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Sample records for adult peripheral nervous

  1. 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.

  2. 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

  3. In vivo peripheral nervous system insulin signaling

    PubMed Central

    Grote, Caleb W.; Ryals, Janelle M.; Wright, Douglas E.

    2014-01-01

    Alterations in peripheral nervous system (PNS) insulin support may contribute to diabetic neuropathy (DN); yet, PNS insulin signaling is not fully defined. Here, we investigated in vivo insulin signaling in the PNS and compared the insulin-responsiveness to that of muscle, liver, and adipose. Nondiabetic mice were administered increasing doses of insulin to define a dose response relationship between insulin and Akt activation in the DRG and sciatic nerve. Resulting EC50 doses were used to characterize the PNS insulin signaling time course and make comparisons between insulin signaling in the PNS and other peripheral tissues (i.e., muscle, liver, adipose). The results demonstrate that the PNS is responsive to insulin and that differences in insulin signaling pathway activation exist between PNS compartments. At a therapeutically relevant dose, Akt was activated in the muscle, liver, and adipose at 30 minutes, correlating with the changes in blood glucose levels. Interestingly, the sciatic nerve showed a similar signaling profile as insulin-sensitive tissues, however there was not a comparable activation in the DRG or spinal cord. These results present new evidence regarding PNS insulin signaling pathways in vivo and provide a baseline for studies investigating the contribution of disrupted PNS insulin signaling to DN pathogenesis. PMID:24028189

  4. Myelin synthesis in the peripheral nervous system.

    PubMed

    Garbay, B; Heape, A M; Sargueil, F; Cassagne, C

    2000-06-01

    By imposing saltatory conduction on the nervous impulse, the principal role of the myelin sheath is to allow the faster propagation of action potentials along the axons which it surrounds. Peripheral nervous system (PNS) myelin is formed by the differentiation of the plasma membrane of Schwann cells. One of the biochemical characteristics that distinguishes myelin from other biological membranes is its high lipid-to-protein ratio. All the major lipid classes are represented in the myelin membrane, while several myelin-specific proteins have been identified. During development, the presence of axons is required for the initiation of myelination, but the nature of the axonal signal is still unknown. The only certainties are that this signal is synthesized by axons whose diameter is greater than 0.7 microm, and that the signal(s) include(s) a diffusible molecule. Morphological studies have provided us with information concerning the timing of myelination, the mechanism by which immature Schwann cells differentiate into a myelinating phenotype and lay down the myelin sheath around the axon, and the accumulation and the structure of the myelin membrane. The last 20 years have seen the identification and the cDNA and gene cloning of the major PNS myelin proteins, which signalled the beginning of the knock-out decade: transgenic null-mutant mice have been created for almost every protein gene. The study of these animals shows that the formation of myelin is considerably less sensitive to molecular alterations than the maintenance of myelin. During the same period, important data has been gathered concerning the synthesis and function of lipids in PNS myelin, although this field has received relatively little attention compared with that of their protein counterparts. PMID:10727776

  5. Role of Neuroactive Steroids in the Peripheral Nervous System

    PubMed Central

    Melcangi, Roberto Cosimo; Giatti, Silvia; Pesaresi, Marzia; Calabrese, Donato; Mitro, Nico; Caruso, Donatella; Garcia-Segura, Luis Miguel

    2011-01-01

    Several reviews have so far pointed out on the relevant physiological and pharmacological role exerted by neuroactive steroids in the central nervous system. In the present review we summarize observations indicating that synthesis and metabolism of neuroactive steroids also occur in the peripheral nerves. Interestingly, peripheral nervous system is also a target of their action. Indeed, as here reported neuroactive steroids are physiological regulators of peripheral nerve functions and they may also represent interesting therapeutic tools for different types of peripheral neuropathy. PMID:22654839

  6. 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. PMID:25824325

  7. Pathology of the peripheral nervous system.

    PubMed

    Fernandez; Marchese; Palma; Lauretti; Procaccini; Pallini

    1999-01-26

    In this review, the first four papers deal with an important chapter in peripheral nerve surgery: cranial nerve reconstruction after injury occurring during skull base surgery. The last paper discusses the problem of peripheral nerves affected by a ganglion cyst. Damage to a cranial nerve is no longer considered to be an absolutely irreparable event. The first two studies are related to facial nerve management during the surgical treatment of vestibular schwannomas. The most common mechanisms responsible for facial nerve injury during tumor removal and the technical means to avoid them are cited. The importance of intraoperative neurophysiologic monitoring to save the facial nerve is stressed. A comparison between microsurgery and radiosurgery results in the conclusion that for vestibular schwannomas, the first choice of treatment is microsurgery. These two large and exceptional series show that by using a refined technique it is possible to obtain both total tumor removal and preservation of the facial nerve in most of the vestibular schwannomas. In the minority of patients in whom the facial nerve is severed, there are several therapeutic options to re-establish facial nerve function. After facial nerve reconstruction, performed immediately during the same tumor operation, a satisfactory reinnervation was obtained in 74% of the cases. After facial nerve reanimation, using as donor nerve the hypoglossus and performed 1 week after the tumor operation, a satisfactory reinnervation was obtained in 96% of the cases. The other two papers deal with the intraoperative transection of the trochlear and abducens nerve during surgery for skull base tumors. These two cranial nerves, owing to their simply organized motor nerve system (they are purely motor nerves and supply one muscle each), show quite a good expectation of functional recovery. The behavior of ganglion cysts involving peripheral nerves is the topic of the last paper reviewed. These cysts are benign lesions

  8. Molecular mechanisms regulating myelination in the peripheral nervous system.

    PubMed

    Pereira, Jorge A; Lebrun-Julien, Frédéric; Suter, Ueli

    2012-02-01

    Glial cells and neurons are engaged in a continuous and highly regulated bidirectional dialog. A remarkable example is the control of myelination. Oligodendrocytes in the central nervous system (CNS) and Schwann cells (SCs) in the peripheral nervous system (PNS) wrap their plasma membranes around axons to organize myelinated nerve fibers that allow rapid saltatory conduction. The functionality of this system is critical, as revealed by numerous neurological diseases that result from deregulation of the system, including multiple sclerosis and peripheral neuropathies. In this review we focus on PNS myelination and present a conceptual framework that integrates crucial signaling mechanisms with basic SC biology. We will highlight signaling hubs and overarching molecular mechanisms, including genetic, epigenetic, and post-translational controls, which together regulate the interplay between SCs and axons, extracellular signals, and the transcriptional network. PMID:22192173

  9. 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.

  10. Markers of inflammation, Vitamin E and peripheral nervous system function

    PubMed Central

    Di Iorio, Angelo; Cherubini, Antonio; Volpato, Stefano; Sparvieri, Eleonora; Lauretani, Fulvio; Franceschi, Claudio; Senin, Umberto; Abate, Giuseppe; Paganelli, Roberto; Martin, Antonio; Andres-Lacueva, Cristina; Ferrucci, Luigi

    2009-01-01

    Background Aging of the peripheral nervous system is associated with several morphologic and functional changes, including a decrease of the nerve conduction velocity. There is evidence that these changes contribute to age-related-decline in muscle strength, sensory discrimination, and autonomic responses. The aim of this study was to characterize the decline in nerve conduction velocity in the peripheral nervous system over the aging process and to identify factors that, independent of age, affect nerve conduction velocity. Methods We measured motor nerve conduction velocity of the right superficial peroneal nerve using a standard neurophysiologic technique in a population-based sample of subjects aged between 20 and 103 years old enrolled in the InCHIANTI study. Results Average conduction velocities in the peripheral nerve decreased linearly with age in both sexes. We found that diabetes, cognitive impairment, uric acid, sIL-6R and α-tocopherol were significant predictors of nerve conduction velocity independently of the potential confounding effect of age, sex, sex × age interaction term, height, lymphocytes, neutrophils number, α1 and α2-globulin serum protein. Conclusion Our findings are consistent with the hypothesis that inflammation and inadequate antioxidant defenses are associated with accelerated decline of nerve conduction velocity over the aging process. PMID:16112778

  11. Effects of lymphoma on the peripheral nervous system.

    PubMed Central

    Hughes, R A; Britton, T; Richards, M

    1994-01-01

    Peripheral nervous system abnormalities occur in 5% of patients with lymphoma and have a wide differential diagnosis. Herpes zoster is the commonest cause. Vinca alkaloids are the only drugs used in lymphoma which commonly cause neuropathy. Compression or infiltration of nerve roots by lymphoma is a rare presenting feature but becomes more common with advanced disease. Radiation plexopathy does not usually develop until at least 6 months after irradiation and can be difficult to distinguish from neoplastic infiltration. Either multifocal infiltration of nerves or lymphoma-associated vasculitis may present as a peripheral neuropathy. The incidence of Guillain-Barré (GBS) syndrome, and possibly chronic idiopathic demyelinating polyradiculoneuropathy, appears to be increased in association with lymphoma, especially Hodgkin's disease. Subacute sensory neuronopathy and subacute lower motor neuronopathy have both been reported as paraneoplastic syndromes associated with Hodgkin's disease. Treatment of the underlying lymphoma is only rarely followed by recovery of the associated neuropathy. PMID:7932460

  12. 75 FR 75681 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-06

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

  13. 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

  14. Control of Prosthetic Hands via the Peripheral Nervous System.

    PubMed

    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

  15. Magnetic resonance imaging of the peripheral nervous system.

    PubMed

    Fritz, R C; Boutin, R D; Boutin, R A

    2001-05-01

    An accurate diagnosis is the essential first step toward a successful treatment plan in patients who present with pain and suspected nerve entrapment. Pain and dysfunction are often related to an acute traumatic event or a classic presentation that leads to a straightforward clinical diagnosis. The diagnostic approach to abnormalities of the peripheral nervous system always begins with a thorough history and physical examination. Imaging may play an important role in confirming the initial clinical [figure: see text] diagnosis so that a rational plan of treatment may be selected. Diagnostic imaging is especially important when there is significant uncertainty regarding the cause of pain and the outcome may be improved by timely implementation of various treatment options. Diagnostic accuracy is important when various conditions in the differential diagnosis would be treated differently from the beginning. Indeed, certain conditions that result in pain and dysfunction related to peripheral nerve entrapment are best treated with initial rest, protection, and rehabilitation whereas other conditions are best treated with prompt surgery. Promptly arriving at an accurate diagnosis is an essential step in designing a rational course of therapy, in achieving a good outcome, and in treating medical conditions in a timely fashion. Indeed, because pain is mediated through peripheral nerves, establishing an accurate diagnosis is especially important in disorders of the peripheral nervous system in which there may be considerable pain and suffering with an incorrect or delayed diagnosis. Moreover, an early diagnosis is desirable [figure: see text] to preserve motor power and sensory function in cases of clinically occult nerve entrapment. Although entrapment syndromes are well described and widely documented in the literature, they may be easily missed in clinical practice in certain instances. Although MR imaging is useful to confirm and characterize a known or suspected case

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

    PubMed

    Andreu, David; Guiraud, David; Souquet, Guillaume

    2009-04-01

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

  17. 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.

  18. Effects of hyperthermia on the peripheral nervous system: a review.

    PubMed

    Haveman, J; Van Der Zee, J; Wondergem, J; Hoogeveen, J F; Hulshof, M C C M

    2004-06-01

    The present paper overviews the current knowledge about effects of hyperthermia at temperatures used in clinical oncology on the peripheral nervous system. From the experimental studies it may be concluded that the heat sensitivity of the nerve is determined by the sensitivity of the nerve vasculature. These studies show that in order to avoid induction of severe neuropathy, application of heat to the peripheral nerves should not be in excess of doses of 30 min at 44 degrees C or equivalent. Using modern equipment for application of loco-regional hyperthermia the incidence of even mild neurological complications is very low. In hyperthermic isolated limb perfusion (HILP) neurotoxicity is an often-mentioned side effect, this is in spite of the fact that in all studies a relatively mild hyperthermic temperature is used that, based on the experimental studies, should be well tolerated by the nerves and other normal tissues in the limbs. It seems that the neurotoxicity observed after HILP results from thermal enhancement of drug toxicity, very probably combined with effects of a high tourniquet pressure that is used to isolate the blood flow in the leg. Whole body hyperthermia (WBH), using anesthesia and appropriate monitoring to avoid cardiovascular stress is at present considered a safe procedure. Still in the recent past cases of neuropathy after treatment have been described. When chemotherapy, and notably cisplatin, is administered before or during hyperthermia there are several clinical and experimental observations that indicate a limited tolerance of the peripheral nervous tissue in such case. Also previous radiotherapy may limit the tolerance of nerves to hyperthermia, notably when radiation is applied with a large field size. Experimental studies show that combined treatment with radiation and heat leads to enhancement of effects of radiation (enhancement ratio approximately 1.5 at 60 min at 44 degrees C). A clear contraindication for the application of

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. 76 FR 3912 - Peripheral and Central Nervous System Drugs Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-21

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

  5. 75 FR 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...

  6. 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...

  7. Mechanisms of immune regulation in the peripheral nervous system.

    PubMed

    Gold, R; Archelos, J J; Hartung, H P

    1999-04-01

    The peripheral nervous system (PNS) is a target for heterogenous immune attacks mediated by different components of the systemic immune compartment. T cells, B cells, and macrophages can interact with endogenous, partially immune-competent glial cells and contribute to local inflammation. Cellular and humoral immune functions of Schwann cells have been well characterized in vitro. In addition, the interaction of the humoral and cellular immune system with the cellular and extracellular components in the PNS may determine the extent of tissue inflammation and repair processes such as remyelination and neuronal outgrowth. The animal model experimental autoimmune neuritis (EAN) allows direct monitoring of these immune responses in vivo. In EAN contributions to regulate autoimmunity in the PNS are made by adhesion molecules and by cytokines that orchestrate cellular interactions. The PNS has a significant potential to eliminate T cell inflammation via apoptosis, which is almost lacking in other tissues such as muscle and skin. In vitro experiments suggest different scenarios how specific cellular and humoral elements in the PNS may sensitize autoreactive T cells for apoptosis in vivo. Interestingly several conventional and novel immunotherapeutic approaches like glucocorticosteroids and high-dose antigen therapy induce T cell apoptosis in situ in EAN. A better understanding of immune regulation and its failure in the PNS may help to develop improved, more specific immunotherapies. PMID:10219750

  8. 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.

  9. Transgenic mice expressing the Peripherin-EGFP genomic reporter display intrinsic peripheral nervous system fluorescence.

    PubMed

    McLenachan, Samuel; Goldshmit, Yona; Fowler, Kerry J; Voullaire, Lucille; Holloway, Timothy P; Turnley, Ann M; Ioannou, Panos A; Sarsero, Joseph P

    2008-12-01

    The development of homologous recombination methods for the precise modification of bacterial artificial chromosomes has allowed the introduction of disease causing mutations or fluorescent reporter genes into human loci for functional studies. We have introduced the EGFP gene into the human PRPH-1 locus to create the Peripherin-EGFP (hPRPH1-G) genomic reporter construct. The hPRPH1-G reporter was used to create transgenic mice with an intrinsically fluorescent peripheral nervous system (PNS). During development, hPRPH1-G expression was concomitant with the acquisition of neuronal cell fate and growing axons could be observed in whole embryo mounts. In the adult, sensory neurons were labeled in both the PNS and central nervous system, while motor neurons in the spinal cord had more limited expression. The fusion protein labeled long neuronal processes, highlighting the peripheral circuitry of hPRPH1-G transgenic mice to provide a useful resource for a range of neurobiological applications. PMID:18709437

  10. Prolonged Complete Response in a Pediatric Patient With Primary Peripheral T-Cell Lymphoma of the Central Nervous System.

    PubMed

    Shalabi, Haneen; Angiolillo, Anne; Vezina, Gilbert; Rubenstein, James L; Pittaluga, Stefania; Raffeld, Mark; Marcus, Leigh

    2015-01-01

    We describe a child with a 2-week history of progressive headaches, blurry vision, and intermittent vomiting. Magnetic resonance imaging (MRI) of the brain showed a deep left hemispheric lesion with extension into the corpus callosum. Histology and immunophenotyping of the lesion was consistent with peripheral T-cell lymphoma, not otherwise specified. Chemotherapy was initiated and a complete remission was achieved. This case illustrates that a chemotherapeutic regimen used in adults with central nervous system (CNS) lymphoma can achieve durable remissions in pediatric patients with peripheral T-cell lymphoma, not otherwise specified of the CNS. PMID:26384083

  11. 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

  12. 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.

  13. [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. PMID:20619163

  14. Beyond the brain: Optogenetic control in the spinal cord and peripheral nervous system.

    PubMed

    Montgomery, Kate L; Iyer, Shrivats M; Christensen, Amelia J; Deisseroth, Karl; Delp, Scott L

    2016-05-01

    Optogenetics offers promise for dissecting the complex neural circuits of the spinal cord and peripheral nervous system and has therapeutic potential for addressing unmet clinical needs. Much progress has been made to enable optogenetic control in normal and disease states, both in proof-of-concept and mechanistic studies in rodent models. In this Review, we discuss challenges in using optogenetics to study the mammalian spinal cord and peripheral nervous system, synthesize common features that unite the work done thus far, and describe a route forward for the successful application of optogenetics to translational research beyond the brain. PMID:27147590

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

    PubMed Central

    Campbell, Preston; Ma, Yun

    2013-01-01

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

  16. Ultrasonic stimulation of peripheral nervous tissue: an investigation into mechanisms

    NASA Astrophysics Data System (ADS)

    Wright, C. J.; Rothwell, J.; Saffari, N.

    2015-01-01

    Neuro-stimulation has wide ranging clinical and research potential but this is currently limited either by low resolution, penetration or by highly invasive procedures. It has been reported in previous studies that ultrasound is able to elicit a neuro-stimulatory effect at a higher resolution than other non-invasive approaches but both the underlying mechanism that makes this possible and the practical details of how it can be implemented are still poorly understood. The current study has identified the main issues that need to be resolved in the field, proposing several different approaches to tackling these areas. An isolated in vitro peripheral nerve bundle was chosen as a simple model to demonstrate and investigate the neuro-stimulatory effect after preliminary results showed successful stimulation in a skin-nerve preparation. Early results from the nerve bundle show successful neurostimulation, indicating that structures in the peripheral nerve axon are sensitive to ultrasound. Further research using this model should reveal more precisely what structures are being affected and how to optimise the effect, helping to inform the design of future procedures and devices used in in vivo applications.

  17. Extranodal Lymphoma with Peripheral Nervous System Involvement in a Dog

    PubMed Central

    UENO, Hiroshi; MIYOSHI, Kenjiro; FUKUI, Sho; KONDO, Yumi; MATSUDA, Kazuya; UCHIDE, Tsuyoshi

    2014-01-01

    ABSTRACT An 8-year-old neutered female Cavalier King Charles spaniel was evaluated for progressing right forelimb lameness. Magnetic resonance imaging revealed that the right-side radial nerves and the caudal brachial plexus were swollen. The histological and molecular biological diagnosis by partial biopsy of the C8 spinal nerve was T-cell lymphoma. Coadministration of lomustine and irradiation was started. However, this therapy was ineffective. At necropsy, neoplastic tissues were seen extending into the subarachnoid space of the spinal cord, liver, pancreas and kidneys as gross findings. A large mass was also identified occupying the caudal thorax. Histologic findings included infiltration in these organs and the mass by neoplastic lymphocytes. To date, involvement of peripheral nerves (neurolymphomatosis) is rarely reported in veterinary species. PMID:24419974

  18. Epineurium-mimicking chitosan conduits for peripheral nervous tissue engineering.

    PubMed

    Nawrotek, Katarzyna; Tylman, Michał; Rudnicka, Karolina; Gatkowska, Justyna; Wieczorek, Marek

    2016-11-01

    In this investigation, we report on a fabrication method of epineurium-mimicking tubular conduits based on electrodeposition from chitosan solution. The pre-enrichment of electrodeposition solution with hyaluronic acid and/or collagen components results in structures which structural, morphological, and physicochemical properties can be controlled. In order to determine the optimal composition of the initial chitosan solution resulting in conduits meeting the requirements imposed on peripheral nerve implants, we perform chemical, physical, and biological studies. Both the molecular weight of hyaluronic acid and the concentration of additives are found to be crucial for the final mechanical as well as biological performance of conduits. Because, the obtained structures show biocompatibility when contacting with a mouse hippocampal cell line (mHippoE-18), we further plan to test their application potential on an animal model. PMID:27516256

  19. 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…

  20. Stimulation of the peripheral nervous system for pain control.

    PubMed

    Long, D M

    1983-01-01

    Transcutaneous stimulation is a proven effective way to relieve pain. Its optimal use requires an accurate patient diagnosis. Treatment of pain as a symptom only is likely to fail. There must be a careful psychosocial evaluation, for the majority of patients who come to the doctor complaining of pain have major psychological, social, or behavioral factors that are most important in the genesis of the complaint. Drug abuse must be corrected. Related symptoms, such as anxiety and depression, must be treated. Then, a thorough trail of transcutaneous stimulation is mandatory. A desultory use will undoubtedly lead to failure. This trial must begin with patient education by experienced personnel. Then the electrodes must be properly applied, and there must be a regular follow-up of stimulation to be certain the patient is utilizing it correctly. The patient must be supported through an adequate trial which should extend over 2-4 weeks before purchase of the device is contemplated. Furthermore, all related nursing and physician personnel must be educated in the proper use of the technique. The uninformed professional who denigrates the therapy is a very effective deterrent to appropriate use. In this situation, transcutaneous electrical stimulation will be of great value in the treatment of acute musculoskeletal injury and acute postoperative pain. It will be effective in the treatment of peripheral nerve injury pain, chronic musculoskeletal abnormalities, chronic pain in the patient who has undergone multiple operations upon the low back and neck, visceral pain, some of the reflex sympathetic dystrophies, and postherpetic neuralgia. Stimulation will not help a complaint which is psychosomatic in origin. It will not influence drug addiction. It is not likely to be useful in any situation where secondary gain is important. The metabolic neuropathies, pain of spinal cord injury, and pain from cerebrovascular accident will not respond frequently enough to warrant more than

  1. Modulation of steroid action in the central and peripheral nervous systems by nuclear receptor coactivators

    PubMed Central

    Tetel, Marc J.

    2009-01-01

    Steroid hormones act in the central and peripheral nervous systems to regulate a variety of functions, including development, cell proliferation, cognition and behavior. Many of these effects of steroid hormones are mediated by their respective receptors, which are members of the nuclear receptor superfamily of transcriptional activators. A variety of cell culture studies reveal that nuclear receptor coactivators are recruited to the steroid receptor complex and are critical in modulating steroid-dependent transcription. Thus, in addition to the availability of the hormone and its receptor, the expression of nuclear receptor coactivators is essential for modulating steroid receptor mediated transcription. This review will discuss the significance of nuclear receptor coactivators in modulating steroid-dependent gene expression in the central and peripheral nervous systems and the regulation of behavior. PMID:19541426

  2. Data supporting the role of Fyn in initiating myelination in the peripheral nervous system.

    PubMed

    Miyamoto, Yuki; Tamano, Moe; Torii, Tomohiro; Kawahara, Kazuko; Nakamura, Kazuaki; Tanoue, Akito; Takada, Shuji; Yamauchi, Junji

    2016-06-01

    Transgenic mice, which express active Fyn tyrosine kinase under the control of a glial fibrillary acidic protein promoter, have been produced. This promoter induces protein expression in the initiation stage of myelination in the peripheral nervous system (PNS) "Phosphorylation of cytohesin-1 by Fyn is required for initiation of myelination and the extent of myelination during development (Yamauchi et al., 2015 [1])". Herein we provide the data regarding myelination-related protein markers and myelin ultrastructure in transgenic mice. PMID:27115022

  3. 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

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

    PubMed

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

    2013-02-19

    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

  5. 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.

  6. Acid-Sensing Ion Channels as Potential Pharmacological Targets in Peripheral and Central Nervous System Diseases.

    PubMed

    Radu, Beatrice Mihaela; Banciu, Adela; Banciu, Daniel Dumitru; Radu, Mihai

    2016-01-01

    Acid-sensing ion channels (ASICs) are widely expressed in the body and represent good sensors for detecting protons. The pH drop in the nervous system is equivalent to ischemia and acidosis, and ASICs are very good detectors in discriminating slight changes in acidity. ASICs are important pharmacological targets being involved in a variety of pathophysiological processes affecting both the peripheral nervous system (e.g., peripheral pain, diabetic neuropathy) and the central nervous system (e.g., stroke, epilepsy, migraine, anxiety, fear, depression, neurodegenerative diseases, etc.). This review discusses the role played by ASICs in different pathologies and the pharmacological agents acting on ASICs that might represent promising drugs. As the majority of above-mentioned pathologies involve not only neuronal dysfunctions but also microvascular alterations, in the next future, ASICs may be also considered as potential pharmacological targets at the vasculature level. Perspectives and limitations in the use of ASICs antagonists and modulators as pharmaceutical agents are also discussed. PMID:26920689

  7. Data supporting the role of Fyn in initiating myelination in the peripheral nervous system

    PubMed Central

    Miyamoto, Yuki; Tamano, Moe; Torii, Tomohiro; Kawahara, Kazuko; Nakamura, Kazuaki; Tanoue, Akito; Takada, Shuji; Yamauchi, Junji

    2016-01-01

    Transgenic mice, which express active Fyn tyrosine kinase under the control of a glial fibrillary acidic protein promoter, have been produced. This promoter induces protein expression in the initiation stage of myelination in the peripheral nervous system (PNS) “Phosphorylation of cytohesin-1 by Fyn is required for initiation of myelination and the extent of myelination during development (Yamauchi et al., 2015 [1])”. Herein we provide the data regarding myelination-related protein markers and myelin ultrastructure in transgenic mice. PMID:27115022

  8. Genetic pathways for differentiation of the peripheral nervous system in ascidians.

    PubMed

    Waki, Kana; Imai, Kaoru S; Satou, Yutaka

    2015-01-01

    Ascidians belong to tunicates, the sister group of vertebrates. Peripheral nervous systems (PNSs) including epidermal sensory neurons (ESNs) in the trunk and dorsal tail regions of ascidian larvae are derived from cells adjacent to the neural plate, as in vertebrates. On the other hand, peripheral ESNs in the ventral tail region are derived from the ventral ectoderm under the control of BMP signalling, reminiscent of sensory neurons of amphioxus and protostomes. In this study, we show that two distinct mechanisms activate a common gene circuit consisting of Msx, Ascl.b, Tox, Delta.b and Pou4 in the dorsal and ventral regions to differentiate ESNs. Our results suggest that ventral ESNs of the ascidian larva are not directly homologous to vertebrate PNSs. The dorsal ESNs might have arisen via co-option of the original PNS gene circuit to the neural plate border in an ancestral chordate. PMID:26515371

  9. ApoE isoform-specific regulation of regeneration in the peripheral nervous system

    PubMed Central

    Comley, Laura H.; Fuller, Heidi R.; Wishart, Thomas M.; Mutsaers, Chantal A.; Thomson, Derek; Wright, Ann K.; Ribchester, Richard R.; Morris, Glenn E.; Parson, Simon H.; Horsburgh, Karen; Gillingwater, Thomas H.

    2011-01-01

    Apolipoprotein E (apoE) is a 34 kDa glycoprotein with three distinct isoforms in the human population (apoE2, apoE3 and apoE4) known to play a major role in differentially influencing risk to, as well as outcome from, disease and injury in the central nervous system. In general, the apoE4 allele is associated with poorer outcomes after disease or injury, whereas apoE3 is associated with better responses. The extent to which different apoE isoforms influence degenerative and regenerative events in the peripheral nervous system (PNS) is still to be established, and the mechanisms through which apoE exerts its isoform-specific effects remain unclear. Here, we have investigated isoform-specific effects of human apoE on the mouse PNS. Experiments in mice ubiquitously expressing human apoE3 or human apoE4 on a null mouse apoE background revealed that apoE4 expression significantly disrupted peripheral nerve regeneration and subsequent neuromuscular junction re-innervation following nerve injury compared with apoE3, with no observable effects on normal development, maturation or Wallerian degeneration. Proteomic isobaric tag for relative and absolute quantitation (iTRAQ) screens comparing healthy and regenerating peripheral nerves from mice expressing apoE3 or apoE4 revealed significant differences in networks of proteins regulating cellular outgrowth and regeneration (myosin/actin proteins), as well as differences in expression levels of proteins involved in regulating the blood–nerve barrier (including orosomucoid 1). Taken together, these findings have identified isoform-specific roles for apoE in determining the protein composition of peripheral nerve as well as regulating nerve regeneration pathways in vivo. PMID:21478199

  10. The peripheral nervous system supports blood cell homing and survival in the Drosophila larva

    PubMed Central

    Makhijani, Kalpana; Alexander, Brandy; Tanaka, Tsubasa; Rulifson, Eric; Brückner, Katja

    2011-01-01

    Interactions of hematopoietic cells with their microenvironment control blood cell colonization, homing and hematopoiesis. Here, we introduce larval hematopoiesis as the first Drosophila model for hematopoietic colonization and the role of the peripheral nervous system (PNS) as a microenvironment in hematopoiesis. The Drosophila larval hematopoietic system is founded by differentiated hemocytes of the embryo, which colonize segmentally repeated epidermal-muscular pockets and proliferate in these locations. Importantly, we show that these resident hemocytes tightly colocalize with peripheral neurons and we demonstrate that larval hemocytes depend on the PNS as an attractive and trophic microenvironment. atonal (ato) mutant or genetically ablated larvae, which are deficient for subsets of peripheral neurons, show a progressive apoptotic decline in hemocytes and an incomplete resident hemocyte pattern, whereas supernumerary peripheral neurons induced by ectopic expression of the proneural gene scute (sc) misdirect hemocytes to these ectopic locations. This PNS-hematopoietic connection in Drosophila parallels the emerging role of the PNS in hematopoiesis and immune functions in vertebrates, and provides the basis for the systematic genetic dissection of the PNS-hematopoietic axis in the future. PMID:22071105

  11. GABA's Control of Stem and Cancer Cell Proliferation in Adult Neural and Peripheral Niches

    PubMed Central

    Young, Stephanie Z.; Bordey, Angélique

    2010-01-01

    Aside from traditional neurotransmission and regulation of secretion, γ-amino butyric acid (GABA) through GABAA receptors negatively regulates proliferation of pluripotent and neural stem cells in embryonic and adult tissue. There has also been evidence that GABAergic signaling and its control over proliferation is not only limited to the nervous system, but is widespread through peripheral organs containing adult stem cells. GABA has emerged as a tumor signaling molecule in the periphery that controls the proliferation of tumor cells and perhaps tumor stem cells. Here, we will discuss GABA's presence as a near-universal signal that may be altered in tumor cells resulting in modified mitotic activity. PMID:19509127

  12. 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. PMID:23684797

  13. DNA Damage Response in Peripheral Nervous System: Coping with Cancer Therapy-Induced DNA Lesions

    PubMed Central

    Englander, Ella W

    2013-01-01

    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. PMID:23684797

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

    PubMed Central

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

    2015-01-01

    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. PMID:26150506

  15. 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. PMID:26150506

  16. Phototherapeutic treatment of patients with peripheral nervous system diseases by means of LED arrays

    NASA Astrophysics Data System (ADS)

    Zharov, Vladimir P.; Kalinin, Konstantin L.; Menyaev, Yulian A.; Zmievskoy, Gregory N.; Savin, Alexei A.; Stulin, Igor D.; Shihkerimov, Raphiz K.; Shapkina, Alla V.; Velsher, Leonid Z.; Stakhanov, Mikhail L.

    2001-05-01

    The further development of new method of phototherapy based on use of light-emitting diodes (LED) arrays has been presented. LEDs array distribution is side of cylindrical surface, covering pathology region, was used for treatment group of patients with an affected peripheral nervous system. The main group consisted of patients with humeral plexopathy - one of possible neurological manifestation of postmastectomic syndrome as result of breast cancer radical treatment. This disease was accompanied also by some other peripheral nervous system diseases: diabetic polyneuropathy, compression ischemic mononeuropathy, festering wounds and others. The phototherapeutic method is just directed on improvement of patient's conditions in combination with other traditional methods of treatment. The main parameters of photomatrix therapeutic system: wavelength - 660 nm, line width - no more than 20 nm, intensity of radiation on the surface of edema - 0.5-3 mW/cm2 (in dependence of apparatuses type). To control and study efficiency of phototreatment ultrasonic dopplerography, thermography, electromyography and viscosimetry have been used.

  17. [Peripheral nervous impairment in a patient with methylmalonic aciduria combined with hyperhomocysteinemia].

    PubMed

    Ji, Tao-yun; Zhang, Yue-hua; Li, Fei-tian; Qin, Jiong; Yang, Yan-ling

    2013-04-18

    Methylmalonic aciduria combined homocysteinemia can cause multisystemic damages, mainly involving central nervous system, while the peripheral nerves are rarely impaired. A 10-year-old boy complained of weakness of both lower extremities for 1 month. His past history showed mildly delay of intelligence as well as motor development. He had proteinuria when he was 3 years old and was diagnosed as epilepsy, which was controlled by sodium valproate when he was 8 years 6 months old. His physical examination showed attenuated bilateral knee jerk reflex, while the bilateral achilles tendon reflex was absent; the examination of sensation was normal and the bilateral Babinski sign was positive. The electromyography indicated injury of peripheral nerves. The elevated levels of urine methylmalonic aciduria and plasma homocysteinemia were consistent with the diagnosis of methylmalonic aciduria combined homocysteinemia. The pathogenic gene was confirmed as MMACHC, on which two pathogenic mutations (c.365A>T and c.609G>A) were detected. cblC defect was confirmed. He was treated by vitamin B12, calcium folinate, L-carnitine and betaine supplementation, and significant improvement was observed after 6 months. According to this case, we suggest that urinary organic acid analysis and plasma homocysteine should be performed in patients with unknown peripheral neuropathy, especially combined with multisystemic damages.Early diagnosis and treatment are important to improve the prognosis. PMID:23591356

  18. 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. PMID:27230462

  19. 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

  20. Molecular Control of the Neural Crest and Peripheral Nervous System Development

    PubMed Central

    Newbern, Jason M.

    2015-01-01

    A transient and unique population of multipotent stem cells, known as neural crest cells (NCCs), generate a bewildering array of cell types during vertebrate development. An attractive model among developmental biologists, the study of NCC biology has provided a wealth of knowledge regarding the cellular and molecular mechanisms important for embryogenesis. Studies in numerous species have defined how distinct phases of NCC specification, proliferation, migration, and survival contribute to the formation of multiple functionally distinct organ systems. NCC contributions to the peripheral nervous system (PNS) are well known. Critical developmental processes have been defined that provide outstanding models for understanding how extracellular stimuli, cell–cell interactions, and transcriptional networks cooperate to direct cellular diversification and PNS morphogenesis. Dissecting the complex extracellular and intracellular mechanisms that mediate the formation of the PNS from NCCs may have important therapeutic implications for neurocristopathies, neuropathies, and certain forms of cancer. PMID:25662262

  1. 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.

  2. 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. PMID:8601299

  3. Central nervous system vasculitis in adults and children.

    PubMed

    Twilt, Marinka; Benseler, Susanne M

    2016-01-01

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

  4. In vitro analysis of transneuronal spread of an alphaherpesvirus infection in peripheral nervous system neurons.

    PubMed

    Feierbach, B; Bisher, M; Goodhouse, J; Enquist, L W

    2007-07-01

    The neurotropic alphaherpesviruses invade and spread in the nervous system in a directional manner between synaptically connected neurons. Until now, this property has been studied only in living animals and has not been accessible to in vitro analysis. In this study, we describe an in vitro system in which cultured peripheral nervous system neurons are separated from their neuron targets by an isolator chamber ring. Using pseudorabies virus (PRV), an alphaherpesvirus capable of transneuronal spread in neural circuits of many animals, we have recapitulated in vitro all known genetic requirements for retrograde and anterograde transneuronal spread as determined previously in vivo. We show that in vitro transneuronal spread requires intact axons and the presence of the viral proteins gE, gI, and Us9. We also show that transneuronal spread is dependent on the viral glycoprotein gB, which is required for membrane fusion, but not on gD, which is required for extracellular spread. We demonstrate ultrastructural differences between anterograde- and retrograde-traveling virions. Finally, we show live imaging of dynamic fluorescent virion components in axons and postsynaptic target neurons. PMID:17459934

  5. Hedgehog signaling regulates myelination in the peripheral nervous system through primary cilia.

    PubMed

    Yoshimura, Kentaro; Takeda, Sen

    2012-02-01

    Myelination is an essential prerequisite for the nervous system to transmit an impulse efficiently by a saltatory conduction. In the peripheral nervous system (PNS), Schwann cells (SCs) engage in myelination. However, a detailed molecular mechanism underlying myelination still remains unclear. In this study, we hypothesized that the primary cilia of SCs are the regulators of Hedgehog (Hh) signaling-mediated myelination. To confirm our hypothesis, we used mouse dorsal root ganglion (DRG)/SC co-cultures, wherein the behavior of SCs could be analyzed by maintaining the interaction of SCs with DRG neurons. Under these conditions, SCs had primary cilia, and Hh signaling molecules accumulated on the primary cilia. When the SCs were stimulated by the addition of desert hedgehog or smoothened agonist, formation of myelin segments on the DRG axons was facilitated. On the contrary, upon administration of cyclopamine, an inhibitor of Hh signaling, myelin segments became comparable to those of controls. Of note, the ratio of SCs harboring primary cilium reached the highest point during the early phase of myelination. Furthermore, the strongest effects of Hh on myelination were encountered during the same stage. These results collectively indicate that Hh signaling regulates myelin formation through primary cilia in the PNS. PMID:22101064

  6. Generation of magnetized olfactory ensheathing cells for regenerative studies in the central and peripheral nervous tissue.

    PubMed

    Riggio, Cristina; Nocentini, Sara; Catalayud, Maria Pilar; Goya, Gerardo Fabian; Cuschieri, Alfred; Raffa, Vittoria; del Río, José Antonio

    2013-01-01

    As olfactory receptor axons grow from the peripheral to the central nervous system (CNS) aided by olfactory ensheathing cells (OECs), the transplantation of OECs has been suggested as a plausible therapy for spinal cord lesions. The problem with this hypothesis is that OECs do not represent a single homogeneous entity, but, instead, a functionally heterogeneous population that exhibits a variety of responses, including adhesion and repulsion during cell-matrix interactions. Some studies report that the migratory properties of OECs are compromised by inhibitory molecules and potentiated by chemical gradients. In this paper, we report a system based on modified OECs carrying magnetic nanoparticles as a proof of concept experiment enabling specific studies aimed at exploring the potential of OECs in the treatment of spinal cord injuries. Our studies have confirmed that magnetized OECs (i) survive well without exhibiting stress-associated cellular responses; (ii) in vitro, their migration can be modulated by magnetic fields; and (iii) their transplantation in organotypic slices of spinal cord and peripheral nerve showed positive integration in the model. Altogether, these findings indicate the therapeutic potential of magnetized OECs for CNS injuries. PMID:23708092

  7. 75 FR 56548 - Joint Meeting of the Peripheral and Central Nervous System Drugs Advisory Committee and the Drug...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-16

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

  8. 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

  9. Glial Elements Contribute to Stress-induced Torsina Expression in the Central and Peripheral Nervous Systems

    PubMed Central

    Zhao, Yu; Xiao, Jianfeng; Ueda, Masayuki; Wang, Yue; Hines, Melissa; Nowak, Thaddeus S.; LeDoux, Mark S.

    2008-01-01

    DYT1 dystonia is caused by a single GAG deletion in Exon 5 of TOR1A, the gene encoding torsinA, a putative chaperone protein. In this study, central and peripheral nervous system perturbations (transient forebrain ischemia and sciatic nerve transection, respectively) were used to examine the systems biology of torsinA. After forebrain ischemia, quantitative real-time RT-PCR identified increased torsinA transcript levels in hippocampus, cerebral cortex, thalamus, striatum, and cerebellum at 24 h and 7 d. Expression declined toward sham values by 14 d in striatum, thalamus and cortex, and by 21 d in cerebellum and hippocampus. TorsinA transcripts were localized to dentate granule cells and pyramidal neurons in control hippocampus and were moderately elevated in these cell populations at 24 h after ischemia, after which CA1 expression was reduced, consistent with the loss of this vulnerable neuronal population. Increased in situ hybridization signal in CA1 stratum radiatum, stratum lacunosum-moleculare, and stratum oriens at 7 d after ischemia was correlated with the detection of torsinA immunoreactivity in interneurons and reactive astrocytes at 7 and 14 days. Sciatic nerve transection increased torsinA transcript levels between 24 h and 7 days in both ipsilateral and contralateral dorsal root ganglia (DRG). However, increased torsinA immunoreactivity was localized to both ganglion cells and satellite cells in ipsilateral DRG but was restricted to satellite cells contralaterally. These results suggest that torsinA participates in the response of neural tissue to central and peripheral insults and its sustained up-regulation indicates that torsinA may contribute to remodeling of neuronal circuitry. The striking induction of torsinA in astrocytes and satellite cells points to the potential involvement of glial elements in the pathobiology of DYT1 dystonia. PMID:18538941

  10. 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. PMID:27197173

  11. Giant neurons and associated synapses in the peripheral nervous system of whip spiders.

    PubMed

    Foelix, R F; Troyer, D

    1980-08-01

    Whip spiders (Amblypygi) are arachnids with a specialized first pair of legs. These legs are unusually long (20-25 cm) and are not used for walking. Instead their lengthy tarsi (7-8 cm) are covered with thousands of sensory hairs (mechano- and chemoreceptors). The legs thus resemble antennae of insects. Each sensory hair is associated with 4-40 neurons whose axons are grouped together to form two large tarsal nerves. The nerves contain about 23 000 sensory axons. Whereas most of the axons measure only 0.1-0.2 microns in diameter, a few are exceptionally large (3-20 microns). These are giant fibres. Their large somata are located in specific segments of the tarsi. The branched dendrites of the giant neurons receive hundreds of chemical synapses, presumably from the sensory axons of the hair sensilla. Since stimulation of the tarsal tip elicits fast withdrawal reaction (greater than or equal to 80 ms), it is likely that the giant fibres provide the pathway for the rapid conduction of nerve impulses to the motor centres of the C.N.S. The system is comparable to the giant fibre system of certain insects. In contrast, however, the giant interneurons and associated synapses of whip spiders are not located in the C.N.S., but lie some 20 cm removed in the periphery. Thus, some primary sensory information already becomes processed in the peripheral nervous system, before it reaches the C.N.S. PMID:7441302

  12. 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

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

    PubMed

    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

  14. P2X receptors and their roles in astroglia in the central and peripheral nervous system.

    PubMed

    Illes, Peter; Verkhratsky, Alexei; Burnstock, Geoffrey; Franke, Heike

    2012-10-01

    Astrocytes are a class of neural cells that control homeostasis at all levels of the central and peripheral nervous system. There is a bidirectional neuron-glia interaction via a number of extracellular signaling molecules, glutamate and ATP being the most widespread. ATP activates ionotropic P2X and metabotropic P2Y receptors, which operate in both neurons and astrocytes. Morphological, biochemical, and functional evidence indicates the expression of astroglial P2X(1/5) heteromeric and P2X(7) homomeric receptors, which mediate physiological and pathophysiological responses. Activation of P2X(1/5) receptors triggers rapid increase of intracellular Na(+) that initiates immediate cellular reactions, such as the depression of the glutamate transporter to keep high glutamate concentrations in the synaptic cleft, the activation of the local lactate shuttle to supply energy substrate to pre- and postsynaptic neuronal structures, and the reversal of the Na(+)/Ca(2+) exchange resulting in additional Ca(2+) entry. The consequences of P2X(7) receptor activation are mostly but not exclusively mediated by the entry of Ca(2+) and result in reorganization of the cytoskeleton, inflammation, apoptosis/necrosis, and proliferation, usually at a prolonged time scale. Thus, astroglia detect by P2X(1/5) and P2X(7) receptors both physiological concentrations of ATP secreted from presynaptic nerve terminals and also much higher concentrations of ATP attained under pathological conditions. PMID:22013151

  15. 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

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

    PubMed

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

    2016-03-01

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

  17. Expression pattern of neuregulin-1 type III during the development of the peripheral nervous system.

    PubMed

    Huang, Liang-Liang; Liu, Zhong-Yang; Huang, Jing-Hui; Luo, Zhuo-Jing

    2015-01-01

    Neuregulin-1 type III is a key regulator in Schwann cell proliferation, committing to a myelinating fate and regulating myelin sheath thickness. However, the expression pattern of neuregulin-1 type III in the peripheral nervous system during developmental periods (such as the premyelinating stage, myelinating stage and postmyelinating stage) has rarely been studied. In this study, dorsal root ganglia were isolated from rats between postnatal day 1 and postnatal day 56. The expression pattern of neuregulin-1 type III in dorsal root ganglia neurons at various developmental stages were compared by quantitative real-time polymerase chain reaction, western blot assay and immunofluorescent staining. The expression of neuregulin-1 type III mRNA reached its peak at postnatal day 3 and then stabilized at a relative high expression level from postnatal day 3 to postnatal day 56. The expression of neuregulin-1 type III protein increased gradually from postnatal day 1, reached a peak at postnatal day 28, and then decreased at postnatal day 56. Immunofluorescent staining results showed a similar tendency to western blot assay results. Experimental findings indicate that the expression of neuregulin-1 type III in rat dorsal root ganglion was increased during the premyelinating (from postnatal day 2 to postnatal day 5) and myelinating stage (from postnatal day 5 to postnatal day 10), but remained at a high level in the postmyelinating stage (after postnatal day 10). PMID:25788922

  18. Myocilin mediates myelination in the peripheral nervous system through ErbB2/3 signaling.

    PubMed

    Kwon, Heung Sun; Johnson, Thomas V; Joe, Myung Kuk; Abu-Asab, Mones; Zhang, Jun; Chan, Chi Chao; Tomarev, Stanislav I

    2013-09-13

    The glaucoma-associated gene, myocilin, is expressed in ocular and non-ocular tissues including the peripheral nervous system, but its functions in these tissues remain poorly understood. We demonstrate that in sciatic nerve, myocilin is expressed in Schwann cells with high concentrations at the nodes of Ranvier. There, myocilin interacts with gliomedin, neurofascin, and NrCAM, which are essential for node formation and function. Treatment of isolated dorsal root ganglion cultures with myocilin stimulates clustering of the nodal proteins neurofascin and sodium channel Nav1.2. Sciatic nerves of myocilin null mice express reduced levels of several myelin-associated and basal membrane proteins compared with those of wild-type littermates. They also demonstrate reduced myelin sheath thickness and partial disorganization of the nodes. Myocilin signaling through ErbB2/3 receptors may contribute to these observed effects. Myocilin binds to ErbB2/ErbB3, activates these receptors, and affects the downstream PI3K-AKT signaling pathway. These data implicate a role for myocilin in the development and/or maintenance of myelination and nodes of Ranvier in sciatic nerve. PMID:23897819

  19. Physiological Notch signaling promotes gliogenesis in the developing peripheral and central nervous systems

    PubMed Central

    Taylor, Merritt K.; Kelly, Yeager; Morrison, Sean J.

    2009-01-01

    Constitutive activation of the Notch pathway can promote gliogenesis by peripheral (PNS) and central (CNS) nervous system progenitors. This raises the question of whether physiological Notch signaling regulates gliogenesis in vivo. To test this, we conditionally deleted Rbpsuh (Rbpj) from mouse PNS or CNS progenitors using Wnt1-Cre or Nestin-Cre. Rbpsuh encodes a DNA-binding protein (RBP/J) that is required for canonical signaling by all Notch receptors. In most regions of the developing PNS and spinal cord, Rbpsuh deletion caused only mild defects in neurogenesis, but severe defects in gliogenesis. These resulted from defects in glial specification or differentiation, not premature depletion of neural progenitors, because we were able to culture undifferentiated progenitors from the PNS and spinal cord despite their failure to form glia in vivo. In spinal cord progenitors, Rbpsuh was required to maintain Sox9 expression during gliogenesis, demonstrating that Notch signaling promotes the expression of a glial-specification gene. These results demonstrate that physiological Notch signaling is required for gliogenesis in vivo, independent of the role of Notch in the maintenance of undifferentiated neural progenitors. PMID:17537790

  20. Peripheral Neuropathy

    MedlinePlus

    ... Enhancing Diversity Find People About NINDS NINDS Peripheral Neuropathy Information Page Condensed from Peripheral Neuropathy Fact Sheet ... Español Additional resources from MedlinePlus What is Peripheral Neuropathy? Peripheral neuropathy describes damage to the peripheral nervous ...

  1. The role of retinoids in the adult nervous system and their therapeutic potential.

    PubMed

    Christie, V B; Marder, T B; Whiting, A; Przyborski, S A

    2008-06-01

    The mode of action of retinoids in relation to their activity in the adult central nervous system and the potential of synthetic retinoid analogues is reviewed. Investigation into the activity of such molecules will further our understanding of the retinoid pathway during nervous system development and in various neurological disease states. PMID:18537715

  2. Zika Kills Vital Nervous System Cells in Adult Mice, Study Finds

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_160505.html Zika Kills Vital Nervous System Cells in Adult Mice, ... 2016 THURSDAY, Aug. 18, 2016 (HealthDay News) -- The Zika virus kills neural stem cells in the brains ...

  3. 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'. PMID:25986697

  4. Karolinska institutet 200-year anniversary. Symposium on traumatic injuries in the nervous system: injuries to the spinal cord and peripheral nervous system - injuries and repair, pain problems, lesions to brachial plexus.

    PubMed

    Sköld, Mattias K; Svensson, Mikael; Tsao, Jack; Hultgren, Thomas; Landegren, Thomas; Carlstedt, Thomas; Cullheim, Staffan

    2011-01-01

    The Karolinska Institutet 200-year anniversary symposium on injuries to the spinal cord and peripheral nervous system gathered expertise in the spinal cord, spinal nerve, and peripheral nerve injury field spanning from molecular prerequisites for nerve regeneration to clinical methods in nerve repair and rehabilitation. The topics presented at the meeting covered findings on adult neural stem cells that when transplanted to the hypoglossal nucleus in the rat could integrate with its host and promote neuron survival. Studies on vascularization after intraspinal replantation of ventral nerve roots and microarray studies in ventral root replantation as a tool for mapping of biological patterns typical for neuronal regeneration were discussed. Different immune molecules in neurons and glia and their very specific roles in synapse plasticity after injury were presented. Novel strategies in repair of injured peripheral nerves with ethyl-cyanoacrylate adhesive showed functional recovery comparable to that of conventional epineural sutures. Various aspects on surgical techniques which are available to improve function of the limb, once the nerve regeneration after brachial plexus lesions and repair has reached its limit were presented. Moreover, neurogenic pain after amputation and its treatment with mirror therapy were shown to be followed by dramatic decrease in phantom limb pain. Finally clinical experiences on surgical techniques to repair avulsed spinal nerve root and the motoric as well as sensoric regain of function were presented. PMID:21629875

  5. 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. PMID:26657078

  6. Selective expression of prion protein in peripheral tissues of the adult mouse.

    PubMed

    Ford, M J; Burton, L J; Morris, R J; Hall, S M

    2002-01-01

    The level of expression of normal cellular prion protein, PrP(c) (cellular prion protein), controls both the rate and the route of neuroinvasive infection, from peripheral entry portal to the CNS. Paradoxically, an overview of the distribution of PrP(c) within tissues outside the CNS is lacking. We have used novel antibodies that recognise cellular prion protein in glutaraldehyde-fixed tissue (in order to optimise immunohistochemical labelling of this conformationally labile protein), in combination with in situ hybridisation, to examine the expression of PrP(c) in peripheral tissues of the adult mouse. We found that although prion protein is expressed in many tissues, it is expressed at high levels only in discrete subpopulations of cells. Prominent amongst these are elements of the "hardwired neuroimmune network" that integrate the body's immune defence and neuroendocrine systems under CNS control. These prion protein-expressing elements include small diameter afferent nerves in the skin and the lamina propria of the aerodigestive tract, sympathetic ganglia and nerves, antigen presenting and processing cells (both follicular and non-follicular dendritic cells) and sub-populations of lymphocytes particularly in skin, gut- and bronchus-associated lymphoid tissues. Prion protein is also expressed in the parasympathetic and enteric nervous systems, in the dispersed neuroendocrine system, and in peripheral nervous system axons and their associated Schwann cells. This selective expression of cellular prion protein provides a variety of alternative routes for the propagation and transport of prion infection entering from peripheral sites, either naturally (via the aerodigestive tract or abraded skin) or experimentally (by intraperitoneal injection) to the brain. Key regulatory cells that express prion protein, and in particular enteroendocrine cells in the mucosal wall of the gut, and dendritic cells that convey pathogens from epithelial layers to secondary lymphoid

  7. 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. PMID:26083325

  8. 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

  9. The role of axonopathy in the mechanisms of development of demyelination processes in the central and peripheral nervous system.

    PubMed

    Merkulov, Yu A; Zavalishin, I A; Merkulova, D M

    2009-01-01

    The role of axonopathy in the development of demyelinating processes in the CNS and peripheral nervous system was addressed in studies of 43 patients with multiple sclerosis (MS) and 144 patients with chronic inflammatory demyelinating polyneuropathy (CIDPN). Patients with MS were found to have foci of reduced MRI intensity in the T1 regime ("black holes," present in 28%) and regional atrophy of the cerebral cortex (in 46%), which showed a significant association with the degree of invalidity on the EDSS (Kendall tau = 0.38 and 0.43; p = 0.038 and 0.021, respectively). The mean fatigue score on the FSS was 4.9 (3.6; 5.4). A significant increase in the central conduction time on the background of fatigue (p = 0.016), along with an absence of signs of impaired reliability of neuromuscular transmission and an absence of past-activation phenomena, suggested that central mechanisms were predominant in the formation of fatigue phenomena in MS. In addition, 34.9% of patients with MS showed signs of peripheral nervous system involvement, while the clinical-electrophysiological pattern in 12.5% of patients with CIDPN showed signs of CNS involvement. These data widen existing concepts of the mechanisms of formation of axonopathy in the CNS, based on evidence for the development of axon-demyelinating processes in CIDPN, which is the most accessible model of demyelination for study using contemporary neurophysiological methods. PMID:19089637

  10. 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

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

    PubMed

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

    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

  12. 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

  13. 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.

  14. Cholinergic neurons and terminal fields revealed by immunohistochemistry for the vesicular acetylcholine transporter. II. The peripheral nervous system.

    PubMed

    Schäfer, M K; Eiden, L E; Weihe, E

    1998-05-01

    The peripheral sympathetic and parasympathetic cholinergic innervation was investigated with antibodies directed against the C-terminus of the rat vesicular acetylcholine transporter. Immunohistochemistry for the vesicular acetylcholine transporter resulted in considerably more detailed visualization of cholinergic terminal fields in the peripheral nervous system than reported previously and was well suited to also identify cholinergic perikarya. Vesicular acetylcholine transporter immunoreactivity completely delineated the preganglionic sympathetic terminals in pre- and paravertebral sympathetic ganglia, and in the adrenal medulla as well as postganglionic cholinergic neurons in the paravertebral chain. Cholinergic terminals of sudomotor and vasomotor nerves of skeletal muscle were optimally visualized. Mixed peripheral ganglia, including periprostatic and uterovaginal ganglia, exhibited extensive preganglionic cholinergic innervation of both noradrenergic and cholinergic postganglionic principal neurons which were intermingled in these ganglia. Varicose vesicular acetylcholine transporter-positive fibres and terminals, representing the cranial parasympathetic innervation of the cerebral vasculature, of salivary and lacrimal glands, of the eye, of the respiratory tract and of the upper digestive tract innervated various target structures including seromucous gland epithelium and myoepithelium, respiratory epithelium, and smooth muscle of the tracheobronchial tree. The only macrovascular elements receiving vesicular acetylcholine transporter-positive innervation were the cerebral arteries. The microvasculature throughout the viscera, with the exception of lymphoid tissues, the liver and kidney, received vesicular acetylcholine transporter-positive innervation while the microvasculature of limb and trunk skeletal muscle appeared to be the only relevant somatic target of vesicular acetylcholine transporter innervation. Vesicular acetylcholine transporter

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

    PubMed Central

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

    2013-01-01

    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. PMID:23903191

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

    PubMed

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

    2015-07-15

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

  17. 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

  18. 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. PMID:25574749

  19. Fampridine-PR (prolonged released 4-aminopyridine) is not effective in patients with inflammatory demyelination of the peripheral nervous system.

    PubMed

    Leussink, Verena-Isabell; Stettner, Mark; Warnke, Clemens; Hartung, Hans-Peter

    2016-06-01

    Fampridine-PR is a voltage-gated potassium channel inhibitor potentially improving nerve conduction in demyelinated axons. Based on its established clinical efficacy in patients with demyelination in the central nervous system, we assessed if fampridine-PR is also effective in patients with inflammatory demyelination of the peripheral nerve. In this small open-label study, 10 patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) were treated with fampridine-PR 10 mg BID for 28 days and assessed clinically as well as by nerve conduction studies. In this study, Fampridine-PR failed to improve CIDP based on clinical measures and nerve conduction studies. Our findings suggest that Fampridine-PR appears to be ineffective in demyelinating polyneuropathies. These observations may indicate a more complex mode of action beyond improving action potential conduction in demyelinated axons. PMID:26968589

  20. Adult T-Cell Lymphoma/Leukemia Presenting as Isolated Central Nervous System T-Cell Lymphoma

    PubMed Central

    Ma, Wei-Li; Li, Chi-Cheng; Yu, Shan-Chi; Tien, Hwei-Fang

    2014-01-01

    Adult T-cell leukemia/lymphoma (ATLL) is a T-cell neoplasm, associated with infection by the retrovirus human T-lymphotropic virus type 1 (HTLV-1). Central nervous system (CNS) involved by ATLL is often occurred in advanced disease, such as acute and lymphomatous variants. On the other hand, isolated CNS lymphoma is rare. We repot a 50-year-old woman who presented with multiple infiltrative brain lesions on the magnetic resonance (MR) imaging. Results of initial biopsy of brain tumor indicated CNS vasculitis. The patient received one course of high-dose methotrexate and MR imaging of brain revealed remission of infiltrative lesions. Two years later, new brain lesions were detected. Histopathologic examination of specimens via craniotomy revealed T-cell lymphoma. The patient responded poorly to subsequent chemotherapy, and salvage whole-brain irradiation was performed. Six months later, the patient had hepatosplenomegaly, hypercalcemia, and multiple lymphocytes with a cloverleaf appearance in circulation. Results of flow cytometry analysis of peripheral blood indicated ATLL and antibodies to human T-lymphotropic virus type 1 (HTLV-1) were detected. Clinicians should screen HTLV-1 infection when patients are diagnosed with peripheral T-cell lymphoma. Combined antiviral therapy and intensive chemotherapy may improve the outcomes of ATLL. PMID:25587470

  1. Adult T-cell lymphoma/leukemia presenting as isolated central nervous system T-cell lymphoma.

    PubMed

    Ma, Wei-Li; Li, Chi-Cheng; Yu, Shan-Chi; Tien, Hwei-Fang

    2014-01-01

    Adult T-cell leukemia/lymphoma (ATLL) is a T-cell neoplasm, associated with infection by the retrovirus human T-lymphotropic virus type 1 (HTLV-1). Central nervous system (CNS) involved by ATLL is often occurred in advanced disease, such as acute and lymphomatous variants. On the other hand, isolated CNS lymphoma is rare. We repot a 50-year-old woman who presented with multiple infiltrative brain lesions on the magnetic resonance (MR) imaging. Results of initial biopsy of brain tumor indicated CNS vasculitis. The patient received one course of high-dose methotrexate and MR imaging of brain revealed remission of infiltrative lesions. Two years later, new brain lesions were detected. Histopathologic examination of specimens via craniotomy revealed T-cell lymphoma. The patient responded poorly to subsequent chemotherapy, and salvage whole-brain irradiation was performed. Six months later, the patient had hepatosplenomegaly, hypercalcemia, and multiple lymphocytes with a cloverleaf appearance in circulation. Results of flow cytometry analysis of peripheral blood indicated ATLL and antibodies to human T-lymphotropic virus type 1 (HTLV-1) were detected. Clinicians should screen HTLV-1 infection when patients are diagnosed with peripheral T-cell lymphoma. Combined antiviral therapy and intensive chemotherapy may improve the outcomes of ATLL. PMID:25587470

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

    PubMed

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

    2016-01-01

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

  3. 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

  4. Serotonin-like immunoreactivity in the central and peripheral nervous systems of the interstitial acochlidean Asperspina sp. (Opisthobranchia).

    PubMed

    Hochberg, Rick

    2007-08-01

    Species of Acochlidea are common members of the marine interstitial environment and defined in part by their minuscule size and highly divergent morphology relative to other benthic opisthobranchs. Despite these differences, acochlideans such as species of Asperspina display many plesiomorphic characteristics, including an unfused condition of their neural ganglia. To gain insight into the distribution of specific neural subsets within acochlidean ganglia, a species of Asperspina was studied by using anti-serotonin immunohistochemistry and epifluorescence and confocal laser scanning microscopy. Results reveal similarities between Asperspina and larger opisthobranchs in the general distribution of serotonergic perikarya in the central nervous system. Specifically, the arrangement of perikarya into regional clusters within the cerebral and pedal ganglia and the absence of immunoreactive perikarya in the pleural ganglia are similar to the model species of Aplysia californica, Pleurobranchaea californica, and Tritonia diomedea. Moreover, serotonergic innervation of the rhinophores in all opisthobranchs, including Asperspina sp., originates from the cerebral ganglion instead of directly from the rhinophoral ganglion. Serotonergic innervation of the body wall, including the epithelium, muscles, and pedal sole, appears to arise exclusively from pedal and accessory ganglia. These observations indicate a general conservation of serotonin-like immunoreactivity in the central and peripheral nervous systems of acochlidean and other benthic opisthobranchs. PMID:17679719

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

    PubMed Central

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

    2015-01-01

    Histamine appears to be an important transmitter throughout the Animal Kingdom. Gastropods, in particular, have been used in numerous studies establishing potential roles for this biogenic amine in the nervous system and showing its involvement in the generation of diverse behaviours. And yet, the distribution of histamine has only previously been described in a small number of molluscan species. The present study examined the localization of histamine-like immunoreactivity in the central and peripheral nervous systems of pulmonate snails of the genus Biomphalaria. This investigation demonstrates immunoreactive cells throughout the buccal, cerebral, pedal, left parietal and visceral ganglia, indicative of diverse regulatory functions in Biomphalaria. Immunoreactivity was also present in statocyst hair cells, supporting a role for histamine in graviception. In the periphery, dense innervation by immunoreactive fibers was observed in the anterior foot, perioral zone, and other regions of the body wall. This study thus shows that histamine is an abundant transmitter in these snails and its distribution suggest involvement in numerous neural circuits. In addition to providing novel subjects for comparative studies of histaminegic neurons in gastropods, Biomphalaria is also the major intermediate host for the digenetic trematode parasite, which causes human schistosomiasis. The study therefore provides a foundation for understanding potential roles for histamine in interactions between the snail hosts and their trematode parasites. PMID:26086611

  6. Contribution of glycogen in supporting axon conduction in the peripheral and central nervous systems: the role of lactate

    PubMed Central

    Chambers, Tom W.; Daly, Timothy P.; Hockley, Adam; Brown, Angus M.

    2014-01-01

    The role of glycogen in the central nervous system is intimately linked with the glycolytic pathway. Glycogen is synthesized from glucose, the primary substrate for glycolysis, and degraded to glucose-6-phosphate. The metabolic cost of shunting glucose via glycogen exceeds that of simple phosphorylation of glucose to glucose-6-phosphate by hexokinase; thus, there must be a metabolic advantage in utilizing this shunt pathway. The dogmatic view of glycogen as a storage depot persists, based on initial descriptions of glycogen supporting neural function in the face of aglycemia. The variable latency to conduction failure, dependent upon tissue glycogen levels, provided convincing evidence of the role played by glycogen in supporting neural function. Glycogen is located predominantly in astrocytes in the central nervous system, thus for glycogen to benefit neural elements, intercellular metabolic communication must exist in the form of astrocyte to neuron substrate transfer. Experimental evidence supports a model where glycogen is metabolized to lactate in astrocytes, with cellular expression of monocarboxylate transporters and enzymes appropriately located for lactate shuttling between astrocytes and neural elements, where lactate acts as a substrate for oxidative metabolism. Biosensor recordings have demonstrated a significant steady concentration of lactate present on the periphery of both central white matter and peripheral nerve under unstimulated baseline conditions, indicating continuous cellular efflux of lactate to the interstitium. The existence of this lactate pool argues we must reexamine the “on demand” shuttling of lactate between cellular elements, and suggests continuous lactate efflux surplus to immediate neural requirements. PMID:25505379

  7. Functional implications of the localization and activity of acid-sensitive channels in rat peripheral nervous system

    PubMed Central

    Alvarez de la Rosa, Diego; Zhang, Ping; Shao, Deren; White, Fletcher; Canessa, Cecilia M.

    2002-01-01

    Acid-sensitive ion channels (ASIC) are proton-gated ion channels expressed in neurons of the mammalian central and peripheral nervous systems. The functional role of these channels is still uncertain, but they have been proposed to constitute mechanoreceptors and/or nociceptors. We have raised specific antibodies for ASIC1, ASIC2, ASIC3, and ASIC4 to examine the distribution of these proteins in neurons from dorsal root ganglia (DRG) and to determine their subcellular localization. Western blot analysis demonstrates that all four ASIC proteins are expressed in DRG and sciatic nerve. Immunohistochemical experiments and functional measurements of unitary currents from the ASICs with the patch–clamp technique indicate that ASIC1 localizes to the plasma membrane of small-, medium-, and large-diameter cells, whereas ASIC2 and ASIC3 are preferentially in medium to large cells. Neurons coexpressing ASIC2 and ASIC3 form predominantly heteromeric ASIC2–3 channels. Two spliced forms, ASIC2a and ASIC2b, colocalize in the same population of DRG neurons. Within cells, the ASICs are present mainly on the plasma membrane of the soma and cellular processes. Functional studies indicate that the pH sensitivity for inactivation of ASIC1 is much higher than the one for activation; hence, increases in proton concentration will inactivate the channel. These functional properties and localization in DRG have profound implications for the putative functional roles of ASICs in the nervous system. PMID:11842212

  8. Functional implications of the localization and activity of acid-sensitive channels in rat peripheral nervous system.

    PubMed

    Alvarez de la Rosa, Diego; Zhang, Ping; Shao, Deren; White, Fletcher; Canessa, Cecilia M

    2002-02-19

    Acid-sensitive ion channels (ASIC) are proton-gated ion channels expressed in neurons of the mammalian central and peripheral nervous systems. The functional role of these channels is still uncertain, but they have been proposed to constitute mechanoreceptors and/or nociceptors. We have raised specific antibodies for ASIC1, ASIC2, ASIC3, and ASIC4 to examine the distribution of these proteins in neurons from dorsal root ganglia (DRG) and to determine their subcellular localization. Western blot analysis demonstrates that all four ASIC proteins are expressed in DRG and sciatic nerve. Immunohistochemical experiments and functional measurements of unitary currents from the ASICs with the patch-clamp technique indicate that ASIC1 localizes to the plasma membrane of small-, medium-, and large-diameter cells, whereas ASIC2 and ASIC3 are preferentially in medium to large cells. Neurons coexpressing ASIC2 and ASIC3 form predominantly heteromeric ASIC2-3 channels. Two spliced forms, ASIC2a and ASIC2b, colocalize in the same population of DRG neurons. Within cells, the ASICs are present mainly on the plasma membrane of the soma and cellular processes. Functional studies indicate that the pH sensitivity for inactivation of ASIC1 is much higher than the one for activation; hence, increases in proton concentration will inactivate the channel. These functional properties and localization in DRG have profound implications for the putative functional roles of ASICs in the nervous system. PMID:11842212

  9. 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. PMID:27157770

  10. 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

  11. 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.

  12. 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

  13. Socioeconomic Inequality and Peripheral Artery Disease Prevalence in US Adults

    PubMed Central

    Pande, Reena L.; Creager, Mark A.

    2014-01-01

    Background Lower socioeconomic status (SES) is associated with cardiovascular disease. We sought to determine whether there is a higher prevalence of peripheral artery disease (PAD) in individuals with lower socioeconomic status. Methods and Results We analyzed data from the National Health and Nutrition Examination Survey (NHANES) 1999–2004. PAD was defined based on an ankle-brachial index (ABI) ≤ 0.90. Measures of SES included poverty-income ratio (PIR), a ratio of self-reported income relative to the poverty line, and attained education level. Of 6791 eligible participants, overall weighted prevalence of PAD was 5.8% (SE 0.3). PAD prevalence was significantly higher in individuals with low income and lower education. Individuals in the lowest of the 6 PIR categories had more than a 2-fold increased odds of PAD compared to those in the highest PIR category (OR 2.69, 95% CI 1.80–4.03, p<0.0001). This association remained significant even after multivariable adjustment (OR 1.64, 95% CI 1.04–2.6, p=0.034). Lower attained education level also associated with higher PAD prevalence (OR 2.8, 95% CI 1.96–4.0, p<0.0001) but was no longer significant after multivariable adjustment. Conclusions Low income and lower attained education level are associated with peripheral artery disease in US adults. These data suggest that individuals of lower socioeconomic status remain at high risk and highlight the need for education and advocacy efforts focused on these at-risk populations. PMID:24987053

  14. 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

  15. 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.

  16. Molecular anatomy and genetics of myelin proteins in the peripheral nervous system.

    PubMed Central

    Snipes, G J; Suter, U

    1995-01-01

    Myelin contains a number of proteins, the major examples of which are protein zero (Po), P2 protein, peripheral myelin protein 22 (PMP22), myelin basic proteins (MBPs), myelin-associated glycoprotein (MAG) and the recently described connexin 32 (Cx32). This list is probably still incomplete. The localisation and possible functions of these proteins are reviewed. In the past few years a number of inherited demyelinating neuropathies in mice and the human have been shown to be due to mutations affecting the genes PMP22, Po and Cx32 so that it has become possible to characterise the molecular pathology of the majority of these disorders. This has provided important insights into the relationships between the structure of myelin and the function of its constituent proteins. Images Fig. 1 PMID:7559122

  17. 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.

  18. 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...

  19. Schwann-Spheres Derived from Injured Peripheral Nerves in Adult Mice - Their In Vitro Characterization and Therapeutic Potential

    PubMed Central

    Takagi, Takehiko; Ishii, Ken; Shibata, Shinsuke; Yasuda, Akimasa; Sato, Momoka; Nagoshi, Narihito; Saito, Harukazu; Okano, Hirotaka J.; Toyama, Yoshiaki; Okano, Hideyuki; Nakamura, Masaya

    2011-01-01

    Multipotent somatic stem cells have been identified in various adult tissues. However, the stem/progenitor cells of the peripheral nerves have been isolated only from fetal tissues. Here, we isolated Schwann-cell precursors/immature Schwann cells from the injured peripheral nerves of adult mice using a floating culture technique that we call “Schwann-spheres." The Schwann-spheres were derived from de-differentiated mature Schwann cells harvested 24 hours to 6 weeks after peripheral nerve injury. They had extensive self-renewal and differentiation capabilities. They strongly expressed the immature-Schwann-cell marker p75, and differentiated only into the Schwann-cell lineage. The spheres showed enhanced myelin formation and neurite growth compared to mature Schwann cells in vitro. Mature Schwann cells have been considered a promising candidate for cell-transplantation therapies to repair the damaged nervous system, whereas these “Schwann-spheres" would provide a more potential autologous cell source for such transplantation. PMID:21720551

  20. The peripheral sensory nervous system in the vertebrate head: a gene regulatory perspective.

    PubMed

    Grocott, Timothy; Tambalo, Monica; Streit, Andrea

    2012-10-01

    In the vertebrate head, crucial parts of the sense organs and sensory ganglia develop from special regions, the cranial placodes. Despite their cellular and functional diversity, they arise from a common field of multipotent progenitors and acquire distinct identity later under the influence of local signalling. Here we present the gene regulatory network that summarises our current understanding of how sensory cells are specified, how they become different from other ectodermal derivatives and how they begin to diversify to generate placodes with different identities. This analysis reveals how sequential activation of sets of transcription factors subdivides the ectoderm over time into smaller domains of progenitors for the central nervous system, neural crest, epidermis and sensory placodes. Within this hierarchy the timing of signalling and developmental history of each cell population is of critical importance to determine the ultimate outcome. A reoccurring theme is that local signals set up broad gene expression domains, which are further refined by mutual repression between different transcription factors. The Six and Eya network lies at the heart of sensory progenitor specification. In a positive feedback loop these factors perpetuate their own expression thus stabilising pre-placodal fate, while simultaneously repressing neural and neural crest specific factors. Downstream of the Six and Eya cassette, Pax genes in combination with other factors begin to impart regional identity to placode progenitors. While our review highlights the wealth of information available, it also points to the lack information on the cis-regulatory mechanisms that control placode specification and of how the repeated use of signalling input is integrated. PMID:22790010

  1. [Pharmacological studies of guanabenz. Effects on the peripheral nervous and other organ systems].

    PubMed

    Ohata, K; Murata, T; Sakamoto, H; Kohno, S; Hojo, M; Yoshida, Y; Nagasaka, Y; Akimoto, Y; Shimada, A; Teramoto, N; Tatsumi, H

    1983-01-01

    General pharmacological properties of guanabenz (GUB), a new anti-hypertensive agent, were studied in comparison with those of clonidine (CLD) and guanethidine (GUD). Intravenous or peroral administration of GUB caused a contraction of the nictitating membrane in cats and mydriasis in mice, while it produced an inhibitions of the gastrointestinal motility in dogs; the motility of isolated rabbit ileum; and chacol transport, salivation and gastric acid secretion in rats. GUB had no or slight inhibitory actions on contractile responses induced by peripheral sympathetic or parasympathetic nerve stimulation in various organs; however, it had antagonistic actions against the norepinephrine-induced contraction of isolated guinea-pig vas deferens. The contractile responses to epinephrine and tyramine in the nictitating membrane and to sympathetic nerve stimulation in isolated guinea-pig vas deferens were potentiated by GUB. GUB specifically antagonized the serotonin-induced contraction of the isolated rat fundus strip and nonspecifically inhibited acetylcholine, histamine or Ba2+-induced contractions of isolated guinea-pig ileum at higher concentrations. GUB exhibited local anesthetic actions and diuretic effects, but had no particular actions on neuromuscular transmission, isolated rat uterus, guinea-pig tracheal muscle and the hematic system. These effects of GUB were found to be almost identical with but less potent than those of CLD. The effects of GUD were basically different from GUB. PMID:6852682

  2. Wireless Recording in the Peripheral Nervous System with Ultrasonic Neural Dust.

    PubMed

    Seo, Dongjin; Neely, Ryan M; Shen, Konlin; Singhal, Utkarsh; Alon, Elad; Rabaey, Jan M; Carmena, Jose M; Maharbiz, Michel M

    2016-08-01

    The emerging field of bioelectronic medicine seeks methods for deciphering and modulating electrophysiological activity in the body to attain therapeutic effects at target organs. Current approaches to interfacing with peripheral nerves and muscles rely heavily on wires, creating problems for chronic use, while emerging wireless approaches lack the size scalability necessary to interrogate small-diameter nerves. Furthermore, conventional electrode-based technologies lack the capability to record from nerves with high spatial resolution or to record independently from many discrete sites within a nerve bundle. Here, we demonstrate neural dust, a wireless and scalable ultrasonic backscatter system for powering and communicating with implanted bioelectronics. We show that ultrasound is effective at delivering power to mm-scale devices in tissue; likewise, passive, battery-less communication using backscatter enables high-fidelity transmission of electromyogram (EMG) and electroneurogram (ENG) signals from anesthetized rats. These results highlight the potential for an ultrasound-based neural interface system for advancing future bioelectronics-based therapies. PMID:27497221

  3. 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

  4. Distribution of EphA5 receptor protein in the developing and adult mouse nervous system

    PubMed Central

    Cooper, Margaret A.; Crockett, David P.; Nowakowski, Richard S.; Gale, Nicholas W.; Zhou, Renping

    2009-01-01

    The EphA5 receptor tyrosine kinase plays key roles in axon guidance during development. However, the presence of EphA5 protein in the nervous system has not been fully characterized. To better examine EphA5 localization, mutant mice, in which the EphA5 cytoplasmic domain was replaced with β-galactosidase, were analyzed for both temporal and regional changes in the distribution of EphA5 protein in the developing and adult nervous system. During embryonic development, high levels of EphA5 protein were found in the retina, olfactory bulb, cerebral neocortex, hippocampus, pretectum, tectum, cranial nerve nuclei, and the spinal cord. Variations in intensity were observed as development proceeded. Staining of pretectal nuclei, tectal nuclei, and other areas of the mesencephalon became more diffuse after maturity whereas the cerebral neocortex gained more robust intensity. In the adult, receptor protein continued to be detected in many areas including the olfactory nuclei, neocortex, piriform cortex, induseum griseum, hippocampus, thalamus, amygdala, hypothalamus and septum. In addition, EphA5 protein was found in the claustrum, stria terminalis, barrel cortex, striatal patches, and along discrete axon tracts within the corpus callosum of the adult. These observations suggest that EphA5 function is not limited to the developing mouse brain and may play a role in synaptic plasticity in the adult. PMID:19326470

  5. 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

  6. 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

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

    PubMed

    Marques, Sueli; Zeisel, Amit; Codeluppi, Simone; van Bruggen, David; Mendanha Falcão, Ana; Xiao, Lin; Li, Huiliang; Häring, Martin; Hochgerner, Hannah; Romanov, Roman A; Gyllborg, Daniel; Muñoz-Manchado, Ana B; 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

    2016-06-10

    Oligodendrocytes have been considered as a functionally homogeneous population in the central nervous system (CNS). We performed single-cell RNA sequencing on 5072 cells of the oligodendrocyte lineage from 10 regions of the mouse juvenile and adult CNS. Thirteen distinct populations were identified, 12 of which represent a continuum from Pdgfra(+) oligodendrocyte precursor cells (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 detected in the adult CNS and were 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

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

    PubMed Central

    El-Tahir, Heba M; Dietz, Frank; Dringen, Ralf; Schwabe, Kerstin; Strenge, Karen; Kelm, Sørge; Abouzied, Mekky M; Gieselmann, Volkmar; Franken, Sebastian

    2006-01-01

    Background Hepatoma-derived growth factor (HDGF) belongs to a polypeptide family containing five additional members called HDGF related proteins 1–4 (HRP-1 to -4) and Lens epithelial derived growth factor. Whereas some family members such as HDGF and HRP-2 are expressed in a wide range of tissues, the expression of others is very restricted. HRP-1 and -4 are only expressed in testis, HRP-3 only in the nervous system. Here we investigated the expression of HDGF, HRP-2 and HRP-3 in the central nervous system of adult mice on the cellular level by immunohistochemistry. In addition we performed Western blot analysis of various brain regions as well as neuronal and glial cell cultures. Results HDGF was rather evenly expressed throughout all brain regions tested with the lowest expression in the substantia nigra. HRP-2 was strongly expressed in the thalamus, prefrontal and parietal cortex, neurohypophysis, and the cerebellum, HRP-3 in the bulbus olfactorius, piriform cortex and amygdala complex. HDGF and HRP-2 were found to be expressed by neurons, astrocytes and oligodendrocytes. In contrast, strong expression of HRP-3 in the adult nervous system is restricted to neurons, except for very weak expression in oligodendrocytes in the brain stem. Although the majority of neurons are HRP-3 positive, some like cerebellar granule cells are negative. Conclusion The coexpression of HDGF and HRP-2 in glia and neurons as well as the coexpression of all three proteins in many neurons suggests different functions of members of the HDGF protein family in cells of the central nervous system that might include proliferation as well as cell survival. In addition the restricted expression of HRP-3 point to a special function of this family member for neuronal cells. PMID:16430771

  9. Rabies virus glycoprotein pseudotyping of lentiviral vectors enables retrograde axonal transport and access to the nervous system after peripheral delivery.

    PubMed

    Mazarakis, N D; Azzouz, M; Rohll, J B; Ellard, F M; Wilkes, F J; Olsen, A L; Carter, E E; Barber, R D; Baban, D F; Kingsman, S M; Kingsman, A J; O'Malley, K; Mitrophanous, K A

    2001-09-15

    In this report it is demonstrated for the first time that rabies-G envelope of the rabies virus is sufficient to confer retrograde axonal transport to a heterologous virus/vector. After delivery of rabies-G pseudotyped equine infectious anaemia virus (EIAV) based vectors encoding a marker gene to the rat striatum, neurons in regions distal from but projecting to the injection site, such as the dopaminergic neurons of the substantia nigra pars compacta, become transduced. This retrograde transport to appropriate distal neurons was also demonstrated after delivery to substantia nigra, hippocampus and spinal cord and did not occur when vesicular stomatitis virus glycoprotein (VSV-G) pseudotyped vectors were delivered to these sites. In addition, peripheral administration of rabies-G pseudotyped vectors to the rat gastrocnemius muscle leads to gene transfer in motoneurons of lumbar spinal cord. In contrast the same vector pseudotyped with VSV-G transduced muscle cells surrounding the injection site, but did not result in expression in any cells in the spinal cord. Long-term expression was observed after gene transfer in the nervous system and a minimal immune response which, together with the possibility of non-invasive administration, greatly extends the utility of lentiviral vectors for gene therapy of human neurological disease. PMID:11590128

  10. 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.

  11. 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. PMID:24918640

  12. 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

  13. 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

  14. 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

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

    PubMed

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

    2015-06-01

    It has been proposed that the adult dorsal root ganglia (DRG) harbor neural stem/progenitor cells (NPCs) derived from the neural crest. However, the thorough characterization of their stemness and differentiation plasticity was not addressed. In this study, we investigated adult DRG-NPC stem cell properties overtime, and their fate when ectopically grafted in the central nervous system. We compared them in vitro and in vivo to the well-characterized adult spinal cord-NPCs derived from the same donors. Using micro-dissection and neurosphere cultures, we demonstrate that adult DRG-NPCs have quasi unlimited self-expansion capacities without compromising their tissue specific molecular signature. Moreover, they differentiate into multiple peripheral lineages in vitro. After transplantation, adult DRG-NPCs generate pericytes in the developing forebrain but remyelinating Schwann cells in response to spinal cord demyelination. In addition, we show that axonal and endothelial/astrocytic factors as well astrocytes regulate the fate of adult DRG-NPCs in culture. Although the adult DRG-NPC multipotency is restricted to the neural crest lineage, their dual responsiveness to developmental and lesion cues highlights their impressive adaptive and repair potentials making them valuable targets for regenerative medicine. PMID:25786382

  16. Approach behavior and sympathetic nervous system reactivity predict substance use in young adults.

    PubMed

    Hinnant, J Benjamin; Forman-Alberti, Alissa B; Freedman, Anna; Byrnes, Lindsay; Degnan, Kathryn A

    2016-07-01

    A behavioral measure of approach (performance on a resource gathering task) in combination with sympathetic nervous system (SNS) reactivity was used to predict substance use in a sample of young adults (n=93). Pre-ejection period reactivity (PEP-R), a cardiac index of SNS reactivity, was recorded during the resource gathering task (task PEP - resting PEP). Higher levels of approach behaviors on the task in combination with less PEP-R (blunted SNS reactivity) predicted the highest levels of substance use. Findings are discussed in the context of behavioral and physiological systems of approach and avoidance. PMID:27178723

  17. Transplacental induction of peripheral nervous tumor in the Syrian golden hamster by N-nitroso-N-ethylurea. A new animal model for von Recklinghausen's neurofibromatosis.

    PubMed Central

    Nakamura, T.; Hara, M.; Kasuga, T.

    1989-01-01

    Multiple peripheral nervous tumors were induced in 45 of 60 (75.0%) Syrian golden hamsters by transplacental administration of N-ethyl-N-nitro-sourea. Moreover, melanomas, pheochromocytomas, and Wilms' tumors developed in six (10.0%), three (5.0%), and 13 (21.7%) animals, respectively. The histologic, immunohistochemical, and electron microscopic findings of the peripheral nervous tumors were similar to those of human neurofibroma, and their growth pattern and distribution resembled those of human von Recklinghausen's neurofibromatosis (VRNF). The occurrence of melanoma, pheochromocytoma, and proliferative foci of melanin-containing cells in neurofibroma suggests that the targets of ENU in hamsters are the neural crest-derived cells. With its high incidence of Wilms' tumor, the hamster with ENU-induced tumors is considered to be a good animal model for human neurocristopathy, including VRNF. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:2551169

  18. 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

  19. 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.

  20. Errors, limitations, and pitfalls in the diagnosis of central and peripheral nervous system lesions in intraoperative cytology and frozen sections

    PubMed Central

    Chand, Priyanka; Amit, Sonal; Gupta, Raghvendra; Agarwal, Asha

    2016-01-01

    Context: Intraoperative cytology and frozen section play an important role in the diagnosis of neurosurgical specimens. There are limitations in both these procedures but understanding the errors and pitfalls may help in increasing the diagnostic yield. Aims: To find the diagnostic accuracy of intraoperative cytology and frozen section for central and peripheral nervous system (PNS) lesions and analyze the errors, pitfalls, and limitations in these procedures. Settings and Design: Eighty cases were included in this prospective study in a span of 1.5 years. Materials and Methods: The crush preparations and the frozen sections were stained with hematoxylin and eosin method. The diagnosis of crush smears and the frozen sections were compared with the diagnosis in the paraffin section, which was considered as the gold standard. Statistical Analyses Used: Diagnostic accuracy, sensitivity, and specificity. Results: The diagnostic accuracy of crush smears was 91.25% with a sensitivity of 95.5% and specificity of 100%. In the frozen sections, the overall diagnostic accuracy was 95%, sensitivity was 96.8%, and specificity was 100%. The categories of pitfalls noted in this study were categorization of spindle cell lesions, differentiation of oligodendroglioma from astrocytoma in frozen sections, differentiation of coagulative tumor necrosis of glioblastoma multiforme (GBM) from the caseous necrosis of tuberculosis, grading of gliomas in frozen section, and differentiation of the normal granular cells of the cerebellum from the lymphocytes in cytological smears. Conclusions: Crush smear and frozen section are complimentary procedures. When both are used together, the diagnostic yield is substantially increased. PMID:27279685

  1. 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. PMID:22401666

  2. 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

  3. Lipoprotein Receptor LRP1 Regulates Leptin Signaling and Energy Homeostasis in the Adult Central Nervous System

    PubMed Central

    Liu, Qiang; Zhang, Juan; Zerbinatti, Celina; Zhan, Yan; Kolber, Benedict J.; Herz, Joachim; Muglia, Louis J.; Bu, Guojun

    2011-01-01

    Obesity is a growing epidemic characterized by excess fat storage in adipocytes. Although lipoprotein receptors play important roles in lipid uptake, their role in controlling food intake and obesity is not known. Here we show that the lipoprotein receptor LRP1 regulates leptin signaling and energy homeostasis. Conditional deletion of the Lrp1 gene in the brain resulted in an obese phenotype characterized by increased food intake, decreased energy consumption, and decreased leptin signaling. LRP1 directly binds to leptin and the leptin receptor complex and is required for leptin receptor phosphorylation and Stat3 activation. We further showed that deletion of the Lrp1 gene specifically in the hypothalamus by Cre lentivirus injection is sufficient to trigger accelerated weight gain. Together, our results demonstrate that the lipoprotein receptor LRP1, which is critical in lipid metabolism, also regulates food intake and energy homeostasis in the adult central nervous system. PMID:21264353

  4. 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

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

    2014-06-28

    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

  5. 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

  6. Peripheral intravenous therapy-related phlebitis rates in an adult population.

    PubMed

    White, S A

    2001-01-01

    To determine the incidence of peripheral intravenous therapy-related phlebitis in an adult population, 305 peripheral i.v. catheter sites were observed from the time of admission of the patient (or initiation of the first peripheral i.v. catheter) to the time of the participant's discharge from the facility (or 48 hours after the removal of the final catheter). Parameters monitored included patient demographics, diagnosis, i.v. fluids and medications, type of peripheral catheter, dwell time, and dressing integrity. Results showed that of the 10 cases of phlebitis found in nine study subjects, all were associated with catheters indwelling less than 72 hours. In three cases, although the catheter site was clear at the time of catheter removal, postinfusion phlebitis developed within 24 hours. Catheter site locations, diagnoses, medications, and i.v. fluids in these cases were varied. PMID:11836840

  7. 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.

  8. Evaluation of the Effects of the Aqueous Extract of Vitex doniana Root-Bark on the Peripheral and Central Nervous System of Laboratory Animals

    NASA Astrophysics Data System (ADS)

    Abdulrahman, F. I.; Onyeyili, P. A.; Sandabe, U. K.; Ogugbuaja, V. O.

    Aim of this study to investigate the effects of aqueous extract of Vitrex doniana on the peripheral and central nervous systems and possibility to use it as folk medicine. The aqueous extract of Vitex doniana was soxhlet extracted with distilled water and concentrated in vacuo to give a yield of 8.5% w/w. The LD50 following intraperitoneal administration was estimated to be 980 mg kgG1. The aqueous extract of Vitex doniana from the study produced substantial depressant effects on both the peripheral and central nervous system. The aqueous extract induced sleep on its own at dose of 400 mg kgG1 and potentiated sodium thiopental sleeping time in a dose dependant manner. It also showed significant (p< 0.05) muscle relaxant activities and produced analgesia and weal anesthetic effect. The extract was able to confer 80% protection to rats treated with convulsive dose of PTZ, while it conferred 100% protection to rats treated with convulsion dose of strychnine.

  9. Assessing the involvement of migratory dendritic cells in the transfer of the scrapie agent from the immune to peripheral nervous systems.

    PubMed

    Raymond, Claudine R; Mabbott, Neil A

    2007-07-01

    Many transmissible spongiform encephalopathy (TSE) agents accumulate upon follicular dendritic cells (FDCs) in lymphoid tissues before spreading to the brain. How TSE agents spread from FDCs to the nervous system is not known as there is no physical FDC-nerve synapse. As FDCs form immobile networks we investigated whether other mobile cells might transfer TSE agents between FDCs and peripheral nerves. We show that scrapie-infected mononuclear cells, B cells and migratory dendritic cells (DCs) were unable to efficiently transmit disease to the peripheral nervous systems (PNSs) of FDC-deficient TNFR1(-/-) mice. These findings differed significantly from a similar study which suggested that scrapie-infected DCs could efficiently transmit disease directly to FDC-deficient RAG1(-/-) mice. Comparison of the innervation in spleens from TNFR1(-/-) mice and RAG1(-/-) mice indicated that the density of sympathetic nerves was much higher in RAG1(-/-) mice. These data imply that DCs could efficiently transmit disease directly to RAG1(-/-) mice because their spleens were highly innervated, but not to TNFR1(-/-) mice because their spleens were less densely innervated. As the density of the innervation in the spleens of wild-type mice also appeared to be much lower than that of RAG1(-/-) mice our data suggest that DCs are unlikely to play a key role in the transfer of TSE agents from FDCs to the PNS of wild-type mice. PMID:17561271

  10. 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

  11. 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

  12. 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. PMID:26873119

  13. Liposomal cytarabine for central nervous system embryonal tumors in children and young adults.

    PubMed

    Partap, Sonia; Murphy, Patricia A; Vogel, Hannes; Barnes, Patrick D; Edwards, Michael S B; Fisher, Paul G

    2011-07-01

    To assess the tolerability and efficacy of liposomal cytarabine (LC), an encapsulated, sustained-release, intrathecal (IT) formulation of cytosine arabinoside, in de novo and relapsed central nervous system (CNS) embryonal tumors in children and young adults. We studied retrospectively all patients less than age 30 at our institution treated consecutively with LC for medulloblastoma (MB), primitive neuroectodermal tumor (PNET), and atypical teratoid rhabdoid tumor (ATRT). Seventeen patients received LC (2 mg/kg up to 50 mg, every 2 weeks to monthly) at diagnosis of high-risk CNS embryonal tumor (2 PNET, 3 ATRT) or relapse of MB (12 MB; 9 had leptomeningeal metastases). Sixteen patients received concurrent systemic chemotherapy. A total of 108 doses were administered (IT 82, intraventricular 26) with a mean of six (range 1-16) treatments per patient. Only three administrations were associated with adverse effects of arachnoiditis or headache. None developed malignant cerebrospinal fluid (CSF) cytology while receiving LC. All the six evaluable patients with malignant CSF cytology and treated with at least two doses cleared their CSF (mean 3 doses, range 1-5). Median overall survival in relapse patients was 9.1 months. Five patients (4 de novo and 1 relapsed) remain alive in complete remission for a median 26.8 months from first LC. Liposomal cytarabine is an easily administered, well-tolerated, and active drug in patients with high-risk embryonal neoplasms. One-third of our cohort remains in remission from otherwise fatal diagnoses. Our findings warrant a phase II trial of LC in newly diagnosed or recurrent CNS embryonal tumors. PMID:20859651

  14. Peripheral venous distension elicits a blood pressure raising reflex in young and middle-aged adults.

    PubMed

    Matthews, Evan L; Brian, Michael S; Coyle, Dana E; Edwards, David G; Stocker, Sean D; Wenner, Megan M; Farquhar, William B

    2016-06-01

    Distension of peripheral veins in humans elicits a pressor and sympathoexcitatory response that is mediated through group III/IV skeletal muscle afferents. There is some evidence that autonomic reflexes mediated by these sensory fibers are blunted with increasing age, yet to date the venous distension reflex has only been studied in young adults. Therefore, we tested the hypothesis that the venous distension reflex would be attenuated in middle-aged compared with young adults. Nineteen young (14 men/5 women, 25 ± 1 yr) and 13 middle-aged (9 men/4 women, 50 ± 2 yr) healthy normotensive participants underwent venous distension via saline infusion through a retrograde intravenous catheter in an antecubital vein during limb occlusion. Beat-by-beat blood pressure, muscle sympathetic nerve activity (MSNA), and model flow-derived cardiac output (Q), and total peripheral resistance (TPR) were recorded throughout the trial. Mean arterial pressure (MAP) increased during the venous distension in both young (baseline 83 ± 2, peak 94 ± 3 mmHg; P < 0.05) and middle-aged adults (baseline 88 ± 2, peak 103 ± 3 mmHg; P < 0.05). MSNA also increased in both groups [young: baseline 886 ± 143, peak 1,961 ± 242 arbitrary units (AU)/min; middle-aged: baseline 1,164 ± 225, peak 2,515 ± 404 AU/min; both P < 0.05]. TPR (P < 0.001), but not Q (P = 0.76), increased during the trial. However, the observed increases in blood pressure, MSNA, and TPR were similar between young and middle-aged adults. Additionally, no correlation was found between age and the response to venous distension (all P > 0.05). These findings suggest that peripheral venous distension elicits a pressor and sympathetic response in middle-aged adults similar to the response observed in young adults. PMID:27053648

  15. 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…

  16. 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.

  17. Peripherally administered antibodies against amyloid beta-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease.

    PubMed

    Bard, F; Cannon, C; Barbour, R; Burke, R L; Games, D; Grajeda, H; Guido, T; Hu, K; Huang, J; Johnson-Wood, K; Khan, K; Kholodenko, D; Lee, M; Lieberburg, I; Motter, R; Nguyen, M; Soriano, F; Vasquez, N; Weiss, K; Welch, B; Seubert, P; Schenk, D; Yednock, T

    2000-08-01

    One hallmark of Alzheimer disease is the accumulation of amyloid beta-peptide in the brain and its deposition as plaques. Mice transgenic for an amyloid beta precursor protein (APP) mini-gene driven by a platelet-derived (PD) growth factor promoter (PDAPP mice), which overexpress one of the disease-linked mutant forms of the human amyloid precursor protein, show many of the pathological features of Alzheimer disease, including extensive deposition of extracellular amyloid plaques, astrocytosis and neuritic dystrophy. Active immunization of PDAPP mice with human amyloid beta-peptide reduces plaque burden and its associated pathologies. Several hypotheses have been proposed regarding the mechanism of this response. Here we report that peripheral administration of antibodies against amyloid beta-peptide, was sufficient to reduce amyloid burden. Despite their relatively modest serum levels, the passively administered antibodies were able to enter the central nervous system, decorate plaques and induce clearance of preexisting amyloid. When examined in an ex vivo assay with sections of PDAPP or Alzheimer disease brain tissue, antibodies against amyloid beta-peptide triggered microglial cells to clear plaques through Fc receptor-mediated phagocytosis and subsequent peptide degradation. These results indicate that antibodies can cross the blood-brain barrier to act directly in the central nervous system and should be considered as a therapeutic approach for the treatment of Alzheimer disease and other neurological disorders. PMID:10932230

  18. 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.

  19. The distribution and localization of /sup 127/m tellurium in normal and pathological nervous tissues of young and adult rats

    SciTech Connect

    Duckett, S.

    1982-11-01

    An equal amount (per weight) of /sup 127/m tellurium (Te) was injected IP into weanling and adult rats, some intoxicated with a diet containing Te, others not. The young intoxicated rats presented a segmental demyelination of the sciatic nerve and paralysis of the hind limbs; the adult intoxicated rats did not. Quantitation of 127m Te in nervous and other tissues was done with a gamma counter. Correlative morphological examination of the nervous tissues was done with light and electron microscopy. This study shows that Te crosses the vascular wall without injuring endothelial cells and invades the surrounding sciatic nerve parenchyma following administration of 127m Te to a weanling or adult rat. However, Te damages the endothelium, crosses the vascular wall of endo and perineurial vessels in weanling rats, causes a perivascular oedema, cytoplasmic anomalies in the Schwann cells, destruction of myelin and apparently invades axones--according to autoradiographic studies--following the administration of 127m Te plus the Te-diet. It is concluded that Te penetrates more quickly and in larger amounts the walls of blood vessels in the sciatic nerve of weanling rats intoxicated with Te, than the same nerve in the other weanling and adults rats. Te in the amounts indicated here penetrates the parenchyma of the CNS but apparently does not cause injury.

  20. Underarousal in Adult ADHD: How Are Peripheral and Cortical Arousal Related?

    PubMed

    Mayer, Kerstin; Wyckoff, Sarah Nicole; Strehl, Ute

    2016-07-01

    In children and adults with attention deficit/hyperactivity disorder (ADHD), a general slowing of spontaneous electroencephalographic (EEG) brain activity and a decrease of event-related potential amplitudes such as the contingent negative variation (CNV) are observed. Additionally, some studies have reported decreased skin conductance level (SCL) in this clinical population leading to the hypothesis of a peripheral hypoarousal, which may be a target of biofeedback treatment in addition to or instead of neurofeedback. To our knowledge, the relationship between SCL and CNV has not been simultaneously investigated in one experiment. Using the theoretical background of the hypoarousal model, this article aims to gain more insight into the differences and correlations of cortical (CNV) and peripheral (SCL) arousal in adults with ADHD. A sample of 23 adults with ADHD and 22 healthy controls underwent an auditory Go-NoGo task with simultaneous 22-channel EEG and SCL recordings. Reaction time (RT) and reaction time variability (RTV) were also measured to assess task performance. Significantly decreased CNV amplitude and significantly higher RTV were observed in the ADHD group, reflecting cortical underarousal and problems with sustained attention. No significant correlation between peripheral underarousal and cortical underarousal was observed in the ADHD group or the control group. The observed cortical underarousal reflected in the decreased CNV supports the notion of a reduced CNV amplitude as a possible biomarker for ADHD. However, the connection between cortical and peripheral arousal is not as clear as is suggested in previous research investigating both separately. Implications of these results for new treatment options for ADHD such as biofeedback are discussed. PMID:25802473

  1. 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

  2. Impact of Treatment Site in Adolescents and Young Adults With Central Nervous System Tumors

    PubMed Central

    Wolfson, Julie; Sun, Can-Lan; Kang, Tongjun; Wyatt, Laura; D’Appuzzo, Massimo

    2014-01-01

    Background Adolescents and young adults (AYAs; aged 15–39 years) have inferior survival in comparison with younger (aged 0–14 years) cancer patients. Impact of care at specialized centers such as National Cancer Institute–designated Comprehensive Cancer Centers (NCICCC) for AYAs of all ages or the Children’s Oncology Group (COG) for AYAs aged 15 to 21 years with central nervous system (CNS) tumors remains unstudied. Methods We constructed a cohort of 560 children and 784 AYAs with CNS tumors reported to the Los Angeles cancer registry from 1998 to 2008. Cox and logistic regression models were used, with two-sided P values from Wald χ2 tests. Results In Cox regression analysis restricted to World Health Organization (WHO) grade II tumors, patients of all ages saw worse outcome if not treated at NCICCC/COG sites (non-NCICCC/COG vs NCICCC/COG: hazard ratio [HR] =1.73; 95% confidence interval [CI] = 1.09 to 2.72). Furthermore, the worse outcome for AYAs compared with children (HR = 1.90; 95% CI = 1.21 to 2.98; P = .005) was abrogated (HR = 1.35; 95% CI = 0.79 to 2.29; P = .27) by care at NCICCC/COGs. Those less likely to receive care at NCICCC/COG sites included young AYAs (aged 15–21 years vs children: odds ratio [OR] = 0.23; 95% CI = 0.11 to 0.48; P < .001) and older AYAs (aged 22–39 years) with low socioeconomic status (OR = 0.39; 95% CI = 0.17 to 0.89; P = .02), public/no insurance (OR = 0.30; 95% CI = 0.12 to 0.71; P < .01), and distance to care greater than 5 miles (OR = 0.29; 95% CI = 0.15 to 0.57; P < .001). Conclusions Population-based data reveal that care at NCICCC/COG sites mitigates inferior outcome in AYAs with WHO grade II CNS tumors compared with children. Compared with children, AYAs are less likely to receive care at NCICCC/COGs. Insurance, socioeconomic status, and distance serve as barriers to care at NCICCCs for older AYAs. PMID:25178694

  3. Safety, tolerability, pharmacokinetics, and pharmacodynamic effects of naloxegol at peripheral and central nervous system receptors in healthy male subjects: A single ascending-dose study.

    PubMed

    Eldon, Michael A; Kugler, Alan R; Medve, Robert A; Bui, Khanh; Butler, Kathleen; Sostek, Mark

    2015-11-01

    This randomized, double-blind, placebo-controlled, ascending-dose, crossover study evaluated single oral doses of naloxegol (NKTR-118; 8, 15, 30, 60, 125, 250, 500, and 1000 mg), a PEGylated derivative of naloxone, for safety and tolerability, antagonism of peripheral and central nervous system (CNS) effects of intravenous morphine, and pharmacokinetics. Healthy men were randomized 1:1 to naloxegol or naloxegol-matching placebo administered with morphine and lactulose in a 2-period crossover design. Periods were separated by a 5- to 7-day washout. Assessments included safety, tolerability, orocecal transit time (OCTT), pupillary miosis, and pharmacokinetics. The study was completed by 46 subjects. The most common adverse events were somnolence, dizziness, headache, and nausea. Greater reversal of morphine-induced delay in OCTT occurred with increasing naloxegol dose, demonstrating dose-ordered antagonism of morphine's peripheral gastrointestinal effects. Forty-four subjects showed no reversal of pupillary miosis; 2 showed potential partial reversal at 250 and 1000 mg, indicating negligible antagonism of morphine's CNS effects at doses ≤ 125 mg. Rapid absorption, linear pharmacokinetics up to 1000 mg, and low to moderate between-subject pharmacokinetic variability was observed. The pharmacokinetics of morphine or its glucuronide metabolites were unaltered by concurrent naloxegol administration. Naloxegol was generally safe and well tolerated at single doses up to 1000 mg. PMID:27137715

  4. Effect of electroacupuncture on P2X3 receptor regulation in the peripheral and central nervous systems of rats with visceral pain caused by irritable bowel syndrome.

    PubMed

    Weng, Z J; Wu, L Y; Zhou, C L; Dou, C Z; Shi, Y; Liu, H R; Wu, H G

    2015-09-01

    The aim of this study is to investigate the role of the purinergic receptor P2X3 in the peripheral and central nervous systems during acupuncture treatment for the visceral pain of irritable bowel syndrome (IBS). A total of 24 8-day-old Sprague-Dawley (SD) neonatal male rats (SPF grade) were stimulated using colorectal distention (CRD) when the rats were awake. The modeling lasted for 2 weeks with one stimulation per day. After 6 weeks, the rats were randomly divided into three groups of eight each: (1) the normal group (NG, n = 8); (2) the model group (MG, n = 8); and (3) the model + electroacupuncture group (EA, n = 8) that received electroacupuncture at a needling depth of 5 mm at the Shangjuxu (ST37, bilateral) and Tianshu (ST25, bilateral) acupoints. The parameters of the Han's acupoint nerve stimulator (HANS) were as follows: sparse-dense wave with a frequency of 2/100 Hz, current of 2 mA, 20 min/stimulation, and one stimulation per day; the treatment was provided for seven consecutive days. At the sixth week after the treatment, the abdominal withdrawal reflex (AWR) score was determined; immunofluorescence and immunohistochemistry were used to measure the expression of the P2X3 receptor in myenteric plexus neurons, prefrontal cortex, and anterior cingulate cortex; and, a real-time PCR assay was performed to measure the expression of P2X3 messenger RNA (mRNA) in the dorsal root ganglion (DRG) and spinal cord. After stimulation with CRD, the expression levels of the P2X3 receptor in the inter-colonic myenteric plexus, DRG, spinal cord, prefrontal cortex, and anterior cingulate cortex were upregulated, and the sensitivity of the rats to IBS visceral pain was increased. Electroacupuncture (EA) could downregulate the expression of the P2X3 receptor and ease the sensitivity to visceral pain. The P2X3 receptor plays an important role in IBS visceral pain. The different levels of P2X3 in the peripheral enteric nervous system and central nervous system mediate the

  5. The choroid plexus is modulated by various peripheral stimuli: implications to diseases of the central nervous system

    PubMed Central

    Marques, Fernanda; Sousa, João C.

    2015-01-01

    The blood brain barrier (BBB) and the blood cerebrospinal fluid barrier (BCSFB) form the barriers of the brain. These barriers are essential not only for the protection of the brain, but also in regulating the exchange of cells and molecules in and out of the brain. The choroid plexus (CP) epithelial cells and the arachnoid membrane form the BCSFB. The CP is structurally divided into two independent compartments: one formed by a unique and continuous line of epithelial cells that rest upon a basal lamina; and, a second consisting of a central core formed by connective and highly vascularized tissue populated by diverse cell types (fibroblasts, macrophages and dendritic cells). Here, we review how the CP transcriptome and secretome vary depending on the nature and duration of the stimuli to which the CP is exposed. Specifically, when the peripheral stimulation is acute the CP response is rapid, strong and transient, whereas if the stimulation is sustained in time the CP response persists but it is weaker. Furthermore, not all of the epithelium responds at the same time to peripheral stimulation, suggesting the existence of a synchrony system between individual CP epithelial cells. PMID:26236190

  6. Histochemical localization of galactose-containing glycoconjugates in sensory neurons and their processes in the central and peripheral nervous system of the rat.

    PubMed

    Streit, W J; Schulte, B A; Balentine, D J; Spicer, S S

    1985-10-01

    We studied the distribution of sugar residues in the oligosaccharide chains of complex carbohydrates in tissue sections of rat spinal cord, brainstem, and sensory ganglia using twelve lectin-horseradish peroxidase conjugates. Glycoconjugates containing terminal galactose residues were localized apparently in the Golgi apparatus in a population of predominantly small B-type neurons in spinal and trigeminal ganglia. Large A-type neurons rarely showed reactivity with galactose-binding lectins. A cells stained for glycoconjugates with N-glycosidically linked oligosaccharides and glycogen. The central and peripheral processes of the small neurons, mostly unmyelinated C fibers in sensory roots and spinal nerves, contained an abundance of glycoconjugates with terminal alpha-galactose residues. The central projections and terminals of small to medium-sized primary sensory neurons in the spinal and trigeminal ganglia were visualized in Lissauer's tract and the substantia gelatinosa in the spinal cord, and in the spinal trigeminal tract and the nucleus trigeminus in the lower medulla with lectins specific for terminal alpha-galactose residues. In addition, fibers of the solitary system and the area postrema were reactive with these lectins. The peripheral and central nervous system elements with affinity for galactopyranosyl-specific lectins correspond in distribution with neuroanatomical regions thought to be involved in the transmission and relay of somatic and visceral afferent inputs such as pain and temperature. Such specific localization of a glycosubstance to a distinct subpopulation of neurons and their peripheral and central processes suggests that the particular glycoconjugate may be of physiological significance. PMID:4045182

  7. Chemotherapy-induced peripheral neuropathy in adults: a comprehensive update of the literature

    PubMed Central

    Argyriou, Andreas A; Kyritsis, Athanasios P; Makatsoris, Thomas; Kalofonos, Haralabos P

    2014-01-01

    Commonly used chemotherapeutic agents in oncology/hematology practice, causing toxic peripheral neuropathy, include taxanes, platinum compounds, vinca alkaloids, proteasome inhibitors, and antiangiogenic/immunomodulatory agents. This review paper intends to put together and discuss the spectrum of chemotherapy-induced peripheral neuropathy (CIPN) characteristics so as to highlight areas of future research to pursue on the topic. Current knowledge shows that the pathogenesis of CIPN still remains elusive, mostly because there are several sites of involvement in the peripheral nervous system. In any case, it is acknowledged that the dorsal root ganglia of the primary sensory neurons are the most common neural targets of CIPN. Both the incidence and severity of CIPN are clinically under- and misreported, and it has been demonstrated that scoring CIPN with common toxicity scales is associated with significant inter-observer variability. Only a proportion of chemotherapy-treated patients develop treatment-emergent and persistent CIPN, and to date it has been impossible to predict high-and low-risk subjects even within groups who receive the same drug regimen. This issue has recently been investigated in the context of pharmacogenetic analyses, but these studies have not implemented a proper methodological approach and their results are inconsistent and not really clinically relevant. As such, a stringent approach has to be implemented to validate that information. Another open issue is that, at present, there is insufficient evidence to support the use of any of the already tested chemoprotective agents to prevent or limit CIPN. The results of comprehensive interventions, including clinical, neurophysiological, and pharmacogenetic approaches, are expected to produce a consistent advantage for both doctors and patients and thus allow the registration and analysis of reliable data on the true characteristics of CIPN, eventually leading to potential preventive and

  8. New trend in neuroscience: low-power laser effect on peripheral and central nervous system (basic science, preclinical and clinical studies).

    PubMed

    Rochkind, S; Ouaknine, G E

    1992-03-01

    The present review summarizes findings in our continuing study of the use of low-power laser irradiation (LPLI) in the treatment of severely injured peripheral (PNS) and central nervous systems (CNS). The radiation method was proposed by Rochkind and has been modified over the last 13 years. LPLI in specific wavelengths and energy density maintains the electrophysiological activity of severely injured peripheral nerve in rats, preventing scar formation (at injury site) as well as degenerative changes in the corresponding motor neurons of the spinal cord, thus accelerating regeneration of the injured nerve. Laser irradiation applied to the spinal cord of dogs following severe spinal cord injury and implantation of a segment of the peripheral nerve into the injured area diminished glial scar formation, induced axonal sprouting in the injured area and restoration of locomotor function. The use of laser irradiation in mammalian CNS transplantation shows that laser therapy prevents extensive glial scar formation (a limiting factor in CNS regeneration) between a neural transplant and the host brain or spinal cord. Abundant capillaries developed in the laser-irradiated transplants, and was of crucial importance in their survival. Intraoperative clinical use of laser therapy following surgical treatment of the tethered spinal cord (resulting from myelomeningocele, lipomyelomeningocele, thickened filum terminale or fibrous scar) increases functional activity of the irradiated spinal cord. In a previous experimental work, we showed that direct laser treatment on nerve tissue promotes restoration of the electrophysiological activity of the severely injured peripheral nerve, prevents degenerative changes in neurons of the spinal cord and induces proliferation of astrocytes and oligodendrocytes. This suggested a higher metabolism in neurons and improved ability for myelin production under the influence of laser treatment. The tethering of the spinal cord causes mechanical

  9. 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. PMID:70155

  10. Functional dissection of the Pax6 paired domain: Roles in neural tube patterning and peripheral nervous system development.

    PubMed

    Huettl, Rosa-Eva; Eckstein, Simone; Stahl, Tessa; Petricca, Stefania; Ninkovic, Jovica; Götz, Magdalena; Huber, Andrea B

    2016-05-01

    During development of the CNS, stem and progenitor cell proliferation, cell fate designation, and patterning decisions are tightly regulated by interdependent networks of key transcriptional regulators. In a genetic approach we analyzed divergent functionality of the PAI and RED sub-domains of the Pax6 Paired domain (PD) during progenitor zone formation, motor and interneuron development, and peripheral connectivity at distinct levels within the neural tube: within the hindbrain, mutation of the PAI sub-domain severely affected patterning of the p3 and pMN domains and establishment of the corresponding motor neurons. Exit point designation of hypoglossal axons was disturbed in embryos harboring either mutations in the PD sub-domains or containing a functional Pax6 Null allele. At brachial spinal levels, we propose a selective involvement of the PAI sub-domain during patterning of ventral p2 and pMN domains, critically disturbing generation of specific motor neuron subtypes and increasing V2 interneuron numbers. Our findings present a novel aspect of how Pax6 not only utilizes its modular structure to perform distinct functions via its paired and homeodomain. Individual sub-domains can exert distinct functions, generating a new level of complexity for transcriptional regulation by one single transcription factor not only in dorso-ventral, but also rostro-caudal neural tube patterning. PMID:26187199

  11. Large-Scale Functional Reorganization in Adult Monkey Cortex after Peripheral Nerve Injury

    NASA Astrophysics Data System (ADS)

    Garraghty, Preston E.; Kaas, Jon H.

    1991-08-01

    In adult monkeys, peripheral nerve injuries induce dramatic examples of neural plasticity in somatosensory cortex. It has been suggested that a cortical distance limit exists and that the amount of plasticity that is possible after injury is constrained by this limit. We have investigated this possibility by depriving a relatively large expanse of cortex by transecting and ligating both the median and the ulnar nerves to the hand. Electrophysiological recording in cortical areas 3b and 1 in three adult squirrel monkeys no less than 2 months after nerve transection has revealed that cutaneous responsiveness is regained throughout the deprived cortex and that a roughly normal topographic order is reestablished for the reorganized cortex.

  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. Neurotoxic and neurotrophic roles of proNGF and the receptor sortilin in the adult and ageing nervous system.

    PubMed

    Al-Shawi, Raya; Hafner, Angela; Olsen, Jessica; Olson, Jessica; Chun, Soyon; Raza, Saba; Thrasivoulou, Christopher; Lovestone, Simon; Killick, Richard; Simons, Paul; Cowen, Timothy

    2008-04-01

    The precursor form of the nerve growth factor (proNGF), forms a heterotrimeric complex with the receptors p75 and sortilin; this complex has been implicated in neuron cell death. However, it is not known whether proNGF and the receptors p75 and sortilin contribute to age- and disease-related neurodegeneration. Here we show that proNGF induces cell death in subpopulations of basal forebrain and peripheral sympathetic neurons of old, but not of young, adult rodents. In contrast, proNGF appears to induce neurite outgrowth rather than cell death of young adult sympathetic neurons. We have examined the neurotoxic role of proNGF in old age, and find that proNGF protein is elevated during ageing in the projection areas of some populations of vulnerable central and peripheral neurons; caloric restriction, which has known neuroprotective effects, partially prevents these increases. Sortilin was found to play a significant part in the observed patterns of age-related proNGF-mediated neurotoxicity. In particular, survival of aged neurons was rescued by neurotensin, an alternative sortilin ligand that blocks the sortilin-mediated effects of proNGF. Furthermore, sortilin immunoreactivity increases markedly in ageing rodent basal forebrain and sympathetic neurons; in contrast, p75 levels are either unchanged or reduced. From these data we propose that selective age-related neuronal atrophy and neurodegeneration may be mediated by increased sortilin expression in neurons, together with elevated levels of proNGF expression in some targets. PMID:18412630

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

    PubMed

    Shepherd, David; Harris, Robin; Williams, Darren W; Truman, James W

    2016-09-01

    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

  15. Growth factor enhanced retroviral gene transfer to the adult central nervous system.

    PubMed

    King, L A; Mitrophanous, K A; Clark, L A; Kim, V N; Rohll, J B; Kingsman, A J; Colello, R J

    2000-07-01

    The use of viral vectors for gene delivery into mammalian cells provides a new approach in the treatment of many human diseases. The first viral vector approved for human clinical trials was murine leukemia virus (MLV), which remains the most commonly used vector in clinical trials to date. However, the application of MLV vectors is limited since MLV requires cells to be actively dividing in order for transduction and therefore gene delivery to occur. This limitation precludes the use of MLV for delivering genes to the adult CNS, where very little cell division is occurring. However, we speculated that this inherent limitation of ML V may be overcome by utilizing the known mitogenic effect of growth factors on cells of the CNS. Specifically, an in vivo application of growth factor to the adult brain, if able to induce cell division, could enhance MLV-based gene transfer to the adult brain. We now show that an exogenous application of basic fibroblast growth factor induces cell division in vivo. Under these conditions, where cells of the adult brain are stimulated to divide, MLV-based gene transfer is significantly enhanced. This novel approach precludes any vector modifications and provides a simple and effective way of delivering genes to cells of the adult brain utilizing MLV-based retroviral vectors. PMID:10918476

  16. 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

  17. Observations on the migratory behaviour of Schwann cells from adult peripheral nerve explant cultures.

    PubMed

    Crang, A J; Blakemore, W F

    1987-06-01

    The migration of Schwann cells from adult sciatic nerve explant cultures has been examined by time-lapse photomicrography. Analysis of Schwann cell migratory behaviour indicates that the initial outwandering by individual Schwann cells was random. Although chance cell-cell contacts resulted in temporary immobilization of pairs of cells, stable multicellular structures did not form during this initial phase. As local cell densities increased, Schwann cells assembled networks within which Schwann cell movement continued to be observed. A second form of Schwann cell outgrowth was observed from degenerating fibres in which arrays of highly oriented Schwann cells migrated away from their basal lamina tubes onto the culture dish. These observations of Schwann cell random migration, network self-assembly and coordinated extratubal migration are considered to highlight aspects of Schwann cell behaviour, independent of axonal influences, which may have relevance to their role in peripheral nerve repair following nerve section. PMID:3612187

  18. Proteome Mapping of Adult Zebrafish Marrow Neutrophils Reveals Partial Cross Species Conservation to Human Peripheral Neutrophils

    PubMed Central

    Singh, Sachin Kumar; Sethi, Sachin; Aravamudhan, Sriram; Krüger, Marcus; Grabher, Clemens

    2013-01-01

    Neutrophil granulocytes are pivotal cells within the first line of host defense of the innate immune system. In this study, we have used a gel-based LC-MS/MS approach to explore the proteome of primary marrow neutrophils from adult zebrafish. The identified proteins originated from all major cellular compartments. Gene ontology analysis revealed significant association of proteins with different immune-related network and pathway maps. 75% of proteins identified in neutrophils were identified in neutrophils only when compared to neutrophil-free brain tissue. Moreover, cross-species comparison with human peripheral blood neutrophils showed partial conservation of immune-related proteins between human and zebrafish. This study provides the first zebrafish neutrophil proteome and may serve as a valuable resource for an understanding of neutrophil biology and innate immunity. PMID:24019943

  19. Utilization of central nervous system resources for preparation and performance of complex walking tasks in older adults

    PubMed Central

    Clark, David J.; Rose, Dorian K.; Ring, Sarah A.; Porges, Eric C.

    2014-01-01

    Introduction: Walking in the home and community often involves performance of complex walking tasks. Understanding the control of such tasks is crucial to preserving independence and quality of life in older adults. However, very little research has been conducted in this area. Here, we assess the extent to which two measures of central nervous system (CNS) activity are responsive to the challenges posed by preparation and performance of complex walking tasks. Prefrontal cortical activity was measured by functional near-infrared spectroscopy (fNIRS) and sympathetic nervous system arousal was measured by skin conductance level (SCL). Materials and methods: Sixteen older men and women (age: 77.2 ± 5.6 years) with mild mobility deficits participated in this study. Participants walked at their preferred speed without distractions along an unobstructed, well-lit course (control task) and also walked on the same course under five separate challenging conditions: performing a cognitive verbal fluency task (verbal task), dim lighting (dim task), carrying a tray (carry task), negotiating obstacles (obstacles task) and wearing a weighted vest (vest task). Mean prefrontal activation and SCL were calculated during the preparation and performance phases of each task. Gait spatiotemporal measurements were acquired by an instrumented gait mat. Results: Prefrontal cortical activity and SCL were elevated during the preparation phase of complex walking tasks relative to the control task. During the performance phase, prefrontal activity remained elevated to a similar level as during task preparation. In contrast, SCL continued to increase beyond the level observed during task preparation. A larger increase in prefrontal activity was found to be linked to preserved quality of gait during complex walking tasks. Discussion: These findings indicate that availability and utilization of CNS resources are important for optimizing performance of complex walking tasks in older adults. PMID

  20. Peripheral, functional and postural asymmetries related to the preferred chewing side in adults with natural dentition.

    PubMed

    Rovira-Lastra, B; Flores-Orozco, E I; Ayuso-Montero, R; Peraire, M; Martinez-Gomis, J

    2016-04-01

    The aim of this cross-sectional study was to determine the preferred chewing side and whether chewing side preference is related to peripheral, functional or postural lateral preferences. One hundred and forty-six adults with natural dentition performed three masticatory assays, each consisting of five trials of chewing three pieces of silicon placed into a latex bag for 20 cycles, either freestyle or unilaterally on the right- or left-hand side. Occlusal contact area in the intercuspal position, maximum bite force, masticatory performance and cycle duration were measured and the lateral asymmetry of these variables was calculated. Laterality tests were performed to determine handedness, footedness, earedness and eyedness as functional preferences, and hand-clasping, arm-folding and leg-crossing as postural lateral preferences. The preferred chewing side was determined using three different methods: assessment of the first chewing cycle for each trial, calculation of the asymmetry index from all cycles and application of a visual analogue scale. Bivariate relationship and multiple linear regression analyses were performed. Among unilateral chewers, 77% of them preferred the right side for chewing. The factors most closely related to the preferred chewing side were asymmetry of bite force, asymmetry of masticatory performance and earedness, which explained up to 16% of the variance. Although several functional or postural lateral preferences seem to be related to the preferred chewing side, peripheral factors such as asymmetry of bite force and of masticatory performance are the most closely related to the preferred chewing side in adults with natural dentition. PMID:26549578

  1. Lipocalin-2 protein deficiency ameliorates experimental autoimmune encephalomyelitis: the pathogenic role of lipocalin-2 in the central nervous system and peripheral lymphoid tissues.

    PubMed

    Nam, Youngpyo; Kim, Jong-Heon; Seo, Minchul; Kim, Jae-Hong; Jin, Myungwon; Jeon, Sangmin; Seo, Jung-wan; Lee, Won-Ha; Bing, So Jin; Jee, Youngheun; Lee, Won Kee; Park, Dong Ho; Kook, Hyun; Suk, Kyoungho

    2014-06-13

    Lipocalin-2 (LCN2) plays an important role in cellular processes as diverse as cell growth, migration/invasion, differentiation, and death/survival. Furthermore, recent studies indicate that LCN2 expression and secretion by glial cells are induced by inflammatory stimuli in the central nervous system. The present study was undertaken to examine the regulation of LCN2 expression in experimental autoimmune encephalomyelitis (EAE) and to determine the role of LCN2 in the disease process. LCN2 expression was found to be strongly increased in spinal cord and secondary lymphoid tissues after EAE induction. In spinal cords astrocytes and microglia were the major cell types expressing LCN2 and its receptor 24p3R, respectively, whereas in spleens, LCN2 and 24p3R were highly expressed in neutrophils and dendritic cells, respectively. Furthermore, disease severity, inflammatory infiltration, demyelination, glial activation, the expression of inflammatory mediators, and the proliferation of MOG-specific T cells were significantly attenuated in Lcn2-deficient mice as compared with wild-type animals. Myelin oligodendrocyte glycoprotein-specific T cells in culture exhibited an increased expression of Il17a, Ifng, Rorc, and Tbet after treatment with recombinant LCN2 protein. Moreover, LCN2-treated glial cells expressed higher levels of proinflammatory cytokines, chemokines, and MMP-9. Adoptive transfer and recombinant LCN2 protein injection experiments suggested that LCN2 expression in spinal cord and peripheral immune organs contributes to EAE development. Taken together, these results imply LCN2 is a critical mediator of autoimmune inflammation and disease development in EAE and suggest that LCN2 be regarded a potential therapeutic target in multiple sclerosis. PMID:24808182

  2. Efficient central nervous system AAVrh10-mediated intrathecal gene transfer in adult and neonate rats.

    PubMed

    Hordeaux, J; Dubreil, L; Deniaud, J; Iacobelli, F; Moreau, S; Ledevin, M; Le Guiner, C; Blouin, V; Le Duff, J; Mendes-Madeira, A; Rolling, F; Cherel, Y; Moullier, P; Colle, M-A

    2015-04-01

    Intracerebral administration of recombinant adeno-associated vector (AAV) has been performed in several clinical trials. However, delivery into the brain requires multiple injections and is not efficient to target the spinal cord, thus limiting its applications. To assess widespread and less invasive strategies, we tested intravenous (IV) or intrathecal (that is, in the cerebrospinal fluid (CSF)) delivery of a rAAVrh10-egfp vector in adult and neonate rats and studied the effect of the age at injection on neurotropism. IV delivery is more efficient in neonates and targets predominantly Purkinje cells of the cerebellum and sensory neurons of the spinal cord and dorsal root ganglia. A single intra-CSF administration of AAVrh10, single strand or oversized self-complementary, is efficient for the targeting of neurons in the cerebral hemispheres, cerebellum, brainstem and spinal cord. Green fluorescent protein (GFP) expression is more widespread in neonates when compared with adults. More than 50% of motor neurons express GFP in the three segments of the spinal cord in neonates and in the cervical and thoracic regions in adults. Neurons are almost exclusively transduced in neonates, whereas neurons, astrocytes and rare oligodendrocytes are targeted in adults. These results expand the possible routes of delivery of AAVrh10, a serotype that has shown efficacy and safety in clinical trials concerning neurodegenerative diseases. PMID:25588740

  3. Long-term effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the peripheral nervous system. Clinical and neurophysiological controlled study on subjects with chloracne from the Seveso area.

    PubMed

    Barbieri, S; Pirovano, C; Scarlato, G; Tarchini, P; Zappa, A; Maranzana, M

    1988-01-01

    This work was set up to investigate the possible presence of peripheral nervous system involvement as a long-term effect of the exposure to dioxin in 152 subjects with chloracne from the Seveso area; 123 age- and sex-matched subjects living in nearby towns with similar environmental pollution formed the control group. The accident in Seveso took place in July, 1976, and this study was carried out from October, 1982, to May, 1983. Although a peripheral neuropathy was not found in any of the subjects, a significant increase of the number of individuals presenting at least two bilateral clinical signs (p less than 0.05) or one abnormal electrophysiological parameter (p less than 0.02) was found in the Seveso group. Principal component analysis did not show any subdivision between these two groups. The Fisher approach to discriminant analysis reveals a clear subdivision between the group of the most exposed subjects and randomly selected subgroups of control subjects. In conclusion, clinical and electrophysiological signs of peripheral nervous system involvement occur with a statistically increased frequency in the Seveso population 6 years after the accident, although a peripheral neuropathy was not evident in any of the chloracne patients using the World Health Organization diagnostic criteria. PMID:2829044

  4. Mechanical and metabolic reflex activation of the sympathetic nervous system in younger adults with metabolic syndrome

    PubMed Central

    Limberg, Jacqueline; Morgan, Barbara; Schrage, William

    2014-01-01

    Aim Based on reports of exaggerated blood pressure responses to whole-body exercise in patients with metabolic syndrome (MetSyn), we tested the hypothesis that MetSyn adults would exhibit augmented sympathetic and pressor responses to mechanoreflex and metaboreflex activation when compared with healthy, age-matched control subjects. Methods We studied 12 adults with MetSyn (34±3 years) and 12 healthy control subjects (34±3 years). Heart rate (HR; ECG), blood pressure (BP; finger photoplethysmography), and MSNA (microneurography of the peroneal nerve) were measured during: (1) Static handgrip exercise at 15% of maximal voluntary contraction (MVC), and (2) Static handgrip exercise at 30% MVC to fatigue, followed by post-exercise ischemia (PEI). Increases in MSNA, HR, and BP were assessed. Results During static exercise at both 15 and 30% MVC, increases in MSNA, HR, and BP were not different between groups. MSNA remained significantly elevated from baseline during PEI and responses were not different between groups. Conclusion Sympathetic and pressor responses to mechanoreflex and metaboreflex activation are not augmented in younger adults with MetSyn. PMID:24680829

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

    PubMed Central

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

    1993-01-01

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

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

    PubMed Central

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

    2015-01-01

    Genome wide association studies (GWAS) have identified approximately 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 twenty 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 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% 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 ≥3,200 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. PMID:26582267

  7. Astroglial cells in the central nervous system of the adult brown anole lizard, Anolis sagrei, revealed by intermediate filament immunohistochemistry.

    PubMed

    Lazzari, Maurizio; Franceschini, Valeria

    2005-09-01

    We analyzed the distribution of intermediate filament molecular markers, glial fibrillary acidic protein (GFAP), and vimentin in the brain and spinal cord of the adult brown anole lizard, Anolis sagrei. The GFAP immunoreactivity is strong and the positive structures are basically represented by fibers of different lengths and thicknesses which are arranged in a regular radial pattern throughout the central nervous system. In the brain regions that have a thicker neural wall, the radial orientation is not so evident as in the thinner areas. These fibers emerge from radial ependymoglia (tanycytes) whose cell bodies are generally GFAP-immunopositive. The glial fibers give rise to endfeet that are apposed to the subpial surface and to blood vessel walls. In the spinal cord, the optic tectum and the lateroventral regions of the mesencephalon and medulla oblongata, star-shaped astrocytes coexist with radial structures. Vimentin-immunoreactive structures are absent in the brain and spinal cord. In A. sagrei the immunohistochemical response of the astroglial intermediate filaments appears typical of a mature astroglial cell lineage, since they fundamentally express GFAP immunoreactivity. A Western-blot analysis reveals a GFAP-positive single band, common to the different nervous areas. This immunohistochemical study shows that the star-shaped astrocytes have a different distribution in saurians and while the glial pattern of A. sagrei is more evolved than in urodeles it remains immature as compared with crocodilians, avians, and mammals. This condition suggests that reptiles represent a fundamental step in the phylogenetic evolution of the vertebrate glial cells. PMID:16086399

  8. Peripheral Nerve Grafts after Cervical Spinal Cord Injury in Adult Cats

    PubMed Central

    Côté, Marie-Pascale; Hanna, Amgad; Lemay, Michel A.; Ollivier-Lanvin, Karen; Santi, Lauren; Miller, Kassi; Monaghan, Rebecca; Houlé, John D.

    2010-01-01

    Peripheral nerve grafts (PNG) into the rat spinal cord support axon regeneration after acute or chronic injury, with synaptic reconnection across the lesion site and some level of behavioral recovery. Here, we grafted a peripheral nerve into the injured spinal cord of cats as a preclinical treatment approach to promote regeneration for eventual translational use. Adult female cats received a partial hemisection lesion at the cervical level (C7) and immediate apposition of an autologous tibial nerve segment to the lesion site. Five weeks later, a dorsal quadrant lesion was performed caudally (T1), the lesion site treated with Chondroitinase ABC two days later to digest growth inhibiting extracellular matrix molecules, and the distal end of the PNG apposed to the injury site. After 4–20 weeks, the grafts survived in 10/12 animals with several thousand myelinated axons present in each graft. The distal end of 9/10 grafts was well apposed to the spinal cord and numerous axons extended beyond the lesion site. Intraspinal stimulation evoked compound action potentials in the graft with an appropriate latency illustrating normal axonal conduction of the regenerated axons. Although stimulation of the PNG failed to elicit responses in the spinal cord distal to the lesion site, the presence of c-Fos immunoreactive neurons close to the distal apposition site indicates that regenerated axons formed functional synapses with host neurons. This study demonstrates the successful application of a nerve grafting approach to promote regeneration after spinal cord injury in a non-rodent, large animal model. PMID:20599980

  9. 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. PMID:26450984

  10. The expression pattern of Adam10 in the central nervous system of adult mice: Detection by in situ hybridization combined with immunohistochemistry staining.

    PubMed

    Guo, Zhi-Bao; Su, Ying-Ying; Wang, Yi-Hui; Wang, Wei; Guo, Da-Zhi

    2016-09-01

    ADAM10 (a disintegrin and metalloprotease 10) is a member of the ADAMs family, which is key in the development of the nervous system, by regulating proliferation, migration, differentiation and survival of various cells, including axonal growth and myelination. Previous studies have investigated the embryonic or postnatal expression of ADAM10, however, detailed information regarding its cellular distribution in the adult stage, to the best of our knowledge, is not available. The present study investigated the expression pattern of the ADAM10 gene in the adult mouse central nervous system (CNS) using an ADAM10 complementary RNA probe for in situ hybridization (ISH). Immunohistochemical staining was used to identify the type of the ISH staining‑positive cells with neuron‑ or astrocyte‑specific antibodies. The results of the current study demonstrated that the ADAM10 gene was predominantly expressed in the neurons of the cerebral cortex, hippocampus, thalamus and cerebellar granular cells in adult mouse CNS. PMID:27431484

  11. The expression pattern of Adam10 in the central nervous system of adult mice: Detection by in situ hybridization combined with immunohistochemistry staining

    PubMed Central

    Guo, Zhi-Bao; Su, Ying-Ying; Wang, Yi-Hui; Wang, Wei; Guo, Da-Zhi

    2016-01-01

    ADAM10 (a disintegrin and metalloprotease 10) is a member of the ADAMs family, which is key in the development of the nervous system, by regulating proliferation, migration, differentiation and survival of various cells, including axonal growth and myelination. Previous studies have investigated the embryonic or postnatal expression of ADAM10, however, detailed information regarding its cellular distribution in the adult stage, to the best of our knowledge, is not available. The present study investigated the expression pattern of the ADAM10 gene in the adult mouse central nervous system (CNS) using an ADAM10 complementary RNA probe for in situ hybridization (ISH). Immunohistochemical staining was used to identify the type of the ISH staining-positive cells with neuron- or astrocyte-specific antibodies. The results of the current study demonstrated that the ADAM10 gene was predominantly expressed in the neurons of the cerebral cortex, hippocampus, thalamus and cerebellar granular cells in adult mouse CNS. PMID:27431484

  12. 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

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

    PubMed Central

    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. PMID:26379506

  14. Nervous System Lyme Disease.

    PubMed

    Halperin, John J

    2015-12-01

    Nervous system involvement occurs in 10% to 15% of patients infected with the tick-borne spirochetes Borrelia burgdorferi, B afzelii, and B garinii. Peripheral nervous system involvement is common. Central nervous system (CNS) involvement, most commonly presenting with lymphocytic meningitis, causes modest cerebrospinal fluid (CSF) pleocytosis. Parenchymal CNS infection is rare. If the CNS is invaded, however, measuring local production of anti-B burgdorferi antibodies in the CSF provides a useful marker of infection. Most cases of neuroborreliosis can be cured with oral doxycycline; parenteral regimens should be reserved for patients with particularly severe disease. PMID:26593257

  15. Propylthiouracil and peripheral neuropathy.

    PubMed

    Van Boekel, V; Godoy, J M; Lamy, L A; Assuf, S; Meyer Neto, J G; Balassiano, S L; Prata, L E

    1992-06-01

    Peripheral neuropathy is a rare manifestation in hyperthyroidism. We describe the neurological manifestations of a 38 year old female with Graves' disease who developed peripheral neuropathy in the course of her treatment with propylthiouracil. After the drug was tapered off, the neurological signs disappeared. Therefore, we call attention for a possible toxic effect on peripheral nervous system caused by this drug. PMID:1339201

  16. Presence of human herpesvirus 6 variants A and B in saliva and peripheral blood mononuclear cells of healthy adults.

    PubMed Central

    Aberle, S W; Mandl, C W; Kunz, C; Popow-Kraupp, T

    1996-01-01

    Saliva and peripheral blood mononuclear cells (PBMCs) from 44 healthy young adults were tested for human herpesvirus 6 variants A and B (HHV-6A and -6B) DNA by a sensitive nested PCR. HHV-6B infection was ascertained in 98% of the subjects, and 95% were found to excrete variant B in their saliva. HHV-6A was found in the PBMCs of 16%, but was not detected in saliva samples. PMID:8940478

  17. Derivation of Neural Stem Cells from Human Adult Peripheral CD34+ Cells for an Autologous Model of Neuroinflammation

    PubMed Central

    Wang, Tongguang; Choi, Elliot; Monaco, Maria Chiara G.; Campanac, Emilie; Medynets, Marie; Do, Thao; Rao, Prashant; Johnson, Kory R.; Elkahloun, Abdel G.; Von Geldern, Gloria; Johnson, Tory; Subramaniam, Sriram; Hoffman, Dax; Major, Eugene; Nath, Avindra

    2013-01-01

    Proinflammatory factors from activated T cells inhibit neurogenesis in adult animal brain and cultured human fetal neural stem cells (NSC). However, the role of inhibition of neurogenesis in human neuroinflammatory diseases is still uncertain because of the difficulty in obtaining adult NSC from patients. Recent developments in cell reprogramming suggest that NSC may be derived directly from adult fibroblasts. We generated NSC from adult human peripheral CD34+ cells by transfecting the cells with Sendai virus constructs containing Sox2, Oct3/4, c-Myc and Klf4. The derived NSC could be differentiated to glial cells and action potential firing neurons. Co-culturing NSC with activated autologous T cells or treatment with recombinant granzyme B caused inhibition of neurogenesis as indicated by decreased NSC proliferation and neuronal differentiation. Thus, we have established a unique autologous in vitro model to study the pathophysiology of neuroinflammatory diseases that has potential for usage in personalized medicine. PMID:24303066

  18. Melatonin preserves superoxide dismutase activity in hypoglossal motoneurons of adult rats following peripheral nerve injury.

    PubMed

    Chang, Hung-Ming; Huang, Yi-Lun; Lan, Chyn-Tair; Wu, Un-In; Hu, Ming-E; Youn, Su-Chung

    2008-03-01

    Peripheral nerve injury (PNI) produces functional changes in lesioned neurons in which oxidative stress is considered to be the main cause of neuronal damage. As superoxide dismutase (SOD) is an important antioxidative enzyme involved in redox regulation of oxidative stress, the present study determined whether melatonin would exert its beneficial effects by preserving the SOD reactivity following PNI. Adult rats subjected to hypoglossal nerve transection were intraperitoneally injected with melatonin at ones for 3, 7, 14, 30 and 60 days successively. The potential neuroprotective effects of melatonin were quantitatively demonstrated by neuronal nitric oxide synthase (nNOS), mitochondrial manganese SOD (Mn-SOD), and cytosolic copper-zinc SOD (Cu/Zn-SOD) immunohistochemistry. The functional recovery of the lesioned neurons was evaluated by choline acetyltransferase (ChAT) immunohistochemistry along with the electromyographic (EMG) recordings of denervation-induced fibrillation activity. The results indicate that following PNI, the nNOS immunoreactivity was significantly increased in lesioned neurons peaking at 14 days. The up-regulation of nNOS temporally coincided with the reduction of ChAT and SOD in which the Cu/Zn-SOD showed a greater diminution than Mn-SOD. However, following melatonin administration, the nNOS augmentation was successfully suppressed and the activities of Mn-SOD, Cu/Zn-SOD, and ChAT were effectively preserved at all postaxotomy periods. EMG data also showed a decreased fibrillation in melatonin-treated groups, suggesting a potential effect of melatonin in promoting functional recovery. In association with its significant capacity in preserving SOD reactivity, melatonin is suggested to serve as a powerful therapeutic agent for treating PNI-relevant oxidative damage. PMID:18289169

  19. Early diagnosis of peripheral nervous system involvement in Fabry disease and treatment of neuropathic pain: the report of an expert panel

    PubMed Central

    2011-01-01

    Background Fabry disease is an inherited metabolic disorder characterized by progressive lysosomal accumulation of lipids in a variety of cell types, including neural cells. Small, unmyelinated nerve fibers are particularly affected and small fiber peripheral neuropathy often clinically manifests at young age. Peripheral pain can be chronic and/or occur as provoked attacks of excruciating pain. Manifestations of dysfunction of small autonomic fibers may include, among others, impaired sweating, gastrointestinal dysmotility, and abnormal pain perception. Patients with Fabry disease often remain undiagnosed until severe complications involving the kidney, heart, peripheral nerves and/or brain have arisen. Methods An international expert panel convened with the goal to provide guidance to clinicians who may encounter unrecognized patients with Fabry disease on how to diagnose these patients early using simple diagnostic tests. A further aim was to offer recommendations to control neuropathic pain. Results We describe the neuropathy in Fabry disease, focusing on peripheral small fiber dysfunction - the hallmark of early neurologic involvement in this disorder. The clinical course of peripheral pain is summarized, and the importance of medical history-taking, including family history, is highlighted. A thorough physical examination (e.g., angiokeratoma, corneal opacities) and simple non-invasive sensory perception tests could provide clues to the diagnosis of Fabry disease. Reported early clinical benefits of enzyme replacement therapy include reduction of neuropathic pain, and adequate management of residual pain to a tolerable and functional level can substantially improve the quality of life for patients. Conclusions Our recommendations can assist in diagnosing Fabry small fiber neuropathy early, and offer clinicians guidance in controlling peripheral pain. This is particularly important since management of pain in young patients with Fabry disease appears to be

  20. 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

  1. 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. PMID:27147984

  2. Involvement of the peripheral sensory and sympathetic nervous system in the vascular endothelial expression of ICAM-1 and the recruitment of opioid-containing immune cells to inhibit inflammatory pain.

    PubMed

    Mousa, Shaaban A; Shaqura, Mohammed; Brendl, Ute; Al-Khrasani, Mahmoud; Fürst, Susanna; Schäfer, Michael

    2010-11-01

    Endogenous opioids are known to be released within certain brain areas following stressful stimuli. Recently, it was shown that also leukocytes are a potential source of endogenously released opioid peptides following stress. They activate sensory neuron opioid receptors and result in the inhibition of local inflammatory pain. An important prerequisite for the recruitment of such leukocytes is the expression of intracellular adhesion molecule-1 (ICAM-1) in blood vessels of inflamed tissue. Here, we investigated the contribution of peripheral sensory and/or sympathetic nerves to the enhanced expression of ICAM-1 simultaneously with the increased recruitment of opioid peptide-containing leukocytes to promote the inhibition of inflammatory pain. Selective degeneration of either peripheral sensory or sympathetic nerve fibers by their respective neurotoxins, capsaicin or 6-hydroxydopamime, significantly reduced the subcutaneous immigration of β-endorphin- (END-) and met-enkephalin- (ENK-)-containing polymorphonuclear leukocytes (PMN) (in the early phase) and mononuclear cells (in the late phase) during painful Freund's complete adjuvant (FCA) rat hind paw inflammation. In contrast, this treatment did not alter the percentage of opioid peptide-containing leukocytes in the circulation. Calcitonin gene-related peptide- (CGRP-) and tyrosine hydroxylase- (TH-) immunoreactive (IR) nerve fibers were in close contact to ICAM-1 IR blood vessels within inflamed subcutaneous tissue. The selective degeneration of sensory or sympathetic nerve fibers attenuated the enhanced expression of vascular endothelial ICAM-1 after intraplantar (i.pl.) FCA and abolished endogenous opioid peptide-mediated peripheral analgesia. Our results suggest that, during localized inflammatory pain, peripheral sensory and sympathetic nerve fibers augment the expression of vascular endothelial ICAM-1 simultaneously with the increased recruitment of opioid peptide-containing leukocytes which consequently

  3. Murine mesenchymal stem cells transplanted to the central nervous system of neonatal versus adult mice exhibit distinct engraftment kinetics and express receptors that guide neuronal cell migration.

    PubMed

    Phinney, Donald G; Baddoo, Melody; Dutreil, Maria; Gaupp, Dina; Lai, Wen Tzu; Isakova, Iryna A

    2006-06-01

    Mesenchymal stem cells (MSCs) have demonstrated efficacy as cellular vectors for treating a variety of nervous system disorders. Nevertheless, few studies have quantified MSC engraftment levels or explored the mechanisms that promote their survival and migration in nervous tissue. In this study, we compared the engraftment kinetics and anatomical distribution of murine, male MSCs injected intracranially into neonatal versus adult female mice using a real-time PCR assay that targets the mouse SRY gene. These analyses revealed that MSCs exhibited low but equivalent engraftment levels in the central nervous system (CNS) of neonatal and adult transplant recipients at 12 days post-injection. However, MSC engraftment levels were significantly greater at 60 and 150 days post-transplantation in neonates as compared to adults. Despite these differences, engrafted MSCs were widely distributed along the neuraxis of the CNS in both transplant groups. Collectively, these data indicate that proliferation, but not engraftment and migration, of MSCs in brain are regulated by the host microenvironment. Using a genomics approach, we also identified MSC subpopulations that express neural adhesion proteins and receptors that regulate neuronal cell migration in brain, including cadherin 2, neurexin 1, ninjurin 1, neogenin 1, neuropilin 2, and roundabout homolog 1 and 4. Functional studies indicate these proteins confer cell adhesion and migration of MSCs in response to the appropriate chemoattractant. On the basis of these findings, we conclude that the unique molecular composition of MSC subpopulations imparts to them an inherent capacity to engraft and migrate in brain. These subpopulations may represent more potent cellular vectors for treating CNS disorders. PMID:16846379

  4. Ectopic expression of polysialylated neural cell adhesion molecule in adult macaque Schwann cells promotes their migration and remyelination potential in the central nervous system

    PubMed Central

    Bachelin, C.; Zujovic, V.; Buchet, D.; Mallet, J.

    2010-01-01

    Recent findings suggested that inducing neural cell adhesion molecule polysialylation in rodents is a promising strategy for promoting tissue repair in the injured central nervous system. Since autologous grafting of Schwann cells is one potential strategy to promote central nervous system remyelination, it is essential to show that such a strategy can be translated to adult primate Schwann cells and is of interest for myelin diseases. Adult macaque Schwann cells were transduced with a lentiviral vector encoding sialyltransferase, an enzyme responsible for neural cell adhesion molecule polysialylation. In vitro, we found that ectopic expression of polysialylate promoted adult macaque Schwann cell migration and improved their integration among astrocytes in vitro without modifying their antigenic properties as either non-myelinating or pro-myelinating. In addition, forced expression of polysialylate in adult macaque Schwann cells decreased their adhesion with sister cells. To investigate the ability of adult macaque Schwann cells to integrate and migrate in vivo, focally induced demyelination was targeted to the spinal cord dorsal funiculus of nude mice, and both control and sialyltransferase expressing Schwann cells overexpressing green fluorescein protein were grafted remotely from the lesion site. Analysis of the spatio-temporal distribution of the grafted Schwann cells performed in toto and in situ, showed that in both groups, Schwann cells migrated towards the lesion site. However, migration of sialyltransferase expressing Schwann cells was more efficient than that of control Schwann cells, leading to their accelerated recruitment by the lesion. Moreover, ectopic expression of polysialylated neural cell adhesion molecule promoted adult macaque Schwann cell interaction with reactive astrocytes when exiting the graft, and their ‘chain-like’ migration along the dorsal midline. The accelerated migration of sialyltransferase expressing Schwann cells to the

  5. Microfluidic Capture of Endothelial Colony-Forming Cells from Human Adult Peripheral Blood: Phenotypic and Functional Validation In Vivo

    PubMed Central

    Lin, Ruei-Zeng; Hatch, Adam; Antontsev, Victor G.; Murthy, Shashi K.

    2015-01-01

    Introduction: Endothelial colony-forming cells (ECFCs) are endothelial progenitors that circulate in peripheral blood and are currently the subject of intensive investigation due to their therapeutic potential. However, in adults, ECFCs comprise a very small subset among circulating cells, which makes their isolation a challenge. Materials and Methods: Currently, the standard method for ECFC isolation relies on the separation of mononuclear cells and erythrocyte lysis, steps that are time consuming and known to increase cell loss. Alternatively, we previously developed a novel disposable microfluidic platform containing antibody-functionalized degradable hydrogel coatings that is ideally suited for capturing low-abundance circulating cells from unprocessed blood. In this study, we reasoned that this microfluidic approach could effectively isolate rare ECFCs by virtue of their CD34 expression. Results: We conducted preclinical experiments with peripheral blood from four adult volunteers and demonstrated that the actual microfluidic capture of circulating CD34+ cells from unprocessed blood was compatible with the subsequent differentiation of these cells into ECFCs. Moreover, the ECFC yield obtained with the microfluidic system was comparable to that of the standard method. Importantly, we unequivocally validated the phenotypical and functional properties of the captured ECFCs, including the ability to form microvascular networks following transplantation into immunodeficient mice. Discussion: We showed that the simplicity and versatility of our microfluidic system could be very instrumental for ECFC isolation while preserving their therapeutic potential. We anticipate our results will facilitate additional development of clinically suitable microfluidic devices by the vascular therapeutic and diagnostic industry. PMID:25091645

  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. PMID:26802725

  7. Decreased glycolytic and tricarboxylic acid cycle intermediates coincide with peripheral nervous system oxidative stress in a murine model of type 2 diabetes

    PubMed Central

    Hinder, Lucy M.; Vivekanandan-Giri, Anuradha; McLean, Lisa L.; Pennathur, Subramaniam; Feldman, Eva L.

    2013-01-01

    Diabetic neuropathy (DN) is the most common complication of diabetes and is characterized by distal-to-proximal loss of peripheral nerve axons. The idea of tissue-specific pathological alterations in energy metabolism in diabetic complications-prone tissues is emerging. Altered nerve metabolism in type 1 diabetes models is observed; however, therapeutic strategies based on these models offer limited efficacy to type 2 diabetic patients with DN. Therefore, understanding how peripheral nerves metabolically adapt to the unique type 2 diabetic environment is critical to develop disease-modifying treatments. In the current study, we utilized targeted LC/MS/MS to characterize the glycolytic and tricarboxylic acid (TCA) cycle metabolomes in sural nerve, sciatic nerve and dorsal root ganglia (DRG) from male type 2 diabetic mice (BKS.Cg-m+/+Leprdb; db/db) and controls (db/+). We report depletion of glycolytic intermediates in diabetic sural nerve and sciatic nerve (glucose-6-phosphate, fructose-6-phosphate, fructose-1,6-bisphosphate (sural nerve only), 3-phosphoglycerate, 2-phosphoglycerate, phosphoenolpyruvate, lactate), with no significant changes in DRG. Citrate and isocitrate TCA cycle intermediates were decreased in sural nerve, sciatic nerve and DRG from diabetic mice. Utilizing LC/ESI/MS/MS and HPLC methods, we also observed increased protein and lipid oxidation (nitrotyrosine; hydroxyoctadecadienoic acids, HODEs) in db/db tissue, with a proximal-to-distal increase in oxidative stress, with associated decreased aconitase enzyme activity. We propose a preliminary model, whereby the greater change in metabolomic profile, increase in oxidative stress, and decrease in TCA cycle enzyme activity may cause distal peripheral nerve to rely on truncated TCA cycle metabolism in the type 2 diabetes environment. PMID:23086140

  8. 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

  9. Latency of the Achilles tendon reflex for detection of reduced functions of the peripheral nervous system in workers exposed to lead.

    PubMed Central

    Ogawa, Y; Hirata, M; Okayama, A; Ichikawa, Y E; Goto, S

    1993-01-01

    The latency of the soleus muscle potential, evoked by a tap of the Achilles tendon, was used in the mass assessment of healthy male workers exposed to lead. Three groups were studied: a control, a low exposure, and a high exposure group. Mean blood lead concentrations were 9.3, 19.2, and 53.1 micrograms/100 ml respectively. Latencies were adjusted for age and height and then compared among the three groups. The mean corrected latency of the high exposure group showed a 4% increase compared with the other two groups (p < 0.01). The latencies of the other two groups showed no between group differences. These results were consistent with previous neurophysiological studies done by many researchers on workers exposed to lead. They suggested that nerve conduction velocities decreased from 3 to 13% among workers whose mean blood lead concentrations were more than 30 micrograms/100 ml. The method was simple, time conserving, non-invasive, and non-aversive, and provided a quantitative measure of the nerve conduction velocities of peripheral nerves. Thus it may be useful for early detection of occupationally related impairment of peripheral nerves. PMID:8457489

  10. 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

  11. Activation and maintenance of peripheral semantic features of unambiguous words after right hemisphere brain damage in adults

    PubMed Central

    Tompkins, Connie A.; Fassbinder, Wiltrud; Scharp, Victoria L.; Meigh, Kimberly M.

    2009-01-01

    Background The right cerebral hemisphere (RH) sustains activation of subordinate, secondary, less common, and/or distantly related meanings of words. Much of the pertinent data come from studies of homonyms, but some evidence also suggests that the RH has a unique maintenance function in relation to unambiguous nouns. In a divided visual field priming study, Atchley, Burgess, and Keeney (1999) reported that only left visual field/RH presentation yielded evidence of continuing activation of peripheral semantic features that were incompatible with the most common image or representation of their corresponding nouns (e.g., rotten for “apple”). Activation for weakly related features that were compatible with the dominant representation (e.g., crunchy) was sustained over time regardless of the visual field/hemisphere of initial stimulus input. Several studies report that unilateral right hemisphere brain damage (RHD) in adults affects the RH’s meaning maintenance function, but this work also has centred on homonyms, and/or more recently metonymic and metaphoric polysemous words. Aims The current investigation examined whether RHD deficits in processing secondary and/or distantly related meanings of words, typically observed in studies of homonyms, would extend to peripheral, weakly related semantic features of unambiguous nouns. Methods & Procedures Participants were 28 adults with unilateral RHD from cerebrovascular accident, and 38 adults without brain damage. Participants listened to spoken sentences that ended with an unambiguous noun. Each sentence was followed by a spoken target phoneme string. Targets included peripheral semantic features of the sentence-final noun that were either compatible or incompatible with the dominant mental images of the noun, and were presented at two intervals after that noun. A lexical decision task was used to gauge both the early activation and maintenance of activation for these weakly related semantic features. Outcomes

  12. The older adult with diabetes: peripheral neuropathy and walking for health.

    PubMed

    Cuaderes, Elena; Lamb, W Lyndon; Alger, Anne

    2014-06-01

    The rate at which older individuals are being diagnosed with diabetes is increasing. Therefore, the ability of older persons with diabetes to successfully age in place is of concern for health care professionals. Diabetic peripheral neuropathy can cause changes to the foot and ankle such as loss of protective sensation, joint dislocations and fractures, and formation of cracks and fissures. With special attention to their needs, practitioners can tell older people with diabetes that walking for health can be safe and without problems and can contribute to their ability to spend the rest of their lives in their own home. PMID:24846466

  13. 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…

  14. Peripheral inflammation facilitates Abeta fiber-mediated synaptic input to the substantia gelatinosa of the adult rat spinal cord.

    PubMed

    Baba, H; Doubell, T P; Woolf, C J

    1999-01-15

    Whole-cell patch-clamp recordings were made from substantia gelatinosa (SG) neurons in thick adult rat transverse spinal cord slices with attached dorsal roots to study changes in fast synaptic transmission induced by peripheral inflammation. In slices from naive rats, primary afferent stimulation at Abeta fiber intensity elicited polysynaptic EPSCs in only 14 of 57 (25%) SG neurons. In contrast, Abeta fiber stimulation evoked polysynaptic EPSCs in 39 of 62 (63%) SG neurons recorded in slices from rats inflamed by an intraplantar injection of complete Freund's adjuvant (CFA) 48 hr earlier (p < 0.001). Although the peripheral inflammation had no significant effect on the threshold and conduction velocities of Abeta, Adelta, and C fibers recorded in dorsal roots, the mean threshold intensity for eliciting EPSCs was significantly lower in cells recorded from rats with inflammation (naive: 33.2 +/- 15.1 microA, n = 57; inflamed: 22.8 +/- 11.3 microA, n = 62, p < 0.001), and the mean latency of EPSCs elicited by Abeta fiber stimulation in CFA-treated rats was significantly shorter than that recorded from naive rats (3.3 +/- 1.8 msec, n = 36 vs 6.0 +/- 3.5 msec, n = 12; p = 0.010). Abeta fiber stimulation evoked polysynaptic IPSCs in 4 of 25 (16%) cells recorded from naive rat preparations and 14 of 26 (54%) SG neurons from CFA-treated rats (p < 0.001). The mean threshold intensity for IPSCs was also significantly lower in CFA-treated rats (naive: 32.5 +/- 15.7 microA, n = 25; inflamed: 21. 9 +/- 9.9 microA, n = 26, p = 0.013). The facilitation of Abeta fiber-mediated input into the substantia gelatinosa after peripheral inflammation may contribute to altered sensory processing. PMID:9880605

  15. Association of body fat distribution with proinflammatory gene expression in peripheral blood mononuclear cells from young adult subjects.

    PubMed

    Hermsdorff, Helen Hermana Miranda; Puchau, Blanca; Zulet, María Angeles; Martínez, José Alfredo

    2010-06-01

    Peripheral blood mononuclear cells (PBMC) measurements have proved useful in recent studies to discern peripheral biomarkers for common complex diseases and for understanding host responses to drugs and nutrition in personalized medicine. Despite the initial promising data from PBMC, there is little information, however, on inflammatory and immune gene regulation in the context of body fat distribution and metabolic features in healthy adults. We investigated the putative association of body fat distribution and related-metabolic features with mRNA levels of proinflammatory markers in PBMC. This study enrolled 136 healthy subjects (85 females/51 males; age: 21.5 +/- 2.5 years). Anthropometrical, clinical, metabolic, and proinflammatory variables were assessed with validated tools. Interestingly, in normal-weight subjects with lower truncal fat (TF) values, mRNA levels of ICAM1, IL1R1, IL6, and TNF-alpha in PBMC were lower (p < 0.05), compared to normal-weight individuals with higher TF (>58.5/50.2% for men/women, respectively) and overweight/obese subjects [body mass index (BMI) >25 kg/m(2)]. After regression analyses were performed, individuals with the highest tertiles of TF and waist circumference displayed higher mRNA gene expressions as well as circulating proinflammatory (C-reactive protein and IL6) and metabolic (blood pressure, HOMA-IR, and LDL-c:HDL-c ratio) variables values (p < 0.05), independent from gender. Our findings collectively suggest that the mRNA expression of certain proinflammatory markers in PBMC is associated with body fat distribution in healthy adult subjects, which in turn, was also related to metabolic features and plasma proinflammatory markers concentrations. PMID:20450441

  16. 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

  17. 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…

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

    MedlinePlus

    ... Emergency Department (ED) Visits Involving Nonmedical Use of Pharmaceuticals* among Adults Aged 18 to 34, by Alcohol ... 2007 2008 2009 2010 2011 * Nonmedical use of pharmaceuticals includes taking more than the prescribed dose of ...

  19. 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

  20. 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

  1. 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. PMID:25504929

  2. Intravenous injection of AAVrh10-GALC after the neonatal period in twitcher mice results in significant expression in the central and peripheral nervous systems and improvement of clinical features.

    PubMed

    Rafi, Mohammad A; Rao, Han Zhi; Luzi, Paola; Luddi, Alice; Curtis, Mark T; Wenger, David A

    2015-03-01

    Globoid cell leukodystrophy (GLD) or Krabbe disease is an autosomal recessive disorder resulting from the defective lysosomal enzyme galactocerebrosidase (GALC). The lack of GALC enzyme leads to severe neurological symptoms. While most human patients are infants who do not survive beyond 2 years of age, older patients are also diagnosed. In addition to human patients, several naturally occurring animal models, including dog, mouse, and monkey, have also been identified. The mouse model of Krabbe disease, twitcher (twi) mouse has been used for many treatment trials including gene therapy. Using the combination of intracerebroventricular, intracerebellar, and intravenous (iv) injection of the adeno-associated virus serotype rh10 (AAVrh10) expressing mouse GALC in neonate twi mice we previously have demonstrated a significantly extended normal life and exhibition of normal behavior in treated mice. In spite of the prolonged healthy life of these treated mice and improved myelination, it is unlikely that using multiple injection sites for viral administration will be approved for treatment of human patients. In this study, we have explored the outcome of the single iv injection of viral vector at post-natal day 10 (PND10). This has resulted in increased GALC activity in the central nervous system (CNS) and high GALC activity in the peripheral nervous system (PNS). As we have shown previously, an iv injection of AAVrh10 at PND2 results in a small extension of life beyond the typical lifespan of the untreated twi mice (~40 days). In this study, we report that mice receiving a single iv injection at PND10 had no tremor and continued to gain weight until a few weeks before they died. On average, they lived 20-25 days longer than untreated mice. We anticipate that this strategy in combination with other therapeutic options may be beneficial and applicable to treatment of human patients. PMID:25533112

  3. 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

  4. 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

  5. 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. PMID:27317362

  6. Population Pharmacokinetics of Azithromycin in Whole Blood, Peripheral Blood Mononuclear Cells, and Polymorphonuclear Cells in Healthy Adults

    PubMed Central

    Sampson, M R; Dumitrescu, T P; Brouwer, K L R; Schmith, V D

    2014-01-01

    Azithromycin's extensive distribution to proinflammatory cells, including peripheral blood mononuclear cells (PBMCs) and polymorphonuclear cells (PMNs), may be important to its antimicrobial and anti-inflammatory properties. The need to simultaneously predict azithromycin concentrations in whole blood (“blood”), PBMCs, and PMNs motivated this investigation. A single-dose study in 20 healthy adults was conducted, and nonlinear mixed effects modeling was used to simultaneously describe azithromycin concentrations in blood, PBMCs, and PMNs (simultaneous PK model). Data were well described by a four-compartment mamillary model. Apparent central clearance and volume of distribution estimates were 67.3 l/hour and 336 l (interindividual variability of 114 and 122%, respectively). Bootstrapping and visual predictive checks showed adequate model performance. Azithromycin concentrations in blood, PBMCs, and PMNs from external studies of healthy adults and cystic fibrosis patients were within the 5th and 95th percentiles of model simulations. This novel empirical model can be used to predict azithromycin concentrations in blood, PBMCs, and PMNs with different dosing regimens. PMID:24599342

  7. 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

  8. Peripheral blood lymphocyte to monocyte ratio identifies high-risk adult patients with sporadic Burkitt lymphoma.

    PubMed

    Wang, Liang; Wang, Hua; Xia, Zhong-Jun; Huang, Hui-Qiang; Jiang, Wen-Qi; Lin, Tong-Yu; Lu, Yue

    2015-10-01

    Adult sporadic Burkitt lymphoma (BL) is a rare subtype of lymphoma. In this retrospective study, we investigated the prognostic value of pretreatment lymphocyte to monocyte ratio (LMR) in a cohort of 62 patients. Using LMR <2.6 as the optimal cutoff point, 24 patients (38.7 %) had LMR <2.6. The complete response rates in high-LMR group and low-LMR group were 90.9 and 65.0 %, respectively (P = 0.019). At a median follow-up time of 41 months, the 3-year progression-free survival (PFS) rate and overall survival (OS) rates were 76 and 80 %, respectively. In a multivariate Cox regression model, it was found that the presence of bone marrow infiltration and low LMR were independently adverse prognostic factors for both PFS and OS. In the whole group, the addition of rituximab to treatment did not benefit patients significantly in PFS and OS. In subgroup analysis, in patients with high LMR, addition of rituximab can significantly improve survival outcomes (P = 0.046). In conclusion, we firstly found that low LMR (<2.60) was an independently adverse prognostic factor in adult patients with sporadic BL. Intensive chemotherapy could cure the majority of patients in our study, and the pretreatment LMR might predict the value of rituximab in this age population. PMID:26082333

  9. [Predictors of antisocial behaviour. Peripheral psychophysiological findings in children and adults with conduct disorder].

    PubMed

    Vloet, T D; Herpertz-Dahlmann, B; Herpertz, S

    2006-07-01

    Many studies have shown that psychophysiological parameters of processing emotional stimuli are associated with different personality traits in children, adolescents, and adults. Individuals with low autonomic baseline arousal, low orienting reaction, accelerated habituation, and reduced excitability particularly to punishing stimuli are characterised by a reduced experience of anxiety, decreased behaviour inhibition, and increased sensation seeking. These characteristics seem to raise the likelihood of dis-social behavior and are perceived as prognostically favourable for the development of antisocial personality disorders in childhood and adolescence. In contrast, an increased disposition towards anxiety, which is associated with increased autonomic reactivity, is recognised as a protective factor. Current data have shown that through special training, child and adolescent autonomic reactivity could be enhanced. Due to its versatility, this biological marker might be used for prevention in children at greater risk of developing antisocial behaviour. PMID:16489425

  10. A protocol for concurrent high-quality immunohistochemical and biochemical analyses in adult mouse central nervous system.

    PubMed

    Notter, Tina; Panzanelli, Patrizia; Pfister, Sandra; Mircsof, Dennis; Fritschy, Jean-Marc

    2014-01-01

    Biochemical analysis of central nervous system proteins and nucleic acids requires fresh-tissue homogenates, whereas immunohistochemistry usually is performed in sections prepared from perfusion-fixed tissue. Post-mortem immersion-fixation is possible, but largely impairs morphological preservation and protein antigenicity. Here, we present a simple, fast and versatile protocol allowing concurrent biochemical and immunohistochemical analysis, including pre-embedding immunoelectron microscopy, using tissue from the same animal. The protocol includes a brief transcardiac perfusion with ice-cold, oxygenated and glucose-supplemented artificial cerebrospinal fluid to maintain brain tissue alive, prior to isolation of regions of interest, followed by homogenisation for biochemistry or immersion-fixation for immunohistochemistry. We provide several examples demonstrating that this protocol allows optimal biochemical and morphological analysis, characterised with optimal sensitivity and preservation of tissue structure, along with a reduction of artefacts typically seen in perfusion-fixed tissue. This protocol should find widespread applications for combining analytical methods in tissue from the same animal, thereby reducing the number of mice required for a given experiment. PMID:24325300

  11. 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.

  12. Peripheral bone mass is not affected by winter vitamin D deficiency in children and young adults from Ushuaia.

    PubMed

    Oliveri, M B; Wittich, A; Mautalen, C; Chaperon, A; Kizlansky, A

    2000-09-01

    Low vitamin D levels in elderly people are associated with reduced bone mass, secondary hyperparathyroidism, and increased fracture risk. Its effect on the growing skeleton is not well known. The aim of this study was to evaluate the possible influence of chronic winter vitamin D deficiency and higher winter parathyroid hormone (PTH) levels on bone mass in prepubertal children and young adults. The study was carried out in male and female Caucasian subjects. A total of 163 prepubertal children (X age +/- 1 SD: 8.9 +/- 0.7 years) and 234 young adults (22.9 +/- 3.6 years) who had never received vitamin D supplementation were recruited from two areas in Argentina: (1)Ushuaia (55 degrees South latitude), where the population is known to have low winter 25OHD levels and higher levels of PTH in winter than in summer, and (2)Buenos Aires (34 degrees S), where ultraviolet (UV) radiation and vitamin D nutritional status in the population are adequate all year round. Bone mineral content (BMC) and bone mineral density (BMD) of the ultradistal and distal radius were measured in the young adults. Only distal radius measurements were taken in the children. Similar results were obtained in age-sex matched groups from both areas. The only results showing significant difference corresponded to comparison among the Ushuaian women: those whose calcium (Ca) intake was below 800 mg/day presented lower BMD and BMC values than those whose Ca intake was above that level (0.469 +/- 0.046 versus 0.498 +/- 0.041 g/cm(2), P < 0.02; 3.131 +/- 0.367 versus 3.339 +/- 0.386 g, P < 0.05, respectively). In conclusion, peripheral BMD and BMC were similar in children and young adults from Ushuaia and Buenos Aires in spite of the previously documented difference between both areas regarding UV radiation and winter vitamin D status. BMD of axial skeletal areas as well the concomitant effect of a low Ca diet and vitamin D deficiency on the growing skeleton should be studied further. PMID:10954776

  13. Peripheral sphingolipids are associated with variation in white matter microstructure in older adults.

    PubMed

    Gonzalez, Christopher E; Venkatraman, Vijay K; An, Yang; Landman, Bennett A; Davatzikos, Christos; Ratnam Bandaru, Veera Venkata; Haughey, Norman J; Ferrucci, Luigi; Mielke, Michelle M; Resnick, Susan M

    2016-07-01

    Sphingolipids serve important structural and functional roles in cellular membranes and myelin sheaths. Plasma sphingolipids have been shown to predict cognitive decline and Alzheimer's disease. However, the association between plasma sphingolipid levels and brain white matter (WM) microstructure has not been examined. We investigated whether plasma sphingolipids (ceramides and sphingomyelins) were associated with magnetic resonance imaging-based diffusion measures, fractional anisotropy (FA), and mean diffusivity, 10.5 years later in 17 WM regions of 150 cognitively normal adults (mean age 67.2). Elevated ceramide species (C20:0, C22:0, C22:1, and C24:1) were associated with lower FA in multiple WM regions, including total cerebral WM, anterior corona radiata, and the cingulum of the cingulate gyrus. Higher sphingomyelins (C18:1 and C20:1) were associated with lower FA in regions such as the anterior corona radiata and body of the corpus callosum. Furthermore, lower sphingomyelin to ceramide ratios (C22:0, C24:0, and C24:1) were associated with lower FA or higher mean diffusivity in regions including the superior and posterior corona radiata. However, although these associations were significant at the a priori p < 0.05, only associations with some regional diffusion measures for ceramide C22:0 and sphingomyelin C18:1 survived correction for multiple comparisons. These findings suggest plasma sphingolipids are associated with variation in WM microstructure in cognitively normal aging. PMID:27255825

  14. 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

  15. 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. PMID:27437149

  16. 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

  17. The effects of retinol on in vitro immunoglobulin synthesis by cord blood and adult peripheral blood mononuclear cells.

    PubMed

    Wang, W; Napoli, J L; Ballow, M

    1993-04-01

    In this study we examined the effects of retinol (ROH), a metabolic precursor of retinoic acid (RA), on Staphylococcus aureus Cowan I (SAC)-induced immunoglobulin synthesis of cord blood mononuclear cells (CBMC) and adult peripheral blood mononuclear cells (PBMC). ROH augmented SAC-induced IgM synthesis of CBMC by 5.9 +/- 1.5-fold (n = 7, mean +/- s.d.), and IgG synthesis of adult PBMC by 16.3 +/- 5.1-fold (n = 3) at optimal concentrations of 10(-6) M and 10(-11) M, respectively. No augmenting effects could be demonstrated for the other immunoglobulin isotypes. Time-course studies showed that the synthesis of IgM by CBMC was accelerated with detectable immunoglobulin in supernatant fluids starting on day 3. ROH augmented immunoglobulin synthesis of CBMC stimulated by Epstein-Barr virus (EBV), a T cell-independent polyclonal activator, and of EBV-transformed B cell clones (2.5 +/- 0.2 and 4.1 +/- 1.5-fold increase, respectively), which suggests that ROH can act directly on B cells to enhance immunoglobulin synthesis. In contrast, when ROH was preincubated with cord blood T cells, washed and added to the B cell-enriched fraction with SAC, no increase (0.9-1.8-fold) in IgM synthesis was obtained. Thus, the principal mechanism(s) by which ROH augments immunoglobulin synthesis is by acting on B cells. This is in contrast to the immunoglobulin-enhancing effects of RA which is mediated by T cells, or T cell products, e.g. cytokine. Our studies suggest that RA and ROH may have different pathways of immunoglobulin-enhancing effects, perhaps mediated by different retinoid binding proteins resulting in gene activation and immunoglobulin synthesis. PMID:8385583

  18. Human eosinophils modulate peripheral blood mononuclear cell response to Schistosoma mansoni adult worm antigen in vitro.

    PubMed

    Tweyongyere, R; Namanya, H; Naniima, P; Cose, S; Tukahebwa, E M; Elliott, A M; Dunne, D W; Wilson, S

    2016-08-01

    High numbers of eosinophils are observed in parasitic infections and allergic diseases, where they are proposed to be terminally differentiated effector cells that play beneficial role in host defence, or cause harmful inflammatory response. Eosinophils have been associated with killing of schistosomulae in vitro, but there is growing evidence that eosinophils can play additional immuno-regulatory role. Here, we report results of a study that examines peripheral blood mononuclear cell (PBMC) cytokine responses to Schistosoma mansoni adult worm antigen (SWA) when stimulated alone or enriched with autologous eosinophils. Production of the Th-2 type cytokines interleukin (IL)-4, IL-5 and IL-13 was lower (P = 0·017, 0·018 and <0·001, respectively) in PBMC + eosinophil cultures than in PBMC-only cultures stimulated with SWA. Substantial levels of IL-13, IL-10, interferon gamma and tumour necrosis factor alpha were recorded in cultures of eosinophils, but none of these cytokines showed significant association with the observed eosinophil-induced drop in cytokine responses of PBMC. Transwell experiments suggested that the observed effect is due to soluble mediators that downmodulate production of Th-2 type cytokines. This study shows that eosinophils may down-modulate schistosome-specific Th-2 type cytokine responses in S. mansoni-infected individuals. The mechanism of this immune modulation remains to be elucidated. PMID:27169695

  19. Conversion of adult human peripheral blood mononuclear cells into induced neural stem cell by using episomal vectors.

    PubMed

    Tang, Xihe; Wang, Shuyan; Bai, Yunfei; Wu, Jianyu; Fu, Linlin; Li, Mo; Xu, Qunyuan; Xu, Zhi-Qing David; Alex Zhang, Y; Chen, Zhiguo

    2016-03-01

    Human neural stem cells (NSCs) hold great promise for research and therapy in neural diseases. Many studies have shown direct induction of NSCs from human fibroblasts, which require an invasive skin biopsy and a prolonged period of expansion in cell culture prior to use. Peripheral blood (PB) is routinely used in medical diagnoses, and represents a noninvasive and easily accessible source of cells. Here we show direct derivation of NSCs from adult human PB mononuclear cells (PB-MNCs) by employing episomal vectors for transgene delivery. These induced NSCs (iNSCs) can expand more than 60 passages, can exhibit NSC morphology, gene expression, differentiation potential, and self-renewing capability and can give rise to multiple functional neural subtypes and glial cells in vitro. Furthermore, the iNSCs carry a specific regional identity and have electrophysiological activity upon differentiation. Our findings provide an easily accessible approach for generating human iNSCs which will facilitate disease modeling, drug screening, and possibly regenerative medicine. PMID:26826927

  20. Expansion of regulatory T cells from umbilical cord blood and adult peripheral blood CD4(+)CD25 (+) T cells.

    PubMed

    Lin, Syh-Jae; Lu, Chun-Hao; Yan, Dah-Chin; Lee, Pei-Tzu; Hsiao, Hsiu-Shan; Kuo, Ming-Ling

    2014-10-01

    CD4(+)CD25(+) regulatory T cells (Treg), if properly expanded from umbilical cord blood (UCB), may provide a promising immunotherapeutic tool. Our previous data demonstrated that UCB CD4(+)CD25(+) T cells with 4-day stimulation have comparable phenotypes and suppressive function to that of adult peripheral blood (APB) CD4(+)CD25(+) T cells. We further examined whether 2-week culture would achieve higher expansion levels of Tregs. UCB CD4(+)CD25(+) T cells and their APB counterparts were stimulated with anti-CD3/anti-CD28 in the presence of IL-2 or IL-15 for 2 weeks. The cell proliferation and forkhead box P3 (FoxP3) expression were examined. The function of the expanded cells was then investigated by suppressive assay. IL-21 was applied to study whether it counteracts the function of UCB and APB CD4(+)CD25(+) T cells. The results indicate that UCB CD4(+)CD25(+) T cells expanded much better than their APB counterparts. IL-2 was superior to expand UCB and APB Tregs for 2 weeks than IL-15. FoxP3 expression which peaked on Day 10-14 was comparable. Most importantly, expanded UCB Tregs showed greater suppressive function in allogeneic mixed lymphocyte reaction. The addition of IL-21, however, counteracted the suppressive function of expanded UCB and APB Tregs. The results support using UCB as a source of Treg cells. PMID:24515612

  1. The influence of moderate-intensity physical effort on peripheral blood in adults with Down syndrome - a pilot study.

    PubMed

    Aleksander-Szymanowicz, P; Marchewka, A; Dabrowski, Z; Teleglow, A; Bac, A; Glodzik, J

    2014-10-01

    The aim of this study was to evaluate the influence of a six-week aerobic training on peripheral blood in adults with Down syndrome. Fifteen men with Down syndrome (average age 22.4 years ± 0.91) with moderate or severe intellectual disability took part in the study. Patients underwent a training program three times a week for six weeks. Venous blood samples of 10 ml were collected from every examined patient, 24 hours before and after the exercise. The blood samples were submitted to hematological examination (hematocrit, fibrinogen, plasma viscosity, red blood cell (RBC) number, RBC indicators: mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular hemoglobin (MCH)), reduced glutathione (GSH) level and number of macrocytes, polikilocytrometric examination of RBC and rheological blood examination (elongation index (EI), aggregation index (AI), syllectogram amplitude (AMP), aggregation half time (t1/2)) was made by LORCA. Amoderate six-week physical training performed on a cycloergometer resulted in a statistically significant decrease in the MCV value, hematocrit and plasma viscosity. The six-week cycloergometer training caused a statistically significant increase in the GSH level and erythrocyte pliability at a shear stress of 0.58 Pa. PMID:25371533

  2. 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. PMID:24259565

  3. The use of microdialysis for the study of drug kinetics: central nervous system pharmacokinetics of diphenhydramine in fetal, newborn, and adult sheep.

    PubMed

    Au-Yeung, Sam C S; Riggs, K Wayne; Gruber, Nancy; Rurak, Dan W

    2007-08-01

    The central nervous system (CNS) pharmacokinetics of the H(1) receptor antagonist diphenhydramine (DPHM) were studied in 100- and 120-day-old fetuses, 10- and 30-day-old newborn lambs, and adult sheep using in vivo microdialysis. DPHM was administered i.v. at five infusion rates, with each step lasting 7 h. In all ages, cerebrospinal fluid (CSF) and extracellular fluid (ECF) concentrations were very similar to each other, which suggests that DPHM between these two compartments is transferred by passive diffusion. In addition, the brain-to-plasma concentration ratios were >or=3 in all age groups, suggesting the existence of a transport process for DPHM into the brain. Both brain and plasma DPHM concentrations increased in a linear fashion over the dose range studied. However, the ECF/unbound plasma and CSF/unbound plasma DPHM concentration ratios were significantly higher in the fetus and lambs (approximately 5 to 6) than in the adult (approximately 3). The factors f(CSF) and f(ECF), the ratios of DPHM areas under the curves (AUCs) in CSF and ECF to the plasma DPHM AUC, respectively, decreased with age, indicating that DPHM is more efficiently removed from the brain with increasing age. The extent of plasma protein binding of the drug increased with age. This study provides evidence for a transporter-mediated mechanism for the influx of DPHM into the brain and also for an efflux transporter for the drug, whose activity increases with age. Moreover, the higher brain DPHM levels in the fetus and lamb compared with the adult may explain the greater CNS effects of the drug at these ages. PMID:17485495

  4. 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

  5. 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

  6. 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

  7. Penetration of Treosulfan and its Active Monoepoxide Transformation Product into Central Nervous System of Juvenile and Young Adult Rats.

    PubMed

    Romański, Michał; Baumgart, Joachim; Böhm, Sonja; Główka, Franciszek K

    2015-12-01

    Treosulfan (TREO) is currently investigated as an alternative treatment of busulfan in conditioning before hematopoietic stem cell transplantation. The knowledge of the blood-brain barrier penetration of the drug is still scarce. In this paper, penetration of TREO and its active monoepoxide (S,S-EBDM) and diepoxide (S,S-DEB) into the CNS was studied in juvenile (JR) and young adult rats (YAR) for the first time. CD rats of both sexes (n = 96) received an intravenous dose of TREO 500 mg/kg b.wt. Concentrations of TREO, S,S-EBDM, and S,S-DEB in rat plasma, brain, and cerebrospinal fluid (CSF, in YAR only) were determined by validated bioanalytical methods. Pharmacokinetic calculations were performed in WinNonlin using a noncompartmental analysis and statistical evaluation was done in Statistica software. In male JR, female JR, male YAR, and female YAR, the brain/plasma area under the curve (AUC) ratio for unbound TREO was 0.14, 0.17, 0.10, and 0.07 and for unbound S,S-EBDM, it was 0.52, 0.48, 0.28, and 0.22, respectively. The CSF/plasma AUC ratio in male and female YAR was 0.12 and 0.11 for TREO and 0.66 and 0.64 for S,S-EBDM, respectively. Elimination rate constants of TREO and S,S-EBDM in all the matrices were sex-independent with a tendency to be lower in the JR. No quantifiable levels of S,S-DEB were found in the studied samples. TREO and S,S-EBDM demonstrated poor and sex-independent penetration into CNS. However, the brain exposure was greater in juvenile rats, so very young children might potentially be more susceptible to high-dose TREO-related CNS exposure than young adults. PMID:26428246

  8. 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

  9. 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

  10. 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

  11. Spontaneous and antibody-dependent cellular cytotoxicity by lymphocyte subpopulations in peripheral blood and spleen from adult untreated patients with Hodgkin's disease.

    PubMed Central

    Gupta, S; Fernandes, G

    1981-01-01

    Subpopulations of lymphocytes in the peripheral blood and spleen from adult untreated patients with Hodgkin's disease were studied for spontaneous (SCMC) and antibody-dependent cellular cytotoxicities (ADCC). Peripheral blood from seven of 24 patients demonstrated abnormally low T cell-mediated SCMC when compared to age- and sex-matched healthy controls. Only two of these patients also demonstrated low T cell ADCC and non-T cell-mediated SCMC and ADCC. T cell ADCC in the peripheral blood of patients with involved spleen was significantly higher (P less than 0.05) when compared to those in whom spleen was not involved. When SCMC and ADCC were compared between peripheral blood and splenic lymphocytes with regard to involvement of spleen by Hodgkin's disease, non-T cell SCMC in the involved spleen was significantly lower (P less than 0.05) than their peripheral blood non-T cell SCMC. SCMC and ADCC tended to be higher in patients with stages III and IV of Hodgkin's disease when compared to those with stages I and II. However, the differences were not statistically significant. No direct relationship was observed between T and SCMC or ADCC and the proportion of T cells with IgG Fc receptors (T gamma). The significance of these observations is discussed. PMID:6975681

  12. A new cell culture protocol for enrichment and genetic modification of adult canine Schwann cells suitable for peripheral nerve tissue engineering.

    PubMed

    Haastert, K; Seef, P; Stein, V M; Tipold, A; Grothe, C

    2009-08-01

    Easily applicable techniques are presented to obtain high numbers of enriched canine Schwann cells (cSC) in a short time-window. The potential of adult SC for tissue engineering of peripheral nerves and ex vivo gene therapy is obvious from physiological events taking place after peripheral nerve transection [Haastert, K., Grothe, C., 2007. Gene therapy in peripheral nerve reconstruction approaches. Curr. Gene Ther. 7, 221-228]. The presented techniques were modified from a protocol for cultivation and expansion of adult cSC by others [Pauls, J., Nolte, C., Forterre, F., Brunnberg, L., 2004. Cultivation and expansion of canine Schwann cells using reexplantation. Berl. Munch. Tierarztl. Wochenschr. 117, 341-352] and own experiences in rodent and human SC cultivation and transfection [Haastert, K., Mauritz, C., Chaturvedi, S., Grothe, C., 2007. Human and rat adult Schwann cell cultures: fast and efficient enrichment and highly effective non-viral transfection protocol. Nat. Protoc. 2, 99-104]. A purity of about 80% cSC achieved by immunopanning techniques and selective culture conditions is 2.5 fold higher as previously reported (Pauls et al., 2004). Additionally, highly enriched cSC populations are available in 3-4 weeks, only half the time period reported previously (Pauls et al., 2004). Furthermore, electroporation and genetic modification of cSC is reported for the first time. PMID:19232653

  13. Selective vulnerability of dorsal root ganglia neurons in experimental rabies after peripheral inoculation of CVS-11 in adult mice.

    PubMed

    Rossiter, John P; Hsu, Lena; Jackson, Alan C

    2009-08-01

    The involvement of dorsal root ganglia was studied in an in vivo model of experimental rabies virus infection using the challenge virus standard (CVS-11) strain. Dorsal root ganglia neurons infected with CVS in vitro show prolonged survival and few morphological changes, and are commonly used to study the infection. It has been established that after peripheral inoculation of mice with CVS the brain and spinal cord show relatively few neurodegenerative changes, but detailed studies of pathological changes in dorsal root ganglia have not previously been performed in this in vivo experimental model. In this study, adult ICR mice were inoculated in the right hindlimb footpad with CVS. Spinal cords and dorsal root ganglia were evaluated at serial time points for histopathological and ultrastructural changes and for biochemical markers of cell death. Light microscopy showed multifocal mononuclear inflammatory cell infiltrates in the sensory ganglia and a spectrum of degenerative neuronal changes. Ultrastructural changes in gangliocytes included features characteristic of the axotomy response, the appearance of numerous autophagic compartments, and aggregation of intermediate filaments, while the neurons retained relatively intact mitochondria and plasma membranes. Later in the process, there were more extensive degenerative neuronal changes without typical features of either apoptosis or necrosis. The degree of degenerative neuronal changes in gangliocytes contrasts with observations in CNS neurons in experimental rabies. Hence, gangliocytes exhibit selective vulnerability in this animal model. This contrasts markedly with the fact that they are, unlike CNS neurons, highly permissive to CVS infection in vitro. Further study is needed to determine mechanisms for this selective vulnerability, which will give us a better understanding of the pathogenesis of rabies. PMID:19252919

  14. Clock gene expression in adult primate suprachiasmatic nuclei and adrenal: is the adrenal a peripheral clock responsive to melatonin?

    PubMed

    Valenzuela, F J; Torres-Farfan, C; Richter, H G; Mendez, N; Campino, C; Torrealba, F; Valenzuela, G J; Serón-Ferré, M

    2008-04-01

    The circadian production of glucocorticoids involves the concerted action of several factors that eventually allow an adequate adaptation to the environment. Circadian rhythms are controlled by the circadian timing system that comprises peripheral oscillators and a central rhythm generator located in the suprachiasmatic nucleus (SCN) of the hypothalamus, driven by the self-regulatory interaction of a set of proteins encoded by genes named clock genes. Here we describe the phase relationship between the SCN and adrenal gland for the expression of selected core clock transcripts (Per-2, Bmal-1) in the adult capuchin monkey, a New World, diurnal nonhuman primate. In the SCN we found a higher expression of Bmal-1 during the h of darkness (2000-0200 h) and Per-2 during daytime h (1400 h). The adrenal gland expressed clock genes in oscillatory fashion, with higher values for Bmal-1 during the day (1400-2000 h), whereas Per-2 was higher at nighttime (about 0200 h), resulting in a 9- to 12-h antiphase pattern. In the adrenal gland, the oscillation of clock genes was accompanied by rhythmic expression of a functional output, the steroidogenic enzyme 3beta-hydroxysteroid dehydrogenase. Furthermore, we show that adrenal explants maintained oscillatory expression of Per-2 and Bmal-1 for at least 36 h in culture. The acrophase of both transcripts, but not its overall expression along the incubation, was blunted by 100 nm melatonin. Altogether, these results demonstrate oscillation of clock genes in the SCN and adrenal gland of a diurnal primate and support an oscillation of clock genes in the adrenal gland that may be modulated by the neurohormone melatonin. PMID:18187542

  15. Peripheral neuropathy

    MedlinePlus

    Peripheral neuritis; Neuropathy - peripheral; Neuritis - peripheral; Nerve disease; Polyneuropathy ... Neuropathy is very common. There are many types and causes. Often, no cause can be found. Some ...

  16. Centralization of the deuterostome nervous system predates chordates.

    PubMed

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

    2009-08-11

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

  17. Molecular background and physiological consequences of altered peripheral serotonin homeostasis in adult rats perinatally treated with tranylcypromine.

    PubMed

    Blazevic, S; Erjavec, I; Brizic, M; Vukicevic, S; Hranilovic, D

    2015-08-01

    Serotonin (5-hydroxytryptamine, 5-HT) is a biologically active molecule present in mammals in the brain and peripheral tissues where it exerts many physiological functions. Developmental exposure to 5-HT-enhancing agents has been reported to induce long-lasting changes in the brain, but the long-term effects of perinatal 5-HT enhancement on 5-HT balance and function in the peripheral compartment have not been explored. Perinatal treatment of rats with monoamine oxidase (MAO) inhibitor tranylcypromine (TCP), leads to persistent imbalance in central (increased 5-HT degradation and decreased 5-HT concentrations in the brain) and peripheral (increased platelet and decreased plasma 5-HT concentrations) 5-HT homeostasis. In this study, we explored the molecular background of peripheral 5-HT imbalance, and its possible consequences on bone remodeling and hematopoiesis. Jejunum, liver and blood samples were collected from TCP- and saline-treated rats on post-natal day 70. Relative mRNA levels for tryptophan hydroxylase 1 (TPH1) and MAO A were analyzed using quantitative RT-PCR, femoral trabecular bone parameters were measured using microcomputed tomography, while peripheral blood cell number was determined by cell counter. TCP-treated rats displayed significant decrease in expression of Tph1, and significant increase in percentage of bone volume, trabecular number, connectivity density, and leukocyte number. In addition, significant negative correlation was observed between relative concentrations of TPH1 mRNA and trabecular bone parameters. Our results: a) show that perinatal exposure to tranylcypromine leads to long-lasting compensatory decrease in Tph1 expression in the peripheral compartment, accompanied with alterations in bone remodeling and hematopoiesis, b) suggest that peripheral and central 5HT compartment use different strategies to compensate for 5-HT imbalances of the same cause, and c) indicate dominant role of peripheral over central 5-HT in the regulation

  18. BMI, HOMA-IR, and Fasting Blood Glucose Are Significant Predictors of Peripheral Nerve Dysfunction in Adult Overweight and Obese Nondiabetic Nepalese Individuals: A Study from Central Nepal

    PubMed Central

    Thapa, Lekhjung; Rana, P. V. S.

    2016-01-01

    Objective. Nondiabetic obese individuals have subclinical involvement of peripheral nerves. We report the factors predicting peripheral nerve function in overweight and obese nondiabetic Nepalese individuals. Methodology. In this cross-sectional study, we included 50 adult overweight and obese nondiabetic volunteers without features of peripheral neuropathy and 50 healthy volunteers to determine the normative nerve conduction data. In cases of abnormal function, the study population was classified on the basis of the number of nerves involved, namely, “<2” or “≥2.” Multivariable logistic regression analysis was carried out to predict outcomes. Results. Fasting blood glucose (FBG) was the significant predictor of motor nerve dysfunction (P = 0.039, 95% confidence interval (CI) = 1.003–1.127). Homeostatic model assessment of insulin resistance (HOMA-IR) was the significant predictor (P = 0.019, 96% CI = 1.420–49.322) of sensory nerve dysfunction. Body mass index (BMI) was the significant predictor (P = 0.034, 95% CI = 1.018–1.577) in case of ≥2 mixed nerves' involvement. Conclusion. FBG, HOMA-IR, and BMI were significant predictors of peripheral nerve dysfunction in overweight and obese Nepalese individuals. PMID:27200189

  19. BMI, HOMA-IR, and Fasting Blood Glucose Are Significant Predictors of Peripheral Nerve Dysfunction in Adult Overweight and Obese Nondiabetic Nepalese Individuals: A Study from Central Nepal.

    PubMed

    Thapa, Lekhjung; Rana, P V S

    2016-01-01

    Objective. Nondiabetic obese individuals have subclinical involvement of peripheral nerves. We report the factors predicting peripheral nerve function in overweight and obese nondiabetic Nepalese individuals. Methodology. In this cross-sectional study, we included 50 adult overweight and obese nondiabetic volunteers without features of peripheral neuropathy and 50 healthy volunteers to determine the normative nerve conduction data. In cases of abnormal function, the study population was classified on the basis of the number of nerves involved, namely, "<2" or "≥2." Multivariable logistic regression analysis was carried out to predict outcomes. Results. Fasting blood glucose (FBG) was the significant predictor of motor nerve dysfunction (P = 0.039, 95% confidence interval (CI) = 1.003-1.127). Homeostatic model assessment of insulin resistance (HOMA-IR) was the significant predictor (P = 0.019, 96% CI = 1.420-49.322) of sensory nerve dysfunction. Body mass index (BMI) was the significant predictor (P = 0.034, 95% CI = 1.018-1.577) in case of ≥2 mixed nerves' involvement. Conclusion. FBG, HOMA-IR, and BMI were significant predictors of peripheral nerve dysfunction in overweight and obese Nepalese individuals. PMID:27200189

  20. Studies of adhesion molecules mediating interactions between cells of peripheral nervous system indicate a major role for L1 in mediating sensory neuron growth on Schwann cells in culture.

    PubMed

    Seilheimer, B; Schachner, M

    1988-07-01

    The involvement of the adhesion molecules L1, N-CAM, and J1 in adhesion and neurite outgrowth in the peripheral nervous system was investigated. We prepared Schwann cells and fibroblasts (from sciatic nerves) and neurons (from dorsal root ganglia) from 1-d mice. These cells were allowed to interact with each other in a short-term adhesion assay. We also measured outgrowth of dorsal root ganglion neurons on Schwann cell and fibroblast monolayers. Schwann cells (which express L1, N-CAM, and J1) adhered most strongly to dorsal root ganglion neurons by an L1-dependent mechanism and less by N-CAM and J1. Schwann cell-Schwann cell adhesion was mediated by L1 and N-CAM, but not J1. Adhesion of fibroblasts (which express N-CAM, but not L1 or J1) to neurons or Schwann cells was mediated by L1 and N-CAM and not J1. However, inhibition by L1 and N-CAM antibodies was found to be less pronounced with fibroblasts than with Schwann cells. N-CAM was also strongly involved in fibroblast-fibroblast adhesion. Neurite outgrowth was most extensive on Schwann cells and less on fibroblasts. A difference in extent of neurite elongation was seen between small- (10-20 microns) and large- (20-35 microns) diameter neurons, with the larger neurons tending to exhibit longer neurites. Fab fragments of polyclonal L1, N-CAM, and J1 antibodies exerted slightly different inhibitory effects on neurite outgrowth, depending on whether the neurites were derived from small or large neurons. L1 antibodies interfered most strikingly with neurite outgrowth on Schwann cells (inhibition of 88% for small and 76% for large neurons), while no inhibition was detectable on fibroblasts. Similarly, although to a smaller extent than L1, N-CAM appeared to be involved in neurite outgrowth on Schwann cells and not on fibroblasts. Antibodies to J1 only showed a very small effect on neurite outgrowth of large neurons on Schwann cells. These observations show for the first time that identified adhesion molecules are potent

  1. 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.

  2. Viral Aetiology of Central Nervous System Infections in Adults Admitted to a Tertiary Referral Hospital in Southern Vietnam over 12 Years

    PubMed Central

    Tan, Le Van; Thai, Le Hong; Phu, Nguyen Hoan; Nghia, Ho Dang Trung; Chuong, Ly Van; Sinh, Dinh Xuan; Phong, Nguyen Duy; Mai, Nguyen Thi Hoang; Man, Dinh Nguyen Huy; Hien, Vo Minh; Vinh, Nguyen Thanh; Day, Jeremy; Chau, Nguyen Van Vinh; Hien, Tran Tinh; Farrar, Jeremy; de Jong, Menno D.; Thwaites, Guy; van Doorn, H. Rogier; Chau, Tran Thi Hong

    2014-01-01

    Background Central nervous system (CNS) infections are important diseases in both children and adults worldwide. The spectrum of infections is broad, encompassing bacterial/aseptic meningitis and encephalitis. Viruses are regarded as the most common causes of encephalitis and aseptic meningitis. Better understanding of the viral causes of the diseases is of public health importance, in order to better inform immunization policy, and may influence clinical management. Methodology/Principal Findings Study was conducted at the Hospital for Tropical Diseases in Ho Chi Minh City, a primary, secondary, and tertiary referral hospital for all southern provinces of Vietnam. Between December 1996 and May 2008, patients with CNS infections of presumed viral origin were enrolled. Laboratory diagnostics consisted of molecular and serological tests targeted at 14 meningitis/encephalitis-associated viruses. Of 291 enrolled patients, fatal outcome and neurological sequelae were recorded in 10% (28/291) and 27% (78/291), respectively. Mortality was especially high (9/19, 47%) amongst those with confirmed herpes simplex encephalitis which is attributed to the limited availability of intravenous acyclovir/valacyclovir. Japanese encephalitis virus, dengue virus, herpes simplex virus, and enteroviruses were the most common viruses detected, responsible for 36 (12%), 19 (6.5%), 19 (6.5%) and 8 (2.7%) respectively, followed by rubella virus (6, 2%), varicella zoster virus (5, 1.7%), mumps virus (2, 0.7%), cytomegalovirus (1, 0.3%), and rabies virus (1, 0.3%). Conclusions/Significance Viral infections of the CNS in adults in Vietnam are associated with high morbidity and mortality. Despite extensive laboratory testing, 68% of the patients remain undiagnosed. Together with our previous reports, the data confirm that Japanese encephalitis virus, dengue virus, herpes simplex virus, and enteroviruses are the leading identified causes of CNS viral infections in Vietnam, suggest that the

  3. 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

  4. 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

  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. Autonomic Nervous System Disorders

    MedlinePlus

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

  7. 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...

  8. Differences in B7 and CD28 family gene expression in the peripheral blood between newly diagnosed young-onset and adult-onset type 1 diabetes patients.

    PubMed

    Pruul, K; Kisand, K; Alnek, K; Metsküla, K; Reimand, K; Heilman, K; Peet, A; Varik, K; Peetsalu, M; Einberg, Ü; Tillmann, V; Uibo, R

    2015-09-01

    Type-1 diabetes (T1D) is a heterogeneous autoimmune disease, and there are pathogenetic differences between young- and adult-onset T1D patients. We hypothesized that the expressions of genes involved in costimulatory immune system pathways in peripheral blood are differently regulated in young- and adult-onset T1D. Study group I consisted of 80 children, adolescents, and young adults (age range 1.4-21.4 y; 31 controls and 49 T1D patients). Study group II consisted of 48 adults (age range 22.0-78.4 y; 30 controls and 18 T1D patients). The mRNA expression levels of CD86, CD28, CD25, CD226, CD40, BTLA, GITR, PDCD1, FoxP3, TGF-β, ICOS, sCTLA4, flCTLA4, and CD80 were measured in peripheral blood. Genetic polymorphisms (HLA haplotypes; rs231806, rs231775, and rs3087243 in CTLA4; rs763361 in CD226; and rs706778 in CD25) and T1D-associated autoantibodies were analyzed. In group I, there was significantly lower expression of CD226 in T1D patients than in the controls. In group II, there were significantly higher expression levels of CD86 and TGF-β in T1D patients than in the controls. In the T1D patients in group I, the upregulated CD80 expression correlated with the expression of both CTLA4 splice variants (sCTLA4 and flCTLA4). In contrast, in group II, upregulated CD86 correlated with TGF-β and CD25. In group I, the inhibitory CD80-CTLA4 pathway was activated, whereas, in group II, the activation CD86-CD28 pathway and TGF-β production were activated. These results emphasize the differences between young-onset and adult-onset T1D in the regulation of costimulatory pathways. These differences should be considered when developing novel treatments for T1D. PMID:25980680

  9. Human nervous system function emulator.

    PubMed

    Frenger, P

    2000-01-01

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

  10. Infections of the nervous system.

    PubMed

    Pruitt, A A

    1998-05-01

    Epidemiologic trends causing infections of the nervous system remain a significant source of morbidity and mortality one half-century after the introduction of penicillin. This article outlines common causes of bacterial meningitis, aseptic meningitis syndrome, encephalitis, abscess, spinal cord syndromes, and cranial and peripheral nerve problems. Recommendations for diagnostic evaluation and both empiric and definitive antimicrobial therapy are offered; controversial management issues are also discussed. The protean manifestations of varicella-zoster virus and Lyme diseases are outlined. In addition, special considerations in the immunocompromised host, including organ transplant recipients, cancer patients, and HIV-positive persons are explained, and antimicrobial therapy is discussed. PMID:9537969

  11. Glucocorticoids and nervous system plasticity

    PubMed Central

    Madalena, Kathryn M.; Lerch, Jessica K.

    2016-01-01

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

  12. The acute effect of maximal exercise on central and peripheral arterial stiffness indices and hemodynamics in children and adults.

    PubMed

    Melo, Xavier; Fernhall, Bo; Santos, Diana A; Pinto, Rita; Pimenta, Nuno M; Sardinha, Luís B; Santa-Clara, Helena

    2016-03-01

    This study compared the effects of a bout of maximal running exercise on arterial stiffness in children and adults. Right carotid blood pressure and artery stiffness indices measured by pulse wave velocity (PWV), compliance and distensibility coefficients, stiffness index α and β (echo-tracking), contralateral carotid blood pressure, and upper and lower limb and central/aortic PWV (applanation tonometry) were taken at rest and 10 min after a bout of maximal treadmill running in 34 children (7.38 ± 0.38 years) and 45 young adults (25.22 ± 0.91 years) having similar aerobic potential. Two-by-two repeated measures analysis of variance and analysis of covariance were used to detect differences with exercise between groups. Carotid pulse pressure (PP; η(2) = 0.394) increased more in adults after exercise (p < 0.05). Compliance (η(2) = 0.385) decreased in particular in adults and in those with high changes in distending pressure, similarly to stiffness index α and β. Carotid PWV increased more in adults and was related to local changes in PP but not mean arterial pressure (MAP). Stiffness in the lower limbs decreased (η(2) = 0.115) but apparently only in those with small MAP changes (η(2) = 0.111). No significant exercise or group interaction effects were found when variables were adjusted to height. An acute bout of maximal exercise can alter arterial stiffness and hemodynamics in the carotid artery and within the active muscle beds. Arterial stiffness and hemodynamic response to metabolic demands during exercise in children simply reflect their smaller body size and may not indicate a particular physiological difference compared with adults. PMID:26842667

  13. The Time to Clearance of Peripheral Blood Blasts Predicts Complete Remission and Survival in Chinese Adults with Acute Myeloid Leukemia.

    PubMed

    Li, Xiaoyang; Zhu, Hongming; Zhang, Yunxiang; Zhao, Weili; Mi, Jianqing; Hu, Jiong; Li, Junmin

    2016-01-01

    The value of clearance of peripheral blood blasts (PBB) as a predictor of outcomes in acute myeloid leukemia (AML) is controversial. To investigate the prognostic significance of the time to clearance of PBB after induction in Chinese patients with AML, a retrospective analysis of 146 patients with newly diagnosed AML at Shanghai Ruijin Hospital was performed. Patients were categorized into early blast clearance (EBC; ≤5 days) and delayed blast clearance (DBC; >5 days) groups based on a receiver operating characteristic analysis. Complete remission (CR) after induction chemotherapy was related to the time to clearance of PBB (p < 0.001). Relapse-free survival (RFS; p = 0.003) and overall survival (p < 0.001) were longer in the EBC group. Multivariate analysis demonstrated that the time to clearance of PBB and cytogenetic risk independently predicted CR and RFS. Early clearance of PBB after induction chemotherapy can be a significant predictor of survival outcomes in AML patients. PMID:26967450

  14. Postnatal high-fat diet leads to spatial deficit, obesity, and central and peripheral inflammation in prenatal dexamethasone adult offspring rats.

    PubMed

    Hsieh, Chih-Sung; Li, Shih-Wen; Sheen, Jiunn-Ming; Yu, Hong-Ren; Tiao, Mao-Meng; Tain, You-Lin; Su, Chung-Hao; Huang, Li-Tung

    2016-08-01

    Synthetic glucocorticoids are frequently used in clinical practice for treating pregnant women at risk of preterm delivery, but their long-term effects on the infant brain are largely unknown. Pregnant Sprague-Dawley rats were administered vehicle or dexamethasone between gestational days 14 and 21. Male offspring were then weaned onto either a standard chow or a high-fat diet. The postnatal levels of insulin-like growth factor I (IGF-1), tumor necrosis factor-α (TNF-α), and asymmetric dimethylarginine (ADMA) in the plasma, liver, and brain were examined, as well as the possible effects of prenatal dexamethasone on cognition. We found that a postnatal high-fat diet led to spatial deficits detected by the Morris water maze in adult offspring administered dexamethasone prenatally. The spatial deficit was accompanied by decreased IGF-1 mRNA and increased ADMA levels in the dorsal hippocampus. In peripheral systems, a postnatal high-fat diet resulted in decreased plasma IGF-1, increased plasma corticosterone, increased concentrations of transaminases, TNF-α mRNA, and ADMA in the liver, and associated obesity in adult offspring administered prenatal dexamethasone. In conclusion, a postnatal high-fat diet led to spatial deficits, obesity, and altered levels of IGF-1, TNF-α, and ADMA in the plasma, liver, or brain. PMID:27272689

  15. AMPA and GABA(A/B) receptor subunit expression in the cuneate nucleus of adult squirrel monkeys during peripheral nerve regeneration.

    PubMed

    Mowery, Todd M; Kostylev, Polina V; Garraghty, Preston E

    2014-01-24

    The primate somatosensory neuroaxis provides an excellent model system with which to investigate adult neural plasticity. Here, we report immunohistochemical staining data for AMPA and GABAA/B receptor subunits in the cuneate nucleus of adult squirrel monkeys 1 and 5 months after median nerve compression. This method of nerve injury allowed the investigation of the way in which patterns of receptor correlates change during peripheral nerve regeneration. These results are compared to cortical data collected within the same animals. As observed in the cortex, the pattern of subunit staining in the brainstem 1 month after nerve compression suggests that the sensory deprived nucleus enters a state of reorganization. That is, the expression of GluR2/3 AMPA receptor subunits is significantly increased, while GABA α1 and GABABR1b receptor subunits are significantly decreased. Five months after nerve injury, the pattern of subunit expression is again very similar to that observed in the infragranular layers of cortex. At this later time we observe a significant increase in GluR2/3 and GABABR1a, with no change in GABAAα1, and a significant decrease in GABABR1b. Together these results suggest that during reorganization and recovery from injury the brainstem and cortex are governed by homogeneous mechanisms of plasticity. PMID:24315976

  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. [Vesalius and the nervous system].

    PubMed

    Van Laere, J

    1993-01-01

    Before we comment the subject of this lecture, we attract the reader's attention towards two remarks. We first want to point out that, although Vesalius is rightly considered as "the father of anatomy", in physiological matters--such as e.g. the physiology of the nervous system--he remained a faithful follower of Galen. A second preliminary remark explains why the books Vesalius devoted to the nervous system, namely the fourth and seventh books, as well as a part of the third book, don't belong to the best parts of the Fabrica, when we compare them with his Osteology and his Myology. We should not forget that some technical discoveries such as keeping brain-tissue in alcohol in order to harden it and colouring methods of Weigert, Marchi and Nissl, that made a refined macro- and microscopic examination of the nervous system possible, were only invented in the 19th century. The fourth book considers the peripheral nervous system. According to Vesalius, there are seven pairs of brain-nerves. His first pair corresponds to our Nervous opticus; his second pair concerns our Nervi oculomotorius, trochlearis and abducens; this third pair embraces a great part of our Nervus trigeminus; his fourth pair corresponds to our Nervus maxillaris; his fifth pair includes our Nervi facialis and acusticus; his sixth pair includes our Nervi vagus and accessorius; his seventh pair our Nervi hypoglossus and pharyngeus. Vesalius counts thirty pairs of spinal nerves. His description of the Plexus brachialis and the Plexus ischiadicus is closely related to the modern views in these matters. However, his teleologic views about them are remarkable, e.g. about the course of the Nervi recurrentes. The seventh book covers the brain. He successively and truly describes the cerebral membranes, the Ventriculi, the Cerebrum; his description relies on a series of horizontal slices. He also describes the brain-stem and the Cerebellum. Vesalius, who had doubts about the existence of the Plexus

  18. Communication Barriers and the Clinical Recognition of Diabetic Peripheral Neuropathy in a Diverse Cohort of Adults: The DISTANCE Study.

    PubMed

    Adams, Alyce S; Parker, Melissa M; Moffet, Howard H; Jaffe, Marc; Schillinger, Dean; Callaghan, Brian; Piette, John; Adler, Nancy E; Bauer, Amy; Karter, Andrew J

    2016-05-01

    The purpose of this study was to explore communication barriers as independent predictors and potential mediators of variation in clinical recognition of diabetic peripheral neuropathy (DPN). In this cross-sectional analysis, we estimated the likelihood of having a DPN diagnosis among 4,436 patients with DPN symptoms. We controlled for symptom frequency, demographic and clinical characteristics, and visit frequency using a modified Poisson regression model. We then evaluated 4 communication barriers as independent predictors of clinical documentation and as possible mediators of racial/ethnic differences: difficulty speaking English, not talking to one's doctor about pain, limited health literacy, and reports of suboptimal patient-provider communication. Difficulty speaking English and not talking with one's doctor about pain were independently associated with not having a diagnosis, though limited health literacy and suboptimal patient-provider communication were not. Limited English proficiency partially attenuated, but did not fully explain, racial/ethnic differences in clinical documentation among Chinese, Latino, and Filipino patients. Providers should be encouraged to talk with their patients about DPN symptoms, and health systems should consider enhancing strategies to improve timely clinical recognition of DPN among patients who have difficult speaking English. More work is needed to understand persistent racial/ethnic differences in diagnosis. PMID:27116591

  19. The effects of aging and maternal protein restriction during lactation on thymic involution and peripheral immunosenescence in adult mice.

    PubMed

    Heppolette, Chantal A A; Chen, Jian-Hua; Carr, Sarah K; Palmer, Donald B; Ozanne, Susan E

    2016-02-01

    Environmental factors such as nutrition during early life can influence long-term health, a concept termed developmental programming. Initial research was focused towards the effects on metabolic health but more recent studies have demonstrated effects on parameters such as lifespan and immunity. In this study we report that maternal protein restriction during lactation in mice, that is known to prolong lifespan, slows aging of the central and peripheral immune systems. Offspring of dams fed a postnatal low-protein (PLP) diet during lactation had a significant increase in thymic cellularity and T cell numbers across their lifespan compared to controls, and a less marked age-associated decrease in thymocyte cluster of differentiation (CD) 3 expression. PLP animals also demonstrated increased relative splenic cellularity, increased naïve: memory CD4+ and CD8+ T cell ratios, increased staining and density of germinal centres, and decreased gene expression of p16 in the spleen, a robust biomarker of aging. A slower rate of splenic aging in PLP animals would be expected to result in decreased susceptibility to infection and neoplasia. In conclusion nutritionally-induced slow postnatal growth leads to delayed aging of the adaptive immune system, which may contribute towards the extended lifespan observed in these animals. PMID:26843625

  20. The effects of aging and maternal protein restriction during lactation on thymic involution and peripheral immunosenescence in adult mice

    PubMed Central

    Heppolette, Chantal A. A.; Chen, Jian-Hua; Carr, Sarah K.; Palmer, Donald B.; Ozanne, Susan E.

    2016-01-01

    Environmental factors such as nutrition during early life can influence long-term health, a concept termed developmental programming. Initial research was focused towards the effects on metabolic health but more recent studies have demonstrated effects on parameters such as lifespan and immunity. In this study we report that maternal protein restriction during lactation in mice, that is known to prolong lifespan, slows aging of the central and peripheral immune systems. Offspring of dams fed a postnatal low-protein (PLP) diet during lactation had a significant increase in thymic cellularity and T cell numbers across their lifespan compared to controls, and a less marked age-associated decrease in thymocyte cluster of differentiation (CD) 3 expression. PLP animals also demonstrated increased relative splenic cellularity, increased naïve: memory CD4+ and CD8+ T cell ratios, increased staining and density of germinal centres, and decreased gene expression of p16 in the spleen, a robust biomarker of aging. A slower rate of splenic aging in PLP animals would be expected to result in decreased susceptibility to infection and neoplasia. In conclusion nutritionally-induced slow postnatal growth leads to delayed aging of the adaptive immune system, which may contribute towards the extended lifespan observed in these animals. PMID:26843625

  1. Structure of the nervous system of Myzostoma cirriferum (Annelida) as revealed by immunohistochemistry and cLSM analyses.

    PubMed

    Müller, M C; Westheide, W

    2000-08-01

    The nervous systems of juvenile and adult Myzostoma cirriferum Leuckart, 1836, were stained with antisera against 5-HT (5-hydroxytryptamine, serotonin), FMRFamide, and acetylated alpha-tubulin in combination with the indirect fluorescence technique and analyzed by confocal laser scanning microscopy. The central nervous system consists of two small cerebral ganglia, connected by a dorsal commissure, a ventral nerve mass, and a pair of long circumesophageal connectives joining the former to the latter. The two neuropil cords within the ventral nerve mass curve outward and are joined to one another anteriorly and posteriorly. They are connected by 12 commissures, forming a ladder-like system. A single median nerve runs along the midventral axis. In addition to the circumesophageal connectives, 11 peripheral nerves arise from each main cord. The first innervates the anterior body region. The others form five groups of two nerves each, the first and thicker nerve of which is the parapodial nerve, innervating the parapodium and two corresponding cirri. Except for those in the most posterior group, the second nerves innervate the lateral organs and the body periphery. Serotonergic perikarya are arranged in six more or less distinct clusters, the first lying in front of and the other five between the main nerve cords. The distribution pattern of the FMRFamidergic perikarya is less clear and the somata lie between and outside the cords. One pair of dorsolateral longitudinal nerves was visualized by tubulin staining. Peripheral nerves and the commissures, in particular, demonstrate a segmental organization of the nervous system of M. cirriferum. Furthermore, their arrangement indicates that the body consists of six segments, the first of which is identifiable only by the first pair of peripheral nerves, the first two commissures, and the anteriormost ventral ganglion. The nervous system M. cirriferum thus exhibits several structures also found in the basic plan of the

  2. 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

  3. Intact sciatic myelinated primary afferent terminals collaterally sprout in the adult rat dorsal horn following section of a neighbouring peripheral nerve.

    PubMed

    Doubell, T P; Mannion, R J; Woolf, C J

    1997-03-31

    Peripheral nerve section induces sprouting of the central terminals of axotomized myelinated primary afferents outside their normal dorsoventral termination zones in lamina I, III, and IV of the dorsal horn into lamina II, an area that normally only receives unmyelinated C-fiber input. This axotomy-induced regenerative sprouting is confined to the somatotopic boundaries of the injured nerve in the spinal cord. We examined whether intact myelinated sciatic afferents are able to sprout novel terminals into neighbouring areas of the dorsal horn in the adult rat following axotomy of two test nerves, either the posterior cutaneous nerve of the thigh or the saphenous nerve. These peripheral nerves have somatotopically organized terminal areas in the dorsal horn that overlap in some areas and are contiguous in others, with that of the sciatic central terminal field. Two weeks after cutting either the posterior cutaneous or the saphenous nerve, intact sciatic myelinated fibers labelled with the B fragment of cholera toxin conjugated to horseradish peroxidase (B-HRP) sprouted into an area of lamina II normally only innervated by the adjacent injured test nerve. This collateral sprouting was strictly limited, however, to those particular areas of the dorsal horn where the A-fiber terminal field of the control sciatic and the C-fiber terminal field of the injured test nerve overlapped in the dorsoventral plane. No mediolateral sprouting was seen into those areas of neuropil solely innervated by the test nerve. We conclude that intact myelinated primary afferents do have the capacity to collaterally sprout, but that any resultant somatotopic reorganization of central projections is limited to the dorsoventral plane. These changes may contribute to sensory hypersensitivity at the edges of denervated skin. PMID:9073085

  4. Prevalence of Peripheral Arterial Disease among Adult Patients Attending Outpatient Clinic at a General Hospital in South Angola.

    PubMed

    Paquissi, Feliciano Chanana; Cuvinje, Arminda Bimbi Paquissi; Cuvinje, Almeida Bailundo

    2016-01-01

    Background. Peripheral arterial disease (PAD) is a common manifestation of atherosclerosis, whose prevalence is increasing worldwide, and is associated with all-cause mortality. However, no study has assessed this disease in Huambo. The aim of this study was to evaluate the prevalence of PAD in patients attending an outpatient clinic at a general hospital in Huambo, South Angola. Methods. A cross-sectional study, including 115 patients aged 40 years and older attending an outpatient service. The evaluation included a basic questionnaire for lifestyle and medical history and ankle-brachial index (ABI) measurement using hand-held Doppler. PAD was defined as an ABI ≤0.9 in either lower limb. Results. Of 115 patients, 62.60% were women with a median age of 52.5 (range of 40 to 91) years. The prevalence of PAD was 42.6% (95% confidence intervals [CI]: 95%: 33.91-52.17%). Among patients with PAD, 95.92% had mild disease and 4.08% moderate to severe disease. The main risk factor for PAD was age (≥60 years) (χ (2) = 3.917, P ≤ 0.05). The prevalence was slightly higher in men and hypertensive subjects, but without statistical significance with ORs of 1.5 (95% CI: 0.69-3.21) and 1.42 (95% CI: 0.64-3.17), respectively. Hypertension was also high in the group (66.95%). Conclusion. The prevalence of PAD was 42.6%, higher in those aged 60 years and older. More studies, with representative samples, are necessary to clarify PAD prevalence and associated risk factors. PMID:27293966

  5. Prevalence of Peripheral Arterial Disease among Adult Patients Attending Outpatient Clinic at a General Hospital in South Angola

    PubMed Central

    Paquissi, Feliciano Chanana; Cuvinje, Arminda Bimbi Paquissi; Cuvinje, Almeida Bailundo

    2016-01-01

    Background. Peripheral arterial disease (PAD) is a common manifestation of atherosclerosis, whose prevalence is increasing worldwide, and is associated with all-cause mortality. However, no study has assessed this disease in Huambo. The aim of this study was to evaluate the prevalence of PAD in patients attending an outpatient clinic at a general hospital in Huambo, South Angola. Methods. A cross-sectional study, including 115 patients aged 40 years and older attending an outpatient service. The evaluation included a basic questionnaire for lifestyle and medical history and ankle-brachial index (ABI) measurement using hand-held Doppler. PAD was defined as an ABI ≤0.9 in either lower limb. Results. Of 115 patients, 62.60% were women with a median age of 52.5 (range of 40 to 91) years. The prevalence of PAD was 42.6% (95% confidence intervals [CI]: 95%: 33.91–52.17%). Among patients with PAD, 95.92% had mild disease and 4.08% moderate to severe disease. The main risk factor for PAD was age (≥60 years) (χ2 = 3.917, P ≤ 0.05). The prevalence was slightly higher in men and hypertensive subjects, but without statistical significance with ORs of 1.5 (95% CI: 0.69–3.21) and 1.42 (95% CI: 0.64–3.17), respectively. Hypertension was also high in the group (66.95%). Conclusion. The prevalence of PAD was 42.6%, higher in those aged 60 years and older. More studies, with representative samples, are necessary to clarify PAD prevalence and associated risk factors. PMID:27293966

  6. Impact of brief exercise on peripheral blood NK cell gene and microRNA expression in young adults

    PubMed Central

    Zaldivar, Frank; Haddad, Fadia; Cooper, Dan M.

    2013-01-01

    Natural killers (NK) cells are unique innate immune cells that increase up to fivefold in the circulating blood with brief exercise and are known to play a key role in first-response defense against pathogens and cancer immunosurveillance. Whether exercise alters NK cell gene and microRNA (miRNA) expression is not known. Thirteen healthy men (20–29 yr old) performed ten 2-min bouts of cycle ergometer exercise at a constant work equivalent to an average of 77% of maximum O2 consumption interspersed with 1-min rest. Blood was drawn before and immediately after the exercise challenge. NK cells were isolated from peripheral blood mononuclear cells using a negative magnetic cell separation method. We used Affymetrix U133+2.0 arrays for gene expression and Agilent Human miRNA V2 Microarray for miRNAs. A stringent statistical approach (false discovery rate < 0.05) was used to determine that exercise significantly altered the expression of 986 genes and 23 miRNAs. Using in silico analysis, we found exercise-related gene pathways where there was a high likelihood of gene-miRNA interactions. These pathways were predominantly associated with cancer and cell communication, including p53 signaling pathway, melanoma, glioma, prostate cancer, adherens junction, and focal adhesion. These data support the hypothesis that exercise affects the gene and miRNA expression pattern in the population of NK cells in the circulation and suggest mechanisms through which physical activity could alter health through the innate immune system. PMID:23288554

  7. Plasma S-adenosylmethionine, DNMT polymorphisms, and peripheral blood LINE-1 methylation among healthy Chinese adults in Singapore

    PubMed Central

    2013-01-01

    Background Global hypomethylation of repetitive DNA sequences is believed to occur early in tumorigenesis. There is a great interest in identifying factors that contribute to global DNA hypomethylation and associated cancer risk. We tested the hypothesis that plasma S-adenosylmethionine (SAM) level alone or in combination with genetic variation in DNA methyltransferases (DNMT1, DNMT3A and DNMT3B) was associated with global DNA methylation extent at long interspersed nucleotide element-1 (LINE-1) sequences. Methods Plasma SAM level and LINE-1 DNA methylation index were measured using stored blood samples collected from 440 healthy Singaporean Chinese adults during 1994-1999. Genetic polymorphisms of 13 loci in DNMT1, DNMT3A and DNMT3B were determined. Results LINE-1 methylation index was significantly higher in men than in women (p = 0.001). LINE-1 methylation index was positively associated with plasma SAM levels (p ≤ 0.01), with a plateau at approximately 78% of LINE-1 methylation index (55 nmol/L plasma SAM) in men and 77% methylation index (50 nmol/L plasma SAM) in women. In men only, the T allele of DNMT1 rs21124724 was associated with a statistically significantly higher LINE-1 methylation index (ptrend = 0.001). The DNMT1 rs2114724 genotype modified the association between plasma SAM and LINE-1 methylation index at low levels of plasma SAM in men. Conclusions Circulating SAM level was associated with LINE-1 methylation status among healthy Chinese adults. The DNMT1 genetic polymorphism may exert a modifying effect on the association between SAM and LINE-1 methylation status in men, especially when plasma SAM level is low. Our findings support a link between plasma SAM and global DNA methylation status at LINE-1 sequences. PMID:23957506

  8. Neurophysiological markers of plastic brain reorganization following central and peripheral lesions.

    PubMed

    Ferreri, Florinda; Guerra, Andrea; Rossini, Paolo Maria

    2014-12-01

    There is increasing evidence supporting the concept that adult brain has the remarkable ability to plastically reorganize itself. Brain plasticity involves distinct functional and structural components and plays a crucial role in reorganizing central nervous system's networks after central and peripheral lesions in order to partly or totally restore lost and/or compromised functions. This plastic rearrangement occurs in fact not only after a central nervous system injury but also following a peripheral lesion. Interestingly, the existence of a certain type of maladaptive plasticity was clearly recognized in the last decade, which gives reason for example to poor out- come performances or aberrant phenomena. In this review we analyze stroke and amputees studies, as illustrative conditions of central and peripheral nervous system damage, and discuss the adaptive as well maladaptive plastic brain changes following these lesions. The emerging possibility, through neuro-imaging and neurophysiological advanced techniques, to clarify some crucial issues underlying brain plasticity will give the chance to modulate these mechanisms in a highly personalized therapy. This approach may have a tremendous impact in a variety of neuropsychiatric disorders opening a new era of restorative medicine. PMID:25987182

  9. [Sports injuries of the nervous system].

    PubMed

    Lang, C; Stefan, H

    1999-08-01

    Almost 1% of all Germans suffer sports injuries each year, almost 5% of all peripheral nerve lesions are due to sports. A review is given on various activities detailing the specific risks for traumata of the central and peripheral nervous system. Specifically these are volleyball, handball, basketball, American football, soccer, bowling, hockey, baseball, tennis, golf, javelin, fencing, wrestling, judo, boxing, running, jumping, dancing, mountain climbing, weight lifting, gymnastics, horse-back riding, swimming, rowing, skiing, skating, shooting, (motor) biking, car racing, flying, and sports for the disabled. The knowledge of typical traumata should enable the neurologist to rapidly and reliably recognize related lesions and to contribute to their prevention or improvement. PMID:10478302

  10. Case report: a balance training program using the Nintendo Wii Fit to reduce fall risk in an older adult with bilateral peripheral neuropathy.

    PubMed

    Hakim, Renée Marie; Salvo, Charles J; Balent, Anthony; Keyasko, Michael; McGlynn, Deidre

    2015-02-01

    A recent systematic review supported the use of strength and balance training for older adults at risk for falls, and provided preliminary evidence for those with peripheral neuropathy (PN). However, the role of gaming systems in fall risk reduction was not explored. The purpose of this case report was to describe the use of the Nintendo® Wii™ Fit gaming system to train standing balance in a community-dwelling older adult with PN and a history of recurrent near falls. A 76-year-old patient with bilateral PN participated in 1 h of Nintendo® Wii™ Fit balance training, two times a week for 6 weeks. Examination was conducted using a Computerized Dynamic Posturography system (i.e. Sensory Organization Test (SOT), Limits of Stability (LOS), Adaptation Test (ADT) and Motor Control Test (MCT) and clinical testing with the Berg Balance Scale (BBS), Timed Up and Go (TUG), Activities-specific Balance Confidence (ABC) scale and 30-s Chair Stand. Following training, sensory integration scores on the SOT were unchanged. Maximum excursion abilities improved by a range of 37-86% on the LOS test. MCT scores improved for amplitude with forward translations and ADT scores improved for downward platform rotations. Clinical scores improved on the BBS (28/56-34/56), ABC (57.5-70.6%) and TUG (14.9-10.9 s) which indicated reduced fall risk. Balance training with a gaming system showed promise as a feasible, objective and enjoyable method to improve physical performance and reduce fall risk in an individual with PN. PMID:25515202

  11. Microglia in central nervous system repair after injury.

    PubMed

    Jin, Xuemei; Yamashita, Toshihide

    2016-05-01

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

  12. Peripheral Blood Monocytes as Adult Stem Cells: Molecular Characterization and Improvements in Culture Conditions to Enhance Stem Cell Features and Proliferative Potential

    PubMed Central

    Ungefroren, Hendrik; Hyder, Ayman; Schulze, Maren; Fawzy El-Sayed, Karim M.; Grage-Griebenow, Evelin; Nussler, Andreas K.; Fändrich, Fred

    2016-01-01

    Adult stem or programmable cells hold great promise in diseases in which damaged or nonfunctional cells need to be replaced. We have recently demonstrated that peripheral blood monocytes can be differentiated in vitro into cells resembling specialized cell types like hepatocytes and pancreatic beta cells. During phenotypic conversion, the monocytes downregulate monocyte/macrophage differentiation markers, being indicative of partial dedifferentiation, and are partially reprogrammed to acquire a state of plasticity along with expression of various markers of pluripotency and resumption of mitosis. Upregulation of stem cell markers and mitotic activity in the cultures was shown to be controlled by autocrine production/secretion of activin A and transforming growth factor-beta (TGF-β). These reprogrammed monocyte derivatives were termed “programmable cells of monocytic origin” (PCMO). Current efforts focus on establishing culture conditions that increase both the plasticity and proliferation potential of PCMO in order to be able to generate large amounts of blood-derived cells suitable for both autologous and allogeneic therapies. PMID:26798361

  13. The increase of intrinsic excitability of layer V pyramidal cells in the prelimbic medial prefrontal cortex of adult mice after peripheral inflammation.

    PubMed

    Wu, Xiao-Bo; Liang, Biao; Gao, Yong-Jing

    2016-01-12

    Symptoms including depression and hypofunction of cognitive and decision-making are commonly associated with chronic pain. Recent studies have shown that the state of the medial prefrontal cortex (mPFC) neurons is important in diverse high-order cognitive and emotional activity in animals and humans. The mPFC layer V neurons mainly integrate information from other brain areas. The abnormal activity and function of pyramidal neurons influence the signal processing in the mPFC. Here we observed the changes of the excitability of the prelimbic mPFC neurons by whole-cell current-clamp recordings in adult mouse with inflammatory pain induced by complete Freund's adjuvant (CFA). Results showed that resting membrane potential and membrane input resistance did not differ between CFA-treated and control animals. Single action potential (AP) did not differ in terms of amplitude, but rheobase, half AP duration, and decay time were significantly decreased, and voltage threshold was more hyperpolarized in CFA group. Although the firing adaptation did not differ in two groups, the repetitive AP firing number and initial firing rate were significantly increased in CFA group. These data suggest that the increase in the intrinsic excitability of prelimbic mPFC layer V pyramidal neurons may be involved, at least in part in peripheral inflammatory pain. PMID:26592167

  14. 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.

  15. 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

    2015-07-01

    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. PMID:25921732

  16. A prospective study of magnetic resonance imaging patterns of central nervous system infections in pediatric age group and young adults and their clinico-biochemical correlation

    PubMed Central

    Gupta, Kamini; Banerjee, Avik; Saggar, Kavita; Ahluwalia, Archana; Saggar, Karan

    2016-01-01

    Background: Infections of the central nervous system (CNS) are common and routinely encountered. Our aim was to evaluate the neuroimaging features of the various infections of the CNS so as to differentiate them from tumoral, vascular, and other entities that warrant a different line of therapy. Aims: Our aim was to analyze the biochemical and magnetic resonance imaging (MRI) features in CNS infections. Settings and Design: This was a longitudinal, prospective study over a period of 1½ years. Subjects and Methods: We studied cerebrospinal fluid (CSF) findings and MRI patterns in 27 patients of 0–20 years age group with clinical features of CNS infections. MRI was performed on MAGNETOM Avanto 18 Channel 1.5 Tesla MR machine by Siemens India Ltd. The MRI protocol consisted of diffusion-weighted and apparent diffusion coefficient imaging, turbo spin echo T2-weighted, spin echo T1-weighted, fluid-attenuated inversion recovery (FLAIR), and gradient-echo in axial, FLAIR in coronal, and T2-weighted in sagittal plane. Contrast-enhanced T1-weighted sequence and MR spectroscopy were done whenever indicated. Results and Conclusions: We found that most of the children belong to 1–10 years age group. Fungal infections were uncommon, mean CSF adenosine deaminase values specific for tuberculosis and mean CSF glucose-lowered in pyogenic. Hemorrhagic involvement of thalamus with/without basal ganglia and brainstem involvement may indicate Japanese encephalitis or dengue encephalitis. Diffusion restriction or hemorrhage in not expected in the brainstem afflicted lesions of rabies. Congenital cytomegalovirus can cause cortical malformations. T1 hyperintensities with diffusion restriction may represent viral encephalitis. Lesions of acute disseminated encephalomyelitis (ADEM) may mimic viral encephalitis. Leptomeningeal enhancement is predominant in pyogenic meningitis. Basilar meningitis in the presence of tuberculomas is highly sensitive and specific for tuberculosis. PMID

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

    PubMed

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

    2009-10-01

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

  18. Neurotic, neuromuscular and autonomic nervous form of magnesium imbalance.

    PubMed

    Durlach, J; Bac, P; Durlach, V; Bara, M; Guiet-Bara, A

    1997-06-01

    The nervous form of magnesium imbalance represents the best documented experimental and clinical aspects of magnesium disorders. The nervous form of primary magnesium deficit (MD) in the adult appears as the best descriptive model for analysis of the symptomatology, aetiology, physiopathology, diagnosis and therapy of the most frequent form of MD. Nervous hyperexcitability due to chronic MD in the adult results in a non-specific clinical pattern with associated central and peripheral neuromuscular symptoms, analogous to the symptomatology previously described in medical literature as latent tetany, hyperventilation syndrome, spasmophilia, chronic fatigue syndrome, neurocirculatory asthenia and idiopathic Barlow's disease. On encountering this non-specific pattern, the signs of neuromuscular hyperexcitability are of much greater importance. Trousseau's sign is less sensitive than Chvostek's sign, but their sensitivities are increased by hyperventilation (Von Bondsdorff's test). Examination of the precordial area will be conducted in order to search clinical stigmata of mitral valve prolapse (MVP) which is a frequent dyskinesia due to chronic MD (about a quarter to one-third of cases). The electromyogram (EMG) shows one (or several) trains of autorhythmic activities beating for more than 2 min of one of the three tetanic activities (uniplets, multiplets or 'complex tonicoclonic tracings') during one of the three facilitation procedures: tourniquet-induced ischaemia lasting 10 min. post-ischaemia lasting 10 min after the removal of the tourniquet and hyperventilation over 5 min. A repetitive EMG constitutes the principal mark of nervous hyperexcitability (NHE) due to MD. The echocardiogram (ECC) is the best tool for detecting MVP, the 2-dimensional ECC with pulsed Doppler being more accurate than time-motion ECC. The routine ionic investigations comprise five static tests: plasma and erythrocyte magnesium, plasma calcium and daily magnesiuria and calciuria. An

  19. 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

  20. 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

  1. Normal adult ramified microglia separated from other central nervous system macrophages by flow cytometric sorting: Phenotypic differences defined and direct ex vivo antigen presentation to myelin basic protein-reactive CD4{sup +} T cells compared

    SciTech Connect

    Ford, A.L.; Goodsall, A.L.; Sedgwick, J.D.

    1995-05-01

    Ramified microglia in the adult central nervous system (CNS) are the principal glial element up-regulating MHC class I and II expression in response to inflammatory events or neuronal damage. A proportion of these cells also express MHC class II constitutively in the normal CNS. The role of microglia as APCs for CD4{sup +} cells extravasating into the CNS remains undefined. In this study, using irradiation bone marrow chimeras in CD45-congenic rats, the phenotype CD45{sup low}CD11b/c{sup +} is shown to identify microglial cells specifically within the CNS. Highly purified populations of microglia and nonmicroglial but CNS-associated macrophages (CD45{sup high}CD11b/c{sup +}) have been obtained directly from the adult CNS, by using flow cytometric sorting. Morphologically, freshly isolated microglia vs other CNS macrophages are quite distinct. Of the two populations recovered from the normal CNS, it is the minority CD45{sup high}CD11 b/c{sup +} transitional macrophage population, and not microglia, that is the effective APC for experimental autoimmune encephalomyelitis-inducing CD4{sup +} myelin basic protein (MBP)-reactive T cells. CD45{sup high}CD11b/c{sup +} CNS macrophages also stimulate MBP-reactive T cells without addition of MBP to culture suggesting presentation of endogenous Ag. This is the first study in which microglia vs other CNS macrophages have been analyzed for APC ability directly from the CNS, with substantial cross-contamination between the two populations eliminated. The heterogeneity of these populations in terms of APC function is clearly demonstrated. Evidence is still lacking that adult CNS microglia have the capacity to interact with and stimulate CD4{sup +} T cells to proliferate or secrete IL-2. 60 refs., 6 figs., 1 tab.

  2. Peripheral neuromodulation in chronic migraine.

    PubMed

    Perini, F; De Boni, A

    2012-05-01

    Patients with chronic migraines are often refractory to medical treatment. Therefore, they might need other strategies to modulate their pain, according to their level of disability. Neuromodulation can be achieved with several tools: meditation, biofeedback, physical therapy, drugs and electric neurostimulation (ENS). ENS can be applied to the central nervous system (brain and spinal cord), either invasively (cortical or deep brain) or non-invasively [cranial electrotherapy stimulation, transcranial direct current stimulation and transcranial magnetic stimulation]. Among chronic primary headaches, cluster headaches are most often treated either through deep brain stimulation or occipital nerve stimulation because there is a high level of disability related to this condition. ENS, employed through several modalities such as transcutaneous electrical nerve stimulation, interferential currents and pulsed radiofrequency, has been applied to the peripheral nervous system at several sites. We briefly review the indications for the use of peripheral ENS at the site of the occipital nerves for the treatment of chronic migraine. PMID:22644166

  3. 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

  4. TAM receptor deficiency affects adult hippocampal neurogenesis.

    PubMed

    Ji, Rui; Meng, Lingbin; Li, Qiutang; Lu, Qingxian

    2015-06-01

    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

  5. Peripheral Neuropathy in Adolescents and Young Adults With Type 1 and Type 2 Diabetes From the SEARCH for Diabetes in Youth Follow-up Cohort

    PubMed Central

    Jaiswal, Mamta; Lauer, Abigail; Martin, Catherine L.; Bell, Ronny A.; Divers, Jasmin; Dabelea, Dana; Pettitt, David J.; Saydah, Sharon; Pihoker, Catherine; Standiford, Debra A.; Rodriguez, Beatriz L.; Pop-Busui, Rodica; Feldman, Eva L.

    2013-01-01

    OBJECTIVE To estimate the prevalence of and risk factors for diabetic peripheral neuropathy (DPN) in a pilot study among youth participating in the SEARCH for Diabetes in Youth study. RESEARCH DESIGN AND METHODS DPN was assessed using the Michigan Neuropathy Screening Instrument (MNSI) (examination for foot abnormalities, distal vibration perception, and ankle reflexes). An MNSI exam (MNSIE) score >2 is diagnostic for DPN. RESULTS The MNSIE was completed in 399 subjects, including 329 youth with type 1 diabetes (mean age 15.7 ± 4.3 years, duration 6.2 ± 0.9 years) and 70 with type 2 diabetes (mean age 21.6 ± 4.1 years, duration 7.6 ± 1.8 years). Glycated hemoglobin (A1C) was similar in both groups (8.8 ± 1.8% for type 1 vs. 8.5 ± 2.9% for type 2). The prevalence of DPN was significantly higher in youth with type 2 compared with those with type 1 diabetes (25.7 vs. 8.2%; P < 0.0001). In unadjusted analyses, diabetes type, older age, longer duration of diabetes, increased waist circumference, elevated blood pressure, lower HDL cholesterol, and presence of microalbuminuria (urinary albumin-to-creatinine ratio >30 mg/g) were associated with DPN. The association between diabetes type and DPN remained significant after adjustment for age and sex (odds ratio 2.29 [95% CI 1.05–5.02], P = 0.03). CONCLUSIONS DPN prevalence among youth with type 2 diabetes approached rates reported in adult populations with diabetes. Our findings suggest not only that youth with diabetes are at risk for DPN but also that many already show measurable signs of DPN. PMID:24144652

  6. 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

  7. Peripheral Neuropathy

    MedlinePlus

    ... can be associated with peripheral neuropathy. Metabolic and endocrine disorders impair the body’s ability to transform nutrients into ... to neuropathies as a result of chemical imbalances. Endocrine disorders that lead to hormonal imbalances can disturb normal ...

  8. Central nervous system transplantation benefited by low-level laser irradiation

    NASA Astrophysics Data System (ADS)

    Rochkind, S.; Lubart, Rachel; Wollman, Yoram; Simantov, Rabi; Nissan, Moshe; Barr-Nea, Lilian

    1990-06-01

    Effect of low-level laser irradiation on the central nervous system transplantation is reported. Ernbryonal brain allografts were transplanted into the brain of 20 adult rats and peripheral nerve graft transplanted into the severely injured spinal cord of 16 dogs. The operated wound of 10 rats and 8 dogs were exposed daily for 21 days to lowpower laser irradiation CW HeNe laser (35 mW, 632.8 run, energy density of 30 J/cm2 at each point for rats and 70 J/cm2 at each point for dogs). This study shows that (i) the low-level laser irradiation prevents extensive glial scar formation (a limiting factor in CNS regeneration) between embryonal transplants and host brain; (ii) Dogs made paraplegic by spinal cord injury were able to walk 3-6 months later. Recovery of these dogs was effected by the implantation of a fragment of autologous sciatic nerve at the site of injury and subsequently exposing the dogs to low-level laser irradiation. The effect of laser irradiation on the embryonal nerve cells grown in tissue culture was also observed. We found that low-level laser irradiation induced intensive migration of neurites outward of the aggregates 15-22 The results of the present study and our previous investigations suggest that low-level laser irradiation is a novel tool for treatment of peripheral and central nervous system injuries.

  9. 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

  10. The polysialic acid mimetics 5-nonyloxytryptamine and vinorelbine facilitate nervous system repair.

    PubMed

    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

  11. 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

  12. 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 ...

  13. 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.

  14. 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

  15. GFRalpha-3, a protein related to GFRalpha-1, is expressed in developing peripheral neurons and ensheathing cells.

    PubMed

    Widenfalk, J; Tomac, A; Lindqvist, E; Hoffer, B; Olson, L

    1998-04-01

    We report here the identification of a gene, termed GFRalpha-3 (glial cell line-derived neurotrophic factor family receptor alpha-3), related to GFRalpha-1 and GFRalpha-2 (also known as GDNFR-alpha and GDNFR-beta), and describe distribution of GDNFalpha-3 in the nervous system and other parts of the mouse body during development and in the adult. GFRalpha-3 in situ hybridization signals were found mainly in the peripheral nervous system, with prominent signals in developing dorsal root and trigeminal ganglia. Sympathetic ganglia were also positive. Developing nerves manifested strong GFRalpha-3 mRNA signals, presumably generated by the Schwann cells. Olfactory ensheathing cells were also positive. Other non-neuronal cells appearing positive during development included chromaffin cells in the adrenal gland and small clusters of cells in the intestinal epithelium. In the central nervous system no robust signals could be detected at any stage investigated with the present probes. Compared with the previously described GFRalpha-1 and GFRalpha-2 mRNAs, which are widely distributed in the central nervous system and peripheral organs, the expression of GFRalpha-3 mRNA is much more restricted. The prominent expression in Schwann cells during development suggests a key role for GFRalpha-3 in the development of the peripheral nervous system. As Schwann cells are known to lack expression of the transducing RET receptor, we propose that a possible function of GFRalpha-3 during development could be to bind Schwann cell-derived GDNF-like ligands, thus presenting such molecules to growing axons. PMID:9749804

  16. Herpesvirus Transport to the Nervous System and Back Again

    PubMed Central

    Smith, Gregory

    2013-01-01

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

  17. In the presence of danger: the extracellular matrix defensive response to central nervous system injury

    PubMed Central

    Jakeman, Lyn B.; Williams, Kent E.; Brautigam, Bryan

    2014-01-01

    Glial cells in the central nervous system (CNS) contribute to formation of the extracellular matrix, which provides adhesive sites, signaling molecules, and a diffusion barrier to enhance efficient neurotransmission and axon potential propagation. In the normal adult CNS, the extracellular matrix (ECM) is relatively stable except in selected regions characterized by dynamic remodeling. However, after trauma such as a spinal cord injury or cortical contusion, the lesion epicenter becomes a focus of acute neuroinflammation. The activation of the surrounding glial cells leads to a dramatic change in the composition of the ECM at the edges of the lesion, creating a perilesion environment dominated by growth inhibitory molecules and restoration of the peripheral/central nervous system border. An advantage of this response is to limit the invasion of damaging cells and diffusion of toxic molecules into the spared tissue regions, but this occurs at the cost of inhibiting migration of endogenous repair cells and preventing axonal regrowth. The following review was prepared by reading and discussing over 200 research articles in the field published in PubMed and selecting those with significant impact and/or controversial points. This article highlights structural and functional features of the normal adult CNS ECM and then focuses on the reactions of glial cells and changes in the perilesion border that occur following spinal cord or contusive brain injury. Current research strategies directed at modifying the inhibitory perilesion microenvironment without eliminating the protective functions of glial cell activation are discussed. PMID:24999352

  18. Prevent Diabetes Problems: Keep Your Nervous System Healthy

    MedlinePlus

    ... spinal cord cranial * nerves—nerves that connect your brain to your head, neck, and face peripheral nervous system—nerves that connect your spinal cord to your entire body, including your organs and your arms, hands, legs, ... carries signals between your brain and other parts of your body through your ...

  19. Illuminating viral infections in the nervous system

    PubMed Central

    McGavern, Dorian B.; Kang, Silvia S.

    2016-01-01

    Viral infections are a major cause of human disease. Although most viruses replicate in peripheral tissues, some have developed unique strategies to move into the nervous system, where they establish acute or persistent infections. Viral infections in the central nervous system (CNS) can alter homeostasis, induce neurological dysfunction and result in serious, potentially life-threatening inflammatory diseases. This Review focuses on the strategies used by neurotropic viruses to cross the barrier systems of the CNS and on how the immune system detects and responds to viral infections in the CNS. A special emphasis is placed on immune surveillance of persistent and latent viral infections and on recent insights gained from imaging both protective and pathogenic antiviral immune responses. PMID:21508982

  20. Lysophosphatidic Acid signaling in the nervous system.

    PubMed

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

    2015-02-18

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

  1. 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...

  2. Signals that initiate myelination in the developing mammalian nervous system.

    PubMed

    Colello, R J; Pott, U

    1997-08-01

    The myelination of axons by oligodendrocytes in the central nervous system and Schwann cells in the peripheral nervous system is essential for the establishment of saltatory conduction. In the absence or destruction of the myelin sheath, as seen in demyelinating diseases, impulse conduction is impeded resulting in severe sensory and motor deficits. Axon myelination is the culmination of a sequence of events that begins with the differentiation of glial cells and proceeds to the transcription and translation of myelin genes, the elaboration of a myelin sheath, and the recognition and ensheathment of axons. This review examines the regulatory mechanisms for each of these steps and compares and contrasts the role of the axon in initiating myelination in the central and peripheral nervous system. PMID:9396006

  3. 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. PMID:26479325

  4. 2016 Expert consensus document on prevention, diagnosis and treatment of short-term peripheral venous catheter-related infections in adult.

    PubMed

    Capdevila, J A; Guembe, M; Barberán, J; de Alarcón, A; Bouza, E; Fariñas, M C; Gálvez, J; Goenaga, M A; Gutiérrez, F; Kestler, M; Llinares, P; Miró, J M; Montejo, M; Muñoz, P; Rodríguez-Creixems, M; Sousa, D; Cuenca, J; Mestres, C A

    2016-08-01

    The use of endovascular catheters is a routine practice in secondary and tertiary care level hospitals. Short peripheral catheters have been found to be associated with the risk of nosocomial bacteremia resulting in morbidity and mortality. Staphyloccus aureus is mostly associated with peripheral catheter insertion. This Consensus Document has been elaborated by a panel of experts of the Spanish Society of Cardiovascular Infections in cooperation with experts from the Spanish Society of Internal Medicine, Spanish Society of Chemotherapy and Spanish Society of Thoracic-Cardiovascular Surgery and aims at define and establish the norm for management of short duration peripheral vascular catheters. The document addresses the indications for insertion, catheter maintenance and registry, diagnosis and treatment of infection, indications for removal and stresses on continuous education as a driver for quality. Implementation of this norm will allow uniformity in usage thus minimizing the risk of infection and its complications. PMID:27580009

  5. Immunolocalization of the mitogen-activated protein kinases p42MAPK and JNK1, and their regulatory kinases MEK1 and MEK4, in adult rat central nervous system.

    PubMed

    Flood, D G; Finn, J P; Walton, K M; Dionne, C A; Contreras, P C; Miller, M S; Bhat, R V

    1998-08-31

    Cell survival, death, and stress signals are transduced from the cell surface to the cytoplasm and nucleus via a cascade of phosphorylation events involving the mitogen-activated protein kinase (MAPK) family. We compared the distribution of p42 mitogen-activated protein kinase (p42MAPK) and its activator MAPK or ERK kinase (MEK1; involved in transduction of growth and differentiation signals), with c-Jun N-terminal kinase (JNK1) and its activator MEK4 (involved in transduction of stress and death signals) in the adult rat central nervous system. All four kinases were present in the cytoplasm, dendrites, and axons of neurons. The presence of p42MAPK and JNK1 in dendrites and axons, as well as in cell bodies, suggests a role for these kinases in phosphorylation and regulation of cytoplasmic targets. A high degree of correspondence was found between the regional distribution of MEK1 and p42MAPK. Immunostaining for MEK1 and p42MAPK was intense in olfactory structures, neocortex, hippocampus, striatum, midline, and interlaminar thalamic nuclei, hypothalamus, brainstem, Purkinje cells, and spinal cord. In addition to neurons, p42MAPK was also present in oligodendrocytes. Whereas MEK4 was ubiquitously distributed, JNK1 was more selective. Immunostaining for MEK4 and JNK1 was intense in the olfactory bulb, lower cortical layers, the cholinergic basal forebrain, most nuclei of the thalamus, medial habenula, and cranial motor nuclei. The distribution of MEK1 and p42MAPK proteins only partially overlapped with that of MEK4 and JNK1. This suggests that the growth/differentiation and death/stress pathways affected by these kinases may not necessarily act to counterbalance each other in response to extracellular stimuli. The differential distribution of these kinases may control the specificity of neuronal function to extracellular signals. PMID:9714150

  6. Transduction patterns of pseudotyped lentiviral vectors in the nervous system.

    PubMed

    Wong, Liang-Fong; Azzouz, Mimoun; Walmsley, Lucy E; Askham, Zoe; Wilkes, Fraser J; Mitrophanous, Kyriacos A; Kingsman, Susan M; Mazarakis, Nicholas D

    2004-01-01

    We have developed a non-primate-based lentiviral vector based on the equine infectious anemia virus (EIAV) for efficient gene transfer to the central and peripheral nervous systems. Previously we have demonstrated that pseudotyping lentiviral vectors with the rabies virus glycoprotein confers retrograde axonal transport to these vectors. In the present study we have successfully produced high-titer EIAV vectors pseudotyped with envelope glycoproteins from Rhabdovirus vesicular stomatitis virus (VSV) serotypes (Indiana and Chandipura strains); rabies virus [various Evelyn-Rokitnicki-Abelseth ERA strains and challenge virus standard (CVS)]; Lyssavirus Mokola virus, a rabies-related virus; and Arenavirus lymphocytic choriomeningitis virus (LCMV). These vectors were delivered to the striatum or spinal cord of adult rats or muscle of neonatal mice by direct injection. We report that the lentiviral vectors pseudotyped with envelopes from the VSV Indiana strain, wild-type ERA, and CVS strains resulted in strong transduction in the striatum, while Mokola- and LCMV-pseudotyped vectors exhibited moderate and weak transduction, respectively. Furthermore ERA- and CVS-pseudotyped lentiviral vectors demonstrated retrograde transport and expression in distal neurons after injection in brain, spinal cord, and muscle. The differences in transduction efficiencies and retrograde transport conferred by these envelope glycoproteins present novel opportunities in designing therapeutic strategies for different neurological diseases. PMID:14741783

  7. 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

  8. Vasculitis Syndromes of the Central and Peripheral Nervous Systems

    MedlinePlus

    ... disturbances, such as double vision, blurred vision, or blindness seizures, convulsions stroke or transient ischemic attack (TIA, ... years and is rarely fatal. Abrupt but reversible blindness is the most dramatic complication of temporal arteritis. ...

  9. Molecular domains of myelinated axons in the peripheral nervous system.

    PubMed

    Salzer, James L; Brophy, Peter J; Peles, Elior

    2008-11-01

    Myelinated axons are organized into a series of specialized domains with distinct molecular compositions and functions. These domains, which include the node of Ranvier, the flanking paranodal junctions, the juxtaparanodes, and the internode, form as the result of interactions with myelinating Schwann cells. This domain organization is essential for action potential propagation by saltatory conduction and for the overall function and integrity of the axon. PMID:18803321

  10. Central and peripheral nervous system involvement in neuromelioidosis.

    PubMed

    Arif, Muhammad A; Abid, Muhammad H; Renganathan, Radhakrishnan; Siddiqui, Khurram A

    2015-01-01

    We report a case of a 33-year-old Sri Lankan man who presented with flaccid quadriparesis with brainstem signs and acute motor axonal polyneuropathy. MRI of the brain showed multiple abscesses with ring enhancement seen predominantly in the brainstem and upper cervical cord. The patient was initially treated with intravenous immunoglobulin, considering this to be a form of Guillain-Barré syndrome. Cerebrospinal fluid, however, showed lymphocytic pleocytosis with raised protein. Tests for Brucella, tuberculosis, toxoplasmosis, syphilis and HIV were negative. Chest X-ray revealed a cavity in the left lung, which, on bronchoscopy, showed a collection of purulent secretions. Culture of these secretions grew Burkholderia pseudomallei. The patient was treated with two courses of intravenous antibiotics, with resultant radiological improvement; however, with significant morbidity. PMID:26494715

  11. Peripheral nervous system origin of phantom limb pain.

    PubMed

    Vaso, Apostol; Adahan, Haim-Moshe; Gjika, Artan; Zahaj, Skerdi; Zhurda, Tefik; Vyshka, Gentian; Devor, Marshall

    2014-07-01

    Nearly all amputees continue to feel their missing limb as if it still existed, and many experience chronic phantom limb pain (PLP). What is the origin of these sensations? There is currently a broad consensus among investigators that PLP is a top-down phenomenon, triggered by loss of sensory input and caused by maladaptive cortical plasticity. We tested the alternative hypothesis that PLP is primarily a bottom-up process, due not to the loss of input but rather to exaggerated input, generated ectopically in axotomized primary afferent neurons in the dorsal root ganglia (DRGs) that used to innervate the limb. In 31 amputees, the local anesthetic lidocaine was applied intrathecally and/or to the DRG surface (intraforaminal epidural block). This rapidly and reversibly extinguished PLP and also nonpainful phantom limb sensation (npPLS). Control injections were ineffective. For intraforaminal block, the effect was topographically appropriate. The suppression of PLP and npPLS could also be demonstrated using dilute lidocaine concentrations that are sufficient to suppress DRG ectopia but not to block the propagation of impulses generated further distally in the nerve. PLP is driven primarily by activity generated within the DRG. We recommend the DRG as a target for treatment of PLP and perhaps also other types of regional neuropathic pain. PMID:24769187

  12. 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…

  13. 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

  14. Animal models of peripheral neuropathy due to environmental toxicants.

    PubMed

    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

  15. Effects of low-energy He-Ne laser irradiation on posttraumatic degeneration of adult rabbit optic nerve

    SciTech Connect

    Schwartz, M.; Doron, A.; Erlich, M.; Lavie, V.; Benbasat, S.; Belkin, M.; Rochkind, S.

    1987-01-01

    Axons of the mammalian peripheral and central nervous systems degenerate after nerve injury. We have recently found that He-Ne laser irradiation may prevent some of the consequences of the injury in peripheral nerves of mammals. In the present study, the efficacy of the laser in treating injured neurons of the mammalian CNS was tested. Optic nerves of adult rabbits were exposed daily for 8-14 days to He-Ne laser irradiation (14 min, 15 mW) through the overlying muscles and skin. As a result of this treatment, the injured nerves maintained their histological integrity, which is invariably lost in injured mammalian CNS neurons.

  16. 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

  17. 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

  18. LGI proteins in the nervous system

    PubMed Central

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

    2013-01-01

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

  19. LGI proteins in the nervous system.

    PubMed

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

    2013-01-01

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

  20. 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.

  1. 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

  2. New models for the In vitro assessment of neurotoxicity in the nervous system and the preliminary validation stages of a 'tiered-test' model.

    PubMed

    Atterwill, C K; Davenport-Jones, J; Goonetilleke, S; Johnston, H; Purcell, W; Thomas, S M; West, M; Williams, S

    1993-09-01

    Many cell culture models are available for the in vitro assessment of neurotoxicity. The use of three culture types has been investigated: neuroblastoma cell lines, primary cultures of rat and chick midbrain, and organotypic whole brain reaggregate cultures. A tiered system has been proposed involving hierarchical testing through three layers of different neural complexities. This scheme is currently undergoing validation under the auspices of FRAME/EC using 40 test chemicals. To determine the performance and suitability of these culture models studies on selected neurotoxins have been performed: ethylcholine mustard aziridinium, vincristine, aluminium, glutamate, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and T(3)-deprivation. Aspects of this work are described, including mechanistic investigations in rat brain reaggregate cultures. In vitro exposure of xenobiotics through a tiered testing system (ranging from simple cell-based assays measuring cytotoxicological parameters to more complex markers in organotypic cultures) may permit detection of central nervous system neurotoxicity in the contexts of both 'screening' and mechanistics. The degree of simplicity, automaticity and transportability of the tests requires consideration as will the possibility of endpoints for specific classes of chemicals, for example cholinesterase for organophosphorus insecticides. Factors such as extrapolation from the central nervous system to the peripheral nervous system, metabolic activation, the blood-brain barrier, degree of neural cell activation, repair mechanisms, and developing versus adult nervous systems are considered. PMID:20732253

  3. Pannexin-1 expression in developing mouse nervous system: new evidence for expression in sensory ganglia.

    PubMed

    Raslan, Abdulrahman; Hainz, Nadine; Beckmann, Anja; Tschernig, Thomas; Meier, Carola

    2016-04-01

    Pannexin1 (Panx1) is one of three members of the pannexin protein family. The expression of Panx1 mRNA has been extensively investigated from late embryonic to adult stages. In contrast, expression during early embryonic development is largely unknown. Our aim is to examine the temporal and spatial expression of Panx1 in mouse embryonic development by focusing on embryonic days (E) 9.5 to 12.5. Whole embryos are investigated in order to provide a comprehensive survey. Analyses were performed at the mRNA level by using reverse transcription plus the polymerase chain reaction and whole-mount in situ hybridization. Panx1 mRNA was detected in the heads and bodies of embryos at all developmental stages investigated (E9.5, E10.5, E11.5, E12.5). In particular, the nervous system expressed Panx1 at an early time point. Interestingly, Panx1 expression was found in afferent ganglia of the cranial nerves and spinal cord. This finding is of particular interest in the context of neuropathic pain and other Panx1-related neurological disorders. Our study shows, for the first time, that Panx1 is expressed in the central and peripheral nervous system during early developmental stages. The consequences of Panx1 deficiency or inhibition in a number of experimental paradigms might therefore be predicated on changes during early development. PMID:26453396

  4. 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

  5. Neuroanatomical Characteristics and Speech Perception in Noise in Older Adults

    PubMed Central

    Wong, Patrick C. M.; Ettlinger, Marc; Sheppard, John P.; Gunasekera, Geshri M.; Dhar, Sumitrajit

    2010-01-01

    Objectives Previous research has attributed older adult’s difficulty with perceiving speech in noise to peripheral hearing loss. Recent studies have suggested a more complex picture, however, and implicate the central nervous system in sensation and sensory deficits. This study examines the relationship between the neuroanatomical structure of cognitive regions and the ability to perceive speech in noise in older adults. In particular, the neuroanatomical characteristics of the left ventral and dorsal prefrontal cortex are considered relative to standard measures of hearing in noise. Design The participants were fifteen older and fourteen younger right-handed native speakers of American English who had no neurological deficits and scored better than normal on standardized cognitive tests. We measured the participants’ peripheral hearing ability as well as their ability to perceive speech in noise using standardized tests. Anatomical magnetic resonance images were taken and analyzed to extract regional volumes and thicknesses of several key neuroanatomical structures. Results The results showed that younger adults had better hearing sensitivity and better speech perception in noise ability than older adults. For the older adults only, the volume of the left pars triangularis and the cortical thickness of the left superior frontal gyrus were significant predictors of performance on the speech-in-noise test. Discussion These findings suggest that, in addition to peripheral structures, the central nervous system also contributes to the ability to perceive speech in noise. In older adults, a decline in the volume and cortical thickness of the prefrontal cortex (PFC) during aging can therefore be a factor in a declining ability to perceive speech in a naturalistic environment. Our study shows a link between anatomy of PFC and speech perception in older adults. These findings are consistent with the decline-compensation hypothesis, which states that a decline in

  6. Autoimmune peripheral neuropathies.

    PubMed

    Bourque, Pierre R; Chardon, Jodi Warman; Massie, Rami

    2015-09-20

    Peripheral nervous system axons and myelin have unique potential protein, proteolipid, and ganglioside antigenic determinants. Despite the existence of a blood-nerve barrier, both humoral and cellular immunity can be directed against peripheral axons and myelin. Molecular mimicry may be triggered at the systemic level, as was best demonstrated in the case of bacterial oligosaccharides. The classification of immune neuropathy has been expanded to take into account specific syndromes that share unique clinical, electrophysiological, prognostic and serological features. Guillain-Barré syndrome encompasses a classical syndrome of acute demyelinating polyradiculoneuropathy and many variants: axonal motor and sensory, axonal motor, Miller-Fisher, autonomic, and sensory. Similarly, chronic immune neuropathy is composed of classic chronic inflammatory demyelinating polyradiculoneuropathy and variants characterized as multifocal (motor or sensorimotor), sensory, distal symmetric, and syndromes associated with monoclonal gammopathy. Among putative biomarkers, myelin associated glycoprotein and several anti-ganglioside autoantibodies have shown statistically significant associations with specific neuropathic syndromes. Currently, the strongest biomarker associations are those linking Miller-Fisher syndrome with anti-GQ1b, multifocal motor neuropathy with anti-GM1, and distal acquired symmetric neuropathy with anti-MAG antibodies. Many other autoantibody associations have been proposed, but presently lack sufficient specificity and sensitivity to qualify as biomarkers. This field of research has contributed to the antigenic characterization of motor and sensory functional systems, as well as helping to define immune neuropathic syndromes with widely different clinical presentation, prognosis and response to therapy. Serologic biomarkers are likely to become even more relevant with the advent of new targeted forms of immunotherapy, such as monoclonal antibodies. PMID:25748038

  7. Magnetic resonance neurography of peripheral nerve tumors and tumorlike conditions.

    PubMed

    Ahlawat, Shivani; Chhabra, Avneesh; Blakely, Jaishri

    2014-02-01

    Peripheral nerve enlargement may be seen in multiple conditions including hereditary or inflammatory neuropathies, sporadic or syndromic peripheral nerve sheath tumors, perineurioma, posttraumatic neuroma, and intraneural ganglion. Malignancies such as neurolymphoma, intraneural metastases, or sarcomas may also affect the peripheral nervous system and result in nerve enlargement. The imaging appearance and differentiating factors become especially relevant in the setting of tumor syndromes such as neurofibromatosis type 1, neurofibromatosis type 2, and schwannomatosis. This article reviews the typical magnetic resonance neurography imaging appearances of neurogenic as well as nonneurogenic neoplasms and tumorlike lesions of peripheral nerves, with emphasis on distinguishing factors. PMID:24210319

  8. 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.

  9. 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

  10. Holothurian Nervous System Diversity Revealed by Neuroanatomical Analysis.

    PubMed

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

    2016-01-01

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

  11. Role of the nervous system in cancer metastasis

    PubMed Central

    LI, SHA; SUN, YANLAI; GAO, DONGWEI

    2013-01-01

    The notion that tumors lack innervation was proposed several years ago. However, nerve fibers are irregulatedly found in some tumor tissues. Their terminals interaction with cancer cells are considered to be neuro-neoplastic synapses. Moreover, neural-related factors, which are important players in the development and activity of the nervous system, have been found in cancer cells. Thus, they establish a direct connection between the nervous system and tumor cells. They modulate the process of metastasis, including degradation of base membranes, cancer cell invasion, migration, extravasation and colonization. Peripheral nerve invasion provides another pathway for the spread of cancer cells when blood and lymphatic metastases are absent, which is based on the interactions between the microenvironments of nerve fibers and tumor cells. The nervous system also modulates angiogenesis, the tumor microenvironment, bone marrow, immune functions and inflammatory pathways to influence metastases. Denervation of the tumor has been reported to enhance cancer metastasis. Stress, social isolation and other emotional factors may increase distant metastasis through releasing hormones from the brain, the hypothalamic-pituitary-adrenal axis and autonomic nervous system. Disruption of circadian rhythms will also promote cancer metastasis through direct and indirect actions of the nervous system. Therefore, the nervous system plays an important role in cancer metastasis. PMID:23599747

  12. Multi-analyte profile analysis of plasma immune proteins: altered expression of peripheral immune factors is associated with neuropsychiatric symptom severity in adults with and without chronic hepatitis C virus infection.

    PubMed

    Huckans, Marilyn; Fuller, Bret E; Olavarria, Hannah; Sasaki, Anna W; Chang, Michael; Flora, Kenneth D; Kolessar, Michael; Kriz, Daniel; Anderson, Jeanne R; Vandenbark, Arthur A; Loftis, Jennifer M

    2014-03-01

    BackgroundThe purpose of this study was to characterize hepatitis C virus (HCV)-associated differences in the expression of 47 inflammatory factors and to evaluate the potential role of peripheral immune activation in HCV-associated neuropsychiatric symptoms-depression, anxiety, fatigue, and pain. An additional objective was to evaluate the role of immune factor dysregulation in the expression of specific neuropsychiatric symptoms to identify biomarkers that may be relevant to the treatment of these neuropsychiatric symptoms in adults with or without HCV. MethodsBlood samples and neuropsychiatric symptom severity scales were collected from HCV-infected adults (HCV+, n = 39) and demographically similar noninfected controls (HCV-, n = 40). Multi-analyte profile analysis was used to evaluate plasma biomarkers. ResultsCompared with HCV- controls, HCV+ adults reported significantly (P < 0.050) greater depression, anxiety, fatigue, and pain, and they were more likely to present with an increased inflammatory profile as indicated by significantly higher plasma levels of 40% (19/47) of the factors assessed (21%, after correcting for multiple comparisons). Within the HCV+ group, but not within the HCV- group, an increased inflammatory profile (indicated by the number of immune factors > the LDC) significantly correlated with depression, anxiety, and pain. Within the total sample, neuropsychiatric symptom severity was significantly predicted by protein signatures consisting of 4-10 plasma immune factors; protein signatures significantly accounted for 19-40% of the variance in depression, anxiety, fatigue, and pain. ConclusionsOverall, the results demonstrate that altered expression of a network of plasma immune factors contributes to neuropsychiatric symptom severity. These findings offer new biomarkers to potentially facilitate pharmacotherapeutic development and to increase our understanding of the molecular pathways associated with neuropsychiatric symptoms in

  13. Multi-analyte profile analysis of plasma immune proteins: altered expression of peripheral immune factors is associated with neuropsychiatric symptom severity in adults with and without chronic hepatitis C virus infection

    PubMed Central

    Huckans, Marilyn; Fuller, Bret E; Olavarria, Hannah; Sasaki, Anna W; Chang, Michael; Flora, Kenneth D; Kolessar, Michael; Kriz, Daniel; Anderson, Jeanne R; Vandenbark, Arthur A; Loftis, Jennifer M

    2014-01-01

    Background The purpose of this study was to characterize hepatitis C virus (HCV)-associated differences in the expression of 47 inflammatory factors and to evaluate the potential role of peripheral immune activation in HCV-associated neuropsychiatric symptoms—depression, anxiety, fatigue, and pain. An additional objective was to evaluate the role of immune factor dysregulation in the expression of specific neuropsychiatric symptoms to identify biomarkers that may be relevant to the treatment of these neuropsychiatric symptoms in adults with or without HCV. Methods Blood samples and neuropsychiatric symptom severity scales were collected from HCV-infected adults (HCV+, n = 39) and demographically similar noninfected controls (HCV−, n = 40). Multi-analyte profile analysis was used to evaluate plasma biomarkers. Results Compared with HCV− controls, HCV+ adults reported significantly (P < 0.050) greater depression, anxiety, fatigue, and pain, and they were more likely to present with an increased inflammatory profile as indicated by significantly higher plasma levels of 40% (19/47) of the factors assessed (21%, after correcting for multiple comparisons). Within the HCV+ group, but not within the HCV− group, an increased inflammatory profile (indicated by the number of immune factors > the LDC) significantly correlated with depression, anxiety, and pain. Within the total sample, neuropsychiatric symptom severity was significantly predicted by protein signatures consisting of 4–10 plasma immune factors; protein signatures significantly accounted for 19–40% of the variance in depression, anxiety, fatigue, and pain. Conclusions Overall, the results demonstrate that altered expression of a network of plasma immune factors contributes to neuropsychiatric symptom severity. These findings offer new biomarkers to potentially facilitate pharmacotherapeutic development and to increase our understanding of the molecular pathways associated with neuropsychiatric

  14. Peripheral leukocyte populations and oxidative stress biomarkers in aged dogs showing impaired cognitive abilities.

    PubMed

    Mongillo, Paolo; Bertotto, Daniela; Pitteri, Elisa; Stefani, Annalisa; Marinelli, Lieta; Gabai, Gianfranco

    2015-06-01

    In the present study, the peripheral blood leukocyte phenotypes, lymphocyte subset populations, and oxidative stress parameters were studied in cognitively characterized adult and aged dogs, in order to assess possible relationships between age, cognitive decline, and the immune status. Adult (N = 16, 2-7 years old) and aged (N = 29, older than 8 years) dogs underwent two testing procedures, for the assessment of spatial reversal learning and selective social attention abilities, which were shown to be sensitive to aging in pet dogs. Based on age and performance in cognitive testing, dogs were classified as adult not cognitively impaired (ADNI, N = 12), aged not cognitively impaired (AGNI, N = 19) and aged cognitively impaired (AGCI, N = 10). Immunological and oxidative stress parameters were compared across groups with the Kruskal-Wallis test. AGCI dogs displayed lower absolute CD4 cell count (p < 0.05) than ADNI and higher monocyte absolute count and percentage (p < 0.05) than AGNI whereas these parameters were not different between AGNI and ADNI. AGNI dogs had higher CD8 cell percentage than ADNI (p < 0.05). Both AGNI and AGCI dogs showed lower CD4/CD8 and CD21 count and percentage and higher neutrophil/lymphocyte and CD3/CD21 ratios (p < 0.05). None of the oxidative parameters showed any statistically significant difference among groups. These observations suggest that alterations in peripheral leukocyte populations may reflect age-related changes occurring within the central nervous system and disclose interesting perspectives for the dog as a model for studying the functional relationship between the nervous and immune systems during aging. PMID:25905581

  15. Peripheral Neuropathy in Rats Exposed to Dichloroacetate

    PubMed Central

    Calcutt, Nigel A.; Lopez, Veronica L.; Bautista, Arjel D.; Mizisin, Leah M.; Torres, Brenda R.; Shroads, Albert L.; Mizisin, Andrew P.; Stacpoole, Peter W.

    2009-01-01

    The use of dichloroacetate (DCA) for treating patients with mitochondrial diseases is limited by the induction of peripheral neuropathy. The mechanisms of DCA-induced neuropathy are not known. Oral DCA treatment (50–500 mg/kg/day for up to 16 weeks) induced tactile allodynia in both juvenile and adult rats; concurrent thermal hypoalgesia developed at higher doses. Both juvenile and adult rats treated with DCA developed nerve conduction slowing that was more pronounced in adult rats. No overt axonal or glial cell abnormalities were identified in peripheral nerves or spinal cord of any DCA-treated rats but morphometric analysis identified a reduction of mean axonal caliber of peripheral nerve myelinated fibers. DCA treatment also caused accumulation of oxidative stress markers in the nerves. These data indicate that behavioral, functional and structural indices of peripheral neuropathy may be induced in both juvenile and adult rats treated with DCA at doses similar to those in clinical use. DCA-induced peripheral neuropathy primarily afflicts axons and involves both metabolic and structural disorders. The DCA-treated rat may provide insight into the pathogenesis of peripheral neuropathy and facilitate development of adjuvant therapeutics to prevent this disorder that currently restricts the clinical use of DCA. PMID:19680144

  16. Opioid overdose with gluteal compartment syndrome and acute peripheral neuropathy

    PubMed Central

    Adrish, Muhammad; Duncalf, Richard; Diaz-Fuentes, Gilda; Venkatram, Sindhaghatta

    2014-01-01

    Patient: Male, 42 Final Diagnosis: Gluteal compartment syndrome • acute peripheral nauropathy Symptoms: — Medication: — Clinical Procedure: — Specialty: Critical Care Medicine Objective: Management of emergency care Background: Heroin addiction is common, with an estimated 3.7 million Americans reporting to have used it at some point in their lives. Complications of opiate overdose include infection, rhabdomyolysis, respiratory depression and central or peripheral nervous system neurological complications. Conclusions: We present a 42-year-old male admitted after heroin use with heroin-related peripheral nervous system complication preceded by an acute gluteal compartment syndrome and severe rhabdomyolysis. Case Report: Early diagnosis and surgical intervention of the compartment syndrome can lead to full recovery while any delay in management can be devastating and can lead to permanent disability. The presence of peripheral nervous system injuries may portend a poor prognosis and can also lead to long term disability. Careful neurological evaluation for signs and symptoms of peripheral nervous system injuries is of paramount importance, as these may be absent at presentation in patients with opioid overdose. There is a potential risk of delaying a necessary treatment like fasciotomy in these patients by falsely attributing clinical symptoms to a preexisting neuropathy. Early EMG and nerve conduction studies should be considered when the etiology of underlying neurological weakness is unclear. PMID:24459539

  17. 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

  18. Peripheral Biomarkers Revisited: Integrative Profiling of Peripheral Samples for Psychiatric Research

    PubMed Central

    Hayashi-Takagi, Akiko; Vawter, Marquis P.; Iwamoto, Kazuya

    2016-01-01

    Peripheral samples, such as blood and skin, have been used for decades in psychiatric research as surrogates for central nervous system samples. Although the validity of the data obtained from peripheral samples has been questioned and other state-of-the-art techniques, such as human brain imaging, genomics, and induced pluripotent stem cells, seem to reduce the value of peripheral cells, accumulating evidence has suggested that revisiting peripheral samples is worthwhile. Here, we re-evaluate the utility of peripheral samples and argue that establishing an understanding of the common signaling and biological processes in the brain and peripheral samples is required for the validity of such models. First, we present an overview of the available types of peripheral cells and describe their advantages and disadvantages. We then briefly summarize the main achievements of omics studies, including epigenome, transcriptome, proteome, and metabolome analyses, as well as the main findings of functional cellular assays, the results of which imply that alterations in neurotransmission, metabolism, the cell cycle, and the immune system may be partially responsible for the pathophysiology of major psychiatric disorders such as schizophrenia. Finally, we discuss the future utility of peripheral samples for the development of biomarkers and tailor-made therapies, such as multimodal assays that are used as a battery of disease and trait pathways and that might be potent and complimentary tools for use in psychiatric research. PMID:24286759

  19. 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)

  20. Reliability and concurrent validity of a peripheral pulse oximeter and health-app system for the quantification of heart rate in healthy adults.

    PubMed

    Losa-Iglesias, Marta Elena; Becerro-de-Bengoa-Vallejo, Ricardo; Becerro-de-Bengoa-Losa, Klark Ricardo

    2016-06-01

    There are downloadable applications (Apps) for cell phones that can measure heart rate in a simple and painless manner. The aim of this study was to assess the reliability of this type of App for a Smartphone using an Android system, compared to the radial pulse and a portable pulse oximeter. We performed a pilot observational study of diagnostic accuracy, randomized in 46 healthy volunteers. The patients' demographic data and cardiac pulse were collected. Radial pulse was measured by palpation of the radial artery with three fingers at the wrist over the radius; a low-cost portable, liquid crystal display finger pulse oximeter; and a Heart Rate Plus for Samsung Galaxy Note®. This study demonstrated high reliability and consistency between systems with respect to the heart rate parameter of healthy adults using three systems. For all parameters, ICC was > 0.93, indicating excellent reliability. Moreover, CVME values for all parameters were between 1.66-4.06 %. We found significant correlation coefficients and no systematic differences between radial pulse palpation and pulse oximeter and a high precision. Low-cost pulse oximeter and App systems can serve as valid instruments for the assessment of heart rate in healthy adults. PMID:25038201

  1. Central Nervous System Lipoproteins

    PubMed Central

    Mahley, Robert W.

    2016-01-01

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

  2. Relationships of peripheral IGF-1, VEGF and BDNF levels to exercise-related changes in memory, hippocampal perfusion and volumes in older adults.

    PubMed

    Maass, Anne; Düzel, Sandra; Brigadski, Tanja; Goerke, Monique; Becke, Andreas; Sobieray, Uwe; Neumann, Katja; Lövdén, Martin; Lindenberger, Ulman; Bäckman, Lars; Braun-Dullaeus, Rüdiger; Ahrens, Dörte; Heinze, Hans-Jochen; Müller, Notger G; Lessmann, Volkmar; Sendtner, Michael; Düzel, Emrah

    2016-05-01

    Animal models point towards a key role of brain-derived neurotrophic factor (BDNF), insulin-like growth factor-I (IGF-I) and vascular endothelial growth factor (VEGF) in mediating exercise-induced structural and functional changes in the hippocampus. Recently, also platelet derived growth factor-C (PDGF-C) has been shown to promote blood vessel growth and neuronal survival. Moreover, reductions of these neurotrophic and angiogenic factors in old age have been related to hippocampal atrophy, decreased vascularization and cognitive decline. In a 3-month aerobic exercise study, forty healthy older humans (60 to 77years) were pseudo-randomly assigned to either an aerobic exercise group (indoor treadmill, n=21) or to a control group (indoor progressive-muscle relaxation/stretching, n=19). As reported recently, we found evidence for fitness-related perfusion changes of the aged human hippocampus that were closely linked to changes in episodic memory function. Here, we test whether peripheral levels of BDNF, IGF-I, VEGF or PDGF-C are related to changes in hippocampal blood flow, volume and memory performance. Growth factor levels were not significantly affected by exercise, and their changes were not related to changes in fitness or perfusion. However, changes in IGF-I levels were positively correlated with hippocampal volume changes (derived by manual volumetry and voxel-based morphometry) and late verbal recall performance, a relationship that seemed to be independent of fitness, perfusion or their changes over time. These preliminary findings link IGF-I levels to hippocampal volume changes and putatively hippocampus-dependent memory changes that seem to occur over time independently of exercise. We discuss methodological shortcomings of our study and potential differences in the temporal dynamics of how IGF-1, VEGF and BDNF may be affected by exercise and to what extent these differences may have led to the negative findings reported here. PMID:26545456

  3. Inconsistent Correlation Between Carotid Artery Intima-Media Thickness and Peripheral Arterial Tonometry: Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

    PubMed

    Lemos, Sara P; Passos, Valéria Maria A; Brant, Luisa C C; Bensenor, Isabela J M; Ribeiro, Antônio Luiz P; Barreto, Sandhi Maria

    2015-08-01

    To estimate the association between 2 markers for atherosclerosis, measurements of carotid artery intima-media thickness (IMT) and of peripheral arterial tonometry (PAT), and to evaluate the role of traditional cardiovascular risk factors in this association.We applied the 2 diagnostic tests to 588 participants from the ELSA-Brazil longitudinal study cohort. The PAT measurements, obtained with the EndoPAT2000, were the reactive hyperemia index (RHI), the Framingham RHI (F-RHI), and the mean basal pulse amplitude (BPA). We used the mean of the mean scores of carotid IMT of the distal layers of the left and right common carotids obtained by ultrasonography after 3 cardiac cycles. We used linear regression and the Spearman correlation coefficient to test the relationship between the 2 markers, and multiple linear regressions to exam the relationship between the RHI/F-RHI scores and the mean BPA and IMT scores after adjusting for cardiovascular risk factors.In the multivariate analysis, RHI (but not F-RHI) was positively correlated with the mean of the means of the IMT values after adjusting for sex and risk factors connected with both measures (β = 0.05, P = 0.02). Mean BPA did not remain significantly associated with IMT after adjusting for common risk factors.We found that the higher the IMT (or the worse the IMT), the higher the RHI (or the better the endothelial function). F-RHI was not associated with IMT. These 2 results are against the direction that one would expect and may imply that digital endothelial function (RHI and F-RHI) and IMT correspond to distinct and independent stages of the complex atherosclerosis process and represent different pathways in the disease's progression. Therefore, IMT and PAT measures may be considered complementary and not interchangeable. PMID:26287431

  4. Monoclonal antibody BM89 recognizes a novel cell surface glycoprotein of the L2/HNK-1 family in the developing mammalian nervous system.

    PubMed

    Merkouri, E; Matsas, R

    1992-09-01

    A monoclonal antibody, BM89, obtained with Triton X-114-treated pig synaptic membranes as an immunogen, recognizes a neuronal antigen in the newborn porcine nervous system. By immunohistochemistry, BM89 staining was observed within the neuropil of all areas of the forebrain and spinal cord tested. In addition, BM89 labeled the cell bodies and proximal dendrites of spinal cord neurons. In the peripheral nervous system, BM89 immunoreactivity was present in a subpopulation of dorsal root ganglion neurons and was predominantly associated with non-myelinated axons in peripheral nerves. Initial biochemical characterization of the antigen in pig brain showed that it is an integral membrane glycoprotein with a molecular weight of 41,000. Moreover, it cross-reacts with the L2/HNK-1 carbohydrate epitope expressed by members of a large family of glycoproteins. Homologous antigens with molecular weights of 41,000-43,000 were identified in the rat, rabbit and fetal human brain. Immunoblotting and immunohistochemistry revealed that the epitope recognized by BM89 is developmentally regulated in the rat nervous system. In cryostat sections from rat cerebellum, spinal cord and dorsal root ganglia, an age-dependent decline of BM89 immunoreactivity was observed during postnatal development. In the cerebellum, the BM89 epitope was very abundant in cells of the external and the internal granular layers between postnatal days 5 and 15. During this period some staining was also identified in the developing molecular layer and the prospective white matter. Subsequently, and in the adult, overall staining was greatly reduced and remaining immunoreactivity was associated only with the internal granular layer. In the spinal cord and dorsal root ganglia, staining was very prominent at postnatal day 5; it decreased considerably thereafter and was barely detectable in the adult. Immunostaining of rat brain and dorsal root ganglion cultures revealed that the BM89 antigen is a cell surface

  5. 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

  6. Cholinergic components of nervous system of Schistosoma mansoni and S. haematobium (Digenea: Schistosomatidae).

    PubMed

    Reda, Enayat S; El-Shabasy, Eman A; Said, Ashraf E; Mansour, Mohamed F A; Saleh, Mai A

    2016-08-01

    A comparison has been made for the first time between the cholinergic components of the nervous system of important human digeneans namely Schistosoma mansoni and Schistosoma haematobium from infected hamster (Cricentus auratus) in Egypt. In each parasite, the central nervous system consists of two cerebral ganglia and three pairs of nerve cords (ventral, lateral, and dorsal) linked together by some transverse connectives and numerous ring commissures. Peripheral cholinergic innervation was detected in oral and ventral suckers and in some parts of female reproductive system in both species, but there were some differences. The possible functions of some of these nervous components are discussed. PMID:27130318

  7. Motoneurons of the adult marmoset can grow axons and reform motor endplates through a peripheral nerve bridge joining the locally injured cervical spinal cord to the denervated biceps brachii muscle.

    PubMed

    Emery, E; Rhrich-Haddout, F; Kassar-Duchossoy, L; Lyoussi, B; Tadié, M; Horvat, J C

    2000-12-15

    Reconnection of the injured spinal cord (SC) of the marmoset with the denervated biceps brachii muscle (BB) was obtained by using a peripheral nerve (PN) bridge. In 13 adult males, a 45 mm segment of the peroneal nerve was removed: one end was implanted unilaterally into the cervical SC of the same animal (autograft), determining a local injury, although the other end was either directly inserted into the BB (Group A) or, alternatively, sutured to its transected motor nerve, the musculocutaneous nerve (Group B). From 2-4 months post-surgery, eight out of the 10 surviving animals responded by a contraction of the BB to electrical stimulations of the PN bridge. All ten were then processed for a morphological study. As documented by retrograde axonal tracing studies using horse radish peroxidase or Fast Blue (FB), a mean number of 314 (Group A) or 45 (Group B) spinal neurons, mainly located close to the site of injury and grafting, re-expressed a capacity to grow and extend axons into the PN bridge. Most of these regenerated axons were able to grow up to the BB and form or reform functional motor endplates. Many of the spinal neurons that were retrogradely labeled with FB simultaneously displayed immunoreactivity for choline acetyl-transferase and consequently were assumed to be motoneurons. Reinnervation and regeneration of the BB were documented by methods revealing axon terminals, endplates and myofibrillary ATPase activity. Our results indicate that motoneurons of the focally injured SC of a small-sized primate can, following the example of the adult rat, re-establish a lost motor function by extending new axons all the way through a PN bridge connected to a denervated skeletal muscle. PMID:11107167

  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. PMID:26580325

  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. Study of the effects of semiconductor laser irradiation on peripheral nerve injury

    NASA Astrophysics Data System (ADS)

    Xiong, G. X.; Li, P.

    2012-11-01

    In order to study to what extent diode laser irradiation effects peripheral nerve injury, the experimental research was made on rabbits. Experimental results show that low-energy semiconductor laser can promote axonal regeneration and improve nervous function. It is also found that simultaneous exposure of the injured peripheral nerve and corresponding spinal segments to laser irradiation may achieve the most significant results.

  11. Brain and nervous system (image)

    MedlinePlus

    The nervous system controls the many complicated and interconnected functions of the body and mind. Motor, sensory cognitive and autonomic function are all coordinated and driven by the brain and nerves. As people age, nerve ...

  12. Brain and nervous system (image)

    MedlinePlus

    The nervous system controls the many complicated and interconnected functions of the body and mind. Motor, sensory cognitive and autonomic function are all coordinated and driven by the brain and nerves. As people age, ...

  13. Peripheral Nerve Disorders

    MedlinePlus

    ... spinal cord. Like static on a telephone line, peripheral nerve disorders distort or interrupt the messages between the brain ... body. There are more than 100 kinds of peripheral nerve disorders. They can affect one nerve or many nerves. ...

  14. MEGF9: a novel transmembrane protein with a strong and developmentally regulated expression in the nervous system.

    PubMed

    Brandt-Bohne, Ulrike; Keene, Douglas R; White, Fletcher A; Koch, Manuel

    2007-01-15

    MEGF9 [multiple EGF (epidermal growth factor)-like-domains 9], a novel transmembrane protein with multiple EGF-like repeats, is predominantly expressed in the developing and adult CNS (central nervous system) and PNS (peripheral nervous system). The domain structure of MEGF9 consists of an N-terminal region with several potential O-glycosylation sites followed by five EGF-like domains, which are highly homologous with the short arms of laminins. Following one single pass transmembrane domain, a highly conserved short intracellular domain with potential phosphorylation sites is present. The protein was recombinantly expressed and characterized as a tissue component. To study the expression pattern further, immunohistochemistry was performed and staining was detected in Purkinje cells of the cerebellum and in glial cells of the PNS. Additional expression was observed in the epidermal layer of skin, papillae of the tongue and the epithelium of the gastrointestinal tract. By immunoelectron microscopy, MEGF9 was detected in glial cells of the sciatic nerve facing the basement membrane. MEGF9 represents a novel putative receptor, expressed in neuronal and non-neuronal tissues, that is regulated during development and could function as a guidance or signalling molecule. PMID:16981854

  15. 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

  16. 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

  17. Controversies related to electromagnetic field exposure on peripheral nerves.

    PubMed

    Say, Ferhat; Altunkaynak, Berrin Zuhal; Coşkun, Sina; Deniz, Ömür Gülsüm; Yıldız, Çağrı; Altun, Gamze; Kaplan, Arife Ahsen; Kaya, Sefa Ersan; Pişkin, Ahmet

    2016-09-01

    Electromagnetic field (EMF) is a pervasive environmental presence in modern society. In recent years, mobile phone usage has increased rapidly throughout the world. As mobile phones are generally held close to the head while talking, studies have mostly focused on the central and peripheral nervous system. There is a need for further research to ascertain the real effect of EMF exposure on the nervous system. Several studies have clearly demonstrated that EMF emitted by cell phones could affect the systems of the body as well as functions. However, the adverse effects of EMF emitted by mobile phones on the peripheral nerves are still controversial. Therefore, this review summarizes current knowledge on the possible positive or negative effects of electromagnetic field on peripheral nerves. PMID:26718608

  18. Abnormal calcium homeostasis in peripheral neuropathies

    PubMed Central

    Fernyhough, Paul; Calcutt, Nigel A.

    2010-01-01

    Abnormal neuronal calcium (Ca2+) homeostasis has been implicated in numerous diseases of the nervous system. The pathogenesis of two increasingly common disorders of the peripheral nervous system, namely neuropathic pain and diabetic polyneuropathy, has been associated with aberrant Ca2+ channel expression and function. Here we review the current state of knowledge regarding the role of Ca2+ dyshomeostasis and associated mitochondrial dysfunction in painful and diabetic neuropathies. The central impact of both alterations of Ca2+ signalling at the plasma membrane and also intracellular Ca2+ handling on sensory neuron function is discussed and related to abnormal endoplasmic reticulum performance. We also present new data highlighting sub-optimal axonal Ca 2+ signalling in diabetic neuropathy and discuss the putative role for this abnormality in the induction of axonal degeneration in peripheral neuropathies. The accumulating evidence implicating Ca2+ dysregulation with both painful and degenerative neuropathies, along with recent advances in understanding of regional variations in Ca2+ channel and pump structures, makes modulation of neuronal Ca2+ handling an increasingly viable approach for therapeutic interventions against the painful and degenerative aspects of many peripheral neuropathies. PMID:20034667

  19. Detection of peripheral nerve pathology

    PubMed Central

    Seelig, Michael J.; Baker, Jonathan C.; Mackinnon, Susan E.; Pestronk, Alan

    2013-01-01

    Objective: To compare accuracy of ultrasound and MRI for detecting focal peripheral nerve pathology, excluding idiopathic carpal or cubital tunnel syndromes. Methods: We performed a retrospective review of patients referred for neuromuscular ultrasound to identify patients who had ultrasound and MRI of the same limb for suspected brachial plexopathy or mononeuropathies, excluding carpal/cubital tunnel syndromes. Ultrasound and MRI results were compared to diagnoses determined by surgical or, if not performed, clinical/electrodiagnostic evaluation. Results: We identified 53 patients who had both ultrasound and MRI of whom 46 (87%) had nerve pathology diagnosed by surgical (n = 39) or clinical/electrodiagnostic (n = 14) evaluation. Ultrasound detected the diagnosed nerve pathology (true positive) more often than MRI (43/46 vs 31/46, p < 0.001). Nerve pathology was correctly excluded (true negative) with equal frequency by MRI and ultrasound (both 6/7). In 25% (13/53), ultrasound was accurate (true positive or true negative) when MRI was not. These pathologies were typically (10/13) long (>2 cm) and only occasionally (2/13) outside the MRI field of view. MRI missed multifocal pathology identified with ultrasound in 6 of 7 patients, often (5/7) because pathology was outside the MRI field of view. Conclusions: Imaging frequently detects peripheral nerve pathology and contributes to the differential diagnosis in patients with mononeuropathies and brachial plexopathies. Ultrasound is more sensitive than MRI (93% vs 67%), has equivalent specificity (86%), and better identifies multifocal lesions than MRI. In sonographically accessible regions ultrasound is the preferred initial imaging modality for anatomic evaluation of suspected peripheral nervous system lesions. PMID:23553474

  20. A gain-of-function screen for genes that affect the development of the Drosophila adult external sensory organ.

    PubMed Central

    Abdelilah-Seyfried, S; Chan, Y M; Zeng, C; Justice, N J; Younger-Shepherd, S; Sharp, L E; Barbel, S; Meadows, S A; Jan, L Y; Jan, Y N

    2000-01-01

    The Drosophila adult external sensory organ, comprising a neuron and its support cells, is derived from a single precursor cell via several asymmetric cell divisions. To identify molecules involved in sensory organ development, we conducted a tissue-specific gain-of-function screen. We screened 2293 independent P-element lines established by P. Rorth and identified 105 lines, carrying insertions at 78 distinct loci, that produced misexpression phenotypes with changes in number, fate, or morphology of cells of the adult external sensory organ. On the basis of the gain-of-function phenotypes of both internal and external support cells, we subdivided the candidate lines into three classes. The first class (52 lines, 40 loci) exhibits partial or complete loss of adult external sensory organs. The second class (38 lines, 28 loci) is associated with increased numbers of entire adult external sensory organs or subsets of sensory organ cells. The third class (15 lines, 10 loci) results in potential cell fate transformations. Genetic and molecular characterization of these candidate lines reveals that some loci identified in this screen correspond to genes known to function in the formation of the peripheral nervous system, such as big brain, extra macrochaetae, and numb. Also emerging from the screen are a large group of previously uncharacterized genes and several known genes that have not yet been implicated in the development of the peripheral nervous system. PMID:10835395

  1. Evaluating Peripheral Displays

    NASA Astrophysics Data System (ADS)

    Matthews, Tara; Hsieh, Gary; Mankoff, Jennifer

    Although peripheral displays have been a domain of inquiry for over a decade now, evaluation criteria and techniques for this area are still being created. Peripheral display evaluation is an acknowledged challenge in a field setting. This chapter first describes models and methods that have been tailored specifically to evaluating peripheral displays (measuring how well they achieve their goals). Then, we present evaluation criteria used in past evaluations of peripheral displays, ranging from issues such as learnability to distraction. After explaining how these criteria have been assessed in the past, we present a case study evaluation of two e-mail peripheral displays that demonstrates the pros and cons of various evaluation techniques.

  2. Peripheral ossifying fibroma: case report.

    PubMed

    Pradeep, A R; Guruprasad, C N; Agarwal, Esha

    2012-01-01

    We present a case of peripheral ossifying fibroma (POF) in a 17-year-old boy. Clinical, radiographic and histologic characteristics are discussed and recommendations regarding differential diagnosis, treatment and follow-up are provided. Lesions histologically similar to POF have been given various names in the existing literature; therefore, the controversial varied nomenclature and possible etiopathogenesis of POF are discussed. A slowly growing soft tissue mass with speckled calcifications in the anterior oral cavity of children or young adults should raise the suspicion of a reactive gingival lesion such as POF. PMID:23252197

  3. Neurotropic Enterovirus Infections in the Central Nervous System

    PubMed Central

    Huang, Hsing-I; Shih, Shin-Ru

    2015-01-01

    Enteroviruses are a group of positive-sense single stranded viruses that belong to the Picornaviridae family. Most enteroviruses infect humans from the gastrointestinal tract and cause mild symptoms. However, several enteroviruses can invade the central nervous system (CNS) and result in various neurological symptoms that are correlated to mortality associated with enteroviral infections. In recent years, large outbreaks of enteroviruses occurred worldwide. Therefore, these neurotropic enteroviruses have been deemed as re-emerging pathogens. Although these viruses are becoming large threats to public health, our understanding of these viruses, especially for non-polio enteroviruses, is limited. In this article, we review recent advances in the trafficking of these pathogens from the peripheral to the central nervous system, compare their cell tropism, and discuss the effects of viral infections in their host neuronal cells. PMID:26610549

  4. Subcortical cytoskeleton periodicity throughout the nervous system.

    PubMed

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

    2016-01-01

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

  5. Role of senescence marker p16 INK4a measured in peripheral blood T-lymphocytes in predicting length of hospital stay after coronary artery bypass surgery in older adults.

    PubMed

    Pustavoitau, Aliaksei; Barodka, Viachaslau; Sharpless, Norman E; Torrice, Chad; Nyhan, Daniel; Berkowitz, Dan E; Shah, Ashish S; Bandeen Roche, Karen J; Walston, Jeremy D

    2016-02-01

    Adults older than 65 years undergo more than 120,000 coronary artery bypass (CAB) procedures each year in the United States. Chronological age alone, though commonly used in prediction models of outcomes after CAB, does not alone reflect variability in aging process; thus, the risk of complications in older adults. We performed a prospective study to evaluate a relationship between senescence marker p16(INK4a) expression in peripheral blood T-lymphocytes (p16 levels in PBTLs) with aging and with perioperative outcomes in older CAB patients. We included 55 patients age 55 and older, who underwent CAB in Johns Hopkins Hospital between September 1st, 2010 and March 25th, 2013. Demographic, clinical and laboratory data following outline of the Society of Thoracic Surgeons data collection form was collected, and p16 mRNA levels in PBTLs were measured using TaqMan® qRT-PCR. Associations between p16 mRNA levels in PBTLs with length of hospital stay, frailty status, p16 protein levels in the aortic and left internal mammary artery tissue, cerebral oxygen saturation, and augmentation index as a measure of vascular stiffness were measured using regression analyses. Length of hospital stay was the primary outcome of interest, and major organ morbidity, mortality, and discharge to a skilled nursing facility were secondary outcomes. In secondary analysis, we evaluated associations between p16 mRNA levels in PBTLs and interleukin-6 levels using regression analyses. Median age of enrolled patients was 63.5 years (range 56-81 years), they were predominantly male (74.55%), of Caucasian descent (85.45%). Median log2(p16 levels in PBTLs) were 4.71 (range 1.10-6.82). P16 levels in PBTLs were significantly associated with chronological age (mean difference 0.06 for each year increase in age, 95% CI 0.01-0.11) and interleukin 6 levels (mean difference 0.09 for each pg/ml increase in IL-6 levels, 95% CI 0.01-0.18). There were no significant associations with frailty status, augmentation

  6. [Research Progress in Seeding Cells of Peripheral Nerve].

    PubMed

    Shi, Gengqiang; Hu, Yi

    2015-04-01

    Seeding cells play an important role in the peripheral nerve damage repair. Seeding cells studied conse- quently in peripheral nerve are Schwann cells, bone marrow mesenchymal stem cells and neural stem cells. Schwann cells, the first seeding cells, are various unique glial cells in the peripheral nervous system, which can form the myelin sheath for insulation and package of the neuron projecting axons in the peripheral nervous system so that the conduction velocity of the nerve signal was accelerated. It can be proved that Schwann cells played an important role in the maintenance of peripheral nerve function and in the regeneration process after peripheral nerve injury. The second, bone marrow mesenchymal stem cells are the various mesenchymal stem cells mainly exist in the systemic connective tissues and organs. These functional stem cells are often studied at present, and it has been found that they have exuberant proliferation and differentiation potentials. Neural stem cells, mentioned the third in sequence, are the kind of pluripotent cells with multi-directional differentiation, which could conduct the self-renewal function, and generate and differentiate neurons, astrocytes and oligodendrocytes through asymmetric cell division. These three types of seed cells are discussed in this paper. PMID:26211274

  7. Central nervous system involvement in T-cell lymphoma: A single center experience.

    PubMed

    Gurion, Ronit; Mehta, Neha; Migliacci, Jocelyn C; Zelenetz, Andrew; Moskowitz, Alison; Lunning, Matthew; Moskowitz, Craig; Hamlin, Paul; Horwitz, Steven

    2016-05-01

    Background We characterized the incidence of central nervous system (CNS) involvement, risk factors and outcome in a large single institution dataset of peripheral T-cell lymphoma (PTCL). Methods Retrospective review of the PTCL database at Memorial Sloan Kettering Cancer Center. We identified 231 patients with any subtype of PTCL between 1994-2011 with a minimum six months of follow-up or an event defined as relapse or death. Results Histologies included peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) (31.6%), angioimmunoblastic (16.9%), anaplastic large cell lymphoma (ALCL), ALK- (12.1%), ALCL, ALK + (6.1%), extranodal NK/T-cell lymphoma (7.4%), adult T-cell leukemia/lymphoma (ATLL) (7.4%), and transformed mycosis fungoides (8.7%). Seventeen patients had CNS disease (7%). Fifteen had CNS involvement with PTCL and two had diffuse large B-cell lymphoma and glioblastoma. Median time to CNS involvement was 3.44 months (0.16-103.1). CNS prophylaxis was given to 24 patients (primarily intrathecal methotrexate). Rates of CNS involvement were not different in patients who received prophylaxis. Univariate analysis identified stage III-IV, bone marrow involvement, >1 extranodal site and ATLL as risk factors for CNS disease. On multivariate analysis, >1 extranodal site and international prognostic index (IPI) ≥ 3 were predictive for CNS involvement. The median survival of patients with CNS involvement was 2.63 months (0.10-75). Conclusions Despite high relapse rates, PTCL, except ATLL, carries a low risk of CNS involvement. Prognosis with CNS involvement is poor and risk factors include: >1 extra nodal site and IPI ≥3. PMID:27046135

  8. Peripheral and central mechanisms of stress resilience

    PubMed Central

    Pfau, Madeline L.; Russo, Scott J.

    2014-01-01

    Viable new treatments for depression and anxiety have been slow to emerge, likely owing to the complex and incompletely understood etiology of these disorders. A budding area of research with great therapeutic promise involves the study of resilience, the adaptive maintenance of normal physiology and behavior despite exposure to marked psychological stress. This phenomenon, documented in both humans and animal models, involves coordinated biological mechanisms in numerous bodily systems, both peripheral and central. In this review, we provide an overview of resilience mechanisms throughout the body, discussing current research in animal models investigating the roles of the neuroendocrine, immune, and central nervous systems in behavioral resilience to stress. PMID:25506605

  9. Atf3 mutant mice show reduced axon regeneration and impaired regeneration-associated gene induction after peripheral nerve injury.

    PubMed

    Gey, Manuel; Wanner, Renate; Schilling, Corinna; Pedro, Maria T; Sinske, Daniela; Knöll, Bernd

    2016-08-01

    Axon injury in the peripheral nervous system (PNS) induces a regeneration-associated gene (RAG) response. Atf3 (activating transcription factor 3) is such a RAG and ATF3's transcriptional activity might induce 'effector' RAGs (e.g. small proline rich protein 1a (Sprr1a), Galanin (Gal), growth-associated protein 43 (Gap43)) facilitating peripheral axon regeneration. We provide a first analysis of Atf3 mouse mutants in peripheral nerve regeneration. In Atf3 mutant mice, facial nerve regeneration and neurite outgrowth of adult ATF3-deficient primary dorsal root ganglia neurons was decreased. Using genome-wide transcriptomics, we identified a neuropeptide-encoding RAG cluster (vasoactive intestinal peptide (Vip), Ngf, Grp, Gal, Pacap) regulated by ATF3. Exogenous administration of neuropeptides enhanced neurite growth of Atf3 mutant mice suggesting that these molecules might be effector RAGs of ATF3's pro-regenerative function. In addition to the induction of growth-promoting molecules, we present data that ATF3 suppresses growth-inhibiting molecules such as chemokine (C-C motif) ligand 2. In summary, we show a pro-regenerative ATF3 function during PNS nerve regeneration involving transcriptional activation of a neuropeptide-encoding RAG cluster. ATF3 is a general injury-inducible factor, therefore ATF3-mediated mechanisms identified herein might apply to other cell and injury types. PMID:27581653

  10. Atf3 mutant mice show reduced axon regeneration and impaired regeneration-associated gene induction after peripheral nerve injury

    PubMed Central

    Gey, Manuel; Wanner, Renate; Schilling, Corinna; Pedro, Maria T.; Sinske, Daniela

    2016-01-01

    Axon injury in the peripheral nervous system (PNS) induces a regeneration-associated gene (RAG) response. Atf3 (activating transcription factor 3) is such a RAG and ATF3's transcriptional activity might induce ‘effector’ RAGs (e.g. small proline rich protein 1a (Sprr1a), Galanin (Gal), growth-associated protein 43 (Gap43)) facilitating peripheral axon regeneration. We provide a first analysis of Atf3 mouse mutants in peripheral nerve regeneration. In Atf3 mutant mice, facial nerve regeneration and neurite outgrowth of adult ATF3-deficient primary dorsal root ganglia neurons was decreased. Using genome-wide transcriptomics, we identified a neuropeptide-encoding RAG cluster (vasoactive intestinal peptide (Vip), Ngf, Grp, Gal, Pacap) regulated by ATF3. Exogenous administration of neuropeptides enhanced neurite growth of Atf3 mutant mice suggesting that these molecules might be effector RAGs of ATF3's pro-regenerative function. In addition to the induction of growth-promoting molecules, we present data that ATF3 suppresses growth-inhibiting molecules such as chemokine (C-C motif) ligand 2. In summary, we show a pro-regenerative ATF3 function during PNS nerve regeneration involving transcriptional activation of a neuropeptide-encoding RAG cluster. ATF3 is a general injury-inducible factor, therefore ATF3-mediated mechanisms identified herein might apply to other cell and injury types. PMID:27581653

  11. Glutamate in peripheral organs: Biology and pharmacology.

    PubMed

    Du, Jie; Li, Xiao-Hui; Li, Yuan-Jian

    2016-08-01

    Glutamate is a versatile molecule existing in both the central nervous system and peripheral organs. Previous studies have mainly focussed on the biological effect of glutamate in the brain. Recently, abundant evidence has demonstrated that glutamate also participates in the regulation of physiopathological functions in peripheral tissues, including the lung, kidney, liver, heart, stomach and immune system, where the glutamate/glutamate receptor/glutamate transporter system plays an important role in the pathogenesis of certain diseases, such as myocardial ischaemia/reperfusion injury and acute gastric mucosa injury. All these findings provide new insight into the biology and pharmacology of glutamate and suggest a potential therapeutic role of glutamate in non-neurological diseases. PMID:27164423

  12. An RNA binding protein promotes axonal integrity in peripheral neurons by destabilizing REST.

    PubMed

    Cargnin, Francesca; Nechiporuk, Tamilla; Müllendorff, Karin; Stumpo, Deborah J; Blackshear, Perry J; Ballas, Nurit; Mandel, Gail

    2014-12-10

    The RE1 Silencing Transcription Factor (REST) acts as a governor of the mature neuronal phenotype by repressing a large consortium of neuronal genes in non-neuronal cells. In the developing nervous system, REST is present in progenitors and downregulated at terminal differentiation to promote acquisition of mature neuronal phenotypes. Paradoxically, REST is still detected in some regions of the adult nervous system, but how REST levels are regulated, and whether REST can still repress neuronal genes, is not known. Here, we report that homeostatic levels of REST are maintained in mature peripheral neurons by a constitutive post-transcriptional mechanism. Specifically, using a three-hybrid genetic screen, we identify the RNA binding protein, ZFP36L2, associated previously only with female fertility and hematopoiesis, and show that it regulates REST mRNA stability. Dorsal root ganglia in Zfp36l2 knock-out mice, or wild-type ganglia expressing ZFP36L2 shRNA, show higher steady-state levels of Rest mRNA and protein, and extend thin and disintegrating axons. This phenotype is due, at least in part, to abnormally elevated REST levels in the ganglia because the axonal phenotype is attenuated by acute knockdown of REST in Zfp36l2 KO DRG explants. The higher REST levels result in lower levels of target genes, indicating that REST can still fine-tune gene expression through repression. Thus, REST levels are titrated in mature peripheral neurons, in part through a ZFP36L2-mediated post-transcriptional mechanism, with consequences for axonal integrity. PMID:25505318

  13. Environmental effects on the central nervous system.

    PubMed Central

    Paulson, G W

    1977-01-01

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

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

    PubMed

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

    2007-10-01

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

  15. The Emerging Roles of the Calcineurin-Nuclear Factor of Activated T-Lymphocytes Pathway in Nervous System Functions and Diseases.

    PubMed

    Kipanyula, Maulilio John; Kimaro, Wahabu Hamisi; Seke Etet, Paul F

    2016-01-01

    The ongoing epidemics of metabolic diseases and increase in the older population have increased the incidences of neurodegenerative diseases. Evidence from murine and cell line models has implicated calcineurin-nuclear factor of activated T-lymphocytes (NFAT) signaling pathway, a Ca(2+)/calmodulin-dependent major proinflammatory pathway, in the pathogenesis of these diseases. Neurotoxins such as amyloid-β, tau protein, and α-synuclein trigger abnormal calcineurin/NFAT signaling activities. Additionally increased activities of endogenous regulators of calcineurin like plasma membrane Ca(2+)-ATPase (PMCA) and regulator of calcineurin 1 (RCAN1) also cause neuronal and glial loss and related functional alterations, in neurodegenerative diseases, psychotic disorders, epilepsy, and traumatic brain and spinal cord injuries. Treatment with calcineurin/NFAT inhibitors induces some degree of neuroprotection and decreased reactive gliosis in the central and peripheral nervous system. In this paper, we summarize and discuss the current understanding of the roles of calcineurin/NFAT signaling in physiology and pathologies of the adult and developing nervous system, with an emphasis on recent reports and cutting-edge findings. Calcineurin/NFAT signaling is known for its critical roles in the developing and adult nervous system. Its role in physiological and pathological processes is still controversial. However, available data suggest that its beneficial and detrimental effects are context-dependent. In view of recent reports calcineurin/NFAT signaling is likely to serve as a potential therapeutic target for neurodegenerative diseases and conditions. This review further highlights the need to characterize better all factors determining the outcome of calcineurin/NFAT signaling in diseases and the downstream targets mediating the beneficial and detrimental effects. PMID:27597899

  16. The Emerging Roles of the Calcineurin-Nuclear Factor of Activated T-Lymphocytes Pathway in Nervous System Functions and Diseases

    PubMed Central

    Kimaro, Wahabu Hamisi; Etet, Paul F. Seke

    2016-01-01

    The ongoing epidemics of metabolic diseases and increase in the older population have increased the incidences of neurodegenerative diseases. Evidence from murine and cell line models has implicated calcineurin-nuclear factor of activated T-lymphocytes (NFAT) signaling pathway, a Ca2+/calmodulin-dependent major proinflammatory pathway, in the pathogenesis of these diseases. Neurotoxins such as amyloid-β, tau protein, and α-synuclein trigger abnormal calcineurin/NFAT signaling activities. Additionally increased activities of endogenous regulators of calcineurin like plasma membrane Ca2+-ATPase (PMCA) and regulator of calcineurin 1 (RCAN1) also cause neuronal and glial loss and related functional alterations, in neurodegenerative diseases, psychotic disorders, epilepsy, and traumatic brain and spinal cord injuries. Treatment with calcineurin/NFAT inhibitors induces some degree of neuroprotection and decreased reactive gliosis in the central and peripheral nervous system. In this paper, we summarize and discuss the current understanding of the roles of calcineurin/NFAT signaling in physiology and pathologies of the adult and developing nervous system, with an emphasis on recent reports and cutting-edge findings. Calcineurin/NFAT signaling is known for its critical roles in the developing and adult nervous system. Its role in physiological and pathological processes is still controversial. However, available data suggest that its beneficial and detrimental effects are context-dependent. In view of recent reports calcineurin/NFAT signaling is likely to serve as a potential therapeutic target for neurodegenerative diseases and conditions. This review further highlights the need to characterize better all factors determining the outcome of calcineurin/NFAT signaling in diseases and the downstream targets mediating the beneficial and detrimental effects. PMID:27597899

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

    PubMed Central

    Beckers, Patrick; Loesel, Rudi; Bartolomaeus, Thomas

    2013-01-01

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

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

    PubMed

    Beckers, Patrick; Loesel, Rudi; Bartolomaeus, Thomas

    2013-01-01

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

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

    PubMed

    Jänig, Wilfrid

    2014-05-01

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

  20. Adult-Onset Fatal Neurohepatopathy in a Woman Caused by MPV17 Mutation.

    PubMed

    Mendelsohn, Bryce A; Mehta, Neil; Hameed, Bilal; Pekmezci, Melike; Packman, Seymour; Ralph, Jeffrey

    2014-01-01

    Hepatocerebral mitochondrial DNA depletion syndromes are classically considered diseases of early childhood, typically affecting the liver, peripheral, and central nervous systems with a rapidly progressive course. Evidence is emerging that initial symptom onset can extend into adulthood, though few such cases have been reported. We describe a 25-year-old woman who presented initially with secondary amenorrhea, followed by a megaloblastic anemia, lactic acidosis, leukoencephalopathy, progressive peripheral neuropathy, and liver cirrhosis. An apparently homozygous P98L mutation was identified in MPV17, a gene associated with a lethal infantile neurohepatopathy. Homozygosity for the same allele was recently reported in a man with a similar hepatic and neurologic phenotype. This is the first clinical report of an adult female with this disorder, and the first to describe amenorrhea and megaloblastic anemia as likely associated symptoms. PMID:24190800

  1. NEW APPROACHES TO PHARMACOTHERAPY OF TUMORS OF THE NERVOUS SYSTEM DURING CHILDHOOD AND ADOLESCENCE

    PubMed Central

    Schor, Nina F.

    2009-01-01

    Tumors of the nervous system are among the most common and most chemoresistant neoplasms of childhood and adolescence. Malignant tumors of the brain collectively account for 21% of all cancers and 24% of all cancer-related deaths in this age group. Neuroblastoma, a peripheral nervous system tumor, is the most common extracranial solid tumor of childhood, and 65% of children with this tumor have only a 10 or 15% chance of living 5 years beyond the time of initial diagnosis. Novel pharmacological approaches to nervous system tumors are urgently needed. This review presents the role of and current challenges to pharmacotherapy of malignant tumors of the nervous system during childhood and adolescence and discusses novel approaches aimed at overcoming these challenges. PMID:19318043

  2. Serotonergic Innervation of the Salivary Glands and Central Nervous System of Adult Glossina pallidipes Austen (Diptera: Glossinidae), and the Impact of the Salivary Gland Hypertrophy Virus (GpSGHV) on the Host

    PubMed Central

    Guerra, Laura; Stoffolano, John G.; Belardinelli, Maria Cristina

    2016-01-01

    Using a serotonin antibody and confocal microscopy, this study reports for the first time direct serotonergic innervation of the muscle sheath covering the secretory region of the salivary glands of adult tsetse fly, Glossina pallidipes Austen. Reports to date, however, note that up until this finding, dipteran species previously studied lack a muscle sheath covering of the secretory region of the salivary glands. Direct innervation of the salivary gland muscle sheath of tsetse would facilitate rapid deployment of saliva into the host, thus delaying a host response. Our results also suggest that the neuronal and abnormal pattern seen in viral infected glands by the Glossina pallidipes salivary gland hypertrophy virus (GpSGHV) is due to a compensatory increased branching of the neurons of the salivary glands, which is associated with the increased size of the salivary glands in viral infected flies. This study shows for the first time serotonin in the cell bodies of the brain and thoracico-abdominal ganglion in adult tsetse, G. pallidipes Austen (Diptera: Glossinidae). A hypothesis is proposed as to whether innervation of the muscle sheath covering of the secretory region of the salivary glands is present in brachyceran compared with nematoceran dipterans; and, a plea is made that more research is needed to develop a blood feeding model, similar to that in the blow flies, for elucidating the various mechanisms involved in production and deployment of saliva. PMID:26798144

  3. Serotonergic Innervation of the Salivary Glands and Central Nervous System of Adult Glossina pallidipes Austen (Diptera: Glossinidae), and the Impact of the Salivary Gland Hypertrophy Virus (GpSGHV) on the Host.

    PubMed

    Guerra, Laura; Stoffolano, John G; Belardinelli, Maria Cristina; Fausto, Anna Maria

    2016-01-01

    Using a serotonin antibody and confocal microscopy, this study reports for the first time direct serotonergic innervation of the muscle sheath covering the secretory region of the salivary glands of adult tsetse fly, Glossina pallidipes Austen. Reports to date, however, note that up until this finding, dipteran species previously studied lack a muscle sheath covering of the secretory region of the salivary glands. Direct innervation of the salivary gland muscle sheath of tsetse would facilitate rapid deployment of saliva into the host, thus delaying a host response. Our results also suggest that the neuronal and abnormal pattern seen in viral infected glands by the Glossina pallidipes salivary gland hypertrophy virus (GpSGHV) is due to a compensatory increased branching of the neurons of the salivary glands, which is associated with the increased size of the salivary glands in viral infected flies. This study shows for the first time serotonin in the cell bodies of the brain and thoracico-abdominal ganglion in adult tsetse, G. pallidipes Austen (Diptera: Glossinidae). A hypothesis is proposed as to whether innervation of the muscle sheath covering of the secretory region of the salivary glands is present in brachyceran compared with nematoceran dipterans; and, a plea is made that more research is needed to develop a blood feeding model, similar to that in the blow flies, for elucidating the various mechanisms involved in production and deployment of saliva. PMID:26798144

  4. Peripheral phlebitis: a point-prevalence study.

    PubMed

    Washington, Georgita T; Barrett, Robin

    2012-01-01

    The purpose of this research study was to determine the factors influencing peripheral phlebitis in the adult medical-surgical population. The authors would then be able to use those data to determine whether a change in practice was warranted. Data collection and analysis of 188 intravenous sites revealed that females with higher doses of medications in intravenous sites of longer dwell times and suboptimal nutrition were at greater risk of developing peripheral phlebitis. The point prevalence was greater than the recommended 5%, which led the authors to review their facility's patient care and documentation practices. PMID:22759829

  5. Primitive neuroectodermal tumor of lungs in adults: a rare series of three cases treated with upfront chemo-radiation

    PubMed Central

    Pathak, Abhishek; Sharma, Neelam; Viswanath, Sundaram; Dutta, Vibha

    2016-01-01

    Primitive neuroectodermal tumors (PNETs) are highly malignant small round blue cell tumors of neuroectodermal origin belonging to either central nervous system, autonomic nervous system or peripheral Askin’s or Ewing’s group of neoplasms. The latter generally arise in soft tissues of trunk or axial skeleton in children and early adolescents. However in adults this entity is very uncommon. Of all peripheral entities, primary PNET of lungs without chest wall or pleural involvement in adults are extremely rare and have been scarcely reported in world literature as single case reports. We hereby report a series of three interesting cases of adult PNET of lung diagnosed and treated in our institute. The chief presenting complaints of these patients were of chest pain, cough and dyspnea. The cases were diagnosed on the basis of imaging and biopsy which confirmed these lesions to be of PNET histology, confirmed by immunopositivity for neuron specific enolase (NSE), synaptophysin, chromogranin, CD 99 and vimentin on immunohistochemistry (IHC). All three were deemed unresectable in view of infiltration of nearby vital organs and high chances of morbidity. They were treated with upfront chemotherapy followed by conformal radiotherapy (RT) to the residual disease to which they showed significant response both clinically and radiologically. Presently these patients are on regular follow-up for over 6 months without any evidence of progression of disease or distant metastasis. PMID:27413716

  6. Peripheral giant cell granuloma.

    PubMed

    Adlakha, V K; Chandna, P; Rehani, U; Rana, V; Malik, P

    2010-01-01

    Peripheral giant cell granuloma is a benign reactive lesion of gingiva. It manifests as a firm, soft, bright nodule or as a sessile or pedunculate mass. This article reports the management of peripheral giant cell granuloma in a 12-year-old boy by surgical excision. PMID:21273719

  7. Peripheral Color Demo

    PubMed Central

    2015-01-01

    A set of structured demonstrations of the vividness of peripheral color vision is provided by arrays of multicolored disks scaled with eccentricity. These demonstrations are designed to correct the widespread misconception that peripheral color vision is weak or nonexistent. PMID:27551354

  8. Peripheral Nociceptors as Immune Sensors in the Development of Pain and Itch.

    PubMed

    Wang, Tao; Ma, Chao

    2016-01-01

    The peripheral nervous system and the immune system perform a series of similar functionalities such as recognizing, responding, and adapting to external or internal stimuli despite significant morphological differences. The peripheral nervous system actively communicates and coordinates with the immune system to function as a unified defense system. The peripheral nervous system is highly regulated by the immune system, especially under inflammatory conditions. On the other hand, the nervous system can modulate the immune system via neurotransmitters and chemokines released by the peripheral nerve endings, particularly from nociceptors. In both physiological and pathological conditions, peripheral nociceptive (including pruriceptive) neurons may express a variety of immune-related receptors, such as chemokine receptors and immunoglobulin (Fc) receptors that are usually found on immune cells. Certain ligands such as chemokines and immune complexes may induce abnormal neuronal hyperexcitability and even ectopic action potential discharges, therefore producing the sensation of pain and/or itch in immune-related diseases. The immune-sensing mechanisms of peripheral nociceptors may play an important role in the development of chronic pain and pruritus and may indicate novel therapeutic strategies for these pathological conditions. PMID:26900064

  9. Role of insulin signaling impairment, adiponectin and dyslipidemia in peripheral and central neuropathy in mice

    PubMed Central

    Anderson, Nicholas J.; King, Matthew R.; Delbruck, Lina; Jolivalt, Corinne G.

    2014-01-01

    One of the tissues or organs affected by diabetes is the nervous system, predominantly the peripheral system (peripheral polyneuropathy and/or painful peripheral neuropathy) but also the central system with impaired learning, memory and mental flexibility. The aim of this study was to test the hypothesis that the pre-diabetic or diabetic condition caused by a high-fat diet (HFD) can damage both the peripheral and central nervous systems. Groups of C57BL6 and Swiss Webster mice were fed a diet containing 60% fat for 8 months and compared to control and streptozotocin (STZ)-induced diabetic groups that were fed a standard diet containing 10% fat. Aspects of peripheral nerve function (conduction velocity, thermal sensitivity) and central nervous system function (learning ability, memory) were measured at assorted times during the study. Both strains of mice on HFD developed impaired glucose tolerance, indicative of insulin resistance, but only the C57BL6 mice showed statistically significant hyperglycemia. STZ-diabetic C57BL6 mice developed learning deficits in the Barnes maze after 8 weeks of diabetes, whereas neither C57BL6 nor Swiss Webster mice fed a HFD showed signs of defects at that time point. By 6 months on HFD, Swiss Webster mice developed learning and memory deficits in the Barnes maze test, whereas their peripheral nervous system remained normal. In contrast, C57BL6 mice fed the HFD developed peripheral nerve dysfunction, as indicated by nerve conduction slowing and thermal hyperalgesia, but showed normal learning and memory functions. Our data indicate that STZ-induced diabetes or a HFD can damage both peripheral and central nervous systems, but learning deficits develop more rapidly in insulin-deficient than in insulin-resistant conditions and only in Swiss Webster mice. In addition to insulin impairment, dyslipidemia or adiponectinemia might determine the neuropathy phenotype. PMID:24764191

  10. Perspectives in regeneration and tissue engineering of peripheral nerves.

    PubMed

    Raimondo, Stefania; Fornaro, Michele; Tos, Pierluigi; Battiston, Bruno; Giacobini-Robecchi, Maria G; Geuna, Stefano

    2011-07-01

    Peripheral nerve injury is a common casualty and although peripheral nerve fibers retain a considerable regeneration potential also in the adult, recovery is usually rather poor, especially in case of large nerve defects. The aim of this paper is to address the perspectives in regeneration and tissue engineering after peripheral nerve injury by reviewing the relevant experimental studies in animal models. After a brief overview of the morphological changes related to peripheral nerve injury and regeneration, the paper will address the evolution of peripheral nerve tissue engineering with special focus on transplantation strategies, from organs and tissues to cells and genes, that can be carried out, particularly in case of severe nerve lesions with substance loss. Finally, the need for integrated research which goes beyond therapeutic strategies based on single approaches is emphasized, and the importance of bringing together the various complimentary disciplines which can contribute to the definition of effective new strategies for regenerating the injured peripheral nerve is outlined. PMID:21474294

  11. HIV Infection Seems to Affect Nervous System

    MedlinePlus

    ... fullstory_159344.html HIV Infection Seems to Affect Nervous System But symptoms tend to subside once antiretroviral drugs ... mild, it is clear that HIV affects the nervous system within days of infection," she said in a ...

  12. Aging changes in the nervous system

    MedlinePlus

    ... ency/article/004023.htm Aging changes in the nervous system To use the sharing features on this page, please enable JavaScript. The brain and nervous system are your body's central control center. They control ...

  13. Infections of the nervous system

    PubMed Central

    Parikh, Vevek; Tucci, Veronica; Galwankar, Sagar

    2012-01-01

    Glycemic control is an important aspect of patient care in the surgical Infections of the nervous system are among the most difficult infections in terms of the morbidity and mortality posed to patients, and thereby require urgent and accurate diagnosis. Although viral meningitides are more common, it is the bacterial meningitides that have the potential to cause a rapidly deteriorating condition that the physician should be familiar with. Viral encephalitis frequently accompanies viral meningitis, and can produce focal neurologic findings and cognitive difficulties that can mimic other neurologic disorders. Brain abscesses also have the potential to mimic and present like other neurologic disorders, and cause more focal deficits. Finally, other infectious diseases of the central nervous system, such as prion disease and cavernous sinus thrombosis, are explored in this review. PMID:22837896

  14. Anatomic evidence for peripheral neural processing in mammalian graviceptors

    NASA Technical Reports Server (NTRS)

    Ross, M. D.

    1985-01-01

    Ultrastructural study of utricular and saccular maculas demonstrates that their innervation patterns are complex. There is a clustering of type I and type II hair cells based upon a sharing of afferents, a system of efferent-type beaded fibers that is of intramacular (mostly calyceal) origin, and a plexus-like arrangement of afferents and efferents at many sites in the neuroepithelium. Results suggest that information concerning linear acceleration is processed peripherally, beginning at the hair cell level, before being sent to the central nervous system. The findings may supply a structural basis for peripheral adaptation to a constant stimulus, and for lateral inhibition to improve signal relative to noise.

  15. Lenalidomide Therapy for Patients With Relapsed and/or Refractory, Peripheral T-Cell Lymphomas

    ClinicalTrials.gov

    2012-04-18

    Peripheral T-cell Lymphomas; Adult T-cell Leukemia; Adult T-cell Lymphoma; Peripheral T-cell Lymphoma Unspecified; Angioimmunoblastic T-cell Lymphoma; Anaplastic Large Cell Lymphoma; T/Null Cell Systemic Type; Cutaneous t-Cell Lymphoma With Nodal/Visceral Disease

  16. The Nervous System and Gastrointestinal Function

    ERIC Educational Resources Information Center

    Altaf, Muhammad A.; Sood, Manu R.

    2008-01-01

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

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

    PubMed

    Osipov, Alexey; Utkin, Yuri

    2012-12-01

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

  18. [American trypanosomiasis (Chagas disease) and the nervous system].

    PubMed

    Spina-Franca, A

    1988-01-01

    Ten to twelve million people irregularly distributed mainly through extensive rural areas of Latin America are afflicted by American trypanosomiasis (Chagas disease). Trypanosoma cruzi is the etiological agent, and it is naturally transmitted to humans by hematophagous hemiptera of Triatominae sub-family. These hemiptera feed by biting and usually defecate in the area near the puncture wound. Mucous membranes of breaks in the continuity of skin serve as passage ways for the parasite present in the excrement of the bug. Acute and chronic forms of American trypanosomiasis occur. Nervous system involvement in the acute form may give rise to meningoencephalitis. Central and/or peripheral signs of nervous system involvement can occur in the chronic form. Neuronal depopulation due to cell destruction by direct parasitism during the acute stage of the disease is the main pathogenetic way pointed out to explain chronic forms of nervous system involvement. Chronic Chagas cardiopathy usually produces mural thrombi. Fragments of thrombus situated in the left ventricle may become detached and migrate with the bloodstream to cause embolic phenomena in distant vessels--as in brain vessels--thus causing embolic cerebrovascular insults. Data on clinical and experimental studies are critically analysed. PMID:3143493

  19. Peripheral Neuropathy: Symptoms and Signs

    MedlinePlus

    ... Research News Make a Difference Symptoms of Peripheral Neuropathy Print This Page Peripheral Neuropathy symptoms usually start ... slowly over many years. The symptoms of peripheral neuropathy often include: A sensation of wearing an invisible “ ...

  20. Visualizing Viral Dissemination in the Mouse Nervous System, Using a Green Fluorescent Protein-Expressing Borna Disease Virus Vector▿

    PubMed Central

    Ackermann, Andreas; Guelzow, Timo; Staeheli, Peter; Schneider, Urs; Heimrich, Bernd

    2010-01-01

    Borna disease virus (BDV) frequently persists in the brain of infected animals. To analyze viral dissemination in the mouse nervous system, we generated a mouse-adapted virus that expresses green fluorescent protein (GFP). This viral vector supported GFP expression for up to 150 days and possessed an extraordinary staining capacity, visualizing complete dendritic arbors as well as individual axonal fibers of infected neurons. GFP-positive cells were first detected in cortical areas from where the virus disseminated through the entire central nervous system (CNS). Late in infection, GFP expression was found in the sciatic nerve, demonstrating viral spread from the central to the peripheral nervous system. PMID:20219925

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

    NASA Astrophysics Data System (ADS)

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

    2015-09-01

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

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

    PubMed

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

    2007-08-01

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

  3. Occlusive Peripheral Arterial Disease

    MedlinePlus

    ... artery. Such people should seek medical care immediately. Did You Know... When people suddenly develop a painful, ... In This Article Animation 1 Peripheral Arterial Disease Did You Know 1 Did You Know... Figure 1 ...

  4. Peripheral Vascular Disease

    MedlinePlus

    ... Information Center Back to previous page En español Aneurysms and Dissections Angina Arrhythmia Bundle Branch Block Cardiomyopathy ... blockage including peripheral artery disease or PAD Aortic aneurysms Buerger's Disease Raynaud's Phenomenon Disease of the veins ...

  5. Peripheral Arterial Disease

    MedlinePlus

    Peripheral arterial disease (PAD) happens when there is a narrowing of the blood vessels outside of your heart. The cause of ... smoking. Other risk factors include older age and diseases like diabetes, high blood cholesterol, high blood pressure, ...

  6. Peripheral artery bypass - leg

    MedlinePlus

    ... P. Peripheral arterial diseases. In: Mann DL, Zipes DP, Libby P, Bonow RO, Braunwald E, eds. Braunwald's ... noncoronary obstructive vascular disease.In: Mann DL, Zipes DP, Libby P, Bonow RO, Braunwald E, eds. Braunwald's ...

  7. Peripheral Artery Disease (PAD)

    MedlinePlus

    ... changes and medication . View an animation of atherosclerosis Atherosclerosis and PAD Atherosclerosis is a disease in which plaque builds up ... of an artery. PAD is usually caused by atherosclerosis in the peripheral arteries (or outer regions away ...

  8. Pathological impact of SMN2 mis-splicing in adult SMA mice

    PubMed Central

    Sahashi, Kentaro; Ling, Karen K Y; Hua, Yimin; Wilkinson, John Erby; Nomakuchi, Tomoki; Rigo, Frank; Hung, Gene; Xu, David; Jiang, Ya-Ping; Lin, Richard Z; Ko, Chien-Ping; Bennett, C Frank; Krainer, Adrian R

    2013-01-01

    Loss-of-function mutations in SMN1 cause spinal muscular atrophy (SMA), a leading genetic cause of infant mortality. The related SMN2 gene expresses suboptimal levels of functional SMN protein, due to a splicing defect. Many SMA patients reach adulthood, and there is also adult-onset (type IV) SMA. There is currently no animal model for adult-onset SMA, and the tissue-specific pathogenesis of post-developmental SMN deficiency remains elusive. Here, we use an antisense oligonucleotide (ASO) to exacerbate SMN2 mis-splicing. Intracerebroventricular ASO injection in adult SMN2-transgenic mice phenocopies key aspects of adult-onset SMA, including delayed-onset motor dysfunction and relevant histopathological features. SMN2 mis-splicing increases during late-stage disease, likely accelerating disease progression. Systemic ASO injection in adult mice causes peripheral SMN2 mis-splicing and affects prognosis, eliciting marked liver and heart pathologies, with decreased IGF1 levels. ASO dose–response and time-course studies suggest that only moderate SMN levels are required in the adult central nervous system, and treatment with a splicing-correcting ASO shows a broad therapeutic time window. We describe distinctive pathological features of adult-onset and early-onset SMA. PMID:24014320

  9. Permanent Peripheral Neuropathy

    PubMed Central

    Higgins, Elizabeth

    2014-01-01

    The health risks and side effects of fluoroquinolone use include the risk of tendon rupture and myasthenia gravis exacerbation, and on August 15, 2013, the Food and Drug Administration updated its warning to include the risk of permanent peripheral neuropathy. We present a case of fluoroquinolone-induced peripheral neuropathy in a patient treated for clinically diagnosed urinary tract infection with ciprofloxacin antibiotic. PMID:26425618

  10. Electrophysiological characterization of adult-onset Niemann-Pick type C disease.

    PubMed

    Iodice, Rosa; Dubbioso, Raffaele; Topa, Antonietta; Ruggiero, Lucia; Pisciotta, Chiara; Esposito, Marcello; Tozza, Stefano; Santoro, Lucio; Manganelli, Fiore

    2015-01-15

    In infantile and juvenile Niemann-Pick type C (NPC) disease electrophysiological studies have shown central (CNS) and peripheral (PNS) nervous system abnormalities. However, an extensive electrophysiological evaluation of CNS and PNS in adult form of NPC is still lacking. The aim of the study is to assess in adult-onset NPC disease the involvement of CNS and PNS by a multimodal electrophysiological approach. Three patients affected by adult form of NPC disease underwent electrophysiological evaluation including nerve conduction study (NCS), magnetic motor (MEPs), visual (VEPs), somatosensory (SSEPs) and brainstem auditory (BAEPs) evoked potentials. NCS, MEPs, VEPs and upper limb SSEPs were normal. Lower limb SSEPs were abnormal in all patients and abnormalities were consistent with a length-dependent process affecting the central somatosensory pathway. BAEPs were abnormal in all patients with both peripheral and central impairment of auditory pathway. Our electrophysiological findings suggest that auditory and lower limb somatosensory pathways are constantly affected in adult-onset form of NPC disease. The involvement of PNS, pyramidal, visual and upper limb somatosensory pathways might occur later during the course of disease. PMID:25537619

  11. Addressing Neuroplastic Changes in Distributed Areas of the Nervous System Associated With Chronic Musculoskeletal Disorders.

    PubMed

    Pelletier, René; Higgins, Johanne; Bourbonnais, Daniel

    2015-11-01

    Present interventions utilized in musculoskeletal rehabilitation are guided, in large part, by a biomedical model where peripheral structural injury is believed to be the sole driver of the disorder. There are, however, neurophysiological changes across different areas of the peripheral and central nervous systems, including peripheral receptors, dorsal horn of the spinal cord, brain stem, sensorimotor cortical areas, and the mesolimbic and prefrontal areas associated with chronic musculoskeletal disorders, including chronic low back pain, osteoarthritis, and tendon injuries. These neurophysiological changes appear not only to be a consequence of peripheral structural injury but also to play a part in the pathophysiology of chronic musculoskeletal disorders. Neurophysiological changes are consistent with a biopsychosocial formulation reflecting the underlying mechanisms associated with sensory and motor findings, psychological traits, and perceptual changes associated with chronic musculoskeletal conditions. These changes, therefore, have important implications in the clinical manifestation, pathophysiology, and treatment of chronic musculoskeletal disorders. Musculoskeletal rehabilitation professionals have at their disposal tools to address these neuroplastic changes, including top-down cognitive-based interventions (eg, education, cognitive-behavioral therapy, mindfulness meditation, motor imagery) and bottom-up physical interventions (eg, motor learning, peripheral sensory stimulation, manual therapy) that induce neuroplastic changes across distributed areas of the nervous system and affect outcomes in patients with chronic musculoskeletal disorders. Furthermore, novel approaches such as the use of transcranial direct current stimulation and repetitive transcranial magnetic stimulation may be utilized to help renormalize neurological function. Comprehensive treatment addressing peripheral structural injury as well as neurophysiological changes occurring across

  12. Peripheral changes in endometriosis-associated pain

    PubMed Central

    Morotti, Matteo; Vincent, Katy; Brawn, Jennifer; Zondervan, Krina T.; Becker, Christian M.

    2014-01-01

    BACKGROUND Pain remains the cardinal symptom of endometriosis. However, to date, the underlying mechanisms are still only poorly understood. Increasing evidence points towards a close interaction between peripheral nerves, the peritoneal environment and the central nervous system in pain generation and processing. Recently, studies demonstrating nerve fibres and neurotrophic and angiogenic factors in endometriotic lesions and their vicinity have led to increased interest in peripheral changes in endometriosis-associated pain. This review focuses on the origin and function of these nerves and factors as well as possible peripheral mechanisms that may contribute to the generation and modulation of pain in women with endometriosis. METHODS We conducted a systematic search using several databases (PubMed, MEDLINE, EMBASE and CINAHL) of publications from January 1977 to October 2013 to evaluate the possible roles of the peripheral nervous system in endometriosis pathophysiology and how it can contribute to endometriosis-associated pain. RESULTS Endometriotic lesions and peritoneal fluid from women with endometriosis had pronounced neuroangiogenic properties with increased expression of new nerve fibres, a shift in the distribution of sensory and autonomic fibres in some locations, and up-regulation of several neurotrophins. In women suffering from deep infiltrating endometriosis and bowel endometriosis, in which the anatomical distribution of lesions is generally more closely related to pelvic pain symptoms, endometriotic lesions and surrounding tissues present higher nerve fibre densities compared to peritoneal lesions and endometriomas. More data are needed to fully confirm a direct correlation between fibre density in these locations and the amount of perceived pain. A better correlation between the presence of nerve fibres and pain symptoms seems to exist for eutopic endometrium. However, this appears not to be exclusive to endometriosis. No correlation between

  13. Lavender and the Nervous System

    PubMed Central

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

    2013-01-01

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

  14. Bortezomib-Induced Painful Peripheral Neuropathy: An Electrophysiological, Behavioral, Morphological and Mechanistic Study in the Mouse

    PubMed Central

    Bardini, Michela; Fazio, Grazia; Chiorazzi, Alessia; Meregalli, Cristina; Oggioni, Norberto; Shanks, Kathleen; Quartu, Marina; Serra, Maria Pina; Sala, Barbara; Cavaletti, Guido; Dorsey, Susan G.

    2013-01-01

    Bortezomib is the first proteasome inhibitor with significant antineoplastic activity for the treatment of relapsed/refractory multiple myeloma as well as other hematological and solid neoplasms. Peripheral neurological complications manifesting with paresthesias, burning sensations, dysesthesias, numbness, sensory loss, reduced proprioception and vibratory sensitivity are among the major limiting side effects associated with bortezomib therapy. Although bortezomib-induced painful peripheral neuropathy is clinically easy to diagnose and reliable models are available, its pathophysiology remains partly unclear. In this study we used well-characterized immune-competent and immune-compromised mouse models of bortezomib-induced painful peripheral neuropathy. To characterize the drug-induced pathological changes in the peripheral nervous system, we examined the involvement of spinal cord neuronal function in the development of neuropathic pain and investigated the relevance of the immune response in painful peripheral neuropathy induced by bortezomib. We found that bortezomib treatment induced morphological changes in the spinal cord, dorsal roots, dorsal root ganglia (DRG) and peripheral nerves. Neurophysiological abnormalities and specific functional alterations in Aδ and C fibers were also observed in peripheral nerve fibers. Mice developed mechanical allodynia and functional abnormalities of wide dynamic range neurons in the dorsal horn of spinal cord. Bortezomib induced increased expression of the neuronal stress marker activating transcription factor-3 in most DRG. Moreover, the immunodeficient animals treated with bortezomib developed a painful peripheral neuropathy with the same features observed in the immunocompetent mice. In conclusion, this study extends the knowledge of the sites of damage induced in the nervous system by bortezomib administration. Moreover, a selective functional vulnerability of peripheral nerve fiber subpopulations was found as well as

  15. Regeneration of respiratory pathways within spinal peripheral nerve grafts.

    PubMed

    Decherchi, P; Lammari-Barreault, N; Gauthier, P

    1996-01-01

    Central respiratory neurons exhibit normal activity after axonal regeneration within blind-ended peripheral nerve grafts (PNGs) inserted near the corresponding cell bodies in the medullary respiratory centers. Part of these medullary respiratory neurons project toward the spinal cord and contribute to descending respiratory pathways that control respiratory motoneurons. The present work investigates to what extent cervical respiratory pathways could be directed out of the central nervous system within PNGs inserted distant to the medullary respiratory nuclei. In adult rats (n = 13), autologous segments of the peroneal nerve were implanted into the ventrolateral part of the C2 spinal cord at the level of the descending respiratory pathways. Two to four months after grafting, electrophysiological recording of teased graft filaments (n = 562) revealed the presence of regenerated nerve fibers with unitary impulse traffic (n = 164) in all tested PNGs (n = 6). Respiratory discharges (n = 52) corresponded to efferent and afferent activity. Efferent respiratory discharges (n = 32) originated from central respiratory neurons which remained functional and preserved afferent connections. Retrograde horseradish peroxidase labeling applied to the distal cut end of PNGs (n = 7) revealed stained (42/1997) neurons in areas where respiratory cells have been described. Afferent respiratory discharges (n = 20) were synchronized with lung inflation but their origin (stretch pulmonary receptors and/or respiratory muscle receptors) was not determined. On the basis of additional data from light and electron microscopy of PNGs, comparison was made between anatomical, retrograde labeling, and electrophysiological data. The main conclusion is that spinal PNGs appear to be able to promote axonal regeneration of functional respiratory efferent and afferent pathways. PMID:8566201

  16. High-Dose Thiotepa Plus Peripheral Stem Cell Transplantation in Treating Patients With Refractory Solid Tumors

    ClinicalTrials.gov

    2013-03-06

    Brain and Central Nervous System Tumors; Childhood Germ Cell Tumor; Extragonadal Germ Cell Tumor; Ovarian Cancer; Retinoblastoma; Testicular Germ Cell Tumor; Unspecified Adult Solid Tumor, Protocol Specific; Unspecified Childhood Solid Tumor, Protocol Specific

  17. Subcortical cytoskeleton periodicity throughout the nervous system

    PubMed Central

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

    2016-01-01

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

  18. Wiring stability of the adult Drosophila olfactory circuit after lesion.

    PubMed

    Berdnik, Daniela; Chihara, Takahiro; Couto, Africa; Luo, Liqun

    2006-03-29

    Neuronal wiring plasticity in response to experience or injury has been reported in many parts of the adult nervous system. For instance, visual or somatosensory cortical maps can reorganize significantly in response to peripheral lesions, yet a certain degree of stability is essential for neuronal circuits to perform their dedicated functions. Previous studies on lesion-induced neuronal reorganization have primarily focused on systems that use continuous neural maps. Here, we assess wiring plasticity in a discrete neural map represented by the adult Drosophila olfactory circuit. Using conditional expression of toxins, we genetically ablated specific classes of neurons and examined the consequences on their synaptic partners or neighboring classes in the adult antennal lobe. We find no alteration of connection specificity between olfactory receptor neurons (ORNs) and their postsynaptic targets, the projection neurons (PNs). Ablating an ORN class maintains PN dendrites within their glomerular borders, and ORN axons normally innervating an adjacent target do not expand. Likewise, ablating PN classes does not alter their partner ORN axon connectivity. Interestingly, an increase in the contralateral ORN axon terminal density occurs in response to the removal of competing ipsilateral ORNs. Therefore, plasticity in this circuit can occur but is confined within a glomerulus, thereby retaining the wiring specificity of ORNs and PNs. We conclude that, although adult olfactory neurons can undergo plastic changes in response to the loss of competition, the olfactory circuit overall is extremely stable in preserving segregated information channels in this discrete map. PMID:16571743

  19. Building a scientific framework for studying hormonal effects on behavior and on the development of the sexually dimorphic nervous system

    EPA Science Inventory

    There has been increasing concern that low-dose exposure to hormonally active chemicals disrupts sexual differentiation of the brain and peripheral nervous system. There also has been active drug development research on the therapeutic potential of hormone therapy on behaviors. T...

  20. Peripheral neuropathies of rheumatologic disease and gluten-related disorders.

    PubMed

    Reda, Haatem; Chin, Russell L

    2014-09-01

    Peripheral nervous system disease is a common and often debilitating feature of many systemic rheumatologic disorders. Such involvement takes many forms, reflecting the variety of underlying pathophysiology, though most patients present with painful multifocal neuropathy (usually vasculitic) or a distal sensory more than motor peripheral neuropathy (sometimes vasculitic and nearly always axonal). The presence of peripheral nervous system involvement is often an early signal of the generalization of inflammatory disease in blood vessels or extravascular tissues, though peripheral neuropathy is not itself an independent predictor of mortality. Nonetheless, progressive multifocal neuropathy, motor neuropathy, small fiber neuropathy, and sensory neuronopathy should be treated early and aggressively with immunosuppression (or the gluten-free diet in appropriate situations) to limit morbidity. Given the rapidly evolving therapeutic landscape, partnership with a rheumatologist is essential. Treatment is usually sustained for 1 to 2 years, and remission is possible in many cases within 6 to 12 months, with variable rates of relapse and treatment resistance. Patients should be meticulously monitored for relapse with serial laboratory testing, electrodiagnostic studies, and clinical examination. Functional rating scores, such as the neuropathy impairment scale and the total neuropathy score are useful for longitudinal assessment. PMID:25369437

  1. Classic Clinical Technique Adapted to Demonstrate Autonomic Nervous System Physiology in an Undergraduate Laboratory Course

    PubMed Central

    Colgan, Wes

    2012-01-01

    The sympathetic skin response can be measured across the hands and feet with a simple bio amplifier. Controlled by the sympathetic nervous system, this response results from the activation of the eccrine sweat glands by many types of stimuli. This classical clinical test is used to evaluate peripheral neuropathies caused by a wide range of diseases, and can easily be adapted to teach a range of physiology applicable to neuroscience curricula. PMID:23494716

  2. Erythromelalgia as a manifestation of autonomic nervous system involvement in multiple sclerosis.

    PubMed

    Adamec, Ivan; Lakoš Jukić, Ines; Habek, Mario

    2016-07-01

    Erythromelalgia is a rare condition characterized by burning pain, erythema and increased temperature of the hands or the feet. Its etiology is not completely understood but it is believed that the underlying cause is a peripheral vascular dysfunction that leads to simultaneous tissue hypoxia and hyperemia. We present a rare co-occurrence of erythromelalgia and multiple sclerosis in a patient with autonomic nervous system dysfunction and propose a causative interconnection. PMID:27456866

  3. Peripheral tachykinin receptors as targets for new drugs.

    PubMed

    Patacchini, R; Maggi, C A

    2001-10-19

    Tachykinins are widely distributed in the peripheral nervous system of the respiratory, urinary and gastrointestinal tract, stored in enteric neurons and in peripheral nerve endings of capsaicin-sensitive primary afferent neurons from which are released by stimuli having both pathological and physiological relevance. The most studied effects produced by tachykinins in these systems are smooth muscle contraction, plasma protein extravasation, mucus secretion and recruitment/activation of immune cells. The use of tachykinin receptor-selective antagonists and knockout animals has enabled to identify the involvement of tachykinin NK(1), NK(2) and NK(3) receptors as mediators of peripheral effects of tachykinins in different systems/species. The bulk of data obtained in experimental animal models suggests that tachykinins could contribute to the genesis of symptoms accompanying various human diseases including asthma/bronchial hyperreactivity, cystitis of various aetiology, inflammatory bowel diseases and irritable bowel syndrome. Tachykinin receptor antagonists are expected to afford therapeutically relevant effects. PMID:11698023

  4. Schwann cells as a therapeutic target for peripheral neuropathies

    PubMed Central

    Lehmann, Helmar C.; Höke, Ahmet

    2014-01-01

    Schwann cells, the myelin forming cells in the peripheral nervous system, play a key role in the pathology of various inflammatory, metabolic and hereditary polyneuropathies. Advances in identifying growth factors and signaling molecules that are expressed by Schwann cells have paved the way to development of new treatment strategies that are aimed to improve the protective and regenerative properties of Schwann cells in peripheral nerve disorders. These include the exogenous application of growth factors and neurohormones, which have been advanced into clinical trials in humans and transplantation paradigms that have been moved into late stage preclinical models. In this review we will discuss the latest developments in these therapeutic approaches with special regard to peripheral nerve disorders, in which the progress in basic research have already been translated into clinical trials including HIV-associated distal sensory polyneuropathy and diabetic neuropathy. PMID:20874704

  5. [A peripheral osteoma].

    PubMed

    Mizbah, K; Soehardi, A; Maal, T J J; Weijs, W L J; Merkx, M A W; Barkhuysen, R

    2012-02-01

    A 43-year-old man appeared with a painless, asymptomatic swelling on the left side of his neck, which had existed for years and had slowly been progressing. After surgical removal, it became clear that it had to do with a peripheral osteoma. This is a benign lesion with a low incidence. Generally, complete surgical removal leads to cure, although recurrence is possible. A peripheral osteoma is mostly located in the mandible, although peripheral osteomata in the frontal or maxillary sinus have been described. The aetiology is unknown. Trauma in the patient's history has been described on occasion. The presence of multiple osteomata in the jawbones is characteristic of Gardner's syndrome. PMID:22428273

  6. Painful Peripheral Neuropathies

    PubMed Central

    Marchettini, P; Lacerenza, M; Mauri, E; Marangoni, C

    2006-01-01

    Peripheral neuropathies are a heterogeneous group of diseases affecting peripheral nerves. The causes are multiple: hereditary, metabolic, infectious, inflammatory, toxic, traumatic. The temporal profile includes acute, subacute and chronic conditions. The majority of peripheral neuropathies cause mainly muscle weakness and sensory loss, positive sensory symptoms and sometimes pain. When pain is present, however, it is usually extremely intense and among the most disabling symptoms for the patients. In addition, the neurological origin of the pain is often missed and patients receive inadequate or delayed specific treatment. Independently of the disease causing the peripheral nerve injury, pain originating from axonal pathology or ganglionopathy privileges neuropathies affecting smaller fibres, a clinical observation that points towards abnormal activity within nociceptive afferents as a main generator of pain. Natural activation of blood vessels or perineurial nociceptive network by pathology also causes intense pain. Pain of this kind, i.e. nerve trunk pain, is among the heralding symptoms of inflammatory or ischemic mononeuropathy and for its intensity represents itself a medical emergency. Neuropathic pain quality rekindles the psychophysical experience of peripheral nerves intraneural microstimulation i.e. a combination of large and small fibres sensation temporally distorted compared to physiological perception evoked by natural stimuli. Pins and needles, burning, cramping mixed with numbness, and tingling are the wording most used by patients. Nociceptive pain instead is most often described as aching, deep and dull. Good command of peripheral nerve anatomy and pathophysiology allows timely recognition of the different pain components and targeted treatment, selected according to intensity, type and temporal profile of the pain. PMID:18615140

  7. [Primary central nervous system vasculitis].

    PubMed

    Schuster, S; Magnus, T

    2015-12-01

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

  8. Enzyme replacement improves nervous system pathology and function in a mouse model for metachromatic leukodystrophy.

    PubMed

    Matzner, Ulrich; Herbst, Eva; Hedayati, Kerstin Khalaj; Lüllmann-Rauch, Renate; Wessig, Carsten; Schröder, Stephan; Eistrup, Carl; Möller, Christer; Fogh, Jens; Gieselmann, Volkmar

    2005-05-01

    A deficiency of arylsulfatase A (ASA) causes the lysosomal storage disease metachromatic leukodystrophy, which is characterized by accumulation of the sphingolipid 3-O-sulfogalactosylceramide (sulfatide). Sphingolipid storage results in progressive demyelination and severe neurologic symptoms. The disease is lethal, and curative therapy is not available. To assess the therapeutic potential of enzyme replacement therapy (ERT), ASA knockout mice were treated by intravenous injection of recombinant human ASA. Plasma levels of ASA declined with a half-time of approximately 40 min, and enzyme was detectable in tissues within minutes after injection. The uptake of injected enzyme was high into liver, moderate into peripheral nervous system (PNS) and kidney and very low into brain. The apparent half-life of endocytosed enzyme was approximately 4 days. A single injection led to a time- and dose-dependent decline of the excess sulfatide in PNS and kidney by up to 70%, but no reduction was seen in brain. Four weekly injections with 20 mg/kg body weight not only reduced storage in peripheral tissues progressively, but also were surprisingly effective in reducing sulfatide storage in brain and spinal cord. The histopathology of kidney and central nervous system was ameliorated. Improved neuromotor coordination capabilities and normalized peripheral compound motor action potential demonstrate the benefits of ERT on the nervous system function. Enzyme replacement may therefore be a promising therapeutic option in this devastating disease. PMID:15772092

  9. Retinoic acid receptor beta2 and neurite outgrowth in the adult mouse spinal cord in vitro.

    PubMed

    Corcoran, Jonathan; So, Po-Lin; Barber, Robert D; Vincent, Karen J; Mazarakis, Nicholas D; Mitrophanous, Kyriacos A; Kingsman, Susan M; Maden, Malcolm

    2002-10-01

    Retinoic acid, acting through the nuclear retinoic acid receptor beta2 (RARbeta2), stimulates neurite outgrowth from peripheral nervous system tissue that has the capacity to regenerate neurites, namely, embryonic and adult dorsal root ganglia. Similarly, in central nervous system tissue that can regenerate, namely, embryonic mouse spinal cord, retinoic acid also stimulates neurite outgrowth and RARbeta2 is upregulated. By contrast, in the adult mouse spinal cord, which cannot regenerate, no such upregulation of RARbeta2 by retinoic acid is observed and no neurites are extended in vitro. To test our hypothesis that the upregulation of RARbeta2 is crucial to neurite regeneration, we have transduced adult mouse or rat spinal cord in vitro with a minimal equine infectious anaemia virus vector expressing RARbeta2. After transduction, prolific neurite outgrowth occurs. Outgrowth does not occur when the cord is transduced with a different isoform of RARbeta nor does it occur following treatment with nerve growth factor. These data demonstrate that RARbeta2 is involved in neurite outgrowth, at least in vitro, and that this gene may in the future be of some therapeutic use. PMID:12235288

  10. Inherited Peripheral Neuropathies

    PubMed Central

    Saporta, Mario A.; Shy, Michael E.

    2013-01-01

    SYNOPSIS Charcot Marie Tooth disease (CMT) is a heterogeneous group of inherited peripheral neuropathies in which the neuropathy is the sole or primary component of the disorder, as opposed to diseases in which the neuropathy is part of a more generalized neurological or multisystem syndrome. Due to the great genetic heterogeneity of this condition, it can be challenging for the general neurologist to diagnose patients with specific types of CMT. Here, we review the biology of the inherited peripheral neuropathies, delineate major phenotypic features of the CMT subtypes and suggest strategies for focusing genetic testing. PMID:23642725

  11. The spatial relationship between the musculature and the NADPH-diaphorase activity, 5-HT and FMRFamide immunoreactivities in redia, cercaria and adult Echinoparyphium aconiatum (Digenea).

    PubMed

    Terenina, N B; Tolstenkov, O; Fagerholm, H-P; Serbina, E A; Vodjanitskaja, S N; Gustafsson, M K S

    2006-04-01

    The spatial relationship between the musculature and the NADPH-diaphorase (NADPH-d) activity, 5-HT and FMRFamide immunoreactivities in redia, cercaria and adult Echinoparyphium aconiatum was studied using scanning electron microscopy (SEM), NADPH-d histochemistry, immunocytochemistry, and confocal scanning laser microscopy (CSLM). TRITC-conjugated phalloidin was used to stain the musculature. Staining for NADPH-d was observed in the central (CNS) and peripheral nervous system (PNS) of all three stages. NADPH-d positive nerves occurred very close to muscle fibres. 5-HT-immunoreactive (5-HT-IR) nerve cells and fibres occurred in the CNS and PNS and close to muscle fibres. FMRFamide-IR nerve fibres were observed in the CNS and PNS of adult worms. This is the first time, the presence of the NADPH-d has been demonstrated in the larval as well as the adult stages of a fluke. PMID:16494908

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

    PubMed Central

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

    2014-01-01

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

  13. Dynamic Changes in Local Protein Synthetic Machinery in Regenerating Central Nervous System Axons after Spinal Cord Injury

    PubMed Central

    Sachdeva, Rahul; Farrell, Kaitlin; McMullen, Mary-Katharine; Twiss, Jeffery L.; Houle, John D.

    2016-01-01

    Intra-axonal localization of mRNAs and protein synthesis machinery (PSM) endows neurons with the capacity to generate proteins locally, allowing precise spatiotemporal regulation of the axonal response to extracellular stimuli. A number of studies suggest that this local translation is a promising target to enhance the regenerative capacity of damaged axons. Using a model of central nervous system (CNS) axons regenerating into intraspinal peripheral nerve grafts (PNGs) we established that adult regenerating CNS axons contain several different mRNAs and protein synthetic machinery (PSM) components in vivo. After lower thoracic level spinal cord transection, ascending sensory axons regenerate into intraspinal PNGs but axon growth is stalled when they reach the distal end of the PNG (3 versus 7 weeks after grafting, resp.). By immunofluorescence with optical sectioning of axons by confocal microscopy, the total and phosphorylated forms of PSMs are significantly lower in stalled compared with actively regenerating axons. Reinjury of these stalled axons increased axonal localization of the PSM proteins, indicative of possible priming for a subcellular response to axotomy. These results suggest that axons downregulate protein synthetic capacity as they cease growing, yet they retain the ability to upregulate PSM after a second injury. PMID:27375904

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

    PubMed Central

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

    2014-01-01

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

  15. Targeting protein kinases in central nervous system disorders

    PubMed Central

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

    2010-01-01

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

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

    PubMed

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

    2016-08-01

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

  17. Evidence of early nervous system dysfunction in Amazonian populations exposed to low-levels of methylmercury.

    PubMed

    Lebel, J; Mergler, D; Lucotte, M; Amorim, M; Dolbec, J; Miranda, D; Arantès, G; Rheault, I; Pichet, P

    1996-01-01

    There is increasing concern about the potential neurotoxic effects of exposure to methylmercury in Amazonian populations due to mercury (Hg) release from gold-mining activities. A preliminary study was undertaken in two villages on the Tapajos River, an effluent of the Amazon, situated over 200 km downstream from the extraction areas. The study population included 29 young adults (< or = 35 years), 14 women and 15 men, randomly chosen from a previous survey. Hair analyses were conducted with cold vapor atomic fluorescence spectrophotometry. Total hair Hg (THg) varied between 5.6 micrograms/g and 38.4 micrograms/gl, with MeHg levels from 72.2% to 93.3% of the THg. A quantitative behavioural neurophysiological test battery, designed for use under standard conditions, in an area without electricity and for persons with minimal education was administered to all participants. The results of visual testing showed that although all participants had good near and far visual acuity, color discrimination capacity (Lanthony D-15 desaturated panel) decreased with increasing THg (F = 4.1; p = 0.05); near visual contrast sensitivity profiles (Vistech 6000) and peripheral visual field profiles (Goldman Perimetry with Targets I and V) were reduced for those with the highest levels of THg. For the women, manual dexterity (Santa Ana, Helsinki version) decreased with increasing THg (F = 16.7; p < 0.01); this was not the case for the men. Although the women showed a tendency towards reduced grip strength, muscular fatigue did not vary with THg for either sex. The findings of this study demonstrate that it is possible, using a sensitive test battery, to detect alterations in nervous system functions, consistent with knowledge on Hg toxicity, at levels below the currently recognized threshold of 50 micrograms/g THg. PMID:8784826

  18. Peripheral nerve morphogenesis induced by scaffold micropatterning

    PubMed Central

    Memon, Danish; Boneschi, Filippo Martinelli; Madaghiele, Marta; Brambilla, Paola; Del Carro, Ubaldo; Taveggia, Carla; Riva, Nilo; Trimarco, Amelia; Lopez, Ignazio D.; Comi, Giancarlo; Pluchino, Stefano; Martino, Gianvito; Sannino, Alessandro; Quattrini, Angelo

    2014-01-01

    Several bioengineering approaches have been proposed for peripheral nervous system repair, with limited results and still open questions about the underlying molecular mechanisms. We assessed the biological processes that occur after the implantation of collagen scaffold with a peculiar porous microstructure of the wall in a rat sciatic nerve transection model compared to commercial collagen conduits and nerve crush injury using functional, histological and genome wide analyses. We demonstrated that within 60 days, our conduit had been completely substituted by a normal nerve. Gene expression analysis documented a precise sequential regulation of known genes involved in angiogenesis, Schwann cells/axons interactions and myelination, together with a selective modulation of key biological pathways for nerve morphogenesis induced by porous matrices. These data suggest that the scaffold’s microstructure profoundly influences cell behaviors and creates an instructive micro-environment to enhance nerve morphogenesis that can be exploited to improve recovery and understand the molecular differences between repair and regeneration. PMID:24559639

  19. Barriers of the peripheral nerve

    PubMed Central

    Peltonen, Sirkku; Alanne, Maria; Peltonen, Juha

    2013-01-01

    This review introduces the traditionally defined anatomic compartments of the peripheral nerves based on light and electron microscopic topography and then explores the cellular and the most recent molecular basis of the different barrier functions operative in peripheral nerves. We also elucidate where, and how, the homeostasis of the normal human peripheral nerve is controlled in situ and how claudin-containing tight junctions contribute to the barriers of peripheral nerve. Also, the human timeline of the development of the barriers of the peripheral nerve is depicted. Finally, potential future therapeutic modalities interfering with the barriers of the peripheral nerve are discussed. PMID:24665400

  20. Autonomic nervous system correlates in movement observation and motor imagery

    PubMed Central

    Collet, C.; Di Rienzo, F.; El Hoyek, N.; Guillot, A.

    2013-01-01

    The purpose of the current article is to provide a comprehensive overview of the literature offering a better understanding of the autonomic nervous system (ANS) correlates in motor imagery (MI) and movement observation. These are two high brain functions involving sensori-motor coupling, mediated by memory systems. How observing or mentally rehearsing a movement affect ANS activity has not been extensively investigated. The links between cognitive functions and ANS responses are not so obvious. We will first describe the organization of the ANS whose main purposes are controlling vital functions by maintaining the homeostasis of the organism and providing adaptive responses when changes occur either in the external or internal milieu. We will then review how scientific knowledge evolved, thus integrating recent findings related to ANS functioning, and show how these are linked to mental functions. In turn, we will describe how movement observation or MI may elicit physiological responses at the peripheral level of the autonomic effectors, thus eliciting autonomic correlates to cognitive activity. Key features of this paper are to draw a step-by step progression from the understanding of ANS physiology to its relationships with high mental processes such as movement observation or MI. We will further provide evidence that mental processes are co-programmed both at the somatic and autonomic levels of the central nervous system (CNS). We will thus detail how peripheral physiological responses may be analyzed to provide objective evidence that MI is actually performed. The main perspective is thus to consider that, during movement observation and MI, ANS activity is an objective witness of mental processes. PMID:23908623

  1. Treatment of peripheral neuropathies.

    PubMed Central

    Hallett, M; Tandon, D; Berardelli, A

    1985-01-01

    There are three general approaches to treatment of peripheral neuropathy. First, an attempt should be made to reverse the pathophysiological process if its nature can be elucidated. Second, nerve metabolism can be stimulated and regeneration encouraged. Third, even if the neuropathy itself cannot be improved, symptomatic therapy can be employed. This review outlines the options available for each approach. PMID:3003254

  2. Peripheral neuropathies 1988

    SciTech Connect

    Assal, J.P.; Liniger, C.

    1990-01-01

    The authors present results and experience in sixteen specific disciplines related to the study of nerve physiopathology, diagnosis and treatment. Twenty-two different peripheral neuropathies are presented, and different models related to health care strategies are discussed. The authors report on Inflammatory and autoimmune neuropathies and Genetic neuropathies.

  3. The Homology Model of PMP22 Suggests Mutations Resulting in Peripheral Neuropathy Disrupt Transmembrane Helix Packing

    PubMed Central

    2015-01-01

    Peripheral myelin protein 22 (PMP22) is a tetraspan membrane protein strongly expressed in myelinating Schwann cells of the peripheral nervous system. Myriad missense mutations in PMP22 result in varying degrees of peripheral neuropathy. We used Rosetta 3.5 to generate a homology model of PMP22 based on the recently published crystal structure of claudin-15. The model suggests that several mutations known to result in neuropathy act by disrupting transmembrane helix packing interactions. Our model also supports suggestions from previous studies that the first transmembrane helix is not tightly associated with the rest of the helical bundle. PMID:25243937

  4. Plasticity and neural stem cells in the enteric nervous system.

    PubMed

    Schäfer, Karl-Herbert; Van Ginneken, Chris; Copray, Sjef

    2009-12-01

    The enteric nervous system (ENS) is a highly organized part of the autonomic nervous system, which innervates the whole gastrointestinal tract by several interconnected neuronal networks. The ENS changes during development and keeps throughout its lifespan a significant capacity to adapt to microenvironmental influences, be it in inflammatory bowel diseases or changing dietary habits. The presence of neural stem cells in the pre-, postnatal, and adult gut might be one of the prerequisites to adapt to changing conditions. During the last decade, the ENS has increasingly come into the focus of clinical neural stem cell research, forming a considerable pool of neural crest derived stem cells, which could be used for cell therapy of dysganglionosis, that is, diseases based on the deficient or insufficient colonization of the gut by neural crest derived stem cells; in addition, the ENS could be an easily accessible neural stem cell source for cell replacement therapies for neurodegenerative disorders or traumatic lesions of the central nervous system. PMID:19943347

  5. Imaging of a glioma using peripheral benzodiazepine receptor ligands

    SciTech Connect

    Starosta-Rubinstein, S.; Ciliax, B.J.; Penney, J.B.; McKeever, P.; Young, A.B.

    1987-02-01

    Two types of benzodiazepine receptors have been demonstrated in mammalian tissues, one which is localized on neuronal elements in brain and the other, on glial cells and in peripheral tissues such as kidney. In vivo administration of /sup 3/H-labeled PK 11195 (1-(2-chlorophenyl-N-methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide) or (/sup 3/H)flunitrazepam with 5 mg of clonazepam per kg to rats with intracranial C6 gliomas resulted in high levels of tritiated-drug binding to the tumor as shown by quantitative autoradiography. Pharmacological studies indicated that the bound drugs labeled the peripheral benzodiazepine binding site. Binding to the peripheral benzodiazepine site was confirmed primarily to malignant cells with little binding to adjacent normal brain tissue or to necrotic tissue. Tumor cell binding was completely inhibited by preadministration of the peripheral benzodiazepine blocking agent PK 11195 at 5 mg/kg. The centrally selective benzodiazepine ligand clonazepam had no effect on PK 11195 binding to the tumor cells. When binding to other tumor cell lines grown in nude mice and nude athymic rats was evaluated, little or no peripheral benzodiazepine binding was detected on human pheochromocytoma (RN1) and neuroblastoma (SK-N-MC, SK-N-SH) tumor cells, respectively. However, high densities of peripheral benzodiazepine binding sites were observed on tumors derived from a human glioma cell line (ATCC HTB 14, U-87 MG). The presence of high concentrations of specific peripheral benzodiazepine receptors on glial tumors suggests that human primary central nervous system tumors could be imaged and diagnosed using peripheral benzodiazepine ligands labeled with positron- or gamma-emitting isotopes.

  6. Novel central nervous system drug delivery systems.

    PubMed

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

    2014-05-01

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

  7. Genomic characterization of primary central nervous system lymphoma.

    PubMed

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

    2016-06-01

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

  8. CXCL12 Signaling in the Development of the Nervous System

    PubMed Central

    Mithal, Divakar S.; Banisadr, Ghazal; Miller, Richard J.

    2015-01-01

    Chemokines are small, secreted proteins that have been shown to be important regulators of leukocyte trafficking and inflammation. All the known effects of chemokines are transduced by action at a family of G protein coupled receptors. Two of these receptors, CCR5 and CXCR4, are also known to be the major cellular receptors for HIV-1. Consideration of the evolution of the chemokine family has demonstrated that the chemokine Stromal cell Derived Factor-1 or SDF1 (CXCL12) and its receptor CXCR4 are the most ancient members of the family and existed in animals prior to the development of a sophisticated immune system. Thus, it appears that the original function of chemokine signaling was in the regulation of stem cell trafficking and development. CXCR4 signaling is important in the development of many tissues including the nervous system. Here we discuss the manner in which CXCR4 signaling can regulate the development of different structures in the central and peripheral nervous systems and the different strategies employed to achieve these effects. PMID:22270883

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

    NASA Technical Reports Server (NTRS)

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

    1997-01-01

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

  10. TrkB/BDNF signalling patterns the sympathetic nervous system

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

    Vaughn, J E

    1989-01-01

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

  13. Enteric nervous system development: migration, differentiation, and disease

    PubMed Central

    Lake, Jonathan I.

    2013-01-01

    The enteric nervous system (ENS) provides the intrinsic innervation of the bowel and is the most neurochemically diverse branch of the peripheral nervous system, consisting of two layers of ganglia and fibers encircling the gastrointestinal tract. The ENS is vital for life and is capable of autonomous regulation of motility and secretion. Developmental studies in model organisms and genetic studies of the most common congenital disease of the ENS, Hirschsprung disease, have provided a detailed understanding of ENS development. The ENS originates in the neural crest, mostly from the vagal levels of the neuraxis, which invades, proliferates, and migrates within the intestinal wall until the entire bowel is colonized with enteric neural crest-derived cells (ENCDCs). After initial migration, the ENS develops further by responding to guidance factors and morphogens that pattern the bowel concentrically, differentiating into glia and neuronal subtypes and wiring together to form a functional nervous system. Molecules controlling this process, including glial cell line-derived neurotrophic factor and its receptor RET, endothelin (ET)-3 and its receptor endothelin receptor type B, and transcription factors such as SOX10 and PHOX2B, are required for ENS development in humans. Important areas of active investigation include mechanisms that guide ENCDC migration, the role and signals downstream of endothelin receptor type B, and control of differentiation, neurochemical coding, and axonal targeting. Recent work also focuses on disease treatment by exploring the natural role of ENS stem cells and investigating potential therapeutic uses. Disease prevention may also be possible by modifying the fetal microenvironment to reduce the penetrance of Hirschsprung disease-causing mutations. PMID:23639815

  14. Peripheral and central myelinopathy in Cockayne's syndrome. Report of 3 siblings.

    PubMed

    Smits, M G; Gabreëls, F J; Renier, W O; Joosten, E M; Gabreëls-Festen, A A; ter Laak, H J; Pinckers, A J; Hombergen, G C; Notermans, S L; Thijssen, H O

    1982-08-01

    Three siblings with Cockayne's syndrome are reported. Sural nerve biopsies revealed segmental de- and remyelination with onion-bulb formation. Disturbed visual and brain-stem auditory evoked responses indicated demyelination of the central nervous system. The peripheral and central myelinopathy increased with age, suggesting a progressive disorder. Our observations support the theory of Cockayne's syndrome being a leukodystrophy. PMID:7133337

  15. A novel subset of enteric neurons revealed by ptf1a:GFP in the developing zebrafish enteric nervous system.

    PubMed

    Uribe, Rosa A; Gu, Tiffany; Bronner, Marianne E

    2016-03-01

    The enteric nervous system, the largest division of the peripheral nervous system, is derived from vagal neural crest cells that invade and populate the entire length of the gut to form diverse neuronal subtypes. Here, we identify a novel population of neurons within the enteric nervous system of zebrafish larvae that express the transgenic marker ptf1a:GFP within the midgut. Genetic lineage analysis reveals that enteric ptf1a:GFP(+) cells are derived from the neural crest and that most ptf1a:GFP(+) neurons express the neurotransmitter 5HT, demonstrating that they are serotonergic. This transgenic line, Tg(ptf1a:GFP), provides a novel neuronal marker for a subpopulation of neurons within the enteric nervous system, and highlights the possibility that Ptf1a may act as an important transcription factor for enteric neuron development. PMID:26865080

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

    ERIC Educational Resources Information Center

    Watters, Christopher

    2006-01-01

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

  17. Autonomic nervous system function in young children with functional abdominal pain or irritable bowel syndrome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Adults with irritable bowel syndrome (IBS) have been reported to have alterations in autonomic nervous system function as measured by vagal activity via heart rate variability. Whether the same is true for children is unknown. We compared young children 7 to 10 years of age with functional abdominal...

  18. Peripheral Artery Disease and Diabetes

    MedlinePlus

    ... High Blood Pressure Tools & Resources Stroke More Peripheral Artery Disease & Diabetes Updated:Jan 26,2016 People with ... developing atherosclerosis, the most common cause of peripheral artery disease (PAD) . And individuals with PAD have a ...

  19. Angioplasty and stent placement -- peripheral arteries

    MedlinePlus

    Percutaneous transluminal angioplasty - peripheral artery; PTA - peripheral artery; Angioplasty - peripheral arteries; Iliac artery -angioplasty; Femoral artery - angioplasty; Popliteal artery - angioplasty; Tibial artery - angioplasty; Peroneal artery - ...

  20. Theoretical foundations for nervous networks

    SciTech Connect

    Hasslacher, B.; Tilden, M.W.

    1997-05-01

    Following three years of study into experimental Nervous Net (Nv) control devices, various successes and several amusing failures have implied some general principles on the nature of capable control systems for autonomous machines and perhaps, we conjecture, even biological organisms. These systems are minimal, elegant, and, depending upon their implementation in a {open_quotes}creature{close_quotes} structure, astonishingly robust. Their only problem seems to be that as they are collections of non-linear asynchronous elements, only complex analysis can adequately extract and explain the emergent competency of their operation. The implications are that so long as Nv non-linear topologies can retain some measure of sub-critically coupled planar stability, the Piexito theorem will guarantee a form of plastic mode-locking necessary for broad-behavior competency. Further experimental evidence also suggests that if Nv topologies are kept in sub-chaotically stable regimes, they can be implemented at any scale and still automatically fall into effective survival strategies in unstructured environments. An explanation for how this is be possible in such minimal structures is presented. {copyright} {ital 1997 American Institute of Physics.}

  1. Radiation response of the central nervous system

    SciTech Connect

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

    1995-03-30

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

  2. Vitamin K and the Nervous System: An Overview of its Actions12

    PubMed Central

    Ferland, Guylaine

    2012-01-01

    The role of vitamin K in the nervous system has been somewhat neglected compared with other physiological systems despite the fact that this nutrient was identified some 40 y ago as essential for the synthesis of sphingolipids. Present in high concentrations in brain cell membranes, sphingolipids are now known to possess important cell signaling functions in addition to their structural role. In the past 20 y, additional support for vitamin K functions in the nervous system has come from the discovery and characterization of vitamin K–dependent proteins that are now known to play key roles in the central and peripheral nervous systems. Notably, protein Gas6 has been shown to be actively involved in cell survival, chemotaxis, mitogenesis, and cell growth of neurons and glial cells. Although limited in number, studies focusing on the relationship between vitamin K nutritional status and behavior and cognition have also become available, pointing to diet and certain drug treatments (i.e., warfarin derivatives) as potential modulators of the action of vitamin K in the nervous system. This review presents an overview of the research that first identified vitamin K as an important nutrient for the nervous system and summarizes recent findings that support this notion. PMID:22516728

  3. Restoring nervous system structure and function using tissue engineered living scaffolds

    PubMed Central

    Struzyna, Laura A.; Harris, James P.; Katiyar, Kritika S.; Chen, H. Isaac; Cullen, D. Kacy

    2015-01-01

    Neural tissue engineering is premised on the integration of engineered living tissue with the host nervous system to directly restore lost function or to augment regenerative capacity following nervous system injury or neurodegenerative disease. Disconnection of axon pathways – the long-distance fibers connecting specialized regions of the central nervous system or relaying peripheral signals – is a common feature of many neurological disorders and injury. However, functional axonal regeneration rarely occurs due to extreme distances to targets, absence of directed guidance, and the presence of inhibitory factors in the central nervous system, resulting in devastating effects on cognitive and sensorimotor function. To address this need, we are pursuing multiple strategies using tissue engineered “living scaffolds”, which are preformed three-dimensional constructs consisting of living neural cells in a defined, often anisotropic architecture. Living scaffolds are designed to restore function by serving as a living labeled pathway for targeted axonal regeneration – mimicking key developmental mechanisms– or by restoring lost neural circuitry via direct replacement of neurons and axonal tracts. We are currently utilizing preformed living scaffolds consisting of neuronal clusters spanned by long axonal tracts as regenerative bridges to facilitate long-distance axonal regeneration and for targeted neurosurgical reconstruction of local circuits in the brain. Although there are formidable challenges in preclinical and clinical advancement, these living tissue engineered constructs represent a promising strategy to facilitate nervous system repair and functional recovery. PMID:26109930

  4. Restoring nervous system structure and function using tissue engineered living scaffolds.

    PubMed

    Struzyna, Laura A; Harris, James P; Katiyar, Kritika S; Chen, H Isaac; Cullen, D Kacy

    2015-05-01

    Neural tissue engineering is premised on the integration of engineered living tissue with the host nervous system to directly restore lost function or to augment regenerative capacity following nervous system injury or neurodegenerative disease. Disconnection of axon pathways - the long-distance fibers connecting specialized regions of the central nervous system or relaying peripheral signals - is a common feature of many neurological disorders and injury. However, functional axonal regeneration rarely occurs due to extreme distances to targets, absence of directed guidance, and the presence of inhibitory factors in the central nervous system, resulting in devastating effects on cognitive and sensorimotor function. To address this need, we are pursuing multiple strategies using tissue engineered "living scaffolds", which are preformed three-dimensional constructs consisting of living neural cells in a defined, often anisotropic architecture. Living scaffolds are designed to restore function by serving as a living labeled pathway for targeted axonal regeneration - mimicking key developmental mechanisms- or by restoring lost neural circuitry via direct replacement of neurons and axonal tracts. We are currently utilizing preformed living scaffolds consisting of neuronal clusters spanned by long axonal tracts as regenerative bridges to facilitate long-distance axonal regeneration and for targeted neurosurgical reconstruction of local circuits in the brain. Although there are formidable challenges in preclinical and clinical advancement, these living tissue engineered constructs represent a promising strategy to facilitate nervous system repair and functional recovery. PMID:26109930

  5. The role of D-serine in peripheral tissues.

    PubMed

    Montesinos Guevara, Camila; Mani, Ali R

    2016-06-01

    A considerable level of D-serine (a free D-amino acid) was discovered, surprisingly, in the mammalian brain in the early 1990s. Since then, D-serine has been considered to be a co-agonist of glutamate at the glycine site of NMDA receptors. D-serine is synthetized by racemization of L-serine in most neural and non-neural cells, and modulates a variety of physiological functions in mammals. In addition to the central nervous system, NMDA receptors have an important function in the modulation of physiological processes in peripheral tissues. Thus, investigations on the functions of D-serine in the peripheral nervous system, as well as the visceral organs, have gained attention in recent years. In this review we summarize the current knowledge on the role of D-serine in the kidneys, skeletal system, skin as well as on the non-adrenergic, non-cholinergic transmission within the autonomic nervous system. PMID:27038518

  6. Chemotherapy-induced peripheral neuropathy: an update on the current understanding

    PubMed Central

    Addington, James; Freimer, Miriam

    2016-01-01

    Chemotherapy-induced peripheral neuropathy is a common side effect of selected chemotherapeutic agents. Previous work has suggested that patients often under report the symptoms of chemotherapy-induced peripheral neuropathy and physicians fail to recognize the presence of such symptoms in a timely fashion. The precise pathophysiology that underlies chemotherapy-induced peripheral neuropathy, in both the acute and the chronic phase, remains complex and appears to be medication specific. Recent work has begun to demonstrate and further clarify potential pathophysiological processes that predispose and, ultimately, lead to the development of chemotherapy-induced peripheral neuropathy. There is increasing evidence that the pathway to neuropathy varies with each agent. With a clearer understanding of how these agents affect the peripheral nervous system, more targeted treatments can be developed in order to optimize treatment and prevent long-term side effects. PMID:27408692

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

    ClinicalTrials.gov

    2016-09-12

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

  8. Ultrasound of Peripheral Nerves

    PubMed Central

    Suk, Jung Im; Walker, Francis O.; Cartwright, Michael S.

    2013-01-01

    Over the last decade, neuromuscular ultrasound has emerged as a useful tool for the diagnosis of peripheral nerve disorders. This article reviews sonographic findings of normal nerves including key quantitative ultrasound measurements that are helpful in the evaluation of focal and possibly generalized peripheral neuropathies. It also discusses several recent papers outlining the evidence base for the use of this technology, as well as new findings in compressive, traumatic, and generalized neuropathies. Ultrasound is well suited for use in electrodiagnostic laboratories where physicians, experienced in both the clinical evaluation of patients and the application of hands-on technology, can integrate findings from the patient’s history, physical examination, electrophysiological studies, and imaging for diagnosis and management. PMID:23314937

  9. Immunotherapy in Peripheral Neuropathies.

    PubMed

    Léger, Jean-Marc; Guimarães-Costa, Raquel; Muntean, Cristina

    2016-01-01

    Immunotherapy has been investigated in a small subset of peripheral neuropathies, including an acute one, Guillain-Barré syndrome, and 3 chronic forms: chronic inflammatory demyelinating polyradiculoneuropathy, multifocal motor neuropathy, and neuropathy associated with IgM anti-myelin-associated glycoprotein. Several experimental studies and clinical data are strongly suggestive of an immune-mediated pathogenesis. Either cell-mediated mechanisms or antibody responses to Schwann cell, compact myelin, or nodal antigens are considered to act together in an aberrant immune response to cause damage to peripheral nerves. Immunomodulatory treatments used in these neuropathies aim to act at various steps of this pathogenic process. However, there are many phenotypic variants and, consequently, there is a significant difference in the response to immunotherapy between these neuropathies, as well as a need to improve our knowledge and long-term management of chronic forms. PMID:26602549

  10. [Ganglia of peripheral nerves].

    PubMed

    Tatagiba, M; Penkert, G; Samii, M

    1993-01-01

    The authors present two different types of ganglion affecting the peripheral nerves: extraneural and intraneural ganglion. Compression of peripheral nerves by articular ganglions is well known. The surgical management involves the complete removal of the lesion with preservation of most nerve fascicles. Intraneural ganglion is an uncommon lesion which affects the nerve diffusely. The nerve fascicles are usually intimately involved between the cysts, making complete removal of all cysts impossible. There is no agreement about the best surgical management to be applied in these cases. Two possibilities are available: opening of the epineural sheath lengthwise and pressing out the lesion; or resection of the affected part of the nerve and performing a nerve reconstruction. While in case of extraneural ganglion the postoperative clinical evolution is very favourable, only long follow up studies will reveal in case of intraneural ganglion the best surgical approach. PMID:8128785

  11. Alternative Quantitative Tools in the Assessment of Diabetic Peripheral and Autonomic Neuropathy.

    PubMed

    Vinik, A I; Casellini, C; Névoret, M-L

    2016-01-01

    Here we review some seldom-discussed presentations of diabetic neuropathy, including large fiber dysfunction and peripheral autonomic dysfunction, emphasizing the impact of sympathetic/parasympathetic imbalance. Diabetic neuropathy is the most common complication of diabetes and contributes additional risks in the aging adult. Loss of sensory perception, loss of muscle strength, and ataxia or incoordination lead to a risk of falling that is 17-fold greater in the older diabetic compared to their young nondiabetic counterparts. A fall is accompanied by lacerations, tears, fractures, and worst of all, traumatic brain injury, from which more than 60% do not recover. Autonomic neuropathy has been hailed as the "Prophet of Doom" for good reason. It is conducive to increased risk of myocardial infarction and sudden death. An imbalance in the autonomic nervous system occurs early in the evolution of diabetes, at a stage when active intervention can abrogate the otherwise relentless progression. In addition to hypotension, many newly recognized syndromes can be attributed to cardiac autonomic neuropathy such as orthostatic tachycardia and bradycardia. Ultimately, this constellation of features of neuropathy conspire to impede activities of daily living, especially in the patient with pain, anxiety, depression, and sleep disorders. The resulting reduction in quality of life may worsen prognosis and should be routinely evaluated and addressed. Early neuropathy detection can only be achieved by assessment of both large and small- nerve fibers. New noninvasive sudomotor function technologies may play an increasing role in identifying early peripheral and autonomic neuropathy, allowing rapid intervention and potentially reversal of small-fiber loss. PMID:27133153

  12. Macrophage-Induced Blood Vessels Guide Schwann Cell-Mediated Regeneration of Peripheral Nerves

    PubMed Central

    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.

    2015-01-01

    Summary 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. PMID:26279190

  13. Peripheral neuropathy and parkinsonism: a large clinical and pathogenic spectrum.

    PubMed

    Vital, Anne; Lepreux, Sebastien; Vital, Claude

    2014-12-01

    Peripheral neuropathy (PN) has been reported in idiopathic and hereditary forms of parkinsonism, but the pathogenic mechanisms are unclear and likely heterogeneous. Levodopa-induced vitamin B12 deficiency has been discussed as a causal factor of PN in idiopathic Parkinson's disease, but peripheral nervous system involvement might also be a consequence of the underlying neurodegenerative process. Occurrence of PN with parkinsonism has been associated with a panel of mitochondrial cytopathies, more frequently related to a nuclear gene defect and mainly polymerase gamma (POLG1) gene. Parkin (PARK2) gene mutations are responsible for juvenile parkinsonism, and possible peripheral nervous system involvement has been reported. Rarely, an association of parkinsonism with PN may be encountered in other neurodegenerative diseases such as fragile X-associated tremor and ataxia syndrome related to premutation CGG repeat expansion in the fragile X mental retardation (FMR1) gene, Machado-Joseph disease related to an abnormal CAG repeat expansion in ataxin-3 (ATXN3) gene, Kufor-Rakeb syndrome caused by mutations in ATP13A2 gene, or in hereditary systemic disorders such as Gaucher disease due to mutations in the β-glucocerebrosidase (GBA) gene and Chediak-Higashi syndrome due to LYST gene mutations. This article reviews conditions in which PN may coexist with parkinsonism. PMID:25582874

  14. Effectiveness of conventional versus virtual reality based vestibular rehabilitation in the treatment of dizziness, gait and balance impairment in adults with unilateral peripheral vestibular loss: a randomised controlled trial

    PubMed Central

    2012-01-01

    Background Unilateral peripheral vestibular loss results in gait and balance impairment, dizziness and oscillopsia. Vestibular rehabilitation benefits patients but optimal treatment remains unkown. Virtual reality is an emerging tool in rehabilitation and provides opportunities to improve both outcomes and patient satisfaction with treatment. The Nintendo Wii Fit Plus® (NWFP) is a low cost virtual reality system that challenges balance and provides visual and auditory feedback. It may augment the motor learning that is required to improve balance and gait, but no trials to date have investigated efficacy. Methods/Design In a single (assessor) blind, two centre randomised controlled superiority trial, 80 patients with unilateral peripheral vestibular loss will be randomised to either conventional or virtual reality based (NWFP) vestibular rehabilitation for 6 weeks. The primary outcome measure is gait speed (measured with three dimensional gait analysis). Secondary outcomes include computerised posturography, dynamic visual acuity, and validated questionnaires on dizziness, confidence and anxiety/depression. Outcome will be assessed post treatment (8 weeks) and at 6 months. Discussion Advances in the gaming industry have allowed mass production of highly sophisticated low cost virtual reality systems that incorporate technology previously not accessible to most therapists and patients. Importantly, they are not confined to rehabilitation departments, can be used at home and provide an accurate record of adherence to exercise. The benefits of providing augmented feedback, increasing intensity of exercise and accurately measuring adherence may improve conventional vestibular rehabilitation but efficacy must first be demonstrated. Trial registration Clinical trials.gov identifier: NCT01442623 PMID:22449224

  15. Choice of Unmanipulated T Cell Replete Graft for Haploidentical Stem Cell Transplant and Posttransplant Cyclophosphamide in Hematologic Malignancies in Adults: Peripheral Blood or Bone Marrow—Review of Published Literature

    PubMed Central

    Farhan, Shatha; Peres, Edward; Janakiraman, Nalini

    2016-01-01

    Allogeneic hematopoietic stem cell transplantation (SCT) is often the only curative option for many patients with malignant and benign hematological stem cell disorders. However, some issues are still of concern regarding finding a donor like shrinking family sizes in many societies, underrepresentation of the ethnic minorities in the registries, genetic variability for some races, and significant delays in obtaining stem cells after starting the search. So there is a considerable need to develop alternate donor stem cell sources. The rapid and near universal availability of the haploidentical donor is an advantage of the haploidentical SCT and an opportunity that is being explored currently in many centers especially using T cell replete graft and posttransplant cyclophosphamide. This is probably because it does not require expertise in graft manipulation and because of the lower costs. However, there are still lots of unanswered questions, like the effect of use of bone marrow versus peripheral blood as the source of stem cells on graft-versus-host disease, graft versus tumor, overall survival, immune reconstitution, and quality of life. Here we review the available publications on bone marrow and peripheral blood experience in the haploidentical SCT setting. PMID:27118973

  16. [Management of peripheral facial nerve palsy in children].

    PubMed

    Tabarki, B

    2014-10-01

    Peripheral facial nerve palsy may (secondary) or may not have a detectable cause (idiopathic facial palsy or Bell's palsy). Idiopathic facial palsy is the common form of facial palsy. It remains diagnosis by exclusion. The prognosis is more favourable in children than in adults. We present current diagnostic procedures and recommendations regarding treatment in children. PMID:25048647

  17. Deaf and Hearing Children: A Comparison of Peripheral Vision Development

    ERIC Educational Resources Information Center

    Codina, Charlotte; Buckley, David; Port, Michael; Pascalis, Olivier

    2011-01-01

    This study investigated peripheral vision (at least 30[degrees] eccentric to fixation) development in profoundly deaf children without cochlear implantation, and compared this to age-matched hearing controls as well as to deaf and hearing adult data. Deaf and hearing children between the ages of 5 and 15 years were assessed using a new,…

  18. Some aspects of the immunolocalization of FMRFamide in the nervous system of turbellarians, Polycelis tenuis and Girardia tigrina. Short communication.

    PubMed

    Kreshchenko, Natalia; Tolstenkov, O O

    2012-01-01

    The details of the morphology of the nervous system has been investigated in two turbellarian species Polycelis tenuis and Girardia tigrina using confocal laser scanning microscopy and immunostaining to neuropeptide FMRFamide. Abundant FMRFamide immunoreactivity (FMRF-IR) has been observed in central and peripheral nervous systems of both species. Intensive staining has been found in the sensory elements: cells and fibres surrounded the mouth opening, in the fibres enclosed the photoreceptors, triangular auricles in the head region of G. tigrina. The possible function of FMRF-IR neurons in the realization of sensory function in turbellarians is discussed. PMID:22776478

  19. Degenerative disease affecting the nervous system.

    PubMed

    Eadie, M J

    1974-03-01

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

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

    PubMed

    Schmutzhard, E

    2010-02-01

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