Science.gov

Sample records for affect nervous system

  1. Degenerative disease affecting the nervous system.

    PubMed

    Eadie, M J

    1974-03-01

    The term "degenerative disease" is one which is rather widely used in relation to the nervous system and yet one which is rarely formally and carefully defined. The term appears to be applied to disorders of the nervous system which often occur in later life and which are of uncertain cause. In the Shorter Oxford Dictionary the word degeneration is defined as "a change of structure by which an organism, or an organ, assumes the form of a lower type". However this is not quite the sense in which the word is applied in human neuropathology, where it is conventional to restrict the use of the word to those organic disorders which are of uncertain or poorly understood cause and in which there is a deterioration or regression in the level of functioning of the nervous system. The concept of degenerative disorder is applied to other organs as well as to the brain, and as disease elsewhere in the body may affect the nervous system, it seems reasonable to include within the topic of degenerative disorder affecting the nervous system those conditions in which the nervous system is involved as a result of primary degenerations in other parts of the body. PMID:25026144

  2. Degenerative disease affecting the nervous system.

    PubMed

    Eadie, M J

    1974-03-01

    The term "degenerative disease" is one which is rather widely used in relation to the nervous system and yet one which is rarely formally and carefully defined. The term appears to be applied to disorders of the nervous system which often occur in later life and which are of uncertain cause. In the Shorter Oxford Dictionary the word degeneration is defined as "a change of structure by which an organism, or an organ, assumes the form of a lower type". However this is not quite the sense in which the word is applied in human neuropathology, where it is conventional to restrict the use of the word to those organic disorders which are of uncertain or poorly understood cause and in which there is a deterioration or regression in the level of functioning of the nervous system. The concept of degenerative disorder is applied to other organs as well as to the brain, and as disease elsewhere in the body may affect the nervous system, it seems reasonable to include within the topic of degenerative disorder affecting the nervous system those conditions in which the nervous system is involved as a result of primary degenerations in other parts of the body.

  3. 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

  4. 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.

  5. 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. PMID:26580325

  6. [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.

  7. Aspects on antidote therapy in acute poisoning affecting the nervous system.

    PubMed

    Persson, H

    1984-01-01

    The number of toxic substances affecting the nervous system through acute or chronic exposure is overwhelming. This survey will elucidate the possibilities of antidote therapy in some acute cases of poisoning, caused by nervous system toxicants. Antidotes exert their therapeutic effects through a variety of mechanisms: Adsorption, formation of inert complexes, inhibited conversion to toxic metabolites, enhancement of endogenous detoxification, interference at receptor sites, and physiological antagonism. The application of these principles in treating some poisonings caused by important nervous system toxicants will be considered. This survey is by no means comprehensive, but rather gives some relevant examples and deals only with acute poisoning.

  8. [Differential diagnosis of late-stage neuroborreliosis with affection of the central nervous system].

    PubMed

    Spirin, N N; Baranova, N S; Fadeeva, O A; Pakhomova, Iu A; Stepanov, I O; Shipova, E G; Kasatkin, D S; Spirina, N N

    2012-01-01

    Chronic neuroborreliosis is an actual problem in neurology due to its under-investigation in Russia, variety of clinical forms, and the absence of well established diagnostic criteria. We present clinical and laboratory differential diagnostic criteria of chronic borrelial encephalomyelitis in comparison with multiple sclerosis. Distinguishing characteristics of Lyme encephalopathy versus vascular encephalopathy are considered. Problems and possibilities of immunological methods for identification of B. burgdorferi are discussed. The results of the antibiotic treatment of different clinical forms of neuroborreliosis with affection of the central nervous system are described.

  9. Autonomic Nervous System Disorders

    MedlinePlus

    Your autonomic nervous system is the part of your nervous system that controls involuntary actions, such as the beating of your heart ... breathing and swallowing Erectile dysfunction in men Autonomic nervous system disorders can occur alone or as the result ...

  10. Gender affects rats' central nervous system histaminergic responses to dietary manipulation.

    PubMed

    Mercer, L P; Kelley, D S; Bundrant, H M; Haq, A U; Humphries, L L

    1996-12-01

    The histaminergic system (histamine and its H1-receptor) of the central nervous system has been implicated in control of food intake. The reported studies were designed to examine the effects of food restriction and very low (1%) protein diets on central nervous system H1-receptors in male and female rats. In a series of experiments, groups of rats were freely fed a 25% protein diet, a 1% protein diet, or fed the 25% protein diet at 4 g/100 g body weight for 14-20 d. When freely fed 25% protein diets, females had higher whole-brain H1-receptor binding than males on d 1 (female 122.36 +/- 4.53 and male 65.78 +/- 3.82 pmol/g protein; P < 0.001). Changing diets affected central H1-receptor binding in both males and females (P < 0.003). When rats were fed both restricted levels of food and 1% protein diets, the receptor binding of males increased by d 5 whereas that of females decreased by d 5 (P < 0.001). When fed 1% protein diets, females had decreased H1-receptor binding (98.4 +/- 2.38 pmol/g protein) and that in males increased to 119.81 +/- 5.09 pmol/g protein. After 15 d, females had eaten significantly more food than males: females 166 +/- 4.9 g, males 124 +/- 1.9 g (P< 0.0007). Males had a significantly greater weight loss than females: males -28.8 +/- 2.6 g, females -17.08 +/- 0.97 g (P < 0.0007). When fed restricted diets, females had decreased H1-receptor binding (93.81 +/- 5.58 pmol/g) whereas binding in males increased to 111.27 +/- 8.55 pmol/g. Preliminary saturation binding studies indicated that restricted food intake lowered receptor density (females consuming 25% protein: 715 +/- 30 pmol/g protein; female restricted: 467 +/- 28 pmol/g protein, P < 0.05), while 1% protein increased receptor sensitivity, i.e., lowered KD (males consuming 25% protein: 15.3 +/- 1.8 nmol; males fed low protein: 2.8 +/- 0.27 nmol). This study suggests that dietary manipulation affects central H1-receptor binding in a gender-specific manner, thereby modulating central

  11. 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.

  12. P-element mutations affecting embryonic peripheral nervous system development in Drosophila melanogaster

    SciTech Connect

    Kania, A.; Salzberg, A.; Bhat, M.

    1995-04-01

    The Drosophila embryonic peripheral nervous system (PNS) is an excellent model system to study the molecular mechanisms governing neural development. To identify genes controlling PNS development, we screened 2000 lethal P-element insertion strains. The PNS of mutant embryos was examined using the neural specific marker MAb 22C10, and 92 mutant strains were retained for further analysis. Genetic and cytological analysis of these strains shows that 42 mutations affect previously isolated genes that are known to be required for PNS development: longitudinals lacking (19), mastermind (15), numb (4), big brain (2), and spitz (2). The remaining 50 mutations were classified into 29 complementation groups and the P-element insertions were cytologically mapped. The mutants were classified in five major classes on the basis of their phenotype: gain of neurons, loss of neurons, organizational defects, pathfinding defects and morphological defects. Herein we report the preliminary phenotypic characterization of each of these complementation groups as well as the embryonic lacZ expression pattern of each P-element strain. Our analysis indicates that in most of the P-element insertion strains, the lacZ reporter gene is not expressed in the developing PNS. 52 refs., 5 figs., 5 tabs.

  13. IL-9 signaling affects central nervous system resident cells during inflammatory stimuli.

    PubMed

    Ding, Xiaoli; Cao, Fang; Cui, Langjun; Ciric, Bogoljub; Zhang, Guang-Xian; Rostami, Abdolmohamad

    2015-12-01

    Interleukin (IL) 9, a dominant cytokine in Th9 cells, has been proven to play a pathogenic role in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), by augmenting T cell activation and differentiation; however, whether IL-9 signaling affects central nervous system (CNS)-resident cells during CNS autoimmunity remains unknown. In the present study, we found that the IL-9 receptor (IL-9R) was highly expressed in astrocytes, oligodendrocyte progenitor cells (OPCs), oligodendrocytes and microglia cells, and that its expression was significantly upregulated in brain and spinal cord during EAE. In addition, IL-9 increased chemokine expression, including CXCL9, CCL20 and MMP3, in primary astrocytes. Although IL-9 had no effect on the proliferation of microglia cells, it decreased OPC proliferation and differentiation when in combination with other pro-inflammatory cytokines, but not with IFN-γ. IL-9 plus IFN-γ promoted OPC proliferation and differentiation. These findings indicate that CNS-restricted IL-9 signaling may be involved in the pathogenesis of MS/EAE, thus providing a potential therapeutic target for future MS/EAE treatment through disruption of CNS cell-specific IL-9 signaling.

  14. Nervous system Lyme disease.

    PubMed

    Halperin, John J

    2014-01-01

    Lyme disease, the multisystem infectious disease caused by the tick-borne spirochete Borrelia burgdorferi involves the nervous system in 10-15% of affected individuals. Manifestations include lymphocytic meningitis, cranial neuritis, radiculoneuritis, and mononeuropathy multiplex. Encephalopathy, identical to that seen in many systemic inflammatory diseases, can occur during active systemic infection. It is not specific to Lyme disease and only rarely is evidence of nervous system infection. Diagnosis of systemic disease is based on demonstration of specific antibodies in peripheral blood by means of two-tier testing with an ELISA and Western blot. Central nervous system infection often results in specific antibody production in the CSF, demonstrable by comparing spinal fluid to blood serologies. Treatment is straightforward and curative in most instances. Many patients can be treated effectively with oral antibiotics such as doxycycline; in severe CNS infection parenteral treatment with ceftriaxone or other similar agents is highly effective. Treatment should usually be for 2 to at most 4 weeks. Longer treatment adds no therapeutic benefit but does add substantial risk.

  15. Radiation from wireless technology affects the blood, the heart, and the autonomic nervous system.

    PubMed

    Havas, Magda

    2013-01-01

    Exposure to electrosmog generated by electric, electronic, and wireless technology is accelerating to the point that a portion of the population is experiencing adverse reactions when they are exposed. The symptoms of electrohypersensitivity (EHS), best described as rapid aging syndrome, experienced by adults and children resemble symptoms experienced by radar operators in the 1940s to the 1960s and are well described in the literature. An increasingly common response includes clumping (rouleau formation) of the red blood cells, heart palpitations, pain or pressure in the chest accompanied by anxiety, and an upregulation of the sympathetic nervous system coincident with a downregulation of the parasympathetic nervous system typical of the "fight-or-flight" response. Provocation studies presented in this article demonstrate that the response to electrosmog is physiologic and not psychosomatic. Those who experience prolonged and severe EHS may develop psychologic problems as a consequence of their inability to work, their limited ability to travel in our highly technologic environment, and the social stigma that their symptoms are imagined rather than real.

  16. Nervous System Lyme Disease.

    PubMed

    Halperin, John J

    2015-12-01

    Nervous system involvement occurs in 10% to 15% of patients infected with the tick-borne spirochetes Borrelia burgdorferi, B afzelii, and B garinii. Peripheral nervous system involvement is common. Central nervous system (CNS) involvement, most commonly presenting with lymphocytic meningitis, causes modest cerebrospinal fluid (CSF) pleocytosis. Parenchymal CNS infection is rare. If the CNS is invaded, however, measuring local production of anti-B burgdorferi antibodies in the CSF provides a useful marker of infection. Most cases of neuroborreliosis can be cured with oral doxycycline; parenteral regimens should be reserved for patients with particularly severe disease.

  17. 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.

  18. The Nervous System Game

    ERIC Educational Resources Information Center

    Corbitt, Cynthia; Carpenter, Molly

    2006-01-01

    For many children, especially those with reading difficulties, a motor-kinesthetic learning activity may be an effective tool to teach complex concepts. With this in mind, the authors developed and tested a game designed to teach fourth- to sixth-grade children some basic principles of nervous system function by allowing the children themselves to…

  19. 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...

  20. Nervous system lyme disease.

    PubMed

    Halperin, John J

    2015-01-01

    Lyme disease, a multisystem spirochetal infection, continues to be the subject of considerable debate, but not controversy. Recent years have seen improvements in diagnostic tools, better understanding of pathophysiology, and increasing evidence of efficacy of standard treatment regimens. Nervous system involvement is particularly confusing to patients and many physicians. A rational approach based on objective findings can clarify the cause and dictate the best treatment of patients' difficulties. Diagnosis for all but the earliest cases rests on the combination of likely contact with infected Ixodes ticks and laboratory confirmation of exposure to the causative organism, Borrelia burgdorferi (two-tier serology, combining ELISA with a confirmatory Western blot). Treatment is generally with oral antimicrobials such as doxycycline. Parenteral regimens are usually necessary only for the most severe cases.

  1. Central Nervous System Lipoproteins

    PubMed Central

    Mahley, Robert W.

    2016-01-01

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

  2. Nervous System Complexity Baffles Scientists.

    ERIC Educational Resources Information Center

    Fox, Jeffrey L.

    1982-01-01

    New research findings about how nerve cells transmit signals are forcing researchers to overhaul their simplistic ideas about the nervous system. Topics highlighted include the multiple role of peptides in the nervous system, receptor molecules, and molecules that form ion channels within membranes. (Author/JN)

  3. Extracellular Matrix: Functions in the Nervous System

    PubMed Central

    Barros, Claudia S.; Franco, Santos J.; Müller, Ulrich

    2011-01-01

    An astonishing number of extracellular matrix glycoproteins are expressed in dynamic patterns in the developing and adult nervous system. Neural stem cells, neurons, and glia express receptors that mediate interactions with specific extracellular matrix molecules. Functional studies in vitro and genetic studies in mice have provided evidence that the extracellular matrix affects virtually all aspects of nervous system development and function. Here we will summarize recent findings that have shed light on the specific functions of defined extracellular matrix molecules on such diverse processes as neural stem cell differentiation, neuronal migration, the formation of axonal tracts, and the maturation and function of synapses in the peripheral and central nervous system. PMID:21123393

  4. Autonomic nervous system and immune system interactions.

    PubMed

    Kenney, M J; Ganta, C K

    2014-07-01

    The present review assesses the current state of literature defining integrative autonomic-immune physiological processing, focusing on studies that have employed electrophysiological, pharmacological, molecular biological, and central nervous system experimental approaches. Central autonomic neural networks are informed of peripheral immune status via numerous communicating pathways, including neural and non-neural. Cytokines and other immune factors affect the level of activity and responsivity of discharges in sympathetic and parasympathetic nerves innervating diverse targets. Multiple levels of the neuraxis contribute to cytokine-induced changes in efferent parasympathetic and sympathetic nerve outflows, leading to modulation of peripheral immune responses. The functionality of local sympathoimmune interactions depends on the microenvironment created by diverse signaling mechanisms involving integration between sympathetic nervous system neurotransmitters and neuromodulators; specific adrenergic receptors; and the presence or absence of immune cells, cytokines, and bacteria. Functional mechanisms contributing to the cholinergic anti-inflammatory pathway likely involve novel cholinergic-adrenergic interactions at peripheral sites, including autonomic ganglion and lymphoid targets. Immune cells express adrenergic and nicotinic receptors. Neurotransmitters released by sympathetic and parasympathetic nerve endings bind to their respective receptors located on the surface of immune cells and initiate immune-modulatory responses. Both sympathetic and parasympathetic arms of the autonomic nervous system are instrumental in orchestrating neuroimmune processes, although additional studies are required to understand dynamic and complex adrenergic-cholinergic interactions. Further understanding of regulatory mechanisms linking the sympathetic nervous, parasympathetic nervous, and immune systems is critical for understanding relationships between chronic disease

  5. Human nervous system function emulator.

    PubMed

    Frenger, P

    2000-01-01

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

  6. The Nervous System and Gastrointestinal Function

    ERIC Educational Resources Information Center

    Altaf, Muhammad A.; Sood, Manu R.

    2008-01-01

    The enteric nervous system is an integrative brain with collection of neurons in the gastrointestinal tract which is capable of functioning independently of the central nervous system (CNS). The enteric nervous system modulates motility, secretions, microcirculation, immune and inflammatory responses of the gastrointestinal tract. Dysphagia,…

  7. [Plasmapheresis in central nervous system disorders].

    PubMed

    Antozzi, Carlo

    2012-01-01

    Therapeutic plasmapheresis (TPE) has an established role in disorders of the peripheral nervous system, but its use in disorders of the central nervous system (CNS) does not rely upon evidence-based data. Nevertheless, TPE is currently used in severe acute forms of demyelinating disease (multiple sclerosis/acute encephalomyelitis) unresponsive to corticosteroids. Recently, antibodies against the water channel aquaporin-4 have been detected in patients affected by neuromyelitis optica (Devic syndrome) and their pathogenetic role has been demonstrated, supporting the use of TPE in this disease. TPE has been reported to be effective in some patients affected by stiff-person syndrome or limbic encephalitis associated with antibodies against voltagegated potassium channels. TPE has also been used in selected patients with treatment-resistant epilepsy or status epilepticus within complex syndromes of various etiologies. The available data still do not support the use of TPE in most paraneoplastic disorders of the CNS. PMID:22388844

  8. Peripheral Nervous System Manifestations of Infectious Diseases

    PubMed Central

    Brizzi, Kate T.

    2014-01-01

    Infectious causes of peripheral nervous system (PNS) disease are underrecognized but potentially treatable. Heightened awareness educed by advanced understanding of the presentations and management of these infections can aid diagnosis and facilitate treatment. In this review, we discuss the clinical manifestations, diagnosis, and treatment of common bacterial, viral, and parasitic infections that affect the PNS. We additionally detail PNS side effects of some frequently used antimicrobial agents. PMID:25360209

  9. Glucocorticoids and nervous system plasticity.

    PubMed

    Madalena, Kathryn M; Lerch, Jessica K

    2016-01-01

    Glucocorticoid and glucocorticoid receptor (GC/GR) interactions alter numerous aspects of neuronal function. These consequences (e.g., anti-inflammatory vs. pro-inflammatory) can vary depending on the duration of GC exposure or central nervous system (CNS) injury model. In this review we discuss how GC/GR interactions impact neuronal recovery after a central or peripheral nerve injury and discuss how GC exposure duration can produce divergent CNS neuronal growth responses. Finally we consider how new findings on gender specific immune cell responses after a nerve injury could intersect with GC/GR interactions to impact pain processing. PMID:26981074

  10. Central Nervous System Device Infections.

    PubMed

    Hasbun, Rodrigo

    2016-11-01

    Nosocomial meningitis can occur in association with central nervous system (CNS) devices such as cerebrospinal shunts or drains, intrathecal pumps, and deep brain stimulators and carry substantial morbidity and mortality. Diagnosing and treating these infections may be challenging to physicians as cerebrospinal fluid cultures may be negative due to previous antibiotic therapy and cerebrospinal abnormalities may be secondary to the primary neurosurgical issue that prompted the placement of the CNS device (e.g., "chemical meningitis" due to intracranial hemorrhage). Besides antibiotic therapy given intravenously and sometimes intrathecally, removal of the device with repeat cultures prior to re-implantation is key in achieving successful outcomes. PMID:27686676

  11. Lavender and the Nervous System

    PubMed Central

    Koulivand, Peir Hossein; Khaleghi Ghadiri, Maryam; Gorji, Ali

    2013-01-01

    Lavender is traditionally alleged to have a variety of therapeutic and curative properties, ranging from inducing relaxation to treating parasitic infections, burns, insect bites, and spasm. There is growing evidence suggesting that lavender oil may be an effective medicament in treatment of several neurological disorders. Several animal and human investigations suggest anxiolytic, mood stabilizer, sedative, analgesic, and anticonvulsive and neuroprotective properties for lavender. These studies raised the possibility of revival of lavender therapeutic efficacy in neurological disorders. In this paper, a survey on current experimental and clinical state of knowledge about the effect of lavender on the nervous system is given. PMID:23573142

  12. Glucocorticoids and nervous system plasticity

    PubMed Central

    Madalena, Kathryn M.; Lerch, Jessica K.

    2016-01-01

    Glucocorticoid and glucocorticoid receptor (GC/GR) interactions alter numerous aspects of neuronal function. These consequences (e.g., anti-inflammatory vs. pro-inflammatory) can vary depending on the duration of GC exposure or central nervous system (CNS) injury model. In this review we discuss how GC/GR interactions impact neuronal recovery after a central or peripheral nerve injury and discuss how GC exposure duration can produce divergent CNS neuronal growth responses. Finally we consider how new findings on gender specific immune cell responses after a nerve injury could intersect with GC/GR interactions to impact pain processing. PMID:26981074

  13. Influence of thyroid in nervous system growth.

    PubMed

    Mussa, G C; Mussa, F; Bretto, R; Zambelli, M C; Silvestro, L

    2001-08-01

    Nervous system growth and differentiation are closely correlated with the presence of iodine and thyroid hormones in initial development stages. In the human species, encephalon maturation during the first quarter of pregnancy is affected according to recent studies by the transplacenta passage of maternal thyroid hormones while it depends on initial iodiothyronin secretion by the foetal gland after the 12th week of pregnancy. Thyroid hormone deficiency during nervous system development causes altered noble nervous cells, such as the pyramidal cortical and Purkinje cells, during glial cell proliferation and differentiation alike. Neurons present cell hypoplasia with reduced axon count, dendritic branching, synaptic spikes and interneuron connections. Oligodendrocytes decrease in number and average myelin content consequently drops. Biochemical studies on hypothyroid rats have demonstrated alterations to neuron intraplasmatic microtubule content and organisation, changed mitochondria number and arrangement and anomalies in T3 nuclear and citoplasmatic receptor maturation. Alterations to microtubules are probably responsible for involvement of the axon-dendrite system, and are the consequence of deficient thyroid hormone action on the mitochondria, the mitochondria enzymes and proteins associated with microtubules. Nuclear and citoplasmatic receptors have been identified and gene clonation studies have shown two families of nuclear receptors that include several sub-groups in their turn. A complex scheme of temporal and spatial expression of these receptors exists, so they probably contribute with one complementary function, although their physiological role differs. The action of thyroid hormones occurs by changing cell protein levels because of their regulation at the transcriptional or post-transcriptional level. Genes submitted to thyroid hormone control are either expressed by oligodendrytes, which are myelin protein coders or glial differentiation mediators, or

  14. Aquaporin Biology and Nervous System

    PubMed Central

    Barbara, Buffoli

    2010-01-01

    Our understanding of the movement of water through cell membranes has been greatly advanced by the discovery of a family of water-specific, membrane-channel proteins: the Aquaporins (AQPs). These proteins are present in organisms at all levels of life, and their unique permeability characteristics and distribution in numerous tissues indicate diverse roles in the regulation of water homeostasis. Phenotype analysis of AQP knock-out mice has confirmed the predicted role of AQPs in osmotically driven transepithelial fluid transport, as occurs in the urinary concentrating mechanism and glandular fluid secretion. Regarding their expression in nervous system, there are evidences suggesting that AQPs are differentially expressed in the peripheral versus central nervous system and that channel-mediated water transport mechanisms may be involved in cerebrospinal fluid formation, neuronal signal transduction and information processing. Moreover, a number of recent studies have revealed the importance of mammalian AQPs in both physiological and pathophysiological mechanisms and have suggested that pharmacological modulation of AQP expression and activity may provide new tools for the treatment of variety of human disorders in which water and small solute transport may be involved. For all the AQPs, new contributions to physiological functions are likely to be discovered with ongoing work in this rapidly expanding field of research. PMID:21119880

  15. Testing the autonomic nervous system.

    PubMed

    Freeman, Roy; Chapleau, Mark W

    2013-01-01

    Autonomic testing is used to define the role of the autonomic nervous system in diverse clinical and research settings. Because most of the autonomic nervous system is inaccessible to direct physiological testing, in the clinical setting the most widely used techniques entail the assessment of an end-organ response to a physiological provocation. The noninvasive measures of cardiovascular parasympathetic function involve the assessment of heart rate variability while the measures of cardiovascular sympathetic function assess the blood pressure response to physiological stimuli. Tilt-table testing, with or without pharmacological provocation, has become an important tool in the assessment of a predisposition to neurally mediated (vasovagal) syncope, the postural tachycardia syndrome, and orthostatic hypotension. Distal, postganglionic, sympathetic cholinergic (sudomotor) function may be evaluated by provoking axon reflex mediated sweating, e.g., the quantitative sudomotor axon reflex (QSART) or the quantitative direct and indirect axon reflex (QDIRT). The thermoregulatory sweat test provides a nonlocalizing measure of global pre- and postganglionic sudomotor function. Frequency domain analyses of heart rate and blood pressure variability, microneurography, and baroreflex assessment are currently research tools but may find a place in the clinical assessment of autonomic function in the future. PMID:23931777

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

    PubMed

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

    2013-09-01

    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.

  17. Sensitivity of the Autonomic Nervous System to Visual and Auditory Affect Across Social and Non-Social Domains in Williams Syndrome

    PubMed Central

    Järvinen, Anna; Dering, Benjamin; Neumann, Dirk; Ng, Rowena; Crivelli, Davide; Grichanik, Mark; Korenberg, Julie R.; Bellugi, Ursula

    2012-01-01

    Although individuals with Williams syndrome (WS) typically demonstrate an increased appetitive social drive, their social profile is characterized by dissociations, including socially fearless behavior coupled with anxiousness, and distinct patterns of “peaks and valleys” of ability. The aim of this study was to compare the processing of social and non-social visually and aurally presented affective stimuli, at the levels of behavior and autonomic nervous system (ANS) responsivity, in individuals with WS contrasted with a typically developing (TD) group, with the view of elucidating the highly sociable and emotionally sensitive predisposition noted in WS. Behavioral findings supported previous studies of enhanced competence in processing social over non-social stimuli by individuals with WS; however, the patterns of ANS functioning underlying the behavioral performance revealed a surprising profile previously undocumented in WS. Specifically, increased heart rate (HR) reactivity, and a failure for electrodermal activity to habituate were found in individuals with WS contrasted with the TD group, predominantly in response to visual social affective stimuli. Within the auditory domain, greater arousal linked to variation in heart beat period was observed in relation to music stimuli in individuals with WS. Taken together, the findings suggest that the pattern of ANS response in WS is more complex than previously noted, with increased arousal to face and music stimuli potentially underpinning the heightened behavioral emotionality to such stimuli. The lack of habituation may underlie the increased affiliation and attraction to faces characterizing individuals with WS. Future research directions are suggested. PMID:23049519

  18. Stress, sex, and the enteric nervous system.

    PubMed

    Million, M; Larauche, M

    2016-09-01

    Made up of millions of enteric neurons and glial cells, the enteric nervous system (ENS) is in a key position to modulate the secretomotor function and visceral pain of the gastrointestinal tract. The early life developmental period, through which most of the ENS development occurs, is highly susceptible to microenvironmental perturbation. Over the past decade, accumulating evidence has shown the impact of stress and early life adversity (ELA) on host gastrointestinal pathophysiology. While most of the focus has been on alterations in brain structure and function, limited experimental work in rodents suggest that the enteric nervous system can also be directly affected, as shown by changes in the number, phenotype, and reactivity of enteric nerves. The work of Medland et al. in the current issue of this journal demonstrates that such alterations also occur in pigs, a larger mammalian species with high translational value to human. This work also highlights a sex-differential susceptibility of the ENS to the effect of ELA, which could contribute to the higher prevalence of GI disorders in women. In this mini-review, we will discuss the development and composition of the ENS and related gastrointestinal sensory motor and secretory functions. We will then focus on the influence of stress on the enteric nervous system, with a particular emphasis on neurodevelopmental changes. Finally, we will discuss the influence of sex on those parameters. PMID:27561694

  19. Metal toxicity in the central nervous system

    SciTech Connect

    Clarkson, T.W.

    1987-11-01

    The nervous system is the principal target for a number of metals. 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 know 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 synthesis 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.

  20. Zolpidem, a clinical hypnotic that affects electronic transfer, alters synaptic activity through potential GABA receptors in the nervous system without significant free radical generation.

    PubMed

    Kovacic, Peter; Somanathan, Ratnasamy

    2009-01-01

    Zolpidem (trade name Ambien) has attracted much interest as a sleep-inducing agent and also in research. Attention has been centered mainly on receptor binding and electrochemistry in the central nervous system which are briefly addressed herein. A novel integrated approach to mode of action is presented. The pathways to be discussed involve basicity, reduction potential, electrostatics, cell signaling, GABA receptor binding, electron transfer (ET), pharmacodynamics, structure activity relationships (SAR) and side effects. The highly conjugated pyridinium salt formed by protonation of the amidine moiety is proposed to be the active form acting as an ET agent. Extrapolation of reduction potentials for related compounds supports the premise that zolpidem may act as an ET species in vivo. From recent literature reports, electrostatics is believed to play a significant role in drug action. The pyridinium cation displays molecular electrostatic potential which may well play a role energetically or as a bridging mechanism. An SAR analysis points to analogy with other physiologically active xenobiotics, namely benzodiazepines and paraquat in the conjugated iminium category. Inactivity of metabolites indicates that the parent is the active form of zolpidem. Absence of reactive oxygen species and oxidative stress is in line with minor side effects. In contrast, generally, the prior literature contains essentially no discussion of these fundamental biochemical relationships. Pharmacodynamics may play an important role. Concerning behavior at the blood-brain barrier, useful insight can be gained from investigations of the related cationic anesthetics that are structurally related to acetyl choline. Evidently, the neutral form of the drug penetrates the neuronal membrane, with the salt form operating at the receptor. The pathways of zolpidem have several clinical implications since the agent affects sedation, electroencephalographic activity, oxidative metabolites and

  1. Sympathetic nervous system and spaceflight

    NASA Astrophysics Data System (ADS)

    Cooke, William H.; Convertino, Victor A.

    2007-02-01

    Purpose: Orthostatic stability on Earth is maintained through sympathetic nerve activation sufficient to increase peripheral vascular resistance and defend against reductions of blood pressure. Orthostatic instability in astronauts upon return from space missions has been linked to blunted vascular resistance responses to standing, introducing the possibility that spaceflight alters normal function between sympathetic efferent traffic and vascular reactivity. Methods: We evaluated published results of spaceflight and relevant ground-based microgravity simulations in an effort to determine responses of the sympathetic nervous system and consequences for orthostatic stability. Results: Direct microneurographic recordings from humans in space revealed that sympathetic nerve activity is increased and preserved in the upright posture after return to Earth (STS-90). However, none of the astronauts studied during STS-90 presented with presyncope postflight, leaving unanswered the question of whether postflight orthostatic intolerance is associated with blunted sympathetic nerve responses or inadequate translation into vascular resistance. Conclusions: There is little evidence to support the concept that spaceflight induces fundamental sympathetic neuroplasticity. The available data seem to support the hypothesis that regardless of whether or not sympathetic traffic is altered during flight, astronauts return with reduced blood volumes and consequent heightened baseline sympathetic activity. Because of this, the ability to withstand an orthostatic challenge postflight is directly proportional to an astronaut's maximal sympathetic activation capacity and remaining sympathetic reserve.

  2. Ctr9, a Key Component of the Paf1 Complex, Affects Proliferation and Terminal Differentiation in the Developing Drosophila Nervous System

    PubMed Central

    Bahrampour, Shahrzad; Thor, Stefan

    2016-01-01

    The Paf1 protein complex (Paf1C) is increasingly recognized as a highly conserved and broadly utilized regulator of a variety of transcriptional processes. These include the promotion of H3K4 and H3K36 trimethylation, H2BK123 ubiquitination, RNA Pol II transcriptional termination, and also RNA-mediated gene silencing. Paf1C contains five canonical protein components, including Paf1 and Ctr9, which are critical for overall complex integrity, as well as Rtf1, Leo1, and Cdc73/Parafibromin(Hrpt2)/Hyrax. In spite of a growing appreciation for the importance of Paf1C from yeast and mammalian studies, there has only been limited work in Drosophila. Here, we provide the first detailed phenotypic study of Ctr9 function in Drosophila. We found that Ctr9 mutants die at late embryogenesis or early larval life, but can be partly rescued by nervous system reexpression of Ctr9. We observed a number of phenotypes in Ctr9 mutants, including increased neuroblast numbers, increased nervous system proliferation, as well as downregulation of many neuropeptide genes. Analysis of cell cycle and regulatory gene expression revealed upregulation of the E2f1 cell cycle factor, as well as changes in Antennapedia and Grainy head expression. We also found reduction of H3K4me3 modification in the embryonic nervous system. Genome-wide transcriptome analysis points to additional downstream genes that may underlie these Ctr9 phenotypes, revealing gene expression changes in Notch pathway target genes, cell cycle genes, and neuropeptide genes. In addition, we find significant effects on the gene expression of metabolic genes. These findings reveal that Ctr9 is an essential gene that is necessary at multiple stages of nervous system development, and provides a starting point for future studies of the Paf1C in Drosophila. PMID:27520958

  3. The sympathetic nervous system and heart failure.

    PubMed

    Zhang, David Y; Anderson, Allen S

    2014-02-01

    Heart failure (HF) is a syndrome characterized by upregulation of the sympathetic nervous system and abnormal responsiveness of the parasympathetic nervous system. Studies in the 1980s and 1990s demonstrated that inhibition of the renin-angiotensin-aldosterone system with angiotensin-converting enzyme inhibitors improved symptoms and mortality in HF resulting from systolic dysfunction, thus providing a framework to consider the use of β-blockers for HF therapy, contrary to the prevailing wisdom of the time. Against this backdrop, this article reviews the contemporary understanding of the sympathetic nervous system and the failing heart.

  4. [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.

  5. Parasitic diseases of the central nervous system.

    PubMed

    Abdel Razek, Ahmed Abdel Khalek; Watcharakorn, Arvemas; Castillo, Mauricio

    2011-11-01

    This article reviews the characteristic imaging appearances of parasitic diseases of the central nervous system, including cysticercosis, toxoplasmosis, cystic echinococcosis, schistosomiasis, amebiasis, malariasis, sparganosis, paragonimiasis, and American and African trypanosomiases. Routine precontrast and postcontrast MR imaging helps in localization, characterization, delineation of extension, and follow-up of the parasitic lesions. Moreover, recently developed tools, such as diffusion, perfusion, and MR spectroscopy, help to differentiate parasitic diseases of the central nervous system from simulating lesions. Combining imaging findings with geographic prevalence, clinical history, and serologic tests is required for diagnosis of parasitic diseases of the central nervous system.

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

    PubMed

    Schmutzhard, E

    2010-02-01

    Central nervous system infections and infestations by protozoa and helminths constitute a problem of increasing importance throughout all of central European and northern/western countries. This is partially due to the globalisation of our society, tourists and business people being more frequently exposed to parasitic infection/infestation in tropical countries than in moderate climate countries. On top of that, migrants may import chronic infestations and infections with parasitic pathogens, eventually also--sometimes exclusively--involving the nervous system. Knowledge of epidemiology, initial clinical signs and symptoms, diagnostic procedures as well as specific chemotherapeutic therapies and adjunctive therapeutic strategies is of utmost important in all of these infections and infestations of the nervous systems, be it by protozoa or helminths. This review lists, mainly in the form of tables, all possible infections and infestations of the nervous systems by protozoa and by helminths. Besides differentiating parasitic diseases of the nervous system seen in migrants, tourists etc., it is very important to have in mind that disease-related (e.g. HIV) or iatrogenic immunosuppression has led to the increased occurrence of a wide variety of parasitic infections and infestations of the nervous system (e. g. babesiosis, Chagas disease, Strongyloides stercoralis infestation, toxoplasmosis, etc.). PMID:20111855

  7. Autonomic nervous system functions in obese children.

    PubMed

    Yakinci, C; Mungen, B; Karabiber, H; Tayfun, M; Evereklioglu, C

    2000-05-01

    Childhood obesity is a complex syndrome, probably due to the multiplicity of contributing factors, contradictory literature information about etiology, prognosis, prevention and treatment. In the recent reports, autonomic nervous system (ANS) dysfunction has been documented in adult obesity. Autonomic nervous system functions in obese children are not clear. This study was planned to investigate autonomic nervous system function in childhood (7-13 years of age) obesity. Study and control groups consisted of 33 simple obese (23 boys and ten girls, mean age 9.5+/-1.4 years) and 30 healthy children (18 boys and 12 girls, mean age 10.1+/-1.8 years), respectively. Four non-invasive autonomic nervous system function tests (Orthostatic test, Valsalva ratio, 30/15 ratio, Heart rate responses to deep breathing) and general ophthalmic examination were performed on both groups. The difference between the obese and control groups was found statistically significant in Valsalva ratio, 30/15 ratio and Heart rate responses to deep breathing (P<0.025), and insignificant in Orthostatic test (P>0.05). Ophthalmic examinations were normal. The result of these tests suggested normal activity of sympathetic, and hypoactivity of parasympathetic nervous system, implying parasympathetic nervous system dysfunction as a risk factor or associated finding in childhood obesity. PMID:10814895

  8. [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.).

  9. Pathogenesis of central nervous system tuberculosis.

    PubMed

    Be, Nicholas A; Kim, Kwang Sik; Bishai, William R; Jain, Sanjay K

    2009-03-01

    Central Nervous System (CNS) tuberculosis is a serious, often fatal form of tuberculosis, predominantly affecting young children. HIV co-infection and drug resistant strains of Mycobacterium tuberculosis are making the diagnosis and treatment of CNS tuberculosis more complicated. Current concepts about the pathogenesis of CNS tuberculosis are based on necropsy studies done in 1933, which suggest that tuberculous meningitis develops subsequent to the rupture into the cerebrospinal fluid of tuberculomas that form around M. tuberculosis deposited in the brain parenchyma and meninges during the initial hematogenous dissemination. Foreign antigens including pathogens deposited in the brain parenchyma are not detected efficiently by the immune system in the CNS. These experimental data may explain the clinical observation of delayed "paradoxical" enlargement or development of intracranial tuberculomas, observed several weeks to months in patients receiving anti-tuberculous therapy. Since severe sequelae are observed even when CNS tuberculosis is treated effectively, it is important to develop preventive strategies for this disease. Recent data utilizing animal models suggests that, in addition to host factors, M. tuberculosis genes and their encoded proteins may contribute specifically to bacterial invasion and survival in the CNS. Understanding how these microbial factors affect CNS disease would be essential to developing such preventive strategies.

  10. 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.

  11. 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.

  12. Comparative anatomy of the autonomic nervous system.

    PubMed

    Nilsson, Stefan

    2011-11-16

    This short review aims to point out the general anatomical features of the autonomic nervous systems of non-mammalian vertebrates. In addition it attempts to outline the similarities and also the increased complexity of the autonomic nervous patterns from fish to tetrapods. With the possible exception of the cyclostomes, perhaps the most striking feature of the vertebrate autonomic nervous system is the similarity between the vertebrate classes. An evolution of the complexity of the system can be seen, with the segmental ganglia of elasmobranchs incompletely connected longitudinally, while well developed paired sympathetic chains are present in teleosts and the tetrapods. In some groups the sympathetic chains may be reduced (dipnoans and caecilians), and have yet to be properly described in snakes. Cranial autonomic pathways are present in the oculomotor (III) and vagus (X) nerves of gnathostome fish and the tetrapods, and with the evolution of salivary and lachrymal glands in the tetrapods, also in the facial (VII) and glossopharyngeal (IX) nerves.

  13. Protective autoimmunity in the nervous system.

    PubMed

    Graber, Jerome J; Dhib-Jalbut, Suhayl

    2009-02-01

    The immune system can play both detrimental and beneficial roles in the nervous system. Multiple arms of the immune system, including T cells, B cells, NK cells, mast cells, macrophages, dendritic cells, microglia, antibodies, complement and cytokines participate in limiting damage to the nervous system during toxic, ischemic, hemorrhagic, infective, degenerative, metabolic and immune-mediated insults and also assist in the process of repair after injury has occurred. Immune cells have been shown to produce neurotrophic growth factors and interact with neurons and glial cells to preserve them from injury and stimulate growth and repair. The immune system also appears to participate in proliferation of neural progenitor stem cells and their migration to sites of injury. Neural stem cells can also modify the immune response in the central and peripheral nervous system to enhance neuroprotective effects. Evidence for protective and reparative functions of the immune system has been found in diverse neurologic diseases including traumatic injury, ischemic and hemorrhagic stroke, multiple sclerosis, infection, and neurodegenerative diseases (Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis). Existing therapies including glatiramer acetate, interferon-beta and immunoglobulin have been shown to augment the protective and regenerative aspects of the immune system in humans, and other experimental interventions such as vaccination, minocycline, antibodies and neural stem cells, have shown promise in animal models of disease. The beneficent aspects of the immune response in the nervous system are beginning to be appreciated and their potential as pharmacologic targets in neurologic disease is being explored. PMID:19000712

  14. The Injured Nervous System: A Darwinian Perspective

    PubMed Central

    Weil, Zachary M.; Norman, Greg J.; DeVries, A. Courtney; Nelson, Randy J.

    2008-01-01

    Much of the permanent damage that occurs in response to nervous system damage (trauma, infection, ischemia, etc.) is mediated by endogenous secondary processes that can contribute to cell death and tissue damage (excitotoxicity, oxidative damage and inflammation). For humans to evolve mechanisms to minimize secondary pathophysiological events following CNS injuries, selection must occur for individuals who survive such insults. Two major factors limit the selection for beneficial responses to CNS insults: for many CNS disease states the principal risk factor is advanced, post-reproductive age and virtually all severe CNS traumas are fatal in the absence of modern medical intervention. An alternative hypothesis for the persistence of apparently maladaptive responses to CNS damage is that the secondary exacerbation of damage is the result of unavoidable evolutionary constraints. That is, the nervous system could not function under normal conditions if the mechanisms that caused secondary damage (e.g., excitotoxicity) in response to injury were decreased or eliminated. However, some vertebrate species normally inhabit environments (e.g. hypoxia in underground burrows) that could potentially damage their nervous systems. Yet, profound neuroprotective mechanisms have evolved in these animals indicating that natural selection can occur for traits that protect animals from nervous system damage. Many of the secondary processes and regeneration-inhibitory factors that exacerbate injuries likely persist because they have been adaptive over evolutionary time in the healthy nervous system. Therefore, it remains important that researchers consider the role of the processes in the healthy or developing nervous system to understand how they become dysregulated following injury. PMID:18602443

  15. Repair in the central nervous system.

    PubMed

    Fitzgerald, J; Fawcett, J

    2007-11-01

    The subject of central nervous system damage includes a wide variety of problems, from the slow selective 'picking off' of characteristic sub-populations of neurons typical of neurodegenerative diseases, to the wholesale destruction of areas of brain and spinal cord seen in traumatic injury and stroke. Experimental repair strategies are diverse and the type of pathology dictates which approach will be appropriate. Damage may be to grey matter (loss of neurons), white matter (cutting of axons, leaving neurons otherwise intact, at least initially) or both. This review will consider four possible forms of treatment for repair of the human central nervous system. PMID:17998174

  16. Vitamin D and the central nervous system.

    PubMed

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

    2013-01-01

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

  17. Evolving specialization of the arthropod nervous system

    PubMed Central

    Jarvis, Erin; Bruce, Heather S.; Patel, Nipam H.

    2012-01-01

    The diverse array of body plans possessed by arthropods is created by generating variations upon a design of repeated segments formed during development, using a relatively small “toolbox” of conserved patterning genes. These attributes make the arthropod body plan a valuable model for elucidating how changes in development create diversity of form. As increasingly specialized segments and appendages evolved in arthropods, the nervous systems of these animals also evolved to control the function of these structures. Although there is a remarkable degree of conservation in neural development both between individual segments in any given species and between the nervous systems of different arthropod groups, the differences that do exist are informative for inferring general principles about the holistic evolution of body plans. This review describes developmental processes controlling neural segmentation and regionalization, highlighting segmentation mechanisms that create both ectodermal and neural segments, as well as recent studies of the role of Hox genes in generating regional specification within the central nervous system. We argue that this system generates a modular design that allows the nervous system to evolve in concert with the body segments and their associated appendages. This information will be useful in future studies of macroevolutionary changes in arthropod body plans, especially in understanding how these transformations can be made in a way that retains the function of appendages during evolutionary transitions in morphology. PMID:22723369

  18. Evolution of basal deuterostome nervous systems.

    PubMed

    Holland, Linda Z

    2015-02-15

    Understanding the evolution of deuterostome nervous systems has been complicated by the by the ambiguous phylogenetic position of the Xenocoelomorpha (Xenoturbellids, acoel flat worms, nemertodermatids), which has been placed either as basal bilaterians, basal deuterostomes or as a sister group to the hemichordate/echinoderm clade (Ambulacraria), which is a sister group of the Chordata. None of these groups has a single longitudinal nerve cord and a brain. A further complication is that echinoderm nerve cords are not likely to be evolutionarily related to the chordate central nervous system. For hemichordates, opinion is divided as to whether either one or none of the two nerve cords is homologous to the chordate nerve cord. In chordates, opposition by two secreted signaling proteins, bone morphogenetic protein (BMP) and Nodal, regulates partitioning of the ectoderm into central and peripheral nervous systems. Similarly, in echinoderm larvae, opposition between BMP and Nodal positions the ciliary band and regulates its extent. The apparent loss of this opposition in hemichordates is, therefore, compatible with the scenario, suggested by Dawydoff over 65 years ago, that a true centralized nervous system was lost in hemichordates.

  19. 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.

  20. Diabetes and the enteric nervous system.

    PubMed

    Chandrasekharan, B; Srinivasan, S

    2007-12-01

    Diabetes is associated with several changes in gastrointestinal (GI) motility and associated symptoms such as nausea, bloating, abdominal pain, diarrhoea and constipation. The pathogenesis of altered GI functions in diabetes is multifactorial and the role of the enteric nervous system (ENS) in this respect has gained significant importance. In this review, we summarize the research carried out on diabetes-related changes in the ENS. Changes in the inhibitory and excitatory enteric neurons are described highlighting the role of loss of inhibitory neurons in early diabetic enteric neuropathy. The functional consequences of these neuronal changes result in altered gastric emptying, diarrhoea or constipation. Diabetes can also affect GI motility through changes in intestinal smooth muscle or alterations in extrinsic neuronal control. Hyperglycaemia and oxidative stress play an important role in the pathophysiology of these ENS changes. Antioxidants to prevent or treat diabetic GI motility problems have therapeutic potential. Recent research on the nerve-immune interactions demonstrates inflammation-associated neurodegeneration which can lead to motility related problems in diabetes. PMID:17971027

  1. 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.

  2. 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

  3. 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

  4. Impact of diabetes on vasculature: focus on nervous system.

    PubMed

    Skljarevski, Vladimir; Veves, Aristidis

    2005-08-01

    Chronic complications of diabetes mellitus represent a major cause of morbidity and mortality among those affected and have an enormous impact on society as a whole. Although these complications manifest as a number of clinically distinct syndromes, the pathology underlying them may be very similar, if not identical. Endothelial dysfunction leading to microcirculatory insufficiency and functional ischemia of tissues are proposed to play a pivotal role in the process of their development and progression. Diabetic complications affecting the nervous system occur not infrequently and may have disastrous consequences. This article reviews diabetic complications affecting central and peripheral nervous systems, focusing on similarities in their underlying microvascular pathology and discussing aspects of potentially successful therapeutic interventions. In addition, the article draws a parallel between microvascular dysfunction observed in persons with overt diabetes and those at risk for it.

  5. [Emotion, amygdala, and autonomic nervous system].

    PubMed

    Ueyama, Takashi

    2012-10-01

    Emotion refers to the dynamic changes of feeling accompanied by the alteration of physical and visceral activities. Autonomic nervous system (sympathetic and parasympathetic) regulates the visceral activities. Therefore, monitoring and analyzing autonomic nervous activity help understand the emotional changes. To this end, the survey of the expression of immediate early genes (IEGs), such as c-Fos in the brain and target organs, and the viral transneuronal labeling method using the pseudorabies virus (PRV) have enabled the visualization of the neurocircuitry of emotion. By comparing c-Fos expression and data from PRV or other neuroanatomical labeling techniques, the central sites that regulate emotional stress-induced autonomic activation can be deduced. Such regions have been identified in the limbic system (e. g., the extended amygdaloid complex; lateral septum; and infralimbic, insular, and ventromedial temporal cortical regions), as well as in several hypothalamic and brainstem nuclei. The amygdala is structurally diverse and comprises several subnuclei, which play a role in emotional process via projections from the cortex and a variety of subcortical structures. All amygdaloid subnuclei receive psychological information from other limbic systems, while the lateral and central subnuclei receive peripheral and sensory information. Output to the hypothalamus and peripheral sympathetic system mainly originates from the medial amygdala. As estrogen receptor α, estrogen receptor β, and androgen receptor are expressed in the medial amygdala, sex steroids may modulate the autonomic nervous activities.

  6. [Central nervous system tumors in pregnancy].

    PubMed

    Podciechowski, Lech; Nowakowska, Dorota; Bielak, Adam; Nowosławska, Emilia; Szymański, Wojciech; Polis, Lech; Krasomski, Grzechorz; Fiks, Tomasz; Wilczyński, Jan

    2003-12-01

    Central nervous system tumour in pregnancy constitutes a serious complication. Considering frequent difficulties in diagnostics and therapy, the aim of the study was to present our experience in management with pregnant women with brain and spinal cord tumours. Between 1988-2000, in The Research Institute Polish Mother's Memorial Hospital in Lodzi, 4 pregnant women had been diagnosed with brain and spinal cord tumours. The incidence of tumours complicating pregnancy was 1/11460. Two patients diagnosed at 29 weeks' gestation, underwent craniotomy and tumour resection during pregnancy. Two other women with central nervous system tumours diagnosed at 39 weeks' gestation, were operated in the postpartum period. The analysis of the postoperative period, gestation and/or postpartum period in all women and well-being of their new-borns confirm undertaken medical decisions. PMID:15029742

  7. Maintaining Genome Stability in the Nervous System

    PubMed Central

    McKinnon, Peter J.

    2014-01-01

    Active maintenance of genome stability is a prerequisite for the development and function of the nervous system. The high replication index during neurogenesis and the long life of mature neurons highlight the need for efficient cellular programs to safeguard genetic fidelity. Multiple DNA damage response pathways ensure that replication stress and other types of DNA lesions such as oxidative damage do not impact neural homeostasis. Numerous human neurologic syndromes result from defective DNA damage signaling and compromised genome integrity. These syndromes can involve different neuropathology, which highlights the diverse maintenance roles required for genome stability in the nervous system. Understanding how DNA damage signaling pathways promote neural development and preserve homeostasis is essential for understanding fundamental brain function. PMID:24165679

  8. Virus Infections in the Nervous System

    PubMed Central

    Koyuncu, Orkide O.; Hogue, Ian B.; Enquist, Lynn W.

    2013-01-01

    Virus infections usually begin in peripheral tissues and can invade the mammalian nervous system (NS), spreading into the peripheral (PNS) and more rarely the central nervous systems (CNS). The CNS is protected from most virus infections by effective immune responses and multi-layer barriers. However, some viruses enter the NS with high efficiency via the bloodstream or by directly infecting nerves that innervate peripheral tissues, resulting in debilitating direct and immune-mediated pathology. Most viruses in the NS are opportunistic or accidental pathogens, but a few, most notably the alpha herpesviruses and rabies virus, have evolved to enter the NS efficiently and exploit neuronal cell biology. Remarkably, the alpha herpesviruses can establish quiescent infections in the PNS, with rare but often fatal CNS pathology. Here we review how viruses gain access to and spread in the well-protected CNS, with particular emphasis on alpha herpesviruses, which establish and maintain persistent NS infections. PMID:23601101

  9. Imaging the fetal central nervous system.

    PubMed

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

    2011-01-01

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

  10. Regeneration in the nervous system with erythropoietin

    PubMed Central

    Maiese, Kenneth

    2015-01-01

    Globally, greater than 30 million individuals are afflicted with disorders of the nervous system accompanied by tens of thousands of new cases annually with limited, if any, treatment options. Erythropoietin (EPO) offers an exciting and novel therapeutic strategy to address both acute and chronic neurodegenerative disorders. EPO governs a number of critical protective and regenerative mechanisms that can impact apoptotic and autophagic programmed cell death pathways through protein kinase B (Akt), sirtuins, mammalian forkhead transcription factors, and wingless signaling. Translation of the cytoprotective pathways of EPO into clinically effective treatments for some neurodegenerative disorders has been promising, but additional work is necessary. In particular, development of new treatments with erythropoiesis-stimulating agents such as EPO brings several important challenges that involve detrimental vascular outcomes and tumorigenesis. Future work that can effectively and safely harness the complexity of the signaling pathways of EPO will be vital for the fruitful treatment of disorders of the nervous system. PMID:26549969

  11. LGI proteins in the nervous system

    PubMed Central

    Kegel, Linde; Aunin, Eerik; Meijer, Dies; Bermingham, John R.

    2013-01-01

    The development and function of the vertebrate nervous system depend on specific interactions between different cell types. Two examples of such interactions are synaptic transmission and myelination. LGI1-4 (leucine-rich glioma inactivated proteins) play important roles in these processes. They are secreted proteins consisting of an LRR (leucine-rich repeat) domain and a so-called epilepsy-associated or EPTP (epitempin) domain. Both domains are thought to function in protein–protein interactions. The first LGI gene to be identified, LGI1, was found at a chromosomal translocation breakpoint in a glioma cell line. It was subsequently found mutated in ADLTE (autosomal dominant lateral temporal (lobe) epilepsy) also referred to as ADPEAF (autosomal dominant partial epilepsy with auditory features). LGI1 protein appears to act at synapses and antibodies against LGI1 may cause the autoimmune disorder limbic encephalitis. A similar function in synaptic remodelling has been suggested for LGI2, which is mutated in canine Benign Familial Juvenile Epilepsy. LGI4 is required for proliferation of glia in the peripheral nervous system and binds to a neuronal receptor, ADAM22, to foster ensheathment and myelination of axons by Schwann cells. Thus, LGI proteins play crucial roles in nervous system development and function and their study is highly important, both to understand their biological functions and for their therapeutic potential. Here, we review our current knowledge about this important family of proteins, and the progress made towards understanding their functions. PMID:23713523

  12. 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.

  13. Comparative anatomy of the autonomic nervous system.

    PubMed

    Nilsson, Stefan

    2011-11-16

    This short review aims to point out the general anatomical features of the autonomic nervous systems of non-mammalian vertebrates. In addition it attempts to outline the similarities and also the increased complexity of the autonomic nervous patterns from fish to tetrapods. With the possible exception of the cyclostomes, perhaps the most striking feature of the vertebrate autonomic nervous system is the similarity between the vertebrate classes. An evolution of the complexity of the system can be seen, with the segmental ganglia of elasmobranchs incompletely connected longitudinally, while well developed paired sympathetic chains are present in teleosts and the tetrapods. In some groups the sympathetic chains may be reduced (dipnoans and caecilians), and have yet to be properly described in snakes. Cranial autonomic pathways are present in the oculomotor (III) and vagus (X) nerves of gnathostome fish and the tetrapods, and with the evolution of salivary and lachrymal glands in the tetrapods, also in the facial (VII) and glossopharyngeal (IX) nerves. PMID:20444653

  14. Classical Neurotransmitters and their Significance within the Nervous System.

    ERIC Educational Resources Information Center

    Veca, A.; Dreisbach, J. H.

    1988-01-01

    Describes some of the chemical compounds involved in the nervous system and their roles in transmitting nerve signals. Discusses acetylcholine, dopamine, norepinephrine, serotonin, histamine, glycine, glutemate, and gamma-aminobutyric acid and their effects within the nervous system. (CW)

  15. What Are the Parts of the Nervous System?

    MedlinePlus

    ... Research Planning Scientific Resources Research A-Z Topics Neuroscience Overview Condition Information Parts of the nervous system ... functions does the nervous system control? Why study neuroscience? What are the areas of neuroscience? NICHD Research ...

  16. The BIRN Project: Imaging the Nervous System

    SciTech Connect

    Ellisman, Mark

    2006-05-22

    The grand goal in neuroscience research is to understand how the interplay of structural, chemical and electrical signals in nervous tissue gives rise to behavior. Experimental advances of the past decades have given the individual neuroscientist an increasingly powerful arsenal for obtaining data, from the level of molecules to nervous systems. Scientists have begun the arduous and challenging process of adapting and assembling neuroscience data at all scales of resolution and across disciplines into computerized databases and other easily accessed sources. These databases will complement the vast structural and sequence databases created to catalogue, organize and analyze gene sequences and protein products. The general premise of the neuroscience goal is simple; namely that with "complete" knowledge of the genome and protein structures accruing rapidly we next need to assemble an infrastructure that will facilitate acquisition of an understanding for how functional complexes operate in their cell and tissue contexts.

  17. The BIRN Project: Imaging the Nervous System

    SciTech Connect

    Ellisman, Mark

    2006-05-22

    The grand goal in neuroscience research is to understand how the interplay of structural, chemical and electrical signals in nervous tissue gives rise to behavior. Experimental advances of the past decades have given the individual neuroscientist an increasingly powerful arsenal for obtaining data, from the level of molecules to nervous systems. Scientists have begun the arduous and challenging process of adapting and assembling neuroscience data at all scales of resolution and across disciplines into computerized databases and other easily accessed sources. These databases will complement the vast structural and sequence databases created to catalogue, organize and analyze gene sequences and protein products. The general premise of the neuroscience goal is simple; namely that with 'complete' knowledge of the genome and protein structures accruing rapidly we next need to assemble an infrastructure that will facilitate acquisition of an understanding for how functional complexes operate in their cell and tissue contexts.

  18. Lysophosphatidic Acid signaling in the nervous system.

    PubMed

    Yung, Yun C; Stoddard, Nicole C; Mirendil, Hope; Chun, Jerold

    2015-02-18

    The brain is composed of many lipids with varied forms that serve not only as structural components but also as essential signaling molecules. Lysophosphatidic acid (LPA) is an important bioactive lipid species that is part of the lysophospholipid (LP) family. LPA is primarily derived from membrane phospholipids and signals through six cognate G protein-coupled receptors (GPCRs), LPA1-6. These receptors are expressed on most cell types within central and peripheral nervous tissues and have been functionally linked to many neural processes and pathways. This Review covers a current understanding of LPA signaling in the nervous system, with particular focus on the relevance of LPA to both physiological and diseased states. PMID:25695267

  19. Nanoneuromedicines for Degenerative, Inflammatory, and Infectious Nervous System Diseases

    PubMed Central

    Gendelman, Howard E.; Anantharam, Vellareddy; Bronich, Tatiana; Ghaisas, Shivani; Jin, Huajun; Kanthasamy, Anumantha G.; Liu, Xinming; McMillan, JoEllyn; Mosley, R. Lee; Narasimhan, Balaji; Mallapragada, Surya K.

    2015-01-01

    Interest in nanoneuromedicine has grown rapidly due to the immediate need for improved biomarkers and therapies for psychiatric, developmental, traumatic, inflammatory, infectious and degenerative nervous system disorders. These, in whole or in part, are a significant societal burden due to growth in numbers of affected people and in disease severity. Lost productivity of the patient and his or her caregiver, and the emotional and financial burden cannot be overstated. The need for improved health care, treatment and diagnostics are immediate. A means to such an end is nanotechnology. Indeed, recent developments of health-care enabling nanotechnologies and nanomedicines range from biomarker discovery including neuroimaging to therapeutic applications for degenerative, inflammatory and infectious disorders of the nervous system. This review focuses on the current and future potential of the field to positively affect clinical outcomes. PMID:25645958

  20. Neuropathological effects of alcohol on the developing nervous system.

    PubMed

    Lewis, P D

    1985-01-01

    The formation of functional neuronal networks in the developing nervous system is dependent on three mechanisms which have been shown to be susceptible to disturbance by alcohol exposure. These are cell acquisition, cell migration and cellular maturation. Cell acquisition can be reduced by either impaired proliferation or increased cell deletion. Effects of alcohol on cell proliferation, both early in development and in the postnatal cerebellum, are overshadowed by cell loss, which in the cerebellum may affect both small and large neurones. Disturbed cell migration in the developing nervous system is well-known, through neuropathological studies on human fetal alcohol syndrome. Related changes have been produced experimentally in primates, and retarded migration of nerve cells may also occur in the developing cerebellum of the alcohol-exposed rat. Altered nerve cell maturation as shown by examination of dendritic arborisation has been described in the developing hippocampus and brainstem of alcohol-exposed animals. The effects of alcohol on the developing nervous system are unlikely to be specific, and nutritional, hormonal and other pharmacological influences may play a part in their genesis. Moreover, diverse experimental methodology clouds the interpretation of some findings. Although developmental alcohol exposure may have severe and multiple neuropathological effects on the nervous system, reversibility of many lesions, and restoration of functional competence, appears possible in the light of nutritional studies.

  1. Neuroimaging in Central Nervous System Lymphoma.

    PubMed

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

    2016-08-01

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

  2. Viral diseases of the central nervous system.

    PubMed

    Swanson, Phillip A; McGavern, Dorian B

    2015-04-01

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

  3. Surgery of the sympathetic nervous system.

    PubMed

    Lee, B Y; Da Silva, M C; Aquino-Chu, G; Herz, B L

    1996-01-01

    This article reviews the innervation of the arterial system of the lower extremity, lumbar sympathectomy in vascular surgery, lumbar sympathectomy for digital gangrene and in the prevention of major amputation of the lower extremity and substance P's role in neurogenic inflammatory modulation. Long-term results of lumbar sympathectomy and direct arterial bypass surgery have also been reviewed. In addition to the pilomotor, sudomotor and vasomotor actions of the sympathetic nervous system via its neurotransmitters, the molecular basis of the chronic neurogenic inflammatory reaction have been addressed with special attention to the discovery of substance P in the lumbar sympathetic chain and ganglia of human beings.

  4. Atopic dermatitis and the nervous system.

    PubMed

    Misery, Laurent

    2011-12-01

    Due to the narrow associations between the skin, immune system, and nervous system, nerve endings are very important in the pathophysiology of inflammatory dermatoses and especially in atopic dermatitis. Many neurotransmitters and nerve growth factors that are released in blood or skin are involved in neurogenic inflammation, which dramatically enhance the inflammation induced by immune cells. During times of stress, their release is highly enhanced. In atopic dermatitis lesions, there are many specific changes in skin neurobiology and neurophysiology. These interesting data suggest that novel therapeutic possibilities can be imagined.

  5. The central nervous system of ascidian larvae.

    PubMed

    Hudson, Clare

    2016-09-01

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

  6. 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

  7. Central nervous system involvement in diabetes mellitus.

    PubMed

    Selvarajah, Dinesh; Tesfaye, Solomon

    2006-12-01

    Diabetic complications result in much morbidity and mortality and considerable consumption of scarce medical resources. Thus, elucidation of the risk factors and pathophysiologic mechanisms underlying diabetic complications is important. The effects of diabetes on the central nervous system (CNS) result in cognitive dysfunction and cerebrovascular disease. Treatment-related hypoglycemia also has CNS consequences. Advances in neuroimaging now provide greater insights into the structural and functional impact of diabetes on the CNS. Greater understanding of CNS involvement could lead to new strategies to prevent or reverse the damage caused by diabetes mellitus.

  8. Microglia: Architects of the Developing Nervous System.

    PubMed

    Frost, Jeffrey L; Schafer, Dorothy P

    2016-08-01

    Microglia are resident macrophages of the central nervous system (CNS), representing 5-10% of total CNS cells. Recent findings reveal that microglia enter the embryonic brain, take up residence before the differentiation of other CNS cell types, and become critical regulators of CNS development. Here, we discuss exciting new work implicating microglia in a range of developmental processes, including regulation of cell number and spatial patterning of CNS cells, myelination, and formation and refinement of neural circuits. Furthermore, we review studies suggesting that these cellular functions result in the modulation of behavior, which has important implications for a variety of neurological disorders.

  9. 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

  10. Did the ctenophore nervous system evolve independently?

    PubMed

    Ryan, Joseph F

    2014-08-01

    Recent evidence supports the placement of ctenophores as the most distant relative to all other animals. This revised animal tree means that either the ancestor of all animals possessed neurons (and that sponges and placozoans apparently lost them) or that ctenophores developed them independently. Differentiating between these possibilities is important not only from a historical perspective, but also for the interpretation of a wide range of neurobiological results. In this short perspective paper, I review the evidence in support of each scenario and show that the relationship between the nervous system of ctenophores and other animals is an unsolved, yet tractable problem. PMID:24986234

  11. Physiology of the Autonomic Nervous System

    PubMed Central

    2007-01-01

    This manuscript discusses the physiology of the autonomic nervous system (ANS). The following topics are presented: regulation of activity; efferent pathways; sympathetic and parasympathetic divisions; neurotransmitters, their receptors and the termination of their activity; functions of the ANS; and the adrenal medullae. In addition, the application of this material to the practice of pharmacy is of special interest. Two case studies regarding insecticide poisoning and pheochromocytoma are included. The ANS and the accompanying case studies are discussed over 5 lectures and 2 recitation sections during a 2-semester course in Human Physiology. The students are in the first-professional year of the doctor of pharmacy program. PMID:17786266

  12. Vascularisation of the central nervous system

    PubMed Central

    Tata, Mathew; Ruhrberg, Christiana; Fantin, Alessandro

    2015-01-01

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

  13. Did the ctenophore nervous system evolve independently?

    PubMed

    Ryan, Joseph F

    2014-08-01

    Recent evidence supports the placement of ctenophores as the most distant relative to all other animals. This revised animal tree means that either the ancestor of all animals possessed neurons (and that sponges and placozoans apparently lost them) or that ctenophores developed them independently. Differentiating between these possibilities is important not only from a historical perspective, but also for the interpretation of a wide range of neurobiological results. In this short perspective paper, I review the evidence in support of each scenario and show that the relationship between the nervous system of ctenophores and other animals is an unsolved, yet tractable problem.

  14. [Sports injuries of the nervous system].

    PubMed

    Lang, C; Stefan, H

    1999-08-01

    Almost 1% of all Germans suffer sports injuries each year, almost 5% of all peripheral nerve lesions are due to sports. A review is given on various activities detailing the specific risks for traumata of the central and peripheral nervous system. Specifically these are volleyball, handball, basketball, American football, soccer, bowling, hockey, baseball, tennis, golf, javelin, fencing, wrestling, judo, boxing, running, jumping, dancing, mountain climbing, weight lifting, gymnastics, horse-back riding, swimming, rowing, skiing, skating, shooting, (motor) biking, car racing, flying, and sports for the disabled. The knowledge of typical traumata should enable the neurologist to rapidly and reliably recognize related lesions and to contribute to their prevention or improvement.

  15. Laboratory Diagnosis of Central Nervous System Infection.

    PubMed

    He, Taojun; Kaplan, Samuel; Kamboj, Mini; Tang, Yi-Wei

    2016-11-01

    Central nervous system (CNS) infections are potentially life threatening if not diagnosed and treated early. The initial clinical presentations of many CNS infections are non-specific, making a definitive etiologic diagnosis challenging. Nucleic acid in vitro amplification-based molecular methods are increasingly being applied for routine microbial detection. These methods are a vast improvement over conventional techniques with the advantage of rapid turnaround and higher sensitivity and specificity. Additionally, molecular methods performed on cerebrospinal fluid samples are considered the new gold standard for diagnosis of CNS infection caused by pathogens, which are otherwise difficult to detect. Commercial diagnostic platforms offer various monoplex and multiplex PCR assays for convenient testing of targets that cause similar clinical illness. Pan-omic molecular platforms possess potential for use in this area. Although molecular methods are predicted to be widely used in diagnosing and monitoring CNS infections, results generated by these methods need to be carefully interpreted in combination with clinical findings. This review summarizes the currently available armamentarium of molecular assays for diagnosis of central nervous system infections, their application, and future approaches. PMID:27686677

  16. 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

  17. Roles of kinins in the nervous system.

    PubMed

    Negraes, Priscilla D; Trujillo, Cleber A; Pillat, Micheli M; Teng, Yang D; Ulrich, Henning

    2015-01-01

    The kallikrein-kinin system (KKS) is an endogenous pathway involved in many biological processes. Although primarily related to blood pressure control and inflammation, its activation goes beyond these effects. Neurogenesis and neuroprotection might be stimulated by bradykinin being of great interest for clinical applications following brain injury. This peptide is also an important player in spinal cord injury pathophysiology and recovery, in which bradykinin receptor blockers represent substantial therapeutic potential. Here, we highlight the participation of kinin receptors and especially bradykinin in mediating ischemia pathophysiology in the central and peripheral nervous systems. Moreover, we explore the recent advances on mechanistic and therapeutic targets for biological, pathological, and neural repair processes involving kinins. PMID:25839228

  18. Exercise and the autonomic nervous system.

    PubMed

    Fu, Qi; Levine, Benjamin D

    2013-01-01

    The autonomic nervous system plays a crucial role in the cardiovascular response to acute (dynamic) exercise in animals and humans. During exercise, oxygen uptake is a function of the triple-product of heart rate and stroke volume (i.e., cardiac output) and arterial-mixed venous oxygen difference (the Fick principle). The degree to which each of the variables can increase determines maximal oxygen uptake (V˙O2max). Both "central command" and "the exercise pressor reflex" are important in determining the cardiovascular response and the resetting of the arterial baroreflex during exercise to precisely match systemic oxygen delivery with metabolic demand. In general, patients with autonomic disorders have low levels of V˙O2max, indicating reduced physical fitness and exercise capacity. Moreover, the vast majority of the patients have blunted or abnormal cardiovascular response to exercise, especially during maximal exercise. There is now convincing evidence that some of the protective and therapeutic effects of chronic exercise training are related to the impact on the autonomic nervous system. Additionally, training induced improvement in vascular function, blood volume expansion, cardiac remodeling, insulin resistance and renal-adrenal function may also contribute to the protection and treatment of cardiovascular, metabolic and autonomic disorders. Exercise training also improves mental health, helps to prevent depression, and promotes or maintains positive self-esteem. Moderate-intensity exercise at least 30 minutes per day and at least 5 days per week is recommended for the vast majority of people. Supervised exercise training is preferable to maximize function capacity, and may be particularly important for patients with autonomic disorders. PMID:24095123

  19. 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.

  20. Advances in Primary Central Nervous System Lymphoma.

    PubMed

    Patrick, Lauren B; Mohile, Nimish A

    2015-12-01

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

  1. Subcortical cytoskeleton periodicity throughout the nervous system.

    PubMed

    D'Este, Elisa; Kamin, Dirk; Velte, Caroline; Göttfert, Fabian; Simons, Mikael; Hell, Stefan W

    2016-01-01

    Superresolution fluorescence microscopy recently revealed a ~190 nm periodic cytoskeleton lattice consisting of actin, spectrin, and other proteins underneath the membrane of cultured hippocampal neurons. Whether the periodic cytoskeleton lattice is a structural feature of all neurons and how it is modified when axons are ensheathed by myelin forming glial cells is not known. Here, STED nanoscopy is used to demonstrate that this structure is a commonplace of virtually all neuron types in vitro. To check how the subcortical meshwork is modified during myelination, we studied sciatic nerve fibers from adult mice. Periodicity of both actin and spectrin was uncovered at the internodes, indicating no substantial differences between unmyelinated and myelinated axons. Remarkably, the actin/spectrin pattern was also detected in glial cells such as cultured oligodendrocyte precursor cells. Altogether our work shows that the periodic subcortical cytoskeletal meshwork is a fundamental characteristic of cells in the nervous system and is not a distinctive feature of neurons, as previously thought. PMID:26947559

  2. [Histopathology of central nervous system cavernomas].

    PubMed

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

    2007-06-01

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

  3. Scaffolds for central nervous system tissue engineering

    NASA Astrophysics Data System (ADS)

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

    2012-03-01

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

  4. Varicella Zoster Virus in the Nervous System

    PubMed Central

    Gilden, Don; Nagel, Maria; Cohrs, Randall; Mahalingam, Ravi; Baird, Nicholas

    2015-01-01

    Varicella zoster virus (VZV) is a ubiquitous, exclusively human alphaherpesvirus. Primary infection usually results in varicella (chickenpox), after which VZV becomes latent in ganglionic neurons along the entire neuraxis. As VZV-specific cell-mediated immunity declines in elderly and immunocompromised individuals, VZV reactivates and causes herpes zoster (shingles), frequently complicated by postherpetic neuralgia. VZV reactivation also produces multiple serious neurological and ocular diseases, such as cranial nerve palsies, meningoencephalitis, myelopathy, and VZV vasculopathy, including giant cell arteritis, with or without associated rash. Herein, we review the clinical, laboratory, imaging, and pathological features of neurological complications of VZV reactivation as well as diagnostic tests to verify VZV infection of the nervous system. Updates on the physical state of VZV DNA and viral gene expression in latently infected ganglia, neuronal, and primate models to study varicella pathogenesis and immunity are presented along with innovations in the immunization of elderly individuals to prevent VZV reactivation. PMID:26918131

  5. Nocardiosis of the Central Nervous System

    PubMed Central

    Anagnostou, Theodora; Arvanitis, Marios; Kourkoumpetis, Themistoklis K.; Desalermos, Athanasios; Carneiro, Herman A.

    2014-01-01

    Abstract Central nervous system (CNS) nocardiosis is a rare disease entity caused by the filamentous bacteria Nocardia species. We present a case series of 5 patients from our hospital and a review of the cases of CNS nocardiosis reported in the literature from January 2000 to December 2011. Our results indicate that CNS nocardiosis can occur in both immunocompromised and immunocompetent individuals and can be the result of prior pulmonary infection or can exist on its own. The most common predisposing factors are corticosteroid use (54% of patients) and organ transplantation (25%). Presentation of the disease is widely variable, and available diagnostic tests are far from perfect, often leading to delayed detection and initiation of treatment. The optimal therapeutic approach is still undetermined and depends on speciation, but lower mortality and relapse rates have been reported with a combination of targeted antimicrobial treatment including trimethoprim/sulfomethoxazole (TMP-SMX) for more than 6 months and neurosurgical intervention. PMID:24378740

  6. Varicella Zoster Virus in the Nervous System.

    PubMed

    Gilden, Don; Nagel, Maria; Cohrs, Randall; Mahalingam, Ravi; Baird, Nicholas

    2015-01-01

    Varicella zoster virus (VZV) is a ubiquitous, exclusively human alphaherpesvirus. Primary infection usually results in varicella (chickenpox), after which VZV becomes latent in ganglionic neurons along the entire neuraxis. As VZV-specific cell-mediated immunity declines in elderly and immunocompromised individuals, VZV reactivates and causes herpes zoster (shingles), frequently complicated by postherpetic neuralgia. VZV reactivation also produces multiple serious neurological and ocular diseases, such as cranial nerve palsies, meningoencephalitis, myelopathy, and VZV vasculopathy, including giant cell arteritis, with or without associated rash. Herein, we review the clinical, laboratory, imaging, and pathological features of neurological complications of VZV reactivation as well as diagnostic tests to verify VZV infection of the nervous system. Updates on the physical state of VZV DNA and viral gene expression in latently infected ganglia, neuronal, and primate models to study varicella pathogenesis and immunity are presented along with innovations in the immunization of elderly individuals to prevent VZV reactivation. PMID:26918131

  7. Advances in Primary Central Nervous System Lymphoma.

    PubMed

    Patrick, Lauren B; Mohile, Nimish A

    2015-12-01

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

  8. Subcortical cytoskeleton periodicity throughout the nervous system.

    PubMed

    D'Este, Elisa; Kamin, Dirk; Velte, Caroline; Göttfert, Fabian; Simons, Mikael; Hell, Stefan W

    2016-03-07

    Superresolution fluorescence microscopy recently revealed a ~190 nm periodic cytoskeleton lattice consisting of actin, spectrin, and other proteins underneath the membrane of cultured hippocampal neurons. Whether the periodic cytoskeleton lattice is a structural feature of all neurons and how it is modified when axons are ensheathed by myelin forming glial cells is not known. Here, STED nanoscopy is used to demonstrate that this structure is a commonplace of virtually all neuron types in vitro. To check how the subcortical meshwork is modified during myelination, we studied sciatic nerve fibers from adult mice. Periodicity of both actin and spectrin was uncovered at the internodes, indicating no substantial differences between unmyelinated and myelinated axons. Remarkably, the actin/spectrin pattern was also detected in glial cells such as cultured oligodendrocyte precursor cells. Altogether our work shows that the periodic subcortical cytoskeletal meshwork is a fundamental characteristic of cells in the nervous system and is not a distinctive feature of neurons, as previously thought.

  9. PET imaging of the autonomic nervous system.

    PubMed

    Thackeray, James T; Bengel, Frank M

    2016-12-01

    The autonomic nervous system is the primary extrinsic control of heart rate and contractility, and is subject to adaptive and maladaptive changes in cardiovascular disease. Consequently, noninvasive assessment of neuronal activity and function is an attractive target for molecular imaging. A myriad of targeted radiotracers have been developed over the last 25 years for imaging various components of the sympathetic and parasympathetic signal cascades. While routine clinical use remains somewhat limited, a number of larger scale studies in recent years have supplied momentum to molecular imaging of autonomic signaling. Specifically, the findings of the ADMIRE HF trial directly led to United States Food and Drug Administration approval of 123I-metaiodobenzylguanidine (MIBG) for Single Photon Emission Computed Tomography (SPECT) assessment of sympathetic neuronal innervation, and comparable results have been reported using the analogous PET agent 11C-meta-hydroxyephedrine (HED). Due to the inherent capacity for dynamic quantification and higher spatial resolution, regional analysis may be better served by PET. In addition, preliminary clinical and extensive preclinical experience has provided a broad foundation of cardiovascular applications for PET imaging of the autonomic nervous system. Recent years have witnessed the growth of novel quantification techniques, expansion of multiple tracer studies, and improved understanding of the uptake of different radiotracers, such that the transitional biology of dysfunctional subcellular catecholamine handling can be distinguished from complete denervation. As a result, sympathetic neuronal molecular imaging is poised to play a role in individualized patient care, by stratifying cardiovascular risk, visualizing underlying biology, and guiding and monitoring therapy. PMID:27611712

  10. 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

  11. Oral intake of γ-aminobutyric acid affects mood and activities of central nervous system during stressed condition induced by mental tasks.

    PubMed

    Yoto, A; Murao, S; Motoki, M; Yokoyama, Y; Horie, N; Takeshima, K; Masuda, K; Kim, M; Yokogoshi, H

    2012-09-01

    γ-Aminobutyric acid (GABA) is a kind of amino acid contained in green tea leaves and other foods. Several reports have shown that GABA might affect brain protein synthesis, improve many brain functions such as memory and study capability, lower the blood pressure of spontaneously hypertensive rats, and may also have a relaxation effect in humans. However, the evidence for its mood-improving function is still not sufficient. In this study, we investigated how the oral intake of GABA influences human adults psychologically and physiologically under a condition of mental stress. Sixty-three adults (28 males, 35 females) participated in a randomized, single blind, placebo-controlled, crossover-designed study over two experiment days. Capsules containing 100 mg of GABA or dextrin as a placebo were used as test samples. The results showed that EEG activities including alpha band and beta band brain waves decreased depending on the mental stress task loads, and the condition of 30 min after GABA intake diminished this decrease compared with the placebo condition. That is to say, GABA might have alleviated the stress induced by the mental tasks. This effect also corresponded with the results of the POMS scores. PMID:22203366

  12. Oral intake of γ-aminobutyric acid affects mood and activities of central nervous system during stressed condition induced by mental tasks.

    PubMed

    Yoto, A; Murao, S; Motoki, M; Yokoyama, Y; Horie, N; Takeshima, K; Masuda, K; Kim, M; Yokogoshi, H

    2012-09-01

    γ-Aminobutyric acid (GABA) is a kind of amino acid contained in green tea leaves and other foods. Several reports have shown that GABA might affect brain protein synthesis, improve many brain functions such as memory and study capability, lower the blood pressure of spontaneously hypertensive rats, and may also have a relaxation effect in humans. However, the evidence for its mood-improving function is still not sufficient. In this study, we investigated how the oral intake of GABA influences human adults psychologically and physiologically under a condition of mental stress. Sixty-three adults (28 males, 35 females) participated in a randomized, single blind, placebo-controlled, crossover-designed study over two experiment days. Capsules containing 100 mg of GABA or dextrin as a placebo were used as test samples. The results showed that EEG activities including alpha band and beta band brain waves decreased depending on the mental stress task loads, and the condition of 30 min after GABA intake diminished this decrease compared with the placebo condition. That is to say, GABA might have alleviated the stress induced by the mental tasks. This effect also corresponded with the results of the POMS scores.

  13. 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

  14. 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.

  15. Knock-down of pantothenate kinase 2 severely affects the development of the nervous and vascular system in zebrafish, providing new insights into PKAN disease.

    PubMed

    Zizioli, Daniela; Tiso, Natascia; Guglielmi, Adele; Saraceno, Claudia; Busolin, Giorgia; Giuliani, Roberta; Khatri, Deepak; Monti, Eugenio; Borsani, Giuseppe; Argenton, Francesco; Finazzi, Dario

    2016-01-01

    Pantothenate Kinase Associated Neurodegeneration (PKAN) is an autosomal recessive disorder with mutations in the pantothenate kinase 2 gene (PANK2), encoding an essential enzyme for Coenzyme A (CoA) biosynthesis. The molecular connection between defects in this enzyme and the neurodegenerative phenotype observed in PKAN patients is still poorly understood. We exploited the zebrafish model to study the role played by the pank2 gene during embryonic development and get new insight into PKAN pathogenesis. The zebrafish orthologue of hPANK2 lies on chromosome 13, is a maternal gene expressed in all development stages and, in adult animals, is highly abundant in CNS, dorsal aorta and caudal vein. The injection of a splice-inhibiting morpholino induced a clear phenotype with perturbed brain morphology and hydrocephalus; edema was present in the heart region and caudal plexus, where hemorrhages with reduction of blood circulation velocity were detected. We characterized the CNS phenotype by studying the expression pattern of wnt1 and neurog1 neural markers and by use of the Tg(neurod:EGFP/sox10:dsRed) transgenic line. The results evidenced that downregulation of pank2 severely impairs neuronal development, particularly in the anterior part of CNS (telencephalon). Whole-mount in situ hybridization analysis of the endothelial markers cadherin-5 and fli1a, and use of Tg(fli1a:EGFP/gata1a:dsRed) transgenic line, confirmed the essential role of pank2 in the formation of the vascular system. The specificity of the morpholino-induced phenotype was proved by the restoration of a normal development in a high percentage of embryos co-injected with pank2 mRNA. Also, addition of pantethine or CoA, but not of vitamin B5, to pank2 morpholino-injected embryos rescued the phenotype with high efficiency. The zebrafish model indicates the relevance of pank2 activity and CoA homeostasis for normal neuronal development and functioning and provides evidence of an unsuspected role for this

  16. Knock-down of pantothenate kinase 2 severely affects the development of the nervous and vascular system in zebrafish, providing new insights into PKAN disease

    PubMed Central

    Zizioli, Daniela; Tiso, Natascia; Guglielmi, Adele; Saraceno, Claudia; Busolin, Giorgia; Giuliani, Roberta; Khatri, Deepak; Monti, Eugenio; Borsani, Giuseppe; Argenton, Francesco; Finazzi, Dario

    2016-01-01

    Pantothenate Kinase Associated Neurodegeneration (PKAN) is an autosomal recessive disorder with mutations in the pantothenate kinase 2 gene (PANK2), encoding an essential enzyme for Coenzyme A (CoA) biosynthesis. The molecular connection between defects in this enzyme and the neurodegenerative phenotype observed in PKAN patients is still poorly understood. We exploited the zebrafish model to study the role played by the pank2 gene during embryonic development and get new insight into PKAN pathogenesis. The zebrafish orthologue of hPANK2 lies on chromosome 13, is a maternal gene expressed in all development stages and, in adult animals, is highly abundant in CNS, dorsal aorta and caudal vein. The injection of a splice-inhibiting morpholino induced a clear phenotype with perturbed brain morphology and hydrocephalus; edema was present in the heart region and caudal plexus, where hemorrhages with reduction of blood circulation velocity were detected. We characterized the CNS phenotype by studying the expression pattern of wnt1 and neurog1 neural markers and by use of the Tg(neurod:EGFP/sox10:dsRed) transgenic line. The results evidenced that downregulation of pank2 severely impairs neuronal development, particularly in the anterior part of CNS (telencephalon). Whole-mount in situ hybridization analysis of the endothelial markers cadherin-5 and fli1a, and use of Tg(fli1a:EGFP/gata1a:dsRed) transgenic line, confirmed the essential role of pank2 in the formation of the vascular system. The specificity of the morpholino-induced phenotype was proved by the restoration of a normal development in a high percentage of embryos co-injected with pank2 mRNA. Also, addition of pantethine or CoA, but not of vitamin B5, to pank2 morpholino-injected embryos rescued the phenotype with high efficiency. The zebrafish model indicates the relevance of pank2 activity and CoA homeostasis for normal neuronal development and functioning and provides evidence of an unsuspected role for this

  17. Knock-down of pantothenate kinase 2 severely affects the development of the nervous and vascular system in zebrafish, providing new insights into PKAN disease.

    PubMed

    Zizioli, Daniela; Tiso, Natascia; Guglielmi, Adele; Saraceno, Claudia; Busolin, Giorgia; Giuliani, Roberta; Khatri, Deepak; Monti, Eugenio; Borsani, Giuseppe; Argenton, Francesco; Finazzi, Dario

    2016-01-01

    Pantothenate Kinase Associated Neurodegeneration (PKAN) is an autosomal recessive disorder with mutations in the pantothenate kinase 2 gene (PANK2), encoding an essential enzyme for Coenzyme A (CoA) biosynthesis. The molecular connection between defects in this enzyme and the neurodegenerative phenotype observed in PKAN patients is still poorly understood. We exploited the zebrafish model to study the role played by the pank2 gene during embryonic development and get new insight into PKAN pathogenesis. The zebrafish orthologue of hPANK2 lies on chromosome 13, is a maternal gene expressed in all development stages and, in adult animals, is highly abundant in CNS, dorsal aorta and caudal vein. The injection of a splice-inhibiting morpholino induced a clear phenotype with perturbed brain morphology and hydrocephalus; edema was present in the heart region and caudal plexus, where hemorrhages with reduction of blood circulation velocity were detected. We characterized the CNS phenotype by studying the expression pattern of wnt1 and neurog1 neural markers and by use of the Tg(neurod:EGFP/sox10:dsRed) transgenic line. The results evidenced that downregulation of pank2 severely impairs neuronal development, particularly in the anterior part of CNS (telencephalon). Whole-mount in situ hybridization analysis of the endothelial markers cadherin-5 and fli1a, and use of Tg(fli1a:EGFP/gata1a:dsRed) transgenic line, confirmed the essential role of pank2 in the formation of the vascular system. The specificity of the morpholino-induced phenotype was proved by the restoration of a normal development in a high percentage of embryos co-injected with pank2 mRNA. Also, addition of pantethine or CoA, but not of vitamin B5, to pank2 morpholino-injected embryos rescued the phenotype with high efficiency. The zebrafish model indicates the relevance of pank2 activity and CoA homeostasis for normal neuronal development and functioning and provides evidence of an unsuspected role for this

  18. Imagery and the autonomic nervous system: some methodological issues.

    PubMed

    Di Giusto, E L; Bond, N W

    1979-04-01

    The present paper is concerned with the role played by image content in the mediation of autonomic nervous system (ANS) arousal. The minimum methodological requirements of such studies are described including controls for imaging, image content, and expectancy effects. Studies meeting these requirements are then reviewed. It is concluded that image content can be a significant modifier of ANS arousal and that this property is not restricted to images containing affective, e.g., phobic, content. These conclusions have relevance to research into techniques such as biofeedback, Transcendental Meditation, and progressive relaxation, where imagery many have a profound influence but where it has received little direct empirical attentiol.

  19. Parasitoses with central nervous system involvement.

    PubMed

    Finsterer, Josef; Frank, Marlies

    2014-10-01

    Most of the parasitoses manifest systemically, including the central nervous system (CNS). Among the most prevalent parasitoses in Central Europe (cysticercosis, toxocarosis, echinococcosis, and toxoplasmosis), cerebral involvement is well recognized and part of the clinical presentation, which cannot be neglected. CNS involvement results from invasion of larvae of these parasites via the blood stream or by direct migration into the CNS. Most frequently larvae reside within the cerebral parenchyma, but sometimes also within the ventricles, in the meningeas within cerebral aneurysms, or in the parenchyma of the spinal cord. Depending on the stage of their development, they cause a local defect or more widespread damage, such as encephalitis, ventriculitis, ependymitis, arachnoiditis, meningitis, myelitis, polyradiculitis, mechanical obstruction of the arterial or cerebrospinal fluid (CSF) flow, or vasculitis with appropriate clinical presentations. These include epilepsy, headache, impaired consciousness, orientation, cognition, focal neurological motor, sensory, or vegetative deficits, or visual impairment. CNS involvement is diagnosed on the clinical presentation, the epidemiological background, blood and CSF investigations, imaging studies, and sometimes biopsy. Treatment is based on various antihelminthic agents and, occasionally, surgery. PMID:25297698

  20. Localized hyperthermia in the central nervous system

    SciTech Connect

    Lyons, B.E. Jr.

    1986-01-01

    A new localized treatment modality for malignant brain tumors is hyperthermia. Primary brain tumors are ideally suited to localized therapies because they are initially found in a single area of the brain and local recurrence is the general rule, despite aggressive multimodality treatment. The potential of hyperthermia is based on the rationale that these tumors contain a heterogeneous anaplastic cell population. In contrast to radiation and chemotherapy, hyperthermia is equally effective against both hypoxic and oxygenated cells. Moreover, higher temperatures result in tissues that have an inability to cool themselves through perfusion. The feasibility of localized heating in normal and malignant brain tissue was investigated using external ultrasound and microwave applicators and an interstitial microwave antenna array. The ability to generate uniform temperature distributions using these systems was tested in thermal dosimetry studies. Lesion threshold studies were performed to define the acute and chronic histopathological effects of localized hyperthermia in normal brain tissue. Results demonstrated that these techniques can effectively heat clinically relevant volumes of brain tissue to therapeutic temperatures in an extremely controlled and precise manner. Thresholds for cytological damage have been defined over a range of time/temperature parameters. Various physical and physiological factors within the central nervous system as they relate to temperature exposure have also been defined. These feasibility and toxicity studies have led to the initiation of Phase I clinical trials of hyperthermia in combination with radiation therapy at several institutions.

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

    PubMed

    Yokota, Hajime; Yamada, Kei

    2015-03-01

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

  2. HIV Infection Seems to Affect Nervous System

    MedlinePlus

    ... is a clinical fellow in the department of neurology at the University of California, San Francisco (UCSF). " ... early [HIV] infection." Valcour is a professor of neurology at UCSF. "Additionally, the ubiquity of symptoms in ...

  3. Is central nervous system an immune-privileged site?

    PubMed

    Shrestha, R; Millington, O; Brewer, J; Bushell, T

    2013-01-01

    The central nervous system (CNS) was once considered to be an immune-privileged area. However, increasing evidence shows that the central nervous system is not an immune-privileged but is an active surveillance site. There is a bi-directional communication between the central nervous system and immune system. Normally, immune cells migrate into the central nervous system microenvironment through choroid plexus and interact with the central nervous system resident cells through either through neuromediators or immunomediators. This finding has led to a significant interest in neuroimmunological interactions and investigation onto the role of the immune system in the pathology of various neurological disorders and examine whether it can be targeted to produce novel therapeutic strategies. PMID:23774427

  4. 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.

  5. Gap junctions in the nervous system.

    PubMed

    Rozental, R; Giaume, C; Spray, D C

    2000-04-01

    Synapses are classically defined as close connections between two nerve cells or between a neuronal cell and a muscle or gland cell across which a chemical signal (i.e., a neurotransmitter) and/or an electrical signal (i.e., current-carrying ions) can pass. The definition of synapse was developed by Charles Sherrington and by Ramon y Cajal at the beginning of this century and refined by John Eccles and Bernard Katz 50 years later; in this collection of papers, the definition of synapses is discussed further in the chapter by Mike Bennett. who provided the first functional demonstration of electrical transmission via gap junction channels between vertebrate neurons. As is evidenced by the range of topics covered in this issue, research dealing with gap junctions in the nervous system has expanded enormously in the past decade, major findings being that specific cell types in the brain expresses specific types of connexins and that expression patterns coincide with tissue compartmentalization and function and that these compartments change during development.

  6. Subcortical cytoskeleton periodicity throughout the nervous system

    PubMed Central

    D’Este, Elisa; Kamin, Dirk; Velte, Caroline; Göttfert, Fabian; Simons, Mikael; Hell, Stefan W.

    2016-01-01

    Superresolution fluorescence microscopy recently revealed a ~190 nm periodic cytoskeleton lattice consisting of actin, spectrin, and other proteins underneath the membrane of cultured hippocampal neurons. Whether the periodic cytoskeleton lattice is a structural feature of all neurons and how it is modified when axons are ensheathed by myelin forming glial cells is not known. Here, STED nanoscopy is used to demonstrate that this structure is a commonplace of virtually all neuron types in vitro. To check how the subcortical meshwork is modified during myelination, we studied sciatic nerve fibers from adult mice. Periodicity of both actin and spectrin was uncovered at the internodes, indicating no substantial differences between unmyelinated and myelinated axons. Remarkably, the actin/spectrin pattern was also detected in glial cells such as cultured oligodendrocyte precursor cells. Altogether our work shows that the periodic subcortical cytoskeletal meshwork is a fundamental characteristic of cells in the nervous system and is not a distinctive feature of neurons, as previously thought. PMID:26947559

  7. Hemoglobin potentiates central nervous system damage.

    PubMed Central

    Sadrzadeh, S M; Anderson, D K; Panter, S S; Hallaway, P E; Eaton, J W

    1987-01-01

    Iron and iron compounds--including mammalian hemoglobins--catalyze hydroxyl radical production and lipid peroxidation. To determine whether hemoglobin-mediated lipid peroxidation might be important in hemorrhagic injuries to the central nervous system (CNS), we studied the effects of purified hemoglobin on CNS homogenates and injected hemoglobin into the spinal cords of anesthetized cats. Hemoglobin markedly inhibits Na/K ATPase activity in CNS homogenates and spinal cords of living cats. Hemoglobin also catalyzes substantial peroxidation of CNS lipids. Importantly, the potent iron chelator, desferrioxamine, blocks these adverse effects of hemoglobin, both in vitro and in vivo. Because desferrioxamine is not known to interact with heme iron, these results indicate that free iron, derived from hemoglobin, is the proximate toxic species. Overall, our data suggest that hemoglobin, released from red cells after trauma, can promote tissue injury through iron-dependent mechanisms. Suppression of this damage by desferrioxamine suggests a rational therapeutic approach to management of trauma-induced CNS injury. Images PMID:3027133

  8. 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

  9. 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

  10. Epidemiology of central nervous system mycoses.

    PubMed

    Chakrabarti, Arunaloke

    2007-01-01

    Fungal infections of the central nervous system (CNS) were considered rare until the 1970s. This is no longer true in recent years due to widespread use of corticosteroids, cytotoxic drugs and antibiotics. Immunocompromised patients with underlying malignancy organ transplantations and acquired immune deficiency syndrome are all candidates for acquiring fungal infections either in meninges or brain. A considerable number of cases of CNS fungal infections even in immunocompetent hosts have been reported. A vast array of fungi may cause infection in the CNS, but barring a few, most of them are anecdotal case reports. Cryptococcus neoformans, Candida albicans, Coccidioides immitis. Histoplasma capsulatum are common causes of fungal meningitis; Aspergillus spp, Candida spp, Zygomycetes and some of the melanized fungi are known to cause mass lesions in brain. Few fungi like C. neoformans, Cladophialophora bantiana, Exophiala dermatitidis, Ramichloridium mackenzie, Ochroconis gallopava are considered as true neurotropic fungi. Most of the fungi causing CNS infection are saprobes with worldwide distribution; a few are geographically restricted like Coccidioides immitis. The infections reach the CNS either by the hematogenous route or by direct extension from colonized sinuses or ear canal or by direct inoculation during neurosurgical procedures. PMID:17921647

  11. Central Nervous System Immune Reconstitution Inflammatory Syndrome

    PubMed Central

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

    2013-01-01

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

  12. 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.

  13. Early animal evolution and the origins of nervous systems.

    PubMed

    Budd, Graham E

    2015-12-19

    Understanding the evolution of early nervous systems is hazardous because we lack good criteria for determining homology between the systems of distant taxa; the timing of the evolutionary events is contested, and thus the relevant ecological and geological settings for them are also unclear. Here I argue that no simple approach will resolve the first issue, but that it remains likely that animals evolved relatively late, and that their nervous systems thus arose during the late Ediacaran, in a context provided by the changing planktonic and benthic environments of the time. The early trace fossil provides the most concrete evidence for early behavioural diversification, but it cannot simply be translated into increasing nervous system complexity: behavioural complexity does not map on a one-to-one basis onto nervous system complexity, both because of possible limitations to behaviour caused by the environment and because we know that even organisms without nervous systems are capable of relatively complex behaviour.

  14. Early animal evolution and the origins of nervous systems

    PubMed Central

    Budd, Graham E.

    2015-01-01

    Understanding the evolution of early nervous systems is hazardous because we lack good criteria for determining homology between the systems of distant taxa; the timing of the evolutionary events is contested, and thus the relevant ecological and geological settings for them are also unclear. Here I argue that no simple approach will resolve the first issue, but that it remains likely that animals evolved relatively late, and that their nervous systems thus arose during the late Ediacaran, in a context provided by the changing planktonic and benthic environments of the time. The early trace fossil provides the most concrete evidence for early behavioural diversification, but it cannot simply be translated into increasing nervous system complexity: behavioural complexity does not map on a one-to-one basis onto nervous system complexity, both because of possible limitations to behaviour caused by the environment and because we know that even organisms without nervous systems are capable of relatively complex behaviour. PMID:26554037

  15. Marine pharmacology in 2009-2011: marine compounds with antibacterial, antidiabetic, antifungal, anti-inflammatory, antiprotozoal, antituberculosis, and antiviral activities; affecting the immune and nervous systems, and other miscellaneous mechanisms of action.

    PubMed

    Mayer, Alejandro M S; Rodríguez, Abimael D; Taglialatela-Scafati, Orazio; Fusetani, Nobuhiro

    2013-07-16

    The peer-reviewed marine pharmacology literature from 2009 to 2011 is presented in this review, following the format used in the 1998-2008 reviews of this series. The pharmacology of structurally-characterized compounds isolated from marine animals, algae, fungi and bacteria is discussed in a comprehensive manner. Antibacterial, antifungal, antiprotozoal, antituberculosis, and antiviral pharmacological activities were reported for 102 marine natural products. Additionally, 60 marine compounds were observed to affect the immune and nervous system as well as possess antidiabetic and anti-inflammatory effects. Finally, 68 marine metabolites were shown to interact with a variety of receptors and molecular targets, and thus will probably contribute to multiple pharmacological classes upon further mechanism of action studies. Marine pharmacology during 2009-2011 remained a global enterprise, with researchers from 35 countries, and the United States, contributing to the preclinical pharmacology of 262 marine compounds which are part of the preclinical pharmaceutical pipeline. Continued pharmacological research with marine natural products will contribute to enhance the marine pharmaceutical clinical pipeline, which in 2013 consisted of 17 marine natural products, analogs or derivatives targeting a limited number of disease categories.

  16. Marine pharmacology in 2007-8: Marine compounds with antibacterial, anticoagulant, antifungal, anti-inflammatory, antimalarial, antiprotozoal, antituberculosis, and antiviral activities; affecting the immune and nervous system, and other miscellaneous mechanisms of action.

    PubMed

    Mayer, Alejandro M S; Rodríguez, Abimael D; Berlinck, Roberto G S; Fusetani, Nobuhiro

    2011-03-01

    The peer-reviewed marine pharmacology literature in 2007-8 is covered in this review, which follows a similar format to the previous 1998-2006 reviews of this series. The preclinical pharmacology of structurally characterized marine compounds isolated from marine animals, algae, fungi and bacteria is discussed in a comprehensive manner. Antibacterial, anticoagulant, antifungal, antimalarial, antiprotozoal, antituberculosis and antiviral activities were reported for 74 marine natural products. Additionally, 59 marine compounds were reported to affect the cardiovascular, immune and nervous systems as well as to possess anti-inflammatory effects. Finally, 65 marine metabolites were shown to bind to a variety of receptors and miscellaneous molecular targets, and thus upon further completion of mechanism of action studies, will contribute to several pharmacological classes. Marine pharmacology research during 2007-8 remained a global enterprise, with researchers from 26 countries, and the United States, contributing to the preclinical pharmacology of 197 marine compounds which are part of the preclinical marine pharmaceuticals pipeline. Sustained preclinical research with marine natural products demonstrating novel pharmacological activities, will probably result in the expansion of the current marine pharmaceutical clinical pipeline, which currently consists of 13 marine natural products, analogs or derivatives targeting a limited number of disease categories.

  17. Marine pharmacology in 2005–6: Marine Compounds with Anthelmintic, Antibacterial, Anticoagulant, Antifungal, Anti-inflammatory, Antimalarial, Antiprotozoal, Antituberculosis, and Antiviral Activities; affecting the Cardiovascular, Immune and Nervous Systems, and other Miscellaneous Mechanisms of Action

    PubMed Central

    Mayer, Alejandro M. S.; Rodriguez, Abimael D.; Berlinck, Roberto G. S.; Hamann, Mark T.

    2009-01-01

    BACKGROUND The review presents the 2005–2006 peer-reviewed marine pharmacology literature, and follows a similar format to the authors’ 1998–2004 reviews. The preclinical pharmacology of chemically characterized marine compounds isolated from marine animals, algae, fungi and bacteria is systematically presented. RESULTS Anthelminthic, antibacterial, anticoagulant, antifungal, antimalarial, antiprotozoal, antituberculosis and antiviral activities were reported for 78 marine chemicals. Additionally 47 marine compounds were reported to affect the cardiovascular, immune and nervous system as well as possess anti-inflammatory effects. Finally, 58 marine compounds were shown to bind to a variety of molecular targets, and thus could potentially contribute to several pharmacological classes. CONCLUSIONS Marine pharmacology research during 2005–2006 was truly global in nature, involving investigators from 32 countries, and the United States, and contributed 183 marine chemical leads to the research pipeline aimed at the discovery of novel therapeutic agents. SIGNIFICANCE Continued preclinical and clinical research with marine natural products demonstrating a broad spectrum of pharmacological activity and will probably result in novel therapeutic agents for the treatment of multiple disease categories. PMID:19303911

  18. Marine Pharmacology in 2009–2011: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis, and Antiviral Activities; Affecting the Immune and Nervous Systems, and other Miscellaneous Mechanisms of Action †

    PubMed Central

    Mayer, Alejandro M. S.; Rodríguez, Abimael D.; Taglialatela-Scafati, Orazio; Fusetani, Nobuhiro

    2013-01-01

    The peer-reviewed marine pharmacology literature from 2009 to 2011 is presented in this review, following the format used in the 1998–2008 reviews of this series. The pharmacology of structurally-characterized compounds isolated from marine animals, algae, fungi and bacteria is discussed in a comprehensive manner. Antibacterial, antifungal, antiprotozoal, antituberculosis, and antiviral pharmacological activities were reported for 102 marine natural products. Additionally, 60 marine compounds were observed to affect the immune and nervous system as well as possess antidiabetic and anti-inflammatory effects. Finally, 68 marine metabolites were shown to interact with a variety of receptors and molecular targets, and thus will probably contribute to multiple pharmacological classes upon further mechanism of action studies. Marine pharmacology during 2009–2011 remained a global enterprise, with researchers from 35 countries, and the United States, contributing to the preclinical pharmacology of 262 marine compounds which are part of the preclinical pharmaceutical pipeline. Continued pharmacological research with marine natural products will contribute to enhance the marine pharmaceutical clinical pipeline, which in 2013 consisted of 17 marine natural products, analogs or derivatives targeting a limited number of disease categories. PMID:23880931

  19. Extraversion, Neuroticism and Strength of the Nervous System

    ERIC Educational Resources Information Center

    Frigon, Jean-Yves

    1976-01-01

    The hypothesized identity of the dimensions of extraversion-introversion and strength of the nervous system was tested on four groups of nine subjects (neurotic extraverts, stable extraverts, neurotic introverts, stable introverts). Strength of the subjects' nervous system was estimated using the electroencephalographic (EEG) variant of extinction…

  20. Extraversion, neuroticism and strength of the nervous system.

    PubMed

    Frigon, J Y

    1976-11-01

    The hypothesized identity of the dimensions of extraversion-introversion and strength of the nervous system was tested on four groups of nine subjects (neurotic extraverts, stable extraverts, neurotic introverts, stable introverts). Strength of the subjects' nervous system was estimated using the electroencephalographic (EEG) variant of extinction with reinforcement. Introverted subjects were found to have weak nervous systems, according to the EEG index, while extraverted subjects had strong nervous systems, thus confirming the hypothesis. It was also found that the dimension of strength of the nervous system was unrelated to differences in neuroticism. The results are interpreted as adding support to Eysenck's theory relating differences in extraversion-introversion to differences in cortical arousal.

  1. The Adverse Effects of Air Pollution on the Nervous System

    PubMed Central

    Genc, Sermin; Zadeoglulari, Zeynep; Fuss, Stefan H.; Genc, Kursad

    2012-01-01

    Exposure to ambient air pollution is a serious and common public health concern associated with growing morbidity and mortality worldwide. In the last decades, the adverse effects of air pollution on the pulmonary and cardiovascular systems have been well established in a series of major epidemiological and observational studies. In the recent past, air pollution has also been associated with diseases of the central nervous system (CNS), including stroke, Alzheimer's disease, Parkinson's disease, and neurodevelopmental disorders. It has been demonstrated that various components of air pollution, such as nanosized particles, can easily translocate to the CNS where they can activate innate immune responses. Furthermore, systemic inflammation arising from the pulmonary or cardiovascular system can affect CNS health. Despite intense studies on the health effects of ambient air pollution, the underlying molecular mechanisms of susceptibility and disease remain largely elusive. However, emerging evidence suggests that air pollution-induced neuroinflammation, oxidative stress, microglial activation, cerebrovascular dysfunction, and alterations in the blood-brain barrier contribute to CNS pathology. A better understanding of the mediators and mechanisms will enable the development of new strategies to protect individuals at risk and to reduce detrimental effects of air pollution on the nervous system and mental health. PMID:22523490

  2. [Components of plastic disrupt the function of the nervous system].

    PubMed

    Szychowski, Konrad Andrzej; Wójtowicz, Anna Katarzyna

    2013-05-27

    Development of the chemical industry leads to the development of new chemical compounds, which naturally do not exist in the environment. These chemicals are used to reduce flammability, increase plasticity, or improve solubility of other substances. Many of these compounds, which are components of plastic, the new generation of cosmetics, medical devices, food packaging and other everyday products, are easily released into the environment. Many studies have shown that a major lipophilicity characterizes substances such as phthalates, BPA, TBBPA and PCBs. This feature allows them to easily penetrate into living cells, accumulate in the tissues and the organs, and affect human and animal health. Due to the chemical structures, these compounds are able to mimic some endogenous hormones such as estradiol and to disrupt the hormone homeostasis. They can also easily pass the placental barrier and the blood-brain barrier. As numerous studies have shown, these chemicals disturb the proper functions of the nervous system from the earliest moments of life. It has been proven that these compounds affect neurogenesis as well as the synaptic transmission process. As a consequence, they interfere with the formation of the sex of the brain, as well as with the learning processes, memory and behavior. Additionally, the cytotoxic and pro-apoptotic effect may cause neurodegenerative diseases. This article presents the current state of knowledge about the effects of phthalates, BPA, TBBPA, and PCBs on the nervous system.

  3. Hypersensitivity Responses in the Central Nervous System

    PubMed Central

    Khorooshi, Reza; Asgari, Nasrin; Mørch, Marlene Thorsen; Berg, Carsten Tue; Owens, Trevor

    2015-01-01

    Immune-mediated tissue damage or hypersensitivity can be mediated by autospecific IgG antibodies. Pathology results from activation of complement, and antibody-dependent cellular cytotoxicity, mediated by inflammatory effector leukocytes include macrophages, natural killer cells, and granulocytes. Antibodies and complement have been associated to demyelinating pathology in multiple sclerosis (MS) lesions, where macrophages predominate among infiltrating myeloid cells. Serum-derived autoantibodies with predominant specificity for the astrocyte water channel aquaporin-4 (AQP4) are implicated as inducers of pathology in neuromyelitis optica (NMO), a central nervous system (CNS) demyelinating disease where activated neutrophils infiltrate, unlike in MS. The most widely used model for MS, experimental autoimmune encephalomyelitis, is an autoantigen-immunized disease that can be transferred to naive animals with CD4+ T cells, but not with antibodies. By contrast, NMO-like astrocyte and myelin pathology can be transferred to mice with AQP4–IgG from NMO patients. This is dependent on complement, and does not require T cells. Consistent with clinical observations that interferon-beta is ineffective as a therapy for NMO, NMO-like pathology is significantly reduced in mice lacking the Type I IFN receptor. In MS, there is evidence for intrathecal synthesis of antibodies as well as blood–brain barrier (BBB) breakdown, whereas in NMO, IgG accesses the CNS from blood. Transfer models involve either direct injection of antibody and complement to the CNS, or experimental manipulations to induce BBB breakdown. We here review studies in MS and NMO that elucidate roles for IgG and complement in the induction of BBB breakdown, astrocytopathy, and demyelinating pathology. These studies point to significance of T-independent effector mechanisms in neuroinflammation. PMID:26500654

  4. Radiation response of the central nervous system

    SciTech Connect

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

    1995-03-30

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

  5. Mechanosensitivity in the enteric nervous system

    PubMed Central

    Mazzuoli-Weber, Gemma; Schemann, Michael

    2015-01-01

    The enteric nervous system (ENS) autonomously controls gut muscle activity. Mechanosensitive enteric neurons (MEN) initiate reflex activity by responding to mechanical deformation of the gastrointestinal wall. MEN throughout the gut primarily respond to compression or stretch rather than to shear force. Some MEN are multimodal as they respond to compression and stretch. Depending on the region up to 60% of the entire ENS population responds to mechanical stress. MEN fire action potentials after mechanical stimulation of processes or soma although they are more sensitive to process deformation. There are at least two populations of MEN based on their sensitivity to different modalities of mechanical stress and on their firing pattern. (1) Rapidly, slowly and ultra-slowly adapting neurons which encode compressive forces. (2) Ultra-slowly adapting stretch-sensitive neurons encoding tensile forces. Rapid adaptation of firing is typically observed after compressive force while slow adaptation or ongoing spike discharge occurs often during tensile stress (stretch). All MEN have some common properties: they receive synaptic input, are low fidelity mechanoreceptors and are multifunctional in that some serve interneuronal others even motor functions. Consequently, MEN possess processes with mechanosensitive as well as efferent functions. This raises the intriguing hypothesis that MEN sense and control muscle activity at the same time as servo-feedback loop. The mechanosensitive channel(s) or receptor(s) expressed by the different MEN populations are unknown. Future concepts have to incorporate compressive and tensile-sensitive MEN into neural circuits that controls muscle activity. They may interact to control various forms of a particular motor pattern or regulate different motor patterns independently from each other. PMID:26528136

  6. Carbon monoxide and the nervous system.

    PubMed

    Raub, J A; Benignus, V A

    2002-12-01

    Carbon monoxide (CO) is a colorless, tasteless, odorless, and non-irritating gas formed when carbon in fuel is not burned completely. It enters the bloodstream through the lungs and attaches to hemoglobin (Hb), the body's oxygen carrier, forming carboxyhemoglobin (COHb) and thereby reducing oxygen (O(2)) delivery to the body's organs and tissues. High COHb concentrations are poisonous. Central nervous system (CNS) effects in individuals suffering acute CO poisoning cover a wide range, depending on severity of exposure: headache, dizziness, weakness, nausea, vomiting, disorientation, confusion, collapse, and coma. At lower concentrations, CNS effects include reduction in visual perception, manual dexterity, learning, driving performance, and attention level. Earlier work is frequently cited to justify the statement that CO exposure sufficient to produce COHb levels of ca. 5% would be sufficient to produce visual sensitivity reduction and various neurobehavioral performance deficits. In a recent literature re-evaluation, however, the best estimate was that [COHb] would have to rise to 15-20% before a 10% reduction in any behavioral or visual measurement could be observed. This conclusion was based on (1) critical review of the literature on behavioral and sensory effects, (2) review and interpretation of the physiological effects of COHb on the CNS, (3) extrapolation from the effects of hypoxic hypoxia to the effects of CO hypoxia, and (4) extrapolation from rat behavioral effects of CO to humans. Also covered in this review article are effects of chronic CO exposure, the discovery of neuroglobin, a summary of the relatively new role for endogenous CO in neurotransmission and vascular homeostasis, groups which might be especially sensitive to CO, and recommendations on further research. The interested reader is directed to other published reviews of the literature on CO and historically seminal references that form our understanding of this ubiquitous gas. PMID

  7. Is There Anything "Autonomous" in the Nervous System?

    ERIC Educational Resources Information Center

    Rasia-Filho, Alberto A.

    2006-01-01

    The terms "autonomous" or "vegetative" are currently used to identify one part of the nervous system composed of sympathetic, parasympathetic, and gastrointestinal divisions. However, the concepts that are under the literal meaning of these words can lead to misconceptions about the actual nervous organization. Some clear-cut examples indicate…

  8. General Information about Childhood Central Nervous System Embryonal Tumors

    MedlinePlus

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

  9. Animal-microbe interactions and the evolution of nervous systems.

    PubMed

    Eisthen, Heather L; Theis, Kevin R

    2016-01-01

    Animals ubiquitously interact with environmental and symbiotic microbes, and the effects of these interactions on animal physiology are currently the subject of intense interest. Nevertheless, the influence of microbes on nervous system evolution has been largely ignored. We illustrate here how taking microbes into account might enrich our ideas about the evolution of nervous systems. For example, microbes are involved in animals' communicative, defensive, predatory and dispersal behaviours, and have likely influenced the evolution of chemo- and photosensory systems. In addition, we speculate that the need to regulate interactions with microbes at the epithelial surface may have contributed to the evolutionary internalization of the nervous system.

  10. Calretinin in the peripheral nervous system of the adult zebrafish

    PubMed Central

    Levanti, M B; Montalbano, G; Laurà, R; Ciriaco, E; Cobo, T; García-Suarez, O; Germanà, A; Vega, J A

    2008-01-01

    Calretinin is a calcium-binding protein found widely distributed in the central nervous system and chemosensory cells of the teleosts, but its presence in the peripheral nervous system of fishes is unknown. In this study we used Western blot analysis and immunohistochemistry to investigate the occurrence and distribution of calretinin in the cranial nerve ganglia, dorsal root ganglia, sympathetic ganglia, and enteric nervous system of the adult zebrafish. By Western blotting a unique and specific protein band with an estimated molecular weight of around 30 kDa was detected, and it was identified as calretinin. Immunohistochemistry revealed that calretinin is selectively present in the cytoplasm of the neurons and never in the satellite glial cells. In both sensory and sympathetic ganglia the density of neurons that were immunolabelled, their size and morphology, as well as the intensity of immunostaining developed within the cytoplasm, were heterogeneous. In the enteric nervous system calretinin immunoreactivity was detected in a subset of enteric neurons as well as in a nerve fibre plexus localized inside the muscular layers. The present results demonstrate that in addition to the central nervous system, calretinin is also present in the peripheral nervous system of zebrafish, and contribute to completing the map of the distribution of this protein in the nervous system of teleosts. PMID:18173770

  11. [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.

  12. Autoantibodies to nervous system-specific proteins are elevated in sera of flight crew members: biomarkers for nervous system injury.

    PubMed

    Abou-Donia, Mohamed B; Abou-Donia, Martha M; ElMasry, Eman M; Monro, Jean A; Mulder, Michel F A

    2013-01-01

    This descriptive study reports the results of assays performed to detect circulating autoantibodies in a panel of 7 proteins associated with the nervous system (NS) in sera of 12 healthy controls and a group of 34 flight crew members including both pilots and attendants who experienced adverse effects after exposure to air emissions sourced to the ventilation system in their aircrafts and subsequently sought medical attention. The proteins selected represent various types of proteins present in nerve cells that are affected by neuronal degeneration. In the sera samples from flight crew members and healthy controls, immunoglobin (IgG) was measured using Western blotting against neurofilament triplet proteins (NFP), tubulin, microtubule-associated tau proteins (tau), microtubule-associated protein-2 (MAP-2), myelin basic protein (MBP), glial fibrillary acidic protein (GFAP), and glial S100B protein. Significant elevation in levels of circulating IgG-class autoantibodies in flight crew members was found. A symptom-free pilot was sampled before symptoms and then again afterward. This pilot developed clinical problems after flying for 45 h in 10 d. Significant increases in autoantibodies were noted to most of the tested proteins in the serum of this pilot after exposure to air emissions. The levels of autoantibodies rose with worsening of his condition compared to the serum sample collected prior to exposure. After cessation of flying for a year, this pilot's clinical condition improved, and eventually he recovered and his serum autoantibodies against nervous system proteins decreased. The case study with this pilot demonstrates a temporal relationship between exposure to air emissions, clinical condition, and level of serum autoantibodies to nervous system-specific proteins. Overall, these results suggest the possible development of neuronal injury and gliosis in flight crew members anecdotally exposed to cabin air emissions containing organophosphates. Thus, increased

  13. The Human Sympathetic Nervous System Response to Spaceflight

    NASA Technical Reports Server (NTRS)

    Ertl, Andrew C.; Diedrich, Andre; Paranjape, Sachin Y.; Biaggioni, Italo; Robertson, Rose Marie; Lane, Lynda D.; Shiavi, Richard; Robertson, David

    2003-01-01

    The sympathetic nervous system is an important part of the autonomic (or automatic) nervous system. When an individual stands up, the sympathetic nervous system speeds the heart and constricts blood vessels to prevent a drop in blood pressure. A significant number of astronauts experience a drop in blood pressure when standing for prolonged periods after they return from spaceflight. Difficulty maintaining blood pressure with standing is also a daily problem for many patients. Indirect evidence available before the Neurolab mission suggested the problem in astronauts while in space might be due partially to reduced sympathetic nervous system activity. The purpose of this experiment was to identify whether sympathetic activity was reduced during spaceflight. Sympathetic nervous system activity can be determined in part by measuring heart rate, nerve activity going to blood vessels, and the release of the hormone norepinephrine into the blood. Norepinephrine is a neurotransmitter discharged from active sympathetic nerve terminals, so its rate of release can serve as a marker of sympathetic nervous system action. In addition to standard cardiovascular measurements (heart rate, blood pressure), we determined sympathetic nerve activity as well as norepinephrine release and clearance on four crewmembers on the Neurolab mission. Contrary to our expectation, the results demonstrated that the astronauts had mildly elevated resting sympathetic nervous system activity in space. Sympathetic nervous system responses to stresses that simulated the cardiovascular effects of standing (lower body negative pressure) were brisk both during and after spaceflight. We concluded that, in the astronauts tested, the activity and response of the sympathetic nervous system to cardiovascular stresses appeared intact and mildly elevated both during and after spaceflight. These changes returned to normal within a few days.

  14. Evolution of eumetazoan nervous systems: insights from cnidarians

    PubMed Central

    Kelava, Iva; Rentzsch, Fabian; Technau, Ulrich

    2015-01-01

    Cnidarians, the sister group to bilaterians, have a simple diffuse nervous system. This morphological simplicity and their phylogenetic position make them a crucial group in the study of the evolution of the nervous system. The development of their nervous systems is of particular interest, as by uncovering the genetic programme that underlies it, and comparing it with the bilaterian developmental programme, it is possible to make assumptions about the genes and processes involved in the development of ancestral nervous systems. Recent advances in sequencing methods, genetic interference techniques and transgenic technology have enabled us to get a first glimpse into the molecular network underlying the development of a cnidarian nervous system—in particular the nervous system of the anthozoan Nematostella vectensis. It appears that much of the genetic network of the nervous system development is partly conserved between cnidarians and bilaterians, with Wnt and bone morphogenetic protein (BMP) signalling, and Sox genes playing a crucial part in the differentiation of neurons. However, cnidarians possess some specific characteristics, and further studies are necessary to elucidate the full regulatory network. The work on cnidarian neurogenesis further accentuates the need to study non-model organisms in order to gain insights into processes that shaped present-day lineages during the course of evolution. PMID:26554048

  15. Bacterial meningitis and other nonviral infections of the nervous system.

    PubMed

    Bleck, Thomas P

    2013-10-01

    Bacteria and fungi, owing to their intrinsic properties and the host responses they produce, result in relatively specific clinical syndromes when they infect the central nervous system. The infecting organism may produce symptoms and signs by interfering with the function of the nervous system tissue being invaded or compressed. The definitive treatment of central nervous system infection depends on correct identification and antimicrobial treatment of the infecting organism, relief of excessive pressure or mass effect that it exerts, and modulation of the host's immune response to allow clearance of the organism while minimizing excessive inflammation. PMID:24094387

  16. 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.

  17. 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

  18. Ultrasonic Transduction of DNA into Central Nervous System Cells

    NASA Astrophysics Data System (ADS)

    Manome, Yoshinobu; Nakayama, Naoto; Furuhata, Hiroshi

    2005-03-01

    Many diseases involving the central nervous system are intractable to conventional therapies, thereby requiring an alternative treatment such as gene therapy. Therapy requires safety since the central nervous system is a critical organ. The choice of non-viral vectors, such as naked plasmid DNA, may have merit. However, transduction efficiencies of these vectors are low. We have investigated the use of ultrasound and found that insonation effectively enhanced transduction of naked plasmid DNA into cultured slices of mouse brain. Since ultrasound successfully facilitated the transduction of naked plasmid DNA into the neural tissue, this approach may have a role in gene therapy for the central nervous system.

  19. Role of Mycobacterium tuberculosis pknD in the Pathogenesis of central nervous system tuberculosis

    PubMed Central

    2012-01-01

    Background Central nervous system disease is the most serious form of tuberculosis, and is associated with high mortality and severe neurological sequelae. Though recent clinical reports suggest an association of distinct Mycobacterium tuberculosis strains with central nervous system disease, the microbial virulence factors required have not been described previously. Results We screened 398 unique M. tuberculosis mutants in guinea pigs to identify genes required for central nervous system tuberculosis. We found M. tuberculosis pknD (Rv0931c) to be required for central nervous system disease. These findings were central nervous system tissue-specific and were not observed in lung tissues. We demonstrated that pknD is required for invasion of brain endothelia (primary components of the blood-brain barrier protecting the central nervous system), but not macrophages, lung epithelia, or other endothelia. M. tuberculosis pknD encodes a "eukaryotic-like" serine-threonine protein kinase, with a predicted intracellular kinase and an extracellular (sensor) domain. Using confocal microscopy and flow cytometry we demonstrated that the M. tuberculosis PknD sensor is sufficient to trigger invasion of brain endothelia, a process which was neutralized by specific antiserum. Conclusions Our findings demonstrate a novel in vivo role for M. tuberculosis pknD and represent an important mechanism for bacterial invasion and virulence in central nervous system tuberculosis, a devastating and understudied disease primarily affecting young children. PMID:22243650

  20. Probing disorders of the nervous system using reprogramming approaches

    PubMed Central

    Ichida, Justin K; Kiskinis, Evangelos

    2015-01-01

    The groundbreaking technologies of induced pluripotency and lineage conversion have generated a genuine opportunity to address fundamental aspects of the diseases that affect the nervous system. These approaches have granted us unrestricted access to the brain and spinal cord of patients and have allowed for the study of disease in the context of human cells, expressing physiological levels of proteins and under each patient's unique genetic constellation. Along with this unprecedented opportunity have come significant challenges, particularly in relation to patient variability, experimental design and data interpretation. Nevertheless, significant progress has been achieved over the past few years both in our ability to create the various neural subtypes that comprise the nervous system and in our efforts to develop cellular models of disease that recapitulate clinical findings identified in patients. In this Review, we present tables listing the various human neural cell types that can be generated and the neurological disease modeling studies that have been reported, describe the current state of the field, highlight important breakthroughs and discuss the next steps and future challenges. PMID:25925386

  1. Vulnerable processes of nervous system development: a review of markers and methods.

    PubMed

    Barone, S; Das, K P; Lassiter, T L; White, L D

    2000-01-01

    The susceptibility of the developing nervous system to damage following exposure to environmental contaminants has been well recognized. More recently, from a regulatory perspective, an increased emphasis has been placed on the vulnerability of the developing nervous system to damage following pesticide exposure. The publication of the National Academy of Sciences (NAS) report on Pesticides in the Diets of Infants and Children (1995) and the passage of the Food Quality Protection Act (FQPA) and Safe Drinking Water Act (SDWA) amendments have significantly escalated the scientific debate regarding age-related susceptibility. Key concerns raised in the NAS report include the qualitative and quantitative differences that distinguish the developing nervous system from that of the adult. It was suggested that neurotoxicity testing on adult animals alone may not be predictive of these differences in susceptibility. The age-related susceptibility of the nervous system is compounded by the protracted period of time over which this complex organ system develops. This temporal vulnerability spans the embryonic, fetal, infant, and adolescent periods. Normal development of the nervous system requires the concomitant and coordinated ontogeny of proliferation, migration, differentiation, synaptogenesis, gliogenesis, myelination and apoptosis to occur in a temporally- and regionally-dependent manner. Perturbations of these processes during development can result in long-term irreversible consequences that affect the structure and function of the nervous system and could account for qualitative differences in age-related susceptibility of the developing nervous system as compared to the adult nervous system. A discussion of developmental milestones and the relevance of transient effects on developmental endpoints are presented. Transient effects following developmental perturbations can be missed or dismissed depending on the experimental design or screening strategy employed. This

  2. The sympathetic nervous system alterations in human hypertension.

    PubMed

    Grassi, Guido; Mark, Allyn; Esler, Murray

    2015-03-13

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

  3. Reinforcement concept in investigations on simple nervous systems.

    PubMed

    Balaban, P M

    1997-01-01

    An analysis of the applicability of the concept of reinforcement to the studies of learning in simple nervous systems of invertebrates is made. Analysis of the literature data and my own results suggests that reinforcement cannot be regarded as an independent behavioral phenomenon. A description of reinforcement as a state of the nervous system which precedes long-term changes of behavior is given. Using the example of aversive conditioning to food in gastropod snails it is shown that a state of the network that can be correlated with the state of reinforcement can be elicited in the simple nervous system by activation of serotonergic pedal cells modulating avoidance behavior of the animal. The conclusion is made that with certain limitations the reinforcement concept can be used in studies on simple nervous systems.

  4. Complex Homology and the Evolution of Nervous Systems

    PubMed Central

    Liebeskind, Benjamin J.; Hillis, David M.; Zakon, Harold H.; Hofmann, Hans A.

    2016-01-01

    We examine the complex evolution of animal nervous systems and discuss the ramifications of this complexity for inferring the nature of early animals. Although reconstructing the origins of nervous systems remains a central challenge in biology, and the phenotypic complexity of early animals remains controversial, a compelling picture is emerging. We now know that the nervous system and other key animal innovations contain a large degree of homoplasy, at least on the molecular level. Conflicting hypotheses about early nervous system evolution are due primarily to differences in the interpretation of this homoplasy. We highlight the need for explicit discussion of assumptions and discuss the limitations of current approaches for inferring ancient phenotypic states. PMID:26746806

  5. 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

  6. [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.

  7. Source characterization of nervous system active pharmaceutical ingredients in healthcare wastewaters

    EPA Science Inventory

    Nervous system active pharmaceutical ingredients (APIs), including anti-depressants and opioids, are important clinically administered pharmaceuticals within healthcare facilities. Concentrations and mass loadings of ten nervous system APIs and three nervous system API metaboli...

  8. Introduction to 'Origin and evolution of the nervous system'.

    PubMed

    Strausfeld, Nicholas J; Hirth, Frank

    2015-12-19

    In 1665, Robert Hooke demonstrated in Micrographia the power of the microscope and comparative observations, one of which revealed similarities between the arthropod and vertebrate eyes. Utilizing comparative observations, Saint-Hilaire in 1822 was the first to propose that the ventral nervous system of arthropods corresponds to the dorsal nervous system of vertebrates. Since then, studies on the origin and evolution of the nervous system have become inseparable from studies about Metazoan origins and the origins of organ systems. The advent of genome sequence data and, in turn, phylogenomics and phylogenetics have refined cladistics and expanded our understanding of Metazoan phylogeny. However, the origin and evolution of the nervous system is still obscure and many questions and problems remain. A recurrent problem is whether and to what extent sequence data provide reliable guidance for comparisons across phyla. Are genetic data congruent with the geological fossil records? How can we reconcile evolved character loss with phylogenomic records? And how informative are genetic data in relation to the specification of nervous system morphologies? These provide some of the background and context for a Royal Society meeting to discuss new data and concepts that might achieve insights into the origin and evolution of brains and nervous systems. PMID:26554035

  9. Introduction to 'Origin and evolution of the nervous system'.

    PubMed

    Strausfeld, Nicholas J; Hirth, Frank

    2015-12-19

    In 1665, Robert Hooke demonstrated in Micrographia the power of the microscope and comparative observations, one of which revealed similarities between the arthropod and vertebrate eyes. Utilizing comparative observations, Saint-Hilaire in 1822 was the first to propose that the ventral nervous system of arthropods corresponds to the dorsal nervous system of vertebrates. Since then, studies on the origin and evolution of the nervous system have become inseparable from studies about Metazoan origins and the origins of organ systems. The advent of genome sequence data and, in turn, phylogenomics and phylogenetics have refined cladistics and expanded our understanding of Metazoan phylogeny. However, the origin and evolution of the nervous system is still obscure and many questions and problems remain. A recurrent problem is whether and to what extent sequence data provide reliable guidance for comparisons across phyla. Are genetic data congruent with the geological fossil records? How can we reconcile evolved character loss with phylogenomic records? And how informative are genetic data in relation to the specification of nervous system morphologies? These provide some of the background and context for a Royal Society meeting to discuss new data and concepts that might achieve insights into the origin and evolution of brains and nervous systems.

  10. A single origin of the central nervous system?

    PubMed

    Telford, Maximilian J

    2007-04-20

    As Denes et al. (2007) reveal in this issue, the expression profile and roles of genes that pattern the nervous system in embryos of chordates and annelids are surprisingly similar. This extraordinary conservation suggests that the patterning mechanism has been inherited largely unchanged from the bilaterian common ancestor and that the central nervous system, although dorsal in fish and ventral in worms, is an ancient characteristic of animals. PMID:17448982

  11. A simple analogy for nervous system plasticity after injury.

    PubMed

    Fouad, Karim; Forero, Juan; Hurd, Caitlin

    2015-04-01

    When considering plasticity, the central nervous system can be viewed as a building block house. After damage, building components might be lost or loosened and may be rearranged by renovation, analogous to neuroplasticity that occurs after central nervous system injury. In both scenarios, the location and severity of damage will determine the efficacy of renovation/rehabilitation and thus the quality of the adapted structure.

  12. Holothurian Nervous System Diversity Revealed by Neuroanatomical Analysis.

    PubMed

    Díaz-Balzac, Carlos A; Lázaro-Peña, María I; Vázquez-Figueroa, Lionel D; Díaz-Balzac, Roberto J; García-Arrarás, José E

    2016-01-01

    The Echinodermata comprise an interesting branch in the phylogenetic tree of deuterostomes. Their radial symmetry which is reflected in their nervous system anatomy makes them a target of interest in the study of nervous system evolution. Until recently, the study of the echinoderm nervous system has been hindered by a shortage of neuronal markers. However, in recent years several markers of neuronal and fiber subpopulations have been described. These have been used to identify subpopulations of neurons and fibers, but an integrative study of the anatomical relationship of these subpopulations is wanting. We have now used eight commercial antibodies, together with three antibodies produced by our group to provide a comprehensive and integrated description and new details of the echinoderm neuroanatomy using the holothurian Holothuria glaberrima (Selenka, 1867) as our model system. Immunoreactivity of the markers used showed: (1) specific labeling patterns by markers in the radial nerve cords, which suggest the presence of specific nerve tracts in holothurians. (2) Nerves directly innervate most muscle fibers in the longitudinal muscles. (3) Similar to other deuterostomes (mainly vertebrates), their enteric nervous system is composed of a large and diverse repertoire of neurons and fiber phenotypes. Our results provide a first blueprint of the anatomical organization of cells and fibers that form the holothurian neural circuitry, and highlight the fact that the echinoderm nervous system shows unexpected diversity in cell and fiber types and their distribution in both central and peripheral nervous components.

  13. Holothurian Nervous System Diversity Revealed by Neuroanatomical Analysis.

    PubMed

    Díaz-Balzac, Carlos A; Lázaro-Peña, María I; Vázquez-Figueroa, Lionel D; Díaz-Balzac, Roberto J; García-Arrarás, José E

    2016-01-01

    The Echinodermata comprise an interesting branch in the phylogenetic tree of deuterostomes. Their radial symmetry which is reflected in their nervous system anatomy makes them a target of interest in the study of nervous system evolution. Until recently, the study of the echinoderm nervous system has been hindered by a shortage of neuronal markers. However, in recent years several markers of neuronal and fiber subpopulations have been described. These have been used to identify subpopulations of neurons and fibers, but an integrative study of the anatomical relationship of these subpopulations is wanting. We have now used eight commercial antibodies, together with three antibodies produced by our group to provide a comprehensive and integrated description and new details of the echinoderm neuroanatomy using the holothurian Holothuria glaberrima (Selenka, 1867) as our model system. Immunoreactivity of the markers used showed: (1) specific labeling patterns by markers in the radial nerve cords, which suggest the presence of specific nerve tracts in holothurians. (2) Nerves directly innervate most muscle fibers in the longitudinal muscles. (3) Similar to other deuterostomes (mainly vertebrates), their enteric nervous system is composed of a large and diverse repertoire of neurons and fiber phenotypes. Our results provide a first blueprint of the anatomical organization of cells and fibers that form the holothurian neural circuitry, and highlight the fact that the echinoderm nervous system shows unexpected diversity in cell and fiber types and their distribution in both central and peripheral nervous components. PMID:26987052

  14. Holothurian Nervous System Diversity Revealed by Neuroanatomical Analysis

    PubMed Central

    Díaz-Balzac, Carlos A.; Lázaro-Peña, María I.; Vázquez-Figueroa, Lionel D.; Díaz-Balzac, Roberto J.; García-Arrarás, José E.

    2016-01-01

    The Echinodermata comprise an interesting branch in the phylogenetic tree of deuterostomes. Their radial symmetry which is reflected in their nervous system anatomy makes them a target of interest in the study of nervous system evolution. Until recently, the study of the echinoderm nervous system has been hindered by a shortage of neuronal markers. However, in recent years several markers of neuronal and fiber subpopulations have been described. These have been used to identify subpopulations of neurons and fibers, but an integrative study of the anatomical relationship of these subpopulations is wanting. We have now used eight commercial antibodies, together with three antibodies produced by our group to provide a comprehensive and integrated description and new details of the echinoderm neuroanatomy using the holothurian Holothuria glaberrima (Selenka, 1867) as our model system. Immunoreactivity of the markers used showed: (1) specific labeling patterns by markers in the radial nerve cords, which suggest the presence of specific nerve tracts in holothurians. (2) Nerves directly innervate most muscle fibers in the longitudinal muscles. (3) Similar to other deuterostomes (mainly vertebrates), their enteric nervous system is composed of a large and diverse repertoire of neurons and fiber phenotypes. Our results provide a first blueprint of the anatomical organization of cells and fibers that form the holothurian neural circuitry, and highlight the fact that the echinoderm nervous system shows unexpected diversity in cell and fiber types and their distribution in both central and peripheral nervous components. PMID:26987052

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

    PubMed

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

    2016-08-01

    Experimental evidence suggests that astrocytes play a crucial role in the physiology of the central nervous system (CNS) by modulating synaptic activity and plasticity. Based on what is currently known we postulate that astrocytes are fundamental, along with neurons, for the information processing that takes place within the CNS. On the other hand, experimental findings and human observations signal that some of the primary degenerative diseases of the CNS, like frontotemporal dementia, Parkinson's disease, Alzheimer's dementia, Huntington's dementia, primary cerebellar ataxias and amyotrophic lateral sclerosis, all of which affect the human species exclusively, may be due to astroglial dysfunction. This hypothesis is supported by observations that demonstrated that the killing of neurons by non-neural cells plays a major role in the pathogenesis of those diseases, at both their onset and their progression. Furthermore, recent findings suggest that astrocytes might be involved in the pathogenesis of some psychiatric disorders as well. PMID:27556379

  16. Rosai-Dorfman Disease of the Central Nervous System

    PubMed Central

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

    2014-01-01

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

  17. 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

  18. Therapeutic Application of Electric Fields in the Injured Nervous System.

    PubMed

    Haan, Niels; Song, Bing

    2014-02-01

    Significance: Nervous system injuries, both in the peripheral nervous system (PNS) and central nervous system are a major cause for pain, loss-of-function, and impairment of daily life. As nervous system injuries commonly heal slowly or incompletely, new therapeutic approaches may be required. Recent Advances: The observation that cultured neurons are able to respond to exogenous electric fields (EFs) by sprouting more neurites and directing growth along the field, along with the presence of endogenous EFs in the developing vertebrate nervous system have led to the suggestion of the use of EFs in a regenerative therapeutic setting. This review discusses the effects of EFs on nervous cells, and their use in the treatment of nervous injuries in the eye, limb nerves, and the spinal cord. Exogenous EFs have been shown to be neuroprotective in various injury models of the eye, including traumatic injury, congenital degenerative retinopathy, and glaucoma. In the PNS, EFs are able to stimulate regrowth and functional recovery in damaged limb nerves. In the spinal cord, axonal regeneration and improved quality of life may be achieved using EF stimulation. Critical Issues: The optimal paradigm for electrical stimulation has not been determined, and the mechanisms behind the effect of EF are still largely unknown. Future Directions: Although the therapeutic use of EFs in the nervous system is still in its infancy, it is a promising therapeutic avenue for otherwise hard to treat injuries. The cellular/molecular mechanisms of such regulation need to be fully investigated, and the efficiency of applied EFs during wound healing needs to be optimized in a systematic approach in both animal models and future clinical trials. PMID:24761356

  19. Vascular endothelial growth factor in central nervous system injuries - a vascular growth factor getting nervous?

    PubMed

    Sköld, Mattias K; Kanje, Martin

    2008-11-01

    Vascular Endothelial Growth Factor (VEGF) is recognized as a central factor in growth, survival and permeability of blood vessels in both physiological and pathological conditions. It is as such of importance for vascular responses in various central nervous system (CNS) disorders. Accumulating evidence suggest that VEGF may also act as a neuroprotective and neurotrophic factor supporting neuronal survival and neuronal regeneration. Findings of neuropilins as shared co-receptors between molecules with such seemingly different functions as the axon guidance molecules semaphorins and VEGF has further boosted the interest in the role of VEGF in neural tissue injury and repair mechanisms. Thus, VEGF most likely act in parallel or concurrent on cells in both the vascular and nervous system. The present review gives a summary of known or potential aspects of the VEGF system in the healthy and diseased nervous system. The potential benefits but also problems and pitfalls in intervening in the actions of such a multifunctional factor as VEGF in the disordered CNS are also covered.

  20. Reactions of the nervous system to magnetic fields

    NASA Technical Reports Server (NTRS)

    Kholodov, Y. A.

    1974-01-01

    This magnetobiological survey considers sensory, nervous, stress and genetic effects of magnetic fields on man and animals. It is shown that the nervous system plays an important role in the reactions of the organism to magnetic fields; the final biological effect is a function of the strength of the magnetic fields, the gradient, direction of the lines of force, duration and location of the action, and the functional status of the organism.

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

    PubMed

    Namekawa, Michito

    2014-08-01

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

  2. The role of the autonomic nervous system in Tourette Syndrome

    PubMed Central

    Hawksley, Jack; Cavanna, Andrea E.; Nagai, Yoko

    2015-01-01

    Tourette Syndrome (TS) is a neurodevelopmental disorder, consisting of multiple involuntary movements (motor tics) and one or more vocal (phonic) tics. It affects up to one percent of children worldwide, of whom about one third continue to experience symptoms into adulthood. The central neural mechanisms of tic generation are not clearly understood, however recent neuroimaging investigations suggest impaired cortico-striato-thalamo-cortical activity during motor control. In the current manuscript, we will tackle the relatively under-investigated role of the peripheral autonomic nervous system, and its central influences, on tic activity. There is emerging evidence that both sympathetic and parasympathetic nervous activity influences tic expression. Pharmacological treatments which act on sympathetic tone are often helpful: for example, Clonidine (an alpha-2 adrenoreceptor agonist) is often used as first choice medication for treating TS in children due to its good tolerability profile and potential usefulness for co-morbid attention-deficit and hyperactivity disorder. Clonidine suppresses sympathetic activity, reducing the triggering of motor tics. A general elevation of sympathetic tone is reported in patients with TS compared to healthy people, however this observation may reflect transient responses coupled to tic activity. Thus, the presence of autonomic impairments in patients with TS remains unclear. Effect of autonomic afferent input to cortico-striato-thalamo-cortical circuit will be discussed schematically. We additionally review how TS is affected by modulation of central autonomic control through biofeedback and Vagus Nerve Stimulation (VNS). Biofeedback training can enable a patient to gain voluntary control over covert physiological responses by making these responses explicit. Electrodermal biofeedback training to elicit a reduction in sympathetic tone has a demonstrated association with reduced tic frequency. VNS, achieved through an implanted device

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. Monophyletic Origin of the Metazoan Nervous System: Characterizing

    NASA Astrophysics Data System (ADS)

    Watkins, Russell; Beckenbach, Andrew

    In the absence of additional cases to be studied, our understanding of the likelihood of intelligent life evolving elsewhere in the universe must be framed within the context of the evolution of intelligence on this planet. Towards this end a valid model of the evolution of animal life, and in particular of the nervous system, is key. Models which describe the development of complexity within the nervous system can be positively misleading if they are not grounded in an accurate model of the true relationships of the animal phyla. If fact the evolution of animal life at its earliest stages, from protists to the sponges, Cnidaria, and Ctenophora and onward to the bilateral animal phyla is poorly characterized. Recently numerous phylogenies of the early animal radiation have been published based upon DNA sequence data, with conflicting and poorly supported results. A polyphyletic origin for the animal nervous system has been implied by the results of several studies, which would lead to the conclusion that some characteristics of the nervous systems of higher and lower animals could be convergent. We show that an equally parsimonious interpretation of the molecular sequence data published thus far is that it reflects rapid speciation events early in animal evolution among the classical ``diploblast'' phyla, as well as accelerated DNA sequence divergence among the higher animals. This could be interpreted as support for a classical phylogeny of the animal kingdom, and thus of a strictly monophyletic origin for the nervous system.

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

    PubMed

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

    2015-01-01

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

  10. Directional Spread of Alphaherpesviruses in the Nervous System

    PubMed Central

    Kramer, Tal; Enquist, Lynn W.

    2013-01-01

    Alphaherpesviruses are pathogens that invade the nervous systems of their mammalian hosts. Directional spread of infection in the nervous system is a key component of the viral lifecycle and is critical for the onset of alphaherpesvirus-related diseases. Many alphaherpesvirus infections originate at peripheral sites, such as epithelial tissues, and then enter neurons of the peripheral nervous system (PNS), where lifelong latency is established. Following reactivation from latency and assembly of new viral particles, the infection typically spreads back out towards the periphery. These spread events result in the characteristic lesions (cold sores) commonly associated with herpes simplex virus (HSV) and herpes zoster (shingles) associated with varicella zoster virus (VZV). Occasionally, the infection spreads transsynaptically from the PNS into higher order neurons of the central nervous system (CNS). Spread of infection into the CNS, while rarer in natural hosts, often results in severe consequences, including death. In this review, we discuss the viral and cellular mechanisms that govern directional spread of infection in the nervous system. We focus on the molecular events that mediate long distance directional transport of viral particles in neurons during entry and egress. PMID:23435239

  11. Bacterial infections of the central nervous system.

    PubMed

    Busl, Katharina M; Bleck, Thomas P

    2013-12-01

    Bacterial CNS infections comprise a wide spectrum of diseases, which may be acquired outside or inside the hospital, affect immunocompetent or immunocompromised patients, and be associated with trauma or procedures, as well as other exposures. PMID:24190736

  12. 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

  13. Guidance Receptors in the Nervous and Cardiovascular Systems.

    PubMed

    Rubina, K A; Tkachuk, V A

    2015-10-01

    Blood vessels and nervous fibers grow in parallel, for they express similar receptors for chemokine substances. Recently, much attention is being given to studying guidance receptors and their ligands besides the growth factors, cytokines, and chemokines necessary to form structures in the nervous and vascular systems. Such guidance molecules determine trajectory for growing axons and vessels. Guidance molecules include Ephrins and their receptors, Neuropilins and Plexins as receptors for Semaphorins, Robos as receptors for Slit-proteins, and UNC5B receptors binding Netrins. Apart from these receptors and their ligands, urokinase and its receptor (uPAR) and T-cadherin are also classified as guidance molecules. The urokinase system mediates local proteolysis at the leading edge of cells, thereby providing directed migration. T-cadherin is a repellent molecule that regulates the direction of growing axons and blood vessels. Guidance receptors also play an important role in the diseases of the nervous and cardiovascular systems.

  14. Potential Autonomic Nervous System Effects of Statins in Heart Failure

    PubMed Central

    Horwich, Tamara; Middlekauff, Holly

    2008-01-01

    Synopsis Sympathetic nervous system activation in heart failure, as indexed by elevated norepinephrine levels, higher muscle sympathetic nerve activity and reduced heart rate variability, is associated with pathologic ventricular remodeling, increased arrhythmias, sudden death, and increased mortality. Recent evidence suggests that HMG-CoA reductase inhibitor (statin) therapy may provide survival benefit in heart failure of both ischemic and non-ischemic etiology, and one potential mechanism of benefit of statins in heart failure is modulation of the autonomic nervous system. Animal models of heart failure demonstrate reduced sympathetic activation and improved sympathovagal balance with statin therapy. Initial human studies have reported mixed results. Ongoing translational studies and outcomes trials will help delineate the potentially beneficial effects of statins on the autonomic nervous system in heart failure. PMID:18433696

  15. Psychoneuroimmunology--cross-talk between the immune and nervous systems.

    PubMed

    Ziemssen, Tjalf; Kern, Simone

    2007-05-01

    Psychoneuroimmunology is a relatively new field of study that investigates interactions between behaviour and the immune system, mediated by the endocrine and nervous systems. The immune and central nervous system (CNS) maintain extensive communication. On the one hand, the brain modulates the immune system by hardwiring sympathetic and parasympathetic nerves (autonomic nervous system) to lymphoid organs. On the other hand, neuroendocrine hormones such as corticotrophin-releasing hormone or substance P regulate cytokine balance. Vice versa, the immune system modulates brain activity including sleep and body temperature. Based on a close functional and anatomical link, the immune and nervous systems act in a highly reciprocal manner. From fever to stress, the influence of one system on the other has evolved in an intricate manner to help sense danger and to mount an appropriate adaptive response. Over recent decades, reasonable evidence has emerged that these brain-to-immune interactions are highly modulated by psychological factors which influence immunity and immune system-mediated disease.

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

    PubMed

    Dean, Brian

    2009-01-01

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

  17. Anticholinergics for overactive bladder therapy: central nervous system effects.

    PubMed

    Chancellor, Michael; Boone, Timothy

    2012-02-01

    The mainstay of pharmacological treatment of overactive bladder (OAB) is anticholinergic therapy using muscarinic receptor antagonists (tertiary or quaternary amines). Muscarinic receptors in the brain play an important role in cognitive function, and there is growing awareness that antimuscarinic OAB drugs may have adverse central nervous system (CNS) effects, ranging from headache to cognitive impairment and episodes of psychosis. This review discusses the physicochemical and pharmacokinetic properties of OAB antimuscarinics that affect their propensity to cause adverse CNS effects, as observed in phase III clinical trials and in specific investigations on cognitive function and sleep architecture. PubMed/MEDLINE was searched for "OAB" plus "muscarinic antagonists" or "anticholinergic drug." Additional relevant literature was identified by examining the reference lists of papers identified through the search. Preclinical and clinical trials in adults were assessed, focusing on the OAB antimuscarinics approved in the United States. The blood-brain barrier (BBB) plays a key role in protecting the CNS, but it is penetrable. The lipophilic tertiary amines, particularly oxybutynin, are more likely to cross the BBB than the hydrophilic quaternary amine trospium chloride, for which there are very few reports of adverse CNS effects. In fact, in 2008 the US product labels for oral oxybutynin were modified to include the potential for anticholinergic CNS events and a warning to monitor patients for adverse CNS effects. Even modest cognitive impairment in the elderly may negatively affect independence; therefore, selection of an antimuscarinic OAB drug with reduced potential for CNS effects is advisable.

  18. 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.

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

    PubMed

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

    2016-05-01

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

  20. 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.

  1. 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

  2. Inflammation and cutaneous nervous system involvement in hypertrophic scarring

    PubMed Central

    Li, Shao-hua; Yang, Heng-lian; Xiao, Hu; Wang, Yi-bing; Wang, De-chang; Huo, Ran

    2015-01-01

    This study aimed to use a mouse model of hypertrophic scarring by mechanical loading on the dorsum of mice to determine whether the nervous system of the skin and inflammation participates in hypertrophic scarring. Results of hematoxylin-eosin and immunohistochemical staining demonstrated that inflammation contributed to the formation of a hypertrophic scar and increased the nerve density in scar tissue.Western blot assay verified that interleukin-13 expression was increased in scar tissue. These findings suggest that inflammation and the cutaneous nervous system play a role in hypertrophic scar formation. PMID:26692869

  3. Sympathetic nervous system regulation of the tumour microenvironment

    PubMed Central

    Cole, Steven W.; Nagaraja, Archana S.; Lutgendorf, Susan K.; Green, Paige A.; Sood, Anil K.

    2016-01-01

    The peripheral autonomic nervous system (ANS) is known to regulate gene expression in primary tumours and their surrounding microenvironment. Activation of the sympathetic division of the ANS in particular modulates gene expression programs that promote metastasis of solid tumours by stimulating macrophage infiltration, inflammation, angiogenesis, epithelial-mesenchymal transition, and tumour invasion, and by inhibiting cellular immune responses and programmed cell death. Haematological cancers are modulated by sympathetic nervous system (SNS) regulation of stem cell biology and hematopoietic differentiation programs. In addition to identifying a molecular basis for physiologic stress effects on cancer, these findings have also identified new pharmacologic strategies to inhibit cancer progression in vivo. PMID:26299593

  4. Infectious diseases of the nervous system: pathogenesis and worldwide impact.

    PubMed

    Berkhout, Ben

    2008-11-01

    The 2008 Infectious Diseases of the Nervous System: Pathogenesis and World Impact conference was held at the Pasteur Institute of Paris, and was the first worldwide conference on neuroinfections. While viral encephalitis and bacterial meningitis are being actively studied in the developed world, much less attention is paid to the often fatal nervous system infections caused by neurotropic viruses, parasites and mycobacteria that represent important health problems in tropical regions. This meeting fostered worldwide interactions between scientists and stimulated the exchange of the latest research results on these neglected neurotropic pathogens. PMID:18988120

  5. Novel RNA Modifications in the Nervous System: Form and Function

    PubMed Central

    Basanta-Sanchez, Maria; Blanco, Sandra; Li, Jin Billy; Meyer, Kate; Pollock, Jonathan; Sadri-Vakili, Ghazaleh; Rybak-Wolf, Agnieszka

    2014-01-01

    Modified RNA molecules have recently been shown to regulate nervous system functions. This mini-review and associated mini-symposium provide an overview of the types and known functions of novel modified RNAs in the nervous system, including covalently modified RNAs, edited RNAs, and circular RNAs. We discuss basic molecular mechanisms involving RNA modifications as well as the impact of modified RNAs and their regulation on neuronal processes and disorders, including neural fate specification, intellectual disability, neurodegeneration, dopamine neuron function, and substance use disorders. PMID:25392485

  6. [CENTRAL NERVOUS SYSTEM INVOLVEMENT IN GRANULOMATOSIS WITH POLYANGIITIS (GPA)].

    PubMed

    Horovitz, Yuval; Lidar, Merav

    2015-05-01

    We present the case of a 75 year-old female with Wegener's Granulomatosis. The patient arrived intubated to the emergency room, following loss of consciousness and a generalized seizure. A magnetic resonance imaging brain scan revealed a space occupying lesion (SOL) in the right temporal region. Subsequent investigation indicated the SOL to be a primary lymphoma of the central nervous system. The clinical manifestations of granulomatosis with polyangiitis on both the central and peripheral nervous systems are reviewed herein, as well as the appropriated treatment modalities and the link between this disease and various malignancies. PMID:26168637

  7. Central nervous system manifestations of Angiostrongylus cantonensis infection

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

    Erta, María; Quintana, Albert; Hidalgo, Juan

    2012-01-01

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

  9. Modelling of pathologies of the nervous system by the example of computational and electronic models of elementary nervous systems

    NASA Astrophysics Data System (ADS)

    Shumilov, V. N.; Syryamkin, V. I.; Syryamkin, M. V.

    2015-11-01

    The paper puts forward principles of action of devices operating similarly to the nervous system and the brain of biological systems. We propose an alternative method of studying diseases of the nervous system, which may significantly influence prevention, medical treatment, or at least retardation of development of these diseases. This alternative is to use computational and electronic models of the nervous system. Within this approach, we represent the brain in the form of a huge electrical circuit composed of active units, namely, neuron-like units and connections between them. As a result, we created computational and electronic models of elementary nervous systems, which are based on the principles of functioning of biological nervous systems that we have put forward. Our models demonstrate reactions to external stimuli and their change similarly to the behavior of simplest biological organisms. The models possess the ability of self-training and retraining in real time without human intervention and switching operation/training modes. In our models, training and memorization take place constantly under the influence of stimuli on the organism. Training is without any interruption and switching operation modes. Training and formation of new reflexes occur by means of formation of new connections between excited neurons, between which formation of connections is physically possible. Connections are formed without external influence. They are formed under the influence of local causes. Connections are formed between outputs and inputs of two neurons, when the difference between output and input potentials of excited neurons exceeds a value sufficient to form a new connection. On these grounds, we suggest that the proposed principles truly reflect mechanisms of functioning of biological nervous systems and the brain. In order to confirm the correspondence of the proposed principles to biological nature, we carry out experiments for the study of processes of

  10. Modelling of pathologies of the nervous system by the example of computational and electronic models of elementary nervous systems

    SciTech Connect

    Shumilov, V. N. Syryamkin, V. I. Syryamkin, M. V.

    2015-11-17

    The paper puts forward principles of action of devices operating similarly to the nervous system and the brain of biological systems. We propose an alternative method of studying diseases of the nervous system, which may significantly influence prevention, medical treatment, or at least retardation of development of these diseases. This alternative is to use computational and electronic models of the nervous system. Within this approach, we represent the brain in the form of a huge electrical circuit composed of active units, namely, neuron-like units and connections between them. As a result, we created computational and electronic models of elementary nervous systems, which are based on the principles of functioning of biological nervous systems that we have put forward. Our models demonstrate reactions to external stimuli and their change similarly to the behavior of simplest biological organisms. The models possess the ability of self-training and retraining in real time without human intervention and switching operation/training modes. In our models, training and memorization take place constantly under the influence of stimuli on the organism. Training is without any interruption and switching operation modes. Training and formation of new reflexes occur by means of formation of new connections between excited neurons, between which formation of connections is physically possible. Connections are formed without external influence. They are formed under the influence of local causes. Connections are formed between outputs and inputs of two neurons, when the difference between output and input potentials of excited neurons exceeds a value sufficient to form a new connection. On these grounds, we suggest that the proposed principles truly reflect mechanisms of functioning of biological nervous systems and the brain. In order to confirm the correspondence of the proposed principles to biological nature, we carry out experiments for the study of processes of

  11. Sympathetic nervous system and inflammation: a conceptual view.

    PubMed

    Jänig, Wilfrid

    2014-05-01

    The peripheral sympathetic nervous system is organized into function-specific pathways that transmit the activity from the central nervous system to its target tissues. The transmission of the impulse activity in the sympathetic ganglia and to the effector tissues is target cell specific and guarantees that the centrally generated command is faithfully transmitted. This is the neurobiological basis of autonomic regulations in which the sympathetic nervous system is involved. Each sympathetic pathway is connected to distinct central circuits in the spinal cord, lower and upper brain stem and hypothalamus. In addition to its conventional functions, the sympathetic nervous system is involved in protection of body tissues against challenges arising from the environment as well as from within the body. This function includes the modulation of inflammation, nociceptors and above all the immune system. Primary and secondary lymphoid organs are innervated by sympathetic postganglionic neurons and processes in the immune tissue are modulated by activity in these sympathetic neurons via adrenoceptors in the membranes of the immune cells (see Bellinger and Lorton, 2014). Are the primary and secondary lymphoid organs innervated by a functionally specific sympathetic pathway that is responsible for the modulation of the functioning of the immune tissue by the brain? Or is this modulation of immune functions a general function of the sympathetic nervous system independent of its specific functions? Which central circuits are involved in the neural regulation of the immune system in the context of neural regulation of body protection? What is the function of the sympatho-adrenal system, involving epinephrine, in the modulation of immune functions? PMID:24525016

  12. Neural Circuit Recording from an Intact Cockroach Nervous System

    PubMed Central

    Titlow, Josh S.; Majeed, Zana R.; Hartman, H. Bernard; Burns, Ellen; Cooper, Robin L.

    2013-01-01

    The cockroach ventral nerve cord preparation is a tractable system for neuroethology experiments, neural network modeling, and testing the physiological effects of insecticides. This article describes the scope of cockroach sensory modalities that can be used to assay how an insect nervous system responds to environmental perturbations. Emphasis here is on the escape behavior mediated by cerci to giant fiber transmission in Periplaneta americana. This in situ preparation requires only moderate dissecting skill and electrophysiological expertise to generate reproducible recordings of neuronal activity. Peptides or other chemical reagents can then be applied directly to the nervous system in solution with the physiological saline. Insecticides could also be administered prior to dissection and the escape circuit can serve as a proxy for the excitable state of the central nervous system. In this context the assays described herein would also be useful to researchers interested in limb regeneration and the evolution of nervous system development for which P. americana is an established model organism. PMID:24300738

  13. Gene therapy for peripheral nervous system diseases.

    PubMed

    Federici, Thais; Boulis, Nicholas

    2007-08-01

    Peripheral nerve diseases, also known as peripheral neuropathies, affect 15-20 million of Americans and diabetic neuropathy is the most common condition. Currently, the treatment of peripheral neuropathies is more focused on managing pain rather than providing permissive conditions for regeneration. Despite advances in microsurgical techniques, including nerve grafting and reanastomosis, axonal regeneration after peripheral nerve injury remains suboptimal. Also, no satisfactory treatments are available at this time for peripheral neurodegeneration occurring in motor neuron diseases (MND), including amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). Peripheral nerves have the inherent capacity of regeneration. Gene therapy strategies focused on neuroprotection may help optimizing axonal regrowth. A better understanding of the cellular and molecular events involved in axonal degeneration and regeneration have helped researchers to identify targets for intervention. This review summarizes the current state on the clinical experience as well as gene therapy strategies for peripheral neuropathies, including MND, peripheral nerve injury, neuropathic pain, and diabetic neuropathy.

  14. 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.

  15. THE SYMPATHETIC NERVOUS SYSTEM ALTERATIONS IN HUMAN HYPERTENSION

    PubMed Central

    Grassi, Guido; Mark, Allyn; Esler, Murray

    2015-01-01

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

  16. The sympathetic nervous system in hypertension: back to the future?

    PubMed

    Esler, Murray

    2015-02-01

    The seventeenth century London neuroanatomical school headed by Thomas Willis published the first images of the sympathetic nervous system. Nineteenth century European physiologists characterised these as the "pressor nerves". Von Euler's demonstration that the sympathetic transmitter was norepinephrine brought the field into the modern era. Sympathetic nervous system responses are regionally differentiated; human regional sympathetic activity is best studied by recording from postganglionic sympathetic efferents directed to the skeletal muscle vasculature (clinical microneurography) and by measurement of organ-specific norepinephrine release to plasma from sympathetic nerves (regional "norepinephrine spillover"). With these techniques, the sympathetic nervous system became accessible to clinical scientists, allowing the demonstration that sympathetic nervous system activation is crucial in the development and outcomes of cardiovascular disorders, most notably heart failure and essential hypertension. Activation of the renal sympathetic outflow is pivotal in the pathogenesis of essential hypertension. An important goal for clinical scientists is translation of knowledge of pathophysiology, such as this, into better treatment for patients. Although disputed, the case is strong that in hypertension, we are now on the cusp of effective "mechanisms to management" transition, with the use of catheter-based renal sympathetic nerve ablation for treating drug-resistant hypertension.

  17. The nervous and the immune systems: conspicuous physiological analogies.

    PubMed

    Sotelo, Julio

    2015-02-01

    From all biological constituents of complex organisms, two are highly sophisticated: the nervous and the immune systems. Interestingly, their goals and processes appear to be distant from each other; however, their physiological mechanisms keep notorious similarities. Both construct intelligence, learn from experience, and keep memory. Their precise responses to innumerable stimuli are delicately modulated, and the exposure of the individual to thousands of potential challenges integrates their functionality; they use a large part of their constituents not in excitatory activities but in the maintenance of inhibitory mechanisms to keep silent vast intrinsic potentialities. The nervous and immune systems are integrated by a basic cell lineage (neurons and lymphocytes, respectively) but each embodies countless cell subgroups with different and specialized deeds which, in contrast with cells from other organs, labyrinthine molecular arrangements conduct to "one cell, one function". Also, nervous and immune actions confer identity that differentiates every individual from countless others in the same species. Both systems regulate and potentiate their responses aided by countless biological resources of variable intensity: hormones, peptides, cytokines, pro-inflammatory molecules, etc. How the immune and the nervous systems buildup memory, learning capability, and exquisite control of excitatory/inhibitory mechanisms constitute major intellectual challenges for contemporary research.

  18. 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…

  19. 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.…

  20. Nervous System Development and Pattern Preference in Infants.

    ERIC Educational Resources Information Center

    Woodruff, Diana S.; Gerrity, Kathleen M.

    This study examined behavioral correlates of the rapid central nervous system changes occurring in the first 4 months of life. It was hypothesized that during the early months of infancy, visual preference would occur as a function of quantitative dimensions of the stimuli (size) which could be mediated at a subcortical level. It was further…

  1. Non-central nervous system fetal magnetic resonance imaging.

    PubMed

    Whitby, Elspeth; Wright, Peter

    2015-06-01

    Fetal magnetic resonance imaging (MRI) is currently offered in a limited number of centers but is predominantly used for suspected fetal central nervous system abnormalities. This article concentrates on the role of the different imaging sequences and their value to clinical practice. It also discusses the future of fetal MRI. PMID:26013057

  2. The Nervous System, Science (Experimental): 5363.02.

    ERIC Educational Resources Information Center

    Weiss, Alan; And Others

    This unit of instruction was designed as an intensive in-depth study of the nervous impulse, neurons, brain, spinal cord, and sensory organs. Also included is a study of the endocrine system in its role of maintaining homeostasis. The booklet lists the relevant state-adopted texts and states the performance objectives for the unit. It provides an…

  3. Dopaminergic agents: influence on serotonin in the molluscan nervous system.

    PubMed

    Stefano, G B; Catapane, E; Aiello, E

    1976-10-29

    Treatment of the mussel Mytilus edulis with 6-hydroxydopamine or with alpha-methyl-p-tyrosine decreased dopamine and increased serotonin in the nervous system. Treatment with dopamine decreased serotonin concentrations and prevented the effect of 6-hydroxydopamine. The serotonin concentration appears to be determined in part by the concentration of dopamine. PMID:973139

  4. Homology and Convergence in Vertebrate and Invertebrate Nervous Systems

    NASA Astrophysics Data System (ADS)

    Sandeman, David

    Each year the meeting of the American Neuroscience Society attracts over 20,000 members, reflecting the explosion of interest in this field that has occurred over the past few decades. Researchers from many disciplines are focusing their skills on the investigation of every aspect of nervous systems, and neuroscience now encompasses the entire range of endeavour from the study of the single molecules that make up neural membranes to the non-invasive observation of neural function in animals behaving in their natural environments. Advances over the past three decades in our understanding of nervous systems are impressive and come from a multifaceted approach to the study of both vertebrate and invertebrate animals. An almost unexpected by-product of the parallel investigation of vertebrate and invertebrate nervous systems that is explored in this article is the emergent view of an intricate web of evolutionary homology and convergence exhibited in the structure and function of the nervous systems of these two large, paraphyletic groups of animals.

  5. Homology and convergence in vertebrate and invertebrate nervous systems.

    PubMed

    Sandeman, D

    1999-08-01

    Each year the meeting of the American Neuroscience Society attracts over 20,000 members, reflecting the explosion of interest in this field that has occurred over the past few decades. Researchers from many disciplines are focusing their skills on the investigation of every aspect of nervous systems, and neuroscience now encompasses the entire range of endeavour from the study of the single molecules that make up neural membranes to the non-invasive observation of neural function in animals behaving in their natural environments. Advances over the past three decades in our understanding of nervous systems are impressive and come from a multifaceted approach to the study of both vertebrate and invertebrate animals. An almost unexpected by-product of the parallel investigation of vertebrate and invertebrate nervous systems that is explored in this article is the emergent view of an intricate web of evolutionary homology and convergence exhibited in the structure and function of the nervous systems of these two large, paraphyletic groups of animals.

  6. Selenoproteins in Nervous System Development and Function

    PubMed Central

    Pitts, Matthew W.; Byrns, China N.; Ogawa, Ashley N.; Kremer, Penny; Berry, Marla J.

    2014-01-01

    Selenoproteins are a distinct class of proteins that are characterized by the co-translational incorporation of selenium (Se) in the form of the 21st amino acid selenocysteine. Selenoproteins provide a key defense against oxidative stress, as many of these proteins participate in oxidation-reduction reactions neutralizing reactive oxygen species, where selenocysteine residues act as catalytic sites. Many selenoproteins are highly expressed in the brain and mouse knockout studies have determined that several are required for normal brain development. In parallel with these laboratory studies, recent reports of rare human cases with mutations in genes involved in selenoprotein biosynthesis have described individuals with an assortment of neurological problems that mirror those detailed in knockout mice. These deficits include impairments in cognition and motor function, seizures, hearing loss, and altered thyroid metabolism. Additionally, due to the fact that oxidative stress is a key feature of neurodegenerative disease, there is considerable interest in the therapeutic potential of selenium supplementation for human neurological disorders. Studies performed in cell culture and rodent models have demonstrated that selenium administration attenuates oxidative stress, prevents neurodegeneration, and counters cell signaling mechanisms known to be dysregulated in certain disease states. However, there is currently no definitive evidence in support of selenium supplementation to prevent and/or treat common neurological conditions in the general population. It appears likely, that in humans, supplementation with selenium may only benefit certain subpopulations, such as those that are either selenium-deficient or possess genetic variants that affect selenium metabolism. PMID:24974905

  7. Elements of a 'nervous system' in sponges.

    PubMed

    Leys, Sally P

    2015-02-15

    Genomic and transcriptomic analyses show that sponges possess a large repertoire of genes associated with neuronal processes in other animals, but what is the evidence these are used in a coordination or sensory context in sponges? The very different phylogenetic hypotheses under discussion today suggest very different scenarios for the evolution of tissues and coordination systems in early animals. The sponge genomic 'toolkit' either reflects a simple, pre-neural system used to protect the sponge filter or represents the remnants of a more complex signalling system and sponges have lost cell types, tissues and regionalization to suit their current suspension-feeding habit. Comparative transcriptome data can be informative but need to be assessed in the context of knowledge of sponge tissue structure and physiology. Here, I examine the elements of the sponge neural toolkit including sensory cells, conduction pathways, signalling molecules and the ionic basis of signalling. The elements described do not fit the scheme of a loss of sophistication, but seem rather to reflect an early specialization for suspension feeding, which fits with the presumed ecological framework in which the first animals evolved.

  8. 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.

  9. Itch Signaling in the Nervous System

    PubMed Central

    Jeffry, Joseph; Kim, Seungil; Chen, Zhou-Feng

    2013-01-01

    Itch is a major somatic sensation, along with pain, temperature and touch, detected and relayed by the somatosensory system. Itch can be an acute sensation, associated with mosquito bite, or a chronic condition, like atopic dermatitis (29, 59). The origins of the stimulus can be localized in the periphery or systemic, and associated with organ failure or cancer. Itch is also a perception originating in the brain. Itch is broadly characterized as either histamine-dependent (histaminergic) or histamine-independent (nonhistaminergic), both of which are relayed by subsets of C-fibers, and by the second-order neurons expressing gastrin-releasing peptide receptor (GRPR) and spinothalamic track (STT) neurons in the spinal cord of rodents. Historically, itch research has been primarily limited to clinical and psychophysical studies, and to histamine-mediated mechanisms. In contrast, little is known about signaling mechanisms underlying nonhistaminergic itch, despite the fact that the majority of chronic itch are mediated by nonhistaminergic mechanisms. During the past few years, important progress has been made in understanding of molecular signaling of itch, largely due to the introduction of mouse genetics. In this review, we examine some of molecular mechanisms underlying itch sensation with an emphasis on recent studies in rodents. PMID:21841076

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

    PubMed

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

    2009-03-01

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

  11. Central nervous system bleeding in patients with rare bleeding disorders.

    PubMed

    Siboni, S M; Zanon, E; Sottilotta, G; Consonni, D; Castaman, G; Mikovic, D; Biondo, F; Tagliaferri, A; Iorio, A; Mannucci, P M; Peyvandi, F

    2012-01-01

    Central nervous system (CNS) bleeding is one of the most severe and debilitating manifestations occurring in patients with rare bleeding disorders (RBDs). The aim of this study was to retrospectively collect data on patients affected with RBDs who had CNS bleeding, to establish incidence of recurrence, death rate, neurological sequences, most frequent location, type of bleeding and efficacy of treatments. Results pertained to 36 CNS bleeding episodes in 24 patients with severe deficiency except one with moderate factor VII (FVII) deficiency. Six patients (25%) experienced a recurrence and two had more than one recurrence. Seven patients (29%) had an early onset of CNS bleeding before the first 2 years of life, others (71%) later in life. In 76% of cases, CNS bleeding was spontaneous. CNS bleeding was intracerebral in 19 cases (53%), extracerebral in 10 (28%) and both intracerebral and extracerebral in two cases (6%). Neurosurgery was performed in 11 cases, in association with replacement therapy in seven cases. Seizures were noted in four patients. Residual psychomotor abnormalities were seen in two patients. No death was recorded. To prevent recurrence, 17/24 patients (71%) were put on secondary prophylaxis. In conclusion, recurrence of CNS bleeding was confirmed to be relatively frequent in patients with severe FV, FX, FVII and FXIII deficiencies. Most patients were managed with replacement therapy alone, surgery being reserved for those with worsening neurological conditions. Our results indicate that some RBDs require early prophylactic treatment to prevent CNS bleeding. Optimal dosage and frequency of treatment need further evaluation.

  12. 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.

  13. 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.

  14. Eosinophilic vasculitis in an isolated central nervous system distribution

    PubMed Central

    Sommerville, R Brian; Noble, James M; Vonsattel, Jean Paul; Delapaz, Robert; Wright, Clinton B

    2009-01-01

    Eosinophilic vasculitis has been described as part of the Churg–Strauss syndrome, but affects the central nervous system (CNS) in <10% of cases. A 39-year-old woman with a history of migraine without aura presented to an institution in an acute confusional state with concurrent headache and left-sided weakness. Laboratory evaluation showed an increased cerebrospinal fluid (CSF) protein level, but otherwise unremarkable serologies. Magnetic resonance imaging showed bifrontal polar gyral-enhancing brain lesions. Her symptoms resolved over two weeks without residual deficits. Eighteen months later the patient presented with similar symptoms and neuroradiological findings showed involvement of territories different from those in her first episode. Brain biopsy showed transmural, predominantly eosinophilic, inflammatory infiltrates and fibrinoid necrosis without granulomas. She improved when treated with corticosteroids. To our knowledge, this is the first case of non-granulomatous eosinophilic vasculitis isolated to the CNS. No aetiology for this patient’s primary CNS eosinophilic vasculitis has yet been identified. PMID:21686608

  15. 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

  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. PMID:24937778

  17. Autoantibody-Associated Central Nervous System Neurologic Disorders.

    PubMed

    Linnoila, Jenny; Pittock, Sean J

    2016-08-01

    Autoimmune neurology is a rapidly evolving new subspecialty driven by the discovery of novel neural- (neuronal- or glial-) specific autoantibodies and their target antigens. The neurologic manifestations affecting the central nervous system include encephalitis, dementia, epilepsy, and movement and sleep disorders. Laboratory testing is now available for most of these neural-specific autoantibodies, which serve as diagnostic markers, in some instances directing the physician toward specific cancer types (e.g., N-methyl-D-aspartic acid receptor antibodies for teratoma, collapsin response mediator protein 5 for small-cell lung cancer) and assisting in therapeutic decision making. Antibodies targeting intracellular proteins serve as markers of cytotoxic effector T-cell-mediated injury, which is generally poorly responsive to immunotherapy. By contrast, antibodies targeting extracellular plasma membrane proteins may act as pathogenic effectors and often infer good responses to immunotherapy. Diagnosing these conditions and implementing treatment as early into the clinical course as possible ensures the best possible clinical outcomes. An adequate immunotherapy trial to assess maximum reversibility of symptoms, as assessed through objective functional measures, is crucial and can help to determine whether maintenance therapy is needed. PMID:27643908

  18. Postnatal Development of the Mouse Enteric Nervous System.

    PubMed

    Foong, Jaime Pei Pei

    2016-01-01

    Owing to over three decades of research, we now have a good understanding of the genetic and molecular control of enteric nervous system (ENS) development during embryonic and prenatal stages. On the other hand, it has only just become clear that a substantial process of ENS maturation occurs after birth (Hao et al. 2013a). During postnatal stages, in addition to genetic influences, ENS development is also potentially affected by the external environment. Thus it is possible that manipulating certain environmental factors could help prevent or reduce motility disorders. However the genetic and environmental factors that regulate postnatal ENS development remain unknown. Researchers have used a variety of animal models that are easy to manipulate genetically or experimentally, and have short gestational periods, to understand the development of the ENS. Notably, due to the availability of mouse models for several human enteric neuropathies, many studies have used the mature and developing murine ENS as a model. Here, I will discuss recent advances in knowledge about postnatal development of the murine ENS, and highlight future directions for this emerging research field. PMID:27379641

  19. Severe central nervous system thrombotic events in hemoglobin Sabine patient.

    PubMed

    Pavlovic, Sonja; Kuzmanovic, Milos; Urosevic, Jelena; Poznanic, Jelena; Zoranovic, Tamara; Djordjevic, Valentina; Rasovic, Nada; Bunjevacki, Gordana; Cvorkov-Drazic, Milica; Colovic, Milica

    2004-01-01

    Hemoglobin (Hb) Sabine is a rare, unstable Hb variant resulting from the point mutation in codon 91 (CTG --> CCG) of beta-globin gene. We report a case of Hb Sabine patient with mild hemolytic anemia, unusually high Hb F level and severe central nervous system thrombotic disturbances. We have tried to elucidate possible genetic background of this unusual Hb Sabine phenotype. Extremely high level of Hb F and rather mild anemia in our patient could be partially explained by the presence of G gamma Xmn I polymorphism. This case of Hb Sabine, unlike all other reported to date, shows extremely severe thromboembolic complications. It is our opinion that the hypercoagulable state described in thalassemia is not the only factor responsible for this specific clinical state. The presence of MTHFR C677T mutation in heterozygous state found in our patient and unstable Hb Sabine molecules could contribute to development of thromboembolic phenomena. However, it remains unclear whether other factors participate in pathogenesis of the disease. In this paper we emphasize different genetic background of father and son both affected with Hb Sabine, but with markedly different severity of the disease.

  20. The nervous systems of basally branching nemertea (palaeonemertea).

    PubMed

    Beckers, Patrick; Loesel, Rudi; Bartolomaeus, Thomas

    2013-01-01

    In recent years, a lot of studies have been published dealing with the anatomy of the nervous system in different spiralian species. The only nemertean species investigated in this context probably shows derived characters and thus the conditions found there are not useful in inferring the relationship between nemerteans and other spiralian taxa. Ingroup relationships within Nemertea are still unclear, but there is some agreement that the palaeonemerteans form a basal, paraphyletic grade. Thus, palaeonemertean species are likely the most informative when comparing with other invertebrate groups. We therefore analyzed the nervous system of several palaeonemertean species by combining histology and immunostaining. 3D reconstructions based on the aligned slices were performed to get an overall impression of the central nervous system, and immunohistochemistry was chosen to reveal fine structures and to be able to compare the data with recently published results. The insights presented here permit a first attempt to reconstruct the primary organization of the nemertean nervous system. This comparative analysis allows substantiating homology hypotheses for nerves of the peripheral nervous system. This study also provides evidence that the nemertean brain primarily consists of two lobes connected by a strong ventral commissure and one to several dorsal commissures. During nemertean evolution, the brain underwent continuous compartmentalization into a pair of dorsal and ventral lobes interconnected by commissures and lateral tracts. Given that this conclusion can be corroborated by cladistic analyses, nemerteans should share a common ancestor with spiralians that primarily have a simple brain consisting of paired medullary, frontally commissurized and reinforced cords. Such an organization resembles the situation found in presumably basally branching annelids or mollusks.

  1. The Nervous Systems of Basally Branching Nemertea (Palaeonemertea)

    PubMed Central

    Beckers, Patrick; Loesel, Rudi; Bartolomaeus, Thomas

    2013-01-01

    In recent years, a lot of studies have been published dealing with the anatomy of the nervous system in different spiralian species. The only nemertean species investigated in this context probably shows derived characters and thus the conditions found there are not useful in inferring the relationship between nemerteans and other spiralian taxa. Ingroup relationships within Nemertea are still unclear, but there is some agreement that the palaeonemerteans form a basal, paraphyletic grade. Thus, palaeonemertean species are likely the most informative when comparing with other invertebrate groups. We therefore analyzed the nervous system of several palaeonemertean species by combining histology and immunostaining. 3D reconstructions based on the aligned slices were performed to get an overall impression of the central nervous system, and immunohistochemistry was chosen to reveal fine structures and to be able to compare the data with recently published results. The insights presented here permit a first attempt to reconstruct the primary organization of the nemertean nervous system. This comparative analysis allows substantiating homology hypotheses for nerves of the peripheral nervous system. This study also provides evidence that the nemertean brain primarily consists of two lobes connected by a strong ventral commissure and one to several dorsal commissures. During nemertean evolution, the brain underwent continuous compartmentalization into a pair of dorsal and ventral lobes interconnected by commissures and lateral tracts. Given that this conclusion can be corroborated by cladistic analyses, nemerteans should share a common ancestor with spiralians that primarily have a simple brain consisting of paired medullary, frontally commissurized and reinforced cords. Such an organization resembles the situation found in presumably basally branching annelids or mollusks. PMID:23785478

  2. Targeting the autonomic nervous system: measuring autonomic function and novel devices for heart failure management.

    PubMed

    Patel, Hitesh C; Rosen, Stuart D; Lindsay, Alistair; Hayward, Carl; Lyon, Alexander R; di Mario, Carlo

    2013-12-10

    Neurohumoral activation, in which enhanced activity of the autonomic nervous system (ANS) is a key component, plays a pivotal role in heart failure. The neurohumoral system affects several organs and currently our knowledge of the molecular and systemic pathways involved in the neurohumoral activation is incomplete. All the methods of assessing the degree of activation of the autonomic system have limitations and they are not interchangeable. The methods considered include noradrenaline spillover, microneurography, radiotracer imaging and analysis of heart rate and blood pressure (heart rate variability, baroreceptor sensitivity, heart rate turbulence). Despite the difficulties, medications that affect the ANS have been shown to improve mortality in heart failure and the mechanism is related to attenuation of the sympathetic nervous system (SNS) and stimulation of the parasympathetic nervous system. However, limitations of compliance with medication, side effects and inadequate SNS attenuation are issues of concern with the pharmacological approach. The newer device based therapies for sympathetic modulation are showing encouraging results. As they directly influence the autonomic nervous system, more mechanistic information can be gleaned if appropriate investigations are performed at the time of the outcome trials. However, clinicians should be reminded that the ANS is an evolutionary survival mechanism and therefore there is a need to proceed with caution when trying to completely attenuate its effects. So our enthusiasm for the application of these devices in heart failure should be controlled, especially as none of the devices have trial data powered to assess effects on mortality or cardiovascular events.

  3. The autonomic nervous system at high altitude

    PubMed Central

    Drinkhill, Mark J.; Rivera-Chira, Maria

    2007-01-01

    The effects of hypobaric hypoxia in visitors depend not only on the actual elevation but also on the rate of ascent. Sympathetic activity increases and there are increases in blood pressure and heart rate. Pulmonary vasoconstriction leads to pulmonary hypertension, particularly during exercise. The sympathetic excitation results from hypoxia, partly through chemoreceptor reflexes and partly through altered baroreceptor function. High pulmonary arterial pressures may also cause reflex systemic vasoconstriction. Most permanent high altitude dwellers show excellent adaptation although there are differences between populations in the extent of the ventilatory drive and the erythropoiesis. Some altitude dwellers, particularly Andeans, may develop chronic mountain sickness, the most prominent characteristic of which being excessive polycythaemia. Excessive hypoxia due to peripheral chemoreceptor dysfunction has been suggested as a cause. The hyperviscous blood leads to pulmonary hypertension, symptoms of cerebral hypoperfusion, and eventually right heart failure and death. PMID:17264976

  4. Temporal Encoding in a Nervous System

    PubMed Central

    Aldworth, Zane N.; Dimitrov, Alexander G.; Cummins, Graham I.; Gedeon, Tomáš; Miller, John P.

    2011-01-01

    We examined the extent to which temporal encoding may be implemented by single neurons in the cercal sensory system of the house cricket Acheta domesticus. We found that these neurons exhibit a greater-than-expected coding capacity, due in part to an increased precision in brief patterns of action potentials. We developed linear and non-linear models for decoding the activity of these neurons. We found that the stimuli associated with short-interval patterns of spikes (ISIs of 8 ms or less) could be predicted better by second-order models as compared to linear models. Finally, we characterized the difference between these linear and second-order models in a low-dimensional subspace, and showed that modification of the linear models along only a few dimensions improved their predictive power to parity with the second order models. Together these results show that single neurons are capable of using temporal patterns of spikes as fundamental symbols in their neural code, and that they communicate specific stimulus distributions to subsequent neural structures. PMID:21573206

  5. Temporal encoding in a nervous system.

    PubMed

    Aldworth, Zane N; Dimitrov, Alexander G; Cummins, Graham I; Gedeon, Tomáš; Miller, John P

    2011-05-01

    We examined the extent to which temporal encoding may be implemented by single neurons in the cercal sensory system of the house cricket Acheta domesticus. We found that these neurons exhibit a greater-than-expected coding capacity, due in part to an increased precision in brief patterns of action potentials. We developed linear and non-linear models for decoding the activity of these neurons. We found that the stimuli associated with short-interval patterns of spikes (ISIs of 8 ms or less) could be predicted better by second-order models as compared to linear models. Finally, we characterized the difference between these linear and second-order models in a low-dimensional subspace, and showed that modification of the linear models along only a few dimensions improved their predictive power to parity with the second order models. Together these results show that single neurons are capable of using temporal patterns of spikes as fundamental symbols in their neural code, and that they communicate specific stimulus distributions to subsequent neural structures.

  6. Molecular clocks and the early evolution of metazoan nervous systems.

    PubMed

    Wray, Gregory A

    2015-12-19

    The timing of early animal evolution remains poorly resolved, yet remains critical for understanding nervous system evolution. Methods for estimating divergence times from sequence data have improved considerably, providing a more refined understanding of key divergences. The best molecular estimates point to the origin of metazoans and bilaterians tens to hundreds of millions of years earlier than their first appearances in the fossil record. Both the molecular and fossil records are compatible, however, with the possibility of tiny, unskeletonized, low energy budget animals during the Proterozoic that had planktonic, benthic, or meiofaunal lifestyles. Such animals would likely have had relatively simple nervous systems equipped primarily to detect food, avoid inhospitable environments and locate mates. The appearance of the first macropredators during the Cambrian would have changed the selective landscape dramatically, likely driving the evolution of complex sense organs, sophisticated sensory processing systems, and diverse effector systems involved in capturing prey and avoiding predation. PMID:26554040

  7. Molecular clocks and the early evolution of metazoan nervous systems.

    PubMed

    Wray, Gregory A

    2015-12-19

    The timing of early animal evolution remains poorly resolved, yet remains critical for understanding nervous system evolution. Methods for estimating divergence times from sequence data have improved considerably, providing a more refined understanding of key divergences. The best molecular estimates point to the origin of metazoans and bilaterians tens to hundreds of millions of years earlier than their first appearances in the fossil record. Both the molecular and fossil records are compatible, however, with the possibility of tiny, unskeletonized, low energy budget animals during the Proterozoic that had planktonic, benthic, or meiofaunal lifestyles. Such animals would likely have had relatively simple nervous systems equipped primarily to detect food, avoid inhospitable environments and locate mates. The appearance of the first macropredators during the Cambrian would have changed the selective landscape dramatically, likely driving the evolution of complex sense organs, sophisticated sensory processing systems, and diverse effector systems involved in capturing prey and avoiding predation.

  8. Marine Pharmacology in 2000: Marine Compounds with Antibacterial, Anticoagulant, Antifungal, Anti-inflammatory, Antimalarial, Antiplatelet, Antituberculosis, and Antiviral Activities; Affecting the Cardiovascular, Immune, and Nervous Systems and Other Miscellaneous Mechanisms of Action

    PubMed Central

    Mayer, Alejandro M. S.; Hamann, Mark T.

    2016-01-01

    During 2000 research on the pharmacology of marine chemicals involved investigators from Australia, Brazil, Canada, Egypt, France, Germany, India, Indonesia, Israel, Italy, Japan, the Netherlands, New Zealand, Phillipines, Singapore, Slovenia, South Korea, Spain, Sweden, Switzerland, United Kingdom, and the United States. This current review, a sequel to the authors’ 1998 and 1999 reviews, classifies 68 peer-reviewed articles on the basis of the reported preclinical pharmacologic properties of marine chemicals derived from a diverse group of marine animals, algae, fungi, and bacteria. Antibacterial, anticoagulant, antifungal, antimalarial, antiplatelet, antituberculosis, or antiviral activity was reported for 35 marine chemicals. An additional 20 marine compounds were shown to have significant effects on the cardiovascular and nervous system, and to possess anti-inflammatory or immunosuppressant properties. Finally, 23 marine compounds were reported to act on a variety of molecular targets and thus could potentially contribute to several pharmacologic classes. Thus, as in 1998 and 1999, during 2000 pharmacologic research with marine chemicals continued to contribute potentially novel chemical leads to the ongoing global search for therapeutic agents in the treatment of multiple disease categories. PMID:14583811

  9. Marine pharmacology in 2003-4: Marine Compounds with Anthelminthic, Antibacterial, Anticoagulant, Antifungal, Anti-inflammatory, Antimalarial, Antiplatelet, Antiprotozoal, Antituberculosis, and Antiviral Activities; affecting the Cardiovascular, Immune and Nervous Systems, and other Miscellaneous Mechanisms of Action

    PubMed Central

    Mayer, Alejandro M.S.; Rodriguez, Abimael D.; Berlinck, Roberto G.S.; Hamann, Mark T.

    2007-01-01

    The current marine pharmacology review that covers the peer-reviewed literature during 2003 and 2004 is a sequel to the authors' 1998-2002 reviews, and highlights the preclinical pharmacology of 166 marine chemicals derived from a diverse group of marine animals, algae, fungi and bacteria. Anthelminthic, antibacterial, anticoagulant, antifungal, antimalarial, antiplatelet, antiprotozoal, antituberculosis or antiviral activities were reported for 67 marine chemicals. Additionally 45 marine compounds were shown to have significant effects on the cardiovascular, immune and nervous system as well as possessing anti-inflammatory effects. Finally, 54 marine compounds were reported to act on a variety of molecular targets and thus may potentially contribute to several pharmacological classes. Thus, during 2003-2004, research on the pharmacology of marine natural products which involved investigators from Argentina, Australia, Brazil, Belgium, Canada, China, France, Germany, India, Indonesia, Israel, Italy, Japan, Mexico, Morocco, the Netherlands, New Zealand, Norway, Panama, the Philippines, Portugal, Russia, Slovenia, South Korea, Spain, Thailand, Turkey, United Kingdom, and the United States, contributed numerous chemical leads for the continued global search for novel therapeutic agents with broad spectrum activity. PMID:17392033

  10. Quest for the basic plan of nervous system circuitry

    PubMed Central

    Swanson, Larry W.

    2007-01-01

    The basic plan of nervous system organization has been investigated since classical antiquity. The first model centered on pneumas pumped from sensory nerves through the ventricular system and out motor nerves to muscles. It was popular well into the seventeenth century and diverted attention from the organization of brain parenchyma itself. Willis focused on gray matter production and white matter conduction of pneumas in 1664, and by the late nineteenth century a clear cellular model of nervous system organization based on sensory, motor, and association neuron classes transmitting nerve impulses was elaborated by Cajal and his contemporaries. Today, revolutionary advances in experimental pathway tracing methods, molecular genetics, and computer science inspire systems neuroscience. Seven minimal requirements are outlined for knowledge management systems capable of describing, analyzing, and modeling the basic plan of nervous system circuitry in general, and the plan evolved for vertebrates, for mammals, and ultimately for humans in particular. The goal remains a relatively simple, easy to understand model analogous to the one Harvey elaborated in 1628 for circulation in the cardiovascular system. As Cajal wrote in 1909, “To extend our understanding of neural function to the most complex human physiological and psychological activities, it is essential that we first generate a clear and accurate view of the structure of the relevant centers, and of the human brain itself, so that the basic plan—the overview—can be grasped in the blink of an eye.” PMID:17267046

  11. [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.

  12. Functional structure and dynamics of the human nervous system

    NASA Technical Reports Server (NTRS)

    Lawrence, J. A.

    1981-01-01

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

  13. Regulation of sympathetic nervous system function after cardiovascular deconditioning

    NASA Technical Reports Server (NTRS)

    Hasser, E. M.; Moffitt, J. A.

    2001-01-01

    Humans subjected to prolonged periods of bed rest or microgravity undergo deconditioning of the cardiovascular system, characterized by resting tachycardia, reduced exercise capability, and a predisposition for orthostatic intolerance. These changes in cardiovascular function are likely due to a combination of factors, including changes in control of body fluid balance or cardiac alterations resulting in inadequate maintenance of stroke volume, altered arterial or venous vascular function, reduced activation of cardiovascular hormones, and diminished autonomic reflex function. There is evidence indicating a role for each of these mechanisms. Diminished reflex activation of the sympathetic nervous system and subsequent vasoconstriction appear to play an important role. Studies utilizing the hindlimb-unloaded (HU) rat, an animal model of deconditioning, evaluated the potential role of altered arterial baroreflex control of the sympathetic nervous system. These studies indicate that HU results in blunted baroreflex-mediated activation of both renal and lumbar sympathetic nerve activity in response to a hypotensive stimulus. HU rats are less able to maintain arterial pressure during hemorrhage, suggesting that diminished ability to increase sympathetic activity has functional consequences for the animal. Reflex control of vasopressin secretion appears to be enhanced following HU. Blunted baroreflex-mediated sympathoexcitation appears to involve altered central nervous system function. Baroreceptor afferent activity in response to changes in arterial pressure is unaltered in HU rats. However, increases in efferent sympathetic nerve activity for a given decrease in afferent input are blunted after HU. This altered central nervous system processing of baroreceptor inputs appears to involve an effect at the rostral ventrolateral medulla (RVLM). Specifically, it appears that tonic GABAA-mediated inhibition of the RVLM is enhanced after HU. Augmented inhibition apparently

  14. Introduction to 'Homology and convergence in nervous system evolution'.

    PubMed

    Strausfeld, Nicholas J; Hirth, Frank

    2016-01-01

    The origin of brains and central nervous systems (CNSs) is thought to have occurred before the Palaeozoic era 540 Ma. Yet in the absence of tangible evidence, there has been continued debate whether today's brains and nervous systems derive from one ancestral origin or whether similarities among them are due to convergent evolution. With the advent of molecular developmental genetics and genomics, it has become clear that homology is a concept that applies not only to morphologies, but also to genes, developmental processes, as well as to behaviours. Comparative studies in phyla ranging from annelids and arthropods to mammals are providing evidence that corresponding developmental genetic mechanisms act not only in dorso-ventral and anterior-posterior axis specification but also in segmentation, neurogenesis, axogenesis and eye/photoreceptor cell formation that appear to be conserved throughout the animal kingdom. These data are supported by recent studies which identified Mid-Cambrian fossils with preserved soft body parts that present segmental arrangements in brains typical of modern arthropods, and similarly organized brain centres and circuits across phyla that may reflect genealogical correspondence and control similar behavioural manifestations. Moreover, congruence between genetic and geological fossil records support the notion that by the 'Cambrian explosion' arthropods and chordates shared similarities in brain and nervous system organization. However, these similarities are strikingly absent in several sister- and outgroups of arthropods and chordates which raises several questions, foremost among them: what kind of natural laws and mechanisms underlie the convergent evolution of such similarities? And, vice versa: what are the selection pressures and genetic mechanisms underlying the possible loss or reduction of brains and CNSs in multiple lineages during the course of evolution? These questions were addressed at a Royal Society meeting to discuss

  15. Introduction to 'Homology and convergence in nervous system evolution'.

    PubMed

    Strausfeld, Nicholas J; Hirth, Frank

    2016-01-01

    The origin of brains and central nervous systems (CNSs) is thought to have occurred before the Palaeozoic era 540 Ma. Yet in the absence of tangible evidence, there has been continued debate whether today's brains and nervous systems derive from one ancestral origin or whether similarities among them are due to convergent evolution. With the advent of molecular developmental genetics and genomics, it has become clear that homology is a concept that applies not only to morphologies, but also to genes, developmental processes, as well as to behaviours. Comparative studies in phyla ranging from annelids and arthropods to mammals are providing evidence that corresponding developmental genetic mechanisms act not only in dorso-ventral and anterior-posterior axis specification but also in segmentation, neurogenesis, axogenesis and eye/photoreceptor cell formation that appear to be conserved throughout the animal kingdom. These data are supported by recent studies which identified Mid-Cambrian fossils with preserved soft body parts that present segmental arrangements in brains typical of modern arthropods, and similarly organized brain centres and circuits across phyla that may reflect genealogical correspondence and control similar behavioural manifestations. Moreover, congruence between genetic and geological fossil records support the notion that by the 'Cambrian explosion' arthropods and chordates shared similarities in brain and nervous system organization. However, these similarities are strikingly absent in several sister- and outgroups of arthropods and chordates which raises several questions, foremost among them: what kind of natural laws and mechanisms underlie the convergent evolution of such similarities? And, vice versa: what are the selection pressures and genetic mechanisms underlying the possible loss or reduction of brains and CNSs in multiple lineages during the course of evolution? These questions were addressed at a Royal Society meeting to discuss

  16. The nervous system of Xenacoelomorpha: a genomic perspective.

    PubMed

    Perea-Atienza, Elena; Gavilán, Brenda; Chiodin, Marta; Abril, Josep F; Hoff, Katharina J; Poustka, Albert J; Martinez, Pedro

    2015-02-15

    Xenacoelomorpha is, most probably, a monophyletic group that includes three clades: Acoela, Nemertodermatida and Xenoturbellida. The group still has contentious phylogenetic affinities; though most authors place it as the sister group of the remaining bilaterians, some would include it as a fourth phylum within the Deuterostomia. Over the past few years, our group, along with others, has undertaken a systematic study of the microscopic anatomy of these worms; our main aim is to understand the structure and development of the nervous system. This research plan has been aided by the use of molecular/developmental tools, the most important of which has been the sequencing of the complete genomes and transcriptomes of different members of the three clades. The data obtained has been used to analyse the evolutionary history of gene families and to study their expression patterns during development, in both space and time. A major focus of our research is the origin of 'cephalized' (centralized) nervous systems. How complex brains are assembled from simpler neuronal arrays has been a matter of intense debate for at least 100 years. We are now tackling this issue using Xenacoelomorpha models. These represent an ideal system for this work because the members of the three clades have nervous systems with different degrees of cephalization; from the relatively simple sub-epithelial net of Xenoturbella to the compact brain of acoels. How this process of 'progressive' cephalization is reflected in the genomes or transcriptomes of these three groups of animals is the subject of this paper.

  17. Fiber optic in vivo imaging in the mammalian nervous system

    PubMed Central

    Mehta, Amit D; Jung, Juergen C; Flusberg, Benjamin A; Schnitzer, Mark J

    2010-01-01

    The compact size, mechanical flexibility, and growing functionality of optical fiber and fiber optic devices are enabling several new modalities for imaging the mammalian nervous system in vivo. Fluorescence microendoscopy is a minimally invasive fiber modality that provides cellular resolution in deep brain areas. Diffuse optical tomography is a non-invasive modality that uses assemblies of fiber optic emitters and detectors on the cranium for volumetric imaging of brain activation. Optical coherence tomography is a sensitive interferometric imaging technique that can be implemented in a variety of fiber based formats and that might allow intrinsic optical detection of brain activity at a high resolution. Miniaturized fiber optic microscopy permits cellular level imaging in the brains of behaving animals. Together, these modalities will enable new uses of imaging in the intact nervous system for both research and clinical applications. PMID:15464896

  18. [The role of metalloprotease in pathogenesis of nervous system diseases].

    PubMed

    Mirowska, D; Członkowska, A

    2001-01-01

    Matrix Metalloproteases (MMPs) comprise a big family of proteolytic enzymes secreted into extracellular matrix and involved in remodelling of many tissues. The MMPs' activity is regulated on many levels. It is also determined by specific inhibitors known as tissue inhibitors of metalloproteases (TIMPs). Several studies revealed that MMPs have a role not only in physiological processes but also in pathophysiology of nervous system diseases, such as multiplex sclerosis, Guillan-Barré syndrome and strokes. Concerning demyelination MMPs are responsible for degradation of myelin components and facilitation of immune cells migration into inflammatory sites by degrading vascular basement membrane. We still investigate substances with positive clinical effect on the nervous system diseases due to MMPs inactivation.

  19. 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.

  20. 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

  1. Measurement of autophagy flux in the nervous system in vivo

    PubMed Central

    Castillo, K; Valenzuela, V; Matus, S; Nassif, M; Oñate, M; Fuentealba, Y; Encina, G; Irrazabal, T; Parsons, G; Court, F A; Schneider, B L; Armentano, D; Hetz, C

    2013-01-01

    Accurate methods to measure autophagic activity in vivo in neurons are not available, and most of the studies are based on correlative and static measurements of autophagy markers, leading to conflicting interpretations. Autophagy is an essential homeostatic process involved in the degradation of diverse cellular components including organelles and protein aggregates. Autophagy impairment is emerging as a relevant factor driving neurodegeneration in many diseases. Moreover, strategies to modulate autophagy have been shown to provide protection against neurodegeneration. Here we describe a novel and simple strategy to express an autophagy flux reporter in the nervous system of adult animals by the intraventricular delivery of adeno-associated viruses (AAV) into newborn mice. Using this approach we efficiently expressed a monomeric tandem mCherry-GFP-LC3 construct in neurons of the peripheral and central nervous system, allowing the measurement of autophagy activity in pharmacological and disease settings. PMID:24232093

  2. Regulation of cadherin expression in nervous system development

    PubMed Central

    Paulson, Alicia F; Prasad, Maneeshi S; Thuringer, Amanda Henke; Manzerra, Pasquale

    2014-01-01

    This review addresses our current understanding of the regulatory mechanisms for classical cadherin expression during development of the vertebrate nervous system. The complexity of the spatial and temporal expression patterns is linked to morphogenic and functional roles in the developing nervous system. While the regulatory networks controlling cadherin expression are not well understood, it is likely that the multiple signaling pathways active in the development of particular domains also regulate the specific cadherins expressed at that time and location. With the growing understanding of the broader roles of cadherins in cell–cell adhesion and non-adhesion processes, it is important to understand both the upstream regulation of cadherin expression and the downstream effects of specific cadherins within their cellular context. PMID:24526207

  3. 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.

  4. Enrico Sereni: research on the nervous system of cephalopods.

    PubMed

    De Leo, A

    2008-01-01

    This essay focuses on a paradigmatic moment in neurobiological studies of invertebrates: the research on the nervous system of cephalopods carried out by Enrico Sereni at the Naples Zoological Station between 1925 and 1931. Although he remained unknown on the historiographic scenario, probably due to his early death, he contributed to Italian science of the first half of the twentieth century. In my paper particular attention will be given to Sereni's study on the pigmentary-effector, neurohumoral, and peripheral nervous systems, since they also accounted for the historical foundation of the experimental vein that, through the years, would lead John Zachary Young, Sereni's follower, to the most well-known discovery of the giant nerve fibers.

  5. The role of leptin in central nervous system diseases

    PubMed Central

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

    2016-01-01

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

  6. Simultaneous central nervous system complications of C. neoformans infection

    PubMed Central

    González-Duarte, Alejandra; Higera Calleja, Jesus; Mitre, Vicente Gijón; Ramos, Guillermo Garcia

    2009-01-01

    The most common neurological manifestation of Cryptococcus neoformans infection is meningitis. Other less common manifestations include parenchymal central nervous system (CNS) granulomatous disease, hydrocephalus and stroke. C. neoformans is often suspected in immunodepressed patients, but it can be easily overlooked in otherwise healthy patients. This paper provides a detailed clinical description of a patient without immunosupression who developed multiple simultaneous neurological manifestations after the infection with C. neoformans. PMID:21577360

  7. Central nervous system infection caused by Morganella morganii.

    PubMed

    Abdalla, Jehad; Saad, Mustafa; Samnani, Imran; Lee, Prescott; Moorman, Jonathan

    2006-01-01

    Central nervous system (CNS) infection with Morganella morganii is very rare. We describe a 38-year-old female patient with frontal brain abscess caused by M morganii who was unsuccessfully treated. We also review all reported cases of Morganella CNS infections with an emphasis on treatment modalities and outcomes. Aggressive surgical management and appropriate antimicrobial therapy can lead to cure, but the mortality rate for these infections remains high.

  8. Neurotensin: immunohistochemical localization in rat central nervous system.

    PubMed Central

    Uhl, G R; Kuhar, M J; Snyder, S H

    1977-01-01

    Neurotensin immunofluorescence was examined in the rat central nervous system using a well-characterized antiserum directed against this tridecapeptide. Morphological characteristics of the fluorescence indicate its association with neuronal cell bodies and processes in the brain and with cells of the anterior pituitary. Fluorescence is seen in many brain areas, with notable densities in the substantia gelatinosa zones of the spinal cord and trigeminal nucleus, central amygdaloid nucleus, anterior pituitary, median eminence, and preoptic and basal hypothalamic areas. Images PMID:333458

  9. Tissue plasminogen activator in central nervous system physiology and pathology

    PubMed Central

    Melchor, Jerry P.; Strickland, Sidney

    2005-01-01

    Summary Although conventionally associated with fibrin clot degradation, recent work has uncovered new functions for the tissue plasminogen activator (tPA)/plasminogen cascade in central nervous system physiology and pathology. This extracellular proteolytic cascade has been shown to have roles in learning and memory, stress, neuronal degeneration, addiction and Alzheimer’s disease. The current review considers the different ways tPA functions in the brain. PMID:15841309

  10. Eph-ephrin signaling in nervous system development

    PubMed Central

    Cramer, Karina S.; Miko, Ilona J.

    2016-01-01

    Ephrins and Eph receptors enable contact-mediated interactions between cells at every stage of nervous system development. In spite of their broad binding affinities, Eph proteins facilitate specificity in neuronal migration and axon targeting. This review focuses on recent studies that demonstrate how these proteins interact with each other, and with other signaling pathways, to guide specificity in a diverse set of developmental processes. PMID:27092247

  11. Centralization of the deuterostome nervous system predates chordates.

    PubMed

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

    2009-08-11

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

  12. Gross anatomy and development of the peripheral nervous system.

    PubMed

    Catala, Martin; Kubis, Nathalie

    2013-01-01

    The nervous system is divided into the central nervous system (CNS) composed of the brain, the brainstem, the cerebellum, and the spinal cord and the peripheral nervous system (PNS) made up of the different nerves arising from the CNS. The PNS is divided into the cranial nerves III to XII supplying the head and the spinal nerves that supply the upper and lower limbs. The general anatomy of the PNS is organized according to the arrangement of the fibers along the rostro-caudal axis. The control of the development of the PNS has been unravelled during the last 30 years. Motor nerves arise from the ventral neural tube. This ventralization is induced by morphogenetic molecules such as sonic hedgehog. In contrast, the sensory elements of the PNS arise from a specific population of cells originating from the roof of the neural tube, namely the neural crest. These cells give rise to the neurons of the dorsal root ganglia, the autonomic ganglia and the paraganglia including the adrenergic neurons of the adrenals. Furthermore, the supportive glial Schwann cells of the PNS originate from the neural crest cells. Growth factors as well as myelinating proteins are involved in the development of the PNS.

  13. Neuritin, a neurotrophic factor in nervous system physiology.

    PubMed

    Zhou, S; Zhou, J

    2014-04-01

    Neuritin (also known as candidate plasticity gene 15, cpg15) is an activity-induced glycosylphosphatidylinositol- anchored axonal protein and is mainly expressed in the brain. Neuritin mRNA expression is modulated by neurotrophic factors, synaptic activity, hormones, sensory experience, and electroconvulsive seizure therapy. Neuritin has several effects in the nervous system, such as promoting neurite outgrowth, modulating neurite outgrowth during neuronal differentiation, protecting motor neuron axons, promoting dendritic growth, shaping dendritic arbors of target neurons, regulating synaptic plasticity, stabilizing active synapses, promoting synaptic maturation and neuronal migration, promoting the development and maturation of visual cortical neurons, regulating apoptosis of proliferative neurons, and regenerating peripheral nerve and spinal axons. Neuritin is also implicated in cerebral ischemia, depression, and cognitive function in schizophrenia, and it upregulates transient outward K(+) currents in neurons, suggesting that neuritin may be a potential therapeutic target in peripheral and central nervous system diseases. This review focuses on the expression, distribution, and physiological functions of neuritin in the nervous system. PMID:24350851

  14. Gangliosides in the Nervous System: Biosynthesis and Degradation

    NASA Astrophysics Data System (ADS)

    Yu, Robert K.; Ariga, Toshio; Yanagisawa, Makoto; Zeng, Guichao

    Gangliosides, abundant in the nervous system, are known to play crucial modulatory roles in cellular recognition, interaction, adhesion, and signal transduction, particularly during early developmental stages. The expression of gangliosides in the nervous system is developmentally regulated and is closely related to the differentiation state of the cell. Ganglioside biosynthesis occurs in intracellular organelles, from which gangliosides are transported to the plasma membrane. During brain development, the ganglioside composition of the nervous system undergoes remarkable changes and is strictly regulated by the activities of glycosyltransferases, which can occur at different levels of control, including glycosyltransferase gene transcription and posttranslational modification. Genes for glycosyltransferase involved in ganglioside biosynthesis have been cloned and classified into families of glycosyltransferases based on their amino acid sequence similarities. The donor and acceptor substrate specificities are determined by enzymatic analysis of the glycosyltransferase gene products. Cell-type specific regulation of these genes has also been studied. Gangliosides are degraded by lysosomal exoglycosidases. The action of these enzymes occurs frequently in cooperation with activator proteins. Several human diseases are caused by defects of degradative enzymes, resulting in massive accumulation of certain glycolipids, including gangliosides in the lysosomal compartment and other organelles in the brain and visceral organs. Some of the representative lysosomal storage diseases (LSDs) caused by the accumulation of lipids in late endosomes and lysosomes will be discussed.

  15. FoxO Proteins in the Nervous System

    PubMed Central

    Maiese, Kenneth

    2015-01-01

    Acute as well as chronic disorders of the nervous system lead to significant morbidity and mortality for millions of individuals globally. Given the ability to govern stem cell proliferation and differentiated cell survival, mammalian forkhead transcription factors of the forkhead box class O (FoxO) are increasingly being identified as potential targets for disorders of the nervous system, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and auditory neuronal disease. FoxO proteins are present throughout the body, but they are selectively expressed in the nervous system and have diverse biological functions. The forkhead O class transcription factors interface with an array of signal transduction pathways that include protein kinase B (Akt), serum- and glucocorticoid-inducible protein kinase (SgK), IκB kinase (IKK), silent mating type information regulation 2 homolog 1 (S. cerevisiae) (SIRT1), growth factors, and Wnt signaling that can determine the activity and integrity of FoxO proteins. Ultimately, there exists a complex interplay between FoxO proteins and their signal transduction pathways that can significantly impact programmed cell death pathways of apoptosis and autophagy as well as the development of clinical strategies for the treatment of neurodegenerative disorders. PMID:26171319

  16. 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.

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

    PubMed Central

    Strank, Cornelia

    2012-01-01

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

  18. 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.

  19. Epigenetics, Nervous System Tumors, and Cancer Stem Cells

    PubMed Central

    Qureshi, Irfan A.; Mehler, Mark F.

    2011-01-01

    Recent advances have begun to elucidate how epigenetic regulatory mechanisms are responsible for establishing and maintaining cell identity during development and adult life and how the disruption of these processes is, not surprisingly, one of the hallmarks of cancer. In this review, we describe the major epigenetic mechanisms (i.e., DNA methylation, histone and chromatin modification, non-coding RNA deployment, RNA editing, and nuclear reorganization) and discuss the broad spectrum of epigenetic alterations that have been uncovered in pediatric and adult nervous system tumors. We also highlight emerging evidence that suggests epigenetic deregulation is a characteristic feature of so-called cancer stem cells (CSCs), which are thought to be present in a range of nervous system tumors and responsible for tumor maintenance, progression, treatment resistance, and recurrence. We believe that better understanding how epigenetic mechanisms operate in neural cells and identifying the etiologies and consequences of epigenetic deregulation in tumor cells and CSCs, in particular, are likely to promote the development of enhanced molecular diagnostics and more targeted and effective therapeutic agents for treating recalcitrant nervous system tumors. PMID:24212967

  20. Equine laryngeal hemiplegia. Part V. Central nervous system pathology.

    PubMed

    Cahill, J I; Goulden, B E

    1986-11-01

    Evidence of long central nerve fibre degeneration (axonal spheroids) in the lateral cuneate nuclei was found in all eight Thoroughbreds affected clinically and subclinically with equine laryngeal hemiplegia, but in only one of six control animals. It was considered that these spheroids may signify a central nervous component of the disease process of laryngeal hemiplegia although until further investigations are performed no firm conclusions regarding the relationship of these findings with laryngeal hemiplegia could be made. Examination of the left and right nucleus ambiguus of clinical and subclinical laryngeal hemiplegic horses revealed no pathological alterations.

  1. Eosinophilic vasculitis in an isolated central nervous system distribution

    PubMed Central

    Sommerville, R B; Noble, J M; Vonsattel, J P; Delapaz, R; Wright, C B

    2007-01-01

    Background Eosinophilic vasculitis has been described as part of the Churg–Strauss syndrome, but affects the central nervous system (CNS) in <10% of cases; presentation in an isolated CNS distribution is rare. We present a case of eosinophilic vasculitis isolated to the CNS. Case report A 39‐year‐old woman with a history of migraine without aura presented to an institution (located in the borough of Queens, New York, USA; no academic affiliation) in an acute confusional state with concurrent headache and left‐sided weakness and numbness. Laboratory evaluation showed increased cerebrospinal fluid (CSF) protein level, but an otherwise unremarkable serological investigation. Magnetic resonance imaging showed bifrontal polar gyral‐enhancing brain lesions. Her symptoms resolved over 2 weeks without residual deficit. After 18 months, later the patient presented with similar symptoms and neuroradiological findings involving territories different from those in her first episode. Again, the CSF protein level was high. She had a raised C reactive protein level and erythrocyte sedimentation rate. Brain biopsy showed transmural, predominantly eosinophilic, inflammatory infiltrates of medium‐sized leptomeningeal arteries without granulomas. She improved, without recurrence, when treated with a prolonged course of corticosteroids. Conclusions To our knowledge, this is the first case of non‐granulomatous eosinophilic vasculitis isolated to the CNS. No aetiology for this patient's primary CNS eosinophilic vasculitis has yet been identified. Spontaneous resolution and recurrence of her syndrome is an unusual feature of the typical CNS vasculitis and may suggest an environmental epitope with immune reaction as the cause. PMID:16926236

  2. 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.

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

    PubMed

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

    2011-03-01

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

  4. Copper signaling in the mammalian nervous system: synaptic effects

    PubMed Central

    Gaier, ED; Eipper, BA; Mains, RE

    2014-01-01

    Copper (Cu) is an essential metal present at high levels in the CNS. Its role as a co-factor in mitochondrial ATP production and in other essential cuproenzymes is well defined. Menkes and Wilson’s diseases are severe neurodegenerative conditions that demonstrate the importance of Cu transport into the secretory pathway. Brain levels of Cu, which is almost entirely protein bound, exceed extracellular levels by more than a hundred-fold. Cu stored in the secretory pathway is released in a Ca2+-dependent manner and can transiently reach concentrations over 100 µM at synapses. The ability of low µM levels of Cu to bind to and modulate the function of γ-aminobutyric acid type A (GABAA) receptors, N-methyl-D-aspartate (NMDA) receptors and voltage-gated Ca2+ channels contributes to its effects on synaptic transmission. Cu also binds to amyloid precursor protein and prion protein; both proteins are found at synapses and brain Cu homeostasis is disrupted in mice lacking either protein. Especially intriguing is the ability of Cu to affect AMP-activated protein kinase (AMPK), a monitor of cellular energy status. Despite this, few investigators have examined the direct effects of Cu on synaptic transmission and plasticity. Although the variability of results demonstrates complex influences of Cu that are highly method-sensitive, these studies nevertheless strongly support important roles for endogenous Cu and new roles for Cu-binding proteins in synaptic function/plasticity and behavior. Further study of the many roles of Cu in nervous system function will reveal targets for intervention in other diseases in which Cu homeostasis is disrupted. PMID:23115049

  5. What Health-Related Functions Are Regulated by the Nervous System?

    MedlinePlus

    ... Research Planning Scientific Resources Research A-Z Topics Neuroscience Overview Condition Information Parts of the nervous system ... functions does the nervous system control? Why study neuroscience? What are the areas of neuroscience? NICHD Research ...

  6. Proton magnetic resonance spectroscopy of leech muscle and nervous system.

    PubMed

    Petroff, O A; Hogan, E; Johansen, J; Kleinhaus, A L

    1987-01-01

    1. Proton nuclear magnetic resonance spectroscopy (1H NMR) was used to measure the major intracellular metabolites in perchloric acid extracts of the Macrobdella decora muscle and nervous systems and the Oryctolagus cuniculus cerebrum. 2. Acetate, alanine, choline, glutamate, inositol, and lactate were assigned in the spectrum of leech ventral cord, leech muscle, and rabbit cerebrum. 3. Hirudonine and propionate were clearly observed only in the spectrum of leech muscle. 4. Creatine, N-acetyl aspartate, gamma aminobutyric acid, aspartate, and taurine, distinctive components of spectra of the mammalian cerebrum, were not seen in the invertebrate spectra. 5. 1H NMR spectroscopy provides a simple and rapid means of characterizing the major organic metabolites found in leech muscle and nervous tissues.

  7. Fourier domain OCT imaging of American cockroach nervous system

    NASA Astrophysics Data System (ADS)

    Wyszkowska, Joanna; Gorczynska, Iwona; Ruminski, Daniel; Karnowski, Karol; Kowalczyk, Andrzej; Stankiewicz, Maria; Wojtkowski, Maciej

    2012-01-01

    In this pilot study we demonstrate results of structural Fourier domain OCT imaging of the nervous system of Periplaneta americana L. (American cockroach). The purpose of this research is to develop an OCT apparatus enabling structural imaging of insect neural system. Secondary purpose of the presented research is to develop methods of the sample preparation and handling during the OCT imaging experiments. We have performed imaging in the abdominal nerve cord excised from the American cockroach. For this purpose we have developed a Fourier domain / spectral OCT system operating at 820 nm wavelength range.

  8. Effects on the nervous system in different groups of workers exposed to aluminium

    PubMed Central

    Iregren, A; Sjogren, B; Gustafsson, K; Hagman, M; Nylen, L; Frech, W; Andersson, M; Ljunggren, K; Wennberg, A

    2001-01-01

    OBJECTIVE—To investigate possible neurotoxic effects in groups of aluminium pot room and foundry workers, aluminium welders, and a small group of workers exposed to aluminium in the production of flake powder.
METHODS—Exposure to aluminium was evaluated with aluminium concentrations in blood and urine as well as a questionnaire. The groups exposed to aluminium were compared with a group of mild steel welders. Neurotoxic effects were studied with mood and symptom questionnaires and several psychological and neurophysiological tests.
RESULTS—The pot room and foundry workers showed very low aluminium uptake as their aluminium concentrations in blood and urine were close to normal, and no effects on the nervous system were detected. The group of workers exposed to flake powder had high concentrations of aluminium in blood and urine, even higher than those of the aluminium welders. However, aluminium could not be shown to affect the functioning of the nervous system in flake powder producers. Although significant effects could not be shown in the present analysis of the data on welders, the performance of the welders exposed to high concentrations of aluminium was affected according to the analyses in the original paper from this group.
CONCLUSIONS—For the pot room and foundry workers no effects related to the exposure to aluminium could be found. For the group of flake powder producers exposed for a short term no effects on the nervous systems were evident despite high levels of exposure. Due to the high concentrations of aluminium in the biological samples of this group, measures to reduce the exposure to aluminium are recommended, as effects on the central nervous system might develop after protracted exposures. However, this assumption needs to be verified in further studies.


Keywords: aluminium; workers; nervous system PMID:11404450

  9. Towards a 'systems'-level understanding of the nervous system and its disorders.

    PubMed

    Qureshi, Irfan A; Mehler, Mark F

    2013-11-01

    It is becoming clear that nervous system development and adult functioning are highly coupled with other physiological systems. Accordingly, neurological and psychiatric disorders are increasingly being associated with a range of systemic comorbidities including, most prominently, impairments in immunological and bioenergetic parameters as well as in the gut microbiome. Here, we discuss various aspects of the dynamic crosstalk between these systems that underlies nervous system development, homeostasis, and plasticity. We believe a better definition of this underappreciated systems physiology will yield important insights into how nervous system diseases with systemic comorbidities arise and potentially identify novel diagnostic and therapeutic strategies.

  10. Developing nervous systems in molluscs: navigating the twists and turns of a complex life cycle.

    PubMed

    Croll, Roger P

    2009-01-01

    Molluscs constitute a richly diversified phylum, containing abundant species that have successfully invaded a variety of habitats. Despite the long-standing importance of its various members as model species for neurobiology, research on the development of the molluscan nervous system has lagged behind that on several other phyla. Recent studies, however, have begun to sketch an overview of neural development during the complex life cycles of these animals, involving multiple larval and postlarval stages and often including processes of torsion and occasionally detorsion affecting the entire body plan. The first neurons appear early in life and innervate a variety of larval organs. The central and peripheral neurons that comprise the adult nervous system generally appear later in larval life. Metamorphosis involves the loss of many neurons and the gain of others, and yet more neurons change to accommodate transitions in modes of locomotion, feeding and habitat. But such large-scale transitions do not stop at metamorphosis as massive changes in body size and behavior occur during juvenile and adult stages, and the nervous system must change accordingly to meet the demands of expanding target tissues and the need to generate new behaviors. Work over the years has gradually revealed some of the genes important in molluscan neural development, but recent whole-genome, EST and microarray projects are now allowing much more rapid progress and providing a valuable molluscan perspective for understanding broader issues concerning the evolution of the nervous system across the animal kingdom.

  11. Nervous system Lyme disease, chronic Lyme disease, and none of the above.

    PubMed

    Halperin, John J

    2016-03-01

    Lyme borreliosis, infection with the tick-borne spirochete Borrelia burgdorferi sensu lato, causes nervous system involvement in 10-15 % of identified infected individuals. Not unlike the other well-known spirochetosis, syphilis, infection can be protracted, but is microbiologically curable in virtually all patients, regardless of disease duration. Diagnosis relies on 2-tier serologic testing, which after the first 4-6 weeks of infection is both highly sensitive and specific. After this early, acute phase, serologic testing should rely only on IgG reactivity. Nervous system involvement most commonly presents with meningitis, cranial neuritis and radiculoneuritis, but can also present with a broader array of peripheral nervous system manifestations. Central nervous system infection typically elicits a cerebrospinal fluid pleocytosis and, often, intrathecal production of specific antibody, findings that should not be expected in disease not affecting the CNS. Treatment with recommended courses of oral or, when necessary, parenteral antibiotics is highly effective. The attribution of chronic, non-specific symptoms to "chronic Lyme disease", in the absence of specific evidence of ongoing B. burgdorferi infection, is inappropriate and unfortunate, leading not only to unneeded treatment and its associated complications, but also to missed opportunities for more appropriate management of patients' often disabling symptoms.

  12. Effects of inhaled rosemary oil on subjective feelings and activities of the nervous system.

    PubMed

    Sayorwan, Winai; Ruangrungsi, Nijsiri; Piriyapunyporn, Teerut; Hongratanaworakit, Tapanee; Kotchabhakdi, Naiphinich; Siripornpanich, Vorasith

    2013-06-01

    Rosemary oil is one of the more famous essential oils widely used in aroma-therapy. However, the effects of rosemary oil on the human body, in particular the nervous system, have not been sufficiently studied. This study investigates the effects of the inhalation of rosemary oil on test subjects' feelings, as well as its effects on various physiological parameters of the nervous system. Twenty healthy volunteers participated in the experiment. All subjects underwent autonomic nervous system (ANS) recording. This consisted of measurements of skin temperature; heart rate; respiratory rate; blood pressure; evaluations of the subjects' mood states; and electroencephalography (EEG) recordings in the pre-, during treatment, and post-rosemary inhalation periods as compared with control conditions. Our results showed significant increases in blood pressure, heart rate, and respiratory rate after rosemary oil inhalation. After the inhalation treatments, subjects were found to have become more active and stated that they felt "fresher". The analysis of EEGs showed a reduction in the power of alpha1 (8-10.99 Hz) and alpha2 (11-12.99 Hz) waves. Moreover, an increment in the beta wave (13-30 Hz) power was observed in the anterior region of the brain. These results confirm the stimulatory effects of rosemary oil and provide supporting evidence that brain wave activity, autonomic nervous system activity, as well as mood states are all affected by the inhalation of the rosemary oil.

  13. Effects of Inhaled Rosemary Oil on Subjective Feelings and Activities of the Nervous System

    PubMed Central

    Sayorwan, Winai; Ruangrungsi, Nijsiri; Piriyapunyporn, Teerut; Hongratanaworakit, Tapanee; Kotchabhakdi, Naiphinich; Siripornpanich, Vorasith

    2013-01-01

    Rosemary oil is one of the more famous essential oils widely used in aroma-therapy. However, the effects of rosemary oil on the human body, in particular the nervous system, have not been sufficiently studied. This study investigates the effects of the inhalation of rosemary oil on test subjects’ feelings, as well as its effects on various physiological parameters of the nervous system. Twenty healthy volunteers participated in the experiment. All subjects underwent autonomic nervous system (ANS) recording. This consisted of measurements of skin temperature; heart rate; respiratory rate; blood pressure; evaluations of the subjects’ mood states; and electroencephalography (EEG) recordings in the pre-, during treatment, and post-rosemary inhalation periods as compared with control conditions. Our results showed significant increases in blood pressure, heart rate, and respiratory rate after rosemary oil inhalation. After the inhalation treatments, subjects were found to have become more active and stated that they felt “fresher”. The analysis of EEGs showed a reduction in the power of alpha1 (8–10.99 Hz) and alpha2 (11–12.99 Hz) waves. Moreover, an increment in the beta wave (13–30 Hz) power was observed in the anterior region of the brain. These results confirm the stimulatory effects of rosemary oil and provide supporting evidence that brain wave activity, autonomic nervous system activity, as well as mood states are all affected by the inhalation of the rosemary oil. PMID:23833718

  14. The midkine family of growth factors: diverse roles in nervous system formation and maintenance

    PubMed Central

    Winkler, C; Yao, S

    2014-01-01

    Midkines are heparin-binding growth factors involved in a wide range of biological processes. Originally identified as retinoic acid inducible genes, midkines are widely expressed during embryogenesis with particularly high levels in the developing nervous system. During postnatal stages, midkine expression generally ceases but is often up-regulated under disease conditions, most notably those affecting the nervous system. Midkines are known as neurotrophic factors, as they promote neurite outgrowth and neuron survival in cell culture. Surprisingly, however, mouse embryos deficient for midkine (knockout mice) are phenotypically normal, which suggests functional redundancy by related growth factors. During adult stages, on the other hand, midkine knockout mice develop striking deficits in neuroprotection and regeneration after drug-induced neurotoxicity and injury. The detailed mechanisms by which midkine controls neuron formation, differentiation and maintenance remain unclear. Recent studies in zebrafish and chick have provided important insight into the role of midkine and its putative receptor, anaplastic lymphoma kinase, in cell cycle control in the central and peripheral nervous systems. A recent structural analysis of zebrafish midkine furthermore revealed essential protein domains required for biological activity that serve as promising novel targets for future drug designs. This review will summarize latest findings in the field that help to better understand the diverse roles of midkine in nervous system formation and maintenance. Linked Articles This article is part of a themed section on Midkine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-4 PMID:24125182

  15. Nervous system Lyme disease, chronic Lyme disease, and none of the above.

    PubMed

    Halperin, John J

    2016-03-01

    Lyme borreliosis, infection with the tick-borne spirochete Borrelia burgdorferi sensu lato, causes nervous system involvement in 10-15 % of identified infected individuals. Not unlike the other well-known spirochetosis, syphilis, infection can be protracted, but is microbiologically curable in virtually all patients, regardless of disease duration. Diagnosis relies on 2-tier serologic testing, which after the first 4-6 weeks of infection is both highly sensitive and specific. After this early, acute phase, serologic testing should rely only on IgG reactivity. Nervous system involvement most commonly presents with meningitis, cranial neuritis and radiculoneuritis, but can also present with a broader array of peripheral nervous system manifestations. Central nervous system infection typically elicits a cerebrospinal fluid pleocytosis and, often, intrathecal production of specific antibody, findings that should not be expected in disease not affecting the CNS. Treatment with recommended courses of oral or, when necessary, parenteral antibiotics is highly effective. The attribution of chronic, non-specific symptoms to "chronic Lyme disease", in the absence of specific evidence of ongoing B. burgdorferi infection, is inappropriate and unfortunate, leading not only to unneeded treatment and its associated complications, but also to missed opportunities for more appropriate management of patients' often disabling symptoms. PMID:26377699

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

    PubMed

    Carney, Joan; Porter, Patricia

    2009-01-01

    Onset of acquired central nervous system (CNS) injury during the normal developmental process of childhood can have impact on cognitive, behavioral, and motor function. This alteration of function often necessitates special education programming, modifications, and accommodations in the education setting for successful school reentry. Special education is not necessarily a special classroom, but an individualized set of educational needs, determined by a multidisciplinary school team, to promote educational success. The purpose of this article is to inform those pediatricians and pediatric allied health professionals treating children with CNS injury of the systems in place to support successful school reentry and their role in contributing to developing an appropriate educational plan. PMID:19489086

  17. Role of the autonomic nervous system in tumorigenesis and metastasis

    PubMed Central

    Magnon, Claire

    2015-01-01

    Convergence of multiple stromal cell types is required to develop a tumorigenic niche that nurtures the initial development of cancer and its dissemination. Although the immune and vascular systems have been shown to have strong influences on cancer, a growing body of evidence points to a role of the nervous system in promoting cancer development. This review discusses past and current research that shows the intriguing role of autonomic nerves, aided by neurotrophic growth factors and axon cues, in creating a favorable environment for the promotion of tumor formation and metastasis. PMID:27308436

  18. Genomics and the evolutionary origins of nervous system complexity.

    PubMed

    Oakley, Todd H; Rivera, Ajna S

    2008-12-01

    Advances in genomics are leading to increased understanding of the evolution of complexity, especially by beginning to bridge genotype and phenotype. Here, using examples from nervous system evolution, we define general patterns of increased complexity seen across levels of biological organization. We also explore specific evolutionary mechanisms that increase complexity, namely those that increase the number of biological units (parts) in a system. We provide specific neurobiological examples of increased complexity in genes, gene networks, cell types, and tissues/organs. These examples illustrate that while a variety of different mechanisms increase biological complexity, they can be understood in a generalized comparative framework. PMID:19152785

  19. Histophysiology of the vegetative peripheral nervous system of skin.

    PubMed

    Förster, F J; Heine, H; Schaeg, G

    1975-12-31

    Preterminal nerve fibers of the peripheral vegetative nervous system make inmediate contact (neuro-effector-areas) to interstitial cells (I.C.). This connection is characterized through a common glycocalyx with the nerve fiber. The I.C. are specific innervated cells and differ morphologically from Schwann-cells, fibrocytes, and histiocytes. The I.C. are able to come into morphologically different contacts with neighbouring cells by microvilli-like cell protrusions. These neighbouring cells then are able to contact other cells by themselves. The results are interpreted in the sense of electro-mechanical feed-back system of information processing in the vegetative periphery.

  20. 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.

  1. RCAN1 links impaired neurotrophin trafficking to aberrant development of the sympathetic nervous system in Down syndrome.

    PubMed

    Patel, Ami; Yamashita, Naoya; Ascaño, Maria; Bodmer, Daniel; Boehm, Erica; Bodkin-Clarke, Chantal; Ryu, Yun Kyoung; Kuruvilla, Rejji

    2015-12-14

    Down syndrome is the most common chromosomal disorder affecting the nervous system in humans. To date, investigations of neural anomalies in Down syndrome have focused on the central nervous system, although dysfunction of the peripheral nervous system is a common manifestation. The molecular and cellular bases underlying peripheral abnormalities have remained undefined. Here, we report the developmental loss of sympathetic innervation in human Down syndrome organs and in a mouse model. We show that excess regulator of calcineurin 1 (RCAN1), an endogenous inhibitor of the calcineurin phosphatase that is triplicated in Down syndrome, impairs neurotrophic support of sympathetic neurons by inhibiting endocytosis of the nerve growth factor (NGF) receptor, TrkA. Genetically correcting RCAN1 levels in Down syndrome mice markedly improves NGF-dependent receptor trafficking, neuronal survival and innervation. These results uncover a critical link between calcineurin signalling, impaired neurotrophin trafficking and neurodevelopmental deficits in the peripheral nervous system in Down syndrome.

  2. RCAN1 links impaired neurotrophin trafficking to aberrant development of the sympathetic nervous system in Down syndrome

    PubMed Central

    Patel, Ami; Yamashita, Naoya; Ascaño, Maria; Bodmer, Daniel; Boehm, Erica; Bodkin-Clarke, Chantal; Ryu, Yun Kyoung; Kuruvilla, Rejji

    2015-01-01

    Down syndrome is the most common chromosomal disorder affecting the nervous system in humans. To date, investigations of neural anomalies in Down syndrome have focused on the central nervous system, although dysfunction of the peripheral nervous system is a common manifestation. The molecular and cellular bases underlying peripheral abnormalities have remained undefined. Here, we report the developmental loss of sympathetic innervation in human Down syndrome organs and in a mouse model. We show that excess regulator of calcineurin 1 (RCAN1), an endogenous inhibitor of the calcineurin phosphatase that is triplicated in Down syndrome, impairs neurotrophic support of sympathetic neurons by inhibiting endocytosis of the nerve growth factor (NGF) receptor, TrkA. Genetically correcting RCAN1 levels in Down syndrome mice markedly improves NGF-dependent receptor trafficking, neuronal survival and innervation. These results uncover a critical link between calcineurin signalling, impaired neurotrophin trafficking and neurodevelopmental deficits in the peripheral nervous system in Down syndrome. PMID:26658127

  3. Measuring Cardiac Autonomic Nervous System (ANS) Activity in Children

    PubMed Central

    van Eijsden, Manon; Gemke, Reinoud J. B. J.; Vrijkotte, Tanja G. M.; de Geus, Eco J.

    2013-01-01

    The autonomic nervous system (ANS) controls mainly automatic bodily functions that are engaged in homeostasis, like heart rate, digestion, respiratory rate, salivation, perspiration and renal function. The ANS has two main branches: the sympathetic nervous system, preparing the human body for action in times of danger and stress, and the parasympathetic nervous system, which regulates the resting state of the body. ANS activity can be measured invasively, for instance by radiotracer techniques or microelectrode recording from superficial nerves, or it can be measured non-invasively by using changes in an organ's response as a proxy for changes in ANS activity, for instance of the sweat glands or the heart. Invasive measurements have the highest validity but are very poorly feasible in large scale samples where non-invasive measures are the preferred approach. Autonomic effects on the heart can be reliably quantified by the recording of the electrocardiogram (ECG) in combination with the impedance cardiogram (ICG), which reflects the changes in thorax impedance in response to respiration and the ejection of blood from the ventricle into the aorta. From the respiration and ECG signals, respiratory sinus arrhythmia can be extracted as a measure of cardiac parasympathetic control. From the ECG and the left ventricular ejection signals, the preejection period can be extracted as a measure of cardiac sympathetic control. ECG and ICG recording is mostly done in laboratory settings. However, having the subjects report to a laboratory greatly reduces ecological validity, is not always doable in large scale epidemiological studies, and can be intimidating for young children. An ambulatory device for ECG and ICG simultaneously resolves these three problems. Here, we present a study design for a minimally invasive and rapid assessment of cardiac autonomic control in children, using a validated ambulatory device 1-5, the VU University Ambulatory Monitoring System (VU

  4. Hypothesis: the regulation of the partial pressure of oxygen by the serotonergic nervous system in hypoxia.

    PubMed

    Devereux, Diana; Ikomi-Kumm, Julie

    2013-03-01

    The regulation of the partial pressure of oxygen by the serotonergic nervous system in hypoxia is a hypothesis, which proposes an inherent operative system in homo sapiens that allows central nervous system and endocrine-mediated vascular system adaption to variables in partial pressure of oxygen, pH and body composition, while maintaining sufficient oxygen saturation for the immune system and ensuring protection of major organs in hypoxic and suboptimal conditions. While acknowledging the importance of the Henderson-Hasselbalch equation in the regulation of acid base balance, the hypothesis seeks to define the specific neuroendocrine/vascular mechanisms at work in regulating acid base balance in hypoxia and infection. The SIA (serotonin-immune-adrenergic) system is proposed as a working model, which allows central nervous system and endocrine-mediated macro- and micro vascular 'fine tuning'. The neurotransmitter serotonin serves as a 'hypoxic sensor' in concert with other operators to orchestrate homeostatic balance in normal and pathological states. The SIA system finely regulates oxygen, fuel and metabolic buffering systems at local sites to ensure optimum conditions for the immune response. The SIA system is fragile and its operation may be affected by infection, stress, diet, environmental toxins and lack of exercise. The hypothesis provides new insight in the area of neuro-gastroenterology, and emphasizes the importance of diet and nutrition as a complement in the treatment of infection, as well as the normalization of intestinal flora following antibiotic therapy.

  5. 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

  6. Characterization of dendritic spines in the Drosophila central nervous system.

    PubMed

    Leiss, Florian; Koper, Ewa; Hein, Irina; Fouquet, Wernher; Lindner, Jana; Sigrist, Stephan; Tavosanis, Gaia

    2009-03-01

    Dendritic spines are a characteristic feature of a number of neurons in the vertebrate nervous system and have been implicated in processes that include learning and memory. In spite of this, there has been no comprehensive analysis of the presence of spines in a classical genetic system, such as Drosophila, so far. Here, we demonstrate that a subset of processes along the dendrites of visual system interneurons in the adult fly central nervous system, called LPTCs, closely resemble vertebrate spines, based on a number of criteria. First, the morphology, size, and density of these processes are very similar to those of vertebrate spines. Second, they are enriched in actin and devoid of tubulin. Third, they are sites of synaptic connections based on confocal and electron microscopy. Importantly, they represent a preferential site of localization of an acetylcholine receptor subunit, suggesting that they are sites of excitatory synaptic input. Finally, their number is modulated by the level of the small GTPase dRac1. Our results provide a basis to dissect the genetics of dendritic spine formation and maintenance and the functional role of spines.

  7. [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.

  8. Do dental infections really cause central nervous system infections?

    PubMed

    Lazow, Stewart K; Izzo, Steven R; Vazquez, David

    2011-11-01

    In the post-World War I antibiotic era, the prevalence of central nervous system (CNS) infections is estimated to be 1 per 100,000 population. The literature is replete with anecdotal case reports of CNS infections of apparent dental etiology. Conversely, it is widely cited that the incidence of CNS infection of dental etiology is only in the range of 1% to 2%. We seek to answer the question if dental infections really cause CNS infections. In this article, we focus on septic cavernous sinus thrombosis and brain abscess and if it is a diagnosis of exclusion or evidence-based.

  9. Clinical implications of thyroid hormones effects on nervous system development.

    PubMed

    Carreón-Rodríguez, Alfonso; Pérez-Martínez, Leonor

    2012-03-01

    Thyroid hormones have an important role throughout prenatal and postnatal nervous system development. They are involved in several processes such as neurogenesis, gliogenesis, myelination, synaptogenesis, etc., as shown in many cases of deficiency like congenital hypothyroidism or hypothyroxinemia. Those pathologies if untreated could lead to severe damages in cognitive, motor, neudoendocrine functions among other effects. Some could be reversed after adequate supplementation of thyroid hormones at birth, however there are other cellular processes highly sensitive to low levels of thyroid hormones and lasting a limited period of time during which if thyroid hormone action is lacking or deficient, the functional and structural damages would produce permanent defects. PMID:22523832

  10. Extracellular vesicles round off communication in the nervous system

    PubMed Central

    Budnik, Vivian; Ruiz-Cañada, Catalina; Wendler, Franz

    2016-01-01

    Functional neural competence and integrity require interactive exchanges among sensory and motor neurons, interneurons and glial cells. Recent studies have attributed some of the tasks needed for these exchanges to extracellular vesicles (such as exosomes and microvesicles), which are most prominently involved in shuttling reciprocal signals between myelinating glia and neurons, thus promoting neuronal survival, the immune response mediated by microglia, and synapse assembly and plasticity. Such vesicles have also been identified as important factors in the spread of neurodegenerative disorders and brain cancer. These extracellular vesicle functions add a previously unrecognized level of complexity to transcellular interactions within the nervous system. PMID:26891626

  11. Chondroitin Sulfate Proteoglycans in the Nervous System: Inhibitors to Repair

    PubMed Central

    Siebert, Justin R.; Conta Steencken, Amanda; Osterhout, Donna J.

    2014-01-01

    Chondroitin sulfate proteoglycans (CSPGs) are widely expressed in the normal central nervous system, serving as guidance cues during development and modulating synaptic connections in the adult. With injury or disease, an increase in CSPG expression is commonly observed close to lesioned areas. However, these CSPG deposits form a substantial barrier to regeneration and are largely responsible for the inability to repair damage in the brain and spinal cord. This review discusses the role of CSPGs as inhibitors, the role of inflammation in stimulating CSPG expression near site of injury, and therapeutic strategies for overcoming the inhibitory effects of CSPGs and creating an environment conducive to nerve regeneration. PMID:25309928

  12. West Nile Virus Infection in the Central Nervous System

    PubMed Central

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

    2016-01-01

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

  13. Nonviral Gene Therapy of the Nervous System: Electroporation.

    PubMed

    Ding, Xue-Feng; Fan, Ming

    2016-01-01

    Electroporation has been widely used to efficiently transfer foreign genes into the mammalian central nervous system (CNS), and thus plays an important role in gene therapeutic studies on some brain disorders. A lot of work concerning electroporation is focused on gene transfer into rodent brains. This technique involves an injection of nucleic acids into the brain ventricle or specific area and then applying appropriate electrical field to the injected area. Here, we briefly introduced the advantages and the basic procedures of gene transfer into the rodent brain using electroporation. Better understanding of electroporation in rodent brain may further facilitate gene therapeutic studies on brain disorders.

  14. Autoimmune T cell responses in the central nervous system

    PubMed Central

    Goverman, Joan

    2010-01-01

    Autoreactive T cell responses have a crucial role in central nervous system (CNS) diseases such as multiple sclerosis. Recent data indicate that CNS autoimmunity can be mediated by two distinct lineages of CD4+ T cells that are defined by the production of either interferon-γ or interleukin-17. The activity of these CD4+ T cell subsets within the CNS influences the pathology and clinical course of disease. New animal models show that myelin-specific CD8+ T cells can also mediate CNS autoimmunity. This Review focuses on recent progress in delineating the pathogenic mechanisms, regulation and interplay between these different T cell subsets in CNS autoimmunity. PMID:19444307

  15. Neuroactive steroids and the peripheral nervous system: An update.

    PubMed

    Giatti, Silvia; Romano, Simone; Pesaresi, Marzia; Cermenati, Gaia; Mitro, Nico; Caruso, Donatella; Tetel, Marc J; Garcia-Segura, Luis Miguel; Melcangi, Roberto C

    2015-11-01

    In the present review we summarize observations to date supporting the concept that neuroactive steroids are synthesized in the peripheral nervous system, regulate the physiology of peripheral nerves and exert notable neuroprotective actions. Indeed, neuroactive steroids have been recently proposed as therapies for different types of peripheral neuropathy, like for instance those occurring during aging, chemotherapy, physical injury and diabetes. Moreover, pharmacological tools able to increase the synthesis of neuroactive steroids might represent new interesting therapeutic strategy to be applied in case of peripheral neuropathy.

  16. 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.

  17. Herpesvirus Transport to the Nervous System and Back Again

    PubMed Central

    Smith, Gregory

    2013-01-01

    Herpes simplex virus, varicella zoster virus, and pseudorabies virus are neurotropic pathogens of the Alphaherpesvirinae subfamily of the Herpesviridae. These viruses efficiently invade the peripheral nervous system and establish lifelong latency in neurons resident in peripheral ganglia. Primary and recurrent infections cycle virus particles between neurons and the peripheral tissues they innervate. This remarkable cycle of infection is the topic of this review. In addition, some of the distinguishing hallmarks of the infections caused by these viruses are evaluated in terms of their underlying similarities. PMID:22726218

  18. Imaging of cancer therapy-induced central nervous system toxicity.

    PubMed

    Dietrich, Jörg; Klein, Joshua P

    2014-02-01

    Cancer therapy, including radiation and chemotherapy, can be associated with harmful effects to the central nervous system. Recognition of classical neurotoxic syndromes is critical to appropriately guide and optimize patient management. As a result of cancer therapy-induced toxicity, patients may present with acute, subacute, and chronic neurologic symptoms that can be misinterpreted as tumor recurrence, infection, or paraneoplastic syndromes. In this review the advantages and limitations of various neuroimaging modalities such as computed tomography, magnetic resonance imaging, and positron emission tomography, frequently used in patients with cancer who present with diverse neurotoxic syndromes, are highlighted. PMID:24287388

  19. Music Attenuated a Decrease in Parasympathetic Nervous System Activity after Exercise

    PubMed Central

    Miura, Misa; Ito, Osamu; Kohzuki, Masahiro

    2016-01-01

    Music and exercise can both affect autonomic nervous system activity. However, the effects of the combination of music and exercise on autonomic activity are poorly understood. Additionally, it remains unknown whether music affects post-exercise orthostatic tolerance. The aim of this study was to evaluate the effects of music on autonomic nervous system activity in orthostatic tolerance after exercise. Twenty-six healthy graduate students participated in four sessions in a random order on four separate days: a sedentary session, a music session, a bicycling session, and a bicycling with music session. Participants were asked to listen to their favorite music and to exercise on a cycle ergometer. We evaluated autonomic nervous system activity before and after each session using frequency analysis of heart rate variability. High frequency power, an index of parasympathetic nervous system activity, was significantly increased in the music session. Heart rate was increased, and high frequency power was decreased, in the bicycling session. There was no significant difference in high frequency power before and after the bicycling with music session, although heart rate was significantly increased. Additionally, both music and exercise did not significantly affect heart rate, systolic blood pressure or also heart rate variability indices in the orthostatic test. These data suggest that music increased parasympathetic activity and attenuated the exercise-induced decrease in parasympathetic activity without altering the orthostatic tolerance after exercise. Therefore, music may be an effective approach for improving post-exercise parasympathetic reactivation, resulting in a faster recovery and a reduction in cardiac stress after exercise. PMID:26840532

  20. Music Attenuated a Decrease in Parasympathetic Nervous System Activity after Exercise.

    PubMed

    Jia, Tiantian; Ogawa, Yoshiko; Miura, Misa; Ito, Osamu; Kohzuki, Masahiro

    2016-01-01

    Music and exercise can both affect autonomic nervous system activity. However, the effects of the combination of music and exercise on autonomic activity are poorly understood. Additionally, it remains unknown whether music affects post-exercise orthostatic tolerance. The aim of this study was to evaluate the effects of music on autonomic nervous system activity in orthostatic tolerance after exercise. Twenty-six healthy graduate students participated in four sessions in a random order on four separate days: a sedentary session, a music session, a bicycling session, and a bicycling with music session. Participants were asked to listen to their favorite music and to exercise on a cycle ergometer. We evaluated autonomic nervous system activity before and after each session using frequency analysis of heart rate variability. High frequency power, an index of parasympathetic nervous system activity, was significantly increased in the music session. Heart rate was increased, and high frequency power was decreased, in the bicycling session. There was no significant difference in high frequency power before and after the bicycling with music session, although heart rate was significantly increased. Additionally, both music and exercise did not significantly affect heart rate, systolic blood pressure or also heart rate variability indices in the orthostatic test. These data suggest that music increased parasympathetic activity and attenuated the exercise-induced decrease in parasympathetic activity without altering the orthostatic tolerance after exercise. Therefore, music may be an effective approach for improving post-exercise parasympathetic reactivation, resulting in a faster recovery and a reduction in cardiac stress after exercise.

  1. Selective response of rat peripheral sympathetic nervous system to various stimuli

    PubMed Central

    Ulus, I. H.; Wurtman, R. J.

    1979-01-01

    1. We utilized the induction of tyrosine hydroxylase, a catecholamine-synthesizing enzyme, in sympathetic ganglia and adrenal medullae to explore the central and peripheral mechanisms through which choline, various environmental stresses, and drugs that alter blood pressure or central neurotransmission affect various portions of the sympathetic nervous system. Animals received each treatment chronically, and enzyme activity was measured in the superior cervical, stellate, and coeliac ganglia and in the adrenal medullae. 2. Choline administration increased tyrosine hydroxylase activity in all four tissues, probably by increasing the release of acetylcholine from preganglionic sympathetic neurones that synapse on catecholamine-producing ganglion and chromaffin cells; carbachol and nicotine had similar effects. 3. Insulin enhanced tyrosine hydroxylase activity primarily in the coeliac ganglion and the adrenal medullae, but not in the superior cervical ganglia. 4. Reserpine and phenoxybenzamine increased the activity of the enzyme in all four tissues. 5. Prolonged exposure to a cold environment increased enzyme activity in all four tissues, but especially in the stellate and coeliac ganglia; forced swimming affected tyrosine hydroxylase only in these two ganglia. 6. Several drugs known to modify central neurotransmission were found to increase tyrosine hydroxylase activity in some portions of the sympathetic nervous system but not in others. 5,7-Dihydroxytryptamine, which destroys terminals of serotoninergic neurones, enhanced enzyme activity in all four tissues, but primarily in the coeliac ganglion and adrenal medullae. ET-495 (a dopaminergic agonist), D-amphetamine, and morphine induced tyrosine hydroxylase activity in the adrenal medullae and the coeliac ganglion, but not in the superior cervical ganglia. Oxotremorine, a centrally acting muscarinic agonist, increased tyrosine hydroxylase activity only in the adrenal medullae; its effect was not blocked by

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

    PubMed

    Ameri, A

    1998-10-01

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

  3. The effect of octopamine on the locust stomatogastric nervous system.

    PubMed

    Rand, David; Knebel, Daniel; Ayali, Amir

    2012-01-01

    Octopamine (OA) is a prominent neuromodulator of invertebrate nervous systems, influencing multiple physiological processes. Among its many roles in insects are the initiation and maintenance of various rhythmic behaviors. Here, the neuromodulatory effects of OA on the components of the locust stomatogastric nervous system were studied, and one putative source of OA modulation of the system was identified. Bath application of OA was found to abolish the endogenous rhythmic output of the fully isolated frontal ganglion (FG), while stimulating motor activity of the fully isolated hypocerebral ganglion (HG). OA also induced rhythmic movements in a foregut preparation with intact HG innervation. Complex dose-dependent effects of OA on interconnected FG-HG preparations were seen: 10(-5) M OA accelerated the rhythmic activity of both the HG and FG in a synchronized manner, while 10(-4) M OA decreased both rhythms. Intracellular stimulation of an identified octopaminergic dorsal unpaired median neuron in the subesophageal ganglion was found to exert a similar effect on the FG motor output as that of OA application. Our findings suggest a mechanism of regulation of insect gut patterns and feeding-related behavior during stress and times of high energy demand. PMID:22934040

  4. 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

  5. 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.

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

    PubMed

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

    2014-08-01

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

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

    ERIC Educational Resources Information Center

    Gordon, Tessa; Gordon, Karen

    2010-01-01

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

  8. The origin and evolution of chordate nervous systems.

    PubMed

    Holland, Linda Z

    2015-12-19

    In the past 40 years, comparisons of developmental gene expression and mechanisms of development (evodevo) joined comparative morphology as tools for reconstructing long-extinct ancestral forms. Unfortunately, both approaches typically give congruent answers only with closely related organisms. Chordate nervous systems are good examples. Classical studies alone left open whether the vertebrate brain was a new structure or evolved from the anterior end of an ancestral nerve cord like that of modern amphioxus. Evodevo plus electron microscopy showed that the amphioxus brain has a diencephalic forebrain, small midbrain, hindbrain and spinal cord with parts of the genetic mechanisms for the midbrain/hindbrain boundary, zona limitans intrathalamica and neural crest. Evodevo also showed how extra genes resulting from whole-genome duplications in vertebrates facilitated evolution of new structures like neural crest. Understanding how the chordate central nervous system (CNS) evolved from that of the ancestral deuterostome has been truly challenging. The majority view is that this ancestor had a CNS with a brain that gave rise to the chordate CNS and, with loss of a discrete brain, to one of the two hemichordate nerve cords. The minority view is that this ancestor had no nerve cord; those in chordates and hemichordates evolved independently. New techniques such as phylostratigraphy may help resolve this conundrum.

  9. Central nervous system effects of local anaesthetic agents.

    PubMed

    Englesson, S; Matousek, M

    1975-02-01

    A review is given of an experimental study on cats where the influence of acid-base changes on central nervous system toxicity of local anaesthetic agents was studied. The conclusion of this study was that a respiratory acidosis increased the central nervous system toxicity of local anaesthetics and that the underlying metabolic conditions modified this increase. Thus a respiratory acidosis increased this toxicity more if it was based on a metabolic acidosis than on a metabolic alkalosis (Englesson, 1974; Englesson and Grevsten, 1974). An extended analysis is presented where automatic frequency analysis was performed on the e.e.g. recordings performed during the i.v. infusion of lignocaine, bupivacaine, L 134, HS 37 and its optical isomers. The preliminary results show that the electrical changes appearing in the e.e.g. from the start of the i.v. infusion until seizure activity were the same if this time interval was as short as 1 min or as long as 8 min. It also revealed remarkable individual differences between agents, for instance lignocaine displaying marked electrical changes already in the first third of this time period where bupivacaine showed no changes until shortly before seizures. PMID:238556

  10. TrkB/BDNF signalling patterns the sympathetic nervous system.

    PubMed

    Kasemeier-Kulesa, Jennifer C; Morrison, Jason A; Lefcort, Frances; Kulesa, Paul M

    2015-01-01

    The sympathetic nervous system is essential for maintaining mammalian homeostasis. How this intricately connected network, composed of preganglionic neurons that reside in the spinal cord and post-ganglionic neurons that comprise a chain of vertebral sympathetic ganglia, arises developmentally is incompletely understood. This problem is especially complex given the vertebral chain of sympathetic ganglia derive secondarily from the dorsal migration of 'primary' sympathetic ganglia that are initially located several hundred microns ventrally from their future pre-synaptic partners. Here we report that the dorsal migration of discrete ganglia is not a simple migration of individual cells but a much more carefully choreographed process that is mediated by extensive interactions of pre-and post-ganglionic neurons. Dorsal migration does not occur in the absence of contact with preganglionic axons, and this is mediated by BDNF/TrkB signalling. Thus BDNF released by preganglionic axons acts chemotactically on TrkB-positive sympathetic neurons, to pattern the developing peripheral nervous system. PMID:26404565

  11. Spectral Mixing in Nervous Systems: Experimental Evidenceand Biologically Plausible Circuits

    NASA Astrophysics Data System (ADS)

    Kleinfeld, D.; Mehta, S. B.

    The ability to compute the difference frequency for two periodic signals depends on a nonlinear operation that mixes those signals. Behavioral and psychophysical evidence suggest that such mixing is likely to occur in the vertebrate nervous system as a means to compare rhythmic sensory signals, such as occurs in human audition, and as a means to lock an intrinsic rhythm to a sensory input. Electrophysiological data from electroreceptors in the immobilized electric fish and somatosensory cortex in the anesthetized rat yield direct evidence for such mixing, providing a neurological substrate for the modulation and demodulation of rhythmic neuronal signals. We consider an analytical model of spectral mixing that makes use of the threshold characteristics of neuronal firing and which has features consistent with the experimental observations. This model serves as a guide for constructing circuits that isolate given mixture components. In particular, such circuits can generate nearly pure difference tones from sinusoidal inputs without the use of band-pass filters, in analogy to an image-reject mixer in communications engineering. We speculate that such computations may play a role in coding of sensory input and feedback stabilization of motor output in nervous systems.

  12. Glycosaminoglycans and glycomimetics in the central nervous system.

    PubMed

    Rowlands, Dáire; Sugahara, Kazuyuki; Kwok, Jessica C F

    2015-02-19

    With recent advances in the construction of synthetic glycans, selective targeting of the extracellular matrix (ECM) as a potential treatment for a wide range of diseases has become increasingly popular. The use of compounds that mimic the structure or bioactive function of carbohydrate structures has been termed glycomimetics. These compounds are mostly synthetic glycans or glycan-binding constructs which manipulate cellular interactions. Glycosaminoglycans (GAGs) are major components of the ECM and exist as a diverse array of differentially sulphated disaccharide units. In the central nervous system (CNS), they are expressed by both neurons and glia and are crucial for brain development and brain homeostasis. The inherent diversity of GAGs make them an essential biological tool for regulating a complex range of cellular processes such as plasticity, cell interactions and inflammation. They are also involved in the pathologies of various neurological disorders, such as glial scar formation and psychiatric illnesses. It is this diversity of functions and potential for selective interventions which makes GAGs a tempting target. In this review, we shall describe the molecular make-up of GAGs and their incorporation into the ECM of the CNS. We shall highlight the different glycomimetic strategies that are currently being used in the nervous system. Finally, we shall discuss some possible targets in neurological disorders that may be addressed using glycomimetics.

  13. Sequelae of central-nervous-system enterovirus infections.

    PubMed

    Sells, C J; Carpenter, R L; Ray, C G

    1975-07-01

    The long-term effects of central-nervous-system enterovirus infections were examined in a controlled follow-up study of 19 children 2 1/2 to eight years of age who had been hospitalized with documented enterovirus infection 17 to 67 months before evaluation. Assessment included medical history, physical and neurologic examination, psychologic testing, and speech and hearing evaluation. Three children (16 per cent) had definite neurologic impairment, five (26 per cent) had possible impairment, and 11 (58 per cent) were free of detectable abnormalities. Children whose illness occurred during the first year of life, when compared to controls, were found to have significantly smaller mean head circumference (50.6 vs. 51.6 cm, P less than 0.033), significantly lower mean I.Q. (97 vs 115, P less than 0.007), and depressed languange and speech skills. Children whose illness occurred after the first year of life were not different from their controls. Children whith central-nervous-system enterovirus infection may have neurologic impairment when infection occurs in the first year of life.

  14. Role of the autonomic nervous system in modulating cardiac arrhythmias.

    PubMed

    Shen, Mark J; Zipes, Douglas P

    2014-03-14

    The autonomic nervous system plays an important role in the modulation of cardiac electrophysiology and arrhythmogenesis. Decades of research has contributed to a better understanding of the anatomy and physiology of cardiac autonomic nervous system and provided evidence supporting the relationship of autonomic tone to clinically significant arrhythmias. The mechanisms by which autonomic activation is arrhythmogenic or antiarrhythmic are complex and different for specific arrhythmias. In atrial fibrillation, simultaneous sympathetic and parasympathetic activations are the most common trigger. In contrast, in ventricular fibrillation in the setting of cardiac ischemia, sympathetic activation is proarrhythmic, whereas parasympathetic activation is antiarrhythmic. In inherited arrhythmia syndromes, sympathetic stimulation precipitates ventricular tachyarrhythmias and sudden cardiac death except in Brugada and J-wave syndromes where it can prevent them. The identification of specific autonomic triggers in different arrhythmias has brought the idea of modulating autonomic activities for both preventing and treating these arrhythmias. This has been achieved by either neural ablation or stimulation. Neural modulation as a treatment for arrhythmias has been well established in certain diseases, such as long QT syndrome. However, in most other arrhythmia diseases, it is still an emerging modality and under investigation. Recent preliminary trials have yielded encouraging results. Further larger-scale clinical studies are necessary before widespread application can be recommended.

  15. Methanol intoxication: pathological changes of central nervous system (17 cases).

    PubMed

    Karayel, Ferah; Turan, Arzu A; Sav, Aydin; Pakis, Isil; Akyildiz, Elif U; Ersoy, Gokhan

    2010-03-01

    The nervous system has increased susceptibility for methanol intoxication. The aim of this study is to investigate various central nervous system lesions of methanol intoxication in 17 cases autopsied in the mortuary department of the Council of Forensic Medicine in Istanbul, Turkey. The reasons of methanol intoxication in the cases was likely the unwitting ingestion of methanol while drinking illegal alcohol. Survival times ranged from several hours to days. In 8 cases (47%), cerebral edema and in 9 cases (53%) at occipital, temporal and parietal cortex, basal ganglia and pons, petechial bleeding was observed. In addition to these findings, hemorrhagic necrosis were observed in thalamus, putamen, and globus pallidus in 5 cases (29.4%) and, in cerebral cortex in another 3 cases (17.6%). In 3 of the cases (17.6%) in which cerebral edema was found, herniation findings accompanied to the situation and in 2 cases (11.7%), pons bleeding was observed. Around the basal ganglia, in 2 of the cases with hemorrhagic necrosis, the situation ended with a ventricular compression. In 7 cases (41%), the associated findings of chronic ischemic changes in cortical neurons, lacunae formation, degeneration of granular cell layer of the cerebellum, and reactive gliosis were considered as the results of chronic alcoholism.

  16. Control of Bone Remodeling by the Peripheral Sympathetic Nervous System

    PubMed Central

    Campbell, Preston; Ma, Yun

    2013-01-01

    The skeleton is no longer seen as a static, isolated, and mostly structural organ. Over the last two decades, a more complete picture of the multiple functions of the skeleton has emerged, and its interactions with a growing number of apparently unrelated organs have become evident. The skeleton not only reacts to mechanical loading and inflammatory, hormonal, and mineral challenges, but also acts of its own accord by secreting factors controlling the function of other tissues, including the kidney and possibly the pancreas and gonads. It is thus becoming widely recognized that it is by nature an endocrine organ, in addition to a structural organ and site of mineral storage and hematopoiesis. Consequently and by definition, bone homeostasis must be tightly regulated and integrated with the biology of other organs to maintain whole body homeostasis, and data uncovering the involvement of the central nervous system (CNS) in the control of bone remodeling support this concept. The sympathetic nervous system (SNS) represents one of the main links between the CNS and the skeleton, based on a number of anatomic, pharmacologic, and genetic studies focused on β-adrenergic receptor (βAR) signaling in bone cells. The goal of this report was to review the data supporting the role of the SNS and βAR signaling in the regulation of skeletal homeostasis. PMID:23765388

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

    PubMed

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

    2016-04-14

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

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

    PubMed

    Vaughn, J E

    1989-01-01

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

  19. Insights into mechanisms of central nervous system myelination using zebrafish.

    PubMed

    Czopka, Tim

    2016-03-01

    Myelin is the multi-layered membrane that surrounds most axons and is produced by oligodendrocytes in the central nervous system (CNS). In addition to its important role in enabling rapid nerve conduction, it has become clear in recent years that myelin plays additional vital roles in CNS function. Myelinating oligodendrocytes provide metabolic support to axons and active myelination is even involved in regulating forms of learning and memory formation. However, there are still large gaps in our understanding of how myelination by oligodendrocytes is regulated. The small tropical zebrafish has become an increasingly popular model organism to investigate many aspects of nervous system formation, function, and regeneration. This is mainly due to two approaches for which the zebrafish is an ideally suited vertebrate model--(1) in vivo live cell imaging using vital dyes and genetically encoded reporters, and (2) gene and target discovery using unbiased screens. This review summarizes how the use of zebrafish has helped understand mechanisms of oligodendrocyte behavior and myelination in vivo and discusses the potential use of zebrafish to shed light on important future questions relating to myelination in the context of CNS development, function and repair.

  20. Neurotrophic effects of neudesin in the central nervous system

    PubMed Central

    Kimura, Ikuo; Nakayama, Yoshiaki; Zhao, Ying; Konishi, Morichika; Itoh, Nobuyuki

    2013-01-01

    Neudesin (neuron-derived neurotrophic factor; NENF) was identified as a neurotrophic factor that is involved in neuronal differentiation and survival. It is abundantly expressed in the central nervous system, and its neurotrophic activity is exerted via the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) pathways. Neudesin is also an anorexigenic factor that suppresses food intake in the hypothalamus. It is a member of the membrane-associated progesterone receptor (MAPR) family and shares key structural motifs with the cytochrome b5-like heme/steroid-binding domain. Progesterone receptor membrane component 1 (PGRMC1), the first to be discovered among the MAPR family, binds progesterone to induce “rapid non-genomic effects” in biological responses that are unrelated to the nuclear progesterone receptors (PRs). Hence, neudesin may also be involved in the rapid non-genomic actions of progesterone. In this review, we summarize the identification, structure, and activity of neudesin in the central nervous system, and present an essential overview of the current understanding of its physiological roles and the prospect of elucidating its non-genomic progesterone effects. PMID:23805070

  1. 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.

  2. 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

  3. Does the Sympathetic Nervous System Adapt to Chronic Altitude Exposure?

    PubMed

    Sander, Mikael

    2016-01-01

    During continued exposure to hypobaric hypoxia in acclimatizing lowlanders increasing norepinephrine levels indirectly indicate sympathoexcitation, and in a few subjects serial measurements have suggested some adaptation over time. A few studies have provided direct microneurographic evidence for markedly increased muscle sympathetic nervous activity (MSNA) after 1-50 days of exposure of lowlanders to altitudes of 4100-5260 m above sea level. Only one study has provided two MSNA-measurements over time (10 and 50 days) in altitude (4100 m above sea level) and continued robust sympathoexcitation without adaptation was found in acclimatizing lowlanders. In this study, norepinephrine levels during rest and exercise also remained highly elevated over time. In comparison, acute exposure to hypoxic breathing (FiO2 0.126) at sea level caused no change in sympathetic nervous activity, although the same oxygen saturation in arterial blood (around 90 %) was present during acute (FiO2 0.126) and chronic hypoxic exposure (4100 m above sea level). These findings strongly suggest that the chemoreflex-mechanisms underlying acute hypoxia-induced increases in MSNA are sensitized over time. Collectively, the MSNA data suggests that sensitization of the sympathoexcitatory chemoreflex is evident but not complete within the first 24 h, but is complete after 10 days of altitude exposure. After return from high altitude to sea level the MSNA remains significantly elevated for at least 5 days but completely normalized after 3 months. The few MSNA measurements in high altitude natives have documented high sympathetic activity in all subjects studied. Because serial measurements of MSNA in high altitude natives during sea level exposure are lacking, it is unclear whether the sympathetic nervous system have somehow adapted to lifelong altitude exposure. PMID:27343109

  4. Breast Cancer Metastasis to the Central Nervous System

    PubMed Central

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

    2005-01-01

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

  5. Breast cancer metastasis to the central nervous system.

    PubMed

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

    2005-10-01

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

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

    PubMed

    Kipnis, Jonathan

    2016-08-19

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

  7. Gene-environment interactions and the enteric nervous system: Neural plasticity and Hirschsprung disease prevention.

    PubMed

    Heuckeroth, Robert O; Schäfer, Karl-Herbert

    2016-09-15

    Intestinal function is primarily controlled by an intrinsic nervous system of the bowel called the enteric nervous system (ENS). The cells of the ENS are neural crest derivatives that migrate into and through the bowel during early stages of organogenesis before differentiating into a wide variety of neurons and glia. Although genetic factors critically underlie ENS development, it is now clear that many non-genetic factors may influence the number of enteric neurons, types of enteric neurons, and ratio of neurons to glia. These non-genetic influences include dietary nutrients and medicines that may impact ENS structure and function before or after birth. This review summarizes current data about gene-environment interactions that affect ENS development and suggests that these factors may contribute to human intestinal motility disorders like Hirschsprung disease or irritable bowel syndrome.

  8. Microbe-host interactions: Influence of the gut microbiota on the enteric nervous system.

    PubMed

    Hyland, Niall P; Cryan, John F

    2016-09-15

    The enteric nervous system (ENS), considered a separate branch of the autonomic nervous system, is located throughout the length of the gastrointestinal (GI) tract as a series of interconnected ganglionated plexi. Given the proximity of the intestinal microbiota to the ENS, it is perhaps not surprising that the gut microbiota can influence its development and function. However, these interactions are complex and may be either direct or indirect, often involving signalling initiated by microbe-derived components, metabolites or host-derived intermediaries which subsequently affect enteric nerve excitability and GI function. Individual microbes and strains can differentially influence ENS activity and neurochemistry. In this review we will briefly summarise the role of the microbiota on ENS development, and, in some more detail, explore the mechanisms by which the microbiota can influence ENS activity and function.

  9. Distribution of feline lymphoma in the central and peripheral nervous systems.

    PubMed

    Mandara, Maria Teresa; Motta, Luca; Calò, Pietro

    2016-10-01

    In cats, lymphoma (lymphosarcoma) is the most common neoplasm affecting the spinal cord and the second most common intracranial tumour. Although lymphoma commonly develops in the spinal cord as a part of a multicentric process, a primary form may occur. Lymphoma can exhibit a wide range of morphological patterns, including intraparenchymal brain mass, lymphomatosis cerebri, intravascular lymphoma, lymphomatous choroiditis and meningitis, extradural, intradural-extramedullary or intramedullary lymphoma in the spinal cord, or neurolymphomatosis in the peripheral nerves. Lymphoma may occur as a paraneoplastic disorder associated with peripheral neuropathies. Magnetic resonance imaging (MRI) and computed tomography (CT) are the techniques of choice for morphological assessment of nervous system lesions in vivo. However, biopsy should be performed to achieve a definitive diagnosis. Knowledge of the different morphological patterns expressed by lymphoma in the nervous system of cats allows veterinary clinicians to suspect lymphoma and to arrange appropriate diagnostic procedures, including immunophenotype and clonality studies, along with therapeutic protocols and prognostic evaluations. PMID:27687936

  10. 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

  11. Ramsay Hunt Syndrome Associated with Central Nervous System Involvement in an Adult.

    PubMed

    Chan, Tommy L H; Cartagena, Ana M; Bombassaro, Anne Marie; Hosseini-Moghaddam, Seyed M

    2016-01-01

    Ramsay Hunt syndrome associated with varicella zoster virus reactivation affecting the central nervous system is rare. We describe a 55-year-old diabetic female who presented with gait ataxia, right peripheral facial palsy, and painful vesicular lesions involving her right ear. Later, she developed dysmetria, fluctuating diplopia, and dysarthria. Varicella zoster virus was detected in the cerebrospinal fluid by polymerase chain reaction. She was diagnosed with Ramsay Hunt syndrome associated with spread to the central nervous system. Her facial palsy completely resolved within 48 hours of treatment with intravenous acyclovir 10 mg/kg every 8 hours. However, cerebellar symptoms did not improve until a tapering course of steroid therapy was initiated. PMID:27366189

  12. Peripheral nervous system plasmalogens regulate Schwann cell differentiation and myelination

    PubMed Central

    da Silva, Tiago Ferreira; Eira, Jessica; Lopes, André T.; Malheiro, Ana R.; Sousa, Vera; Luoma, Adrienne; Avila, Robin L.; Wanders, Ronald J.A.; Just, Wilhelm W.; Kirschner, Daniel A.; Sousa, Mónica M.; Brites, Pedro

    2014-01-01

    Rhizomelic chondrodysplasia punctata (RCDP) is a developmental disorder characterized by hypotonia, cataracts, abnormal ossification, impaired motor development, and intellectual disability. The underlying etiology of RCDP is a deficiency in the biosynthesis of ether phospholipids, of which plasmalogens are the most abundant form in nervous tissue and myelin; however, the role of plasmalogens in the peripheral nervous system is poorly defined. Here, we used mouse models of RCDP and analyzed the consequence of plasmalogen deficiency in peripheral nerves. We determined that plasmalogens are crucial for Schwann cell development and differentiation and that plasmalogen defects impaired radial sorting, myelination, and myelin structure. Plasmalogen insufficiency resulted in defective protein kinase B (AKT) phosphorylation and subsequent signaling, causing overt activation of glycogen synthase kinase 3β (GSK3β) in nerves of mutant mice. Treatment with GSK3β inhibitors, lithium, or 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8) restored Schwann cell defects, effectively bypassing plasmalogen deficiency. Our results demonstrate the requirement of plasmalogens for the correct and timely differentiation of Schwann cells and for the process of myelination. In addition, these studies identify a mechanism by which the lack of a membrane phospholipid causes neuropathology, implicating plasmalogens as regulators of membrane and cell signaling. PMID:24762439

  13. Autonomic Nervous System Responses to Concussion: Arterial Pulse Contour Analysis.

    PubMed

    La Fountaine, Michael F; Toda, Michita; Testa, Anthony J; Hill-Lombardi, Vicci

    2016-01-01

    The arterial pulse wave (APW) has a distinct morphology whose contours reflect dynamics in cardiac function and peripheral vascular tone as a result of sympathetic nervous system (SNS) control. With a transition from rest to increased metabolic demand, the expected augmentation of SNS outflow will not only affect arterial blood pressure and heart rate but it will also induce changes to the contours of the APW. Following a sports concussion, a transient state cardiovascular autonomic dysfunction is present. How this state affects the APW has yet to be described. A prospective, parallel-group study on cardiovascular autonomic control (i.e., digital electrocardiogram and continuous beat-to-beat blood pressure) was performed in the seated upright position in 10 athletes with concussion and 7 non-injured control athletes. Changes in APW were compared at rest and during the first 60 s (F60) of an isometric handgrip test (IHGT) in concussed athletes and non-injured controls within 48 h and 1 week of injury. The concussion group was further separated by the length of time until they were permitted to return to play (RTP > 1week; RTP ≤ 1week). SysSlope, an indirect measurement of stroke volume, was significantly lower in the concussion group at rest and during F60 at 48 h and 1week; a paradoxical decline in SysSlope occurred at each visit during the transition from rest to IHGT F60. The RTP > 1week group had lower SysSlope (405 ± 200; 420 ± 88; 454 ± 236 mmHg/s, respectively) at rest 48 h compared to the RTP ≤ 1week and controls. Similarly at 48 h rest, several measurements of arterial stiffness were abnormal in RTP > 1week compared to RTP ≤ 1week and controls: peak-to-notch latency (0.12 ± 0.04; 0.16 ± 0.02; 0.17 ± 0.05, respectively), notch relative amplitude (0.70 ± 0.03; 0.71 ± 0.04; 0.66 ± 0.14, respectively), and stiffness index (6.4 ± 0.2; 5.7 ± 0.4; 5.8 ± 0

  14. Autonomic Nervous System Responses to Concussion: Arterial Pulse Contour Analysis

    PubMed Central

    La Fountaine, Michael F.; Toda, Michita; Testa, Anthony J.; Hill-Lombardi, Vicci

    2016-01-01

    The arterial pulse wave (APW) has a distinct morphology whose contours reflect dynamics in cardiac function and peripheral vascular tone as a result of sympathetic nervous system (SNS) control. With a transition from rest to increased metabolic demand, the expected augmentation of SNS outflow will not only affect arterial blood pressure and heart rate but it will also induce changes to the contours of the APW. Following a sports concussion, a transient state cardiovascular autonomic dysfunction is present. How this state affects the APW has yet to be described. A prospective, parallel-group study on cardiovascular autonomic control (i.e., digital electrocardiogram and continuous beat-to-beat blood pressure) was performed in the seated upright position in 10 athletes with concussion and 7 non-injured control athletes. Changes in APW were compared at rest and during the first 60 s (F60) of an isometric handgrip test (IHGT) in concussed athletes and non-injured controls within 48 h and 1 week of injury. The concussion group was further separated by the length of time until they were permitted to return to play (RTP > 1week; RTP ≤ 1week). SysSlope, an indirect measurement of stroke volume, was significantly lower in the concussion group at rest and during F60 at 48 h and 1week; a paradoxical decline in SysSlope occurred at each visit during the transition from rest to IHGT F60. The RTP > 1week group had lower SysSlope (405 ± 200; 420 ± 88; 454 ± 236 mmHg/s, respectively) at rest 48 h compared to the RTP ≤ 1week and controls. Similarly at 48 h rest, several measurements of arterial stiffness were abnormal in RTP > 1week compared to RTP ≤ 1week and controls: peak-to-notch latency (0.12 ± 0.04; 0.16 ± 0.02; 0.17 ± 0.05, respectively), notch relative amplitude (0.70 ± 0.03; 0.71 ± 0.04; 0.66 ± 0.14, respectively), and stiffness index (6.4 ± 0.2; 5.7 ± 0.4; 5.8 ± 0

  15. Autonomic Nervous System Responses to Concussion: Arterial Pulse Contour Analysis.

    PubMed

    La Fountaine, Michael F; Toda, Michita; Testa, Anthony J; Hill-Lombardi, Vicci

    2016-01-01

    The arterial pulse wave (APW) has a distinct morphology whose contours reflect dynamics in cardiac function and peripheral vascular tone as a result of sympathetic nervous system (SNS) control. With a transition from rest to increased metabolic demand, the expected augmentation of SNS outflow will not only affect arterial blood pressure and heart rate but it will also induce changes to the contours of the APW. Following a sports concussion, a transient state cardiovascular autonomic dysfunction is present. How this state affects the APW has yet to be described. A prospective, parallel-group study on cardiovascular autonomic control (i.e., digital electrocardiogram and continuous beat-to-beat blood pressure) was performed in the seated upright position in 10 athletes with concussion and 7 non-injured control athletes. Changes in APW were compared at rest and during the first 60 s (F60) of an isometric handgrip test (IHGT) in concussed athletes and non-injured controls within 48 h and 1 week of injury. The concussion group was further separated by the length of time until they were permitted to return to play (RTP > 1week; RTP ≤ 1week). SysSlope, an indirect measurement of stroke volume, was significantly lower in the concussion group at rest and during F60 at 48 h and 1week; a paradoxical decline in SysSlope occurred at each visit during the transition from rest to IHGT F60. The RTP > 1week group had lower SysSlope (405 ± 200; 420 ± 88; 454 ± 236 mmHg/s, respectively) at rest 48 h compared to the RTP ≤ 1week and controls. Similarly at 48 h rest, several measurements of arterial stiffness were abnormal in RTP > 1week compared to RTP ≤ 1week and controls: peak-to-notch latency (0.12 ± 0.04; 0.16 ± 0.02; 0.17 ± 0.05, respectively), notch relative amplitude (0.70 ± 0.03; 0.71 ± 0.04; 0.66 ± 0.14, respectively), and stiffness index (6.4 ± 0.2; 5.7 ± 0.4; 5.8 ± 0

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

    PubMed

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

    2015-12-01

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

  17. 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

  18. 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.

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

    PubMed Central

    Nallar, Shreeram C.

    2014-01-01

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

  20. Interferons, signal transduction pathways, and the central nervous system.

    PubMed

    Nallar, Shreeram C; Kalvakolanu, Dhan V

    2014-08-01

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

  1. Control of Prosthetic Hands via the Peripheral Nervous System

    PubMed Central

    Ciancio, Anna Lisa; Cordella, Francesca; Barone, Roberto; Romeo, Rocco Antonio; Bellingegni, Alberto Dellacasa; Sacchetti, Rinaldo; Davalli, Angelo; Di Pino, Giovanni; Ranieri, Federico; Di Lazzaro, Vincenzo; Guglielmelli, Eugenio; Zollo, Loredana

    2016-01-01

    This paper intends to provide a critical review of the literature on the technological issues on control and sensorization of hand prostheses interfacing with the Peripheral Nervous System (i.e., PNS), and their experimental validation on amputees. The study opens with an in-depth analysis of control solutions and sensorization features of research and commercially available prosthetic hands. Pros and cons of adopted technologies, signal processing techniques and motion control solutions are investigated. Special emphasis is then dedicated to the recent studies on the restoration of tactile perception in amputees through neural interfaces. The paper finally proposes a number of suggestions for designing the prosthetic system able to re-establish a bidirectional communication with the PNS and foster the prosthesis natural control. PMID:27092041

  2. The effect of space radiation of the nervous system

    NASA Astrophysics Data System (ADS)

    Gauger, Grant E.; Tobias, Cornelius A.; Yang, Tracy; Whitney, Monroe

    The long-term effects of irradiation by accelerated heavy ions on the structure and function of the nervous system have not been studied extensively. Although the adult brain is relatively resistant to low LET radiation, cellular studies indicate that individual heavy ions can produce serious membrane lesions and multiple chromatin breaks. Capillary hemorrhages may follow high LET particle irradiation of the developing brain as high RBE effects. Evidence has been accumulating that the glial system and blood-brain barrier (BBB) are relatively sensitive to injury by ionizing radiation. While DNA repair is active in neural systems, it may be assumed that a significant portion of this molecular process is misrepair. Since the expression of cell lethality usually requires cell division, and nerve cells have an extremely low rate of division, it is possible that some of the characteristic changes of premature aging may represent a delayed effect of chromatin misrepair in brain. Altered microcirculation, decreased local metabolism, entanglement and reduction in synaptic density, premature loss of neurons, myelin degeneration, and glial proliferation are late signs of such injuries. HZE particles are very efficient in producing carcinogenic cell transformation, reaching a peak for iron particles. The promotion of viral transformation is also efficient up to an energy transfer of approximately 300 keV/micron. The RBE for carcinogenesis in nerve tissues remains unknown. On the basis of available information concerning HZE particle flux in interplanetary space, only general estimates of the magnitude of the effects of long-term spaceflight on some nervous system parameters may be constructed.

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

    PubMed

    Dumas, Marc-Emmanuel; Davidovic, Laetitia

    2015-09-01

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

  4. [Chronic toxic effects of aluminum on nervous system in rabbits].

    PubMed

    Zhang, W Q; Xu, G S; Huang, G W

    1994-05-01

    Twenty-one male rabbits were administered with alum (aluminum potassium sulfate) for 32 weeks to study the accumulative toxic effects of aluminum in food additives on central nervous system. Results showed aluminum levels in blood and brain tissue of the animals increased significantly with intake of alum (P < 0.01). Blood zinc levels, and activities of superoxide dismutase (SOD) and monoamine oxidase B (MAO-B) correlated negatively with aluminum levels in blood and brain, and SOD activity correlated negatively to accumulative aluminum deposit and positively to lipid oxide level in brain. Pathological examinations showed lesions in gyrus centralis anterior, gyrus hippocampi and spinal cord of the animals got more severely and extensively with aluminum intake and brain aluminum content, with disarrangement of neurofilaments and neurotubule, and deformation of synaptic structures.

  5. Homeoprotein signaling in the developing and adult nervous system

    PubMed Central

    2016-01-01

    Summary Signaling classically involves the secretion of diverse molecules that bind specific cellsurface receptors and engage intracellular transduction cascades. Some exceptions, namely lipophilic agents, can cross plasma membranes to bind intracellular receptors and be carried to the nucleus to regulate transcription. Homeoprotein transcription factors are among the few proteins with such a capacity. Here, we review the signaling activities of homeoproteins in the developing and adult nervous system, with particular emphasis on axon/cell migration and postnatal critical periods of cerebral cortex plasticity. We also describe homeoprotein non-cell autonomous mechanisms and explore how this “novel” signaling pathway impacts emerging research in brain development and physiology. In this context, we explore hypotheses on the evolution of signaling, the role of homeoproteins as early morphogens, and their therapeutic potential for neurological and psychiatric diseases. PMID:25741720

  6. “Central nervous system integration of satiety signals”

    PubMed Central

    Chambers, Adam P.; Sandoval, Darleen A.; Seeley, Randy J.

    2013-01-01

    Individual meals are products of a complex interaction of signals related to both short-term and long-term availability of energy stores. In addition to maintaining the metabolic demands of the individual in the short term, levels of energy intake must also maintain and defend body weight over longer periods. To accomplish this, satiety pathways are regulated by a sophisticated network of endocrine and neuroendocrine pathways. Higher brain centers modulate meal-size through descending inputs to caudal brainstem regions responsible for the motor pattern generators associated with ingestion. Gastric and intestinal signals interact with central nervous system pathways to terminate food intake. These inputs can be modified as a function of internal metabolic signals, external environmental influences, and learning to regulate meal-size. PMID:23660361

  7. Generating neuronal diversity in the Drosophila central nervous system.

    PubMed

    Lin, Suewei; Lee, Tzumin

    2012-01-01

    Generating diverse neurons in the central nervous system involves three major steps. First, heterogeneous neural progenitors are specified by positional cues at early embryonic stages. Second, neural progenitors sequentially produce neurons or intermediate precursors that acquire different temporal identities based on their birth-order. Third, sister neurons produced during asymmetrical terminal mitoses are given distinct fates. Determining the molecular mechanisms underlying each of these three steps of cellular diversification will unravel brain development and evolution. Drosophila has a relatively simple and tractable CNS, and previous studies on Drosophila CNS development have greatly advanced our understanding of neuron fate specification. Here we review those studies and discuss how the lessons we have learned from fly teach us the process of neuronal diversification in general.

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

    PubMed

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

    2016-08-01

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

  9. 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

  10. 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

  11. 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.

  12. Optimized optical clearing method for imaging central nervous system

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

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

  13. Fungal central nervous system infections: prevalence and diagnosis.

    PubMed

    Kourbeti, Irene S; Mylonakis, Eleftherios

    2014-02-01

    Fungal infections of the central nervous system (CNS) are rare but they pose a significant challenge. Their prevalence spans a wide array of hosts including immunosuppressed and immunocompetent individuals, patients undergoing neurosurgical procedures and those carrying implantable CNS devices. Cryptococcus neoformans and Aspergillus spp. remain the most common pathogens. Magnetic resonance imaging can help localize the lesions, but diagnosis is challenging since invasive procedures may be needed for the retrieval of tissue, especially in cases of fungal abscesses. Antigen and antibody tests are available and approved for use in the cerebrospinal fluid (CSF). PCR-based techniques are promising but they are not validated for use in the CSF. This review provides an overview on the differential diagnosis of the fungal CNS disease based on the host and the clinical syndrome and suggests the optimal use of diagnostic techniques. It also summarizes the emergence of Cryptococcus gatti and an unanticipated outbreak caused by Exserohilum rostratum.

  14. 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.

  15. Oligodendrocyte precursors migrate along vasculature in the developing nervous system.

    PubMed

    Tsai, Hui-Hsin; Niu, Jianqin; Munji, Roeben; Davalos, Dimitrios; Chang, Junlei; Zhang, Haijing; Tien, An-Chi; Kuo, Calvin J; Chan, Jonah R; Daneman, Richard; Fancy, Stephen P J

    2016-01-22

    Oligodendrocytes myelinate axons in the central nervous system and develop from oligodendrocyte precursor cells (OPCs) that must first migrate extensively during brain and spinal cord development. We show that OPCs require the vasculature as a physical substrate for migration. We observed that OPCs of the embryonic mouse brain and spinal cord, as well as the human cortex, emerge from progenitor domains and associate with the abluminal endothelial surface of nearby blood vessels. Migrating OPCs crawl along and jump between vessels. OPC migration in vivo was disrupted in mice with defective vascular architecture but was normal in mice lacking pericytes. Thus, physical interactions with the vascular endothelium are required for OPC migration. We identify Wnt-Cxcr4 (chemokine receptor 4) signaling in regulation of OPC-endothelial interactions and propose that this signaling coordinates OPC migration with differentiation. PMID:26798014

  16. The effects of space travel on the nervous system.

    PubMed

    Angel, A

    1989-08-01

    The translation of man from terrestrial to an extra terrestrial environment is accompanied by an upset in the servo-control of movement engendered by the removal of the normal gravitational signal. Unfortunately the "natural" response of the nervous system, to ocular and vestibular confusion, is to cause varying degrees of sickness which can only be avoided by choice of suitable space travellers i.e., those who are least upset by gravitational chaos. This will remain so until much more is learned about the fundamental physiological mechanisms whereby man maintains a correct head/trunk, head/eye, trunk/limb and eye/limb positional coordination and why if these are upset man's natural response is to vomit.

  17. Epithelioid solitary fibrous tumor of the central nervous system.

    PubMed

    Fu, Jing; Zhang, Rui; Zhang, Hongying; Bu, Hong; Chen, Huijiao; Yin, Xiangli; Zhang, Zhang; Wei, Bing

    2012-01-01

    Epithelioid solitary fibrous tumor (SFT) has recently been reported and is an extremely rare soft-tissue neoplasm. Herein we present an epithelioid SFT attached to the falx cerebri occurring in a Chinese woman. This patient underwent gross-total tumor resection at the age of 30 years and recurred 68 months following the initial total resection. Histologically, the initial lesion exhibited features of classic spindle cell SFT. In contrast, the recurrent tumor demonstrated exclusively epithelioid morphology with significant atypia. Both the original and recurrent lesions showed positivity for vimentin, CD34, Bcl-2, and CD99, whereas were negative for all the remaining antibodies. The epithelioid feature in SFT seems to be associated with a more aggressive clinical behavior in this case and more cases are awaited to verify this possibility. To the best of authors' knowledge, the present case is the first published example of SFT with epithelioid feature in the central nervous system.

  18. 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.

  19. Fractals in the nervous system: conceptual implications for theoretical neuroscience.

    PubMed

    Werner, Gerhard

    2010-01-01

    This essay is presented with two principal objectives in mind: first, to document the prevalence of fractals at all levels of the nervous system, giving credence to the notion of their functional relevance; and second, to draw attention to the as yet still unresolved issues of the detailed relationships among power-law scaling, self-similarity, and self-organized criticality. As regards criticality, I will document that it has become a pivotal reference point in Neurodynamics. Furthermore, I will emphasize the not yet fully appreciated significance of allometric control processes. For dynamic fractals, I will assemble reasons for attributing to them the capacity to adapt task execution to contextual changes across a range of scales. The final Section consists of general reflections on the implications of the reviewed data, and identifies what appear to be issues of fundamental importance for future research in the rapidly evolving topic of this review.

  20. 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. PMID:22473811

  1. 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

  2. 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

  3. 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

  4. Autonomic nervous system dysfunction: implication in sickle cell disease.

    PubMed

    Connes, Philippe; Coates, Thomas D

    2013-03-01

    Sickle cell disease is an inherited hemoglobinopathy caused by a single amino acid substitution in the β chain of hemoglobin that causes the hemoglobin to polymerize in the deoxy state. The resulting rigid, sickle-shaped red cells obstruct blood flow causing hemolytic anemia, tissue damage, and premature death. Hemolysis is continual. However, acute exacerbations of sickling called vaso-occlusive crises (VOC) resulting in severe pain occur, often requiring hospitalization. Blood rheology, adhesion of cellular elements of blood to vascular endothelium, inflammation, and activation of coagulation decrease microvascular flow and increase likelihood of VOC. What triggers the transition from steady state to VOC is unknown. This review discusses the interaction of blood rheological factors and the role that autonomic nervous system (ANS) induced vasoconstriction may have in triggering crisis as well as the mechanism of ANS dysfunction in SCD. PMID:23643396

  5. Emerging Viral Infections of the Central Nervous System

    PubMed Central

    Tyler, Kenneth L.

    2010-01-01

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

  6. Primary central nervous system lymphoma a report of nine cases.

    PubMed

    Lakshmaiah, K C; Lokanath, D; Ramesh, C; Babu, K G; Rao, C R; Swamy, K

    1996-06-01

    Primary Central Nervous System Lymphoma (PCNSL) is a rare neoplasm of B cell origin and constitute less than 1% of Non-Hodgkin's lymphoma (NHL). Histology is mainly of high grade and intermediate type. Although NHL is known to be highly sensitive to both irradiation and cytotoxic drugs, being a curable malignancy, the therapeutic results remain disappointing. Clinical observations on nine cases of PCNSL seen in one of the major cancer centres in India is presented in this paper. Radiotherapy combined with Chemotherapy although yielded encouraging initial response in these patients, the long term response was unsatisfactory with median survival for these patients being only 19 months. This warrants an alternative therapeutic approach to improve the dismal prognosis of PCNSL. PMID:8979473

  7. Fractals in the Nervous System: Conceptual Implications for Theoretical Neuroscience

    PubMed Central

    Werner, Gerhard

    2010-01-01

    This essay is presented with two principal objectives in mind: first, to document the prevalence of fractals at all levels of the nervous system, giving credence to the notion of their functional relevance; and second, to draw attention to the as yet still unresolved issues of the detailed relationships among power-law scaling, self-similarity, and self-organized criticality. As regards criticality, I will document that it has become a pivotal reference point in Neurodynamics. Furthermore, I will emphasize the not yet fully appreciated significance of allometric control processes. For dynamic fractals, I will assemble reasons for attributing to them the capacity to adapt task execution to contextual changes across a range of scales. The final Section consists of general reflections on the implications of the reviewed data, and identifies what appear to be issues of fundamental importance for future research in the rapidly evolving topic of this review. PMID:21423358

  8. 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

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

    PubMed

    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.

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

    PubMed Central

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

    1984-01-01

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

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

    PubMed

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

    2016-03-01

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

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

    PubMed

    Dingwall, Kylie M; Cairney, Sheree

    2011-01-01

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

  13. Electrical stimuli in the central nervous system microenvironment.

    PubMed

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

    2014-07-11

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

  14. Is Bone a Target-Tissue for the Nervous System?

    PubMed Central

    García-Castellano, José M; Díaz-Herrera, Pilar; Morcuende, José A

    2000-01-01

    Bone cells respond in specific ways to various hormones and growth factors, but the biology of skeletal innervation and its physiologic significance in bone metabolism is poorly understood. With the introduction of immunohistochemical staining techniques and new molecular biology tools, the knowledge in this field has significantly improved. In this review, we update current understanding of the effects of neuropeptides on bone metabolism, specifically vasoactive intestinal peptide (VIP) and calcitonin-gene related peptide (CGRP). In addition, new information concerning the role of growth factors, such as neurotrophins, is also discussed. There is strong evidence to suggest that bone can be a target of the nervous system. Further investigations in this field will allow us to answer questions related to pre-natal development, bone growth, fracture healing, osteoporosis, osteoarthritis or neoplasias of mesoderm origin. PMID:10934625

  15. 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. PMID:26024799

  16. Isolated central nervous system relapse of acute lymphoblastic leukemia.

    PubMed

    Sung, Sang-Hyun; Jang, In-Seok

    2014-10-01

    Acute lymphoblastic leukemia (ALL) is the most common form of childhood cancer and may exhibit central nervous system (CNS) involvement. Advances in chemotherapy and effective CNS prophylaxis have significantly decreased the incidence of CNS relapse of ALL to 5-10%. Here, we report the case of a patient with isolated CNS relapse of standard risk group pre-B-cell type ALL in an 11-year-old girl, relapsed 3 years after successful completion of chemotherapy. An 11-year-old girl visited our hospital complaining of headache, dizziness, vomiting, and visual field defects. Neurological examination revealed left-side homonymous hemianopsia. Brain magnetic resonance imaging showed a large irregular dural-based sulcal hematoma in the right parietal and occipital lobes. Surgery to remove the hematoma revealed the existence of hematopoietic malignancy after pathologic evaluation. Bone marrow biopsy was subsequently performed but showed no evidence of malignancy. PMID:25408936

  17. Dendrimer Advances for the Central Nervous System Delivery of Therapeutics

    PubMed Central

    2013-01-01

    The effectiveness of noninvasive treatment for central nervous system (CNS) diseases is generally limited by the poor access of therapeutic agents into the CNS. Most CNS drugs cannot permeate into the brain parenchyma because of the blood-brain barrier (BBB), and overcoming this has become one of the most significant challenges in the development of CNS therapeutics. Rapid advances in nanotechnology have provided promising solutions to this challenge. This review discusses the latest applications of dendrimers in the treatment of CNS diseases with an emphasis on brain tumors. Dendrimer-mediated drug delivery, imaging, and diagnosis are also reviewed. The toxicity, biodistribution, and transport mechanisms in dendrimer-mediated delivery of CNS therapeutic agents bypassing or crossing the BBB are also discussed. Future directions and major challenges of dendrimer-mediated delivery of CNS therapeutic agents are included. PMID:24274162

  18. Oligodendrocyte precursors migrate along vasculature in the developing nervous system.

    PubMed

    Tsai, Hui-Hsin; Niu, Jianqin; Munji, Roeben; Davalos, Dimitrios; Chang, Junlei; Zhang, Haijing; Tien, An-Chi; Kuo, Calvin J; Chan, Jonah R; Daneman, Richard; Fancy, Stephen P J

    2016-01-22

    Oligodendrocytes myelinate axons in the central nervous system and develop from oligodendrocyte precursor cells (OPCs) that must first migrate extensively during brain and spinal cord development. We show that OPCs require the vasculature as a physical substrate for migration. We observed that OPCs of the embryonic mouse brain and spinal cord, as well as the human cortex, emerge from progenitor domains and associate with the abluminal endothelial surface of nearby blood vessels. Migrating OPCs crawl along and jump between vessels. OPC migration in vivo was disrupted in mice with defective vascular architecture but was normal in mice lacking pericytes. Thus, physical interactions with the vascular endothelium are required for OPC migration. We identify Wnt-Cxcr4 (chemokine receptor 4) signaling in regulation of OPC-endothelial interactions and propose that this signaling coordinates OPC migration with differentiation.

  19. Modulation of Tumor Tolerance in Primary Central Nervous System Malignancies

    PubMed Central

    Johnson, Theodore S.; Munn, David H.; Maria, Bernard L.

    2012-01-01

    Central nervous system tumors take advantage of the unique immunology of the CNS and develop exquisitely complex stromal networks that promote growth despite the presence of antigen-presenting cells and tumor-infiltrating lymphocytes. It is precisely this immunological paradox that is essential to the survival of the tumor. We review the evidence for functional CNS immune privilege and the impact it has on tumor tolerance. In this paper, we place an emphasis on the role of tumor-infiltrating myeloid cells in maintaining stromal and vascular quiescence, and we underscore the importance of indoleamine 2,3-dioxygenase activity as a myeloid-driven tumor tolerance mechanism. Much remains to be discovered regarding the tolerogenic mechanisms by which CNS tumors avoid immune clearance. Thus, it is an open question whether tumor tolerance in the brain is fundamentally different from that of peripheral sites of tumorigenesis or whether it simply stands as a particularly strong example of such tolerance. PMID:22312408

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

    PubMed

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

    2006-10-01

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

  1. Building global capacity for brain and nervous system disorders research.

    PubMed

    Cottler, Linda B; Zunt, Joseph; Weiss, Bahr; Kamal, Ayeesha Kamran; Vaddiparti, Krishna

    2015-11-19

    The global burden of neurological, neuropsychiatric, substance-use and neurodevelopmental disorders in low- and middle-income countries is worsened, not only by the lack of targeted research funding, but also by the lack of relevant in-country research capacity. Such capacity, from the individual to the national level, is necessary to address the problems within a local context. As for many health issues in these countries, the ability to address this burden requires development of research infrastructure and a trained cadre of clinicians and scientists who can ask the right questions, and conduct, manage, apply and disseminate research for practice and policy. This Review describes some of the evolving issues, knowledge and programmes focused on building research capacity in low- and middle-income countries in general and for brain and nervous system disorders in particular. PMID:26580329

  2. Building global capacity for brain and nervous system disorders research.

    PubMed

    Cottler, Linda B; Zunt, Joseph; Weiss, Bahr; Kamal, Ayeesha Kamran; Vaddiparti, Krishna

    2015-11-19

    The global burden of neurological, neuropsychiatric, substance-use and neurodevelopmental disorders in low- and middle-income countries is worsened, not only by the lack of targeted research funding, but also by the lack of relevant in-country research capacity. Such capacity, from the individual to the national level, is necessary to address the problems within a local context. As for many health issues in these countries, the ability to address this burden requires development of research infrastructure and a trained cadre of clinicians and scientists who can ask the right questions, and conduct, manage, apply and disseminate research for practice and policy. This Review describes some of the evolving issues, knowledge and programmes focused on building research capacity in low- and middle-income countries in general and for brain and nervous system disorders in particular.

  3. 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

  4. 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

  5. Larval nervous systems: true larval and precocious adult.

    PubMed

    Nielsen, Claus

    2015-02-15

    The apical organ of ciliated larvae of cnidarians and bilaterians is a true larval organ that disappears before or at metamorphosis. It appears to be sensory, probably involved in metamorphosis, but knowledge is scant. The ciliated protostome larvae show ganglia/nerve cords that are retained as the adult central nervous system (CNS). Two structures can be recognized, viz. a pair of cerebral ganglia, which form the major part of the adult brain, and a blastoporal (circumblastoporal) nerve cord, which becomes differentiated into a perioral loop, paired or secondarily fused ventral nerve cords and a small perianal loop. The anterior loop becomes part of the brain. This has been well documented through cell-lineage studies in a number of spiralians, and homologies with similar structures in the ecdysozoans are strongly indicated. The deuterostomes are generally difficult to interpret, and the nervous systems of echinoderms and enteropneusts appear completely enigmatic. The ontogeny of the chordate CNS can perhaps be interpreted as a variation of the ontogeny of the blastoporal nerve cord of the protostomes, and this is strongly supported by patterns of gene expression. The presence of 'deuterostomian' blastopore fates both in an annelid and in a mollusk, which are both placed in families with the 'normal' spiralian gastrulation type, and in the chaetognaths demonstrates that the chordate type of gastrulation could easily have evolved from the spiralian type. This indicates that the latest common ancestor of the deuterostomes was very similar to the latest common pelago-benthic ancestor of the protostomes as described by the trochaea theory, and that the neural tube of the chordates is morphologically ventral.

  6. The Function of the Autonomic Nervous System during Spaceflight

    PubMed Central

    Mandsager, Kyle Timothy; Robertson, David; Diedrich, André

    2015-01-01

    Introduction Despite decades of study, a clear understanding of autonomic nervous system activity in space remains elusive. Differential interpretation of fundamental data have driven divergent theories of sympathetic activation and vasorelaxation. Methods This paper will review the available in-flight autonomic and hemodynamic data in an effort to resolve these discrepancies. The NASA NEUROLAB mission, the most comprehensive assessment of autonomic function in microgravity to date, will be highlighted. The mechanisms responsible for altered autonomic activity during spaceflight, which include the effects of hypovolemia, cardiovascular deconditioning, and altered central processing, will be presented. Results The NEUROLAB experiments demonstrated increased sympathetic activity and impairment of vagal baroreflex function during short-duration spaceflight. Subsequent non-invasive studies of autonomic function during spaceflight have largely reinforced these findings, and provide strong evidence that sympathetic activity is increased in space relative to the supine position on Earth. Others have suggested that microgravity induces a state of relative vasorelaxation and increased vagal activity when compared to upright posture on Earth. These ostensibly disparate theories are not mutually exclusive, but rather directly reflect different pre-flight postural controls. Conclusion When these results are taken together, they demonstrate that the effectual autonomic challenge of spaceflight is small, and represents an orthostatic stress less than that of upright posture on Earth. In-flight countermeasures, including aerobic and resistance exercise, as well as short-arm centrifugation have been successfully deployed to counteract these mechanisms. Despite subtle changes in autonomic activity during spaceflight, underlying neurohumoral mechanisms of the autonomic nervous system remain intact and cardiovascular function remains stable during long-duration flight. PMID:25820827

  7. ADAMTS expression and function in central nervous system injury and disorders

    PubMed Central

    Gottschall, Paul E.; Howell, Matthew D.

    2016-01-01

    The components of the adult extracellular matrix in the central nervous system form a lattice-like structure that is deposited as perineuronal nets, around axon initial segments and as synapse-associated matrix. An abundant component of this matrix is the lecticans, chondroitin sulfate-bearing proteoglycans that are the major substrate for several members of the ADAMTSs (a disintegrin and metalloproteinase with thrombospondin motifs) family. Since lecticans are key regulators of neural plasticity, ADAMTS cleavage of lecticans would likely also contribute to neuroplasticity. Indeed, many studies have examined the neuroplastic contribution of the ADAMTSs to damage and recovery after injury and in central nervous system disease. Much of this data supports a role for the ADAMTSs in recovery and repair following spinal cord injury by stimulating axonal outgrowth after degradation of a glial scar and improving synaptic plasticity following seizure-induced neural damage in the brain. The action of the ADAMTSs in chronic diseases of the central nervous system appears to be more complex and less well-defined. Increasing evidence indicates that lecticans participate in synaptic plasticity in neurodegenerative disease states. It will be interesting to examine how ADAMTS expression and action would affect the progression of these diseases. PMID:25622912

  8. ADAMTS expression and function in central nervous system injury and disorders.

    PubMed

    Gottschall, Paul E; Howell, Matthew D

    2015-01-01

    The components of the adult extracellular matrix in the central nervous system form a lattice-like structure that is deposited as perineuronal nets, around axon initial segments and as synapse-associated matrix. An abundant component of this matrix is the lecticans, chondroitin sulfate-bearing proteoglycans that are the major substrate for several members of the ADAMTSs (a disintegrin and metalloproteinase with thrombospondin motifs) family. Since lecticans are key regulators of neural plasticity, ADAMTS cleavage of lecticans would likely also contribute to neuroplasticity. Indeed, many studies have examined the neuroplastic contribution of the ADAMTSs to damage and recovery after injury and in central nervous system disease. Much of this data supports a role for the ADAMTSs in recovery and repair following spinal cord injury by stimulating axonal outgrowth after degradation of a glial scar and improving synaptic plasticity following seizure-induced neural damage in the brain. The action of the ADAMTSs in chronic diseases of the central nervous system appears to be more complex and less well-defined. Increasing evidence indicates that lecticans participate in synaptic plasticity in neurodegenerative disease states. It will be interesting to examine how ADAMTS expression and action would affect the progression of these diseases.

  9. Trigonelline: a plant alkaloid with therapeutic potential for diabetes and central nervous system disease.

    PubMed

    Zhou, J; Chan, L; Zhou, S

    2012-01-01

    There is evidence that Trigonella foenum-graecum L. (fenugreek), a traditional Chinese herb, and its components are beneficial in the prevention and treatment of diabetes and central nervous system disease. The pharmacological activities of trigonelline, a major alkaloid component of fenugreek, have been more thoroughly evaluated than fenugreek's other components, especially with regard to diabetes and central nervous system disease. Trigonelline has hypoglycemic, hypolipidemic, neuroprotective, antimigraine, sedative, memory-improving, antibacterial, antiviral, and anti-tumor activities, and it has been shown to reduce diabetic auditory neuropathy and platelet aggregation. It acts by affecting β cell regeneration, insulin secretion, activities of enzymes related to glucose metabolism, reactive oxygen species, axonal extension, and neuron excitability. However, further study of trigonelline's pharmacological activities and exact mechanism is warranted, along with application of this knowledge to its clinical usage. This review aims to give readers a survey of the pharmacological effects of trigonelline, especially in diabetes, diabetic complications and central nervous system disease. In addition, because of its pharmacological value and low toxicity, the reported adverse effects of trigonelline in experimental animal models and humans are briefly reviewed, and the pharmacokinetics of trigonelline are also discussed.

  10. 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. PMID:27230413

  11. 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

  12. Glaucoma and concomitant status of autonomic nervous system.

    PubMed

    Kumar, R; Ahuja, V M

    1998-01-01

    There is much clinical evidence to suggest that certain types of Glaucoma are related to activity of autonomic nervous system (ANS). Although some local changes have been documented but systemic association has not been established, so far. Hence, the present study was initiated and an attempt was made to bring out the association of systemic autonomic functions with glaucoma (especially Primary Closed Angle Glaucoma (PCAG)) if any. This study was carried out in the Department of Physiology, Maulana Azad Medical College in association with Glaucoma Clinic of Guru Nanak Eye Centre, New Delhi from June 1993-August 94. ANS function tests were conducted using Polyrite-8-Medicare System. The subjects were confirmed cases of PCAG with 10P-22.1 +/- 4.4 mmHg and possibility of autonomic neuropathy due to any other cause was ruled out. They were matched with normal subjects for their age, anthropometry and were compared for their sympathetic activity of ANS by Galvanic Skin Resistance (GSR); Cold Pressor Response (CPR); corrected QT interval (QTc) and T-wave amplitude (TWA) and for parasympathetic activity of ANS by Resting Heart Rate (RHR); Standing to Lying Ratio (SLR) and Valsalva Ratio and analysed statistically using standard 't' test. The results obtained in this study indicated increase in sympathetic activity in 61% of PCAG subjects and decreased parasympathic activity in 80% of the PCAG subjects when compared with control group of subjects, suggesting association of autonomic neuropathy with PCAG.

  13. THE RESUSCITATION OF THE CENTRAL NERVOUS SYSTEM OF MAMMALS.

    PubMed

    Stewart, G N; Guthrie, C C; Burns, R L; Pike, F H

    1906-03-26

    the same side as the stimulus, crossing of reflexes, to involve the other side, not occurring till later. As a rule, all reflexes return, and a short period of quiet follows. The anterior part of the cord again becomes irritable to strychnine, but succumbs to its action before the normal part. Spasms, of tonic, clonic, or mixed type, then appear, terminating in (a) death, (b) partial or (c) complete recovery. In partial recovery, disturbances of locomotion, such as walking in a circle, paralysis, dementia, loss of sight, hearing, and general intelligence, characterize the post-convulsive period. After complete recovery, there is a return to normal deportment. No gross lesions of the nervous system, other than a congested appearance of the previously anaemic area, were observed. Transection of the spinal cord stops the spasms below the level of section. Hemisection of the cord stops the spasms on the same side, below the level of section. Death, without any return of the reflexes after release of the cerebral arteries, has followed an occlusion of seven and one-half minutes. Respiration has returned after an occlusion of one hour. Five animals have recovered completely after an occlusion of seven minutes or more. Only one animal has recovered completely after an occlusion of fifteen minutes. No animal has recovered completely after an occlusion of twenty minutes. In Herzen's (26) resuscitation of an animal after several hours of cerebral anaemia, there must have been some anastomotic channels to the brain. Mayer's (27) limit of ten to fifteen minutes of cerebral anaemia, beyond which resuscitation is not practicable, is close to the correct one. It appears to us that, in cases of resuscitation two hours after cessation of the heart-beat, (Prus., loc.cit.) the auricles must have kept up a slow but, in some degree, an efficient movement of the blood through the brain. The truth of this suggestion might be tested by introducing some easily recognized, non

  14. THE RESUSCITATION OF THE CENTRAL NERVOUS SYSTEM OF MAMMALS.

    PubMed

    Stewart, G N; Guthrie, C C; Burns, R L; Pike, F H

    1906-03-26

    the same side as the stimulus, crossing of reflexes, to involve the other side, not occurring till later. As a rule, all reflexes return, and a short period of quiet follows. The anterior part of the cord again becomes irritable to strychnine, but succumbs to its action before the normal part. Spasms, of tonic, clonic, or mixed type, then appear, terminating in (a) death, (b) partial or (c) complete recovery. In partial recovery, disturbances of locomotion, such as walking in a circle, paralysis, dementia, loss of sight, hearing, and general intelligence, characterize the post-convulsive period. After complete recovery, there is a return to normal deportment. No gross lesions of the nervous system, other than a congested appearance of the previously anaemic area, were observed. Transection of the spinal cord stops the spasms below the level of section. Hemisection of the cord stops the spasms on the same side, below the level of section. Death, without any return of the reflexes after release of the cerebral arteries, has followed an occlusion of seven and one-half minutes. Respiration has returned after an occlusion of one hour. Five animals have recovered completely after an occlusion of seven minutes or more. Only one animal has recovered completely after an occlusion of fifteen minutes. No animal has recovered completely after an occlusion of twenty minutes. In Herzen's (26) resuscitation of an animal after several hours of cerebral anaemia, there must have been some anastomotic channels to the brain. Mayer's (27) limit of ten to fifteen minutes of cerebral anaemia, beyond which resuscitation is not practicable, is close to the correct one. It appears to us that, in cases of resuscitation two hours after cessation of the heart-beat, (Prus., loc.cit.) the auricles must have kept up a slow but, in some degree, an efficient movement of the blood through the brain. The truth of this suggestion might be tested by introducing some easily recognized, non

  15. Simple rules for a “simple” nervous system? Molecular and biomathematical approaches to enteric nervous system formation and malformation

    PubMed Central

    Newgreen, Donald F.; Dufour, Sylvie; Howard, Marthe J.; Landman, Kerry A.

    2013-01-01

    We review morphogenesis of the enteric nervous system from migratory neural crest cells, and defects of this process such as Hirschsprung disease, centering on cell motility and assembly, and cell adhesion and extracellular matrix molecules, along with cell proliferation and growth factors. We then review continuum and agent-based (cellular automata) models with rules of cell movement and logistical proliferation. Both movement and proliferation at the individual cell level are modeled with stochastic components from which stereotyped outcomes emerge at the population level. These models reproduced the wave-like colonization of the intestine by enteric neural crest cells, and several new properties emerged, such as colonization by frontal expansion, which were later confirmed biologically. These models predict a surprising level of clonal heterogeneity both in terms of number and distribution of daughter cells. Biologically, migrating cells form stable chains made up of unstable cells, but this is not seen in the initial model. We outline additional rules for cell differentiation into neurons, axon extension, cell-axon and cell-cell adhesions, chemotaxis and repulsion which can reproduce chain migration. After the migration stage, the cells rearrange as a network of ganglia. Changes in cell adhesion molecules parallel this, and we describe additional rules based on Steinberg's Differential Adhesion Hypothesis, reflecting changing levels of adhesion in neural crest cells and neurons. This was able to reproduce enteric ganglionation in a model. Mouse mutants with disturbances of enteric nervous system morphogenesis are discussed, and these suggest future refinement of the models. The modeling suggests a relatively simple set of cell behavioral rules could account for complex patterns of morphogenesis. The model has allowed the proposal that Hirschsprung disease is mostly an enteric neural crest cell proliferation defect, not a defect of cell migration. In addition

  16. Role of the autonomic nervous system and baroreflex in stress-evoked cardiovascular responses in rats.

    PubMed

    Dos Reis, Daniel Gustavo; Fortaleza, Eduardo Albino Trindade; Tavares, Rodrigo Fiacadori; Corrêa, Fernando Morgan Aguiar

    2014-07-01

    Restraint stress (RS) is an experimental model to study stress-related cardiovascular responses, characterized by sustained pressor and tachycardiac responses. We used pharmacologic and surgical procedures to investigate the role played by sympathetic nervous system (SNS) and parasympathetic nervous system (PSNS) in the mediation of stress-evoked cardiovascular responses. Ganglionic blockade with pentolinium significantly reduced RS-evoked pressor and tachycardiac responses. Intravenous treatment with homatropine methyl bromide did not affect the pressor response but increased tachycardia. Pretreatment with prazosin reduced the pressor and increased the tachycardiac response. Pretreatment with atenolol did not affect the pressor response but reduced tachycardia. The combined treatment with atenolol and prazosin reduced both pressor and tachycardiac responses. Adrenal demedullation reduced the pressor response without affecting tachycardia. Sinoaortic denervation increased pressor and tachycardiac responses. The results indicate that: (1) the RS-evoked cardiovascular response is mediated by the autonomic nervous system without an important involvement of humoral factors; (2) hypertension results primarily from sympathovascular and sympathoadrenal activation, without a significant involvement of the cardiac sympathetic component (CSNS); (3) the abrupt initial peak in the hypertensive response to restraint is sympathovascular-mediated, whereas the less intense but sustained hypertensive response observed throughout the remaining restraint session is mainly mediated by sympathoadrenal activation and epinephrine release; (4) tachycardia results from CSNS activation, and not from PSNS inhibition; (5) RS evokes simultaneous CSNS and PSNS activation, and heart rate changes are a vector of both influences; (6) the baroreflex is functional during restraint, and modulates both the vascular and cardiac responses to restraint.

  17. Somite polarity and segmental patterning of the peripheral nervous system.

    PubMed

    Kuan, C-Y Kelly; Tannahill, David; Cook, Geoffrey M W; Keynes, Roger J

    2004-09-01

    The analysis of the outgrowth pattern of spinal axons in the chick embryo has shown that somites are polarized into anterior and posterior halves. This polarity dictates the segmental development of the peripheral nervous system: migrating neural crest cells and outgrowing spinal axons traverse exclusively the anterior halves of the somite-derived sclerotomes, ensuring a proper register between spinal axons, their ganglia and the segmented vertebral column. Much progress has been made recently in understanding the molecular basis for somite polarization, and its linkage with Notch/Delta, Wnt and Fgf signalling. Contact-repulsive molecules expressed by posterior half-sclerotome cells provide critical guidance cues for axons and neural crest cells along the anterior-posterior axis. Diffusible repellents from surrounding tissues, particularly the dermomyotome and notochord, orient outgrowing spinal axons in the dorso-ventral axis ('surround repulsion'). Repulsive forces therefore guide axons in three dimensions. Although several molecular systems have been identified that may guide neural crest cells and axons in the sclerotome, it remains unclear whether these operate together with considerable overall redundancy, or whether any one system predominates in vivo.

  18. A distributed architecture for activating the peripheral nervous system.

    PubMed

    Andreu, David; Guiraud, David; Souquet, Guillaume

    2009-04-01

    We present a new system for functional electrical stimulation (FES) applications based on networked stimulation units. They embed an advanced analog circuit, which provides multipolar and multiphasic stimulation profiles, and digital circuits, which ensure safety, locally executed programmed profiles, and communication with the master controller. This architecture is thus based on distributed stimulation units (DSU) that need only a two-wire bus to communicate, regardless of the number of poles of each DSU-driven electrode. This structure minimizes the required bandwidth between master and distributed units, increases the safety and stimulation features and decreases the complexity of the surgical approach. We have successfully tested this network-based stimulation architecture on benchtop stimulators. This original approach allows broad exploration of all possible methods to stimulate peripheral nerves, particularly in the goal of restoring the motor function. It provides a powerful research device to determine the optimal, least aggressive and the most efficient way to activate the peripheral nervous system using an implanted FES system that is less invasive than other existing devices.

  19. A distributed architecture for activating the peripheral nervous system.

    PubMed

    Andreu, David; Guiraud, David; Souquet, Guillaume

    2009-04-01

    We present a new system for functional electrical stimulation (FES) applications based on networked stimulation units. They embed an advanced analog circuit, which provides multipolar and multiphasic stimulation profiles, and digital circuits, which ensure safety, locally executed programmed profiles, and communication with the master controller. This architecture is thus based on distributed stimulation units (DSU) that need only a two-wire bus to communicate, regardless of the number of poles of each DSU-driven electrode. This structure minimizes the required bandwidth between master and distributed units, increases the safety and stimulation features and decreases the complexity of the surgical approach. We have successfully tested this network-based stimulation architecture on benchtop stimulators. This original approach allows broad exploration of all possible methods to stimulate peripheral nerves, particularly in the goal of restoring the motor function. It provides a powerful research device to determine the optimal, least aggressive and the most efficient way to activate the peripheral nervous system using an implanted FES system that is less invasive than other existing devices. PMID:19213992

  20. 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

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

    PubMed Central

    Price, Richard W.; Spudich, Serena

    2008-01-01

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

  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. Amoeba angeitic lesions of the central nervous system in Balamuthia mandrilaris amoebiasis.

    PubMed

    Recavarren-Arce, S; Velarde, C; Gotuzzo, E; Cabrera, J

    1999-03-01

    Balamuthia mandrilaris amoebiasis is a fatal disease. It primarily affects the nasal pyramid or the skin, producing granulomatous amoebic lesions. The amoeba spread from the primary nasal lesion to the meninges where they infiltrate vessels. Thrombotic amoebic angitis produce infarcts of the central nervous system substance which then become infiltrated by amoeba. The primary cutaneous lesion can be present for weeks or even months. However, the appearance of neurological disease predicts a poor prognosis, in which death usually occurs within a few days or weeks. PMID:10088544

  4. IL-21 optimizes T cell and humoral responses in the central nervous system during viral encephalitis

    PubMed Central

    Phares, Timothy W.; DiSano, Krista D.; Hinton, David R.; Hwang, Mihyun; Zajac, Allan J.; Stohlman, Stephen A.; Bergmann, Cornelia C.

    2013-01-01

    Acute coronavirus encephalomyelitis is controlled by T cells while humoral responses suppress virus persistence. This study defines the contribution of interleukin (IL)-21, a regulator of T and B cell function, to central nervous system (CNS) immunity. IL-21 receptor deficiency did not affect peripheral T cell activation or trafficking, but dampened granzyme B, gamma interferon and IL-10 expression by CNS T cells and reduced serum and intrathecal humoral responses. Viral control was already lost prior to humoral CNS responses, but demyelination remained comparable. These data demonstrate a critical role of IL-21 in regulating CNS immunity, sustaining viral persistence and preventing mortality. PMID:23992866

  5. The sympathetic nervous system and baroreflexes in hypertension and hypotension.

    PubMed

    Izzo, J L; Taylor, A A

    1999-06-01

    Blood pressure and blood volume are closely regulated by the interrelated actions of the sympathetic nervous system (SNS) and the renin-angiotensin-aldosterone system (RAAS). Reflex vasoconstriction caused by parallel SNS and RAAS activation is modulated by two interactive negative feedback systems called baroreflex. The aortic-carotid baroreflex systems respond to momentary changes in systolic blood pressure, adjusting the degree of SNS-dependent peripheral vasoconstriction and cardiac output to allow maintenance of a relatively constant perfusion pressure. Cardiopulmonary baroreflexes respond to momentary changes in cardiac filling, adjusting the degree of peripheral venoconstriction and venous return to maintain cardiac preload and stroke volume. Under normal conditions, each baroreflex system exhibits a degree of tonic negative feedback so that it can alter SNS output immediately, providing counterregulatory increases or decreases in pressure or volume to maintain homeostasis. The SNS is inappropriately active in obesity and hypertension and plays a causal or permissive role in all forms of chronic hypertension. If the negative feedback control exerted by the baroreflexes over the SNS and renin-angiotensin-aldosterone system (RAAS) were perfect, chronic hypertension would not occur. Activity of the baroreflexes, however, is chronically altered by maladaptive changes such as cardiac and vascular fibrosis and hypertrophy. Long-term increases in SNS and RAAS activity also exert ongoing deleterious effects on the heart and vasculature by directly facilitating further cardiac hypertrophy and arterial stiffening. These effects appear to contribute to a vicious cycle of chronic hypertension and target organ damage. Other syndromes of abnormal blood pressure (BP) control, including orthostatic hypotension and baroreflex failure are examples of abnormal baroreflex activity and SNS control. PMID:10981075

  6. 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

  7. Iron Homeostasis in Peripheral Nervous System, Still a Black Box?

    PubMed Central

    Taveggia, Carla

    2014-01-01

    Abstract Significance: Iron is the most abundant transition metal in biology and an essential cofactor for many cellular enzymes. Iron homeostasis impairment is also a component of peripheral neuropathies. Recent Advances: During the past years, much effort has been paid to understand the molecular mechanism involved in maintaining systemic iron homeostasis in mammals. This has been stimulated by the evidence that iron dyshomeostasis is an initial cause of several disorders, including genetic and sporadic neurodegenerative disorders. Critical Issues: However, very little has been done to investigate the physiological role of iron in peripheral nervous system (PNS), despite the development of suitable cellular and animal models. Future Directions: To stimulate research on iron metabolism and peripheral neuropathy, we provide a summary of the knowledge on iron homeostasis in the PNS, on its transport across the blood–nerve barrier, its involvement in myelination, and we identify unresolved questions. Furthermore, we comment on the role of iron in iron-related disorder with peripheral component, in demyelinating and metabolic peripheral neuropathies. Antioxid. Redox Signal. 21, 634–648. PMID:24409826

  8. Lost among the trees? The autonomic nervous system and paediatrics.

    PubMed

    Rees, Corinne A

    2014-06-01

    The autonomic nervous system (ANS) has been strikingly neglected in Western medicine. Despite its profound importance for regulation, adjustment and coordination of body systems, it lacks priority in training and practice and receives scant attention in numerous major textbooks. The ANS is integral to manifestations of illness, underlying familiar physical and psychological symptoms. When ANS activity is itself dysfunctional, usual indicators of acute illness may prove deceptive. Recognising the relevance of the ANS can involve seeing the familiar through fresh eyes, challenging assumptions in clinical assessment and in approaches to practice. Its importance extends from physical and psychological well-being to parenting and safeguarding, public services and the functioning of society. Exploration of its role in conditions ranging from neurological, gastrointestinal and connective tissue disorders, diabetes and chronic fatigue syndrome, to autism, behavioural and mental health difficulties may open therapeutic avenues. The ANS offers a mechanism for so-called functional illnesses and illustrates the importance of recognising that 'stress' takes many forms, physical, psychological and environmental, desirable and otherwise. Evidence of intrauterine and post-natal programming of ANS reactivity suggests that neonatal care and safeguarding practice may offer preventive opportunity, as may greater understanding of epigenetic change of ANS activity through, for example, accidental or psychological trauma or infection. The aim of this article is to accelerate recognition of the importance of the ANS throughout paediatrics, and of the potential physical and psychological cost of neglecting it.

  9. Evolution of centralized nervous systems: two schools of evolutionary thought.

    PubMed

    Northcutt, R Glenn

    2012-06-26

    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.

  10. 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

  11. 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

  12. Lost among the trees? The autonomic nervous system and paediatrics.

    PubMed

    Rees, Corinne A

    2014-06-01

    The autonomic nervous system (ANS) has been strikingly neglected in Western medicine. Despite its profound importance for regulation, adjustment and coordination of body systems, it lacks priority in training and practice and receives scant attention in numerous major textbooks. The ANS is integral to manifestations of illness, underlying familiar physical and psychological symptoms. When ANS activity is itself dysfunctional, usual indicators of acute illness may prove deceptive. Recognising the relevance of the ANS can involve seeing the familiar through fresh eyes, challenging assumptions in clinical assessment and in approaches to practice. Its importance extends from physical and psychological well-being to parenting and safeguarding, public services and the functioning of society. Exploration of its role in conditions ranging from neurological, gastrointestinal and connective tissue disorders, diabetes and chronic fatigue syndrome, to autism, behavioural and mental health difficulties may open therapeutic avenues. The ANS offers a mechanism for so-called functional illnesses and illustrates the importance of recognising that 'stress' takes many forms, physical, psychological and environmental, desirable and otherwise. Evidence of intrauterine and post-natal programming of ANS reactivity suggests that neonatal care and safeguarding practice may offer preventive opportunity, as may greater understanding of epigenetic change of ANS activity through, for example, accidental or psychological trauma or infection. The aim of this article is to accelerate recognition of the importance of the ANS throughout paediatrics, and of the potential physical and psychological cost of neglecting it. PMID:24573884

  13. 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

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

    PubMed Central

    2013-01-01

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

  15. Cross-education of strength and skill: an old idea with applications in the aging nervous system.

    PubMed

    Barss, Trevor S; Pearcey, Gregory E P; Zehr, E Paul

    2016-03-01

    Edward Wheeler Scripture's 1894 work out of the Yale Psychological Laboratory has been influential in identifying the nervous system's contribution to the bilateral improvements that are seen with unilateral strength and skill training. Scripture coined the term "cross-education" to describe this improvement in the untrained contralateral limb. While physiological changes accompany aging that may negatively affect the performance of physical tasks, far too much credit has been given to the natural aging process rather than the effects of inactivity. Emerging evidence indicates strength or skill training interventions induce significant neuroplasticity in an aging population. The model of unilateral training provides a unique approach in which to elicit such plasticity. This brief review highlights the innate ability of the nervous system to adapt to unilateral strength and skill training interventions, regardless of age, and provides a novel perspective on the robust plastic ability of the aging nervous system.

  16. Cross-education of strength and skill: an old idea with applications in the aging nervous system.

    PubMed

    Barss, Trevor S; Pearcey, Gregory E P; Zehr, E Paul

    2016-03-01

    Edward Wheeler Scripture's 1894 work out of the Yale Psychological Laboratory has been influential in identifying the nervous system's contribution to the bilateral improvements that are seen with unilateral strength and skill training. Scripture coined the term "cross-education" to describe this improvement in the untrained contralateral limb. While physiological changes accompany aging that may negatively affect the performance of physical tasks, far too much credit has been given to the natural aging process rather than the effects of inactivity. Emerging evidence indicates strength or skill training interventions induce significant neuroplasticity in an aging population. The model of unilateral training provides a unique approach in which to elicit such plasticity. This brief review highlights the innate ability of the nervous system to adapt to unilateral strength and skill training interventions, regardless of age, and provides a novel perspective on the robust plastic ability of the aging nervous system. PMID:27505019

  17. Measuring Cardiac Autonomic Nervous System (ANS) Activity in Toddlers - Resting and Developmental Challenges.

    PubMed

    Bush, Nicole R; Caron, Zoe K; Blackburn, Katherine S; Alkon, Abbey

    2016-01-01

    The autonomic nervous system (ANS) consists of two branches, the parasympathetic and sympathetic nervous systems, and controls the function of internal organs (e.g., heart rate, respiration, digestion) and responds to everyday and adverse experiences (1). ANS measures in children have been found to be related to behavior problems, emotion regulation, and health (2-7). Therefore, understanding the factors that affect ANS development during early childhood is important. Both branches of the ANS affect young children's cardiovascular responses to stimuli and have been measured noninvasively, via external monitoring equipment, using valid and reliable measures of physiological change (8-11). However, there are few studies of very young children with simultaneous measures of the parasympathetic and sympathetic nervous systems, which limits understanding of the integrated functioning of the two systems. In addition, the majority of existing studies of young children report on infants' resting ANS measures or their reactivity to commonly used mother-child interaction paradigms, and less is known about ANS reactivity to other challenging conditions. We present a study design and standardized protocol for a non-invasive and rapid assessment of cardiac autonomic control in 18 month old children. We describe methods for continuous monitoring of the parasympathetic and sympathetic branches of the ANS under resting and challenge conditions during a home or laboratory visit and provide descriptive findings from our sample of 140 ethnically diverse toddlers using validated equipment and scoring software. Results revealed that this protocol can produce a range of physiological responses to both resting and developmentally challenging conditions, as indicated by changes in heart rate and indices of parasympathetic and sympathetic activity. Individuals demonstrated variability in resting levels, responses to challenges, and challenge reactivity, which provides additional evidence

  18. Electrical stimulation of the nervous system for pain control.

    PubMed

    Long, D M

    1978-01-01

    Transcutaneous electrical stimulation appears to be a valid technique for the treatment of many pain states. Its use in chronic pain is limited and it appears to be much more likely to be effective in the relief of acute painful states. Nevertheless, since it provides a simple way to treat a significant number of patients whose pain would otherwise by intractable, it has been a valuable addition to the armamentarium of the physician dealing with chronic pain. Peripheral nerve stimulation is an excellent way to relieve pain of peripheral nerve injury origin and certain painful, poorly understood, vasopastic or reflex sympathetic states. Spinal cord stimulation has been revived by the advent of percutaneous stimulators. The technique is currently the best available for the treatment of the patient suffering from the chronic low back syndrome with severe arachnoiditis, for whom no definitive therapy is available. Brain stimulation has been relegated to therapy for pain of central nervous system origin. It is a most promising technique though its application appears to be limited at this point to a few specific problems. The seriousness of potential complications has kept it from being widely applicable to date. There is little information concerning the mechanism whereby these various techniques are effective. Transcutaneous and peripheral nerve stimulation might have their effect through peripheral mechanisms or through a gating mechanism in the posterior horn (Melzack and Wall 1965; Campbell and Taub 1973). Spinal cord stimulation could act through a retrograde effect upon a dorsal horn gate or have more central actions. Brain stimulation in the opiate receptor system may be effective through activation of this system. The mechanisms of action of stimulation in the sensory system centrally are certainly not well understood (Bloedel 1974).

  19. Cancer stem cells in the mammalian central nervous system.

    PubMed

    Pilkington, G J

    2005-12-01

    Malignant tumours intrinsic to the central nervous system (CNS) are among the most difficult of neoplasms to treat effectively. The major biological features of these tumours that preclude successful therapy include their cellular heterogeneity, which renders them highly resistant to both chemotherapy and radiotherapy, and the propensity of the component tumour cells to invade, diffusely, the contiguous nervous tissues. The tumours are classified according to perceived cell of origin, gliomas being the most common generic group. In the 1970s transplacental administration of the potent neurocarcinogen, N-ethyl-N-nitrosourea (ENU), enabled investigation of the sequential development of brain and spinal neoplasms by electron microscopy and immunohistochemistry. The significance of the primitive cells of the subependymal plate in cellular origin and evolution of a variety of glial tumours was thereby established. Since then, the development of new cell culture methods, including the in vitro growth of neurospheres and multicellular tumour spheroids, and new antigenic markers of stem cells and glial/neuronal cell precursor cells, including nestin, Mushashi-1 and CD133, have led to a reappraisal of the histological classification and origins of CNS tumours. Moreover, neural stem cells may also provide new vectors in exciting novel therapeutic strategies for these tumours. In addition to the gliomas, stem cells may have been identified in paediatric tumours including cerebellar medulloblastoma, thought to be of external granule cell neuronal derivation. Interestingly, while the stem cell marker CD133 is expressed in these primitive neuroectodermal tumours (PNETs), the chondroitin sulphate proteoglycan neuronal/glial 2 (NG2), which appears to denote increased proliferative, but reduced migratory activity in adult gliomas, is rarely expressed. This is in contrast to the situation in the histologically similar supratentorial PNETs. A possible functional 'switch' between

  20. Nervous control of the cerebrovascular system: doubts and facts.

    PubMed

    Sándor, P

    1999-09-01

    Increased function of the central neurons results in increased neuronal metabolism and, as a consequence, increased concentration of metabolic end-products (H+, K+, adenosin) results in an increased cerebral blood flow (CBF). There is a general agreement among investigators that products of cerebral tissue metabolism as well as chemical stimuli are key factors that determine the rate of blood flow in the brain. CBF, however, may increase out of proportion to metabolic demands, may increase without significant change in local metabolism, and may increase much faster than the accumulation of the metabolic end-products. Therefore, the 100-year-old metabolic hypothesis of Roy and Sherrington, cannot fully explain the increases of CBF during increased functional activity of the central neurons. The tight coupling of neuronal activity and blood flow in the brain is demonstrated by a large amount of data. Therefore, the likelihood exists that neurogenic stimuli via perivascular nerve endings may act as rapid initiators, to induce a moment-to-moment dynamic adjustment of CBF to the metabolic demands, and further maintenance of these adjusted parameters is ensured by the metabolic and chemical factors. Perivascular nerve endings were identified in the outer smooth muscle layer of the cerebral arteries, arterioles and veins. Their axonterminals contain a large variety of neurotransmitters, often co-localised in synaptic vesicles. Stimulation of the nerves results in a release of transmitters into the narrow neuromuscular synaptic clefts in the cerebrovascular smooth muscle, close to specific receptor sites in the vessel wall. In spite of these facts, however, and in spite of the large number of new experimental evidences, the role of the nervous control of the cerebrovascular system is underestimated both in medical textbooks and in the common medical knowledge since decades. In the last 20 years major advances have been made that make it necessary to revise this false view

  1. Effects of radiation on development, especially of the nervous system

    SciTech Connect

    Hicks, S.P.; D'Amato, C.J.

    1980-12-01

    Humans and other organisms are exposed to ionizing radiations from a variety of natural and man-made sources. Radiation may cause mutations and chromosome abnormalities, cell-killing, alterations and transformations in cell growth, and carcinogenetic changes. This paper considers principally the cell-killing and nonlethal cell alterations in developing laboratory mammals and humans, especially the nervous system, that follow irradiation and often lead to malformation and disturbed function, but at certain stages to restitution of the injury. Most of what researchers know about the mechanisms of these radiation effects in man is derived from animal experiments, especially with rats. The few observations in humans have corresponded closely to them. Researchers illustrate the cellular effects and malformative results with an example of cell-killing in the developing cortex of a human fetus exposed to therapeutic radiation in utero; a current timetable of the malformative and other effects of radiation on rats during development from which expectations of human effects might be extrapolated; examples of hydrocephalus produced in rats; low-dose alterations of nerve cells in rats; and a microcephalic Japanese boy exposed in utero to the atomic bomb at Hiroshima in 1945.

  2. 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.

  3. Possible microwave mechanisms of the mammalian nervous system.

    PubMed

    Stocklin, P L; Stocklin, B F

    1979-01-01

    The hypothesis is examined that the living mammal generates and uses electromagnetic waves in the lower microwave frequency region as an integral part of the functioning of central and peripheral nervous systems. Analysis of the potential energy of a protein integral to the neural membrane compared to that of an extracellular positive ion yields major known features of action potential generation, and identification of the integral protein as a microwave emitter and absorber by changes in rotational energy state. Prolate spheroidal analysis of the adult human brain/skull cavity shows capability to support modes in the range 200 MHz to 3 GHz; spatial mode properties correspond to gross anatomy and neuromorphology of the brain. Phase-lock loop interaction between lower microwave modes and action potential conduction results in pulse microwave/action potential generation observable by EEG instrumentation as brain waves; alpha waves occur if the corpus callosum is the major neural tract involved. Spatially consistent Lorentz forces of standing microwaves provide physical basis for correspondence of spatial properties of microwave modes with brain anatomy, and for the formation of myelin sheath and the nodes of Ranvier on larger neurons.

  4. Autonomic nervous system pulmonary vasoregulation after hypoperfusion in conscious dogs.

    PubMed

    Clougherty, P W; Nyhan, D P; Chen, B B; Goll, H M; Murray, P A

    1988-05-01

    We investigated the role of the autonomic nervous system (ANS) in the pulmonary vascular response to increasing cardiac index after a period of hypoperfusion (defined as reperfusion) in conscious dogs. Base-line and reperfusion pulmonary vascular pressure-cardiac index (P/Q) plots were generated by stepwise constriction and release, respectively, of an inferior vena caval occluder to vary Q. Surprisingly, after 10-15 min of hypoperfusion (Q decreased from 139 +/- 9 to 46 +/- 3 ml.min-1.kg-1), the pulmonary vascular pressure gradient (pulmonary arterial pressure-pulmonary capillary wedge pressure) was unchanged over a broad range of Q during reperfusion compared with base line when the ANS was intact. In contrast, pulmonary vasoconstriction was observed during reperfusion after combined sympathetic beta-adrenergic and cholinergic receptor block, after beta-block alone, but not after cholinergic block alone. The pulmonary vasoconstriction during reperfusion was entirely abolished by combined sympathetic alpha- and beta-block. Although sympathetic alpha-block alone caused pulmonary vasodilation compared with the intact, base-line P/Q relationship, no further vasodilation was observed during reperfusion. Thus the ANS actively regulates the pulmonary circulation during reperfusion in conscious dogs. With the ANS intact, sympathetic beta-adrenergic vasodilation offsets alpha-adrenergic vasoconstriction and prevents pulmonary vasoconstriction during reperfusion. PMID:2896465

  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. 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.

  7. Clinical proton MR spectroscopy in central nervous system disorders.

    PubMed

    Oz, Gülin; 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, Kantarci; Klomp, Dennis W J; Kreis, Roland; Kruiskamp, Marijn J; Leach, Martin O; Lin, Alexander P; Luijten, Peter R; Marjańska, Malgorzata; 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; Schuster, Christian; Smith, Ian C P; Soher, Brian J; Tkáč, Ivan; Vigneron, Daniel B; Kauppinen, Risto A

    2014-03-01

    A large body of published work shows that proton (hydrogen 1 [(1)H]) 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 (1)H MR spectroscopy in the clinical evaluation of disorders of the central nervous system. The clinical usefulness of (1)H 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 (1)H 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.

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

    PubMed

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

    2009-03-01

    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. 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.

  10. Decoding transcriptional repressor complexes in the adult central nervous system.

    PubMed

    Adachi, Megumi; Monteggia, Lisa M

    2014-05-01

    Cells maintain precise gene expression by balancing transcriptional activation and repression. While much work has focused on elucidating transcriptional activation in the central nervous system (CNS), little is known about transcriptional repression. One means to repress gene expression is to initiate binding of transcription factors to DNA, which then recruit co-repressors as well as other accessory proteins, forming a multi-protein repressor complex. These multi-protein repressor complexes include histone modifying enzymes that trigger processes such as histone acetylation, methylation, and ubiquitylation, altering chromatin structures to impact gene expression. Within these complexes transcriptional repressor proteins per se do not exhibit enzymatic reactions to remodel chromatin structure, whereas histone modifying enzymes lack intrinsic DNA binding activity but have an ability to process post-translational modifications on histones. Thus, the mutual association between transcriptional repressors and histone modifying enzymes is essential to sculpt chromatin to favor transcriptional repression and down regulate gene expression. Additionally, co-repressors are integral components in the context of gene repression as they bridge the association of transcriptional repressors and histone modifying enzymes. In this review, we will discuss the roles of some of the major components of these repressor complex in the CNS as well as their cellular functions that may underlie fundamental behavior in animals.

  11. 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

  12. 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

  13. Motor execution detection based on autonomic nervous system responses.

    PubMed

    Marchal-Crespo, Laura; Zimmermann, Raphael; Lambercy, Olivier; Edelmann, Janis; Fluet, Marie-Christine; Wolf, Martin; Gassert, Roger; Riener, Robert

    2013-01-01

    Triggered assistance has been shown to be a successful robotic strategy for provoking motor plasticity, probably because it requires neurologic patients' active participation to initiate a movement involving their impaired limb. Triggered assistance, however, requires sufficient residual motor control to activate the trigger and, thus, is not applicable to individuals with severe neurologic injuries. In these situations, brain and body-computer interfaces have emerged as promising solutions to control robotic devices. In this paper, we investigate the feasibility of a body-machine interface to detect motion execution only monitoring the autonomic nervous system (ANS) response. Four physiological signals were measured (blood pressure, breathing rate, skin conductance response and heart rate) during an isometric pinching task and used to train a classifier based on hidden Markov models. We performed an experiment with six healthy subjects to test the effectiveness of the classifier to detect rest and active pinching periods. The results showed that the movement execution can be accurately classified based only on peripheral autonomic signals, with an accuracy level of 84.5%, sensitivity of 83.8% and specificity of 85.2%. These results are encouraging to perform further research on the use of the ANS response in body-machine interfaces. PMID:23248174

  14. Hydrogels Derived from Central Nervous System Extracellular Matrix

    PubMed Central

    Medberry, Christopher J.; Crapo, Peter M.; Siu, Bernard F.; Carruthers, Christopher A.; Wolf, Matthew T.; Nagarkar, Shailesh P.; Agrawal, Vineet; Jones, Kristen E.; Kelly, Jeremy; Johnson, Scott A.; Velankar, Sachin S.; Watkins, Simon C.; Modo, Michel

    2012-01-01

    Biologic scaffolds composed of extracellular matrix (ECM) are commonly used repair devices in preclinical and clinical settings; however the use of these scaffolds for peripheral and central nervous system (CNS) repair has been limited. Biologic scaffolds developed from brain and spinal cord tissue have recently been described, yet the conformation of the harvested ECM limits therapeutic utility. An injectable CNS-ECM derived hydrogel capable of in vivo polymerization and conformation to irregular lesion geometries may aid in tissue reconstruction efforts following complex neurologic trauma. The objectives of the present study were to develop hydrogel forms of brain and spinal cord ECM and compare the resulting biochemical composition, mechanical properties, and neurotrophic potential of a brain derived cell line to a non-CNS-ECM hydrogel, urinary bladder matrix. Results showed distinct differences between compositions of brain ECM, spinal cord ECM, and urinary bladder matrix. The rheologic modulus of spinal cord ECM hydrogel was greater than that of brain ECM and urinary bladder matrix. All ECMs increased the number of cells expressing neurites, but only brain ECM increased neurite length, suggesting a possible tissue-specific effect. All hydrogels promoted three-dimensional uni- or bi-polar neurite outgrowth following 7 days in culture. These results suggest that CNS-ECM hydrogels may provide supportive scaffolding to promote in vivo axonal repair. PMID:23158935

  15. [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.

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

    PubMed

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

    2015-10-01

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

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

    PubMed

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

    2015-10-01

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

  18. STIM and ORAI proteins in the nervous system

    PubMed Central

    Kraft, Robert

    2015-01-01

    Stromal interaction molecules (STIM) 1 and 2 are sensors of the calcium concentration in the endoplasmic reticulum. Depletion of endoplasmic reticulum calcium stores activates STIM proteins which, in turn, bind and open calcium channels in the plasma membrane formed by the proteins ORAI1, ORAI2, and ORAI3. The resulting store-operated calcium entry (SOCE), mostly controlled by the principal components STIM1 and ORAI1, has been particularly characterized in immune cells. In the nervous system, all STIM and ORAI homologs are expressed. This review summarizes current knowledge on distribution and function of STIM and ORAI proteins in central neurons and glial cells, i.e. astrocytes and microglia. STIM2 is required for SOCE in hippocampal synapses and cortical neurons, whereas STIM1 controls calcium store replenishment in cerebellar Purkinje neurons. In microglia, STIM1, STIM2, and ORAI1 regulate migration and phagocytosis. The isoforms ORAI2 and ORAI3 are candidates for SOCE channels in neurons and astrocytes, respectively. Due to the role of SOCE in neuronal and glial calcium homeostasis, dysfunction of STIM and ORAI proteins may have consequences for the development of neurodegenerative disorders, such as Alzheimer's disease. PMID:26218135

  19. Glial biomarkers in human central nervous system disease.

    PubMed

    Garden, Gwenn A; Campbell, Brian M

    2016-10-01

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

  20. 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.

  1. Guidelines on surgery of the thoracic sympathetic nervous system.

    PubMed

    Moreno Balsalobre, Ramón; Moreno Mata, Nicolás; Ramos Izquierdo, Ricard; Aragón Valverde, Francisco Javier; Molins López-Rodo, Laureano; Rivas de Andrés, Juan José; García Fernández, José Luis; Cañizares Carretero, Miguel Ángel; Congregado Loscertales, Miguel; Carbajo Carbajo, Miguel

    2011-02-01

    Thoracic sympathetic nervous system (TSNS) surgery has increased in importance in the last few years, generating great expectations among the general population and the scientific community. This has been due to the excellent results obtained by videothoracoscopy-assisted thoracic sympathectomy in the treatment of essential hyperhidrosis and other TSNS disorders. This minimally invasive surgical technique has been shown to be effective, and with a low morbidity it is accepted as one of the best therapeutic options for the treatment of palmar and bilateral axillary hyperhidrosis and the number of patients consulting with the intention of having the operation has increased considerably. Although compensatory sweating, which is occasionally intense, often occurs after the surgery, this and other secondary effects of the technique are well tolerated by patients. The current evidence on TSNS and the treatment of essential hyperhidrosis is based on observational studies, making it difficult to compare series and draw conclusions. There has been much discussion on standardising the technique, defining the most favourable levels for clipping, and choosing the type of denervation with least secondary effects. This has led to the need to draw up these guidelines which should clarify and standardise the criteria for managing patients with disorders of TSNS. PMID:21342743

  2. The endocannabinoid nervous system: unique opportunities for therapeutic intervention.

    PubMed

    Porter, A C; Felder, C C

    2001-04-01

    The active principle in marijuana, Delta(9)-tetrahydrocannabinol (THC), has been shown to have wide therapeutic application for a number of important medical conditions, including pain, anxiety, glaucoma, nausea, emesis, muscle spasms, and wasting diseases. Delta(9)-THC binds to and activates two known cannabinoid receptors found in mammalian tissue, CB1 and CB2. The development of cannabinoid-based therapeutics has focused predominantly on the CB1 receptor, based on its predominant and abundant localization in the CNS. Like most of the known cannabinoid agonists, Delta(9)-THC is lipophilic and relatively nonselective for both receptor subtypes. Clinical studies show that nonselective cannabinoid agonists are relatively safe and provide therapeutic efficacy, but that they also induce psychotropic side effects. Recent studies of the biosynthesis, release, transport, and disposition of anandamide are beginning to provide an understanding of the role of lipid transmitters in the CNS. This review attempts to link current understanding of the basic biology of the endocannabinoid nervous system to novel opportunities for therapeutic intervention. This new knowledge may facilitate the development of cannabinoid receptor-targeted therapeutics with improved safety and efficacy profiles.

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

    PubMed

    Morita, Akihiko; Ishihara, Masaki; Konno, Michiko

    2016-04-01

    Central nervous system (CNS) mycosis is a potentially life-threatening but treatable neurological emergency. CNS mycoses progress slowly and are sometimes difficult to distinguish from dementia. Though most patients with CNS mycosis have an underlying disease, such as human immunodeficiency virus (HIV) infection, cancer, diabetes mellitus, and/or use of immunosuppressants, cryptococcosis can occur in non-immunosuppressed persons. One of the major difficulties in accurate diagnosis is to detect the pathogen in patients' cerebrospinal fluid (CSF) cultures. Thus, the clinical diagnosis is often made by combining circumstantial evidence, including mononuclear cell-dominant pleocytosis with low glucose and protein elevation in the CSF, as well as positive results from an antigen-based assay and a (1-3)-beta-D-glucan assay using plasma and/or CSF. Polymerase chain reaction (PCR)-based diagnostics, which are not performed as routine examinations and are mostly performed as part of academic research in Japan, are sensitive tools for the early diagnosis of CNS mycosis. Mognetic resonance imaging (MRI) is useful to assess the complications of fungal meningitis, such as abscess, infarction, and hydrocephalus. Clinicians should realize the advantages and disadvantages of these diagnostic tools. Early and accurate diagnosis, including identification of the particular fungal species, enables optimal antifungal treatment that produces good outcomes in patients with CNS mycosis. PMID:27056851

  4. Prevalence of peripheral nervous system complications after major heart surgery.

    PubMed

    Gavazzi, Armando; de Rino, Francesca; Boveri, Maria Claudia; Picozzi, Anna; Franceschi, Massimo

    2016-02-01

    We evaluated 374 consecutive patients from May 2013 to April 2014 who underwent major cardiac surgery. Each patient had an interview and a neurological clinical examination during the rehabilitation period. Patients with possible peripheral nervous system (PNS) complications underwent further electrodiagnostic tests. Among 374 patients undergoing major heart surgery (coronary artery bypass grafting, valvular heart surgery, ascending aortic aneurysm repair) 23 (6.1 %) developed 34 new PNS complications. We found four brachial plexopathies; four carpal tunnel syndromes; five critical illness neuropathies; three worsening of pre-existing neuropathies; two involvement of X, one of IX and one of XII cranial nerves; three peroneal (at knee), one saphenous, two median (at Struthers ligament), six ulnar (at elbow) mononeuropathies; two meralgia parestheticas. Diabetes is a strong risk factor for PNS complications (p = 0.002); we could not find any other relationship of PNS complications with clinical conditions, demographic data (gender, age) or type of surgical intervention. The mononeuropathies of right arms can be related to ipsilateral vein cannulation; position of body and stretching from chest wall retraction may be the cause of mononeuropathies of left arms (more frequent); the use of saphenous vein and position of the limbs may be the cause of mononeuropathies of the legs; surgical and anesthetical procedures can injure cranial nerves; respiratory failure and infection during the first days after surgery can cause critical illness neuropathies. Careful preoperative assessment and intraoperative management may reduce the risk of long-term PNS complications after cardiac surgery.

  5. Microglia in Infectious Diseases of the Central Nervous System

    PubMed Central

    Mariani, Monica M.; Kielian, Tammy

    2010-01-01

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

  6. Non-linear HRV indices under autonomic nervous system blockade.

    PubMed

    Bolea, Juan; Pueyo, Esther; Laguna, Pablo; Bailón, Raquel

    2014-01-01

    Heart rate variability (HRV) has been studied as a non-invasive technique to characterize the autonomic nervous system (ANS) regulation of the heart. Non-linear methods based on chaos theory have been used during the last decades as markers for risk stratification. However, interpretation of these nonlinear methods in terms of sympathetic and parasympathetic activity is not fully established. In this work we study linear and non-linear HRV indices during ANS blockades in order to assess their relation with sympathetic and parasympathetic activities. Power spectral content in low frequency (0.04-0.15 Hz) and high frequency (0.15-0.4 Hz) bands of HRV, as well as correlation dimension, sample and approximate entropies were computed in a database of subjects during single and dual ANS blockade with atropine and/or propranolol. Parasympathetic blockade caused a significant decrease in the low and high frequency power of HRV, as well as in correlation dimension and sample and approximate entropies. Sympathetic blockade caused a significant increase in approximate entropy. Sympathetic activation due to postural change from supine to standing caused a significant decrease in all the investigated non-linear indices and a significant increase in the normalized power in the low frequency band. The other investigated linear indices did not show significant changes. Results suggest that parasympathetic activity has a direct relation with sample and approximate entropies.

  7. Effects of radiation on development, especially of the nervous system.

    PubMed

    Hicks, S P; D'Amato, C J

    1980-12-01

    Humans and other organisms are exposed to ionizing radiations from a variety of natural and man-made sources. Radiation may cause mutations and chromosome abnormalities, cell-killing, alterations and transformations in cell growth, and carcinogenetic changes. This paper considers principally the cell-killing and nonlethal cell alterations in developing laboratory mammals and humans, especially the nervous system, that follow irradiation and often lead to malformation and disturbed function, but at certain stages to restitution of the injury. Most of what we know about the mechanisms of these radiation effects in man is derived from animal experiments, especially with rats. The few observations in humans have corresponded closely to them. We illustrate the cellular effects and malformative results with an example of cell-killing in the developing cortex of a human fetus exposed to therapeutic radiation in utero; a current timetable of the malformative and other effects of radiation on rats during development from which expectations of human effects might be extrapolated; examples of hydrocephalus produced in rats; low-dose alterations of nerve cells in rats; and a microcephalic Japanese boy exposed in utero to the atomic bomb at Hiroshima in 1945.

  8. 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

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

    PubMed Central

    Schindler, Stephanie M.; Little, Jonathan P.

    2014-01-01

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

  10. The role of microbiome in central nervous system disorders

    PubMed Central

    Wang, Yan; Kasper, Lloyd H.

    2014-01-01

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

  11. Evolution of a neuroprotective function of central nervous system myelin.

    PubMed

    Yin, Xinghua; Baek, Rena C; Kirschner, Daniel A; Peterson, Alan; Fujii, Yasuhisa; Nave, Klaus-Armin; Macklin, Wendy B; Trapp, Bruce D

    2006-01-30

    The central nervous system (CNS) of terrestrial vertebrates underwent a prominent molecular change when a tetraspan membrane protein, myelin proteolipid protein (PLP), replaced the type I integral membrane protein, P0, as the major protein of myelin. To investigate possible reasons for this molecular switch, we genetically engineered mice to express P0 instead of PLP in CNS myelin. In the absence of PLP, the ancestral P0 provided a periodicity to mouse compact CNS myelin that was identical to mouse PNS myelin, where P0 is the major structural protein today. The PLP-P0 shift resulted in reduced myelin internode length, degeneration of myelinated axons, severe neurological disability, and a 50% reduction in lifespan. Mice with equal amounts of P0 and PLP in CNS myelin had a normal lifespan and no axonal degeneration. These data support the hypothesis that the P0-PLP shift during vertebrate evolution provided a vital neuroprotective function to myelin-forming CNS glia. PMID:16449196

  12. Central Nervous System Tuberculosis: Pathogenesis and Clinical Aspects

    PubMed Central

    Rock, R. Bryan; Olin, Michael; Baker, Cristina A.; Molitor, Thomas W.; Peterson, Phillip K.

    2008-01-01

    Summary: Tuberculosis of the central nervous system (CNS) is a highly devastating form of tuberculosis, which, even in the setting of appropriate antitubercular therapy, leads to unacceptable levels of morbidity and mortality. Despite the development of promising molecular diagnostic techniques, diagnosis of CNS tuberculosis relies largely on microbiological methods that are insensitive, and as such, CNS tuberculosis remains a formidable diagnostic challenge. Insights into the basic neuropathogenesis of Mycobacterium tuberculosis and the development of an appropriate animal model are desperately needed. The optimal regimen and length of treatment are largely unknown, and with the rising incidence of multidrug-resistant strains of M. tuberculosis, the development of well-tolerated and effective antibiotics remains a continued need. While the most widely used vaccine in the world largely targets this manifestation of tuberculosis, the BCG vaccine has not fulfilled the promise of eliminating CNS tuberculosis. We put forth this review to highlight the current understanding of the neuropathogenesis of M. tuberculosis, to discuss certain epidemiological, clinical, diagnostic, and therapeutic aspects of CNS tuberculosis, and also to underscore the many unmet needs in this important field. PMID:18400795

  13. Central Nervous System Agents for Ischemic Stroke: Neuroprotection Mechanisms

    PubMed Central

    Pandya, Rachna S.; Mao, Lijuan; Zhou, Hua; Zhou, Shuanhu; Zeng, Jiang; Popp, A. John; Wang, Xin

    2011-01-01

    Stroke is the third leading cause of mortality and disability in the United States. Ischemic stroke constitutes 85% of all stroke cases. However, no effective treatment has been found to prevent damage to the brain in such cases except tissue plasminogen activator with narrow therapeutic window, and there is an unmet need to develop therapeutics for neuroprotection from ischemic stroke. Studies have shown that mechanisms including apoptosis, necrosis, inflammation, immune modulation, and oxidative stress and mediators such as excitatory amino acids, nitric oxide, inflammatory mediators, neurotransmitters, reactive oxygen species, and withdrawal of trophic factors may lead to the development of the ischemic cascade. Hence, it is essential to develop neuroprotective agents targeting either the mechanisms or the mediators leading to development of ischemic stroke. This review focuses on central nervous system agents targeting these biochemical pathways and mediators of ischemic stroke, mainly those that counteract apoptosis, inflammation, and oxidation, and well as glutamate inhibitors which have been shown to provide neuroprotection in experimental animals. All these agents have been shown to improve neurological outcome after ischemic insult in experimental animals in vivo, organotypic brain slice/acute slice ex vivo, and cell cultures in vitro and may therefore aid in preventing long-term morbidity and mortality associated with ischemic stroke. PMID:21521165

  14. Glial biomarkers in human central nervous system disease.

    PubMed

    Garden, Gwenn A; Campbell, Brian M

    2016-10-01

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

  15. Mutational analysis of primary central nervous system lymphoma

    PubMed Central

    Bruno, Aurélie; Boisselier, Blandine; Labreche, Karim; Marie, Yannick; Polivka, Marc; Jouvet, Anne; Adam, Clovis; Figarella-Branger, Dominique; Miquel, Catherine; Eimer, Sandrine; Houillier, Caroline; Soussain, Carole; Mokhtari, Karima; Daveau, Romain; Hoang-Xuan, Khê

    2014-01-01

    Little is known about the genomic basis of primary central nervous system lymphoma (PCNSL) tumorigenesis. To investigate the mutational profile of PCNSL, we analyzed nine paired tumor and germline DNA samples from PCNSL patients by high throughput exome sequencing. Eight genes of interest have been further investigated by focused resequencing in 28 additional PCNSL tumors to better estimate their incidence. Our study identified recurrent somatic mutations in 37 genes, some involved in key signaling pathways such as NFKB, B cell differentiation and cell cycle control. Focused resequencing in the larger cohort revealed high mutation rates for genes already described as mutated in PCNSL such as MYD88 (38%), CD79B (30%), PIM1 (22%) and TBL1XR1 (19%) and for genes not previously reported to be involved in PCNSL tumorigenesis such as ETV6 (16%), IRF4 (14%), IRF2BP2 (11%) and EBF1 (11%). Of note, only 3 somatically acquired SNVs were annotated in the COSMIC database. Our results demonstrate a high genetic heterogeneity of PCNSL and mutational pattern similarities with extracerebral diffuse large B cell lymphomas, particularly of the activated B-cell (ABC) subtype, suggesting shared underlying biological mechanisms. The present study provides new insights into the mutational profile of PCNSL and potential targets for therapeutic strategies. PMID:24970810

  16. 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.

  17. 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.

  18. 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

  19. Radiochemical microassay for aspartate aminotransferase activity in the nervous system

    SciTech Connect

    Garrison, D.; Beattie, J.; Namboodiri, M.A.

    1988-07-01

    A radiochemical procedure for measuring aspartate aminotransferase activity in the nervous system is described. The method is based on the exchange of tritium atoms at positions 2 and 3 of L-2,3-(/sup 3/H)aspartate with water when this amino acid is transaminated in the presence of alpha-ketoglutarate to form oxaloacetate. The tritiated water is separated from the radiolabeled aspartate by passing the reaction mixture over a cation exchange column. Confirmation that the radioactivity in the product is associated with water was obtained by separating it by anion exchange HPLC and by evaporation. The product formation is linear with time up to 120 min and with tissue in the 0.05- to 10-micrograms range. The apparent Km for aspartate in the rat brain homogenate is found to be 0.83 mM and that for alpha-ketoglutarate to be 0.12 mM. Methods that further improve the sensitivity of the assay are also discussed.

  20. Binocular visual integration in the crustacean nervous system.

    PubMed

    Sztarker, Julieta; Tomsic, Daniel

    2004-11-01

    Although the behavioral repertoire of crustaceans is largely guided by visual information their visual nervous system has been little explored. In search for central mechanisms of visual integration, this study was aimed at identifying and characterizing brain neurons in the crab involved in binocular visual processing. The study was performed in the intact animal, by recording intracellularly the response to visual stimuli of neurons from one of the two optic lobes. Identified neurons recorded from the medulla (second optic neuropil), which include sustaining neurons, dimming neurons, depolarizing and hyperpolarizing tonic neurons and on-off neurons, all presented exclusively monocular (ipsilateral) responses. In contrast, all wide field movement detector neurons recorded from the lobula (third optic neuropil) responded to moving stimuli presented to the ipsilateral and to the contralateral eye. In these cells, the responses evoked by ipsilateral or contralateral stimulation were almost identical, as revealed by analysing the number and amplitude of the elicited postsynaptic potentials and spikes, and the ability to habituate upon repeated visual stimulation. The results demonstrate that in crustaceans important binocular processing takes place at the level of the lobula.

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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...

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

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-04

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

  7. 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...

  8. 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...

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

    PubMed Central

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

    2009-01-01

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

  10. Marital Conflict and Growth in Children's Internalizing Symptoms: The Role of Autonomic Nervous System Activity

    ERIC Educational Resources Information Center

    El-Sheikh, Mona; Keiley, Margaret; Erath, Stephen; Dyer, W. Justin

    2013-01-01

    We assessed trajectories of children's internalizing symptoms, indexed through anxiety and depression, with a focus on the role of interactions between interparental marital conflict, children's sympathetic nervous system activity indexed by skin conductance level (SCL), and parasympathetic nervous system activity indexed by respiratory sinus…

  11. Cross-education of strength and skill: an old idea with applications in the aging nervous system

    PubMed Central

    Barss, Trevor S.; Pearcey, Gregory E.P.; Zehr, E. Paul

    2016-01-01

    Edward Wheeler Scripture’s 1894 work out of the Yale Psychological Laboratory has been influential in identifying the nervous system’s contribution to the bilateral improvements that are seen with unilateral strength and skill training. Scripture coined the term “cross-education” to describe this improvement in the untrained contralateral limb. While physiological changes accompany aging that may negatively affect the performance of physical tasks, far too much credit has been given to the natural aging process rather than the effects of inactivity. Emerging evidence indicates strength or skill training interventions induce significant neuroplasticity in an aging population. The model of unilateral training provides a unique approach in which to elicit such plasticity. This brief review highlights the innate ability of the nervous system to adapt to unilateral strength and skill training interventions, regardless of age, and provides a novel perspective on the robust plastic ability of the aging nervous system. PMID:27505019

  12. Engrailed is expressed in larval development and in the radial nervous system of Patiriella sea stars.

    PubMed

    Byrne, Maria; Cisternas, Paula; Elia, Laura; Relf, Bronwyn

    2005-12-01

    We documented expression of the pan-metazoan neurogenic gene engrailed in larval and juvenile Patiriella sea stars to determine if this gene patterns bilateral and radial echinoderm nervous systems. Engrailed homologues, containing conserved En protein domains, were cloned from the radial nerve cord. During development, engrailed was expressed in ectodermal (nervous system) and mesodermal (coeloms) derivatives. In larvae, engrailed was expressed in cells lining the larval and future adult coeloms. Engrailed was not expressed in the larval nervous system. As adult-specific developmental programs were switched on during metamorphosis, engrailed was expressed in the central nervous system and peripheral nervous system (PNS), paralleling the pattern of neuropeptide immunolocalisation. Engrailed was first seen in the developing nerve ring and appeared to be up-regulated as the nervous system developed. Expression of engrailed in the nerve plexus of the tube feet, the lobes of the hydrocoel along the adult arm axis, is similar to the reiterated pattern of expression seen in other animals. Engrailed expression in developing nervous tissue reflects its conserved role in neurogenesis, but its broad expression in the adult nervous system of Patiriella differs from the localised expression seen in other bilaterians. The role of engrailed in patterning repeated PNS structures indicates that it may be important in patterning the fivefold organisation of the ambulacrae, a defining feature of the Echinodermata.

  13. Pharyngeal pumping continues after laser killing of the pharyngeal nervous system of C. elegans

    SciTech Connect

    Avery, L.; Horvitz, H.R. )

    1989-10-01

    Using a laser microbeam to kill specific subsets of the pharyngeal nervous system of C. elegans, we found that feeding was accomplished by two separately controlled muscle motions, isthmus peristalsis and pumping. The single neuron M4 was necessary and sufficient for isthmus peristalsis. The MC neurons were necessary for normal stimulation of pumping in response to food, but pumping continued and was functional in MC- worms. The remaining 12 neuron types were also unnecessary for functional pumping. No operation we did, including destruction of the entire pharyngeal nervous system, abolished pumping altogether. When we killed all pharyngeal neurons except M4, the worms were viable and fertile, although retarded and starved. Since feeding is one of the few known essential actions controlled by the nervous system, we suggest that most of the C. elegans nervous system is dispensable in hermaphrodites under laboratory conditions. This may explain the ease with which nervous system mutants are isolated and handled in C. elegans.

  14. Neuroregulatory properties of substance P in the enteric nervous system

    SciTech Connect

    Smith, K.E.

    1985-01-01

    Substance P (SP) is a putative neurotransmitter in both central and peripheral nervous systems. Its presence in intrinsic neurons of the gut, combined with its potent biological effects on this tissue, suggest that endogenous SP may play a role in the physiological regulation of gastrointestinal function. SP elicits potent, atropine-resistant contractions of guinea-pig ileum which mimic the effects of high-frequency electrical field stimulation. In addition, SP-like immunoreactivity was found to be released from segments of guinea-pig ileum in a calcium-dependent fashion by electrical stimulation. A SP radioligand binding assay was developed in order to characterize SP receptors in the rat gut. /sup 3/H-SP binds with specificity and high-affinity to membranes of rat small intestine; Scatchard plots of saturation data are curved, indicating the presence of multiple binding sites. The K/sub D/ for the high-affinity site is 0.25 nM as determined by computerized non-linear least squares analysis. Specific binding is linear with protein, dependent on temperature, and reversible. The rate constants for association and dissociation of 0.5 nm /sup 3/H-SP are: value derived form these constants, 0.34nM, agrees well with K/sub D/ derived from Scatchard plots. The rank order of potency for various tachykinins in inhibiting /sup 3/H-SP binding indicates that the high-affinity site is a P-type tachykinin receptor. Specific /sup 3/H-SP binding is modulated in a dose-related fashion by guanine nucleotides; a reduction in binding is seen which can be largely attributed to an increase in the rate of dissociation of /sup 3/H-SP in the presence of GTP. This suggests that the binding site is a receptor linked to an effector system by a GTP-binding protein.

  15. Nervous and muscle system development in Phascolion strombus (Sipuncula).

    PubMed

    Wanninger, Andreas; Koop, Demian; Bromham, Lindell; Noonan, Erin; Degnan, Bernard M

    2005-10-01

    Recent interpretations of developmental gene expression patterns propose that the last common metazoan ancestor was segmented, although most animal phyla show no obvious signs of segmentation. Developmental studies of non-model system trochozoan taxa may shed light on this hypothesis by assessing possible cryptic segmentation patterns. In this paper, we present the first immunocytochemical data on the ontogeny of the nervous system and the musculature in the sipunculan Phascolion strombus. Myogenesis of the first anlagen of the body wall ring muscles occurs synchronously and not subsequently from anterior to posterior as in segmented spiralian taxa (i.e. annelids). The number of ring muscles remains constant during the initial stages of body axis elongation. In the anterior-posteriorly elongated larva, newly formed ring muscles originate along the entire body axis between existing myocytes, indicating that repeated muscle bands do not form from a posterior growth zone. During neurogenesis, the Phascolion larva expresses a non-metameric, paired, ventral nerve cord that fuses in the mid-body region in the late-stage elongated larva. Contrary to other trochozoans, Phascolion lacks any larval serotonergic structures. However, two to three FMRFamide-positive cells are found in the apical organ. In addition, late larvae show commissure-like neurones interconnecting the two ventral nerve cords, while early juveniles exhibit a third, medially placed FMRFamidergic ventral nerve. Although we did not find any indications for cryptic segmentation, certain neuro-developmental traits in Phascolion resemble the conditions found in polychaetes (including echiurans) and myzostomids and support a close relationship of Sipuncula and Annelida. PMID:16133569

  16. 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

  17. Systemic and Central Nervous System Correction of Lysosomal Storage in Mucopolysaccharidosis Type VII Mice

    PubMed Central

    Stein, Colleen S.; Ghodsi, Abdi; Derksen, Todd; Davidson, Beverly L.

    1999-01-01

    Mucopolysaccharidosis (MPS) type VII patients lack functional β-glucuronidase, leading to systemic and central nervous system dysfunction. In this study we tested whether recombinant adenovirus that encodes β-glucuronidase (Adβgluc), delivered intravenously and into the brain parenchyma of MPS type VII mice, could provide long-term transgene expression and correction of lysosomal distension. We also tested whether systemic treatment with the immunosuppressive anti-CD40 ligand antibody, MR-1, affected transgene expression. We found substantial plasma β-glucuronidase activity for over 9 weeks after gene transfer in the MR-1- treated group, with subsequent decline in activity corresponding to a delayed anti-β-glucuronidase antibody response. At 16 weeks, near wild-type amounts of β-glucuronidase activity and striking reduction of lysosomal pathology were detected in livers from mice that had received either MR-1 cotreatment or control antibody. In the lung and kidney, β-glucuronidase activity was markedly higher for the MR-1-treated group. β-Glucuronidase activity in the brain persisted independently of MR-1 treatment. Activity was intense in the injected hemisphere and was also evident in the noninjected cortex and striatum, with dramatic improvements in storage deposits in areas of both hemispheres. These results indicate that prolonged enzyme expression from transgenes delivered to deficient liver and brain can mediate pervasive correction and illustrate the potential for gene therapy of MPS and other lysosomal storage diseases. PMID:10074197

  18. Ventriculoperitoneal shunt for hydrocephalus caused by central nervous system metastasis.

    PubMed

    Lee, Seung Hoon; Kong, Doo Sik; Seol, Ho Joon; Nam, Do-Hyun; Lee, Jung-Il

    2011-09-01

    The development of better diagnostic tools and therapeutic modalities has increased the incidence of central nervous system (CNS) metastasis in malignant tumor patients. Hydrocephalus can result from CNS metastasis and frustrate cancer treatment. The authors sought to investigate the outcomes and the roles of ventriculoperitoneal shunts (VPS) in patients with CNS metastasis. The medical records of 50 consecutive patients who underwent VPS for hydrocephalus related to CNS metastasis were analyzed retrospectively. Data included features of primary malignancies, CNS involvement, clinical course and surgical outcome. Median patient age was 55.0 years (range 25-77), and 30 female and 20 male patients were included in the study. At the time of VPS, 10 patients had parenchymal metastases only and 40 patients had leptomeningeal seeding (LMS). Symptom improvement was observed postoperatively in 40 patients (80%), mean Karnofsky performance status (KPS) scale change was from 37.8 to 46.0, and median survival from VPS was 3.0 months (2 days to 54 months). A ventricular opening pressure of >30 cmH(2)O (HR 6.44, 95% CI 1.26-32.9, P = 0.02) and further cancer treatment after VPS (HR 0.17, 95% CI 0.07-0.42, P < 0.0001) were found to be independent risk factors of poorer and better survival, respectively. Hydrocephalus in CNS metastasis requiring VPS is commonly associated with LMS. VPS is an effective palliative measure and an adequate cancer treatment after VPS may provide the best means of improving survival.

  19. Regional research priorities in brain and nervous system disorders.

    PubMed

    Ravindranath, Vijayalakshmi; Dang, Hoang-Minh; Goya, Rodolfo G; Mansour, Hader; Nimgaonkar, Vishwajit L; Russell, Vivienne Ann; Xin, Yu

    2015-11-19

    The characteristics of neurological, psychiatric, developmental and substance-use disorders in low- and middle-income countries are unique and the burden that they have will be different from country to country. Many of the differences are explained by the wide variation in population demographics and size, poverty, conflict, culture, land area and quality, and genetics. Neurological, psychiatric, developmental and substance-use disorders that result from, or are worsened by, a lack of adequate nutrition and infectious disease still afflict much of sub-Saharan Africa, although disorders related to increasing longevity, such as stroke, are on the rise. In the Middle East and North Africa, major depressive disorders and post-traumatic stress disorder are a primary concern because of the conflict-ridden environment. Consanguinity is a serious concern that leads to the high prevalence of recessive disorders in the Middle East and North Africa and possibly other regions. The burden of these disorders in Latin American and Asian countries largely surrounds stroke and vascular disease, dementia and lifestyle factors that are influenced by genetics. Although much knowledge has been gained over the past 10 years, the epidemiology of the conditions in low- and middle-income countries still needs more research. Prevention and treatments could be better informed with more longitudinal studies of risk factors. Challenges and opportunities for ameliorating nervous-system disorders can benefit from both local and regional research collaborations. The lack of resources and infrastructure for health-care and related research, both in terms of personnel and equipment, along with the stigma associated with the physical or behavioural manifestations of some disorders have hampered progress in understanding the disease burden and improving brain health. Individual countries, and regions within countries, have specific needs in terms of research priorities. PMID:26580328

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

    PubMed

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

    1996-01-01

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