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Sample records for adult peripheral nervous

  1. Neurogenesis in the adult peripheral nervous system☆

    PubMed Central

    Czaja, Krzysztof; Fornaro, Michele; Geuna, Stefano

    2012-01-01

    Most researchers believe that neurogenesis in mature mammals is restricted only to the subgranular zone of the dentate gyrus and the subventricular zone of the lateral ventricle in the central nervous system. In the peripheral nervous system, neurogenesis is thought to be active only during prenatal development, with the exception of the olfactory neuroepithelium. However, sensory ganglia in the adult peripheral nervous system have been reported to contain precursor cells that can proliferate in vitro and be induced to differentiate into neurons. The occurrence of insult-induced neurogenesis, which has been reported by several investigators in the brain, is limited to a few recent reports for the peripheral nervous system. These reports suggest that damage to the adult nervous system induces mechanisms similar to those that control the generation of new neurons during prenatal development. Understanding conditions under which neurogenesis can be induced in physiologically non-neurogenic regions in adults is one of the major challenges for developing therapeutic strategies to repair neurological damage. However, the induced neurogenesis in the peripheral nervous system is still largely unexplored. This review presents the history of research on adult neurogenesis in the peripheral nervous system, which dates back more than 100 years and reveals the evidence on the under estimated potential for generation of new neurons in the adult peripheral nervous system. PMID:25722694

  2. Neurogenesis in the adult peripheral nervous system.

    PubMed

    Czaja, Krzysztof; Fornaro, Michele; Geuna, Stefano

    2012-05-15

    Most researchers believe that neurogenesis in mature mammals is restricted only to the subgranular zone of the dentate gyrus and the subventricular zone of the lateral ventricle in the central nervous system. In the peripheral nervous system, neurogenesis is thought to be active only during prenatal development, with the exception of the olfactory neuroepithelium. However, sensory ganglia in the adult peripheral nervous system have been reported to contain precursor cells that can proliferate in vitro and be induced to differentiate into neurons. The occurrence of insult-induced neurogenesis, which has been reported by several investigators in the brain, is limited to a few recent reports for the peripheral nervous system. These reports suggest that damage to the adult nervous system induces mechanisms similar to those that control the generation of new neurons during prenatal development. Understanding conditions under which neurogenesis can be induced in physiologically non-neurogenic regions in adults is one of the major challenges for developing therapeutic strategies to repair neurological damage. However, the induced neurogenesis in the peripheral nervous system is still largely unexplored. This review presents the history of research on adult neurogenesis in the peripheral nervous system, which dates back more than 100 years and reveals the evidence on the under estimated potential for generation of new neurons in the adult peripheral nervous system.

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

    NASA Astrophysics Data System (ADS)

    David, Samuel; Aguayo, Albert J.

    1981-11-01

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

  4. Expression patterns of Slit and Robo family members in adult mouse spinal cord and peripheral nervous system.

    PubMed

    Carr, Lauren; Parkinson, David B; Dun, Xin-Peng

    2017-01-01

    The secreted glycoproteins, Slit1-3, are classic axon guidance molecules that act as repulsive cues through their well characterised receptors Robo1-2 to allow precise axon pathfinding and neuronal migration. The expression patterns of Slit1-3 and Robo1-2 have been most characterized in the rodent developing nervous system and the adult brain, but little is known about their expression patterns in the adult rodent peripheral nervous system. Here, we report a detailed expression analysis of Slit1-3 and Robo1-2 in the adult mouse sciatic nerve as well as their expression in the nerve cell bodies within the ventral spinal cord (motor neurons) and dorsal root ganglion (sensory neurons). Our results show that, in the adult mouse peripheral nervous system, Slit1-3 and Robo1-2 are expressed in the cell bodies and axons of both motor and sensory neurons. While Slit1 and Robo2 are only expressed in peripheral axons and their cell bodies, Slit2, Slit3 and Robo1 are also expressed in satellite cells of the dorsal root ganglion, Schwann cells and fibroblasts of peripheral nerves. In addition to these expression patterns, we also demonstrate the expression of Robo1 in blood vessels of the peripheral nerves. Our work gives important new data on the expression patterns of Slit and Robo family members within the peripheral nervous system that may relate both to nerve homeostasis and the reaction of the peripheral nerves to injury.

  5. Expression patterns of Slit and Robo family members in adult mouse spinal cord and peripheral nervous system

    PubMed Central

    Carr, Lauren; Parkinson, David B.; Dun, Xin-peng

    2017-01-01

    The secreted glycoproteins, Slit1-3, are classic axon guidance molecules that act as repulsive cues through their well characterised receptors Robo1-2 to allow precise axon pathfinding and neuronal migration. The expression patterns of Slit1-3 and Robo1-2 have been most characterized in the rodent developing nervous system and the adult brain, but little is known about their expression patterns in the adult rodent peripheral nervous system. Here, we report a detailed expression analysis of Slit1-3 and Robo1-2 in the adult mouse sciatic nerve as well as their expression in the nerve cell bodies within the ventral spinal cord (motor neurons) and dorsal root ganglion (sensory neurons). Our results show that, in the adult mouse peripheral nervous system, Slit1-3 and Robo1-2 are expressed in the cell bodies and axons of both motor and sensory neurons. While Slit1 and Robo2 are only expressed in peripheral axons and their cell bodies, Slit2, Slit3 and Robo1 are also expressed in satellite cells of the dorsal root ganglion, Schwann cells and fibroblasts of peripheral nerves. In addition to these expression patterns, we also demonstrate the expression of Robo1 in blood vessels of the peripheral nerves. Our work gives important new data on the expression patterns of Slit and Robo family members within the peripheral nervous system that may relate both to nerve homeostasis and the reaction of the peripheral nerves to injury. PMID:28234971

  6. Calcium-activated potassium channel SK1 is widely expressed in the peripheral nervous system and sensory organs of adult zebrafish.

    PubMed

    Cabo, R; Zichichi, R; Viña, E; Guerrera, M C; Vázquez, G; García-Suárez, O; Vega, J A; Germanà, A

    2013-10-25

    Sensory cells contain ion channels involved in the organ-specific transduction mechanisms that convert different types of stimuli into electric energy. Here we focus on small-conductance calcium-activated potassium channel 1 (SK1) which plays an important role in all excitable cells acting as feedback regulators in after-hyperpolarization. This study was undertaken to analyze the pattern of expression of SK1 in the zebrafish peripheral nervous system and sensory organs using RT-PRC, Westernblot and immunohistochemistry. Expression of SK1 mRNA was observed at all developmental stages analyzed (from 10 to 100 days post fertilization, dpf), and the antibody used identified a protein with a molecular weight of 70kDa, at 100dpf (regarded to be adult). Cell expressing SK1 in adult animals were neurons of dorsal root and cranial nerve sensory ganglia, sympathetic neurons, sensory cells in neuromasts of the lateral line system and taste buds, crypt olfactory neurons and photoreceptors. Present results report for the first time the expression and the distribution of SK1 in the peripheral nervous system and sensory organs of adult zebrafish, and may contribute to set zebrafish as an interesting experimental model for calcium-activated potassium channels research. Moreover these findings are of potential interest because the potential role of SK as targets for the treatment of neurological diseases and sensory disorders.

  7. Sarcoidosis of the peripheral nervous system.

    PubMed

    Said, Gérard

    2013-01-01

    Neurological manifestations of sarcoidosis are relatively rare but constitute a treatable cause of central and peripheral neurological manifestations. Regarding the peripheral nervous system, cranial nerves are predominantly affected, and peripheral facial nerve palsy, often bilateral, is the most common neurological manifestation of sarcoidosis. Multifocal peripheral neuropathy is a rare event in sarcoidosis. In some cases, however, peripheral neuropathy is the presenting manifestation and seemingly the only organ affected. Definite diagnosis of sarcoidosis rests ideally on histological demonstration of sarcoid granulomas in tissue biopsy specimens.

  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. Paraneoplastic disorders of the peripheral nervous system.

    PubMed

    Antoine, Jean-Christophe; Camdessanché, Jean-Philippe

    2013-06-01

    Paraneoplastic neurological syndromes are rare but can affect any part of the peripheral nervous system (PNS) including motor neurons, sensory ganglia, nerve roots, plexuses, cranial and peripheral nerves, and neuromuscular junctions. The type of cancer, lymphoma or solid tumour, is a determinant factor of the underlying mechanism. With solid tumour, antibodies directed to intracellular (anti-Hu or anti-CV2/CRMP5 antibodies) or surface antigens (anti-VGCC,or LGI1 and Caspr2 antibodies) have been identified while with lymphoma, the neuropathy is usually linked to a monoclonal gammopathy. This review discusses the different etiologies and mechanisms of paraneoplastic disorders of the PNS in patients emphasising their evaluation, diagnosis and treatment.

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

    PubMed

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

    2014-12-01

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

  11. Peripheral nervous system manifestations in systemic autoimmune diseases.

    PubMed

    Cojocaru, Inimioara Mihaela; Cojocaru, Manole; Silosi, Isabela; Vrabie, Camelia Doina

    2014-09-01

    The peripheral nervous system refers to parts of the nervous system outside the brain and spinal cord. Systemic autoimmune diseases can affect both the central and peripheral nervous systems in a myriad of ways and through a heterogeneous number of mechanisms leading to many different clinical manifestations. As a result, neurological complications of these disorders can result in significant morbidity and mortality. The most common complication of peripheral nervous system (PNS) involvement is peripheral neuropathy, with symptoms of numbness, sensory paresthesias, weakness, or gait imbalance. The neuropathy may be multifocal and asymmetric or, less frequently, distal and symmetric.

  12. Vasculitis Syndromes of the Central and Peripheral Nervous Systems

    MedlinePlus

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

  13. 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.

  14. Combining an autologous peripheral nervous system "bridge" and matrix modification by chondroitinase allows robust, functional regeneration beyond a hemisection lesion of the adult rat spinal cord.

    PubMed

    Houle, John D; Tom, Veronica J; Mayes, Debra; Wagoner, Gail; Phillips, Napoleon; Silver, Jerry

    2006-07-12

    Chondroitinase-ABC (ChABC) was applied to a cervical level 5 (C5) dorsal quadrant aspiration cavity of the adult rat spinal cord to degrade the local accumulation of inhibitory chondroitin sulfate proteoglycans. The intent was to enhance the extension of regenerated axons from the distal end of a peripheral nerve (PN) graft back into the C5 spinal cord, having bypassed a hemisection lesion at C3. ChABC-treated rats showed (1) gradual improvement in the range of forelimb swing during locomotion, with some animals progressing to the point of raising their forelimb above the nose, (2) an enhanced ability to use the forelimb in a cylinder test, and (3) improvements in balance and weight bearing on a horizontal rope. Transection of the PN graft, which cuts through regenerated axons, greatly diminished these functional improvements. Axonal regrowth from the PN graft correlated well with the behavioral assessments. Thus, many more axons extended for much longer distances into the cord after ChABC treatment and bridge insertion compared with the control groups, in which axons regenerated into the PN graft but growth back into the spinal cord was extremely limited. These results demonstrate, for the first time, that modulation of extracellular matrix components after spinal cord injury promotes significant axonal regeneration beyond the distal end of a PN bridge back into the spinal cord and that regenerating axons can mediate the return of useful function of the affected limb.

  15. Herpes virus infection of the peripheral nervous system.

    PubMed

    Steiner, Israel

    2013-01-01

    Among the human herpes viruses, three are neurotropic and capable of producing severe neurological abnormalities: herpes simplex virus type 1 and 2 (HSV-1 and HSV-2) and varicella-zoster virus (VZV). Both the acute, primary infection and the reactivation from the site of latent infection, the dorsal sensory ganglia, are associated with severe human morbidity and mortality. The peripheral nervous system is one of the major loci affected by these viruses. The present review details the virology and molecular biology underlying the human infection. This is followed by detailed description of the symtomatology, clinical presentation, diagnosis, course, therapy, and prognosis of disorders of the peripheral nervous system caused by these viruses.

  16. Molecular signaling mechanisms of axon-glia communication in the peripheral nervous system.

    PubMed

    Grigoryan, Tamara; Birchmeier, Walter

    2015-05-01

    In this article we discuss the molecular signaling mechanisms that coordinate interactions between Schwann cells and the neurons of the peripheral nervous system. Such interactions take place perpetually during development and in adulthood, and are critical for the homeostasis of the peripheral nervous system (PNS). Neurons provide essential signals to control Schwann cell functions, whereas Schwann cells promote neuronal survival and allow efficient transduction of action potentials. Deregulation of neuron-Schwann cell interactions often results in developmental abnormalities and diseases. Recent investigations have shown that during development, neuronally provided signals, such as Neuregulin, Jagged, and Wnt interact to fine-tune the Schwann cell lineage progression. In adult, the signal exchange between neurons and Schwann cells ensures proper nerve function and regeneration. Identification of the mechanisms of neuron-Schwann cell interactions is therefore essential for our understanding of the development, function and pathology of the peripheral nervous system as a whole.

  17. Detrimental impact of hyperlipidemia on the peripheral nervous system

    PubMed Central

    Wu, Song; Cao, Xu; He, Rongzhen; Xiong, Kun

    2012-01-01

    Recently, epidemiological studies on the etiology of peripheral neuropathies have revealed that hyperlipidemia is a novel risk factor. Plasma lipid levels were confirmed to be associated with the incidence of many peripheral neuropathies including axonal distal polyneuropathy, vision and hearing loss, motor nerve system lesions and sympathetic nerve system dysfunction. Moreover, different lipid components such as cholesterol, triacylglycerols and lipoprotein are involved in the pathogenesis of these neuropathies. This review aimed to discuss the effect of hyperlipidemia on the peripheral nervous system and its association with peripheral neuropathies. Furthermore, a detailed discussion focusing on the explicit mechanisms related to hyperlipidemia-induced peripheral neuropathies is presented here. These mechanisms, including intracellular oxidative stress, inflammatory lesions, ischemia and dysregulation of local lipid metabolism, share pathways and interact mutually. In addition, we examined current information on clinical trials to prevent and treat peripheral neuropathies caused by hyperlipidemia, with a predictive discussion regarding the orientation of future investigations. PMID:25774180

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

    PubMed

    Stüve, O; Zettl, U

    2014-03-01

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

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

    PubMed Central

    Stüve, O; Zettl, U

    2014-01-01

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

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

    PubMed

    Kamm, Christoph; Zettl, Uwe K

    2012-01-01

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

  1. 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.

  2. 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

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

    PubMed

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

    2017-01-01

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

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

    PubMed Central

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

    2017-01-01

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

  5. Current and future imaging of the peripheral nervous system.

    PubMed

    Ohana, M; Moser, T; Moussaouï, A; Kremer, S; Carlier, R Y; Liverneaux, P; Dietemann, J-L

    2014-01-01

    Peripheral nervous system (PNS) imaging is usually carried out by ultrasound and MRI. Thanks to its wide availability and excellent spatial resolution, ultrasound is a mature investigation with clearly established indications, particularly in entrapment syndromes and tumors. MRI is generally a second-line examination, which provides decisive additional information thanks to its excellent contrast resolution and its multiplanar abilities. This review describes the current methods for imaging the PNS, concentrating on acquisition techniques, normal results and basic pathological semiology. Ongoing and future developments are described in order to underline the forthcoming changes in this very dynamic field of musculoskeletal radiology.

  6. Insulin-like growth factors in the peripheral nervous system.

    PubMed

    Sakowski, Stacey A; Feldman, Eva L

    2012-06-01

    Insulin-like growth factors (IGFs) play an integral role in development, growth, and survival. This article details the current understanding of the effects of IGFs in the peripheral nervous system (PNS) during health and disease, and introduces how the IGF system regulates PNS development and impacts growth and survival of PNS cells. Also discussed are implications of IGF signaling in neurodegeneration and the status and prospects of IGF therapies for PNS conditions. There is substantial support for the application of IGF therapies in the treatment of PNS injury and disease.

  7. Pediatric Hashimoto's encephalopathy with peripheral nervous system involvement.

    PubMed

    Salpietro, Vincenzo; Mankad, Kshitij; Polizzi, Agata; Sugawara, Yuji; Granata, Francesca; David, Emanuele; Ferraù, Valeria; Gallizzi, Romina; Tortorella, Gaetano; Ruggieri, Martino

    2014-06-01

    Hashimoto encephalopathy is a syndrome of encephalopathy associated with elevated concentration of circulating serum anti-thyroid antibodies usually responsive to steroid therapy. We report a 13-year-old girl with Hashimoto encephalopathy and peripheral nervous system involvement. The child had experienced high-grade pyrexia, global headache and sleeplessness. After admission she had an ileus with a distended urinary bladder, hallucinations and cognitive impairment. She had reduced deep tendon reflexes and distal sensory deficiency. Anti-thyroglobulin antibodies were raised at 2121 IU/mL (normal, 0-40) and the anti-thyroperoxidase was high at 886 IU/mL (normal, 0-50). Progressive neurological and psychiatric remission was noted after i.v. methylprednisolone. Follow-up magnetic resonance imaging showed complete resolution of the foci of signal abnormality previously yielded. This case report is the first, to the best of our knowledge, to describe peripheral nervous system involvement in a child with a diagnosis of Hashimoto's encephalopathy.

  8. 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.

  9. 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

  10. Sexual dysfunction in patients with peripheral nervous system lesions.

    PubMed

    Podnar, Simon; Vodušek, David B

    2015-01-01

    Peripheral nervous system (PNS) disorders may cause sexual dysfunction (SD) in patients of both genders. These disorders include mainly polyneuropathies (particularly those affecting the autonomic nervous system (ANS)) and localized lesions affecting the innervation of genital organs. Impaired neural control may produce a malfunction of the genital response consisting of loss of genital sensitivity, erectile dysfunction, loss of vaginal lubrication, ejaculation disorder, and orgasmic disorder. In addition, there is often a loss of desire which actually has a complex pathogenesis, which goes beyond the mere loss of relevant nerve function. In patients who have no manifest health problems - particularly men with erectile dysfunction - one should always consider the possibility of an underlying polyneuropathy; in patients with SD after suspected denervation lesions of the innervation of genital organs within the lumbosacral spinal canal and in the pelvis, clinical neurophysiologic testing may clarify the PNS involvement. SD can alter self-esteem and lower patients' quality of life; opening up a discussion on sexual issues should be a part of the management of patients with PNS disorders. They may greatly benefit from counseling, education on coping strategies, and specific treatments.

  11. Fast optical signals in the peripheral nervous system

    NASA Astrophysics Data System (ADS)

    Tong, Yunjie; Martin, Jeffrey M.; Sassaroli, Angelo; Clervil, Patricia R.; Bergethon, Peter R.; Fantini, Sergio

    2006-07-01

    We present a study of the near-infrared optical response to electrical stimulation of peripheral nerves. The sural nerve of six healthy subjects between the ages of 22 and 41 was stimulated with transcutaneous electrical pulses in a region located approximately 10 cm above the ankle. A two-wavelength (690 and 830 nm) tissue spectrometer was used to probe the same sural nerve below the ankle. We measured optical changes that peaked 60 to 160 ms after the electrical stimulus. On the basis of the strong wavelength dependence of these fast optical signals, we argue that their origin is mostly from absorption rather than scattering. From these absorption changes, we obtain oxy- and deoxy-hemoglobin concentration changes that describe a rapid hemodynamic response to electrical nerve activation. In five out of six subjects, this hemodynamic response is an increase in total (oxy+deoxy) hemoglobin concentration, consistent with a fast vasodilation. Our findings support the hypothesis that the peripheral nervous system undergoes neurovascular coupling, even though more data is needed to prove such hypothesis.

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

    PubMed

    Mariotto, Sara; Ferrari, Sergio; Monaco, Salvatore

    2014-01-01

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

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

    PubMed Central

    Mariotto, Sara; Ferrari, Sergio; Monaco, Salvatore

    2014-01-01

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

  14. 78 FR 63481 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-24

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

  15. 77 FR 20037 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-03

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

  16. 75 FR 17417 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-06

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

  17. 75 FR 36428 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-25

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

  18. 78 FR 63478 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-24

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

  19. 78 FR 20328 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-04

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

  20. 76 FR 3912 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-21

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

  1. 75 FR 12768 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-17

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

  2. Mouse forward genetics in the study of the peripheral nervous system and human peripheral neuropathy

    PubMed Central

    Douglas, Darlene S.; Popko, Brian

    2009-01-01

    Forward genetics, the phenotype-driven approach to investigating gene identity and function, has a long history in mouse genetics. Random mutations in the mouse transcend bias about gene function and provide avenues towards unique discoveries. The study of the peripheral nervous system is no exception; from historical strains such as the trembler mouse, which led to the identification of PMP22 as a human disease gene causing multiple forms of peripheral neuropathy, to the more recent identification of the claw paw and sprawling mutations, forward genetics has long been a tool for probing the physiology, pathogenesis, and genetics of the PNS. Even as spontaneous and mutagenized mice continue to enable the identification of novel genes, provide allelic series for detailed functional studies, and generate models useful for clinical research, new methods, such as the piggyBac transposon, are being developed to further harness the power of forward genetics. PMID:18481175

  3. Transcriptional regulation of the peripheral nervous system in Ciona intestinalis.

    PubMed

    Joyce Tang, W; Chen, Jerry S; Zeller, Robert W

    2013-06-15

    The formation of the sensory organs and cells that make up the peripheral nervous system (PNS) relies on the activity of transcription factors encoded by proneural genes (PNGs). Although PNGs have been identified in the nervous systems of both vertebrates and invertebrates, the complexity of their interactions has complicated efforts to understand their function in the context of their underlying regulatory networks. To gain insight into the regulatory network of PNG activity in chordates, we investigated the roles played by PNG homologs in regulating PNS development of the invertebrate chordate Ciona intestinalis. We discovered that in Ciona, MyT1, Pou4, Atonal, and NeuroD-like are expressed in a sequential regulatory cascade in the developing epidermal sensory neurons (ESNs) of the PNS and act downstream of Notch signaling, which negatively regulates these genes and the number of ESNs along the tail midlines. Transgenic embryos mis-expressing any of these proneural genes in the epidermis produced ectopic midline ESNs. In transgenic embryos mis-expressing Pou4, and MyT1 to a lesser extent, numerous ESNs were produced outside of the embryonic midlines. In addition we found that the microRNA miR-124, which inhibits Notch signaling in ESNs, is activated downstream of all the proneural factors we tested, suggesting that these genes operate collectively in a regulatory network. Interestingly, these factors are encoded by the same genes that have recently been demonstrated to convert fibroblasts into neurons. Our findings suggest the ascidian PNS can serve as an in vivo model to study the underlying regulatory mechanisms that enable the conversion of cells into sensory neurons.

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

    NASA Astrophysics Data System (ADS)

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

    2012-02-01

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

  5. 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.

  6. 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.

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

    PubMed Central

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

    1996-01-01

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

  8. Peripheral nervous system lesion syndromes and the mechanisms of their formation in connective tissue diseases.

    PubMed

    Spirin, N N; Bulanova, V A; Pizova, N V; Shilkina, N P

    2007-01-01

    Systemic rheumatological diseases are often accompanied by the development of central and peripheral nervous system pathology. Data providing evidence of the high incidence of peripheral nervous system lesions in systemic lupus erythematosus and systemic scleroderma are presented. These diseases in particular are characterized by polyneuropathies and tunnel syndromes. Our own observations, along with published data, revealed the following major pathogenetic mechanisms of peripheral nervous system lesions in diffuse connective tissue diseases - ischemic, immunological, and metabolic. Consideration of these mechanisms will lead to pathogenetically based treatment and improved therapeutic outcomes.

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

    SciTech Connect

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

    1991-01-01

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

  10. Experience with examination of the spinal cord and peripheral nervous system (PNS) in mice: A brief overview.

    PubMed

    Krinke, Georg J; Herrmann, Annika; Körner, Annette; Landes, Christian; Sauner, Francine

    2014-09-01

    The representative areas for examination of the mouse peripheral nervous system are the spinal cord, containing central components of the peripheral nervous system that needs to be examined at least at cervical and lumbar level, the sciatic and the tibial nerve. Skeletal muscle samples should include the soleus muscle and the quadriceps femoris or long digital extensor, as well as the medial gastrocnemius. Examination can be extended to the thoracic spinal cord, lumbar dorsal root ganglia and spinal nerve roots, as well as the plantar nerve, and other areas of interest. Perfusion fixation is considered optimal for the nervous system; however, immersion fixation allows producing microscopic sections of excellent quality as well. Paraffin-embedded, hematoxylin and eosin-stained sections can be made from all areas, save for small nerves such as the tibial or plantar nerve, which are examined with advantage in hard plastic sections. It is possible to produce hard plastic sections also of the vertebral column, including the spinal cord, dorsal root ganglia and nerve roots. For special investigations, mice can be fixed in toto, decalcified, embedded and sectioned to reveal the areas of interest. In the mouse peripheral nerves, myelination progresses until the adult age. In aging peripheral nerves there is axonal atrophy, degeneration, nerve fiber loss, increase of collagen and sporadic demyelination, especially radiculoneuropathy. The dorsal root ganglia of untreated control animals show frequent cytoplasmic vacuolation. Axonal degeneration is distally, primary demyelination proximally accentuated. Mouse is not very sensitive to peripheral neurotoxicity: to induce toxic peripheral neuropathy mostly parenteral administration and/or newborn animals are used. Naturally occurring infection affecting the spinal cord and peripheral nerves is Theiler's encephalomyelitis virus inducing acute poliomyelitis or chronic demyelination. Any experimental results are to be assessed

  11. [Syndromes of peripheral nervous system lesions and mechanisms of their formation in disorders of connective tissue].

    PubMed

    Spirin, N N; Bulanova, V A; Pizova, N V; Shilkina, N P

    2005-01-01

    Systemic rheumatoid diseases are often concomitant with the development of central and peripheral systems pathologies. Presented are the results revealing high frequency of peripheral nervous system lesions (lupus erythematosus and systemic scleroderma), which characterized by polyneuropathy and tunnel syndromes. Based on the results of literature and own studies, pathological mechanisms of peripheral nervous system lesions in diffusion disorders of connective tissue were singled out as follows: ischemic, immunological and metabolic. Taking these mechanisms into account will permit to conduct pathogenetically valid therapy and to improve its results.

  12. Water channel proteins in the peripheral nervous system in health and disease.

    PubMed

    Ma, Tonghui; Gao, Hongwen; Fang, Xuedong; Yang, Hong

    2012-01-01

    The expression and function of aquaporins (AQPs) in the peripheral nervous system is a relatively under-investigated subject. Since the original description of AQP1 mRNA expression in the trigeminal ganglion in 2004, there has been significant progress in describing the expression, regulation and function of AQPs in the peripheral nervous system. Three out of the 13 mammalian AQPs (AQP1, AQP2 and AQP4) have been localized to neurons or glial cells in trigeminal ganglia, periodontal Ruffini endings, dorsal root ganglia and the enteric nervous system. Functional studies using knockout mice have suggested the involvement of AQP1 in peripheral pain perception. This review discusses current progress in this field and the possible involvement of AQPs in peripheral neuropathies.

  13. 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

  14. Reflections on osteopathic fascia treatment in the peripheral nervous system

    PubMed Central

    Bordoni, Bruno; Bordoni, Giovanni

    2015-01-01

    The peripheral nerve is composed of several layers of fascia tissue, which can become a source of pain if the way they slide is impeded. It is only recently that fascial osteopathy research has been aimed at understanding what happens to the fascia following treatment, and as a result of previous studies, we are able to highlight some of the benefits, including a reduction in local pain and inflammation. The osteopathic approach to the fascial system of the peripheral nerve does not have a grounding in scientific research, being based instead on the clinical experience of individual operators, despite peripheral nerve palpation being used as a method to evaluate and test its function. The authors wish to encourage the initiation of new research in the fields of academic and clinical osteopathy that is aimed at quantifying the possible benefits a patient may derive from osteopathic treatment of the peripheral nerve. PMID:26586962

  15. Neurogenic inflammation and the peripheral nervous system in host defense and immunopathology.

    PubMed

    Chiu, Isaac M; von Hehn, Christian A; Woolf, Clifford J

    2012-07-26

    The peripheral nervous and immune systems are traditionally thought of as serving separate functions. The line between them is, however, becoming increasingly blurred by new insights into neurogenic inflammation. Nociceptor neurons possess many of the same molecular recognition pathways for danger as immune cells, and, in response to danger, the peripheral nervous system directly communicates with the immune system, forming an integrated protective mechanism. The dense innervation network of sensory and autonomic fibers in peripheral tissues and high speed of neural transduction allows rapid local and systemic neurogenic modulation of immunity. Peripheral neurons also seem to contribute to immune dysfunction in autoimmune and allergic diseases. Therefore, understanding the coordinated interaction of peripheral neurons with immune cells may advance therapeutic approaches to increase host defense and suppress immunopathology.

  16. Developmental study of tripeptidyl peptidase I activity in the mouse central nervous system and peripheral organs.

    PubMed

    Dimitrova, Mashenka; Deleva, Denislava; Pavlova, Velichka; Ivanov, Ivaylo

    2011-11-01

    Tripeptidyl peptidase I (TPPI) - a lysosomal serine protease - is encoded by the CLN2 gene, mutations that cause late-infantile neuronal ceroid lipofuscinosis (LINCL) connected with profound neuronal loss, severe clinical symptoms and early death at puberty. Developmental studies of TPPI activity levels and distribution have been done in the human and rat central nervous systems (CNS) and visceral organs. Similar studies have not been performed in mouse. In this paper, we follow up on the developmental changes in the enzyme activity and localization pattern in the CNS and visceral organs of mouse over the main periods of life - embryonic, neonate, suckling, infantile, juvenile, adult and aged - using biochemical assays and enzyme histochemistry. In the studied peripheral organs (liver, kidney, spleen, pancreas and lung) TPPI is present at birth but further its pattern is not consistent in different organs over different life periods. TPPI activity starts to be expressed in the brain at the 10th embryonic day but in most neuronal types it appears at the early infantile period, increases during infancy, reaches high activity levels in the juvenile period and is highest in adult and aged animals. Thus, in mice TPPI activity becomes crucial for the neuronal functions later in development (juvenile period) than in humans and does not decrease with aging. These results are essential as a basis for comparison between normal and pathological TPPI patterns in mice. They can be valuable in view of the use of animal models for studying LINCL and other neurodegenerative disorders.

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

    SciTech Connect

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

    1988-01-01

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

  18. [When prions use the systems of communication between the immune system and the peripheral nervous system].

    PubMed

    Dorban, Gauthier; Antoine, Nadine; Defaweux, Valérie

    2010-01-01

    Prion disease pathogenesis has been largely studied since the inter-species transmissibility of the infectious protein (PrPSc), the oral uptake as natural route of infection and the exceptional implication in a problem of public health were highlighted. Two sequential preclinical stages are observed before the development of irreversible and fatal lesions in the central nervous system: the lymphoinvasion and the neuroinvasion. The first is characterized by the accumulation of PrPSc within lymphoid tissues and the second by PrPSc scattering the peripheral nervous system towards the central nervous system. The mechanisms involved in the communication between the immune and the peripheral nervous system are still debated. Recent studies even suggest that neuroinvasion can occur through the hematogenous route, independently of the peripheral nervous system. This review analyses (i) the role of immune cells, implicated in prion pathogenesis: dendritic cells as PrPSc vehicle, follicular dendritic cells as PrPSc accumulator and nerve fibres as PrPSc driver and (ii) the respective relations they maintain with peripheral nerve fibres to migrate to the brain.

  19. Immunocytochemical Localization of Monoamine Oxidase Type B in Rat's Peripheral Nervous System.

    PubMed

    Chen, Qiang; Xu, Yang; Zhang, Hui; Tan, Xiao; Liu, Shu Hui; Yan, Fen

    2015-11-01

    Immunohistochemistry is used to investigate subcellular localization of monoamine oxidase type B (MAOB) in the axon of the rat's peripheral nervous system. Through light and electron microscopy, the presence of MAOB-immunoreactive structures in the propria lamina of tongue and on the outer membranes of mitochondria in both myelinated and unmyelinated axons can be detected. As a result, MAOB may potentially play a crucial role in the axons of the rat's peripheral nervous system and may be closely associated with both axonal transport and nerve conduction.

  20. The glia of the adult Drosophila nervous system

    PubMed Central

    Kremer, Malte C.; Jung, Christophe; Batelli, Sara; Rubin, Gerald M.

    2017-01-01

    Glia play crucial roles in the development and homeostasis of the nervous system. While the GLIA in the Drosophila embryo have been well characterized, their study in the adult nervous system has been limited. Here, we present a detailed description of the glia in the adult nervous system, based on the analysis of some 500 glial drivers we identified within a collection of synthetic GAL4 lines. We find that glia make up ∼10% of the cells in the nervous system and envelop all compartments of neurons (soma, dendrites, axons) as well as the nervous system as a whole. Our morphological analysis suggests a set of simple rules governing the morphogenesis of glia and their interactions with other cells. All glial subtypes minimize contact with their glial neighbors but maximize their contact with neurons and adapt their macromorphology and micromorphology to the neuronal entities they envelop. Finally, glial cells show no obvious spatial organization or registration with neuronal entities. Our detailed description of all glial subtypes and their regional specializations, together with the powerful genetic toolkit we provide, will facilitate the functional analysis of glia in the mature nervous system. GLIA 2017 GLIA 2017;65:606–638 PMID:28133822

  1. Influence of cadmium on the distribution of Cu, Zn, and Fe in different regions of central and peripheral nervous system of rats

    SciTech Connect

    Saxena, D.K.; Murthy, R.C.; Jain, V.K.; Chandra, S.V.

    1986-03-01

    Growing and adult rats were exposed to cadmium (100 ppm through drinking water) daily for 120 days to investigate the distribution of cadmium, zinc, copper and iron in various parts of central and peripheral nervous regions. The study indicates marked cadmium accumulation in growing rats as compared to the adults. Besides, decrease in Cu and Zn and increase in Fe contents of various nervous regions was observed which was more marked in cerebral cortex and cerebellar regions of the rats exposed since 21 days of age than in adulthood.

  2. 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.

  3. 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…

  4. Nervous system involvement in clinical peripheral inflammation: A description of three pediatric cases.

    PubMed

    Vitaliti, Giovanna; Tabatabaie, Omidreza; Matin, Nassim; Giugno, Giovanni Roberto; Pavone, Piero; Lubrano, Riccardo; Falsaperla, Raffaele

    2016-01-01

    Latest research data have emphasized the interaction between the nervous and the immune systems. In this regard, it has been demonstrated that the disruption of the blood-brain barrier (BBB) secondary to peripheral inflammation may play a key role in this relationship. This assumption is linked to recent findings according to which units that constitute the BBB are not only simply neurologic but have also been reconsidered as "neurovascular" elements, through which immune system molecules are vehiculated within the central nervous system (CNS). Herein, we report two cases of food allergy (FA) and one case of infective gastroenteritis, associated with a spectrum of neurologic disorders involving both the CNS and the peripheral nervous system (PNS), postulating some etiopathogenic hypotheses to explain the link between peripheral inflammation and diseases of the nervous system (NS). Three pediatric cases of secondary NS involvement after gastrointestinal (GI) inflammation of different nature have been reported. The first case highlights the link between FA and CNS; the second one is based on a description of a link between GI infection and CNS involvement while the third one describes the relationship between FA and PNS. The importance of these reports relies on the clinical demonstration of a link between the immune system and the NS. The relationship between immune system and NS seems to have pleiotropic aspects, involving different areas of the NS, such as CNS and PNS, which also seem to be in some way interconnected.

  5. 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.

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

    PubMed

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

    2012-09-01

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

  7. CFTR-deficient pigs display peripheral nervous system defects at birth

    PubMed Central

    Reznikov, Leah R.; Dong, Qian; Chen, Jeng-Haur; Moninger, Thomas O.; Park, Jung Min; Zhang, Yuzhou; Hildebrand, Michael S.; Smith, Richard J. H.; Randak, Christoph O.; Stoltz, David A.; Welsh, Michael J.

    2013-01-01

    Peripheral nervous system abnormalities, including neuropathy, have been reported in people with cystic fibrosis. These abnormalities have largely been attributed to secondary manifestations of the disease. We tested the hypothesis that disruption of the cystic fibrosis transmembrane conductance regulator (CFTR) gene directly influences nervous system function by studying newborn CFTR−/− pigs. We discovered CFTR expression and activity in Schwann cells, and loss of CFTR caused ultrastructural myelin sheath abnormalities similar to those in known neuropathies. Consistent with neuropathic changes, we found increased transcripts for myelin protein zero, a gene that, when mutated, can cause axonal and/or demyelinating neuropathy. In addition, axon density was reduced and conduction velocities of the trigeminal and sciatic nerves were decreased. Moreover, in vivo auditory brainstem evoked potentials revealed delayed conduction of the vestibulocochlear nerve. Our data suggest that loss of CFTR directly alters Schwann cell function and that some nervous system defects in people with cystic fibrosis are likely primary. PMID:23382208

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

    PubMed

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

    1981-01-01

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

  9. Plastic fantastic: Schwann cells and repair of the peripheral nervous system.

    PubMed

    Kim, Haesun A; Mindos, Thomas; Parkinson, David B

    2013-08-01

    Repair in the peripheral nervous system (PNS) depends upon the plasticity of the myelinating cells, Schwann cells, and their ability to dedifferentiate, direct axonal regrowth, remyelinate, and allow functional recovery. The ability of such an exquisitely specialized myelinating cell to revert to an immature dedifferentiated cell that can direct repair is remarkable, making Schwann cells one of the very few regenerative cell types in our bodies. However, the idea that the PNS always repairs after injury, in contrast to the central nervous system, is not true. Repair in patients after nerve trauma can be incredibly variable, depending on the site and type of injury, and only a relatively small number of axons may fully regrow and reinnervate their targets. Recent research has shown that it is an active process that drives Schwann cells back to an immature state after injury and that this requires activity of the p38 and extracellular-regulated kinase 1/2 mitogen-activated protein kinases, as well as the transcription factor cJun. Analysis of the events after peripheral nerve transection has shown how signaling from nerve fibroblasts forms Schwann cells into cords in the newly generated nerve bridge, via Sox2 induction, to allow the regenerating axons to cross the gap. Understanding these pathways and identifying additional mechanisms involved in these processes raises the possibility of both boosting repair after PNS trauma and even, possibly, blocking the inappropriate demyelination seen in some disorders of the peripheral nervous system.

  10. Conduction block in the peripheral nervous system in experimental allergic encephalomyelitis

    NASA Astrophysics Data System (ADS)

    Pender, M. P.; Sears, T. A.

    1982-04-01

    Experimental allergic encephalomyelitis (EAE) has been widely studied as a model of multiple sclerosis, a central nervous system (CNS) disease of unknown aetiology. The clinical features of both EAE and multiple sclerosis provide the only guide to the progress and severity of these diseases, and are used to assess the response to treatment. In such comparisons the clinical features of EAE are assumed to be due to lesions in the CNS, but in this disease there is also histological evidence of damage to the peripheral nervous system1-8. However, the functional consequences of such peripheral lesions have been entirely ignored. To examine this we have studied nerve conduction in rabbits with EAE. We report here that most of the large diameter afferent fibres are blocked in the region of the dorsal root ganglion and at the dorsal root entry zone, thus accounting for the loss of tendon jerks and also, through the severe loss of proprioceptive information, the ataxia of these animals. We conclude that whenever clinical comparisons are made between EAE and multiple sclerosis, the pathophysiology associated with the histological damage of the peripheral nervous system must be taken into account.

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

    PubMed

    Ungerer, Petra; Geppert, Maria; Wolff, Carsten

    2011-03-01

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

  12. Adult peripheral neuroepithelioma in Meckel's cave.

    PubMed

    Midroni, G; Dhanani, A N; Gray, T; Tucker, W S; Bilbao, J M

    1991-02-01

    A case of peripheral neuroepithelioma arising from the trigeminal nerve in Meckel's cave is presented. The discussion emphasizes the pathological criteria for the diagnosis of a peripheral neuroepithelioma and the current controversy about the classification of this and related tumors.

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

    PubMed Central

    Sengupta, Dola; Kar, Sandip

    2016-01-01

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

  14. Neuronal ADAM10 Promotes Outgrowth of Small-Caliber Myelinated Axons in the Peripheral Nervous System.

    PubMed

    Meyer zu Horste, Gerd; Derksen, Angelika; Stassart, Ruth; Szepanowski, Fabian; Thanos, Melissa; Stettner, Mark; Boettcher, Christina; Lehmann, Helmar C; Hartung, Hans-Peter; Kieseier, Bernd C

    2015-11-01

    The regulation of myelination and axonal outgrowth in the peripheral nervous system is controlled by a complex signaling network involving various signaling pathways. Members of the A Disintegrin And Metalloproteinase (ADAM) family are membrane-anchored proteinases with both proteolytic and disintegrin characteristics that modulate the function of signaling molecules. One family member, ADAM17, is known to influence myelination by cleaving and thus regulating one of the key signals, neuregulin-1, which controls peripheral nervous system myelination. A similar function for ADAM10 had been suggested by previous in vitro studies. Here, we assessed whether ADAM10 exerts a similar function in vivo and deleted ADAM10 in a cell type-specific manner in either neurons or Schwann cells. We found that ADAM10 is not required in either Schwann cells or neurons for normal myelination during development or for remyelination after injury. Instead, ADAM10 is required specifically in neurons for the outgrowth of myelinated small-fiber axons in vitro and after injury in vivo. Thus, we report for the first time a neuron-intrinsic function of ADAM10 in axonal regeneration that is distinct from that of the related protein family member ADAM17 and that may have implications for targeting ADAM function in nervous system diseases.

  15. From classical to current: analyzing peripheral nervous system and spinal cord lineage and fate.

    PubMed

    Butler, Samantha J; Bronner, Marianne E

    2015-02-15

    During vertebrate development, the central (CNS) and peripheral nervous systems (PNS) arise from the neural plate. Cells at the margin of the neural plate give rise to neural crest cells, which migrate extensively throughout the embryo, contributing to the majority of neurons and all of the glia of the PNS. The rest of the neural plate invaginates to form the neural tube, which expands to form the brain and spinal cord. The emergence of molecular cloning techniques and identification of fluorophores like Green Fluorescent Protein (GFP), together with transgenic and electroporation technologies, have made it possible to easily visualize the cellular and molecular events in play during nervous system formation. These lineage-tracing techniques have precisely demonstrated the migratory pathways followed by neural crest cells and increased knowledge about their differentiation into PNS derivatives. Similarly, in the spinal cord, lineage-tracing techniques have led to a greater understanding of the regional organization of multiple classes of neural progenitor and post-mitotic neurons along the different axes of the spinal cord and how these distinct classes of neurons assemble into the specific neural circuits required to realize their various functions. Here, we review how both classical and modern lineage and marker analyses have expanded our knowledge of early peripheral nervous system and spinal cord development.

  16. Effects of alpha-glucosylhesperidin on the peripheral body temperature and autonomic nervous system.

    PubMed

    Takumi, Hiroko; Fujishima, Noboru; Shiraishi, Koso; Mori, Yuka; Ariyama, Ai; Kometani, Takashi; Hashimoto, Shinichi; Nadamoto, Tomonori

    2010-01-01

    We studied the effects of alpha-glucosylhesperidin (G-Hsp) on the peripheral body temperature and autonomic nervous system in humans. We first conducted a survey of 97 female university students about excessive sensitivity to the cold; 74% of them replied that they were susceptible or somewhat susceptible to the cold. We subsequently conducted a three-step experiment. In the first experiment, G-Hsp (500 mg) was proven to prevent a decrease in the peripheral body temperature under an ambient temperature of 24 degrees C. In the second experiment, a warm beverage containing G-Hsp promoted blood circulation and kept the finger temperature higher for a longer time. We finally used a heart-rate variability analysis to study whether G-Hsp changed the autonomic nervous activity. The high-frequency (HF) component tended to be higher, while the ratio of the low-frequency (LF)/HF components tended to be lower after the G-Hsp administration. These results suggest that the mechanism for temperature control by G-Hsp might involve an effect on the autonomic nervous system.

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

    PubMed

    Abrams, Charles K; Freidin, Mona

    2015-06-01

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

  18. Activities and functions of peripheral neurons in the enteric nervous system of Aplysia and Lymnaea.

    PubMed

    Kurokawa, M; Ito, S; Okamoto, T

    2008-01-01

    In order to explore the functions of the peripheral neurons in the enteric nervous system (ENS) of the gastropods, Aplysia and Lymnaea, we investigated the correlation between peripheral neuronal activities and movements of the digestive tract. In Aplysia, movements of the gizzard were distinguished into two types of contraction: a large constriction of the whole gizzard following bursting activities of the neurons on the gizzard and EJP-like potentials in the musculature; and a small contraction of a restricted part of the gizzard following a slow muscle potential. When TTX was applied to isolated gizzard preparation, the bursting activities were blocked and the EJP-like potentials and the subsequent constriction disappeared, whereas the slow potentials in the musculature and partial contractions appeared to be unaffected. Therefore, it was suggested that the peripheral neurons on the gizzard were motor neurons for constriction, while the partial contraction was thought to be myogenic. In Lymnaea, we recorded periodic bursting activities in the enteric nervous system that were followed by EJP-like potentials and gastrointestinal movements. The results show that, in both species, there may exist motor neurons in the ENS that are responsible for neurogenic movements of the digestive tract.

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

    PubMed Central

    Matoba, Ken; Muramatsu, Rieko; Yamashita, Toshihide

    2017-01-01

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

  20. [The brothers of Jumiege--the peripheral nervous system in early French mythology].

    PubMed

    Brean, Are

    2002-03-20

    This article reviews the process of discovery of the nervous system from Pythagoras (570-500 BC) to Galen (130-201 AD). After Galen, no anatomical studies were performed before the renaissance. According to a legend, probably produced for political reasons, two brothers, sons of the French king Clovis II, revolted against their father and were sentenced to loose their physical powers by having the nerves of their arms and legs cut. They were then set adrift on the river Seine, stranding at the Jumiège monastery. The earliest written version of this legend stems from the fourteenth century; it was probably a part of the local French mythology. This indicates that the existence of the peripheral nervous system, and therefore also in part the knowledge contained in the early anatomical works, quite early may have been more or less known outside academic circles.

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

    PubMed

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

    2012-08-21

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

  2. Malignant involvement of the peripheral nervous system in patients with cancer: multimodality imaging and pathologic correlation.

    PubMed

    Crush, Andrew Bryce; Howe, Benjamin Matthew; Spinner, Robert J; Amrami, Kimberly K; Hunt, Christopher Harker; Johnson, Geoffrey B; Murphy, Robert C; Morreale, Robert F; Peller, Patrick J

    2014-01-01

    The clinical and imaging evaluation of peripheral neuropathies in patients with cancer is challenging. It is critically important to differentiate malignant invasion of the peripheral nervous system from nonmalignant causes, such as radiation-induced neuritis, neuropathy associated with chemotherapy, and inflammatory neuropathies. Contrast material-enhanced magnetic resonance (MR) imaging is the initial noninvasive test of choice; however, interpretation can be challenging when the anatomic features are distorted by prior surgery, radiation, or both. Fluorine 18 ((18)F)-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is an imaging adjunct to MR imaging that is particularly helpful for evaluating peripheral nerves because the metabolic activity depicted with (18)F-FDG PET/CT helps differentiate malignant from benign disease and assists in making certain management decisions. For example, sites of high (18)F-FDG activity in a peripheral nerve can be targeted to increase the diagnostic yield of a biopsy because malignant involvement of peripheral nerves can be patchy. Of note, (18)F-FDG PET/CT can show clinically unsuspected metastases elsewhere in the body. If cancer is found, (18)F-FDG PET/CT allows excellent assessment of treatment response. (18)F-FDG PET/CT is also useful in evaluating primary nerve sheath tumors in that such tumors with low metabolic activity on FDG PET/CT images are unlikely to be malignant, although the specificity is limited. It is essential to have a good understanding of the imaging characteristics of benign and malignant causes of peripheral neuropathy if (18)F-FDG PET/CT is to be used effectively for accurate diagnosis.

  3. DNA damage response in peripheral nervous system: coping with cancer therapy-induced DNA lesions.

    PubMed

    Englander, Ella W

    2013-08-01

    In the absence of blood brain barrier (BBB) the DNA of peripheral nervous system (PNS) neurons is exposed to a broader spectrum of endogenous and exogenous threats compared to that of the central nervous system (CNS). Hence, while CNS and PNS neurons cope with many similar challenges inherent to their high oxygen consumption and vigorous metabolism, PNS neurons are also exposed to circulating toxins and inflammatory mediators due to relative permeability of PNS blood nerve barrier (BNB). Consequently, genomes of PNS neurons incur greater damage and the question awaiting investigation is whether specialized repair mechanisms for maintenance of DNA integrity have evolved to meet the additional needs of PNS neurons. Here, I review data showing how PNS neurons manage collateral DNA damage incurred in the course of different anti-cancer treatments designed to block DNA replication in proliferating tumor cells. Importantly, while PNS neurotoxicity and concomitant chemotherapy-induced peripheral neuropathy (CIPN) are among major dose limiting barriers in achieving therapy goals, CIPN is partially reversible during post-treatment nerve recovery. Clearly, cell recovery necessitates mobilization of the DNA damage response and underscores the need for systematic investigation of the scope of DNA repair capacities in the PNS to help predict post-treatment risks to recovering neurons.

  4. A case report of gastric cancer with brain metastasis: Rare peripheral nervous system symptoms.

    PubMed

    Yang, Ge-Liang; Luo, Tian-Hang; Zhang, Hui-Qing; Ling, Chang-Quan; Li, Bai

    2016-04-01

    Gastric cancer with brain metastasis is rare. The present study reports a case of gastric cancer with isolated brain metastasis 1 year after gastrectomy. To the best of our knowledge, there have been no prior reports of solitary brain metastasis from gastric cancer with peripheral nervous system symptoms. A distal gastrectomy was performed on a 60-year-old male patient with gastric cancer in November 2012. Postoperative pathological analysis revealed a moderately differentiated adenocarcinoma with tumor invasion into the serosa and metastasis to one dissected lymph node. No abnormalities were found at follow-up examination. However, a tumor representing metastasis to the brain was recognized by a cranial enhanced magnetic resonance imaging examination 1 year after gastrectomy, which was performed when the patient exhibited numbness and thigmesthesia. The patient was administered 30 Gy of stereotactic radiotherapy, delivered in 5 fractions. The patient succumbed to disease 10 months subsequent to undergoing radiotherapy. This case report suggests that gastric cancer may re-present as brain metastasis with peripheral nervous system symptoms.

  5. Endoplasmic reticulum stress in the peripheral nervous system is a significant driver of neuropathic pain.

    PubMed

    Inceoglu, Bora; Bettaieb, Ahmed; Trindade da Silva, Carlos A; Lee, Kin Sing Stephen; Haj, Fawaz G; Hammock, Bruce D

    2015-07-21

    Despite intensive effort and resulting gains in understanding the mechanisms underlying neuropathic pain, limited success in therapeutic approaches have been attained. A recently identified, nonchannel, nonneurotransmitter therapeutic target for pain is the enzyme soluble epoxide hydrolase (sEH). The sEH degrades natural analgesic lipid mediators, epoxy fatty acids (EpFAs), therefore its inhibition stabilizes these bioactive mediators. Here we demonstrate the effects of EpFAs on diabetes induced neuropathic pain and define a previously unknown mechanism of pain, regulated by endoplasmic reticulum (ER) stress. The activation of ER stress is first quantified in the peripheral nervous system of type I diabetic rats. We demonstrate that both pain and markers of ER stress are reversed by a chemical chaperone. Next, we identify the EpFAs as upstream modulators of ER stress pathways. Chemical inducers of ER stress invariably lead to pain behavior that is reversed by a chemical chaperone and an inhibitor of sEH. The rapid occurrence of pain behavior with inducers, equally rapid reversal by blockers and natural incidence of ER stress in diabetic peripheral nervous system (PNS) argue for a major role of the ER stress pathways in regulating the excitability of the nociceptive system. Understanding the role of ER stress in generation and maintenance of pain opens routes to exploit this system for therapeutic purposes.

  6. FlyPNS, a database of the Drosophila embryonic and larval peripheral nervous system

    PubMed Central

    Orgogozo, Virginie; Grueber, Wesley B

    2005-01-01

    Background The embryonic and larval peripheral nervous system of Drosophila melanogaster is extensively studied as a very powerful model of developmental biology. One main advantage of this system is the ability to study the origin and development of individual sensory cells. However, there remain several discrepancies regarding the organization of sensory organs in each abdominal segment A1-A7. Description We have constructed a web site called FlyPNS (for Fly Peripheral Nervous System) that consolidates a wide range of published and unpublished information about the embryonic and larval sensory organs. It communicates (1) a PNS pattern that solves the discrepancies that have been found in the recent literature, (2) the correspondence between the different nomenclatures that have been used so far, (3) a comprehensive description of each sensory organ, and (4) a list of both published and unpublished markers to reliably identify each PNS cell. Conclusions The FlyPNS database integrates disparate data and nomenclature and thus helps understanding the conflicting observations that have been published recently. Furthermore, it is designed to provide assistance in the identification and study of individual sensory cells. We think it will be a useful resource for any researcher with interest in Drosophila sensory organs. PMID:15717925

  7. Mechanistic relationship between the vagal afferent pathway, central nervous system and peripheral organs in appetite regulation.

    PubMed

    Ueno, Hiroaki; Nakazato, Masamitsu

    2016-11-01

    The hypothalamus is a center of food intake and energy metabolism regulation. Information signals from peripheral organs are mediated through the circulation or the vagal afferent pathway and input into the hypothalamus, where signals are integrated to determine various behaviors, such as eating. Numerous appetite-regulating peptides are expressed in the central nervous system and the peripheral organs, and interact in a complex manner. Of such peptides, gut peptides are known to bind to receptors at the vagal afferent pathway terminal that extend into the mucosal layer of the digestive tract, modulate the electrical activity of the vagus nerve, and subsequently send signals to the solitary nucleus and furthermore to the hypothalamus. All peripheral peptides other than ghrelin suppress appetite, and they synergistically suppress appetite through the vagus nerve. In contrast, the appetite-enhancing peptide, ghrelin, antagonizes the actions of appetite-suppressing peptides through the vagus nerve, and appetite-suppressing peptides have attenuated effects in obesity as a result of inflammation in the vagus nerve. With greater understanding of the mechanism for food intake and energy metabolism regulation, medications that apply the effects of appetite-regulating peptides or implantable devices that electrically stimulate the vagus nerve are being investigated as novel treatments for obesity in basic and clinical studies.

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

    PubMed Central

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

    1979-01-01

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

  9. 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

  10. 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.

  11. Robust Central Nervous System Pathology in Transgenic Mice following Peripheral Injection of α-Synuclein Fibrils.

    PubMed

    Ayers, Jacob I; Brooks, Mieu M; Rutherford, Nicola J; Howard, Jasie K; Sorrentino, Zachary A; Riffe, Cara J; Giasson, Benoit I

    2017-01-15

    Misfolded α-synuclein (αS) is hypothesized to spread throughout the central nervous system (CNS) by neuronal connectivity leading to widespread pathology. Increasing evidence indicates that it also has the potential to invade the CNS via peripheral nerves in a prion-like manner. On the basis of the effectiveness following peripheral routes of prion administration, we extend our previous studies of CNS neuroinvasion in M83 αS transgenic mice following hind limb muscle (intramuscular [i.m.]) injection of αS fibrils by comparing various peripheral sites of inoculations with different αS protein preparations. Following intravenous injection in the tail veins of homozygous M83 transgenic (M83(+/+)) mice, robust αS pathology was observed in the CNS without the development of motor impairments within the time frame examined. Intraperitoneal (i.p.) injections of αS fibrils in hemizygous M83 transgenic (M83(+/-)) mice resulted in CNS αS pathology associated with paralysis. Interestingly, injection with soluble, nonaggregated αS resulted in paralysis and pathology in only a subset of mice, whereas soluble Δ71-82 αS, human βS, and keyhole limpet hemocyanin (KLH) control proteins induced no symptoms or pathology. Intraperitoneal injection of αS fibrils also induced CNS αS pathology in another αS transgenic mouse line (M20), albeit less robustly in these mice. In comparison, i.m. injection of αS fibrils was more efficient in inducing CNS αS pathology in M83 mice than i.p. or tail vein injections. Furthermore, i.m. injection of soluble, nonaggregated αS in M83(+/-) mice also induced paralysis and CNS αS pathology, although less efficiently. These results further demonstrate the prion-like characteristics of αS and reveal its efficiency to invade the CNS via multiple routes of peripheral administration.

  12. Central Nervous System-Peripheral Immune System Dialogue in Neurological Disorders: Possible Application of Neuroimmunology in Urology

    PubMed Central

    2016-01-01

    Previous concepts of immune-privileged sites obscured the role of peripheral immune cells in neurological disorders and excluded the consideration of the potential benefits of immunotherapy. Recently, however, numerous studies have demonstrated that the blood–brain barrier in the central nervous system is an educational barrier rather than an absolute barrier to peripheral immune cells. Emerging knowledge of immune-privileged sites suggests that peripheral immune cells can infiltrate these sites via educative gates and that crosstalk can occur between infiltrating immune cells and the central nervous system parenchyma. This concept can be expanded to the testis, which has long been considered an immune-privileged site, and to neurogenic bladder dysfunction. Thus, we propose that the relationship between peripheral immune cells, the brain, and the urologic system should be considered as an additional possible mechanism in urologic diseases, and that immunotherapy might be an alternative therapeutic strategy in treating neurogenic bladder dysfunction. PMID:27230462

  13. Central Nervous System-Peripheral Immune System Dialogue in Neurological Disorders: Possible Application of Neuroimmunology in Urology.

    PubMed

    Park, Hyun-Sun; Park, Min-Jung; Kwon, Min-Soo

    2016-05-01

    Previous concepts of immune-privileged sites obscured the role of peripheral immune cells in neurological disorders and excluded the consideration of the potential benefits of immunotherapy. Recently, however, numerous studies have demonstrated that the blood-brain barrier in the central nervous system is an educational barrier rather than an absolute barrier to peripheral immune cells. Emerging knowledge of immune-privileged sites suggests that peripheral immune cells can infiltrate these sites via educative gates and that crosstalk can occur between infiltrating immune cells and the central nervous system parenchyma. This concept can be expanded to the testis, which has long been considered an immune-privileged site, and to neurogenic bladder dysfunction. Thus, we propose that the relationship between peripheral immune cells, the brain, and the urologic system should be considered as an additional possible mechanism in urologic diseases, and that immunotherapy might be an alternative therapeutic strategy in treating neurogenic bladder dysfunction.

  14. Schwann cell-derived exosomes enhance axonal regeneration in the peripheral nervous system.

    PubMed

    Lopez-Verrilli, María Alejandra; Picou, Frederic; Court, Felipe A

    2013-11-01

    Axonal regeneration in the peripheral nervous system is greatly supported by Schwann cells (SCs). After nerve injury, SCs dedifferentiate to a progenitor-like state and efficiently guide axons to their original target tissues. Contact and soluble factors participate in the crosstalk between SCs and axons during axonal regeneration. Here we show that dedifferentiated SCs secrete nano-vesicles known as exosomes which are specifically internalized by axons. Surprisingly, SC-derived exosomes markedly increase axonal regeneration in vitro and enhance regeneration after sciatic nerve injury in vivo. Exosomes shift the growth cone morphology to a pro-regenerating phenotype and decrease the activity of the GTPase RhoA, involved in growth cone collapse and axon retraction. Altogether, our work identifies a novel mechanism by which SCs communicate with neighboring axons during regenerative processes. We propose that SC exosomes represent an important mechanism by which these cells locally support axonal maintenance and regeneration after nerve damage.

  15. Immunoadsorption in patients with autoimmune ion channel disorders of the peripheral nervous system.

    PubMed

    Antozzi, Carlo

    2013-01-01

    Autoimmune ion channel disorders of the peripheral nervous system include myasthenia gravis, the Lambert-Eaton myasthenic syndrome, acquired neuromyotonia and autoimmune autonomic ganglionopathies. These disorders are characterized by the common feature of being mediated by IgG autoantibodies against identified target antigens, i.e. the acetylcholine receptor, the voltage-gated calcium and potassium channels, and the neuronal acetylcholine receptor. Moreover, experimental animal models have been identified for these diseases that respond to immunotherapy and are improved by plasmapheresis. On this basis, autoimmune ion channel disorders represent the ideal candidate for therapeutic apheresis. Immunoadsorption can be the treatment of choice when intensive apheretic protocols or long-term treatments must be performed, in patients needing frequent apheresis to keep a stable clinical condition, in case of unresponsiveness to corticosteroids and immunosuppressive treatments, or failure with TPE or intravenous immunoglobulins, and in patients with severe contraindications to long-term corticosteroids.

  16. Microtubule dynamics in the peripheral nervous system: A matter of balance.

    PubMed

    Almeida-Souza, Leonardo; Timmerman, Vincent; Janssens, Sophie

    2011-11-01

    The special architecture of neurons in the peripheral nervous system, with axons extending for long distances, represents a major challenge for the intracellular transport system. Two recent studies show that mutations in the small heat shock protein HSPB1, which cause an axonal type of Charcot-Marie-Tooth (CMT) neuropathy, affect microtubule dynamics and impede axonal transport. Intriguingly, while at presymptomatic age the neurons in the mutant HSPB1 mouse show a hyperstable microtubule network, at postsymptomatic age, the microtubule network completely lost its stability as reflected by a marked decrease in tubulin acetylation levels. We here propose a model explaining the role of microtubule stabilization and tubulin acetylation in the pathogenesis of HSPB1 mutations.

  17. Proliferative and nonproliferative lesions of the rat and mouse central and peripheral nervous systems.

    PubMed

    Kaufmann, Wolfgang; Bolon, Brad; Bradley, Alys; Butt, Mark; Czasch, Stephanie; Garman, Robert H; George, Catherine; Gröters, Sibylle; Krinke, Georg; Little, Peter; McKay, Jenny; Narama, Isao; Rao, Deepa; Shibutani, Makoto; Sills, Robert

    2012-06-01

    Harmonization of diagnostic nomenclature used in the pathology analysis of tissues from rodent toxicity studies will enhance the comparability and consistency of data sets from different laboratories worldwide. The INHAND Project (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) is a joint initiative of four major societies of toxicologic pathology to develop a globally recognized nomenclature for proliferative and nonproliferative lesions in rodents. This article recommends standardized terms for classifying changes observed in tissues of the mouse and rat central (CNS) and peripheral (PNS) nervous systems. Sources of material include academic, government, and industrial histopathology databases from around the world. Covered lesions include frequent, spontaneous, and aging-related changes as well as principal toxicant-induced findings. Common artifacts that might be confused with genuine lesions are also illustrated. The neural nomenclature presented in this document is also available electronically on the Internet at the goRENI website (http://www.goreni.org/).

  18. Peripheral nervous control of cold-induced reduction in the respiratory quotient of the rat

    NASA Astrophysics Data System (ADS)

    Refinetti, Roberto

    1990-03-01

    Cold-exposed rats show a reduction in the respiratory quotient which is indicative of a relative shift from carbohydrates to lipids as substrates for oxidative metabolism. In the present study, the effects of food deprivation and cold exposure on the respiratory quotient were observed. In addition, the involvement of the three main branches of the peripheral nervous system (sympathetic, parasympathetic, and somatic) was investigated by means of synaptic blockade with propranolol, atropine, and quinine, respectively. Both propranolol and quinine blocked the cold-induced decrease in respiratory quotient and increase in heat production, whereas atropine had only minor and very brief effects. It is concluded that both the sympathetic and somatic branches are involved in the metabolic changes associated with cold-induced thermogenesis and that the increase in metabolic heat production involves a shift from carbohydrate to lipid utilization irrespective of which of the two branches is activated.

  19. Nitric oxide synthase in the peripheral nervous system of the goldfish, Carassius auratus.

    PubMed

    Brüning, G; Hattwig, K; Mayer, B

    1996-04-01

    Neuronal nitric oxide synthase was located in various organs of the goldfish by NADPH-diaphorase histochemistry and immunohistochemistry. Positive cells were detected throughout the digestive tract. A particularly dense plexus of nitric-oxide-synthase-containing fibers was present at the opening of the pneumatic duct into the esophagus and at the intestinal sphincter separating the esophagus and the intestinal bulb. The nitroxergic innervation was mainly confined to the muscularis. The muscular layer of the swim bladder and of the pneumatic duct was densely equipped with stained neurons and fibers. In the heart, the majority of small neurons located at the sinu-atrial junction was found to be positive for nitric oxide synthase. The muscularis of the urinary duct was supplied by fibers originating from many intramural ganglia harboring intensely stained neurons. These results suggest that nitric oxide represents a widespread transmitter in the peripheral nervous system of teleost species.

  20. Contribution of semaphorins to the formation of the peripheral nervous system in higher vertebrates.

    PubMed

    Masuda, Tomoyuki; Taniguchi, Masahiko

    2016-11-01

    Semaphorins are a large family of proteins characterized by sema domains and play a key role not only in the formation of neural circuits, but in the immune system, angiogenesis, tumor progression, and bone metabolism. To date, 15 semaphorins have been reported to be involved in the formation of the peripheral nervous system (PNS) in higher vertebrates. A number of experiments have revealed their functions in the PNS, where they act mainly as axonal guidance cues (as repellents or attractants). Semaphorins also play an important role in the migration of neurons and formation of sensory-motor connections in the PNS. This review summarizes recent knowledge regarding the functions of higher vertebrate semaphorins in the formation of the PNS.

  1. Contribution of semaphorins to the formation of the peripheral nervous system in higher vertebrates

    PubMed Central

    Masuda, Tomoyuki; Taniguchi, Masahiko

    2016-01-01

    ABSTRACT Semaphorins are a large family of proteins characterized by sema domains and play a key role not only in the formation of neural circuits, but in the immune system, angiogenesis, tumor progression, and bone metabolism. To date, 15 semaphorins have been reported to be involved in the formation of the peripheral nervous system (PNS) in higher vertebrates. A number of experiments have revealed their functions in the PNS, where they act mainly as axonal guidance cues (as repellents or attractants). Semaphorins also play an important role in the migration of neurons and formation of sensory-motor connections in the PNS. This review summarizes recent knowledge regarding the functions of higher vertebrate semaphorins in the formation of the PNS. PMID:27715392

  2. Intrinsic facilitation of adult peripheral nerve regeneration by the Sonic hedgehog morphogen.

    PubMed

    Martinez, Jose A; Kobayashi, Masaki; Krishnan, Anand; Webber, Christine; Christie, Kimberly; Guo, GuiFang; Singh, Vandana; Zochodne, Douglas W

    2015-09-01

    Intrinsic molecular determinants of neurodevelopmental outcomes assume new, albeit related roles during adult neural regeneration. Here we studied and identified a facilitatory role for Sonic hedgehog protein (Shh), a morphogen that influences motor neuron floor plate architecture, during adult peripheral neuron regeneration. Shh and its receptors were expressed in adult dorsal root ganglia (DRG) neurons, axons and glia and trended toward higher levels following axotomy injury. Knockdown of Shh in adult sensory neurons resulted in decreased outgrowth and branching in vitro, identifying a role for Shh in facilitating outgrowth. The findings argued for an intrinsic action to support neuron regeneration. Support of advancement and turning however, were not identified in adult sensory neuron growth cones in response to local extrinsic gradients of Shh. That intrinsic Shh supported the regrowth of peripheral nerves after injury was confirmed by the analysis of axon regrowth from the proximal stumps of transected sciatic nerves. By exposing regenerating axons to local infusions of Shh siRNA in vivo within a conduit bridging the transected proximal and distal stumps, we achieved local knockdown of Shh. In response, there was attenuated axonal and Schwann cell outgrowth beyond the transection zone. Unlike its role during neurodevelopment, Shh facilitates but does not confer regenerative outgrowth properties to adult neurons alone. Exploring the differing properties of morphogens and related proteins in the adult nervous system identifies new and important roles for them.

  3. Barrier function in the peripheral and central nervous system-a review.

    PubMed

    Reinhold, A K; Rittner, H L

    2017-01-01

    The peripheral (PNS) and central nervous system (CNS) are delicate structures, highly sensitive to homeostatic changes-and crucial for basic vital functions. Thus, a selection of barriers ensures the protection of the nervous system from noxious blood-borne or surrounding stimuli. In this chapter, anatomy and functioning of the blood-nerve (BNB), the blood-brain (BBB), and the blood-spinal cord barriers (BSCB) are presented and the key tight junction (TJ) proteins described: claudin-1, claudin-3, claudin-5, claudin-11, claudin-12, claudin-19, occludin, Zona occludens-1 (ZO-1), and tricellulin are by now identified as relevant for nerval barriers. Different diseases can lead to or be accompanied by neural barrier disruption, and impairment of these barriers worsens pathology. Peripheral nerve injury and inflammatory polyneuropathy cause an increased permeability of BNB as well as BSCB, while, e.g., diseases of the CNS such as amyotrophic lateral sclerosis, multiple sclerosis, spinal cord injury, or Alzheimer's disease can progress and worsen through barrier dysfunction. Moreover, the complex role and regulation of the BBB after ischemic stroke is described. On the other side, PNS and CNS barriers hamper the delivery of drugs in diseases when the barrier is intact, e.g., in certain neurodegenerative diseases or inflammatory pain. Understanding of the barrier - regulating processes has already lead to the discovery of new molecules as drug enhancers. In summary, the knowledge of all of these mechanisms might ultimately lead to the invention of drugs to control barrier function to help ameliorating or curing neurological diseases.

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

    NASA Astrophysics Data System (ADS)

    Gros, Thomas Richard

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

  5. Aged PrP null mice show defective processing of neuregulins in the peripheral nervous system.

    PubMed

    Benvegnù, Stefano; Gasperini, Lisa; Legname, Giuseppe

    2011-05-01

    A prion, a protease-resistant conformer of the cellular prion protein (PrP(C)), is the causative agent of transmissible spongiform encephalopathies or prion diseases. While this property is well established for the aberrantly folded protein, the physiological function of PrP(C) remains elusive. Among different putative functions, the non-pathogenic protein isoform PrP(C) is involved in several cellular processes. Here, we show that PrP(C) regulates the cleavage of neuregulin-1 proteins (NRG1). Neuregulins provide key axonal signals that regulate several processes, including glial cells proliferation, survival and myelination. Interestingly, mice devoid of PrP(C) (Prnp⁰/⁰) were recently shown to have a late-onset demyelinating disease in the peripheral nervous system (PNS) but not in the central nervous system (CNS). We found that NRG1 processing is developmentally regulated in the PNS and, by comparing wildtype and Prnp⁰/⁰ mice, that PrP(C) influences NRG1 processing in old, but not in young, animals. In addition, we found that also the processing of neuregulin-3, another neuregulin family member, is altered in the PNS of Prnp⁰/⁰ mice. These differences in neuregulin proteins processing are not paralleled in the CNS, thus suggesting a different cellular function for PrP(C) between the CNS and the PNS.

  6. Development of the embryonic and larval peripheral nervous system of Drosophila.

    PubMed

    Singhania, Aditi; Grueber, Wesley B

    2014-01-01

    The peripheral nervous system (PNS) of embryonic and larval stage Drosophila consists of diverse types of sensory neurons positioned along the body wall. Sensory neurons, and associated end organs, show highly stereotyped locations and morphologies. Many powerful genetic tools for gene manipulation available in Drosophila make the PNS an advantageous system for elucidating basic principles of neural development. Studies of the Drosophila PNS have provided key insights into molecular mechanisms of cell fate specification, asymmetric cell division, and dendritic morphogenesis. A canonical lineage gives rise to sensory neurons and associated organs, and cells within this lineage are diversified through asymmetric cell divisions. Newly specified sensory neurons develop specific dendritic patterns, which are controlled by numerous factors including transcriptional regulators, interactions with neighboring neurons, and intracellular trafficking systems. In addition, sensory axons show modality specific terminations in the central nervous system, which are patterned by secreted ligands and their receptors expressed by sensory axons. Modality-specific axon projections are critical for coordinated larval behaviors. We review the molecular basis for PNS development and address some of the instances in which the mechanisms and molecules identified are conserved in vertebrate development.

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

    PubMed

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

    2015-01-01

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

  8. Lower urinary tract dysfunction in patients with peripheral nervous system lesions.

    PubMed

    Podnar, Simon; Vodušek, David B

    2015-01-01

    The prevalence of lower urinary tract (LUT) dysfunction in peripheral nervous system (PNS) disorders is larger than in comparable control populations. This is particularly true for polyneuropathies with autonomic nervous system involvement, and for localized lesions with LUT innervation. LUT symptoms may be the guide to the diagnosis of processes localized in the lumbosacral spinal canal (as in cauda equina syndrome), and in the pelvis. Typical LUT dysfunctions (LUTD) caused by PNS involvement include bladder and sphincter hypoactivity with poor emptying, and incontinence. Paradoxically, bladder overactivity may also occur in pure PNS lesions. The acute cauda equina syndrome is an emergency requiring magnetic resonance imaging and surgery; in chronic neurogenic LUTD due to PNS involvement, the diagnosis of the lesion may be clarified by clinical neurophysiologic testing. Other important causes of neurogenic LUT dysfunction are perineoabdominal and pelvic surgeries. Surgeons are devising nerve-sparing techniques to prevent such major and often persistent complications in patients who are otherwise cured of the underlying disease. LUTD significantly affects the quality of life in patients and may lead to recurring urinary infections and upper urinary tract involvement. Thorough assessment of LUT function by urodynamics may be necessary in patients who are not improved by simple conservative measures.

  9. Peripheral Nervous System Genes Expressed in Central Neurons Induce Growth on Inhibitory Substrates

    PubMed Central

    Buchser, William J.; Smith, Robin P.; Pardinas, Jose R.; Haddox, Candace L.; Hutson, Thomas; Moon, Lawrence; Hoffman, Stanley R.; Bixby, John L.; Lemmon, Vance P.

    2012-01-01

    Trauma to the spinal cord and brain can result in irreparable loss of function. This failure of recovery is in part due to inhibition of axon regeneration by myelin and chondroitin sulfate proteoglycans (CSPGs). Peripheral nervous system (PNS) neurons exhibit increased regenerative ability compared to central nervous system neurons, even in the presence of inhibitory environments. Previously, we identified over a thousand genes differentially expressed in PNS neurons relative to CNS neurons. These genes represent intrinsic differences that may account for the PNS’s enhanced regenerative ability. Cerebellar neurons were transfected with cDNAs for each of these PNS genes to assess their ability to enhance neurite growth on inhibitory (CSPG) or permissive (laminin) substrates. Using high content analysis, we evaluated the phenotypic profile of each neuron to extract meaningful data for over 1100 genes. Several known growth associated proteins potentiated neurite growth on laminin. Most interestingly, novel genes were identified that promoted neurite growth on CSPGs (GPX3, EIF2B5, RBMX). Bioinformatic approaches also uncovered a number of novel gene families that altered neurite growth of CNS neurons. PMID:22701605

  10. Development of the embryonic and larval peripheral nervous system of Drosophila

    PubMed Central

    Singhania, Aditi; Grueber, Wesley B.

    2014-01-01

    The peripheral nervous system (PNS) of embryonic and larval stage Drosophila consists of diverse types of sensory neurons positioned along the body wall. Sensory neurons, and associated end organs, show highly stereotyped locations and morphologies. The many powerful genetic tools for gene manipulation available in Drosophila make the PNS an advantageous system for elucidating basic principles of neural development. Studies of the Drosophila PNS have provided key insights into molecular mechanisms of cell fate specification, asymmetric cell division, and dendritic morphogenesis. A canonical lineage gives rise to sensory neurons and associated organs, and cells within this lineage are diversified through asymmetric cell divisions. Newly specified sensory neurons develop specific dendritic patterns, which are controlled by numerous factors including transcriptional regulators, interactions with neighboring neurons, and intracellular trafficking systems. In addition, sensory axons show modality specific terminations in the central nervous system, which are patterned by secreted ligands and their receptors expressed by sensory axons. Modality-specific axon projections are critical for coordinated larval behaviors. We review the molecular basis for PNS development and address some of the instances in which the mechanisms and molecules identified are conserved in vertebrate development. PMID:24896657

  11. Peripheral nervous system genes expressed in central neurons induce growth on inhibitory substrates.

    PubMed

    Buchser, William J; Smith, Robin P; Pardinas, Jose R; Haddox, Candace L; Hutson, Thomas; Moon, Lawrence; Hoffman, Stanley R; Bixby, John L; Lemmon, Vance P

    2012-01-01

    Trauma to the spinal cord and brain can result in irreparable loss of function. This failure of recovery is in part due to inhibition of axon regeneration by myelin and chondroitin sulfate proteoglycans (CSPGs). Peripheral nervous system (PNS) neurons exhibit increased regenerative ability compared to central nervous system neurons, even in the presence of inhibitory environments. Previously, we identified over a thousand genes differentially expressed in PNS neurons relative to CNS neurons. These genes represent intrinsic differences that may account for the PNS's enhanced regenerative ability. Cerebellar neurons were transfected with cDNAs for each of these PNS genes to assess their ability to enhance neurite growth on inhibitory (CSPG) or permissive (laminin) substrates. Using high content analysis, we evaluated the phenotypic profile of each neuron to extract meaningful data for over 1100 genes. Several known growth associated proteins potentiated neurite growth on laminin. Most interestingly, novel genes were identified that promoted neurite growth on CSPGs (GPX3, EIF2B5, RBMX). Bioinformatic approaches also uncovered a number of novel gene families that altered neurite growth of CNS neurons.

  12. [MR neurography for lesion localization in the peripheral nervous system. Why, when and how?].

    PubMed

    Pham, M

    2014-02-01

    Peripheral neuropathies are frequent disorders which are often challenging in the diagnostic work-up. Diagnostic difficulties first and foremost arise with regard to lesion localization and the precise definition of spatial lesion patterns. Magnetic resonance (MR) neurography as a diagnostic imaging tool directly visualizes nerve lesions thereby facilitating lesion localization not only in traumatic nerve lesions but also in the large and heterogeneous group of intrinsic, spontaneously occurring non-focal neuropathies. The major diagnostic sign for lesion detection and localization is the T2 lesion which can be evaluated with high spatial resolution at the anatomical level of nerve fascicles. Lesion detection at the fascicular level by MR neurography advances the diagnostic work-up in the peripheral nervous system (PNS), because fascicular and partial nerve lesions of spontaneously occurring intrinsic neuropathies and polyneuropathies present a classical diagnostic pitfall for traditional localization by means of physical findings and electrophysiology. With the appropriate techniques and strategies MR neurography can now cover large anatomical areas of the PNS in a single examination session.

  13. Persistent Peripheral Nervous System Damage in Simian Immunodeficiency Virus-Infected Macaques Receiving Antiretroviral Therapy.

    PubMed

    Dorsey, Jamie L; Mangus, Lisa M; Hauer, Peter; Ebenezer, Gigi J; Queen, Suzanne E; Laast, Victoria A; Adams, Robert J; Mankowski, Joseph L

    2015-11-01

    Human immunodeficiency virus (HIV)-induced peripheral neuropathy is the most common neurologic complication associated with HIV infection. In addition to virus-mediated injury of the peripheral nervous system (PNS), treatment of HIV infection with combination antiretroviral therapy (cART) may induce toxic neuropathy as a side effect. Antiretroviral toxic neuropathy is clinically indistinguishable from the sensory neuropathy induced by HIV; in some patients, these 2 processes are likely superimposed. To study these intercurrent PNS disease processes, we first established a simian immunodeficiency virus (SIV)/pigtailed macaque model in which more than 90% of animals developed PNS changes closely resembling those seen in HIV-infected individuals with distal sensory neuropathy. To determine whether cART alters the progression of SIV-induced PNS damage, dorsal root ganglia and epidermal nerve fibers were evaluated in SIV-infected macaques after long-term suppressive cART. Although cART effectively suppressed SIV replication and reduced macrophage activation in the dorsal root ganglia, PGP 9.5 immunostaining and measurements of epidermal nerve fibers in the plantar surface of the feet of treated SIV-infected macaques clearly showed that cART did not normalize epidermal nerve fiber density. These findings illustrate that significant PNS damage persists in SIV-infected macaques on suppressive cART.

  14. Acid-Sensing Ion Channels and nociception in the peripheral and central nervous systems.

    PubMed

    Deval, Emmanuel; Lingueglia, Eric

    2015-07-01

    Since their molecular cloning in the late 90's, Acid-Sensing Ion Channels (ASICs) have been shown to be involved in many aspects of nociception, both in peripheral and central neurons. In rodents, the combination of specific or non-specific pharmacological modulators of ASICs, together with in vivo knockdown and/or knockout animals has revealed their contribution to the detection, the modulation and the sensitization of the pain message by primary and secondary sensory neurons. Functional ASICs are homo or heterotrimers of different homologous subunits (ASIC1-3). Channels containing ASIC3 or ASIC1 subunits, appear to be important in peripheral nociceptors, where they are subject to intense regulation, while ASIC1a-containing channels also have a prominent role in central neurons, including spinal cord neurons that modulate and transmit the pain signal to the brain. In humans, experiments performed in healthy volunteers using drugs already used in the clinic and acting as poorly-selective inhibitors of ASICs, together with recent in vitro data obtained from stem cell-derived sensory neurons both support a role for these channels in nociception. These data thus suggest a real translational potential in the development of inhibitory strategies of ASICs for the treatment of pain. This article is part of the Special Issue entitled 'Acid-Sensing Ion Channels in the Nervous System'.

  15. The histamine H4-receptor and the central and peripheral nervous system: A critical analysis of the literature.

    PubMed

    Schneider, Erich H; Seifert, Roland

    2016-07-01

    Expression and function of histamine H4R in central and peripheral nervous system have been a matter of controversy for more than a decade. The scientific discussion is often limited to a few publications postulating the presence of functional H4R on neurons of the central and peripheral nervous system, but the even larger number of reports showing negative data is often neglected. In this article, we critically review the existing literature on H4R in central and peripheral nervous system and discuss the weak points often overlooked by the community. We identified as most important problems (i) insufficient validation or quality of antibodies, (ii) missing knockout controls, (iii) uncritical interpretation of RT-PCR results instead of qPCR experiments, (iv) insufficient controls to confirm specificity of pharmacological tools, (v) uncritical reliance on results produced by a single method and (vi) uncritical reliance on results not reproduced by independent research groups. Additionally, there may be a publication as well as a citation bias favoring the awareness of positive results, but neglecting negative data. We conclude that H4R expression on neurons of the brain is not convincingly supported by the current literature, at least as long as the positive data are not reproduced by independent research groups. Expression and function of H4R on peripheral neurons or non-neuronal cells of the nervous system, specifically on microglia is an interesting alternative hypothesis that, however, requires further verification. This article is part of a Special Issue entitled 'Histamine Receptors'.

  16. Tailored transgene expression to specific cell types in the central nervous system after peripheral injection with AAV9

    PubMed Central

    Dashkoff, Jonathan; Lerner, Eli P; Truong, Nhi; Klickstein, Jacob A; Fan, Zhanyun; Mu, Dakai; Maguire, Casey A; Hyman, Bradley T; Hudry, Eloise

    2016-01-01

    The capacity of certain adeno-associated virus (AAV) vectors to cross the blood–brain barrier after intravenous delivery offers a unique opportunity for noninvasive brain delivery. However, without a well-tailored system, the use of a peripheral route injection may lead to undesirable transgene expression in nontarget cells or organs. To refine this approach, the present study characterizes the transduction profiles of new self-complementary AAV9 (scAAV9) expressing the green fluorescent protein (GFP) either under an astrocyte (glial fibrillary acidic (GFA) protein) or neuronal (Synapsin (Syn)) promoter, after intravenous injection of adult mice (2 × 1013 vg/kg). ScAAV9-GFA-GFP and scAAV9-Syn-GFP robustly transduce astrocytes (11%) and neurons (17%), respectively, without aberrant expression leakage. Interestingly, while the percentages of GFP-positive astrocytes with scAAV9-GFA-GFP are similar to the performances observed with scAAV9-CBA-GFP (broadly active promoter), significant higher percentages of neurons express GFP with scAAV9-Syn-GFP. GFP-positive excitatory as well as inhibitory neurons are observed, as well as motor neurons in the spinal cord. Additionally, both activated (GFAP-positive) and resting astrocytes (GFAP-negative) express the reporter gene after scAAV9-GFA-GFP injection. These data thoroughly characterize the gene expression specificity of AAVs fitted with neuronal and astrocyte-selective promoters after intravenous delivery, which will prove useful for central nervous system (CNS) gene therapy approaches in which peripheral expression of transgene is a concern. PMID:27933308

  17. Distribution of C-type natriuretic peptide and its messenger RNA in rat central nervous system and peripheral tissue.

    PubMed

    Minamino, N; Aburaya, M; Kojima, M; Miyamoto, K; Kangawa, K; Matsuo, H

    1993-11-30

    In rat, the highest concentration of immunoreactive (ir-) C-type natriuretic peptide (CNP) was found in the central nervous system, as is the case in pig and human. Although its concentration in peripheral tissue was much lower than that in brain, CNP was present mainly as CNP-53 in ileum-jejunum, colon-cecum, stomach, kidney, lung, testis and submaxillary gland, but not in heart. By Northern blot analysis, CNP mRNA was detected in ileum-jejunum, testis, thymus, adrenal gland and submaxillary gland as well as in brain and spinal cord. CNP mRNA was further verified by reverse transcription-polymerase chain reaction to be present in most peripheral tissue, including aorta and bone marrow. These results indicate that CNP is synthesized in peripheral tissue and possibly functions as a local regulator in addition to acting as a neuropeptide in the central nervous system.

  18. Salicylic acid-derived poly(anhydride-ester) electrospun fibers designed for regenerating the peripheral nervous system

    PubMed Central

    Griffin, Jeremy; Delgado-Rivera, Roberto; Meiners, Sally; Uhrich, Kathryn E.

    2011-01-01

    Continuous biomaterial advances and the regenerating potential of the adult human peripheral nervous system offer great promise for restoring full function to innervated tissue following traumatic injury via synthetic nerve guidance conduits. To most effectively facilitate nerve regeneration, a tissue engineering scaffold within a conduit must be similar to the linear microenvironment of the healthy nerve. To mimic the native nerve structure, aligned poly(lactic-co-glycolic acid)/bioactive polyanhydride fibrous substrates were fabricated through optimized electrospinning parameters with diameters of 600 ± 200 nm. Scanning electron microscopy images show fibers with a high degree of alignment. Schwann cells and dissociated rat dorsal root ganglia demonstrated elongated and healthy proliferation in a direction parallel to orientated electrospun fibers with significantly longer Schwann cell process length and neurite outgrowth when compared to randomly orientated fibers. Results suggest that an aligned polyanhydride fiber mat holds tremendous promise as a supplement scaffold for the interior of a degradable polymer nerve guidance conduit. Bioactive salicylic acid based polyanhydride fibers are not limited to nerve regeneration and offer exciting promise for a wide variety of biomedical applications. PMID:21442724

  19. The insulin receptor is required for the development of the Drosophila peripheral nervous system.

    PubMed

    Dutriaux, Annie; Godart, Aurélie; Brachet, Anna; Silber, Joël

    2013-01-01

    The Insulin Receptor (InR) in Drosophila presents features conserved in its mammalian counterparts. InR is required for growth; it is expressed in the central and embryonic nervous system and modulates the time of differentiation of the eye photoreceptor without altering cell fate. We show that the InR is required for the formation of the peripheral nervous system during larval development and more particularly for the formation of sensory organ precursors (SOPs) on the fly notum and scutellum. SOPs arise in the proneural cluster that expresses high levels of the proneural proteins Achaete (Ac) and Scute (Sc). The other cells will become epidermis due to lateral inhibition induced by the Notch (N) receptor signal that prevents its neighbors from adopting a neural fate. In addition, misexpression of the InR or of other components of the pathway (PTEN, Akt, FOXO) induces the development of an abnormal number of macrochaetes that are Drosophila mechanoreceptors. Our data suggest that InR regulates the neural genes ac, sc and sens. The FOXO transcription factor which is localized in the cytoplasm upon insulin uptake, displays strong genetic interaction with the InR and is involved in Ac regulation. The genetic interactions between the epidermal growth factor receptor (EGFR), Ras and InR/FOXO suggest that these proteins cooperate to induce neural gene expression. Moreover, InR/FOXO is probably involved in the lateral inhibition process, since genetic interactions with N are highly significant. These results show that the InR can alter cell fate, independently of its function in cell growth and proliferation.

  20. Sustained Accumulation of Microtubule-Binding Chemotherapy Drugs in the Peripheral Nervous System: Correlations with Time Course and Neurotoxic Severity.

    PubMed

    Wozniak, Krystyna M; Vornov, James J; Wu, Ying; Nomoto, Kenichi; Littlefield, Bruce A; DesJardins, Christopher; Yu, Yanke; Lai, George; Reyderman, Larisa; Wong, Nancy; Slusher, Barbara S

    2016-06-01

    Chemotherapy-induced peripheral neuropathy is a dose-limiting side effect of many antineoplastic agents, but the mechanisms underlying the toxicities are unclear. At their MTDs, the microtubule-binding drugs paclitaxel and ixabepilone induce more severe neuropathy in mice relative to eribulin mesylate, paralleling their toxicity profiles in clinic. We hypothesized that the severity of their neurotoxic effects might be explained by the levels at which they accumulate in the peripheral nervous system. To test this hypothesis, we compared their pharmacokinetics and distribution in peripheral nerve tissue. After administration of a single intravenous dose, each drug was rapidly cleared from plasma but all persisted in the dorsal root ganglia (DRG) and sciatic nerve (SN) for up to 72 hours. Focusing on paclitaxel and eribulin, we performed a 2-week MTD-dosing regimen, followed by a determination of drug pharmacokinetics, tissue distribution, and multiple functional measures of peripheral nerve toxicity for 4 weeks. Consistent with the acute dosing study, both drugs persisted in peripheral nervous tissues for weeks, in contrast to their rapid clearance from plasma. Notably, although eribulin exhibited greater DRG and SN penetration than paclitaxel, the neurotoxicity observed functionally was consistently more severe with paclitaxel. Overall, our results argue that sustained exposure of microtubule-binding chemotherapeutic agents in peripheral nerve tissues cannot by itself account for their associated neurotoxicity. Cancer Res; 76(11); 3332-9. ©2016 AACR.

  1. Long-term survival and integration of transplanted engineered nervous tissue constructs promotes peripheral nerve regeneration.

    PubMed

    Huang, Jason H; Cullen, D Kacy; Browne, Kevin D; Groff, Robert; Zhang, Jun; Pfister, Bryan J; Zager, Eric L; Smith, Douglas H

    2009-07-01

    Although peripheral nerve injury is a common consequence of trauma or surgery, there are insufficient means for repair. In particular, there is a critical need for improved methods to facilitate regeneration of axons across major nerve lesions. Here, we engineered transplantable living nervous tissue constructs to provide a labeled pathway to guide host axonal regeneration. These constructs consisted of stretch-grown, longitudinally aligned living axonal tracts inserted into poly(glycolic acid) tubes. The constructs (allogenic) were transplanted to bridge an excised segment of sciatic nerve in the rat, and histological analyses were performed at 6 and 16 weeks posttransplantation to determine graft survival, integration, and host regeneration. At both time points, the transplanted constructs were found to have maintained their pretransplant geometry, with surviving clusters of graft neuronal somata at the extremities of the constructs spanned by tracts of axons. Throughout the transplanted region, there was an intertwining plexus of host and graft axons, suggesting that the transplanted axons mediated host axonal regeneration across the lesion. By 16 weeks posttransplant, extensive myelination of axons was observed throughout the transplant region. Further, graft neurons had extended axons beyond the margins of the transplanted region, penetrating into the host nerve. Notably, this survival and integration of the allogenic constructs occurred in the absence of immunosuppression therapy. These findings demonstrate the promise of living tissue-engineered axonal constructs to bridge major nerve lesions and promote host regeneration, potentially by providing axon-mediated axonal outgrowth and guidance.

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

    PubMed

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

    2016-03-01

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

  3. Peripheral nervous system defects in a mouse model for peroxisomal biogenesis disorders.

    PubMed

    Hanson, M Gartz; Fregoso, Veronica L; Vrana, Justin D; Tucker, Chandra L; Niswander, Lee A

    2014-11-01

    Peroxisome biogenesis disorders (PBD) are autosomal recessive disorders in humans characterized by skeletal, eye and brain abnormalities. Despite the fact that neurological deficits, including peripheral nervous system (PNS) defects, can be observed at birth in some PBD patients including those with PEX10 mutations, the embryological basis of the PNS defects is unclear. Using a forward genetic screen, we identified a mouse model for Pex10 deficiency that exhibits neurological abnormalities during fetal development. Homozygous Pex10 mutant mouse embryos display biochemical abnormalities related to a PBD deficiency. During late embryogenesis, Pex10 homozygous mutant mice experience progressive loss of movement and at birth they become cyanotic and die shortly thereafter. Homozygous Pex10 mutant fetuses display decreased integrity of axons and synapses, over-extension of axons in the diaphragm and decreased Schwann cell numbers. Our neuropathological, molecular and electrophysiological studies provide new insights into the embryological basis of the PNS deficits in a PBD model. Our findings identify PEX10 function, and likely other PEX proteins, as an essential component of the spinal locomotor circuit.

  4. 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.

  5. Central nervous system relapse in peripheral T-cell lymphomas: a Swedish Lymphoma Registry study.

    PubMed

    Ellin, Fredrik; Landström, Jenny; Jerkeman, Mats; Relander, Thomas

    2015-07-02

    Central nervous system (CNS) relapse in non-Hodgkin lymphoma (NHL) carries a very poor prognosis. Risk factors and outcome have been studied in aggressive B-cell lymphomas, but very little is known about the risk in peripheral T-cell lymphoma (PTCL). We aimed at analyzing risk factors for CNS involvement at first relapse or progression, as well as the outcome of these patients, in a large population-based cohort of patients with PTCL. Twenty-eight out of 625 patients (4.5%) developed CNS disease over time. In multivariable analysis, disease characteristics at diagnosis independently associated with an increased risk for later CNS involvement were involvement of more than 1 extranodal site (hazard ratio [HR], 2.60; 95% confidence interval [CI], 1.07-6.29; P = .035) and skin (HR, 3.51; 95% CI, 1.26-9.74; P = .016) and gastrointestinal involvement (HR, 3.06; 95% CI, 1.30-7.18; P = .010). The outcome of relapsed/refractory patients was very poor, and CNS involvement was not associated with a significantly worse outcome compared with relapsed/refractory patients without CNS involvement in multivariable analysis (HR, 1.6; 95% CI, 0.96-2.6; P = .074). The results from the present study indicate that CNS relapse in PTCL occurs at a frequency similar to what is seen in aggressive B-cell lymphomas, but the poor outcomes in relapse are largely driven by systemic rather than CNS disease.

  6. Neuroprotective activity of thioctic acid in central nervous system lesions consequent to peripheral nerve injury.

    PubMed

    Tomassoni, Daniele; Amenta, Francesco; Di Cesare Mannelli, Lorenzo; Ghelardini, Carla; Nwankwo, Innocent E; Pacini, Alessandra; Tayebati, Seyed Khosrow

    2013-01-01

    Peripheral neuropathies are heterogeneous disorders presenting often with hyperalgesia and allodynia. This study has assessed if chronic constriction injury (CCI) of sciatic nerve is accompanied by increased oxidative stress and central nervous system (CNS) changes and if these changes are sensitive to treatment with thioctic acid. Thioctic acid is a naturally occurring antioxidant existing in two optical isomers (+)- and (-)-thioctic acid and in the racemic form. It has been proposed for treating disorders associated with increased oxidative stress. Sciatic nerve CCI was made in spontaneously hypertensive rats (SHRs) and in normotensive reference cohorts. Rats were untreated or treated intraperitoneally for 14 days with (+/-)-, (+)-, or (-)-thioctic acid. Oxidative stress, astrogliosis, myelin sheets status, and neuronal injury in motor and sensory cerebrocortical areas were assessed. Increase of oxidative stress markers, astrogliosis, and neuronal damage accompanied by a decreased expression of neurofilament were observed in SHR. This phenomenon was more pronounced after CCI. Thioctic acid countered astrogliosis and neuronal damage, (+)-thioctic acid being more active than (+/-)- or (-)-enantiomers. These findings suggest a neuroprotective activity of thioctic acid on CNS lesions consequent to CCI and that the compound may represent a therapeutic option for entrapment neuropathies.

  7. Peripheral nervous system defects in a mouse model for peroxisomal biogenesis disorders

    PubMed Central

    Hanson, M. Gartz; Fregoso, Veronica; Vrana, Justin D.; Tucker, Chandra L.; Niswander, Lee A.

    2014-01-01

    Peroxisome biogenesis disorders (PBD) are autosomal recessive disorders in humans characterized by skeletal, eye and brain abnormalities. Despite the fact that neurological deficits, including peripheral nervous system (PNS) defects, can be observed at birth in some PBD patients including those with PEX10 mutations, the embryological basis of the PNS defects is unclear. Using a forward genetic screen, we identified a mouse model for Pex10 deficiency that exhibits neurological abnormalities during fetal development. Homozygous Pex10 mutant mouse embryos display biochemical abnormalities related to a PBD deficiency. During late embryogenesis, Pex10 homozygous mutant mice experience progressive loss of movement and at birth they become cyanotic and die shortly thereafter. Homozygous Pex10 mutant fetuses display decreased integrity of axons and synapses, over-extension of axons in the diaphragm and decreased Schwann cell numbers. Our neuropathological, molecular and electrophysiological studies provide new insights into the embryological basis of the PNS deficits in a PBD model. Our findings identify PEX10 function, and likely other PEX proteins, as an essential component of the spinal locomotor circuit. PMID:25176044

  8. The Lin28/let-7 axis is critical for myelination in the peripheral nervous system

    PubMed Central

    Gökbuget, Deniz; Pereira, Jorge A.; Bachofner, Sven; Marchais, Antonin; Ciaudo, Constance; Stoffel, Markus; Schulte, Johannes H.; Suter, Ueli

    2015-01-01

    MicroRNAs (miRNAs) are crucial regulators of myelination in the peripheral nervous system (PNS). However, the miRNAs species involved and the underlying mechanisms are largely unknown. We found that let-7 miRNAs are highly abundant during PNS myelination and that their levels are inversely correlated to the expression of lin28 homolog B (Lin28B), an antagonist of let-7 accumulation. Sustained expression of Lin28B and consequently reduced levels of let-7 miRNAs results in a failure of Schwann cell myelination in transgenic mouse models and in cell culture. Subsequent analyses revealed that let-7 miRNAs promote expression of the myelination-driving master transcription factor Krox20 (also known as Egr2) through suppression of myelination inhibitory Notch signalling. We conclude that the Lin28B/let-7 axis acts as a critical driver of PNS myelination, in particular by regulating myelination onset, identifying this pathway also as a potential therapeutic target in demyelinating diseases. PMID:26466203

  9. Neuroprotective Activity of Thioctic Acid in Central Nervous System Lesions Consequent to Peripheral Nerve Injury

    PubMed Central

    Ghelardini, Carla; Nwankwo, Innocent E.; Pacini, Alessandra

    2013-01-01

    Peripheral neuropathies are heterogeneous disorders presenting often with hyperalgesia and allodynia. This study has assessed if chronic constriction injury (CCI) of sciatic nerve is accompanied by increased oxidative stress and central nervous system (CNS) changes and if these changes are sensitive to treatment with thioctic acid. Thioctic acid is a naturally occurring antioxidant existing in two optical isomers (+)- and (−)-thioctic acid and in the racemic form. It has been proposed for treating disorders associated with increased oxidative stress. Sciatic nerve CCI was made in spontaneously hypertensive rats (SHRs) and in normotensive reference cohorts. Rats were untreated or treated intraperitoneally for 14 days with (+/−)-, (+)-, or (−)-thioctic acid. Oxidative stress, astrogliosis, myelin sheets status, and neuronal injury in motor and sensory cerebrocortical areas were assessed. Increase of oxidative stress markers, astrogliosis, and neuronal damage accompanied by a decreased expression of neurofilament were observed in SHR. This phenomenon was more pronounced after CCI. Thioctic acid countered astrogliosis and neuronal damage, (+)-thioctic acid being more active than (+/−)- or (−)-enantiomers. These findings suggest a neuroprotective activity of thioctic acid on CNS lesions consequent to CCI and that the compound may represent a therapeutic option for entrapment neuropathies. PMID:24527432

  10. Foveal Processing Under Concurrent Peripheral Load in Profoundly Deaf Adults.

    PubMed

    Dye, Matthew W G

    2016-04-01

    Development of the visual system typically proceeds in concert with the development of audition. One result is that the visual system of profoundly deaf individuals differs from that of those with typical auditory systems. While past research has suggested deaf people have enhanced attention in the visual periphery, it is still unclear whether or not this enhancement entails deficits in central vision. Profoundly deaf and typically hearing adults were administered a variant of the useful field of view task that independently assessed performance on concurrent central and peripheral tasks. Identification of a foveated target was impaired by a concurrent selective peripheral attention task, more so in profoundly deaf adults than in the typically hearing. Previous findings of enhanced performance on the peripheral task were not replicated. These data are discussed in terms of flexible allocation of spatial attention targeted towards perceived task demands, and support a modified "division of labor" hypothesis whereby attentional resources co-opted to process peripheral space result in reduced resources in the central visual field.

  11. Genetic Tracing of Cav3.2 T-Type Calcium Channel Expression in the Peripheral Nervous System

    PubMed Central

    Bernal Sierra, Yinth A.; Haseleu, Julia; Kozlenkov, Alexey; Bégay, Valérie; Lewin, Gary R.

    2017-01-01

    Characterizing the distinct functions of the T-type ion channel subunits Cav3.1, 3.2 or 3.3 has proven difficult due to their highly conserved amino-acid sequences and the lack of pharmacological blockers specific for each subunit. To precisely determine the expression pattern of the Cav3.2 channel in the nervous system we generated two knock-in mouse strains that express EGFP or Cre recombinase under the control of the Cav3.2 gene promoter. We show that in the brains of these animals, the Cav3.2 channel is predominantly expressed in the dentate gyrus of the hippocampus. In the peripheral nervous system, the activation of the promoter starts at E9.5 in neural crest cells that will give rise to dorsal root ganglia (DRG) neurons, but not sympathetic neurons. As development progresses the number of DRG cells expressing the Cav3.2 channel reaches around 7% of the DRG at E16.5, and remains constant until E18.5. Characterization of sensory neuron subpopulations at E18.5 showed that EGFP+ cells are a heterogeneous population consisting mainly of TrkB+ and TrkC+ cells, while only a small percentage of DRG cells were TrkA+. Genetic tracing of the sensory nerve end-organ innervation of the skin showed that the activity of the Cav3.2 channel promoter in sensory progenitors marks many mechanoreceptor and nociceptor endings, but spares slowly adapting mechanoreceptors with endings associated with Merkel cells. Our genetic analysis reveals for the first time that progenitors that express the Cav3.2 T-type calcium channel, defines a sensory specific lineage that populates a large proportion of the DRG. Using our Cav3.2-Cre mice together with AAV viruses containing a conditional fluorescent reporter (tdTomato) we could also show that Cre expression is largely restricted to two functionally distinct sensory neuron types in the adult ganglia. Cav3.2 positive neurons innervating the skin were found to only form lanceolate endings on hair follicles and are probably identical to D

  12. Inflammation and programmed cell death in Alzheimer's disease: comparison of the central nervous system and peripheral blood.

    PubMed

    Macchi, Beatrice; Marino-Merlo, Francesca; Frezza, Caterina; Cuzzocrea, Salvatore; Mastino, Antonio

    2014-10-01

    Although the central nervous system (CNS) has been defined as a privileged site in Alzheimer's disease (AD), periphery can be more than simply witness of events leading to neurodegeneration. The CNS and peripheral blood can mutually communicate through cells and factors trafficking from the circulation into the brain and vice versa. A number of articles have reviewed inflammatory profiles and programmed cell death (PCD) in AD, separately in the CNS and at the peripheral level. This review does not provide an exhaustive account of what has been published on inflammation and PCD in AD. Rather, the aim of this review is to focus on possible linkages between the central and the peripheral compartments during AD progression, by critically analyzing, in a comparative manner, phenomena occurring in the CNS as well as the peripheral blood. In fact, growing evidence suggests that CNS and peripheral inflammation might present common features in the disease. Microarrays and metabolomics revealed that dysfunction of the glycolytic and oxidative pathways is similar in the brain and in the periphery. Moreover, dysregulated autophagosome/lysosomal molecular machinery, both at the CNS and the peripheral level, in AD-related cell damage, has been observed. Possible implications of these observations have been discussed.

  13. Cinnamamide Derivatives for Central and Peripheral Nervous System Disorders--A Review of Structure-Activity Relationships.

    PubMed

    Gunia-Krzyżak, Agnieszka; Pańczyk, Katarzyna; Waszkielewicz, Anna M; Marona, Henryk

    2015-08-01

    The cinnamamide scaffold has been incorporated in to the structure of numerous organic compounds with therapeutic potential. The scaffold enables multiple interactions, such as hydrophobic, dipolar, and hydrogen bonding, with important molecular targets. Additionally, the scaffold has multiple substitution options providing the opportunity to optimize and modify the pharmacological activity of the derivatives. In particular, cinnamamide derivatives have exhibited therapeutic potential in animal models of both central and peripheral nervous system disorders. Some have undergone clinical trials and were introduced on to the pharmaceutical market. The diverse activities observed in the nervous system included anticonvulsant, antidepressant, neuroprotective, analgesic, anti-inflammatory, muscle relaxant, and sedative properties. Over the last decade, research has focused on the molecular mechanisms of action of these derivatives, and the data reported in the literature include targeting the γ-aminobutyric acid type A (GABAA ) receptors, N-methyl-D-aspartate (NMDA) receptors, transient receptor potential (TRP) cation channels, voltage-gated potassium channels, histone deacetylases (HDACs), prostanoid receptors, opioid receptors, and histamine H3 receptors. Here, the literature data from reports evaluating cinnamic acid amide derivatives for activity in target-based or phenotypic assays, both in vivo and in vitro, relevant to disorders of the central and peripheral nervous systems are analyzed and structure-activity relationships discussed.

  14. Spread of classic BSE prions from the gut via the peripheral nervous system to the brain.

    PubMed

    Kaatz, Martin; Fast, Christine; Ziegler, Ute; Balkema-Buschmann, Anne; Hammerschmidt, Bärbel; Keller, Markus; Oelschlegel, Anja; McIntyre, Leila; Groschup, Martin H

    2012-08-01

    An experimental oral bovine spongiform encephalopathy (BSE) challenge study was performed to elucidate the route of infectious prions from the gut to the central nervous system in preclinical and clinical infected animals. Tissue samples collected from the gut and the central and autonomic nervous system from animals sacrificed between 16 and 44 months post infection (mpi) were examined for the presence of the pathological prion protein (PrP(Sc)) by IHC. Moreover, parts of these samples were also bioassayed using bovine cellular prion protein (PrP(C)) overexpressing transgenic mice (Tgbov XV) that lack the species barrier for bovine prions. A distinct accumulation of PrP(Sc) was observed in the distal ileum, confined to follicles and/or the enteric nervous system, in almost all animals. BSE prions were found in the sympathetic nervous system starting at 16 mpi, and in the parasympathetic nervous system from 20 mpi. A clear dissociation between prion infectivity and detectable PrP(Sc) deposition became obvious. The earliest presence of infectivity in the brain stem was detected at 24 mpi, whereas PrP(Sc) accumulation was first detected after 28 mpi. In summary, our results decipher the centripetal spread of BSE prions along the autonomic nervous system to the central nervous system, starting already halfway in the incubation time.

  15. Tissue distribution of glutamate carboxypeptidase II (GCPII) with a focus on the central and peripheral nervous system.

    PubMed

    Marmiroli, P; Slusher, B; Cavaletti, G

    2012-01-01

    Glutamate carboxypeptidase II, also known as prostate specific membrane antigen or folate hydrolase I, is a type II transmembrane 750 amino acid membrane-bound glycoprotein, with a molecular weight in the human form of approximately 100 kDa and a demonstrated metallopeptidase activity. At the synaptic level it hydrolyzes N-acetylaspartylglutamate to N-acetyl-aspartate and glutamate. Its localization in the animal and human nervous system has only recently been clearly established, since many of the older studies gave conflicting results, likely due to the use of poorly characterized antibodies lacking epitope mapping and proper controls (i.e. immunohistochemistry complemented by western blot analysis and enzyme activity determination). In this chapter, we will review the available literature describing the animal and human distribution of glutamate carboxypeptidase in the central and peripheral nervous system.

  16. Adult plasticity and cortical reorganization after peripheral lesions.

    PubMed

    Sammons, Rosanna P; Keck, Tara

    2015-12-01

    Following loss of input due to peripheral lesions, functional reorganization occurs in the deprived cortical region in adults. Over a period of hours to months, cells in the lesion projection zone (LPZ) begin to respond to novel stimuli. This reorganization is mediated by two processes: a reduction of inhibition in a gradient throughout the cortex and input remapping via sprouting of axonal arbors from cortical regions spatially adjacent to the LPZ, and strengthening of pre-existing subthreshold inputs. Together these inputs facilitate receptive field remapping of cells in the LPZ. Recent experiments have revealed time courses and potential interactions of the mechanisms associated with functional reorganization, suggesting that large scale reorganization in the adult may utilize plasticity mechanisms prominent during development.

  17. Primary peripheral T-cell lymphoma, not otherwise specified, of the central nervous system in a child.

    PubMed

    Momota, Hiroyuki; Kato, Seiichi; Fujii, Masazumi; Tsujiuchi, Takashi; Takahashi, Yoshiyuki; Kojima, Seiji; Wakabayashi, Toshihiko

    2015-10-01

    Primary peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), is a rare disease that infrequently involves the central nervous system (CNS), and it is even rarer in pediatric patients. Here, we report of a 13-year-old male with primary CNS PTCL-NOS who exhibited a malignant clinical course with recurrence after radiochemotherapy followed by bone marrow transplantation; he died 43 months after diagnosis. Pathology revealed the proliferation of cytotoxic T-cells and clonal T-cell receptor gene rearrangements. Although the optimal therapy for PTCL remains controversial, intensive radiochemotherapy may be required for some patients.

  18. Ex vivo and in vivo coherent Raman imaging of the peripheral and central nervous system

    NASA Astrophysics Data System (ADS)

    Huff, Terry Brandon

    A hallmark of nervous system disorders is damage or degradation of the myelin sheath. Unraveling the mechanisms underlying myelin degeneration and repair represent one of the great challenges in medicine. This thesis work details the development and utilization of advanced optical imaging methods to gain insight into the structure and function of myelin in both healthy and diseased states in the in vivo environment. This first part of this thesis discusses ex vivo studies of the effects of high-frequency stimulation of spinal tissues on the structure of the node of Ranvier as investigated by coherent anti-Stokes Raman scattering (CARS) imaging (manuscript submitted to Journal of Neurosciece). Reversible paranodal myelin retraction at the nodes of Ranvier was observed during 200 Hz electrical stimulation, beginning minutes after the onset and continuing for up to 10 min after stimulation was ceased. A mechanistic study revealed a Ca2+ dependent pathway: high-frequency stimulation induced paranodal myelin retraction via pathologic calcium influx into axons, calpain activation, and cytoskeleton degradation through spectrin break-down. Also, the construction of dual-scanning CARS microscope for large area mapping of CNS tissues is detailed (Optics Express, 2008, 16:19396-193409). A confocal scanning head equipped with a rotating polygon mirror provides high speed, high resolution imaging and is coupled with a motorized sample stage to generate high-resolution large-area images of mouse brain coronal section and guinea pig spinal cord cross section. The polygon mirror decreases the mosaic acquisition time significantly without reducing the resolution of individual images. The ex vivo studies are then extended to in vivo imaging of mouse sciatic nerve tissue by CARS and second harmonic generation (SHG) imaging (Journal of Microscopy, 2007, 225: 175-182). Following a minimally invasive surgery to open the skin, CARS imaging of myelinated axons and SHG imaging of the

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

    PubMed

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

    2012-02-01

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

  20. GlcNAc6ST-1 regulates sulfation of N-glycans and myelination in the peripheral nervous system

    PubMed Central

    Yoshimura, Takeshi; Hayashi, Akiko; Handa-Narumi, Mai; Yagi, Hirokazu; Ohno, Nobuhiko; Koike, Takako; Yamaguchi, Yoshihide; Uchimura, Kenji; Kadomatsu, Kenji; Sedzik, Jan; Kitamura, Kunio; Kato, Koichi; Trapp, Bruce D.; Baba, Hiroko; Ikenaka, Kazuhiro

    2017-01-01

    Highly specialized glial cells wrap axons with a multilayered myelin membrane in vertebrates. Myelin serves essential roles in the functioning of the nervous system. Axonal degeneration is the major cause of permanent neurological disability in primary myelin diseases. Many glycoproteins have been identified in myelin, and a lack of one myelin glycoprotein results in abnormal myelin structures in many cases. However, the roles of glycans on myelin glycoproteins remain poorly understood. Here, we report that sulfated N-glycans are involved in peripheral nervous system (PNS) myelination. PNS myelin glycoproteins contain highly abundant sulfated N-glycans. Major sulfated N-glycans were identified in both porcine and mouse PNS myelin, demonstrating that the 6-O-sulfation of N-acetylglucosamine (GlcNAc-6-O-sulfation) is highly conserved in PNS myelin between these species. P0 protein, the most abundant glycoprotein in PNS myelin and mutations in which at the glycosylation site cause Charcot-Marie-Tooth neuropathy, has abundant GlcNAc-6-O-sulfated N-glycans. Mice deficient in N-acetylglucosamine-6-O-sulfotransferase-1 (GlcNAc6ST-1) failed to synthesize sulfated N-glycans and exhibited abnormal myelination and axonal degeneration in the PNS. Taken together, this study demonstrates that GlcNAc6ST-1 modulates PNS myelination and myelinated axonal survival through the GlcNAc-6-O-sulfation of N-glycans on glycoproteins. These findings may provide novel insights into the pathogenesis of peripheral neuropathy. PMID:28186137

  1. MHC-I and PirB Upregulation in the Central and Peripheral Nervous System following Sciatic Nerve Injury

    PubMed Central

    Bombeiro, André Luis; Thomé, Rodolfo; Oliveira Nunes, Sérgio Luiz; Monteiro Moreira, Bárbara; Verinaud, Liana; de Oliveira, Alexandre Leite Rodrigues

    2016-01-01

    Major histocompatibility complex class one (MHC-I) antigen-presenting molecules participate in central nervous system (CNS) synaptic plasticity, as does the paired immunoglobulin-like receptor B (PirB), an MHC-I ligand that can inhibit immune-cells and bind to myelin axon growth inhibitors. Based on the dual roles of both molecules in the immune and nervous systems, we evaluated their expression in the central and peripheral nervous system (PNS) following sciatic nerve injury in mice. Increased PirB and MHC-I protein and gene expression is present in the spinal cord one week after nerve transection, PirB being mostly expressed in the neuropile region. In the crushed nerve, MHC-I protein levels increased 2 weeks after lesion (wal) and progressively decreased over the next eight weeks. The same kinetics were observed for infiltrating cytotoxic T lymphocytes (CTLs) but not for PirB expression, which continuously increased. Both MHC-I and PirB were found in macrophages and Schwann cells but rarely in axons. Interestingly, at 8 wal, PirB was mainly restricted to the myelin sheath. Our findings reinforce the participation of MHC-I and PirB in CNS plasticity events. In contrast, opposing expression levels of these molecules were found in the PNS, so that MHC-I and PirB seem to be mostly implicated in antigen presentation to CTLs and axon myelination, respectively. PMID:27551751

  2. Effects on the central and peripheral nervous activity in rats elicited by acute administration of lead, mercury and manganese, and their combinations.

    PubMed

    Papp, András; Pecze, László; Szabó, Andrea; Vezér, Tünde

    2006-01-01

    Adult male Wistar rats were treated with inorganic lead, mercury and manganese, and their double combinations, in acute application. The aim was to study the effects on spontaneous and stimulus-evoked cortical, and evoked peripheral, nervous activity, to detect any interaction of the metals and any correlation between the changes caused in the spontaneous and stimulus-evoked electrical activity of the primary somatosensory cortical area, and the compound action potential of the tail nerve. In the frequency distribution of the spontaneous cortical activity, a shift to lower frequencies was seen. The cortical responses evoked by whisker or tail stimulation showed an increase of the peak-to-peak amplitude and peak latency on administration of the metals and metal combinations. With the metal combinations, synergism was observed. Correlations found between alterations of the spontaneous and evoked, or between cortical and peripheral, activity were evaluated in terms of mechanism. According to the results, combined exposure to the three heavy metals studied might lead to synergistic action, indicating an increased health risk in settings with exposure to several heavy metals.

  3. Expression of doublecortin in tumours of the central and peripheral nervous system and in human non-neuronal tissues.

    PubMed

    Bernreuther, Christian; Salein, Nora; Matschke, Jakob; Hagel, Christian

    2006-03-01

    Doublecortin is a microtubule-associated phosphoprotein involved in neuronal migration and differentiation expressed in migrating neuroblasts in the central nervous system. We systematically analysed doublecortin expression in 179 tumours of the central and 65 tumours of peripheral nervous system as well as in 74 different non-neuronal tissues to evaluate the specificity of doublecortin as a marker for neuronal differentiation in glioneuronal tumours. Glioneuronal tumours and oligodendrogliomas grade II and III uniformly showed a high intensity and frequency of doublecortin staining, whereas intermediate doublecortin expression was observed in astrocytic tumours of grade II-IV. In pilocytic astrocytomas and ependymomas only scattered doublecortin positive cells were detected. In the peripheral nervous system, doublecortin expression was found in neurofibroma but was absent in schwannoma. Double staining of tumour tissue revealed co-expression of doublecortin and neurofilament in cells of gangliocytomas and gangliogliomas and co-expression of doublecortin with S100 protein or GFAP in glial tumours, respectively. In a tissue array comprised of 74 different normal non-neuronal human tissues, doublecortin expression was demonstrated in epithelia of the kidney, liver, salivary glands and duodenum among others. Interestingly, doublecortin expression could not be shown in brain metastases of tumours originating from these tissues. Immunohistochemical data was further corroborated by Western blot analysis and reverse transcription polymerase chain reaction. In conclusion, doublecortin can be regarded as specific neuronal marker only in normal developing brain, but lacks specificity in glioneuronal and glial tumours and other non-neuronal human tissues where it is expressed in a wide variety of tumours and tissues.

  4. Development and optimization of herpes simplex virus vectors for multiple long-term gene delivery to the peripheral nervous system.

    PubMed

    Palmer, J A; Branston, R H; Lilley, C E; Robinson, M J; Groutsi, F; Smith, J; Latchman, D S; Coffin, R S

    2000-06-01

    Herpes simplex virus (HSV) has often been suggested as a suitable vector for gene delivery to the peripheral nervous system as it naturally infects sensory nerve terminals before retrograde transport to the cell body in the spinal ganglia where latency is established. HSV vectors might therefore be particularly appropriate for the study and treatment of chronic pain following vector administration by relatively noninvasive peripheral routes. However parameters allowing safe and efficient gene delivery to spinal ganglia following peripheral vector inoculation, or the long-term expression of delivered genes, have not been comprehensively studied. We have identified combinations of deletions from the HSV genome which allow highly efficient gene delivery to spinal dorsal root ganglia (DRGs) following either footpad or sciatic nerve injection. These vectors have ICP34.5 deleted and have inactivating mutations in vmw65. We also report that peripheral replication is probably necessary for the efficient establishment of latency in vivo, as fully replication-incompetent HSV vectors allow efficient gene expression in DRGs only after peripheral inoculation at a high virus dose. Very low transduction efficiencies are otherwise achieved. In parallel, promoters have been developed that allow the long-term expression of individual or pairs of genes in DRGs by using elements from the latently active region of the virus to confer a long-term activity onto a number of promoters which otherwise function only in the short term. This work further defines elements and mechanisms within the latently active region that are necessary for long-term gene expression and for the first time allows multiple inserted genes to be expressed from HSV vectors during latency.

  5. Alzheimer-associated Aβ oligomers impact the central nervous system to induce peripheral metabolic deregulation

    PubMed Central

    Clarke, Julia R; Lyra e Silva, Natalia M; Figueiredo, Claudia P; Frozza, Rudimar L; Ledo, Jose H; Beckman, Danielle; Katashima, Carlos K; Razolli, Daniela; Carvalho, Bruno M; Frazão, Renata; Silveira, Marina A; Ribeiro, Felipe C; Bomfim, Theresa R; Neves, Fernanda S; Klein, William L; Medeiros, Rodrigo; LaFerla, Frank M; Carvalheira, Jose B; Saad, Mario J; Munoz, Douglas P; Velloso, Licio A; Ferreira, Sergio T; De Felice, Fernanda G

    2015-01-01

    Alzheimer's disease (AD) is associated with peripheral metabolic disorders. Clinical/epidemiological data indicate increased risk of diabetes in AD patients. Here, we show that intracerebroventricular infusion of AD-associated Aβ oligomers (AβOs) in mice triggered peripheral glucose intolerance, a phenomenon further verified in two transgenic mouse models of AD. Systemically injected AβOs failed to induce glucose intolerance, suggesting AβOs target brain regions involved in peripheral metabolic control. Accordingly, we show that AβOs affected hypothalamic neurons in culture, inducing eukaryotic translation initiation factor 2α phosphorylation (eIF2α-P). AβOs further induced eIF2α-P and activated pro-inflammatory IKKβ/NF-κB signaling in the hypothalamus of mice and macaques. AβOs failed to trigger peripheral glucose intolerance in tumor necrosis factor-α (TNF-α) receptor 1 knockout mice. Pharmacological inhibition of brain inflammation and endoplasmic reticulum stress prevented glucose intolerance in mice, indicating that AβOs act via a central route to affect peripheral glucose homeostasis. While the hypothalamus has been largely ignored in the AD field, our findings indicate that AβOs affect this brain region and reveal novel shared molecular mechanisms between hypothalamic dysfunction in metabolic disorders and AD. PMID:25617315

  6. Intralipid therapy for inadvertent peripheral nervous system blockade resulting from local anesthetic overdose.

    PubMed

    Kamel, Ihab; Trehan, Gaurav; Barnette, Rodger

    2015-01-01

    Although local anesthetics have an acceptable safety profile, significant morbidity and mortality have been associated with their use. Inadvertent intravascular injection of local anesthetics and/or the use of excessive doses have been the most frequent causes of local anesthetic systemic toxicity (LAST). Furthermore, excessive doses of local anesthetics injected locally into the tissues may lead to inadvertent peripheral nerve infiltration and blockade. Successful treatment of LAST with intralipid has been reported. We describe a case of local anesthetic overdose that resulted in LAST and in unintentional blockade of peripheral nerves of the lower extremity; both effects completely resolved with administration of intralipid.

  7. Acetyl-L-carnitine: from a biological curiosity to a drug for the peripheral nervous system and beyond.

    PubMed

    Onofrj, Marco; Ciccocioppo, Fausta; Varanese, Sara; di Muzio, Antonio; Calvani, Menotti; Chiechio, Santina; Osio, Maurizio; Thomas, Astrid

    2013-08-01

    Acetyl-L-carnitine (ALC) is a molecule derived from acetylation of carnitine in the mitochondria. Carnitine acetylation enables the function of CoA and facilitates elimination of oxidative products. Beyond this metabolic activity, ALC provides acetyl groups for acetylcholine synthesis, exerts a cholinergic effect and optimizes the balance of energy processes. Acetylcarnitine supplementation induces neuroprotective, neurotrophic and analgesic effects in the peripheral nervous system. In the recent studies, ALC, by acting as a donor of acetyl groups to NF-kb p65/RelA, enhanced the transcription of the GRM2 gene encoding the mGLU2 receptors, inducing long-term upregulation of the mGluR2, evidencing therefore that its long-term analgesic effects are dependent on epigenetic modifications. Several studies, including double-blind, placebo-controlled, parallel group studies and few open studies showed the effect of ALC in diseases characterized by neuropathies and neuropathic pain: the studies included diabetic neuropathy, HIV and antiretroviral therapy-induced neuropathies, neuropathies due to compression and chemotherapeutic agents. Double-blinded studies involved 1773 patients. Statistical evaluations evidenced reduction of pain, improvements of nerve function and trophism. In conclusion, ALC represents a consistent therapeutic option for peripheral neuropathies, and its complex effects, neurotrophic and analgesic, based on epigenetic mechanism, open new pathways in the study of peripheral nerve disease management.

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

    PubMed Central

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

    2009-01-01

    Intranasal application of vesicular stomatitis virus (VSV) causes acute infection of the central nervous system (CNS). However, VSV encephalitis is not invariably fatal, suggesting that the CNS may contain a professional antigen-presenting cell (APC) capable of inducing or propagating a protective antiviral immune response. To examine this possibility, we first characterized the cellular elements that infiltrate the brain as well as the activation status of resident microglia in the brains of normal and transgenic mice acutely ablated of peripheral dendritic cells (DCs) in vivo. VSV encephalitis was characterized by a pronounced infiltrate of myeloid cells (CD45highCD11b+) and CD8+ T cells containing a subset that was specific for the immunodominant VSV nuclear protein epitope. This T cell response correlated temporally with a rapid and sustained upregulation of MHC class I expression on microglia, whereas class II expression was markedly delayed. Ablation of peripheral DCs profoundly inhibited the inflammatory response as well as infiltration of virus-specific CD8+ T cells. Unexpectedly, the VSV-induced interferon-gamma (IFN-γ) response in the CNS remained intact in DC-deficient mice. Thus, both the inflammatory and certain components of the adaptive primary antiviral immune response in the CNS are dependent on peripheral DCs in vivo. PMID:19264338

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

    SciTech Connect

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

    2009-04-25

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

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

    PubMed

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

    2009-04-25

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

  11. Neurosteroids are excitatory in supraoptic neurons but inhibitory in the peripheral nervous system: it is all about oxytocin and progesterone receptors.

    PubMed

    Viero, Cedric; Dayanithi, Govindan

    2008-01-01

    Neuroactive steroids synthesized from the brain or peripheral sources are called neurosteroids. Beside their common nuclear effects, they are considered to be potent neuromodulators, acting rapidly mainly in a non-genomic manner, either through allosteric regulation of ionic channels, or through membrane-bound steroid receptors. In contrast to the situation in the adult, the neurotransmitter GABA is excitatory during development and plays a trophic role, in particular inducing calcium signals necessary for the regulation of excitability and neuronal maturation. We demonstrated that the primary metabolite of progesterone (Proges), allopregnanolone (Allo), evoked a robust Ca(2+) influx in foetal hypothalamic neurons and in postnatal supraoptic nucleus (SON) neurons. In the latter, this led to oxytocin and arginine vasopressin release. Interestingly, these responses were GABA(A) and oxytocin-receptor-dependent. Allo is a well-known positive allosteric modulator of GABA(A) receptors. It is noteworthy that two other steroids, Proges and 17-beta-estradiol, displayed the same effect on Ca(2+) and oxytocin release but to a lesser extent. Importantly, no effect was observed in adult neurons from the SON, or in neurohypophysial axon terminals, regardless of the stage. The molecular mechanisms of the neurosteroid actions are multifaceted and depend on the type of cells, and are thus extremely interesting and challenging. In the peripheral nervous system, Allo and Proges surprisingly inhibited the GABA-induced Ca(2+) increases in embryonic dorsal root ganglion neurons. We propose that this rapid, reversible and dose-dependent phenomenon (at very low concentrations) was mediated by membrane Proges receptors, since transcripts for a newly discovered receptor protein, 25-Dx, were detected in our model. Recently, novel families of membrane steroid receptors, activating intracellular-signalling pathways such as MAP kinases, have been identified and described. This opens new

  12. Ependymal cells of chordate larvae are stem-like cells that form the adult nervous system.

    PubMed

    Horie, Takeo; Shinki, Ryoko; Ogura, Yosuke; Kusakabe, Takehiro G; Satoh, Nori; Sasakura, Yasunori

    2011-01-27

    In ascidian tunicates, the metamorphic transition from larva to adult is accompanied by dynamic changes in the body plan. For instance, the central nervous system (CNS) is subjected to extensive rearrangement because its regulating larval organs are lost and new adult organs are created. To understand how the adult CNS is reconstructed, we traced the fate of larval CNS cells during ascidian metamorphosis by using transgenic animals and imaging technologies with photoconvertible fluorescent proteins. Here we show that most parts of the ascidian larval CNS, except for the tail nerve cord, are maintained during metamorphosis and recruited to form the adult CNS. We also show that most of the larval neurons disappear and only a subset of cholinergic motor neurons and glutamatergic neurons are retained. Finally, we demonstrate that ependymal cells of the larval CNS contribute to the construction of the adult CNS and that some differentiate into neurons in the adult CNS. An unexpected role of ependymal cells highlighted by this study is that they serve as neural stem-like cells to reconstruct the adult nervous network during chordate metamorphosis. Consequently, the plasticity of non-neuronal ependymal cells and neuronal cells in chordates should be re-examined by future studies.

  13. Predetermined embryonic glial cells form the distinct glial sheaths of the Drosophila peripheral nervous system.

    PubMed

    von Hilchen, Christian M; Bustos, Alvaro E; Giangrande, Angela; Technau, Gerhard M; Altenhein, Benjamin

    2013-09-01

    One of the numerous functions of glial cells in Drosophila is the ensheathment of neurons to isolate them from the potassium-rich haemolymph, thereby establishing the blood-brain barrier. Peripheral nerves of flies are surrounded by three distinct glial cell types. Although all embryonic peripheral glia (ePG) have been identified on a single-cell level, their contribution to the three glial sheaths is not known. We used the Flybow system to label and identify each individual ePG in the living embryo and followed them into third instar larva. We demonstrate that all ePG persist until the end of larval development and some even to adulthood. We uncover the origin of all three glial sheaths and describe the larval differentiation of each peripheral glial cell in detail. Interestingly, just one ePG (ePG2) exhibits mitotic activity during larval stages, giving rise to up to 30 glial cells along a single peripheral nerve tract forming the outermost perineurial layer. The unique mitotic ability of ePG2 and the layer affiliation of additional cells were confirmed by in vivo ablation experiments and layer-specific block of cell cycle progression. The number of cells generated by this glial progenitor and hence the control of perineurial hyperplasia correlate with the length of the abdominal nerves. By contrast, the wrapping and subperineurial glia layers show enormous hypertrophy in response to larval growth. This characterisation of the embryonic origin and development of each glial sheath will facilitate functional studies, as they can now be addressed distinctively and genetically manipulated in the embryo.

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

    PubMed

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

    2015-07-15

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

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

    PubMed Central

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

    2015-01-01

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

  16. Mitofusin 2 expression dominates over mitofusin 1 exclusively in mouse dorsal root ganglia - a possible explanation for peripheral nervous system involvement in Charcot-Marie-Tooth 2A.

    PubMed

    Kawalec, Maria; Zabłocka, Barbara; Kabzińska, Dagmara; Neska, Jacek; Beręsewicz, Małgorzata

    2014-01-01

    Mitofusin 2 (Mfn2), a protein of the mitochondrial outer membrane, is essential for mitochondrial fusion and contributes to the maintenance and operation of the mitochondrial network. Mutations in the mitofusin 2 gene cause axonal Charcot-Marie-Tooth type 2A (CMT2A), an inherited disease affecting peripheral nerve axons. The precise mechanism by which mutations in MFN2 selectively cause the degeneration of long peripheral axons is not known. There is a hypothesis suggesting the involvement of reduced expression of a homologous protein, mitofusin 1 (Mfn1), in the peripheral nervous system, and less effective compensation of defective mitofusin 2 by mitofusin 1. We therefore aimed to perform an analysis of the mitofusin 1 and mitofusin 2 mRNA and protein expression profiles in different mouse tissues, with special attention paid to dorsal root ganglia (DRGs), as parts of the peripheral nervous system. Quantitative measurement relating to mRNA revealed that expression of the Mfn2 gene dominates over Mfn1 mainly in mouse DRG, as opposed to other nervous system samples and other tissues studied. This result was further supported by Western blot evaluation. Both these sets of data confirm the hypothesis that the cellular consequences of mutations in the mitofusin 2 gene can mostly be manifested in the peripheral nervous system.

  17. 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

  18. Peripheral Axons of the Adult Zebrafish Maxillary Barbel Extensively Remyelinate During Sensory Appendage Regeneration

    PubMed Central

    Moore, Alex C.; Mark, Tiffany E.; Hogan, Ann K.; Topczewski, Jacek; LeClair, Elizabeth E.

    2013-01-01

    Myelination is a cellular adaptation allowing rapid conduction along axons. We have investigated peripheral axons of the zebrafish maxillary barbel (ZMB), an optically clear sensory appendage. Each barbel carries taste buds, solitary chemosensory cells, and epithelial nerve endings, all of which regenerate after amputation (LeClair and Topczewski [2010] PLoS One 5:e8737). The ZMB contains axons from the facial nerve; however, myelination within the barbel itself has not been established. Transcripts of myelin basic protein (mbp) are expressed in normal and regenerating adult barbels, indicating activity in both maintenance and repair. Myelin was confirmed in situ by using toluidine blue, an anti-MBP antibody, and transmission electron microscopy (TEM). The adult ZMB contains ~180 small-diameter axons (<2 μm), approximately 60% of which are myelinated. Developmental myelination was observed via whole-mount immunohistochemistry 4-6 weeks postfertilization, showing myelin sheaths lagging behind growing axons. Early-regenerating axons (10 days postsurgery), having no or few myelin layers, were disorganized within a fibroblast-rich collagenous scar. Twenty-eight days postsurgery, barbel axons had grown out several millimeters and were organized with compact myelin sheaths. Fiber types and axon areas were similar between normal and regenerated tissue; within 4 weeks, regenerating axons restored ~85% of normal myelin thickness. Regenerating barbels express multiple promyelinating transcription factors (sox10, oct6 = pou3f1; krox20a/b = egr2a/b) typical of Schwann cells. These observations extend our understanding of the zebrafish peripheral nervous system within a little-studied sensory appendage. The accessible ZMB provides a novel context for studying axon regeneration, Schwann cell migration, and remyelination in a model vertebrate. PMID:22592645

  19. Peripheral nervous system injury after high-dose single-fraction image-guided stereotactic radiosurgery for spine tumors.

    PubMed

    Stubblefield, Michael D; Ibanez, Katarzyna; Riedel, Elyn R; Barzilai, Ori; Laufer, Ilya; Lis, Eric; Yamada, Yoshiya; Bilsky, Mark H

    2017-03-01

    OBJECTIVE The object of this study was to determine the percentage of high-dose (1800-2600 cGy) single-fraction stereotactic radiosurgery (SF-SRS) treatments to the spine that result in peripheral nervous system (PNS) injury. METHODS All patients treated with SF-SRS for primary or metastatic spine tumors between January 2004 and May 2013 and referred to the Rehabilitation Medicine Service for evaluation and treatment of neuromuscular, musculoskeletal, or functional impairments or pain were retrospectively identified. RESULTS Five hundred fifty-seven SF-SRS treatments in 447 patients resulted in 14 PNS injuries in 13 patients. All injures resulted from SF-SRS delivered to the cervical or lumbosacral spine at 2400 cGy. The overall percentage of SF-SRS treatments resulting in PNS injury was 2.5%, increasing to 4.5% when the thoracic spine was excluded from analysis. The median time to symptom onset following SF-SRS was 10 months (range 4-32 months). The plexus (cervical, brachial, and/or lumbosacral) was affected clinically and/or electrophysiologically in 12 (86%) of 14 cases, the nerve root in 2 (14%) of 14, and both in 6 (43%) of 14 cases. All patients experienced pain and most (93%) developed weakness. Peripheral nervous system injuries were CTCAE Grade 1 in 14% of cases, 2 in 64%, and 3 in 21%. No dose relationship between SF-SRS dose and PNS injury was detected. CONCLUSIONS Single-fraction SRS to the spine can result in PNS injury with major implications for function and quality of life.

  20. Histamine Immunoreactive Elements in the Central and Peripheral Nervous Systems of the Snail, Biomphalaria spp., Intermediate Host for Schistosoma mansoni.

    PubMed

    Habib, Mohamed R; Mohamed, Azza H; Osman, Gamalat Y; Sharaf El-Din, Ahmed T; Mossalem, Hanan S; Delgado, Nadia; Torres, Grace; Rolón-Martínez, Solymar; Miller, Mark W; Croll, Roger P

    2015-01-01

    Histamine appears to be an important transmitter throughout the Animal Kingdom. Gastropods, in particular, have been used in numerous studies establishing potential roles for this biogenic amine in the nervous system and showing its involvement in the generation of diverse behaviours. And yet, the distribution of histamine has only previously been described in a small number of molluscan species. The present study examined the localization of histamine-like immunoreactivity in the central and peripheral nervous systems of pulmonate snails of the genus Biomphalaria. This investigation demonstrates immunoreactive cells throughout the buccal, cerebral, pedal, left parietal and visceral ganglia, indicative of diverse regulatory functions in Biomphalaria. Immunoreactivity was also present in statocyst hair cells, supporting a role for histamine in graviception. In the periphery, dense innervation by immunoreactive fibers was observed in the anterior foot, perioral zone, and other regions of the body wall. This study thus shows that histamine is an abundant transmitter in these snails and its distribution suggest involvement in numerous neural circuits. In addition to providing novel subjects for comparative studies of histaminegic neurons in gastropods, Biomphalaria is also the major intermediate host for the digenetic trematode parasite, which causes human schistosomiasis. The study therefore provides a foundation for understanding potential roles for histamine in interactions between the snail hosts and their trematode parasites.

  1. Effect of insulin-induced hypoglycaemia on the peripheral nervous system: focus on adaptive mechanisms, pathogenesis and histopathological changes.

    PubMed

    Jensen, V F H; Mølck, A-M; Bøgh, I B; Lykkesfeldt, J

    2014-08-01

    Insulin-induced hypoglycaemia (IIH) is a common acute side effect in type 1 and type 2 diabetic patients, especially during intensive insulin therapy. The peripheral nervous system (PNS) depends on glucose as its primary energy source during normoglycaemia and, consequently, it may be particularly susceptible to IIH damage. Possible mechanisms for adaption of the PNS to IIH include increased glucose uptake, utilisation of alternative energy substrates and the use of Schwann cell glycogen as a local glucose reserve. However, these potential adaptive mechanisms become insufficient when the hypoglycaemic state exceeds a certain level of severity and duration, resulting in a sensory-motor neuropathy with associated skeletal muscle atrophy. Large myelinated motor fibres appear to be particularly vulnerable. Thus, although the PNS is not an obligate glucose consumer, as is the brain, it appears to be more prone to IIH than the central nervous system when hypoglycaemia is not severe (blood glucose level ≤ 2 mm), possibly reflecting a preferential protection of the brain during periods of inadequate glucose availability. With a primary focus on evidence from experimental animal studies investigating nondiabetic IIH, the present review discusses the effect of IIH on the PNS with a focus on adaptive mechanisms, pathogenesis and histological changes.

  2. Identification and characterization of two neuromedin U receptors differentially expressed in peripheral tissues and the central nervous system.

    PubMed

    Raddatz, R; Wilson, A E; Artymyshyn, R; Bonini, J A; Borowsky, B; Boteju, L W; Zhou, S; Kouranova, E V; Nagorny, R; Guevarra, M S; Dai, M; Lerman, G S; Vaysse, P J; Branchek, T A; Gerald, C; Forray, C; Adham, N

    2000-10-20

    Two structurally related, G-protein-coupled receptors were identified as receptors for the neuropeptide, neuromedin U. This peptide is found in highest levels in the gut and genitourinary system where it potently contracts smooth muscle but is also expressed in the spinal cord and discrete regions of the brain. Binding sites for neuromedin U have been characterized in rat uterus, however, little is known about the activity of this peptide in the regions of the central nervous system where it is expressed. The receptors characterized in this report are activated by neuromedin U at nanomolar potency in heterologous expression systems and bind radiolabeled neuromedin U with high affinity. Localization of the receptor RNA by quantitative reverse transcription-polymerase chain reaction in a variety of human tissues shows distinct expression patterns for the two receptors. NMU1 is expressed predominantly in peripheral tissues, whereas NMU2 is more highly expressed in the central nervous system. Identification of neuromedin U receptor subtypes will greatly aid in the determination of the physiological roles of this peptide.

  3. Locus coeruleus lesions and PCOS: role of the central and peripheral sympathetic nervous system in the ovarian function of rat

    PubMed Central

    Zafari Zangeneh, Farideh; Abdollahi, Alireza; Aminee, Fatemeh; Naghizadeh, Mohammad Mahdi

    2012-01-01

    Background: “Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder associated with ovulatory dysfunction”. “Autonomic and central nervous systems play important roles in the regulation of ovarian physiology”. The noradrenergic nucleus locus coeruleus (LC) plays a central role in the regulation of the sympathetic nervous system and synaptically connected to the preganglionic cell bodies of the ovarian sympathetic pathway and its activation is essential to trigger spontaneous or induced LH surges. This study evaluates sympathetic outflow in central and peripheral pathways in PCO rats. Objective: Our objectives in this study were (1) to estimate LC activity in rats with estradiol valerate (EV)-induced PCO; (2) to antagonized alpha2a adrenoceptor in systemic conditions with yohimbine. Materials and Methods: Forty two rats were divided into two groups: 1) LC and yohimbine and 2) control. Every group subdivided in two groups: eighteen rats were treated with estradiol valerate for induction of follicular cysts and the remainders were sesame oil groups. Results: Estradiol concentration was significantly augmented by the LC lesion in PCO rats (p<0.001), while LC lesion could not alter serum concentrations of LH and FSH, like yohimbine. The morphological observations of ovaries of LC lesion rats showed follicles with hyperthecosis, but yohimbine reduced the number of cysts, increased corpus lutea and developed follicles. Conclusion: Rats with EV-induced PCO increased sympathetic activity. LC lesion and yohimbine decreased the number of cysts and yohimbine increased corpus lutea and developed follicles in PCO rats. PMID:25242983

  4. Advances in peripheral nervous system regenerative therapeutic strategies: A biomaterials approach.

    PubMed

    Dalamagkas, Kyriakos; Tsintou, Magdalini; Seifalian, Alexander

    2016-08-01

    Peripheral nerve injury is a very common medical condition with varying clinical severity but always great impact on the patients' productivity and the quality of life. Even the current 1st-choice surgical therapeutic approach or the "gold standard" as frequently called in clinical practice, is not addressing the problem efficiently and cost-effectively, increasing the mortality through the need of a second surgical intervention, while it does not take into account the several different types of nerves involved in peripheral nerve injuries. Neural tissue engineering approaches could potentially offer a very promising and attractive tool for the efficient peripheral nerve injury management, not only by mechanically building the gap, but also by inducing neuroregenerative mechanisms in a well-regulated microenvironment which would mimic the natural environment of the specific nerve type involved in the injury to obtain an optimum clinical outcome. There is still room for a lot of optimizations in regard to the conduits which have been developed with the help of neural engineering since many parameters affect the clinical outcome and the underlying mechanisms are still not well understood. Especially the intraluminal cues controlling the microenvironment of the conduits are in an infantile stage but there is profound potential in the application of the scaffolds. The aim of our review is to provide a quick reference to the recent advances in the field, focusing on the parameters that can significantly affect the clinical potentials of each approach, with suggestions for future improvements that could take the current work from bench to bedside. Thus, further research could shed light to those questions and it might hold the key to discover new more efficient and cost-effective therapies.

  5. Human neurocysticercosis: in vivo expansion of peripheral regulatory T cells and their recruitment in the central nervous system.

    PubMed

    Adalid-Peralta, Laura; Fleury, Agnes; García-Ibarra, Teresa M; Hernández, Marisela; Parkhouse, Michael; Crispín, José Carlos; Voltaire-Proaño, Jefferson; Cárdenas, Graciela; Fragoso, Gladis; Sciutto, Edda

    2012-02-01

    Human neurocysticercosis (NC) is caused by Taenia solium larvae lodged in the central nervous system. Most cases occur with no, or mild, neurological symptoms. However, in some patients, neuroinflammation is exacerbated, leading to severe forms of the disease. Considering the critical role of regulatory T cells (Tregs) in balancing inflammation in chronic diseases, their participation in restraining the inflammatory response in NC was explored in the present study. The frequency of Tregs and their relationship with the level of the proliferative response, the level of activated lymphocytes, and the cytokines expressed were determined in severe NC patients compared with those from healthy donors. Significantly increased peripheral Tregs (CD4(+)CD25(high) and CD4(+)CD25(high)FoxP3(+), CD4(+)CD25(high)CTLA4(+), and CD4(+)CD25(high) IL10(+)) and a significant decrease in activated (CD38(+) and CD69(+)) T cells were observed in 19 NC patients versus 10 healthy subjects. Significantly increased Tregs in NC are accompanied by a depressed specific, and non-specific, lymphocyte proliferative response, and they negatively correlate with activated CD4(+)CD69(+) lymphocytes. Treg frequencies were also determined in cerebral spinal fluid for 8 of the 19 NC patients. A positive significant correlation between peripheral and local Tregs was observed. Here, we report for the first time data that support the possible contribution of local and systemic Tregs in limiting neuroinflammation in NC.

  6. Systemic effects of low-power laser irradiation on the peripheral and central nervous system, cutaneous wounds, and burns

    SciTech Connect

    Rochkind, S.; Rousso, M.; Nissan, M.; Villarreal, M.; Barr-Nea, L.; Rees, D.G.

    1989-01-01

    In this paper, we direct attention to the systemic effect of low-power helium-neon (HeNe) laser irradiation on the recovery of the injured peripheral and central nervous system, as well as healing of cutaneous wounds and burns. Laser irradiation on only the right side in bilaterally inflicted cutaneous wounds enhanced recovery in both sides compared to the nonirradiated control group (P less than .01). Similar results were obtained in bilateral burns: irradiating one of the burned sites also caused accelerated healing in the nonirradiated site (P less than .01). However, in the nonirradiated control group, all rats suffered advanced necrosis of the feet and bilateral gangrene. Low-power HeNe laser irradiation applied to a crushed injured sciatic nerve in the right leg in a bilaterally inflicted crush injury, significantly increased the compound action potential in the left nonirradiated leg as well. The statistical analysis shows a highly significant difference between the laser-treated group and the control nonirradiated group (P less than .001). Finally, the systemic effect was found in the spinal cord segments corresponding to the crushed sciatic nerves. The bilateral retrograde degeneration of the motor neurons of the spinal cord expected after the bilateral crush injury of the peripheral nerves was greatly reduced in the laser treated group. The systemic effects reported here are relevant in terms of the clinical application of low-power laser irradiation as well as for basic research into the possible mechanisms involved.

  7. Identification of mammalian noggin and its expression in the adult nervous system.

    PubMed

    Valenzuela, D M; Economides, A N; Rojas, E; Lamb, T M; Nuñez, L; Jones, P; Lp, N Y; Espinosa, R; Brannan, C I; Gilbert, D J

    1995-09-01

    The multiple roles of noggin during dorsal fate specification in Xenopus embryos, together with noggin's ability to directly induce neural tissue, inspired an effort to determine whether a similar molecule exists in mammals. Here we describe the identification of human and rat noggin and explore their expression patterns; we also localize the human NOGGIN gene to chromosome 17q22, and the mouse gene to a syntenic region of chromosome 11. Mammalian noggin is remarkably similar in its sequence to Xenopus noggin, and is similarly active in induction assays performed on Xenopus embryo tissues. In the adult mammal, noggin is most notably expressed in particular regions of the nervous system, such as the tufted cells of the olfactory bulb, the piriform cortex of the brain, and the Purkinje cells of the cerebellum, suggesting that one of the earliest acting neural inducers also has important roles in the adult nervous system.

  8. Targeted Drug Delivery to the Peripheral Nervous System using Gene Therapy

    PubMed Central

    Wolfe, Darren; Mata, Marina; Fink, David J.

    2012-01-01

    Gene transfer to target delivery of neurotrophic factors to the primary sensory afferent for treatment of polyneuropathy, or of inhibitory neurotransmitters for relief of chronic pain, offers the possibility of a highly selective targeted release of bioactive molecules within the nervous system. Preclinical studies with non-replicating herpes simplex virus (HSV)-based vectors injected into the skin to transduce neurons in the dorsal root ganglion have demonstrated efficacy in reducing-pain related behaviors in animal models of inflammatory pain, neuropathic pain, and pain caused by cancer, and in preventing progression of sensory neuropathy caused by toxins, chemotherapeutic drugs or resulting from diabetes. Successful completion of the first phase 1 clinical trial of HSV-mediated gene transfer in patients with intractable pain from cancer has set the stage for further clinical trials of this approach. PMID:22565023

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

    PubMed Central

    2015-01-01

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

  10. [Changes in the central and peripheral nervous system in cows after laparotomy].

    PubMed

    Eustachiewicz, R; Welento, J; Flieger, S; Szalak, M; Boratyński, Z; Krzyzanowski, J; Sławomirski, J

    1984-01-01

    Two sexually mature cows were used for the studies in which operations were performed, consisting in cutting the abdominal tunics at a length of 30 cm in the left iliac region. The cows were kept alive for 21 days after the operation. Then they were slaughtered, taking the following material for studies: The spinal cord, bilateral spinal ganglions, bilateral subvertebral sympathetic ganglions and autonomous ganglions of abdominal and pelvic cavities. The material was embedded in paraffin and cut into 15 n sections, which were stained with methylene blue according to Nissel. Regressive changes in cells of many nervous centres due to the operations performed were found. They were found in: spinal ganglions of the lumbar and sacral segment, nuclei of spinal grey matter (nucleus motorius, nucleus dorsalis, nucleus intermediomedialis, nucleus intermediolateralis) in the lumbar and sacral segment and in the sympathetic subvertebral ganglions of the lumbar and sacral segment. Degeneration changes of the cells were observed only on the operated side.

  11. The Role of the Peripheral and Central Nervous Systems in Rotator Cuff Disease

    PubMed Central

    Bachasson, Damien; Singh, Anshuman; Shah, Sameer; Lane, John G.; Ward, Samuel R.

    2015-01-01

    Rotator cuff (RC) disease is an extremely common condition associated with shoulder pain, reduced functional capacities and impaired quality of life. It primarily involves alterations in tendon health and mechanical properties that can ultimately lead to tendon failure. RC tendon tears induce progressive muscular changes that negatively impact surgical reparability of the RC tendons and clinical outcomes. At the same time, a significant base of clinical data suggests a relatively weak relationship between RC integrity and clinical presentation, emphasizing the multifactorial aspects of RC disease. This review aims to summarize the potential contribution of peripheral, spinal and supraspinal neural factors that may: (i) exacerbate structural and functional muscle changes induced by tendon tear, (ii) compromise the reversal of these changes during surgery and rehabilitation, (iii) contribute to pain generation and persistence of pain, iv) impair shoulder function through reduced proprioception, kinematics and muscle recruitment, and iv) help to explain interindividual differences and response to treatment. Given the current clinical and scientific interest in peripheral nerve injury in the context of RC disease and surgery, we carefully reviewed this body of literature with a particular emphasis for suprascapular neuropathy that has generated a large number of studies in the past decade. Within this process, we highlight the gaps in current knowledge and suggest research avenues for scientists and clinicians. PMID:26189809

  12. The role of the peripheral and central nervous systems in rotator cuff disease.

    PubMed

    Bachasson, Damien; Singh, Anshuman; Shah, Sameer B; Lane, John G; Ward, Samuel R

    2015-08-01

    Rotator cuff (RC) disease is an extremely common condition associated with shoulder pain, reduced functional capacities, and impaired quality of life. It primarily involves alterations in tendon health and mechanical properties that can ultimately lead to tendon failure. RC tendon tears induce progressive muscle changes that have a negative impact on surgical reparability of the RC tendons and clinical outcomes. At the same time, a significant base of clinical data suggests a relatively weak relationship between RC integrity and clinical presentation, emphasizing the multifactorial aspects of RC disease. This review aims to summarize the potential contribution of peripheral, spinal, and supraspinal neural factors that may (1) exacerbate structural and functional muscle changes induced by tendon tear, (2) compromise the reversal of these changes during surgery and rehabilitation, (3) contribute to pain generation and persistence of pain, (4) impair shoulder function through reduced proprioception, kinematics, and muscle recruitment, and (5) help explain interindividual differences and response to treatment. Given the current clinical and scientific interest in peripheral nerve injury in the context of RC disease and surgery, we carefully reviewed this body of literature with a particular emphasis on suprascapular neuropathy that has generated a large number of studies in the past decade. Within this process, we highlight the gaps in current knowledge and suggest research avenues for scientists and clinicians.

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

    PubMed

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

    2016-12-01

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

  14. Dynamic analysis of mental sweating and the peripheral vessels for the activity of the autonomic nervous system by optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Ohmi, Masato; Takada, Daisuke; Wada, Yuki; Haruna, Masamitsu

    2012-01-01

    OCT is highly potential for dynamic analysis of physiological functions of mental sweating and peripheral vessels as demonstrated by the authors. Both mental sweating and the peripheral vessels reflect the activity of the sympathetic nerve of the autonomic nervous system (ANS). The sympathetic nerve also exhibits the LF/HF ratio of the heart rate variability (HRV). In this paper, we demonstrate dynamic analysis of mental sweating and the peripheral vessels for the external stimulus by SS-OCT. In the experiment, the Kraepelin test as a continuous stimulus was applied to the volunteer to discuss in detail dynamics of the physiological function of such small organs in response to the HRV.

  15. Human central nervous system response to peripheral action of low-intensity millimeter waves

    SciTech Connect

    Lebedeva, N.N.

    1994-07-01

    We employ a modification of a psychophysical method developed by Kholodov to study electromagnetic field induced skin sensations. The main part of the setup is a program controller, which provides for the timed delivery of EMF signals and also false presentations. The EMF signals are fed in random order with a uniform distribution. The response-strength index and the false-alarm level were used to evaluate MF sensitivity. In addition, the subjects determined the presence or absence of a field according to four criteria. Forty healthy subjects ages 17 to 35 were tested on their right and left hands. Sensory data was analyzed via computer. EEG responses to peripheral action were studied in depth.

  16. THE ROLE OF ANDROGENS AND ESTROGENS IN THE DEVELOPMENT OF BRAIN AND PERIPHERAL NERVOUS SYSTEM: APPROACHES TO DEVELOPING ANIMAL MODELS FOR SEXUALLY DIMORPHIC BEHAVIORS

    EPA Science Inventory

    This presentation provides an overview of research on the effects of hormonally active chemicals on sexual differentiation of the brain including (a) research on the role of androgens and estrogens in the development of the brain and peripheral nervous system, (b) approaches to d...

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

    PubMed

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

    2007-01-01

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

  18. Reduced BACE1 activity enhances clearance of myelin debris and regeneration of axons in the injured peripheral nervous system

    PubMed Central

    Farah, Mohamed H.; Pan, Bao Han; Hoffman, Paul N.; Ferraris, Dana; Tsukamoto, Takashi; Nguyen, Thien; Wong, Philip C.; Price, Donald L.; Slusher, Barbara S.; Griffin, John W.

    2012-01-01

    β- site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) is an aspartyl protease best known for its role in generating the amyloid β peptides that are present in plaques of Alzheimer's Disease. BACE1 has been an attractive target for drug development. In cultured embryonic neurons BACE1-cleaved N-terminal APP is further processed to generate a fragment that can trigger axonal degeneration, suggesting a vital role for BACE1 in axonal health. In addition, BACE1 cleaves neuregulin 1 type III, a protein critical for myelination of peripheral axons by Schwann cells during development. Here, we asked if axonal degeneration or axonal regeneration in adult nerves might be affected by inhibition or elimination of BACE1. We report that BACE1 knockout and wild-type nerves degenerated at a similar rate after axotomy and to a similar extent in the experimental neuropathies produced by administration of paclitaxel and acrylamide. These data indicate N-APP is not the sole culprit in axonal degeneration in adult nerves. Unexpectedly, however, we observed that BACE1 knockout mice had markedly enhanced clearance of axonal and myelin debris from degenerated fibers, accelerated axonal regeneration, and earlier reinnervation of neuromuscular junctions, compared to littermate controls. These observations were reproduced in part by pharmacological inhibition of BACE1. These data suggest BACE1 inhibition as a therapeutic approach to accelerate regeneration and recovery after peripheral nerve damage. PMID:21490216

  19. Activated neu oncogene sequences in primary tumors of the peripheral nervous system induced in rats by transplacental exposure to ethylnitrosourea.

    PubMed Central

    Perantoni, A O; Rice, J M; Reed, C D; Watatani, M; Wenk, M L

    1987-01-01

    Neurogenic tumors were selectively induced in high incidence in F344 rats by a single transplacental exposure to the direct-acting alkylating agent N-ethyl-N-nitrosourea (EtNU). We prepared DNA for transfection of NIH 3T3 cells from primary glial tumors of the brain and from schwannomas of the cranial and spinal nerves that developed in the transplacentally exposed offspring between 20 and 40 weeks after birth. DNA preparations from 6 of 13 schwannomas, but not from normal liver, kidney, or intestine of tumor-bearing rats, transformed NIH 3T3 cells. NIH 3T3 clones transformed by schwannoma DNA contained rat repetitive DNA sequences, and all isolates contained rat neu oncogene sequences. One schwannoma yielded a transformant with rat-specific sequences for both neu and N-ras. A point mutation in the transmembrane region of the putative protein product of neu was identified in all six transformants and in the primary tumors from which they were derived as well as in 5 of 6 schwannomas tested that did not transform NIH 3T3 cells. Of 59 gliomas, only one yielded transforming DNA, and an activated N-ras oncogene was identified. The normal cellular neu sequence for the transmembrane region, but not the mutated sequence, was identified in DNA from all 11 gliomas surveyed by oligonucleotide hybridization. Activation of the neu oncogene, originally identified [Schechter, A.L., Stern, D.F., Vaidyanathan, L., Decker, S.J., Drebin, J.A., Greene, M.I. & Weinberg, R.A. (1984) Nature (London) 312, 513-516] in cultured cell lines derived from EtNU-induced neurogenic tumors that by biochemical but not histologic criteria were thought to originate in the central nervous system in BD-IX rats, appears specifically associated with tumors of the peripheral nervous system in the F344 inbred strain. Images PMID:3476947

  20. Marchi-positive myelinoid bodies at the transition between the central and the peripheral nervous system in some vertebrates.

    PubMed Central

    Corneliuson, O; Berthold, C H; Fabricius, C; Gatzinsky, K; Carlstedt, T

    1989-01-01

    The CNS-PNS (central nervous system-peripheral nervous system) transitional region of cranial and spinal nerve roots in some vertebrate species was analysed with respect to the occurrence and the distribution of myelinoid Marchi-positive bodies. Both cranial and spinal nerve roots contained more Marchi-positive bodies in their CNS than in their PNS segments. An accumulation of Marchi-positive bodies was usually noted just central to the CNS-PNS borderline. Comparisons between calibre spectra and Marchi index in the cat revealed a particularly high number of Marchi-positive bodies in nerve roots with a high content of myelinated fibres with diameters greater than or equal to 5 microns. Marchi-positive bodies were absent in CNS tissue lacking myelinated nerve fibres. CNS borderline internodes measuring between 200 and 300 microns in length were noted in fibres as thick as 15 microns in feline S1 ventral and dorsal roots. The general picture was similar in all analysed species. Noteworthy however, was the small difference in number of Marchi-positive bodies between CNS and PNS tissue in Xenopus. The chicken contained many myelinoid bodies of similar size and texture as the Marchi-positive bodies but without the Marchi-positive staining properties. The results show that normally occurring Marchi-positive bodies in the CNS are more numerous along paranodal segments than along mid-internodal segments of myelinated nerve fibres and thus support the hypothesis that Marchi-positive bodies are preferentially derived from paranodal myelin. Images Fig. 3 Fig. 4 PMID:2558098

  1. Mutations affecting the development of the peripheral nervous system in Drosophila: a molecular screen for novel proteins.

    PubMed Central

    Prokopenko, S N; He, Y; Lu, Y; Bellen, H J

    2000-01-01

    In our quest for novel genes required for the development of the embryonic peripheral nervous system (PNS), we have performed three genetic screens using MAb 22C10 as a marker of terminally differentiated neurons. A total of 66 essential genes required for normal PNS development were identified, including 49 novel genes. To obtain information about the molecular nature of these genes, we decided to complement our genetic screens with a molecular screen. From transposon-tagged mutations identified on the basis of their phenotype in the PNS we selected 31 P-element strains representing 26 complementation groups on the second and third chromosomes to clone and sequence the corresponding genes. We used plasmid rescue to isolate and sequence 51 genomic fragments flanking the sites of these P-element insertions. Database searches using sequences derived from the ends of plasmid rescues allowed us to assign genes to one of four classes: (1) previously characterized genes (11), (2) first mutations in cloned genes (1), (3) P-element insertions in genes that were identified, but not characterized molecularly (1), and (4) novel genes (13). Here, we report the cloning, sequence, Northern analysis, and the embryonic expression pattern of candidate cDNAs for 10 genes: astray, chrowded, dalmatian, gluon, hoi-polloi, melted, pebble, skittles, sticky ch1, and vegetable. This study allows us to draw conclusions about the identity of proteins required for the development of the nervous system in Drosophila and provides an example of a molecular approach to characterize en masse transposon-tagged mutations identified in genetic screens. PMID:11102367

  2. Cardiovascular effects of CDP-choline and its metabolites: involvement of peripheral autonomic nervous system.

    PubMed

    Cansev, Mehmet; Yilmaz, Mustafa Sertac; Ilcol, Yesim Ozarda; Hamurtekin, Emre; Ulus, Ismail Hakki

    2007-12-22

    Intraperitoneal administration of CDP-choline (200-900 micromol/kg) increased blood pressure and decreased heart rate of rats in a dose- and time-dependent manner. These responses were accompanied by elevated serum concentrations of CDP-choline and its metabolites phosphocholine, choline, cytidine monophosphate and cytidine. Blood pressure increased by intraperitoneal phosphocholine (200-900 micromol/kg), while it decreased by choline (200-600 micromol/kg) administration; phosphocholine or choline administration (up to 600 micromol/kg) decreased heart rate. Intraperitoneal cytidine monophosphate (200-600 micromol/kg) or cytidine (200-600 micromol/kg) increased blood pressure without affecting heart rate. Pressor responses to CDP-choline, phosphocholine, cytidine monophosphate or cytidine were not altered by pretreatment with atropine methyl nitrate or hexamethonium while hypotensive effect of choline was reversed to pressor effect by these pretreatments. Pretreatment with atropine plus hexamethonium attenuated or blocked pressor response to CDP-choline or phosphocholine, respectively. Heart rate responses to CDP-choline, phosphocholine and choline were blocked by atropine and reversed by hexamethonium. Cardiovascular responses to CDP-choline, phosphocholine and choline, but not cytidine monophosphate or cytidine, were associated with elevated plasma catecholamines concentrations. Blockade of alpha-adrenoceptors by prazosin or yohimbine attenuated pressor response to CDP-choline while these antagonists blocked pressor responses to phosphocholine or choline. Neither bilateral adrenalectomy nor chemical sympathectomy altered cardiovascular responses to CDP-choline, choline, cytidine monophosphate or cytidine. Sympathectomy attenuated pressor response to phosphocholine. Results show that intraperitoneal administration of CDP-choline and its metabolites alter cardiovascular parameters and suggest that peripheral cholinergic and adrenergic receptors are involved in these

  3. Radial glia and neural progenitors in the adult zebrafish central nervous system.

    PubMed

    Than-Trong, Emmanuel; Bally-Cuif, Laure

    2015-08-01

    The adult central nervous system (CNS) of the zebrafish, owing to its enrichment in constitutive neurogenic niches, is becoming an increasingly used model to address fundamental questions pertaining to adult neural stem cell (NSC) biology, adult neurogenesis and neuronal repair. Studies conducted in several CNS territories (notably the telencephalon, retina, midbrain, cerebellum and spinal cord) highlighted the presence, in these niches, of progenitor cells displaying NSC-like characters. While pointing to radial glial cells (RG) as major long-lasting, constitutively active and/or activatable progenitors in most domains, these studies also revealed a high heterogeneity in the progenitor subtypes used at the top of neurogenic hierarchies, including the persistence of neuroepithelial (NE) progenitors in some areas. Likewise, dissecting the molecular pathways underlying RG maintenance and recruitment under physiological conditions and upon repair in the zebrafish model revealed shared processes but also specific cascades triggering or sustaining reparative NSC recruitment. Together, the zebrafish adult brain reveals an extensive complexity of adult NSC niches, properties and control pathways, which extends existing understanding of adult NSC biology and gives access to novel mechanisms of efficient NSC maintenance and recruitment in an adult vertebrate brain.

  4. Peripheral insensate neuropathy--a tall problem for US adults?

    PubMed

    Cheng, Yiling J; Gregg, Edward W; Kahn, Henry S; Williams, Desmond E; De Rekeneire, Nathalie; Narayan, K M Venkat

    2006-11-01

    The relation between height and lower extremity peripheral insensate neuropathy among persons with and without diabetes was examined by use of the 1999-2002 US National Health and Nutrition Examination Survey with 5,229 subjects aged 40 or more years. A monofilament was used to determine whether any of three areas on each foot were insensate. Peripheral insensate neuropathy was defined as the presence of one or more insensate areas. Its prevalence was nearly twice as high among persons with diabetes (21.2%) as among those without diabetes (11.5%; p < 0.001). Men (16.2%) had 1.7 times the prevalence of peripheral insensate neuropathy as did women (9.4%), but the difference was not significant after adjustment for height. Greater height was associated with increased peripheral insensate neuropathy prevalence among persons with and without diabetes (p < 0.001). This association was characterized by a sharp increase in prevalence among persons who were taller than 175.5 cm. Peripheral insensate neuropathy risk was significantly higher among those taller than 175.5 cm (adjusted odds ratio = 2.3, 95% confidence interval: 1.5, 3.5). The authors conclude that body height is an important correlate of peripheral insensate neuropathy. This association largely accounts for the difference in peripheral insensate neuropathy prevalence between men and women. Height may help health-care providers to identify persons at high risk of peripheral insensate neuropathy.

  5. Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system

    PubMed Central

    Codeluppi, Simone; van Bruggen, David; Mendanha Falcão, Ana; Xiao, Lin; Li, Huiliang; Häring, Martin; Hochgerner, Hannah; Romanov, Roman A.; Gyllborg, Daniel; Muñoz Manchado, Ana; La Manno, Gioele; Lönnerberg, Peter; Floriddia, Elisa M.; Rezayee, Fatemah; Ernfors, Patrik; Arenas, Ernest; Hjerling-Leffler, Jens; Harkany, Tibor; Richardson, William D.; Linnarsson, Sten; Castelo-Branco, Gonçalo

    2016-01-01

    Oligodendrocytes have been considered as a functionally homogenous population in the central nervous system (CNS). We performed single-cell RNA-Seq on 5072 cells of the oligodendrocyte lineage from ten regions of the mouse juvenile/adult CNS. Twelve populations were identified, representing a continuum from Pdgfra+ oligodendrocyte precursors (OPCs) to distinct mature oligodendrocytes. Initial stages of differentiation were similar across the juvenile CNS, whereas subsets of mature oligodendrocytes were enriched in specific regions in the adult brain. Newly-formed oligodendrocytes were found to be resident in the adult CNS and responsive to complex motor learning. A second Pdgfra+ population, distinct from OPCs, was found along vessels. Our study reveals the dynamics of oligodendrocyte differentiation and maturation, uncoupling them at a transcriptional level and highlighting oligodendrocyte heterogeneity in the CNS. PMID:27284195

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

    PubMed Central

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

    2011-01-01

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

  7. Screening for Peripheral Artery Disease and Cardiovascular Disease Risk Assessment with Ankle Brachial Index in Adults

    MedlinePlus

    Understanding Task Force Recommendations Screening for Peripheral Artery Disease and Cardiovascular Disease Risk Assessment with Ankle Brachial Index in Adults The U.S. Preventive Services Task Force (Task Force) has issued a ...

  8. Short-term nutritional folate deficiency in rats has a greater effect on choline and acetylcholine metabolism in the peripheral nervous system than in the brain, and this effect escalates with age

    PubMed Central

    Crivello, Natalia A.; Blusztajn, Jan K.; Joseph, James A.; Shukitt-Hale, Barbara; Smith, Donald E.

    2010-01-01

    The hypothesis of this study is that a folate-deficient diet (FD) has a greater effect on cholinergic system in the peripheral nervous system than in the brain, and that this effect escalates with age. It was tested by comparing choline and acetylcholine levels in male Sprague Dawley rats fed either control or folate-deficient diets for 10 weeks, starting at age 4 weeks (the young group) or 9 months (the adult group). FD consumption resulted in depletion of plasma folate in both age groups. In young folate-deficient rats, liver and lung choline levels were significantly lower than those in the respective controls. No other significant effects of FD on choline and acetylcholine metabolism were found in young rats. In adult rats, FD consumption markedly decreased choline levels in the liver, kidneys, and heart; furthermore, choline levels in the cortex and striatum were moderately elevated, although hippocampal choline levels were not affected. Acetylcholine levels were higher in the heart, cortex, and striatum but lower in the hippocampus in adult folate-deficient rats, as compared to controls. Higher acetylcholine levels in the striatum in adult folate-deficient rats were also associated with higher dopamine release in the striatal slices. Thus, both age groups showed higher cholinergic metabolic sensitivity to FD in the peripheral nervous system than in the brain. However, compensatory abilities appeared to be better in the young group, implicating the adult group as a preferred model for further investigation of folate-choline-acetylcholine interactions and their role in brain plasticity and cognitive functions. PMID:21056288

  9. Ventral tegmental area neurons are either excited or inhibited by cocaine’s actions in the peripheral nervous system

    PubMed Central

    Mejías-Aponte, Carlos A.; Kiyatkin, Eugene A.

    2012-01-01

    Cocaine’s multiple pharmacological substrates are ubiquitously present in the peripheral and central nervous system. Thus, upon its administration, cocaine acts in the periphery before directly acting in the brain. We determined whether cocaine alters ventral tegmental area (VTA) neuronal activity via peripheral actions, and whether this precedes its central actions. In urethane-anesthetized rats, we recorded VTA neurons responses to intravenous injections of two cocaine analogs: cocaine-hydrochloride (HCl, 0.25 mg/kg) that readily cross the blood-brain barrier (BBB) and cocaine-methiodide (MI, 0.33 mg/kg) that does not cross the BBB. Both cocaine analogs produced sustained changes in discharge rates that began 5s after the initiation of a 10s drug infusion. Within the first 90s post-injection the magnitudes of neuronal responsive of both cocaine analogs were comparable, but later in time the effects of cocaine-HCl were stronger and persisted longer than those of cocaine-MI. The proportion of neurons responsive to cocaine-HCl was twice to that of cocaine-MI (74% and 35% respectively). Both analogs also differed in the response onsets. Cocaine-MI rarely evoked responses after 1 min whereas cocaine-HCl continued to evoke responses within 3 min post-injection. VTA neurons were either excited or inhibited by both cocaine analogs. Most units responsive to cocaine-MI, regardless of excitation or inhibition, had electrophysiological characteristics of putative DA neurons. Units inhibited by cocaine-HCl also had characteristic of DA neurons whereas excited neurons had widely varying action potential durations and discharge rates. Cocaine-MI and cocaine-HCl each produced changes in VTA neuron activity under full DA receptor blockade. However, the duration of inhibition was shortened, the number of excitations increased, and they occurred with an earlier onset during DA receptor blockade. These findings indicate that cocaine acts peripherally with a short latency and

  10. Defining peripheral nervous system dysfunction in the SOD-1G93A transgenic rat model of amyotrophic lateral sclerosis.

    PubMed

    Riva, Nilo; Chaabane, Linda; Peviani, Marco; Ungaro, Daniela; Domi, Teuta; Dina, Giorgia; Bianchi, Francesca; Spano, Giorgia; Cerri, Federica; Podini, Paola; Corbo, Massimo; Carro, Ubaldo Del; Comi, Giancarlo; Bendotti, Caterina; Quattrini, Angelo

    2014-07-01

    Growing evidence indicates that alterations within the peripheral nervous system (PNS) are involved at an early stage in the amyotrophic lateral sclerosis (ALS) pathogenetic cascade. In this study, magnetic resonance imaging (MRI), neurophysiologic analyses, and histologic analyses were used to monitor the extent of PNS damage in the hSOD-1 ALS rat model. The imaging signature of the disease was defined using in vivo MRI of the sciatic nerve. Initial abnormalities were detected in the nerves by an increase in T2 relaxation time before the onset of clinical disease; diffusion MRI showed a progressive increase in mean and radial diffusivity and reduction of fractional anisotropy at advanced stages of disease. Histologic analysis demonstrated early impairment of the blood-nerve barrier followed by acute axonal degeneration associated with endoneurial edema and macrophage response in motor nerve compartments. Progressive axonal degeneration and motor nerve fiber loss correlated with MRI and neurophysiologic changes. These functional and morphologic investigations of the PNS might be applied in following disease progression in preclinical therapeutic studies. This study establishes the PNS signature in this rat ALS model (shedding new light into pathogenesis) and provides a rationale for translating into future systematic MRI studies of PNS involvement in patients with ALS.

  11. Classification of Activity Engagement in Individuals with Severe Physical Disabilities Using Signals of the Peripheral Nervous System

    PubMed Central

    Kushki, Azadeh; Andrews, Alexander J.; Power, Sarah D.; King, Gillian; Chau, Tom

    2012-01-01

    Communication barriers often result in exclusion of children and youth with disabilities from activities and social settings that are essential to their psychosocial development. In particular, difficulties in describing their experiences of activities and social settings hinder our understanding of the factors that promote inclusion and participation of this group of individuals. To address this specific communication challenge, we examined the feasibility of developing a language-free measure of experience in youth with severe physical disabilities. To do this, we used the activity of the peripheral nervous system to detect patterns of psychological arousal associated with activities requiring different patterns of cognitive/affective and interpersonal involvement (activity engagement). We demonstrated that these signals can differentiate among patterns of arousal associated with these activities with high accuracy (two levels: 81%, three levels: 74%). These results demonstrate the potential for development of a real-time, motor- and language-free measure for describing the experiences of children and youth with disabilities. PMID:22363432

  12. Activated neu oncogene sequences in primary tumors of the peripheral nervous system induced in rats by transplacental exposure to ethylnitrosourea

    SciTech Connect

    Perantoni, A.O.; Rice, J.M.; Reed, C.D.; Watatani, M.; Wenk, M.L.

    1987-09-01

    Neurogenic tumors were selectively induced in high incidence in F344 rats by a single transplacental exposure to the direct-acting alkylating agent N-ethyl-N-nitrosourea (EtNU). The authors prepared DNA for transfection of NIH 3T3 cells from primary glial tumors of the brain and form schwannomas of the cranial and spinal nerves that developed in the transplacentally exposed offspring between 20 and 40 weeks after birth. DNA preparations from 6 of 13 schwannomas, but not from normal liver, kidney, or intestine of tumor-bearing rats, transformed NIH 3T3 cells. NIH 3T3 clones transformed by schwannoma DNA contained rat repetitive DNA sequences, and all isolates contained rat neu oncogene sequences. A point mutation in the transmembrane region of the putative protein product of neu was identified in all six transformants and in the primary tumors from which they were derived as well as in 5 of 6 schwannomas tested that did not transform NIH 3T3 cells. Of 59 gliomas, only one yielded transforming DNA, and an activated N-ras oncogen was identified. The normal cellular neu sequence for the transmembrane region, but not the mutated sequence, was identified in DNA from all 11 gliomas surveyed by oligonucleotide hybridization. Activation of the neu oncogene, originally identified in cultured cell lines derived from EtNU-induced neurogenic tumors appears specifically associated with tumors of the peripheral nervous system in the F344 inbred strain.

  13. Peripheral Nervous System Function and Organophosphate Pesticide Use among Licensed Pesticide Applicators in the Agricultural Health Study

    PubMed Central

    Starks, Sarah E.; Hoppin, Jane A.; Kamel, Freya; Lynch, Charles F.; Jones, Michael P.; Alavanja, Michael C.; Sandler, Dale P.

    2012-01-01

    Background: Evidence is limited that long-term human exposure to organophosphate (OP) pesticides, without poisoning, is associated with adverse peripheral nervous system (PNS) function. Objective: We investigated associations between OP pesticide use and PNS function by administering PNS tests to 701 male pesticide applicators in the Agricultural Health Study (AHS). Methods: Participants completed a neurological physical examination (NPx) and electrophysiological tests as well as tests of hand strength, sway speed, and vibrotactile threshold. Self-reported information on lifetime use of 16 OP pesticides was obtained from AHS interviews and a study questionnaire. Associations between pesticide use and measures of PNS function were estimated with linear and logistic regression controlling for age and outcome-specific covariates. Results: Significantly increased odds ratios (ORs) were observed for associations between ever use of 10 of the 16 OP pesticides and one or more of six NPx outcomes. Most notably, abnormal toe proprioception was significantly associated with ever use of 6 OP pesticides, with ORs ranging from 2.03 to 3.06; monotonic increases in strength of association with increasing use was observed for 3 of the 6 pesticides. Mostly null associations were observed between OP pesticide use and electrophysiological tests, hand strength, sway speed, and vibrotactile threshold. Conclusions: This study provides some evidence that long-term exposure to OP pesticides is associated with signs of impaired PNS function among pesticide applicators. PMID:22262687

  14. Integrin-linked kinase is required for radial sorting of axons and Schwann cell remyelination in the peripheral nervous system

    PubMed Central

    Pereira, Jorge A.; Benninger, Yves; Baumann, Reto; Gonçalves, Ana Filipa; Özçelik, Murat; Thurnherr, Tina; Tricaud, Nicolas; Meijer, Dies; Fässler, Reinhard; Suter, Ueli

    2009-01-01

    During development, Schwann cells (SCs) interpret different extracellular cues to regulate their migration, proliferation, and the remarkable morphological changes associated with the sorting, ensheathment, and myelination of axons. Although interactions between extracellular matrix proteins and integrins are critical to some of these processes, the downstream signaling pathways they control are still poorly understood. Integrin-linked kinase (ILK) is a focal adhesion protein that associates with multiple binding partners to link integrins to the actin cytoskeleton and is thought to participate in integrin and growth factor–mediated signaling. Using SC-specific gene ablation, we report essential functions for ILK in radial sorting of axon bundles and in remyelination in the peripheral nervous system. Our in vivo and in vitro experiments show that ILK negatively regulates Rho/Rho kinase signaling to promote SC process extension and to initiate radial sorting. ILK also facilitates axon remyelination, likely by promoting the activation of downstream molecules such as AKT/protein kinase B. PMID:19349584

  15. Growth Arrest Specific 1 (GAS1) Is Abundantly Expressed in the Adult Mouse Central Nervous System

    PubMed Central

    Zarco, Natanael; Bautista, Elizabeth; Cuéllar, Manola; Vergara, Paula; Flores-Rodriguez, Paola; Aguilar-Roblero, Raúl

    2013-01-01

    Growth arrest specific 1 (GAS1) is a pleiotropic protein that induces apoptosis and cell arrest in different tumors, but it is also involved in the development of the nervous system and other tissues and organs. This dual ability is likely caused by its capacity to interact both by inhibiting the intracellular signaling cascade induced by glial cell-line derived neurotrophic factor and by facilitating the activity of the sonic hedgehog pathway. The presence of GAS1 mRNA has been described in adult mouse brain, and here we corroborated this observation. We then proceeded to determine the distribution of the protein in the adult central nervous system (CNS). We detected, by western blot analysis, expression of GAS1 in olfactory bulb, caudate-putamen, cerebral cortex, hippocampus, mesencephalon, medulla oblongata, cerebellum, and cervical spinal cord. To more carefully map the expression of GAS1, we performed double-label immunohistochemistry and noticed expression of GAS1 in neurons in all brain areas examined. We also observed expression of GAS1 in astroglial cells, albeit the pattern of expression was more restricted than that seen in neurons. Briefly, in the present article, we report the widespread distribution and cellular localization of the GAS1 native protein in adult mammalian CNS. PMID:23813868

  16. Heterogeneous generation of new cells in the adult echinoderm nervous system

    PubMed Central

    Mashanov, Vladimir S.; Zueva, Olga R.; García-Arrarás, José E.

    2015-01-01

    Adult neurogenesis, generation of new functional cells in the mature central nervous system (CNS), has been documented in a number of diverse organisms, ranging from humans to invertebrates. However, the origin and evolution of this phenomenon is still poorly understood for many of the key phylogenetic groups. Echinoderms are one such phylum, positioned as a sister group to chordates within the monophyletic clade Deuterostomia. They are well known for the ability of their adult organs, including the CNS, to completely regenerate after injury. Nothing is known, however, about production of new cells in the nervous tissue under normal physiological conditions in these animals. In this study, we show that new cells are continuously generated in the mature radial nerve cord (RNC) of the sea cucumber Holothuria glaberrima. Importantly, this neurogenic activity is not evenly distributed, but is significantly more extensive in the lateral regions of the RNC than along the midline. Some of the new cells generated in the apical region of the ectoneural neuroepithelium leave their place of origin and migrate basally to populate the neural parenchyma. Gene expression analysis showed that generation of new cells in the adult sea cucumber CNS is associated with transcriptional activity of genes known to be involved in regulation of various aspects of neurogenesis in other animals. Further analysis of one of those genes, the transcription factor Myc, showed that it is expressed, in some, but not all radial glial cells, suggesting heterogeneity of this CNS progenitor cell population in echinoderms. PMID:26441553

  17. Clinical outcomes of children and adults with central nervous system primitive neuroectodermal tumor.

    PubMed

    Lester, Rachael A; Brown, Lindsay C; Eckel, Laurence J; Foote, Robert T; NageswaraRao, Amulya A; Buckner, Jan C; Parney, Ian F; Wetjen, Nicholas M; Laack, Nadia N

    2014-11-01

    Central nervous system primitive neuroectodermal tumors (CNS PNETs) predominantly occur in children and rarely in adults. Because of the rarity of this tumor, its outcomes and prognostic variables are not well characterized. The purpose of this study was to evaluate clinical outcomes and prognostic factors for children and adults with CNS PNET. The records of 26 patients (11 children and 15 adults) with CNS PNET from 1991 to 2011 were reviewed retrospectively. Disease-free survival (DFS) and overall survival (OS) were estimated with the Kaplan-Meier method, and relevant prognostic factors were analyzed. For the cohort, both the 5-year DFS and the OS were 46 %. For pediatric patients, the 5-year DFS was 78 %; for adult patients, it was 22 % (P = 0.004). Five-year OS for the pediatric and adult patients was 67 and 33 %, respectively (P = 0.07). With bivariate analysis including chemotherapy regimen (high dose vs. standard vs. nonstandard) or risk stratification (standard vs. high) and age, the increased risk of disease recurrence in adults persisted. A nonsignificant tendency toward poorer OS in adult patients relative to pediatric patients also persisted. High-dose chemotherapy with stem cell rescue was associated with a statistically significant improvement in OS and a tendency toward improved DFS, although the findings were mitigated when the effect of age was considered. Local recurrence was the primary pattern of treatment failure in both adults and children. Our results suggest that adult patients with CNS PNETs have inferior outcomes relative to the pediatric cohort. Further research is needed to improve outcomes for CNS PNET in populations of all ages.

  18. Distribution of constitutively expressed MEF-2A in adult rat and human nervous systems.

    PubMed

    Ruffle, Rebecca A; Mapley, Andrew C; Malik, Manmeet K; Labruzzo, Salvatore V; Chabla, Janet M; Jose, Riya; Hallas, Brian H; Yu, Han-Gang; Horowitz, Judith M; Torres, German

    2006-06-15

    Myocyte enhancer factor 2A (MEF-2A) is a calcium-regulated transcription factor that promotes cell survival during nervous system development. To define and further characterize the distribution pattern of MEF-2A in the adult mammalian brain, we used a specific polyclonal antiserum against human MEF-2A to identify nuclear-localized MEF-2A protein in hippocampal and frontal cortical regions. Western blot and immunocytochemical analyses showed that MEF-2A was expressed not only in laminar structures but also in blood vessels of rat and human brains. MEF-2A was colocalized with doublecortin (DCX), a microtubule-associated protein expressed by migrating neuroblasts, in CA1 and CA2 boundaries of the hippocampus. MEF-2A was expressed heterogeneously in additional structures of the rat brain, including the striatum, thalamus, and cerebellum. Furthermore, we found a strong nuclear and diffuse MEF-2A labeling pattern in spinal cord cells of rat and human material. Finally, the neurovasculature of adult rats and humans not only showed a strong expression of MEF-2A but also labeled positive for hyperpolarization-activated, cyclic nucleotide-regulated (HCN) channels. This study further characterizes the distribution pattern of MEF-2A in the mammalian nervous system, demonstrates that MEF-2A colocalizes with DCX in selected neurons, and finds MEF-2A and HCN1 proteins in the neurovasculature network.

  19. Lineage mapping identifies molecular and architectural similarities between the larval and adult Drosophila central nervous system

    PubMed Central

    Lacin, Haluk; Truman, James W

    2016-01-01

    Neurogenesis in Drosophila occurs in two phases, embryonic and post-embryonic, in which the same set of neuroblasts give rise to the distinct larval and adult nervous systems, respectively. Here, we identified the embryonic neuroblast origin of the adult neuronal lineages in the ventral nervous system via lineage-specific GAL4 lines and molecular markers. Our lineage mapping revealed that neurons born late in the embryonic phase show axonal morphology and transcription factor profiles that are similar to the neurons born post-embryonically from the same neuroblast. Moreover, we identified three thorax-specific neuroblasts not previously characterized and show that HOX genes confine them to the thoracic segments. Two of these, NB2-3 and NB3-4, generate leg motor neurons. The other neuroblast is novel and appears to have arisen recently during insect evolution. Our findings provide a comprehensive view of neurogenesis and show how proliferation of individual neuroblasts is dictated by temporal and spatial cues. DOI: http://dx.doi.org/10.7554/eLife.13399.001 PMID:26975248

  20. Investigation of medico-biological action of intravasular irradiation of blood on the immune system of an organism at some pathological state of the peripheral nervous system

    NASA Astrophysics Data System (ADS)

    Lapina, Victoria A.; Tanina, Raisa M.

    1994-02-01

    We investigated the influence of intravenous laser irradiation of blood (ILIB) on the immune system of the organism at vertebrogenic disorders of the peripheral nervous system (PNS) with a prominent pain syndrome. It has been found that ILIB produces a positive effect on the immunity T-link increasing the proliferative activity of T-lymphocytes, has positive dynamics in clinics, doesn't cause any side or negative effects.

  1. Peripheral Visual Reaction Time Is Faster in Deaf Adults and British Sign Language Interpreters than in Hearing Adults.

    PubMed

    Codina, Charlotte J; Pascalis, Olivier; Baseler, Heidi A; Levine, Alexandra T; Buckley, David

    2017-01-01

    Following auditory deprivation, the remaining sense of vision has shown selective enhancement in visual cognition, especially in the area of near peripheral vision. Visual acuity is poor in the far periphery and may be an area where sound confers the greatest advantage in hearing persons. Experience with a visuospatial language such as British Sign Language (BSL) makes additional demands on the visual system. To test the different and separable effects of deafness and use of a visuo-spatial language on far peripheral visual processing, we investigated visual reaction times (RTs) and response accuracy to visual stimuli, between 30° and 85° along the four cardinal and four inter-cardinal meridians. We used three luminances of static, briefly illuminated stimuli in visually normal adults. The cohort tested included profoundly congenitally deaf adults (N = 17), hearing fluent BSL users (N = 8) and hearing non-signing adults (N = 18). All participants were tested using a peripheral forced choice paradigm designed previously to test deaf and hearing children (Codina et al., 2011a). Deaf adults demonstrated significantly faster RTs to all far peripheral stimuli and exceeded the abilities of both signing and non-signing hearing adults. Deaf adults were significantly faster than BSL interpreters, who in turn were significantly faster than hearing non-signing adults. The differences in RT demonstrated between groups were consistent across all visual field meridians and were not localized to any one region of the visual field. There were no differences found between any groups in accuracy of detecting these static stimuli at any retinal location. Early onset auditory deprivation appears to lead to a response time visual advantage in far peripheral responses to briefly presented, static LED stimuli, especially in the right visual field. Fluency in BSL facilitates faster visuo-motor responses in the peripheral visual field, but to a lesser extent than congenital, profound

  2. Peripheral Visual Reaction Time Is Faster in Deaf Adults and British Sign Language Interpreters than in Hearing Adults

    PubMed Central

    Codina, Charlotte J.; Pascalis, Olivier; Baseler, Heidi A.; Levine, Alexandra T.; Buckley, David

    2017-01-01

    Following auditory deprivation, the remaining sense of vision has shown selective enhancement in visual cognition, especially in the area of near peripheral vision. Visual acuity is poor in the far periphery and may be an area where sound confers the greatest advantage in hearing persons. Experience with a visuospatial language such as British Sign Language (BSL) makes additional demands on the visual system. To test the different and separable effects of deafness and use of a visuo-spatial language on far peripheral visual processing, we investigated visual reaction times (RTs) and response accuracy to visual stimuli, between 30° and 85° along the four cardinal and four inter-cardinal meridians. We used three luminances of static, briefly illuminated stimuli in visually normal adults. The cohort tested included profoundly congenitally deaf adults (N = 17), hearing fluent BSL users (N = 8) and hearing non-signing adults (N = 18). All participants were tested using a peripheral forced choice paradigm designed previously to test deaf and hearing children (Codina et al., 2011a). Deaf adults demonstrated significantly faster RTs to all far peripheral stimuli and exceeded the abilities of both signing and non-signing hearing adults. Deaf adults were significantly faster than BSL interpreters, who in turn were significantly faster than hearing non-signing adults. The differences in RT demonstrated between groups were consistent across all visual field meridians and were not localized to any one region of the visual field. There were no differences found between any groups in accuracy of detecting these static stimuli at any retinal location. Early onset auditory deprivation appears to lead to a response time visual advantage in far peripheral responses to briefly presented, static LED stimuli, especially in the right visual field. Fluency in BSL facilitates faster visuo-motor responses in the peripheral visual field, but to a lesser extent than congenital, profound

  3. Development of the spinal cord and peripheral nervous system in platypus (Ornithorhynchus anatinus) and short-beaked echidna (Tachyglossus aculeatus).

    PubMed

    Ashwell, Ken W S

    2012-01-01

    The modern monotremes (platypus and echidnas) are characterized by development of their young in a leathery egg that is laid into a nest or abdominal pouch. At hatching, the young are externally immature, with forelimbs capable of digitopalmar prehension, but hindlimbs little advanced beyond limb buds. The embryological collections at the Museum für Naturkunde in Berlin were used to examine the development of the spinal cord and early peripheral nervous system in developing monotremes and to correlate this with known behavioural development. Ventral root outgrowth to the bases of both the fore- and hindlimbs occurs at 6.0 mm crown-rump length (CRL), but invasion of both limbs does not happen until about 8.0-8.5 mm CRL. Differentiation of the ventral horn precedes the dorsal horn during incubation and separate medial and lateral motor columns can be distinguished before hatching. Rexed's laminae begin to appear in the dorsal horn in the first week after hatching, and gracile and cuneate fasciculi emerge during the first two post-hatching months. Qualitative and quantitative comparisons of the structure of the cervicothoracic junction spinal cord in the two monotremes with that in a diprotodont marsupial (the brush-tailed possum, Trichosurus vulpecula) of similar size at birth, did not reveal any significant structural differences between the monotremes and the marsupial. The precocious development of motor systems in the monotreme spinal cord is consistent with the behavioural requirements of the peri-hatching period, that is, rupture of embryonic membranes and egg, and digitopalmar prehension to grasp maternal hair or nest material.

  4. Infected peripheral blood mononuclear cells transmit latent varicella zoster virus infection to the guinea pig enteric nervous system.

    PubMed

    Gan, Lin; Wang, Mingli; Chen, Jason J; Gershon, Michael D; Gershon, Anne A

    2014-10-01

    Latent wild-type (WT) and vaccine (vOka) varicella zoster virus (VZV) are found in the human enteric nervous system (ENS). VZV also infects guinea pig enteric neurons in vitro, establishes latency and can be reactivated. We therefore determined whether lymphocytes infected in vitro with VZV secrete infectious virions and can transfer infection in vivo to the ENS of recipient guinea pigs. T lymphocytes (CD3-immunoreactive) were preferentially infected following co-culture of guinea pig or human peripheral blood mononuclear cells with VZV-infected HELF. VZV proliferated in the infected T cells and expressed immediate early and late VZV genes. Electron microscopy confirmed that VZV-infected T cells produced encapsulated virions. Extracellular virus, however, was pleomorphic, suggesting degradation occurred prior to release, which was confirmed by the failure of VZV-infected T cells to secrete infectious virions. Intravenous injection of WT- or vOka-infected PBMCs, nevertheless, transmitted VZV to recipient animals (guinea pig > human lymphocytes). Two days post-inoculation, lung and liver, but not gut, contained DNA and transcripts encoding ORFs 4, 40, 66 and 67. Twenty-eight days after infection, gut contained DNA and transcripts encoding ORFs 4 and 66 but neither DNA nor transcripts could any longer be found in lung or liver. In situ hybridization revealed VZV DNA in enteric neurons, which also expressed ORF63p (but not ORF68p) immunoreactivity. Observations suggest that VZV infects T cells, which can transfer VZV to and establish latency in enteric neurons in vivo. Guinea pigs may be useful for studies of VZV pathogenesis in the ENS.

  5. Infected Peripheral Blood Mononuclear Cells Transmit Latent Varicella Zoster Virus Infection to the Guinea Pig Enteric Nervous System

    PubMed Central

    Gan, Lin; Wang, Mingli; Chen, Jason J.; Gershon, Michael D.; Gershon, Anne A.

    2014-01-01

    Latent wild-type (WT) and vaccine (vOka) varicella-zoster virus (VZV) are found in the human enteric nervous system (ENS). VZV also infects guinea pig enteric neurons in vitro, establishes latency and can be reactivated. We therefore determined whether lymphocytes infected in vitro with VZV secrete infectious virions and can transfer infection in vivo to the ENS of recipient guinea pigs. T lymphocytes (CD3-immunoreactive) were preferentially infected following co-culture of guinea pig or human peripheral blood mononuclear cells with VZV-infected HELF. VZV proliferated in the infected T cells and expressed immediate early and late VZV genes. Electron microscopy confirmed that VZV-infected T cells produced encapsulated virions. Extracellular virus, however, was pleomorphic, suggesting degradation occurred prior to release, which was confirmed by the failure of VZV-infected T cells to secrete infectious virions. Intravenous injection of WT- or vOka-infected PBMCs, nevertheless, transmitted VZV to recipient animals (guinea pig > human lymphocytes). Two days post-inoculation, lung and liver, but not gut, contained DNA and transcripts encoding ORFs 4, 40, 66 and 67. Twenty-eight days after infection, gut contained DNA and transcripts encoding ORFs 4 and 66 but neither DNA nor transcripts could any longer be found in lung or liver. In situ hybridization revealed VZV DNA in enteric neurons, which also expressed ORF63p (but not ORF68p) immunoreactivity. Observations suggest that VZV infects T cells, which can transfer VZV to and establish latency in enteric neurons in vivo. Guinea pigs may be useful for studies of VZV pathogenesis in the ENS. PMID:24965252

  6. Integration of complex larval chemosensory organs into the adult nervous system of Drosophila.

    PubMed

    Gendre, Nanaë; Lüer, Karin; Friche, Sandrine; Grillenzoni, Nicola; Ramaekers, Ariane; Technau, Gerhard M; Stocker, Reinhard F

    2004-01-01

    The sense organs of adult Drosophila, and holometabolous insects in general, derive essentially from imaginal discs and hence are adult specific. Experimental evidence presented here, however, suggests a different developmental design for the three largely gustatory sense organs located along the pharynx. In a comprehensive cellular analysis, we show that the posteriormost of the three organs derives directly from a similar larval organ and that the two other organs arise by splitting of a second larval organ. Interestingly, these two larval organs persist despite extensive reorganization of the pharynx. Thus, most of the neurons of the three adult organs are surviving larval neurons. However, the anterior organ includes some sensilla that are generated during pupal stages. Also, we observe apoptosis in a third larval pharyngeal organ. Hence, our experimental data show for the first time the integration of complex, fully differentiated larval sense organs into the nervous system of the adult fly and demonstrate the embryonic origin of their neurons. Moreover, they identify metamorphosis of this sensory system as a complex process involving neuronal persistence, generation of additional neurons and neuronal death. Our conclusions are based on combined analysis of reporter expression from P[GAL4] driver lines, horseradish peroxidase injections into blastoderm stage embryos, cell labeling via heat-shock-induced flip-out in the embryo, bromodeoxyuridine birth dating and staining for programmed cell death. They challenge the general view that sense organs are replaced during metamorphosis.

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

    PubMed

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

    2002-02-01

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

  8. Detection of a cell surface antigen found on rat peripheral nervous system neurons and multiple glia: astrocytes, oligodendrocytes, and Schwann cells.

    PubMed

    Akeson, R; Warren, S L

    1984-01-01

    A cell surface component has been identified that is found on cultured rat dorsal root ganglion neurons and Schwann cells and also cultured brain astrocytes and oligodendrocytes. This component was detected with a monoclonal antibody originally generated to the NG108 (N18 mouse neuroblastoma X C6 rat astrocytoma) hybrid cell line. The antibody, designated B2C11, binds to cultured peripheral nervous system cells: intact dorsal root ganglion and trigeminal neurons and cultured dorsal root ganglion and sciatic nerve Schwann cells. The binding of B2C11 to dorsal root ganglion neurons in vivo was confirmed by immunofluorescence analysis of cryostat sections. However, cultured embryonic rat central neurons showed no detectable binding of B2C11. Cultured brain cells containing glial fibrillary acidic protein (astrocytes) and also oligodendrocytes cultured from corpus collosum did bind B2C11 on their surfaces. B2C11 immunoprecipitation of detergent-solubilized membrane proteins from both lactoperoxidase iodinated C6 and PC12 rat pheochromocytoma cells indicated a single band with an apparent molecular weight of 21,000-23,000. Analysis of B2C11 binding to particulate protein preparations from adult rat organs showed highest specific activity in dorsal root ganglia. Other neural tissues had substantial binding. Some nonneural tissues (lung, kidney, and small intestine) expressed significant antigen levels, whereas others (heart, liver, and skeletal muscle) had a B2C11 antigen-specific activity less than 5% of that of dorsal root ganglia. Thus the B2C11 antigen is enriched in neural tissues, where it is found on the surfaces of a unique set of neuronal and glial cells.

  9. Hereditary absence of complement C5 in adult mice influences Wallerian degeneration, but not retrograde responses, following injury to peripheral nerve.

    PubMed

    Liu, L; Lioudyno, M; Tao, R; Eriksson, P; Svensson, M; Aldskogius, H

    1999-01-01

    We have examined the role of complement component 5 (C5) in peripheral nerve fiber degeneration and regeneration, as well as in glial and neuronal cell responses in the central nervous system (CNS). Adult congenic mice lacking C5 (C5(-)) and the corresponding normal strain (C5(+)) were used. Macrophage recruitment as well as axonal and myelin sheath elimination were delayed from 1 to 21 days postinjury in C5(-) mice compared to the C5(+) group after sciatic nerve crush. Despite this, recovery of motor function was not delayed. In the CNS, microglial cells and astrocytes responded in the same way from 3 to 21 days after sciatic nerve injury in C5(-) and C5(+) mice, and the extent of neuron death following hypoglossal nerve avulsion was the same in both groups. These findings suggest that C5 and/or its derivatives play an important role in initiating the recruitment of macrophages to the injured nerve and, probably indirectly, in early remyelination of regenerating axons, but does not influence the longterm functional restoration or axotomy-induced nerve cell death. C5-derived molecules do not appear to participate in central glial cell responses to peripheral nerve injury. These findings elucidate new aspects on the functional role of the complement system in the peripheral nervous system following peripheral nerve injury.

  10. Perforated microelectrode arrays implanted in the regenerating adult central nervous system.

    PubMed

    Heiduschka, P; Romann, I; Stieglitz, T; Thanos, S

    2001-09-01

    Adult mammalian optic nerve axons are able to regenerate, when provided with the permissive environment of an autologous peripheral nerve graft, which is usually the sciatic nerve. This study demonstrates the ability of adult rat optic nerve axons to regenerate through the preformed perforations of a polyimide electrode carrier implanted at the interface between the proximal stump of the cut optic nerve and the stump of the peripheral nerve piece used for grafting. Evidence that retinal ganglion cells regenerated their axons through the perforated electrode carrier was obtained by retrograde labeling with a fluorescent dye deposited into the sciatic nerve graft beyond the nerve-carrier-nerve junction. The number of regenerating cells could be enhanced by injecting neuroprotective drugs like aurintricarboxylic acid and cortisol intravitreally. A second line of evidence was obtained by immunohistochemical staining with antibodies to neurofilament. Third, electrical activity of the regenerating nerves was recorded after stimulating the retina with a flash of light. The results suggest that a regenerating central nerve tract may serve as an experimental model to implant artificial microdevices to monitor the physiological and topographical properties of neurites passing through the device or to stimulate them, thus interfering with their potential to grow. This study reports for the first time that the optic nerve has unique properties, which aids in the realization of these goals.

  11. SOD1 Lysine 123 Acetylation in the Adult Central Nervous System.

    PubMed

    Kaliszewski, Michael; Kennedy, Austin K; Blaes, Shelby L; Shaffer, Robert S; Knott, Andrew B; Song, Wenjun; Hauser, Henry A; Bossy, Blaise; Huang, Ting-Ting; Bossy-Wetzel, Ella

    2016-01-01

    Superoxide dismutase 1 (SOD1) knockout (Sod1(-/-)) mice exhibit an accelerated aging phenotype. In humans, SOD1 mutations are linked to familial amyotrophic lateral sclerosis (ALS), and post-translational modification (PTM) of wild-type SOD1 has been associated with sporadic ALS. Reversible acetylation regulates many enzymes and proteomic studies have identified SOD1 acetylation at lysine 123 (K123). The function and distribution of K123-acetylated SOD1 (Ac-K123 SOD1) in the nervous system is unknown. Here, we generated polyclonal rabbit antibodies against Ac-K123 SOD1. Sod1 deletion in Sod1(-/-) mice, K123 mutation or preabsorption with Ac-K123 peptide all abolished antibody binding. Using immunohistochemistry, we assessed Ac-K123 SOD1 distribution in the normal adult mouse nervous system. In the cerebellum, Ac-K123 SOD1 staining was prominent in cell bodies of the granular cell layer (GCL) and Purkinje cell dendrites and interneurons of the molecular cell layer. In the hippocampus, Ac-K123 SOD1 staining was strong in the fimbria, subiculum, pyramidal cells and Schaffer collateral fibers of the cornus ammonis field 1 (CA1) region and granule and neuronal progenitor cells of the dentate gyrus. In addition, labeling was observed in the choroid plexus (CP) and the ependyma of the brain ventricles and central canal of the spinal cord. In the olfactory bulb, Ac-K123 SOD1 staining was prominent in axons of sensory neurons, in cell bodies of interneurons and neurites of the mitral and tufted cells. In the retina, labeling was strong in the retinal ganglion cell layer (RGCL) and axons of retinal ganglion cells (RGCs), the inner nuclear layer (INL) and cone photoreceptors of the outer nuclear layer (ONL). In summary, our findings describe Ac-K123 SOD1 distribution to distinct regions and cell types of the normal nervous system.

  12. SOD1 Lysine 123 Acetylation in the Adult Central Nervous System

    PubMed Central

    Kaliszewski, Michael; Kennedy, Austin K.; Blaes, Shelby L.; Shaffer, Robert S.; Knott, Andrew B.; Song, Wenjun; Hauser, Henry A.; Bossy, Blaise; Huang, Ting-Ting; Bossy-Wetzel, Ella

    2016-01-01

    Superoxide dismutase 1 (SOD1) knockout (Sod1−/−) mice exhibit an accelerated aging phenotype. In humans, SOD1 mutations are linked to familial amyotrophic lateral sclerosis (ALS), and post-translational modification (PTM) of wild-type SOD1 has been associated with sporadic ALS. Reversible acetylation regulates many enzymes and proteomic studies have identified SOD1 acetylation at lysine 123 (K123). The function and distribution of K123-acetylated SOD1 (Ac-K123 SOD1) in the nervous system is unknown. Here, we generated polyclonal rabbit antibodies against Ac-K123 SOD1. Sod1 deletion in Sod1−/− mice, K123 mutation or preabsorption with Ac-K123 peptide all abolished antibody binding. Using immunohistochemistry, we assessed Ac-K123 SOD1 distribution in the normal adult mouse nervous system. In the cerebellum, Ac-K123 SOD1 staining was prominent in cell bodies of the granular cell layer (GCL) and Purkinje cell dendrites and interneurons of the molecular cell layer. In the hippocampus, Ac-K123 SOD1 staining was strong in the fimbria, subiculum, pyramidal cells and Schaffer collateral fibers of the cornus ammonis field 1 (CA1) region and granule and neuronal progenitor cells of the dentate gyrus. In addition, labeling was observed in the choroid plexus (CP) and the ependyma of the brain ventricles and central canal of the spinal cord. In the olfactory bulb, Ac-K123 SOD1 staining was prominent in axons of sensory neurons, in cell bodies of interneurons and neurites of the mitral and tufted cells. In the retina, labeling was strong in the retinal ganglion cell layer (RGCL) and axons of retinal ganglion cells (RGCs), the inner nuclear layer (INL) and cone photoreceptors of the outer nuclear layer (ONL). In summary, our findings describe Ac-K123 SOD1 distribution to distinct regions and cell types of the normal nervous system. PMID:28066183

  13. The macrophage in acute neural injury: changes in cell numbers over time and levels of cytokine production in mammalian central and peripheral nervous systems.

    PubMed

    Leskovar, A; Moriarty, L J; Turek, J J; Schoenlein, I A; Borgens, R B

    2000-06-01

    We evaluated the timing and density of ED-1-positive macrophage accumulation (ED 1 is the primary antibody for the macrophage) and measured cytokine production by macrophages in standardized compression injuries to the spinal cord and sciatic nerves of individual rats 3, 5, 10 and 21 days post-injury. The actual site of mechanical damage to the nervous tissue, and a more distant site where Wallerian degeneration had occurred, were evaluated in both the peripheral nervous system (PNS) and the central nervous system (CNS) at these time points. The initial accumulation of activated macrophages was similar at both the central and peripheral sites of damage. Subsequently, macrophage densities at all locations studied were statistically significantly higher in the spinal cord than in the sciatic nerve at every time point but one. The peak concentrations of three cytokines, tumor necrosis factor &agr; (TNF &agr; ), interleukin-1 (IL-1) and interleukin-6 (IL-6), appeared earlier and were statistically significantly higher in injured spinal cord than in injured sciatic nerve. We discuss the meaning of these data relative to the known differences in the reparative responses of the PNS and CNS to injury.

  14. Developmental origin of the adult nervous system in a holothurian: an attempt to unravel the enigma of neurogenesis in echinoderms.

    PubMed

    Mashanov, Vladimir S; Zueva, Olga R; Heinzeller, Thomas; Aschauer, Beate; Dolmatov, Igor Yu

    2007-01-01

    In adult echinoderms, the nervous system includes the ectoneural and hyponeural subsystems. The former has been believed to develop from the ectoderm, whereas the latter is considered to be mesodermal in origin. However, this view has not been substantially supported by embryological examinations. Our study deals with the developmental origin of the nervous system in the direct-developing sea cucumber Eupentacta fraudatrix. The rudiment of the adult nervous system develops from ectodermally derived cells, which ingress into the primary body cavity from the floor of the vestibule. At the earliest stages, only the rudiment of the ectoneural nerve ring is laid down. The radial nerve cords and tentacular nerves grow out from this subcutaneous rudiment. The ectoneural cords do not develop simultaneously but make their appearance in the following order: unpaired mid-ventral cord, paired dorsal lateral cords, and ventral lateral cords. These transitional developmental stages probably recapitulate the evolution of the echinoderm body plan. The holothurian hyponeural subsystem, as other regions of the metazoan nervous system, has an ectodermal origin. It originally appears as a narrow band of tissue, which bulges out of the basal region of the ectoneural neuroepithelium. Our data combined with those of other workers strongly suggest that the adult nervous tissue in echinoderms develops separately from the superficial larval system of ciliary nerves. Therefore, our data are neither in strict accordance with Garstang's hypothesis nor do they allow to refuse it. Nevertheless, in addition to ciliary bands, other areas of neurogenetic epidermis must be taken into account.

  15. Genetically engineered mouse models shed new light on the pathogenesis of neurofibromatosis type I-related neoplasms of the peripheral nervous system.

    PubMed

    Brossier, Nicole M; Carroll, Steven L

    2012-05-01

    Neurofibromatosis type 1 (NF1), the most common genetic disorder affecting the human nervous system, is characterized by the development of multiple benign Schwann cell tumors in skin and large peripheral nerves. These neoplasms, which are termed dermal and plexiform neurofibromas respectively, have distinct clinical courses; of particular note, plexiform, but not dermal, neurofibromas often undergo malignant progression to form malignant peripheral nerve sheath tumors (MPNSTs), the most common malignancy occurring in NF1 patients. In recent years, a number of genetically engineered mouse models have been created to investigate the molecular mechanisms driving the pathogenesis of these tumors. These models have been designed to address key questions including: (1) whether NF1 loss in the Schwann cell lineage is essential for tumorigenesis; (2) what cell type(s) in the Schwann cell lineage gives rise to dermal neurofibromas, plexiform neurofibromas and MPNSTs; (3) how the tumor microenvironment contributes to neoplasia; (4) what additional mutations contribute to neurofibroma-MPNST progression; (5) what role different neurofibromin-regulated Ras proteins play in this process and (6) how dysregulated growth factor signaling facilitates PNS tumorigenesis. In this review, we summarize the major findings from each of these models and their limitations as well as how discrepancies between these models may be reconciled. We also discuss how information gleaned from these models can be synthesized to into a comprehensive model of tumor formation in peripheral nervous system and consider several of the major questions that remain unanswered about this process.

  16. Adult tethered cord syndrome resembling plantar fasciitis and peripheral neuropathy.

    PubMed

    Amiri, Amir Reza; Kanesalingam, Kavitha; Srinivasan, Venkataramanan; Price, Rupert Francis

    2013-12-05

    Adult tethered cord syndrome without spinal dysraphism is rare, and can present with subtle symptoms that could mimic other pathologies. As a result, timely diagnosis of this condition has proved to be a significant challenge. It is crucial for clinicians to be aware of adult tethered cord syndrome and its presenting symptoms in order to achieve early diagnosis and subsequent management. We present such a case with particular attention to the presenting history and examination. Following diagnosis, the patient underwent a laminectomy and cord untethering, resulting in significant improvement to his symptoms.

  17. Thrombospondin-4, an extracellular matrix protein expressed in the developing and adult nervous system promotes neurite outgrowth

    PubMed Central

    1995-01-01

    Extracellular matrix (ECM) molecules are involved in multiple aspects of cell-to-cell signaling during development and in the adult. In nervous system development, specific recognition processes, e.g., during axonal pathfinding and synaptogenesis involve modulation and signaling by ECM components. Much less is known about their presence and possible roles in the adult nervous system. We now report that thrombospondin-4 (TSP-4), a recently discovered member of the TSP gene family is expressed by neurons, promotes neurite outgrowth, and accumulates at the neuromuscular junction and at certain synapse-rich structures in the adult. To search for muscle genes that may be involved in neuromuscular signaling, we isolated cDNAs induced in adult skeletal muscle by denervation. One of these cDNAs coded for the rat homologue of TSP-4. In skeletal muscle, it was expressed by muscle interstitial cells. The transcript was further detected in heart and in the developing and adult nervous system, where it was expressed by a wide range of neurons. An antiserum to the unique carboxyl-terminal end of the protein allowed to specifically detect TSP-4 in transfected cells in vitro and on cryostat sections in situ. TSP-4 associated with ECM structures in vitro and in vivo. In the adult, it accumulated at the neuromuscular junction and at synapse-rich structures in the cerebellum and retina. To analyze possible activities of TSP-4 towards neurons, we carried out coculture experiments with stably transfected COS cells and motor, sensory, or retina neurons. These experiments revealed that TSP-4 was a preferred substrate for these neurons, and promoted neurite outgrowth. The results establish TSP-4 as a neuronal ECM protein associated with certain synapse-rich structures in the adult. Its activity towards embryonic neurons in vitro and its distribution in vivo suggest that it may be involved in local signaling in the developing and adult nervous system. PMID:7490284

  18. Central Nervous System Involvement in Adult Acute Lymphoblastic Leukemia: Diagnostic Tools, Prophylaxis, and Therapy

    PubMed Central

    Del Principe, Maria Ilaria; Maurillo, Luca; Buccisano, Francesco; Sconocchia, Giuseppe; Cefalo, Mariagiovanna; De Santis, Giovanna; Di Veroli, Ambra; Ditto, Concetta; Nasso, Daniela; Postorino, Massimiliano; Refrigeri, Marco; Attrotto, Cristina; Del Poeta, Giovanni; Lo-Coco, Francesco; Amadori, Sergio; Venditti, Adriano

    2014-01-01

    In adult patients with acute lymphoblastic leukemia (ALL), Central Nervous System (CNS) involvement is associated with a very poor prognosis. The diagnostic assessment of this condition relies on the use of neuroradiology, conventional cytology (CC) and flow cytometry (FCM). Among these approaches, which is the gold standard it is still a matter of debate. Neuroradiology and CC have a limited sensitivity with a higher rate of false negative results. FCM demonstrated a superior sensitivity over CC, particularly when low levels of CNS infiltrating cells are present. Although prospective studies of a large series of patients are still awaited, a positive finding by FCM appears to anticipate an adverse outcome even if CC shows no infiltration. Current strategies for adult ALL CNS-directed prophylaxis or therapy involve systemic and intrathecal chemotherapy and radiation therapy. An early and frequent intrathecal injection of cytostatic combined with systemic chemotherapy is the most effective strategy to reduce the frequency of CNS involvement. In patients with CNS overt ALL, at diagnosis or upon relapse, allogeneic hematopoietic stem cell transplantation might be considered. This review discusses risk factors, diagnostic techniques for identification of CNS infiltration and modalities of prophylaxis and therapy to manage it. PMID:25408861

  19. The Effect of a Single Session of Whole-Body Vibration Training in Recreationally Active Men on the Excitability of the Central and Peripheral Nervous System

    PubMed Central

    Chmielewska, Daria; Piecha, Magdalena; Błaszczak, Edward; Król, Piotr; Smykla, Agnieszka; Juras, Grzegorz

    2014-01-01

    Vibration training has become a popular method used in professional sports and recreation. In this study, we examined the effect of whole-body vibration training on the central nervous system and muscle excitability in a group of 28 active men. Subjects were assigned randomly to one of two experimental groups with different variables of vibrations. The chronaximetry method was used to evaluate the effect of a single session of whole-body vibration training on the excitability of the rectus femoris and brachioradialis muscles. The examination of the fusing and flickering frequencies of the light stimulus was performed. An increase in the excitability of the quadriceps femoris muscle due to low intensity vibrations (20 Hz frequency, 2 mm amplitude) was noted, and a return to the initial values was observed 30 min after the application of vibration. High intensity vibrations (60 Hz frequency, 4 mm amplitude) caused elongations of the chronaxy time; however, these differences were not statistically significant. Neither a low intensity vibration amplitude of 2 mm (frequency of 20 Hz) nor a high intensity vibration amplitude of 4 mm (frequency of 60 Hz) caused a change in the excitability of the central nervous system, as revealed by the average frequency of the fusing and flickering of the light stimulus. A single session of high intensity whole-body vibration did not significantly decrease the excitability of the peripheral nervous system while the central nervous system did not seem to be affected. PMID:25114735

  20. Birth weight modifies the association between central nervous system gene variation and adult body mass index.

    PubMed

    Ruiz-Narváez, Edward A; Haddad, Stephen A; Rosenberg, Lynn; Palmer, Julie R

    2016-03-01

    Genome wide association studies have identified ~100 loci associated with body mass index (BMI). Persons with low birth weight have an increased risk of metabolic disorders. We postulate that normal mechanisms of body weight regulation are disrupted in subjects with low birth weight. The present analyses included 2215 African American women from the Black Women's Health Study, and were based on genotype data on 20 BMI-associated loci and self-reported data on birth weight, weight at age 18 and adult weight. We used general linear models to assess the association of individual single-nucleotide polymorphisms (SNPs) with BMI at age 18 and later in adulthood within strata of birth weight (above and below the median, 3200 g). Three SNPs (rs1320330 near TMEM18, rs261967 near PCSK1 and rs17817964 in FTO), and a genetic score combining these three variants, showed significant interactions with birth weight in relation to BMI. Among women with birth weight <3200 g, there was an inverse association between genetic score and BMI; beta-coefficient=-0.045 (95% confidence intervals (CI) -0.104, 0.013) for BMI at age 18, and -0.055 (95% CI -0.112, 0.002) for adult BMI. Among women with birth weight ⩾3200 g, genetic score was positively associated with BMI: beta-coefficient=0.110 (95% CI 0.051, 0.169) for BMI at age 18 (P for interaction=0.0002), and 0.112 (95% CI 0.054, 0.170) for adult BMI (P for interaction<0.0001). Because TMEM18, PCSK1 and FTO are highly expressed in the central nervous system (CNS), our results suggest that low-birth weight may disrupt mechanisms of CNS body weight regulation.

  1. Evaluation of the peripheral nervous system among workers employed in the production of chemicals contaminated with 2,3,7. 8-tetra-chlorodibenzo-p-dioxin. Final report

    SciTech Connect

    Sweeney, M.H.; Fingerhut, M.A.; Connally, L.B.; Hornung, R.

    1990-07-01

    The long term effects on the peripheral nervous system in workers with past exposure to production products contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (1746016) (TCDD) were evaluated. The severity of the current neurologic status was compared to the levels of TCDD measured in the serum of study subjects. Workers who were employed at two chemical factories at which chemicals contaminated with TCDD were manufactured, and a group of unexposed referents were assessed in a cross sectional medical study in 1987 through 1988. Questionnaires were used to collect follow-up data. There were 281 workers and 260 referents who were interviewed and medically examined. Peripheral neuropathy was found in about 18% of workers and 19% of referents. Serum TCDD levels ranged from 2 to 3390 parts per trillion (ppt) for 272 workers and from 2 to 20ppt for 86 referents tested. No dose-response relationship was observed between TCDD levels present at the time of the examination and the occurrence of peripheral neuropathy in the previously exposed population. The authors conclude that exposure to TCDD caused no excess chronic peripheral neuropathy in a group of exposed workers compared to unexposed referents.

  2. Novel Adult Stem Cells for Peripheral Nerve Regeneration

    DTIC Science & Technology

    2012-09-01

    Circulation 103, 882–888 (2001). 52. Biernaskie, J. et al. SKPs derive from hair follicle precursors and exhibit properties of adult dermal stem cells...3). * indicates significant difference between indicated groups using Holm’s t- test . (P < 0.01). (l–s) Immunostaining of isolated sm-mHC − cells...and the tissue from which the cells were derived using student’s t- test (P < 0.05). † indicates significant difference between inferior vena cava and

  3. A Systematic Review of Peripheral and Central Nervous System Involvement of Rheumatoid Arthritis, Systemic Lupus Erythematosus, Primary Sjögren's Syndrome, and Associated Immunological Profiles

    PubMed Central

    Bougea, Anastasia; Anagnostou, Evangelos; Konstantinos, Giatas; George, Paraskevas; Triantafyllou, Nikolaos; Kararizou, Evangelia

    2015-01-01

    Both central (CNS) and peripheral nervous system (PNS) complications are frequent and varied in connective tissue diseases. A systematic review was conducted between 1989 and 2014 in the databases Medline, Scopus, and Cochrane Library using the search terms, peripheral and central nervous complications and immunological profiles, to identify studies in specific connective tissue disorders such as rheumatoid arthritis, systemic lupus erythematosus, and primary Sjögren's syndrome. A total of 675 references were identified, of which 118 were selected for detailed analysis and 22 were included in the final review with a total of 2338 participants. Our search focused only on studies upon connective tissue disorders such as rheumatoid arthritis, systemic lupus erythematosus, and primary Sjögren's syndrome associated with seroimmunological data. The reported prevalence of CNS involvement ranges from 9 to 92% across the reported studies. However, the association between CNS and PNS manifestations and seroimmunological profiles remains controversial. Τo date, no laboratory test has been shown as pathognomonic neither for CNS nor for PNS involvement. PMID:26688829

  4. Adult peripheral blood mononuclear cells transdifferentiate in vitro and integrate into the retina in vivo.

    PubMed

    Liu, Qian; Guan, Liping; Huang, Bing; Li, Weihua; Su, Qiao; Yu, Minbin; Xu, Xiaoping; Luo, Ting; Lin, Shaochun; Sun, Xuerong; Chen, Mengfei; Chen, Xigu

    2011-06-01

    Adult peripheral blood-derived cells are able to differentiate into a variety of cell types, including nerve cells, liver-like cells and epithelial cells. However, their differentiation into retina-like cells is controversial. In the present study, transdifferentiation potential of human adult peripheral blood mononuclear cells into retina-like cells and integration into the retina of mice were investigated. Freshly isolated adult peripheral blood mononuclear cells were divided into two groups: cells in group I were cultured in neural stem cell medium, and cells in group II were exposed to conditioned medium from rat retinal tissue culture. After 5 days, several distinct cell morphologies were observed, including standard mononuclear, neurons with one or two axons and elongated glial-like cells. Immunohistochemical analysis of neural stem cell, neuron and retina cell markers demonstrated that cells in both groups were nestin-, MAP2 (microtubule-associated protein)- and GFAP (glial fibrillary acidic protein)-positive. Flow cytometry results suggested a significant increase in nestin-, MAP2- and CD16-positive cells in group I and nestin-, GFAP-, MAP2-, vimentin- and rhodopsin-positive cells in group II. To determine survival, migration and integration in vivo, cell suspensions (containing group I or group II cells) were injected into the vitreous or the peritoneum. Tissue specimens were obtained and immunostained 4 weeks after transplantation. We found that cells delivered by intravitreal injection integrated into the retina. Labelled cells were not detected in the retina of mice receiving differentiated cells by intraperitoneal injection, but cells (groups I and II) were detected in the liver and spleen. Our findings revealed that human adult peripheral blood mononuclear cells could be induced to transdifferentiate into neural precursor cells and retinal progenitor cells in vitro, and the differentiated peripheral blood mononuclear cells can migrate and integrate

  5. Aging, the Central Nervous System, and Mobility in Older Adults: Neural Mechanisms of Mobility Impairment

    PubMed Central

    Cruz-Almeida, Yenisel; Clark, David J.; Viswanathan, Anand; Scherzer, Clemens R.; De Jager, Philip; Csiszar, Anna; Laurienti, Paul J.; Hausdorff, Jeffery M.; Chen, Wen G.; Ferrucci, Luiggi; Rosano, Caterina; Studenski, Stephanie A.; Black, Sandra E.; Lipsitz, Lewis A.

    2015-01-01

    Background. Mobility is crucial for successful aging and is impaired in many older adults. We know very little about the subtle, subclinical age-related changes in the central nervous system (CNS) that mediate mobility impairment. Methods. A conference series focused on aging, the CNS, and mobility was launched. The second conference addressed major age-associated mechanisms of CNS-mediated mobility impairment. Speakers and conference attendees recommended key areas for future research, identified barriers to progress, and proposed strategies to overcome them. Results. Priorities identified for future research include (a) studying interactions among different mechanisms; (b) examining effects of interventions targeting these mechanisms; (c) evaluating the effect of genetic polymorphisms on risks and course of age-related mobility impairment; and (d) examining the effect of age on CNS repair processes, neuroplasticity, and neuronal compensatory mechanisms. Key strategies to promote research include (a) establish standard measures of mobility across species; (b) evaluate the effect of aging in the absence of disease on CNS and mobility; and (c) use advanced computational methods to better evaluate the interactions between CNS and other systems involved in mobility. Conclusions. CNS is a major player in the process, leading to mobility decline with aging. Future research in this area has the potential to prolong independence in older persons. Better interactions among disciplines and shared research paradigms are needed to make progress. Research priorities include the development of innovative approaches to integrate research on aging, cognition, and movement with attention to neurovascular function, neuroplasticity, and neurophysiological reserve. PMID:26386013

  6. Clinical Characteristics, Pathophysiology, and Management of Noncentral Nervous System Cancer-Related Cognitive Impairment in Adults

    PubMed Central

    Wefel, Jeffrey S.; Kesler, Shelli R.; Noll, Kyle R.; Schagen, Sanne B.

    2014-01-01

    Over the past few decades, a body of research has emerged confirming what many adult patients with noncentral nervous system cancer have long reported—that cancer and its treatment are frequently associated with cancer-related cognitive impairment (CRCI). The severity of CRCI varies, and symptoms can emerge early or late in the disease course. Nonetheless, CRCI is typically mild to moderate in nature and primarily involves the domains of memory, attention, executive functioning, and processing speed. Animal models and novel neuroimaging techniques have begun to unravel the pathophysiologic mechanisms underlying CRCI, including the role of inflammatory cascades, direct neurotoxic effects, damage to progenitor cells, white matter abnormalities, and reduced functional connectivity, among others. Given the paucity of research on CRCI with other cancer populations, this review synthesizes the current literature with a deliberate focus on CRCI within the context of breast cancer. A hypothetical case-study approach is used to illustrate how CRCI often presents clinically and how current science can inform practice. While the literature regarding intervention for CRCI is nascent, behavioral and pharmacologic approaches are discussed. PMID:25483452

  7. Development of the synganglion and morphology of the adult nervous system in the mite Archegozetes longisetosus Aoki (Chelicerata, Actinotrichida, Oribatida).

    PubMed

    Hartmann, Konstantin; Laumann, Michael; Bergmann, Paavo; Heethoff, Michael; Schmelzle, Sebastian

    2016-04-01

    Small arthropods show a highly condensed central nervous system, which is accompanied by the loss of the ancestral metameric organization. This results in the formation of one solid mass, a synganglion. Although numerous studies investigated the morphology of Archegozetes longisetosus, the organization of the nervous system is to date unknown. Using synchrotron X-ray microtomography, we investigated the organization of the nervous system in the adult stage and the development of the synganglion over all five free-living life stages (larva, proto-, deuto-, tritonymph and adult). The general morphology of the synganglion resembles that of other studied mites (in the classic sense) and ticks, being subdivided into a sub- and supraesophageal region, and consisting of cortex and neuropil. All nerves entering the walking legs except the first consist of two rami. This split is not based on a functional division into a motor and a sensory ramus, but both rami contain motor and sensory neurites. Within the synganglion, we found structures that resemble the ancestral metameric organization of the nervous system of arthropods. The development of the synganglion of A. longisetosus shows a more or less linear increase in volume, but cortex and neuropil grow at different rates over the five life stages. Between the second and third nymphal stage, the volume of the neuropil increases at a faster rate than the cortex.

  8. Evidence for the presence of thyroid stimulating hormone, thyroglobulin and their receptors in Eisenia fetida: a multilevel hormonal interface between the nervous system and the peripheral tissues.

    PubMed

    Wilhelm, Márta; Koza, Anna; Engelmann, Péter; Németh, Péter; Csoknya, Mária

    2006-06-01

    The present study describes the localization and distribution of thyroid-stimulating hormone (TSH), thyroglobulin (TGB) and their receptors in Eisenia fetida (Annelida, Oligochaeta) as revealed by immunohistological methods. Immunopositive neuronal and non-neuronal cells are present in both the central nervous system and some peripheral organs (e.g. foregut and coelomocytes). TSH- and TGB-immunopositive neurons in the various ganglia of the central nervous system are differentially distributed. Most of the immunoreactive cells are found in the suboesophageal ganglion. The stained cells also differ in their shapes (round, oval, pear-shaped) and sizes (small, 12-25 microm; medium, 20-35 microm; large, 30-50 microm). In all ganglia of the central nervous system, TSH-positive neurons additionally show gamma aminobutyric acid (GABA) immunopositivity. Non-neuronal cells also take part in hormone secretion and transport. Elongated TSH-positive cells have been detected in the capsule of the central ganglia and bear granules or vacuoles in areas lacking neurons. Many of capillaries show immunoreactivity for all four tested antibodies in the entire central nervous system and foregut. Among the coelomocytes, granulocytes and eleocytes stain for TSH and its receptor and for TGB but not for thyroid hormone receptor. Most of the granulocytes are large (25-50 microm) but a population of small cells (10-25 microm) are also immunoreactive. None of the coelomocytes stain for GABA. We therefore suggest that the members of this hormone system can modify both metabolism and immune functions in Eisenia. Coelomocytes might be able to secrete, transport and eliminate hormones in this system.

  9. Microenvironmental determinants of adult neural stem cell proliferation and lineage commitment in the healthy and injured central nervous system.

    PubMed

    Moyse, Emmanuel; Segura, Stéphanie; Liard, Oliver; Mahaut, Stéphanie; Mechawar, Naguib

    2008-09-01

    The discovery of neural stem cells (NSC) which ensure continuous neurogenesis in the adult mammalian brain, has led to a conceptual revolution in basic neuroscience and to high hopes for clinical nervous tissue repair. However, several research issues remain to address before neural stem cells can be harnessed for regenerative therapies. The presence of NSC in a nervous structure is demonstrated in vitro by primary culture of dissociated adult nervous tissue in the presence of the specific mitogens EGF and bFGF. This leads to spherical masses of proliferating cells endowed with capacities for self-renewal and, after growth factor removal, differentiation into the three characteristic cell types of nervous tissue (neurons, astrocytes, oligodendrocytes). In vivo, neurogenesis per se, i.e. production of new neurons, occurs only in a small subset of NSC-endowed structures. The production of oligodendrocytes, i.e. myelinating glial cells, is similarly restricted. Such in vivo restrictions were formally demonstrated to arise from the tissular microenvironnement, which led to the emerging concept of "neurogenic niche". In this context, major challenges now consist in identifying the nature of tissue-specific extracellular signals that determine lineage commitment of NSC progeny, understanding why NSCs display weak in vivo reactivity to lesions compared to other stem cell types in adults, and identifying the factors behind the very high resistance to tumorigenesis displayed by NSCs. Altogether, the current data offer hope for the future use of adult NSCs in regenerative therapies, provided that tissue-specific signals are identified in view of counteracting the intrinsic repression of new cell genesis and/or stimulating endogenous NSC recruitment to lesion sites.

  10. Immunocytochemical detection of vasoactive intestinal peptide-like and peptide histidine isoleucine-like peptides in the nervous system and the excretory system of adult Nippostrongylus brasiliensis.

    PubMed

    Foster, N

    1998-05-01

    Vasoactive intestinal peptide-like and peptide histidine isoleucine-like immunoreactivities were detected in the excretory duct of adult male and female Nippostrongylus brasiliensis, thus indicating the source of these two physiologically active peptides previously isolated from the excretory/secretory products of adult N. brasiliensis. In the nervous system immunoreactivity to both these peptides was confined to females and was found in the neurons of the ovijector associated ganglion. This is consistent with co-synthesis of vasoactive intestinal peptide-like and peptide histidine isoleucine-like peptides which has also been shown to occur in all mammalian vasoactive intestinal peptid-ergic neurons studied to date. However, in addition to this, and in common to some previous studies on helminth vasoactive intestinal peptide and peptide histidine isoleucine immunoreactivities, co-synthesis of the peptides was not indicated in a pair of branched neurons which projected posteriorly and peripherally from the ganglion associated with the ovijector of females and which terminated in two pairs of ganglia also exhibiting vasoactive intestinal peptide-like immunoreactivity only. The position of these ganglia indicated that they innervate muscles close to the body wall and may be responsible for the muscular contractions required for expulsion of eggs from female Nippostrongylus brasiliensis. This is also the first study to successfully detect these peptides in the excretory system of gastrointestinal nematodes.

  11. Enhancing nerve regeneration in the peripheral nervous system using polymeric scaffolds, stem cell engineering and nanoparticle delivery system

    NASA Astrophysics Data System (ADS)

    Sharma, Anup Dutt

    Peripheral nerve regeneration is a complex biological process responsible for regrowth of neural tissue following a nerve injury. The main objective of this project was to enhance peripheral nerve regeneration using interdisciplinary approaches involving polymeric scaffolds, stem cell therapy, drug delivery and high content screening. Biocompatible and biodegradable polymeric materials such as poly (lactic acid) were used for engineering conduits with micropatterns capable of providing mechanical support and orientation to the regenerating axons and polyanhydrides for fabricating nano/microparticles for localized delivery of neurotrophic growth factors and cytokines at the site of injury. Transdifferentiated bone marrow stromal cells or mesenchymal stem cells (MSCs) were used as cellular replacements for lost native Schwann cells (SCs) at the injured nerve tissue. MSCs that have been transdifferentiated into an SC-like phenotype were tested as a substitute for the myelinating SCs. Also, genetically modified MSCs were engineered to hypersecrete brain- derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) to secrete therapeutic factors which Schwann cell secrete. To further enhance the regeneration, nerve growth factor (NGF) and interleukin-4 (IL4) releasing polyanhydrides nano/microparticles were fabricated and characterized in vitro for their efficacy. Synergistic use of these proposed techniques was used for fabricating a multifunctional nerve regeneration conduit which can be used as an efficient tool for enhancing peripheral nerve regeneration.

  12. A Controlled Study of Autonomic Nervous System Function in Adults with Attention-Deficit/Hyperactivity Disorder Treated with Stimulant Medications: Results of a Pilot Study

    ERIC Educational Resources Information Center

    Schubiner, Howard; Hassunizadeh, Bischan; Kaczynski, Richard

    2006-01-01

    Objective: Despite the fact that autonomic nervous system (ANS) abnormalities are commonly found in adults and predict increased cardiovascular mortality, no studies have assessed ANS function in adults with attention-deficit/hyperactivity disorder (ADHD) taking stimulants. Method: This pilot study evaluated ANS function in adults with ADHD in…

  13. Reading speed in the peripheral visual field of older adults: Does it benefit from perceptual learning?

    PubMed

    Yu, Deyue; Cheung, Sing-Hang; Legge, Gordon E; Chung, Susana T L

    2010-04-21

    Enhancing reading ability in peripheral vision is important for the rehabilitation of people with central-visual-field loss from age-related macular degeneration (AMD). Previous research has shown that perceptual learning, based on a trigram letter-recognition task, improved peripheral reading speed among normally-sighted young adults (Chung, Legge, & Cheung, 2004). Here we ask whether the same happens in older adults in an age range more typical of the onset of AMD. Eighteen normally-sighted subjects, aged 55-76years, were randomly assigned to training or control groups. Visual-span profiles (plots of letter-recognition accuracy as a function of horizontal letter position) and RSVP reading speeds were measured at 10 degrees above and below fixation during pre- and post-tests for all subjects. Training consisted of repeated measurements of visual-span profiles at 10 degrees below fixation, in four daily sessions. The control subjects did not receive any training. Perceptual learning enlarged the visual spans in both trained (lower) and untrained (upper) visual fields. Reading speed improved in the trained field by 60% when the trained print size was used. The training benefits for these older subjects were weaker than the training benefits for young adults found by Chung et al. Despite the weaker training benefits, perceptual learning remains a potential option for low-vision reading rehabilitation among older adults.

  14. Reading Speed in the peripheral visual field of older adults: Does it benefit from perceptual learning?

    PubMed Central

    Yu, Deyue; Cheung, Sing-Hang; Legge, Gordon E.; Chung, Susana T. L.

    2010-01-01

    Enhancing reading ability in peripheral vision is important for the rehabilitation of people with central-visual-field loss from age-related macular degeneration (AMD). Previous research has shown that perceptual learning, based on a trigram letter-recognition task, improved peripheral reading speed among normally-sighted young adults (Chung, Legge & Cheung, 2004). Here we ask whether the same happens in older adults in an age range more typical of the onset of AMD. Eighteen normally-sighted subjects, aged 55 to 76 years, were randomly assigned to training or control groups. Visual-span profiles (plots of letter-recognition accuracy as a function of horizontal letter position) and RSVP reading speeds were measured at 10° above and below fixation during pre- and post-tests for all subjects. Training consisted of repeated measurements of visual-span profiles at 10° below fixation, in 4 daily sessions. The control subjects did not receive any training. Perceptual learning enlarged the visual spans in both trained (lower) and untrained (upper) visual fields. Reading speed improved in the trained field by 60% when the trained print size was used. The training benefits for these older subjects were weaker than the training benefits for young adults found by Chung et al. Despite the weaker training benefits, perceptual learning remains a potential option for low-vision reading rehabilitation among older adults. PMID:20156473

  15. Autonomic nervous system dysfunction in workers exposed to lead, zinc, and copper in relation to peripheral nerve conduction: a study of R-R interval variability

    SciTech Connect

    Murata, K.; Araki, S. )

    1991-01-01

    Quantitative assessment of the autonomic neurotoxicity due to lead was undertaken by measuring variability in the electrocardiographic R-R interval (CVRR) in 16 male workers exposed to lead, zinc, copper, and tin and in 16 unexposed control subjects. Two component coefficients of variation in the R-R interval, the C-CVRSA (respiratory sinus arrhythmia) and C-CVMWSA (Mayer wave related sinus arrhythmia), were examined; these indices are considered to reflect parasympathetic and sympathetic activities, respectively. Maximal motor and sensory conduction velocities (MCV and SCV) in the median nerve were also measured. In the 16 exposed workers, blood lead concentrations ranged from 16 to 60 (mean 34) micrograms/dl. The CVRR and C-CVRSA were found to be significantly reduced in the workers with elevated lead, zinc, and copper absorption as compared to unexposed control subjects; also, the MCV and SCV were significantly slowed. The C-CVMWSA was not significantly reduced, and was positively related to plasma zinc concentrations. No significant relationships were found between indicators of lead and copper absorption and these electrophysiological measurements. These data suggest that subclinical toxicity of lead occurs in the parasympathetic component of the autonomic nervous system as well as in the peripheral nerves. Zinc may antagonize the autonomic nervous dysfunction caused by lead.

  16. The Challenge of Cancer Genomics in Rare Nervous System Neoplasms: Malignant Peripheral Nerve Sheath Tumors as a Paradigm for Cross-Species Comparative Oncogenomics.

    PubMed

    Carroll, Steven L

    2016-03-01

    Comprehensive genomic analyses of common nervous system cancers provide new insights into their pathogenesis, diagnosis, and treatment. Although analogous studies of rare nervous system tumors are needed, there are major barriers to performing such studies. Cross-species comparative oncogenomics, identifying driver mutations in mouse cancer models and validating them in human tumors, is a promising alternative. Although still in its infancy, this approach is being applied to malignant peripheral nerve sheath tumors (MPNSTs), rare Schwann cell-derived malignancies that occur sporadically, after radiotherapy, and in neurofibromatosis type 1. Studies of human neurofibromatosis type 1-associated tumors suggest that NF1 tumor suppressor loss in Schwann cells triggers cell-autonomous and intercellular changes, resulting in development of benign neurofibromas; subsequent neurofibroma-MPNST progression is caused by aberrant growth factor signaling and mutations affecting the p16(INK4A)-cyclin D1-CDK4-Rb and p19(ARF)-Mdm2-p53 cell cycle pathways. Mice with Nf1, Trp53, and/or Cdkn2a mutations that overexpress the Schwann cell mitogen neuregulin-1 or overexpress the epidermal growth factor receptor validate observations in human tumors and, to various degrees, model human tumorigenesis. Genomic analyses of MPNSTs arising in neuregulin-1 and epidermal growth factor receptor-overexpressing mice and forward genetic screens with Sleeping Beauty transposons implicate additional signaling cascades in MPNST pathogenesis. These studies confirm the utility of mouse models for MPNST driver gene discovery and provide new insights into the complexity of MPNST pathogenesis.

  17. Choline, CDP-choline or phosphocholine increases plasma glucagon in rats: involvement of the peripheral autonomic nervous system.

    PubMed

    Cansev, Mehmet; Ilcol, Yesim Ozarda; Yilmaz, Mustafa Sertac; Hamurtekin, Emre; Ulus, Ismail H

    2008-07-28

    The present study was designed to test the effects of choline, cytidine-5'-diphosphocholine (CDP-choline) and phosphocholine on plasma glucagon concentrations in rats. Intraperitoneal (i.p.) injection of 200-600 micromol/kg of choline, CDP-choline or phosphocholine produced a dose-dependent increase in plasma glucagon and choline concentrations. Pretreatment with hexamethonium (15 mg/kg; i.p.), a peripherally-acting ganglionic nicotinic acetylcholine receptor antagonist, entirely blocked the increases in plasma glucagon by 600 micromol/kg of choline, CDP-choline or phosphocholine. The increases in plasma glucagon by these choline compounds was reduced significantly (P<0.01) by about 25% by pretreatment with atropine methylnitrate (2 mg/kg), a peripherally-acting muscarinic acetylcholine receptor antagonist. Blockade of central acetylcholine receptors did not alter the increase in plasma glucagon induced by i.p. choline (600 micromol/kg). While alpha(2)-adrenoceptor blockade or bilateral adrenalectomy attenuated the increase in plasma glucagon evoked by choline compounds, blockade of alpha(1)- or beta-adrenoceptors or chemical sympathectomy failed to alter this increase. Intracerebroventricular (i.c.v.) choline (1.5 micromol) administration also increased plasma glucagon; the effect was blocked by central pretreatment with a neuronal type nicotinic acetylcholine receptor antagonist, mecamylamine (50 microg; i.c.v.) or the neuronal choline uptake inhibitor, hemicholinium-3 (20 microg; i.c.v.). These data show that choline, CDP-choline or phosphocholine increases plasma glucagon concentrations by increasing peripheral nicotinic and muscarinic cholinergic neurotransmissions. Central choline also increases plasma glucagon by augmenting central nicotinic cholinergic neurotransmission by acting presynaptically. Stimulation of adrenal medullary catecholamine release and subsequent activation of alpha(2)-adrenoceptors are mainly involved in the increase in plasma glucagon

  18. Magnetic stimulation of the human brain and peripheral nervous system: an introduction and the results of an initial clinical evaluation.

    PubMed

    Barker, A T; Freeston, I L; Jalinous, R; Jarratt, J A

    1987-01-01

    This report describes a novel method of stimulating the motor cortex and deep peripheral nerves in humans. The technique, developed in the Department of Medical Physics of Sheffield University, uses a large pulse of magnetic field to induce currents within the body and is painless. The basic principles of magnetic stimulation are described, and the technique is compared with conventional electrical stimulation. Safety aspects are discussed with reference to established clinical electrical and magnetic procedures. The results of the first clinical study using magnetic stimulation are described and show clear central motor pathway slowing in multiple sclerosis patients.

  19. An Update of the Mayo Clinic Cohort of Patients With Adult Primary Central Nervous System Vasculitis

    PubMed Central

    Salvarani, Carlo; Brown, Robert D.; Christianson, Teresa; Miller, Dylan V.; Giannini, Caterina; Huston, John; Hunder, Gene G.

    2015-01-01

    Abstract Primary central nervous system vasculitis (PCNSV) is an uncommon condition in which lesions are limited to vessels of the brain and spinal cord. Because the clinical manifestations are not specific, the diagnosis is often difficult, and permanent disability and death are frequent outcomes. This study is based on a cohort of 163 consecutive patients with PCNSV who were examined at the Mayo Clinic over a 29-year period from 1983 to 2011. The aim of the study was to define the characteristics of these patients, which represents the largest series in adults reported to date. A total of 105 patients were diagnosed by angiographic findings and 58 by biopsy results. The patients diagnosed by biopsy more frequently had at presentation cognitive dysfunction, greater cerebrospinal fluid total protein concentrations, less frequent cerebral infarcts, and more frequent leptomeningeal gadolinium-enhanced lesions on magnetic resonance imaging (MRI), along with less mortality and disability at last follow-up. The patients diagnosed by angiograms more frequently had at presentation hemiparesis or a persistent neurologic deficit or stroke, more frequent infarcts on MRI and an increased mortality. These differences were mainly related to the different size of the vessels involved in the 2 groups. Although most patients responded to therapy with glucocorticoids alone or in conjunction with cyclophosphamide and tended to improve during the follow-up period, an overall increased mortality rate was observed. Relapses occurred in one-quarter of the patients and were less frequent in patients treated with prednisone and cyclophosphamide compared with those treated with prednisone alone. The mortality rate and degree of disability at last follow-up were greater in those with increasing age, cerebral infarctions on MRI, angiographic large vessel involvement, and diagnosis made by angiography alone, but were lower in those with gadolinium-enhanced lesions on MRI and in those with

  20. Observations on the morphology at the transition between the peripheral and the central nervous system in the cat. V. A light microscopical and histochemical study of S1 dorsal rootlets in developing kittens.

    PubMed

    Berthold, C H; Carlstedt, T

    1977-01-01

    The postnatal development of the transitional region (TR) i.e. the proximal free part of a spinal rootlet that contains both PNS and CNS tissue, was studied light-microscopically in semi-thin sections and after histochemical staining according to the Marchi and OTAN methods for the demonstration of degenerating myelin and according to the Gomori method for the demonstration of acid phosphatase activity. In the newborn kitten the PNS tissue extended well up to the spinal cord surface and the rootlets lacked a transitional region. The CNS tissue entered the root during the second postnatal week, and a trasitional region was fully established at the beginning of the second month. The degree of myelination in the group of large fibres differed on the two sides of the PNS-CNS borderline: well myelinated PNS fibres were transformed into poorly myelinated or apparently unmyelinated CNS-fibres. PNS and CNS myelin sheaths of large fibres appeared to be of equal thickness in the 4 week old kitten. During the first postnatal month large amounts of Marchi positive material and a high acid phosphatase activity occurred in complex paranodes and very short internodes in the PNS compartment just distally to the PNS-CNS borderline. In the adult cat Marchi positive bodies were numerous in the CNS compartment just proximally to the PNS-CNS borderline. The results are discussed against previous studies on focal demyelination as found during the normal development of the feline peripheral nervous system.

  1. Sympathetic nervous system activity is associated with obesity-induced subclinical organ damage in young adults.

    PubMed

    Lambert, Elisabeth; Sari, Carolina Ika; Dawood, Tye; Nguyen, Julie; McGrane, Mariee; Eikelis, Nina; Chopra, Reena; Wong, Chiew; Chatzivlastou, Kanella; Head, Geoff; Straznicky, Nora; Esler, Murray; Schlaich, Markus; Lambert, Gavin

    2010-09-01

    Excess weight is established as a major risk factor for cardiovascular diseases, particularly in young individuals. To get a better understanding of the pathophysiology underlying increased cardiovascular disease risk, we evaluated early signs of organ damage and their possible relationship to sympathetic nervous activity. Eighteen lean (body mass index <25 kg/m(2)) and 25 overweight or obese (body mass index >25 kg/m(2)) healthy university students were included in the study. We comprehensively assessed subclinical target organ damage, including the following: (1) assessment of renal function; (2) left ventricular structure and systolic and diastolic function; and (3) endothelial function. Muscle sympathetic nervous activity was assessed by microneurography. Participants with excess weight had decreased endothelial function (P<0.01), elevated creatinine clearance (P<0.05), increased left ventricular mass index (P<0.05), increased left ventricular wall thickness (P<0.01), lower systolic and diastolic function (P<0.01), and elevated muscle sympathetic nervous activity (P<0.001) compared with lean individuals. In multiple regression analysis, endothelial function was inversely related to muscle sympathetic nervous activity (R(2)=0.244; P<0.05), whereas creatinine clearance and left ventricular mass index were positively related to muscle sympathetic nervous activity, after adjustment for body mass index, sex, and blood pressure (R(2)=0.318, P<0.01 and R(2)=0.312, P<0.05, respectively). Excess weight in young individuals is associated with subclinical alterations in renal and endothelial function, as well as in the structure of the heart, even in the absence of hypertension. Sympathetic activity is closely associated with cardiovascular and renal alterations observed in these subjects.

  2. An inflammatory gene signature distinguishes neurofibroma Schwann cells and macrophages from cells in the normal peripheral nervous system

    PubMed Central

    Choi, Kwangmin; Komurov, Kakajan; Fletcher, Jonathan S.; Jousma, Edwin; Cancelas, Jose A.; Wu, Jianqiang; Ratner, Nancy

    2017-01-01

    Neurofibromas are benign peripheral nerve tumors driven by NF1 loss in Schwann cells (SCs). Macrophages are abundant in neurofibromas, and macrophage targeted interventions may have therapeutic potential in these tumors. We generated gene expression data from fluorescence-activated cell sorted (FACS) SCs and macrophages from wild-type and mutant nerve and neurofibroma to identify candidate pathways involved in SC-macrophage cross-talk. While in 1-month-old Nf1 mutant nerve neither SCs nor macrophages significantly differed from their normal counterparts, both macrophages and SCs showed significantly altered cytokine gene expression in neurofibromas. Computationally reconstructed SC-macrophage molecular networks were enriched for inflammation-associated pathways. We verified that neurofibroma SC conditioned medium contains macrophage chemo-attractants including colony stimulation factor 1 (CSF1). Network analysis confirmed previously implicated pathways and predict novel paracrine and autocrine loops involving cytokines, chemokines, and growth factors. Network analysis also predicted a central role for decreased type-I interferon signaling. We validated type-I interferon expression in neurofibroma by protein profiling, and show that treatment of neurofibroma-bearing mice with polyethylene glycolyated (PEGylated) type-I interferon-α2b reduces the expression of many cytokines overexpressed in neurofibroma. These studies reveal numerous potential targetable interactions between Nf1 mutant SCs and macrophages for further analyses. PMID:28256556

  3. Amantadine reduces glucagon and enhances insulin secretion throughout the oral glucose tolerance test: central plus peripheral nervous system mechanisms

    PubMed Central

    Lechin, Fuad; van der Dijs, Bertha; Pardey-Maldonado, Betty; Rivera, Jairo E; Lechin, Marcel E; Baez, Scarlet

    2009-01-01

    Objective The purpose of the trial was to examine the effects of amantadine, a N-methyl-D-aspartate (NMDA) antagonist, on the oral glucose tolerance test (OGTT) plus insulin, glucagon and neurotransmitters circulating levels. Previous findings showed that hyperinsulinism and type 2 diabetes are positively associated with neural sympathetic and adrenal sympathetic activities, respectively. These peripheral sympathetic branches depend on the pontine (A5-noradrenergic) and the rostral ventrolateral (C1-adrenergic) medullary nuclei. They are excited by glutamate axons which act at NMDA postsynaptic receptors. Research design and methods One OGTT plus placebo and one OGTT plus oral amantadine test were carried out two weeks apart in 15 caucasic normal voluntary humans. Noradrenaline, adrenaline, dopamine, plasma-free serotonin, platelet serotonin, glucose, glucagon, and insulin were measured throughout the 180-minute testing period. Results Maximal reductions of plasma glucose and glucagon plus exacerbated insulin rises were significantly greater throughout the oral glucose plus amantadine test than those registered throughout the oral glucose plus placebo challenge. The above findings were paralleled by greater than normal noradrenaline/adrenaline plasma ratio increases. In addition, maximal reductions of the platelet serotonin and plasma serotonin circulating values contrasted with the normal rises of these parameters, always registered during the glucose load plus placebo challenge. Conclusion This study supports the theory that amantadine might be a powerful antidiabetic tool and could be added to the therapeutic arsenal against type 2 diabetes. PMID:21437134

  4. Single-neuron diversity generated by Protocadherin-β cluster in mouse central and peripheral nervous systems.

    PubMed

    Hirano, Keizo; Kaneko, Ryosuke; Izawa, Takeshi; Kawaguchi, Masahumi; Kitsukawa, Takashi; Yagi, Takeshi

    2012-01-01

    The generation of complex neural circuits depends on the correct wiring of neurons with diverse individual characteristics. To understand the complexity of the nervous system, the molecular mechanisms for specifying the identity and diversity of individual neurons must be elucidated. The clustered protocadherins (Pcdh) in mammals consist of approximately 50 Pcdh genes (Pcdh-α, Pcdh-β, and Pcdh-γ) that encode cadherin-family cell surface adhesion proteins. Individual neurons express a random combination of Pcdh-α and Pcdh-γ, whereas the expression patterns for the Pcdh-β genes, 22 one-exon genes in mouse, are not fully understood. Here we show that the Pcdh-β genes are expressed in a 3'-polyadenylated form in mouse brain. In situ hybridization using a pan-Pcdh-β probe against a conserved Pcdh-β sequence showed widespread labeling in the brain, with prominent signals in the olfactory bulb, hippocampus, and cerebellum. In situ hybridization with specific probes for individual Pcdh-β genes showed their expression to be scattered in Purkinje cells from P10 to P150. The scattered expression patterns were confirmed by performing a newly developed single-cell 3'-RACE analysis of Purkinje cells, which clearly demonstrated that the Pcdh-β genes are expressed monoallelically and combinatorially in individual Purkinje cells. Scattered expression patterns of individual Pcdh-β genes were also observed in pyramidal neurons in the hippocampus and cerebral cortex, neurons in the trigeminal and dorsal root ganglion, GABAergic interneurons, and cholinergic neurons. Our results extend previous observations of diversity at the single-neuron level generated by Pcdh expression and suggest that the Pcdh-β cluster genes contribute to specifying the identity and diversity of individual neurons.

  5. [Reference intervals for peripheral blood lymphocyte subsets in healthy adults in Lima, Peru].

    PubMed

    Cóndor, José M; Álvarez, Marco; Cano, Luis; Matos, Edgar; Leiva, Christian; Paredes, José A

    2013-04-01

    In order to establish the reference intervals (RIs) of peripheral blood lymphocyte subsets (PBL) in healthy adults in Lima (Peru), a cross-sectional study was conducted among blood donors taken in between 2011 and 2012. Based on the criteria obtained from the guidelines of the Clinical and Laboratory Standards Institute (CLSI C28-A3), 318 samples were processed, 61.9% (197/318) coming from male donors. For PBL count, a flow cytometer with a simple platform was used. The RIs are established for each PBL in adults based on sex with their respective reference limits and 90% confidence intervals. Differences were found in CD3+ percentage counts (p=0.001) and in CD3-CD56+ absolute (p=0.003) and percentage counts (p?0.001). The RIs found are different to those described in studies conducted in other countries due to the characteristics of the population and the study model.

  6. TRPA1 receptor localisation in the human peripheral nervous system and functional studies in cultured human and rat sensory neurons.

    PubMed

    Anand, U; Otto, W R; Facer, P; Zebda, N; Selmer, I; Gunthorpe, M J; Chessell, I P; Sinisi, M; Birch, R; Anand, P

    2008-06-20

    TRPA1 is a receptor expressed by sensory neurons, that is activated by low temperature (<17 degrees C) and plant derivatives such as cinnamaldehyde and isoeugenol, to elicit sensations including pain. Using immunohistochemistry, we have, for the first time, localised TRPA1 in human DRG neurons, spinal cord motoneurones and nerve roots, peripheral nerves, intestinal myenteric plexus neurones, and skin basal keratinocytes. TRPA1 co-localised with a subset of hDRG neurons positive for TRPV1, the heat and capsaicin receptor. The number of small/medium TRPA1 positive neurons (< or =50 microm) was increased after hDRG avulsion injury [percentage of cells, median (range): controls 16.5 (7-23); injured 46 (34-55); P<0.005], but the number of large TRPA1 neurons was unchanged [control 19.5 (13-31); injured 21 (11-35)]. Similar TRPA1 changes were observed in cultured hDRG neurons, after exposure to a combination of key neurotrophic factors NGF, GDNF and NT-3 (NTFs) in vitro. We used calcium imaging to examine responses of HEK cells transfected with hTRPA1 cDNA, and of human and rat DRG neurons cultured with or without added NTFs, to cinnamaldehyde (CA) and isoeugenol (IE). Exposure to NTFs in vitro sensitized cultured human sensory neuronal responses to CA; repeated CA exposure produced desensitisation. In rDRG neurons, low (225 microM) CA preincubation enhanced capsaicin responses, while high (450 microM and 2mM) CA caused inhibition which was partially reversed in the presence of 8 bromo cAMP, indicating receptor dephosphorylation. While TRPA1 localisation is more widespread than TRPV1, it represents a promising novel drug target for the treatment of chronic pain and hypersensitivity.

  7. Central nervous system involvement in adult patients with diffuse large B-cell lymphoma: Influence of rituximab

    PubMed Central

    CAO, BING; ZHOU, XIAOYAN; JI, DONGMEI; CAO, JUNNING; GUO, YE; ZHANG, QUNLING; WU, XIANGHUA; LI, JUNMIN; WANG, JIANMIN; CHEN, FANGYUAN; WANG, CHUN; ZOU, SHANHUA; HONG, XIAONAN

    2012-01-01

    CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone)-like chemotherapy, in combination with rituximab (R-CHOP-like), improves outcome in patients with diffuse large B-cell lymphoma (DLBCL). We aimed to investigate the impact of rituximab on central nervous system (CNS) disease in adult patients. We studied 315 patients (aged 18–60 years old) from six hospitals between July 2003 and May 2008. All patients received CHOP-like (n=165) or R-CHOP-like (n=150) regimen every 3 weeks. With a median follow-up of 3.69 years, 10 patients (3.17%) developed CNS disease. The cumulative risk of CNS occurrence was not significantly different between the two treatment groups (P=0.871). We conclude that the addition of rituximab did not reduce the risk of CNS disease in adult patients with DLBCL. PMID:22970053

  8. Multipotent caudal neural progenitors derived from human pluripotent stem cells that give rise to lineages of the central and peripheral nervous system.

    PubMed

    Denham, Mark; Hasegawa, Kouichi; Menheniott, Trevelyan; Rollo, Ben; Zhang, Dongcheng; Hough, Shelley; Alshawaf, Abdullah; Febbraro, Fabia; Ighaniyan, Samiramis; Leung, Jessie; Elliott, David A; Newgreen, Donald F; Pera, Martin F; Dottori, Mirella

    2015-06-01

    The caudal neural plate is a distinct region of the embryo that gives rise to major progenitor lineages of the developing central and peripheral nervous system, including neural crest and floor plate cells. We show that dual inhibition of the glycogen synthase kinase 3β and activin/nodal pathways by small molecules differentiate human pluripotent stem cells (hPSCs) directly into a preneuroepithelial progenitor population we named "caudal neural progenitors" (CNPs). CNPs coexpress caudal neural plate and mesoderm markers, and, share high similarities to embryonic caudal neural plate cells in their lineage differentiation potential. Exposure of CNPs to BMP2/4, sonic hedgehog, or FGF2 signaling efficiently directs their fate to neural crest/roof plate cells, floor plate cells, and caudally specified neuroepithelial cells, respectively. Neural crest derived from CNPs differentiated to neural crest derivatives and demonstrated extensive migratory properties in vivo. Importantly, we also determined the key extrinsic factors specifying CNPs from human embryonic stem cell include FGF8, canonical WNT, and IGF1. Our studies are the first to identify a multipotent neural progenitor derived from hPSCs, that is the precursor for major neural lineages of the embryonic caudal neural tube.

  9. Central Nervous System and Peripheral Expression of CCL19, CCL21 and Their Receptor CCR7 in Experimental Model of Multiple Sclerosis.

    PubMed

    Bielecki, Bartosz; Jatczak-Pawlik, Izabela; Wolinski, Pawel; Bednarek, Andrzej; Glabinski, Andrzej

    2015-10-01

    It is well documented that inflammatory chemokines play a significant role in the development of multiple sclerosis (MS) and its model, experimental autoimmune encephalomyelitis (EAE). Recently, the involvement of homeostatic (or lymphoid) chemokines in the pathogenesis of autoimmune diseases has become an object of intensive study. In this work, quantitative analysis of CCL19, CCL21 and CCR7 expression in the central nervous system (CNS), as well as in inflammatory mononuclear cells isolated from several organs during the first attack, remission and the second attack of chronic-relapsing EAE (ChREAE), was performed. Using real-time PCR, RNAse Protection Assay and immunohistochemistry, the expression of both chemokines, as well as of their common receptor CCR7, was analyzed in the brain, spleen, lymph nodes and peripheral blood mononuclear cells. Increased expression of CCL19 and CCL21 was observed mostly in mononuclear inflammatory cells isolated from the CNS during active ChREAE. At the same time the expression of CCR7 in blood mononuclear leukocytes was reduced. This observation extends our current knowledge about the possible role of chemokines CCL19, CCL21 and their receptor CCR7 in the pathogenesis of ChREAE and, by extension, MS.

  10. Multipotent Caudal Neural Progenitors Derived from Human Pluripotent Stem Cells That Give Rise to Lineages of the Central and Peripheral Nervous System

    PubMed Central

    Hasegawa, Kouichi; Menheniott, Trevelyan; Rollo, Ben; Zhang, Dongcheng; Hough, Shelley; Alshawaf, Abdullah; Febbraro, Fabia; Ighaniyan, Samiramis; Leung, Jessie; Elliott, David A.; Newgreen, Donald F.; Pera, Martin F.

    2015-01-01

    Abstract The caudal neural plate is a distinct region of the embryo that gives rise to major progenitor lineages of the developing central and peripheral nervous system, including neural crest and floor plate cells. We show that dual inhibition of the glycogen synthase kinase 3β and activin/nodal pathways by small molecules differentiate human pluripotent stem cells (hPSCs) directly into a preneuroepithelial progenitor population we named “caudal neural progenitors” (CNPs). CNPs coexpress caudal neural plate and mesoderm markers, and, share high similarities to embryonic caudal neural plate cells in their lineage differentiation potential. Exposure of CNPs to BMP2/4, sonic hedgehog, or FGF2 signaling efficiently directs their fate to neural crest/roof plate cells, floor plate cells, and caudally specified neuroepithelial cells, respectively. Neural crest derived from CNPs differentiated to neural crest derivatives and demonstrated extensive migratory properties in vivo. Importantly, we also determined the key extrinsic factors specifying CNPs from human embryonic stem cell include FGF8, canonical WNT, and IGF1. Our studies are the first to identify a multipotent neural progenitor derived from hPSCs, that is the precursor for major neural lineages of the embryonic caudal neural tube. Stem Cells 2015;33:1759–1770 PMID:25753817

  11. Tumors of the peripheral nervous system: analysis of prognostic factors in a series with long-term follow-up and review of the literature.

    PubMed

    Montano, Nicola; D'Alessandris, Quintino Giorgio; D'Ercole, Manuela; Lauretti, Liverana; Pallini, Roberto; Di Bonaventura, Rina; La Rocca, Giuseppe; Bianchi, Federico; Fernandez, Eduardo

    2016-08-01

    .0003 and p = 0.0001 for ≤ 3 cm and 3-5 cm tumors, respectively). Sensory function showed a statistically significant improvement also in patients who had undergone resection of tumors involving the lower limb (p = 0.0118). Total resection was associated with statistically significant improvement of motor strength (p = 0.0251) and sensory function (p < 0.0001). In univariate analysis, a history of NF (p = 0.0034), a diagnosis of MPNST or PNNST (p < 0.0001), and subtotal resection (p = 0.0042) were associated with higher risk of tumor recurrence. In multivariate analysis (logistic regression analysis), a history of NF (OR 9.28%, 95% CI 1.62-52.94, p = 0.0121) and a diagnosis of MPNST (OR 0.03%, 95% CI 0.002-0.429, p = 0.0098) or PNNST (OR 0.081%, 95% CI 0.013-0.509, p = 0.0077) emerged as independent prognostic factors for tumor recurrence. CONCLUSIONS A total resection should be attempted in all cases of peripheral nervous system tumors (irrespective of the supposed diagnosis and tumor dimensions) because it is associated with better prognosis in term of functional outcome and overall survival. Moreover, a total resection predicts a lower risk of tumor recurrence. Patients with a history of NF and tumors with malignant histology remain a challenge both for neurosurgeons and oncologists due to higher recurrence rates and the lack of standardized adjuvant therapies.

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

    PubMed Central

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

    2006-01-01

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

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

    PubMed

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

    2014-12-01

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

  14. Regeneration strategies after the adult mammalian central nervous system injury—biomaterials

    PubMed Central

    Gao, Yudan; Yang, Zhaoyang; Li, Xiaoguang

    2016-01-01

    The central nervous system (CNS) has very restricted intrinsic regeneration ability under the injury or disease condition. Innovative repair strategies, therefore, are urgently needed to facilitate tissue regeneration and functional recovery. The published tissue repair/regeneration strategies, such as cell and/or drug delivery, has been demonstrated to have some therapeutic effects on experimental animal models, but can hardly find clinical applications due to such methods as the extremely low survival rate of transplanted cells, difficulty in integrating with the host or restriction of blood–brain barriers to administration patterns. Using biomaterials can not only increase the survival rate of grafts and their integration with the host in the injured CNS area, but also sustainably deliver bioproducts to the local injured area, thus improving the microenvironment in that area. This review mainly introduces the advances of various strategies concerning facilitating CNS regeneration. PMID:27047678

  15. The equine enteric nervous system--neuron characterization and distribution in adults and juveniles.

    PubMed

    Doxey, D L; Pearson, G T; Milne, E M; Gilmour, J S; Chisholm, H K

    1995-01-01

    A study of myenteric and submucosal plexuses was undertaken in the jejunum and ileum of horses and ponies in which no clinical or pathological evidence of intestinal abnormality was apparent. Complete transverse sections of the intestine, stained by a modified haematoxylin and eosin method, were examined using up to 20 sequential sections per animal. Information was gathered from adult, juvenile and fetal equidae. In adults, the longitudinal muscle layers were thinner than the circular muscle layers and the ileum had thicker layers compared to the jejunum. In adults, the submucosal plexus had more neurons per section than the myenteric plexus by mean ratios of 1:3 in the jejunum and 1:1.9 in the ileum. In juveniles, the ratios were respectively 1:1.8 and 1:1.5 and in the fetus 1:2.5 and 1:1.3. The three-dimensional distribution of neurons in both plexuses varied from animal to animal and no consistent pattern was observed. Groups of neurons contained between one and 42 cells per section examined and their length in a cranio-caudal direction varied from 10 to over 100 microns. There were few statistical differences observed between the cranial, middle and caudal portions of either the jejunum or the ileum when neuron groups or neuron numbers per section were examined in 10 adult animals.

  16. Early central nervous complications after umbilical cord blood transplantation for adults.

    PubMed

    Narimatsu, Hiroto; Miyamura, Koichi; Iida, Hiroatsu; Hamaguchi, Motohiro; Uchida, Toshiki; Morishita, Yoshihisa

    2009-01-01

    Early central nervous complications (CNS) are significant after allogeneic stem cell transplantation; however, the clinical characteristics of early CNS complications have not yet been well described. The medical record of 77 patients who underwent cord blood transplantation (CBT) between March 2001 and November 2005, at 8 centers of the Nagoya Blood and Marrow Transplantation Group were retrospectively reviewed. The preparative regimen included myeloablative CBT (n = 31) or reduced-intensity (RI)-CBT (n = 46). Of the 77 patients, 10 (13%) developed early CNS complications. Causes included Cyclosporine encephalopathy (n = 5), tacrolimus encephalopathy (n = 2), thrombocytic microangiopathy (n = 1), and unknown (n = 3). The median time of onset was 19 days (range: 2-58 days). All of the 10 patients developed impaired consciousness. Seizures developed in 6 patients. Early CNS complications spontaneously subsided in 3 patients. Three patients responded to cyclosporine or tacrolimus discontinuation. The remaining 4 patients died within 30 days of developing of early CNS complications. No relationship was detected between the preparative regimen and the onset of early CNS complications, while an HLA disparity showed borderline significance (hazard ratio, 3.24; 95% confidential interval, 0.94-11.20; P = .06). Early CNS complications are a significant problem after CBT, and the clinician has to be aware of the possibility of these complications.

  17. Primary central nervous system ALK-positive anaplastic large cell lymphoma in an adult

    PubMed Central

    Dong, Xiaoqin; Li, Jun; Huo, Na; Wang, Yan; Wu, Zhao; Lin, Xiaohong; Zhao, Hong

    2016-01-01

    Abstract Rationale: Anaplastic large cell lymphoma (ALCL) is an aggressive non-Hodgkin lymphoma. It mostly invades lymph nodes with extranodal involvement observed in the soft tissue, bone, and skin. Patient concerns: We report a 34-year-old Chinese male patient who presented with headache, diplopia, and vomit. Cerebrospinal fluid (CSF) analysis via lumbar puncture showed elevated CSF pressure, elevated CSF protein concentrations, decreased CSF glucose and chloride concentration significantly, and pleocytosis of 68 to 350 × 106/L, in which lymphocytes and monocytes were predominant. These changes could be suggestive of tuberculous (TB) meningitis. Enhanced magnetic resonance imaging of spinal cord delineated multiple enhancing nodules in spinal cord, cauda equina, and cristae membrane, and multiple abnormal enhancing lesions in bilateral lumbar intervertebral foramen. Diagnoses: Spinal dura mater biopsy and paraffin pathology examination revealed anaplastic lymphoma kinase positive ALCL. Interventions: High-dose methotrexate, cytosine arabinoside craniospinal, and radiotherapy. Outcomes: Last follow-up on September 22, 2015 showed no evidence of tumor recurrence and the lower extremity muscle strength recovered to 4/5. Lessons: ALCL of primary central nervous system is an exceedingly rare tumor, which is usually misdiagnosed as meningitis (especially TB meningitis) according to clinical manifestation and laboratory examination. Thus closely monitoring patient's conditions and timely adjusting therapeutic regimen during treatment are necessary. PMID:27930548

  18. Morphological alterations of central nervous system (CNS) myelin in vanadium (V)-exposed adult rats.

    PubMed

    García, Graciela B; Quiroga, Ariel D; Stürtz, Nelson; Martinez, Alejandra I; Biancardi, María E

    2004-08-01

    In the present work we show morphological data of the in vivo susceptibility of CNS myelin to sodium metavanadate [V(+5)] in adult rats. The possible role of vanadium in behavioral alterations and in brain lipid peroxidation was also investigated. Animals were injected intraperitoneally (i.p.) with 3 mg/kg body weight (bw) of sodium metavanadate [1.25 V/kg bw/day] for 5 consecutive days. Open field and rotarod tests were performed the day after the last dose had been administered and then animals were sacrificed by different methods for histological and lipid peroxidation studies. The present results show that intraperitoneal administration of V(+5) to adult rats resulted in changes in locomotor activity, specific myelin stainings and lipid peroxidation in some brain areas. They support the notion that CNS myelin could be a preferential target of V(+5)-mediated lipid peroxidation in adult rats. The mechanisms underlying this action could affect the myelin sheath leading to behavioral perturbations.

  19. Peripheral pulmonary artery stenosis as a cause of pulmonary hypertension in adults

    PubMed Central

    Ahmed, Mostafa; Hamed, Fadi; Prieto, Lourdes R.

    2015-01-01

    Abstract Peripheral pulmonary artery stenosis (PPAS) is an underrecognized condition in the adult population. PPAS can lead to pulmonary hypertension but is likely misdiagnosed as either idiopathic pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension. We retrospectively identified adult patients with PPAS either in its isolated form or related to other congenital defects from January 1998 to September 2012. We reviewed the patients’ clinical data by using our hospital electronic medical records and/or their paper charts. We identified 6 adult patients with PPAS with an age range of 16–56 years (1 woman and the rest men). Presenting signs and symptoms were thoracic murmurs, progressive dyspnea, and syncope. Three patients had Williams-Beuren syndrome. Pulmonary angiography showed that PPAS was predominantly located in main branches or lobar pulmonary arteries in 5 patients, while in 1 patient the arterial narrowing was at the level of the segmental pulmonary arteries. Right heart catheterization showed a mean pulmonary artery pressure (PAP) ranging from 35 to 60 mmHg. Balloon dilation was performed in all patients, predominantly in the lobar arteries, and it caused a decrease in mean PAP that ranged from 16% to 46% in 5 patients. In 1 patient the mean PAP did not decrease. All but 1 patient had follow-up echocardiograms at 1 year that showed stable echocardiographic findings. Pulmonary hypertension due to PPAS continues to presents a diagnostic challenge. Therefore, a high index of suspicion during the initial evaluation of pulmonary hypertension is essential for its prompt diagnosis and adequate treatment. PMID:25992283

  20. Magnitude of GAP-43 induction following peripheral axotomy of adult rat dorsal root ganglion neurons is independent of lesion distance.

    PubMed

    Liabotis, S; Schreyer, D J

    1995-09-01

    Regenerative axon growth in peripheral neurons is accompanied by increased expression of the growth-associated protein GAP-43. We examined the increase of GAP-43 immunoreactivity in DRG neurons following lesions at different distances along the sciatic nerve, using immunocytochemistry. To control for the variable involvement of DRG axons following injury at different sites, injured neurons were identified by retrograde labeling with Fluoro-Gold. GAP-43 labeling was similar for proximal, distal, and far-distal injuries when only injured neurons are considered. Our results stand in contrast to studies which show that GAP-43 upregulation in neurons of the central nervous system occurs only when lesions are made close to the cell body. This suggests that the mechanisms which control GAP-43 expression following injury differ between central and peripheral neurons.

  1. 5-HT4 receptor-mediated neuroprotection and neurogenesis in the enteric nervous system of adult mice

    PubMed Central

    Liu, Min-Tsai; Kuan, Yung-Hui; Wang, Jingwen; Hen, René; Gershon, Michael D.

    2009-01-01

    Although the mature enteric nervous system (ENS) has been shown to retain stem cells, enteric neurogenesis has not previously been demonstrated in adults. The relative number of enteric neurons in wild-type (WT) mice and those lacking 5-HT4 receptors (KO) was found to be similar at birth; however, the abundance of ENS neurons increased during the first 4 months after birth in WT but not KO littermates. Enteric neurons subsequently decreased in both WT and KO but at 12 months were significantly more numerous in WT. We tested the hypothesis that stimulation of the 5-HT4 receptor promotes enteric neuron survival and/or neurogenesis. In vitro, 5-HT4 agonists increased enteric neuronal development/survival, decreased apoptosis, and activated CREB. In vivo, in WT but not KO mice, 5-HT4 agonists induced bromodeoxyuridine (BrdU) incorporation into cells that expressed markers of neurons (HuC/D, doublecortin), neural precursors (Sox10, nestin, Phox2b), or stem cells (Musashi-1). This is the first demonstration of adult enteric neurogenesis; our results suggest that 5-HT4 receptors are required postnatally for ENS growth and maintenance. PMID:19657021

  2. Postembryonic lineages of the Drosophila ventral nervous system: Neuroglian expression reveals the adult hemilineage associated fiber tracts in the adult thoracic neuromeres

    PubMed Central

    Harris, Robin; Williams, Darren W.; Truman, James W.

    2016-01-01

    During larval life most of the thoracic neuroblasts (NBs) in Drosophila undergo a second phase of neurogenesis to generate adult‐specific neurons that remain in an immature, developmentally stalled state until pupation. Using a combination of MARCM and immunostaining with a neurotactin antibody, Truman et al. (2004; Development 131:5167–5184) identified 24 adult‐specific NB lineages within each thoracic hemineuromere of the larval ventral nervous system (VNS), but because of the neurotactin labeling of lineage tracts disappearing early in metamorphosis, they were unable extend the identification of these lineages into the adult. Here we show that immunostaining with an antibody against the cell adhesion molecule neuroglian reveals the same larval secondary lineage projections through metamorphosis and bfy identifying each neuroglian‐positive tract at selected stages we have traced the larval hemilineage tracts for all three thoracic neuromeres through metamorphosis into the adult. To validate tract identifications we used the genetic toolkit developed by Harris et al. (2015; Elife 4) to preserve hemilineage‐specific GAL4 expression patterns from larval into the adult stage. The immortalized expression proved a powerful confirmation of the analysis of the neuroglian scaffold. This work has enabled us to directly link the secondary, larval NB lineages to their adult counterparts. The data provide an anatomical framework that 1) makes it possible to assign most neurons to their parent lineage and 2) allows more precise definitions of the neuronal organization of the adult VNS based in developmental units/rules. J. Comp. Neurol. 524:2677–2695, 2016. © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. PMID:26878258

  3. The insulin-like growth factor 1 receptor is essential for axonal regeneration in adult central nervous system neurons.

    PubMed

    Dupraz, Sebastián; Grassi, Diego; Karnas, Diana; Nieto Guil, Alvaro F; Hicks, David; Quiroga, Santiago

    2013-01-01

    Axonal regeneration is an essential condition to re-establish functional neuronal connections in the injured adult central nervous system (CNS), but efficient regrowth of severed axons has proven to be very difficult to achieve. Although significant progress has been made in identifying the intrinsic and extrinsic mechanisms involved, many aspects remain unresolved. Axonal development in embryonic CNS (hippocampus) requires the obligate activation of the insulin-like growth factor 1 receptor (IGF-1R). Based on known similarities between axonal growth in fetal compared to mature CNS, we decided to examine the expression of the IGF-1R, using an antibody to the βgc subunit or a polyclonal anti-peptide antibody directed to the IGF-R (C20), in an in vitro model of adult CNS axonal regeneration, namely retinal ganglion cells (RGC) derived from adult rat retinas. Expression of both βgc and the β subunit recognized by C20 antibody were low in freshly isolated adult RGC, but increased significantly after 4 days in vitro. As in embryonic axons, βgc was localised to distal regions and leading growth cones in RGC. IGF-1R-βgc co-localised with activated p85 involved in the phosphatidylinositol-3 kinase (PI3K) signaling pathway, upon stimulation with IGF-1. Blocking experiments using either an antibody which neutralises IGF-1R activation, shRNA designed against the IGF-1R sequence, or the PI3K pathway inhibitor LY294002, all significantly reduced axon regeneration from adult RGC in vitro (∼40% RGC possessed axons in controls vs 2-8% in the different blocking studies). Finally, co-transfection of RGC with shRNA to silence IGF-1R together with a vector containing a constitutively active form of downstream PI3K (p110), fully restored axonal outgrowth in vitro. Hence these data demonstrate that axonal regeneration in adult CNS neurons requires re-expression and activation of IGF-1R, and targeting this system may offer new therapeutic approaches to enhancing axonal

  4. Cord blood T cells mediate enhanced antitumor effects compared with adult peripheral blood T cells.

    PubMed

    Hiwarkar, Prashant; Qasim, Waseem; Ricciardelli, Ida; Gilmour, Kimberly; Quezada, Sergio; Saudemont, Aurore; Amrolia, Persis; Veys, Paul

    2015-12-24

    Unrelated cord blood transplantation (CBT) without in vivo T-cell depletion is increasingly used to treat high-risk hematologic malignancies. Following T-replete CBT, naïve CB T cells undergo rapid peripheral expansion with memory-effector differentiation. Emerging data suggest that unrelated CBT, particularly in the context of HLA mismatch and a T-replete graft, may reduce leukemic relapse. To study the role of CB T cells in mediating graft-versus-tumor responses and dissect the underlying immune mechanisms for this, we compared the ability of HLA-mismatched CB and adult peripheral blood (PB) T cells to eliminate Epstein-Barr virus (EBV)-driven human B-cell lymphoma in a xenogeneic NOD/SCID/IL2rg(null) mouse model. CB T cells mediated enhanced tumor rejection compared with equal numbers of PB T cells, leading to improved survival in the CB group (P < .0003). Comparison of CB T cells that were autologous vs allogeneic to the lymphoma demonstrated that this antitumor effect was mediated by alloreactive rather than EBV-specific T cells. Analysis of tumor-infiltrating lymphocytes demonstrated that CB T cells mediated this enhanced antitumor effect by rapid infiltration of the tumor with CCR7(+)CD8(+) T cells and prompt induction of cytotoxic CD8(+) and CD4(+) T-helper (Th1) T cells in the tumor microenvironment. In contrast, in the PB group, this antilymphoma effect is impaired because of delayed tumoral infiltration of PB T cells and a relative bias toward suppressive Th2 and T-regulatory cells. Our data suggest that, despite being naturally programmed toward tolerance, reconstituting T cells after unrelated T-replete CBT may provide superior Tc1-Th1 antitumor effects against high-risk hematologic malignancies.

  5. Individual, social and environmental predictors of regular exercise among adults with type 2 diabetes and peripheral neuropathy in China.

    PubMed

    Pei, Li; Wang, Yan; Sun, Chunyan Y; Zhang, Qing

    2016-10-01

    The purpose of the study was to explore the individual, social and environmental factors influencing regular exercise on the basis of the theoretical framework of social ecological model among adults with type 2 diabetes and peripheral neuropathy. A total of 122 participants were chosen from Tianjin Metabolic Disease Hospital from November 2013 to May 2014. Information on exercise status and influencing factors was collected. Most participants took walking as the mode of exercise and exercised alone. Only 59.8% of participants were reported to carry out regular exercise. Logistic regression analysis suggested that being male, longer duration with diabetic peripheral neuropathy, higher self-efficacy for exercise and higher objective support were associated with regular exercise. Exercise status was clearly not ideal among adults with type 2 diabetes and peripheral neuropathy. The study highlighted the need to take measures to improve self-efficacy for exercise and social support in order to promote exercise participation among adults with type 2 diabetes and peripheral neuropathy.

  6. Mitochondrial Respiration after One Session of Calf Raise Exercise in Patients with Peripheral Vascular Disease and Healthy Older Adults

    PubMed Central

    Wohlwend, Martin; Rognmo, Øivind; Mattsson, Erney J. R.

    2016-01-01

    Purpose Mitochondria are essential for energy production in the muscle cell and for this they are dependent upon a sufficient supply of oxygen by the circulation. Exercise training has shown to be a potent stimulus for physiological adaptations and mitochondria play a central role. Whether changes in mitochondrial respiration are seen after exercise in patients with a reduced circulation is unknown. The aim of the study was to evaluate the time course and whether one session of calf raise exercise stimulates mitochondrial respiration in the calf muscle of patients with peripheral vascular disease. Methods One group of patients with peripheral vascular disease (n = 11) and one group of healthy older adults (n = 11) were included. Patients performed one session of continuous calf raises followed by 5 extra repetitions after initiation of pain. Healthy older adults performed 100 continuous calf raises. Gastrocnemius muscle biopsies were collected at baseline and 15 minutes, one hour, three hours and 24 hours after one session of calf raise exercise. A multi substrate (octanoylcarnitine, malate, adp, glutamate, succinate, FCCP, rotenone) approach was used to analyze mitochondrial respiration in permeabilized fibers. Mixed-linear model for repeated measures was used for statistical analyses. Results Patients with peripheral vascular disease have a lower baseline respiration supported by complex I and they increase respiration supported by complex II at one hour post-exercise. Healthy older adults increase respiration supported by electron transfer flavoprotein and complex I at one hour and 24 hours post-exercise. Conclusion Our results indicate a shift towards mitochondrial respiration supported by complex II as being a pathophysiological component of peripheral vascular disease. Furthermore exercise stimulates mitochondrial respiration already after one session of calf raise exercise in patients with peripheral vascular disease and healthy older adults. Trial

  7. Toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the peripheral nervous system of developing red seabream (Pagrus major).

    PubMed

    Iida, Midori; Kim, Eun-Young; Murakami, Yasunori; Shima, Yasuhiro; Iwata, Hisato

    2013-03-15

    We investigated 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced effects on the morphology of peripheral nervous system (PNS) in the developing red seabream (Pagrus major) embryos. The embryos at 10h post-fertilization (hpf) were treated with 0, 0.1, 0.4 or 1.7 μg/L of TCDD in seawater for 80 min. The morphology of PNS was microscopically observed with florescence staining using an anti-acetylated tubulin antibody at 48, 78, 120 and 136 hpf. Axon length of facial nerve (VII) was found to be shortened by TCDD exposure. Axon guidance in the glossopharyngeal nerve (IX) and vagus nerve (X) was altered at 120 and 136 hpf in a TCDD dose-dependent manner. Lowest observable effect level of TCDD (0.1 μg/L) that induced the morphological alteration of PNS was lower than those of other endpoints on morphological deformities so far reported. Given that the growth cone at the tip of growing nerve axons advances under the influence of its surrounding tissues, we hypothesized that TCDD exposure would affect (1) the nerve cell proliferation/differentiation, (2) the structure of muscle as an axon target and (3) the nerve guidance factor in the embryos. By the immunostaining of embryos with an antibody against the neuronal specific RNA-binding protein, HuD, and an antibody against the sarcomeric myosin, no morphological effects were observed on the neural proliferation/differentiation and the structure of facial muscles of TCDD-treated embryos. In contrast, whole mount in situ hybridization of semaphorin 3A (Sema3A), a secretory axon repulsion factor, revealed the altered expression pattern of its transcripts in TCDD-treated embryos. Our findings suggest that TCDD treatment affects the projection of PNS in the developing red seabream embryos through the effects on the axonal growth cone guidance molecule such as Sema3A, but not on the neuronal differentiation/proliferation and axon target. The PNS in developing embryos may be one of the most sensitive biomarkers to the exposure

  8. The influence of peripheral vision induced by moving people on postural control in healthy adults

    PubMed Central

    Kim, Soo-Han; Park, Du-Jin

    2016-01-01

    This study was conducted to examine the influence of the peripheral vision (PV) induced by moving people on postural control in healthy adults. The subjects consisted of 12 healthy adult volunteers (5 males, 7 females) who had been informed of the study purpose and procedure. The visual interventions were composed of three types. PV1 and PV2 were stimulated using a one-way vertical striped pattern and a two-way vertical striped pattern, respectively. To embody the features of moving people reflected in the mirrors, researchers recorded movements of people or objects provided by mirrors on video image. In this study, this was named PV3. The subjects were exposed to each of the visual stimuli for 3 min in a random order, and their postural control was then evaluated. All the subjects were allowed to practice once prior to performing the one leg stand test, functional reaching test and body sway test. All the evaluations were made before and after the visual intervention, and the subjects rested for 30 min between each intervention. PV3 ranked second in before and after differences of trace length and velocity and had no significant difference from PV2, demonstrating that the PV3, as well as PV2, affected the amount and velocity of body sway. In addition, the standard deviation velocity, trace length and velocity values of PV3 were higher than the PV1 values. Therefore, the treatment of those who have difficulty with postural control and balance maintenance should take place in a controlled therapeutic environment. PMID:27807518

  9. Susceptibility of neonatal T cells and adult thymocytes to peripheral tolerance to allogeneic stimuli

    PubMed Central

    do Canto, Fábio B; Lima, Celso; Teixeira, Ivan A; Bellio, Maria; Nóbrega, Alberto; Fucs, Rita

    2008-01-01

    We studied the tolerization of neonatal thymocytes (NT), neonatal splenocytes (NS) and adult thymocytes (AT), transferred to syngeneic nude (nu/nu) hosts previously injected with semi-allogeneic splenocytes, without any supportive immunosuppressive treatment. This protocol allows the study of peripheral tolerance in the absence of the thymus. BALB/c neonatal T cells and ATs were able to expand in syngeneic BALB/c nu/nu mice and functionally reconstituted an allogeneic response, rejecting (BALB/c × B6.Ba) F1 splenocytes transferred 3–4 weeks after injection of BALB/c cells. However, if (BALB/c × B6.Ba) F1 cells were injected into BALB/c nude hosts 30 days before transfer of NT, NS or AT cells, the F1 population was preserved and specific tolerance to B6 allografts was established. Furthermore, transfer to lymphopenic F1 nu/nu showed that tolerance could be established only for neonatal populations, showing that unique properties of neonatal T cells allow their tolerization in both lymphopenic and non-lymphopenic conditions, in the absence of suppressive immunotherapy. These results bring empirical support to the possibility of T-cell engraftment in immunodeficient patients showing partial identity with donor major histocompatibility complex (MHC) genes; the manipulation of immunological maturity of donor T cells may be the key for successful reconstitution of immunocompetence without induction of graft-versus-host disease. PMID:18462348

  10. Differential Distribution of Major Brain Gangliosides in the Adult Mouse Central Nervous System

    PubMed Central

    Vajn, Katarina; Viljetić, Barbara; Degmečić, Ivan Večeslav; Schnaar, Ronald L.; Heffer, Marija

    2013-01-01

    Gangliosides - sialic acid-bearing glycolipids - are major cell surface determinants on neurons and axons. The same four closely related structures, GM1, GD1a, GD1b and GT1b, comprise the majority of total brain gangliosides in mammals and birds. Gangliosides regulate the activities of proteins in the membranes in which they reside, and also act as cell-cell recognition receptors. Understanding the functions of major brain gangliosides requires knowledge of their tissue distribution, which has been accomplished in the past using biochemical and immunohistochemical methods. Armed with new knowledge about the stability and accessibility of gangliosides in tissues and new IgG-class specific monoclonal antibodies, we investigated the detailed tissue distribution of gangliosides in the adult mouse brain. Gangliosides GD1b and GT1b are widely expressed in gray and white matter. In contrast, GM1 is predominately found in white matter and GD1a is specifically expressed in certain brain nuclei/tracts. These findings are considered in relationship to the hypothesis that gangliosides GD1a and GT1b act as receptors for an important axon-myelin recognition protein, myelin-associated glycoprotein (MAG). Mediating axon-myelin interactions is but one potential function of the major brain gangliosides, and more detailed knowledge of their distribution may help direct future functional studies. PMID:24098718

  11. [Neuropeptide Y and autonomic nervous system].

    PubMed

    Nozdrachev, A D; Masliukov, P M

    2011-01-01

    Neuropeptide Y (NPY) containing 36 amino acid residues belongs to peptides widely spread in the central and peripheral nervous system. NPY and its receptors play an extremely diverse role in the nervous system, including regulation of satiety, of emotional state, of vascular tone, and of gastrointestinal secretion. In mammals, NPY has been revealed in the majority of sympathetic ganglion neurons, in a high number of neurons of parasympathetic cranial ganglia as well as of intramural ganglia of the metasympathetic nervous system. At present, six types of receptors to NPY (Y1-Y6) have been identified. All receptors to NPY belong to the family of G-bound proteins. Action of NPY on peripheral organs-targets is predominantly realized through postsynaptic receptors Y1, Y3-Y5, and presynaptic receptors of the Y2 type. NPY is present in large electron-dense vesicles and is released at high-frequency stimulation. NPY affects not only vascular tone, frequency and strength of heart contractions, motorics and secretion of the gastrointestinal tract, but also has trophic effect and produces proliferation of cells of organs-targets, specifically of vessels, myocardium, and adipose tissue. In early postnatal ontogenesis the percent of the NPY-containing neurons in ganglia of the autonomic nervous system increases. In adult organisms, this parameter decreases. This seems to be connected with the trophic NPY effect on cells-targets as well as with regulation of their functional state.

  12. Modular and coordinated expression of immune system regulatory and signaling components in the developing and adult nervous system.

    PubMed

    Monzón-Sandoval, Jimena; Castillo-Morales, Atahualpa; Crampton, Sean; McKelvey, Laura; Nolan, Aoife; O'Keeffe, Gerard; Gutierrez, Humberto

    2015-01-01

    During development, the nervous system (NS) is assembled and sculpted through a concerted series of neurodevelopmental events orchestrated by a complex genetic programme. While neural-specific gene expression plays a critical part in this process, in recent years, a number of immune-related signaling and regulatory components have also been shown to play key physiological roles in the developing and adult NS. While the involvement of individual immune-related signaling components in neural functions may reflect their ubiquitous character, it may also reflect a much wider, as yet undescribed, genetic network of immune-related molecules acting as an intrinsic component of the neural-specific regulatory machinery that ultimately shapes the NS. In order to gain insights into the scale and wider functional organization of immune-related genetic networks in the NS, we examined the large scale pattern of expression of these genes in the brain. Our results show a highly significant correlated expression and transcriptional clustering among immune-related genes in the developing and adult brain, and this correlation was the highest in the brain when compared to muscle, liver, kidney and endothelial cells. We experimentally tested the regulatory clustering of immune system (IS) genes by using microarray expression profiling in cultures of dissociated neurons stimulated with the pro-inflammatory cytokine TNF-alpha, and found a highly significant enrichment of immune system-related genes among the resulting differentially expressed genes. Our findings strongly suggest a coherent recruitment of entire immune-related genetic regulatory modules by the neural-specific genetic programme that shapes the NS.

  13. Adenosine 5' triphosphate evoked mobilization of intracellular calcium in central nervous system white matter of adult mouse optic nerve.

    PubMed

    James, G; Butt, A M

    1999-06-11

    Although it has been established that immature glial cells express functional purinergic receptors, the responsiveness of mature glial cells in vivo had not been elucidated. This question was addressed using fura-2 ratiometric measurements of [Ca2+]i in the adult mouse optic nerve, a central nervous system (CNS) white matter tract, taking advantage of the facts that (i), the optic nerve contains glial cells but not neurons and (ii), that fura-2 loads primarily astrocytes in isolated intact optic nerves. We show that adenosine 5' triphosphate (ATP) evoked an increase in [Ca2+]i in a concentration-dependent manner with a half-maximal effect at 3 microm ATP, and with a rank order of agonist potency of ATP > ADP > alpha,beta-methyline-ATP > UDP > adenosine. The results indicate mainly P2Y and P2X components, consistent with the in vitro astroglial purinergic receptor profile. The in vivo response of mature glia to ATP may be important in their response to CNS damage.

  14. Multiparametric immunophenotyping of B cells in peripheral blood of healthy adults by flow cytometry.

    PubMed Central

    Höffkes, H G; Schmidtke, G; Uppenkamp, M; Schmücker, U

    1996-01-01

    The investigation of patients suffering from malignant lymphomas of the B-cell type requires flow cytometric immunophenotyping. Several reports described the expression of almost all B lineage antigens on normal and abnormal B lymphocytes. Thus, immunophenotyping of lymphomas must be interpreted in the context of the reference values obtained for healthy control individuals. For this purpose multiparametric flow cytometric analysis offers the unique feature for lymphocyte subset analysis. In the present study B lymphocytes in the peripheral blood of healthy adults were investigated by multiparametric flow cytometric immunophenotyping for the detection of the frequency (in percent) of antigens provided by the revised European-American classification of lymphoid neoplasms (REAL) classification. Thus, 84 healthy adults were investigated and grouped by age (average ages were as follows: group 1, 25.38 years; group 2, 33.86 years; group 3, 44.17 years; group 4, 55.67 years; group 5, 66.67 years). Analysis was done for surface immunoglobulins (kappa and lambda chains of immunoglobulin M [IgM] and IgD) as well as CD10, CD11c, CD23, CD38, CD103, FMC-7, and B-B4. Three-color immunophenotyping was performed for kappa/CD19/CD5, lambda/CD19/CD5, surface IgM/surface IgD/CD19, FMC-7/CD19/CD5, CD103/CD11c/CD19, CD10/CD23/CD19, and CD38/B-B4/CD19 by live gating of CD19+ events (n = 2,000). Although some numerical differences could be obtained for the different groups, statistical differences (P < 0.005) could only be obtained for the CD19+/CD5+ B-cell subset, which was decreased in the elderly patients (group 5). The established two-color and three-color stainings will serve as a basis for future multiparametric immunophenotyping of abnormal lymphocytes (e.g., for patients suffering from non-Hodgkin's lymphoma of the B-cell type). PMID:8770500

  15. Differences in the peripheral immune response between lambs and adult ewes experimentally infected with Mycobacterium avium subspecies paratuberculosis.

    PubMed

    Delgado, Laetitia; Juste, Ramón A; Muñoz, María; Morales, Silvia; Benavides, Julio; Ferreras, M Carmen; Marín, J Francisco García; Pérez, Valentín

    2012-01-15

    The peripheral immune response, and its relationship with the outcome of the infection according to the age of the animal, has been investigated in young lambs and adult ewes experimentally infected with two different doses of Mycobacterium avium subspecies paratuberculosis (Map). Sixteen 1.5-month-old lambs out of 24 and 23 adult ewes out of 30 were orally challenged with an ovine Map field isolate. Animals were divided into two groups: HD, infected with a higher dose of Map and LD, with a lower dose. The remaining animals were used as uninfected control groups. Animals were euthanized at 110-120 and 210-220 days post-infection (dpi). Along the experiment, the humoral response and the specific and non-specific IFN-γ production were assessed. An intradermal skin test (IDT), using avian PPD, was also performed at 90 and 195 dpi. Samples of intestine and related lymphoid tissue were taken for histological, bacteriological and PCR studies. The Ab and IFN-γ production as well as the IDT response appeared earlier and with more intensity in the adult ewes compared to the lambs. The basal non-specific IFN-γ levels increased only in the adult ewes from the HD group. Animals from the LD and HD groups were positive to PCR; however, lesions consistent with paratuberculosis were exclusively observed in the HD group, both in lambs and in adult sheep, but they only progressed to more advanced stages in the former. These results suggest that the peripheral immune response induced by Map infection in the adult ewes is more efficient to control the progression of the infection than in lambs. This could likely be due to the existence of previous contacts with Map or other mycobacteria in the adult sheep compared to the young lambs.

  16. Intrathecal administration of nerve growth factor delays GAP 43 expression and early phase regeneration of adult rat peripheral nerve.

    PubMed

    Hirata, Akira; Masaki, Toshihiro; Motoyoshi, Kazuo; Kamakura, Keiko

    2002-07-19

    Whether nerve growth factor (NGF) promotes peripheral nerve regeneration in vivo, in particular in adults, is controversial. We therefore examined the effect of exogenous NGF on nerve regeneration and the expression of GAP 43 (growth-associated protein 43) in adult rats. NGF was infused intrathecally via an osmotic mini-pump, while control rats received artificial cerebrospinal fluid. Two days after the infusion was initiated, the right sciatic nerves were transected or crushed, and the animals allowed to survive for 3 to 11 days. The right DRG, the right proximal stump of the transected sciatic nerve, and the posterior horn of the spinal cord were examined by Western blotting, immunohistochemistry, and electron microscopy. GAP 43 immunoreactivity in the NGF-treated animals was significantly lower than in the aCSF-treated controls. Electron microscopy showed that the number of myelinated and unmyelinated axons decreased significantly in the NGF-treated rats as compared with the controls. These findings are indicative that exogenous NGF delayed GAP 43 induction and the early phase of peripheral nerve regeneration and supports the hypothesis that the loss of NGF supply from peripheral targets via retrograde transport caused by axotomy serves as a signal for DRG neurons to invoke regenerative responses. NGF administered intrathecally may delay the neurons' perception of the reduction of the endogenous NGF, causing a delay in conversion of DRG neurons from the normal physiological condition to regrowth state.

  17. The immunohistochemical expression profile of osteopontin in normal human tissues using two site-specific antibodies reveals a wide distribution of positive cells and extensive expression in the central and peripheral nervous systems.

    PubMed

    Kunii, Yasuto; Niwa, Shin-ichi; Hagiwara, Yoshiaki; Maeda, Masahiro; Seitoh, Tsutomu; Suzuki, Toshimitsu

    2009-09-01

    To elucidate the cellular distribution of osteopontin (OPN) in normal human tissues, we undertook immunohistochemistry using two site-specific OPN antibodies. The 10A16 monoclonal antibody was raised against the amino acid sequence just downstream of the thrombin cleavage site, while the O-17 polyclonal antibody was raised against the N-terminal peptide. Each antibody has been confirmed previously to react with both whole OPN and its relevant fragments. The expression pattern for these two antibodies was similar in distribution. In addition, we also identified expression in Ebner's gland, type II pneumocytes, Kupffer cells, cells of the endocrine organs, anterior lens capsule and ciliary body, synovial type A cells, mesothelia, adipocytes, and mast cells. Neurons and glia in the central nervous system and spinal cord, cranial and peripheral nerve sheaths, ganglion cells in the sympathetic ganglion, intestinal plexuses, retina, and choroid plexus also regularly exhibited OPN positivity. Testicular germ cells, pancreatic exocrine cells, and follicular dendritic cells reacted with 10A16 only, whereas lutein cells and taste bud cells exhibited O-17 reactivity alone. These minor differences were hypothesized to reflect the state of OPN in the cells; that is, whether OPN was in its whole molecule or fragmented form. In conclusion, we demonstrate that OPN is widely distributed in normal human cells, particularly those comprising the central and peripheral nervous systems.

  18. Co-expression studies of the orphan carrier protein Slc10a4 and the vesicular carriers VAChT and VMAT2 in the rat central and peripheral nervous system.

    PubMed

    Burger, S; Döring, B; Hardt, M; Beuerlein, K; Gerstberger, R; Geyer, J

    2011-10-13

    The orphan carrier protein Slc10a4 represents a novel member of the so-called "sodium-bile acid co-transporter family," SLC10. Slc10a4 has a close phylogenetic relationship with the liver bile acid carrier Ntcp (Slc10a1), but has no transport activity for bile acids. In a previous study Slc10a4 proved to be predominantly expressed in the rat brain, where it was localized within cholinergic neurons. However, whether this cholinergic expression pattern was exclusive for Slc10a4 and whether this protein might also be expressed in the peripheral nervous system or other peripheral organs, remained unclear. Therefore, in the present study we analyzed the expression of Slc10a4 in neuronal and non-neuronal rat tissues more systematically, employing immunofluorescence co-localization studies of the vesicular acetylcholine transporter VAChT and the vesicular monoamine transporter VMAT2. The Slc10a4 protein was found to be widely expressed throughout structures of the CNS and peripheral nervous system. In addition to cholinergic neurons in the CNS, the retina, the neuromuscular junction and parasympathetic innervations, Slc10a4 was also localized in certain monoaminergic neurons and nerve fibers in the substantia nigra, the spinal cord and sympathetic innervations. Slc10a4 expression was also detected in granules of rat peritoneal and tissue mast cells using immunofluorescence and electron microscopy. Western blot and immunoprecipitation experiments with rat brain vesicle preparations revealed that the Slc10a4 protein was expressed in synaptic vesicles where it co-localized with synaptophysin, VAChT and VMAT2. This vesicular expression pattern was also shown in the rat adrenal pheochromocytoma cell line PC12 by immunofluorescence. Based on the findings of the present study we can speculate about the function of Slc10a4 as follows: (I) Slc10a4 could be a novel vesicular transporter for cholinergic and/or various monoaminergic neurotransmitters in the central and peripheral

  19. ADULT TERTIAN MALARIAL PARASITES ATTACHED TO PERIPHERAL CORPUSCULAR MOUNDS. THE EXTRACELLULAR RELATION OF THE PARASITES TO THE RED CORPUSCLES.

    PubMed

    Lawson, M R

    1915-06-01

    1. The malarial parasite is extracellular throughout its entire life cycle; that is, when it is not free in the blood serum, it is attached to the external surface of the red corpuscle. 2. Adult parasites follow the same procedure in attaching themselves to the outer surface of the red corpuscles as do the young parasites. 3. Adult parasites are most frequently seen attached to surface corpuscular mounds. 4. Corpuscular mounds projecting at the periphery of the red corpuscles and encircled by the pseudopodia of adult parasites, are proof positive of the extracellular relation of the adult parasite to the red corpuscle. 5. Adult parasites attached to peripheral corpuscular mounds are only found in appreciable numbers when the red corpuscles are not badly damaged, so that the mounds show more or less hemoglobin content. 6. The nuclei or protoplasm of adult parasites extending beyond the periphery of the red corpuscles is additional evidence of the extracellular relation of the parasites to the red corpuscle.

  20. Effect of dietary selenium and cancer cell xenograft on peripheral T and B lymphocytes in adult nude mice.

    PubMed

    Cheng, Wen-Hsing; Holmstrom, Alexandra; Li, Xiangdong; Wu, Ryan T Y; Zeng, Huawei; Xiao, Zhengguo

    2012-05-01

    Selenium (Se) is known to regulate tumorigenesis and immunity at the nutritional and supranutritional levels. Because the immune system provides critical defenses against cancer and the athymic, immune-deficient NU/J nude mice are known to gradually develop CD8(+) and CD4(+) T cells, we investigated whether B and T cell maturation could be modulated by dietary Se and by tumorigenesis in nude mice. Fifteen homozygous nude mice were fed a Se-deficient, Torula yeast basal diet alone (Se-) or supplemented with 0.15 (Se+) or 1.0 (Se++) mg Se/kg (as Na(2)SeO(4)) for 6 months, followed by a 7-week time course of PC-3 prostate cancer cell xenograft (2 × 10(6) cells/site, 2 sites/mouse). Here, we show that peripheral B cell levels decreased in nude mice fed the Se -  or Se++ diet and the CD4(+) T cell levels increased in mice fed the Se++ diet. During the PC-3 cell tumorigenesis, dietary Se status did not affect peripheral CD4(+) or CD8(+) T cells in nude mice whereas mice fed with the Se++ diet appeared to exhibit greater peripheral CD25(+)CD4(+) T cells on day 9. Dietary Se status did not affect spleen weight in nude mice 7 weeks after the xenograft. Spleen weight was associated with frequency of peripheral CD4(+), but not CD8(+) T cells. Taken together, dietary Se at the nutritional and supranutritional levels regulates peripheral B and T cells in adult nude mice before and after xenograft with PC-3 prostate cancer cells.

  1. Increased telomere length and proliferative potential in peripheral blood mononuclear cells of adults of different ages stimulated with concanavalin A

    PubMed Central

    2013-01-01

    Background Recently, a direct correlation with telomere length, proliferative potential and telomerase activity has been found in the process of aging in peripheral blood cells. The objective of the study was to evaluate telomere length and proliferative potential in peripheral blood mononuclear cells (PBMCs) after stimulation with Concanavalin A (ConA) of young adults compared with older adults. Methods Blood samples were obtained from 20 healthy young males (20–25 years old) (group Y) and 20 males (60–65 years old) (group O). We compared PBMC proliferation before and after stimulation with ConA. DNA was isolated from cells separated before and after culture with ConA for telomeric measurement by real-time polymerase chain reaction. Results In vitro stimulation of PBMCs from young subjects induced an increase of telomere length as well as a higher replicative capacity of cell proliferation. Samples from older adults showed higher loss of telomeric DNA (p = 0.03) and higher levels of senescent (≤6.2 kb) telomeric DNA (p = 0.02) and displayed a marked decrease of proliferation capacity. Viability cell counts and CFSE tracking in 72-h-old cell cultures indicated that group O PBMCs (CD8+ and CD4+ T cells) underwent fewer mitotic cycles and had shorter telomeres than group Y (p = 0.04). Conclusions Our findings confirm that telomere length in older-age adults is shorter than in younger subjects. After stimulation with ConA, cells are not restored to the previous telomere length and undergo replicative senescence. This is in sharp contrast to the response observed in young adults after ConA stimulation where cells increase in telomere length and replicative capacity. The mechanisms involved in this phenomenon are not yet clear and merit further investigation. PMID:24063536

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

    PubMed

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

    2017-03-02

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

  3. The Cajal School in the Peripheral Nervous System: The Transcendent Contributions of Fernando de Castro on the Microscopic Structure of Sensory and Autonomic Motor Ganglia.

    PubMed

    de Castro, Fernando

    2016-01-01

    The fine structure of the autonomic nervous system was largely unknown at the beginning of the second decade of the 20th century. Although relatively anatomists and histologists had studied the subject, even the assays by the great Russian histologist Alexander Dogiel and the Spanish Nobel Prize laureate, Santiago Ramón y Cajal, were incomplete. In a time which witnessed fundamental discoveries by Langley, Loewi and Dale on the physiology of the autonomic nervous system, both reputed researchers entrusted one of their outstanding disciples to the challenge to further investigate autonomic structures: the Russian B.I. Lawrentjew and the Spanish Fernando de Castro developed new technical approaches with spectacular results. In the mid of the 1920's, both young neuroscientists were worldwide recognized as the top experts in the field. In the present work we describe the main discoveries by Fernando de Castro in those years regarding the structure of sympathetic and sensory ganglia, the organization of the synaptic contacts in these ganglia, and the nature of their innervation, later materialized in their respective chapters, personally invited by the editor, in Wilder Penfield's famous textbook on Neurology and the Nervous System. Most of these discoveries remain fully alive today.

  4. The Cajal School in the Peripheral Nervous System: The Transcendent Contributions of Fernando de Castro on the Microscopic Structure of Sensory and Autonomic Motor Ganglia

    PubMed Central

    de Castro, Fernando

    2016-01-01

    The fine structure of the autonomic nervous system was largely unknown at the beginning of the second decade of the 20th century. Although relatively anatomists and histologists had studied the subject, even the assays by the great Russian histologist Alexander Dogiel and the Spanish Nobel Prize laureate, Santiago Ramón y Cajal, were incomplete. In a time which witnessed fundamental discoveries by Langley, Loewi and Dale on the physiology of the autonomic nervous system, both reputed researchers entrusted one of their outstanding disciples to the challenge to further investigate autonomic structures: the Russian B.I. Lawrentjew and the Spanish Fernando de Castro developed new technical approaches with spectacular results. In the mid of the 1920’s, both young neuroscientists were worldwide recognized as the top experts in the field. In the present work we describe the main discoveries by Fernando de Castro in those years regarding the structure of sympathetic and sensory ganglia, the organization of the synaptic contacts in these ganglia, and the nature of their innervation, later materialized in their respective chapters, personally invited by the editor, in Wilder Penfield’s famous textbook on Neurology and the Nervous System. Most of these discoveries remain fully alive today. PMID:27147984

  5. Trajectories of peripheral interleukin-6, structure of the hippocampus, and cognitive impairment over 14 years in older adults

    PubMed Central

    Metti, Andrea L.; Aizenstein, Howard; Yaffe, Kristine; Boudreau, Robert M.; Newman, Anne; Launer, Lenore; Gianaros, Peter J.; Lopez, Oscar L.; Saxton, Judith; Ives, Diane G.; Kritchevsky, Stephen; Vallejo, Abbe N.; Rosano, Caterina

    2015-01-01

    We aimed to investigate if trajectory components (baseline level, slope and variability) of peripheral IL-6 over time were related to cognitive impairment and smaller hippocampal volume, and if hippocampal volume explained the associations between IL-6 and cognitive impairment. Multivariable regression models were used to test the association between IL-6 trajectory components with change in neuroimaging measures of the hippocampus, and with cognitive impairment among 135 older adults (70–79 years at baseline) from the Healthy Brain Project over 14 years. IL-6 variability was positively associated with cognitive impairment (OR = 5.86, 95% CI:1.24, 27.61) and with greater decrease per year of gray matter volume of the hippocampus (β=−0.008, SE=0.004, p=0.03). After adjustment for hippocampal volume, the odds ratio of cognitive impairment decreased for each unit of IL-6 variability, and confidence intervals widened (OR=4.36, 95% CI: 0.67, 28.29). Neither baseline levels nor slopes of IL-6 were related to cognitive impairment or hippocampal volume. We believe this has potential clinical and public health implications by suggesting adults with stable levels of peripheral IL-6 may be better targets for intervention studies for slowing or preventing cognitive decline. PMID:26279115

  6. Behavioral and monoamine perturbations in adult male mice with chronic inflammation induced by repeated peripheral lipopolysaccharide administration.

    PubMed

    Krishna, Saritha; Dodd, Celia A; Filipov, Nikolay M

    2016-04-01

    Considering the limited information on the ability of chronic peripheral inflammation to induce behavioral alterations, including on their persistence after inflammatory stimuli termination and on associated neurochemical perturbations, this study assessed the effects of chronic (0.25 mg/kg; i.p.; twice weekly) lipopolysaccharide (LPS) treatment on selected behavioral, neurochemical and molecular measures at different time points in adult male C57BL/6 mice. Behaviorally, LPS-treated mice were hypoactive after 6 weeks, whereas significant hyperactivity was observed after 12 weeks of LPS and 11 weeks after 13 week LPS treatment termination. Similar biphasic responses, i.e., early decrease followed by a delayed increase were observed in the open field test center time, suggestive of, respectively, increased and decreased anxiety. In a forced swim test, mice exhibited increased immobility (depressive behavior) at all times they were tested. Chronic LPS also produced persistent increase in splenic serotonin (5-HT) and time-dependent, brain region-specific alterations in striatal and prefrontocortical dopamine and 5-HT homeostasis. Microglia, but not astrocytes, were activated by LPS early and late, but their activation did not persist after LPS treatment termination. Above findings demonstrate that chronic peripheral inflammation initially causes hypoactivity and increased anxiety, followed by persistent hyperactivity and decreased anxiety. Notably, chronic LPS-induced depressive behavior appears early, persists long after LPS termination, and is associated with increased splenic 5-HT. Collectively, our data highlight the need for a greater focus on the peripheral/central monoamine alterations and lasting behavioral deficits induced by chronic peripheral inflammation as there are many pathological conditions where inflammation of a chronic nature is a hallmark feature.

  7. Behavioral and monoamine perturbations in adult male mice with chronic inflammation induced by repeated peripheral lipopolysaccharide administration

    PubMed Central

    Krishna, Saritha; Dodd, Celia A.; Filipov, Nikolay M.

    2016-01-01

    Considering the limited information on the ability of chronic peripheral inflammation to induce behavioral alterations, including on their persistence after inflammatory stimuli termination and on associated neurochemical perturbations, this study assessed the effects of chronic (0.25 mg/kg; i.p.; twice weekly) lipopolysaccharide (LPS) treatment on selected behavioral, neurochemical and molecular measures at different time points in adult male C57BL/6 mice. Behaviorally, LPS-treated mice were hypoactive after 6 weeks, whereas significant hyperactivity was observed after 12 weeks of LPS and 11 weeks after 13 week LPS treatment termination. Similar biphasic responses, i.e., early decrease followed by a delayed increase were observed in the open field test center time, suggestive of, respectively, increased and decreased anxiety. In a forced swim test, mice exhibited increased immobility (depressive behavior) at all times they were tested. Chronic LPS also produced persistent increase in splenic serotonin (5-HT) and time-dependent, brain region-specific alterations in striatal and prefrontocortical dopamine and 5-HT homeostasis. Microglia, but not astrocytes, were activated by LPS early and late, but their activation did not persist after LPS treatment termination. Above findings demonstrate that chronic peripheral inflammation initially causes hypoactivity and increased anxiety, followed by persistent hyperactivity and decreased anxiety. Notably, chronic LPS-induced depressive behavior appears early, persists long after LPS termination, and is associated with increased splenic 5-HT. Collectively, our data highlight the need for a greater focus on the peripheral/central monoamine alterations and lasting behavioral deficits induced by chronic peripheral inflammation as there are many pathological conditions where inflammation of a chronic nature is a hallmark feature. PMID:26802725

  8. Direct control of peripheral lipid deposition by CNS GLP-1 receptor signaling is mediated by the sympathetic nervous system and blunted in diet-induced obesity.

    PubMed

    Nogueiras, Ruben; Pérez-Tilve, Diego; Veyrat-Durebex, Christelle; Morgan, Donald A; Varela, Luis; Haynes, William G; Patterson, James T; Disse, Emmanuel; Pfluger, Paul T; López, Miguel; Woods, Stephen C; DiMarchi, Richard; Diéguez, Carlos; Rahmouni, Kamal; Rohner-Jeanrenaud, Françoise; Tschöp, Matthias H

    2009-05-06

    We investigated a possible role of the central glucagon-like peptide (GLP-1) receptor system as an essential brain circuit regulating adiposity through effects on nutrient partitioning and lipid metabolism independent from feeding behavior. Both lean and diet-induced obesity mice were used for our experiments. GLP-1 (7-36) amide was infused in the brain for 2 or 7 d. The expression of key enzymes involved in lipid metabolism was measured by real-time PCR or Western blot. To test the hypothesis that the sympathetic nervous system may be responsible for informing adipocytes about changes in CNS GLP-1 tone, we have performed direct recording of sympathetic nerve activity combined with experiments in genetically manipulated mice lacking beta-adrenergic receptors. Intracerebroventricular infusion of GLP-1 in mice directly and potently decreases lipid storage in white adipose tissue. These effects are independent from nutrient intake. Such CNS control of adipocyte metabolism was found to depend partially on a functional sympathetic nervous system. Furthermore, the effects of CNS GLP-1 on adipocyte metabolism were blunted in diet-induced obese mice. The CNS GLP-1 system decreases fat storage via direct modulation of adipocyte metabolism. This CNS GLP-1 control of adipocyte lipid metabolism appears to be mediated at least in part by the sympathetic nervous system and is independent of parallel changes in food intake and body weight. Importantly, the CNS GLP-1 system loses the capacity to modulate adipocyte metabolism in obese states, suggesting an obesity-induced adipocyte resistance to CNS GLP-1.

  9. Acute peripheral neuropathy in adults. Guillain-Barré syndrome and related disorders.

    PubMed

    Pascuzzi, R M; Fleck, J D

    1997-08-01

    Acute paralysis in adults has an extensive assortment of etiologies. Guillian-Barré syndrome is the most common cause of acute neuropathy in adults. This review emphasizes pathophysiology, clinical features, differential diagnosis, and a practical approach to the laboratory work-up for patients with suspected Guillian-Barré syndrome. The current status of immunotherapy is reviewed.

  10. Expression of a retinoic acid receptor (RAR)-like protein in the embryonic and adult nervous system of a protostome species.

    PubMed

    Carter, Christopher J; Rand, Christopher; Mohammad, Imtiaz; Lepp, Amanda; Vesprini, Nicholas; Wiebe, Olivia; Carlone, Robert; Spencer, Gaynor E

    2015-01-01

    The vitamin A metabolite, retinoic acid, is an important molecule in nervous system development and regeneration in vertebrates. Retinoic acid signaling in vertebrates is mediated by two classes of nuclear receptors, the retinoid X receptors (RXRs) and the retinoic acid receptors (RARs). Recently, evidence has emerged to suggest that many effects of retinoic acid are conserved between vertebrate and invertebrate nervous systems, even though the RARs were previously thought to be a vertebrate innovation and to not exist in non-chordates. We have cloned a full-length putative RAR from the CNS of the mollusc Lymnaea stagnalis (LymRAR). Immunoreactivity for the RAR protein was found in axons of adult neurons in the central nervous system and in growth cones of regenerating neurons in vitro. A vertebrate RAR antagonist blocked growth cone turning induced by exogenous all-trans retinoic acid, possibly suggesting a role for this receptor in axon guidance. We also provide immunostaining evidence for the presence of RAR protein in the developing, embryonic CNS, where it is also found in axonal processes. Using qPCR, we determined that LymRAR mRNA is detectable in the early veliger stage embryo and that mRNA levels increase significantly during embryonic development. Putative disruption of retinoid signaling in Lymnaea embryos using vertebrate RAR antagonists resulted in abnormal eye and shell development and in some instances completely halted development, resembling the effects of all-trans retinoic acid. This study provides evidence for RAR functioning in a protostome species.

  11. Expression of sept3, sept5a and sept5b in the Developing and Adult Nervous System of the Zebrafish (Danio rerio)

    PubMed Central

    Helmprobst, Frederik; Lillesaar, Christina; Stigloher, Christian

    2017-01-01

    Septins are a highly conserved family of small GTPases that form cytoskeletal filaments. Their cellular functions, especially in the nervous system, still remain largely enigmatic, but there are accumulating lines of evidence that septins play important roles in neuronal physiology and pathology. In order to further dissect septin function in the nervous system a detailed temporal resolved analysis in the genetically well tractable model vertebrate zebrafish (Danio rerio) is crucially necessary. To close this knowledge gap we here provide a reference dataset describing the expression of selected septins (sept3, sept5a and sept5b) in the zebrafish central nervous system. Strikingly, proliferation zones are devoid of expression of all three septins investigated, suggesting that they have a role in post-mitotic neural cells. Our finding that three septins are mainly expressed in non-proliferative regions was further confirmed by double-stainings with a proliferative marker. Our RNA in situ hybridization (ISH) study, detecting sept3, sept5a and sept5b mRNAs, shows that all three septins are expressed in largely overlapping regions of the developing brain. However, the expression of sept5a is much more confined compared to sept3 and sept5b. In contrast, the expression of all the three analyzed septins is largely similar in the adult brain. PMID:28261064

  12. Autonomic nervous activation triggered during induction of reactive hyperemia exerts a greater influence on the measured reactive hyperemia index by peripheral arterial tonometry than on flow-mediated vasodilatation of the brachial artery in patients with hypertension.

    PubMed

    Tomiyama, Hirofumi; Yoshida, Masanobu; Higashi, Yukihito; Takase, Bonpei; Furumoto, Tomoo; Kario, Kazuomi; Ohya, Yusuke; Yamashina, Akira

    2014-10-01

    Flow-mediated vasodilatation of the brachial artery (FMD) and reactive hyperemia index (RHI) measured by peripheral arterial tonometry are known to be weakly associated with one another, but the mechanisms underlying this weak association remain to be clarified. We examined whether the autonomic nervous activation induced by the 5 min forearm clamping used to induce reactive hyperemia might exert any influence on the FMD and RHI in subjects with hypertension. In 115 subjects with hypertension (age 61±1 years), the FMD and RHI were measured simultaneously, and the heart rate variability (HRV) parameters (low-frequency component (LF), high-frequency component (HF), and the ratio (LF/HF) between the two) were calculated from the electrocardiographic recordings obtained before and after the start of forearm clamping. A multivariate linear regression analysis with adjustments for confounding variables demonstrated that the RHI, but not the FMD, was significantly associated with the percent change of the LF/HF associated with forearm clamping (beta=-0.204, P=0.043). In conclusion, autonomic nervous system activation, especially sympathetic activation, induced by 5-min forearm clamping utilized to provoke reactive hyperemia may significantly affect the RHI rather than FMD in subjects with hypertension.

  13. Assessing Basal and Acute Autophagic Responses in the Adult Drosophila Nervous System: The Impact of Gender, Genetics and Diet on Endogenous Pathway Profiles

    PubMed Central

    Molina, Brandon; Mauntz, Ruth E.; Gonzalez, Arysa; Barekat, Ayeh; El-Mecharrafie, Nadja; Garza, Shannon; Gurney, Michael A.; Achal, Madhulika; Linton, Phyllis-Jean; Harris, Greg L.; Finley, Kim D.

    2016-01-01

    The autophagy pathway is critical for the long-term homeostasis of cells and adult organisms and is often activated during periods of stress. Reduced pathway efficacy plays a central role in several progressive neurological disorders that are associated with the accumulation of cytotoxic peptides and protein aggregates. Previous studies have shown that genetic and transgenic alterations to the autophagy pathway impacts longevity and neural aggregate profiles of adult Drosophila. In this study, we have identified methods to measure the acute in vivo induction of the autophagy pathway in the adult fly CNS. Our findings indicate that the genotype, age, and gender of adult flies can influence pathway responses. Further, we demonstrate that middle-aged male flies exposed to intermittent fasting (IF) had improved neuronal autophagic profiles. IF-treated flies also had lower neural aggregate profiles, maintained more youthful behaviors and longer lifespans, when compared to ad libitum controls. In summary, we present methodology to detect dynamic in vivo changes that occur to the autophagic profiles in the adult Drosophila CNS and that a novel IF-treatment protocol improves pathway response in the aging nervous system. PMID:27711219

  14. Immunohistochemical detection of disease-associated prion protein in the peripheral nervous system in experimental H-type bovine spongiform encephalopathy.

    PubMed

    Okada, H; Iwamaru, Y; Yokoyama, T; Mohri, S

    2013-07-01

    H-type bovine spongiform encephalopathy (BSE) has been identified in aged cattle in Europe and North America. To determine the localization of disease-associated prion protein (PrP(Sc)) in the peripheral nerve tissues of cattle affected with H-type BSE, we employed highly sensitive immunohistochemical and immunofluorescence techniques with the tyramide signal amplification (TSA) system. PrP(Sc) deposition was detected in the inferior ganglia, sympathetic nerve trunk, vagus nerve, spinal nerves, cauda equina, and adrenal medulla, using this system. Notably, granular PrP(Sc) deposits were present mainly in the Schwann cells and fibroblast-like cells and occasionally along certain nerve fibers at the surface of the axons. In the adrenal gland, PrP(Sc) immunolabeling was observed within the sympathetic nerve fibers and nerve endings in the adrenal medulla. Although our results were limited to only 3 experimental cases, these results suggest that the TSA system, a highly sensitive immunohistochemical procedure, may help in elucidating the peripheral pathogenesis of H-type BSE.

  15. Nitric Oxide Synthase in the Central Nervous System and Peripheral Organs of Stramonita haemastoma: Protein Distribution and Gene Expression in Response to Thermal Stress

    PubMed Central

    Toni, Mattia; De Angelis, Federica; Bonaccorsi di Patti, Maria Carmela; Cioni, Carla

    2015-01-01

    Nitric oxide (NO) is generated via the oxidation of l-arginine by the enzyme NO synthase (NOS) both in vertebrates and invertebrates. Three NOS isoforms, nNOS, iNOS and eNOS, are known in vertebrates, whereas a single NOS isoform is usually expressed in invertebrates, sharing structural and functional characteristics with nNOS or iNOS depending on the species. The present paper is focused on the constitutive Ca2+/calmodulin-dependent nNOS recently sequenced by our group in the neogastropod Stramonita haemastoma (ShNOS). In this paper we provide new data on cellular distribution of ShNOS in the CNS (pedal ganglion) and peripheral organs (osphradium, tentacle, eye and foot) obtained by WB, IF, CM and NADPHd. Results demonstrated that NOS-like proteins are widely expressed in sensory receptor elements, neurons and epithelial cells. The detailed study of NOS distribution in peripheral and central neurons suggested that NOS is both intracellular and presynaptically located. Present findings confirm that NO may have a key role in the central neuronal circuits of gastropods and in sensory perception. The physiological relevance of NOS enzymes in the same organs was suggested by thermal stress experiments demonstrating that the constitutive expression of ShNOS is modulated in a time- and organ-dependent manner in response to environmental stressors. PMID:26528988

  16. The principal neuronal gD-type 3-O-sulfotransferases and their products in central and peripheral nervous system tissues

    PubMed Central

    Lawrence, Roger; Yabe, Tomio; HajMohammadi, Sassan; Rhodes, John; McNeely, Melissa; Liu, Jian; Lamperti, Edward D.; Toselli, Paul A.; Lech, Miroslaw; Spear, Patricia G.; Rosenberg, Robert D.; Shworak, Nicholas W.

    2007-01-01

    Within the nervous system, heparan sulfate (HS) of the cell surface and extracellular matrix influences developmental, physiologic and pathologic processes. HS is a functionally diverse polysaccharide that employs motifs of sulfate groups to selectively bind and modulate various effector proteins. Specific HS activities are modulated by 3-O-sulfated glucosamine residues, which are generated by a family of seven 3-O-sulfotransferases (3-OSTs). Most isoforms we herein designate as gD-type 3-OSTs because they generate HSgD+, 3-O-sulfated motifs that bind the gD envelope protein of herpes simplex virus 1 (HSV-1) and thereby mediate viral cellular entry. Certain gD-type isoforms are anticipated to modulate neurobiologic events, because a Drosophila gD-type 3-OST is essential for a conserved neurogenic signaling pathway regulated by Notch. Information about 3-OST isoforms expressed in the nervous system of mammals is incomplete. Here, we identify the 3-OST isoforms having properties compatible with their participation in neurobiologic events. We show that 3-OST-2 and 3-OST-4 are principal isoforms of brain. We find these are gD-type enzymes, as they produce products similar to a prototypical gD-type isoform, and they can modify HS to generate receptors for HSV-1 entry into cells. Therefore, 3-OST-2 and 3-OST-4 catalyze modifications similar or identical to those made by the Drosophila gD-type 3-OST that has a role in regulating Notch signaling. We also find that 3-OST-2 and 3-OST-4 are the predominant isoforms expressed in neurons of the trigeminal ganglion, and 3-OST-2/4-type 3-O-sulfated residues occur in this ganglion and in select brain regions. Thus, 3-OST-2 and 3-OST-4 are the major neural gD-type 3-OSTs, and so are prime candidates for participating in HS-dependent neurobiologic events. PMID:17482450

  17. Distribution of carnosine-like peptides in the nervous system of developing and adult zebrafish (Danio rerio) and embryonic effects of chronic carnosine exposure

    PubMed Central

    Azher, Seema; Margolis, Frank L.; Patel, Kamakshi; Mousa, Ahmad; Majid, Arshad

    2013-01-01

    Carnosine-like peptides (carnosine-LP) are a family of histidine derivatives that are present in the nervous system of various species and that exhibit antioxidant, anti-matrix-metalloproteinase, anti-excitotoxic, and free-radical scavenging properties. They are also neuroprotective in animal models of cerebral ischemia. Although the function of carnosine-LP is largely unknown, the hypothesis has been advanced that they play a role in the developing nervous system. Since the zebrafish is an excellent vertebrate model for studying development and disease, we have examined the distribution pattern of carnosine-LP in the adult and developing zebrafish. In the adult, immunoreactivity for carnosine-LP is specifically concentrated in sensory neurons and non-sensory cells of the olfactory epithelium, the olfactory nerve, and the olfactory bulb. Robust staining has also been observed in the retinal outer nuclear layer and the corneal epithelium. Developmental studies have revealed immunostaining for carnosine-LP as early as 18 h, 24 h, and 7 days post-fertilization in, respectively, the olfactory, corneal, and retinal primordia. These data suggest that carnosine-LP are involved in olfactory and visual function. We have also investigated the effects of chronic (7 days) exposure to carnosine on embryonic development and show that 0.01 μM to 10 mM concentrations of carnosine do not elicit significant deleterious effects. Conversely, treatment with 100 mM carnosine results in developmental delay and compromised larval survival. These results indicate that, at lower concentrations, exogenously administered carnosine can be used to explore the role of carnosine in development and developmental disorders of the nervous system. PMID:19440736

  18. Pediatric and adult malignant peripheral nerve sheath tumors: an analysis of data from the surveillance, epidemiology, and end results program.

    PubMed

    Amirian, E Susan; Goodman, J Clay; New, Pamela; Scheurer, Michael E

    2014-02-01

    Malignant peripheral nerve sheath tumors (MPNSTs) are rare soft tissue sarcomas that arise predominantly from Schwann cells. Despite the fact that MPNSTs have high local recurrence rates and are generally associated with poor prognosis, little is known about prognostic factors or effective clinical management for this tumor type. The purpose of this study was to describe the distributions of patient and tumor characteristics and to identify predictors of cause-specific survival among MPNST cases reported to SEER between 1973 and 2008. Patient and tumor characteristics were compared between pediatric and adult MPNST cases. Cox regression and tree-based survival analysis were used to examine factors associated with MPNST-related mortality separately among adults and children. A total of 1,315 MPNST cases were isolated from the 1973-2008 SEER dataset. Among pediatric cases, sex, race, and radiation therapy predicted MPNST survival, whereas among adults, tumor site, tumor grade, number of primary tumors, and tumor size were significant predictors. As tumor size at diagnosis/resection may be the only somewhat "modifiable" prognostic factor, future studies should aim to identify biological and social attributes associated with tumor size at diagnosis, separately among individuals with and without NF-1, in order to help identify earlier opportunities for clinical intervention.

  19. Central nervous action of interleukin-1 mediates activation of limbic structures and behavioural depression in response to peripheral administration of bacterial lipopolysaccharide.

    PubMed

    Konsman, J P; Veeneman, J; Combe, C; Poole, S; Luheshi, G N; Dantzer, R

    2008-12-01

    Although receptors for the pro-inflammatory cytokine interleukin-1 have long been known to be expressed in the brain, their role in fever and behavioural depression observed during the acute phase response (APR) to tissue infection remains unclear. This may in part be due to the fact that interleukin-1 in the brain is bioactive only several hours after peripheral administration of bacterial lipopolysaccharide (LPS). To study the role of cerebral interleukin-1 action in temperature and behavioural changes, and activation of brain structures during the APR, interleukin-1 receptor antagonist (IL-1ra; 100 microg) was infused into the lateral brain ventricle 4 h after intraperitoneal (i.p.) LPS injection (250 microg/kg) in rats. I.p. LPS administration induced interleukin-1beta (IL-1beta) production in systemic circulation as well as in brain circumventricular organs and the choroid plexus. Intracerebroventricular (i.c.v.) infusion of IL-1ra 4 h after i.p. LPS injection attenuated the reduction in social interaction, a cardinal sign of behavioural depression during sickness, and c-Fos expression in the amygdala and bed nucleus of the stria terminalis. However, LPS-induced fever, rises in plasma corticosterone, body weight loss and c-Fos expression in the hypothalamus and caudal brainstem were not altered by i.c.v. infusion of IL-1ra. These findings, together with our previous observations showing that i.c.v. infused IL-1ra diffuses throughout perivascular spaces, where macrophages express interleukin-1 receptors, can be interpreted to suggest that circulating or locally produced brain IL-1beta acts on these cells to bring about behavioural depression and activation of limbic structures during the APR after peripheral LPS administration.

  20. Perceptions of Young Adult Central Nervous System Cancer Survivors and Their Parents Regarding Career Development and Employment

    ERIC Educational Resources Information Center

    Strauser, David R.; Wagner, Stacia; Chan, Fong; Wong, Alex W. K.

    2014-01-01

    Purpose: Identify barriers to career development and employment from both the survivor and parent perspective. Method: Young adult survivors (N = 43) and their parents participated in focus groups to elicit information regarding perceptions regarding career development and employment. Results: Perceptions of both the young adults and parents…

  1. Long-lasting neonatal inflammation enhances pain responses to subsequent inflammation, but not peripheral nerve injury in adult rats.

    PubMed

    Lim, Eun Jeong; Back, Seung Keun; Kim, Myung Ah; Li, Chengjin; Lee, Jaehee; Jeong, Keun Yeong; Na, Heung Sik

    2009-05-01

    The early postnatal period has been suggested to be the vulnerable time for structural and functional reorganization of sensory systems, and painful stimuli at this time may alter neuronal circuits, thereby leading to changes in an individual's response to pain later in life. In the present study, we examined whether inflammatory experience in the early life can affect pain responses to subsequent noxious insults later in life. The two groups of neonatal rats, treated with an inflammatory irritant and untreated, were subjected to inflammation and peripheral nerve injury in adulthood. Neonatal inflammation was induced by injection of complete Freund's adjuvant (CFA, 25 microl) into the hindpaw or tail of newborn rat pups. Adult rats which had suffered from neonatal paw inflammation at P0 were subjected to re-injection of CFA into the paw neonatally exposed to CFA or L5 spinal nerve ligation. Paw thickness and histology of inflamed paw were examined to assess the neonatal inflammation. Adult animals whose tail had been subjected to CFA injection on P3 received tail-innervating nerve injury. The results showed that the neonatal CFA-treated rats suffered from chronic inflammation, confirmed by persistent increase of paw thickness and histological result of inflamed paw. These animals showed enhanced pain responses to re-inflammatory challenge by injection of CFA (200 microl) into the neonatally inflamed paw 8 weeks after birth compared with the neonatally untreated animals. However, neuropathic pain on the hindpaw and the tail which had been induced by peripheral nerve injury in the neonatal CFA-treated group were not different from those of the untreated group. The present data suggest that early neonatal long-lasting inflammation differentially affects pain responses later in life, depending on the types of subsequent noxious insults.

  2. Functional Imaging of Working Memory and Peripheral Endothelial Function in Middle-Aged Adults

    ERIC Educational Resources Information Center

    Gonzales, Mitzi M.; Tarumi, Takashi; Tanaka, Hirofumi; Sugawara, Jun; Swann-Sternberg, Tali; Goudarzi, Katayoon; Haley, Andreana P.

    2010-01-01

    The current study examined the relationship between a prognostic indicator of vascular health, flow-mediated dilation (FMD), and working memory-related brain activation in healthy middle-aged adults. Forty-two participants underwent functional magnetic resonance imaging while completing a 2-Back working memory task. Brachial artery…

  3. Balance and mobility assessment for ruling-out the peripheral neuropathy of the lower limbs in older adults.

    PubMed

    Caronni, Antonio; Cattalini, Claudio; Previtera, Antonino Michele

    2016-10-01

    The peripheral neuropathy of the lower limbs (PNLL) is an important cause of balance and mobility impairment in older adults. The nerve conduction study (NCS) is the gold standard for PNLL diagnosis. Aim of this work is to establish the sensitivity (Sn) and the specificity (Sp) of the balance and mobility examination for the PNLL in older adults. This study consecutively recruited 72 participants (>65years) who accessed to the clinical neurophysiology outpatient clinic for suspected PNLL. Participants were given the NCS and four clinical tests. Mobility was evaluated by the Timed Up and Go (TUG) test, the Performance Oriented Mobility Assessment (POMA) and the de Morton Mobility Index (DEMMI). In addition the Clinical Evaluation of Static Upright Stance (CELSIUS) scale was developed for a selective evaluation of static balance. Based on the NCS, 36% of participants had PNLL. The CELSIUS scale (cutoff: 19.5/24), the TUG test (cutoff: 9.6s) and the DEMMI scale (cutoff: 17.5/19) have high Sn (0.92÷0.96), but low Sp (0.28÷0.43) for the PNLL in the older adult. POMA scale (cutoff: 14.5/16) has low Sn (0.73), but acceptable Sp (0.85). In addition, CELSIUS, DEMMI and TUG negative likelihood ratios are 0.13, 0.17 and 0.12, respectively. Balance and mobility examination have high sensitivity for PNLL. CELSIUS score>19/24, DEMMI score>17/19 or TUG time≤9.6s substantially reduce PNLL likelihood. These clinical measures are thus recommended for ruling-out PNLL in the older adult.

  4. Aging of immune system: Immune signature from peripheral blood lymphocyte subsets in 1068 healthy adults

    PubMed Central

    Qin, Ling; Jing, Xie; Qiu, Zhifeng; Cao, Wei; Jiao, Yang; Routy, Jean-Pierre; Li, Taisheng

    2016-01-01

    Aging is a major risk factor for several conditions including neurodegenerative, cardiovascular diseases and cancer. Functional impairments in cellular pathways controlling genomic stability, and immune control have been identified. Biomarker of immune senescence is needed to improve vaccine response and to develop therapy to improve immune control. To identify phenotypic signature of circulating immune cells with aging, we enrolled 1068 Chinese healthy volunteers ranging from 18 to 80 years old. The decreased naïve CD4+ and CD8+ T cells, increased memory CD4+ or CD8+ T cells, loss of CD28 expression on T cells and reverse trend of CD38 and HLA-DR, were significant for aging of immune system. Conversely, the absolute counts and percentage of NK cells and CD19+B cells maintained stable in aging individuals. The Chinese reference ranges of absolute counts and percentage of peripheral lymphocyte in this study might be useful for future clinical evaluation. PMID:26886066

  5. Aging of immune system: Immune signature from peripheral blood lymphocyte subsets in 1068 healthy adults.

    PubMed

    Qin, Ling; Jing, Xie; Qiu, Zhifeng; Cao, Wei; Jiao, Yang; Routy, Jean-Pierre; Li, Taisheng

    2016-05-01

    Aging is a major risk factor for several conditions including neurodegenerative, cardiovascular diseases and cancer. Functional impairments in cellular pathways controlling genomic stability, and immune control have been identified. Biomarker of immune senescence is needed to improve vaccine response and to develop therapy to improve immune control. To identify phenotypic signature of circulating immune cells with aging, we enrolled 1068 Chinese healthy volunteers ranging from 18 to 80 years old. The decreased naïve CD4+ and CD8+ T cells, increased memory CD4+ or CD8+ T cells, loss of CD28 expression on T cells and reverse trend of CD38 and HLA-DR, were significant for aging of immune system. Conversely, the absolute counts and percentage of NK cells and CD19+B cells maintained stable in aging individuals. The Chinese reference ranges of absolute counts and percentage of peripheral lymphocyte in this study might be useful for future clinical evaluation.

  6. Alterations in Activation, Cytotoxic Capacity and Trafficking Profile of Peripheral CD8 T Cells in Young Adult Binge Drinkers

    PubMed Central

    Zaldivar Fujigaki, José Luis; Arroyo Valerio, América Guadalupe; López Alvarenga, Juan Carlos; Gutiérrez Reyes, Esperanza Gabriela; Kershenobich, David; Hernández Ruiz, Joselin

    2015-01-01

    Background Excess of alcohol consumption is a public health problem and has documented effects on the immune system of humans and animals. Animal and in vitro studies suggest that alcohol abuse changes CD8 T cell (CD8) characteristics, however it remains unknown if the CD8 profile of binge drinkers is different in terms of activation, trafficking and cytotoxic capacity. Aim To analyze the peripheral CD8 cytotoxic capacity, activation and trafficking phenotypic profile of Mexican young adults with regard to alcohol consumption pattern. Methods 55 Mexican young adults were stratified as Light (20), Intermediate (18) or Binge drinkers (17) according to their reported alcohol consumption pattern. Blood samples were obtained and hematic biometry and liver enzyme analysis were performed. Peripheral CD8 profile was established by expression of Granzyme B (GB), CD137, CD127, CD69, TLR4, PD1, CCR2, CCR4, CCR5 and CXCR4 by FACS. Data was analyzed by ANOVA, posthoc DMS and Tamhane, and principal component analysis (PCA) with varimax rotation, p<0.05. Results The Binge drinking group showed increased γGT together with increased expression of CD69 and reduced expression of TLR4, PD1, CCR2 and CXCR4 in peripheral CD8 cells. Other parameters were also specific to Binge drinkers. PCA established 3 factors associated with alcohol consumption: “Early Activation” represented by CD69 and TLR4 expression in the CD8 population; “Effector Activation” by CD69 expression in CD8 CD127+CD137+ and CD8 CD25+ CD137+; and Trafficking by CXCR4 expression on total CD8 and CD8 GB+CXCR4+, and CCR2 expression on total CD8. Binge drinking pattern showed low expression of Early Activation and Trafficking factors while Light drinking pattern exhibited high expression of Effector Activation factor. Conclusions Alcohol consumption affects the immune phenotype of CD8 cells since binge drinking pattern was found to be associated with high CD69 and low TLR4, CXCR4 and CCR2 expression, which suggest

  7. 3H-delta9-tetrahydrocannabinol tissue and subcellular distribution in the central nervous system and tissue distribution in peripheral organs of tolerant and nontolerant dogs.

    PubMed

    Martin, B R; Dewey, W L; Harris, L S; Beckner, J S

    1976-01-01

    Tolerant and nontolerant dogs received one i.v. administration of 0.5 mg/kg of 3H-delta9-tetrahydrocannabinol 30 minutes before they were sacrificed. Plasma, peripheral and brain tissues, as well as subcellular fractions of brain tissues from both treatment groups, were analyzed for radioactivity. Throughout the time period before sacrifice, the plasma concentrations of radioactivity in the tolerant and nontolerant dogs were not significantly different. The percentage of radioactivity in brain and plasma that was due to either unchanged delta9-tetrahydrocannabinol or a major metabolite was the same in each group. Of the radioactivity in brain, 46% was identified as delta9-tetrahydrocannabinol. Regardless of treatment, there was a specific accumulation of radioactivity in adrenals, liver, kidney, heart and pancreas. The only significant differences in radioactivity between tolerant and nontolerant peripheral tissues were found in liver, kidney cortex, heart and lymph nodes. Although all brain areas from tolerant dogs contained less radioactivity than the comparable brain areas from nontolerant animals, only pituitary and putamen were significantly less. There was a specific accumulation of radioactivity in some brain areas that could be associated with behavioral effects. The concentration in cerebellar and cerebral gray was significantly greater than that in white, and there was a marked reduction in the concentration in gray after tolerance developed. The mean percentage of radioactivity in each subcellular fraction was as follows: 23% crude nuclei, 44% mitochondria, 8% cholinergic nerve endings, 7% noncholinergic nerve endings, 2% free mitochondria and 6% synaptic vesicles. The quantity of radioactivity in homogenates of brains from tolerant dogs was 17% less than brains of nontolerant animals, which was merely a reflection of the respective plasma concentrations. The distribution of radioactivity was similar in both groups, although most of the subcellular

  8. Upregulation of human immunodeficiency virus (HIV) replication by CD4 cross-linking in peripheral blood mononuclear cells of HIV-infected adults.

    PubMed Central

    Than, S; Oyaizu, N; Tetali, S; Romano, J; Kaplan, M; Pahwa, S

    1997-01-01

    This study was conducted with peripheral blood mononuclear cells from 67 human immunodeficiency virus (HIV)-infected adults. It supports the hypothesis that cross-linking of CD4 molecules by HIV gp120 can result in HIV upregulation and spread of infection. Underlying mechanisms include activation of latent infection by factors in addition to, or other than, tumor necrosis factor alpha. PMID:9223523

  9. Upregulation of human immunodeficiency virus (HIV) replication by CD4 cross-linking in peripheral blood mononuclear cells of HIV-infected adults.

    PubMed

    Than, S; Oyaizu, N; Tetali, S; Romano, J; Kaplan, M; Pahwa, S

    1997-08-01

    This study was conducted with peripheral blood mononuclear cells from 67 human immunodeficiency virus (HIV)-infected adults. It supports the hypothesis that cross-linking of CD4 molecules by HIV gp120 can result in HIV upregulation and spread of infection. Underlying mechanisms include activation of latent infection by factors in addition to, or other than, tumor necrosis factor alpha.

  10. Peripheral tactile sensory perception of older adults improved using subsensory electrical noise stimulation.

    PubMed

    Breen, Paul P; Serrador, Jorge M; O'Tuathail, Claire; Quinlan, Leo R; McIntosh, Caroline; ÓLaighin, Gearóid

    2016-08-01

    Loss of tactile sensory function is common with aging and can lead to numbness and difficulty with balance and gait. In previous work we found that subsensory electrical noise stimulation (SENS) applied to the tibial nerve improved tactile perception in the soles of the feet of healthy adults. In this work we aimed to determine if SENS remained effective in an older adult population with significant levels of sensory loss. Older adult subjects (N=8, female = 4, aged 65-80) had SENS applied via surface electrodes placed proximally to the medial and lateral malleoli. Vibration perception thresholds (VPTs) were assessed in six conditions, two control conditions (no SENS) and four SENS conditions (zero mean ±15µA, 30µA, 45µA and 60µA SD). VPT was assessed at three sites on the plantar aspect of the foot. Vibration perception was significantly improved in the presence of ±30µA SENS and by 16.2±2.4% (mean ± s.e.m.) when optimised for each subject. The improvement in perception was similar across all VPT test sites.

  11. Plasticity of connections underlying locomotor recovery after central and/or peripheral lesions in the adult mammals

    PubMed Central

    Rossignol, Serge

    2006-01-01

    This review discusses some aspects of plasticity of connections after spinal injury in adult animal models as a basis for functional recovery of locomotion. After reviewing some pitfalls that must be avoided when claiming functional recovery and the importance of a conceptual framework for the control of locomotion, locomotor recovery after spinal lesions, mainly in cats, is summarized. It is concluded that recovery is partly due to plastic changes within the existing spinal locomotor networks. Locomotor training appears to change the excitability of simple reflex pathways as well as more complex circuitry. The spinal cord possesses an intrinsic capacity to adapt to lesions of central tracts or peripheral nerves but, as a rule, adaptation to lesions entails changes at both spinal and supraspinal levels. A brief summary of the spinal capacity of the rat, mouse and human to express spinal locomotor patterns is given, indicating that the concepts derived mainly from work in the cat extend to other adult mammals. It is hoped that some of the issues presented will help to evaluate how plasticity of existing connections may combine with and potentiate treatments designed to promote regeneration to optimize remaining motor functions. PMID:16939980

  12. Serum-free bioprocessing of adult human and rodent skin-derived Schwann cells: implications for cell therapy in nervous system injury.

    PubMed

    Mirfeizi, Leila; Stratton, Jo Anne; Kumar, Ranjan; Shah, Prajay; Agabalyan, Natacha; Stykel, Morgan G; Midha, Rajiv; Biernaskie, Jeff; Kallos, Michael S

    2017-02-08

    Peripheral nerve injury affects 2.8% of trauma patients with severe cases often resulting in long-lived permanent disability, despite nerve repair surgery. Autologous Schwann cell (SC) therapy currently provides an exciting avenue for improved outcomes for these patients, particularly with the possibility to derive SCs from easily-accessible adult skin. However, due to current challenges regarding the efficient expansion of these cells, further optimization is required before they can be seriously considered for clinical application. Here, a microcarrier-based bioreactor system is proposed as a means to scale-up large numbers of adult skin-derived SCs for transplantation into the injured nerve. Bioprocessing parameters that allow for the expansion of adult rodent SCs have been identified, whilst maintaining similar rates of proliferation (as compared to static-grown SCs), expression of SC markers, and, importantly, their capacity to myelinate axons following transplant into the injured sciatic nerve. The same bioprocessing parameters can be applied to SCs derived from adult human skin, and like rodent cells, they sustain their proliferative potential and expression of SC markers. Taken together, this dataset demonstrates the basis for a scalable bioprocess for the production of SCs, an important step towards clinical use of these cells as an adjunct therapy for nerve repair. Copyright © 2017 John Wiley & Sons, Ltd.

  13. A Dose–Response Study of Arsenic Exposure and Global Methylation of Peripheral Blood Mononuclear Cell DNA in Bangladeshi Adults

    PubMed Central

    Niedzwiecki, Megan M.; Hall, Megan N.; Liu, Xinhua; Oka, Julie; Harper, Kristin N.; Slavkovich, Vesna; Ilievski, Vesna; Levy, Diane; van Geen, Alexander; Mey, Jacob L.; Alam, Shafiul; Siddique, Abu B.; Parvez, Faruque; Graziano, Joseph H.

    2013-01-01

    Background: Several studies employing cell culture and animal models have suggested that arsenic (As) exposure induces global DNA hypomethylation. However, As has been associated with global DNA hypermethylation in human study populations. We hypothesized that this discrepancy may reflect a nonlinear relationship between As dose and DNA methylation. Objective: The objective of this study was to examine the dose–response relationship between As and global methylation of peripheral blood mononuclear cell (PBMC) DNA in apparently healthy Bangladeshi adults chronically exposed to a wide range of As concentrations in drinking water. Methods: Global PBMC DNA methylation, plasma folate, blood S-adenosylmethionine (SAM), and concentrations of As in drinking water, blood, and urine were measured in 320 adults. DNA methylation was measured using the [3H]-methyl incorporation assay, which provides disintegration-per-minute (DPM) values that are negatively associated with global DNA methylation. Results: Water, blood, and urinary As were positively correlated with global PBMC DNA methylation (p < 0.05). In multivariable-adjusted models, 1-μg/L increases in water and urinary As were associated with 27.6-unit (95% CI: 6.3, 49.0) and 22.1-unit (95% CI: 0.5, 43.8) decreases in DPM per microgram DNA, respectively. Categorical models indicated that estimated mean levels of PBMC DNA methylation were highest in participants with the highest As exposures. Conclusions: These results suggest that As is positively associated with global methylation of PBMC DNA over a wide range of drinking water As concentrations. Further research is necessary to elucidate underlying mechanisms and physiologic implications. Citation: Niedzwiecki MM, Hall MN, Liu X, Oka J, Harper KN, Slavkovich V, Ilievski V, Levy D, van Geen A, Mey JL, Alam S, Siddique AB, Parvez F, Graziano JH, Gamble MV. 2013. A dose–response study of arsenic exposure and global methylation of peripheral blood mononuclear cell DNA

  14. Solution-Phase Crosstalk and Regulatory Interactions Between Multipotent Adult Progenitor Cells and Peripheral Blood Mononuclear Cells

    PubMed Central

    van’t Hof, Wouter; Reddy, Ashok P.; Wilmarth, Phillip A.; David, Larry L.; Raber, Amy; Bogaerts, Annelies; Timmerman, Lien; Pinxteren, Jef; Roobrouck, Valerie D.; Deans, Robert J.; Maziarz, Richard T.

    2015-01-01

    Multipotent adult progenitor cells (MAPCs) are adult adherent stromal stem cells currently being assessed in clinical trials for acute graft versus host disease with demonstrated immunomodulatory capabilities and the potential to ameliorate detrimental autoimmune and inflammation-related processes. Anti-CD3/anti-CD28 (3/28) activation of T cells within the peripheral blood mononuclear cell (PBMC) compartment was performed in the presence or absence of MAPCs. Liquid chromatography-coupled tandem mass spectrometry was used to characterize the differential secretion of proteins, and transcriptional profiling was used to monitor mRNA expression changes in both cell populations. Overall, 239 secreted and/or ectodomain-shed proteins were detected in the secretomes of PBMCs and MAPCs. In addition, 3/28 activation of PBMCs induced differential expression of 2,925 genes, and 22% of these transcripts were differentially expressed on exposure to MAPCs in Transwell. MAPCs exposed to 3/28-activated PBMCs showed differential expression of 1,247 MAPC genes. Crosstalk was demonstrated by reciprocal transcriptional regulation. Secretome proteins and transcriptional signatures were used to predict molecular activities by which MAPCs could dampen local and systemic inflammatory responses. These data support the hypothesis that MAPCs block PBMC proliferation via cell cycle arrest coupled to metabolic stress in the form of tryptophan depletion, resulting in GCN2 kinase activation, downstream signaling, and inhibition of cyclin D1 translation. These data also provide a plausible explanation for the immune privilege reported with administration of donor MAPCs. Although most components of the major histocompatibility complex class II antigen presentation pathway were markedly transcriptionally upregulated, cell surface expression of human leukocyte antigen-DR is minimal on MAPCs exposed to 3/28-activated PBMCs. Significance This study documents experiments quantifying solution

  15. The Effects of Tai Chi on Peripheral Somatosensation, Balance, and Fitness in Hispanic Older Adults with Type 2 Diabetes: A Pilot and Feasibility Study

    PubMed Central

    Cavegn, Elisabeth I.; Riskowski, Jody L.

    2015-01-01

    Peripheral neuropathy and loss of somatosensation in older adults with type 2 diabetes can increase risk of falls and disability. In nondiabetic older adult population Tai Chi has been shown to enhance balance and fitness through improvements in somatosensation and neuromuscular control, and it is unclear if Tai Chi would elicit similar benefits in older adults with diabetes. Therefore, the purpose of this study was to investigate the effects of an 8-week, three-hour-per-week Tai Chi intervention on peripheral somatosensation in older adults with type 2 diabetes. Participants were eight Hispanic older adults with type 2 diabetes who participated in the Tai Chi intervention and a convenience sample of Hispanic older adults as a referent group. Baseline and postintervention assessments included ankle proprioception, foot tactile sense, plantar pressure distribution, balance, and fitness. After intervention, older adults with type 2 diabetes showed significant improvements in ankle proprioception and fitness and decreased plantar pressure in the forefoot, with no statistical effect noted in balance or tactile sensation. Study results suggest that Tai Chi may be beneficial for older adults with diabetes as it improves ankle proprioception; however, study findings need to be confirmed in a larger sample size randomized controlled trial. PMID:26600865

  16. A Spontaneous Missense Mutation in Branched Chain Keto Acid Dehydrogenase Kinase in the Rat Affects Both the Central and Peripheral Nervous Systems.

    PubMed

    Zigler, J Samuel; Hodgkinson, Colin A; Wright, Megan; Klise, Andrew; Sundin, Olof; Broman, Karl W; Hejtmancik, Fielding; Huang, Hao; Patek, Bonnie; Sergeev, Yuri; Hose, Stacey; Brayton, Cory; Xaiodong, Jiao; Vasquez, David; Maragakis, Nicholas; Mori, Susumu; Goldman, David; Hoke, Ahmet; Sinha, Debasish

    2016-01-01

    A novel mutation, causing a phenotype we named frogleg because its most obvious characteristic is a severe splaying of the hind limbs, arose spontaneously in a colony of Sprague-Dawley rats. Frogleg is a complex phenotype that includes abnormalities in hind limb function, reduced brain weight with dilated ventricles and infertility. Using micro-satellite markers spanning the entire rat genome, the mutation was mapped to a region of rat chromosome 1 between D1Rat131 and D1Rat287. Analysis of whole genome sequencing data within the linkage interval, identified a missense mutation in the branched-chain alpha-keto dehydrogenase kinase (Bckdk) gene. The protein encoded by Bckdk is an integral part of an enzyme complex located in the mitochondrial matrix of many tissues which regulates the levels of the branched-chain amino acids (BCAAs), leucine, isoleucine and valine. BCAAs are essential amino acids (not synthesized by the body), and circulating levels must be tightly regulated; levels that are too high or too low are both deleterious. BCKDK phosphorylates Ser293 of the E1α subunit of the BCKDH protein, which catalyzes the rate-limiting step in the catabolism of the BCAAs, inhibiting BCKDH and thereby, limiting breakdown of the BCAAs. In contrast, when Ser293 is not phosphorylated, BCKDH activity is unchecked and the levels of the BCAAs will decrease dramatically. The mutation is located within the kinase domain of Bckdk and is predicted to be damaging. Consistent with this, we show that in rats homozygous for the mutation, phosphorylation of BCKDH in the brain is markedly decreased relative to wild type or heterozygous littermates. Further, circulating levels of the BCAAs are reduced by 70-80% in animals homozygous for the mutation. The frogleg phenotype shares important characteristics with a previously described Bckdk knockout mouse and with human subjects with Bckdk mutations. In addition, we report novel data regarding peripheral neuropathy of the hind limbs.

  17. A Spontaneous Missense Mutation in Branched Chain Keto Acid Dehydrogenase Kinase in the Rat Affects Both the Central and Peripheral Nervous Systems

    PubMed Central

    Zigler, J. Samuel; Hodgkinson, Colin A.; Wright, Megan; Klise, Andrew; Broman, Karl W.; Huang, Hao; Patek, Bonnie; Sergeev, Yuri; Hose, Stacey; Xaiodong, Jiao; Vasquez, David; Maragakis, Nicholas; Mori, Susumu; Goldman, David; Sinha, Debasish

    2016-01-01

    A novel mutation, causing a phenotype we named frogleg because its most obvious characteristic is a severe splaying of the hind limbs, arose spontaneously in a colony of Sprague-Dawley rats. Frogleg is a complex phenotype that includes abnormalities in hind limb function, reduced brain weight with dilated ventricles and infertility. Using micro-satellite markers spanning the entire rat genome, the mutation was mapped to a region of rat chromosome 1 between D1Rat131 and D1Rat287. Analysis of whole genome sequencing data within the linkage interval, identified a missense mutation in the branched-chain alpha-keto dehydrogenase kinase (Bckdk) gene. The protein encoded by Bckdk is an integral part of an enzyme complex located in the mitochondrial matrix of many tissues which regulates the levels of the branched-chain amino acids (BCAAs), leucine, isoleucine and valine. BCAAs are essential amino acids (not synthesized by the body), and circulating levels must be tightly regulated; levels that are too high or too low are both deleterious. BCKDK phosphorylates Ser293 of the E1α subunit of the BCKDH protein, which catalyzes the rate-limiting step in the catabolism of the BCAAs, inhibiting BCKDH and thereby, limiting breakdown of the BCAAs. In contrast, when Ser293 is not phosphorylated, BCKDH activity is unchecked and the levels of the BCAAs will decrease dramatically. The mutation is located within the kinase domain of Bckdk and is predicted to be damaging. Consistent with this, we show that in rats homozygous for the mutation, phosphorylation of BCKDH in the brain is markedly decreased relative to wild type or heterozygous littermates. Further, circulating levels of the BCAAs are reduced by 70–80% in animals homozygous for the mutation. The frogleg phenotype shares important characteristics with a previously described Bckdk knockout mouse and with human subjects with Bckdk mutations. In addition, we report novel data regarding peripheral neuropathy of the hind limbs

  18. rhG-CSF does not affect the phenotype of adult donor peripheral blood NK cells.

    PubMed

    Lassailly, F; Sielleur, I; Blaise, D; Chabannon, C

    2005-01-01

    Considerable evidence in preclinical models as well as in human transplantation now suggests that donor-derived natural killer (NK) cells can contribute to alloimmune recognition of recipient residual tumour cells. This makes the NK cell population an attractive target for in vitro or in vivo manipulations, in order to improve the antitumour effect of allogeneic transplantation. However, conditions in which allogeneic donor cells are collected vary; several reports have emphasised the different phenotypic and functional properties of T cells derived from marrow, cord blood or mobilised peripheral blood grafts; others have demonstrated different clinical outcomes following blood or marrow transplantation after myeloablative conditioning regimens. NK cells have been examined in this setting; the availability of new tools to study the expression of a variety of surface antigens that are involved in the control of NK cell activity offered us an opportunity to extensively characterise the phenotypic properties of NK cells from donors, before and after administration of pharmacological doses of rhG-CSF used for haematopoietic progenitor mobilisation. Our study suggests that rhG-CSF does not reproducibly alter blood NK cell phenotype in normal individuals, and thus that donor-derived cells are fully equipped to exert their potential antitumour effect.

  19. Relation between aggression exposure in adolescence and adult posttraumatic stress symptoms: Moderating role of the parasympathetic nervous system.

    PubMed

    Barry, Samantha A; Rabkin, Ari N; Olezeski, Christy L; Rivers, Alison J; Gordis, Elana B

    2015-03-15

    The present study examines the impact of the parasympathetic nervous system (PNS), as measured by respiratory sinus arrhythmia (RSA), on the link between family aggression experienced during adolescence and posttraumatic stress symptoms during young adulthood. Participants completed retrospective self-report measures of interparental aggression and harsh parenting exposure during adolescence and measures of current posttraumatic stress symptoms. RSA indexed PNS activity. Among females, the three-way interaction between harsh parenting, interparental aggression, and resting RSA was significant in accounting for young adulthood PTSD symptoms. At higher values of resting RSA and higher levels of interparental aggression exposure, harsh parenting experienced during adolescence was positively associated with adulthood PTSD symptoms. Among males, adolescent aggression exposure and resting RSA did not significantly account for variation in adulthood PTSD symptoms. Thus, this study suggests that resting PNS activity may play an important role in the relationship between stressors during adolescence and later PTSD in females.

  20. Functional Imaging of Working Memory and Peripheral Endothelial Function in Middle-Aged Adults

    PubMed Central

    Gonzales, Mitzi M.; Tarumi, Takashi; Tanaka, Hirofumi; Sugawara, Jun; Swann-Sternberg, Tali; Goudarzi, Katyoon; Haley, Andreana P.

    2010-01-01

    The current study examined the relationship between a prognostic indicator of vascular health, flow-mediated dilation (FMD), and working memory-related brain activation in healthy middle-aged adults. Forty-two participants underwent functional magnetic resonance imaging while completing a 2-Back working memory task. Brachial artery endothelial-dependent flow-mediated dilation (FMD) was assessed using B-mode ultrasound. The relationship between FMD and task-related brain activation in a priori regions of interest was modeled using hierarchical linear regression. Brachial FMD, was significantly related to reduced working memory-related activation in the right superior parietal lobule (β=0.338, p=0.027), independent of age, sex, systolic blood pressure, and full scale IQ (F(5,36)=2.66, p=0.038). These data provide preliminary support for the association between a preclinical marker of endothelial dysfunction and cerebral hemodynamic alterations in healthy middle-aged adults. Considering the modifiable nature of endothelial function, additional investigations on the prognostic significance of FMD on future cognitive impairment are warranted. PMID:20493622

  1. A microarray gene analysis of peripheral whole blood in normal adult male rats after long-term GH gene therapy.

    PubMed

    Qin, Ying; Tian, Ya-Ping

    2010-06-01

    The main aims of this study were to determine the effects of GH gene abuse/misuse in normal animals and to discover genes that could be used as candidate biomarkers for the detection of GH gene therapy abuse/misuse in humans. We determined the global gene expression profile of peripheral whole blood from normal adult male rats after long-term GH gene therapy using CapitalBio 27 K Rat Genome Oligo Arrays. Sixty one genes were found to be differentially expressed in GH gene-treated rats 24 weeks after receiving GH gene therapy, at a two-fold higher or lower level compared to the empty vector group (p < 0.05). These genes were mainly associated with angiogenesis, oncogenesis, apoptosis, immune networks, signaling pathways, general metabolism, type I diabetes mellitus, carbon fixation, cell adhesion molecules, and cytokine-cytokine receptor interaction. The results imply that exogenous GH gene expression in normal subjects is likely to induce cellular changes in the metabolism, signal pathways and immunity. A real-time qRT-PCR analysis of a selection of the genes confirmed the microarray data. Eight differently expressed genes were selected as candidate biomarkers from among these 61 genes. These 8 showed five-fold higher or lower expression levels after the GH gene transduction (p < 0.05). They were then validated in real-time PCR experiments using 15 single-treated blood samples and 10 control blood samples. In summary, we detected the gene expression profiles of rat peripheral whole blood after long-term GH gene therapy and screened eight genes as candidate biomarkers based on the microarray data. This will contribute to an increased mechanistic understanding of the effects of chronic GH gene therapy abuse/misuse in normal subjects.

  2. Peripherally Inserted Central Catheter-Related Infections in a Cohort of Hospitalized Adult Patients

    SciTech Connect

    Bouzad, Caroline; Duron, Sandrine; Bousquet, Aurore; Arnaud, François-Xavier; Valbousquet, Laura; Weber-Donat, Gabrielle Teriitehau, Christophe Baccialone, Jacques Potet, Julien

    2016-03-15

    PurposeTo determine the incidence and the risks factors of peripherally inserted central catheter (PICC)-related infectious complications.Materials and MethodsMedical charts of every in-patient that underwent a PICC insertion in our hospital between January 2010 and October 2013 were reviewed. All PICC-related infections were recorded and categorized as catheter-related bloodstream infections (CR-BSI), exit-site infections, and septic thrombophlebitis.ResultsNine hundred and twenty-three PICCs were placed in 644 unique patients, mostly male (68.3 %) with a median age of 58 years. 31 (3.4 %) PICC-related infections occurred during the study period corresponding to an infection rate of 1.64 per 1000 catheter-days. We observed 27 (87.1 %) CR-BSI, corresponding to a rate of 1.43 per 1000 catheter-days, 3 (9.7 %) septic thrombophlebitis, and 1 (3.2 %) exit-site infection. Multivariate logistic regression analysis showed a higher PICC-related infection rate with chemotherapy (odds ratio (OR) 7.2–confidence interval (CI) 95 % [1.77–29.5]), auto/allograft (OR 5.9–CI 95 % [1.2–29.2]), and anti-coagulant therapy (OR 2.2–95 % [1.4–12]).ConclusionChemotherapy, auto/allograft, and anti-coagulant therapy are associated with an increased risk of developing PICC-related infections.Clinical AdvanceChemotherapy, auto/allograft, and anti-coagulant therapy are important predictors of PICC-associated infections. A careful assessment of these risk factors may be important for future success in preventing PICC-related infections.

  3. The proof-of-concept of ASS234: Peripherally administered ASS234 enters the central nervous system and reduces pathology in a male mouse model of Alzheimer disease

    PubMed Central

    Serrano, Mari Paz; Herrero-Labrador, Raquel; Futch, Hunter S.; Serrano, Julia; Romero, Alejandro; Fernandez, Ana Patricia; Samadi, Abdelouahid; Unzeta, Mercedes; Marco-Contelles, Jose; Martínez-Murillo, Ricardo

    2017-01-01

    Background The heterogeneity of Alzheimer disease requires the development of multitarget drugs for treating the symptoms of the disease and its progression. Both cholinergic and monoamine oxidase dysfunctions are involved in the pathological process. Thus, we hypothesized that the development of therapies focused on these targets might be effective. We have developed and assessed a new product, coded ASS234, a multipotent acetyl and butyrylcholinesterase/monoamine oxidase A–B inhibitor with a potent inhibitory effect on amyloid-β aggregation as well as antioxidant and antiapoptotic properties. But there is a need to reliably correlate in vitro and in vivo drug release data. Methods We examined the effect of ASS234 on cognition in healthy adult C57BL/6J mice in a model of scopolamine-induced cognitive impairment that often accompanies normal and pathological aging. Also, in a characterized transgenic APPswe/PS1ΔE9 mouse model of Alzheimer disease, we examined the effects of short-term ASS234 treatment on plaque deposition and gliosis using immunohistochemistry. Toxicology of ASS234 was assessed using a quantitative high-throughput in vitro cytotoxicity screening assay following the MTT assay method in HepG2 liver cells. Results In vivo, ASS234 significantly decreased scopolamine-induced learning deficits in C57BL/6J mice. Also, reduction of amyloid plaque burden and gliosis in the cortex and hippocampus was assessed. In vitro, ASS234 exhibited lesser toxicity than donepezil and tacrine. Limitations The study was conducted in male mice only. Although the Alzheimer disease model does not recapitulate all features of the human disease, it exhibits progressive monoaminergic neurodegeneration. Conclusion ASS234 is a promising alternative drug of choice to treat the cognitive decline and neurodegeneration underlying Alzheimer disease. PMID:27636528

  4. Expression of c-fos gene in central nervous system of adult medaka (Oryzias latipes) after hypergravity stimulation

    NASA Astrophysics Data System (ADS)

    Shimomura, S.; Ijiri, K.

    The immediate-early genes serve as useful neurobiological tools for mapping brain activity induced by a sensory stimulation. In this study, we have examined brain activity related to gravity perception of medaka (Oryzias latipes) by use of c-fos. The gene, which is homologous to the c-fos genes of other vertebrates, was identified in medaka. Functionally important domains are highly conserved among all the vertebrate species analyzed. Intraperitoneal administration of kainic acid transiently induced the c-fos mRNAs in medaka brain. The results indicate that the expression of c-fos can be utilized as a suitable anatomical marker for the increased neural activities in the central nervous system of medaka. Fish were continuously exposed to 3G hypergravity by centrifugation. Investigation of c-fos mRNA expression showed that c-fos mRNA significantly increased 30 minutes after a start of 3G exposure. The distribution of its transcripts within brains was analyzed by an in situ hybridization method. The 3G-treated medakas displayed c-fos positive cells in their brainstem regions, which are related to vestibular function, such as torus semicircularis, posterior octavu nucleus, nucleus tangentialis and inferior olive. Our results established the method to trace the activated area in the fish brain following gravity stimulation. The method will be a useful tool for understanding gravity perception in the brain.

  5. Satb2 determines miRNA expression and long-term memory in the adult central nervous system

    PubMed Central

    Jaitner, Clemens; Reddy, Chethan; Abentung, Andreas; Whittle, Nigel; Rieder, Dietmar; Delekate, Andrea; Korte, Martin; Jain, Gaurav; Fischer, Andre; Sananbenesi, Farahnaz; Cera, Isabella; Singewald, Nicolas

    2016-01-01

    SATB2 is a risk locus for schizophrenia and encodes a DNA-binding protein that regulates higher-order chromatin configuration. In the adult brain Satb2 is almost exclusively expressed in pyramidal neurons of two brain regions important for memory formation, the cerebral cortex and the CA1-hippocampal field. Here we show that Satb2 is required for key hippocampal functions since deletion of Satb2 from the adult mouse forebrain prevents the stabilization of synaptic long-term potentiation and markedly impairs long-term fear and object discrimination memory. At the molecular level, we find that synaptic activity and BDNF up-regulate Satb2, which itself binds to the promoters of coding and non-coding genes. Satb2 controls the hippocampal levels of a large cohort of miRNAs, many of which are implicated in synaptic plasticity and memory formation. Together, our findings demonstrate that Satb2 is critically involved in long-term plasticity processes in the adult forebrain that underlie the consolidation and stabilization of context-linked memory. DOI: http://dx.doi.org/10.7554/eLife.17361.001 PMID:27897969

  6. The Effects of Acute Physical Exercise on Memory, Peripheral BDNF, and Cortisol in Young Adults.

    PubMed

    Hötting, Kirsten; Schickert, Nadine; Kaiser, Jochen; Röder, Brigitte; Schmidt-Kassow, Maren

    2016-01-01

    In animals, physical activity has been shown to induce functional and structural changes especially in the hippocampus and to improve memory, probably by upregulating the release of neurotrophic factors. In humans, results on the effect of acute exercise on memory are inconsistent so far. Therefore, the aim of the present study was to assess the effects of a single bout of physical exercise on memory consolidation and the underlying neuroendocrinological mechanisms in young adults. Participants encoded a list of German-Polish vocabulary before exercising for 30 minutes with either high intensity or low intensity or before a relaxing phase. Retention of the vocabulary was assessed 20 minutes after the intervention as well as 24 hours later. Serum BDNF and salivary cortisol were measured at baseline, after learning, and after the intervention. The high-intensity exercise group showed an increase in BDNF and cortisol after exercising compared to baseline. Exercise after learning did not enhance the absolute number of recalled words. Participants of the high-intensity exercise group, however, forgot less vocabulary than the relaxing group 24 hours after learning. There was no robust relationship between memory scores and the increase in BDNF and cortisol, respectively, suggesting that further parameters have to be taken into account to explain the effects of exercise on memory in humans.

  7. Receptive-field changes induced by peripheral nerve stimulation in SI of adult cats.

    PubMed

    Recanzone, G H; Allard, T T; Jenkins, W M; Merzenich, M M

    1990-05-01

    1. Receptive fields (RFs) of neurons in the primary somatosensory (SI) cortex were defined before, during, and after electrical stimulation of myelinated fibers in the dorsal cutaneous branch of the ulnar nerve in adult pentobarbital sodium-anesthetized cats. 2. This stimulation resulted in an approximately threefold increase of SI multiunit RF sizes. Substantial changes were first recorded within 1-2 h of stimulation. RFs typically enlarged continuously over a several-hour stimulation period, then stabilized. 3. RF-area increases were observed within both the forepaw and hindpaw representational zones in the SI cortex contralateral to the stimulated forepaw nerve. RF sizes did not increase in the ipsilateral SI body surface representation or in sham-stimulation control animals. 4. Preliminary studies indicate that stimulation-induced changes can be halted and often reversed by the intravenous administration of the opiate antagonist naloxone. 5. These observations suggest a global naloxone-sensitive modulatory system that operates on large-diameter afferent inputs in the cat somatosensory system. The increases in RF size occur under nerve-stimulation conditions similar to those that result in the generation of widespread analgesia (Chung et al. 1984a,b; Gamble and Milne 1986; Toda and Ichioka 1978).

  8. The Effects of Acute Physical Exercise on Memory, Peripheral BDNF, and Cortisol in Young Adults

    PubMed Central

    Röder, Brigitte; Schmidt-Kassow, Maren

    2016-01-01

    In animals, physical activity has been shown to induce functional and structural changes especially in the hippocampus and to improve memory, probably by upregulating the release of neurotrophic factors. In humans, results on the effect of acute exercise on memory are inconsistent so far. Therefore, the aim of the present study was to assess the effects of a single bout of physical exercise on memory consolidation and the underlying neuroendocrinological mechanisms in young adults. Participants encoded a list of German-Polish vocabulary before exercising for 30 minutes with either high intensity or low intensity or before a relaxing phase. Retention of the vocabulary was assessed 20 minutes after the intervention as well as 24 hours later. Serum BDNF and salivary cortisol were measured at baseline, after learning, and after the intervention. The high-intensity exercise group showed an increase in BDNF and cortisol after exercising compared to baseline. Exercise after learning did not enhance the absolute number of recalled words. Participants of the high-intensity exercise group, however, forgot less vocabulary than the relaxing group 24 hours after learning. There was no robust relationship between memory scores and the increase in BDNF and cortisol, respectively, suggesting that further parameters have to be taken into account to explain the effects of exercise on memory in humans. PMID:27437149

  9. Generation of New Neurons in Dorsal Root Ganglia in Adult Rats after Peripheral Nerve Crush Injury

    PubMed Central

    2015-01-01

    The evidence of neurons generated ex novo in sensory ganglia of adult animals is still debated. In the present study, we investigated, using high resolution light microscopy and stereological analysis, the changes in the number of neurons in dorsal root ganglia after 30 days from a crush lesion of the rat brachial plexus terminal branches. Results showed, as expected, a relevant hypertrophy of dorsal root ganglion neurons. In addition, we reported, for the first time in the literature, that neuronal hypertrophy was accompanied by massive neuronal hyperplasia leading to a 42% increase of the number of primary sensory neurons. Moreover, ultrastructural analyses on sensory neurons showed that there was not a relevant neuronal loss as a consequence of the nerve injury. The evidence of BrdU-immunopositive neurons and neural progenitors labeled with Ki67, nanog, nestin, and sox-2 confirmed the stereological evidence of posttraumatic neurogenesis in dorsal root ganglia. Analysis of morphological changes following axonal damage in addition to immunofluorescence characterization of cell phenotype suggested that the neuronal precursors which give rise to the newly generated neurons could be represented by satellite glial cells that actively proliferate after the lesion and are able to differentiate toward the neuronal lineage. PMID:25722894

  10. The Relationship Between Brain Volume and Walking Outcomes in Older Adults With and Without Diabetic Peripheral Neuropathy

    PubMed Central

    Manor, Brad; Newton, Elizabeth; Abduljalil, Amir; Novak, Vera

    2012-01-01

    OBJECTIVE Diabetic peripheral neuropathy (DPN) alters walking. Yet, the compensatory role of central locomotor circuits remains unclear. We hypothesized that walking outcomes would be more closely related to regional gray matter volumes in older adults with DPN as compared with nonneuropathic diabetic patients and nondiabetic control subjects. RESEARCH DESIGN AND METHODS Clinically important outcomes of walking (i.e., speed, stride duration variability, and double support time) were measured in 29 patients with DPN (type 2 diabetes with foot-sole somatosensory impairment), 68 diabetic (DM) patients (type 2 diabetes with intact foot-sole sensation), and 89 control subjects. Global and regional gray matter volumes were calculated from 3 Tesla magnetic resonance imaging. RESULTS DPN subjects walked more slowly (P = 0.005) with greater stride duration variability (P < 0.001) and longer double support (P < 0.001) as compared with DM and control subjects. Diabetes was associated with less cerebellar gray matter volume (P < 0.001), but global gray matter volume was similar between groups. DPN subjects with lower gray matter volume globally (P < 0.004) and regionally (i.e., cerebellum, right-hemisphere dorsolateral prefrontal cortex, basal ganglia, P < 0.005) walked more slowly with greater stride duration variability and/or longer double support. Each relationship was stronger in DPN than DM subjects. In control subjects, brain volumes did not relate to walking patterns. CONCLUSIONS Strong relationships between brain volumes and walking outcomes were observed in the DPN group and to a lesser extent the DM group, but not in control subjects. Individuals with DPN may be more dependent upon supraspinal elements of the motor control system to regulate several walking outcomes linked to poor health in elderly adults. PMID:22665216

  11. Trends in central nervous system tumor incidence relative to other common cancers in adults, adolescents, and children in the United States, 2000 to 2010

    PubMed Central

    Gittleman, Haley R; Ostrom, Quinn T; Rouse, Chaturia D; Dowling, Jacqueline A; de Blank, Peter M; Kruchko, Carol A; Elder, J Bradley; Rosenfeld, Steven S; Selman, Warren R; Sloan, Andrew E; Barnholtz-Sloan, Jill S

    2015-01-01

    BACKGROUND Time trends in cancer incidence rates (IR) are important to measure the changing burden of cancer on a population over time. The overall IR of cancer in the United States is declining. Although central nervous system tumors (CNST) are rare, they contribute disproportionately to mortality and morbidity. In this analysis, the authors examined trends in the incidence of the most common cancers and CNST between 2000 and 2010. METHODS The current analysis used data from the United States Cancer Statistics publication and the Central Brain Tumor Registry of the United States. Age-adjusted IR per 100,000 population with 95% confidence intervals and the annual percent change (APC) with 95% confidence intervals were calculated for selected common cancers and CNST overall and by age, sex, race/ethnicity, selected histologies, and malignancy status. RESULTS In adults, there were significant decreases in colon (2000-2010: APC, −3.1), breast (2000-2010: APC, −0.8), lung (2000-2010: APC, −1.1), and prostate (2000-2010: APC, −2.4) cancer as well as malignant CNST (2008-2010: APC, −3.1), but a significant increase was noted in nonmalignant CNST (2004-2010: APC, 2.7). In adolescents, there were significant increases in malignant CNST (2000-2008: APC, 1.0) and nonmalignant CNST (2004-2010: APC, 3.9). In children, there were significant increases in acute lymphocytic leukemia (2000-2010: APC, 1.0), non-Hodgkin lymphoma (2000-2010: APC, 0.6), and malignant CNST (2000-2010: APC, 0.6). CONCLUSIONS Surveillance of IR trends is an important way to measure the changing public health and economic burden of cancer. In the current study, there were significant decreases noted in the incidence of adult cancer, whereas adolescent and childhood cancer IR were either stable or increasing. Cancer 2015;121:102–112. © 2014 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. Time trends in cancer incidence rates are important to

  12. Signaling through ERK1/2 controls myelin thickness during myelin repair in the adult central nervous system.

    PubMed

    Fyffe-Maricich, Sharyl L; Schott, Alexandra; Karl, Molly; Krasno, Janet; Miller, Robert H

    2013-11-20

    Oligodendrocytes, the myelin-forming cells of the CNS, exquisitely tailor the thickness of individual myelin sheaths to the diameter of their target axons to maximize the speed of action potential propagation, thus ensuring proper neuronal connectivity and function. Following demyelinating injuries to the adult CNS, newly formed oligodendrocytes frequently generate new myelin sheaths. Following episodes of demyelination such as those that occur in patients with multiple sclerosis, however, the matching of myelin thickness to axon diameter fails leaving remyelinated axons with thin myelin sheaths potentially compromising function and leaving axons vulnerable to damage. How oligodendrocytes determine the appropriate thickness of myelin for an axon of defined size during repair is unknown and identifying the signals that regulate myelin thickness has obvious therapeutic implications. Here, we show that sustained activation of extracellular-regulated kinases 1 and 2 (ERK1/2) in oligodendrocyte lineage cells results in accelerated myelin repair after injury, and is sufficient for the generation of thick myelin sheaths around remyelinated axons in the adult mouse spinal cord. Our findings suggest a model where ERK1/2 MAP kinase signaling acts as a myelin thickness rheostat that instructs oligodendrocytes to generate axon-appropriate quantities of myelin.

  13. Chronic prenatal ethanol exposure alters expression of central and peripheral insulin signaling molecules in adult guinea pig offspring.

    PubMed

    Dobson, Christine C; Thevasundaram, Kersh; Mongillo, Daniel L; Winterborn, Andrew; Holloway, Alison C; Brien, James F; Reynolds, James N

    2014-11-01

    Maternal ethanol consumption during pregnancy can produce a range of teratogenic outcomes in offspring. The mechanism of ethanol teratogenicity is multi-faceted, but may involve alterations in insulin and insulin-like growth factor (IGF) signaling pathways. These pathways are not only important for metabolism, but are also critically involved in neuronal survival and plasticity, and they can be altered by chronic prenatal ethanol exposure (CPEE). The objective of this study was to test the hypothesis that CPEE alters expression of insulin and IGF signaling molecules in the prefrontal cortex and liver of adult guinea pig offspring. Pregnant Dunkin-Hartley-strain guinea pigs received ethanol (4 g/kg maternal body weight/day) or isocaloric-sucrose/pair-feeding (nutritional control) throughout gestation. Fasting blood glucose concentration was measured in male and female offspring at postnatal day 150-200, followed by euthanasia, collection of prefrontal cortex and liver, and RNA extraction. IGF-1, IGF-1 receptor (IGF-1R), IGF-2, IGF-2 receptor (IGF-2R), insulin receptor substrate (IRS)-1, IRS-2, and insulin receptor (INSR) mRNA expression levels were measured in tissues using quantitative real-time PCR. The mean maternal blood ethanol concentration was 281 ± 15 mg/dL at 1 h after the second divided dose of ethanol on GD 57. CPEE resulted in increased liver weight in adult offspring, but produced no difference in fasting blood glucose concentration compared with nutritional control. In the liver, CPEE decreased mRNA expression of IGF-1, IGF-1R, and IGF-2, and increased IRS-2 mRNA expression in male offspring only compared with nutritional control. Female CPEE offspring had decreased INSR hepatic mRNA expression compared with male CPEE offspring. In the prefrontal cortex, IRS-2 mRNA expression was increased in CPEE offspring compared with nutritional control. The data demonstrate that CPEE alters both central and peripheral expression of insulin and IGF signaling

  14. Central nervous system involvement in adult acute lymphoblastic leukemia at diagnosis: results from the international ALL trial MRC UKALL XII/ECOG E2993

    PubMed Central

    Lazarus, Hillard M.; Richards, Susan M.; Chopra, Raj; Litzow, Mark R.; Burnett, Alan K.; Wiernik, Peter H.; Franklin, Ian M.; Tallman, Martin S.; Cook, Lucy; Buck, Georgina; Durrant, I. Jill; Rowe, Jacob M.; Goldstone, Anthony H.

    2006-01-01

    Outcome of acute lymphoblastic leukemia (ALL) in adults with central nervous system (CNS) disease at diagnosis is unclear. We treated 1508 de novo ALL patients with 2-phase induction and then high-dose methotrexate with l-asparaginase. Patients up to 50 years old in first remission (CR1) with a matched related donor (MRD) underwent an allogeneic stem cell transplantation (SCT); the remainder in CR1 were randomized to an autologous SCT or intensive consolidation followed by maintenance chemotherapy. Philadelphia chromosome (Ph)–positive patients were offered a matched unrelated donor (MUD) allogeneic SCT. Seventy-seven of 1508 (5%) patients a median age of 29 years had CNS leukemia at presentation; 13 of the 77 (17%) had Ph-positive ALL. Sixty-nine of 77 (90%) patients attained CR1. Thirty-six patients underwent transplantation in CR1 (25 MRD, 5 MUD, and 6 autografts). Eleven of 25 patients with MRD transplantation remain alive at 21 to 102 months, 2 of 5 with MUD at 42 and 71 months, and 1 of 6 with autologous SCT at 35 months. Seven of 27 treated with consolidation/maintenance remain in CR1 56 to 137 months after diagnosis. Overall survival at 5 years was 29% in those with CNS involvement at diagnosis versus 38% (P = .03) for those without. CNS leukemia in adult ALL is uncommon at diagnosis. Adult Ph-negative ALL patients, however, can attain long-term disease-free survival using SCT as well as conventional chemotherapy. PMID:16556888

  15. Evaluation of 5-ethynyl-2'-deoxyuridine staining as a sensitive and reliable method for studying cell proliferation in the adult nervous system.

    PubMed

    Zeng, Chenbo; Pan, Fenghui; Jones, Lynne A; Lim, Miranda M; Griffin, Elizabeth A; Sheline, Yvette I; Mintun, Mark A; Holtzman, David M; Mach, Robert H

    2010-03-10

    Recently, a novel method for detection of DNA synthesis has been developed based on the incorporation of 5-ethynyl-2'-deoxyuridine (EdU), a thymidine analogue, into cellular DNA and the subsequent reaction of EdU with a fluorescent azide in a copper-catalyzed [3+2] cycloaddition ("Click" reaction). In the present study, we evaluated this method for studying cell proliferation in the adult central nervous system in comparison with the "gold standard" method of 5-bromo-2'-deoxyuridine (BrdU) staining using two behavioral paradigms, voluntary exercise and restraint stress. Our data demonstrate that the number of EdU-positive cells in the dentate gyrus of the hippocampus (DG) slightly increased in an EdU dose-dependent manner in both the control and voluntary exercise (running) mouse groups. The number of EdU-labeled cells was comparable to the number of BrdU-labeled cells in both the control and running mice. Furthermore, EdU and BrdU co-localized to the same cells within the DG. Voluntary exercise significantly increased the number of EdU- and BrdU-positive cells in the DG. In contrast, restraint stress significantly decreased the number of EdU-positive cells. The EdU-positive cells differentiated into mature neurons. EdU staining is compatible with immunohistochemical staining of other antigens. Moreover, our data demonstrated EdU staining can be combined with BrdU staining, providing a valuable tool of double labeling DNA synthesis, e.g., for tracking the two populations of neurons generated at different time points. In conclusion, our results suggest that EdU staining is a fast, sensitive and reproducible method to study cell proliferation in the central nervous system.

  16. Region-specific vulnerability to lipid peroxidation and evidence of neuronal mechanisms for polyunsaturated fatty acid biosynthesis in the healthy adult human central nervous system.

    PubMed

    Naudí, Alba; Cabré, Rosanna; Dominguez-Gonzalez, Mayelin; Ayala, Victoria; Jové, Mariona; Mota-Martorell, Natalia; Piñol-Ripoll, Gerard; Gil-Villar, Maria Pilar; Rué, Montserrat; Portero-Otín, Manuel; Ferrer, Isidre; Pamplona, Reinald

    2017-02-07

    Lipids played a determinant role in the evolution of the brain. It is postulated that the morphological and functional diversity among neural cells of the human central nervous system (CNS) is projected and achieved through the expression of particular lipid profiles. The present study was designed to evaluate the differential vulnerability to oxidative stress mediated by lipids through a cross-regional comparative approach. To this end, we compared 12 different regions of CNS of healthy adult subjects, and the fatty acid profile and vulnerability to lipid peroxidation, were determined by gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS), respectively. In addition, different components involved in PUFA biosynthesis, as well as adaptive defense mechanisms against lipid peroxidation, were also measured by western blot and immunohistochemistry, respectively. We found that: i) four fatty acids (18.1n-9, 22:6n-3, 20:1n-9, and 18:0) are significant discriminators among CNS regions; ii) these differential fatty acid profiles generate a differential selective neural vulnerability (expressed by the peroxidizability index); iii) the cross-regional differences for the fatty acid profiles follow a caudal-cranial gradient which is directly related to changes in the biosynthesis pathways which can be ascribed to neuronal cells; and iv) the higher the peroxidizability index for a given human brain region, the lower concentration of the protein damage markers, likely supported by the presence of adaptive antioxidant mechanisms. In conclusion, our results suggest that there is a region-specific vulnerability to lipid peroxidation and offer evidence of neuronal mechanisms for polyunsaturated fatty acid biosynthesis in the human central nervous system.

  17. 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

  18. The Coupling of Peripheral Blood Pressure and Ventilatory Responses during Exercise in Young Adults with Cystic Fibrosis

    PubMed Central

    Van Iterson, Erik H.; Wheatley, Courtney M.; Baker, Sarah E.; Olson, Thomas P.; Morgan, Wayne J.; Snyder, Eric M.

    2016-01-01

    Purpose Cystic fibrosis (CF) is commonly recognized as a pulmonary disease associated with reduced airway function. Another primary symptom of CF is low exercise capacity where ventilation and gas-exchange are exacerbated. However, an independent link between pathophysiology of the pulmonary system and abnormal ventilatory and gas-exchange responses during cardiopulmonary exercise testing (CPET) has not been established in CF. Complicating this understanding, accumulating evidence suggests CF demonstrate abnormal peripheral vascular function; although, the clinical implications are unclear. We hypothesized that compared to controls, relative to total work performed (WorkTOT), CF would demonstrate increased ventilation accompanied by augmented systolic blood pressure (SBP) during CPET. Methods 16 CF and 23 controls (age: 23±4 vs. 27±4 years, P = 0.11; FEV1%predicted: 73±14 vs. 96±5, P<0.01) participated in CPET. Breath-by-breath oxygen uptake (V˙O2), ventilation (V˙E), and carbon dioxide output (V˙CO2) were measured continuously during incremental 3-min stage step-wise cycle ergometry CPET. SBP was measured via manual sphygmomanometry. Linear regression was used to calculate V˙E/V˙CO2 slope from rest to peak-exercise. Results Compared to controls, CF performed less WorkTOT during CPET (90±19 vs. 43±14 kJ, respectively, P<0.01). With WorkTOT as a covariate, peak V˙E (62±8 vs. 90±4 L/min, P = 0.76), V˙CO2 (1.8±0.3 vs. 2.7±0.1 L/min, P = 0.40), and SBP (144±13 vs. 152±6 mmHg, P = 0.88) were similar between CF and controls, respectively; whereas CF demonstrated increased V˙E/V˙CO2 slope (38±4 vs. 28±2, P = 0.02) but lower peak V˙O2 versus controls (22±5 vs. 33±4 mL/kg/min, P<0.01). There were modest-to-moderate correlations between peak SBP with V˙O2 (r = 0.30), V˙E (r = 0.70), and V˙CO2 (r = 0.62) in CF. Conclusions These data suggest that relative to WorkTOT, young adults with mild-to-moderate severity CF demonstrate augmented V˙E/V˙CO2

  19. Proteomic Analysis of the Ubiquitin Landscape in the Drosophila Embryonic Nervous System and the Adult Photoreceptor Cells

    PubMed Central

    Ramirez, Juanma; Martinez, Aitor; Lectez, Benoit; Lee, So Young; Franco, Maribel; Barrio, Rosa; Dittmar, Gunnar; Mayor, Ugo

    2015-01-01

    Background Ubiquitination is known to regulate physiological neuronal functions as well as to be involved in a number of neuronal diseases. Several ubiquitin proteomic approaches have been developed during the last decade but, as they have been mostly applied to non-neuronal cell culture, very little is yet known about neuronal ubiquitination pathways in vivo. Methodology/Principal Findings Using an in vivo biotinylation strategy we have isolated and identified the ubiquitinated proteome in neurons both for the developing embryonic brain and for the adult eye of Drosophila melanogaster. Bioinformatic comparison of both datasets indicates a significant difference on the ubiquitin substrates, which logically correlates with the processes that are most active at each of the developmental stages. Detection within the isolated material of two ubiquitin E3 ligases, Parkin and Ube3a, indicates their ubiquitinating activity on the studied tissues. Further identification of the proteins that do accumulate upon interference with the proteasomal degradative pathway provides an indication of the proteins that are targeted for clearance in neurons. Last, we report the proof-of-principle validation of two lysine residues required for nSyb ubiquitination. Conclusions/Significance These data cast light on the differential and common ubiquitination pathways between the embryonic and adult neurons, and hence will contribute to the understanding of the mechanisms by which neuronal function is regulated. The in vivo biotinylation methodology described here complements other approaches for ubiquitome study and offers unique advantages, and is poised to provide further insight into disease mechanisms related to the ubiquitin proteasome system. PMID:26460970

  20. Ankyrin-binding proteins related to nervous system cell adhesion molecules: candidates to provide transmembrane and intercellular connections in adult brain

    PubMed Central

    1993-01-01

    A major class of ankyrin-binding glycoproteins have been identified in adult rat brain of 186, 155, and 140 kD that are alternatively spliced products of the same pre-mRNA. Characterization of cDNAs demonstrated that ankyrin-binding glycoproteins (ABGPs) share 72% amino acid sequence identity with chicken neurofascin, a membrane-spanning neural cell adhesion molecule in the Ig super-family expressed in embryonic brain. ABGP polypeptides have the following features consistent with a role as ankyrin-binding proteins in vitro and in vivo: (a) ABGPs and ankyrin associate as pure proteins in a 1:1 molar stoichiometry; (b) the ankyrin-binding site is located in the COOH-terminal 21 kD of ABGP186 which contains the predicted cytoplasmic domain; (c) ABGP186 is expressed at approximately the same levels as ankyrin (15 pmoles/milligram of membrane protein); and (d) ABGP polypeptides are co- expressed with the adult form of ankyrinB late in postnatal development and are colocalized with ankyrinB by immunofluorescence. Similarity in amino acid sequence and conservation of sites of alternative splicing indicate that genes encoding ABGPs and neurofascin share a common ancestor. However, the major differences in developmental expression reported for neurofascin in embryos versus the late postnatal expression of ABGPs suggest that ABGPs and neurofascin represent products of gene duplication events that have subsequently evolved in parallel with distinct roles. The predicted cytoplasmic domains of rat ABGPs and chicken neurofascin are nearly identical to each other and closely related to a group of nervous system cell adhesion molecules with variable extracellular domains, which includes L1, Nr-CAM, and Ng- CAM of vertebrates, and neuroglian of Drosophila. The ankyrin-binding site of rat ABGPs is localized to the C-terminal 200 residues which encompass the cytoplasmic domain, suggesting the hypothesis that ability to associate with ankyrin may be a shared feature of neurofascin and

  1. An Inherited Genetic Variant in CEP72 Promoter Predisposes to Vincristine-Induced Peripheral Neuropathy in Adults With Acute Lymphoblastic Leukemia.

    PubMed

    Stock, W; Diouf, B; Crews, K R; Pei, D; Cheng, C; Laumann, K; Mandrekar, S J; Luger, S; Advani, A; Stone, R M; Larson, R A; Evans, W E

    2017-03-01

    Peripheral neuropathy is a major toxicity of vincristine, yet no strategies exist for identifying adult patients at high-risk. We used a case-control design of 48 adults receiving protocol therapy for acute lymphoblastic leukemia (ALL) who developed vincristine-induced neuropathy (NCI grade 2-4) during treatment, and 48 matched controls who did not develop grade 2-4 neuropathy. Peripheral neuropathy was prospectively graded by National Cancer Institute (NCI) criteria. CEP72 promoter genotype (rs924607) was determined using polymerase chain reaction (PCR)-based single nucleotide polymorphism (SNP) genotyping. Frequency of the CEP72 T/T genotype was higher in cases (31% vs. 10%, P = 0.0221) and the incidence of vincristine-induced neuropathy (grades 2-4) was significantly higher in patients homozygous for the CEP72 T/T genotype. 75% of the 20 patients homozygous for the CEP72 T allele developed grade 2-4 neuropathy, compared to 44% of patients with CEP72 CC or CT genotype (P = 0.0221). The CEP72 polymorphism can identify adults at increased risk of vincristine-induced peripheral neuropathy.

  2. Transcriptome Analysis of the Central and Peripheral Nervous Systems of the Spider Cupiennius salei Reveals Multiple Putative Cys-Loop Ligand Gated Ion Channel Subunits and an Acetylcholine Binding Protein.

    PubMed

    Torkkeli, Päivi H; Liu, Hongxia; French, Andrew S

    2015-01-01

    Invertebrates possess a diverse collection of pentameric Cys-loop ligand gated ion channel (LGIC) receptors whose molecular structures, evolution and relationships to mammalian counterparts have been intensely investigated in several clinically and agriculturally important species. These receptors are targets for a variety of control agents that may also harm beneficial species. However, little is known about Cys-loop receptors in spiders, which are important natural predators of insects. We assembled de novo transcriptomes from the central and peripheral nervous systems of the Central American wandering spider Cupiennius salei, a model species for neurophysiological, behavioral and developmental studies. We found 15 Cys-loop receptor subunits that are expected to form anion or cation permeable channels, plus a putative acetylcholine binding protein (AChBP) that has only previously been reported in molluscs and one annelid. We used phylogenetic and sequence analysis to compare the spider subunits to homologous receptors in other species and predicted the 3D structures of each protein using the I-Tasser server. The quality of homology models improved with increasing sequence identity to the available high-resolution templates. We found that C. salei has orthologous γ-aminobutyric acid (GABA), GluCl, pHCl, HisCl and nAChα LGIC subunits to other arthropods, but some subgroups are specific to arachnids, or only to spiders. C. salei sequences were phylogenetically closest to gene fragments from the social spider, Stegodyphus mimosarum, indicating high conservation within the Araneomorphae suborder of spiders. C. salei sequences had similar ligand binding and transmembrane regions to other invertebrate and vertebrate LGICs. They also had motifs associated with high sensitivity to insecticides and antiparasitic agents such as fipronil, dieldrin and ivermectin. Development of truly selective control agents for pest species will require information about the molecular

  3. Transcriptome Analysis of the Central and Peripheral Nervous Systems of the Spider Cupiennius salei Reveals Multiple Putative Cys-Loop Ligand Gated Ion Channel Subunits and an Acetylcholine Binding Protein

    PubMed Central

    Torkkeli, Päivi H.; Liu, Hongxia; French, Andrew S.

    2015-01-01

    Invertebrates possess a diverse collection of pentameric Cys-loop ligand gated ion channel (LGIC) receptors whose molecular structures, evolution and relationships to mammalian counterparts have been intensely investigated in several clinically and agriculturally important species. These receptors are targets for a variety of control agents that may also harm beneficial species. However, little is known about Cys-loop receptors in spiders, which are important natural predators of insects. We assembled de novo transcriptomes from the central and peripheral nervous systems of the Central American wandering spider Cupiennius salei, a model species for neurophysiological, behavioral and developmental studies. We found 15 Cys-loop receptor subunits that are expected to form anion or cation permeable channels, plus a putative acetylcholine binding protein (AChBP) that has only previously been reported in molluscs and one annelid. We used phylogenetic and sequence analysis to compare the spider subunits to homologous receptors in other species and predicted the 3D structures of each protein using the I-Tasser server. The quality of homology models improved with increasing sequence identity to the available high-resolution templates. We found that C. salei has orthologous γ-aminobutyric acid (GABA), GluCl, pHCl, HisCl and nAChα LGIC subunits to other arthropods, but some subgroups are specific to arachnids, or only to spiders. C. salei sequences were phylogenetically closest to gene fragments from the social spider, Stegodyphus mimosarum, indicating high conservation within the Araneomorphae suborder of spiders. C. salei sequences had similar ligand binding and transmembrane regions to other invertebrate and vertebrate LGICs. They also had motifs associated with high sensitivity to insecticides and antiparasitic agents such as fipronil, dieldrin and ivermectin. Development of truly selective control agents for pest species will require information about the molecular

  4. The Safety, Pharmacokinetics, and Nervous System Effects of Two Natural Sources of Caffeine in Healthy Adult Males.

    PubMed

    Krieger, D R; Kalman, D S; Feldman, S; Arnillas, L; Goldberg, D; Gisbert, O; Nader, S

    2016-06-20

    This double-blind crossover clinical trial randomized 12 adult males to receive 200 mg of caffeine from a green coffee extract, a guayusa leaf extract, and a synthetic control to compare their safety, absorption, and effect on neurotransmitters. The results showed no statistically significant changes in blood pressure or heart rate from baseline to 120 min postdose of each natural source compared with changes from baseline in the control (0.094 < = P < = 0.910). The ratios of Cmax , AUC0-4 , and AUC0-∞ of each natural source to the control were bioequivalent by US Food and Drug Administration standards (90% CI within 80-125%). The guayusa leaf extract stimulated a significantly lower increase in epinephrine compared with the control (+0.5 vs. +2.78 μg/gCr, P = 0.04), while the green coffee extract provoked an increase in epinephrine similar to the control (+3.21 vs. +2.78 μg/gCr, P = 0.569). Implications for future clinical research are discussed.

  5. [Peripheral nervous system and speech disorders].

    PubMed

    Ferri, Lluís

    2014-02-24

    Introduccion. Las afectaciones de la neurona motora inferior en la infancia, de etiologia congenita o adquirida, provocan dificultades en la respuesta motriz del habla en un periodo especialmente critico para el desarrollo del lenguaje. El interes por esta patologia radica en su baja incidencia, en su comorbilidad con otras afectaciones cerebrales y en su pronostico incierto. Objetivo. Hacer una revision de las alteraciones motoras del habla, de la valoracion funcional y de la intervencion logopedica en la disartria flacida. Desarrollo. Se plantea la caracterizacion clinica de las alteraciones en la produccion verbal de origen periferico, concretamente de la disartria flacida y sus manifestaciones respiratorias, fonatorias, de resonancia, de articulacion y de prosodia. Seguidamente, se esboza la valoracion funcional y se plantean las lineas de intervencion para su tratamiento. Conclusiones. Las manifestaciones clinicas de la disartria flacida son muy heterogeneas y van desde leves dificultades articulatorias a graves trastornos que limitan gravemente la capacidad para la expresion verbal. En la mayoria de los casos, la exploracion funcional proporciona hallazgos valiosos para su identificacion y tipificacion, para determinar la necesidad de valoraciones complementarias y para establecer el programa idoneo de intervencion logopedica. La participacion guiada de la familia y el abordaje interdisciplinar son factores que contribuyen decisivamente a mejorar estos procesos.

  6. Clinical features, outcomes, and cerebrospinal fluid findings in adult patients with central nervous system (CNS) infections caused by varicella-zoster virus: comparison with enterovirus CNS infections.

    PubMed

    Hong, Hyo-Lim; Lee, Eun Mi; Sung, Heungsup; Kang, Joong Koo; Lee, Sang-Ahm; Choi, Sang-Ho

    2014-12-01

    Varicella-zoster virus (VZV) is known to be associated with central nervous system (CNS) infections in adults. However, the clinical characteristics of VZV CNS infections are not well characterized. The aim of this study was to compare the clinical manifestations, outcomes, and cerebrospinal fluid (CSF) findings in patients with VZV CNS infections with those in patients with enterovirus (EV) CNS infections. This retrospective cohort study was performed at a 2,700-bed tertiary care hospital. Using a clinical microbiology computerized database, all adults with CSF PCR results positive for VZV or EV that were treated between January 1999 and February 2013 were identified. Thirty-eight patients with VZV CNS infection and 68 patients with EV CNS infection were included in the study. Compared with the EV group, the median age in the VZV group was higher (VZV, 35 years vs. EV, 31 years; P = 0.02), and showed a bimodal age distribution with peaks in the third and seventh decade. Encephalitis was more commonly encountered in the VZV group (VZV, 23.7% vs. EV, 4.4%; P = 0.01). The median lymphocyte percentage in the CSF (VZV, 81% vs. EV, 36%; P < 0.001) and the CSF protein level (VZV, 100 mg/dl vs. EV, 46 mg/dl; P < 0.001) were higher in the VZV group. Compared with patients with EV CNS infection, patients with VZV CNS infection developed encephalitis more often and exhibited more intense inflammatory reaction. Nevertheless, both VZV and EV CNS infections were associated with excellent long-term prognosis.

  7. Peripheral Polyneuropathy and Mefloquine Prophylaxis

    PubMed Central

    Chester, Alexander C.; Sandroni, Paola

    2011-01-01

    We describe a case of a woman who developed a peripheral polyneuropathy shortly after completing 4 weekly doses of mefloquine hydrochloride (250 mg) malaria prophylaxis. Although mefloquine-related central nervous system neuropathy is well described in the literature, peripheral polyneuropathy similar to this case has been documented only once before, to our knowledge. PMID:22144435

  8. Ratio of Monocytes to Lymphocytes in Peripheral Blood Identifies Adults at Risk of Incident Tuberculosis Among HIV-Infected Adults Initiating Antiretroviral Therapy

    PubMed Central

    Naranbhai, Vivek; Hill, Adrian V. S.; Abdool Karim, Salim S.; Naidoo, Kogieleum; Abdool Karim, Quarraisha; Warimwe, George M.; McShane, Helen; Fletcher, Helen

    2014-01-01

    Background. Eight decades ago, the ratio of monocytes to lymphocytes (hereafter, the “ML ratio”) was noted to affect outcomes of mycobacterial infection in rabbits. Recent transcriptomic studies support a role for relative proportions of myeloid and lymphoid transcripts in tuberculosis outcomes. The ML ratio in peripheral blood is known to be governed by hematopoietic stem cells with distinct biases. Methods. The predictive value of the baseline ML ratio was modeled in 2 prospective cohorts of HIV-infected adults starting cART in South Africa (primary cohort, 1862 participants; replication cohort, 345 participants). Incident tuberculosis was diagnosed with clinical, radiographic, and microbiologic methods per contemporary guidelines. Kaplan-Meier survival analyses and Cox proportional hazards modeling were conducted. Results. The incidence rate of tuberculosis differed significantly by baseline ML ratio: 32.61 (95% confidence interval [CI], 15.38–61.54), 16.36 (95% CI, 12.39–21.23), and 51.80 (95% CI, 23.10–101.71) per 1000 patient-years for ML ratios of less than the 5th percentile, between the 5th and 95th percentiles, and greater than the 95th percentile, respectively (P = .007). Neither monocyte counts nor lymphocyte counts alone were associated with tuberculosis. After adjustment for sex, World Health Organization human immunodeficiency virus disease stage, CD4+ T-cell counts, and previous history of tuberculosis, hazards of disease were significantly higher for patients with ML ratios of less than the 5th percentile or greater than the 95th percentile (adjusted hazard ratio, 2.47; 95% CI, 1.39–4.40; P = .002). Conclusions. The ML ratio may be a useful, readily available tool to stratify the risk of tuberculosis and suggests involvement of hematopoietic stem cell bias in tuberculosis pathogenesis. PMID:24041796

  9. AMIGO3 is an NgR1/p75 co-receptor signalling axon growth inhibition in the acute phase of adult central nervous system injury.

    PubMed

    Ahmed, Zubair; Douglas, Michael R; John, Gabrielle; Berry, Martin; Logan, Ann

    2013-01-01

    Axon regeneration in the injured adult CNS is reportedly inhibited by myelin-derived inhibitory molecules, after binding to a receptor complex comprised of the Nogo-66 receptor (NgR1) and two transmembrane co-receptors p75/TROY and LINGO-1. However, the post-injury expression pattern for LINGO-1 is inconsistent with its proposed function. We demonstrated that AMIGO3 levels were significantly higher acutely than those of LINGO-1 in dorsal column lesions and reduced in models of dorsal root ganglion neuron (DRGN) axon regeneration. Similarly, AMIGO3 levels were raised in the retina immediately after optic nerve crush, whilst levels were suppressed in regenerating optic nerves, induced by intravitreal peripheral nerve implantation. AMIGO3 interacted functionally with NgR1-p75/TROY in non-neuronal cells and in brain lysates, mediating RhoA activation in response to CNS myelin. Knockdown of AMIGO3 in myelin-inhibited adult primary DRG and retinal cultures promoted disinhibited neurite growth when cells were stimulated with appropriate neurotrophic factors. These findings demonstrate that AMIGO3 substitutes for LINGO-1 in the NgR1-p75/TROY inhibitory signalling complex and suggests that the NgR1-p75/TROY-AMIGO3 receptor complex mediates myelin-induced inhibition of axon growth acutely in the CNS. Thus, antagonizing AMIGO3 rather than LINGO-1 immediately after CNS injury is likely to be a more effective therapeutic strategy for promoting CNS axon regeneration when combined with neurotrophic factor administration.

  10. Centralization of the deuterostome nervous system predates chordates.

    PubMed

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

    2009-08-11

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

  11. Distinctions Among Circulating Antibody Secreting Cell Populations, Including B-1 Cells, in Human Adult Peripheral Blood1

    PubMed Central

    Quách, Tâm D.; Rodríguez-Zhurbenko, Nely; Hopkins, Thomas J.; Guo, Xiaoti; Vázquez, Ana María Hernández; Li, Wentian; Rothstein, Thomas L.

    2015-01-01

    Human antibody secreting cell (ASC) populations in circulation are not well studied. In addition to B-1 (CD20+CD27+CD38lo/intCD43+) cell and the conventional plasmablast (CD20-CD27hiCD38hi) cell populations, here we identified a novel B cell population termed 20+38hi B cells (CD20+CD27hiCD38hi) that spontaneously secretes antibody. At steady state, 20+38hi B cells are distinct from plasmablasts on the basis of CD20 expression, amount of antibody production, frequency of mutation, and diversity of B cell receptor repertoire. However, cytokine treatment of 20+38hi B cells induces loss of CD20 and acquisition of CD138, suggesting that 20+38hi B cells are precursors to plasmablasts, or pre-plasmablasts. We then evaluated similarities and differences between CD20+CD27+CD38lo/intCD43+ B-1 cells, CD20+CD27hiCD38hi 20+38hi B cells, CD20-CD27hiCD38hi plasmablasts, and CD20+CD27+CD38lo/intCD43- memory B cells. We found that B-1 cells differ from 20+38hi B cells and plasmablasts in numbers of ways, including antigen expression, morphological appearance, transcriptional profiling, antibody skewing, antibody repertoire, and secretory response to stimulation. In terms of gene expression, B-1 cells align more closely with memory B cells than with 20+38hi B cells or plasmablasts, but differ in that memory B cells do not express antibody secretion related genes. We found that, B-1 cell antibodies utilize Vh4-34, which is often associated with autoreactivity, 3 to 6-fold more often than other B cell populations. Along with selective production of IgM anti-PC, this data suggests that human B-1 cells might be preferentially selected for autoreactivity/natural-specificity. In sum, our results indicate that human healthy adult peripheral blood at steady state consists of 3 distinct ASC populations. PMID:26740107

  12. Cloning of the GABAB Receptor Subunits B1 and B2 and their Expression in the Central Nervous System of the Adult Sea Lamprey

    PubMed Central

    Romaus-Sanjurjo, Daniel; Fernández-López, Blanca; Sobrido-Cameán, Daniel; Barreiro-Iglesias, Antón; Rodicio, María Celina

    2016-01-01

    In vertebrates, γ-aminobutyric acid (GABA) is the main inhibitory transmitter in the central nervous system (CNS) acting through ionotropic (GABAA) and metabotropic (GABAB) receptors. The GABAB receptor produces a slow inhibition since it activates second messenger systems through the binding and activation of guanine nucleotide-binding proteins [G-protein-coupled receptors (GPCRs)]. Lampreys are a key reference to understand molecular evolution in vertebrates. The importance of the GABAB receptor for the modulation of the circuits controlling locomotion and other behaviors has been shown in pharmacological/physiological studies in lampreys. However, there is no data about the sequence of the GABAB subunits or their expression in the CNS of lampreys. Our aim was to identify the sea lamprey GABAB1 and GABAB2 transcripts and study their expression in the CNS of adults. We cloned two partial sequences corresponding to the GABAB1 and GABAB2 cDNAs of the sea lamprey as confirmed by sequence analysis and comparison with known GABAB sequences of other vertebrates. In phylogenetic analyses, the sea lamprey GABAB sequences clustered together with GABABs sequences of vertebrates and emerged as an outgroup to all gnathostome sequences. We observed a broad and overlapping expression of both transcripts in the entire CNS. Expression was mainly observed in neuronal somas of the periventricular regions including the identified reticulospinal cells. No expression was observed in identifiable fibers. Comparison of our results with those reported in other vertebrates indicates that a broad and overlapping expression of the GABAB subunits in the CNS is a conserved character shared by agnathans and gnathostomes. PMID:28008311

  13. Impact of Cranial Irradiation Added to Intrathecal Conditioning in Hematopoietic Cell Transplantation in Adult Acute Myeloid Leukemia With Central Nervous System Involvement

    SciTech Connect

    Mayadev, Jyoti S.; Douglas, James G.; Storer, Barry E.; Appelbaum, Frederick R.; Storb, Rainer

    2011-05-01

    Purpose: Neither the prognostic importance nor the appropriate management of central nervous system (CNS) involvement is known for patients with acute myeloid leukemia (AML) undergoing hematopoietic cell transplantation (HCT). We examined the impact of a CNS irradiation boost to standard intrathecal chemotherapy (ITC). Methods and Materials: From 1995 to 2005, a total of 648 adult AML patients received a myeloablative HCT: 577 patients were CNS negative (CNS-), and 71 were CNS positive (CNS+). Of the 71 CNS+ patients, 52 received intrathecal chemotherapy alone (CNS+ITC), and 19 received ITC plus an irradiation boost (CNS+RT). Results: The CNS-, CNS+ITC, and CNS+RT patients had 1- and 5-year relapse-free survivals (RFS) of 43% and 35%, 15% and 6%, and 37% and 32%, respectively. CNS+ITC patients had a statistically significant worse RFS compared with CNS- patients (hazard ratio [HR], 2.65; 95% confidence interval [CI], 2.0-3.6; p < 0.0001). CNS+RT patients had improved relapse free survival over that of CNS+ITC patients (HR, 0.45; 95% CI, 0.2-0.8; p = 0.01). The 1- and 5-year overall survivals (OS) of patients with CNS-, CNS+ITC, and CNS+RT, were 50% and 38%, 21% and 6%, and 53% and 42%, respectively. The survival of CNS+RT were significantly better than CNS+ITC patients (p = 0.004). After adjusting for known risk factors, CNS+RT patients had a trend toward lower relapse rates and reduced nonrelapse mortality. Conclusions: CNS+ AML is associated with a poor prognosis. The role of a cranial irradiation boost to intrathecal chemotherapy appears to mitigate the risk of CNS disease, and needs to be further investigated to define optimal treatment strategies.

  14. Mobilization and collection of peripheral blood stem cells: guidelines for blood volume to process, based on CD34-positive blood cell count in adults and children.

    PubMed

    Anguita-Compagnon, A T; Dibarrart, M T; Palma, J; Paredes, L; Mosso, C; Montalva, R; Salas, L; Araos, D; Delgado, I; Majlis, A

    2010-01-01

    We report 189 mobilizations and 489 collections of peripheral blood stem cells (PBSC) performed in 139 autologous transplantation patients and in 28 donors for allogeneic transplantations whose ages ranged from 2-68 years. We observed a correlation (P < .001; Pearson's coefficient 0.64) between CD34-positive cells and granulocyte-macrophage colony-forming units examined to estimate PBSC. In a subset of 287 collections (97 adults and 49 children) we obtained peripheral blood (PB) CD34-positive cell counts at 2 to 4 hours before leukapheresis. We noted a correlation between PB CD34-positive cell counts before leukapheresis and the number of CD34-positive cells per kilogram of body weight collected in the whole apheresis of the day (P < .001; Pearson's coefficient 0.82). An even better correlation was obtained between PB CD34-positive cells preapheresis and the yield of each individual blood volume (BV) processed (P < .001; Pearson's coefficient 0.87). Healthy donors and patients in each age group behaved similarly. In addition, the collection yield was greater among children than adults. These findings allowed us to develop a simple predictive model to estimate the BV to process for a target dose of CD34-positive cells per kilogram, based on the level of PBSC before apheresis in children and adults.

  15. Iatrogenic chylothorax due to pleural cavity extravasation of total parenteral nutrition in two adults receiving nutrition through a peripherally inserted central catheter.

    PubMed

    Johnson, Thomas J; Jamous, Fady G; Kooistra, Alma; Zawada, Edward T

    2010-02-01

    Extravasation of total parenteral nutrition (TPN) delivered via central lines is a known potential complication, but significant extravasations of infusate into the pleural space when using peripherally inserted central catheters (PICCs) have not been reported in adults. We report 2 cases ofpleural cavity extravasation ofTPN delivered via a PICC. Measurement of the glucose level of the effusate is a quick way to determine the presence of TPN and should be considered in any patient receiving TPN via any type of central line with a rapidly developing effusion.

  16. Current progress in use of adipose derived stem cells in peripheral nerve regeneration

    PubMed Central

    Zack-Williams, Shomari DL; Butler, Peter E; Kalaskar, Deepak M

    2015-01-01

    Unlike central nervous system neurons; those in the peripheral nervous system have the potential for full regeneration after injury. Following injury, recovery is controlled by schwann cells which replicate and modulate the subsequent immune response. The level of nerve recovery is strongly linked to the severity of the initial injury despite the significant advancements in imaging and surgical techniques. Multiple experimental models have been used with varying successes to augment the natural regenerative processes which occur following nerve injury. Stem cell therapy in peripheral nerve injury may be an important future intervention to improve the best attainable clinical results. In particular adipose derived stem cells (ADSCs) are multipotent mesenchymal stem cells similar to bone marrow derived stem cells, which are thought to have neurotrophic properties and the ability to differentiate into multiple lineages. They are ubiquitous within adipose tissue; they can form many structures resembling the mature adult peripheral nervous system. Following early in vitro work; multiple small and large animal in vivo models have been used in conjunction with conduits, autografts and allografts to successfully bridge the peripheral nerve gap. Some of the ADSC related neuroprotective and regenerative properties have been elucidated however much work remains before a model can be used successfully in human peripheral nerve injury (PNI). This review aims to provide a detailed overview of progress made in the use of ADSC in PNI, with discussion on the role of a tissue engineered approach for PNI repair. PMID:25621105

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

    PubMed

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

    2014-03-01

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

  18. Blood Culture Collection through Peripheral Intravenous Catheters Increases the Risk of Specimen Contamination among Adult Emergency Department Patients

    PubMed Central

    Self, Wesley H.; Speroff, Theodore; McNaughton, Candace D.; Wright, Patty W.; Miller, Geraldine; Johnson, James G.; Daniels, Titus L.; Talbot, Thomas R.

    2017-01-01

    Five hundred five blood cultures collected through a peripheral intravenous catheter (PIV) in an emergency department were matched to cultures obtained by dedicated venipuncture from the same patient within 10 minutes. The relative risk of contamination for cultures collected through PIVs compared with dedicated venipuncture was 1.83 (95% confidence interval, 1.08–3.11). PMID:22476282

  19. Blood culture collection through peripheral intravenous catheters increases the risk of specimen contamination among adult emergency department patients.

    PubMed

    Self, Wesley H; Speroff, Theodore; McNaughton, Candace D; Wright, Patty W; Miller, Geraldine; Johnson, James G; Daniels, Titus L; Talbot, Thomas R

    2012-05-01

    Five hundred five blood cultures collected through a peripheral intravenous catheter (PIV) in an emergency department were matched to cultures obtained by dedicated venipuncture from the same patient within 10 minutes. The relative risk of contamination for cultures collected through PIVs compared with dedicated venipuncture was 1.83 (95% confidence interval, 1.08-3.11).

  20. Baseline peripheral refractive error and changes in axial refraction during one year in a young adult population

    PubMed Central

    Hartwig, Andreas; Charman, William Neil; Radhakrishnan, Hema

    2015-01-01

    Purpose To determine whether the initial characteristics of individual patterns of peripheral refraction relate to subsequent changes in refraction over a one-year period. Methods 54 myopic and emmetropic subjects (mean age: 24.9 ± 5.1 years; median 24 years) with normal vision were recruited and underwent conventional non-cycloplegic subjective refraction. Peripheral refraction was also measured at 5° intervals over the central 60° of horizontal visual field, together with axial length. After one year, measurements of subjective refraction and axial length were repeated on the 43 subjects who were still available for examination. Results In agreement with earlier studies, higher myopes tended to show greater relative peripheral hyperopia. There was, however, considerable inter-subject variation in the pattern of relative peripheral refractive error (RPRE) at any level of axial refraction. Across the group, mean one-year changes in axial refraction and axial length did not differ significantly from zero. There was no correlation between changes in these parameters for individual subjects and any characteristic of their RPRE. Conclusion No evidence was found to support the hypothesis that the pattern of RPRE is predictive of subsequent refractive change in this age group. PMID:26188389

  1. Allogeneic stem cell transplantation for adult patients with acute lymphoblastic leukemia who had central nervous system involvement: a study from the Adult ALL Working Group of the Japan Society for Hematopoietic Cell Transplantation.

    PubMed

    Shigematsu, Akio; Kako, Shinichi; Mitsuhashi, Kenjiro; Iwato, Koji; Uchida, Naoyuki; Kanda, Yoshinobu; Fukuda, Takahiro; Sawa, Masashi; Senoo, Yasushi; Ogawa, Hiroyasu; Miyamura, Koichi; Takada, Satoru; Nagamura-Inoue, Tokiko; Morishima, Yasuo; Ichinohe, Tatsuo; Atsuta, Yoshiko; Mizuta, Shuichi; Tanaka, Junji

    2017-02-14

    The prognosis for adult acute lymphoblastic leukemia (ALL) patients with central nervous system (CNS) involvement (CNS+) who received allogeneic hematopoietic stem cell transplantation (allo-SCT) remains unclear. We retrospectively compared the outcomes of allo-SCT for patients with CNS involvement and for patients without CNS involvement (CNS-) using a database in Japan. The eligibility criteria for this study were as follows: diagnosis of ALL, aged more than 16 years, allo-SCT between 2005 and 2012, and first SCT. Data for 2582 patients including 136 CNS+ patients and 2446 CNS- patients were used for analyses. As compared with CNS- patients, CNS+ patients were younger, had worse disease status at SCT and had poorer performance status (PS) at SCT (P < 0.01). Incidence of relapse was higher in CNS+ patients (P = 0.02), and incidence of CNS relapse was also higher (P < 0.01). The probability of 3-year overall survival (OS) was better in CNS- patients (P < 0.01) by univariate analysis. However, in patients who received SCT in CR, there was no difference in the probability of OS between CNS+ and CNS- patients (P = 0.38) and CNS involvement did not have an unfavorable effect on OS by multivariate analysis. CNS+ patients who achieved CR showed OS comparable to that of CNS- patients.

  2. Peripheral Neuropathy

    MedlinePlus

    Peripheral neuropathy Overview By Mayo Clinic Staff Peripheral neuropathy, a result of damage to your peripheral nerves, often causes weakness, numbness and pain, usually in your hands and feet. It can also ...

  3. Peripheral nerve regeneration and NGF-dependent neurite outgrowth of adult sensory neurons converge on STAT3 phosphorylation downstream of neuropoietic cytokine receptor gp130.

    PubMed

    Quarta, Serena; Baeumer, Bastian E; Scherbakov, Nadja; Andratsch, Manfred; Rose-John, Stefan; Dechant, Georg; Bandtlow, Christine E; Kress, Michaela

    2014-09-24

    After nerve injury, adult sensory neurons can regenerate peripheral axons and reconnect with their target tissue. Initiation of outgrowth, as well as elongation of neurites over long distances, depends on the signaling of receptors for neurotrophic growth factors. Here, we investigated the importance of gp130, the signaling subunit of neuropoietic cytokine receptors in peripheral nerve regeneration. After sciatic nerve crush, functional recovery in vivo was retarded in SNS-gp130(-/-) mice, which specifically lack gp130 in sensory neurons. Correspondingly, a significantly reduced number of free nerve endings was detected in glabrous skin from SNS-gp130(-/-) compared with control mice after nerve crush. Neurite outgrowth and STAT3 activation in vitro were severely reduced in cultures in gp130-deficient cultured neurons. Surprisingly, in neurons obtained from SNS-gp130(-/-) mice the increase in neurite length was reduced not only in response to neuropoietic cytokine ligands of gp130 but also to nerve growth factor (NGF), which does not bind to gp130-containing receptors. Neurite outgrowth in the absence of neurotrophic factors was partially rescued in gp130-deficient neurons by leptin, which activates STAT3 downstream of leptic receptor and independent of gp130. The neurite outgrowth response of gp130-deficient neurons to NGF was fully restored in the presence of leptin. Based on these findings, gp130 signaling via STAT3 activation is suggested not only to be an important regulator of peripheral nerve regeneration in vitro and in vivo, but as determining factor for the growth promoting action of NGF in adult sensory neurons.

  4. Effects of strawberry supplementation on mobility and cognition in older adults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    During aging, functional changes in the central and peripheral nervous system can alter mobility and cognition - in some cases leading to early cognitive decline, disability, or injurious falls among older adults. Previously, we have shown that two months of dietary supplementation with berry fruit...

  5. 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 ...

  6. A primary primitive neuroectodermal tumor of the central nervous system in a 51-year-old woman: a case report and literature review.

    PubMed

    Ašmonienė, Virginija; Skiriutė, Daina; Gudinavičienė, Inga; Tamašauskas, Šarūnas; Skauminas, Kęstutis; Deltuva, Vytenis Pranas; Tamašauskas, Arimantas

    2011-01-01

    Primitive neuroectodermal tumors are a group of rare, aggressive, and highly malignant embryonal tumors of unknown etiology of the central and peripheral nervous systems. It is a term for a group of small round cell tumors thought to be derived from fetal neuroectodermal precursor cells. Primitive neuroectodermal tumor is usually described as a tumor of children younger than 15 years and is very rare in adults. The article presents a short literature review and a rare case of a primary primitive neuroectodermal tumor of the central nervous system diagnosed in a 51-year-old woman.

  7. Ambient geothermal hydrogen sulfide exposure and peripheral neuropathy.

    PubMed

    Pope, Karl; So, Yuen T; Crane, Julian; Bates, Michael N

    2017-02-14

    The mechanism of toxicity of hydrogen sulfide (H2S) gas is thought mainly to operate through effects on the nervous system. The gas has high acute toxicity, but whether chronic exposure causes effects, including peripheral neuropathy, is yet unclear. The city of Rotorua, New Zealand, sits on an active geothermal field and the population has some of the highest measured ambient H2S exposures. A previous study in Rotorua provided evidence that H2S is associated with peripheral neuropathy. Using clinical methods, the present study sought to investigate and possibly confirm this association in the Rotorua population. The study population comprised 1635 adult residents of Rotorua, aged 18-65. Collected data relevant to the peripheral neuropathy investigation included symptoms, ankle stretch reflex, vibration sensitivity, as measured by the timed-tuning fork test and a Bio-Thesiometer (Bio-Medical Instrument Co., Ohio), and light touch sensitivity measured by monofilaments. An exposure metric, estimating time-weighted H2S exposure across the last 30 years was used. Principal components analysis was used to combine data across the various indicators of possible peripheral neuropathy. The main data analysis used linear regression to examine associations between the peripheral nerve function indicators and H2S exposure. None of the peripheral nerve function indicators were associated with H2S exposure, providing no evidence that H2S exposure at levels found in Rotorua is a cause of peripheral neuropathy. The earlier association between H2S exposure and peripheral neuropathy diagnoses may be attributable to the ecological study design used. The possibility that H2S exposure misclassification could account for the lack of association found cannot be entirely excluded.

  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. Nervous system (image)

    MedlinePlus

    Peripheral Neuropathy is not a distinct disease, but the manifestation of many conditions that damage the peripheral nerves ( ... abnormal. Damaged motor nerves impair movement or function. Peripheral neuropathy may be caused by direct or indirect injury, ...

  10. Cholinergic, serotoninergic and peptidergic components of the nervous system of Discocotyle sagittata (Monogenea:Polyopisthocotylea).

    PubMed

    Cable, J; Marks, N J; Halton, D W; Shaw, C; Johnston, C F; Tinsley, R C; Gannicott, A M

    1996-12-01

    Cholinergic, serotoninergic (5-HT) and peptidergic neuronal pathways have been demonstrated in both central and peripheral nervous systems of adult Discocotyle sagittata, using enzyme histochemistry and indirect immunocytochemistry in conjunction with confocal scanning laser microscopy. Antisera to 2 native flatworm neuropeptides, neuropeptide F and the FMRFamide-related peptide (FaRP), GNFFRFamide, were employed to detect peptide immunoreactivity. The CNS is composed of paired cerebral ganglia and connecting dorsal commissure, together with several paired longitudinal nerve cords. The main longitudinal nerve cords (lateral, ventral and dorsal) are interconnected at intervals by a series of annular cross-connectives, producing a ladder-like arrangement typical of the platyhelminth nervous system. At the level of the haptor, the ventral cords provide nerve roots which innervate each of the 9 clamps. Cholinergic and peptidergic neuronal organisation was similar, but distinct from that of the serotoninergic components. The PNS and reproductive system are predominantly innervated by peptidergic neurones.

  11. Pleiotrophin and peripheral nerve injury.

    PubMed

    Jin, Li; Jianghai, Chen; Juan, Liu; Hao, Kang

    2009-10-01

    The proto-oncogene pleiotrophin, discovered in 1989, was considered as a multifunctional growth factor, which played an important role in tumor occurrence, development, and central nervous system. The latest research showed that pleiotrophin signal pathway probably participated in neural repair after peripheral nerve injury, especially in the following critical points, such as the protection of spinal cord neuron, the promotion of the speed of neuron axon regeneration, the guidance of neuron axon regeneration, skeleton muscle reinnervation, and so on. It potentially plays a key role in the guidance of neural axon regeneration in peripheral nervous system and muscle reinnervation. With the deepening of related researches, pleiotrophin gene would become a controllable target for improving the repairing effect of peripheral nerve injury and reconstruction of the neuromuscular junction.

  12. Enhanced genetic modification of adult growth factor mobilized peripheral blood hematopoietic stem and progenitor cells with rapamycin.

    PubMed

    Li, Lijing; Torres-Coronado, Mónica; Gu, Angel; Rao, Anitha; Gardner, Agnes M; Epps, Elizabeth W; Gonzalez, Nancy; Tran, Chy-Anh; Wu, Xiwei; Wang, Jin-Hui; DiGiusto, David L

    2014-10-01

    Genetic modification of adult human hematopoietic stem and progenitor cells (HSPCs) with lentiviral vectors leads to long-term gene expression in the progeny of the HSPCs and has been used to successfully treat several monogenic diseases. In some cases, the gene-modified cells have a selective growth advantage over nonmodified cells and eventually are the dominant engrafted population. However, in disease indications for which the gene-modified cells do not have a selective advantage, optimizing transduction of HSPC is paramount to successful stem cell-based gene therapy. We demonstrate here that transduction of adult CD34+ HSPCs with lentiviral vectors in the presence of rapamycin, a widely used mTORC1 inhibitor, results in an approximately threefold increase in stable gene marking with minimal effects on HSPC growth and differentiation. Using this approach, we have demonstrated that we can enhance the frequency of gene-modified HSPCs that give rise to clonogenic progeny in vitro without excessive increases in the number of vector copies per cell or changes in integration pattern. The genetic marking of HSPCs and expression of transgenes is durable, and transplantation of gene-modified HSPCs into immunodeficient mice results in high levels of gene marking of the lymphoid and myeloid progeny in vivo. The prior safe clinical history of rapamycin in other applications supports the use of this compound to generate gene-modified autologous HSPCs for our HIV gene therapy clinical trials.

  13. Injury signals cooperate with Nf1 loss to relieve the tumor-suppressive environment of adult peripheral nerve.

    PubMed

    Ribeiro, Sara; Napoli, Ilaria; White, Ian J; Parrinello, Simona; Flanagan, Adrienne M; Suter, Ueli; Parada, Luis F; Lloyd, Alison C

    2013-10-17

    Schwann cells are highly plastic cells that dedifferentiate to a progenitor-like state following injury. However, deregulation of this plasticity, may be involved in the formation of neurofibromas, mixed-cell tumors of Schwann cell (SC) origin that arise upon loss of NF1. Here, we show that adult myelinating SCs (mSCs) are refractory to Nf1 loss. However, in the context of injury, Nf1-deficient cells display opposing behaviors along the wounded nerve; distal to the injury, Nf1(-/-) mSCs redifferentiate normally, whereas at the wound site Nf1(-/-) mSCs give rise to neurofibromas in both Nf1(+/+) and Nf1(+/-) backgrounds. Tracing experiments showed that distinct cell types within the tumor derive from Nf1-deficient SCs. This model of neurofibroma formation demonstrates that neurofibromas can originate from adult SCs and that the nerve environment can switch from tumor suppressive to tumor promoting at a site of injury. These findings have implications for both the characterization and treatment of neurofibromas.

  14. Peripheral doses from pediatric IMRT

    SciTech Connect

    Klein, Eric E.; Maserang, Beth; Wood, Roy; Mansur, David

    2006-07-15

    Peripheral dose (PD) data exist for conventional fields ({>=}10 cm) and intensity-modulated radiotherapy (IMRT) delivery to standard adult-sized phantoms. Pediatric peripheral dose reports are limited to conventional therapy and are model based. Our goal was to ascertain whether data acquired from full phantom studies and/or pediatric models, with IMRT treatment times, could predict Organ at Risk (OAR) dose for pediatric IMRT. As monitor units (MUs) are greater for IMRT, it is expected IMRT PD will be higher; potentially compounded by decreased patient size (absorption). Baseline slab phantom peripheral dose measurements were conducted for very small field sizes (from 2 to 10 cm). Data were collected at distances ranging from 5 to 72 cm away from the field edges. Collimation was either with the collimating jaws or the multileaf collimator (MLC) oriented either perpendicular or along the peripheral dose measurement plane. For the clinical tests, five patients with intracranial or base of skull lesions were chosen. IMRT and conventional three-dimensional (3D) plans for the same patient/target/dose (180 cGy), were optimized without limitation to the number of fields or wedge use. Six MV, 120-leaf MLC Varian axial beams were used. A phantom mimicking a 3-year-old was configured per Center for Disease Control data. Micro (0.125 cc) and cylindrical (0.6 cc) ionization chambers were appropriated for the thyroid, breast, ovaries, and testes. The PD was recorded by electrometers set to the 10{sup -10} scale. Each system set was uniquely calibrated. For the slab phantom studies, close peripheral points were found to have a higher dose for low energy and larger field size and when MLC was not deployed. For points more distant from the field edge, the PD was higher for high-energy beams. MLC orientation was found to be inconsequential for the small fields tested. The thyroid dose was lower for IMRT delivery than that predicted for conventional (ratio of IMRT/cnventional ranged

  15. Long-term delivery of FGF-6 changes the fiber type and fatigability of muscle reinnervated from embryonic neurons transplanted into adult rat peripheral nerve.

    PubMed

    Grumbles, Robert M; Casella, Gizelda T B; Rudinsky, Michelle J; Wood, Patrick M; Sesodia, Sanjay; Bent, Melissa; Thomas, Christine K

    2007-07-01

    Motoneuron death leads to muscle denervation and atrophy. Transplantation of embryonic neurons into peripheral nerves results in reinnervation and provides a strategy to rescue muscles from atrophy independent of neuron replacement in a damaged or diseased spinal cord. But the count of regenerating axons always exceeds the number of motor units in this model, so target-derived trophic factor levels may limit reinnervation. Our aim was to examine whether long-term infusion of fibroblast growth factor-6 (FGF-6) into denervated medial gastrocnemius muscles improved the function of muscles reinnervated from neurons transplanted into nerve of adult Fischer rats. Factor delivery (10 microg, 4 weeks) began after sciatic nerve transection. After a week of nerve degeneration, 1 million embryonic day 14-15 ventral spinal cord cells were transplanted into the distal tibial stump as a neuron source. Ten weeks later, neurons that expressed motoneuron markers survived in the nerves. More myelinated axons were in nerves to saline-treated muscles than in FGF-6-treated muscles. However, each group showed comparable reductions in muscle fiber atrophy because of reinnervation. Mean reinnervated fiber area was 43%-51% of non-denervated fibers. Denervated fiber area averaged 11%. FGF-6-treated muscles were more fatigable than other reinnervated muscles but had stronger motor units and fewer type I fibers than did saline-treated muscles. FGF-6 thus influenced function by changing the type of fiber reinnervated by transplanted neurons. Deficits in FGF-6 may also contribute to the increase in type I fibers in muscles reinnervated from peripheral axons, suggesting that the effects of FGF-6 on fiber type are independent of the neuron source used for reinnervation.

  16. 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.

  17. 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

  18. Dietary intake and peripheral arterial disease incidence in middle-aged adults: the Atherosclerosis Risk in Communities (ARIC) Study.

    PubMed

    Ogilvie, Rachel P; Lutsey, Pamela L; Heiss, Gerardo; Folsom, Aaron R; Steffen, Lyn M

    2017-03-01

    Background: Peripheral arterial disease (PAD) is a costly source of morbidity and mortality among older persons in the United States. Dietary intake plays a role in the development of atherosclerotic cardiovascular disease; however, few studies have examined the relation of food intake or dietary patterns with PAD.Objective: We examined the relation between habitual dietary intake at midlife and incident PAD over ∼20 y of follow-up.Design: Among 14,082 participants enrolled in the ARIC (Atherosclerosis Risk in Communities) Study initially free of PAD, dietary intake was assessed at baseline in 1987-1989 by using a modified Harvard food-frequency questionnaire. Food groups were created, and principal components analysis was used to develop "healthy" and "Western" dietary patterns; both were categorized into quintiles or quartiles. Incident PAD was determined by an ankle-brachial index <0.9 assessed at 2 subsequent examinations and hospital discharge codes through 2012. Multivariate-adjusted Cox proportional hazards regression was used.Results: During a mean follow-up of 19.9 y, 1569 participants developed incident PAD. In models adjusted for demographic characteristics, behaviors, and food groups, the HRs (95% CIs) for incident PAD increased across quintiles of meat consumption [quintile 1: reference, quintile 2: 1.38 (1.16, 1.65), quintile 3: 1.38 (1.16, 1.65), quintile 4: 1.45 (1.20, 1.74), quintile 5: 1.66 (1.36, 2.03); P-trend <0.001]. Compared with those who drank no alcohol, those who had 1-6 drinks/wk had a lower risk of incident PAD [0.78 (0.68, 0.89)]. For coffee, ≥4 cups/d compared with none was inversely associated with incident PAD [quintile 5 compared with quintile 1: 0.84 (0.75, 1.00); P-trend = 0.014]. There was no association between other food groups or patterns and incident PAD.Conclusions: In this prospective cohort study, greater meat consumption was associated with a higher risk, and moderate alcohol consumption was associated with a lower

  19. The tumor suppressor HHEX inhibits axon growth when prematurely expressed in developing central nervous system neurons

    PubMed Central

    Simpson, Matthew T; Venkatesh, Ishwariya; Callif, Ben L; Thiel, Laura K; Coley, Denise M; Winsor, Kristen N; Wang, Zimei; Kramer, Audra A; Lerch, Jessica K; Blackmore, Murray G

    2015-01-01

    Neurons in the embryonic and peripheral nervous system respond to injury by activating transcriptional programs supportive of axon growth, ultimately resulting in functional recovery. In contrast, neurons in the adult central nervous system (CNS) possess a limited capacity to regenerate axons after injury, fundamentally constraining repair. Activating pro-regenerative gene expression in CNS neurons is a promising therapeutic approach, but progress is hampered by incomplete knowledge of the relevant transcription factors. An emerging hypothesis is that factors implicated in cellular growth and motility outside the nervous system may also control axon growth in neurons. We therefore tested sixty-nine transcription factors, previously identified as possessing tumor suppressive or oncogenic properties in non-neuronal cells, in assays of neurite outgrowth. This screen identified YAP1 and E2F1 as enhancers of neurite outgrowth, and PITX1, RBM14, ZBTB16, and HHEX as inhibitors. Follow-up experiments focused on the tumor suppressor HHEX, one of the strongest growth inhibitors. HHEX is widely expressed in adult CNS neurons, including corticospinal tract neurons after spinal injury, but is present in only trace amounts in immature cortical neurons and adult peripheral neurons. HHEX overexpression in early postnatal cortical neurons reduced both initial axonogenesis and the rate of axon elongation, and domain deletion analysis strongly implicated transcriptional repression as the underlying mechanism. These findings suggest a role for HHEX in restricting axon growth in the developing CNS, and substantiate the hypothesis that previously identified oncogenes and tumor suppressors can play conserved roles in axon extension. PMID:26306672

  20. Effect of peripheral kisspeptin administration on adiponectin, leptin, and resistin secretion under fed and fasting conditions in the adult male rhesus monkey (Macaca mulatta).

    PubMed

    Wahab, F; Bano, R; Jabeen, S; Irfan, S; Shahab, M

    2010-07-01

    In the last few years, kisspeptin-KISS1R signaling has appeared as a major regulator of the reproductive function in several vertebrate species. However, KISS1(encoding kisspeptin) and its putative receptor, KISS1R, are expressed in several other tissues. Adipose tissue, which secretes many peptides with diverse functions in normal physiology, expresses KISS1, which is modulated by gonadal steroids as well as by body nutritional status. Similarly, KISS1Rexpression is also found in adipose tissue, but the local role of kisspeptin in adipocyte function is currently unknown. Therefore, in the present study the effects of exogenous human kisspeptin-10 (KP10) were studied on three important adipokines, namely, adiponectin, leptin, and resistin in a set of four chair-restraint habituated intact adult male rhesus monkeys under; 1) normal fed conditions, 2) 24-h fasting conditions, and 3) 48-h fasting conditions. Plasma resistin and leptin levels decreased (p<0.01), whereas adiponectin levels increased (p<0.05) in fasted monkeys. Kisspeptin administration significantly increased (p<0.05) mean plasma adiponectin levels under fed and 24-h fasting conditions as compared to pretreatment or vehicle-treatment levels. A stimulatory effect was also observed on the 48-h fasting stimulated plasma adiponectin levels, but it lacked statistical significance. In contrast, no effect of kisspeptin was observed on mean plasma leptin and resistin levels. Thus, the present study demonstrated a stimulatory effect of peripheral kisspeptin administration on the plasma adiponectin levels under fed and 24-h fasting conditions in the adult male rhesus monkey. These findings, therefore, assign a novel role to kisspeptin, a regulator of adipocyte function in higher primate.

  1. A protein related to p21-activated kinase (PAK) that is involved in neurogenesis in the Drosophila adult central nervous system.

    PubMed

    Melzig, J; Rein, K H; Schäfer, U; Pfister, H; Jäckle, H; Heisenberg, M; Raabe, T

    1998-11-05

    Brains are organized by the developmental processes generating them. The embryonic neurogenic phase of Drosophila melanogaster has been studied in detail at the genetic, cellular and molecular level. In contrast, much of what is known of postembryonic brain development has been gathered by neuroanatomical and gene expression studies. The molecular mechanisms underlying cellular diversity and structural organisation in the adult brain, such as the establishment of the correct neuroblast number, the spatial and temporal control of neuroblast proliferation, cell fate determination, and the generation of the precise pattern of neuronal connectivity, are largely unknown. In a screen for viable mutations affecting adult central brain structures, we isolated the mushroom bodies tiny (mbt) gene of Drosophila, which encodes a protein related to p21-activated kinase (PAK). We show that mutations in mbt primarily interfere with the generation or survival of the intrinsic cells (Kenyon cells) of the mushroom body, a paired neuropil structure in the adult brain involved in learning and memory.

  2. Highly Expression of CD11b and CD32 on Peripheral Blood Mononuclear Cells from Patients with Adult-Onset Still’s Disease

    PubMed Central

    Kim, Hyoun-Ah; Choi, Bunsoon; Suh, Chang-Hee; Han, Mi Hwa; Jung, Ju-Yang; Sayeed, Hasan M.; Kim, Ye Won; Sohn, Seonghyang

    2017-01-01

    Background: We investigated the potential role of several pattern-recognition receptors (PRRs; CD11b, CD11c, CD32, CD206, CD209, and dectin-1) in adult-onset Still’s disease (AOSD). Methods: The study included 13 untreated AOSD patients, 19 rheumatoid arthritis (RA) patients (as a disease control), and 19 healthy controls (HCs). The PRRs were quantified in peripheral blood using flow cytometry. The serum levels of interleukin-17 (IL-17), IL-18, and IL-23 were measured by enzyme-linked immunosorbent assay. Results: Significantly higher mean frequencies of cells presenting CD11b and CD32 from whole blood were observed in patients with AOSD than in patients with RA or HC. The levels of IL-17, IL-18, and IL-23 were elevated in AOSD patients compared to HCs. CD11b frequencies from whole cells correlated with systemic scores, lactate dehydrogenase (LDH) levels, aspartate transaminase levels, interleukin-23 (IL-23) levels, and IL-18. Frequencies of CD209 from granulocytes were significantly correlated with systemic scores, and the erythrocyte sedimentation rate and levels of C-reactive protein, ferritin, LDH, IL-23, and interleukin-18 (IL-18). Conclusions: Elevated frequencies of circulating CD11b-positive cells and positive correlations with disease activity markers suggest that circulating CD11b-positive cells contribute to the pathogenesis of AOSD. PMID:28106835

  3. Super-oxide anion production and antioxidant enzymatic activities associated with the executive functions in peripheral blood mononuclear cells of healthy adult samples.

    PubMed

    Pesce, M; Rizzuto, A; La Fratta, I; Tatangelo, R; Campagna, G; Iannasso, M; Ferrone, A; Franceschelli, S; Speranza, L; Patruno, A; De Lutiis, M A; Felaco, M; Grilli, A

    2016-05-01

    Executive Functions (EFs) involve a set of high cognitive abilities impairment which have been successfully related to a redox omeostasis imbalance in several psychiatric disorders. Firstly, we aimed to investigate the relationship between executive functioning and some oxidative metabolism parameters in Peripheral Blood Mononuclear Cells (PBMCs) from healthy adult samples. The Brown Attention-Deficit Disorder Scales were administered to assess five specific facets of executive functioning. Total superoxide anion production, Super Oxide Dismutase (SOD), Catalase (CAT), Glutathione Reductase (GR) and Glutathione Peroxidase (GPx) activities were evaluated on proteins extracted from the PBMCs. We found significant positive correlations between superoxide anion production and the total score of the 'Brown' Scale and some of its clusters. The GPx and CAT activities were negatively associated with the total score and some clusters. In a linear regression analysis, these biological variables were indicated as the most salient predictors of the total score, explaining the 24% variance (adjusted R(2)=0.24, ANOVA, p<.001). This study provides novel evidence that Executive Functions have underpinnings in the oxidative metabolism, as ascertained in healthy subjects.

  4. Microglia in central nervous system repair after injury.

    PubMed

    Jin, Xuemei; Yamashita, Toshihide

    2016-05-01

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

  5. Biomarkers of adult and developmental neurotoxicity

    SciTech Connect

    Slikker, William

    2005-08-07

    Neurotoxicity may be defined as any adverse effect on the structure or function of the central and/or peripheral nervous system by a biological, chemical, or physical agent. A multidisciplinary approach is necessary to assess adult and developmental neurotoxicity due to the complex and diverse functions of the nervous system. The overall strategy for understanding developmental neurotoxicity is based on two assumptions: (1) significant differences in the adult versus the developing nervous system susceptibility to neurotoxicity exist and they are often developmental stage dependent; (2) a multidisciplinary approach using neurobiological, including gene expression assays, neurophysiological, neuropathological, and behavioral function is necessary for a precise assessment of neurotoxicity. Application of genomic approaches to developmental studies must use the same criteria for evaluating microarray studies as those in adults including consideration of reproducibility, statistical analysis, homogenous cell populations, and confirmation with non-array methods. A study using amphetamine to induce neurotoxicity supports the following: (1) gene expression data can help define neurotoxic mechanism(s) (2) gene expression changes can be useful biomarkers of effect, and (3) the site-selective nature of gene expression in the nervous system may mandate assessment of selective cell populations.

  6. Embryonic exposure to 10 μg L(-1) lead results in female-specific expression changes in genes associated with nervous system development and function and Alzheimer's disease in aged adult zebrafish brain.

    PubMed

    Lee, Jinyoung; Freeman, Jennifer L

    2016-06-01

    A developmental lead (Pb) exposure has been proposed as an environmental risk factor for adult neurodegenerative diseases including Alzheimer's disease (AD). Recent animal studies showed pathological characteristics of AD in adults with a developmental Pb exposure, but additional studies are needed to investigate this phenomenon. To further assess the relationship between an embryonic Pb exposure and latent neurological alterations, the brain of adult female and male zebrafish aged 12 months that were exposed to a control treatment or 10 μg L(-1) Pb only during embryogenesis (1-72 hours after fertilization) were analyzed on a zebrafish-specific microarray platform. Gene ontology and pathway analysis revealed similarities in the top disease and functional categories in both sexes, but females had 4.3 times more genes altered than males. In addition, alterations in genes associated with nervous system development and function were more pronounced with a set of 89 genes associated with AD including amyloid precursor protein (APP), apolipoprotein (APOE), and sortlin-related receptor precursor (SORL1) observed to be changed in adult females. Our observations suggest that an embryonic exposure to Pb at levels as low as 10 μg L(-1) disturb global gene expression patterns in a sex-specific manner that could lead to neurological alterations in later life. With these findings, future studies investigating the adverse neurological outcomes of these changes in gene expression will facilitate our understanding of the impact of an embryonic 10 μg L(-1) Pb exposure on neurological disease pathogenesis and the inclusion of additional concentrations will broaden our knowledge of dose-dependent changes.

  7. Responses of Six-Weeks Aquatic Exercise on the Autonomic Nervous System, Peak Nasal Inspiratory Flow and Lung Functions in Young Adults with Allergic Rhinitis.

    PubMed

    Janyacharoen, Taweesak; Kunbootsri, Narupon; Arayawichanon, Preeda; Chainansamit, Seksun; Sawanyawisuth, Kittisak

    2015-06-01

    Allergic rhinitis is a chronic respiratory disease. Sympathetic hypofunction is identified in all of the allergic rhinitis patients. Moreover, allergic rhinitis is associated with decreased peak nasal inspiratory flow (PNIF) and impaired lung functions. The aim of this study was to investigate effects of six-week of aquatic exercise on the autonomic nervous system function, PNIF and lung functions in allergic rhinitis patients. Twenty-six allergic rhinitis patients, 12 males and 14 females were recruited in this study. Subjects were diagnosed by a physician based on history, physical examination, and positive reaction to a skin prick test. Subjects were randomly assigned to two groups. The control allergic rhinitis group received education and maintained normal life. The aquatic group performed aquatic exercise for 30 minutes a day, three days a week for six weeks. Heart rate variability, PNIF and lung functions were measured at the beginning, after three weeks and six weeks. There were statistically significant increased low frequency normal units (LF n.u.), PNIF and showed decreased high frequency normal units (HF n.u.) at six weeks after aquatic exercise compared with the control group. Six weeks of aquatic exercise could increase sympathetic activity and PNIF in allergic rhinitis patients.

  8. Impact of epidemiological characteristics of supratentorial gliomas in adults brought about by the 2016 world health organization classification of tumors of the central nervous system.

    PubMed

    Jiang, Haihui; Cui, Yong; Wang, Junmei; Lin, Song

    2016-11-24

    The latest World Health Organization (WHO) classification of tumors of the central nervous system (CNS) integrates both histological and molecular features in the definition of diagnostic entities. This new approach enrolls novel entities of gliomas. In this study, we aimed to reveal the epidemiological characteristics, including age at diagnosis, gender ratio, tumor distribution and survival, of these new entities. We retrospectively reclassified 1210 glioma samples according to the 2016 CNS WHO diagnostic criteria. In our cohort, glioblastoma multiforme (GBM) with wildtype isocitrate dehydrogenase (IDH) was the most common malignant tumor in the brain. Almost all gliomas were more prevalent in males, especially in the cluster of WHO grade III gliomas and IDH-wildtype GBM. Age at diagnosis was directly proportional to tumor grade. With respect to the distribution by histology, we found that gliomas concurrent with IDH-mutant and 1p/19q-codeleted or with single IDH-mutant were mainly distributed in frontal lobe, while those with IDH-wildtype were dominant in temporal lobe. Lesions located in insular lobe were more likely to be IDH-mutant astrocytoma. In summary, our results elucidated the epidemiological characteristics as well as the regional constituents of these new gliomas entities, which could bring insights into tumorigenesis and personalized treatment of Chinese glioma population.

  9. [Nervous system involvement in Madelung's syndrome].

    PubMed

    Tolubaev, N S; Gerasimovich, L A; Tolubaeva, N I

    1992-04-01

    Due to proliferation of the fatty tissue in the neck and depending on the degree of compression of the pharynx, larynx, vessels, nerve trunks the patients show, respiratory disorders, swallowing disturbances, dysarthria, stenocardia, neck and occipital pain, scalenus syndrome, cervicobrachialgia, posterior cervical sympathetic syndrome, disorders of the cerebral and spinal blood circulation. Involvement of both the central and peripheral nervous system are observed in Madelung's disease.

  10. Extrinsic cellular and molecular mediators of peripheral axonal regeneration.

    PubMed

    Bosse, Frank

    2012-07-01

    The ability of injured peripheral nerves to regenerate and reinnervate their original targets is a characteristic feature of the peripheral nervous system (PNS). On the other hand, neurons of the central nervous system (CNS), including retinal ganglion cell (RGC) axons, are incapable of spontaneous regeneration. In the adult PNS, axonal regeneration after injury depends on well-orchestrated cellular and molecular processes that comprise a highly reproducible series of degenerative reactions distal to the site of injury. During this fine-tuned process, named Wallerian degeneration, a remodeling of the distal nerve fragment prepares a permissive microenvironment that permits successful axonal regrowth originating from the proximal nerve fragment. Therefore, a multitude of adjusted intrinsic and extrinsic factors are important for surviving neurons, Schwann cells, macrophages and fibroblasts as well as endothelial cells in order to achieve successful regeneration. The aim of this review is to summarize relevant extrinsic cellular and molecular determinants of successful axonal regeneration in rodents that contribute to the regenerative microenvironment of the PNS.

  11. The effect of mild traumatic brain injury on peripheral nervous system pathology in wild-type mice and the G93A mutant mouse model of motor neuron disease.

    PubMed

    Evans, T M; Jaramillo, C A; Sataranatarajan, K; Watts, L; Sabia, M; Qi, W; Van Remmen, H

    2015-07-09

    Traumatic brain injury (TBI) is associated with a risk of neurodegenerative disease. Some suggest a link between TBI and motor neuron disease (MND), including amyotrophic lateral sclerosis (ALS). To investigate the potential mechanisms linking TBI to MND, we measured motor function and neuropathology following mild-TBI in wild-type and a transgenic model of ALS, G93A mutant mice. Mild-TBI did not alter the lifespan of G93A mice or age of onset; however, rotarod performance was impaired in G93A verses wild-type mice. Grip strength was reduced only in G93A mice after mild-TBI. Increased electromyography (EMG) abnormalities and markers of denervation (AchR, Runx1) indicate that mild-TBI may result in peripheral effects that are exaggerated in G93A mice. Markers of inflammation (cell edema, astrogliosis and microgliosis) were detected at 24 and 72h in the brain and spinal cord in wild-type and G93A mice. Levels of F2-isoprostanes, a marker of oxidative stress, were increased in the spinal cord 24h post mild-TBI in wild-type mice but were not affected by TBI in G93A mice. In summary, our data demonstrate that mild-TBI induces inflammation and oxidative stress and negatively impacts muscle denervation and motor performance, suggesting mild-TBI can potentiate motor neuron pathology and influence the development of MND in mice.

  12. A gene catalogue of the amphioxus nervous system

    PubMed Central

    Benito-Gutiérrez, Èlia

    2006-01-01

    The elaboration of extremely complex nervous systems is a major success of evolution. However, at the dawn of the post-genomic era, few data have helped yet to unravel how a nervous system develops and evolves to complexity. On the evolutionary road to vertebrates, amphioxus occupies a key position to tackle this exciting issue. Its “simple” nervous system basically consists of a dorsal nerve cord and a diffuse net of peripheral neurons, which contrasts greatly with the complexity of vertebrate nervous systems. Notwithstanding, increasing data on gene expression has faced up this simplicity by revealing a mounting level of cryptic complexity, with unexpected levels of neuronal diversity, organisation and regionalisation of the central and peripheral nervous systems. Furthermore, recent gene expression data also point to the high neurogenic potential of the epidermis of amphioxus, suggestive of a skin-brain track for the evolution of the vertebrate nervous system. Here I attempt to catalogue and synthesise current gene expression data in the amphioxus nervous system. From this global point of view, I suggest scenarios for the evolutionary origin of complex features in the vertebrate nervous system, with special emphasis on the evolutionary origin of placodes and neural crest, and postulate a pre-patterned migratory pathway of cells, which, in the epidermis, may represent an intermediate state towards the deployment of one of the most striking innovative features of vertebrates: the neural crest and its derivatives. PMID:16763675

  13. TAM receptor deficiency affects adult hippocampal neurogenesis

    PubMed Central

    Ji, Rui; Meng, Lingbin; Li, Qiutang; Lu, Qingxian

    2014-01-01

    The Tyro3, Axl and Mertk (TAM) subfamily of receptor protein tyrosine kinases functions in cell growth, differentiation, survival, and most recently found, in the regulation of immune responses and phagocytosis. All three receptors and their ligands, Gas6 (growth arrest-specific gene 6) and protein S, are expressed in the central nervous system (CNS). TAM receptors play pivotal roles in adult hippocampal neurogenesis. Loss of these receptors causes a comprised neurogenesis in the dentate gyrus of adult hippocampus. TAM receptors have a negative regulatory effect on microglia and peripheral antigen-presenting cells, and play a critical role in preventing overproduction of pro-inflammatory cytokines detrimental to the proliferation, differentiation, and survival of adult neuronal stem cells (NSCs). Besides, these receptors also play an intrinsic trophic function in supporting NSC survival, proliferation, and differentiation into immature neurons. All these events collectively ensure a sustained neurogenesis in adult hippocampus. PMID:25487541

  14. Lophotrochozoan neuroanatomy: An analysis of the brain and nervous system of Lineus viridis(Nemertea) using different staining techniques

    PubMed Central

    2011-01-01

    Background The now thriving field of neurophylogeny that links the morphology of the nervous system to early evolutionary events relies heavily on detailed descriptions of the neuronal architecture of taxa under scrutiny. While recent accounts on the nervous system of a number of animal clades such as arthropods, annelids, and molluscs are abundant, in depth studies of the neuroanatomy of nemerteans are still wanting. In this study, we used different staining techniques and confocal laser scanning microscopy to reveal the architecture of the nervous system of Lineus viridis with high anatomical resolution. Results In L. viridis, the peripheral nervous system comprises four distinct but interconnected nerve plexus. The central nervous system consists of a pair of medullary cords and a brain. The brain surrounds the proboscis and is subdivided into four voluminous lobes and a ring of commissural tracts. The brain is well developed and contains thousands of neurons. It does not reveal compartmentalized neuropils found in other animal groups with elaborate cerebral ganglia. Conclusions The detailed analysis of the nemertean nervous system presented in this study does not support any hypothesis on the phylogenetic position of Nemertea within Lophotrochozoa. Neuroanatomical characters that are described here are either common in other lophotrochozoan taxa or are seemingly restricted to nemerteans. Since detailed descriptions of the nervous system of adults in other nemertean species have not been available so far, this study may serve as a basis for future studies that might add data to the unsettled question of the nemertean ground pattern and the position of this taxon within the phylogenetic tree. PMID:21771310

  15. 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

  16. In Vivo Transplantation of Neurosphere-Like Bodies Derived from the Human Postnatal and Adult Enteric Nervous System: A Pilot Study

    PubMed Central

    Hetz, Susan; Acikgoez, Ali; Voss, Ulrike; Nieber, Karen; Holland, Heidrun; Hegewald, Cindy; Till, Holger; Metzger, Roman; Metzger, Marco

    2014-01-01

    Recent advances in the in vitro characterization of human adult enteric neural progenitor cells have opened new possibilities for cell-based therapies in gastrointestinal motility disorders. However, whether these cells are able to integrate within an in vivo gut environment is still unclear. In this study, we transplanted neural progenitor-containing neurosphere-like bodies (NLBs) in a mouse model of hypoganglionosis and analyzed cellular integration of NLB-derived cell types and functional improvement. NLBs were propagated from postnatal and adult human gut tissues. Cells were characterized by immunohistochemistry, quantitative PCR and subtelomere fluorescence in situ hybridization (FISH). For in vivo evaluation, the plexus of murine colon was damaged by the application of cationic surfactant benzalkonium chloride which was followed by the transplantation of NLBs in a fibrin matrix. After 4 weeks, grafted human cells were visualized by combined in situ hybridization (Alu) and immunohistochemistry (PGP9.5, GFAP, SMA). In addition, we determined nitric oxide synthase (NOS)-positive neurons and measured hypertrophic effects in the ENS and musculature. Contractility of treated guts was assessed in organ bath after electrical field stimulation. NLBs could be reproducibly generated without any signs of chromosomal alterations using subtelomere FISH. NLB-derived cells integrated within the host tissue and showed expected differentiated phenotypes i.e. enteric neurons, glia and smooth muscle-like cells following in vivo transplantation. Our data suggest biological effects of the transplanted NLB cells on tissue contractility, although robust statistical results could not be obtained due to the small sample size. Further, it is unclear, which of the NLB cell types including neural progenitors have direct restoring effects or, alternatively may act via ‘bystander’ mechanisms in vivo. Our findings provide further evidence that NLB transplantation can be considered as

  17. In vivo transplantation of neurosphere-like bodies derived from the human postnatal and adult enteric nervous system: a pilot study.

    PubMed

    Hetz, Susan; Acikgoez, Ali; Voss, Ulrike; Nieber, Karen; Holland, Heidrun; Hegewald, Cindy; Till, Holger; Metzger, Roman; Metzger, Marco

    2014-01-01

    Recent advances in the in vitro characterization of human adult enteric neural progenitor cells have opened new possibilities for cell-based therapies in gastrointestinal motility disorders. However, whether these cells are able to integrate within an in vivo gut environment is still unclear. In this study, we transplanted neural progenitor-containing neurosphere-like bodies (NLBs) in a mouse model of hypoganglionosis and analyzed cellular integration of NLB-derived cell types and functional improvement. NLBs were propagated from postnatal and adult human gut tissues. Cells were characterized by immunohistochemistry, quantitative PCR and subtelomere fluorescence in situ hybridization (FISH). For in vivo evaluation, the plexus of murine colon was damaged by the application of cationic surfactant benzalkonium chloride which was followed by the transplantation of NLBs in a fibrin matrix. After 4 weeks, grafted human cells were visualized by combined in situ hybridization (Alu) and immunohistochemistry (PGP9.5, GFAP, SMA). In addition, we determined nitric oxide synthase (NOS)-positive neurons and measured hypertrophic effects in the ENS and musculature. Contractility of treated guts was assessed in organ bath after electrical field stimulation. NLBs could be reproducibly generated without any signs of chromosomal alterations using subtelomere FISH. NLB-derived cells integrated within the host tissue and showed expected differentiated phenotypes i.e. enteric neurons, glia and smooth muscle-like cells following in vivo transplantation. Our data suggest biological effects of the transplanted NLB cells on tissue contractility, although robust statistical results could not be obtained due to the small sample size. Further, it is unclear, which of the NLB cell types including neural progenitors have direct restoring effects or, alternatively may act via 'bystander' mechanisms in vivo. Our findings provide further evidence that NLB transplantation can be considered as

  18. Spinal Cord Repair with Engineered Nervous Tissue

    DTIC Science & Technology

    2014-04-01

    in order to minimize scarring and injected dissociated adult DRGs rostral to a dorsal column transection of the spinal cord. From the sensory... columns were dissected and post-fixed overnight in 4% paraformaldehyde, and then spinal cords were dissected from spinal columns and cryoprotected...AD______________ Award Number: W81XWH-10-1-0941 TITLE: Spinal Cord Repair with Engineered Nervous Tissue

  19. Confocal analysis of nervous system architecture in direct-developing juveniles of Neanthes arenaceodentata (Annelida, Nereididae)

    PubMed Central

    2010-01-01

    Background Members of Family Nereididae have complex neural morphology exemplary of errant polychaetes and are leading research models in the investigation of annelid nervous systems. However, few studies focus on the development of their nervous system morphology. Such data are particularly relevant today, as nereidids are the subjects of a growing body of "evo-devo" work concerning bilaterian nervous systems, and detailed knowledge of their developing neuroanatomy facilitates the interpretation of gene expression analyses. In addition, new data are needed to resolve discrepancies between classic studies of nereidid neuroanatomy. We present a neuroanatomical overview based on acetylated α-tubulin labeling and confocal microscopy for post-embryonic stages of Neanthes arenaceodentata, a direct-developing nereidid. Results At hatching (2-3 chaetigers), the nervous system has developed much of the complexity of the adult (large brain, circumesophageal connectives, nerve cords, segmental nerves), and the stomatogastric nervous system is partially formed. By the 5-chaetiger stage, the cephalic appendages and anal cirri are well innervated and have clear connections to the central nervous system. Within one week of hatching (9-chaetigers), cephalic sensory structures (e.g., nuchal organs, Langdon's organs) and brain substructures (e.g., corpora pedunculata, stomatogastric ganglia) are clearly differentiated. Additionally, the segmental-nerve architecture (including interconnections) matches descriptions of other, adult nereidids, and the pharynx has developed longitudinal nerves, nerve rings, and ganglia. All central roots of the stomatogastric nervous system are distinguishable in 12-chaetiger juveniles. Evidence was also found for two previously undescribed peripheral nerve interconnections and aspects of parapodial muscle innervation. Conclusions N. arenaceodentata has apparently lost all essential trochophore characteristics typical of nereidids. Relative to the

  20. STP Position Paper: Recommended Practices for Sampling and Processing the Nervous System (Brain, Spinal Cord, Nerve, and Eye) during Nonclinical General Toxicity Studies

    EPA Science Inventory

    The Society of Toxicologic Pathology charged a Nervous System Sampling Working Group with devising recommended practices to routinely screen the central and peripheral nervous systems in Good Laboratory Practice-type nonclinical general toxicity studies. Brains should be trimmed ...

  1. How Necessary is the Vasculature in the Life of Neural Stem and Progenitor Cells? Evidence from Evolution, Development and the Adult Nervous System

    PubMed Central

    Koutsakis, Christos; Kazanis, Ilias

    2016-01-01

    Augmenting evidence suggests that such is the functional dependance of neural stem cells (NSCs) on the vasculature that they normally reside in “perivascular niches”. Two examples are the “neurovascular” and the “oligovascular” niches of the adult brain, which comprise specialized microenvironments where NSCs or oligodendrocyte progenitor cells survive and remain mitotically active in close proximity to blood vessels (BVs). The often observed co-ordination of angiogenesis and neurogenesis led to these processes being described as “coupled”. Here, we adopt an evo-devo approach to argue that some stages in the life of a NSC, such as specification and commitment, are independent of the vasculature, while stages such as proliferation and migration are largely dependent on BVs. We also explore available evidence on the possible involvement of the vasculature in other phenomena such as the diversification of NSCs during evolution and we provide original data on the senescence of NSCs in the subependymal zone stem cell niche. Finally, we will comment on the other side of the story; that is, on how much the vasculature is dependent on NSCs and their progeny. PMID:26909025

  2. Baseline Functioning and Stress Reactivity in Maltreating Parents and At-Risk Adults: Review and Meta-Analyses of Autonomic Nervous System Studies.

    PubMed

    Reijman, Sophie; Bakermans-Kranenburg, Marian J; Hiraoka, Regina; Crouch, Julie L; Milner, Joel S; Alink, Lenneke R A; van IJzendoorn, Marinus H

    2016-07-26

    We reviewed and meta-analyzed 10 studies (N = 492) that examined the association between (risk for) child maltreatment perpetration and basal autonomic activity, and 10 studies (N = 471) that examined the association between (risk for) child maltreatment and autonomic stress reactivity. We hypothesized that maltreating parents/at-risk adults would show higher basal levels of heart rate (HR) and skin conductance (SC) and lower levels of HR variability (HRV) and would show greater HR and SC stress reactivity, but blunted HRV reactivity. A narrative review showed that evidence from significance testing within and across studies was mixed. The first set of meta-analyses revealed that (risk for) child maltreatment was associated with higher HR baseline activity (g = 0.24), a possible indication of allostatic load. The second set of meta-analyses yielded no differences in autonomic stress reactivity between maltreating/at-risk participants and nonmaltreating/low-risk comparison groups. Cumulative meta-analyses showed that positive effects for sympathetic stress reactivity as a risk factor for child maltreatment were found in a few early studies, whereas each subsequently aggregated study reduced the combined effect size to a null effect, an indication of the winner's curse Most studies were underpowered. Future directions for research are suggested.

  3. The role of the miR-17-92 cluster in neurogenesis and angiogenesis in the central nervous system of adults.

    PubMed

    Yang, Ping; Cai, Linghu; Zhang, Guan; Bian, Zhiqun; Han, Gaofeng

    2016-11-21

    It is well known that neurogenesis is not the only concern for the fully functional recovery after brain or spinal cord injury, as it has been shed light on the critical role of angiogenesis in improving neurological functional recovery. Angiogenesis and neurogenesis coordinately interact with each other in the developing and adult brain, during which they may respond to similar mediators and receptors, in which they share a common posttranscriptional regulator: the miR-17-92 cluster. The miR-17-92 cluster was initially described as an oncogene and was later demonstrated to drive key physiological and pathological responses during development and diseases respectively. It has been reported that the miR-17-92 cluster regulates both neurogenesis and angiogenesis. The miR-17-92 cluster modulates neural progenitor cells proliferation not only during development but also during neurological disorders such as stroke. It has also been shown that the endothelial miR-17-92 cluster regulates angiogenesis during embryonic stage and adulthood. In this review, we have discussed the actions of the miR-17-92 cluster in neuronal and vascular plasticity, and its potential as a novel therapeutic strategy for CNS injury. © 2016 Wiley Periodicals, Inc.

  4. Peripheral Artery Disease

    MedlinePlus

    ... Physician Resources Professions Site Index A-Z Peripheral Artery Disease (PAD) Peripheral artery disease (PAD) refers to ... is peripheral artery disease treated? What is peripheral artery disease (PAD)? Peripheral artery disease, or PAD, refers ...

  5. A Systems-Level Analysis of the Peripheral Nerve Intrinsic Axonal Growth Program

    PubMed Central

    Chandran, Vijayendran; Coppola, Giovanni; Nawabi, Homaira; Omura, Takao; Versano, Revital; Huebner, Eric A.; Zhang, Alice; Costigan, Michael; Yekkirala, Ajay; Barrett, Lee; Blesch, Armin; Michaelevski, Izhak; Davis-Turak, Jeremy; Gao, Fuying; Langfelder, Peter; Horvath, Steve; He, Zhigang; Benowitz, Larry; Fainzilber, Mike; Tuszynski, Mark; Woolf, Clifford J.; Geschwind, Daniel H.

    2016-01-01

    SUMMARY The regenerative capacity of the injured CNS in adult mammals is severely limited, yet axons in the peripheral nervous system (PNS) regrow, albeit to a limited extent, after injury. We reasoned that coordinate regulation of gene expression in injured neurons involving multiple pathways was central to PNS regenerative capacity. To provide a framework for revealing pathways involved in PNS axon regrowth after injury, we applied a comprehensive systems biology approach, starting with gene expression profiling of dorsal root ganglia (DRGs) combined with multi-level bioinformatic analyses and experimental validation of network predictions. We used this rubric to identify a drug that accelerates DRG neurite outgrowth in vitro and optic nerve outgrowth in vivo by inducing elements of the identified network. The work provides a functional genomics foundation for understanding neural repair and proof of the power of such approaches in tackling complex problems in nervous system biology. PMID:26898779

  6. Peripheral nerve conduits: technology update

    PubMed Central

    Arslantunali, D; Dursun, T; Yucel, D; Hasirci, N; Hasirci, V

    2014-01-01

    Peripheral nerve injury is a worldwide clinical problem which could lead to loss of neuronal communication along sensory and motor nerves between the central nervous system (CNS) and the peripheral organs and impairs the quality of life of a patient. The primary requirement for the treatment of complete lesions is a tension-free, end-to-end repair. When end-to-end repair is not possible, peripheral nerve grafts or nerve conduits are used. The limited availability of autografts, and drawbacks of the allografts and xenografts like immunological reactions, forced the researchers to investigate and develop alternative approaches, mainly nerve conduits. In this review, recent information on the various types of conduit materials (made of biological and synthetic polymers) and designs (tubular, fibrous, and matrix type) are being presented. PMID:25489251

  7. An altered form of pp60/sup c-src/ is expressed primarily in the central nervous system

    SciTech Connect

    Le Beau, J.M.; Wiestler, O.D.; Walter, G.

    1987-11-01

    The expression of two forms of pp60/sup c-scr/, pp60 and pp60/sup +/, was measured in the central nervous system (CNS) and the peripheral nervous system. Both forms were expressed in the CNS, whereas only pp60 was primarily detected in the peripheral nervous system. Our findings suggest that pp60/sup +/ may play a role in events important to the CNS.

  8. Imaging calcium dynamics in the nervous system by means of ballistic delivery of indicators.

    PubMed

    Kettunen, Petronella; Demas, Jay; Lohmann, Christian; Kasthuri, Narayanan; Gong, Yandao; Wong, Rachel O L; Gan, Wen-Biao

    2002-09-15

    The use of fluorescence-based calcium indicators has, over the years, unraveled important calcium-dependent mechanisms underlying neuronal function and development. However, difficulties associated with the loading of calcium indicators have limited their widespread use, particularly for the study of neuronal processing in the adult nervous system. Here, we show that in the central and peripheral nervous systems, populations of neurons and their processes, including dendritic spines and filopodia, can be labeled rapidly and efficiently by delivering calcium indicator-coated particles using a 'gene gun'. Importantly, neuronal labeling occurred both in vitro and in vivo, and across a wide range of ages and preparations. The labeled cells demonstrate spontaneous and evoked calcium transients, indicating that particle-mediated delivery is not deleterious to neuronal function. Furthermore, unlike loading with patch pipettes, cytoplasmic content is preserved following ballistic loading. This enables the study of calcium-dependent second messenger pathways without loss of signaling components. The ballistic delivery of calcium indicators thus opens up many new avenues for further exploration of the structure and function of the nervous system from single spines to neuronal networks.

  9. The polysialic acid mimetics 5-nonyloxytryptamine and vinorelbine facilitate nervous system repair

    PubMed Central

    Saini, Vedangana; Lutz, David; Kataria, Hardeep; Kaur, Gurcharan; Schachner, Melitta; Loers, Gabriele

    2016-01-01

    Polysialic acid (PSA) is a large negatively charged glycan mainly attached to the neural cell adhesion molecule (NCAM). Several studies have shown that it is important for correct formation of brain circuitries during development and for synaptic plasticity, learning and memory in the adult. PSA also plays a major role in nervous system regeneration following injury. As a next step for clinical translation of PSA based therapeutics, we have previously identified the small organic compounds 5-nonyloxytryptamine and vinorelbine as PSA mimetics. Activity of 5-nonyloxytryptamine and vinorelbine had been confirmed in assays with neural cells from the central and peripheral nervous system in vitro and shown to be independent of their function as serotonin receptor 5-HT1B/1D agonist or cytostatic drug, respectively. As we show here in an in vivo paradigm for spinal cord injury in mice, 5-nonyloxytryptamine and vinorelbine enhance regain of motor functions, axonal regrowth, motor neuron survival and remyelination. These data indicate that 5-nonyloxytryptamine and vinorelbine may be re-tasked from their current usage as a 5-HT1B/1D agonist or cytostatic drug to act as mimetics for PSA to stimulate regeneration after injury in the mammalian nervous system. PMID:27324620

  10. Treatment of adult ALL with central nervous system involvement at diagnosis using autologous and allogeneic transplantation: a study from the Société Française de Greffe de Moelle et de Thérapie Cellulaire.

    PubMed

    Chantepie, S P; Mohty, M; Tabrizi, R; Robin, M; Deconinck, E; Buzyn, A; Contentin, N; Raus, N; Lhéritier, V; Reman, O

    2013-05-01

    To assess the role of hematopoietic SCT (HSCT) in adult ALL patients with central nervous system involvement at diagnosis, we retrospectively analyzed 90 patients who underwent autologous HSCT (auto-HSCT group; n=27) or allogeneic HSCT (allo-HSCT group; n=63) and reported to the Société Française de Greffe de Moelle et de Thérapie Cellulaire registry between 1994 and 2008. At the time of transplantation, 67 patients (74%) were in first CR, 15 (17%) in CR2 and 8 (9%) with progressive disease. The 5-year probabilities of overall survival (OS) and disease-free survival (DFS) were 52% and 46% for the allo-HSCT and 37% and 33% for the auto-HSCT groups, respectively (P=NS). The TRM at 5 years was 29.8% for the allo-HSCT group and 3.7% for the auto-HSCT group. Using univariate analysis, a time for transplantation of <12 months, the remission status at transplantation, the use of high-dose TBI and the number of the transplant were all determined to be prognostic factors for improved DFS and OS probabilities. Using multivariate analysis, we demonstrated that both the use of high-dose TBI and the remission status had a favorable impact on OS. Although the DFS and OS were better in the allo-HSCT group, the differences were not statistically significant.

  11. Brain and Nervous System

    MedlinePlus

    ... such as the beating of your heart, the digestion of your food, and yes, even the amount ... functions, like breathing, heart rate, blood pressure, swallowing, digestion, and blinking. previous continue How the Nervous System ...

  12. Relationships among metabolic homeostasis, diet, and peripheral afferent neuron biology

    Technology Transfer Automated Retrieval System (TEKTRAN)

    It is well-established that food intake behavior and energy balance are regulated by cross-talk between peripheral organ systems and the central nervous system (CNS), for instance through the actions of peripherally-derived leptin on hindbrain and hypothalamic loci. Diet- or obesity-associated dist...

  13. Ontogeny of the calcium binding protein calbindin D-28k in the rat nervous system.

    PubMed

    Enderlin, S; Norman, A W; Celio, M R

    1987-01-01

    Calbindin D-28k immunoreactivity appeared at embryonal day 14 (E14) in the central nervous system as well as in the sensory organs and at E15 in the peripheral nervous system of the rat. At E14 the infundibular process of the diencephalon, cells of the posterior hypothalamus and of the dorsal thalamus were the only structures strongly immunostained in the brain, whereas neurons of the basal plate of the spinal cord, medulla oblongata and of the outermost layer of the cerebral cortex were only faintly labeled. Calbindin positive cerebellar Purkinje cells could be discerned at E15 together with a few cells in the hippocampus and in ganglia of the cranial nerves. At E19 various mesencephalic and metencephalic structures, spinal ganglion cells and basal ganglia displayed calbindin immunoreactive cells. The adult pattern of calbindin immunoreactivity (Garcia Segura et al. 1984) was reached before birth in most brain regions. In general, cells which displayed calbindin during brain development were also calbindin positive in the adult animal. Exceptions to this rule were cells of deep nuclei of the cerebellum and non-neuronal cells which transiently expressed calbindin during development. Calbindin appeared in a given brain region almost invariably 1 or 2 days after the cessation of cell division and the beginning of neuronal migration and extension of neuronal processes. The calcium binding protein calbindin might influence these Ca2+-dependent processes.

  14. Plasticity and therapeutic potential of mesenchymal stem cells in the nervous system.

    PubMed

    Phinney, Donald G; Isakova, Iryna

    2005-01-01

    Mesenchymal stem cells resident in adult bone marrow are best characterized by their capacity to differentiate into connective tissue cell types such as adipocytes, chondrocytes, osteoblasts and hematopoiesis-supporting stroma. Accordingly, these cells are being evaluated in human clinical trials for efficacy in treating genetic diseases of bone, to speed hematopoietic recovery after bone marrow transplantation and reduce the severity of graft versus host disease. In the past few years MSCs have also been reported to exhibit a broad degree of plasticity commensurate with other adult stem cell populations, including the ability to differentiate in vitro and in vivo into non-mesodermal cell types such as neurons and astrocytes. MSCs have also been reported to promote repair and regeneration of nervous tissue within the central and peripheral nervous system, although the mechanism by which this occurs remains indeterminate. Herein, we review evidence purporting the differentiation of MSCs into neural cell lineages and evaluate the utility of MSCs as cellular vectors for treating neurological disorders and spinal cord injury. Based on our analysis of their transcriptome, we also theorize how the varied functions of MSCs and their progeny in bone marrow may extrapolate to a therapeutic benefit in models of neurological disease.

  15. 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.

  16. Comparison of three neurotropic viruses reveals differences in viral dissemination to the central nervous system.

    PubMed

    Luethy, Lauren N; Erickson, Andrea K; Jesudhasan, Palmy R; Ikizler, Mine; Dermody, Terence S; Pfeiffer, Julie K

    2016-01-01

    Neurotropic viruses initiate infection in peripheral tissues prior to entry into the central nervous system (CNS). However, mechanisms of dissemination are not completely understood. We used genetically marked viruses to compare dissemination of poliovirus, yellow fever virus 17D (YFV-17D), and reovirus type 3 Dearing in mice from a hind limb intramuscular inoculation site to the sciatic nerve, spinal cord, and brain. While YFV-17D likely entered the CNS via blood, poliovirus and reovirus likely entered the CNS by transport through the sciatic nerve to the spinal cord. We found that dissemination was inefficient in adult immune-competent mice for all three viruses, particularly reovirus. Dissemination of all viruses was more efficient in immune-deficient mice. Although poliovirus and reovirus both accessed the CNS by transit through the sciatic nerve, stimulation of neuronal transport by muscle damage enhanced dissemination only of poliovirus. Our results suggest that these viruses access the CNS using different pathways.

  17. Comparison of three neurotropic viruses reveals differences in viral dissemination to the central nervous system

    PubMed Central

    Luethy, Lauren N.; Erickson, Andrea K; Jesudhasan, Palmy R.; Ikizler, Mine; Dermody, Terence S.; Pfeiffer, Julie K.

    2015-01-01

    Neurotropic viruses initiate infection in peripheral tissues prior to entry into the central nervous system (CNS). However, mechanisms of dissemination are not completely understood. We used genetically marked viruses to compare dissemination of poliovirus, yellow fever virus 17D (YFV-17D), and reovirus type 3 Dearing in mice from a hind limb intramuscular inoculation site to the sciatic nerve, spinal cord, and brain. While YFV-17D likely entered the CNS via blood, poliovirus and reovirus likely entered the CNS by transport through the sciatic nerve to the spinal cord. We found that dissemination was inefficient in adult immune-competent mice for all three viruses, particularly reovirus. Dissemination of all viruses was more efficient in immune-deficient mice. Although poliovirus and reovirus both accessed the CNS by transit through the sciatic nerve, stimulation of neuronal transport by muscle damage enhanced dissemination only of poliovirus. Our results suggest that these viruses access the CNS using different pathways. PMID:26479325

  18. HCV-Related Nervous System Disorders

    PubMed Central

    Monaco, Salvatore; Ferrari, Sergio; Gajofatto, Alberto; Zanusso, Gianluigi; Mariotto, Sara

    2012-01-01

    Chronic infection with hepatitis C virus (HCV) is associated with a wide spectrum of extrahepatic manifestations, affecting different organ systems. Neurological complications occur in a large number of patients and range from peripheral neuropathy to cognitive impairment. Pathogenetic mechanisms responsible for nervous system dysfunction are mainly related to the upregulation of the host immune response with production of autoantibodies, immune complexes, and cryoglobulins. Alternative mechanisms include possible extrahepatic replication of HCV in neural tissues and the effects of circulating inflammatory cytokines and chemokines. PMID:22899946

  19. Mitochondrial DNA: impacting central and peripheral nervous systems

    PubMed Central

    Carelli, Valerio

    2014-01-01

    Because of their high-energy metabolism, neurons are highly dependent on mitochondria, which generate cellular ATP through oxidative phosphorylation. The mitochondrial genome encodes for critical components of the oxidative phosphorylation pathway machinery, and therefore mutations in mitochondrial DNA (mtDNA) cause energy production defects that frequently have severe neurological manifestations. Here, we review the principles of mitochondrial genetics and focus on prototypical mitochondrial diseases to illustrate how primary defects in mtDNA or secondary defects in mtDNA due to nuclear genome mutations can cause prominent neurological and multisystem features. In addition, we discuss the pathophysiological mechanisms underlying mitochondrial diseases, the cellular mechanisms that protect mitochondrial integrity, and the prospects for therapy. PMID:25521375

  20. Animal Models of Peripheral Neuropathy Due to Environmental Toxicants

    PubMed Central

    Rao, Deepa B.; Jortner, Bernard S.; Sills, Robert C.

    2014-01-01

    Despite the progress in our understanding of pathogeneses and the identification of etiologies of peripheral neuropathy, idiopathic neuropathy remains common. Typically, attention to peripheral neuropathies resulting from exposure to environmental agents is limited relative to more commonly diagnosed causes of peripheral neuropathy (diabetes and chemotherapeutic agents). Given that there are more than 80,000 chemicals in commerce registered with the Environmental Protection Agency and that at least 1000 chemicals are known to have neurotoxic potential, very few chemicals have been established to affect the peripheral nervous system (mainly after occupational exposures). A wide spectrum of exposures, including pesticides, metals, solvents, nutritional sources, and pharmaceutical agents, has been related, both historically and recently, to environmental toxicant-induced peripheral neuropathy. A review of the literature shows that the toxicity and pathogeneses of chemicals adversely affecting the peripheral nervous system have been studied using animal models. This article includes an overview of five prototypical environmental agents known to cause peripheral neuropathy—namely, organophosphates, carbon disulfide, pyridoxine (Vitamin B6), acrylamide, and hexacarbons (mainly n-hexane, 2,5-hexanedione, methyl n-butyl ketone). Also included is a brief introduction to the structural components of the peripheral nervous system and pointers on common methodologies for histopathologic evaluation of the peripheral nerves. PMID:24615445

  1. Autonomic nervous system dysregulation in pediatric hypertension.

    PubMed

    Feber, Janusz; Ruzicka, Marcel; Geier, Pavel; Litwin, Mieczyslaw

    2014-05-01

    Historically, primary hypertension (HTN) has been prevalent typically in adults. Recent data however, suggests an increasing number of children diagnosed with primary HTN, mainly in the setting of obesity. One of the factors considered in the etiology of HTN is the autonomous nervous system, namely its dysregulation. In the past, the sympathetic nervous system (SNS) was regarded as a system engaged mostly in buffering major acute changes in blood pressure (BP), in response to physical and emotional stressors. Recent evidence suggests that the SNS plays a much broader role in the regulation of BP, including the development and maintenance of sustained HTN by a chronically elevated central sympathetic tone in adults and children with central/visceral obesity. Consequently, attempts have been made to reduce the SNS hyperactivity, in order to intervene early in the course of the disease and prevent HTN-related complications later in life.

  2. 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.

  3. 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…

  4. Peripheral arterial disease

    PubMed Central

    2011-01-01

    Introduction Up to 20% of adults aged over 55 years have detectable peripheral arterial disease of the legs, but this may cause symptoms of intermittent claudication in only a small proportion of affected people. The main risk factors are smoking and diabetes mellitus, but other risk factors for cardiovascular disease are also associated with peripheral arterial disease. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for people with chronic peripheral arterial disease? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2010. Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review. We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 70 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review, we present information relating to the effectiveness and safety of the following interventions: antiplatelet agents, bypass surgery, cilostazol, exercise, pentoxifylline, percutaneous transluminal angioplasty (PTA), prostaglandins, smoking cessation, and statins. PMID:21477401

  5. Peripheral arterial disease

    PubMed Central

    2009-01-01

    Introduction Up to 20% of adults aged over 55 years have detectable peripheral arterial disease of the legs, but this may cause symptoms of intermittent claudication in only a small proportion of affected people. The main risk factors are smoking and diabetes mellitus, but other risk factors for cardiovascular disease are also associated with peripheral arterial disease. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for people with chronic peripheral arterial disease? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2009. (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 59 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: antiplatelet agents; bypass surgery; cilostazol; exercise; pentoxifylline; percutaneous transluminal angioplasty (PTA); prostaglandins; smoking cessation; and statins. PMID:19454099

  6. Peripheral androgen action helps modulate vocal production in a suboscine passerine

    PubMed Central

    Fuxjager, Matthew J.; Heston, Jonathan B.; Schlinger, Barney A.

    2015-01-01

    Androgenic activation of intracellular androgen receptors (AR) influences avian vocal production, though this has largely been investigated at the level of the brain. We investigated the influence of predominantly peripheral AR on vocal output in wild Golden-collared Manakins (Manacus vitellinus). In this suboscine species, males court females by performing acrobatic displays and by producing relatively simple chee-poo vocalizations. To assess whether peripheral AR influences the acoustic structure of these vocal signals, we treated reproductively active adult males with the peripherally selective antiandrogen bicalutamide and then measured phonation performance. Inhibiting AR outside of the central nervous system increased the duration of the chee note and decreased the fundamental frequency of the poo note. This treatment caused no discernable change to chee-poo frequency modulation or entropy. Our results show that activation of peripheral AR mediates note-specific changes to temporal and pitch characteristics of the Golden-collared Manakin’s main sexual call. Thus, our study provides one of the first demonstrations that androgenic action originating outside of the brain and likely on musculoskeletal targets can modulate avian vocal production. PMID:25780269

  7. Peripheral androgen action helps modulate vocal production in a suboscine passerine.

    PubMed

    Fuxjager, Matthew J; Heston, Jonathan B; Schlinger, Barney A

    2014-07-01

    Androgenic activation of intracellular androgen receptors (AR) influences avian vocal production, though this has largely been investigated at the level of the brain. We investigated the influence of predominantly peripheral AR on vocal output in wild Golden-collared Manakins (Manacus vitellinus). In this suboscine species, males court females by performing acrobatic displays and by producing relatively simple chee-poo vocalizations. To assess whether peripheral AR influences the acoustic structure of these vocal signals, we treated reproductively active adult males with the peripherally selective antiandrogen bicalutamide and then measured phonation performance. Inhibiting AR outside of the central nervous system increased the duration of the chee note and decreased the fundamental frequency of the poo note. This treatment caused no discernable change to chee-poo frequency modulation or entropy. Our results show that activation of peripheral AR mediates note-specific changes to temporal and pitch characteristics of the Golden-collared Manakin's main sexual call. Thus, our study provides one of the first demonstrations that androgenic action originating outside of the brain and likely on musculoskeletal targets can modulate avian vocal production.

  8. Your Brain and Nervous System

    MedlinePlus

    ... los dientes Video: Getting an X-ray Your Brain & Nervous System KidsHealth > For Kids > Your Brain & Nervous ... The coolest wetsuit? Nope — he needs his cerebellum! Brain Stem Keeps You Breathing — and More Another brain ...

  9. Your Brain and Nervous System

    MedlinePlus

    ... Room? What Happens in the Operating Room? Your Brain & Nervous System KidsHealth > For Kids > Your Brain & Nervous ... The coolest wetsuit? Nope — he needs his cerebellum! Brain Stem Keeps You Breathing — and More Another brain ...

  10. Late evolutionary appearance of 'peripheral-type' binding sites for benzodiazepines.

    PubMed

    Bolger, G T; Weissman, B A; Lueddens, H; Basile, A S; Mantione, C R; Barrett, J E; Witkin, J M; Paul, S M; Skolnick, P

    1985-07-15

    Four classes of non-mammalian vertebrates were examined for the presence of both 'brain-specific' and 'peripheral-type' binding sites for benzodiazepines in the central nervous system. 'Brain-specific' binding sites for benzodiazepines were found in the central nervous systems of all non-mammalian vertebrates studied. However, in contrast to mammals, either very low or undetectable levels of 'peripheral-type' binding sites for benzodiazepines were observed in the central nervous systems of these non-mammalian vertebrates. Furthermore, the density of 'peripheral-type' binding sites for benzodiazepines in non-mammalian vertebrate heart was less than or equal to 2% of that found in mammalian cardiac tissue. These findings suggest a very late evolutionary appearance of 'peripheral-type' binding sites for benzodiazepines, implying that these sites may have (a) highly specialized function(s) in both peripheral tissues and the central nervous system.

  11. Raman microspectroscopy for visualization of peripheral nerves

    NASA Astrophysics Data System (ADS)

    Minamikawa, Takeo; Harada, Yoshinori; Koizumi, Noriaki; Takamatsu, Tetsuro

    2013-02-01

    The peripheral nervous system plays an important role in motility, sensory, and autonomic functions of the human body. Preservation of peripheral nerves in surgery is essential for improving quality of life of patients. To preserve peripheral nerves, detection of ne peripheral nerves that cannot be identi ed by human eye or under white light imaging is necessary. In this study, we sought to provide a proof-of-principle demonstration of a label-free detection technique of peripheral nerve tissues against adjacent tissues that employs spontaneous Raman microspectroscopy. A line-illumination confocal Raman microscope was used for the experiment. A laser operating at the wavelength of 532 nm was used as an excitation laser light. We obtained Raman spectra of peripheral nerve, brous connective tissue, skeletal muscle, blood vessel, and adipose tissue of Wistar rats, and extracted speci c spectral features of peripheral nerves and adjacent tissues. By applying multivariate image analysis, peripheral nerves were clearly detected against adjacent tissues without any preprocessing neither xation nor staining. These results suggest the potential of the Raman spectroscopic observation for noninvasive and label-free nerve detection, and we expect this method could be a key technique for nerve-sparing surgery.

  12. Na(v)1.7 and Na(v)1.3 are the only tetrodotoxin-sensitive sodium channels expressed by the adult guinea pig enteric nervous system.

    PubMed

    Sage, D; Salin, P; Alcaraz, G; Castets, F; Giraud, P; Crest, M; Mazet, B; Clerc, N

    2007-10-01

    The types of sodium channels that are expressed by neurons shape the rising phase of action potentials and influence patterns of action potential discharge. With regard to the enteric nervous system (ENS), there is uncertainty about which channels are expressed, and in particular it is unknown whether Na(v)1.7 is present. We designed specific probes for the guinea pig Na(v)1.7 alpha subunit as well as for the other tetrodotoxin (TTX)-sensitive alpha subunits (Na(v)1.1, Na(v)1.2, Na(v)1.3, and Na(v)1.6) in order to perform in situ hybridization (ISH) histochemistry on guinea pig myenteric ganglia. We established that only Na(v)1.7 mRNA and Na(v)1.3 mRNA are expressed in these ganglia. The ISH signal for Na(v)1.7 transcripts was found in seemingly all the myenteric neurons. The expression of the Na(v)1.3 alpha subunit was confirmed by immunohistochemistry in a large proportion (62%) of the myenteric neuron population. This population included enteric sensory neurons. Na(v)1.6 immunoreactivity, absent from myenteric neurons, was detected in glial cells only when a high anti-Na(v)1.6 antibody concentration was used. This suggests that the Na(v)1.6 alpha subunit and mRNA are present only at low levels, which is consistent with the fact that no Na(v)1.6 mRNA could be detected in the ENS by ISH. The fact that adult myenteric neurons are endowed with only two TTX-sensitive alpha subunits, namely, Na(v)1.3 and Na(v)1.7, emphasizes the singularity of the ENS. Both these subunits, known to have slow-inactivation kinetics, are well adapted for generating action potentials from slow excitatory postsynaptic potentials, a mode of synaptic transmission that applies to all ENS neuron types.

  13. MONOAMINERGIC MECHANISMS IN NERVOUS TISSUE.

    DTIC Science & Technology

    AMINES, AUTONOMIC NERVOUS SYSTEM), (*NERVE FIBERS, HISTOLOGICAL TECHNIQUES), ACETYLCHOLINESTERASE, METHYLENE BLUE , BIOLOGICAL STAINS, HISTAMINE, FLUORESCENCE, HYPOTHERMIA, HEART, NEUROMUSCULAR TRANSMISSION, SWEDEN

  14. Imaging nervous system activity.

    PubMed

    Fields, Douglas R; Shneider, Neil; Mentis, George Z; O'Donovan, Michael J

    2009-10-01

    This unit describes methods for loading ion- and voltage-sensitive dyes into neurons, with a particular focus on the spinal cord as a model system. In addition, we describe the use of these dyes to visualize neural activity. Although the protocols described here concern spinal networks in culture or an intact in vitro preparation, they can be, and have been, widely used in other parts of the nervous system.

  15. LGI proteins in the nervous system.

    PubMed

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

    2013-06-25

    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.

  16. 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

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

    PubMed

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

    2009-03-01

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

  18. Fast Neurotransmission Related Genes Are Expressed in Non Nervous Endoderm in the Sea Anemone Nematostella vectensis

    PubMed Central

    Oren, Matan; Brikner, Itzchak; Appelbaum, Lior; Levy, Oren

    2014-01-01

    Cnidarian nervous systems utilize chemical transmission to transfer signals through synapses and neurons. To date, ample evidence has been accumulated for the participation of neuropeptides, primarily RFamides, in neurotransmission. Yet, it is still not clear if this is the case for the classical fast neurotransmitters such as GABA, Glutamate, Acetylcholine and Monoamines. A large repertoire of cnidarian Fast Neurotransmitter related Genes (FNGs) has been recently identified in the genome of the sea anemone, Nematostella vectensis. In order to test whether FNGs are localized in cnidarian neurons, we characterized the expression patterns of eight Nematostella genes that are closely or distantly related to human central and peripheral nervous systems genes, in adult Nematostella and compared them to the RFamide localization. Our results show common expression patterns for all tested genes, in a single endodermal cell layer. These expressions did not correspond with the RFamide expressing nerve cell network. Following these results we suggest that the tested Nematostella genes may not be directly involved in vertebrate-like fast neurotransmission. PMID:24705400

  19. Identification of a Peripheral Nerve Neurite Growth-Promoting Activity by Development and Use of an in vitro Bioassay

    NASA Astrophysics Data System (ADS)

    Sandrock, Alfred W.; Matthew, William D.

    1987-10-01

    The effective regeneration of severed neuronal axons in the peripheral nerves of adult mammals may be explained by the presence of molecules in situ that promote the effective elongation of neurites. The absence of such molecules in the central nervous system of these animals may underlie the relative inability of axons to regenerate in this tissue after injury. In an effort to identify neurite growth-promoting molecules in tissues that support effective axonal regeneration, we have developed an in vitro bioassay that is sensitive to substrate-bound factors of peripheral nerve that influence the growth of neurites. In this assay, neonatal rat superior cervical ganglion explants are placed on longitudinal cryostat sections of fresh-frozen sciatic nerve, and the regrowing axons are visualized by catecholamine histofluorescence. Axons are found to regenerate effectively over sciatic nerve tissue sections. When ganglia are similarly explanted onto cryostat sections of adult rat central nervous system tissue, however, axonal regeneration is virtually absent. We have begun to identify the molecules in peripheral nerve that promote effective axonal regeneration by examining the effect of antibodies that interfere with the activity of previously described neurite growth-promoting factors. Axonal elongation over sciatic nerve tissue was found to be sensitive to the inhibitory effects of INO (for inhibitor of neurite outgrowth), a monoclonal antibody that recognizes and inhibits a neurite growth-promoting activity from PC-12 cell-conditioned medium. The INO antigen appears to be a molecular complex of laminin and heparan sulfate proteoglycan. In contrast, a rabbit antiserum that recognizes laminin purified from mouse Engelbreth-Holm-Swarm (EHS) sarcoma, stains the Schwann cell basal lamina of peripheral nerve, and inhibits neurite growth over purified laminin substrata has no detectable effect on the rate of axonal regeneration in our assay.

  20. Imaging nervous system activity.

    PubMed

    Fields, R D; O'Donovan, M J

    2001-05-01

    Optical imaging methods rely upon visualization of three types of signals: (1) intrinsic optical signals, including light scattering and reflectance, birefringence, and spectroscopic changes of intrinsic molecules, such as NADH or oxyhemoglobin; (2) changes in fluorescence or absorbance of voltage-sensitive membrane dyes; and (3) changes in fluorescence or absorbance of calcium-sensitive indicator dyes. Of these, the most widely used approach is fluorescent microscopy of calcium-sensitive dyes. This unit describes protocols for the use of calcium-sensitive dyes and voltage-dependent dyes for studies of neuronal activity in culture, tissue slices, and en-bloc preparations of the central nervous system.

  1. 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

  2. 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.

  3. Plexin a4 expression in adult rat cranial nerves.

    PubMed

    Gutekunst, Claire-Anne; Gross, Robert E

    2014-11-01

    PlexinsA1-A4 participate in class 3 semaphorin signaling as co-receptors to neuropilin 1 and 2. PlexinA4 is the latest member of the PlexinA subfamily to be identified. In previous studies, we described the expression of PlexinA4 in the brain and spinal cord of the adult rat. Here, antibodies to PlexinA4 were used to reveal immunolabeling in most of the cranial nerve surveyed. Labeling was found in the olfactory, optic, oculomotor, trochlear, trigeminal, abducens, facial, vestibulocochlear, glossopharyngeal, vagus, and hypoglossal nerves. This is the first detailed description of the cellular and subcellular distribution of PlexinA4 in the adult cranial nerves. The findings will set the basis for future studies on the potential role of PlexinA4 in regeneration and repair of the adult central and peripheral nervous system.

  4. Peripheral vision and child pedestrian accidents.

    PubMed

    David, S S; Chapman, A J; Foot, H C; Sheehy, N P

    1986-11-01

    In both adults and children, peripheral vision is poorer than foveal vision, but there is evidence that detection in peripheral vision is relatively poorer in children than it is in adults. That may contribute to the particularly high pedestrian accident rates of children. Two laboratory experiments investigated peripheral vision in men and women and in boys and girls aged 7, 9 and 11. Using an array of stationary lights, Expt 1 examined reactions to apparent movement (the phi phenomenon) in mid and extreme periphery; and, using film sequences of a moving car, Expt 2 included a comparison of foveal and peripheral fields. Overall there was little evidence to support the hypothesis that children have poorer peripheral vision than adults relative to their foveal vision. Nonetheless there were some experimental differences: in Expt 1, 7-year-olds made fewer detections, particularly in the extreme periphery; and, in both experiments, detections tended to be slower. The relatively complex car movements in Expt 2 were detected faster in foveal than peripheral vision. There were no sex differences. Children detected more movements on the left. In Expt 2 these detections were faster, and children made relatively more simulated road crossings when the car approached from the left (all adults 'crossed' in all trials).

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

    DTIC Science & Technology

    2014-03-01

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

  6. Getting nervous about immunity.

    PubMed

    Kelley, Keith W; McCusker, Robert H

    2014-10-01

    Twenty-five years ago, immunologists and neuroscientists had little science of mutual interest. This is no longer the case. Neuroscientists now know that the first formally defined cytokine, IL-1, activates a discrete population of hypothalamic neurons. This interaction leads to the release of glucocorticoids from the adrenal gland, a hormone that has a long history in immunoregulation. Immunologists have been surprised to learn that lymphoid cells synthesize acetylcholine, the first formally recognized neurotransmitter. This neurotransmitter suppresses the synthesis of TNF. These discoveries blur the distinction of neuroscience and immunology as distinct disciplines. There are now 37 formally recognized cytokines and their receptors, and at least 60 classical neurotransmitters plus over 50 neuroactive peptides. These findings explain why both immunologists and neuroscientists are getting nervous about immunity and highlight a real need to apply integrative physiological approaches in biomedical research.

  7. Getting nervous about immunity

    PubMed Central

    Kelley, Keith W.; McCusker, Robert H.

    2014-01-01

    Twenty-five years ago, immunologists and neuroscientists had little science of mutual interest. This is no longer the case. Neuroscientists now know that the first formally defined cytokine, IL-1, activates a discrete population of hypothalamic neurons. This interaction leads to the release of glucocorticoids from the adrenal gland, a hormone that has a long history in immunoregulation. Immunologists have been surprised to learn that lymphoid cells synthesize acetylcholine, the first formally recognized neurotransmitter. This neurotransmitter suppresses the synthesis of TNF. These discoveries blur the distinction of neuroscience and immunology as distinct disciplines. There are now 37 formally recognized cytokines and their receptors, and at least 60 classical neurotransmitters plus over 50 neuroactive peptides. These findings explain why both immunologists and neuroscientists are getting nervous about immunity and highlight a real need to apply integrative physiological approaches in biomedical research. PMID:24556600

  8. Prognostic significance of Epstein-Barr virus in nodal peripheral T-cell lymphoma, unspecified: A Groupe d'Etude des Lymphomes de l'Adulte (GELA) study.

    PubMed

    Dupuis, Jehan; Emile, Jean-François; Mounier, Nicolas; Gisselbrecht, Christian; Martin-Garcia, Nadine; Petrella, Tony; Bouabdallah, Reda; Berger, Françoise; Delmer, Alain; Coiffier, Bertrand; Reyes, Félix; Gaulard, Philippe

    2006-12-15

    Peripheral T-cell lymphomas (PTCLs) are rare and have a dismal prognosis. The most frequent subtype is PTCL, unspecified. Epstein-Barr virus (EBV) has been detected in around 40% of cases, but its prognostic significance is not fully established. Lymph node samples from 110 patients with PTCL, unspecified included in LNH87 and LNH93 trials were available. EBV status was studied by EBV-encoded small RNA in situ hybridization (EBER-ISH). EBER-ISH showed positive cells in 45 (41%) of 110 patients. Pretreatment characteristics were comparable between positive and negative cases, except for male sex (80% versus 60%, respectively, P = .02). Only 50% of patients achieved complete remission with a 5-year event-free survival (EFS) and overall survival (OS) of 21% and 30%, respectively. EBER-ISH positivity was the sole factor linked with worse EFS, with a 5-year probability of 11% for positive patients. In univariate analysis, factors affecting OS were EBER-ISH positivity, high LDH level, and age older than 60 years. In multivariate analysis, EBER-ISH was associated with a worse OS in the elderly population. Time-dependent analysis showed that the negative impact of EBV was essentially seen in the first 2 years following diagnosis. These results warrant further studies regarding pathogenesis and specific treatment approaches for EBV-associated PTCL patients.

  9. Initial fluconazole prophylaxis may not be required in adults with acute leukemia or myelodysplastic/myeloproliferative disorders after reduced intensity conditioning peripheral blood stem cell allogeneic transplantation.

    PubMed

    Brissot, Eolia; Cahu, Xavier; Guillaume, Thierry; Delaunay, Jacques; Ayari, Sameh; Peterlin, Pierre; Le Bourgeois, Amandine; Harousseau, Jean-Luc; Milpied, Noel; Bene, Marie-Christine; Moreau, Philippe; Mohty, Mohamad; Chevallier, Patrice

    2015-04-01

    In the myeloablative transplant setting, the early use of fluconazole prophylaxis provides a benefit in overall survival. Recent changes in transplantation practices, including the use of peripheral blood stem cells (PBSC) and/or reduced intensity conditioning (RIC) regimen may have favorably impacted the epidemiology of invasive fungal infections (IFI) after allogeneic stem cell transplantation (allo-SCT). Yet, the impact of removing fluconazole prophylaxis after RIC PBSC allotransplant is ill known. Here, a retrospective analysis was performed comparing patients who received fluconazole as antifungal prophylaxis (n = 53) or not (n = 56) after allo-SCT for acute leukemia or myelodysplastic/myeloproliferative syndrome. Sixteen IFI were documented (14 %) at a median time of 103 days after transplantation, including eight before day +100, at a similar rate, whether the patients received fluconazole prophylaxis (13 %) or not (16 %). IFI were due mainly to Aspergillus species (87 %), and only two Candida-related IFI (13 %) were documented in the non-fluconazole group before day +100. The incidences of IFI (overall, before or after day +100) as well as 3-year overall and disease-free survival, non-relapse mortality, or acute and chronic graft-versus-host disease (GVHD) were similar between both groups. In conclusion, this study suggests that fluconazole may not be required at the initial phase of RIC allo-SCT using PBSC. This result has to be confirmed prospectively while Aspergillus prophylaxis should be discussed in this particular setting.

  10. Regional thermal specialisation in a mammal: temperature affects power output of core muscle more than that of peripheral muscle in adult mice (Mus musculus).

    PubMed

    James, Rob S; Tallis, Jason; Angilletta, Michael J

    2015-01-01

    In endotherms, such as mammals and birds, internal organs can specialise to function within a narrow thermal range. Consequently, these organs should become more sensitive to changes in body temperature. Yet, organs at the periphery of the body still experience considerable fluctuations in temperature, which could select for lower thermal sensitivity. We hypothesised that the performance of soleus muscle taken from the leg would depend less on temperature than would the performance of diaphragm muscle taken from the body core. Soleus and diaphragm muscles were isolated from mice and subjected to isometric and work-loop studies to analyse mechanical performance at temperatures between 15 and 40 °C. Across this thermal range, soleus muscle took longer to generate isometric force and longer to relax, and tended to produce greater normalised maximal force (stress) than did diaphragm muscle. The time required to produce half of maximal force during isometric tetanus and the time required to relax half of maximal force were both more sensitive to temperature in soleus than they were in diaphragm. However, thermal sensitivities of maximal force during isometric tetani were similar for both muscles. Consistent with our hypothesis, power output (the product of speed and force) was greater in magnitude and more thermally sensitive in diaphragm than it was in soleus. Our findings, when combined with previous observations of muscles from regionally endothermic fish, suggest that endothermy influences the thermal sensitivities of power output in core and peripheral muscles.

  11. Reevaluating and Refining Peripherality.

    ERIC Educational Resources Information Center

    Thomas, Erik R.

    The idea that vowel nuclei in many northern European languages can be divided into peripheral and non-peripheral categories is discussed. Peripheral vowels are those located at the edge of the vowel envelope, and non-peripheral nuclei are those located on the inside. This assertion has not received as much scrutiny as it should. There are at least…

  12. Current trends in autoimmunity and the nervous system.

    PubMed

    Selmi, Carlo; Barin, Jobert G; Rose, Noel R

    2016-12-01

    In the broad field of autoimmunity and clinical immunology, experimental evidence over the past few years have demonstrated several connections between the immune system and the nervous system, both central and peripheral, leading to the definition of neuroimmunology and of an immune-brain axis. Indeed, the central nervous system as an immune-privileged site, thanks to the blood-brain barrier, is no longer a dogma as the barrier may be altered during chronic inflammation with disruptive changes of endothelial cells and tight junctions, largely mediated by adenosine receptors and the expression of CD39/CD73. The diseases that encompass the neuroimmunology field vary from primary nervous diseases such as multiple sclerosis to systemic conditions with neuropsychiatric complications, such as systemic lupus erythematosus or vasculitidies. Despite potentially similar clinical manifestations, the pathogenesis of each condition is different, but the interaction between the ultra-specialized structure that is the nervous system and inflammation mediators are crucial. Two examples come from anti-dsDNA cross-reacting with anti-N-Methyl-d-Aspartate receptor (NMDAR) antibodies in neuropsychiatric lupus or the new family of antibody-associated neuronal autoimmune diseases including classic paraneoplastic syndromes with antibodies directed to intracellular antigens (Hu, Yo, Ri) and autoimmune encephalitis. In the case of multiple sclerosis, the T cell paradigm is now complicated by the growing evidence of a B cell involvement, particularly via aquaporin antibodies, and their influence on Th1 and Th17 lineages. Inspired by a productive AARDA-sponsored colloquium among experts we provide a critical review of the literature on the pathogenesis of different immune-mediated diseases with neurologic manifestations and we discuss the basic immunology of the central nervous system and the interaction between immune cells and the peripheral nervous system.

  13. [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.

  14. 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

  15. Metal toxicity in the central nervous system.

    PubMed Central

    Clarkson, T W

    1987-01-01

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

  16. Brain imaging correlates of peripheral nerve stimulation

    PubMed Central

    Bari, Ausaf A.; Pouratian, Nader

    2012-01-01

    Direct peripheral nerve stimulation is an effective treatment for a number of disorders including epilepsy, depression, neuropathic pain, cluster headache, and urological dysfunction. The efficacy of this stimulation is ultimately due to modulation of activity in the central nervous system. However, the exact brain regions involved in each disorder and how they are modulated by peripheral nerve stimulation is not fully understood. The use of functional neuroimaging such as SPECT, PET and fMRI in patients undergoing peripheral nerve stimulation can help us to understand these mechanisms. We review the literature for functional neuroimaging performed in patients implanted with peripheral nerve stimulators for the above-mentioned disorders. These studies suggest that brain activity in response to peripheral nerve stimulation is a complex interaction between the stimulation parameters, disease type and severity, chronicity of stimulation, as well as nonspecific effects. From this information we may be able to understand which brain structures are involved in the mechanism of peripheral nerve stimulation as well as define the neural substrates underlying these disorders. PMID:23230531

  17. 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)

  18. Macrophage-Induced Blood Vessels Guide Schwann Cell-Mediated Regeneration of Peripheral Nerves.

    PubMed

    Cattin, Anne-Laure; Burden, Jemima J; Van Emmenis, Lucie; Mackenzie, Francesca E; Hoving, Julian J A; Garcia Calavia, Noelia; Guo, Yanping; McLaughlin, Maeve; Rosenberg, Laura H; Quereda, Victor; Jamecna, Denisa; Napoli, Ilaria; Parrinello, Simona; Enver, Tariq; Ruhrberg, Christiana; Lloyd, Alison C

    2015-08-27

    The peripheral nervous system has remarkable regenerative capacities in that it can repair a fully cut nerve. This requires Schwann cells to migrate collectively to guide regrowing axons across a 'bridge' of new tissue, which forms to reconnect a severed nerve. Here we show that blood vessels direct the migrating cords of Schwann cells. This multicellular process is initiated by hypoxia, selectively sensed by macrophages within the bridge, which via VEGF-A secretion induce a polarized vasculature that relieves the hypoxia. Schwann cells then use the blood vessels as "tracks" to cross the bridge taking regrowing axons with them. Importantly, disrupting the organization of the newly formed blood vessels in vivo, either by inhibiting the angiogenic signal or by re-orienting them, compromises Schwann cell directionality resulting in defective nerve repair. This study provides important insights into how the choreography of multiple cell-types is required for the regeneration of an adult tissue.

  19. Spatiotemporal development of the embryonic nervous system of Saccoglossus kowalevskii.

    PubMed

    Cunningham, Doreen; Casey, Elena Silva

    2014-02-01

    Defining the organization and temporal onset of key steps in neurogenesis in invertebrate deuterostomes is critical to understand the evolution of the bilaterian and deuterostome nervous systems. Although recent studies have revealed the organization of the nervous system in adult hemichordates, little attention has been paid to neurogenesis during embryonic development in this third major phylum of deuterostomes. We examine the early events of neural development in the enteropneust hemichordate Saccoglossus kowalevskii by analyzing the expression of 11 orthologs of key genes associated with neurogenesis in an expansive range of bilaterians. Using in situ hybridization (ISH) and RT-PCR, we follow the course of neural development to track the transition of the early embryonic diffuse nervous system to the more regionalized midline nervous system of the adult. We show that in Saccoglossus, neural progenitor markers are expressed maternally and broadly encircle the developing embryo. An increase in their expression and the onset of pan neural markers, indicate that neural specification occurs in late blastulae - early gastrulae. By mid-gastrulation, punctate expression of markers of differentiating neurons encircling the embryo indicate the presence of immature neurons, and at the end of gastrulation when the embryo begins to elongate, markers of mature neurons are expressed. At this stage, expression of a subset of neuronal markers is concentrated along the trunk ventral and dorsal midlines. These data indicate that the diffuse embryonic nervous system of Saccoglossus is transient and quickly reorganizes before hatching to resemble the adult regionalized, centralized nervous system. This regionalization occurs at a much earlier developmental stage than anticipated indicating that centralization is not linked in S. kowalevskii to a lifestyle change of a swimming larva metamorphosing to a crawling worm-like adult.

  20. Primary central nervous system posttransplant lymphoproliferative disorders.

    PubMed

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

    2004-02-01

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

  1. Alternative generation of CNS neural stem cells and PNS derivatives from neural crest-derived peripheral stem cells.

    PubMed

    Weber, Marlen; Apostolova, Galina; Widera, Darius; Mittelbronn, Michel; Dechant, Georg; Kaltschmidt, Barbara; Rohrer, Hermann

    2015-02-01

    Neural crest-derived stem cells (NCSCs) from the embryonic peripheral nervous system (PNS) can be reprogrammed in neurosphere (NS) culture to rNCSCs that produce central nervous system (CNS) progeny, including myelinating oligodendrocytes. Using global gene expression analysis we now demonstrate that rNCSCs completely lose their previous PNS characteristics and acquire the identity of neural stem cells derived from embryonic spinal cord. Reprogramming proceeds rapidly and results in a homogenous population of Olig2-, Sox3-, and Lex-positive CNS stem cells. Low-level expression of pluripotency inducing genes Oct4, Nanog, and Klf4 argues against a transient pluripotent state during reprogramming. The acquisition of CNS properties is prevented in the presence of BMP4 (BMP NCSCs) as shown by marker gene expression and the potential to produce PNS neurons and glia. In addition, genes characteristic for mesenchymal and perivascular progenitors are expressed, which suggests that BMP NCSCs are directed toward a pericyte progenitor/mesenchymal stem cell (MSC) fate. Adult NCSCs from mouse palate, an easily accessible source of adult NCSCs, display strikingly similar properties. They do not generate cells with CNS characteristics but lose the neural crest markers Sox10 and p75 and produce MSC-like cells. These findings show that embryonic NCSCs acquire a full CNS identity in NS culture. In contrast, MSC-like cells are generated from BMP NCSCs and pNCSCs, which reveals that postmigratory NCSCs are a source for MSC-like cells up to the adult stage.

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

    PubMed

    Petrov, A A; Zaitseva, O V

    2012-08-01

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

  3. 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

  4. Pharmacokinetic and Maximum Tolerated Dose Study of Micafungin in Combination with Fluconazole versus Fluconazole Alone for Prophylaxis of Fungal Infections in Adult Patients Undergoing a Bone Marrow or Peripheral Stem Cell Transplant

    PubMed Central

    Hiemenz, J.; Cagnoni, P.; Simpson, D.; Devine, S.; Chao, N.; Keirns, J.; Lau, W.; Facklam, D.; Buell, D.

    2005-01-01

    In this dose escalation study, 74 adult cancer patients undergoing bone marrow or peripheral blood stem cell transplantation received fluconazole (400 mg/day) and either normal saline (control) (12 subjects) or micafungin (12.5 to 200 mg/day) (62 subjects) for up to 4 weeks. The maximum tolerated dose (MTD) of micafungin was not reached, based on the development of Southwest Oncology Group criteria for grade 3 toxicity; drug-related toxicities were rare. Commonly occurring adverse events considered related to micafungin were headache (6.8%), arthralgia (6.8%), hypophosphatemia (4.1%), insomnia (4.1%), maculopapular rash (4.1%), and rash (4.1%). Pharmacokinetic profiles for micafungin on days 1 and 7 were similar. The mean half-life was approximately 13 h, with little variance after repeated or increasing doses. Mean maximum concentrations of the drug in serum and areas under the concentration-time curve from 0 to 24 h were approximately proportional to dose. There was no clinical or kinetic evidence of interaction between micafungin and fluconazole. Five of 12 patients (42%) in the control group and 14 of 62 (23%) in the micafungin-plus-fluconazole groups had a suspected fungal infection during treatment which resulted in empirical treatment with amphotericin B. The combination of micafungin and fluconazole was found to be safe in this high-risk patient population. The MTD of micafungin was not reached even at doses up to 200 mg/day for 4 weeks. The pharmacokinetic profile of micafungin in adult cancer patients with blood or marrow transplants is consistent with the profile in healthy volunteers, and the area under the curve is proportional to dose. PMID:15793107

  5. Pharmacokinetic and maximum tolerated dose study of micafungin in combination with fluconazole versus fluconazole alone for prophylaxis of fungal infections in adult patients undergoing a bone marrow or peripheral stem cell transplant.

    PubMed

    Hiemenz, J; Cagnoni, P; Simpson, D; Devine, S; Chao, N; Keirns, J; Lau, W; Facklam, D; Buell, D

    2005-04-01

    In this dose escalation study, 74 adult cancer patients undergoing bone marrow or peripheral blood stem cell transplantation received fluconazole (400 mg/day) and either normal saline (control) (12 subjects) or micafungin (12.5 to 200 mg/day) (62 subjects) for up to 4 weeks. The maximum tolerated dose (MTD) of micafungin was not reached, based on the development of Southwest Oncology Group criteria for grade 3 toxicity; drug-related toxicities were rare. Commonly occurring adverse events considered related to micafungin were headache (6.8%), arthralgia (6.8%), hypophosphatemia (4.1%), insomnia (4.1%), maculopapular rash (4.1%), and rash (4.1%). Pharmacokinetic profiles for micafungin on days 1 and 7 were similar. The mean half-life was approximately 13 h, with little variance after repeated or increasing doses. Mean maximum concentrations of the drug in serum and areas under the concentration-time curve from 0 to 24 h were approximately proportional to dose. There was no clinical or kinetic evidence of interaction between micafungin and fluconazole. Five of 12 patients (42%) in the control group and 14 of 62 (23%) in the micafungin-plus-fluconazole groups had a suspected fungal infection during treatment which resulted in empirical treatment with amphotericin B. The combination of micafungin and fluconazole was found to be safe in this high-risk patient population. The MTD of micafungin was not reached even at doses up to 200 mg/day for 4 weeks. The pharmacokinetic profile of micafungin in adult cancer patients with blood or marrow transplants is consistent with the profile in healthy volunteers, and the area under the curve is proportional to dose.

  6. Spinal Cord Repair with Engineered Nervous Tissue

    DTIC Science & Technology

    2013-10-01

    transplanted nervous tissue constructs on...recovery of motor function. Specific Aim 2: Evaluation of the survival and integration of transplanted living nervous tissue constructs and host... Nervous Tissue PRINCIPAL INVESTIGATOR: Douglas H. Smith, M.D. CONTRACTING

  7. Peripheral artery bypass - leg

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/007394.htm Peripheral artery bypass - leg To use the sharing features on this page, please enable JavaScript. Peripheral artery bypass is surgery to reroute the blood supply ...

  8. 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.

  9. 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

  10. Noise in the nervous system.

    PubMed

    Faisal, A Aldo; Selen, Luc P J; Wolpert, Daniel M

    2008-04-01

    Noise--random disturbances of signals--poses a fundamental problem for information processing and affects all aspects of nervous-system function. However, the nature, amount and impact of noise in the nervous system have only recently been addressed in a quantitative manner. Experimental and computational methods have shown that multiple noise sources contribute to cellular and behavioural trial-to-trial variability. We review the sources of noise in the nervous system, from the molecular to the behavioural level, and show how noise contributes to trial-to-trial variability. We highlight how noise affects neuronal networks and the principles the nervous system applies to counter detrimental effects of noise, and briefly discuss noise's potential benefits.

  11. Central and peripheral demyelination

    PubMed Central

    Mehndiratta, Man Mohan; Gulati, Natasha Singh

    2014-01-01

    Several conditions cause damage to the inherently normal myelin of central nervous system, perepheral nervous system or both central and perepheral nervous system and hence termed as central demyelinating diseases, perepheral demyelinating diseases and combined central and perepheral demyelinating diseases respectively. Here we analysed and foccused on the etiology, prevalance, incidence and age of these demyelinating disorders. Clinical attention and various diagnostic tests are needed to adequately assess all these possibilities. PMID:24741263

  12. Diagnostic approach to peripheral neuropathy

    PubMed Central

    Misra, Usha Kant; Kalita, Jayantee; Nair, Pradeep P.

    2008-01-01

    Peripheral neuropathy refers to disorders of the peripheral nervous system. They have numerous causes and diverse presentations; hence, a systematic and logical approach is needed for cost-effective diagnosis, especially of treatable neuropathies. A detailed history of symptoms, family and occupational history should be obtained. General and systemic examinations provide valuable clues. Neurological examinations investigating sensory, motor and autonomic signs help to define the topography and nature of neuropathy. Large fiber neuropathy manifests with the loss of joint position and vibration sense and sensory ataxia, whereas small fiber neuropathy manifests with the impairment of pain, temperature and autonomic functions. Electrodiagnostic (EDx) tests include sensory, motor nerve conduction, F response, H reflex and needle electromyography (EMG). EDx helps in documenting the extent of sensory motor deficits, categorizing demyelinating (prolonged terminal latency, slowing of nerve conduction velocity, dispersion and conduction block) and axonal (marginal slowing of nerve conduction and small compound muscle or sensory action potential and dennervation on EMG). Uniform demyelinating features are suggestive of hereditary demyelination, whereas difference between nerves and segments of the same nerve favor acquired demyelination. Finally, neuropathy is classified into mononeuropathy commonly due to entrapment or trauma; mononeuropathy multiplex commonly due to leprosy and vasculitis; and polyneuropathy due to systemic, metabolic or toxic etiology. Laboratory investigations are carried out as indicated and specialized tests such as biochemical, immunological, genetic studies, cerebrospinal fluid (CSF) examination and nerve biopsy are carried out in selected patients. Approximately 20% patients with neuropathy remain undiagnosed but the prognosis is not bad in them. PMID:19893645

  13. Using Stem Cells to Grow Artificial Tissue for Peripheral Nerve Repair

    PubMed Central

    Bhangra, Kulraj Singh; Busuttil, Francesca

    2016-01-01

    Peripheral nerve injury continues to pose a clinical hurdle despite its frequency and advances in treatment. Unlike the central nervous system, neurons of the peripheral nervous system have a greater ability to regenerate. However, due to a number of confounding factors, this is often both incomplete and inadequate. The lack of supportive Schwann cells or their inability to maintain a regenerative phenotype is a major factor. Advances in nervous system tissue engineering technology have led to efforts to build Schwann cell scaffolds to overcome this and enhance the regenerative capacity of neurons following injury. Stem cells that can differentiate along a neural lineage represent an essential resource and starting material for this process. In this review, we discuss the different stem cell types that are showing promise for nervous system tissue engineering in the context of peripheral nerve injury. We also discuss some of the biological, practical, ethical, and commercial considerations in using these different stem cells for future clinical application. PMID:27212954

  14. Controversies related to electromagnetic field exposure on peripheral nerves.