivity for the mu-opioid receptor (MOP-R) of all known mammalian opioids. They were isolated from bovine and human brain, and are structurally distinct from the other endogenous opioids. Both EM-1 and EM-2 have potent antinociceptive activity in a variety of animal models of acute, neuropathic and allodynic pain. They regulate cellular signaling processes in a manner consistent with MOP-R-mediated effects. The EMs are implicated in the natural modulation of pain by extensive data localizing EM-like immunoreactivity (EM-LI) near MOP-Rs in several regions of the nervous system known to regulate pain. These include the primary afferents and their terminals in the spinal cord dorsal horn, where EM-2 is well-positioned to modulate pain in its earliest stages of perception. In a nerve-injury model of chronic pain, a loss of spinal EM2-LI occurs concomitant with the onset of chronic pain. The distribution of the EMs in other areas of the nervous system is consistent with a role in the modulation of diverse functions, including autonomic, neuroendocrine and reward functions as well as modulation of responses to pain and stress. Unlike several other mu opioids, the threshold dose of EM-1 for analgesia is well below that for respiratory depression. In addition, rewarding effects of EM-1 can be separated from analgesic effects. These results indicate a favorable therapeutic profile of EM-1 relative to other mu opioids. Thus, the pharmacology and distribution of EMs provide new avenues both for therapeutic development and for understanding the neurobiology of opioids.

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

    PubMed

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

    2015-01-01

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

  11. Immunobiology of congenital cytomegalovirus infection of the central nervous system—the murine cytomegalovirus model.

    PubMed

    Slavuljica, Irena; Kveštak, Daria; Huszthy, Peter Csaba; Kosmac, Kate; Britt, William J; Jonjić, Stipan

    2015-03-01

    Congenital human cytomegalovirus infection is a leading infectious cause of long-term neurodevelopmental sequelae, including mental retardation and hearing defects. Strict species specificity of cytomegaloviruses has restricted the scope of studies of cytomegalovirus infection in animal models. To investigate the pathogenesis of congenital human cytomegalovirus infection, we developed a mouse cytomegalovirus model that recapitulates the major characteristics of central nervous system infection in human infants, including the route of neuroinvasion and neuropathological findings. Following intraperitoneal inoculation of newborn animals with mouse cytomegalovirus, the virus disseminates to the central nervous system during high-level viremia and replicates in the brain parenchyma, resulting in a focal but widespread, non-necrotizing encephalitis. Central nervous system infection is coupled with the recruitment of resident and peripheral immune cells as well as the expression of a large number of pro-inflammatory cytokines. Although infiltration of cellular constituents of the innate immune response characterizes the early immune response in the central nervous system, resolution of productive infection requires virus-specific CD8(+) T cells. Perinatal mouse cytomegalovirus infection results in profoundly altered postnatal development of the mouse central nervous system and long-term motor and sensory disabilities. Based on an enhanced understanding of the pathogenesis of this infection, prospects for novel intervention strategies aimed to improve the outcome of congenital human cytomegalovirus infection are proposed.

  12. Nanoparticles and blood-brain barrier: the key to central nervous system diseases.

    PubMed

    Domínguez, Alazne; Suárez-Merino, Blanca; Goñi-de-Cerio, Felipe

    2014-01-01

    Major central nervous system disorders represent a significant and worldwide public health problem. In fact, the therapeutic success of many pharmaceuticals developed to treat central nervous system diseases is still moderate, since the blood-brain barrier (BBB) limits the access of systemically administered compounds to the brain. Therefore, they require the application of a large total dose of a drug, and cause numerous toxic effects. The development of nanotechnological systems are useful tools to deliver therapeutics and/or diagnostic probes to the brain due to nanocarriers having the potential to improve the therapeutic effect of drugs and to reduce their side effects. This review provides a brief overview of the variety of carriers employed for central nervous system drug and diagnostic probes delivery. Further, this paper focuses on the novel nanocarriers developed to enhance brain delivery across the blood-brain barrier. Special attention is paid to liposomes, micelles, polymeric and lipid-based nanoparticles, dendrimers and carbon nanotubes. The recent developments in nanocarrier implementation through size/charge optimization and surface modifications (PEGylation, targeting delivery, and coating with surfactants) have been discussed. And a detailed description of the nanoscaled pharmaceutical delivery devices employed for the treatment of central nervous system disorders have also been defined. The aim of the review is to evaluate the nanotechnology-based drug delivery strategies to treat different central nervous system disorders.

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

    PubMed

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

    2016-11-10

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

  14. 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.

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

    PubMed

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

    2014-03-01

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

  16. Burkitt Lymphoma with Initial Clinical Presentation due to Infiltration of the Central Nervous System and Eye Orbits

    PubMed Central

    Camilo, Gustavo Bittencourt; Machado, Dequitier Carvalho; de Oliveira, Celso Estevão; Lacerda, Letícia da Silva; de Oliveira, Romulo Varella; de França Silva, Monique; Lopes, Agnaldo José

    2014-01-01

    Patient: Male, 17 Final Diagnosis: Burkitt lymphoma Symptoms: Anisocoria, ipsilateral ptosis, opthalmoparesis, paresis Medication: — Clinical Procedure: — Specialty: Oncology Objective: Unusual clinical course Background: Burkitt lymphoma rarely affects the central nervous system and ocular region. Under these conditions, computed tomography and (particularly) magnetic resonance imaging of the skull increase the diagnostic accuracy, as they objectively show the topography of lesions and the effect of neoplasia on structures. Case Report: We report here the case of a 17-year-old male whose initial clinical manifestations were related to neurological impairment and to the ocular musculature and ocular innervation. The diagnosis of Burkitt lymphoma with leukemization and infiltration of the central nervous system was confirmed. Conclusions: In this case, it is important to recognize that the neuroimaging findings were fundamentally important in indicating the initial form of the disease and in directing the appropriate clinical management. PMID:25243420

  17. A templated agarose scaffold for axon guidance in the central and peripheral nervous system

    NASA Astrophysics Data System (ADS)

    Gros, Thomas Richard

    This thesis examined the hypothesis that axonal guidance could be improved in the central and peripheral nervous systems using a highly linearized templated agarose scaffold. In the present study we examined whether a templated agarose scaffold improved axon retention across a large central nervous system (CNS) lesion and how cellular and axonal orientation was affected within the scaffold channels. The "physical" guidance from the scaffold was applied to an existing CNS "chemical" guidance strategy, shown to promote axons beyond the lesion site, to enhance the number of crossing axons in larger, disorganized, lesions. Specifically, there was the greatest number of long-tract sensory axons reaching the distal aspect of the lesion when the templated agarose scaffold was combined with a neurotrophic source of NT-3 beyond the lesion site and a conditioning lesion, to enhance chemical axon guidance and the intrinsic growth state of axons, respectively. When comparing the scaffold implant to a cell suspension grafts, we found a higher retention of long-tract ascending (sensory) axons and descending (motor) axons crossing large lesions (2mm). The enhanced axon retention may be attributed to the finding that cellular orientation within the scaffold channels is highly linear, thus promoting a less tortuous environment for axon orientation and bridging. Although an enhanced number of axons were able to cross the lesion, the axons did not repenetrate the host tissue due to a reactive cell layer, present only in scaffold the implant groups. Additionally, a peripheral nerve conduit, with the agarose scaffold as the core, displayed biocompatiablility and supported axon growth and vasculature beyond the clinically applicable distance of 4mm. Thus, the templated agarose scaffold enhances axon retention and guidance within CNS injury sites and has potential applications to the PNS.

  18. Treatment of central nervous system involvement associated with primary Sjögren's syndrome.

    PubMed

    Ozgocmen, Salih; Gur, Ali

    2008-01-01

    Sjögren's syndrome (SS) is a chronic autoimmune disease that mainly affects the exocrine glands and usually presents with sicca symptoms of the main mucosal surfaces. The prevalence and the type of central nervous system (CNS) tissue damage caused by SS are debatable. The wide spectrum of CNS manifestations, different classification criteria used and unclear inclusion or exclusion criteria pose some difficulty reviewing these studies. Careful examination of the SS patients and to be aware of neurological findings which may be associated with suspicious CNS involvement is highly important. Central nervous system may also hypothetically have a role in the pathophysiology of SS. The wide spectrum of CNS involvement includes focal (sensorial and motor deficits, brain stem, cerebellar lesions, seizure, migraine etc.) or non-focal (encephalomyelitis, aseptic meningitis, neuropsychiatric dysfunctions), spinal cord (myelopathy, transverse myelitis, motor neuron disease etc.) findings or multiple sclerosis-like illness and optic neuritis. Evolving imaging techniques such as single photon emission computed tomography (SPECT), magnetic resonance spectroscopy or magnetization transfer imaging are promising for better understanding the nature of CNS involvement in SS. Treatments usually comprise symptomatic approach in milder cases however, pulse cyclophosphamide and steroids or other immunosuppressants (chlorambucil or azathioprine) are required in cases with progressive symptoms leading to neurological impairment. Anti-TNF agents (infliximab and etanercept) and B cell targeted therapies (rituximab and epratuzumab) are used in primary SS however their efficacy on CNS manifestation is still unclear. Randomized, multicenter studies are warranted to confirm the efficacy of treatment regimes which were reported to be effective in anecdotal reports or in small uncontrolled series. This article reviews the clinical approach to current therapy of CNS involvement in patients with

  19. Promoting central nervous system regeneration: lessons from cranial nerve I.

    PubMed

    Ruitenberg, Marc J; Vukovic, Jana

    2008-01-01

    The olfactory nerve differs from cranial nerves III-XII in that it contains a specialised type of glial cell, called 'olfactory ensheathing cell' (OEC), rather than Schwann cells. In addition, functional neurogenesis persists postnatally in the olfactory system, i.e. the primary olfactory pathway continuously rebuilds itself throughout adult life. The presence of OECs in the olfactory nerve is thought to be critical to this continuous growth process. Because of this intrinsic capacity for self-repair, the mammalian olfactory system has proved as a useful model in neuroregeneration studies. In addition, OECs have been used in transplantation studies to promote pathway regeneration elsewhere in the nervous system. Here, we have reviewed the parameters that allow for repair within the primary olfactory pathway and the role that OECs are thought to play in this process. We conclude that, in addition to intrinsic growth potential, the presence of an aligned substrate to the target structure is a fundamental prerequisite for appropriate restoration of connectivity with the olfactory bulb. Hence, strategies to promote regrowth of injured nerve pathways should incorporate usage of aligned, oriented substrates of OECs or other cellular conduits with additional intervention to boost neuronal cell body responses to injury and/or neutralisation of putative inhibitors.

  20. 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:27572166

  1. 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.

  2. 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…

  3. 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

  4. The role of the central nervous system in osteoarthritis pain and implications for rehabilitation.

    PubMed

    Murphy, Susan L; Phillips, Kristine; Williams, David A; Clauw, Daniel J

    2012-12-01

    It has been known for some time that central nervous system (CNS) pain amplification is present in some individuals with osteoarthritis; the implications of this involvement, however, are just starting to be realized. In the past year, several research reviews have focused on evidence supporting shared mechanisms across chronic pain conditions for how pain is generated and maintained in the CNS, irrespective of the underlying structural pathology. This review article focuses on current literature describing CNS amplification in osteoarthritis by discussing peripheral sensitization, central sensitization, and central augmentation, and the clinical manifestation of central augmentation referred to as centralized pain, and offers considerations for rehabilitation treatment and future directions for research.

  5. [Opiate receptors and endorphins at the central nervous system level].

    PubMed

    Simon, E J

    1978-01-01

    Four years ago, sterospecific sites for the bending of opiates were discovered within the brain of animals and the human being. All of the properties of these sites are in conformity with the proposition that they are pharmacological receptors which have long been postulated for these drugs. The binding of morphine or of one of its derivatives to these sites should result in chemical or physical reactions leading to well known pharmacological responses. These reactions following the binding of drugs to the receptors are not yet known, but there is some evidence that cyclical nucleotides play a role. The affinity of a whole series of morphine derivatives, agonists and atagonists, is well correlated with their pharmacological effectiveness. In the presence of sodium salts, antagonists become more strongly bound and agonists less strongly than in the absence of sodium. The evidence is presented. This is explained by an equilibrium between two formations of the receptor: one characteristic of the absence of sodium and one of its presence. Receptors are found in the nervous system of all vertebrates and their distribution has been studied in the human brain. The regions with the highest concentration of receptors are those of the limbic system. A high level exists also in the "substantia gelatinosa" of the spinal cord, which is involved in the passage of painful messages. Study of the function of morphine receptors has led to the isolation, in animal brain, of a number of peptides with morphine properties named endorphines. The first two endorphines isolated were pentapeptides named encephalins. The properties of endorphines from the subject of several lecture in this course.

  6. 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.

  7. Immunological Barriers to Stem Cell Therapy in the Central Nervous System

    PubMed Central

    Tullis, Gregory E.; Kirk, Mark D.

    2014-01-01

    The central nervous system is vulnerable to many neurodegenerative disorders such as Alzheimer's disease that result in the extensive loss of neuronal cells. Stem cells have the ability to differentiate into many types of cells, which make them ideal for treating such disorders. Although stem cell therapy has shown some promising results in animal models for many brain disorders it has yet to translate into the clinic. A major hurdle to the translation of stem cell therapy into the clinic is the immune response faced by stem cell transplants. Here, we focus on immunological and related hurdles to stem cell therapies for central nervous system disorders. PMID:25165476

  8. FMRFamide-like immunoreactivity in the central nervous system and alimentary tract of the non-hematophagous blow fly, Phormia regina, and the hematophagous horse fly, Tabanus nigrovittatus.

    PubMed

    Haselton, Aaron T; Yin, Chih-Ming; Stoffolano, John G

    2008-01-01

    FMRFamide-related peptides (FaRPs) are a diverse and physiologically important class of neuropepeptides in the metazoa. In insects, FaRPs function as brain-gut neuropeptides and have been immunolocalized throughout the nervous system and alimentary tract where they have been shown to affect feeding behavior. The occurrence of FMRFamide-like immunoreactivity (FLI) was examined in the central nervous system and alimentary tract of non-hematophagous blow fly, Phormia regina Meigen (Diptera: Calliphoridae), and the hematophagous horse fly, Tabanus nigrovittatus Macquart (Diptera:Tabanidae). Although the central nervous system and alimentary anatomy differ between these two dipteran species, many aspects of FLI remain similar. FLI was observed throughout the central and stomatogastric nervous systems, foregut, and midgut in both flies. In the central nervous system, cells and processes with FLI occurred in the brain, subesophageal ganglion, and ventral nerve cord. FLI was associated with neurohemal areas of the brain and ventral nerve cord. A neurohemal plexus of fibers with FLI was present on the dorsal region of the thoracic central nervous system in both species. In the gut, processes with FLI innervated the crop duct, crop and anterior midgut. Endocrine cells with FLI were present in the posterior midgut. The distribution of FLI in these two flies, in spite of their different feeding habits, further supports the role of FaRPs as important components of the braingut neurochemical axis in these insects and implicates FaRPs as regulators of insect feeding physiology among divergent insect taxa.

  9. 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

  10. 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

  11. Environmental Complexity and Central Nervous System Development and Function

    ERIC Educational Resources Information Center

    Lewis, Mark H.

    2004-01-01

    Environmental restriction or deprivation early in development can induce social, cognitive, affective, and motor abnormalities similar to those associated with autism. Conversely, rearing animals in larger, more complex environments results in enhanced brain structure and function, including increased brain weight, dendritic branching,…

  12. Gpr124 is essential for blood-brain barrier integrity in central nervous system disease.

    PubMed

    Chang, Junlei; Mancuso, Michael R; Maier, Carolina; Liang, Xibin; Yuki, Kanako; Yang, Lu; Kwong, Jeffrey W; Wang, Jing; Rao, Varsha; Vallon, Mario; Kosinski, Cynthia; Zhang, J J Haijing; Mah, Amanda T; Xu, Lijun; Li, Le; Gholamin, Sharareh; Reyes, Teresa F; Li, Rui; Kuhnert, Frank; Han, Xiaoyuan; Yuan, Jenny; Chiou, Shin-Heng; Brettman, Ari D; Daly, Lauren; Corney, David C; Cheshier, Samuel H; Shortliffe, Linda D; Wu, Xiwei; Snyder, Michael; Chan, Pak; Giffard, Rona G; Chang, Howard Y; Andreasson, Katrin; Kuo, Calvin J

    2017-04-01

    Although blood-brain barrier (BBB) compromise is central to the etiology of diverse central nervous system (CNS) disorders, endothelial receptor proteins that control BBB function are poorly defined. The endothelial G-protein-coupled receptor (GPCR) Gpr124 has been reported to be required for normal forebrain angiogenesis and BBB function in mouse embryos, but the role of this receptor in adult animals is unknown. Here Gpr124 conditional knockout (CKO) in the endothelia of adult mice did not affect homeostatic BBB integrity, but resulted in BBB disruption and microvascular hemorrhage in mouse models of both ischemic stroke and glioblastoma, accompanied by reduced cerebrovascular canonical Wnt-β-catenin signaling. Constitutive activation of Wnt-β-catenin signaling fully corrected the BBB disruption and hemorrhage defects of Gpr124-CKO mice, with rescue of the endothelial gene tight junction, pericyte coverage and extracellular-matrix deficits. We thus identify Gpr124 as an endothelial GPCR specifically required for endothelial Wnt signaling and BBB integrity under pathological conditions in adult mice. This finding implicates Gpr124 as a potential therapeutic target for human CNS disorders characterized by BBB disruption.

  13. [Architectonics of the central nervous system in Acoela, Plathelminthes, and Rotifera].

    PubMed

    Kotikova, E A; Raĭĭkova, O I

    2008-01-01

    Based on the literature and own data, consecutive stages of development of the central nervous system (CNS) in the lower Bilateria are considered - separation of brain from parenchyma, formation of its own envelopes, and development of the stem and orthogonal nervous system. Results of histochemical (cholinergic and catecholaminergic) and immunocytochemical (5-HT- and FMRFamid immunoreactive) studies of the CNS in representatives of Acoela, free living and parasitizing Plathelminthes and Rotifera are considered. The comparative analysis makes it possible to describe development and complication of the initially primitive Bilateria plexus nervous system. A special attention will be paid to the Acoela phylogenesis, based on molecular-biology data and results of study of their nervous system.

  14. Central nervous system administration of interleukin-6 produces splenic sympathoexcitation

    PubMed Central

    Helwig, Bryan G.; Craig, Robin A.; Fels, Richard J.; Blecha, Frank; Kenney, Michael J.

    2008-01-01

    Interleukin-6 (IL-6) is a multifunctional cytokine that has been shown to play a pivotal role in centrally-mediated physiological responses including activation of the hypothalamic-pituitary-adrenal axis. Cerebral spinal fluid (CSF) concentrations of IL-6 are elevated in multiple pathophysiological conditions including Alzheimer’s disease, autoimmune disease, and meningitis. Despite this, the effect of IL-6 on central regulation of sympathetic nerve discharge (SND) remains unknown which limits understanding of sympathetic-immune interactions in health and disease. In the present study we determined the effect of intracerebroventricular (icv, lateral ventricle) administration of IL-6 on splenic SND in urethane-chloralose-anesthetized rats. A second goal was to determine if icv injected IL-6 enters the brain parenchyma and acts as a volume transmission signal to access areas of the brain involved in regulation of sympathetic nerve outflow. Icv administration of IL-6 (10 ng, 100 ng, and 400 ng) significantly and progressively increased splenic SND from control levels in baroreceptor denervated Sprague-Dawley rats. Administration of 100 ng and 400 ng IL-6 resulted in significantly higher SND responses when compared to those elicited with a 10 ng dose. Sixty minutes following icv administration, fluorescently labeled IL-6 was not distributed throughout the parenchyma of the brain but was localized to the periventricular areas of the ventricular system. Brain sections counter-stained for the IL-6 receptor (IL-6R) revealed that IL-6 and the IL-6R were co-localized in periventricular areas adjoining the third ventricle. These results demonstrate that icv IL-6 administration increases splenic SND, an effect likely achieved via signaling mechanisms originating in the periventricular cells. PMID:18547874

  15. [An autosomal recessive syndrome with myopathy and central and peripheral nervous system involvement (author's transl)].

    PubMed

    Warter, J M; Marescaux, C; Coquillat, G; Walter, P; Micheletti, G; Rohmer, F

    1981-01-01

    Three of 11 children, offspring of a consanguineous marriage, presented a progressive myopathy and seizures, associated with symptoms suggesting both central and peripheral nervous system involvement. The ultrastructural muscular lesions were not specific. The association of severe impairment of muscle tissue and of central nervous system is rare, being described in centronuclear myopathy, cerebromuscular dystrophy, Kearns-Sayre syndrome and in a few isolated cases. Clinically only these isolated observations and especially the Kearns-Sayre syndrome demonstrate analogies to our observations. These data lead us to the discussion of the specificity of ultrastructural lesions, especially mitochondrial abnormalities. Some authors consider these abnormalities to be the biochemical hallmark for ophthalmoplegia plus, whereas for others, especially Drachman, they are an inconstant and nonspecific finding, merely the consequence and not the cause of this disease. These observations argue for the relationship between muscular pathology and nervous system dysfunction.

  16. [Pharmacological correction of central nervous system function in exposure to Coriolis acceleration].

    PubMed

    Karkishchenko, N N; Dimitriadi, N A; Molchanovskiĭ, V V

    1986-01-01

    Healthy volunteers with a low vestibular tolerance were exposed to Coriolis acceleration. Potassium orotate, pyracetame and riboxine were used as prophylactic measures against disorders in the function of the vestibular apparatus and higher compartments of the higher nervous system. The central nervous function was assessed with respect to the spectral power of electroencephalograms, short-term memory and mental performance. Potassium orotate given at a dose of 40 mg/kg body weight/day during 12-14 days as well as pyracetame given at a dose of 30 mg/kg body weight/day during 3 or 7 days increased significantly statokinetic tolerance and produced a protective effect on the central nervous function against Coriolis acceleration.

  17. Genomic deletions in cell lines derived from primitive neuroectodermal tumors of the central nervous system.

    PubMed

    Dallas, Peter B; Terry, Philippa A; Kees, Ursula R

    2005-06-01

    Extensive genomic deletions affecting a variety of chromosomes are a common finding in primitive neuroectodermal tumors of the central nervous system (CNS-PNETs), implicating the loss of multiple tumor suppressor genes in the pathogenesis of these tumors. We have used representational difference analysis, microsatellite mapping, and quantitative polymerase chain reaction to identify and verify the presence of genomic deletions on a number of chromosomes in CNS-PNET cell lines. This systematic approach has confirmed the importance of deletions at 10q, 16q, and 17p in PNET pathology and has revealed other regions of deletion not commonly described (e.g., Xq, 1p, 7p, and 13q). These data highlight the prevalence of hemizygous loss in CNS-PNET cells, suggesting that haploinsufficiency affecting multiple tumor suppressor genes may play a fundamental role in CNS-PNET pathogenesis. The identification of specific genes and signaling pathways that are compromised in CNS-PNET cells is crucial for development of more efficacious and less invasive treatments, as are urgently needed.

  18. 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

  19. A case of central nervous system nocardiosis in a patient with lupus treated with belimumab

    PubMed Central

    Lai, Richard HC; Kim, Deborah; Constantinescu, Florina

    2016-01-01

    Belimumab was approved by the United States Food and Drug Administration in March 2011 as the first biological agent for treating active systemic lupus erythematosus (SLE). To the best of our knowledge, this is the first case report regarding a patient with SLE treated with belimumab who was diagnosed with central nervous system nocardiosis. PMID:28149666

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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.…

  6. 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...

  7. 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…

  8. Diagnostic and Therapeutic Challenges in a Liver Transplant Recipient with Central Nervous System Invasive Aspergillosis

    PubMed Central

    Dionissios, Neofytos; Shmuel, Shoham; Kerry, Dierberg; Katharine, Le; Simon, Dufresne; Sean, Zhang X; Kieren, Marr A

    2012-01-01

    This is a case report of central nervous system (CNS) invasive aspergillosis (IA) in a liver transplant recipient, which illustrates the utility of enzyme-based diagnostic tools for the timely and accurate diagnosis of IA, the treatment challenges and poor outcomes associated with CNS IA in liver transplant recipients. PMID:22676861

  9. Disseminated Tuberculosis of Central Nervous System : Spinal Intramedullary and Intracranial Tuberculomas

    PubMed Central

    Lim, Yu Seok; Kim, Min Ki; Lim, Young Jin

    2013-01-01

    As a cause of spinal cord compression, intramedullary spinal tuberculoma with central nervous system (CNS) involvement is rare. Aurthors report a 66-year-old female presented with multiple CNS tuberculomas including spinal intramedullary tuberculoma manifesting paraparesis and urinary dysfunction. We review the clinical menifestation and experiences of previous reported literature. PMID:24044085

  10. 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…

  11. 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.

  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. Central nervous system infection due to Mycobacterium haemophilum in a patient with acquired immunodeficiency syndrome.

    PubMed

    Buppajarntham, Aubonphan; Apisarnthanarak, Anucha; Rutjanawech, Sasinuj; Khawcharoenporn, Thana

    2015-03-01

    Mycobacterium haemophilum is an environmental organism that rarely causes infections in humans. We report a patient with acquired immunodeficiency syndrome who had central nervous system infection due to M. haemophilum. The diagnosis required brain tissue procurement and molecular identification method while the treatment outcome was unfavourable.

  14. Concepts and mechanisms of generalized central nervous system arousal.

    PubMed

    Pfaff, Donald; Ribeiro, Ana; Matthews, James; Kow, Lee-Ming

    2008-01-01

    A concept of generalized arousal of the CNS is presented and given an operational definition that leads to quantitative physical measures. Because this primitive arousal function underlies all motivated behavioral responses, cognitive functions, and emotional expression, disorders of generalized arousal can be associated with a large number of problems in medicine and public health, including vegetative states, attentional disorders, depression, occupational hazards, and problems with sleep and anesthesia. Some of its known mechanisms are briefly reviewed, at the levels of neuroanatomy, neurophysiology, and functional genomics. Generalized arousal contributes to the excitement and the activation of behaviors during specific arousal states. Data are summarized for four genomic/neurochemical systems through which changes in generalized arousal could affect sexual arousal, two of which heighten, and the other two of which reduce arousal.

  15. The Use of Central Nervous System Active Drugs During Pregnancy

    PubMed Central

    Källén, Bengt; Borg, Natalia; Reis, Margareta

    2013-01-01

    CNS-active drugs are used relatively often during pregnancy. Use during early pregnancy may increase the risk of a congenital malformation; use during the later part of pregnancy may be associated with preterm birth, intrauterine growth disturbances and neonatal morbidity. There is also a possibility that drug exposure can affect brain development with long-term neuropsychological harm as a result. This paper summarizes the literature on such drugs used during pregnancy: opioids, anticonvulsants, drugs used for Parkinson’s disease, neuroleptics, sedatives and hypnotics, antidepressants, psychostimulants, and some other CNS-active drugs. In addition to an overview of the literature, data from the Swedish Medical Birth Register (1996–2011) are presented. The exposure data are either based on midwife interviews towards the end of the first trimester or on linkage with a prescribed drug register. An association between malformations and maternal use of anticonvulsants and notably valproic acid is well known from the literature and also demonstrated in the present study. Some other associations between drug exposure and outcome were found. PMID:24275849

  16. Cardiovascular and autonomic modulation by the central nervous system after aerobic exercise training.

    PubMed

    Martins-Pinge, M C

    2011-09-01

    The autonomic nervous system plays a key role in maintaining homeostasis under normal and pathological conditions. The sympathetic tone, particularly for the cardiovascular system, is generated by sympathetic discharges originating in specific areas of the brainstem. Aerobic exercise training promotes several cardiovascular adjustments that are influenced by the central areas involved in the output of the autonomic nervous system. In this review, we emphasize the studies that investigate aerobic exercise training protocols to identify the cardiovascular adaptations that may be the result of central nervous system plasticity due to chronic exercise. The focus of our study is on some groups of neurons involved in sympathetic regulation. They include the nucleus tractus solitarii, caudal ventrolateral medulla and the rostral ventrolateral medulla that maintain and regulate the cardiac and vascular autonomic tonus. We also discuss studies that demonstrate the involvement of supramedullary areas in exercise training modulation, with emphasis on the paraventricular nucleus of the hypothalamus, an important area of integration for autonomic and neuroendocrine responses. The results of these studies suggest that the beneficial effects of physical activity may be due, at least in part, to reductions in sympathetic nervous system activity. Conversely, with the recent association of physical inactivity with chronic disease, these data may also suggest that increases in sympathetic nervous system activity contribute to the increased incidence of cardiovascular diseases associated with a sedentary lifestyle.

  17. Primary breast lymphoma sequentially relapsed in the peripheral and central nervous system.

    PubMed

    Tang, Tzung-Chih; Chang, Hung; Chuang, Wen-Yu

    2012-09-01

    Primary breast lymphoma (PBL) is an uncommon extranodal type of lymphoma, exhibiting more aggressive behavior and poorer prognosis. Patients with PBL have a higher incidence to relapse in central nervous system (CNS), which is always leading to a dismal outcome even treating with high intensity chemotherapy plus radiotherapy. Lymphoma involving the peripheral nervous system (PNS), either primarily or secondarily, is also rare. But no PBL with PNS relapse has been reported before. Herein, we reported a case of PBL who presented with subsequent relapse in two discrete sites of the PNS followed by the CNS.

  18. Invasion of the central nervous system in a porcine host by nipah virus.

    PubMed

    Weingartl, Hana; Czub, Stefanie; Copps, John; Berhane, Yohannes; Middleton, Deborah; Marszal, Peter; Gren, Jason; Smith, Greg; Ganske, Shelley; Manning, Lisa; Czub, Markus

    2005-06-01

    Nipah virus, a newly emerged zoonotic paramyxovirus, infects a number of species. Human infections were linked to direct contact with pigs, specifically with their body fluids. Clinical signs in human cases indicated primarily involvement of the central nervous system, while in pigs the respiratory system was considered the primary virus target, with only rare involvement of the central nervous system. Eleven 5-week-old piglets were infected intranasally, orally, and ocularly with 2.5 x 10(5) PFU of Nipah virus per animal and euthanized between 3 and 8 days postinoculation. Nipah virus caused neurological signs in two out of eleven inoculated pigs. The rest of the pigs remained clinically healthy. Virus was detected in the respiratory system (turbinates, nasopharynx, trachea, bronchus, and lung in titers up to 10(5.3) PFU/g) and in the lymphoreticular system (endothelial cells of blood and lymphatic vessels, submandibular and bronchiolar lymph nodes, tonsil, and spleen with titers up to 10(6) PFU/g). Virus presence was confirmed in the nervous system of both sick and apparently healthy animals (cranial nerves, trigeminal ganglion, brain, and cerebrospinal fluid, with titers up to 10(7.7) PFU/g of tissue). Nipah virus distribution was confirmed by immunohistochemistry. The study presents novel findings indicating that Nipah virus invaded the central nervous system of the porcine host via cranial nerves as well as by crossing the blood-brain barrier after initial virus replication in the upper respiratory tract.

  19. Mutation of the central nervous system neuroblast proliferation repressor ana leads to defects in larval olfactory behavior.

    PubMed

    Park, Y; Caldwell, M C; Datta, S

    1997-08-01

    In the developing nervous system, interactions between glia and immature neurons or neuroblasts regulate axon pathfinding, migration, and cell division, and therefore affect structure and function. Glial control of neuroblast cell division has been documented by studies of the anachronism (ana) gene of Drosophila melanogaster. ana encodes a glycoprotein which, in the developing larval central nervous system, is secreted by glia that neighbor regulated neuroblasts. Mutations in ana lead to premature neuroblast proliferation in the larval brain. Examination of lacZ expression from an ana enhancer trap line as well as detection of the ana protein show that ana is also expressed in the larval antennal-maxillary complex (AMC) at all larval stages. As previously reported for the central nervous system, ana expression in the AMC appears to be confined to glial cells. Larval olfactory system function in ana mutants was assayed in a behavioral paradigm. When tested with the three different chemoattractants, third instar ana9 mutant larvae showed diminished olfactory response compared to controls. Examination of a second ana allele revealed aberrant olfactory response to ethyl acetate, demonstrating that more than one mutation in ana can give rise to abnormal larval olfactory behavior. Assays of early first instar ana9 mutant larvae revealed defective olfactory behavior, implying that the olfactory phenotype stems from early larval AMC and/or embryonic origins. This is consistent with proliferation analysis in the early larval AMC region which uncovered a significantly higher number of S-phase cells in ana9 mutants.

  20. Maintenance of Fura-2 fluorescence in glial cells and neurons of the leech central nervous system.

    PubMed

    Munsch, T; Deitmer, J W

    1995-04-01

    Identified glial cells and neurones of the leech central nervous system (CNS) were injected iontophoretically with the calcium indicator dye Fura-2 to measure intracellular Ca2+, while simultaneously recording the membrane potential using a double-barrelled theta-type microelectrode. Both glial cells and neurones responded with Ni(2+)-sensitive Ca2+ transients upon membrane depolarization, indicating Ca2+ influx through voltage-gated Ca2+ channels. In contrast to neurones, the glial cells showed a rapid loss of fluorescence with a half-time of 6.3 +/- 1.8 min (n = 6) after dye injection. Both kinetics and amplitudes of the stimulus-induced Ca2+ transients were affected by this rapid dye loss. The anion exchange inhibitor probenicid (2 mM) significantly reduced, but did not prevent, the loss of Fura-2 fluorescence, suggesting that some dye left the glial cell via an anion exchanger. In order to compensate this fluorescence loss, we injected Fura-2 throughout the experiment. Under this condition, similar Ca2+ transients could be elicited repeatedly for more than 1 h. In Retzius neurones single injections of Fura-2 yielded enough intracellularly trapped dye to allow measurement of intracellular Ca2+ for up to 30 min after the end of injection without large decrease in absolute fluorescence.

  1. Mini Review: Circular RNAs as Potential Clinical Biomarkers for Disorders in the Central Nervous System

    PubMed Central

    Lu, Dan; Xu, An-Ding

    2016-01-01

    Circular RNAs (circRNAs) are a type of non-coding RNAs (ncRNAs), produced in eukaryotic cells during post-transcriptional processes. They are more stable than linear RNAs, and possess spatio-temporal properties. CircRNAs do not distribute equally in the neuronal compartments in the brain, but largely enriched in the synapses. These ncRNA species can be used as potential clinical biomarkers in complex disorders of the central nervous system (CNS), which is supported by recent findings. For example, ciRS-7 was found to be a natural microRNAs sponge for miRNA-7 and regulate Parkinson’s disease/Alzheimer’s disease-related genes; circPAIP2 is an intron-retaining circRNA which upregulates memory-related parental genes PAIP2 to affect memory development through PABP reactivation. The quantity of circRNAs carry important messages, either when they are inside the cells, or in circulation, or in exosomes released from synaptoneurosomes and endothelial. In addition, small molecules such as microRNAs and microvesicles can pass through the blood–brain barrier (BBB) and get into blood. For clinical applications, the study population needs to be phenotypically well-defined. CircRNAs may be combined with other biomarkers and imaging tools to improve the diagnostic power. PMID:27092176

  2. Strategies for delivery of therapeutics into the central nervous system for treatment of lysosomal storage disorders.

    PubMed

    Muro, Silvia

    2012-06-01

    Lysosomal storage disorders (LSDs) are a group of about fifty life-threatening conditions caused by genetic defects affecting lysosomal components. The underscoring molecular deficiency leads to widespread cellular dysfunction through most tissues in the body, including peripheral organs and the central nervous system (CNS). Efforts during the last few decades have rendered a remarkable advance regarding our knowledge, medical awareness, and early detection of these genetic defects, as well as development of several treatment modalities. Clinical and experimental strategies encompassing enzyme replacement, gene and cell therapies, substrate reduction, and chemical chaperones are showing considerable potential in attenuating the peripheral pathology. However, a major drawback has been encountered regarding the suboptimal impact of these approaches on the CNS pathology. Particular anatomical and biochemical constraints of this tissue pose a major obstacle to the delivery of therapeutics into the CNS. Approaches to overcome these obstacles include modalities of local administration, strategies to enhance the blood-CNS permeability, intranasal delivery, use of exosomes, and those exploiting targeting of transporters and transcytosis pathways in the endothelial lining. The later two approaches are being pursued at the time by coupling therapeutic agents to affinity moieties and drug delivery systems capable of targeting these natural transport routes. This approach is particularly promising, as using paths naturally active at this interface may render safe and effective delivery of LSD therapies into the CNS.

  3. Metabolic interactions of central nervous system medications and selective serotonin reuptake inhibitors.

    PubMed

    Naranjo, C A; Sproule, B A; Knoke, D M

    1999-05-01

    Selective serotonin reuptake inhibitors (SSRIs) are prescribed alone and in combination with other psychotropic medications in the treatment of a variety of psychiatric disorders. Such combinations create the potential for pharmacokinetic interactions by affecting the activity of the cytochromes P450 (CYP450), drug metabolizing oxidative enzymes. SSRIs are not equivalent in their potential for interactions when combined with other central nervous system (CNS) medication. Generally citalopram and sertraline are characterized by weaker inhibition of CYP450 enzymes and, therefore, hold less potential for interaction than the other SSRIs. Paroxetine potently inhibits CYP2D6, which can result in increased neuroleptic serum concentrations, accompanied by increased CNS side-effects. Similarly, as a potent inhibitor of CYP2D6, fluoxetine can increase serum concentrations of neuroleptics and antidepressants and numerous case reports have documented concomitant adverse events. Fluoxetine also inhibits CYP3A and CYP2C19, increasing serum concentrations of some benzodiazepines. Fluvoxamine is a potent inhibitor of CYP1A2, a moderate inhibitor of CYP3A and a mild inhibitor of CYP2D6. Therefore, interactions with clozapine and benzodiazepines are evident.

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

    PubMed Central

    Kim, Jinho

    2016-01-01

    Primary central nervous system lymphoma (PCNSL) is an extranodal Non-Hodgkin's lymphoma that is confined to the brain, eyes, and/or leptomeninges without evidence of a systemic primary tumor. Although the tumor can affect all age groups, it is rare in childhood; thus, its incidence and prognosis in children have not been well defined and the best treatment strategy remains unclear. A nine-year old presented at our department with complaints of diplopia, dizziness, dysarthria, and right side hemiparesis. Magnetic resonance image suggested a diffuse brain stem glioma with infiltration into the right cerebellar peduncle. The patient was surgically treated by craniotomy and frameless stereotactic-guided biopsy, and unexpectedly, the histopathology of the mass was consistent with diffuse large B cell lymphoma, and immunohistochemical staining revealed positivity for CD20 and CD79a. Accordingly, we performed a staging work-up for systemic lymphoma, but no evidence of lymphoma elsewhere in the body was obtained. In addition, she had a negative serologic finding for human immunodeficient virus, which confirmed the histopathological diagnosis of PCNSL. She was treated by radiosurgery at 12 Gy and subsequent adjuvant combination chemotherapy based on high dose methotrexate. Unfortunately, 10 months after the tissue-based diagnosis, she succumbed due to an acute hydrocephalic crisis. PMID:27867930

  5. Brain-derived neurotrophic factor and glucocorticoids: reciprocal influence on the central nervous system.

    PubMed

    Numakawa, T; Adachi, N; Richards, M; Chiba, S; Kunugi, H

    2013-06-03

    Brain-derived neurotrophic factor (BDNF) has multiple roles in the central nervous system (CNS), including maintaining cell survival and regulation of synaptic function. In CNS neurons, BDNF triggers activation of phospholipase Cγ (PLCγ), mitogen-activated protein/extracellular signal-regulated kinase (MAPK/ERK), and phosphoinositide 3-kinase (PI3K)/Akt pathways, influencing neuronal cells beneficially through these intracellular signaling cascades. There is evidence to suggest that decreased BDNF expression or function is related to the pathophysiology of brain diseases including psychiatric disorders. Additionally, glucocorticoids, which are critical stress hormones, also influence neuronal function in the CNS, and are putatively involved in the onset of depression when levels are abnormally high. In animal models of depression, changes in glucocorticoid levels, expression of glucocorticoid receptor (GR), and alterations in BDNF signaling are observed. Interestingly, several studies using in vivo and in vitro systems suggest that glucocorticoids interact with BDNF to ultimately affect CNS function. In the present review, we provide an overview of recent evidence concerning the interaction between BDNF and glucocorticoids.

  6. Age-related changes in pharmacodynamics: focus on drugs acting on central nervous and cardiovascular systems.

    PubMed

    Trifirò, Gianluca; Spina, Edoardo

    2011-09-01

    Aging is characterized by progressive impairment of functional capacities of all system organs, reduction in homeostatic mechanisms, and altered response to receptor stimulation. These age-related physiologic changes influence both pharmacokinetics and pharmacodynamics of drugs in elderly patients. Pharmacokinetic and pharmacodynamics changes as well as polypharmacy and comorbidities may alter significantly the effect of pharmacological treatment with advancing age. With the same drug concentration at the site of action, significant differences in the response to several drugs have been observed in older patients as compared to younger patients. Elderly patients are particularly suceptibles to the effects of frequently prescribed drugs acting on central nervous system, such as benzodiazepines, antidepressants, antipsychotics and lithium, with high potential for adverse drug reactions. Moreover, in older patients increased sensitivity to warfarin resulting in increased risk of bleeding has been previously documented. On the other hand, reduced effectiveness of conventional doses of cardiovascular drugs, such as diuretics and β-blockers, has been observed. Due to pharmacodynamic changes, therefore, dose adjustment of the above mentioned cardiovascular and psychotropic drugs is recommended in elderly. Clinicians should be aware of the age-related physiologic changes affecting several organ systems and their implications on the effect of drugs that are commonly prescribed to elderly patients.

  7. 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.

  8. Genome-wide analysis uncovers novel recurrent alterations in primary central nervous system lymphomas

    PubMed Central

    Braggio, Esteban; Van Wier, Scott; Ojha, Juhi; McPhail, Ellen; Asmann, Yan W.; Egan, Jan; da Silva, Jackline Ayres; Schiff, David; Lopes, M Beatriz; Decker, Paul A; Valdez, Riccardo; Tibes, Raoul; Eckloff, Bruce; Witzig, Thomas E.; Stewart, A Keith; Fonseca, Rafael; O’Neill, Brian Patrick

    2015-01-01

    Purpose Primary central nervous system lymphoma (PCNSL) is an aggressive non-Hodgkin lymphoma confined to the CNS. Whether there is a PCNSL-specific genomic signature and, if so, how it differs from systemic diffuse large B-cell lymphoma (DLBCL) is uncertain. Experimental design We performed a comprehensive genomic study of tumor samples from 19 immunocompetent PCNSL patients. Testing comprised array-comparative genomic hybridization and whole exome sequencing. Results Biallelic inactivation of TOX and PRKCD were recurrently found in PCNSL but not in systemic DLBCL, suggesting a specific role in PCNSL pathogenesis. Additionally, we found a high prevalence of MYD88 mutations (79%) and CDKN2A biallelic loss (60%). Several genes recurrently affected in PCNSL were common with systemic DLBCL, including loss of TNFAIP3, PRDM1, GNA13, TMEM30A, TBL1XR1, B2M, CD58, activating mutations of CD79B, CARD11 and translocations IgH-BCL6. Overall, BCR/TLR/NF-κB pathways were altered in >90% of PNCSL, highlighting its value for targeted therapeutic approaches. Furthermore, integrated analysis showed enrichment of pathways associated with immune response, proliferation, apoptosis, and lymphocyte differentiation. Conclusions In summary, genome-wide analysis uncovered novel recurrent alterations, including TOX and PRKCD, helping to differentiate PCNSL from systemic DLBCL and related lymphomas. PMID:25991819

  9. Functional biomarkers for the acute effects of alcohol on the central nervous system in healthy volunteers

    PubMed Central

    Zoethout, Remco W M; Delgado, Wilson L; Ippel, Annelies E; Dahan, Albert; van Gerven, Joop M A

    2011-01-01

    The central nervous system (CNS) effects of acute alcohol administration have been frequently assessed. Such studies often use a wide range of methods to study each of these effects. Unfortunately, the sensitivity of these tests has not completely been ascertained. A literature search was performed to recognize the most useful tests (or biomarkers) for identifying the acute CNS effects of alcohol in healthy volunteers. All tests were grouped in clusters and functional domains. Afterwards, the effect of alcohol administration on these tests was scored as improvement, impairment or as no effect. Furthermore, dose–response relationships were established. A total number of 218 studies, describing 342 different tests (or test variants) were evaluated. Alcohol affected a wide range of CNS domains. Divided attention, focused attention, visuo-motor control and scales of feeling high and of subjective drug effects were identified as the most sensitive functional biomarkers for the acute CNS effects of alcohol. The large number of CNS tests that are used to determine the effects of alcohol interferes with the identification of the most sensitive ones and of drug–response relationships. Our results may be helpful in selecting rational biomarkers for studies investigating the acute CNS effects of alcohol or for future alcohol- interaction studies. PMID:21284693

  10. [Effects of electromagnetic field from cellular phones on selected central nervous system functions: a literature review].

    PubMed

    Bak, Marek; Zmyślony, Marek

    2010-01-01

    In the opinion of some experts, a growing emission of man-made electromagnetic fields (EMF), also known as electromagnetic is a source of continuously increasing health hazards to the general population. Due to their large number and very close proximity to the user's head, mobile phones deserve special attention. This work is intended to give a systematic review of objective studies, assessing the effects of mobile phone EMF on the functions of the central nervous system (CNS) structures. Our review shows that short exposures to mobile phone EMF, experienced by telephone users during receiving calls, do not affect the cochlear function. Effects of GSM mobile phone EMF on the conduction of neural impulses from the inner car neurons to the brainstem auditory centres have not been detected either. If Picton's principle, saying that P300 amplitude varies with the improbability of the targets and its latency varies with difficulty of discriminating the target stimulus from standard stimuli, is true, EMF changes the improbability of the targets without hindering their discrimination. Experiments with use of indirect methods do not enable unequivocal verification of EMF effects on the cognitive functions due to the CNS anatomical and functional complexity. Thus, it seems advisable to develop a model of EMF effects on the excitable brain structures at the cellular level.

  11. [Cannabis: Effects in the Central Nervous System. Therapeutic, societal and legal consequences].

    PubMed

    Rivera-Olmos, Víctor Manuel; Parra-Bernal, Marisela C

    2016-01-01

    The consumption of marijuana extracted from Cannabis sativa and indica plants involves an important cultural impact in Mexico. Their psychological stimulatory effect is widely recognized; their biochemical and molecular components interact with CB1 and CB2 (endocannabinoid system) receptors in various central nervous system structures (CNS) and immune cells. The psychoactive element Δ-9-tetrahydrocannabinol (THC) can be reproduced synthetically. Systematic reviews show evidence of therapeutic effectiveness of therapeutic marijuana only for certain symptoms of multiple sclerosis (spasticity, spasms and pain), despite attempts for its widespread use, including refractory childhood epilepsy. Evidence indicates significant adverse effects of smoked marijuana on the structure, functioning and brain connectivity. Cannabis exposure during pregnancy affects fetal brain development, potentially leading to later behavioral problems in children. Neuropsychological tests and advanced imaging techniques show involvement in the learning process in adolescents with substance use. Also, marijuana increases the cognitive impairment in patients with multiple sclerosis. Social and ethical consequences to legally free marijuana for recreational use may be deleterious transcendentally. The medicinal or psychoactive cannabinol no addictive effect requires controlled proven efficacy and safety before regulatory approval studies.

  12. [Retrospective study of 48 cases of primary central nervous system lymphoma].

    PubMed

    Alessandro, Lucas; Pastor Rueda, José M; Villalonga, Juan F; Bruno, Verónica A; Carpani, Federico; Blaquier, Juan B; Tognarelli, Sofía; Varela, Francisco J; Muggeri, Alejandro

    2017-01-01

    Primary central nervous system lymphoma (PCNSL) is an infrequent form of non-Hodgkin lymphoma restricted to the CNS. More than 90% are type B and mainly affect patients aged 50-70 years. Immunodeficiency is the most important risk factor. The aim of our study was to evaluate the immune status, clinical presentation and findings in complementary studies of PCNSL patients. A retrospective analysis of 48 cases treated in our center between January 1992 and May 2015 was performed. Median age at diagnosis was 61 years (range 25-84); with male predominance (2.1:1). Forty one cases (85%) were immunocompetent patients. Brain MRI findings showed parenchymal involvement in 45 cases (94%), 43% with frontal lobe and 35% basal ganglia, 4% had meningeal involvement and 2% had ophthalmic involvement at diagnosis. Fifty-five percent had restricted signal on diffusion weighted imaging and contrast enhancement was found in 89%. Pyramidal syndrome was the main initial clinical manifestation (56%). There were abnormal findings in 62% of CSF samples, but in only 11.1% positive cytology results were detected. The most frequent type was diffuse large B-cell lymphoma (83%), being B-cell type the most common form between them (96%). In our series PCNSL was more frequent in immunocompetent elderly male subjects. At initial evaluation, clinical manifestations and MRI findings were variable. The initial suspicion of this entity would allow an early diagnosis, avoiding empirical treatments that may confuse or delay diagnosis.

  13. Neural stem cells and their role in the pathology and classification of central nervous system tumors.

    PubMed

    Tihan, Tarik; Pekmezci, Melike; Karnezis, Anthony

    2011-01-01

    Today, one of the most popular and controversial topics in medicine is undoubtedly the rapidly developing field of stem cell research. Some of the controversy in this field arises from lack of uniform terminology and different interpretation of concepts such as brain tumor stem cells. In addition, lack of reliable and universal markers that can identify stem cells and define precursor cells in a particular differentiation pathway further confounds the interpretation of results in many studies. Stem cells are undoubtedly critical in normal cellular development as well as tumor biology and better characterization of these cells is likely to have profound influence on the classification schemes of tumors. In this manuscript, we present the generally accepted definitions of key concepts in stem cell biology and review some of the related molecular pathways. In addition, we put forth our position on how progress in this field should be affecting the future classification schemes of central nervous system neoplasia. We strongly believe that the ever increasing knowledge in the field of neural and brain tumor stem cells should be influential in the subsequent attempts to classify brain tumors.

  14. The role of the surface on microglia function: implications for central nervous system tissue engineering

    PubMed Central

    Pires, Liliana R.; Rocha, Daniela N.; Ambrosio, Luigi; Pêgo, Ana Paula

    2015-01-01

    In tissue engineering, it is well accepted that a scaffold surface has a decisive impact on cell behaviour. Here we focused on microglia—the resident immune cells of the central nervous system (CNS)—and on their response to poly(trimethylene carbonate-co-ε-caprolactone) (P(TMC-CL)) fibrous and flat surfaces obtained by electrospinning and solvent cast, respectively. This study aims to provide cues for the design of instructive surfaces that can contribute to the challenging process of CNS regeneration. Cell morphology was evidently affected by the substrate, mirroring the surface main features. Cells cultured on flat substrates presented a round shape, while cells with elongated processes were observed on the electrospun fibres. A higher concentration of the pro-inflammatory cytokine tumour necrosis factor-α was detected in culture media from microglia on fibres. Still, astrogliosis is not exacerbated when astrocytes are cultured in the presence of microglia-conditioned media obtained from cultures in contact with either substrate. Furthermore, a significant percentage of microglia was found to participate in the process of myelin phagocytosis, with the formation of multinucleated giant cells being observed only on films. Altogether, the results presented suggest that microglia in contact with the tested substrates may contribute to the regeneration process, putting forward P(TMC-CL) substrates as supporting matrices for nerve regeneration. PMID:25540243

  15. The role of the surface on microglia function: implications for central nervous system tissue engineering.

    PubMed

    Pires, Liliana R; Rocha, Daniela N; Ambrosio, Luigi; Pêgo, Ana Paula

    2015-02-06

    In tissue engineering, it is well accepted that a scaffold surface has a decisive impact on cell behaviour. Here we focused on microglia-the resident immune cells of the central nervous system (CNS)-and on their response to poly(trimethylene carbonate-co-ε-caprolactone) (P(TMC-CL)) fibrous and flat surfaces obtained by electrospinning and solvent cast, respectively. This study aims to provide cues for the design of instructive surfaces that can contribute to the challenging process of CNS regeneration. Cell morphology was evidently affected by the substrate, mirroring the surface main features. Cells cultured on flat substrates presented a round shape, while cells with elongated processes were observed on the electrospun fibres. A higher concentration of the pro-inflammatory cytokine tumour necrosis factor-α was detected in culture media from microglia on fibres. Still, astrogliosis is not exacerbated when astrocytes are cultured in the presence of microglia-conditioned media obtained from cultures in contact with either substrate. Furthermore, a significant percentage of microglia was found to participate in the process of myelin phagocytosis, with the formation of multinucleated giant cells being observed only on films. Altogether, the results presented suggest that microglia in contact with the tested substrates may contribute to the regeneration process, putting forward P(TMC-CL) substrates as supporting matrices for nerve regeneration.

  16. Vitamin C transport and its role in the central nervous system

    PubMed Central

    May, James M.

    2013-01-01

    Vitamin C, or ascorbic acid, is important as an antioxidant and participates in numerous cellular functions. Although it circulates in plasma in micromolar concentrations, it reaches millimolar concentrations in most tissues. These high ascorbate cellular concentrations are thought to be generated and maintained by the SVCT2 (Slc23a2), a specific transporter for ascorbate. The vitamin is also readily recycled from its oxidized forms inside cells. Neurons in the central nervous system (CNS) contain some of the highest ascorbic acid concentrations of mammalian tissues. Intracellular ascorbate serves several functions in the CNS, including antioxidant protection, peptide amidation, myelin formation, synaptic potentiation, and protection against glutamate toxicity. The importance of the SVCT2 for CNS function is supported by the finding that its targeted deletion in mice causes widespread cerebral hemorrhage and death on post-natal day one. Neuronal ascorbate content as maintained by this protein also has relevance for human disease, since ascorbate supplements decrease infarct size in ischemia-reperfusion injury models of stroke, and since ascorbate may protect neurons from the oxidant damage associated with neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s. The aim of this review is to assess the role of the SVCT2 in regulating neuronal ascorbate homeostasis and the extent to which ascorbate affects brain function and antioxidant defenses in the CNS. PMID:22116696

  17. Neuroinflammation as Fuel for Axonal Regeneration in the Injured Vertebrate Central Nervous System

    PubMed Central

    Van houcke, Jessie

    2017-01-01

    Damage to the central nervous system (CNS) is one of the leading causes of morbidity and mortality in elderly, as repair after lesions or neurodegenerative disease usually fails because of the limited capacity of CNS regeneration. The causes underlying this limited regenerative potential are multifactorial, but one critical aspect is neuroinflammation. Although classically considered as harmful, it is now becoming increasingly clear that inflammation can also promote regeneration, if the appropriate context is provided. Here, we review the current knowledge on how acute inflammation is intertwined with axonal regeneration, an important component of CNS repair. After optic nerve or spinal cord injury, inflammatory stimulation and/or modification greatly improve the regenerative outcome in rodents. Moreover, the hypothesis of a beneficial role of inflammation is further supported by evidence from adult zebrafish, which possess the remarkable capability to repair CNS lesions and even restore functionality. Lastly, we shed light on the impact of aging processes on the regenerative capacity in the CNS of mammals and zebrafish. As aging not only affects the CNS, but also the immune system, the regeneration potential is expected to further decline in aged individuals, an element that should definitely be considered in the search for novel therapeutic strategies. PMID:28203046

  18. Immune System Activation and Depression: Roles of Serotonin in the Central Nervous System and Periphery.

    PubMed

    Robson, Matthew J; Quinlan, Meagan A; Blakely, Randy D

    2017-04-03

    Serotonin (5-hydroxytryptamine, 5-HT) has long been recognized as a key contributor to the regulation of mood and anxiety and is strongly associated with the etiology of major depressive disorder (MDD). Although more known for its roles within the central nervous system (CNS), 5-HT is recognized to modulate several key aspects of immune system function that may contribute to the development of MDD. Copious amounts of research have outlined a connection between alterations in immune system function, inflammation status, and MDD. Supporting this connection, peripheral immune activation results in changes in the function and/or expression of many components of 5-HT signaling that are associated with depressive-like phenotypes. How 5-HT is utilized by the immune system to effect CNS function and ultimately behaviors related to depression is still not well understood. This Review summarizes the evidence that immune system alterations related to depression affect CNS 5-HT signaling that can alter MDD-relevant behaviors and that 5-HT regulates immune system signaling within the CNS and periphery. We suggest that targeting the interrelationships between immune and 5-HT signaling may provide more effective treatments for subsets of those suffering from inflammation-associated MDD.

  19. Depletion of somatostatin-like immunoreactivity in the rat central nervous system by cysteamine

    SciTech Connect

    Sagar, S.M.; Landry, D.; Millard, W.J.; Badger, T.M.; Arnold, M.A.; Martin, J.B.

    1982-02-01

    Selective neurotoxins have been of value in providing a means for specifically interfering with the actions of endogenous neurotransmitter candidates. Others have shown cysteamine (CSH) to deplete the gastrointestinal tract and hypothalamus of rats of immunoreactive somatostatin, suggesting a toxic action of that compound directed against somatostatin-containing cells. The present study further defines the actions of cysteamine on somatostatin in the central nervous system. (CNS). Cysteamine hydrochloride administered subcutaneously results in a depletion of somatostatin-like immunoreactivity (SLI) in the retina, brain, and cervical spinal cord of rats. The effect is demonstrable at doses of 30 mg/kg of body weight and above, occurs within 2 to 4 hr of a single injection of the drug, and is largely reversible within 1 week. The mean depletion of SLI observed within the CNS varies from 38% in cerebral cortex to 65% in cervical spinal cord 24 hr following administration of CSH, 300 mg/kg of body weight, s.c. By gel permeation chromatography, all molecular weight forms of SLI are affected, with the largest reductions in those forms that co-chromatograph with synthetic somatostatin-14 and somatostatin-28. These results indicate that CSH has a generalized, rapid, and largely reversible effect in depleting SLI from the rat CNS.

  20. Intranasal drug delivery to the central nervous system: present status and future outlook.

    PubMed

    Tayebati, Seyed Khosrow; Nwankwo, Innocent Ejike; Amenta, Francesco

    2013-01-01

    Pharmacological treatment of disorders affecting the central nervous system (CNS) is a complex task. Different parameters may negatively influence effective targeting of the CNS and drug compliance, for example, poor brain-blood barrier (BBB) permeability, patient forgetfulness or neglect, and lack of collaboration between caregivers and patients. Pharmaceutical science is constantly looking for new administration strategies for efficient drug delivery to the CNS that could obviate these problems. Drugs can reach the brain through the skin, nasal cavity and oral cavity, and while effective transport of drugs from skin and nasal cavity to the CNS has been documented, these studies did not stimulate the introduction of a substantial number of new drug formulations to treat CNS disorders. Nasal drug delivery, generally used to administer locally acting molecules, is not common for systemic administration, although the possibility and importance of such systemic administration is suggested by several studies. This paper reviewed different anatomical and pharmaceutical factors related to drug administration through the nasal route, and explored whether nasal delivery of selected CNS drugs could improve their pharmacokinetics and patient compliance. This route offers attractive advantages, and pharmaceutical scientists and anatomists should collaborate to improve CNS drug compliance and to increase the number of compounds that can be administered intranasally.

  1. Omega-3 Fatty Acids and their Role in Central Nervous System - A Review.

    PubMed

    Wysoczański, Tomasz; Sokoła-Wysoczańska, Ewa; Pękala, Jolanta; Lochyński, Stanisław; Czyż, Katarzyna; Bodkowski, Robert; Herbinger, Grzegorz; Patkowska-Sokoła, Bożena; Librowski, Tadeusz

    2016-01-01

    Polyunsaturated fatty acids (PUFAs) are crucial for our health and wellbeing; therefore, they have been widely investigated for their roles in maintaining human health and in disease treatment. Most Western diets include significant amount of saturated and omega-6 fatty acids and insufficient quantity of omega-3; however, the balance between omega-6 and omega-3 PUFA, in particular, is essential for the formation of pro- and anti-inflammatory lipids to promote health and prevent disease. As our daily diet affects our health, this paper draws attention to unique representatives of the omega-3 fatty acid group: alpha-linolenic acid and its derivatives. Recently, this has been shown to be effective in treating and preventing various diseases. It has been confirmed that omega-3 PUFAs may act as therapeutic agents as well and their significant role against inflammatory diseases, such as cardiovascular and neurodegenerative diseases, has been described. Some of nutritional factors have been described as a significant modifiers, which can influence brain elasticity and thus, effect on central nervous system functioning. Therefore, appropriate dietary management appears to be a non-invasive and effective approach to counteract neurological and cognitive disorders.

  2. Indian data on central nervous tumors: A summary of published work

    PubMed Central

    Dasgupta, Archya; Gupta, Tejpal; Jalali, Rakesh

    2016-01-01

    Tumors of the central nervous system (CNS) constitute approximately 2% of all malignancies. Although relatively rare, the associated morbidity and mortality and the significant proportion of affected young and middle-aged individuals has a major bearing on the death-adjusted life years compared to other malignancies. CNS tumors encompass a very broad spectrum with regards to age, location, histology, and clinical outcomes. Advances in diagnostic imaging, surgical techniques, radiotherapy equipment, and generation of newer chemotherapeutic and targeted agents over the past few years have helped improving treatment outcome. Further insights into the molecular pathways leading to the development of tumors made in the past decade are being incorporated into routine clinical practice. Several focused groups within India have been working on a range of topics related to CNS tumors, and a significant body of work from India, in the recent years, is being increasingly recognized throughout the world. The present article summarizes key published work with particular emphasis on gliomas and medulloblastoma, the two commonly encountered tumors. PMID:27606302

  3. Projections of Drosophila multidendritic neurons in the central nervous system: links with peripheral dendrite morphology.

    PubMed

    Grueber, Wesley B; Ye, Bing; Yang, Chung-Hui; Younger, Susan; Borden, Kelly; Jan, Lily Y; Jan, Yuh-Nung

    2007-01-01

    Neurons establish diverse dendritic morphologies during development, and a major challenge is to understand how these distinct developmental programs might relate to, and influence, neuronal function. Drosophila dendritic arborization (da) sensory neurons display class-specific dendritic morphology with extensive coverage of the body wall. To begin to build a basis for linking dendrite structure and function in this genetic system, we analyzed da neuron axon projections in embryonic and larval stages. We found that multiple parameters of axon morphology, including dorsoventral position, midline crossing and collateral branching, correlate with dendritic morphological class. We have identified a class-specific medial-lateral layering of axons in the central nervous system formed during embryonic development, which could allow different classes of da neurons to develop differential connectivity to second-order neurons. We have examined the effect of Robo family members on class-specific axon lamination, and have also taken a forward genetic approach to identify new genes involved in axon and dendrite development. For the latter, we screened the third chromosome at high resolution in vivo for mutations that affect class IV da neuron morphology. Several known loci, as well as putative novel mutations, were identified that contribute to sensory dendrite and/or axon patterning. This collection of mutants, together with anatomical data on dendrites and axons, should begin to permit studies of dendrite diversity in a combined developmental and functional context, and also provide a foundation for understanding shared and distinct mechanisms that control axon and dendrite morphology.

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

    PubMed Central

    Nieder, Carsten; Andratschke, Nicolaus; Astner, Sabrina T

    2007-01-01

    Several experimental strategies of radiation-induced central nervous system toxicity prevention have recently resulted in encouraging data. The present review summarizes the background for this research and the treatment results. It extends to the perspectives of tissue regeneration strategies, based for example on stem and progenitor cells. Preliminary data suggest a scenario with individually tailored strategies where patients with certain types of comorbidity, resulting in impaired regeneration reserve capacity, might be considered for toxicity prevention, while others might be "salvaged" by delayed interventions that circumvent the problem of normal tissue specificity. Given the complexity of radiation-induced changes, single target interventions might not suffice. Future interventions might vary with patient age, elapsed time from radiotherapy and toxicity type. Potential components include several drugs that interact with neurodegeneration, cell transplantation (into the CNS itself, the blood stream, or both) and creation of reparative signals and a permissive microenvironment, e.g., for cell homing. Without manipulation of the stem cell niche either by cell transfection or addition of appropriate chemokines and growth factors and by providing normal perfusion of the affected region, durable success of such cell-based approaches is hard to imagine. PMID:17603905

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

    PubMed

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

    2016-05-01

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

  6. [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.

  7. Natural plant products and extracts that reduce immunoexcitotoxicity-associated neurodegeneration and promote repair within the central nervous system

    PubMed Central

    Blaylock, Russell L.; Maroon, Joseph

    2012-01-01

    Our understanding of the pathophysiological and biochemical basis of a number of neurological disorders has increased enormously over the last three decades. Parallel with this growth of knowledge has been a clearer understanding of the mechanism by which a number of naturally occurring plant extracts, as well as whole plants, can affect these mechanisms so as to offer protection against injury and promote healing of neurological tissues. Curcumin, quercetin, green tea catechins, balcalein, and luteolin have been extensively studied, and they demonstrate important effects on cell signaling that go far beyond their antioxidant effects. Of particular interest is the effect of these compounds on immunoexcitotoxicity, which, the authors suggest, is a common mechanism in a number of neurological disorders. By suppressing or affecting microglial activation states as well as the excitotoxic cascade and inflammatory mediators, these compounds dramatically affect the pathophysiology of central nervous system disorders and promote the release and generation of neurotrophic factors essential for central nervous system healing. We discuss the various aspects of these processes and suggest future directions for study. PMID:22439110

  8. Kynurenine pathway inhibition reduces central nervous system inflammation in a model of human African trypanosomiasis.

    PubMed

    Rodgers, Jean; Stone, Trevor W; Barrett, Michael P; Bradley, Barbara; Kennedy, Peter G E

    2009-05-01

    Human African trypanosomiasis, or sleeping sickness, is caused by the protozoan parasites Trypanosoma brucei rhodesiense or Trypanosoma brucei gambiense, and is a major cause of systemic and neurological disability throughout sub-Saharan Africa. Following early-stage disease, the trypanosomes cross the blood-brain barrier to invade the central nervous system leading to the encephalitic, or late stage, infection. Treatment of human African trypanosomiasis currently relies on a limited number of highly toxic drugs, but untreated, is invariably fatal. Melarsoprol, a trivalent arsenical, is the only drug that can be used to cure both forms of the infection once the central nervous system has become involved, but unfortunately, this drug induces an extremely severe post-treatment reactive encephalopathy (PTRE) in up to 10% of treated patients, half of whom die from this complication. Since it is unlikely that any new and less toxic drug will be developed for treatment of human African trypanosomiasis in the near future, increasing attention is now being focussed on the potential use of existing compounds, either alone or in combination chemotherapy, for improved efficacy and safety. The kynurenine pathway is the major pathway in the metabolism of tryptophan. A number of the catabolites produced along this pathway show neurotoxic or neuroprotective activities, and their role in the generation of central nervous system inflammation is well documented. In the current study, Ro-61-8048, a high affinity kynurenine-3-monooxygenase inhibitor, was used to determine the effect of manipulating the kynurenine pathway in a highly reproducible mouse model of human African trypanosomiasis. It was found that Ro-61-8048 treatment had no significant effect (P = 0.4445) on the severity of the neuroinflammatory pathology in mice during the early central nervous system stage of the disease when only a low level of inflammation was present. However, a significant (P = 0.0284) reduction in

  9. 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

  10. 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.

  11. Xylazine Activates Adenosine Monophosphate-Activated Protein Kinase Pathway in the Central Nervous System of Rats

    PubMed Central

    Shi, Xing-Xing; Yin, Bai-Shuang; Yang, Peng; Chen, Hao; Li, Xin; Su, Li-Xue; Fan, Hong-Gang; Wang, Hong-Bin

    2016-01-01

    Xylazine is a potent analgesic extensively used in veterinary and animal experimentation. Evidence exists that the analgesic effect can be inhibited using adenosine 5’-monophosphate activated protein kinase (AMPK) inhibitors. Considering this idea, the aim of this study was to investigate whether the AMPK signaling pathway is involved in the central analgesic mechanism of xylazine in the rat. Xylazine was administrated via the intraperitoneal route. Sprague-Dawley rats were sacrificed and the cerebral cortex, cerebellum, hippocampus, thalamus and brainstem were collected for determination of liver kinase B1 (LKB1) and AMPKα mRNA expression using quantitative real-time polymerase chain reaction (qPCR), and phosphorylated LKB1 and AMPKα levels using western blot. The results of our study showed that compared with the control group, xylazine induced significant increases in AMPK activity in the cerebral cortex, hippocampus, thalamus and cerebellum after rats received xylazine (P < 0.01). Increased AMPK activities were accompanied with increased phosphorylation levels of LKB1 in corresponding regions of rats. The protein levels of phosphorylated LKB1 and AMPKα in these regions returned or tended to return to control group levels. However, in the brainstem, phosphorylated LKB1 and AMPKα protein levels were decreased by xylazine compared with the control (P < 0.05). In conclusion, our data indicates that xylazine alters the activities of LKB1 and AMPK in the central nervous system of rats, which suggests that xylazine affects the regulatory signaling pathway of the analgesic mechanism in the rat brain. PMID:27049320

  12. Corticotropin Releasing Factor (CRF) Receptor Signaling in the Central Nervous System: New Molecular Targets

    PubMed Central

    Hauger, Richard L.; Risbrough, Victoria; Brauns, Olaf; Dautzenberg, Frank M.

    2007-01-01

    Corticotropin-releasing factor (CRF) and the related urocortin peptides mediate behavioral, cognitive, autonomic, neuroendocrine and immunologic responses to aversive stimuli by activating CRF1 or CRF2 receptors in the central nervous system and anterior pituitary. Markers of hyperactive central CRF systems, including CRF hypersecretion and abnormal hypothalamic-pituitary-adrenal axis functioning, have been identified in subpopulations of patients with anxiety, stress and depressive disorders. Because CRF receptors are rapidly desensitized in the presence of high agonist concentrations, CRF hypersecretion alone may be insufficient to account for the enhanced CRF neurotransmission observed in these patients. Concomitant dysregulation of mechanisms stringently controlling magnitude and duration of CRF receptor signaling also may contribute to this phenomenon. While it is well established that the CRF1 receptor mediates many anxiety- and depression-like behaviors as well as HPA axis stress responses, CRF2 receptor functions are not well understood at present. One hypothesis holds that CRF1 receptor activation initiates fear and anxiety-like responses, while CRF2 receptor activation re-establishes homeostasis by counteracting the aversive effects of CRF1 receptor signaling. An alternative hypothesis posits that CRF1 and CRF2 receptors contribute to opposite defensive modes, with CRF1 receptors mediating active defensive responses triggered by escapable stressors, and CRF2 receptors mediating anxiety- and depression-like responses induced by inescapable, uncontrollable stressors. CRF1 receptor antagonists are being developed as novel treatments for affective and stress disorders. If it is confirmed that the CRF2 receptor contributes importantly to anxiety and depression, the development of small molecule CRF2 receptor antagonists would be therapeutically useful. PMID:16918397

  13. Immunophenotyping of inflammatory cells associated with Schmallenberg virus infection of the central nervous system of ruminants.

    PubMed

    Herder, Vanessa; Hansmann, Florian; Wohlsein, Peter; Peters, Martin; Varela, Mariana; Palmarini, Massimo; Baumgärtner, Wolfgang

    2013-01-01

    Schmallenberg virus (SBV) is a recently discovered Bunyavirus associated mainly with abortions, stillbirths and malformations of the skeletal and central nervous system (CNS) in newborn ruminants. In this study, a detailed immunophenotyping of the inflammatory cells of the CNS of affected animals was carried out in order to increase our understanding of SBV pathogenesis. A total of 82 SBV-polymerase chain reaction (PCR) positive neonatal ruminants (46 sheep lambs, 34 calves and 2 goat kids) were investigated for the presence of inflammation in the brain and spinal cord. The study focused on 15 out of 82 animals (18.3%) showing inflammation in the CNS. All 15 neonates displayed lymphohistiocytic meningoencephalomyelitis affecting most frequently the mesencephalon and the parietal and temporal lobes. The majority of infiltrating cells were CD3-positive T cells, followed by CD79α-positive B cells and CD68-positive microglia/macrophages. Malformations like por- and hydranencephaly, frequently found in the temporal lobe, showed associated demyelination and axonal loss. SBV antigen was detected in 37 out of 82 (45.1%) neonatal brains by immunohistochemistry. In particular, SBV antigen was found in 93.3% (14 out of 15 ruminants) and 32.8% (22 out of 67 ruminants) of animals with and without encephalitis, respectively. Highest amounts of virus-protein expression levels were found in the temporal lobe. Our findings suggest that: (i) different brain regions display differential susceptibility to SBV infection; (ii) inflammatory cells in the CNS are found only in a minority of virus infected animals; (iii) malformations occur in association with and without inflammation in the CNS; and (iv) viral antigen is strongly associated with the presence of inflammation in naturally infected animals. Further studies are required to explore the cell tropism and pathogenesis of SBV infection in ruminants.

  14. Molecular mechanisms underlying the effects of statins in the central nervous system.

    PubMed

    McFarland, Amelia J; Anoopkumar-Dukie, Shailendra; Arora, Devinder S; Grant, Gary D; McDermott, Catherine M; Perkins, Anthony V; Davey, Andrew K

    2014-11-10

    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.

  15. Superficial siderosis of the central nervous system secondary to spinal ependymoma.

    PubMed

    Pikis, Stylianos; Cohen, José E; Vargas, Andres A; Gomori, J Moshe; Harnof, Sagi; Itshayek, Eyal

    2014-11-01

    Superficial siderosis of the central nervous system is a syndrome caused by deposition of hemosiderin in the subpial layers of the central nervous system, occurring as a result of recurrent asymptomatic or symptomatic bleeding into the subarachnoid space. We report a rare case of superficial siderosis in a 33-year-old man who presented with sensorineural hearing loss. The diagnosis of superficial siderosis on MRI brain studies led to further investigations with detection of a spinal ependymoma at L1-L2, compressing the cauda equina. Gross total resection of the tumor arrested the progression of the neurological deterioration. Our report underlies the importance of early diagnosis and surgical management, with imaging examination of the full neuroaxis to identify the source of bleeding, to halt disease progression and improve prognosis.

  16. Primary angiitis of the central nervous system mimicking tumor-like lesion--case report.

    PubMed

    Tanei, Takafumi; Nakahara, Norimoto; Takebayashi, Shigenori; Ito, Masafumi; Hashizume, Yoshio; Wakabayashi, Toshihiko

    2011-01-01

    A 60-year-old man presented with a rare case of primary angiitis of the central nervous system mimicking a tumor-like lesion and manifesting as slight disorientation, left hemiparesis, and motor aphasia. Computed tomography showed multiple low density lesions in the left frontal lobe, brain stem, and right parietal lobe. Magnetic resonance images revealed a slightly enhanced mass lesion in the right parietal lobe with surrounding brain edema. Serum, cerebrospinal fluid, and other image examinations did not show any abnormal findings, so surgical removal of the right parietal mass was performed. Histological examination revealed that the mass consisted of hemorrhagic infarction without cellular atypia. Proliferations of endothelial cells in small and medium arteries, and infiltration of macrophages in the perivascular space were detected in the infarction tissues. The histological diagnosis was primary angiitis of the central nervous system.

  17. 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.

  18. Coma blisters after poisoning caused by central nervous system depressants: case report including histopathological findings.

    PubMed

    Branco, Maira Migliari; Capitani, Eduardo Mello De; Cintra, Maria Letícia; Hyslop, Stephen; Carvalho, Adriana Camargo; Bucaretchi, Fabio

    2012-01-01

    Blister formation and eccrine sweat gland necrosis is a cutaneous manifestation associated with states of impaired consciousness, most frequently reported after overdoses of central nervous system depressants, particularly phenobarbital. The case of a 45-year-old woman who developed "coma blisters" at six distinct anatomic sites after confirmed (laboratory) phenobarbital poisoning, associated with other central nervous system depressants (clonazepam, promethazine, oxcarbazepine and quetiapine), is presented. A biopsy from the left thumb blister taken on day 4 revealed focal necrosis of the epidermis and necrosis of sweat gland epithelial cells; direct immunofluorescence was strongly positive for IgG in superficial blood vessel walls but negative for IgM, IgA, C3 and C1q. The patient was discharged on day 21 with no sequelae.

  19. 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.

  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. [Infiltration of central nervous system and meninges in lymphomas with leukemic conversion].

    PubMed

    de Freitas, M R; Moreira Filho, P F; Praxedes, H; Hahn, M D

    1981-12-01

    The cases of four patients with lymphoma with leukemic conversion, who exhibited neoplastic infiltration of the central nervous system and of the meninges are reported. The anatomo-pathologic study showed the presence of small nodules of leukemic cells, in two patients. The other two patients had clinical improvement after the use of metotrexate by spinal route so that the anatomopathologic study of their CNS and meninges showed no abnormality.

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

    PubMed

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

    2016-12-01

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

  3. LATENT HERPES SIMPLEX VIRUS IN THE CENTRAL NERVOUS SYSTEM OF RABBITS AND MICE

    PubMed Central

    Knotts, F. B.; Cook, M. L.; Stevens, J. G.

    1973-01-01

    Herpes simplex virus (HSV) type 1 induces a long-standing latent infection in the central nervous system of mice and rabbits. The infection was extablished in the brain stems of rabbits after corneal inoculation of the virus, and in the spinal cords of mice after rear footpad infection. In these animals, infectious virus could not be recovered by direct isolation from tissues; it was detected only after the tissues were maintained as organ cultures in vitro. PMID:4353820

  4. 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.

  5. Differential diagnosis of central nervous system involvement in a patient treated with acyclovir.

    PubMed

    von Euler, Mia; Axelsson, Gudmundur; Helldén, Anders

    2013-08-01

    Acyclovir-induced neuropsychiatric symptoms (AINSs) may resemble several diseases of the central nervous system. Laboratory testing of acyclovir may be critical in supporting the diagnosis of AINSs when there is doubt. We present a case of suspected herpes encephalitis in which the diagnosis of AINSs was supported by therapeutic drug monitoring of plasma and cerebrospinal fluid concentrations of acyclovir and its main metabolite 9-carboxymethoxymethylguanine.

  6. 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.

  7. [References for prenatal diagnosis of morphological defects including the central nervous system].

    PubMed

    Blohmer, J U; Caemmerer, C D; Bollmann, R; Bartho, S

    1993-02-01

    Clinical and autopsy records of 209 stillborn and 81 miscarried infants with 484 congenital defects of the central nervous system were analysed. Sets of more than one defect were retrospectively classified by pathogenetic criteria as syndrome, sequence, association and midline defects. Pathogenetic thinking makes the prenatal diagnosis of further defects easier if one has already been diagnosed. Statements regarding the most probable localisation of neural tube defects have been made.

  8. Review: apoptotic mechanisms in bacterial infections of the central nervous system

    PubMed Central

    Parthasarathy, Geetha; Philipp, Mario T.

    2012-01-01

    In this article we review the apoptotic mechanisms most frequently encountered in bacterial infections of the central nervous system (CNS). We focus specifically on apoptosis of neural cells (neurons and glia), and provide first an overview of the phenomenon of apoptosis itself and its extrinsic and intrinsic pathways. We then describe apoptosis in the context of infectious diseases and inflammation caused by bacteria, and review its role in the pathogenesis of the most relevant bacterial infections of the CNS. PMID:23060884

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

    PubMed Central

    Harrison-Brown, Meredith; Liu, Guo-Jun; Banati, Richard

    2016-01-01

    Myeloid cells are a unique subset of leukocytes with a diverse array of functions within the central nervous system during health and disease. Advances in understanding of the unique properties of these cells have inspired interest in their use as delivery vehicles for therapeutic genes, proteins, and drugs, or as “assistants” in the clean-up of aggregated proteins and other molecules when existing drainage systems are no longer adequate. The trafficking of myeloid cells from the periphery to the central nervous system is subject to complex cellular and molecular controls with several ‘checkpoints’ from the blood to their destination in the brain parenchyma. As important components of the neurovascular unit, the functional state changes associated with lineage heterogeneity of myeloid cells are increasingly recognized as important for disease progression. In this review, we discuss some of the cellular elements associated with formation and function of the neurovascular unit, and present an update on the impact of myeloid cells on central nervous system (CNS) diseases in the laboratory and the clinic. We then discuss emerging strategies for harnessing the potential of site-directed myeloid cell homing to the CNS, and identify promising avenues for future research, with particular emphasis on the importance of untangling the functional heterogeneity within existing myeloid subsets. PMID:27918464

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

    PubMed

    Harrison-Brown, Meredith; Liu, Guo-Jun; Banati, Richard

    2016-12-02

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

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

    PubMed

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

    2015-05-01

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

  12. 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

  13. 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

  14. Muscarinic receptors: their roles in disorders of the central nervous system and potential as therapeutic targets.

    PubMed

    Scarr, Elizabeth

    2012-05-01

    Phylogenetically, acetylcholine is an ancient neurochemical. Therefore, it is not surprising that cholinergic neurons project extensively throughout the central nervous system, innervating a wide range of structures within the brain. In fact, acetylcholine is involved in processes that underpin some of our most basic central functions. Both muscarinic and nicotinic receptor families, which mediate cholinergic transmission, have been implicated in the pathophysiology of psychiatric and neurological disorders. The question that remains to be definitively answered is whether or not these receptors are viable targets for the development of future therapeutic agents.

  15. Reconstitution of the central and peripheral nervous system during salamander tail regeneration.

    PubMed

    McHedlishvili, Levan; Mazurov, Vladimir; Grassme, Kathrin S; Goehler, Kerstin; Robl, Bernhard; Tazaki, Akira; Roensch, Kathleen; Duemmler, Annett; Tanaka, Elly M

    2012-08-21

    We show that after tail amputation in Ambystoma mexicanum (Axolotl) the correct number and spacing of dorsal root ganglia are regenerated. By transplantation of spinal cord tissue and nonclonal neurospheres, we show that the central spinal cord represents a source of peripheral nervous system cells. Interestingly, melanophores migrate from preexisting precursors in the skin. Finally, we demonstrate that implantation of a clonally derived spinal cord neurosphere can result in reconstitution of all examined cell types in the regenerating central spinal cord, suggesting derivation of a cell with spinal cord stem cell properties.

  16. The enteric nervous system and gastrointestinal innervation: integrated local and central control.

    PubMed

    Furness, John B; Callaghan, Brid P; Rivera, Leni R; Cho, Hyun-Jung

    2014-01-01

    The digestive system is innervated through its connections with the central nervous system (CNS) and by the enteric nervous system (ENS) within the wall of the gastrointestinal tract. The ENS works in concert with CNS reflex and command centers and with neural pathways that pass through sympathetic ganglia to control digestive function. There is bidirectional information flow between the ENS and CNS and between the ENS and sympathetic prevertebral ganglia.The ENS in human contains 200-600 million neurons, distributed in many thousands of small ganglia, the great majority of which are found in two plexuses, the myenteric and submucosal plexuses. The myenteric plexus forms a continuous network that extends from the upper esophagus to the internal anal sphincter. Submucosal ganglia and connecting fiber bundles form plexuses in the small and large intestines, but not in the stomach and esophagus. The connections between the ENS and CNS are carried by the vagus and pelvic nerves and sympathetic pathways. Neurons also project from the ENS to prevertebral ganglia, the gallbladder, pancreas and trachea.The relative roles of the ENS and CNS differ considerably along the digestive tract. Movements of the striated muscle esophagus are determined by neural pattern generators in the CNS. Likewise the CNS has a major role in monitoring the state of the stomach and, in turn, controlling its contractile activity and acid secretion, through vago-vagal reflexes. In contrast, the ENS in the small intestine and colon contains full reflex circuits, including sensory neurons, interneurons and several classes of motor neuron, through which muscle activity, transmucosal fluid fluxes, local blood flow and other functions are controlled. The CNS has control of defecation, via the defecation centers in the lumbosacral spinal cord. The importance of the ENS is emphasized by the life-threatening effects of some ENS neuropathies. By contrast, removal of vagal or sympathetic connections with the

  17. Thymic stromal lymphopoietin is expressed in the intact central nervous system and upregulated in the myelin-degenerative central nervous system

    PubMed Central

    Kitic, Maja; Wimmer, Isabella; Adzemovic, Milena; Kögl, Nikolaus; Rudel, Antonia; Lassmann, Hans; Bradl, Monika

    2014-01-01

    Thymic stromal lymphopoietin (TSLP) is an epithelial cytokine expressed at barrier surfaces of the skin, gut, nose, lung, and the maternal/fetal interphase. At these sites, it is important for the generation and maintenance of non-inflammatory, tissue-resident dendritic cell responses. We show here that TSLP is also expressed in the central nervous system (CNS) where it is produced by choroid plexus epithelial cells and astrocytes in the spinal cord. Under conditions of low-grade myelin degeneration, the numbers of TSLP-expressing astrocytes increase, and microglia express transcripts for the functional TSLP receptor dimer indicating that these cells are targets for TSLP in the myelin-degenerative CNS. PMID:24668732

  18. 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.

  19. Expression and distribution of CD9 in myelin of the central and peripheral nervous systems.

    PubMed Central

    Nakamura, Y.; Iwamoto, R.; Mekada, E.

    1996-01-01

    CD9 is a member of the newly identified tetra-membrane-spanning protein family. We show here that CD9 is a constituent of myelin in the central and peripheral nervous systems. Expression of CD9 was detected in human cerebral white matter and sciatic nerve by Northern and Western blotting. Myelin in the central and peripheral nervous systems was strongly stained with a monoclonal antibody against human CD9 antigen in paraffin-embedded sections. CD9 was detected in adult nervous tissue but not in developing brain at less than 20 weeks of gestation. Immunohistochemical studies indicated that expression of CD9 is correlated with myelination and is somewhat delayed compared with expression of myelin basic protein, a major component protein of myelin. In the central nervous system, CD9 was detected along the outermost membrane of compact myelin but not inside compact myelin or the periaxonal region. Although the membrane-anchored form of heparin-binding epidermal-growth-factor-like growth factor (proHB-EGF), which is identical to the diphtheria toxin receptor, forms a complex with CD9 in some human and monkey cell lines, proHB-EGF was not detected in myelin immunocytochemically. The distribution of CD9 in the outer surface of myelin and its relatively late developmental appearance suggest that CD9 may interact with the extracellular matrix or cell adhesion molecules and participate in the maintenance of the entire myelin sheath. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:8701996

  20. Guidelines for diagnosis, prevention and management of central nervous system involvement in diffuse large B-cell lymphoma patients by the Spanish Lymphoma Group (GELTAMO).

    PubMed

    Peñalver, Francisco-Javier; Sancho, Juan-Manuel; de la Fuente, Adolfo; Olave, María-Teresa; Martín, Alejandro; Panizo, Carlos; Pérez, Elena; Salar, Antonio; Orfao, Alberto

    2017-02-01

    Diffuse large B-cell lymphoma patients have a 5% overall risk of central nervous system events (relapse or progression), which account for high morbidity and frequently fatal outcomes,(1) and shortened overall survival of <6 months.(2) Early diagnosis of central nervous system events is critical for successful treatment and improved prognosis. Identification of patients at risk of central nervous system disease is critical to accurately identify candidates for central nervous system prophylaxis vs.

  1. 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

  2. Axogenesis in the central and peripheral nervous system of the amphipod crustacean Orchestia cavimana.

    PubMed

    Ungerer, Petra; Geppert, Maria; Wolff, Carsten

    2011-03-01

    We describe the formation of the major axon pathways in the embryonic central and peripheral nervous systems of the amphipod crustacean Orchestia cavimana Heller, 1865 by means of antibody staining against acetylated alpha-tubulin. The data add to a long list of previous studies of various other aspects of development in Orchestia and provide a basis for future studies of neurogenesis on a deeper cellular and molecular level. Orchestia exhibits a tripartite dorsal brain, which is a characteristic feature of euarthropods. Its anlagen are the first detectable structures in the developing nervous system and can be traced back to distinct neuronal cell clusters in the early embryo. The development of the ventral nervous system proceeds with an anteroposterior gradient of development. In each trunk segment, the longitudinal connectives and the anterior commissure form first, followed by the intersegmental nerve, the posterior commissure and segmental nerves, respectively. A single commissure of a vestigial seventh pleonal segment is found. In the peripheral nervous system we observe a spatial and temporal pattern of leg innervation, which is strikingly similar in both limb types, the uniramous pereopods and the biramous pleopods. A proximal leg nerve splitting distally into two separated nerves probably reflects a general feature of crustaceans.

  3. Central nervous system control of gastrointestinal motility and secretion and modulation of gastrointestinal functions.

    PubMed

    Browning, Kirsteen N; Travagli, R Alberto

    2014-10-01

    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.

  4. Water and Ion Channels: Crucial in the Initiation and Progression of Apoptosis in Central Nervous System?

    PubMed Central

    Jessica Chen, Minghui; Sepramaniam, Sugunavathi; Armugam, Arunmozhiarasi; Shyan Choy, Meng; Manikandan, Jayapal; Melendez, Alirio J; Jeyaseelan, Kandiah; Sang Cheung, Nam

    2008-01-01

    Programmed cell death (PCD), is a highly regulated and sophisticated cellular mechanism that commits cell to isolated death fate. PCD has been implicated in the pathogenesis of numerous neurodegenerative disorders. Countless molecular events underlie this phenomenon, with each playing a crucial role in death commitment. A precedent event, apoptotic volume decrease (AVD), is ubiquitously observed in various forms of PCD induced by different cellular insults. Under physiological conditions, cells when subjected to osmotic fluctuations will undergo regulatory volume increase/decrease (RVI/RVD) to achieve homeostatic balance with neurons in the brain being additionally protected by the blood-brain-barrier. However, during AVD following apoptotic trigger, cell undergoes anistonic shrinkage that involves the loss of water and ions, particularly monovalent ions e.g. K+, Na+ and Cl-. It is worthwhile to concentrate on the molecular implications underlying the loss of these cellular components which posed to be significant and crucial in the successful propagation of the apoptotic signals. Microarray and real-time PCR analyses demonstrated several ion and water channel genes are regulated upon the onset of lactacystin (a proteosomal inhibitor)-mediated apoptosis. A time course study revealed that gene expressions of water and ion channels are being modulated just prior to apoptosis, some of which are aquaporin 4 and 9, potassium channels and chloride channels. In this review, we shall looked into the molecular protein machineries involved in the execution of AVD in the central nervous system (CNS), and focus on the significance of movements of each cellular component in affecting PCD commitment, thus provide some pharmacological advantages in the global apoptotic cell death. PMID:19305791

  5. Endogenous neuro-protectants in ammonia toxicity in the central nervous system: facts and hypotheses.

    PubMed

    Albrecht, Jan; Wegrzynowicz, Michał

    2005-12-01

    The paper overviews experimental evidence suggestive of the engagement of three endogenous metabolites: taurine, kynurenic acid, and glutathione (GSH) in the protection of central nervous system (CNS) cells against ammonia toxicity. Intrastriatal administration of taurine via microdialysis probe attenuates ammonia-induced accumulation of extracellular cyclic guanosine monophosphate (cGMP) resulting from over-activation of the N-methyl-D: -aspartate/nitric oxide (NMDA/NO) pathway, and this effect involves agonistic effect of taurine on the GABA-A and glycine receptors. Taurine also counteracts generation of free radicals, increased release of dopamine, and its metabolism to dihydroxyphenylacetic acid (DOPAC). Taurine reduces ammonia-induced increase of cell volume (edema) in cerebrocortical slices by a mechanism involving GABA-A receptors. Massive release of radiolabeled or endogenous taurine from CNS tissues by ammonia in vivo and in vitro is thought to promote its neuroprotective action, by making the amino acid available for interaction with cell membranes and/or by driving excess water out of the CNS cells (astrocytes) that underwent ammonia-induced swelling. Ammonia in vivo and in vitro affects in variable ways the synthesis of kynurenic acid (KYNA). Since KYNA is an endogenous NMDA receptor antagonist with a high affinity towards its glycine site, changes in its content may counter over-activation or depression of glutaminergic transmission observed at the different stages of hyperammonemia. GSH is a major antioxidant in the CNS whose synthesis is partly compartmented between neurons and astrocytes: astrocytic GSH is a source of precursors for the synthesis of neuronal GSH. Ammonia in vitro stimulates GSH synthesis in cultured astrocytes, which may compensate for increased GSH consumption (decreased GSH/GSSG ratio) in neurons.

  6. New insight in colistin induced neurotoxicity with the mitochondrial dysfunction in mice central nervous tissues.

    PubMed

    Dai, Chongshan; Li, Jichang; Li, Jian

    2013-09-01

    In the present study, the mechanism of colistin-induced neurotoxicity was investigated with a focus on behavioral characters, mitochondrial ultrastructures and functions of the central nerve tissues in mice followed by administrating intravenously 15 (divided into two dose and 12 h apart), 7.5 and 5 mg/kgbw colistin sulfate for 1, 3 or 7 days successively. To assess the recoverability of colistin-induced neurotoxicity, the neurotoxicity was also examined on day 15 (8 post colistin sulfate administration for 7 days). The results showed that, the spontaneous activities of mice were significantly decreased on days 3 and 7 in the 15 mg/kg group compared with the correspondingly control group. The abnormal ultrastructure changes of mitochondria were presented in their nervous tissues and changed in a dose- and time-dependent manner, e.g. severe vacuolation and fission on days 3 and 7 in the 15 mg/kg group and more slight on day 7 in the 7.5 mg/kg group. In addition, mitochondrial permeability transition (MPT), membrane potential (Δψm) and activities of mitochondrial succinate dehydrogenase changed, showing that colistin affected the mitochondrial functions. The recoverability of colistin-induced neurotoxicity was showed and only slight injury occurred in the nerve tissues of mice on day 15 in the 15 mg/kg group and it had no abnormal changes in the behavioral and neuropathology characters in mice on day 15 in the 7.5 and 5 mg/kg groups. The results suggested that mitochondrial dysfunction might partly account for the mechanism of neurotoxicity induced by colistin sulfate.

  7. The serotonergic central nervous system of the Drosophila larva: anatomy and behavioral function.

    PubMed

    Huser, Annina; Rohwedder, Astrid; Apostolopoulou, Anthi A; Widmann, Annekathrin; Pfitzenmaier, Johanna E; Maiolo, Elena M; Selcho, Mareike; Pauls, Dennis; von Essen, Alina; Gupta, Tripti; Sprecher, Simon G; Birman, Serge; Riemensperger, Thomas; Stocker, Reinhard F; Thum, Andreas S

    2012-01-01

    The Drosophila larva has turned into a particularly simple model system for studying the neuronal basis of innate behaviors and higher brain functions. Neuronal networks involved in olfaction, gustation, vision and learning and memory have been described during the last decade, often up to the single-cell level. Thus, most of these sensory networks are substantially defined, from the sensory level up to third-order neurons. This is especially true for the olfactory system of the larva. Given the wealth of genetic tools in Drosophila it is now possible to address the question how modulatory systems interfere with sensory systems and affect learning and memory. Here we focus on the serotonergic system that was shown to be involved in mammalian and insect sensory perception as well as learning and memory. Larval studies suggested that the serotonergic system is involved in the modulation of olfaction, feeding, vision and heart rate regulation. In a dual anatomical and behavioral approach we describe the basic anatomy of the larval serotonergic system, down to the single-cell level. In parallel, by expressing apoptosis-inducing genes during embryonic and larval development, we ablate most of the serotonergic neurons within the larval central nervous system. When testing these animals for naïve odor, sugar, salt and light perception, no profound phenotype was detectable; even appetitive and aversive learning was normal. Our results provide the first comprehensive description of the neuronal network of the larval serotonergic system. Moreover, they suggest that serotonin per se is not necessary for any of the behaviors tested. However, our data do not exclude that this system may modulate or fine-tune a wide set of behaviors, similar to its reported function in other insect species or in mammals. Based on our observations and the availability of a wide variety of genetic tools, this issue can now be addressed.

  8. Neural progenitor cell transplants into the developing and mature central nervous system.

    PubMed

    Sakaguchi, D S; Van Hoffelen, S J; Grozdanic, S D; Kwon, Y H; Kardon, R H; Young, M J

    2005-05-01

    When developing cell transplant strategies to repair the diseased or injured central nervous system (CNS), it is essential to consider host-graft interactions and how they may influence the outcome of the transplants. Recent studies have demonstrated that transplanted neural progenitor cells (NPCs) can differentiate and integrate morphologically into developing mammalian retinas. Is the ability to differentiate and to undergo structural integration into the CNS unique to specific progenitor cells, or is this plasticity a function of host environment, or both? To address these issues we have used the developing retina of the Brazilian opossum and have compared the structural integration of brain and retinal progenitor cells transplanted into the eyes at different developmental stages. The Brazilian opossum, Monodelphis domestica, is a small pouchless marsupial native to South America. This animal's lack of a pouch and fetal-like nature at birth circumvents the need for in utero surgical procedures, and thus provides an ideal environment in which to study the interactions between developing host tissues and transplanted NPCs. To test whether NPCs affect visual function we transplanted adult hippocampal progenitor cells (AHPCs) into normal, healthy adult rat eyes and performed noninvasive functional recordings. Monitoring of the retina and optic nerve over time by electroretinography and pupillometry revealed no severe perturbation in visual function in the transplant recipient eyes. Taken together, our findings suggest that the age of the host environment can strongly influence NPC differentiation and that transplantation of neural progenitor cells may be a useful strategy aimed at treating neurodegeneration and pathology of the CNS.

  9. Simultaneous Detection of Both GDNF and GFRα1 Expression Patterns in the Mouse Central Nervous System

    PubMed Central

    Ortega-de San Luis, Clara; Pascual, Alberto

    2016-01-01

    Glial cell line-derived neurotrophic factor (GDNF) is proposed as a therapeutic tool in Parkinson’s disease, addiction-related disorders, and neurodegenerative conditions affecting motor neurons (MNs). Despite the high amount of work about GDNF therapeutic application, the neuronal circuits requiring GDNF trophic support in the brain and spinal cord (SC) are poorly characterized. Here, we defined GDNF and GDNF family receptor-α 1 (GFRα1) expression pattern in the brain and SC of newborn and adult mice. We performed systematic and simultaneous detection of EGFP and LacZ expressing alleles in reporter mice and asked whether modifications of this signaling pathway lead to a significant central nervous system (CNS) alteration. GFRα1 was predominantly expressed by neurons but also by an unexpected population of non-neuronal cells. GFRα1 expression pattern was wider in neonatal than in adult CNS and GDNF expression was restricted in comparison with GFRα1 at both developmental time points. The use of confocal microscopy to imaging X-gal deposits and EGFP allowed us to identify regions containing cells that expressed both proteins and to discriminate between auto and non-autotrophic signaling. We also suggested long-range GDNF-GFRα1 circuits taking advantage of the ability of the EGFP genetically encoded reporter to label long distance projecting axons. The complete elimination of either the ligand or the receptor during development did not produce major abnormalities, suggesting a preponderant role for GDNF signaling during adulthood. In the SC, our results pointed to local modulatory interneurons as the main target of GDNF produced by Clarke’s column (CC) cells. Our work increases the understanding on how GDNF signals in the CNS and establish a crucial framework for posterior studies addressing either the biological role of GDNF or the optimization of trophic factor-based therapies. PMID:27445711

  10. Unraveling the differential dynamics of developmental fate in central and peripheral nervous systems

    PubMed Central

    Sengupta, Dola; Kar, Sandip

    2016-01-01

    Bone morphogenetic protein 2 (BMP2), differentially regulates the developmental lineage commitment of neural stem cells (NSC’s) in central and peripheral nervous systems. However, the precise mechanism beneath such observations still remains illusive. To decipher the intricacies of this mechanism, we propose a generic mathematical model of BMP2 driven differentiation regulation of NSC’s. The model efficiently captures the dynamics of the wild-type as well as various mutant and over-expression phenotypes for NSC’s in central nervous system. Our model predicts that the differential developmental dynamics of the NSC’s in peripheral nervous system can be reconciled by altering the relative positions of the two mutually interconnected bi-unstable switches inherently present in the steady state dynamics of the crucial developmental fate regulatory proteins as a function of BMP2 dose. This model thus provides a novel mechanistic insight and has the potential to deliver exciting therapeutic strategies for neuronal regeneration from NSC’s of different origin. PMID:27805068

  11. 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

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

    SciTech Connect

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

    1981-07-01

    The effect of central nervous system prophylaxis (cranial radiation and intrathecal chemotherapy) on intellectual function was studied in 24 children with acute lymphocytic leukemia. The Wechsler Intelligence tests were administered to these children and to a sample of their healthy siblings, who served as a comparison group. The mean Full Scale lQ was 98.6 for the patients and 112.5 for the sibling controls (p less than 0.001 level). Those patients who received central nervous system preventive treatment at a young age exhibited a greater decrement in intellectual abilities than did patients who were older when they received this treatment. In contrast, leukemia patients who had not received central nervous system prophylaxis had IQs that did not differ statistically from those of their siblings. These data suggest that central nervous system prophylaxis may have an adverse effect on the intellectual capability of children with acute lymphocytic leukemia.

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

    PubMed

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

    2016-05-06

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

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

    PubMed Central

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

    2016-01-01

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

  15. Synthetic lethal screening in the mammalian central nervous system identifies Gpx6 as a modulator of Huntington's disease.

    PubMed

    Shema, Reut; Kulicke, Ruth; Cowley, Glenn S; Stein, Rachael; Root, David E; Heiman, Myriam

    2015-01-06

    Huntington's disease, the most common inherited neurodegenerative disease, is characterized by a dramatic loss of deep-layer cortical and striatal neurons, as well as morbidity in midlife. Human genetic studies led to the identification of the causative gene, huntingtin. Recent genomic advances have also led to the identification of hundreds of potential interacting partners for huntingtin protein and many hypotheses as to the molecular mechanisms whereby mutant huntingtin leads to cellular dysfunction and death. However, the multitude of possible interacting partners and cellular pathways affected by mutant huntingtin has complicated efforts to understand the etiology of this disease, and to date no curative therapeutic exists. To address the general problem of identifying the disease-phenotype contributing genes from a large number of correlative studies, here we develop a synthetic lethal screening methodology for the mammalian central nervous system, called SLIC, for synthetic lethal in the central nervous system. Applying SLIC to the study of Huntington's disease, we identify the age-regulated glutathione peroxidase 6 (Gpx6) gene as a modulator of mutant huntingtin toxicity and show that overexpression of Gpx6 can dramatically alleviate both behavioral and molecular phenotypes associated with a mouse model of Huntington's disease. SLIC can, in principle, be used in the study of any neurodegenerative disease for which a mouse model exists, promising to reveal modulators of neurodegenerative disease in an unbiased fashion, akin to screens in simpler model organisms.

  16. The activation pattern of macrophages in giant cell (temporal) arteritis and primary angiitis of the central nervous system.

    PubMed

    Mihm, Bernhard; Bergmann, Markus; Brück, Wolfgang; Probst-Cousin, Stefan

    2014-06-01

    To determine if the pattern of macrophage activation reflects differences in the pathogenesis and clinical presentation of giant cell arteritis and primary angiitis of the central nervous system, specimens of 10 patients with giant cell arteritis and five with primary angiitis of the central nervous system were immunohistochemically studied and the expression of the macrophage activation markers 27E10, MRP14, MRP8 and 25F9 was determined in the vasculitic infiltrates. Thus, a partly different expression pattern of macrophage activation markers in giant cell arteritis and primary angiitis of the central nervous system was observed. The group comparison revealed that giant cell arteritis cases had significantly higher numbers of acute activated MRP14-positive macrophages, whereas primary angiitis of the central nervous system is characterized by a tendency toward more MRP8-positive intermediate/late activated macrophages. Furthermore, in giant cell arteritis comparably fewer CD8-positive lymphocytes were observed. These observations suggest, that despite their histopathological similarities, giant cell arteritis and primary angiitis of the central nervous system appear to represent either distinct entities within the spectrum of granulomatous vasculitides or different stages of similar disease processes. Their discrete clinical presentation is reflected by different activation patterns of macrophages, which may characterize giant cell arteritis as a more acute process and primary angiitis of the central nervous system as a more advanced inflammatory process.

  17. Modulatory Effects of Gut Microbiota on the Central Nervous System: How Gut Could Play a Role in Neuropsychiatric Health and Diseases

    PubMed Central

    Yarandi, Shadi S; Peterson, Daniel A; Treisman, Glen J; Moran, Timothy H; Pasricha, Pankaj J

    2016-01-01

    Gut microbiome is an integral part of the Gut-Brain axis. It is becoming increasingly recognized that the presence of a healthy and diverse gut microbiota is important to normal cognitive and emotional processing. It was known that altered emotional state and chronic stress can change the composition of gut microbiome, but it is becoming more evident that interaction between gut microbiome and central nervous system is bidirectional. Alteration in the composition of the gut microbiome can potentially lead to increased intestinal permeability and impair the function of the intestinal barrier. Subsequently, neuro-active compounds and metabolites can gain access to the areas within the central nervous system that regulate cognition and emotional responses. Deregulated inflammatory response, promoted by harmful microbiota, can activate the vagal system and impact neuropsychological functions. Some bacteria can produce peptides or short chain fatty acids that can affect gene expression and inflammation within the central nervous system. In this review, we summarize the evidence supporting the role of gut microbiota in modulating neuropsychological functions of the central nervous system and exploring the potential underlying mechanisms. PMID:27032544

  18. Modulatory Effects of Gut Microbiota on the Central Nervous System: How Gut Could Play a Role in Neuropsychiatric Health and Diseases.

    PubMed

    Yarandi, Shadi S; Peterson, Daniel A; Treisman, Glen J; Moran, Timothy H; Pasricha, Pankaj J

    2016-04-30

    Gut microbiome is an integral part of the Gut-Brain axis. It is becoming increasingly recognized that the presence of a healthy and diverse gut microbiota is important to normal cognitive and emotional processing. It was known that altered emotional state and chronic stress can change the composition of gut microbiome, but it is becoming more evident that interaction between gut microbiome and central nervous system is bidirectional. Alteration in the composition of the gut microbiome can potentially lead to increased intestinal permeability and impair the function of the intestinal barrier. Subsequently, neuro-active compounds and metabolites can gain access to the areas within the central nervous system that regulate cognition and emotional responses. Deregulated inflammatory response, promoted by harmful microbiota, can activate the vagal system and impact neuropsychological functions. Some bacteria can produce peptides or short chain fatty acids that can affect gene expression and inflammation within the central nervous system. In this review, we summarize the evidence supporting the role of gut microbiota in modulating neuropsychological functions of the central nervous system and exploring the potential underlying mechanisms.

  19. 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.

  20. Central Nervous Insulin Administration before Nocturnal Sleep Decreases Breakfast Intake in Healthy Young and Elderly Subjects

    PubMed Central

    Santiago, João C. P.; Hallschmid, Manfred

    2017-01-01

    Peripheral insulin acts on the brain to regulate metabolic functions, in particular decreasing food intake and body weight. This concept has been supported by studies in humans relying on the intranasal route of administration, a method that permits the direct permeation of insulin into the CNS without substantial absorption into the blood stream. We investigated if intranasal insulin administration before nocturnal sleep, a period of reduced metabolic activity and largely absent external stimulation, affects food intake and energy turnover on the subsequent morning. Healthy participants who were either young (16 men and 16 women; mean age ± SEM, 23.68 ± 0.40 years, mean BMI ± SEM, 22.83 ± 0.33 kg/m2) or elderly (10 men, 9 women; 70.79 ± 0.81 years, 25.27 ± 0.60 kg/m2) were intranasally administered intranasal insulin (160 IU) or placebo before a night of regular sleep that was polysomnographically recorded. Blood was repeatedly sampled for the determination of circulating glucose, insulin, leptin and total ghrelin. In the morning, energy expenditure was assessed via indirect calorimetry and subjects were offered a large standardized breakfast buffet from which they could eat ad libitum. Insulin compared to placebo reduced breakfast size by around 110 kcal (1,054.43 ± 50.91 vs. 1,162.36 ± 64.69 kcal, p = 0.0095), in particular decreasing carbohydrate intake (502.70 ± 25.97 vs. 589.82 ± 35.03 kcal, p = 0.0080). This effect was not dependent on sex or age (all p > 0.11). Sleep architecture, blood glucose and hormonal parameters as well as energy expenditure were not or only marginally affected. Results show that intranasal insulin administered to healthy young and elderly humans before sleep exerts a delayed inhibitory effect on energy intake that is not compensated for by changes in energy expenditure. While the exact underlying mechanisms cannot be derived from our data, findings indicate a long-lasting catabolic effect of central nervous insulin delivery

  1. Central Nervous Insulin Administration before Nocturnal Sleep Decreases Breakfast Intake in Healthy Young and Elderly Subjects.

    PubMed

    Santiago, João C P; Hallschmid, Manfred

    2017-01-01

    Peripheral insulin acts on the brain to regulate metabolic functions, in particular decreasing food intake and body weight. This concept has been supported by studies in humans relying on the intranasal route of administration, a method that permits the direct permeation of insulin into the CNS without substantial absorption into the blood stream. We investigated if intranasal insulin administration before nocturnal sleep, a period of reduced metabolic activity and largely absent external stimulation, affects food intake and energy turnover on the subsequent morning. Healthy participants who were either young (16 men and 16 women; mean age ± SEM, 23.68 ± 0.40 years, mean BMI ± SEM, 22.83 ± 0.33 kg/m(2)) or elderly (10 men, 9 women; 70.79 ± 0.81 years, 25.27 ± 0.60 kg/m(2)) were intranasally administered intranasal insulin (160 IU) or placebo before a night of regular sleep that was polysomnographically recorded. Blood was repeatedly sampled for the determination of circulating glucose, insulin, leptin and total ghrelin. In the morning, energy expenditure was assessed via indirect calorimetry and subjects were offered a large standardized breakfast buffet from which they could eat ad libitum. Insulin compared to placebo reduced breakfast size by around 110 kcal (1,054.43 ± 50.91 vs. 1,162.36 ± 64.69 kcal, p = 0.0095), in particular decreasing carbohydrate intake (502.70 ± 25.97 vs. 589.82 ± 35.03 kcal, p = 0.0080). This effect was not dependent on sex or age (all p > 0.11). Sleep architecture, blood glucose and hormonal parameters as well as energy expenditure were not or only marginally affected. Results show that intranasal insulin administered to healthy young and elderly humans before sleep exerts a delayed inhibitory effect on energy intake that is not compensated for by changes in energy expenditure. While the exact underlying mechanisms cannot be derived from our data, findings indicate a long-lasting catabolic effect of central nervous insulin

  2. Nonclinical Pharmacokinetics of Oseltamivir and Oseltamivir Carboxylate in the Central Nervous System▿

    PubMed Central

    Hoffmann, Gerhard; Funk, Christoph; Fowler, Stephen; Otteneder, Michael B.; Breidenbach, Alexander; Rayner, Craig R.; Chu, Tom; Prinssen, Eric P.

    2009-01-01

    Oseltamivir, a potent and selective inhibitor of influenza A and B virus neuraminidases, is a prodrug that is systemically converted into the active metabolite oseltamivir carboxylate. In light of reported neuropsychiatric events in influenza patients, including some taking oseltamivir, and as part of a full assessment to determine whether oseltamivir could contribute to, or exacerbate, such events, we undertook a series of nonclinical studies. In particular, we investigated (i) the distribution of oseltamivir and oseltamivir carboxylate in the central nervous system of rats after single intravenous doses of oseltamivir and oseltamivir carboxylate and oral doses of oseltamivir, (ii) the active transport of oseltamivir and oseltamivir carboxylate in vitro by transporters located in the blood-brain barrier, and (iii) the extent of local conversion of oseltamivir to oseltamivir carboxylate in brain fractions. In all experiments, results showed that the extent of partitioning of oseltamivir and especially oseltamivir carboxylate to the central nervous system was low. Brain-to-plasma exposure ratios were approximately 0.2 for oseltamivir and 0.01 for oseltamivir carboxylate. Apart from oseltamivir being a good substrate for the P-glycoprotein transporter, no other active transport processes were observed. The conversion of the prodrug to the active metabolite was slow and limited in human and rat brain S9 fractions. Overall, these studies indicate that the potential for oseltamivir and oseltamivir carboxylate to reach the central nervous system in high quantities is low and, together with other analyses and studies, that their involvement in neuropsychiatric events in influenza patients is unlikely. PMID:19721074

  3. Activation of mTor Signaling by Gene Transduction to Induce Axon Regeneration in the Central Nervous System Following Neural Injury

    DTIC Science & Technology

    2014-03-01

    Transduction to Induce Axon Regeneration in the Central Nervous System Following Neural Injury PRINCIPAL INVESTIGATOR: Robert E. Burke, MD...SUBTITLE 5a. CONTRACT NUMBER Activation of mTor Signaling by Gene Transduction to Induce Axon Regeneration in the Central Nervous System...has been that the mature mammalian central nervous system (CNS), unlike the peripheral nervous system (PNS), is incapable of axon regeneration. There

  4. Toxoplasmosis of the central nervous system in the acquired immunodeficiency syndrome.

    PubMed

    Lanjewar, D N; Surve, K V; Maheshwari, M B; Shenoy, B P; Hira, S K

    1998-04-01

    Acute encephalitis caused by Toxoplasma gondi was diagnosed at autopsy in 10 (20.4%) of the 49 patients. All patients had under lying immunodeficiency due to AIDS and showed selective involvement of central nervous system at autopsy. Sexual promiscuity was the risk factor in nine cases while one case had a history of blood transfusion. Diagnosis of toxoplasmosis was hampered by a lack of suspicion that Toxoplasma could be the agent causing necrotising encephalitis. The large number of cases of CNS toxoplasmosis appearing in AIDs patients emphasize the necessity of including toxoplasmosis in the differential diagnosis of encephalitis of unknown aetiology.

  5. Noncoding RNA Regulation of Dopamine Signaling in Diseases of the Central Nervous System

    PubMed Central

    Carrick, William T.; Burks, Brandi; Cairns, Murray J.; Kocerha, Jannet

    2016-01-01

    Dopaminergic neurotransmission mediates a majority of the vital central nervous system functions. Disruption of these synaptic events provokes a multitude of neurological pathologies, including Parkinson's, schizophrenia, depression, and addiction. Growing evidence supports a key role for noncoding RNA (ncRNA) regulation in the synapse. This review will discuss the role of both short and long ncRNAs in dopamine signaling, including bioinformatic examination of the pathways they target. Specifically, we focus on the contribution of ncRNAs to dopaminergic dysfunction in neurodegenerative as well as psychiatric disease. PMID:27826551

  6. Innate immune interactions within the central nervous system modulate pathogenesis of viral infections

    PubMed Central

    Nair, Sharmila; Diamond, Michael S.

    2015-01-01

    The innate immune system mediates protection against neurotropic viruses that replicate in the central nervous system (CNS). Virus infection within specific cells of the CNS triggers activation of several families of pattern recognition receptors including Toll-like receptors, retinoic acid-inducible gene 1 like receptors, nucleotide-binding oligomerization domain-like receptors, and cytosolic DNA sensors. In this review, we highlight recent advances in our understanding of how cell-intrinsic host defenses within the CNS modulate infection of different DNA and RNA viruses. PMID:26163762

  7. [Disturbances of water metabolism in two dogs and one cat with central nervous system disorders].

    PubMed

    Weingart, A; Gruber, A D; Kershaw, O; Kohn, B

    2013-08-01

    Hypernatremia due to different pathophysiological mechanisms results in a rise in plasma osmolality. Dependent on its severity and on the speed of its development hyperosmolality can be life-threatening. This article describes 2 dogs and 1 cat with central nervous system disorders (adenoma of the pituitary gland, cerebral trauma). All patients developed normovolemic hypernatremia due to pituitary gland and hypothalamus dysfunction, respectively. Plasma sodium concentrations ranged from 163 to 185 mmol/l. Neurological examinations revealed lethargy, disturbances of consciousness, and ataxia, respectively. The dogs had to be euthanased due to the grave prognosis, the cat with cerebral trauma survived.

  8. Visualizing Chemokine-Dependent T Cell Activation and Migration in Response to Central Nervous System Infection

    PubMed Central

    Carson, Monica J.; Wilson, Emma H.

    2014-01-01

    In response to central nervous system (CNS) injury and infection, astrocytes, neurons, and CNS vasculature express several chemokines, including CCL21. Quantitative polymerase chain reaction (qPCR), western blot, and immunohistochemical methods can quantify mRNA and protein expression. However, these methods do not quantify chemokine bioavailability and bioactivity, variables modified by many environ mental factors including composition of extracellular matrix (ECM). Here we illustrate how two-photon microscopy and carboxyfluorescein succinimidyl ester (CFSE or CFDA SE) labeling of T cells coupled with flow cytometry can be used as tools to assess chemokine-mediated regulation of T cell proliferation, activation, and migration. PMID:23625499

  9. Immunotherapy for cancer in the central nervous system: Current and future directions.

    PubMed

    Binder, David C; Davis, Andrew A; Wainwright, Derek A

    2016-02-01

    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.

  10. 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.

  11. Central nervous system myeloid cells as drug targets: current status and translational challenges.

    PubMed

    Biber, Knut; Möller, Thomas; Boddeke, Erik; Prinz, Marco

    2016-02-01

    Myeloid cells of the central nervous system (CNS), which include parenchymal microglia, macrophages at CNS interfaces and monocytes recruited from the circulation during disease, are increasingly being recognized as targets for therapeutic intervention in neurological and psychiatric diseases. The origin of these cells in the immune system distinguishes them from ectodermal neurons and other glia and endows them with potential drug targets distinct from classical CNS target groups. However, despite the identification of several promising therapeutic approaches and molecular targets, no agents directly targeting these cells are currently available. Here, we assess strategies for targeting CNS myeloid cells and address key issues associated with their translation into the clinic.

  12. The function of NOD-like receptors in central nervous system diseases.

    PubMed

    Kong, Xiangxi; Yuan, Zengqiang; Cheng, Jinbo

    2016-12-28

    NOD-like receptors (NLRs) are critical cytoplasmic pattern-recognition receptors (PRRs) that play an important role in the host innate immune response and immunity homeostasis. There is a growing body of evidence that NLRs are involved in a wide range of inflammatory diseases, including cancer, metabolic diseases, and autoimmune disorders. Recent studies have indicated that the proteins of the NLR family are linked with the pathophysiology of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS), and psychological diseases. In this review, we mainly focus on the role of NLRs and the underlying signaling pathways in central nervous system (CNS) diseases. © 2016 Wiley Periodicals, Inc.

  13. 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

  14. Central nervous system mucormycosis caused by Cunninghamella bertholletiae in a bottlenose dolphin (Tursiops truncatus).

    PubMed

    Isidoro-Ayza, Marcos; Pérez, Lola; Cabañes, F Javier; Castellà, Gemma; Andrés, Marina; Vidal, Enric; Domingo, Mariano

    2014-07-01

    In May 2012, an adult, male bottlenose dolphin (Tursiops truncatus) was found stranded and dead on the Spanish Mediterranean coast. At necropsy, several areas of malacia were macroscopically observed in the periventricular parenchyma of the cerebrum. Microscopically a severe, diffuse, pyogranulomatous, and necrotizing meningoencephalomyelitis was associated with numerous intralesional highly pleomorphic fungal structures. After culture, the fungus, Cunninghamella bertholletiae, was identified by culture and PCR. To our knowledge, this is the first reported case of central nervous system mucormycosis due to Cunninghamella bertholletiae in a cetacean.

  15. A Dual Case of Peritonitis and Central Nervous System Infection Caused by Nutritionally Variant Streptococcal Species

    PubMed Central

    Vivar, Sussi; Girotto, Jennifer E.

    2017-01-01

    Nutritional variant streptococci (NVS) are difficult to identify bacteria that can cause invasive infections such as endocarditis and meningitis. NVS as a cause of peritonitis has not been routinely described. This case of NVS as the etiology of peritonitis associated with previous neurosurgery and ventriculoperitoneal (VP) shunt revision demonstrates its potential role as a significant pathogen in patients with peritonitis and VP shunts. Therapy consists of vancomycin plus a second agent but since there are no standards for susceptibility testing, clinical response remains the standard for determining the efficacy of treatment. When there is central nervous system (CNS) involvement it is important to include drugs with appropriate CNS penetration. PMID:28239499

  16. Multiplexed Molecular Diagnostics for Respiratory, Gastrointestinal, and Central Nervous System Infections.

    PubMed

    Hanson, Kimberly E; Couturier, Marc Roger

    2016-11-15

    The development and implementation of highly multiplexed molecular diagnostic tests have allowed clinical microbiology laboratories to more rapidly and sensitively detect a variety of pathogens directly in clinical specimens. Current US Food and Drug Administration-approved multiplex panels target multiple different organisms simultaneously and can identify the most common pathogens implicated in respiratory viral, gastrointestinal, or central nervous system infections. This review summarizes the test characteristics of available assays, highlights the advantages and limitations of multiplex technology for infectious diseases, and discusses potential utilization of these new tests in clinical practice.

  17. 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.

  18. 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

  19. NOA-03 trial of high-dose methotrexate in primary central nervous system lymphoma: final report.

    PubMed

    Herrlinger, Ulrich; Küker, Wilhelm; Uhl, Martin; Blaicher, Hans-Peter; Karnath, Hans-Otto; Kanz, Lothar; Bamberg, Michael; Weller, Michael

    2005-06-01

    The NOA-03 trial explored high-dose methotrexate alone in 37 patients with primary central nervous system lymphoma. The overall median survival was 25 months. After 4 years, the rate of leukoencephalopathy in patients surviving more than 12 months was 58% with and 10% without whole-brain radiotherapy given at relapse (p = 0.11). Attention deficits were found in all six tested patients, and memory deficits in four patients. Two patients had normal, three had moderately restricted, and one had markedly restricted quality of life. Thus, high-dose methotrexate with deferred radiotherapy had only moderate efficacy and was associated with significant neurotoxicity in long-term surviving patients.

  20. Autoantibodies at the neuromuscular junction - link to the central nervous system.

    PubMed

    Vincent, A

    2014-10-01

    Antibodies to different membrane proteins, namely acetylcholine receptor, muscle specific kinase and low density lipoprotein receptor-related protein 4, at the neuromuscular junction are well recognised in myasthenia gravis, although the mechanisms responsible for the muscle distribution and fluctuations in function are still not very clear, and some of the issues are discussed below. In addition, the involvement of antibodies to the potassium channel complex proteins in neuromyotonia, help to lead to a better understanding of immunotherapy-responsive central nervous system diseases.

  1. 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...

  2. 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.

  3. Links among glaucoma, neurodegenerative, and vascular diseases of the central nervous system.

    PubMed

    Nucci, Carlo; Martucci, Alessio; Cesareo, Massimo; Garaci, Francesco; Morrone, Luigi Antonio; Russo, Rossella; Corasaniti, Maria Tiziana; Bagetta, Giacinto; Mancino, Raffaele

    2015-01-01

    Glaucoma is the leading cause of irreversible blindness worldwide. Although the intraocular pressure (IOP) has been considered for long time the key point and the only treatable risk factor of the disease, there are cases in which glaucoma continues to progress despite normal IOP values. Vision loss in glaucoma is related to a selective decrease in the number of retinal ganglion cells by apoptosis that is associated to alterations of the central visual pathways. Interestingly, similar events have been also described in disorders of the central nervous system (CNS), such as Alzheimer's disease, Parkinson's disease, Leber's hereditary optic neuropathy, and cerebrovascular diseases. In this review, we discuss recent evidence supporting pathological links between glaucoma and disorders of the CNS.

  4. 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.

  5. 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.

  6. The intrinsic electrophysiological properties of mammalian neurons: insights into central nervous system function.

    PubMed

    Llinás, R R

    1988-12-23

    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, autorhythmic 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.

  7. Genetic and Epigenetic Regulation of the Brain-Derived Neurotrophic Factor in the Central Nervous System

    PubMed Central

    Martínez-Levy, Gabriela A.; Cruz-Fuentes, Carlos S.

    2014-01-01

    The BDNF is required for the development and proper function of the central nervous system, where it is involved in a variety of neural and molecular events relevant to cognition, learning, and memory processes. Although only a functional mature protein is synthesized, the human BDNF gene possesses an extensive structural complexity, including the presence of multiple promoters, splicing events, and 3´UTR poly-adenylation sites, resulting in an intricate transcriptional regulation and numerous messengers RNA. Recent data support specific cellular roles of these transcripts. Moreover, a central role of epigenetic modifications on the regulation of BDNF gene transcription is also emerging. The present essay aims to summarize the published information on the matter, emphasizing their possible implications in health and disease or in the treatment of different neurologic and psychiatric disorders. PMID:24910563

  8. 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

  9. [Origin of olfactory and rhinosensory evoked cortical potentials in diseases of the central nervous system].

    PubMed

    Westhofen, M; Herberhold, C; Thayssen, G; Jend, H H

    1985-08-01

    This is the first report to be published on olfactory evoked potentials in patients with well-defined lesions of the central nervous system and the trigeminal nerve. Absence of olfactory evoked potentials is seen in post-central and parietotemporal lesions. The first peak of the so-called olfactory evoked twin potential is absent in lesions of the basal nuclei and sectioning of the trigeminal or ophthalmic nerve, whereas there is no second peak in subcortico-frontal and cortico-temporal lesions. Tumours of the corpus callosum and sectioning of the maxillary and mandibular nerves do not disturb the olfactory evoked potentials. The anatomically different localisation and the functional synergism of the olfactory and trigeminal systems in the perception of odours and the processing of olfactory evoked potentials are pointed out.

  10. 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.

  11. Atypical presentation of CLIPPERS syndrome: a new entity in the differential diagnosis of central nervous system rheumatologic diseases.

    PubMed

    Gul, Maryam; Chaudhry, Ammar A; Chaudhry, Abbas A; Sheikh, Mubashir A; Carsons, Steven

    2015-04-01

    Numerous autoimmune diseases can affect the central nervous system (CNS), and variable clinical presentations confound the differential diagnosis. The challenging task of properly characterizing various CNS autoimmune diseases enables patients to be rapidly triaged and appropriately treated. In this review article, we aim to explore different CNS manifestations of rheumatologic diseases with emphasis on the utility of imaging and cerebrospinal fluid findings. We review the classic physical examination findings, characteristic imaging features, cerebrospinal fluid results, and serum biomarkers. In addition, we also present a unique case of newly described autoimmune entity CLIPPERS syndrome. Our case is unique in that this is the first case which demonstrates involvement of the supratentorial perivascular spaces in addition to the classic infratentorial involvement as initially described by Pittock et al (Brain. 2010;133:2626-2634).

  12. Surface-modified gatifloxacin nanoparticles with potential for treating central nervous system tuberculosis

    PubMed Central

    Marcianes, Patricia; Negro, Sofia; García-García, Luis; Montejo, Consuelo; Barcia, Emilia; Fernández-Carballido, Ana

    2017-01-01

    A new nanocarrier is developed for the passage of gatifloxacin through the blood–brain barrier to treat central nervous system tuberculosis. Gatifloxacin nanoparticles were prepared by nanoprecipitation using poly(lactic-co-glycolic acid) (PLGA) 502 and polysorbate 80 or Labrafil as surface modifiers. The evaluation of in vivo blood–brain barrier transport was carried out in male Wistar rats using rhodamine-loaded PLGA nanoparticles prepared with and without the surface modifiers. At 30 and 60 minutes after administration, nanoparticle biodistribution into the brain (hippocampus and cortex), lungs, and liver was studied. The results obtained from the cerebral cortex and hippocampus showed that functionalization of rhodamine nanoparticles significantly increased their passage into the central nervous system. At 60 minutes, rhodamine concentrations decreased in both the lungs and the liver but were still high in the cerebral cortex. To distinguish the effect between the surfactants, gatifloxacin-loaded PLGA nanoparticles were prepared. The best results corresponded to the formulation prepared with polysorbate 80 with regard to encapsulation efficiency (28.2%), particle size (176.5 nm), and ζ-potential (−20.1 mV), thereby resulting in a promising drug delivery system to treat cerebral tuberculosis. PMID:28331318

  13. 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.

  14. Embryonic and paralarval development of the central nervous system of the loliginid squid Sepioteuthis lessoniana.

    PubMed

    Shigeno, S; Tsuchiya, K; Segawa, S

    2001-09-03

    The embryonic development of the central nervous system (CNS) in the oval squid Sepioteuthis lessoniana is described. It has three distinct phases: (1) The ganglionic accumulation phase: Ganglionic cell clusters develop by ingression, migration, and accumulation of neuroblasts. (2) The lobe differentiation phase: Ganglia differentiate into lobes. The phase is identified by the beginning of an axogenesis. During this phase, neuropils are first formed in the suboesophageal mass, then in the basal lobe system, and finally in the inferior frontal lobes and the superior frontal-vertical lobe systems. (3) The neuropil increment phase: After the shape of the lobes reached its typical form, neuropil growth occurs, specifically in the vertical lobe. The paralarval central nervous system (CNS) is characterized by neuronal gigantism of the giant fibers and some suboesophageal commissures and connectives. The neuropil formation in the CNS of S. lessoniana occurs somewhat earlier than in Octopus vulgaris, although the principal developmental plan is quite conservative among the other coleoids investigated. Some phylogenetic aspects are discussed based on the similarities in the morphologic organization of their brains.

  15. Cloning and expression analysis of cadherin7 in the central nervous system of the embryonic zebrafish.

    PubMed

    Liu, Bei; Joel Duff, R; Londraville, Richard L; Marrs, J A; Liu, Qin

    2007-01-01

    Cadherin cell adhesion molecules exhibit unique expression patterns during development of the vertebrate central nervous system. In this study, we obtained a full-length cDNA of a novel zebrafish cadherin using reverse transcriptase-polymerase chain reaction (RT-PCR) and 5' and 3' rapid amplification of cDNA ends (RACE). The deduced amino acid sequence of this molecule is most similar to the published amino acid sequences of chicken and mammalian cadherin7 (Cdh7), a member of the type II cadherin subfamily. cadherin7 message (cdh7) expression in embryonic zebrafish was studied using in situ hybridization and RT-PCR methods. cdh7 expression begins at about 12h postfertilization (hpf) in a small patch in the anterior neural keel, and along the midline of the posterior neural keel. By 24 hpf, cdh7 expression in the brain shows a distinct segmental pattern that reflects the neuromeric organization of the brain, while its expression domain in the spinal cord is continuous, but confined to the middle region of the spinal cord. As development proceeds, cdh7 expression is detected in more regions of the brain, including the major visual structures in the fore- and midbrains, while its expression domain in the hindbrain becomes more restricted, and its expression in the spinal cord becomes undetectable. cdh7 expression becomes reduced in 3-day old embryos. Our results show that cdh7 expression in the zebrafish developing central nervous system is both spatially and temporally regulated.

  16. Spatial distribution and characterization of non-apical progenitors in the zebrafish embryo central nervous system

    PubMed Central

    Norris, Joseph

    2017-01-01

    Studies of non-apical progenitors (NAPs) have been largely limited to the developing mammalian cortex. They are postulated to generate the increase in neuron numbers that underlie mammalian brain expansion. Recently, NAPs have also been reported in the retina and central nervous system of non-mammalian species; in the latter, however, they remain poorly characterized. Here, we characterize NAP location along the zebrafish central nervous system during embryonic development, and determine their cellular and molecular characteristics and renewal capacity. We identified a small population of NAPs in the spinal cord, hindbrain and telencephalon of zebrafish embryos. Live-imaging analysis revealed at least two types of mitotic behaviour in the telencephalon: one NAP subtype retains the apical attachment during division, while another divides in a subapical position disconnected from the apical surface. All NAPs observed in spinal cord lost apical contact prior to mitoses. These NAPs express HuC and produce two neurons from a single division. Manipulation of Notch activity reveals that neurons and NAPs in the spinal cord use similar regulatory mechanisms. This work suggests that the majority of spinal NAPs in zebrafish share characteristics with basal progenitors in mammalian brains. PMID:28148823

  17. Cytokine expression in the rat central nervous system following perinatal Borna disease virus infection.

    PubMed

    Sauder, C; de la Torre, J C

    1999-04-01

    Borna disease virus (BDV) causes central nervous system (CNS) disease in several vertebrate species, which is frequently accompanied by behavioral abnormalities. In the adult rat, intracerebral (i.c.) BDV infection leads to immunomediated meningoencephalitis. In contrast, i.c. infection of neonates causes a persistent infection in the absence of overt signs of brain inflammation. These rats (designated PTI-NB) display distinct behavioral and neurodevelopmental abnormalities. However, the molecular mechanisms for these virally induced CNS disturbances are unknown. Cytokines play an important role in CNS function, both under normal physiological and pathological conditions. Astrocytes and microglia are the primary resident cells of the central nervous system with the capacity to produce cytokines. Strong reactive astrocytosis is observed in the PTI-NB rat brain. We have used a ribonuclease protection assay to investigate the mRNA expression levels of proinflammatory cytokines in different brain regions of PTI-NB and control rats. We show here evidence of a chronic upregulation of proinflammatory cytokines interleukin-6, tumor necrosis factor alpha, interleukins-1alpha, and -1beta in the hippocampus and cerebellum of the PTI-NB rat brain. These brain regions exhibited only a very mild and transient immune infiltration. In contrast, in addition to reactive astrocytes, a strong and sustained microgliosis was observed in the PTI-NB rat brains. Our data suggest that CNS resident cells, namely astrocytes and microglia, are the major source of cytokine expression in the PTI-NB rat brain. The possible implications of these findings are discussed.

  18. Localization of PPARdelta in murine central nervous system: expression in oligodendrocytes and neurons.

    PubMed

    Woods, John W; Tanen, Michael; Figueroa, David J; Biswas, Chhabi; Zycband, Emanuel; Moller, David E; Austin, Christopher P; Berger, Joel P

    2003-06-13

    The peroxisome proliferator-activated receptors (PPARs), PPARdelta, PPARgamma and PPARalpha, comprise a subclass of the supergene family of nuclear receptors. As such they are ligand-regulated transcription factors whose major effects are mediated by altering expression of target genes. PPARdelta has been shown to be ubiquitously expressed in mammals. However, its primary biological role(s) has yet to be defined. Several recent studies have demonstrated that PPARdelta is the most highly expressed PPAR isoform in the central nervous system, but ambiguity still exists as to the specific brain sub-regions and cells in which it is expressed. Here, utilizing novel, isoform-selective PPARdelta riboprobes and an anti-peptide antibody, we performed a series of in situ hybridization and immunolocalization studies to determine the distribution of PPARdelta in the central nervous system (CNS) of mice. We found that PPARdelta mRNA and protein is expressed throughout the brain, with particularly high levels in the entorhinal cortex, hypothalamus and hippocampus, and lower levels in the corpus callosum and caudate putamen. At the cellular level, PPARdelta mRNA and protein were found to be expressed in oligodendrocytes and neurons but not astrocytes. Such results suggest a role for PPARdelta in both myelination and neuronal functioning within the CNS.

  19. Guideline on the prevention of secondary central nervous system lymphoma: British Committee for Standards in Haematology.

    PubMed

    McMillan, Andrew; Ardeshna, Kirit M; Cwynarski, Kate; Lyttelton, Matthew; McKay, Pam; Montoto, Silvia

    2013-10-01

    The guideline group was selected to be representative of UK-based medical experts. Ovid MEDLINE, EMBASE and NCBI Pubmed were searched systematically for publications in English from 1980 to 2012 using the MeSH subheading 'lymphoma, CNS', 'lymphoma, central nervous system', 'lymphoma, high grade', 'lymphoma, Burkitt's', 'lymphoma, lymphoblastic' and 'lymphoma, diffuse large B cell' as keywords, as well as all subheadings. The writing group produced the draft guideline, which was subsequently revised by consensus by members of the Haemato-oncology Task Force of the British Committee for Standards in Haematology (BCSH). The guideline was then reviewed by a sounding board of ~50 UK haematologists, the BCSH and the British Society for Haematology (BSH) Committee and comments incorporated where appropriate. The 'GRADE' system was used to quote levels and grades of evidence, details of which can be found in Appendix I. The objective of this guideline is to provide healthcare professionals with clear guidance on the optimal prevention of secondary central nervous system (CNS) lymphoma. The guidance may not be appropriate to patients of all lymphoma sub-types and in all cases individual patient circumstances may dictate an alternative approach. Acronyms are defined at time of first use.

  20. [Central nervous system leukemia mimicking rapidly progressive HTLV-1 associated myelopathy].

    PubMed

    Haruki, Hiroyo; Tanaka, Shinichiro; Koga, Michiaki; Kawai, Motoharu; Negoro, Kiyoshi; Kanda, Takashi

    2009-03-01

    A 79-year-old woman was suffered from rapidly progressive paresthesia of lower limbs and gait disturbance. After one month, she showed flaccid paraplegia and hyperreflexia in the lower limbs with positive Babinski signs. Anti-HTLV-1 antibody titer was elevated in the serum, but negative in the cerebrospinal fluid (CSF). CSF examination showed mild pleocytosis, elevated protein, and normal glucose content. Adult T cell lymphoma (ATL)-like cells were seen in the CSF. MRI showed no abnormal intensity in the spinal cord and brain. Two months later, she showed rapid worsening of the paraplegia and she became unable to stand. A tentative diagnosis of rapidly progressive HTLV-1 associated myelopathy (HAM) was given, but intravenous methylprednisolone was ineffective. Six months later, she developed pneumonia, and abundant ATL cells were seen in the peripheral blood, suggesting a diagnosis of ATL. Direct infiltration of ATL cells to central nervous system was therefore suggested to have caused neurological abnormalities in this case. One may consider central nervous system leukemia when rapidly progressive HAM-like symptoms and signs are recognized, especially without positive anti-HTLV-1 antibody in the CSF.

  1. Mosaic expression of Atrx in the mouse central nervous system causes memory deficits

    PubMed Central

    Tamming, Renee J.; Siu, Jennifer R.; Jiang, Yan; Prado, Marco A. M.; Beier, Frank

    2017-01-01

    ABSTRACT The rapid modulation of chromatin organization is thought to play a crucial role in cognitive processes such as memory consolidation. This is supported in part by the dysregulation of many chromatin-remodelling proteins in neurodevelopmental and psychiatric disorders. A key example is ATRX, an X-linked gene commonly mutated in individuals with syndromic and nonsyndromic intellectual disability. The consequences of Atrx inactivation for learning and memory have been difficult to evaluate because of the early lethality of hemizygous-null animals. In this study, we evaluated the outcome of brain-specific Atrx deletion in heterozygous female mice. These mice exhibit a mosaic pattern of ATRX protein expression in the central nervous system attributable to the location of the gene on the X chromosome. Although the hemizygous male mice die soon after birth, heterozygous females survive to adulthood. Body growth is stunted in these animals, and they have low circulating concentrations of insulin growth factor 1. In addition, they are impaired in spatial, contextual fear and novel object recognition memory. Our findings demonstrate that mosaic loss of ATRX expression in the central nervous system leads to endocrine defects and decreased body size and has a negative impact on learning and memory. PMID:28093507

  2. The roles of phosphodiesterase 2 in the central nervous and peripheral systems.

    PubMed

    Zhang, Chong; Yu, Yingcong; Ruan, Lina; Wang, Chuang; Pan, Jianchun; Klabnik, Jonathan; Lueptow, Lindsay; Zhang, Han-Ting; O'Donnell, James M; Xu, Ying

    2015-01-01

    Phosphodiesterase 2 (PDE2) is a ubiquitous enzyme whose major role is to hydrolyze the important second messengers cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). In the central nervous system, pharmacological inhibition of PDE2 results in boosted cAMP and/or cGMP signaling, which is responsible for series of changes in protein expression relevant to psychiatric and learning and memory disorders, such as depression, anxiety, and cognition deficits in Alzheimer's disease. In the periphery, inhibition of PDE2 exhibits beneficial effects in the diseased cardiovascular system, the respiratory system, skeletal muscles and Candida albicans-caused systemic infections. Even though blood-brain barrier penetration properties and selectivity of currently available PDE2 inhibitors have hindered them from entering clinical trials, PDE2 is still of great potential therapeutic values in different categories of diseases, and there is demand for development of new generation drugs targeting PDE2 for treatment of diseases in central nervous and peripheral systems.

  3. Primary central nervous system anaplastic large-cell lymphoma mimicking lymphomatosis cerebri.

    PubMed

    Sugino, Toshiya; Mikami, Takeshi; Akiyama, Yukinori; Wanibuchi, Masahiko; Hasegawa, Tadashi; Mikuni, Nobuhiro

    2013-01-01

    Primary central nervous system lymphoma (PCNSL) is usually diffuse large B-cell lymphoma. Anaplastic large-cell lymphoma (ALCL) rarely occurs in the central nervous system. PCNSL always presents as single or multiple nodular contrast-enhancing mass lesions within T2-hyperintense areas on magnetic resonance imaging (MRI). Infrequently, diffuse infiltrating change with little contrast enhancement called lymphomatosis cerebri can be seen in PCNSL. In this report, we describe a 75-year-old immunocompetent man who had progressive dementia. On MRI, diffuse white matter lesions with little contrast enhancement were observed to gradually progress, which was clinically consistent with his worsening condition. A biopsy specimen revealed non-destructive, diffusely infiltrating, anaplastic large CD30-positive lymphoma, indicating a diagnosis of ALCL. After the biopsy, he was treated by whole brain irradiation (total 46 Gy) and focal boost irradiation (total 14 Gy). However, his performance status worsened and there was no symptom improvement. The patient died 8 months after symptom onset. The clinical course, diagnostic workup, pathologic correlates, and treatment outcomes are described herein.

  4. Radiotherapy in the treatment of primary central nervous system lymphoma (PCNSL).

    PubMed

    Nelson, D F

    1999-07-01

    The use of radiotherapy alone to treat primary central nervous system lymphoma (PCNSL) does not produce the high local control and survival rates that it does in limited extranodal non-Hodgkin's lymphoma outside the central nervous system (CNS). Even with doses of whole brain radiation therapy (WBRT) to 40+20 Gy boost, the Radiation Therapy Oncology Group (RTOG) reported a local control rate of 39%. Seventy-nine percent of recurrences were in the 60 Gy region. The median survival was 11.6 months. This response to local radiotherapy is quite different from the response of non-CNS Diffuse Large Cell Lymphoma where doses of 30-40 and >40 Gy have a 75-90% local control rate. Neither systemic lymphoma nor PCNSL have a classic radiotherapy dose response. For PCNSL there appears to be a threshold dose that ranges in the literature between 30 and > 50 Gy with a median of 40 Gy. Therefore, when radiotherapy is combined with chemotherapy that crosses the BBB, WBRT and/or boost doses may be able to be decreased, especially in patients achieving a complete response. Promising data from the Centre Leon Berard suggest that this is possible. When such chemotherapy was combined with intrathecal chemotherapy and 20 Gy WBRT, they obtained a 56% actuarial 5 year survival rate. Confirmation of single institution reports of favorable results such as these are needed. Cooperative group and intergroup trials are needed to define optimal therapy.

  5. Aptamers as promising molecular recognition elements for diagnostics and therapeutics in the central nervous system.

    PubMed

    McConnell, Erin M; Holahan, Matthew R; DeRosa, Maria C

    2014-12-01

    Oligonucleotide aptamers are short, synthetic, single-stranded DNA or RNA able to recognize and bind to a multitude of targets ranging from small molecules to cells. Aptamers have emerged as valuable tools for fundamental research, clinical diagnosis, and therapy. Due to their small size, strong target affinity, lack of immunogenicity, and ease of chemical modification, aptamers are an attractive alternative to other molecular recognition elements, such as antibodies. Although it is a challenging environment, the central nervous system and related molecular targets present an exciting potential area for aptamer research. Aptamers hold promise for targeted drug delivery, diagnostics, and therapeutics. Here we review recent advances in aptamer research for neurotransmitter and neurotoxin targets, demyelinating disease and spinal cord injury, cerebrovascular disorders, pathologies related to protein aggregation (Alzheimer's, Parkinson's, and prions), brain cancer (glioblastomas and gliomas), and regulation of receptor function. Challenges and limitations posed by the blood brain barrier are described. Future perspectives for the application of aptamers to the central nervous system are also discussed.

  6. Histopathology and immunohistochemistry of tissues outside central nervous system in bovine rabies.

    PubMed

    Abreu, Camila C; Nakayama, Priscilla A; Nogueira, Clayton I; Mesquita, Leonardo P; Lopes, Priscila F R; Wouters, Flademir; Varaschin, Mary S; Bezerra, Pedro S

    2014-08-01

    We performed a histopathological and immunohistochemical study of tissues outside the central nervous system in 48 cases of bovine rabies confirmed by direct immunofluorescence and/or immunohistochemistry (IHC) of the central nervous system. In the bovines of this study, mononuclear inflammation in all ganglia (trigeminal, spinal, stellate, and celiac) and adrenal medulla was observed. This injury also occurred in 85 % of neuro-pituitaries in 55 % of pars intermediate and 15 % of the pars distalis of pituitary evaluated. IHC was positive in 92.31 % of lumbar spinal ganglia, 90.9 % of trigeminal ganglia, stellate ganglia of 41.67 and 16.67 % of the celiac ganglia. One of the evaluated adrenal (1/17) showed strong immunohistochemical labeling in the cytoplasm of pheochromocytes. The pituitary IHC was positive in one case in the neurohypophysis (1/20) and in one case in the pars intermedia of the adenohypophysis (1/20). Data from this study indicate that in suspected cases of rabies, besides the complex pituitary rete mirabile and trigeminal ganglion, the evaluation of other ganglia, particularly the lumbar spinal, and adrenal may also contribute to the diagnosis and understanding of the clinical presentation and pathogenesis of the disease in bovines.

  7. Effect of Probiotics on Central Nervous System Functions in Animals and Humans: A Systematic Review

    PubMed Central

    Wang, Huiying; Lee, In-Seon; Braun, Christoph; Enck, Paul

    2016-01-01

    To systematically review the effects of probiotics on central nervous system function in animals and humans, to summarize effective interventions (species of probiotic, dose, duration), and to analyze the possibility of translating preclinical studies. Literature searches were conducted in Pubmed, Medline, Embase, and the Cochrane Library. Only randomized controlled trials were included. In total, 38 studies were included: 25 in animals and 15 in humans (2 studies were conducted in both). Most studies used Bifidobacterium (eg, B. longum, B. breve, and B. infantis) and Lactobacillus (eg, L. helveticus, and L. rhamnosus), with doses between 109 and 1010 colony-forming units for 2 weeks in animals and 4 weeks in humans. These probiotics showed efficacy in improving psychiatric disorder-related behaviors including anxiety, depression, autism spectrum disorder (ASD), obsessive-compulsive disorder, and memory abilities, including spatial and non-spatial memory. Because many of the basic science studies showed some efficacy of probiotics on central nervous system function, this background may guide and promote further preclinical and clinical studies. Translating animal studies to human studies has obvious limitations but also suggests possibilities. Here, we provide several suggestions for the translation of animal studies. More experimental designs with both behavioral and neuroimaging measures in healthy volunteers and patients are needed in the future. PMID:27413138

  8. Application of Targeted Mass Spectrometry for the Quantification of Sirtuins in the Central Nervous System

    PubMed Central

    Jayasena, T.; Poljak, A.; Braidy, N.; Zhong, L.; Rowlands, B.; Muenchhoff, J.; Grant, R.; Smythe, G.; Teo, C.; Raftery, M.; Sachdev, P.

    2016-01-01

    Sirtuin proteins have a variety of intracellular targets, thereby regulating multiple biological pathways including neurodegeneration. However, relatively little is currently known about the role or expression of the 7 mammalian sirtuins in the central nervous system. Western blotting, PCR and ELISA are the main techniques currently used to measure sirtuin levels. To achieve sufficient sensitivity and selectivity in a multiplex-format, a targeted mass spectrometric assay was developed and validated for the quantification of all seven mammalian sirtuins (SIRT1-7). Quantification of all peptides was by multiple reaction monitoring (MRM) using three mass transitions per protein-specific peptide, two specific peptides for each sirtuin and a stable isotope labelled internal standard. The assay was applied to a variety of samples including cultured brain cells, mammalian brain tissue, CSF and plasma. All sirtuin peptides were detected in the human brain, with SIRT2 being the most abundant. Sirtuins were also detected in human CSF and plasma, and guinea pig and mouse tissues. In conclusion, we have successfully applied MRM mass spectrometry for the detection and quantification of sirtuin proteins in the central nervous system, paving the way for more quantitative and functional studies. PMID:27762282

  9. Trypanosoma cruzi: experimental parasitism in the central nervous system of albino mice.

    PubMed

    Morocoima, Antonio; Socorro, Grace; Avila, Régulo; Hernández, Ana; Merchán, Solángel; Ortiz, Diana; Primavera, Gabriela; Chique, José; Herrera, Leidi; Urdaneta-Morales, Servio

    2012-11-01

    Trypanosoma cruzi causes a pan-infection, Chagas disease, in American mammals through fecal transmission by triatomine insects, resulting in an acute phase parasitemia with intracellularity mainly in the myocells and cells of the central nervous system (CNS).The parasites, due to the immune response, then decrease in number, characteristic of the life-long chronicity of the disease. We infected a mouse model with isolates obtained from reservoirs and vectors from rural and urban endemic areas in Venezuela. Intracellular proliferation and differentiation of the parasite in astrocytes, microglia, neurons, endothelial cells of the piarachnoid, cells of the Purkinje layer, and spinal ganglion cells, as well as extracellularly in the neuropil, were evaluated during the acute phase. Damages were identified as meningoencephalitis, astrocytosis, reactive microglia, acute neuronal degeneration by central chromatolysis, endothelial cell hyperplasia, edema of the neuropil, and satellitosis. This is the first time that satellitosis has been reported from a mammal infected with T. cruzi. Intracellular T. cruzi and inflammatory infiltrates were found in cardiac and skeletal myocytes and liver cells. No parasitism or alterations to the CNS were observed in the chronic mice, although they did show myocarditis and myocitis with extensive infiltrates. Our results are discussed in relation to hypotheses that deny the importance of the presence of tissue parasites versus the direct relationship between these and the damages produced during the chronic phase of Chagas disease. We also review the mechanisms proposed as responsible for the nervous phase of this parasitosis.

  10. The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems.

    PubMed

    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.

  11. 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.

  12. Application of Targeted Mass Spectrometry for the Quantification of Sirtuins in the Central Nervous System

    NASA Astrophysics Data System (ADS)

    Jayasena, T.; Poljak, A.; Braidy, N.; Zhong, L.; Rowlands, B.; Muenchhoff, J.; Grant, R.; Smythe, G.; Teo, C.; Raftery, M.; Sachdev, P.

    2016-10-01

    Sirtuin proteins have a variety of intracellular targets, thereby regulating multiple biological pathways including neurodegeneration. However, relatively little is currently known about the role or expression of the 7 mammalian sirtuins in the central nervous system. Western blotting, PCR and ELISA are the main techniques currently used to measure sirtuin levels. To achieve sufficient sensitivity and selectivity in a multiplex-format, a targeted mass spectrometric assay was developed and validated for the quantification of all seven mammalian sirtuins (SIRT1-7). Quantification of all peptides was by multiple reaction monitoring (MRM) using three mass transitions per protein-specific peptide, two specific peptides for each sirtuin and a stable isotope labelled internal standard. The assay was applied to a variety of samples including cultured brain cells, mammalian brain tissue, CSF and plasma. All sirtuin peptides were detected in the human brain, with SIRT2 being the most abundant. Sirtuins were also detected in human CSF and plasma, and guinea pig and mouse tissues. In conclusion, we have successfully applied MRM mass spectrometry for the detection and quantification of sirtuin proteins in the central nervous system, paving the way for more quantitative and functional studies.

  13. Identification of TPO receptors on central nervous system-a preliminary report.

    PubMed

    Yang, Mo; Xia, Wen-Jie; Li, Karen; Pong, Nga-Hin; Chik, Ki-Wai; Li, Chi-Kong; Ng, Margaret H L; Ng, Ho-Keung; Fung, Kwok-Pui; Fok, Tai-Fai

    2004-08-01

    To identify the expression of thrombopoietin (TPO) receptors (c-mpl) on central nervous system (CNS) and to evaluate the role of TPO on neural cell proliferation and protection, immunohistochemical staining, RT-PCR, MTT, and annexin-V methods were used in this study. The results showed the expression of TPO receptor on human CNS and murine neural cells. C-mpl mRNA was identified in human cerebral hemispheres and cerebellum, and mouse neural cell line C17.2 by RT-PCR. C-mpl was also confirmed in human cerebral hemispheres by immunohistostaining with con-focal microscopy. Furthermore, TPO had a stimulating effect on the growth of in vitro neural cell C17.2 by MTT assay. The anti-apoptotic effect of TPO on C17.2 cells was also demonstrated by staining with annexin-V and PI. In conclusion, the first evidence showed the expression of TPO receptor c-mpl in central nervous system. Moreover, the effect of TPO on neural cell proliferation and anti-apoptosis was also demonstrated on in vitro neural cells.

  14. Enhanced Histochemical Detection of Iron in Paraffin Sections of Mouse Central Nervous System Tissue

    PubMed Central

    Sands, Scott A.; Leung-Toung, Regis; Wang, Yingsheng; Connelly, John

    2016-01-01

    Histochemical methods of detecting iron in the rodent brain result mainly in the labeling of oligodendrocytes, but as all cells utilize iron, this observation suggests that much of the iron in the central nervous system goes undetected. Paraffin embedding of tissue is a standard procedure that is used to prepare sections for microscopic analysis. In the present study, we questioned whether we could modify the iron histochemical procedure to enable a greater detection of iron in paraffin sections. Indeed, various modifications led to the widespread labeling of iron in mouse brain tissue (for instance, labeling of neurons and neuropil). Sites of focal concentrations, such as cytoplasmic punctate or nucleolar staining, were also observed. The modified procedures were applied to paraffin sections of a mouse model (APP/PS1) of Alzheimer’s disease. Iron was revealed in the plaque core and rim. The plaque rim had a fibrillary or granular appearance, and it frequently contained iron-labeled cells. Further analysis indicated that the iron was tightly associated with the core of the plaque, but less so with the rim. In conclusion, modifications to the histochemical staining revealed new insights into the deposition of iron in the central nervous system. In theory, the approach should be transferrable to organs besides the brain and to other species, and the underlying principles should be incorporable into a variety of staining methods. PMID:27683879

  15. 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.

  16. Contribution of central nervous system endothelial nitric oxide synthase to neurohumoral activation in heart failure rats.

    PubMed

    Biancardi, Vinicia C; Son, Sook J; Sonner, Patrick M; Zheng, Hong; Patel, Kaushik P; Stern, Javier E

    2011-09-01

    Neurohumoral activation, a hallmark in heart failure (HF), is linked to the progression and mortality of HF patients. Thus, elucidating its precise underlying mechanisms is of critical importance. Other than its classic peripheral vasodilatory actions, the gas NO is a pivotal neurotransmitter in the central nervous system control of the circulation. While accumulating evidence supports a contribution of blunted NO function to neurohumoral activation in HF, the precise cellular sources, and NO synthase (NOS) isoforms involved, remain unknown. Here, we used a multidisciplinary approach to study the expression, cellular distribution, and functional relevance of the endothelial NOS isoform within the hypothalamic paraventricular nucleus in sham and HF rats. Our results show high expression of endothelial NOS in the paraventricular nucleus (mostly confined to astroglial cells), which contributes to constitutive NO bioavailability, as well as tonic inhibition of presympathetic neuronal activity and sympathoexcitatory outflow from the paraventricular nucleus. A diminished endothelial NOS expression and endothelial NOS-derived NO availability were found in the paraventricular nucleus of HF rats, resulting, in turn, in blunted NO inhibitory actions on neuronal activity and sympathoexcitatory outflow. Taken together, our study supports blunted central nervous system endothelial NOS-derived NO as a pathophysiological mechanism underlying neurohumoral activation in HF.

  17. 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.

  18. Knowledge-Based, Central Nervous System (CNS) Lead Selection and Lead Optimization for CNS Drug Discovery

    PubMed Central

    2011-01-01

    The central nervous system (CNS) is the major area that is affected by aging. Alzheimer’s disease (AD), Parkinson’s disease (PD), brain cancer, and stroke are the CNS diseases that will cost trillions of dollars for their treatment. Achievement of appropriate blood–brain barrier (BBB) penetration is often considered a significant hurdle in the CNS drug discovery process. On the other hand, BBB penetration may be a liability for many of the non-CNS drug targets, and a clear understanding of the physicochemical and structural differences between CNS and non-CNS drugs may assist both research areas. Because of the numerous and challenging issues in CNS drug discovery and the low success rates, pharmaceutical companies are beginning to deprioritize their drug discovery efforts in the CNS arena. Prompted by these challenges and to aid in the design of high-quality, efficacious CNS compounds, we analyzed the physicochemical property and the chemical structural profiles of 317 CNS and 626 non-CNS oral drugs. The conclusions derived provide an ideal property profile for lead selection and the property modification strategy during the lead optimization process. A list of substructural units that may be useful for CNS drug design was also provided here. A classification tree was also developed to differentiate between CNS drugs and non-CNS oral drugs. The combined analysis provided the following guidelines for designing high-quality CNS drugs: (i) topological molecular polar surface area of <76 Å2 (25–60 Å2), (ii) at least one (one or two, including one aliphatic amine) nitrogen, (iii) fewer than seven (two to four) linear chains outside of rings, (iv) fewer than three (zero or one) polar hydrogen atoms, (v) volume of 740–970 Å3, (vi) solvent accessible surface area of 460–580 Å2, and (vii) positive QikProp parameter CNS. The ranges within parentheses may be used during lead optimization. One violation to this proposed profile may be acceptable. The

  19. 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

  20. 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

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

    PubMed Central

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

    2012-01-01

    Background Despite all the advances in the treatment of childhood acute lymphoblastic leukemia, central nervous system relapse remains an important obstacle to curing these patients. This study analyzed the incidence of central nervous system relapse and the risk factors for its occurrence in children and adolescents with acute lymphoblastic leukemia. Methods This study has a retrospective cohort design. The studied population comprised 199 children and adolescents with a diagnosis of acute lymphoblastic leukemia followed up at Hospital das Clinicas, Universidade Federal de Minas Gerais (HC-UFMG) between March 2001 and August 2009 and submitted to the Grupo Brasileiro de Tratamento de Leucemia da Infância - acute lymphoblastic leukemia (GBTLI-LLA-99) treatment protocol. Results The estimated probabilities of overall survival and event free survival at 5 years were 69.5% (± 3.6%) and 58.8% (± 4.0%), respectively. The cumulative incidence of central nervous system (isolated or combined) relapse was 11.0% at 8 years. The estimated rate of isolated central nervous system relapse at 8 years was 6.8%. In patients with a blood leukocyte count at diagnosis ≥ 50 x 109/L, the estimated rate of isolated or combined central nervous system relapse was higher than in the group with a count < 50 x 109/L (p-value = 0.0008). There was no difference in cumulative central nervous system relapse (isolated or combined) for the other analyzed variables: immunophenotype, traumatic lumbar puncture, interval between diagnosis and first lumbar puncture and place where the procedure was performed. Conclusions These results suggest that a leukocyte count > 50 x 109/L at diagnosis seems to be a significant prognostic factor for a higher incidence of central nervous system relapse in childhood acute lymphoblastic leukemia. PMID:23323068

  2. The Effect of a Single Session of Whole-Body Vibration Training in Recreationally Active Men on the Excitability of the Central and Peripheral Nervous System

    PubMed Central

    Chmielewska, Daria; Piecha, Magdalena; Błaszczak, Edward; Król, Piotr; Smykla, Agnieszka; Juras, Grzegorz

    2014-01-01

    Vibration training has become a popular method used in professional sports and recreation. In this study, we examined the effect of whole-body vibration training on the central nervous system and muscle excitability in a group of 28 active men. Subjects were assigned randomly to one of two experimental groups with different variables of vibrations. The chronaximetry method was used to evaluate the effect of a single session of whole-body vibration training on the excitability of the rectus femoris and brachioradialis muscles. The examination of the fusing and flickering frequencies of the light stimulus was performed. An increase in the excitability of the quadriceps femoris muscle due to low intensity vibrations (20 Hz frequency, 2 mm amplitude) was noted, and a return to the initial values was observed 30 min after the application of vibration. High intensity vibrations (60 Hz frequency, 4 mm amplitude) caused elongations of the chronaxy time; however, these differences were not statistically significant. Neither a low intensity vibration amplitude of 2 mm (frequency of 20 Hz) nor a high intensity vibration amplitude of 4 mm (frequency of 60 Hz) caused a change in the excitability of the central nervous system, as revealed by the average frequency of the fusing and flickering of the light stimulus. A single session of high intensity whole-body vibration did not significantly decrease the excitability of the peripheral nervous system while the central nervous system did not seem to be affected. PMID:25114735

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

    PubMed

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

    2017-04-01

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

  4. Effects of physical exercise on central nervous system functions: a review of brain region specific adaptations.

    PubMed

    Morgan, Julie A; Corrigan, Frances; Baune, Bernhard T

    2015-01-01

    Pathologies of central nervous system (CNS) functions are involved in prevalent conditions such as Alzheimer's disease, depression, and Parkinson's disease. Notable pathologies include dysfunctions of circadian rhythm, central metabolism, cardiovascular function, central stress responses, and movement mediated by the basal ganglia. Although evidence suggests exercise may benefit these conditions, the neurobiological mechanisms of exercise in specific brain regions involved in these important CNS functions have yet to be clarified. Here we review murine evidence about the effects of exercise on discrete brain regions involved in important CNS functions. Exercise effects on circadian rhythm, central metabolism, cardiovascular function, stress responses in the brain stem and hypothalamic pituitary axis, and movement are examined. The databases Pubmed, Web of Science, and Embase were searched for articles investigating regional brain adaptations to exercise. Brain regions examined included the brain stem, hypothalamus, and basal ganglia. We found evidence of multiple regional adaptations to both forced and voluntary exercise. Exercise can induce molecular adaptations in neuronal function in many instances. Taken together, these findings suggest that the regional physiological adaptations that occur with exercise could constitute a promising field for elucidating molecular and cellular mechanisms of recovery in psychiatric and neurological health conditions.

  5. 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.

  6. Identification of N-glycosylated proteins from the central nervous system of Drosophila melanogaster.

    PubMed

    Koles, Kate; Lim, Jae-Min; Aoki, Kazuhiro; Porterfield, Mindy; Tiemeyer, Michael; Wells, Lance; Panin, Vlad

    2007-12-01

    Although the function of many glycoproteins in the nervous system of fruit flies is well understood, information about the glycosylation profile and glycan attachment sites for such proteins is scarce. In order to fill this gap and to facilitate the analysis of N-linked glycosylation in the nervous system, we have performed an extensive survey of membrane-associated glycoproteins and their N-glycosylation sites isolated from the adult Drosophila brain. Following subcellular fractionation and trypsin digestion, we used different lectin affinity chromatography steps to isolate N-glycosylated glycopeptides. We identified a total of 205 glycoproteins carrying N-linked glycans and revealed their 307 N-glycan attachment sites. The size of the resulting dataset furthermore allowed the statistical characterization of amino acid distribution around the N-linked glycosylation sites. Glycan profiles were analyzed separately for glycopeptides that were strongly and weakly bound to Concanavalin A (Con A), or that failed to bind Concanavalin A, but did bind to wheat germ agglutinin (WGA). High- or paucimannosidic glycans dominated each of the profiles, although the wheat germ agglutinin-bound glycan population was enriched in more extensively processed structures. A sialylated glycan structure was unambiguously detected in the wheat germ agglutinin-bound fraction. Despite the large amount of starting material, insufficient amount of glycopeptides was retained by the Wisteria floribunda (WFA) and Sambucus nigra columns to allow glycan or glycoprotein identification, providing further evidence that the vast majority of glycoproteins in the adult Drosophila brain carry primarily high-mannose, paucimannose, and hybrid glycans. The obtained results should facilitate future genetic and molecular approaches addressing the role of N-glycosylation in the central nervous system (CNS) of Drosophila.

  7. The tumor suppressor HHEX inhibits axon growth when prematurely expressed in developing central nervous system neurons

    PubMed Central

    Simpson, Matthew T; Venkatesh, Ishwariya; Callif, Ben L; Thiel, Laura K; Coley, Denise M; Winsor, Kristen N; Wang, Zimei; Kramer, Audra A; Lerch, Jessica K; Blackmore, Murray G

    2015-01-01

    Neurons in the embryonic and peripheral nervous system respond to injury by activating transcriptional programs supportive of axon growth, ultimately resulting in functional recovery. In contrast, neurons in the adult central nervous system (CNS) possess a limited capacity to regenerate axons after injury, fundamentally constraining repair. Activating pro-regenerative gene expression in CNS neurons is a promising therapeutic approach, but progress is hampered by incomplete knowledge of the relevant transcription factors. An emerging hypothesis is that factors implicated in cellular growth and motility outside the nervous system may also control axon growth in neurons. We therefore tested sixty-nine transcription factors, previously identified as possessing tumor suppressive or oncogenic properties in non-neuronal cells, in assays of neurite outgrowth. This screen identified YAP1 and E2F1 as enhancers of neurite outgrowth, and PITX1, RBM14, ZBTB16, and HHEX as inhibitors. Follow-up experiments focused on the tumor suppressor HHEX, one of the strongest growth inhibitors. HHEX is widely expressed in adult CNS neurons, including corticospinal tract neurons after spinal injury, but is present in only trace amounts in immature cortical neurons and adult peripheral neurons. HHEX overexpression in early postnatal cortical neurons reduced both initial axonogenesis and the rate of axon elongation, and domain deletion analysis strongly implicated transcriptional repression as the underlying mechanism. These findings suggest a role for HHEX in restricting axon growth in the developing CNS, and substantiate the hypothesis that previously identified oncogenes and tumor suppressors can play conserved roles in axon extension. PMID:26306672

  8. SOD1 Lysine 123 Acetylation in the Adult Central Nervous System.

    PubMed

    Kaliszewski, Michael; Kennedy, Austin K; Blaes, Shelby L; Shaffer, Robert S; Knott, Andrew B; Song, Wenjun; Hauser, Henry A; Bossy, Blaise; Huang, Ting-Ting; Bossy-Wetzel, Ella

    2016-01-01

    Superoxide dismutase 1 (SOD1) knockout (Sod1(-/-)) mice exhibit an accelerated aging phenotype. In humans, SOD1 mutations are linked to familial amyotrophic lateral sclerosis (ALS), and post-translational modification (PTM) of wild-type SOD1 has been associated with sporadic ALS. Reversible acetylation regulates many enzymes and proteomic studies have identified SOD1 acetylation at lysine 123 (K123). The function and distribution of K123-acetylated SOD1 (Ac-K123 SOD1) in the nervous system is unknown. Here, we generated polyclonal rabbit antibodies against Ac-K123 SOD1. Sod1 deletion in Sod1(-/-) mice, K123 mutation or preabsorption with Ac-K123 peptide all abolished antibody binding. Using immunohistochemistry, we assessed Ac-K123 SOD1 distribution in the normal adult mouse nervous system. In the cerebellum, Ac-K123 SOD1 staining was prominent in cell bodies of the granular cell layer (GCL) and Purkinje cell dendrites and interneurons of the molecular cell layer. In the hippocampus, Ac-K123 SOD1 staining was strong in the fimbria, subiculum, pyramidal cells and Schaffer collateral fibers of the cornus ammonis field 1 (CA1) region and granule and neuronal progenitor cells of the dentate gyrus. In addition, labeling was observed in the choroid plexus (CP) and the ependyma of the brain ventricles and central canal of the spinal cord. In the olfactory bulb, Ac-K123 SOD1 staining was prominent in axons of sensory neurons, in cell bodies of interneurons and neurites of the mitral and tufted cells. In the retina, labeling was strong in the retinal ganglion cell layer (RGCL) and axons of retinal ganglion cells (RGCs), the inner nuclear layer (INL) and cone photoreceptors of the outer nuclear layer (ONL). In summary, our findings describe Ac-K123 SOD1 distribution to distinct regions and cell types of the normal nervous system.

  9. SOD1 Lysine 123 Acetylation in the Adult Central Nervous System

    PubMed Central

    Kaliszewski, Michael; Kennedy, Austin K.; Blaes, Shelby L.; Shaffer, Robert S.; Knott, Andrew B.; Song, Wenjun; Hauser, Henry A.; Bossy, Blaise; Huang, Ting-Ting; Bossy-Wetzel, Ella

    2016-01-01

    Superoxide dismutase 1 (SOD1) knockout (Sod1−/−) mice exhibit an accelerated aging phenotype. In humans, SOD1 mutations are linked to familial amyotrophic lateral sclerosis (ALS), and post-translational modification (PTM) of wild-type SOD1 has been associated with sporadic ALS. Reversible acetylation regulates many enzymes and proteomic studies have identified SOD1 acetylation at lysine 123 (K123). The function and distribution of K123-acetylated SOD1 (Ac-K123 SOD1) in the nervous system is unknown. Here, we generated polyclonal rabbit antibodies against Ac-K123 SOD1. Sod1 deletion in Sod1−/− mice, K123 mutation or preabsorption with Ac-K123 peptide all abolished antibody binding. Using immunohistochemistry, we assessed Ac-K123 SOD1 distribution in the normal adult mouse nervous system. In the cerebellum, Ac-K123 SOD1 staining was prominent in cell bodies of the granular cell layer (GCL) and Purkinje cell dendrites and interneurons of the molecular cell layer. In the hippocampus, Ac-K123 SOD1 staining was strong in the fimbria, subiculum, pyramidal cells and Schaffer collateral fibers of the cornus ammonis field 1 (CA1) region and granule and neuronal progenitor cells of the dentate gyrus. In addition, labeling was observed in the choroid plexus (CP) and the ependyma of the brain ventricles and central canal of the spinal cord. In the olfactory bulb, Ac-K123 SOD1 staining was prominent in axons of sensory neurons, in cell bodies of interneurons and neurites of the mitral and tufted cells. In the retina, labeling was strong in the retinal ganglion cell layer (RGCL) and axons of retinal ganglion cells (RGCs), the inner nuclear layer (INL) and cone photoreceptors of the outer nuclear layer (ONL). In summary, our findings describe Ac-K123 SOD1 distribution to distinct regions and cell types of the normal nervous system. PMID:28066183

  10. 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

  11. Kynurenines and Multiple Sclerosis: The Dialogue between the Immune System and the Central Nervous System.

    PubMed

    Rajda, Cecilia; Majláth, Zsófia; Pukoli, Dániel; Vécsei, László

    2015-08-06

    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.

  12. 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

  13. 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

  14. Development of the serotonergic system in the central nervous system of the sea lamprey.

    PubMed

    Abalo, Xesús M; Villar-Cheda, Begoña; Meléndez-Ferro, Miguel; Pérez-Costas, Emma; Anadón, Ramón; Rodicio, María Celina

    2007-09-01

    Lampreys belong to the most primitive extant group of vertebrates, the Agnathans, which is considered the sister group of jawed vertebrates. Accordingly, characterization of neuronal groups and their development appears useful for understanding early evolution of the nervous system in vertebrates. Here, the development of the serotonergic system in the central nervous system of the sea lamprey, Petromyzon marinus, was investigated by immunohistochemical analysis of specimens ranging from embryos to adults. The different serotonin-immunoreactive (5-HT-ir) neuronal populations that are found in adults were observed between the embryonic and metamorphic stages. The earliest serotonergic neurons were observed in the basal plate of the isthmus region of late embryos. In prolarvae, progressive appearance of new serotonergic cell groups was observed: firstly in the spinal cord, then in the pineal organ, tuberal region, zona limitans intrathalamica, rostral isthmus, and the caudal part of the rhombencephalon. In early larvae a new group of serotonergic cells was observed in the mammillary region, whereas in the pretectal region and the parapineal organ the first serotonergic cells were seen in the middle and late larval stages, respectively. The first serotonergic fibres appeared in early prolarvae, with fibres that ascend and descend from the isthmic cell group, and the number of immunoreactive fibres increased progressively until the adult stage. The results reveal strong resemblances between lampreys and other vertebrates in the spatio-temporal pattern of development of brainstem populations. This study also reveals a shared pattern of early ascending and descending serotonergic pathways in lampreys and jawed vertebrates.

  15. Peripheral Nervous System Genes Expressed in Central Neurons Induce Growth on Inhibitory Substrates

    PubMed Central

    Buchser, William J.; Smith, Robin P.; Pardinas, Jose R.; Haddox, Candace L.; Hutson, Thomas; Moon, Lawrence; Hoffman, Stanley R.; Bixby, John L.; Lemmon, Vance P.

    2012-01-01

    Trauma to the spinal cord and brain can result in irreparable loss of function. This failure of recovery is in part due to inhibition of axon regeneration by myelin and chondroitin sulfate proteoglycans (CSPGs). Peripheral nervous system (PNS) neurons exhibit increased regenerative ability compared to central nervous system neurons, even in the presence of inhibitory environments. Previously, we identified over a thousand genes differentially expressed in PNS neurons relative to CNS neurons. These genes represent intrinsic differences that may account for the PNS’s enhanced regenerative ability. Cerebellar neurons were transfected with cDNAs for each of these PNS genes to assess their ability to enhance neurite growth on inhibitory (CSPG) or permissive (laminin) substrates. Using high content analysis, we evaluated the phenotypic profile of each neuron to extract meaningful data for over 1100 genes. Several known growth associated proteins potentiated neurite growth on laminin. Most interestingly, novel genes were identified that promoted neurite growth on CSPGs (GPX3, EIF2B5, RBMX). Bioinformatic approaches also uncovered a number of novel gene families that altered neurite growth of CNS neurons. PMID:22701605

  16. Conditional Mutation of Rb Causes Cell Cycle Defects without Apoptosis in the Central Nervous System

    PubMed Central

    MacPherson, D.; Sage, J.; Crowley, D.; Trumpp, A.; Bronson, R. T.; Jacks, T.

    2003-01-01

    Targeted disruption of the retinoblastoma gene in mice leads to embryonic lethality in midgestation accompanied by defective erythropoiesis. Rb−/− embryos also exhibit inappropriate cell cycle activity and apoptosis in the central nervous system (CNS), peripheral nervous system (PNS), and ocular lens. Loss of p53 can prevent the apoptosis in the CNS and lens; however, the specific signals leading to p53 activation have not been determined. Here we test the hypothesis that hypoxia caused by defective erythropoiesis in Rb-null embryos contributes to p53-dependent apoptosis. We show evidence of hypoxia in CNS tissue from Rb−/− embryos. The Cre-loxP system was then used to generate embryos in which Rb was deleted in the CNS, PNS and lens, in the presence of normal erythropoiesis. In contrast to the massive CNS apoptosis in Rb-null embryos at embryonic day 13.5 (E13.5), conditional mutants did not have elevated apoptosis in this tissue. There was still significant apoptosis in the PNS and lens, however. Rb−/− cells in the CNS, PNS, and lens underwent inappropriate S-phase entry in the conditional mutants at E13.5. By E18.5, conditional mutants had increased brain size and weight as well as defects in skeletal muscle development. These data support a model in which hypoxia is a necessary cofactor in the death of CNS neurons in the developing Rb mutant embryo. PMID:12529408

  17. 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

  18. 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

  19. 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.

  20. Pyrokinin/PBAN-like peptides in the central nervous system of mosquitoes.

    PubMed

    Hellmich, Erica; Nusawardani, Tyasning; Bartholomay, Lyric; Jurenka, Russell

    2014-04-01

    The pyrokinin/pheromone biosynthesis activating neuropeptide (PBAN) family of peptides is characterized by a common C-terminal pentapeptide, FXPRLamide, which is required for diverse physiological functions in various insects. Polyclonal antisera against the C-terminus was utilized to determine the location of cell bodies and axons in the central nervous systems of larval and adult mosquitoes. Immunoreactive material was detected in three groups of neurons in the subesophageal ganglion of larvae and adults. The corpora cardiaca of both larvae and adults contained immunoreactivity indicating potential release into circulation. The adult and larval brains had at least one pair of immunoreactive neurons in the protocerebrum with the adult brain having additional immunoreactive neurons in the dorsal medial part of the protocerebrum. The ventral ganglia of both larvae and adults each contained one pair of neurons that sent their axons to a perisympathetic organ associated with each abdominal ganglion. These results indicate that the mosquito nervous system contains pyrokinin/PBAN-like peptides and that these peptides could be released into the hemolymph. The peptides in insects and mosquitoes are produced by two genes, capa and pk/pban. Utilizing PCR protocols, we demonstrate that products of the capa gene could be produced in the abdominal ventral ganglia and the products of the pk/pban gene could be produced in the subesophageal ganglion. Two receptors for pyrokinin peptides were differentially localized to various tissues.