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Sample records for nerve growth cone

  1. Morphology and nanomechanics of sensory neurons growth cones following peripheral nerve injury.

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    Marta Martin

    Full Text Available A prior peripheral nerve injury in vivo, promotes a rapid elongated mode of sensory neurons neurite regrowth in vitro. This in vitro model of conditioned axotomy allows analysis of the cellular and molecular mechanisms leading to an improved neurite re-growth. Our differential interference contrast microscopy and immunocytochemistry results show that conditioned axotomy, induced by sciatic nerve injury, did not increase somatic size of adult lumbar sensory neurons from mice dorsal root ganglia sensory neurons but promoted the appearance of larger neurites and growth cones. Using atomic force microscopy on live neurons, we investigated whether membrane mechanical properties of growth cones of axotomized neurons were modified following sciatic nerve injury. Our data revealed that neurons having a regenerative growth were characterized by softer growth cones, compared to control neurons. The increase of the growth cone membrane elasticity suggests a modification in the ratio and the inner framework of the main structural proteins.

  2. Muscarinic receptor activation stimulates B-50/GAP43 phosphorylation in isolated nerve growth cones

    NARCIS (Netherlands)

    Gispen, W.H.; Hooff, C.O.M. van; Graan, P.N.E. de; Oestreicher, A.B.

    1989-01-01

    A characteristic feature of neurite formation is high expression of the phosphoprotein B-50/GAP43. Previous studies with growth cone membranes have indicated that this neuron-specific protein kinase C substrate may be involved in transmembrane signal transduction at the growth cone. We monitored the

  3. Nerve growth factor stimulates axon outgrowth through negative regulation of growth cone actomyosin restraint of microtubule advance.

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    Turney, Stephen G; Ahmed, Mostafa; Chandrasekar, Indra; Wysolmerski, Robert B; Goeckeler, Zoe M; Rioux, Robert M; Whitesides, George M; Bridgman, Paul C

    2016-02-01

    Nerve growth factor (NGF) promotes growth, differentiation, and survival of sensory neurons in the mammalian nervous system. Little is known about how NGF elicits faster axon outgrowth or how growth cones integrate and transform signal input to motor output. Using cultured mouse dorsal root ganglion neurons, we found that myosin II (MII) is required for NGF to stimulate faster axon outgrowth. From experiments inducing loss or gain of function of MII, specific MII isoforms, and vinculin-dependent adhesion-cytoskeletal coupling, we determined that NGF causes decreased vinculin-dependent actomyosin restraint of microtubule advance. Inhibition of MII blocked NGF stimulation, indicating the central role of restraint in directed outgrowth. The restraint consists of myosin IIB- and IIA-dependent processes: retrograde actin network flow and transverse actin bundling, respectively. The processes differentially contribute on laminin-1 and fibronectin due to selective actin tethering to adhesions. On laminin-1, NGF induced greater vinculin-dependent adhesion-cytoskeletal coupling, which slowed retrograde actin network flow (i.e., it regulated the molecular clutch). On fibronectin, NGF caused inactivation of myosin IIA, which negatively regulated actin bundling. On both substrates, the result was the same: NGF-induced weakening of MII-dependent restraint led to dynamic microtubules entering the actin-rich periphery more frequently, giving rise to faster elongation. © 2016 Turney et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  4. A photon-driven micromotor can direct nerve fibre growth

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    Wu, Tao; Nieminen, Timo A.; Mohanty, Samarendra; Miotke, Jill; Meyer, Ronald L.; Rubinsztein-Dunlop, Halina; Berns, Michael W.

    2012-01-01

    Axonal path-finding is important in the development of the nervous system, nerve repair and nerve regeneration. The behaviour of the growth cone at the tip of the growing axon determines the direction of axonal growth and migration. We have developed an optical-based system to control the direction of growth of individual axons (nerve fibres) using laser-driven spinning birefringent spheres. One or two optical traps position birefringent beads adjacent to growth cones of cultured goldfish retinal ganglion cell axons. Circularly polarized light with angular momentum causes the trapped bead to spin. This creates a localized microfluidic flow generating an estimated 0.17 pN shear force against the growth cone that turns in response to the shear. The direction of axonal growth can be precisely manipulated by changing the rotation direction and position of this optically driven micromotor. A physical model estimating the shear force density on the axon is described.

  5. GSK3 controls axon growth via CLASP-mediated regulation of growth cone microtubules

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    Hur, Eun-Mi; Saijilafu; Lee, Byoung Dae; Kim, Seong-Jin; Xu, Wen-Lin; Zhou, Feng-Quan

    2011-01-01

    Suppression of glycogen synthase kinase 3 (GSK3) activity in neurons yields pleiotropic outcomes, causing both axon growth promotion and inhibition. Previous studies have suggested that specific GSK3 substrates, such as adenomatous polyposis coli (APC) and collapsin response mediator protein 2 (CRMP2), support axon growth by regulating the stability of axonal microtubules (MTs), but the substrate(s) and mechanisms conveying axon growth inhibition remain elusive. Here we show that CLIP (cytoplasmic linker protein)-associated protein (CLASP), originally identified as a MT plus end-binding protein, displays both plus end-binding and lattice-binding activities in nerve growth cones, and reveal that the two MT-binding activities regulate axon growth in an opposing manner: The lattice-binding activity mediates axon growth inhibition induced by suppression of GSK3 activity via preventing MT protrusion into the growth cone periphery, whereas the plus end-binding property supports axon extension via stabilizing the growing ends of axonal MTs. We propose a model in which CLASP transduces GSK3 activity levels to differentially control axon growth by coordinating the stability and configuration of growth cone MTs. PMID:21937714

  6. Functional complexity of the axonal growth cone: a proteomic analysis.

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    Adriana Estrada-Bernal

    Full Text Available The growth cone, the tip of the emerging neurite, plays a crucial role in establishing the wiring of the developing nervous system. We performed an extensive proteomic analysis of axonal growth cones isolated from the brains of fetal Sprague-Dawley rats. Approximately 2000 proteins were identified at ≥ 99% confidence level. Using informatics, including functional annotation cluster and KEGG pathway analysis, we found great diversity of proteins involved in axonal pathfinding, cytoskeletal remodeling, vesicular traffic and carbohydrate metabolism, as expected. We also found a large and complex array of proteins involved in translation, protein folding, posttranslational processing, and proteasome/ubiquitination-dependent degradation. Immunofluorescence studies performed on hippocampal neurons in culture confirmed the presence in the axonal growth cone of proteins representative of these processes. These analyses also provide evidence for rough endoplasmic reticulum and reveal a reticular structure equipped with Golgi-like functions in the axonal growth cone. Furthermore, Western blot revealed the growth cone enrichment, relative to fetal brain homogenate, of some of the proteins involved in protein synthesis, folding and catabolism. Our study provides a resource for further research and amplifies the relatively recently developed concept that the axonal growth cone is equipped with proteins capable of performing a highly diverse range of functions.

  7. Nerve growth factor receptor immunostaining suggests an extrinsic origin for hypertrophic nerves in Hirschsprung's disease.

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    Kobayashi, H; O'Briain, D S; Puri, P

    1994-01-01

    The expression of nerve growth factor receptor in colon from 20 patients with Hirshsprung's disease and 10 controls was studied immunohistochemically. The myenteric and submucous plexuses in the ganglionic bowel and hypertrophic nerve trunks in the aganglionic bowel displayed strong expression of nerve growth factor receptor. The most important finding was the identical localisation of nerve growth factor receptor immunoreactivity on the perineurium of both hypertrophic nerve trunks in Hirshs...

  8. Bidirectional remodeling of β1-integrin adhesions during chemotropic regulation of nerve growth

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    Carlstrom Lucas P

    2011-11-01

    Full Text Available Abstract Background Chemotropic factors in the extracellular microenvironment guide nerve growth by acting on the growth cone located at the tip of extending axons. Growth cone extension requires the coordination of cytoskeleton-dependent membrane protrusion and dynamic adhesion to the extracellular matrix, yet how chemotropic factors regulate these events remains an outstanding question. We demonstrated previously that the inhibitory factor myelin-associated glycoprotein (MAG triggers endocytic removal of the adhesion receptor β1-integrin from the growth cone surface membrane to negatively remodel substrate adhesions during chemorepulsion. Here, we tested how a neurotrophin might affect integrin adhesions. Results We report that brain-derived neurotropic factor (BDNF positively regulates the formation of substrate adhesions in axonal growth cones during stimulated outgrowth and prevents removal of β1-integrin adhesions by MAG. Treatment of Xenopus spinal neurons with BDNF rapidly triggered β1-integrin clustering and induced the dynamic formation of nascent vinculin-containing adhesion complexes in the growth cone periphery. Both the formation of nascent β1-integrin adhesions and the stimulation of axon extension by BDNF required cytoplasmic calcium ion signaling and integrin activation at the cell surface. Exposure to MAG decreased the number of β1-integrin adhesions in the growth cone during inhibition of axon extension. In contrast, the BDNF-induced adhesions were resistant to negative remodeling by MAG, correlating with the ability of BDNF pretreatment to counteract MAG-inhibition of axon extension. Pre-exposure to MAG prevented the BDNF-induced formation of β1-integrin adhesions and blocked the stimulation of axon extension by BDNF. Conclusions Altogether, these findings demonstrate the neurotrophin-dependent formation of integrin-based adhesions in the growth cone and reveal how a positive regulator of substrate adhesions can block

  9. Enhanced peripheral nerve regeneration through asymmetrically porous nerve guide conduit with nerve growth factor gradient.

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    Oh, Se Heang; Kang, Jun Goo; Kim, Tae Ho; Namgung, Uk; Song, Kyu Sang; Jeon, Byeong Hwa; Lee, Jin Ho

    2018-01-01

    In this study, we fabricated a nerve guide conduit (NGC) with nerve growth factor (NGF) gradient along the longitudinal direction by rolling a porous polycaprolactone membrane with NGF concentration gradient. The NGF immobilized on the membrane was continuously released for up to 35 days, and the released amount of the NGF from the membrane gradually increased from the proximal to distal NGF ends, which may allow a neurotrophic factor gradient in the tubular NGC for a sufficient period. From the in vitro cell culture experiment, it was observed that the PC12 cells sense the NGF concentration gradient on the membrane for the cell proliferation and differentiation. From the in vivo animal experiment using a long gap (20 mm) sciatic nerve defect model of rats, the NGC with NGF concentration gradient allowed more rapid nerve regeneration through the NGC than the NGC itself and NGC immobilized with uniformly distributed NGF. The NGC with NGF concentration gradient seems to be a promising strategy for the peripheral nerve regeneration. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 52-64, 2018. © 2017 Wiley Periodicals, Inc.

  10. Cone dysfunctions in retinitis pigmentosa with retinal nerve fiber layer thickening.

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    Sobacı, Güngör; Ozge, Gökhan; Gündoğan, Fatih Ç

    2012-01-01

    To investigate whether or not thicker retinal nerve fiber layer (RNFL) in retinitis pigmentosa (RP) patients relates to functional abnormalities of the photoreceptors. Optical coherence tomography-based RNFL thickness was measured by Stratus-3™ (Zeiss, Basel, Switzerland) optical coherence tomography and electroretinogram (ERG) recordings made using the RETI-port(®) system (Roland, Wiesbaden, Germany) in 27 patients with retinitis pigmentosa and in 30 healthy subjects. Photopic ERG b-wave amplitude, cone ERG b-wave latency, 30 Hz flicker amplitude, and 30 Hz flicker latency had significant correlations to the RNFL-temporal (r = -0.55, P = 0.004, r = 0.68, P = 0.001, r = -0.65, P = 0.001, and r = -0.52, P = 0.007, respectively). Eyes with thicker RNFL (ten eyes) differed significantly from those with thinner RNFL (eight eyes) regarding cone ERG b-wave latency values only (P = 0.001). Thicker RNFL in patients with retinitis pigmentosa may be associated with functional abnormality of the cone system.

  11. Accelerating axon growth to overcome limitations in functional recovery after peripheral nerve injury.

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    Gordon, Tessa; Chan, K Ming; Sulaiman, Olawale A R; Udina, Esther; Amirjani, Nasim; Brushart, Thomas M

    2009-10-01

    Injured peripheral nerves regenerate at very slow rates. Therefore, proximal injury sites such as the brachial plexus still present major challenges, and the outcomes of conventional treatments remain poor. This is in part attributable to a progressive decline in the Schwann cells' ability to provide a supportive milieu for the growth cone to extend and to find the appropriate target. These challenges are compounded by the often considerable delay of regeneration across the site of nerve laceration. Recently, low-frequency electrical stimulation (as brief as an hour) has shown promise, as it significantly accelerated regeneration in animal models through speeding of axon growth across the injury site. To test whether this might be a useful clinical tool, we carried out a randomized controlled trial in patients who had experienced substantial axonal loss in the median nerve owing to severe compression in the carpal tunnel. To further elucidate the potential mechanisms, we applied rolipram, a cyclic adenosine monophosphate agonist, to rats after axotomy of the femoral nerve. We demonstrated that effects similar to those observed in animal studies could also be attained in humans. The mechanisms of action of electrical stimulation likely operate through up-regulation of neurotrophic factors and cyclic adenosine monophosphate. Indeed, the application of rolipram significantly accelerated nerve regeneration. With new mechanistic insights into the influencing factors of peripheral nerve regeneration, the novel treatments described above could form part of an armament of synergistic therapies that could make a meaningful difference to patients with peripheral nerve injuries.

  12. Nerve growth factor promotes human hemopoietic colony growth and differentiation

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    Matsuda, H.; Coughlin, M.D.; Bienenstock, J.; Denburg, J.A.

    1988-01-01

    Nerve growth factor (NGF) is a neurotropic polypeptide necessary for the survival and growth of some central neurons, as well as sensory afferent and sympathetic neurons. Much is now known of the structural and functional characteristics of NGF, whose gene has recently been clones. Since it is synthesized in largest amounts by the male mouse submandibular gland, its role exclusively in nerve growth is questionable. These experiments indicate that NGF causes a significant stimulation of granulocyte colonies grown from human peripheral blood in standard hemopoietic methylcellulose assays. Further, NGF appears to act in a relatively selective fashion to induce the differentiation of eosinophils and basophils/mast cells. Depletion experiments show that the NGF effect may be T-cell dependent and that NGF augments the colony-stimulating effect of supernatants from the leukemic T-cell (Mo) line. The hemopoietic activity of NGF is blocked by 125 I-polyclonal and monoclonal antibodies to NGF. The authors conclude that NGF may indirectly act as a local growth factor in tissues other than those of the nervous system by causing T cells to synthesize or secrete molecules with colony-stimulating activity. In view of the synthesis of NGF in tissue injury, the involvement of basophils/mast cells and eosinophils in allergic and other inflammatory processes, and the association of mast cells with fibrosis and tissue repair, they postulate that NGF plays an important biological role in a variety of repair processes

  13. A comparison of neuronal growth cone and cell body membrane: electrophysiological and ultrastructural properties.

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    Guthrie, P B; Lee, R E; Kater, S B

    1989-10-01

    This study investigated a broad set of general electrophysiological and ultrastructural features of growth cone and cell body membrane of individual neurons where membrane from different regions of the same neuron can be directly compared. Growth cones were surgically isolated from identified adult Helisoma neurons in culture and compared with the cell body using whole-cell patch-clamp recording techniques. All isolated growth cones generated overshooting regenerative action potentials. Five neurons (buccal neurons B4, B5, and B19; pedal neurons P1 and P5) were selected that displayed distinctive action potential waveforms. In all cases, the growth cone action potential was indistinguishable from the cell body action potential and different from growth cones from other identified neurons. Two of these neurons (B5 and B19) were studied further using voltage-clamp procedures; growth cones and cell bodies again revealed major similarities within one neuron type and differences between neuron types. The only suggested difference between the growth cone and cell body was an apparent reduction in the magnitude of the A-current in the growth cone. Peak inward and outward current densities, as with other electrophysiological features, were different between neuron types, but were, again, similar between the growth cone and the cell body of the same neuron. Freeze-fracture analysis of intramembraneous particles (IMPs) was also performed on identified regions of the same neuron in culture. Both the density and the size distribution of IMPs were the same in growth cone, cell body, and neurite membranes. In these general electrophysiological and ultrastructural characteristics, therefore, growth cone membranes appear to retain the identity of the parent neuron cell body membrane.

  14. Nerve growth factor actions on the brain

    International Nuclear Information System (INIS)

    Martinez, H.J.

    1989-01-01

    We examined the effect of the trophic protein, nerve growth factor (NGF), on cultures of fetal rat neostriatum and basal forebrain-medial septal area (BF-MS) to define its role in brain development. Treatment of cultures with NGF resulted in an increase in the specific activity of the cholinergic enzyme choline acetyltransferase (CAT) in both brain areas. CAT was immunocytochemically localized to neurons. In the BF-MS, NGF treatment elicited a marked increase in staining intensity and an apparent increase in the number of CAT-positive neurons. Moreover, treatment of BF-MS cultures with NGF increased the activity of acetylcholinesterase, suggesting that the cholinergic neuron as a whole was affected. To begin defining mechanisms of action of NGF in the BF-MS, we detected NGF receptors by two independent methods. Receptors were localized to two different cellular populations: neuron-like cells, and non-neuron-like cells. Dissociation studies with [ 125 I]NGF suggested that high affinity receptors were localized to the neuron-like population. Only low-affinity receptors were localized to the non-neuron-like cells. Moreover, employing combined immunocytochemistry and [ 125 I]NGF autoradiography, we detected a subpopulation of CAT-containing neutrons that exhibited high-affinity binding. Unexpectedly, a gamma-aminobutyric acid (GABA)-containing cell group also expressed high affinity binding. However, only subsets of cholinergic or GABA neurons expressed high-affinity biding, suggesting that these transmitter populations are composed of differentially response subpopulations

  15. Complementary effects of two growth factors in multifunctionalized silk nanofibers for nerve reconstruction.

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    Tony M Dinis

    Full Text Available With the aim of forming bioactive guides for peripheral nerve regeneration, silk fibroin was electrospun to obtain aligned nanofibers. These fibers were functionalized by incorporating Nerve Growth Factor (NGF and Ciliary NeuroTrophic Factor (CNTF during electrospinning. PC12 cells grown on the fibers confirmed the bioavailability and bioactivity of the NGF, which was not significantly released from the fibers. Primary neurons from rat dorsal root ganglia (DRGs were grown on the nanofibers and anchored to the fibers and grew in a directional fashion based on the fiber orientation, and as confirmed by growth cone morphology. These biofunctionalized nanofibers led to a 3-fold increase in neurite length at their contact, which was likely due to the NGF. Glial cell growth, alignment and migration were stimulated by the CNTF in the functionalized nanofibers. Organotypic culture of rat fetal DRGs confirmed the complementary effect of both growth factors in multifunctionalized nanofibers, which allowed glial cell migration, alignment and parallel axonal growth in structures resembling the 'bands of Bungner' found in situ. Graftable multi-channel conduits based on biofunctionalized aligned silk nanofibers were developed as an organized 3D scaffold. Our bioactive silk tubes thus represent new options for a biological and biocompatible nerve guidance conduit.

  16. Facilitation of facial nerve regeneration using chitosan-β-glycerophosphate-nerve growth factor hydrogel.

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    Chao, Xiuhua; Xu, Lei; Li, Jianfeng; Han, Yuechen; Li, Xiaofei; Mao, YanYan; Shang, Haiqiong; Fan, Zhaomin; Wang, Haibo

    2016-06-01

    Conclusion C/GP hydrogel was demonstrated to be an ideal drug delivery vehicle and scaffold in the vein conduit. Combined use autologous vein and NGF continuously delivered by C/GP-NGF hydrogel can improve the recovery of facial nerve defects. Objective This study investigated the effects of chitosan-β-glycerophosphate-nerve growth factor (C/GP-NGF) hydrogel combined with autologous vein conduit on the recovery of damaged facial nerve in a rat model. Methods A 5 mm gap in the buccal branch of a rat facial nerve was reconstructed with an autologous vein. Next, C/GP-NGF hydrogel was injected into the vein conduit. In negative control groups, NGF solution or phosphate-buffered saline (PBS) was injected into the vein conduits, respectively. Autologous implantation was used as a positive control group. Vibrissae movement, electrophysiological assessment, and morphological analysis of regenerated nerves were performed to assess nerve regeneration. Results NGF continuously released from C/GP-NGF hydrogel in vitro. The recovery rate of vibrissae movement and the compound muscle action potentials of regenerated facial nerve in the C/GP-NGF group were similar to those in the Auto group, and significantly better than those in the NGF group. Furthermore, larger regenerated axons and thicker myelin sheaths were obtained in the C/GP-NGF group than those in the NGF group.

  17. The effects of functional magnetic nanotubes with incorporated nerve growth factor in neuronal differentiation of PC12 cells

    International Nuclear Information System (INIS)

    Xie Jining; Chen Linfeng; Varadan, Vijay K; Yancey, Justin; Srivatsan, Malathi

    2008-01-01

    In this in vitro study the efficiency of magnetic nanotubes to bind with nerve growth factor (NGF) and the ability of NGF-incorporated magnetic nanotubes to release the bound NGF are investigated using rat pheochromocytoma cells (PC12 cells). It is found that functional magnetic nanotubes with NGF incorporation enabled the differentiation of PC12 cells into neurons exhibiting growth cones and neurite outgrowth. Microscope observations show that filopodia extending from neuron growth cones were in close proximity to the NGF-incorporated magnetic nanotubes, at times appearing to extend towards or into them. These results show that magnetic nanotubes can be used as a delivery vehicle for NGF and thus may be exploited in attempts to treat neurodegenerative disorders such as Parkinson's disease with neurotrophins. Further neurite outgrowth can be controlled by manipulating magnetic nanotubes with external magnetic fields, thus helping in directed regeneration

  18. Domain requirements for the Dock adapter protein in growth- cone signaling.

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    Rao, Y; Zipursky, S L

    1998-03-03

    Tyrosine phosphorylation has been implicated in growth-cone guidance through genetic, biochemical, and pharmacological studies. Adapter proteins containing src homology 2 (SH2) domains and src homology 3 (SH3) domains provide a means of linking guidance signaling through phosphotyrosine to downstream effectors regulating growth-cone motility. The Drosophila adapter, Dreadlocks (Dock), the homolog of mammalian Nck containing three N-terminal SH3 domains and a single SH2 domain, is highly specialized for growth-cone guidance. In this paper, we demonstrate that Dock can couple signals in either an SH2-dependent or an SH2-independent fashion in photoreceptor (R cell) growth cones, and that Dock displays different domain requirements in different neurons.

  19. Concentration of membrane antigens by forward transport and trapping in neuronal growth cones.

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    Sheetz, M P; Baumrind, N L; Wayne, D B; Pearlman, A L

    1990-04-20

    Formation of the nervous system requires that neuronal growth cones follow specific paths and then stop at recognition signals, sensed at the growth cone's leading edge. We used antibody-coated gold particles viewed by video-enhanced differential interference contrast microscopy to observe the distribution and movement of two cell surface molecules, N-CAM and the 2A1 antigen, on growth cones of cultured cortical neurons. Gold particles are occasionally transported forward at 1-2 microns/s to the leading edge where they are trapped but continue to move. Concentration at the edge persists after cytochalasin D treatment or ATP depletion, but active movements to and along edges cease. We also observed a novel outward movement of small cytoplasmic aggregates at 1.8 microns/s in filopodia. We suggest that active forward transport and trapping involve reversible attachment of antigens to and transport along cytoskeletal elements localized to edges of growth cones.

  20. Neuroprotective effects of ultrasound-guided nerve growth factor injections after sciatic nerve injury

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    Hong-fei Li

    2015-01-01

    Full Text Available Nerve growth factor (NGF plays an important role in promoting neuroregeneration after peripheral nerve injury. However, its effects are limited by its short half-life; it is therefore important to identify an effective mode of administration. High-frequency ultrasound (HFU is increasingly used in the clinic for high-resolution visualization of tissues, and has been proposed as a method for identifying and evaluating peripheral nerve damage after injury. In addition, HFU is widely used for guiding needle placement when administering drugs to a specific site. We hypothesized that HFU guiding would optimize the neuroprotective effects of NGF on sciatic nerve injury in the rabbit. We performed behavioral, ultrasound, electrophysiological, histological, and immunohistochemical evaluation of HFU-guided NGF injections administered immediately after injury, or 14 days later, and compared this mode of administration with intramuscular NGF injections. Across all assessments, HFU-guided NGF injections gave consistently better outcomes than intramuscular NGF injections administered immediately or 14 days after injury, with immediate treatment also yielding better structural and functional results than when the treatment was delayed by 14 days. Our findings indicate that NGF should be administered as early as possible after peripheral nerve injury, and highlight the striking neuroprotective effects of HFU-guided NGF injections on peripheral nerve injury compared with intramuscular administration.

  1. Nerve growth factor reduces apoptotic cell death in rat facial motor neurons after facial nerve injury.

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    Hui, Lian; Yuan, Jing; Ren, Zhong; Jiang, Xuejun

    2015-01-01

    To assess the effects of nerve growth factor (NGF) on motor neurons after induction of a facial nerve lesion, and to compare the effects of different routes of NGF injection on motor neuron survival. This study was carried out in the Department of Otolaryngology Head & Neck Surgery, China Medical University, Liaoning, China from October 2012 to March 2013. Male Wistar rats (n = 65) were randomly assigned into 4 groups: A) healthy controls; B) facial nerve lesion model + normal saline injection; C) facial nerve lesion model + NGF injection through the stylomastoid foramen; D) facial nerve lesion model + intraperitoneal injection of NGF. Apoptotic cell death was detected using the terminal deoxynucleotidyl transferase dUTP nick end-labeling assay. Expression of caspase-3 and p53 up-regulated modulator of apoptosis (PUMA) was determined by immunohistochemistry. Injection of NGF significantly reduced cell apoptosis, and also greatly decreased caspase-3 and PUMA expression in injured motor neurons. Group C exhibited better efficacy for preventing cellular apoptosis and decreasing caspase-3 and PUMA expression compared with group D (pfacial nerve injury in rats. The NGF injected through the stylomastoid foramen demonstrated better protective efficacy than when injected intraperitoneally.

  2. Domain requirements for the Dock adapter protein in growth- cone signaling

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    Rao, Yong; Zipursky, S. Lawrence

    1998-01-01

    Tyrosine phosphorylation has been implicated in growth-cone guidance through genetic, biochemical, and pharmacological studies. Adapter proteins containing src homology 2 (SH2) domains and src homology 3 (SH3) domains provide a means of linking guidance signaling through phosphotyrosine to downstream effectors regulating growth-cone motility. The Drosophila adapter, Dreadlocks (Dock), the homolog of mammalian Nck containing three N-terminal SH3 domains and a single SH2 domain, is highly speci...

  3. Microtubule and Cell Contact Dependency of ER-bound PTP1B Localization in Growth Cones

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    Fuentes, Federico

    2009-01-01

    PTP1B is an ER-bound protein tyrosine phosphatase implied in the regulation of cell adhesion. Here we investigated mechanisms involved in the positioning and dynamics of PTP1B in axonal growth cones and evaluated the role of this enzyme in axons. In growth cones, PTP1B consistently localizes in the central domain, and occasionally at the peripheral region and filopodia. Live imaging of GFP-PTP1B reveals dynamic excursions of fingerlike processes within the peripheral region and filopodia. PTP1B and GFP-PTP1B colocalize with ER markers and coalign with microtubules at the peripheral region and redistribute to the base of the growth cone after treatment with nocodazole, a condition that is reversible. Growth cone contact with cellular targets is accompanied by invasion of PTP1B and stable microtubules in the peripheral region aligned with the contact axis. Functional impairment of PTP1B causes retardation of axon elongation, as well as reduction of growth cone filopodia lifetime and Src activity. Our results highlight the role of microtubules and cell contacts in the positioning of ER-bound PTP1B to the peripheral region of growth cones, which may be required for the positive role of PTP1B in axon elongation, filopodia stabilization, and Src activity. PMID:19158394

  4. Composition and structure of ion-bombardment-induced growth cones on InP

    International Nuclear Information System (INIS)

    Malherbe, J.B.; Lakner, H.; Gries, W.H.

    1991-01-01

    The previously reported effect of low-energy (several keV) ion bombardment on the surface topography of InP was investigated by scanning transmission electron microscopy. Convergent beam electron diffraction patterns of the surface growth 'cones' induced by argon ion bombardment of (100) InP between 7 and 10 keV proved the cones to consist of crystalline InP (and not metallic indium, as has sometimes been claimed). The investigation showed that the irradiated surface region is not rendered completely amorphous but that it recrystallizes from the crystalline/amorphous interface in a columnar growth pattern, often terminating in growth cones protruding above the surface. Weak beam investigations revealed that the overwhelming majority of the cones have the orientation of the substrate. These phenomena were observed at all dose densities from 7 x 10 15 to 2 x 10 17 cm -2 . (author)

  5. Nerve Growth Factor in Cancer Cell Death and Survival

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    Molloy, Niamh H.; Read, Danielle E.; Gorman, Adrienne M., E-mail: adrienne.gorman@nuigalway.ie [Apoptosis Research Centre, School of Natural Sciences, National University of Ireland, Galway (Ireland)

    2011-02-01

    One of the major challenges for cancer therapeutics is the resistance of many tumor cells to induction of cell death due to pro-survival signaling in the cancer cells. Here we review the growing literature which shows that neurotrophins contribute to pro-survival signaling in many different types of cancer. In particular, nerve growth factor, the archetypal neurotrophin, has been shown to play a role in tumorigenesis over the past decade. Nerve growth factor mediates its effects through its two cognate receptors, TrkA, a receptor tyrosine kinase and p75{sup NTR}, a member of the death receptor superfamily. Depending on the tumor origin, pro-survival signaling can be mediated by TrkA receptors or by p75{sup NTR}. For example, in breast cancer the aberrant expression of nerve growth factor stimulates proliferative signaling through TrkA and pro-survival signaling through p75{sup NTR}. This latter signaling through p75{sup NTR} promotes increased resistance to the induction of cell death by chemotherapeutic treatments. In contrast, in prostate cells the p75{sup NTR} mediates cell death and prevents metastasis. In prostate cancer, expression of this receptor is lost, which contributes to tumor progression by allowing cells to survive, proliferate and metastasize. This review focuses on our current knowledge of neurotrophin signaling in cancer, with a particular emphasis on nerve growth factor regulation of cell death and survival in cancer.

  6. Nerve Growth Factor in Cancer Cell Death and Survival

    International Nuclear Information System (INIS)

    Molloy, Niamh H.; Read, Danielle E.; Gorman, Adrienne M.

    2011-01-01

    One of the major challenges for cancer therapeutics is the resistance of many tumor cells to induction of cell death due to pro-survival signaling in the cancer cells. Here we review the growing literature which shows that neurotrophins contribute to pro-survival signaling in many different types of cancer. In particular, nerve growth factor, the archetypal neurotrophin, has been shown to play a role in tumorigenesis over the past decade. Nerve growth factor mediates its effects through its two cognate receptors, TrkA, a receptor tyrosine kinase and p75 NTR , a member of the death receptor superfamily. Depending on the tumor origin, pro-survival signaling can be mediated by TrkA receptors or by p75 NTR . For example, in breast cancer the aberrant expression of nerve growth factor stimulates proliferative signaling through TrkA and pro-survival signaling through p75 NTR . This latter signaling through p75 NTR promotes increased resistance to the induction of cell death by chemotherapeutic treatments. In contrast, in prostate cells the p75 NTR mediates cell death and prevents metastasis. In prostate cancer, expression of this receptor is lost, which contributes to tumor progression by allowing cells to survive, proliferate and metastasize. This review focuses on our current knowledge of neurotrophin signaling in cancer, with a particular emphasis on nerve growth factor regulation of cell death and survival in cancer

  7. Nerve growth factor loaded heparin/chitosan scaffolds for accelerating peripheral nerve regeneration.

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    Li, Guicai; Xiao, Qinzhi; Zhang, Luzhong; Zhao, Yahong; Yang, Yumin

    2017-09-01

    Artificial chitosan scaffolds have been widely investigated for peripheral nerve regeneration. However, the effect was not as good as that of autologous grafts and therefore could not meet the clinical requirement. In the present study, the nerve growth factor (NGF) loaded heparin/chitosan scaffolds were fabricated via electrostatic interaction for further improving nerve regeneration. The physicochemical properties including morphology, wettability and composition were measured. The heparin immobilization, NGF loading and release were quantitatively and qualitatively characterized, respectively. The effect of NGF loaded heparin/chitosan scaffolds on nerve regeneration was evaluated by Schwann cells culture for different periods. The results showed that the heparin immobilization and NGF loading did not cause the change of bulk properties of chitosan scaffolds except for morphology and wettability. The pre-immobilization of heparin in chitosan scaffolds could enhance the stability of subsequently loaded NGF. The NGF loaded heparin/chitosan scaffolds could obviously improve the attachment and proliferation of Schwann cells in vitro. More importantly, the NGF loaded heparin/chitosan scaffolds could effectively promote the morphology development of Schwann cells. The study may provide a useful experimental basis to design and develop artificial implants for peripheral nerve regeneration and other tissue regeneration. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Nerve growth factor mRNA in brain: localization by in situ hybridization

    International Nuclear Information System (INIS)

    Rennert, P.D.; Heinrich, G.

    1986-01-01

    Nerve Growth Factor is a 118 amino acid polypeptide that plays an important role in the differentiation and survival of neurons. The recent discovery that a mRNA that encodes beta Nerve Growth Factor is present in brain suggests that the Nerve Growth Factor gene may not only regulate gene expression of peripheral but also of central neurons. To identify the site(s) of Nerve Growth Factor mRNA production in the brain and to determine which cells express the Nerve Growth Factor gene, the technique of in situ hybridization was employed. A 32P-labeled RNA probe complementary to Nerve Growth Factor mRNA hybridized to cells in the stratum granulosum of the dentate gyrus and the stratum pyramidale of the hippocampus. These observations identify for the first time cellular sites of Nerve Growth Factor gene expression in the central nervous system, and suggest that Nerve Growth Factor mRNA is produced by neurons

  9. Birth order dependent growth cone segregation determines synaptic layer identity in the Drosophila visual system.

    Science.gov (United States)

    Kulkarni, Abhishek; Ertekin, Deniz; Lee, Chi-Hon; Hummel, Thomas

    2016-03-17

    The precise recognition of appropriate synaptic partner neurons is a critical step during neural circuit assembly. However, little is known about the developmental context in which recognition specificity is important to establish synaptic contacts. We show that in the Drosophila visual system, sequential segregation of photoreceptor afferents, reflecting their birth order, lead to differential positioning of their growth cones in the early target region. By combining loss- and gain-of-function analyses we demonstrate that relative differences in the expression of the transcription factor Sequoia regulate R cell growth cone segregation. This initial growth cone positioning is consolidated via cell-adhesion molecule Capricious in R8 axons. Further, we show that the initial growth cone positioning determines synaptic layer selection through proximity-based axon-target interactions. Taken together, we demonstrate that birth order dependent pre-patterning of afferent growth cones is an essential pre-requisite for the identification of synaptic partner neurons during visual map formation in Drosophila.

  10. Topical administration of adrenergic receptor pharmaceutics and nerve growth factor

    OpenAIRE

    Steinle, Jena

    2010-01-01

    Jena J SteinleDepartments of Ophthalmology and Anatomy and Neurobiology, Hamilton Eye Institute, University of Tennessee Health Science Center, Memphis, TN 38163, USAAbstract: Topical application of nerve growth factor (NGF) and adrenergic receptor pharmaceutics are currently in use for corneal ulcers and glaucoma. A recent interest in the neuroprotective abilities of NGF has led to a renewed interest in NGF as a therapeutic for retinal and choroidal diseases. NGF can promote cell proliferati...

  11. Curative effect of surgery combined with nerve growth factor preparation treatment of acute cerebral hemorrhage

    Directory of Open Access Journals (Sweden)

    Fei Luo

    2017-01-01

    Conclusion: Surgery combined with nerve growth factor preparation treatment of acute cerebral hemorrhage can improve neural nutritional status and reduce nerve injury degree, and it is beneficial to the recovery of neural function.

  12. Drosophila growth cones: a genetically tractable platform for the analysis of axonal growth dynamics.

    Science.gov (United States)

    Sánchez-Soriano, Natalia; Gonçalves-Pimentel, Catarina; Beaven, Robin; Haessler, Ulrike; Ofner-Ziegenfuss, Lisa; Ballestrem, Christoph; Prokop, Andreas

    2010-01-01

    The formation of neuronal networks, during development and regeneration, requires outgrowth of axons along reproducible paths toward their appropriate postsynaptic target cells. Axonal extension occurs at growth cones (GCs) at the tips of axons. GC advance and navigation requires the activity of their cytoskeletal networks, comprising filamentous actin (F-actin) in lamellipodia and filopodia as well as dynamic microtubules (MTs) emanating from bundles of the axonal core. The molecular mechanisms governing these two cytoskeletal networks, their cross-talk, and their response to extracellular signaling cues are only partially understood, hindering our conceptual understanding of how regulated changes in GC behavior are controlled. Here, we introduce Drosophila GCs as a suitable model to address these mechanisms. Morphological and cytoskeletal readouts of Drosophila GCs are similar to those of other models, including mammals, as demonstrated here for MT and F-actin dynamics, axonal growth rates, filopodial structure and motility, organizational principles of MT networks, and subcellular marker localization. Therefore, we expect fundamental insights gained in Drosophila to be translatable into vertebrate biology. The advantage of the Drosophila model over others is its enormous amenability to combinatorial genetics as a powerful strategy to address the complexity of regulatory networks governing axonal growth. Thus, using pharmacological and genetic manipulations, we demonstrate a role of the actin cytoskeleton in a specific form of MT organization (loop formation), known to regulate GC pausing behavior. We demonstrate these events to be mediated by the actin-MT linking factor Short stop, thus identifying an essential molecular player in this context.

  13. Nerve growth factor expression by PLG-mediated lipofection.

    Science.gov (United States)

    Whittlesey, Kevin J; Shea, Lonnie D

    2006-04-01

    Biomaterials capable of efficient gene delivery provide a fundamental tool for basic and applied research models, such as promoting neural regeneration. We developed a system for the encapsulation and sustained release of plasmid DNA complexed with a cationic lipid and investigated their efficacy using in vitro models of neurite outgrowth. Sustained lipoplex release was obtained for up to 50 days, with rates controlled by the fabrication conditions. Released lipoplexes retained their activity, transfecting 48.2+/-8.3% of NIH3T3 cells with luciferase activity of 3.97x10(7)RLU/mg. Expression of nerve growth factor (NGF) was employed in two models of neurite outgrowth: PC12 and primary dorsal root ganglia (DRG) co-culture. Polymer-mediated lipofection of PC12 produced bioactive NGF, eliciting robust neurite outgrowth. An EGFP/NGF dual-expression vector identified transfected cells (GFP-positive) while neurite outgrowth verified NGF secretion. A co-culture model examined the ability of NGF secretion by an accessory cell population to stimulate DRG neurite outgrowth. Polymer-mediated transfection of HEK293T with an NGF-encoding plasmid induced outgrowth by DRG neurons. This system could be fabricated as implants or nerve guidance conduits to support cellular and tissue regeneration. Combining this physical support with the ability to locally express neurotrophic factors will potentiate regeneration in nerve injury and disease models.

  14. Association of nerve growth factor receptors with the triton X-100 cytoskeleton of PC12 cells

    International Nuclear Information System (INIS)

    Vale, R.D.; Ignatius, M.J.; Shooter, E.M.

    1985-01-01

    Triton X-100 solubilizes membranes of PC12 cells and leaves behind a nucleus and an array of cytoskeletal filaments. Nerve growth factor (NGF) receptors are associated with this Triton X-100-insoluble residue. Two classes of NGF receptors are found on PC12 cells which display rapid and slow dissociating kinetics. Although rapidly dissociating binding is predominant (greater than 75%) in intact cells, the majority of binding to the Triton X-100 cytoskeleton is slowly dissociating (greater than 75%). Rapidly dissociating NGF binding on intact cells can be converted to a slowly dissociating form by the plant lectin wheat germ agglutinin (WGA). This lectin also increases the number of receptors which associate with the Triton X-100 cytoskeleton by more than 10-fold. 125 I-NGF bound to receptors can be visualized by light microscopy autoradiography in Triton X-100-insoluble residues of cell bodies, as well as growth cones and neurites. The WGA-induced association with the cytoskeleton, however, is not specific for the NGF receptor. Concentrations of WGA which change the Triton X-100 solubility of membrane glycoproteins are similar to those required to alter the kinetic state of the NGF receptor. Both events may be related to the crossbridging of cell surface proteins induced by this multivalent lectin

  15. Genetic modification of human sural nerve segments by a lentiviral vector encoding nerve growth factor

    NARCIS (Netherlands)

    Tannemaat, Martijn R; Boer, Gerard J; Verhaagen, J.; Malessy, Martijn J A

    2007-01-01

    OBJECTIVE: Autologous nerve grafts are used to treat severe peripheral nerve injury, but recovery of nerve function after grafting is rarely complete. Exogenous application of neurotrophic factors may enhance regeneration, but thus far the application of neurotrophic factors has been hampered by

  16. DRG axon elongation and growth cone collapse rate induced by Sema3A are differently dependent on NGF concentration.

    Science.gov (United States)

    Kaselis, Andrius; Treinys, Rimantas; Vosyliūtė, Rūta; Šatkauskas, Saulius

    2014-03-01

    Regeneration of embryonic and adult dorsal root ganglion (DRG) sensory axons is highly impeded when they encounter neuronal growth cone-collapsing factor semaphorin3A (Sema3A). On the other hand, increasing evidence shows that DRG axon's regeneration can be stimulated by nerve growth factor (NGF). In this study, we aimed to evaluate whether increased NGF concentrations can counterweight Sema3A-induced inhibitory responses in 15-day-old mouse embryo (E15) DRG axons. The DRG explants were grown in Neurobasal-based medium with different NGF concentrations ranging from 0 to 100 ng/mL and then treated with Sema3A at constant 10 ng/mL concentration. To evaluate interplay between NGF and Sema3A number of DRG axons, axon outgrowth distance and collapse rate were measured. We found that the increased NGF concentrations abolish Sema3A-induced inhibitory effect on axon outgrowth, while they have no effect on Sema3A-induced collapse rate.

  17. Mast Cells Synthesize, Store, and Release Nerve Growth Factor

    Science.gov (United States)

    Leon, A.; Buriani, A.; dal Toso, R.; Fabris, M.; Romanello, S.; Aloe, L.; Levi-Montalcini, R.

    1994-04-01

    Mast cells and nerve growth factor (NGF) have both been reported to be involved in neuroimmune interactions and tissue inflammation. In many peripheral tissues, mast cells interact with the innervating fibers. Changes in the behaviors of both of these elements occur after tissue injury/inflammation. As such conditions are typically associated with rapid mast cell activation and NGF accumulation in inflammatory exudates, we hypothesized that mast cells may be capable of producing NGF. Here we report that (i) NGF mRNA is expressed in adult rat peritoneal mast cells; (ii) anti-NGF antibodies clearly stain vesicular compartments of purified mast cells and mast cells in histological sections of adult rodent mesenchymal tissues; and (iii) medium conditioned by peritoneal mast cells contains biologically active NGF. Mast cells thus represent a newly recognized source of NGF. The known actions of NGF on peripheral nerve fibers and immune cells suggest that mast cell-derived NGF may control adaptive/reactive responses of the nervous and immune systems toward noxious tissue perturbations. Conversely, alterations in normal mast cell behaviors may provoke maladaptive neuroimmune tissue responses whose consequences could have profound implications in inflammatory disease states, including those of an autoimmune nature.

  18. Molecular analysis of the nerve growth factor receptor

    International Nuclear Information System (INIS)

    Hempstead, B.; Patil, N.; Olson, K.; Chao, M.

    1988-01-01

    An essential molecule in the translocation of information by nerve growth factor (NGF) to responsive cells is the cell-surface receptor for NGF. This paper presents information on the genomic structure of the NGF receptor gene, NGF receptor models, and transfection of NGF receptors. Equilibrium binding of [ 125 I]NGF to cells reveals two distinct affinity states for the NGF receptor. The human NGF receptor gene is a single-copy gene, consisting of six exons that span 23 kb. The receptor gene is capable of being transferred to fibroblast cells from human genomic DNA and expressed at high levels. The constitutive nature of the receptor promoter sequence is a partial explanation of why this tissue-specific gene is expressed efficiently in a variety of nonneuronal cells after genomic gene transfer. The two kinetic forms of the NGF receptor appear to be encoded by the same protein, which is the product of a single gene

  19. Pannexin 1 Modulates Axonal Growth in Mouse Peripheral Nerves

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    Steven M. Horton

    2017-11-01

    Full Text Available The pannexin family of channels consists of three members—pannexin-1 (Panx1, pannexin-2 (Panx2, and pannexin-3 (Panx3 that enable the exchange of metabolites and signaling molecules between intracellular and extracellular compartments. Pannexin-mediated release of intracellular ATP into the extracellular space has been tied to a number of cellular activities, primarily through the activity of type P2 purinergic receptors. Previous work indicates that the opening of Panx1 channels and activation of purinergic receptors by extracellular ATP may cause inflammation and apoptosis. In the CNS (central nervous system and PNS (peripheral nervous system, coupled pannexin, and P2 functions have been linked to peripheral sensitization (pain pathways. Purinergic pathways are also essential for other critical processes in the PNS, including myelination and neurite outgrowth. However, whether such pathways are pannexin-dependent remains to be determined. In this study, we use a Panx1 knockout mouse model and pharmacological inhibitors of the Panx1 and the ATP-mediated signaling pathway to fill gaps in our understanding of Panx1 localization in peripheral nerves, roles for Panx1 in axonal outgrowth and myelination, and neurite extension. Our data show that Panx1 is localized to axonal, myelin, and vascular compartments of the peripheral nerves. Knockout of Panx1 gene significantly increased axonal caliber in vivo and axonal growth rate in cultured dorsal root ganglia (DRG neurons. Furthermore, genetic knockout of Panx1 or inhibition of components of purinergic signaling, by treatment with probenecid and apyrase, resulted in denser axonal outgrowth from cultured DRG explants compared to untreated wild-types. Our findings suggest that Panx1 regulates axonal growth in the peripheral nervous system.

  20. The discovery of the growth cone and its influence on the study of axon guidance

    Directory of Open Access Journals (Sweden)

    Elisa eTamariz

    2015-05-01

    Full Text Available For over a century, there has been a great deal of interest in understanding how neural connectivity is established during development and regeneration. Interest in the latter arises from the possibility that knowledge of this process can be used to reestablish lost connections after lesion or neurodegeneration. At the end of the XIX century, Santiago Ramón y Cajal discovered that the distal tip of growing axons contained a structure that he called the growth cone. He proposed that this structure enabled the axon’s oriented growth in response to attractants, now known as chemotropic molecules. He further proposed that the physical properties of the surrounding tissues could influence the growth cone and the direction of growth. This seminal discovery afforded a plausible explanation for directed axonal growth and has led to the discovery of axon guidance mechanisms that include diffusible attractants and repellants and guidance cues anchored to cell membranes or extracellular matrix. In this review the major events in the development of this field are discussed.

  1. Exposure to nerve growth factor worsens nephrotoxic effect induced by Cyclosporine A in HK-2 cells.

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    Donatella Vizza

    Full Text Available Nerve growth factor is a neurotrophin that promotes cell growth, differentiation, survival and death through two different receptors: TrkA(NTR and p75(NTR. Nerve growth factor serum concentrations increase during many inflammatory and autoimmune diseases, glomerulonephritis, chronic kidney disease, end-stage renal disease and, particularly, in renal transplant. Considering that nerve growth factor exerts beneficial effects in the treatment of major central and peripheral neurodegenerative diseases, skin and corneal ulcers, we asked whether nerve growth factor could also exert a role in Cyclosporine A-induced graft nephrotoxicity. Our hypothesis was raised from basic evidence indicating that Cyclosporine A-inhibition of calcineurin-NFAT pathway increases nerve growth factor expression levels. Therefore, we investigated the involvement of nerve growth factor and its receptors in the damage exerted by Cyclosporine A in tubular renal cells, HK-2. Our results showed that in HK-2 cells combined treatment with Cyclosporine A + nerve growth factor induced a significant reduction in cell vitality concomitant with a down-regulation of Cyclin D1 and up-regulation of p21 levels respect to cells treated with Cyclosporine A alone. Moreover functional experiments showed that the co-treatment significantly up-regulated human p21promoter activity by involvement of the Sp1 transcription factor, whose nuclear content was negatively regulated by activated NFATc1. In addition we observed that the combined exposure to Cyclosporine A + nerve growth factor promoted an up-regulation of p75 (NTR and its target genes, p53 and BAD leading to the activation of intrinsic apoptosis. Finally, the chemical inhibition of p75(NTR down-regulated the intrinsic apoptotic signal. We describe two new mechanisms by which nerve growth factor promotes growth arrest and apoptosis in tubular renal cells exposed to Cyclosporine A.

  2. Co-immobilization of semaphorin3A and nerve growth factor to guide and pattern axons.

    Science.gov (United States)

    McCormick, Aleesha M; Jarmusik, Natalie A; Leipzig, Nic D

    2015-12-01

    Immobilization of axon guidance cues offers a powerful tissue regenerative strategy to control the presentation and spatial location of these biomolecules. We use our previously developed immobilization strategy to specifically tether recombinant biotinylated nerve growth factor (bNGF) and biotinylated semaphorin3A (bSema3A) to chitosan films as an outgrowth and guidance platform. DRG neurite length and number for a range of single cues of immobilized bNGF or bSema3A were examined to determine a concentration response. Next single and dual cues of bNGF and bSema3A were immobilized and DRG guidance was assessed in response to a step concentration change from zero. Overall, immobilized groups caused axon extension, retraction and turning depending on the ratio of bNGF and bSema3A immobilized in the encountered region. This response indicated the exquisite sensitivity of DRG axons to both attractive and repulsive tethered cues. bSema3A concentrations of 0.10 and 0.49 ng/mm(2), when co-immobilized with bNGF (at 0.86 and 0.43 ng/mm(2) respectively), caused axons to turn away from the co-immobilized region. Immunocytochemical analysis showed that at these bSema3A concentrations, axons inside the co-immobilized region display microtubule degradation and breakdown of actin filaments. At the lowest bSema3A concentration (0.01 ng/mm(2)) co-immobilized with a higher bNGF concentration (2.16 ng/mm(2)), neurite lengths are shorter in the immobilized area, but bNGF dominates the guidance mechanism as neurites are directed toward the immobilized region. Future applications can pattern these cues in various geometries and gradients in order to better modulate axon guidance in terms of polarity, extension and branching. Nervous system formation and regeneration requires key molecules for guiding the growth cone and nervous system patterning. In vivo these molecules work in conjunction with one another to modulate axon guidance, and often they are tethered to limit spatial

  3. Effect of nerve activity on transport of nerve growth factor and dopamine β-hydroxylase antibodies in sympathetic neurones

    International Nuclear Information System (INIS)

    Lees, G.; Chubb, I.; Freeman, C.; Geffen, L.; Rush, R.

    1981-01-01

    The effect of nerve activity on the uptake and retrograde transport of nerve growth factor (NGF) and dopamine β-hydroxylase (DBH) antibodies was studied by injecting 125 I-labelled NGF and anti-DBH into the anterior eye chamber of guinea-pigs. Decentralization of the ipsilateral superior cervical ganglion (SCG) had no significant effect on the retrograde transport of either NGF or anti-DBH. Phenoxybenzamine produced a 50% increase in anti-DBH but not NGF accumulation and this effect was prevented by prior decentralization. This demonstrates that NGF is taken up independently of the retrieval of synaptic vesicle components. (Auth.)

  4. Topical administration of adrenergic receptor pharmaceutics and nerve growth factor

    Directory of Open Access Journals (Sweden)

    Jena J Steinle

    2010-06-01

    Full Text Available Jena J SteinleDepartments of Ophthalmology and Anatomy and Neurobiology, Hamilton Eye Institute, University of Tennessee Health Science Center, Memphis, TN 38163, USAAbstract: Topical application of nerve growth factor (NGF and adrenergic receptor pharmaceutics are currently in use for corneal ulcers and glaucoma. A recent interest in the neuroprotective abilities of NGF has led to a renewed interest in NGF as a therapeutic for retinal and choroidal diseases. NGF can promote cell proliferation through actions of the TrkA receptor or promote apoptosis through receptor p75NTR. This understanding has led to novel interest in the role of NGF for diseases of the posterior eye. The role of β-adrenergic receptor agonists and antagonists for treatments of glaucoma, diabetic retinopathy, and their potential mechanisms of action, are still under investigation. This review discusses the current knowledge and applications of topical NGF and adrenergic receptor drugs for ocular disease.Keywords: NGF, β-adrenergic receptor agents, α-adrenergic receptor agents, retina, cornea, glaucoma

  5. Retrograde axonal transport of 125I-nerve growth factor in rat ileal mesenteric nerves. Effect of streptozocin diabetes

    International Nuclear Information System (INIS)

    Schmidt, R.E.; Plurad, S.B.; Saffitz, J.E.; Grabau, G.G.; Yip, H.K.

    1985-01-01

    The retrograde axonal transport of intravenously (i.v.) administered 125 I-nerve growth factor ( 125 I-NGF) was examined in mesenteric nerves innervating the small bowel of rats with streptozocin (STZ) diabetes using methods described in detail in the companion article. The accumulation of 125 I-NGF distal to a ligature on the ileal mesenteric nerves of diabetic animals was 30-40% less than in control animals. The inhibition of accumulation of 125 I-NGF in diabetic animals was greater at a ligature tied 2 h after i.v. administration than at a ligature tied after 14 h, which suggests that the diabetic animals may have a lag in initiation of NGF transport in the terminal axon or retardation of transport at some site along the axon. The 125 I-NGF transport defect was observed as early as 3 days after the induction of diabetes, a time before the development of structural axonal lesions, and did not worsen at later times when dystrophic axonopathy is present. Both the ileal mesenteric nerves, which eventually develop dystrophic axonopathy in experimental diabetes, and the jejunal mesenteric nerves, which never develop comparable structural alterations, showed similar 125 I-NGF transport deficits, suggesting that the existence of the transport abnormality does not predict the eventual development of dystrophic axonal lesions. Autoradiographic localization of 125 I-NGF in the ileal mesenteric nerves of animals that had been diabetic for 11-13 mo demonstrated decreased amounts of 125 I-NGF in transit in unligated paravascular nerve fascicles. There was, however, no evidence for focal retardation of transported 125 I-NGF at the sites of dystrophic axonal lesions

  6. The glucuronyltransferase GlcAT-P is required for stretch growth of peripheral nerves in Drosophila.

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    Rahul Pandey

    Full Text Available During development, the growth of the animal body is accompanied by a concomitant elongation of the peripheral nerves, which requires the elongation of integrated nerve fibers and the axons projecting therein. Although this process is of fundamental importance to almost all organisms of the animal kingdom, very little is known about the mechanisms regulating this process. Here, we describe the identification and characterization of novel mutant alleles of GlcAT-P, the Drosophila ortholog of the mammalian glucuronyltransferase b3gat1. GlcAT-P mutants reveal shorter larval peripheral nerves and an elongated ventral nerve cord (VNC. We show that GlcAT-P is expressed in a subset of neurons in the central brain hemispheres, in some motoneurons of the ventral nerve cord as well as in central and peripheral nerve glia. We demonstrate that in GlcAT-P mutants the VNC is under tension of shorter peripheral nerves suggesting that the VNC elongates as a consequence of tension imparted by retarded peripheral nerve growth during larval development. We also provide evidence that for growth of peripheral nerve fibers GlcAT-P is critically required in hemocytes; however, glial cells are also important in this process. The glial specific repo gene acts as a modifier of GlcAT-P and loss or reduction of repo function in a GlcAT-P mutant background enhances VNC elongation. We propose a model in which hemocytes are required for aspects of glial cell biology which in turn affects the elongation of peripheral nerves during larval development. Our data also identifies GlcAT-P as a first candidate gene involved in growth of integrated peripheral nerves and therefore establishes Drosophila as an amenable in-vivo model system to study this process at the cellular and molecular level in more detail.

  7. The glucuronyltransferase GlcAT-P is required for stretch growth of peripheral nerves in Drosophila.

    Science.gov (United States)

    Pandey, Rahul; Blanco, Jorge; Udolph, Gerald

    2011-01-01

    During development, the growth of the animal body is accompanied by a concomitant elongation of the peripheral nerves, which requires the elongation of integrated nerve fibers and the axons projecting therein. Although this process is of fundamental importance to almost all organisms of the animal kingdom, very little is known about the mechanisms regulating this process. Here, we describe the identification and characterization of novel mutant alleles of GlcAT-P, the Drosophila ortholog of the mammalian glucuronyltransferase b3gat1. GlcAT-P mutants reveal shorter larval peripheral nerves and an elongated ventral nerve cord (VNC). We show that GlcAT-P is expressed in a subset of neurons in the central brain hemispheres, in some motoneurons of the ventral nerve cord as well as in central and peripheral nerve glia. We demonstrate that in GlcAT-P mutants the VNC is under tension of shorter peripheral nerves suggesting that the VNC elongates as a consequence of tension imparted by retarded peripheral nerve growth during larval development. We also provide evidence that for growth of peripheral nerve fibers GlcAT-P is critically required in hemocytes; however, glial cells are also important in this process. The glial specific repo gene acts as a modifier of GlcAT-P and loss or reduction of repo function in a GlcAT-P mutant background enhances VNC elongation. We propose a model in which hemocytes are required for aspects of glial cell biology which in turn affects the elongation of peripheral nerves during larval development. Our data also identifies GlcAT-P as a first candidate gene involved in growth of integrated peripheral nerves and therefore establishes Drosophila as an amenable in-vivo model system to study this process at the cellular and molecular level in more detail.

  8. Expression of β-nerve growth factor and homeobox A10 in experimental cryptorchidism treated with exogenous nerve growth factor.

    Science.gov (United States)

    Xian, Hua; Xian, Yun; Liu, Lili; Wang, Yongjun; He, Jianghong; Huang, Jianfei

    2015-04-01

    With the exception of standard inguinal orchidopexy, treatment of cryptorchidism with human chorionic gonadotropin has been performed for several years; however, its side effects have limited its application. The β‑nerve growth factor (NGF) and homeobox A10 (HoxA10) genes are closely associated with the development of the testes. To the best of our knowledge, whether exogenous NGF alters the endogenous levels of NGF and HoxA10 in cryptorchidism in rats remains to be elucidated. The aim of the present study was to evaluate the gene and protein expression of NGF and HoxA10 in experimental cryptorchidism following treatment with exogenous NGF. A unilateral mechanical cryptorchidism model in Sprague-Dawley rats was established and different concentrations of exogenous NGF were administered to observe the effects of NGF on cryptorchidism. Changes in the gene and protein expression levels of NGF and HoxA10 in the cryptorchid tissues of each group were identified using one step reverse transcription-quantitative polymerase chain reaction, in situ hybridization with digoxigenin‑labeled‑β‑NGF RNA probes, immunofluorescence and immunohistochemistry, respectively. The expression levels of NGF and HoxA10 were markedly higher in the group treated with a high dose of exogenous NGF compared with the group treated with a low dose of exogenous NGF and the group treated with human chorionic gonadotropin. These results confirmed the potential therapeutic effect of exogenous NGF in human cryptorchidism.

  9. Baseline effects of lysophosphatidylcholine and nerve growth factor in a rat model of sciatic nerve regeneration after crush injury

    Directory of Open Access Journals (Sweden)

    Ryan L Wood

    2018-01-01

    Full Text Available Schwann cells play a major role in helping heal injured nerves. They help clear debris, produce neurotrophins, upregulate neurotrophin receptors, and form bands of Büngner to guide the healing nerve. But nerves do not always produce enough neurotrophins and neurotrophin receptors to repair themselves. Nerve growth factor (NGF is an important neurotrophin for promoting nerve healing and lysophosphatidylcholine (LPC has been shown to stimulate NGF receptors (NGFR. This study tested the administration of a single intraneural injection of LPC (1 mg/mL for single LPC injection and 10 mg/mL for multiple LPC injections at day 0 and one (day 7, two (days 5 and 7, or three (days 5, 7, and 9 injections of NGF (160 ng/mL for single injections and 80 ng/mL for multiple injections to determine baseline effects on crushed sciatic nerves in rats. The rats were randomly divided into four groups: control, crush, crush-NGF, and crush-LPC-NGF. The healing of the nerves was measured weekly by monitoring gait; electrophysiological parameters: compound muscle action potential (CMAP amplitudes; and morphological parameters: total fascicle areas, myelinated fiber counts, fiber densities, fiber packing, and mean g-ratio values at weeks 3 and 6. The crush, crush-NGF, and crush-LPC-NGF groups statistically differed from the control group for all six weeks for the electrophysiological parameters but only differed from the control group at week 3 for the morphological parameters. The crush, crush-NGF, and crush-LPC-NGF groups did not differ from each other over the course of the study. Single injections of LPC and NGF one week apart or multiple treatments of NGF at 5, 7 and 9 days post-injury did not alter the healing rate of the sciatic nerves during weeks 1-6 of the study. These findings are important to define the baseline effects of NGF and LPC injections, as part of a larger effort to determine the minimal dose regimen of NGF to regenerate peripheral nerves.

  10. Developmental regulation of human truncated nerve growth factor receptor

    Energy Technology Data Exchange (ETDEWEB)

    DiStefano, P.S.; Clagett-Dame, M.; Chelsea, D.M.; Loy, R. (Abbott Laboratories, Abbott Park, IL (USA))

    1991-01-01

    Monoclonal antibodies (designated XIF1 and IIIG5) recognizing distinct epitopes of the human truncated nerve growth factor receptor (NGF-Rt) were used in a two-site radiometric immunosorbent assay to monitor levels of NGF-Rt in human urine as a function of age. Urine samples were collected from 70 neurologically normal subjects ranging in age from 1 month to 68 years. By using this sensitive two-site radiometric immunosorbent assay, NGF-Rt levels were found to be highest in urine from 1-month old subjects. By 2.5 months, NGF-Rt values were half of those seen at 1 month and decreased more gradually between 0.5 and 15 years. Between 15 and 68 years, urine NGF-Rt levels were relatively constant at 5% of 1-month values. No evidence for diurnal variation of adult NGF-Rt was apparent. Pregnant women in their third trimester showed significantly elevated urine NGF-Rt values compared with age-matched normals. Affinity labeling of NGF-Rt with 125I-NGF followed by immunoprecipitation with ME20.4-IgG and gel autoradiography indicated that neonatal urine contained high amounts of truncated receptor (Mr = 50 kd); decreasingly lower amounts of NGF-Rt were observed on gel autoradiograms with development, indicating that the two-site radiometric immunosorbent assay correlated well with the affinity labeling technique for measuring NGF-Rt. NGF-Rt in urines from 1-month-old and 36-year-old subjects showed no differences in affinities for NGF or for the monoclonal antibody IIIG5. These data show that NGF-Rt is developmentally regulated in human urine, and are discussed in relation to the development and maturation of the peripheral nervous system.

  11. Developmental regulation of human truncated nerve growth factor receptor

    International Nuclear Information System (INIS)

    DiStefano, P.S.; Clagett-Dame, M.; Chelsea, D.M.; Loy, R.

    1991-01-01

    Monoclonal antibodies (designated XIF1 and IIIG5) recognizing distinct epitopes of the human truncated nerve growth factor receptor (NGF-Rt) were used in a two-site radiometric immunosorbent assay to monitor levels of NGF-Rt in human urine as a function of age. Urine samples were collected from 70 neurologically normal subjects ranging in age from 1 month to 68 years. By using this sensitive two-site radiometric immunosorbent assay, NGF-Rt levels were found to be highest in urine from 1-month old subjects. By 2.5 months, NGF-Rt values were half of those seen at 1 month and decreased more gradually between 0.5 and 15 years. Between 15 and 68 years, urine NGF-Rt levels were relatively constant at 5% of 1-month values. No evidence for diurnal variation of adult NGF-Rt was apparent. Pregnant women in their third trimester showed significantly elevated urine NGF-Rt values compared with age-matched normals. Affinity labeling of NGF-Rt with 125I-NGF followed by immunoprecipitation with ME20.4-IgG and gel autoradiography indicated that neonatal urine contained high amounts of truncated receptor (Mr = 50 kd); decreasingly lower amounts of NGF-Rt were observed on gel autoradiograms with development, indicating that the two-site radiometric immunosorbent assay correlated well with the affinity labeling technique for measuring NGF-Rt. NGF-Rt in urines from 1-month-old and 36-year-old subjects showed no differences in affinities for NGF or for the monoclonal antibody IIIG5. These data show that NGF-Rt is developmentally regulated in human urine, and are discussed in relation to the development and maturation of the peripheral nervous system

  12. Mental disorders, functional impairment, and nerve growth factor

    Directory of Open Access Journals (Sweden)

    Salles FHM

    2016-12-01

    Full Text Available Fanny Helena Martins Salles,1 Pedro San Martin Soares,1 Carolina David Wiener,1 Thaise Campos Mondin,1 Paula Moraes da Silva,1 Karen Jansen,1–3 Luciano Dias de Mattos Souza,1 Ricardo Azevedo da Silva,1 Jean Pierre Oses1–3 1Translational Science on Brain Disorders, Department of Health and Behavior, Catholic University of Pelotas, Pelotas, Rio Grande do Sul, Brazil; 2Translational Psychiatry Program, 3Center of Excellence on Mood Disorders, Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston (UTHealth Medical School, Houston, TX, USA Abstract: Nerve growth factor (NGF is an important member of the neurotrophin family and its alteration has been associated with psychiatric disorders. Functionality consists of the activities that an individual can perform, as well as their social participation, which is an important factor in analyzing the carrier living conditions of subjects with psychiatric suffering. Several studies have evaluated functionality in bipolar disorder; however, no studies have evaluated the functionality in other mental disorders. There are also few studies investigating the association between functionality and the biological bases of mental disorders. This study aimed to evaluate the serum NGF levels in psychiatric patients and to verify a possible association between the serum neurotrophic levels and functionality. This was a cross-sectional study with a convenient sample obtained from the Public Mental Health Service from the south of Brazil. The final sample was composed of 286 patients enrolled from July 2013 to October 2014. Data was collected using a sociodemographic questionnaire, and the diagnosis was confirmed using the Mini International Neuropsychiatric Interview (M.I.N.I and a Functioning Assessment Short Test. The serum NGF levels were determined using the enzyme-linked immunosorbent assay method. Statistical analyses were performed using IBM SPSS Statistic

  13. The chemokine CXCL12 mediates the anti-amyloidogenic action of painless human nerve growth factor.

    Science.gov (United States)

    Capsoni, Simona; Malerba, Francesca; Carucci, Nicola Maria; Rizzi, Caterina; Criscuolo, Chiara; Origlia, Nicola; Calvello, Mariantonietta; Viegi, Alessandro; Meli, Giovanni; Cattaneo, Antonino

    2017-01-01

    Nerve growth factor is a therapeutic candidate for Alzheimer's disease. Due to its pain-inducing activity, in current clinical trials nerve growth factor is delivered locally into the brain by neurosurgery, but data on the efficacy of local nerve growth factor delivery in decreasing amyloid-β deposition are not available. To reduce the nerve growth factor pain-inducing side effects, thus avoiding the need for local brain injection, we developed human painless nerve growth factor (hNGFp), inspired by the human genetic disease hereditary sensory and autonomic neuropathy type V. hNGFp has identical neurotrophic potency as wild-type human nerve growth factor, but a 10-fold lower pain sensitizing activity. In this study we first mimicked, in the 5xFAD mouse model, the intraparenchymal delivery of hNGFp used in clinical trials and found it to be ineffective in decreasing amyloid-β plaque load. On the contrary, the same dose of hNGFp delivered intranasally, which was widely biodistributed in the brain and did not induce pain, showed a potent anti-amyloidogenic action and rescued synaptic plasticity and memory deficits. We found that hNGFp acts on glial cells, modulating inflammatory proteins such as the soluble TNFα receptor II and the chemokine CXCL12. We further established that the rescuing effect by hNGFp is mediated by CXCL12, as pharmacological inhibition of CXCL12 receptor CXCR4 occludes most of hNGFp effects. These findings have significant therapeutic implications: (i) we established that a widespread exposure of the brain is required for nerve growth factor to fully exert its neuroprotective actions; and (ii) we have identified a new anti-neurodegenerative pathway as a broad target for new therapeutic opportunities for neurodegenerative diseases. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.

  14. Effects of a synthetic bioactive peptide on neurite growth and nerve growth factor release in chondroitin sulfate hydrogels

    OpenAIRE

    Conovaloff, Aaron W.; Beier, Brooke L.; Irazoqui, Pedro P.; Panitch, Alyssa

    2011-01-01

    Previous work has revealed robust dorsal root ganglia neurite growth in hydrogels of chondroitin sulfate. In the current work, it was determined whether addition of a synthetic bioactive peptide could augment neurite growth in these matrices via enhanced binding and sequestering of growth factors. Fluorescence recovery after photobleaching studies revealed that addition of peptide slowed nerve growth factor diffusivity in chondroitin sulfate gels, but not in control gels of hyaluronic acid. F...

  15. Neonatal hyperthyroidism impairs epinephrine-provoked secretion of nerve growth factor and epidermal growth factor in mouse saliva.

    Science.gov (United States)

    Lakshmanan, J; Landel, C P

    1986-07-01

    We examined long-term effects of neonatal hyperthyroidism on salivary secretions of nerve growth factor and epidermal growth factor in male and female mice at the age of 31 days. Hyperthyroidism was induced by thyroxine (T4) injections (0.4 microgram/g body weight/day) during days 0-6. Littermate control mice were treated with vehicle. T4 treatment did not alter the amounts of protein secreted into saliva but hormone administration induced alteration in the types of protein secreted. T4 treatment decreased the contents of both nerve growth factor and epidermal growth factor secreted into the saliva. A Sephadex G-200 column chromatographic profile revealed the presence of two distinct nerve growth factor immunoreactive peaks, while epidermal growth factor immunoreactivity predominantly eluted as a single low molecular weight form. T4 treatment did not alter the molecular nature of their secretion, but the treatment decreased their contents. These results indicate an impairment in salivary secretion of nerve growth factor and epidermal growth factor long after T4 treatment has been discontinued.

  16. [Influence of trigeminal nerve lesion on facial growth: study of two cases of Goldenhar syndrome].

    Science.gov (United States)

    Darris, Pierre; Treil, Jacques; Marchal-Sixou, Christine; Baron, Pascal

    2015-06-01

    This cases report confirms the hypothesis that embryonic and maxillofacial growth are influenced by the peripheral nervous system, including the trigeminal nerve (V). So, it's interesting to use the stigma of the trigeminal nerve as landmarks to analyze the maxillofacial volume and understand its growth. The aim of this study is to evaluate the validity of the three-dimensional cephalometric analysis of Treil based on trigeminal landmarks. The first case is a caucasian female child with Goldenhar syndrome. The second case is a caucasian male adult affected by the same syndrome. In both cases, brain MRI showed an unilateral trigeminal nerve lesion, ipsilateral to the facial dysmorphia. The results of this radiological study tend to prove the primary role of the trigeminal nerve in craniofacial growth. These cases demonstrate the validity of the theory of Moss. They are one of anatomo-functional justifications of the three-dimensional cephalometric biometry of Treil based on trigeminal nerve landmarks. © EDP Sciences, SFODF, 2015.

  17. Variation in Location of the Mandibular Foramen/Inferior Alveolar Nerve Complex Given Anatomic Landmarks Using Cone-beam Computed Tomographic Scans.

    Science.gov (United States)

    Blacher, Jonathan; Van DaHuvel, Scott; Parashar, Vijay; Mitchell, John C

    2016-03-01

    The inferior alveolar nerve (IAN) injection is 1 of the most commonly administered and useful injections in the field of dentistry. Practitioners use intraoral anatomic landmarks, which vary greatly among patients. The objective of this study was to assist practitioners by identifying a range of normal variability within certain landmarks used in delivering IAN anesthesia. A total of 203 randomly selected retrospective cone-beam computed tomographic scans were obtained from the Midwestern University Dental Institute cone-beam computed tomographic database. InVivoDental5.0 volumetric imaging software (Anatomage, San Jose, CA) was used to measure 2 important parameters used in locating the mandibular foramen (MF)/IAN complex: (1) the angle from the contralateral premolar contact area to the MF and (2) the distance above the mandibular occlusal plane to the center of the MF. The variation of these measurements was compared with established reference values and statistically analyzed using a 1-sample t test. The angle from the contralateral premolar contact area to the MF for the right and left sides was 42.99° and 42.57°, respectively. The angulations varied significantly from the reference value of 45° (P < .001). The minimum height above the mandibular occlusal plane for the right and left sides was 9.85 mm and 9.81 mm, respectively. The heights varied significantly from the minimum reference value of 6 mm but not the maximum reference value of 10 mm (P < .001). Orienting the syringe barrel at an angulation slightly less than 45° and significantly higher than 6 mm above the mandibular occlusal plane can aid in successfully administering anesthesia to the MF/IAN complex. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  18. Extracellular Nm23H1 stimulates neurite outgrowth from dorsal root ganglia neurons in vitro independently of nerve growth factor supplementation or its nucleoside diphosphate kinase activity

    International Nuclear Information System (INIS)

    Wright, K.T.; Seabright, R.; Logan, A.; Lilly, A.J.; Khanim, F.; Bunce, C.M.; Johnson, W.E.B.

    2010-01-01

    Research highlights: → Extracellular Nm23H1 stimulates nerve growth. → Extracellular Nm23H1 provides pathfinding cues to growth cones. → The neurotrophic activity of Nm23H1 is independent of NDP kinase activity. → The neurotrophic activity of Nm23H1 is independent of NGF. -- Abstract: The nucleoside diphosphate (NDP) kinase, Nm23H1, is a highly expressed during neuronal development, whilst induced over-expression in neuronal cells results in increased neurite outgrowth. Extracellular Nm23H1 affects the survival, proliferation and differentiation of non-neuronal cells. Therefore, this study has examined whether extracellular Nm23H1 regulates nerve growth. We have immobilised recombinant Nm23H1 proteins to defined locations of culture plates, which were then seeded with explants of embryonic chick dorsal root ganglia (DRG) or dissociated adult rat DRG neurons. The substratum-bound extracellular Nm23H1 was stimulatory for neurite outgrowth from chick DRG explants in a concentration-dependent manner. On high concentrations of Nm23H1, chick DRG neurite outgrowth was extensive and effectively limited to the location of the Nm23H1, i.e. neuronal growth cones turned away from adjacent collagen-coated substrata. Nm23H1-coated substrata also significantly enhanced rat DRG neuronal cell adhesion and neurite outgrowth in comparison to collagen-coated substrata. These effects were independent of NGF supplementation. Recombinant Nm23H1 (H118F), which does not possess NDP kinase activity, exhibited the same activity as the wild-type protein. Hence, a novel neuro-stimulatory activity for extracellular Nm23H1 has been identified in vitro, which may function in developing neuronal systems.

  19. Extracellular Nm23H1 stimulates neurite outgrowth from dorsal root ganglia neurons in vitro independently of nerve growth factor supplementation or its nucleoside diphosphate kinase activity

    Energy Technology Data Exchange (ETDEWEB)

    Wright, K.T. [Keele University at the RJAH Orthopaedic Hospital, Oswestry, Shropshire (United Kingdom); Seabright, R.; Logan, A. [Neuropharmacology and Neurobiology, School of Clinical and Experimental Medicine, Birmingham University, Birmingham (United Kingdom); Lilly, A.J.; Khanim, F.; Bunce, C.M. [Biosciences, Birmingham University, Birmingham (United Kingdom); Johnson, W.E.B., E-mail: w.e.johnson@aston.ac.uk [Life and Health Sciences, Aston University, Birmingham (United Kingdom)

    2010-07-16

    Research highlights: {yields} Extracellular Nm23H1 stimulates nerve growth. {yields} Extracellular Nm23H1 provides pathfinding cues to growth cones. {yields} The neurotrophic activity of Nm23H1 is independent of NDP kinase activity. {yields} The neurotrophic activity of Nm23H1 is independent of NGF. -- Abstract: The nucleoside diphosphate (NDP) kinase, Nm23H1, is a highly expressed during neuronal development, whilst induced over-expression in neuronal cells results in increased neurite outgrowth. Extracellular Nm23H1 affects the survival, proliferation and differentiation of non-neuronal cells. Therefore, this study has examined whether extracellular Nm23H1 regulates nerve growth. We have immobilised recombinant Nm23H1 proteins to defined locations of culture plates, which were then seeded with explants of embryonic chick dorsal root ganglia (DRG) or dissociated adult rat DRG neurons. The substratum-bound extracellular Nm23H1 was stimulatory for neurite outgrowth from chick DRG explants in a concentration-dependent manner. On high concentrations of Nm23H1, chick DRG neurite outgrowth was extensive and effectively limited to the location of the Nm23H1, i.e. neuronal growth cones turned away from adjacent collagen-coated substrata. Nm23H1-coated substrata also significantly enhanced rat DRG neuronal cell adhesion and neurite outgrowth in comparison to collagen-coated substrata. These effects were independent of NGF supplementation. Recombinant Nm23H1 (H118F), which does not possess NDP kinase activity, exhibited the same activity as the wild-type protein. Hence, a novel neuro-stimulatory activity for extracellular Nm23H1 has been identified in vitro, which may function in developing neuronal systems.

  20. Effect of α-lipoic acid combined with nerve growth factor on bone metabolism, oxidative stress and nerve conduction function after femoral fracture surgery

    Directory of Open Access Journals (Sweden)

    An-Jun Cao

    2017-11-01

    Full Text Available Objective: To discuss the effect of 毩 -lipoic acid combined with nerve growth factor on bone metabolism, oxidative stress and nerve conduction function after femoral fracture surgery. Methods: A total of 110 patients with femoral fracture who received surgical treatment in the hospital between January 2015 and January 2017 were collected and divided into the control group (n=55 and study group (n=55 by random number table. Control group received postoperative nerve growth factor therapy, and study group received postoperative 毩 -lipoic acid combined with nerve growth factor therapy. The differences in the contents of bone metabolism and oxidative stress indexes as well as the levels of nerve conduction function indexes were compared between the two groups before and after treatment. Results: Before treatment, the differences in the contents of bone metabolism and oxidative stress indexes as well as the levels of nerve conduction function indexes were not statistically significant between the two groups. After treatment, serum bone metabolism indexes BGP and PⅠNP contents of study group were higher than those of control group while CTX-Ⅰ and TRAP contents were lower than those of control group; serum oxidative stress indexes TAC, CAT and SOD contents of study group were higher than those of control group while MDA content was lower than that of control group; limb nerve conduction velocity SCV and MCV levels of study group were higher than those of control group. Conclusion: 毩 -lipoic acid combined with nerve growth factor therapy after femoral fracture surgery can effectively balance osteoblast/ osteoclast activity, reduce oxidative stress and improve limb nerve conduction velocity.

  1. Persistent growth of a young andesite lava cone: Bagana volcano, Papua New Guinea

    Science.gov (United States)

    Wadge, G.; McCormick Kilbride, B. T.; Edmonds, M.; Johnson, R. W.

    2018-05-01

    Bagana, an andesite lava cone on Bougainville Island, Papua New Guinea, is thought to be a very young central volcano. We have tested this idea by estimating the volumes of lava extruded over different time intervals (1-, 2-, 3-, 9-, 15-, 70-years) using digital elevation models (DEMs), mainly created from satellite data. Our results show that the long-term extrusion rate at Bagana, measured over years to decades, has remained at about 1.0 m3 s-1. We present models of the total edifice volume, and show that, if our measured extrusion rates are representative, the volcano could have been built in only 300 years. It could also possibly have been built at a slower rate during a longer, earlier period of growth. Six kilometres NNW of Bagana, an andesite-dacite volcano, Billy Mitchell, had a large, caldera-forming plinian eruption 437 years ago. We consider the possibility that, as a result of this eruption, the magma supply was diverted from Billy Mitchell to Bagana. It seems that Bagana is a rare example of a very youthful, polygenetic, andesite volcano. The characteristics of such a volcano, based on the example of Bagana, are: a preponderance of lava products over pyroclastic products, a high rate of lava extrusion maintained for decades, a very high rate of SO2 emission, evidence of magma batch fractionation and location in a trans-tensional setting at the end of an arc segment above a very steeply dipping and rapidly converging subduction zone.

  2. An Automated Strategy for Unbiased Morphometric Analyses and Classifications of Growth Cones In Vitro.

    Directory of Open Access Journals (Sweden)

    Daryan Chitsaz

    Full Text Available During neural circuit development, attractive or repulsive guidance cue molecules direct growth cones (GCs to their targets by eliciting cytoskeletal remodeling, which is reflected in their morphology. The experimental power of in vitro neuronal cultures to assay this process and its molecular mechanisms is well established, however, a method to rapidly find and quantify multiple morphological aspects of GCs is lacking. To this end, we have developed a free, easy to use, and fully automated Fiji macro, Conographer, which accurately identifies and measures many morphological parameters of GCs in 2D explant culture images. These measurements are then subjected to principle component analysis and k-means clustering to mathematically classify the GCs as "collapsed" or "extended". The morphological parameters measured for each GC are found to be significantly different between collapsed and extended GCs, and are sufficient to classify GCs as such with the same level of accuracy as human observers. Application of a known collapse-inducing ligand results in significant changes in all parameters, resulting in an increase in 'collapsed' GCs determined by k-means clustering, as expected. Our strategy provides a powerful tool for exploring the relationship between GC morphology and guidance cue signaling, which in particular will greatly facilitate high-throughput studies of the effects of drugs, gene silencing or overexpression, or any other experimental manipulation in the context of an in vitro axon guidance assay.

  3. An Automated Strategy for Unbiased Morphometric Analyses and Classifications of Growth Cones In Vitro.

    Science.gov (United States)

    Chitsaz, Daryan; Morales, Daniel; Law, Chris; Kania, Artur

    2015-01-01

    During neural circuit development, attractive or repulsive guidance cue molecules direct growth cones (GCs) to their targets by eliciting cytoskeletal remodeling, which is reflected in their morphology. The experimental power of in vitro neuronal cultures to assay this process and its molecular mechanisms is well established, however, a method to rapidly find and quantify multiple morphological aspects of GCs is lacking. To this end, we have developed a free, easy to use, and fully automated Fiji macro, Conographer, which accurately identifies and measures many morphological parameters of GCs in 2D explant culture images. These measurements are then subjected to principle component analysis and k-means clustering to mathematically classify the GCs as "collapsed" or "extended". The morphological parameters measured for each GC are found to be significantly different between collapsed and extended GCs, and are sufficient to classify GCs as such with the same level of accuracy as human observers. Application of a known collapse-inducing ligand results in significant changes in all parameters, resulting in an increase in 'collapsed' GCs determined by k-means clustering, as expected. Our strategy provides a powerful tool for exploring the relationship between GC morphology and guidance cue signaling, which in particular will greatly facilitate high-throughput studies of the effects of drugs, gene silencing or overexpression, or any other experimental manipulation in the context of an in vitro axon guidance assay.

  4. Val66Met polymorphism of BDNF alters prodomain structure to induce neuronal growth cone retraction.

    Science.gov (United States)

    Anastasia, Agustin; Deinhardt, Katrin; Chao, Moses V; Will, Nathan E; Irmady, Krithi; Lee, Francis S; Hempstead, Barbara L; Bracken, Clay

    2013-01-01

    A common single-nucleotide polymorphism (SNP) in the human brain-derived neurotrophic factor (BDNF) gene results in a Val66Met substitution in the BDNF prodomain region. This SNP is associated with alterations in memory and with enhanced risk to develop depression and anxiety disorders in humans. Here we show that the isolated BDNF prodomain is detected in the hippocampus and that it can be secreted from neurons in an activity-dependent manner. Using nuclear magnetic resonance spectroscopy and circular dichroism, we find that the prodomain is intrinsically disordered, and the Val66Met substitution induces structural changes. Surprisingly, application of Met66 (but not Val66) BDNF prodomain induces acute growth cone retraction and a decrease in Rac activity in hippocampal neurons. Expression of p75(NTR) and differential engagement of the Met66 prodomain to the SorCS2 receptor are required for this effect. These results identify the Met66 prodomain as a new active ligand, which modulates neuronal morphology.

  5. Closing the Border on a New Frontier : The Problem With Salivary Nerve Growth Factor

    NARCIS (Netherlands)

    Turner, J.E.; Bosch, J.A.

    In 2013, a study appeared in Psychosomatic Medicine showing that salivary levels of nerve growth factor (sNGF) rapidly increase (to +45% of baseline levels) in response to an acute psychosocial stress task that involved discussing an unresolved conflict with a romantic partner (1). NGF, also

  6. Growth Factor and Laminin Effect with Muscular Fiber Sheath on Repairing of the Sciatica Nerve

    Directory of Open Access Journals (Sweden)

    S Torabi

    2014-01-01

    Background & aim: Peripheral nerve injuries which can lead to a physical disability. If the defect is very low, direct suture without tension on both ends of the cut nerve regeneration is considered as a standard procedure. Otherwise, to reconstruct the axons, the gap must be filled by graft material in order to the guidance. Due to the similarity of the matrix tubular skeletal muscle and nerve muscles graft was used to repair in this study. Methods: In the present experimental study, 42 female Wistar rats were divided into three groups and underwent surgery. In the first group a narrow strip of muscle was prepared by freezing – thawing, and later sutured between the distal and proximal sciatic nerve. In the second group, the gap caused by muscle graft was regenerated and the nerve growth factor and laminin was injected into the graft. In the control group, the two ends of the cut nerve were hidden beneath the adjacent muscles. Next, a group of rats with sciatic functional index was investigated for the behavioral. On the other group were examined for histological studies after two months. Results: Sciatic functional index and Mean counts of myelinated fibers in two graft groups compared with the control group was significant p<0.05. Statistical analysis was performed using ANOVA test. Conclusion: co-axially aligned muscle grafts were an appropriate alternative substitute for repairing. It seems that the nerve growth factor and laminin have a positive role in axonal regeneration and functional recovery acceleration. Key words: Sciatic Functional Index, muscle graft, NGF, Laminin

  7. The Reliability of Panoramic Radiography Versus Cone Beam Computed Tomography when Evaluating the Distance to the Alveolar Nerve in the Site of Lateral Teeth.

    Science.gov (United States)

    Česaitienė, Gabrielė; Česaitis, Kęstutis; Junevičius, Jonas; Venskutonis, Tadas

    2017-07-04

    BACKGROUND The aim of this study was to compare the reliability of panoramic radiography (PR) and cone beam computed tomography (CBCT) in the evaluation of the distance of the roots of lateral teeth to the inferior alveolar nerve canal (IANC). MATERIAL AND METHODS 100 PR and 100 CBCT images that met the selection criteria were selected from the database. In PR images, the distances were measured using an electronic caliper with 0.01 mm accuracy and white light x-ray film reviewer. Actual values of the measurements were calculated taking into consideration the magnification used in PR images (130%). Measurements on CBCT images were performed using i-CAT Vision software. Statistical data analysis was performed using R software and applying Welch's t-test and the Wilcoxon test. RESULTS There was no statistically significant difference in the mean distance from the root of the second premolar and the mesial and distal roots of the first molar to the IANC between PR and CBCT images. The difference in the mean distance from the mesial and distal roots of the second and the third molars to the IANC measured in PR and CBCT images was statistically significant. CONCLUSIONS PR may be uninformative or misleading when measuring the distance from the mesial and distal roots of the second and the third molars to the IANC.

  8. Three-dimensional evaluation of pharyngeal airway in individuals with varying growth patterns using cone beam computed tomography

    OpenAIRE

    Rohan Diwakar; Maninder Singh Sidhu; Mona Prabhakar; Seema Grover; Ritu Phogat

    2015-01-01

    Introduction: The purpose of this study was to evaluate the pharyngeal airway volume in individuals with different vertical growth patterns. Methods: Cone beam computed tomography scans were evaluated of 40 subjects with the age range from 14 to 25 years and were divided into three groups. Horizontal growers consisted of 13 subjects, normal growers consisted of 14 subjects, and the vertical growers consisted of 13 subjects. The pharyngeal airway volume was measured using In Vivo Dental 5.1 so...

  9. Effects of nerve growth factor on the neurotization of denervated muscles.

    Science.gov (United States)

    Menderes, Adnan; Yilmaz, Mustafa; Vayvada, Haluk; Ozer, Erdener; Barutçu, Ali

    2002-04-01

    Studies on surgical repair techniques of the peripheral nerve are still trying to improve the outcome. There are many studies on the effects of various neurotrophic factors on the transected peripheral nerve. Muscular neurotization, which is the direct implantation of the nerve to the target denervated skeletal muscle, is one of the techniques used when the primary repair of the peripheral nerves is not possible. The effects of nerve growth factor (NGF), which is one of the primary neurotrophic factors, on the reinnervation of denervated muscles by neurotization is investigated in this experimental study. The denervated soleus muscle was neurotized via peroneal nerve implantation (group 1), and NGF was administered to the neurotized muscle (group 2). All animals were evaluated at weeks 8, 10, and 12 using electromyography. Muscle contractility, muscle weight, and histological morphometric tests were performed at week 12. The experimental groups were compared with each other and normal control values. Electromyographically, group 2 (direct nerve implantation + NGF) demonstrated better reinnervation in all evaluations. The study of muscle weight showed that the muscle mass was 75% of the normal soleus muscle in group 1 and was 85% of the normal side in group 2 at the end of week 12. In group 1, the twitch force was 56% of the normal soleus muscle and was 71% in group 2. Tetanic force was 53% of the normal soleus muscle in group 1 and 68% in group 2. Histological morphometric studies revealed that there was a decrease in the density of the motor end plates in group 1, but there was no statistically significant difference between the normal soleus muscles and the NGF applied to group 2. The positive effects of NGF on the neurotization of denervated muscles seen in this study suggest that it may be useful for treating some difficult reconstructions caused by denervation.

  10. Effect of mouse nerve growth factor combined with mecobalamine on treatment of diabetic peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    De-Rong Hu

    2016-06-01

    Full Text Available Objective: To observe the clinical effect of mouse nerve growth fact (NGF combined with mecobalamine on treatment of diabetic peripheral n-europathy (DPN. Methods: A total of 84 cases of patients with DPN treated in ourhospital between April 2012 and June 2015 were selected, and divided into study group and control group randomly (n=42; Control group was only given mecobalamine treatment, while study group was given mouse nerve growth factor combined with mecobalamine treatment for 4 weeks. TThe motor nerve conduction velocity median nerve (MNCV, sensory nerve conduction velocity (SNCV, serum high sensitivity c-reactive protein (hs-CRP and Toronto clinical scoring system (TCSS changes of median nerve and nervus peroneus communis before and after treatment were compared. Results: There were no significant differences in MNCV, SNCV of mediannerve and nervus peroneus communis before treatment. MNCV and SNCV of both groups after treatment were significantly increased. MNCV, SNCV of mediannerve and nervus peroneus communis in study group was significantly higher than that in control group. hs-CRP and TCSS scoring of both groups before treatment showed no statistic significant difference. hs-CRP scoring of both groups after treatment showed no significant difference. TCSS scoring was significantly lower than that in control group. Adverse reaction total occurrence rate after given drug in study group was 16.67% (7/42, compared with 7.14% (3/42 in control group, difference was significant. Conclusions: Mouse NGF combined with mecobalamine could achieve good curative effect. It is of higher safety in the treatment of patients with DPN, and deserves popularization and application.

  11. NERVE REGENERATION THROUGH A 2-PLY BIODEGRADABLE NERVE GUIDE IN THE RAT AND THE INFLUENCE OF ACTH4-9 NERVE GROWTH-FACTOR

    NARCIS (Netherlands)

    ROBINSON, PH; VANDERLEI, B; HOPPEN, HJ; LEENSLAG, JW; PENNINGS, AJ; NIEUWENHUIS, P

    1991-01-01

    Biodegradable polyurethane-based (PU) nerve guides, instilled with or without ACTH4-9 analog (a melanocortin) were used for bridging an 8 mm gap in the rat sciatic nerve and were evaluated for function and histological appearance after 16 weeks of implantation. Autologous nerve grafts functioned as

  12. Comparison of the force exerted by hippocampal and DRG growth cones.

    Science.gov (United States)

    Amin, Ladan; Ercolini, Erika; Ban, Jelena; Torre, Vincent

    2013-01-01

    Mechanical properties such as force generation are fundamental for neuronal motility, development and regeneration. We used optical tweezers to compare the force exerted by growth cones (GCs) of neurons from the Peripheral Nervous System (PNS), such as Dorsal Root Ganglia (DRG) neurons, and from the Central Nervous System (CNS) such as hippocampal neurons. Developing GCs from dissociated DRG and hippocampal neurons were obtained from P1-P2 and P10-P12 rats. Comparing their morphology, we observed that the area of GCs of hippocampal neurons was 8-10 µm(2) and did not vary between P1-P2 and P10-P12 rats, but GCs of DRG neurons were larger and their area increased from P1-P2 to P10-P12 by 2-4 times. The force exerted by DRG filopodia was in the order of 1-2 pN and never exceeded 5 pN, while hippocampal filopodia exerted a larger force, often in the order of 5 pN. Hippocampal and DRG lamellipodia exerted lateral forces up to 20 pN, but lamellipodia of DRG neurons could exert a vertical force larger than that of hippocampal neurons. Force-velocity relationships (Fv) in both types of neurons had the same qualitative behaviour, consistent with a common autocatalytic model of force generation. These results indicate that molecular mechanisms of force generation of GC from CNS and PNS neurons are similar but the amplitude of generated force is influenced by their cytoskeletal properties.

  13. Influence of Electrical and Electromagnetic Stimulation on Nerve Regeneration in the Transected Mouse Sciatic Nerve : An Electron Microscopic Study

    OpenAIRE

    Ogata, Akiko; Matsumoto, Tomoko; Matsubara, Takako; Miki, Akinori

    2001-01-01

    Influence of electrical and electromagnetic stimulation on nerve regeneration was electron microscopically examined in the transected mouse sciatic nerve. Two days after the transection, several thin regenerating axons (daughter axons) were observed between the myelin sheath and basal lamina of Schwann cells in the proximal stump. Growth cones of the daughter axons contained several small round vesicles and mitochondria, and the shaft of them, neurofilaments, neurotubules and profiles of smoo...

  14. Insulin-like growth factors act synergistically with basic fibroblast growth factor and nerve growth factor to promote chromaffin cell proliferation

    DEFF Research Database (Denmark)

    Frödin, M; Gammeltoft, S

    1994-01-01

    We have investigated the effects of insulin-like growth factors (IGFs), basic fibroblast growth factor (bFGF), and nerve growth factor (NGF) on DNA synthesis in cultured chromaffin cells from fetal, neonatal, and adult rats by using 5-bromo-2'-deoxyuridine (BrdUrd) pulse labeling for 24 or 48 h...... implications for improving the survival of chromaffin cell implants in diseased human brain....

  15. Expression of growth-associated protein B-50/GAP43 in dorsal root ganglia and sciatic nerve during regenerative sprouting

    NARCIS (Netherlands)

    Gispen, W.H.; Zee, C.E.E.M. van der; Nielander, H.B.; Vos, J.P.; Lopes da Silva, S.; Verhaagen, J.; Oestreicher, J.; Schrama, L.H.

    1989-01-01

    Recently it has been shown that B-50 is identical to the neuron- specific, growth-associated protein GAP43. The present study reports on the fate of B-50/GAP43 mRNA and B-50/GAP43 protein, determined by radioimmunoassay, in a rat model of peripheral nerve regeneration (sciatic nerve crush) over a

  16. Molecular cloning of a human gene that is a member of the nerve growth factor family

    Energy Technology Data Exchange (ETDEWEB)

    Jones, K.R.; Reichardt, L.F. (Howard Hughes Medical Institute, San Francisco, CA (USA))

    1990-10-01

    Cell death within the developing vertebrate nervous system is regulated in part by interactions between neurons and their innervation targets that are mediated by neurotrophic factors. These factors also appear to have a role in the maintenance of the adult nervous system. Two neurotrophic factors, nerve growth factor and brain-derived neurotrophic factor, share substantial amino acid sequence identity. The authors have used a screen that combines polymerase chain reaction amplification of genomic DNA and low-stringency hybridization with degenerate oligonucleotides to isolate human BDNF and a human gene, neurotrophin-3, that is closely related to both nerve growth factor and brain-derived neurotrophic factor. mRNA products of the brain-derived neurotrophic factor and neurotrophin-3 genes were detected in the adult human brain, suggesting that these proteins are involved in the maintenance of the adult nervous system. Neurotrophin-3 is also expected to function in embryonic neural development.

  17. Chondroitinase C Selectively Degrades Chondroitin Sulfate Glycosaminoglycans that Inhibit Axonal Growth within the Endoneurium of Peripheral Nerve.

    Directory of Open Access Journals (Sweden)

    James B Graham

    Full Text Available The success of peripheral nerve regeneration is highly dependent on the regrowth of axons within the endoneurial basal lamina tubes that promote target-oriented pathfinding and appropriate reinnervation. Restoration of nerve continuity at this structural level after nerve transection injury by direct repair and nerve grafting remains a major surgical challenge. Recently, biological approaches that alter the balance of growth inhibitors and promoters in nerve have shown promise to improve appropriate axonal regeneration and recovery of peripheral nerve function. Chondroitin sulfate proteoglycans (CSPGs are known inhibitors of axonal growth. This growth inhibition is mainly associated with a CSPG's glycosaminoglycan chains. Enzymatic degradation of these chains with chondroitinase eliminates this inhibitory activity and, when applied in vivo, can improve the outcome of nerve repair. To date, these encouraging findings were obtained with chondroitinase ABC (a pan-specific chondroitinase. The aim of this study was to examine the distribution of CSPG subtypes in rodent, rabbit, and human peripheral nerve and to test more selective biological enzymatic approaches to improve appropriate axonal growth within the endoneurium and minimize aberrant growth. Here we provide evidence that the endoneurium, but not the surrounding epineurium, is rich in CSPGs that have glycosaminoglycan chains readily degraded by chondroitinase C. Biochemical studies indicate that chondroitinase C has degradation specificity for 6-sulfated glycosaminoglycans found in peripheral nerve. We found that chondroitinase C degrades and inactivates inhibitory CSPGs within the endoneurium but not so much in the surrounding nerve compartments. Cryoculture bioassays (neurons grown on tissue sections show that chondroitinase C selectively and significantly enhanced neuritic growth associated with the endoneurial basal laminae without changing growth-inhibiting properties of the surrounding

  18. Chondroitinase C Selectively Degrades Chondroitin Sulfate Glycosaminoglycans that Inhibit Axonal Growth within the Endoneurium of Peripheral Nerve.

    Science.gov (United States)

    Graham, James B; Muir, David

    2016-01-01

    The success of peripheral nerve regeneration is highly dependent on the regrowth of axons within the endoneurial basal lamina tubes that promote target-oriented pathfinding and appropriate reinnervation. Restoration of nerve continuity at this structural level after nerve transection injury by direct repair and nerve grafting remains a major surgical challenge. Recently, biological approaches that alter the balance of growth inhibitors and promoters in nerve have shown promise to improve appropriate axonal regeneration and recovery of peripheral nerve function. Chondroitin sulfate proteoglycans (CSPGs) are known inhibitors of axonal growth. This growth inhibition is mainly associated with a CSPG's glycosaminoglycan chains. Enzymatic degradation of these chains with chondroitinase eliminates this inhibitory activity and, when applied in vivo, can improve the outcome of nerve repair. To date, these encouraging findings were obtained with chondroitinase ABC (a pan-specific chondroitinase). The aim of this study was to examine the distribution of CSPG subtypes in rodent, rabbit, and human peripheral nerve and to test more selective biological enzymatic approaches to improve appropriate axonal growth within the endoneurium and minimize aberrant growth. Here we provide evidence that the endoneurium, but not the surrounding epineurium, is rich in CSPGs that have glycosaminoglycan chains readily degraded by chondroitinase C. Biochemical studies indicate that chondroitinase C has degradation specificity for 6-sulfated glycosaminoglycans found in peripheral nerve. We found that chondroitinase C degrades and inactivates inhibitory CSPGs within the endoneurium but not so much in the surrounding nerve compartments. Cryoculture bioassays (neurons grown on tissue sections) show that chondroitinase C selectively and significantly enhanced neuritic growth associated with the endoneurial basal laminae without changing growth-inhibiting properties of the surrounding epineurium

  19. A local anesthetic, ropivacaine, suppresses activated microglia via a nerve growth factor-dependent mechanism and astrocytes via a nerve growth factor-independent mechanism in neuropathic pain

    Directory of Open Access Journals (Sweden)

    Sakamoto Atsuhiro

    2011-01-01

    Full Text Available Abstract Background Local anesthetics alleviate neuropathic pain in some cases in clinical practice, and exhibit longer durations of action than those predicted on the basis of the pharmacokinetics of their blocking effects on voltage-dependent sodium channels. Therefore, local anesthetics may contribute to additional mechanisms for reversal of the sensitization of nociceptive pathways that occurs in the neuropathic pain state. In recent years, spinal glial cells, microglia and astrocytes, have been shown to play critical roles in neuropathic pain, but their participation in the analgesic effects of local anesthetics remains largely unknown. Results Repetitive epidural administration of ropivacaine reduced the hyperalgesia induced by chronic constrictive injury of the sciatic nerve. Concomitantly with this analgesia, ropivacaine suppressed the increases in the immunoreactivities of CD11b and glial fibrillary acidic protein in the dorsal spinal cord, as markers of activated microglia and astrocytes, respectively. In addition, epidural administration of a TrkA-IgG fusion protein that blocks the action of nerve growth factor (NGF, which was upregulated by ropivacaine in the dorsal root ganglion, prevented the inhibitory effect of ropivacaine on microglia, but not astrocytes. The blockade of NGF action also abolished the analgesic effect of ropivacaine on neuropathic pain. Conclusions Ropivacaine provides prolonged analgesia possibly by suppressing microglial activation in an NGF-dependent manner and astrocyte activation in an NGF-independent manner in the dorsal spinal cord. Local anesthetics, including ropivacaine, may represent a new approach for glial cell inhibition and, therefore, therapeutic strategies for neuropathic pain.

  20. [Effect of deep electroacupuncture stimulation of "Huantiao" (GB 30) on changes of function and nerve growth factor expression of the injured sciatic nerve in rats].

    Science.gov (United States)

    Liu, Yu-Li; Li, Ye; Ren, Lu; Dai, Li-Li; Bai, Zeng-Hua; Bai, Ru; Ma, Tie-Ming

    2014-04-01

    OBJECTIVE; To observe the effect of deep electroacupuncture (EA) stimulation of "Huantiao"(GB 30) on the functional and pathological changes and nerve growth factor (NGF) expression of the damaged sciatic nerve in rats, so as to study its mechanisms underlying reliving sciatica. Forty-eight SD rats were randomly divided into normal, model, deep EA and shallow EA groups (n = 12 in each group). The sciatic nerve injury model was established by mechanical clamp of the sciatic nerve stem. For deep and shallow EA, the acupuncture needles were inserted into GB 30 about 16 mm and 7 mm, respectively. The EA treatment was given 20 min, once daily for 14 days. The evoked potentials of the injured sciatic nerve stem responding to electrical stimulation were recorded by using a biophysiological experimental system for calculating the motor conduction velocity. Pathological changes of the sciatic nerve were displayed by H. E. stain. The expression of NGF and Fos proteins was detected by immunohistochemistry. In comparison with the normal group, the conduction velocity and the amplitude of the evoked potentials of the sciatic nerve were significantly decreased in the model group (P 0.05), and no significant changes of latencies of the evoked potentials inthe four groups (P > 0.05). In the model group, the disorganized nerve fibers axons, myelin and Schwann cells of the damaged sciatic nerve were found, which became milder in the EA groups particularly in the deep EA group. In regard to the NGF and Fos immunoactivity of the injured sciatic nerve, the expression levels of both NGF and Fos proteins were obviously higher in the model group than in the normal group (P stimulation, NGF expression was further significantly up-regulated in both deep and shallow EA groups (P stimulation of GB 30 can improve the pathological changes and function of the injured sciatic nerve in the rat, which is closely associated with its effects in up-regulating NGF expression and down-regulating Fos

  1. Secretion of Growth Hormone in Response to Muscle Sensory Nerve Stimulation

    Science.gov (United States)

    Grindeland, Richard E.; Roy, R. R.; Edgerton, V. R.; Gosselink, K. L.; Grossman, E. J.; Sawchenko, P. E.; Wade, Charles E. (Technical Monitor)

    1994-01-01

    Growth hormone (GH) secretion is stimulated by aerobic and resistive exercise and inhibited by exposure to actual or simulated (bedrest, hindlimb suspension) microgravity. Moreover, hypothalamic growth hormone-releasing factor (GRF) and preproGRF mRNA are markedly decreased in spaceflight rats. These observations suggest that reduced sensory input from inactive muscles may contribute to the reduced secretion of GH seen in "0 G". Thus, the aim of this study was to determine the effect of muscle sensory nerve stimulation on secretion of GH. Fed male Wistar rats (304 +/- 23 g) were anesthetized (pentobarbital) and the right peroneal (Pe), tibial (T), and sural (S) nerves were cut. Electrical stimulation of the distal (D) or proximal (P) ends of the nerves was implemented for 15 min. to mimic the EMG activity patterns of ankle extensor muscles of a rat walking 1.5 mph. The rats were bled by cardiac puncture and their anterior pituitaries collected. Pituitary and plasma bioactive (BGH) and immunoactive (IGH) GH were measured by bioassay and RIA.

  2. Inhibitory Activity of Yokukansankachimpihange against Nerve Growth Factor-Induced Neurite Growth in Cultured Rat Dorsal Root Ganglion Neurons

    Directory of Open Access Journals (Sweden)

    Chiaki Murayama

    2015-08-01

    Full Text Available Chronic pruritus is a major and distressing symptom of many cutaneous diseases, however, the treatment remains a challenge in the clinic. The traditional Chinese-Japanese medicine (Kampo medicine is a conservative and increasingly popular approach to treat chronic pruritus for both patients and medical providers. Yokukansankachimpihange (YKH, a Kampo formula has been demonstrated to be effective in the treatment of itching of atopic dermatitis in Japan although its pharmacological mechanism is unknown clearly. In an attempt to clarify its pharmacological actions, in this study, we focused on the inhibitory activity of YKH against neurite growth induced with nerve growth factor (NGF in cultured rat dorsal root ganglion (DRG neurons because epidermal hyperinnervation is deeply related to itch sensitization. YKH showed approximately 200-fold inhibitory activity against NGF-induced neurite growth than that of neurotropin (positive control, a drug used clinically for treatment of chronic pruritus. Moreover, it also found that Uncaria hook, Bupleurum root and their chemical constituents rhynchophylline, hirsutine, and saikosaponin a, d showed inhibitory activities against NGF-induced neurite growth, suggesting they should mainly contribute to the inhibitory activity of YKH. Further study on the effects of YKH against epidermal nerve density in “itch-scratch” animal models is under investigation.

  3. Incorporation of chitosan microspheres into collagen-chitosan scaffolds for the controlled release of nerve growth factor.

    Directory of Open Access Journals (Sweden)

    Wen Zeng

    Full Text Available Artifical nerve scaffold can be used as a promising alternative to autologous nerve grafts to enhance the repair of peripheral nerve defects. However, current nerve scaffolds lack efficient microstructure and neurotrophic support.Microsphere-Scaffold composite was developed by incorporating chitosan microspheres loaded with nerve growth factor (NGF-CMSs into collagen-chitosan scaffolds (CCH with longitudinally oriented microchannels (NGF-CMSs/CCH. The morphological characterizations, in vitro release kinetics study, neurite outgrowth assay, and bioactivity assay were evaluated. After that, a 15-mm-long sciatic nerve gap in rats was bridged by the NGF-CMSs/CCH, CCH physically absorbed NGF (NGF/CCH, CCH or nerve autograft. 16 weeks after implantation, electrophysiology, fluoro-gold retrograde tracing, and nerve morphometry were performed.The NGF-CMSs were evenly distributed throughout the longitudinally oriented microchannels of the scaffold. The NGF-CMSs/CCH was capable of sustained release of bioactive NGF within 28 days as compared with others in vitro. In vivo animal study demonstrated that the outcomes of NGF-CMSs/CCH were better than those of NGF/CCH or CCH.Our findings suggest that incorporation of NGF-CMSs into the CCH may be a promising tool in the repair of peripheral nerve defects.

  4. Time-Dependent Nerve Growth Factor Signaling Changes in the Rat Retina During Optic Nerve Crush-Induced Degeneration of Retinal Ganglion Cells

    Directory of Open Access Journals (Sweden)

    Louise A. Mesentier-Louro

    2017-01-01

    Full Text Available Nerve growth factor (NGF is suggested to be neuroprotective after nerve injury; however, retinal ganglion cells (RGC degenerate following optic-nerve crush (ONC, even in the presence of increased levels of endogenous NGF. To further investigate this apparently paradoxical condition, a time-course study was performed to evaluate the effects of unilateral ONC on NGF expression and signaling in the adult retina. Visually evoked potential and immunofluorescence staining were used to assess axonal damage and RGC loss. The levels of NGF, proNGF, p75NTR, TrkA and GFAP and the activation of several intracellular pathways were analyzed at 1, 3, 7 and 14 days after crush (dac by ELISA/Western Blot and PathScan intracellular signaling array. The progressive RGC loss and nerve impairment featured an early and sustained activation of apoptotic pathways; and GFAP and p75NTR enhancement. In contrast, ONC-induced reduction of TrkA, and increased proNGF were observed only at 7 and 14 dac. We propose that proNGF and p75NTR contribute to exacerbate retinal degeneration by further stimulating apoptosis during the second week after injury, and thus hamper the neuroprotective effect of the endogenous NGF. These findings might aid in identifying effective treatment windows for NGF-based strategies to counteract retinal and/or optic-nerve degeneration.

  5. Time-Dependent Nerve Growth Factor Signaling Changes in the Rat Retina During Optic Nerve Crush-Induced Degeneration of Retinal Ganglion Cells.

    Science.gov (United States)

    Mesentier-Louro, Louise A; De Nicolò, Sara; Rosso, Pamela; De Vitis, Luigi A; Castoldi, Valerio; Leocani, Letizia; Mendez-Otero, Rosalia; Santiago, Marcelo F; Tirassa, Paola; Rama, Paolo; Lambiase, Alessandro

    2017-01-05

    Nerve growth factor (NGF) is suggested to be neuroprotective after nerve injury; however, retinal ganglion cells (RGC) degenerate following optic-nerve crush (ONC), even in the presence of increased levels of endogenous NGF. To further investigate this apparently paradoxical condition, a time-course study was performed to evaluate the effects of unilateral ONC on NGF expression and signaling in the adult retina. Visually evoked potential and immunofluorescence staining were used to assess axonal damage and RGC loss. The levels of NGF, proNGF, p75 NTR , TrkA and GFAP and the activation of several intracellular pathways were analyzed at 1, 3, 7 and 14 days after crush (dac) by ELISA/Western Blot and PathScan intracellular signaling array. The progressive RGC loss and nerve impairment featured an early and sustained activation of apoptotic pathways; and GFAP and p75 NTR enhancement. In contrast, ONC-induced reduction of TrkA, and increased proNGF were observed only at 7 and 14 dac. We propose that proNGF and p75 NTR contribute to exacerbate retinal degeneration by further stimulating apoptosis during the second week after injury, and thus hamper the neuroprotective effect of the endogenous NGF. These findings might aid in identifying effective treatment windows for NGF-based strategies to counteract retinal and/or optic-nerve degeneration.

  6. Nerve growth factor concentration and implications in photorefractive keratectomy vs laser in situ keratomileusis.

    Science.gov (United States)

    Lee, Hyung Keun; Lee, Kyung Sub; Kim, Hyeon Chang; Lee, Sung Ho; Kim, Eung Kweon

    2005-06-01

    To determine whether tear nerve growth factor (NGF) concentration correlates with corneal sensation and ocular surface dryness after photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK). Prospective, nonrandomized comparative clinical trial. Seventy eyes of 35 patients and 76 eyes of 38 patients underwent PRK and LASIK procedures to correct myopia and myopic astigmatism, respectively. Total tear protein level, tear NGF concentration, tear film breakup time (BUT) and Schirmer values were measured before and 1 day, 1 week, 1 month, 3 months, and 6 months after surgery. The postoperative mean tear NGF/total tear protein (NGF/tP) ratio increased in both PRK and LASIK patients compared with preoperative levels (P PRK than in LASIK subjects (P LASIK in the ablated zone was lower than the preoperative sensation (P PRK subjects. Mean BUT and Schirmer values were significantly lower in LASIK-treated eyes compared with PRK-treated eyes up to 6 months postoperatively (P PRK-treated and LASIK-treated eyes might be related to the difference in the early postoperative levels of NGF, which is a potent nerve growth stimulator.

  7. Cold knife cone biopsy

    Science.gov (United States)

    ... biopsy; Pap smear - cone biopsy; HPV - cone biopsy; Human papilloma virus - cone biopsy; Cervix - cone biopsy; Colposcopy - cone biopsy Images Female reproductive anatomy Cold cone biopsy Cold cone removal References Baggish ...

  8. Factors affecting cone production in Pinus pinaster Ait.: lack of growth-reproduction trade-offs but significant effects of climate and tree and stand characteristics

    Directory of Open Access Journals (Sweden)

    Felipe Bravo

    2017-10-01

    Full Text Available Aim of study: Our main goal is to determine the relationship between cone production and radial growth in Pinus pinaster Ait. under different climatic conditions across the Iberian Peninsula. Area of study: Coca Intensive Sampling Plateau, Northern Plateau (Spain. Material and methods: Cone counts were conducted on an intensive monitoring plot in Coca (North-Central Spain during the years 2000, 2006 and 2007. A ZIP (zero-inflated Poisson model was adjusted for simultaneously estimating the probability of obtaining crop cones and its amount. The Northern Atlantic Oscillation (NAO index was used as explanatory variable, together with a wide variety of tree and local stand variables. Climate (as evaluated by NAO, local stand density (here estimated from the six nearest trees, tree size and vigor, competition and growth efficiency significantly influenced both occurrence and intensity of cone production. Main results: ZIP models for predicting reproductive effort seems an adequate tool to predict reproductive responses to climatic fluctuations and the resulting future species distribution in the face of climate change, as well as to identify silviculture actions that would promote reproductive success in naturally-regenerated stands, list and discuss relevant results (including numeric values of experimental results. Research highlights: Climate, stand density and tree conditions (size and vigor, competition and growth efficiency influence significantly both cone occurrence and intensity of fruiting as shown by a ZIP model. As the climate variables included in the model (based on Northern Atlantic Oscillation, NAO are general and easily obtained, the proposed model has practical applicability to predicting Pinus pinaster cone production in the Iberian Peninsula.

  9. Factors affecting cone production in Pinus pinaster Ait.: lack of growth-reproduction trade-offs but significant effects of climate and tree and stand characteristics

    Energy Technology Data Exchange (ETDEWEB)

    Bravo, F.; Maguire, D.A.; González-Martínez, S.G.

    2017-11-01

    Aim of study: Our main goal is to determine the relationship between cone production and radial growth in Pinus pinaster Ait. under different climatic conditions across the Iberian Peninsula. Area of study: Coca Intensive Sampling Plateau, Northern Plateau (Spain). Material and methods: Cone counts were conducted on an intensive monitoring plot in Coca (North-Central Spain) during the years 2000, 2006 and 2007. A ZIP (zero-inflated Poisson) model was adjusted for simultaneously estimating the probability of obtaining crop cones and its amount. The Northern Atlantic Oscillation (NAO) index was used as explanatory variable, together with a wide variety of tree and local stand variables. Climate (as evaluated by NAO), local stand density (here estimated from the six nearest trees), tree size and vigor, competition and growth efficiency significantly influenced both occurrence and intensity of cone production. Main results: ZIP models for predicting reproductive effort seems an adequate tool to predict reproductive responses to climatic fluctuations and the resulting future species distribution in the face of climate change, as well as to identify silviculture actions that would promote reproductive success in naturally-regenerated stands, list and discuss relevant results (including numeric values of experimental results). Research highlights: Climate, stand density and tree conditions (size and vigor, competition and growth efficiency) influence significantly both cone occurrence and intensity of fruiting as shown by a ZIP model. As the climate variables included in the model (based on Northern Atlantic Oscillation, NAO) are general and easily obtained, the proposed model has practical applicability to predicting Pinus pinaster cone production in the Iberian Peninsula.

  10. Factors affecting cone production in Pinus pinaster Ait.: lack of growth-reproduction trade-offs but significant effects of climate and tree and stand characteristics

    International Nuclear Information System (INIS)

    Bravo, F.; Maguire, D.A.; González-Martínez, S.G.

    2017-01-01

    Aim of study: Our main goal is to determine the relationship between cone production and radial growth in Pinus pinaster Ait. under different climatic conditions across the Iberian Peninsula. Area of study: Coca Intensive Sampling Plateau, Northern Plateau (Spain). Material and methods: Cone counts were conducted on an intensive monitoring plot in Coca (North-Central Spain) during the years 2000, 2006 and 2007. A ZIP (zero-inflated Poisson) model was adjusted for simultaneously estimating the probability of obtaining crop cones and its amount. The Northern Atlantic Oscillation (NAO) index was used as explanatory variable, together with a wide variety of tree and local stand variables. Climate (as evaluated by NAO), local stand density (here estimated from the six nearest trees), tree size and vigor, competition and growth efficiency significantly influenced both occurrence and intensity of cone production. Main results: ZIP models for predicting reproductive effort seems an adequate tool to predict reproductive responses to climatic fluctuations and the resulting future species distribution in the face of climate change, as well as to identify silviculture actions that would promote reproductive success in naturally-regenerated stands, list and discuss relevant results (including numeric values of experimental results). Research highlights: Climate, stand density and tree conditions (size and vigor, competition and growth efficiency) influence significantly both cone occurrence and intensity of fruiting as shown by a ZIP model. As the climate variables included in the model (based on Northern Atlantic Oscillation, NAO) are general and easily obtained, the proposed model has practical applicability to predicting Pinus pinaster cone production in the Iberian Peninsula.

  11. Balanced levels of nerve growth factor are required for normal pregnancy progression.

    Science.gov (United States)

    Frank, Pierre; Barrientos, Gabriela; Tirado-González, Irene; Cohen, Marie; Moschansky, Petra; Peters, Eva M; Klapp, Burghard F; Rose, Matthias; Tometten, Mareike; Blois, Sandra M

    2014-08-01

    Nerve growth factor (NGF), the first identified member of the family of neurotrophins, is thought to play a critical role in the initiation of the decidual response in stress-challenged pregnant mice. However, the contribution of this pathway to physiological events during the establishment and maintenance of pregnancy remains largely elusive. Using NGF depletion and supplementation strategies alternatively, in this study, we demonstrated that a successful pregnancy is sensitive to disturbances in NGF levels in mice. Treatment with NGF further boosted fetal loss rates in the high-abortion rate CBA/J x DBA/2J mouse model by amplifying a local inflammatory response through recruitment of NGF-expressing immune cells, increased decidual innervation with substance P(+) nerve fibres and a Th1 cytokine shift. Similarly, treatment with a NGF-neutralising antibody in BALB/c-mated CBA/J mice, a normal-pregnancy model, also induced abortions associated with increased infiltration of tropomyosin kinase receptor A-expressing NK cells to the decidua. Importantly, in neither of the models, pregnancy loss was associated with defective ovarian function, angiogenesis or placental development. We further demonstrated that spontaneous abortion in humans is associated with up-regulated synthesis and an aberrant distribution of NGF in placental tissue. Thus, a local threshold of NGF expression seems to be necessary to ensure maternal tolerance in healthy pregnancies, but when surpassed may result in fetal rejection due to exacerbated inflammation. © 2014 Society for Reproduction and Fertility.

  12. Identification and quantification of mRNA for nerve growth factor in histological preparations

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, P A; Rush, R A; Scott, J; Penschow, J; Coghlan, J

    1986-03-14

    Hybridization histochemistry has been used to detect mRNA for nerve growth factor (NGF) in histological preparations of mouse salivary glands and rat iris using a /sup 32/P-labelled cDNA probe and autoradiography. Label was visible over the tubular cells of the male mouse submaxillary gland but not the sublingual gland. A much lower label density was found over the tubular cells of the female submaxillary gland, whereas sections of liver and pancreas were negative. Quantitative autoradiography allowed the detection of low levels of mRNA for NGF in the rat iris which was elevated by prior culture of the tissue. The results provide direct histological evidence for the presence of specific NGF-mRNA in the mouse submaxillary gland and rat iris, with increased levels following culture. 15 refs.

  13. Expression and localization of nerve growth factor (NGF in the testis of alpaca (llama pacos

    Directory of Open Access Journals (Sweden)

    Haidong Wang

    2011-04-01

    Full Text Available During alpaca testis development and spermatogenesis, nerve growth factor (NGF may play an importantrole. The main aim of this study was to determine the expression and localization of NGF in the alpacatestis, and to discuss the important role of NGF in alpaca reproductive characteristics. Immunohistochemicalstaining technique and real-time PCR were used. The expression of NGF in the same cells one-month old(newborn alpacas 12-month, and 24-month old alpacas showed significant differences (p 0.05; NGF at different cell stages showed nosignificant differences (p > 0.05. It suggests that NGF may be involved in the regulation of spermatogenesis,which provides direct evidence for NGF action in the alpaca testis during postnatal development and spermatogenesis.

  14. Flavonoid glycosides from Hosta longipes, their inhibition on NO production, and nerve growth factor inductive effects

    International Nuclear Information System (INIS)

    Kim, Chung Sub; Lee, Kang Ro; Kwon, Oh Wook; Kim, Sun Yeou

    2014-01-01

    An extended phytochemical investigation of the leaves of Hosta longipes identified the new flavonoid glycoside, kaempferol-3-O-β-D-glucopyranosyl-(1→2)- [6 ' -O-acetyl-β-D-glucopyranoside]-7-O-β-D-glucopyranoside and five known flavonoid derivatives. The structures of two compounds were revealed by extensive NMR methods ( 1 H and 13 C NMR, 1 H- 1 H COSY, HMQC and HMBC) and chemical hydrolysis. NMR data of one of them are published for the first time. Bioactivities of six compounds revealed that five strongly inhibited the production of nitric oxide (NO) with IC 50 values of 11.56-15.97 μm in lipopolysaccharide (LPS)-stimulated BV-2 cells without cell toxicity. Two compounds showed moderate induction of secretion of nerve growth factor (NGF) in C6 glioma cells (124.70 ± 7.71% and 117.02 ± 3.60%, respectively). (author)

  15. Nerve growth factor, clinical applications and production of the recombinant protei

    Directory of Open Access Journals (Sweden)

    M. Zangi

    2017-01-01

    Full Text Available The mammalian neurotrophin family proteins, nerve growth factor (NGF, brain-derived neurotrophic factor (BDNF, neurotrophin-3 (NT-3 and neurotrophin-4/5 (NT-4/5 are known as neuronal survival factors. NGF, one of the most important cytokines, is composed of 118 amino acids. NGF is involved in the growth and differentiation of neural cells of the vertebrate peripheral sympathetic nerve as well as basal forebrain cholinergic neurons which degenerate in Alzheimer’s disease. In addition, it is implicated in the regulation of synaptic transmission and synaptogenesis in the central nervous system. NGF is produced by a variety of immune cells, including B cells, T cells, monocytes and mast cells as well as nervous system and binds through two distinct receptors, TrkA and p75NTR which signaling through them leads to the neuronal differentiation and cell death respectively. Considering the importance of this protein as a drug, NGF has been proposed for the treatment of neuron degenerative diseases such as Alzheimer's, Parkinson's and multiple sclerosis. To produce enough protein for research and clinical applications, genetic engineering techniques are used to produce recombinant forms. To date, there are no reports about the systems for production of the recombinant human NGF in an effective, low cost, with industrial production. Plants as a safe host generally offer major advantages such as free of animal pathogens, low costs, the ability to produce a protein similar to natural protein, and industrial production in large scale. Then they are suitable for the production of recombinant human NGF.

  16. Enhanced bioavailability of nerve growth factor with phytantriol lipid-based crystalline nanoparticles in cochlea

    Directory of Open Access Journals (Sweden)

    Bu M

    2015-11-01

    Full Text Available Meng Bu,1,2 Jingling Tang,3 Yinghui Wei,4 Yanhui Sun,1 Xinyu Wang,1 Linhua Wu,2 Hongzhuo Liu1 1School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China; 2Department of Pharmacy, the Second Affiliated Hospital, 3School of Pharmacy, Harbin Medical University, Harbin, People’s Republic of China; 4College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China Purpose: Supplementation of exogenous nerve growth factor (NGF into the cochlea of deafened animals rescues spiral ganglion cells from degeneration. However, a safe and potent delivery of therapeutic proteins, such as NGF, to spiral ganglion cells remains one of the greatest challenges. This study presents the development of self-assembled cubic lipid-based crystalline nanoparticles to enhance inner ear bioavailability of bioactive NGF via a round window membrane route.Methods: A novel nanocarrier-entrapped NGF was developed based on phytantriol by a liquid precursor dilution, with Pluronic® F127 and propylene glycol as the surfactant and solubilizer, respectively. Upon dilution of the liquid lipid precursors, monodispersed submicron-sized particles with a slight negative charge formed spontaneously.Results: Biological activity of entrapped NGF was assessed using pheochromocytoma cells with NGF-loaded reservoirs to induce significant neuronal outgrowth, similar to that seen in free NGF-treated controls. Finally, a 3.28-fold increase in inner ear bioavailability was observed after administration of phytantriol lipid-based crystalline nanoparticles as compared to free drug, contributing to an enhanced drug permeability of the round window membrane. Conclusion: Data presented here demonstrate the potential of lipid-based crystalline nanoparticles to improve the outcomes of patients bearing cochlear implants. Keywords: nerve growth factor, lipid-based crystalline nanoparticles, PC12 cells, inner ear drug

  17. Efficacy and safety of nerve growth factor for the treatment of neurological diseases:a meta-analysis of 64 randomized controlled trials involving 6,297 patients

    Institute of Scientific and Technical Information of China (English)

    Meng Zhao; Xiao-yan Li; Chun-ying Xu; Li-ping Zou

    2015-01-01

    OBJECTIVE:China is the only country where nerve growth factor is approved for large-scale use as a clinical medicine. More than 10 years ago, in 2003, nerve growth factor injection was listed as a national drug. The goal of this article is to evaluate comprehensively the efifcacy and safety of nerve growth factor for the treatment of neurological diseases. DATA RETRIEVAL:A computer-based retrieval was performed from six databases, including the Cochrane Library, PubMed, EMBASE, Sino Med, CNKI, and the VIP database, searching from the clinical establishment of nerve growth factor for treatment until December 31, 2013. The key words for the searches were “nerve growth factor, randomized controlled trials” in Chinese and in English. DATA SELECTION:Inclusion criteria: any study published in English or Chinese referring to randomized controlled trials of nerve growth factor; patients with neurological diseases such as peripheral nerve injury, central nerve injury, cranial neuropathy, and nervous system infections;patients older than 7 years; similar research methods and outcomes assessing symptoms; and measurement of nerve conduction velocities. The meta-analysis was conducted using Review Manager 5.2.3 software. MAIN OUTCOME MEASURES:The total effective rate, the incidence of adverse effects, and the nerve conduction velocity were recorded for each study. RESULTS:Sixty-four studies involving 6,297 patients with neurological diseases were included. The total effective rate in the group treated with nerve growth factor was significantly higher than that in the control group (P < 0.0001,RR: 1.35, 95%CI: 1.30–1.40). The average nerve conduction velocity in the nerve growth factor group was signiifcantly higher than that in the control group (P < 0.00001,MD: 4.59 m/s, 95%CI: 4.12–5.06). The incidence of pain or sclero-ma at the injection site in the nerve growth factor group was also higher than that in the control group (P < 0.00001,RR: 6.30, 95%CI: 3.53–11

  18. Long-term delivery of nerve growth factor by encapsulated cell biodelivery in the Göttingen minipig basal forebrain

    DEFF Research Database (Denmark)

    Fjord-Larsen, L; Kusk, P; Tornøe, Jens

    2010-01-01

    Nerve growth factor (NGF) prevents cholinergic degeneration in Alzheimer's disease (AD) and improves memory in AD animal models. In humans, the safe delivery of therapeutic doses of NGF is challenging. For clinical use, we have therefore developed an encapsulated cell (EC) biodelivery device...

  19. Hypertrophy of neurons within cardiac ganglia in human, canine, and rat heart failure: the potential role of nerve growth factor.

    Science.gov (United States)

    Singh, Sanjay; Sayers, Scott; Walter, James S; Thomas, Donald; Dieter, Robert S; Nee, Lisa M; Wurster, Robert D

    2013-08-19

    Autonomic imbalances including parasympathetic withdrawal and sympathetic overactivity are cardinal features of heart failure regardless of etiology; however, mechanisms underlying these imbalances remain unknown. Animal model studies of heart and visceral organ hypertrophy predict that nerve growth factor levels should be elevated in heart failure; whether this is so in human heart failure, though, remains unclear. We tested the hypotheses that neurons in cardiac ganglia are hypertrophied in human, canine, and rat heart failure and that nerve growth factor, which we hypothesize is elevated in the failing heart, contributes to this neuronal hypertrophy. Somal morphology of neurons from human (579.54±14.34 versus 327.45±9.17 μm(2); Phearts (767.80±18.37 versus 650.23±9.84 μm(2); Pneurons from spontaneously hypertensive rat hearts (327.98±3.15 versus 271.29±2.79 μm(2); Pneurons in cardiac ganglia compared with controls. Western blot analysis shows that nerve growth factor levels in the explanted, failing human heart are 250% greater than levels in healthy donor hearts. Neurons from cardiac ganglia cultured with nerve growth factor are significantly larger and have greater dendritic arborization than neurons in control cultures. Hypertrophied neurons are significantly less excitable than smaller ones; thus, hypertrophy of vagal postganglionic neurons in cardiac ganglia would help to explain the parasympathetic withdrawal that accompanies heart failure. Furthermore, our observations suggest that nerve growth factor, which is elevated in the failing human heart, causes hypertrophy of neurons in cardiac ganglia.

  20. Exploring Serum Levels of Brain Derived Neurotrophic Factor and Nerve Growth Factor Across Glaucoma Stages.

    Directory of Open Access Journals (Sweden)

    Francesco Oddone

    Full Text Available To investigate the serum levels of Brain Derived Neurotrophic Factor (BDNF and Nerve Growth Factor (NGF in patients affected by primary open angle glaucoma with a wide spectrum of disease severity compared to healthy controls and to explore their relationship with morphological and functional glaucoma parameters.45 patients affected by glaucoma at different stages and 15 age-matched healthy control subjects underwent visual field testing, peripapillary retinal nerve fibre layer thickness measurement using Spectral Domain Optical Coherence Tomography and blood collection for both neurotrophins detection by Enzyme-Linked Immunosorbent Assay. Statistical analysis and association between biostrumental and biochemical data were investigated.Serum levels of BDNF in glaucoma patients were significantly lower than those measured in healthy controls (261.2±75.0 pg/ml vs 313.6±79.6 pg/ml, p = 0.03. Subgroups analysis showed that serum levels of BDNF were significantly lower in early (253.8±40.7 pg/ml, p = 0.019 and moderate glaucoma (231.3±54.3 pg/ml, p = 0.04 but not in advanced glaucoma (296.2±103.1 pg/ml, p = 0.06 compared to healthy controls. Serum levels of NGF in glaucoma patients were significantly lower than those measured in the healthy controls (4.1±1 pg/mL vs 5.5±1.2 pg/mL, p = 0.01. Subgroups analysis showed that serum levels of NGF were significantly lower in early (3.5±0.9 pg/mL, p = 0.0008 and moderate glaucoma (3.8±0.7 pg/ml, p<0.0001 but not in advanced glaucoma (5.0±0.7 pg/ml, p = 0.32 compared to healthy controls. BDNF serum levels were not related to age, visual field mean deviation or retinal nerve fibre layer thickness either in glaucoma or in controls while NGF levels were significantly related to visual field mean deviation in the glaucoma group (r2 = 0.26, p = 0.004.BDNF and NGF serum levels are reduced in the early and moderate glaucoma stages, suggesting the possibility that both factors could be further investigated

  1. The role of nerve growth factor in the prophylaxis and treatment of diabetic foot ulcers

    Science.gov (United States)

    Tiaka, Elisavet K; Papanas, Nikolaos; Manolakis, Anastassios C; Maltezos, Efstratios

    2011-01-01

    Diabetic foot ulcers are still particularly difficult to heal. Therefore, preventing and therapeutic adjuncts are increasingly being explored. Nerve growth factor (NGF) is a promising agent exhibiting beneficial actions on both diabetic peripheral neuropathy, one of the main causes of foot ulcers, and on ulcer healing. Indeed, preclinical research in animal models of diabetes has revealed the trophic effect of NGF on small C-fibres, while phase 2 human trials have provided evidence for a favourable effect on sensory neuropathy. However, the results of a phase 3 trial were moderate and, therefore, not enough to encourage widespread use of NGF in the treatment of diabetic neuropathy. Available literature on the role of NGF on diabetic wound healing is sparse but encouraging. Exogenous supplementation of NGF or the use of alternative techniques to increase its endogenous expression could emerge as a protective and therapeutic modality for diabetic foot ulcers in addition to standard treatment and other growth factors. The present review provides an outlook on the role of NGF in the prophylaxis and treatment of diabetic foot ulcers. PMID:22928161

  2. Three-dimensional evaluation of pharyngeal airway in individuals with varying growth patterns using cone beam computed tomography

    Directory of Open Access Journals (Sweden)

    Rohan Diwakar

    2015-01-01

    Full Text Available Introduction: The purpose of this study was to evaluate the pharyngeal airway volume in individuals with different vertical growth patterns. Methods: Cone beam computed tomography scans were evaluated of 40 subjects with the age range from 14 to 25 years and were divided into three groups. Horizontal growers consisted of 13 subjects, normal growers consisted of 14 subjects, and the vertical growers consisted of 13 subjects. The pharyngeal airway volume was measured using In Vivo Dental 5.1 software (Anatomage, Anatomy Imaging Software, San Jose, CA, USA. Results: The results obtained were analyzed statistically. The statistical test used for the analysis of the result was Student′s t-test. The independent t-test was done to compare the mean of the pharyngeal airway between the normal growers and horizontal growers and between the normal growers and the vertical growers. No statistically significant difference between the three groups was found in the volumetric measurements of the various sections of airway. Conclusions: Pharyngeal airway volume does not differ significantly in different vertical jaw relationships. It was possible to evaluate the pharyngeal airway volume three dimensionally.

  3. EMA: a developmentally regulated cell-surface glycoprotein of CNS neurons that is concentrated at the leading edge of growth cones.

    Science.gov (United States)

    Baumrind, N L; Parkinson, D; Wayne, D B; Heuser, J E; Pearlman, A L

    1992-08-01

    To identify cell-surface molecules that mediate interactions between neurons and their environment during neural development, we used monoclonal antibody techniques to define a developmentally regulated antigen in the central nervous system of the mouse. The antibody we produced (2A1) immunolabels cells throughout the central nervous system; we analyzed its distribution in the developing cerebral cortex, where it is expressed on cells very soon after they complete mitosis and leave the periventricular proliferative zone. Expression continues into adult life. The antibody also labels the epithelium of the choroid plexus and the renal proximal tubules, but does not label neurons of the peripheral nervous system in the dorsal root ganglia. In dissociated cell culture of embryonic cerebral cortex, 2A1 labels the surface of neurons but not glia. Immunolabeling of neurons in tissue culture is particularly prominent on the edge of growth cones, including filopodia and the leading edge of lamellipodia, when observed with either immunofluorescence or freeze-etch immunoelectron microscopy. Immunopurification with 2A1 of a CHAPS-extracted membrane preparation from brains of neonatal mice produces a broad (32-36 kD) electrophoretic band and a less prominent 70 kD band that are sensitive to N-glycosidase but not endoglycosidase H. Thus the 2A1 antibody recognizes a developmentally regulated, neuronal cell surface glycoprotein (or glycoproteins) with complex N-linked oligosaccharide side chains. We have termed the glycoprotein antigen EMA because of its prominence on the edge membrane of growth cones. EMA is similar to the M6 antigen (Lagenaur et al: J. Neurobiol. 23:71-88, 1992) in apparent molecular weight, distribution in tissue sections, and immunoreactivity on Western blots, suggesting that the two antigens are similar or identical. Expression of EMA is a very early manifestation of neuronal differentiation; its distribution on growth cones suggests a role in mediating the

  4. Role of CD44 in Malignant Peripheral Nerve Sheath Tumor Growth and Metastasis

    National Research Council Canada - National Science Library

    Sherman, Larry

    2003-01-01

    Malignant peripheral nerve sheath tumors (MPNST) are aggressive, difficult to treat tumors that occur in type I neurofibromatosis patients with an increased incidence compared to the general population...

  5. Role of CD44 in Malignant Peripheral Nerve Sheath Tumor Growth and Metastasis

    National Research Council Canada - National Science Library

    Sherman, Larry

    2001-01-01

    Malignant peripheral nerve sheath tumors (MPNST) are aggressive, difficult to treat tumors that occur in type I neurofibromatosis patients with an increased incidence compared to the general population...

  6. Effects of age and insulin-like growth factor-1 on rat neurotrophin receptor expression after nerve injury.

    Science.gov (United States)

    Luo, T David; Alton, Timothy B; Apel, Peter J; Cai, Jiaozhong; Barnwell, Jonathan C; Sonntag, William E; Smith, Thomas L; Li, Zhongyu

    2016-10-01

    Neurotrophin receptors, such as p75(NTR) , direct neuronal response to injury. Insulin-like growth factor-1 receptor (IGF-1R) mediates the increase in p75(NTR) during aging. The aim of this study was to examine the effect of aging and insulin-like growth factor-1 (IGF-1) treatment on recovery after peripheral nerve injury. Young and aged rats underwent tibial nerve transection with either local saline or IGF-1 treatment. Neurotrophin receptor mRNA and protein expression were quantified. Aged rats expressed elevated baseline IGF-1R (34% higher, P = 0.01) and p75(NTR) (68% higher, P < 0.01) compared with young rats. Post-injury, aged animals expressed significantly higher p75(NTR) levels (68.5% above baseline at 4 weeks). IGF-1 treatment suppressed p75(NTR) gene expression at 4 weeks (17.2% above baseline, P = 0.002) post-injury. Local IGF-1 treatment reverses age-related declines in recovery after peripheral nerve injuries by suppressing p75(NTR) upregulation and pro-apoptotic complexes. IGF-1 may be considered a viable adjuvant therapy to current treatment modalities. Muscle Nerve 54: 769-775, 2016. © 2016 Wiley Periodicals, Inc.

  7. Nerve Growth Factor Gene Therapy Activates Neuronal Responses in Alzheimer’s Disease

    Science.gov (United States)

    Tuszynski, Mark H.; Yang, Jennifer H.; Barba, David; U, H S.; Bakay, Roy; Pay, Mary M.; Masliah, Eliezer; Conner, James M.; Kobalka, Peter; Roy, Subhojit; Nagahara, Alan H.

    2016-01-01

    IMPORTANCE Alzheimer’s disease (AD) is the most common neurodegenerative disorder, and lacks effective disease modifying therapies. In 2001 we initiated a clinical trial of Nerve Growth Factor (NGF) gene therapy in AD, the first effort at gene delivery in an adult neurodegenerative disorder. This program aimed to determine whether a nervous system growth factor prevents or reduces cholinergic neuronal degeneration in AD patients. We present post-mortem findings in 10 subjects with survival times ranging from 1 to 10 years post-treatment. OBJECTIVE To determine whether degenerating neurons in AD retain an ability to respond to a nervous system growth factor delivered after disease onset. DESIGN, SETTING, AND PARTICIPANTS 10 patients with early AD underwent NGF gene therapy using either ex vivo or in vivo gene transfer. The brains of all eight patients in the first Phase 1 ex vivo trial and two patients in a subsequent Phase 1 in vivo trial were examined. MAIN OUTCOME MEASURES Brains were immunolabeled to evaluate in vivo gene expression, cholinergic neuronal responses to NGF, and activation of NGF-related cell signaling. In two cases, NGF protein levels were measured by ELISA. RESULTS Degenerating neurons in the AD brain respond to NGF. All patients exhibited a trophic response to NGF, in the form of axonal sprouting toward the NGF source. Comparing treated and non-treated sides of the brain in three patients that underwent unilateral gene transfer, cholinergic neuronal hypertrophy occurred on the NGF-treated side (P>0.05). Activation of cellular signaling and functional markers were present in two patients that underwent AAV2-mediated NGF gene transfer. Neurons exhibiting tau pathology as well as neurons free of tau expressed NGF, indicating that degenerating cells can be infected with therapeutic genes with resulting activation of cell signaling. No adverse pathological effects related to NGF were observed. CONCLUSIONS AND RELEVANCE These findings indicate that

  8. Nerve Growth Factor Gene Therapy: Activation of Neuronal Responses in Alzheimer Disease.

    Science.gov (United States)

    Tuszynski, Mark H; Yang, Jennifer H; Barba, David; U, Hoi-Sang; Bakay, Roy A E; Pay, Mary M; Masliah, Eliezer; Conner, James M; Kobalka, Peter; Roy, Subhojit; Nagahara, Alan H

    2015-10-01

    Alzheimer disease (AD) is the most common neurodegenerative disorder and lacks effective disease-modifying therapies. In 2001, we initiated a clinical trial of nerve growth factor (NGF) gene therapy in AD, the first effort at gene delivery in an adult neurodegenerative disorder. This program aimed to determine whether a nervous system growth factor prevents or reduces cholinergic neuronal degeneration in patients with AD. We present postmortem findings in 10 patients with survival times ranging from 1 to 10 years after treatment. To determine whether degenerating neurons in AD retain an ability to respond to a nervous system growth factor delivered after disease onset. Patients in this anatomicopathological study were enrolled in clinical trials from March 2001 to October 2012 at the University of California, San Diego, Medical Center in La Jolla. Ten patients with early AD underwent NGF gene therapy using ex vivo or in vivo gene transfer. The brains of all 8 patients in the first phase 1 ex vivo trial and of 2 patients in a subsequent phase 1 in vivo trial were examined. Brains were immunolabeled to evaluate in vivo gene expression, cholinergic neuronal responses to NGF, and activation of NGF-related cell signaling. In 2 patients, NGF protein levels were measured by enzyme-linked immunosorbent assay. Among 10 patients, degenerating neurons in the AD brain responded to NGF. All patients exhibited a trophic response to NGF in the form of axonal sprouting toward the NGF source. Comparing treated and nontreated sides of the brain in 3 patients who underwent unilateral gene transfer, cholinergic neuronal hypertrophy occurred on the NGF-treated side (P < .05). Activation of cellular signaling and functional markers was present in 2 patients who underwent adeno-associated viral vectors (serotype 2)-mediated NGF gene transfer. Neurons exhibiting tau pathology and neurons free of tau expressed NGF, indicating that degenerating cells can be infected with therapeutic

  9. Flavonoid glycosides from Hosta longipes, their inhibition on NO production, and nerve growth factor inductive effects

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Chung Sub; Lee, Kang Ro, E-mail: krlee@skku.edu [Natural Products Laboratory, School of Pharmacy, Sungkyunkwan University (Korea, Republic of); Kwon, Oh Wook [Graduate School of East-West Medical Science, Kyung Hee University Global Campus (Korea, Republic of); Kim, Sun Yeou [College of Pharmacy, Gachon University (Korea, Republic of)

    2014-05-15

    An extended phytochemical investigation of the leaves of Hosta longipes identified the new flavonoid glycoside, kaempferol-3-O-β-D-glucopyranosyl-(1→2)- [6{sup '}-O-acetyl-β-D-glucopyranoside]-7-O-β-D-glucopyranoside and five known flavonoid derivatives. The structures of two compounds were revealed by extensive NMR methods ({sup 1}H and {sup 13}C NMR, {sup 1}H-{sup 1}H COSY, HMQC and HMBC) and chemical hydrolysis. NMR data of one of them are published for the first time. Bioactivities of six compounds revealed that five strongly inhibited the production of nitric oxide (NO) with IC{sub 50} values of 11.56-15.97 μm in lipopolysaccharide (LPS)-stimulated BV-2 cells without cell toxicity. Two compounds showed moderate induction of secretion of nerve growth factor (NGF) in C6 glioma cells (124.70 ± 7.71% and 117.02 ± 3.60%, respectively). (author)

  10. Nanotechnological strategies for nerve growth factor delivery: Therapeutic implications in Alzheimer's disease.

    Science.gov (United States)

    Faustino, Célia; Rijo, Patrícia; Reis, Catarina Pinto

    2017-06-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder associated with amyloid-β peptide misfolding and aggregation. Neurotrophic factors, such as nerve growth factor (NGF), can prevent neuronal damage and rescue the cholinergic neurons that undergo cell death in AD, reverse deposition of extracellular amyloid plaques and improve cognitive deficits. However, NGF administration is hampered by the poor pharmacokinetic profile of the therapeutic protein and its inability to cross the blood-brain barrier, which requires specialised drug delivery systems (DDS) for efficient NGF delivery to the brain. This review covers the main therapeutic approaches that have been developed for NGF delivery targeting the brain, from polymeric implants to gene and cell-based therapies, focusing on the role of nanoparticulate systems for the sustained release of NGF in the brain as a neuroprotective and disease-modifying approach toward AD. Lipid- and polymer-based delivery systems, magnetic nanoparticles and quantum dots are specifically addressed as promising nanotechnological strategies to overcome the current limitations of NGF-based therapies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. From genes to pain: nerve growth factor and hereditary sensory and autonomic neuropathy type V.

    Science.gov (United States)

    Capsoni, Simona

    2014-02-01

    Hereditary sensory and autonomic neuropathy type V (HSAN V) is an autosomal recessive disorder characterized by the loss of deep pain perception. The anomalous pain and temperature sensations are due to the absence of nociceptive sensory innervation. The neurotrophin nerve growth factor (NGF), by binding to tropomyosin receptor A (TrkA) and p75NTR receptors, is essential for the development and survival of sensory neurons, and for pain perception during adulthood. Recently a homozygous missense mutation (R100W) in the NGF gene has been identified in HSAN V patients. Interestingly, alterations in NGF signalling, due to mutations in the NGF TRKA gene, have also been involved in another congenital insensitivity to pain, HSAN IV, characterized not only by absence of reaction to painful stimuli, but also anhidrosis and mental retardation. These symptoms are absent in HSAN V patients. Unravelling the mechanisms that underlie the differences between HSAN IV and V could assist in better understanding NGF biology. This review highlights the recent key findings in the understanding of HSAN V, including insights into the molecular mechanisms of the disease, derived from genetic studies of patients with this disorder. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  12. Serum nerve growth factor (NGF) levels in children with attention deficit/hyperactivity disorder (ADHD).

    Science.gov (United States)

    Guney, Esra; Ceylan, Mehmet Fatih; Kara, Mehmet; Tekin, Neslihan; Goker, Zeynep; Senses Dinc, Gulser; Ozturk, Onder; Eker, Sevda; Kizilgun, Murat

    2014-02-07

    Attention deficit/hyperactivity disorder (ADHD) is the most commonly diagnosed neurobehavioral disorder of childhood. The etiopathogeny of ADHD has not been totally defined. Recent reports have suggested a pathophysiological role of neurotrophins in ADHD. In this study, we evaluated serum levels of nerve growth factor (NGF) in patients with ADHD. The sample population consisted of 44 child or adolescent patients diagnosed with ADHD according to DSM-IV criteria; 36 healthy subjects were included in the study as controls. Venous blood samples were collected, and NGF levels were measured. The mean serum NGF levels of the ADHD patients were significantly higher than those of the controls. Age and gender of the patients were not correlated with serum NGF levels. There were no significant differences in NGF levels among the combined and predominantly inattentive subtypes of ADHD. Our study suggests that there are higher levels of serum NGF in drug naive ADHD patients, and that increased levels of NGF might have an important role in the pathophysiology of ADHD. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  13. Expression of nerve growth factor and its receptor, tyrosine kinase receptor A, in rooster testes.

    Science.gov (United States)

    Ma, Wei; Wang, Chunqiang; Su, Yuhong; Tian, Yumin; Zhu, Hongyan

    2015-10-01

    Nerve growth factor (NGF), which is required for the survival and differentiation of the nervous system, is also thought to play an important role in the development of mammalian reproductive tissues. To explore the function of NGF in the male reproductive system of non-mammalian animals, we determined the presence of NGF and its receptor, tyrosine kinase receptor A (TrkA), in rooster testes and investigated the regulation of NGF and TrkA expression by follicle-stimulating hormone (FSH). The mRNA and protein levels of NGF and TrkA in 6-week-old rooster testes were lower than those in 12-, 16- or 20-week age groups; levels were highest in the 16-week group. Immunohistochemistry showed that NGF and TrkA were both detected in spermatogonia, spermatocytes and spermatids. NGF immunoreactivity was observed in Leydig cells and strong TrkA signals were present in Sertoli cells. Meanwhile, FSH increased TrkA transcript levels in rooster testes in a dose-dependent manner. We present novel evidence for the developmental and FSH-regulated expression of the NGF/TrkA system, and our findings suggest that the NGF/TrkA system may play a prominent role in chicken spermatogenesis. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Expression of nerve growth factor and heme oxygenase-1 predict poor survival of breast carcinoma patients

    International Nuclear Information System (INIS)

    Noh, Sang Jae; Chung, Myoung Ja; Moon, Woo Sung; Kang, Myoung Jae; Jang, Kyu Yun; Bae, Jun Sang; Jamiyandorj, Urangoo; Park, Ho Sung; Kwon, Keun Sang; Jung, Sung Hoo; Youn, Hyun Jo; Lee, Ho; Park, Byung-Hyun

    2013-01-01

    Nerve growth factor (NGF) is a neurotrophin and has been suggested to induce heme oxygenase-1 (HO1) expression. Although the role of HO1 in tumorigenesis remains controversial, recent evidence suggests NGF and HO1 as tumor-progressing factors. However, the correlative role of NGF and HO1 and their prognostic impact in breast carcinoma is unknown. We investigated the expression and prognostic significance of the expression of NGF and HO1 in 145 cases of breast carcinoma. Immunohistochemical expression of NGF and HO1 was observed in 31% and 49% of breast carcinoma, respectively. The expression of NGF and HO1 significantly associated with each other, and both have a significant association with histologic grade, HER2 expression, and latent distant metastasis. The expression of NGF and HO1 predicted shorter overall survival of breast carcinoma by univariate and multivariate analysis. NGF expression was an independent prognostic indicator for relapse-free survival by multivariate analysis. The combined expression pattern of NGF and HO1 was also an independent prognostic indicator of overall survival and relapse-free survival. The patients with tumors expressing NGF had the shortest survival and the patients with tumor, which did not express NGF or HO1 showed the longest survival time. This study has demonstrated that individual expression of NGF or HO1, and the combined NGF/HO1 expression pattern could be prognostic indicators for breast carcinoma patients

  15. The Multiple Life of Nerve Growth Factor: Tribute to Rita Levi-Montalcini (1909-2012

    Directory of Open Access Journals (Sweden)

    Luigi Aloe

    2013-03-01

    Full Text Available At the end of the 19th century, it was envisaged by Santiago Ramon y Cajal, but not, proven, that life at the neuronal level requires trophic support. The proof was obtained in the early 1950's by work initiated by Rita Levi-Montalcini (RLM discovering the nerve growth factor (NGF. Today, NGF and its relatives, collectively designated neurotrophins, are well recognized as mediators of multiple biological phenomena in health and disease, ranging from the neurotrophic through immunotrophic and epitheliotrophic to metabotrophic effects. Consequently, NGF and other neurotrophins are implicated in the pathogenesis of a large spectrum of neuronal and non-neuronal diseases, from Alzheimer's and other neurodegenerative diseases to atherosclerosis and other cardiometabolic diseases. Recent studies demonstrated the therapeutic potentials of NGF in these diseases, including ocular and cutaneous diseases. Furthermore, NGF TrkA receptor antagonists emerged as novel drugs for pain, prostate and breast cancer, melanoma, and urinary bladder syndromes. Altogether, NGF's multiple potential in health and disease is briefly described here.

  16. Ghrelin ameliorates nerve growth factor Dysmetabolism and inflammation in STZ-induced diabetic rats.

    Science.gov (United States)

    Zhao, Yuxing; Shen, Zhaoxing; Zhang, Dongling; Luo, Huiqiong; Chen, Jinliang; Sun, Yue; Xiao, Qian

    2017-06-01

    Diabetic encephalopathy is characterized by cognitive impairment and neuroinflammation, deficient neurotrophic support, and neuronal and synaptic loss. Ghrelin, a 28 amino acid peptide, is associated with neuromodulation and cognitive improvement, which has been considered as a potential protective agent for several neurodegenerative diseases. Here we sought to investigate the role of ghrelin in preventing diabetic-related neuropathology. We found that ghrelin attenuated astrocytic activation and reduced levels of interleukin-6 and tumor necrosis factor-α in streptozotocin-induced diabetic rats. In addition, ghrelin inhibited p38 mitogen-associated protein kinase activation. The upregulation of nerve growth factor (NGF) precursor and matrix metalloproteinase (MMP)-9 and downregulation of mature NGF and MMP-7 in the diabetic brain were reversed by ghrelin. Treatment with ghrelin elevated synaptophysin expression and synaptic density in diabetic rats. Taken together, our results demonstrate that ghrelin ameliorates diabetes-related neurodegeneration by preventing NGF dysmetabolism and synaptic degeneration through regulating MMP levels as well as inhibiting neuroinflammation.

  17. [Clinical efficacy of mouse nerve growth factor in treatment of occupational hand-arm vibration disease].

    Science.gov (United States)

    Fan, Chunyue; Wang, Yanyan; Zhang, Ying; Lang, Li; Deng, Xiaofeng; Cheng, Ying

    2014-12-01

    To investigate the efficacy of mouse nerve growth factor (mNGF) in treating occupational hand-arm vibration disease (HAVD). Sixty-four patients with HAVD were equally and randomly divided into treatment group and control group. The control group was given Salvia miltiorrhiza Bunge and deproteinized extract of calf blood to improve circulation, and also given methylcobalamin tablets and vitamin B6 for neurotrophic treatment. In addition to the above treatments for the control group, the treatment group was also given 30 µg/d mNGF by intramuscular injection for two courses (4 weeks for each course) with a 15-day interval. Both the treatment group and the control group showed significant improvements in clinical symptoms and signs (hand numbness and pain, and reduced senses of touch, pain, and vibration), cold water loading test (CWLT), and electroneuromyography (ENMG) after treatments (P hand numbness and pain, reduced senses of touch, pain, and vibration, CWLT, and ENMG, so it has better clinical effect and safety in treating HAVD. Early diagnosis and treatment can improve the outcome of patients with HAVD.

  18. Targeting of liposomes to cells bearing nerve growth factor receptors mediated by biotinylated NGF

    International Nuclear Information System (INIS)

    Rosenberg, M.B.

    1986-01-01

    Previous studies of liposome targeting have concentrated on immunological systems, the use of ligand-receptor interactions has received little attention. The protein hormone beta-nerve growth factor (NGF) was modified by biotinylation via carboxyl group substitution (C-bio-NGF) under reaction conditions that yielded an average of 3 biotin additions per NGF subunit. NGF was also biotinylated through amino group substitution to produce derivatives with ratios of 1, 2 and 4 biotin moieties per NGF subunit (N-bio-NGF). These derivatives were compared with native NGF for their ability to compete with 125 I-NGF for binding to NGF receptors on rat pheochromocytoma (PC 12) cells at 4 0 C. C-bio-NGF was as effective as native NGF in binding to NGF receptors, while N-bio-NGF containing 1 biotin per NGF subunit was only 28% as active in binding as native NGF. C-bio-NGF, but not N-bio-NGF, mediated the specific binding of 125 I-streptavidin to PC12 cells. Biocytin-NGF, a derivative of C-bio-NGF with an extended spacer chain, was also synthesized and retained full biological and receptor binding activities. C-bio-NGF and biocytin-NGF were as effective as native NGF in a bioassay involving induction of neurite outgrowth from PC12 cells

  19. Increased Nerve Growth Factor Signaling in Sensory Neurons of Early Diabetic Rats Is Corrected by Electroacupuncture

    Directory of Open Access Journals (Sweden)

    Stefania Lucia Nori

    2013-01-01

    Full Text Available Diabetic polyneuropathy (DPN, characterized by early hyperalgesia and increased nerve growth factor (NGF, evolves in late irreversible neuropathic symptoms with reduced NGF support to sensory neurons. Electroacupuncture (EA modulates NGF in the peripheral nervous system, being effective for the treatment of DPN symptoms. We hypothesize that NGF plays an important pathogenic role in DPN development, while EA could be useful in the therapy of DPN by modulating NGF expression/activity. Diabetes was induced in rats by streptozotocin (STZ injection. One week after STZ, EA was started and continued for three weeks. NGF system and hyperalgesia-related mediators were analyzed in the dorsal root ganglia (DRG and in their spinal cord and skin innervation territories. Our results show that four weeks long diabetes increased NGF and NGF receptors and deregulated intracellular signaling mediators of DRG neurons hypersensitization; EA in diabetic rats decreased NGF and NGF receptors, normalized c-Jun N-terminal and p38 kinases activation, decreased transient receptor potential vanilloid-1 ion channel, and possibly activated the nuclear factor kappa-light-chain-enhancer of activated B cells (Nf-κB. In conclusion, NGF signaling deregulation might play an important role in the development of DPN. EA represents a supportive tool to control DPN development by modulating NGF signaling in diabetes-targeted neurons.

  20. The multiple life of nerve growth factor: tribute to rita levi-montalcini (1909-2012).

    Science.gov (United States)

    Aloe, Luigi; Chaldakov, George N

    2013-03-01

    At the end of the 19(th) century, it was envisaged by Santiago Ramon y Cajal, but not, proven, that life at the neuronal level requires trophic support. The proof was obtained in the early 1950's by work initiated by Rita Levi-Montalcini (RLM) discovering the nerve growth factor (NGF). Today, NGF and its relatives, collectively designated neurotrophins, are well recognized as mediators of multiple biological phenomena in health and disease, ranging from the neurotrophic through immunotrophic and epitheliotrophic to metabotrophic effects. Consequently, NGF and other neurotrophins are implicated in the pathogenesis of a large spectrum of neuronal and non-neuronal diseases, from Alzheimer's and other neurodegenerative diseases to atherosclerosis and other cardiometabolic diseases. Recent studies demonstrated the therapeutic potentials of NGF in these diseases, including ocular and cutaneous diseases. Furthermore, NGF TrkA receptor antagonists emerged as novel drugs for pain, prostate and breast cancer, melanoma, and urinary bladder syndromes. Altogether, NGF's multiple potential in health and disease is briefly described here.

  1. Binding and internalization of nerve growth factor by PC12 cells

    International Nuclear Information System (INIS)

    Kasaian, M.T.

    1987-01-01

    The interaction of nerve growth factor (NGF) with its cell surface receptors has been studied using both fluorescent- and radio-labelled NGF. The fluorescence studies were done by flow cytometry, and gave information about the concentration dependence and time course of NGF binding to rat pheochromocytoma cells (PC12) and human melanoma cells (A875). 125 I-NGF was used to study the fate of NGF in PC12 cells following its association with cell surface receptors. Variations of the PC12 binding assay were used to distinguish ligand bound to fast and slowly dissociating receptors at the cell surface, internalized ligand, and cytoskeletally-associated NGF. Ligand uptake into each of these pools was followed in untreated cells, as well as in cells exposed to colchicine and/or cytochalasin B to disrupt the cytoskeleton. NGF degradation was also followed in these cells, and chloroquine was used to inhibit this process. In a separate project, NGF activity was assayed in samples of human amniotic fluid and cerebrospinal fluid (CSF). A range of activities was found in these samples, with the CSF samples containing somewhat more activity than the amniotic fluid samples

  2. Nerve growth factor regulates neurolymphatic remodeling during corneal inflammation and resolution.

    Directory of Open Access Journals (Sweden)

    Darci M Fink

    Full Text Available The cellular and physiologic mechanisms that regulate the resolution of inflammation remain poorly defined despite their widespread importance in improving inflammatory disease outcomes. We studied the resolution of two cardinal signs of inflammation-pain and swelling-by investigating molecular mechanisms that regulate neural and lymphatic vessel remodeling during the resolution of corneal inflammation. A mouse model of corneal inflammation and wound recovery was developed to study this process in vivo. Administration of nerve growth factor (NGF increased pain sensation and inhibited neural remodeling and lymphatic vessel regression processes during wound recovery. A complementary in vivo approach, the corneal micropocket assay, revealed that NGF-laden pellets stimulated lymphangiogenesis and increased protein levels of VEGF-C. Adult human dermal lymphatic endothelial cells did not express canonical NGF receptors TrkA and p75NTR or activate downstream MAPK- or Akt-pathway effectors in the presence of NGF, although NGF treatment increased their migratory and tubulogenesis capacities in vitro. Blockade of the VEGF-R2/R3 signaling pathway ablated NGF-mediated lymphangiogenesis in vivo. These findings suggest a hierarchical relationship with NGF functioning upstream of the VEGF family members, particularly VEGF-C, to stimulate lymphangiogenesis. Taken together, these studies show that NGF stimulates lymphangiogenesis and that NGF may act as a pathogenic factor that negatively regulates the normal neural and lymphatic vascular remodeling events that accompany wound recovery.

  3. Neuroprotective Role of Nerve Growth Factor in Hypoxic-Ischemic Brain Injury

    Directory of Open Access Journals (Sweden)

    Antonio Chiaretti

    2013-06-01

    Full Text Available Hypoxic-ischemic brain injuries (HIBI in childhood are frequently associated with poor clinical and neurological outcome. Unfortunately, there is currently no effective therapy to restore neuronal loss and to determine substantial clinical improvement. Several neurotrophins, such as Nerve Growth Factor (NGF, Brain-Derived Neurotrophic Factor (BDNF, and Glial Derived Neurotrophic Factor (GDNF, play a key role in the development, differentiation, and survival of the neurons of the peripheral and central nervous system. Experimental animal studies demonstrated their neuroprotective role in HIBI, while only a few studies examined the neuroprotective mechanisms in patients with severe HIBI. We report two cases of children with HIBI and prolonged comatose state who showed a significant improvement after intraventricular NGF administration characterized by amelioration of electroencephalogram (EEG and cerebral perfusion at single-photon emission computed tomography (SPECT. The improvement in motor and cognitive functions of these children could be related to the neuroprotective role exerted by NGF in residual viable cholinergic neurons, leading to the restoration of neuronal networks in the damaged brain.

  4. Prolonged controlled delivery of nerve growth factor using porous silicon nanostructures.

    Science.gov (United States)

    Zilony, Neta; Rosenberg, Michal; Holtzman, Liran; Schori, Hadas; Shefi, Orit; Segal, Ester

    2017-07-10

    Although nerve growth factor (NGF) is beneficial for the treatment of numerous neurological and non-neurological diseases, its therapeutic administration represents a significant challenge, due to the difficulty to locally deliver relevant doses in a safe and non-invasive manner. In this work, we employ degradable nanostructured porous silicon (PSi) films as carriers for NGF, allowing its continuous and prolonged release, while retaining its bioactivity. The PSi carriers exhibit high loading efficacy (up to 90%) of NGF and a continuous release, with no burst, over a period of>26days. The released NGF bioactivity is compared to that of free NGF in both PC12 cells and dissociated dorsal root ganglion (DRG) neurons. We show that the NGF has retained its bioactivity and induces neurite outgrowth and profound differentiation (of >50% for PC12 cells) throughout the period of release within a single administration. Thus, this proof-of-concept study demonstrates the immense therapeutic potential of these tunable carriers as long-term implants of NGF reservoirs and paves the way for new localized treatment strategies of neurodegenerative diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Serum levels of nerve growth factor (NGF) in patients with major depression disorder and suicide risk.

    Science.gov (United States)

    Wiener, Carolina David; de Mello Ferreira, Sharon; Pedrotti Moreira, Fernanda; Bittencourt, Guilherme; de Oliveira, Jacqueline Flores; Lopez Molina, Mariane; Jansen, Karen; de Mattos Souza, Luciano Dias; Rizzato Lara, Diogo; Portela, Luiz Valmor; da Silva, Ricardo Azevedo; Oses, Jean Pierre

    2015-09-15

    Nerve growth factor (NGF) is an important member of the neurotrophins group and their involvement in the pathophysiology of major depression disorder (MDD) and suicide risk (SR) has been recently suggested. The aim of this study is to evaluate the changes in NGF serum levels in individuals with MDD and with or without risk of suicide, in subjects from a young population-based sample. This is a paired cross-sectional study nested in a population-based study. Individuals were rated for MDD and SR by a diagnostic interview--Mini International Neuropsychiatric Interview (M.I.N.I). The total population of the sample was comprised of 141 subjects distributed in three groups: 47 healthy controls, 47 subjects with current depressive episode without SR (MDD) and 47 subjects with current depressive episode and with SR (MDD + SR). NGF serum levels were significantly reduced in the MDD and MDD + SR groups when compared with controls (p ≤ 0.001). However, there were no differences in NGF levels between the MDD and MDD + SR groups (p = 1.000). These results suggest that reduced NGF serum levels can be a possible biomarker of MDD. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Hypertrophy of Neurons Within Cardiac Ganglia in Human, Canine, and Rat Heart Failure: The Potential Role of Nerve Growth Factor

    OpenAIRE

    Singh, Sanjay; Sayers, Scott; Walter, James S.; Thomas, Donald; Dieter, Robert S.; Nee, Lisa M.; Wurster, Robert D.

    2013-01-01

    Background Autonomic imbalances including parasympathetic withdrawal and sympathetic overactivity are cardinal features of heart failure regardless of etiology; however, mechanisms underlying these imbalances remain unknown. Animal model studies of heart and visceral organ hypertrophy predict that nerve growth factor levels should be elevated in heart failure; whether this is so in human heart failure, though, remains unclear. We tested the hypotheses that neurons in cardiac ganglia are hyper...

  7. Effects of chronic aluminum exposure on learning and memory and brain-derived nerve growth factor in rats

    Institute of Scientific and Technical Information of China (English)

    潘宝龙

    2013-01-01

    Objective To investigate the effects of chronic aluminum exposure on the learning and memory abilities and brain-derived nerve growth factor (BDNF) in SpragueDawley (SD) rats.Methods Thirty-two male SD rats were randomly and equally divided into 4 groups:control group and high-,middle-,and low-dose exposure groups.The rats in high-,middle-,and low-dose expo-

  8. Effect of the Nerve Growth Factor Mimetic GK-2 on Brain Structural and Functional State in the Early Postresuscitation Period

    Directory of Open Access Journals (Sweden)

    M. Sh. Avrushchenko

    2012-01-01

    Full Text Available Objective: to evaluate the efficacy of the nerve growth factor mimetic GK-2 used to improve the structural and functional state of the brain in the early postresuscitation period. Material and methods. Cardiac arrest was induced in mature male albino rats for 12 minutes, followed by resuscitation. The neurological state of the resuscitated animals was assessed by a scoring scale. On postresuscitation day 7, the density and composition of neuronal populations of Purkinje cells in the lateral cerebellar region and pyramidal neurons in the hippocampal CA1 sector were determined by a differential morphometric analysis. The results were statistically processed using the ANOVA method. Results. The use of GK-2 was found to accelerate neurological recovery in the resuscitated animals. On day 7 after 12-minute cardiac arrest, the resuscitated animals showed neuronal dystrophic changes and death in the neuronal populations highly susceptible to ischemia. It was shown that the systemic administration of the nerve growth factor mimetic GK-2 contributed to a reduction in the magnitude and depth of postresuscitation changes in the cerebellar Purkinje cells and prevented dystrophic changes in the pyramidal cells of the hippocampal CA1 sector. The findings suggest that GK-2 has a neuroprotective effect in the recovery period after total body ischemia. Conclusion. The results of this study indicate the efficiency of the systemic administration of the nerve growth factor mimetic GK-2 in improving the brain structural and functional state in the early postresuscitation period. This determines perspectives for the use of GK-2 to prevent and correct posthypoxic encephalopathies. Key words: the nerve growth factor mimetic GK-2, postresuscitation period, neuronal dystrophic changes and death, neurological status.

  9. Corallocins A-C, Nerve Growth and Brain-Derived Neurotrophic Factor Inducing Metabolites from the Mushroom Hericium coralloides.

    Science.gov (United States)

    Wittstein, Kathrin; Rascher, Monique; Rupcic, Zeljka; Löwen, Eduard; Winter, Barbara; Köster, Reinhard W; Stadler, Marc

    2016-09-23

    Three new natural products, corallocins A-C (1-3), along with two known compounds were isolated from the mushroom Hericium coralloides. Their benzofuranone and isoindolinone structures were elucidated by spectral methods. All corallocins induced nerve growth factor and/or brain-derived neurotrophic factor expression in human 1321N1 astrocytes. Furthermore, corallocin B showed antiproliferative activity against HUVEC and human cancer cell lines MCF-7 and KB-3-1.

  10. Ocular Nerve Growth Factor (NGF) and NGF Eye Drop Application as Paradigms to Investigate NGF Neuroprotective and Reparative Actions.

    Science.gov (United States)

    Tirassa, Paola; Rosso, Pamela; Iannitelli, Angela

    2018-01-01

    The eye is a central nervous system structure that is uniquely accessible to local treatment. Through the ocular surface, it is possible to access the retina, optic nerve, and brain. Animal models of retina degeneration or optic nerve crush could thus serve as tools to investigate whether and how factors, which are anterogradely or retrogradely transported through the optic nerve, might contribute to activate neuroprotection and eventually regeneration. Among these factors, nerve growth factor (NGF) plays a crucial role during development of the visual system, as well as during the entire life span, and in pathological conditions. The ability of NGF to exert survival and trophic actions on the retina and brain cells when applied intraocularly and topically as eye drops is critically reviewed here, together with the effects of ocular neurotrophins on neuronal pathways influencing body rhythm, cognitions, and behavioral functions. The latest data from animal models and humans are presented, and the mechanism of action of ocularly administered NGF is discussed. NGF eye drops are proposed as an experimental strategy to investigate the role and cellular targets of neurotrophins in the mechanism(s) underlying neurodegeneration/regeneration and their involvement in the regulation of neurological and behavioral dysfunctions.

  11. Effect of β-nerve growth factor on differentiation of endothelial ...

    African Journals Online (AJOL)

    (Ad-EGFP-hβ-NGF) on the differentiation of endothelial progenitor cells (EPCs) in rats. Methods: The successfully ... may contribute to angiopoiesis or vascular repair. Keywords: β-Nerve ... angiogenesis in damaged tissues [6]. In this study ...

  12. A meta-analysis of peripheral blood nerve growth factor levels in patients with schizophrenia.

    Science.gov (United States)

    Qin, X-Y; Wu, H-T; Cao, C; Loh, Y P; Cheng, Y

    2017-09-01

    Neurotrophins particularly brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are crucial modulators in the neurodevelopment and maintenance of central and peripheral nervous systems. Neurotrophin hypothesis of schizophrenia (SCZ) postulated that the changes in the brains of SCZ patients are the result of disturbances of developing processes involving neurotrophic factors. This hypothesis was mainly supported by the abnormal regulation of BDNF in SCZ, especially the decreased peripheral blood BDNF levels in SCZ patients validated by several meta-analyses. However, the regulation of NGF in SCZ remains unclear because of the inconsistent findings from the clinical studies. Therefore, we undertook, to the best of our knowledge, the first systematic review with a meta-analysis to quantitatively summarize the peripheral blood NGF data in SCZ patients compared with healthy control (HC) subjects. A systematic search of Pubmed, PsycINFO and Web of Science identified 13 articles encompassing a sample of 1693 individuals for the meta-analysis. Random-effects meta-analysis showed that patients with SCZ had significantly decreased peripheral blood levels of NGF when compared with the HC subjects (Hedges's g=-0.633, 95% confidence interval (CI)=-0.948 to -0.318, Pmeta-regression analyses showed that age, gender and sample size had no moderating effects on the outcome of the meta-analysis, whereas disease severity might be a confounding factor for the meta-analysis. These results demonstrated that patients with SCZ are accompanied by the decreased peripheral blood NGF levels, strengthening the clinical evidence of an abnormal neurotrophin profile in the patients with SCZ.

  13. [Nerve Growth Factor in Patients With Arterial Hypertension: Neuropsychical, Hemodynamic, Metabolic Relationships].

    Science.gov (United States)

    Ushakov, A V; Ivanchenko, V S; Gordienko, A I; Khimich, N V; Gagarina, A A

    2018-02-01

    To investigate the changes of serum nerve growth factor (NGF) level in patients with arterial hypertension (AH) and obesity in dependence on the degree of psycho-emotional stress and physical activity. We examined 76 male patients with stage I and II AH with mean age 46.75±0.56 years (36 patients with and 40 without obesity). Control group consisted of 26 individuals without AH, obesity, and cardiovascular diseases. All patients underwent ambulatory blood pressure (BP) monitoring. Serum concentrations of NGF β-subunit and cortisol were determined by enzyme linked immunosorbent assay. For assessment of levels of psycho-emotional stress, reactive and personal anxiety, and physical activity we used Psychological Stress Measure (PSM-25), the Spielberger-Khanin questionnaire, and brief International Physical Activity Questionnaire (IPAQ), respectively. Level of NGF in patients with AH and obesity (0.94±0.28 ρg/ml) was higher than in non-obese patients with AH (0.21±0.06 ρg/ml; p=0.018) with highest figures in patients with insufficient physical activity and high level of psychoemotional stress. In all groups of patients there was unidirectional reverse correlation between serum NGF and cortisol levels. According to ambulatory BP monitoring, NGF level was inversely proportional to systolic and diastolic BP variability in patients with AH and obesity and in the control group. Reduced serum concentration of NGF was associated with increased levels of reactive and personal anxiety. Obtained data suggests that NGF plays an important role in complex multifactorial interactions between neuropsychic, cardiovascular and metabolic processes.

  14. Urinary Nerve Growth Factor as a Potential Biomarker of Treatment Outcomes in Overactive Bladder Patients

    Directory of Open Access Journals (Sweden)

    Yoon Seok Suh

    2017-12-01

    Full Text Available Purpose The aim of this study was to investigate urinary nerve growth factor (NGF as a biomarker of treatment efficacy and recurrence in overactive bladder (OAB patients. Methods We enrolled 189 OAB subjects who visited our outpatient clinic from February 2010 to February 2015. All subjects with OAB received antimuscarinic treatment. A 3-day voiding diary and questionnaire were collected from each patient. Urinary levels of NGF were evaluated at baseline, the beginning of antimuscarinic treatment, and the end of antimuscarinic treatment. Urinary NGF was normalized to urine creatinine (Cr. Between-group comparisons of baseline characteristics were made using the Mann-Whitney U-test. Multivariate logistic regression analyses were used to predict responses to anticholinergic treatment and recurrence. The Wilcoxon signed-rank test with the Bonferroni correction was used for intragroup comparisons. A receiver operating characteristic curve was used to analyze the utility of this biomarker. Results Urinary levels of NGF/Cr tended to decrease in patients who responded to treatment (n=62, but this was not significant (P=0.260. Urinary NGF levels were higher at baseline in patients who did not experience recurrence than in those who did (P=0.047. In those who did not experience recurrence (n=29, urinary NGF/Cr decreased at the end of treatment compared to baseline, and this reduction was maintained at 12 weeks after the end of treatment (P<0.05. Conclusions Urinary NGF is a potential biomarker for predicting the outcome of antimuscarinic treatment in OAB patients. This may provide useful information when deciding to stop antimuscarinic treatment in responders.

  15. Correlation between Nerve Growth Factor (NGF with Brain Derived Neurotropic Factor (BDNF in Ischemic Stroke Patient

    Directory of Open Access Journals (Sweden)

    Joko Widodo

    2016-05-01

    Full Text Available Background: The neurotrophins nerve growth factor (NGF and brain-derived neurotrophic factor (BDNF is a family of polypeptides that play critical role during neuronal development, appear to mediate protective role on neurorepair in ischemic stroke. Naturally in adult brain neurorepair process consist of: angiogenesis, neurogenesis, and neuronal plasticity, it can also be stimulated by endogenous neurorepair. In this study we observed correlation between NGF and BDNF ischemic stroke patient’s onset: 7-30 and over 30 days. Methods: This is cross sectional study on 46 subjects aged 38 – 74 years old with ischemic stroke from The Indonesian Central Hospital of Army Gatot Subroto Jakarta. Diagnosis of ischemic stroke was made using clinical examination and magnetic resonance imaging (MRI by neurologist. Subjects were divided into 2 groups based on stroke onset: 7 – 30 days (Group A: 19 subjects and > 30 days (Group B: 27 Subjects. Serum NGF levels were measured with ELISA method and BDNF levels were measured using multiplex method with Luminex Magpix. Results: Levels of NGF and BDNF were significantly different between onset group A and B (NGF p= 0.022, and BDNF p=0.008, with mean levels NGF in group A higher than group B, indicating that BDNF levels is lower in group A than group B. There was no significant correlation between NGF and BDNF levels in all groups. Conclusion: The variations in neurotrophic factor levels reflect an endogenous attempt at neuroprotection against biochemical and molecular changes after ischemic stroke. NGF represents an early marker of brain injury while BDNF recovery is most prominent during the first 14 days after onsite but continuous for more than 30 days. There is no significant correlation between NGF and BDNF in each group.  

  16. Optic nerve size evaluated by magnetic resonance imaging in children with optic nerve hypoplasia, multiple pituitary hormone deficiency, isolated growth hormone deficiency, and idiopathic short stature.

    Science.gov (United States)

    Birkebaek, Niels Holtum; Patel, Leena; Wright, Neville Bryce; Grigg, John Russell; Sinha, Smeeta; Hall, Catherine Margaret; Price, David Anthony; Lloyd, Ian Christopher; Clayton, Peter Ellis

    2004-10-01

    To objectively define criteria for intracranial optic nerve (ON) size in ON hypoplasia (ONH) on magnetic resonance imaging (MRI) scans. Intracranial ON sizes from MRI were compared between 46 children with ONH diagnosed by ophthalmoscopy (group 1, isolated ONH, 8 children; and group 2, ONH associated with abnormalities of the hypothalamic-pituitary axis and septum pellucidum, 38 children) and children with multiple pituitary hormone deficiency (group 3, multiple pituitary hormone deficiency, 14 children), isolated growth hormone deficiency (group 4, isolated growth hormone deficiency, 15 children), and idiopathic short stature (group 5, idiopathic short stature, 10 children). Intracranial ON size was determined by the cross-sectional area, calculated as [pi x (1/2) height x (1/2) width]. Groups 1 and 2 had lower intracranial ON size than did groups 3, 4, and 5 (P imaging of the ONs with cross-sectional area short child more than 12 months of age, with or without hypothalamic-pituitary axis abnormalities, confirms the clinical diagnosis of ONH.

  17. Chronic mild stress influences nerve growth factor through a matrix metalloproteinase-dependent mechanism.

    Science.gov (United States)

    Kucharczyk, Mateusz; Kurek, Anna; Detka, Jan; Slusarczyk, Joanna; Papp, Mariusz; Tota, Katarzyna; Basta-Kaim, Agnieszka; Kubera, Marta; Lason, Wladyslaw; Budziszewska, Bogusława

    2016-04-01

    Stress is generally a beneficial experience that motivates an organism to action to overcome the stressful challenge. In particular situations, when stress becomes chronic might be harmful and devastating. The hypothalamus is a critical coordinator of stress and the metabolic response; therefore, disruptions in this structure may be a significant cause of the hormonal and metabolic disturbances observed in depression. Chronic stress induces adverse changes in the morphology of neural cells that are often associated with a deficiency of neurotrophic factors (NTFs); additionally, many studies indicate that insufficient NTF synthesis may participate in the pathogenesis of depression. The aim of the present study was to determine the expression of the nerve growth factor (NGF) in the hypothalamus of male rats subjected to chronic mild stress (CMS) or to prenatal stress (PS) and to PS in combination with an acute stress event (AS). It has been found that chronic mild stress, but not prenatal stress, acute stress or a combination of PS with AS, decreased the concentration of the mature form of NGF (m-NGF) in the rat hypothalamus. A discrepancy between an increase in the Ngf mRNA and a decrease in the m-NGF levels suggested that chronic mild stress inhibited NGF maturation or enhanced the degradation of this factor. We have shown that NGF degradation in the hypothalamus of rats subjected to chronic mild stress is matrix metalloproteinase-dependent and related to an increase in the active forms of some metalloproteinases (MMP), including MMP2, MMP3, MMP9 and MMP13, while the NGF maturation process does not seem to be changed. We suggested that activated MMP2 and MMP9 potently cleave the mature but not the pro- form of NGF into biologically inactive products, which is the reason for m-NGF decomposition. In turn, the enhanced expression of Ngf in the hypothalamus of these rats is an attempt to overcome the reduced levels of m-NGF. Additionally, the decreased level of m

  18. Noise Stress Induces an Epidermal Growth Factor Receptor/Xeroderma Pigmentosum-A Response in the Auditory Nerve.

    Science.gov (United States)

    Guthrie, O'neil W

    2017-03-01

    In response to toxic stressors, cancer cells defend themselves by mobilizing one or more epidermal growth factor receptor (EGFR) cascades that employ xeroderma pigmentosum-A (XPA) to repair damaged genes. Recent experiments discovered that neurons within the auditory nerve exhibit basal levels of EGFR+XPA co-expression. This finding implied that auditory neurons in particular or neurons in general have the capacity to mobilize an EGFR+XPA defense. Therefore, the current study tested the hypothesis that noise stress would alter the expression pattern of EGFR/XPA within the auditory nerve. Design-based stereology was used to quantify the proportion of neurons that expressed EGFR, XPA, and EGFR+XPA with and without noise stress. The results revealed an intricate neuronal response that is suggestive of alterations to both co-expression and individual expression of EGFR and XPA. In both the apical and middle cochlear coils, the noise stress depleted EGFR+XPA expression. Furthermore, there was a reduction in the proportion of neurons that expressed XPA-alone in the middle coils. However, the noise stress caused a significant increase in the proportion of neurons that expressed EGFR-alone in the middle coils. The basal cochlear coils failed to mobilize a significant response to the noise stress. These results suggest that EGFR and XPA might be part of the molecular defense repertoire of the auditory nerve.

  19. Noise Stress Induces an Epidermal Growth Factor Receptor/Xeroderma Pigmentosum–A Response in the Auditory Nerve

    Science.gov (United States)

    Guthrie, O’neil W.

    2017-01-01

    In response to toxic stressors, cancer cells defend themselves by mobilizing one or more epidermal growth factor receptor (EGFR) cascades that employ xeroderma pigmentosum–A (XPA) to repair damaged genes. Recent experiments discovered that neurons within the auditory nerve exhibit basal levels of EGFR+XPA co-expression. This finding implied that auditory neurons in particular or neurons in general have the capacity to mobilize an EGFR+XPA defense. Therefore, the current study tested the hypothesis that noise stress would alter the expression pattern of EGFR/XPA within the auditory nerve. Design-based stereology was used to quantify the proportion of neurons that expressed EGFR, XPA, and EGFR+XPA with and without noise stress. The results revealed an intricate neuronal response that is suggestive of alterations to both co-expression and individual expression of EGFR and XPA. In both the apical and middle cochlear coils, the noise stress depleted EGFR+XPA expression. Furthermore, there was a reduction in the proportion of neurons that expressed XPA-alone in the middle coils. However, the noise stress caused a significant increase in the proportion of neurons that expressed EGFR-alone in the middle coils. The basal cochlear coils failed to mobilize a significant response to the noise stress. These results suggest that EGFR and XPA might be part of the molecular defense repertoire of the auditory nerve. PMID:28056182

  20. The Rat Homolog of the Schizophrenia Susceptibility Gene ZNF804A Is Highly Expressed during Brain Development, Particularly in Growth Cones.

    Directory of Open Access Journals (Sweden)

    Katja Hvid Hinna

    Full Text Available A single nucleotide polymorphism in the ZNF804A gene, rs1344706, is associated with schizophrenia. The polymorphism has been suggested to alter fetal expression of ZNF804A. It has also been reported to be associated with altered cortical functioning and neural connectivity in the brain. Since developmental mechanisms are suggested in the pathophysiology for schizophrenia, expression of Zfp804A, the rat homolog of ZNF804A, was investigated in the developing rat brain. We found that expression of Zfp804A in most brain regions is developmentally regulated and peaks around birth, where after it decreases towards adult levels. This time point is developmentally the equivalent to the second trimester of fetal development in humans. An exception to this expression pattern is the hippocampus where the expression of Zfp804A appears to increase again in the adult brain. Using laser capture and quantitative PCR we found that Zfp804A mRNA expression in the adult rat hippocampus is highest in the CA1 sub region, where the overall firing rates of neurons is higher than in the CA3 region. In cultured cortical neurons Zfp804A mRNA expression peaked at day 4 and then decreased. The ZFP804A protein expression was therefore investigated with immunochemistry in such cultures. Interestingly, before day 4, the protein is mostly found in the perinuclear region of the cell but at day 4, ZFP804A was instead found throughout the cell and particularly in the growth cones. In conclusion we demonstrate that Zfp804A increases in the rat brain at the time of birth, coinciding with neuronal differentiation. We also show that ZFP804A is localized to growth cones of growing neurites. These data implicate ZFP804A in growth cone function and neurite elongation. The polymorphism rs1344706 lowers expression of ZNF804A during prenatal brain development. This may affect ZNF804A's role in cone function and neurite elongation leading to synaptic deficits and altered neural connectivity.

  1. Nerve Blocks

    Science.gov (United States)

    ... News Physician Resources Professions Site Index A-Z Nerve Blocks A nerve block is an injection to ... the limitations of Nerve Block? What is a Nerve Block? A nerve block is an anesthetic and/ ...

  2. Immunohistochemical profile of cytokines and growth factors expressed in vestibular schwannoma and in normal vestibular nerve tissue.

    Science.gov (United States)

    Taurone, Samanta; Bianchi, Enrica; Attanasio, Giuseppe; Di Gioia, Cira; Ierinó, Rocco; Carubbi, Cecilia; Galli, Daniela; Pastore, Francesco Saverio; Giangaspero, Felice; Filipo, Roberto; Zanza, Christian; Artico, Marco

    2015-07-01

    Vestibular schwannomas, also known as acoustic neuromas, are benign tumors, which originate from myelin-forming Schwann cells. They develop in the vestibular branch of the eighth cranial nerve in the internal auditory canal or cerebellopontine angle. The clinical progression of the condition involves slow and progressive growth, eventually resulting in brainstem compression. The objective of the present study was to investigate the expression level and the localization of the pro-inflammatory cytokines, transforming growth factor-β1 (TGF-β1) interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α), as well as the adhesion molecules, intracellular adhesion molecule-1 and vascular endothelial growth factor (VEGF), in order to determine whether these factors are involved in the transformation and development of human vestibular schwannoma. The present study investigated whether changes in inflammation are involved in tumor growth and if so, the mechanisms underlying this process. The results of the current study demonstrated that pro-inflammatory cytokines, including TGF-β1, IL-1β and IL-6 exhibited increased expression in human vestibular schwannoma tissue compared with normal vestibular nerve samples. TNF-α was weakly expressed in Schwann cells, confirming that a lower level of this cytokine is involved in the proliferation of Schwann cells. Neoplastic Schwann cells produce pro-inflammatory cytokines that may act in an autocrine manner, stimulating cellular proliferation. In addition, the increased expression of VEGF in vestibular schwannoma compared with that in normal vestibular nerve tissue, suggests that this factor may induce neoplastic growth via the promotion of angiogenesis. The present findings suggest that inflammation may promote angiogenesis and consequently contribute to tumor progression. In conclusion, the results of the present study indicated that VEGF and pro-inflammatory cytokines may be potential therapeutic targets in vestibular

  3. Deficiency of the Survival of Motor Neuron Protein Impairs mRNA Localization and Local Translation in the Growth Cone of Motor Neurons.

    Science.gov (United States)

    Fallini, Claudia; Donlin-Asp, Paul G; Rouanet, Jeremy P; Bassell, Gary J; Rossoll, Wilfried

    2016-03-30

    Spinal muscular atrophy (SMA) is a neurodegenerative disease primarily affecting spinal motor neurons. It is caused by reduced levels of the survival of motor neuron (SMN) protein, which plays an essential role in the biogenesis of spliceosomal small nuclear ribonucleoproteins in all tissues. The etiology of the specific defects in the motor circuitry in SMA is still unclear, but SMN has also been implicated in mediating the axonal localization of mRNA-protein complexes, which may contribute to the axonal degeneration observed in SMA. Here, we report that SMN deficiency severely disrupts local protein synthesis within neuronal growth cones. We also identify the cytoskeleton-associated growth-associated protein 43 (GAP43) mRNA as a new target of SMN and show that motor neurons from SMA mouse models have reduced levels ofGAP43mRNA and protein in axons and growth cones. Importantly, overexpression of two mRNA-binding proteins, HuD and IMP1, restoresGAP43mRNA and protein levels in growth cones and rescues axon outgrowth defects in SMA neurons. These findings demonstrate that SMN plays an important role in the localization and local translation of mRNAs with important axonal functions and suggest that disruption of this function may contribute to the axonal defects observed in SMA. The motor neuron disease spinal muscular atrophy (SMA) is caused by reduced levels of the survival of motor neuron (SMN) protein, which plays a key role in assembling RNA/protein complexes that are essential for mRNA splicing. It remains unclear whether defects in this well characterized housekeeping function cause the specific degeneration of spinal motor neurons observed in SMA. Here, we describe an additional role of SMN in regulating the axonal localization and local translation of the mRNA encoding growth-associated protein 43 (GAP43). This study supports a model whereby SMN deficiency impedes transport and local translation of mRNAs important for neurite outgrowth and stabilization

  4. Ultrasound-guided plasma rich in growth factors injections and scaffolds hasten motor nerve functional recovery in an ovine model of nerve crush injury.

    Science.gov (United States)

    Sánchez, Mikel; Anitua, E; Delgado, D; Prado, R; Sánchez, P; Fiz, N; Guadilla, J; Azofra, J; Pompei, O; Orive, G; Ortega, M; Yoshioka, T; Padilla, S

    2017-05-01

    In the present study we evaluated the motor recovery process of peripheral nerve injury (PNI), based on electrophysiological and histomorphometric criteria, after treatment with plasma rich in growth factors (PRGF) injections and scaffolds in an ovine model. Three groups of sheep underwent a nerve crush lesion: the first group (n = 3) was left to recover spontaneously (SR); the second group was administered saline injections (SI; n = 5) and a third group (n = 6) received PRGF injections and scaffolds immediately after the crush injury. At post-intervention week 8, 70% of sheep in the PRGF group were CMAP-positive, with no electrophysiological response in the rest of the groups. Histomorphometric analysis 12 weeks after the surgical intervention revealed that the average axonal density of the SR (1184 ± 864 axons/µm 2 ) and SI (3109 ± 2450 axons/µm 2 ) groups was significantly inferior to the control (8427 ± 2433 axons/µm 2 ) and also inferior to the PRGF group (5276 ± 4148 axons/µm 2 ), showing no significant differences between the control and PRGF groups. The axonal size of the SR and SI groups was significantly smaller compared with the control group (18 ± 4 µm 2 ), whereas the axonal size of the PRGF group (6 ± 5 µm 2 ) did not show statistical differences from the control. Morphometry of the target muscles indicated that the PRGF group had the lowest percentage volume reduction 12 weeks after the crush injury. The PRGF group had larger muscle fibre areas than the SI and SR groups, although the differences did not reach statistical significance. Overall, these data suggest that the PRGF injections and scaffolds hastened functional axon recovery and dampened atrophy of the target muscles in an ovine model. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  5. Influence of minimally invasive hematoma evacuation combined with nerve growth factor preparation on neurological function injury in patients with hypertensive cerebral hemorrhage

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    Jiang Tao

    2017-05-01

    Full Text Available Objective: To study the influence of minimally invasive hematoma evacuation combined with nerve growth factor preparation on neurological function injury in patients with hypertensive cerebral hemorrhage. Methods: A total of 112 patients with hypertensive cerebral hemorrhage who were treated in our hospital between July 2013 and February 2016 were collected, and according to random number table, they were divided into the control group (n=56 who underwent minimally invasive hematoma evacuation therapy and the observation group (n=56 who underwent minimally invasive hematoma evacuation combined with nerve growth factor preparation therapy. Serum contents of inflammatory mediators, nerve injury indexes and neurotransmitters were compared between two groups of patients before and after treatment. Results: Before treatment, there were no significant differences in serum contents of inflammatory mediators, nerve injury indexes and neurotransmitters between the two groups. After treatment, serum contents of inflammatory mediators such as CRP, PCT, IL-1β and IL-6 in observation group were lower than those in control group; serum contents of nerve injury indexes such as NSE, S100B, GEAP and MBP were lower than those in control group; serum contents of neurotransmitters such as SP, NPY, Glu and Asp were lower than those in control group while GABA and Gly were higher than those in control group. Conclusion: Minimally invasive hematoma evacuation combined with nerve growth factor preparation can effectively reduce neurological function injury, and has positive clinical significance.

  6. Ex Vivo Assay of Electrical Stimulation to Rat Sciatic Nerves: Cell Behaviors and Growth Factor Expression.

    Science.gov (United States)

    Du, Zhiyong; Bondarenko, Olexandr; Wang, Dingkun; Rouabhia, Mahmoud; Zhang, Ze

    2016-06-01

    Neurite outgrowth and axon regeneration are known to benefit from electrical stimulation. However, how neuritis and their surroundings react to electrical field is difficult to replicate by monolayer cell culture. In this work freshly harvested rat sciatic nerves were cultured and exposed to two types of electrical field, after which time the nerve tissues were immunohistologically stained and the expression of neurotrophic factors and cytokines were evaluated. ELISA assay was used to confirm the production of specific proteins. All cell populations survived the 48 h culture with little necrosis. Electrical stimulation was found to accelerate Wallerian degeneration and help Schwann cells to switch into migratory phenotype. Inductive electrical stimulation was shown to upregulate the secretion of multiple neurotrophic factors. Cellular distribution in nerve tissue was altered upon the application of an electrical field. This work thus presents an ex vivo model to study denervated axon in well controlled electrical field, bridging monolayer cell culture and animal experiment. It also demonstrated the critical role of electrical field distribution in regulating cellular activities. © 2015 Wiley Periodicals, Inc.

  7. Vascular endothelial growth factor gene therapy improves nerve regeneration in a model of obstetric brachial plexus palsy.

    Science.gov (United States)

    Hillenbrand, Matthias; Holzbach, Thomas; Matiasek, Kaspar; Schlegel, Jürgen; Giunta, Riccardo E

    2015-03-01

    The treatment of obstetric brachial plexus palsy has been limited to conservative therapies and surgical reconstruction of peripheral nerves. In addition to the damage of the brachial plexus itself, it also leads to a loss of the corresponding motoneurons in the spinal cord, which raises the need for supportive strategies that take the participation of the central nervous system into account. Based on the protective and regenerative effects of VEGF on neural tissue, our aim was to analyse the effect on nerve regeneration by adenoviral gene transfer of vascular endothelial growth factor (VEGF) in postpartum nerve injury of the brachial plexus in rats. In the present study, we induced a selective crush injury to the left spinal roots C5 and C6 in 18 rats within 24 hours after birth and examined the effect of VEGF-gene therapy on nerve regeneration. For gene transduction an adenoviral vector encoding for VEGF165 (AdCMV.VEGF165) was used. In a period of 11 weeks, starting 3 weeks post-operatively, functional regeneration was assessed weekly by behavioural analysis and force measurement of the upper limb. Morphometric evaluation was carried out 8 months post-operatively and consisted of a histological examination of the deltoid muscle and the brachial plexus according to defined criteria of degeneration. In addition, atrophy of the deltoid muscle was evaluated by weight determination comparing the left with the right side. VEGF expression in the brachial plexus was quantified by an enzyme-linked immunosorbent assay (ELISA). Furthermore the motoneurons of the spinal cord segment C5 were counted comparing the left with the right side. On the functional level, VEGF-treated animals showed faster nerve regeneration. It was found less degeneration and smaller mass reduction of the deltoid muscle in VEGF-treated animals. We observed significantly less degeneration of the brachial plexus and a greater number of surviving motoneurons (P reason for these effects. The clinical use

  8. Fabrication of bioactive conduits containing the fibroblast growth factor 1 and neural stem cells for peripheral nerve regeneration across a 15 mm critical gap

    International Nuclear Information System (INIS)

    Ni, Hsiao-Chiang; Tseng, Ting-Chen; Hsu, Shan-hui; Chen, Jeng-Rung; Chiu, Ing-Ming

    2013-01-01

    Nerve conduits are often used in combination with bioactive molecules and stem cells to enhance peripheral nerve regeneration. In this study, the acidic fibroblast growth factor 1 (FGF1) was immobilized onto the microporous/micropatterned poly (D, L-lactic acid) (PLA) nerve conduits after open air plasma treatment. PLA substrates grafted with chitosan in the presence of a small amount of gold nanoparticles (nano Au) showed a protective effect on the activity of the immobilized FGF1 in vitro. Different conduits were tested for their ability to bridge a 15 mm critical gap defect in a rat sciatic nerve injury model. Axon regeneration and functional recovery were evaluated by histology, walking track analysis and electrophysiology. Among different conduits, PLA conduits grafted with chitosan–nano Au and the FGF1 after plasma activation had the greatest regeneration capacity and functional recovery in the experimental animals. When the above conduit was seeded with aligned neural stem cells, the efficacy was further enhanced and it approached that of the autograft group. This work suggested that microporous/micropatterned nerve conduits containing bioactive growth factors may be successfully fabricated by micropatterning techniques, open plasma activation, and immobilization, which, combined with aligned stem cells, may synergistically contribute to the regeneration of the severely damaged peripheral nerve. (paper)

  9. Expression of growth-associated protein 43 in the skin nerve fibers of patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Bursova, Sarka; Dubovy, Petr; Vlckova-Moravcova, Eva; Nemec, Martin; Klusakova, Ilona; Belobradkova, Jana; Bednarik, Josef

    2012-04-15

    The growth-associated protein 43 (GAP-43) is known as a marker of regenerating nerve fibers and their continuous remodeling in the adult human skin. The purpose of this pilot study was to investigate a possible role for GAP-43 in the detection of the early stages of small-fiber neuropathy in patients with type 2 diabetes mellitus (DM2) as compared with a well- established and validated parameter - intra-epidermal nerve fiber density (IENFD) of protein gene product 9.5 (PGP 9.5) immunoreactive intra-epidermal C fibers. In a group of 21 patients with DM2 within three years of diagnosis (13 men, 8 women; mean age 53.9±12.8; range 30-74) and a group of 17 healthy volunteers (8 men, 9 women; mean age 55.8±8.5; range 45-70 years), skin punch biopsies were taken from a distal calf and double immunostained with both PGP 9.5 and GAP-43. In healthy controls, 96.8% of 629 PGP 9.5 immunoreactive fibers were immunostained with GAP-43; the proportion of PGP 9.5 intra-epidermal nerve fibers immunoreactive for GAP-43 in control subjects ranged from 86.5 to 100%. In DM2 patients, IENFD was significantly lower compared to controls (median, 1.5 vs. 11.2/mm; pDM2 patients compared to healthy controls (73.6% of 337 PGP 9.5 positive fibers; p<0.001); ranged from 0 to 98.1%. In conclusion, these results show that impaired regeneration of intra-epidermal C fibers in the early stages of type 2 diabetes mellitus, as indicated by GAP-43, might be a marker of incipient diabetic neuropathy. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. Nerve growth factor induces facial heat hyperalgesia and plays a role in trigeminal neuropathic pain in rats.

    Science.gov (United States)

    Dos Reis, Renata C; Kopruszinski, Caroline M; Nones, Carina F M; Chichorro, Juliana G

    2016-09-01

    There is preclinical evidence that nerve growth factor (NGF) contributes toward inflammatory hyperalgesia in the orofacial region, but the mechanisms underlying its hyperalgesic effect as well as its role in trigeminal neuropathic pain require further investigation. This study investigated the ability of NGF to induce facial heat hyperalgesia and the involvement of tyrosine kinase receptor A, transient receptor potential vanilloid 1, and mast cells in NGF pronociceptive effects. In addition, the role of NGF in heat hyperalgesia in a model of trigeminal neuropathic pain was evaluated. NGF injection into the upper lip of naive rats induced long-lasting heat hyperalgesia. Pretreatment with an antibody anti-NGF, antagonists of tyrosine kinase receptor A, and transient receptor potential vanilloid 1 receptors or compound 48/80, to induce mast-cell degranulation, all attenuated NGF-induced hyperalgesia. In a rat model of trigeminal neuropathic pain, local treatment with anti-NGF significantly reduced heat hyperalgesia. In addition, increased NGF levels were detected in the ipsilateral infraorbital nerve branch at the time point that represents the peak of heat hyperalgesia. The results suggest that NGF is a prominent hyperalgesic mediator in the trigeminal system and it may represent a potential therapeutic target for the management of painful orofacial conditions, including trigeminal neuropathic pain.

  11. The Rat Homolog of the Schizophrenia Susceptibility Gene ZNF804A Is Highly Expressed during Brain Development, Particularly in Growth Cones

    DEFF Research Database (Denmark)

    Hinna, Katja Hvid; Rich, Karen; Fex Svenningsen, Åsa

    2015-01-01

    it decreases towards adult levels. This time point is developmentally the equivalent to the second trimester of fetal development in humans. An exception to this expression pattern is the hippocampus where the expression of Zfp804A appears to increase again in the adult brain. Using laser capture...... developmental mechanisms are suggested in the pathophysiology for schizophrenia, expression of Zfp804A, the rat homolog of ZNF804A, was investigated in the developing rat brain. We found that expression of Zfp804A in most brain regions is developmentally regulated and peaks around birth, where after...... expression was therefore investigated with immunochemistry in such cultures. Interestingly, before day 4, the protein is mostly found in the perinuclear region of the cell but at day 4, ZFP804A was instead found throughout the cell and particularly in the growth cones. In conclusion we demonstrate that Zfp...

  12. Sonic Hedgehog switches on Wnt/planar cell polarity signaling in commissural axon growth cones by reducing levels of Shisa2

    Science.gov (United States)

    Onishi, Keisuke

    2017-01-01

    Commissural axons switch on responsiveness to Wnt attraction during midline crossing and turn anteriorly only after exiting the floor plate. We report here that Sonic Hedgehog (Shh)-Smoothened signaling downregulates Shisa2, which inhibits the glycosylation and cell surface presentation of Frizzled3 in rodent commissural axon growth cones. Constitutive Shisa2 expression causes randomized turning of post-crossing commissural axons along the anterior–posterior (A–P) axis. Loss of Shisa2 led to precocious anterior turning of commissural axons before or during midline crossing. Post-crossing commissural axon turning is completely randomized along the A–P axis when Wntless, which is essential for Wnt secretion, is conditionally knocked out in the floor plate. This regulatory link between Shh and planar cell polarity (PCP) signaling may also occur in other developmental processes. PMID:28885142

  13. Expression and localization of nerve growth factor (NGF in the testis of alpaca (llama pacos

    Directory of Open Access Journals (Sweden)

    Changsheng Dong

    2011-04-01

    Full Text Available During alpaca testis development and spermatogenesis, nerve growth factor (NGF may play an important role. The main aim of this study was to determine the expression and localization of NGF in the alpaca testis, and to discuss the important role of NGF in alpaca reproductive characteristics. Immunohistochemical staining technique and real-time PCR were used. The expression of NGF in the same cells one-month old (newborn alpacas 12-month, and 24-month old alpacas showed significant differences (p < 0.05; 12- and 24-month old alpacas showed no significant differences (p > 0.05; NGF at different cell stages showed no significant differences (p > 0.05. It suggests that NGF may be involved in the regulation of spermatogenesis, which provides direct evidence for NGF action in the alpaca testis during postnatal development and spermatogenesis. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 1, pp. 55–61

  14. Physiological and Molecular Characterization of Biosurfactant Producing Endophytic Fungi Xylaria regalis from the Cones of Thuja plicata as a Potent Plant Growth Promoter with Its Potential Application

    Directory of Open Access Journals (Sweden)

    Mohd Adnan

    2018-01-01

    Full Text Available Currently, there is an absolute concern for all nations in agricultural productivity to meet growing demands of human population. In recent time, biosurfactants produced by diverse group of microorganisms are used to achieve such demands as it is known for its ecofriendly use in elimination of plant pathogens and for increasing the bioavailability of nutrients for plants. Endophytic fungi are the important source of secondary metabolites and novel bioactive compounds for different biological applications. In the present study, endophytic fungi Xylaria regalis (X. regalis recovered from the cones of Thuja plicata was evaluated for its biosurfactant producing ability and plant growth-promoting abilities through various screening methods and also via its antagonistic activity against phytopathogens like Fusarium oxysporum and Aspergillus niger. In addition, X. regalis was also tested in vivo for a various range of growth parameters in chilli under greenhouse conditions. Significant increase in shoot and root length, dry matter production of shoot and root, chlorophyll, nitrogen, and phosphorus contents of chilli seedlings was found, which reveals its ability to improve the growth of crop plants. Hence, this study suggests the possibility of biosurfactant producing endophytic fungi X. regalis as a source of novel green biosurfactant for sustainable agriculture to achieve growing demands.

  15. INCREASED PRODUCTION OF NERVE GROWTH FACTOR, NEUROTROPHIN-3, AND NEUROTROPHIN-4 IN A PENICILLIUM CHRYSOGENUM -INDUCED ALLERGIC ASTHMA MODEL IN MICE

    Science.gov (United States)

    Increased levels of neurotrophins (nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], neurotrophin [NT]-3, and/or NT-4) have been associated with asthmatics and in animal models of allergic asthma. In our mouse model for fungal allergic asthma, repeated pulmona...

  16. DOSE-DEPENDENT INCREASE IN THE PRODUCTION OF NERVE GROWTH FACTOR, NEUROTROPHIN-3, AND NEUROTROPHIN-4 IN A PENICILLIUM CHRYSOGENUM-INDUCED ALLERGIC ASTHMA MODEL

    Science.gov (United States)

    Increased levels of neurotrophins (nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], neurotrophin [NT]-3, and/or NT-4) have been associated with asthma as well as in animal models of allergic asthma. In our mouse model for fungal allergic asthma, repeated ...

  17. Disruption of spinal cord white matter and sciatic nerve geometry inhibits axonal growth in vitro in the absence of glial scarring

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    Crutcher Keith A

    2001-05-01

    Full Text Available Abstract Background Axons within the mature mammalian central nervous system fail to regenerate following injury, usually resulting in long-lasting motor and sensory deficits. Studies involving transplantation of adult neurons into white matter implicate glial scar-associated factors in regeneration failure. However, these studies cannot distinguish between the effects of these factors and disruption of the spatial organization of cells and molecular factors (disrupted geometry. Since white matter can support or inhibit neurite growth depending on the geometry of the fiber tract, the present study sought to determine whether disrupted geometry is sufficient to inhibit neurite growth. Results Embryonic chick sympathetic neurons were cultured on unfixed longitudinal cryostat sections of mature rat spinal cord or sciatic nerve that had been crushed with forceps ex vivo then immediately frozen to prevent glial scarring. Neurite growth on uncrushed portions of spinal cord white matter or sciatic nerve was extensive and highly parallel with the longitudinal axis of the fiber tract but did not extend onto crushed portions. Moreover, neurite growth from neurons attached directly to crushed white matter or nerve tissue was shorter and less parallel compared with neurite growth on uncrushed tissue. In contrast, neurite growth appeared to be unaffected by crushed spinal cord gray matter. Conclusions These observations suggest that glial scar-associated factors are not necessary to block axonal growth at sites of injury. Disruption of fiber tract geometry, perhaps involving myelin-associated neurite-growth inhibitors, may be sufficient to pose a barrier to regenerating axons in spinal cord white matter and peripheral nerves.

  18. Identification of retrograde transport vesicles containing nerve growth factor in vivo

    International Nuclear Information System (INIS)

    Weible, M.W.; Sandow, S.L.; Ozsarac, N.; Hendry, I.A.; Grimes, M.L.

    2002-01-01

    Full text: Survival, differentiation, and development of responsive neurons are regulated by neurotrophins secreted from the target cells that they innervate. These responsive neurons must meet the challenge of transporting the neurotrophins chemical message from the target tissue to the soma; the distance of which may be a few millimetres to many meters. One hypothesis involves the formation of a signalling organelle at the neurite tip and subsequent retrograde axonal transport to the soma. This signalling vesicle is derived from the endocytosis of the neurotrophin-receptor complex. By modifying a method developed to isolate signalling endosomes from PC12 cells, we are able to isolate signalling vesicles from rat and mouse sciatic tissue. Approximately, 4 mole of I 125 -labelled neurotrophin was injected into the rodent foot pad and the sciatic nerve ligated under 88 μ/g ketamine and 16 μ/g rompun (i.p.) anaesthetic. All experiments had the approval of the ANU animal ethics committee. We achieved a recovery of 23% and 34% in the mouse and rat respectively of total transported iodinated neurotrophin accumulating on the distal side of the ligation. The homogenized tissue was characterized via differential centrifugation, blotted, and probed using antibodies to the neurotrophin receptors. Electron microscopy confirmed that the membrane pellet containing the transported neurotrophin from this in vivo preparation contained vesicular structures. Copyright (2002) Australian Neuroscience Society

  19. Nerve growth factor delivery by ultrasound-mediated nanobubble destruction as a treatment for acute spinal cord injury in rats

    Science.gov (United States)

    Song, Zhaojun; Wang, Zhigang; Shen, Jieliang; Xu, Shengxi; Hu, Zhenming

    2017-01-01

    Background Spinal cord injuries (SCIs) can cause severe disability or death. Treatment options include surgical intervention, drug therapy, and stem cell transplantation. However, the efficacy of these methods for functional recovery remains unsatisfactory. Purpose This study was conducted to explore the effect of ultrasound (US)-mediated destruction of poly(lactic-co-glycolic acid) (PLGA) nanobubbles (NBs) expressing nerve growth factor (NGF) (NGF/PLGA NBs) on nerve regeneration in rats following SCI. Materials and methods Adult male Sprague Dawley rats were randomly divided into four treatment groups after Allen hit models of SCI were established. The groups were normal saline (NS) group, NGF and NBs group, NGF and US group, and NGF/PLGA NBs and US group. Histological changes after SCI were observed by hematoxylin and eosin staining. Neuron viability was determined by Nissl staining. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining was used to examine cell apoptosis. NGF gene and protein expressions were detected by quantitative reverse transcription polymerase chain reaction and Western blotting. Green fluorescent protein expression in the spinal cord was examined using an inverted fluorescence microscope. The recovery of neural function was determined using the Basso, Beattie, and Bresnahan test. Results NGF therapy using US-mediated NGF/PLGA NBs destruction significantly increased NGF expression, attenuated histological injury, decreased neuron loss, inhibited neuronal apoptosis in injured spinal cords, and increased BBB scores in rats with SCI. Conclusion US-mediated NGF/PLGA NBs destruction effectively transfects the NGF gene into target tissues and has a significant effect on the injured spinal cord. The combination of US irradiation and gene therapy through NGF/PLGA NBs holds great promise for the future of nanomedicine and the development of noninvasive treatment options for SCI and other diseases. PMID:28280337

  20. Music exposure differentially alters the levels of brain-derived neurotrophic factor and nerve growth factor in the mouse hypothalamus.

    Science.gov (United States)

    Angelucci, Francesco; Ricci, Enzo; Padua, Luca; Sabino, Andrea; Tonali, Pietro Attilio

    2007-12-18

    It has been reported that music may have physiological effects on blood pressure, cardiac heartbeat, respiration, and improve mood state in people affected by anxiety, depression and other psychiatric disorders. However, the physiological bases of these phenomena are not clear. Hypothalamus is a brain region involved in the regulation of body homeostasis and in the pathophysiology of anxiety and depression through the modulation of hypothalamic-pituitary-adrenal (HPA) axis. Hypothalamic functions are also influenced by the presence of the neurotrophins brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), which are proteins involved in the growth, survival and function of neurons in the central nervous system. The aim of this study was to investigate the effect of music exposure in mice on hypothalamic levels of BDNF and NGF. We exposed young adult mice to slow rhythm music (6h per day; mild sound pressure levels, between 50 and 60 dB) for 21 consecutive days. At the end of the treatment mice were sacrificed and BDNF and NGF levels in the hypothalamus were measured by enzyme-linked immunosorbent assay (ELISA). We found that music exposure significantly enhanced BDNF levels in the hypothalamus. Furthermore, we observed that music-exposed mice had decreased NGF hypothalamic levels. Our results demonstrate that exposure to music in mice can influence neurotrophin production in the hypothalamus. Our findings also suggest that physiological effects of music might be in part mediated by modulation of neurotrophins.

  1. Intranasal Nerve Growth Factor administration improves cerebral functions in a child with severe traumatic brain injury: A case report.

    Science.gov (United States)

    Chiaretti, Antonio; Conti, Giorgio; Falsini, Benedetto; Buonsenso, Danilo; Crasti, Matteo; Manni, Luigi; Soligo, Marzia; Fantacci, Claudia; Genovese, Orazio; Calcagni, Maria Lucia; Di Giuda, Daniela; Mattoli, Maria Vittoria; Cocciolillo, Fabrizio; Ferrara, Pietro; Ruggiero, Antonio; Staccioli, Susanna; Colafati, Giovanna Stefania; Riccardi, Riccardo

    2017-01-01

    Nerve growth factor (NGF) promotes neural recovery after experimental traumatic brain injury (TBI) supporting neuronal growth, differentiation and survival of brain cells and up-regulating the neurogenesis-associated protein Doublecortin (DCX). Only a few studies reported NGF administration in paediatric patients with severe TBI. A four-year-old boy in a persistent unresponsive wakefulness syndrome (UWS) was treated with intranasal murine NGF administration 6 months after severe TBI. The patient received four cycles of intranasal NGF (0.1 mg/kg, twice a day for 10 consecutive days). NGF administration improved functional [Positron Emission Tomography/Computed Tomography (PET/CT); Single photon emission/Computed Tomography (SPECT/CT) and Magnetic Resonance Imaging (MRI)] assessment, electrophysiological [Electroencephalogram (EEG) and Visual Evoked Potential (VEP)] studies and clinical conditions. He showed improvements in voluntary movements, facial mimicry, phonation, attention and verbal comprehension, ability to cry, cough reflex, oral motility, feeding capacity, and bowel and urinary functions. After NGF administration, raised levels of both NGF and DCX were found in the cerebrospinal fluid of the patient. No side effects were reported. Although further studies are needed for better understanding the neuroprotective role of this neurotrophin, intranasal NGF administration appears to be a promising and safe rescuing strategy treatment in children with neurological impairment after TBI.

  2. Effects of nerve and fibroblast growth factors on the production of nitric oxide in experimental model of Huntington's disease

    Directory of Open Access Journals (Sweden)

    Maksimović Ivana D.

    2002-01-01

    Full Text Available The role of nitric oxide (NO in neurological diseases represents one of the most studied, yet controversial subjects in physiology. The aim was to examine the effects of intrastriatal injection neurotrophins (nerve growth factors-NGF, fibroblast growth factors-FGF in order to investigate the possible involvement of NO in quinolinic acid (QA induced striatum toxicity in the rat model of Huntington's disease (HD. QA was administered unilaterally into the striatum of adult Wistar rats in a single dose of 150 nM. The other two groups of animals were pretreated immediately before QA application with NGF and FGF, respectively. Control group was treated with 0.9% saline solution in the same manner. Animals were decapitated 7 days after the treatment. Nitrite levels were significantly decreased both in the ipsi- and contra lateral striatum and forebrain cortex of NGF- and FGF-treated animals compared with QA treatment. These results indicated a temporal and spatial propagation of oxidative stress and spread protective effects of NGF and FGF on the forebrain cortex, the distant structure, but tightly connected with striatum, the place of direct neurotoxin damage. Neurotrophins could be the potential neuroprotective agents in HD.

  3. Structural and Functional Substitution of Deleted Primary Sensory Neurons by New Growth from Intrinsic Spinal Cord Nerve Cells: An Alternative Concept in Reconstruction of Spinal Cord Circuits

    Directory of Open Access Journals (Sweden)

    Nicholas D. James

    2017-07-01

    Full Text Available In a recent clinical report, return of the tendon stretch reflex was demonstrated after spinal cord surgery in a case of total traumatic brachial plexus avulsion injury. Peripheral nerve grafts had been implanted into the spinal cord to reconnect to the peripheral nerves for motor and sensory function. The dorsal root ganglia (DRG containing the primary sensory nerve cells had been surgically removed in order for secondary or spinal cord sensory neurons to extend into the periphery and replace the deleted DRG neurons. The present experimental study uses a rat injury model first to corroborate the clinical finding of a re-established spinal reflex arch, and second, to elucidate some of the potential mechanisms underlying these findings by means of morphological, immunohistochemical, and electrophysiological assessments. Our findings indicate that, after spinal cord surgery, the central nervous system sensory system could replace the traumatically detached original peripheral sensory connections through new neurite growth from dendrites.

  4. Pinched Nerve

    Science.gov (United States)

    ... You are here Home » Disorders » All Disorders Pinched Nerve Information Page Pinched Nerve Information Page What research is being done? Within the NINDS research programs, pinched nerves are addressed primarily through studies associated with pain ...

  5. Nerve growth factor, brain-derived neurotrophic factor, and the chronobiology of mood: a new insight into the "neurotrophic hypothesis"

    Directory of Open Access Journals (Sweden)

    Tirassa P

    2015-10-01

    Full Text Available Paola Tirassa,1 Adele Quartini,2 Angela Iannitelli2–4 1National Research Council (CNR, Institute of Cell Biology and Neurobiology (IBCN, 2Department of Medical-Surgical Sciences and Biotechnologies, Faculty of Pharmacy and Medicine – "Sapienza" University of Rome, 3Italian Psychoanalytical Society (SPI, Rome, Italy; 4International Psychoanalytical Association (IPA, London, UKAbstract: The light information pathways and their relationship with the body rhythms have generated a new insight into the neurobiology and the neurobehavioral sciences, as well as into the clinical approaches to human diseases associated with disruption of circadian cycles. Light-based strategies and/or drugs acting on the circadian rhythms have widely been used in psychiatric patients characterized by mood-related disorders, but the timing and dosage use of the various treatments, although based on international guidelines, are mainly dependent on the psychiatric experiences. Further, many efforts have been made to identify biomarkers able to disclose the circadian-related aspect of diseases, and therefore serve as diagnostic, prognostic, and therapeutic tools in clinic to assess the different mood-related symptoms, including pain, fatigue, sleep disturbance, loss of interest or pleasure, appetite, psychomotor changes, and cognitive impairments. Among the endogenous factors suggested to be involved in mood regulation, the neurotrophins, nerve growth factor, and brain-derived neurotrophic factor show anatomical and functional link with the circadian system and mediate some of light-induced effects in brain. In addition, in humans, both nerve growth factor and brain-derived neurotrophic factor have showed a daily rhythm, which correlate with the morningness–eveningness dimensions, and are influenced by light, suggesting their potential role as biomarkers for chronotypes and/or chronotherapy. The evidences of the relationship between the diverse mood-related disorders

  6. Adeno-Associated Viral Vector (Serotype 2)-Nerve Growth Factor for Patients With Alzheimer Disease: A Randomized Clinical Trial.

    Science.gov (United States)

    Rafii, Michael S; Tuszynski, Mark H; Thomas, Ronald G; Barba, David; Brewer, James B; Rissman, Robert A; Siffert, Joao; Aisen, Paul S

    2018-03-26

    Nerve growth factor (NGF) is an endogenous neurotrophic factor that prevents the death and augments the functional state of cholinergic neurons of the basal forebrain, a cell population that undergoes extensive degeneration in Alzheimer disease (AD). To determine whether stereotactically guided intracerebral injections of adeno-associated viral vector (serotype 2)-nerve growth factor (AAV2-NGF) are well tolerated and exhibit preliminary evidence of impact on cognitive decline in mild to moderate AD-associated dementia. In a multicenter phase 2 trial, 49 participants with mild to moderate AD were randomly assigned in a 1:1 ratio to receive stereotactically guided intracerebral injections of AAV2-NGF or sham surgery. Participants were enrolled between November 2009 and December 2012. Analyses began in February 2015. The study was conducted at 10 US academic medical centers. Eligibility required a diagnosis of mild to moderate dementia due to AD and individuals aged 55 to 80 years. A total of 39 participants did not pass screening; the most common reason was Mini-Mental State Examination scores below cutoff. Analyses were intention-to-treat. Stereotactically guided intracerebral injections of AAV2-NGF into the nucleus basalis of Meynert of each hemisphere or sham surgery. Change from baseline on the Alzheimer Disease Assessment Scale-cognitive subscale at month 24. Among 49 participants, 21 (43%) were women, 42 (86%) self-identified as white, and the mean (SD) age was 68 (6.4) years. AAV2-NGF was safe and well-tolerated through 24 months. No significant difference was noted between the treatment group and placebo on the primary outcome measure, the Alzheimer Disease Assessment Scale-cognitive subscale (mean [SD] score, 14.52 [4.66] vs 9.11 [4.65], P = .17). This multicenter randomized clinical trial demonstrated the feasibility of sham-surgery-controlled stereotactic gene delivery studies in patients with AD. AAV2-NGF delivery was well-tolerated but did not

  7. Control of Growth Within Drosophila Peripheral Nerves by Ras and Protein Kinase A

    Science.gov (United States)

    2009-02-01

    Genes Dev 17:2006 –2020. Rodriguez-Viciana P, Warne PH, Dhand R, Vanhaesebroeck B, Gout I, Fry MJ, Waterfield MD, Downward J (1994...we hope that these methodologies will enable us ultimately to identify all of the relevant genes that interact with NF1 to control growth, and place...NF1 and these partner genes in as complete a mechanistic context as possible. Then this mechanism could be tested and refined in systems more

  8. Nerve growth factor enhances the CRE-dependent transcriptional activity activated by nobiletin in PC12 cells.

    Science.gov (United States)

    Takito, Jiro; Kimura, Junko; Kajima, Koji; Uozumi, Nobuyuki; Watanabe, Makoto; Yokosuka, Akihito; Mimaki, Yoshihiro; Nakamura, Masanori; Ohizumi, Yasushi

    2016-07-01

    Prevention and treatment of Alzheimer disease are urgent problems for elderly people in developed countries. We previously reported that nobiletin, a poly-methoxylated flavone from the citrus peel, improved the symptoms in various types of animal models of memory loss and activated the cAMP responsive element (CRE)-dependent transcription in PC12 cells. Nobiletin activated the cAMP/PKA/MEK/Erk/MAPK signaling pathway without using the TrkA signaling activated by nerve growth factor (NGF). Here, we examined the effect of combination of nobiletin and NGF on the CRE-dependent transcription in PC12 cells. Although NGF alone had little effect on the CRE-dependent transcription, NGF markedly enhanced the CRE-dependent transcription induced by nobiletin. The NGF-induced enhancement was neutralized by a TrkA antagonist, K252a. This effect of NGF was effective on the early signaling event elicited by nobiletin. These results suggested that there was crosstalk between NGF and nobiletin signaling in activating the CRE-dependent transcription in PC12 cells.

  9. Nerve growth factor affects 11C-nicotine binding, blood flow, EEG, and verbal episodic memory in an Alzheimer patient

    International Nuclear Information System (INIS)

    Olson, L.; Nordberg, A.; Holst, H. von

    1992-01-01

    Based on animal research suggesting that nerve growth factor (NGF) can stimulate central cholinergic neurons, the known losses of cholinergic innervation of the cortices in Alzheimer's disease (AD), and our experience of infusing NGF to support adrenal grafts in parkinsonian patients, we have initiated clinical trials of NGF infusions into the brain of patients with AD. Here we report a follow-up of our first case, a 69-year-old woman, with symptoms of dementia since 8 years. Intraventricular infusion of 6.6 mg NGF during three months resulted in a marked transient increase in uptake and binding of 11 C-nicotine in frontal and temporal cortex and a persistent increase in cortical blood flow as measured by PET as well as progressive decreases of slow wave EEG activity. After one month of NGF, tests of verbal episodic memory were improved whereas other cognitive tests were not. No adverse effects could be ascribed to the NGF infusion. Taken together, the results of this case study indicate that NGF may counteract cholinergic deficits in AD, and suggest that further clinical trials of NGF infusion in AD are warranted. (authors)

  10. Strip biosensor for amplified detection of nerve growth factor-beta based on a molecular translator and catalytic DNA circuit.

    Science.gov (United States)

    Liu, Jun; Lai, Ting; Mu, Kejie; Zhou, Zheng

    2014-10-07

    We have demonstrated a new visual detection approach based on a molecular translator and a catalytic DNA circuit for the detection of nerve growth factor-beta (NGF-β). In this assay, a molecular translator based on the binding-induced DNA strand-displacement reaction was employed to convert the input protein to an output DNA signal. The molecular translator is composed of a target recognition element and a signal output element. Target recognition is achieved by the binding of the anti-NGF-β antibody to the target protein. Polyclonal anti-NGF-β antibody is conjugated to DNA1 and DNA2. The antibody conjugated DNA1 is initially hybridized to DNA3 to form a stable DNA1/DNA3 duplex. In the presence of NGF-β, the binding of the same target protein brings DNA1 and DNA2 into close proximity, resulting in an increase in their local effective concentration. This process triggers the strand-displacement reaction between DNA2 and DNA3 and releases the output DNA3. The released DNA3 is further amplified by a catalytic DNA circuit. The product of the catalytic DNA circuit is detected by a strip biosensor. This proposed assay has high sensitivity and selectivity with a dynamic response ranging from 10 fM to 10 pM, and its detection limit is 10 fM of NGF-β. This work provides a sensitive, enzyme-free, and universal strategy for the detection of other proteins.

  11. Vascular and neuronal protection induced by the ocular administration of nerve growth factor in diabetic-induced rat encephalopathy.

    Science.gov (United States)

    Tirassa, Paola; Maccarone, Mattia; Florenzano, Fulvio; Cartolano, Sara; De Nicolò, Sara

    2013-05-01

    Based on our previous findings on the efficacy of ocular applied nerve growth factor as eye drops (oNGF) to act in brain and counteract neuronal damage, we hypothesized that oNGF treatment might revert neuronal atrophy occurring in diabetic brain also by controlling neurotrophin system changes. The major NGF brain target areas, such as the septum and the hippocampus, were used as an experimental paradigma to test this hypothesis. Bilateral oNGF treatment was performed twice a day for 2 weeks in full-blown streptozotocin-treated adult male rats. The forebrain distribution of cholinergic and endothelial cell markers and NGF receptors were studied by confocal microscopy. The septo-hippocampal content of NGF mature and precursor form and NGF receptors expression were also analyzed by Elisa and Western blot. oNGF treatment recovers the morphological alterations and the neuronal atrophy in septum and normalized the expression of mature and pro-NGF, as well as NGF receptors in the septum and hippocampus of diabetic rats. In addition, oNGF stimulated brain vascularization and up-regulated the TRKA receptor in vessel endothelium. Our findings confirm that reduced availability of mature NGF and NGF signaling impairment favors vascular and neuronal alterations in diabetic septo-hippocampal areas and corroborate the ability of oNGF to act as a neuroprotective agent in brain. © 2013 Blackwell Publishing Ltd.

  12. Influence of estrogen replacement and aging on the expression of nerve growth factor in the urethra of female rats.

    Science.gov (United States)

    Zucchi, Eliana V M; Jármy-Di Bella, Zsuzsanna I K; Castro, Rodrigo A; Takano, Claudia C; Simões, Manuel J; Girão, Manoel J B C; Sartori, Marair G F

    2012-06-01

    To evaluate the expression of nerve growth factor (NGF) in the urethra of adult female rats in different hormonal status using immunohistochemical assay. Forty-eight rats (Rattus norvegicus albinus, Rodentia, Mammalia) from the CEDEME-UNIFESP laboratory animal facility were used in the study. Rats were divided into four groups: group A, 12 non-neutered rats; group B, 12 oophorectomized rats; group C, 12 castrated rats treated with 17β-estradiol for 30 days; and group D, 12 aging rats. Animals were killed by lethal injection and their urethra was removed. NGF expression was evaluated by means of immunohistochemistry using mouse monoclonal primary IgG antibody anti-NGF diluted 1:600, and read under 400× magnification. Digital analysis of the images was done by Imagelab software. The intensity of the dark brown color was used as a measure of NGF cytoplasmatic expression, and was used to quantify the percentage of epithelial and muscular layer cells showing this neurotrophin. After oophorectomy, rats showed a significant increase in NGF expression in the periurethral muscular layer. Compared with oophorectomized rats, NGF expression increased in the epithelial layer and diminished in the periurethral smooth muscle following estrogen administration. In 18-month-old rats, NGF expression was diminished in both epithelial and muscular layers. Hormonal status led to significant differences in NGF protein expression in urethral epithelium and periurethral smooth muscle. Copyright © 2012 Wiley Periodicals, Inc.

  13. Nerve growth factor and diarrhea-predominant irritable bowel syndrome (IBS-D): a potential therapeutic target?

    Science.gov (United States)

    Xu, Xiao-juan; Liu, Liang; Yao, Shu-kun

    2016-01-01

    Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder characterized by recurrent abdominal pain or discomfort associated with abnormal bowel habits. Diarrhea-predominant IBS (IBS-D) is a major subtype of IBS, the predominant manifestations of which are abdominal pain and diarrhea. The pathogenesis of IBS-D remained unknown until recently. The effects of psychosocial stress, central hypervigilance, neuroendocrine abnormality, disturbed gastrointestinal motility, mucosal immune activation, intestinal barrier dysfunction, visceral hypersensitivity (VH), altered gut flora, and genetic susceptibility may be involved in its development. Recently, increased attention has been placed on the neural-immune-endocrine network mechanism in IBS-D, especially the role of various neuroendocrine mediators. As a member of the neurotrophin family, nerve growth factor (NGF) has diverse biological effects, and participates in the pathogenesis of many diseases. Basic studies have demonstrated that NGF is associated with inflammatory- and stress-related VH, as well as stress-related intestinal barrier dysfunction. The aim of this study is to summarize recent literature and discuss the role of NGF in the pathophysiology of IBS-D, especially in VH and intestinal barrier dysfunction, as well as its potential as a therapeutic target in IBS-D.

  14. Hepatocyte growth factor promotes long-term survival and axonal regeneration of retinal ganglion cells after optic nerve injury: comparison with CNTF and BDNF.

    Science.gov (United States)

    Wong, Wai-Kai; Cheung, Anny Wan-Suen; Yu, Sau-Wai; Sha, Ou; Cho, Eric Yu Pang

    2014-10-01

    Different trophic factors are known to promote retinal ganglion cell survival and regeneration, but each had their own limitations. We report that hepatocyte growth factor (HGF) confers distinct advantages in supporting ganglion cell survival and axonal regeneration, when compared to two well-established trophic factors ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF). Ganglion cells in adult hamster were injured by cutting the optic nerve. HGF, CNTF, or BDNF was injected at different dosages intravitreally after injury. Ganglion cell survival was quantified at 7, 14, or 28 days postinjury. Peripheral nerve (PN) grafting to the cut optic nerve of the growth factor-injected eye was performed either immediately after injury or delayed until 7 days post-injury. Expression of heat-shock protein 27 and changes in microglia numbers were quantified in different growth factor groups. The cellular distribution of c-Met in the retina was examined by anti-c-Met immunostaining. Hepatocyte Growth Factor (HGF) was equally potent as BDNF in promoting short-term survival (up to 14 days post-injury) and also supported survival at 28 days post-injury when ganglion cells treated by CNTF or BDNF failed to be sustained. When grafting was performed without delay, HGF stimulated twice the number of axons to regenerate compared with control but was less potent than CNTF. However, in PN grafting delayed for 7 days after optic nerve injury, HGF maintained a better propensity of ganglion cells to regenerate than CNTF. Unlike CNTF, HGF application did not increase HSP27 expression in ganglion cells. Microglia proliferation was prolonged in HGF-treated retinas compared with CNTF or BDNF. C-Met was localized to both ganglion cells and Muller cells, suggesting HGF could be neuroprotective via interacting with both neurons and glia. Compared with CNTF or BDNF, HGF is advantageous in sustaining long-term ganglion cell survival and their propensity to respond to

  15. Influence of minimally invasive hematoma evacuation combined with nerve growth factor preparation on neurological function injury in patients with hypertensive cerebral hemorrhage

    OpenAIRE

    Jiang Tao; Feng Ai-Ping; Liu Lun-Bo; Huang Qi-Jun; Du Chen

    2017-01-01

    Objective: To study the influence of minimally invasive hematoma evacuation combined with nerve growth factor preparation on neurological function injury in patients with hypertensive cerebral hemorrhage. Methods: A total of 112 patients with hypertensive cerebral hemorrhage who were treated in our hospital between July 2013 and February 2016 were collected, and according to random number table, they were divided into the control group (n=56) who underwent minimally invasive he...

  16. CSK negatively regulates nerve growth factor induced neural differentiation and augments AKT kinase activity

    International Nuclear Information System (INIS)

    Dey, Nandini; Howell, Brian W.; De, Pradip K.; Durden, Donald L.

    2005-01-01

    Src family kinases are involved in transducing growth factor signals for cellular differentiation and proliferation in a variety of cell types. The activity of all Src family kinases (SFKs) is controlled by phosphorylation at their C-terminal 527-tyrosine residue by C-terminal SRC kinase, CSK. There is a paucity of information regarding the role of CSK and/or specific Src family kinases in neuronal differentiation. Pretreatment of PC12 cells with the Src family kinase inhibitor, PP1, blocked NGF-induced activation of SFKs and obliterated neurite outgrowth. To confirm a role for CSK and specific isoforms of SFKs in neuronal differentiation, we overexpressed active and catalytically dead CSK in the rat pheochromocytoma cell line, PC12. CSK overexpression caused a profound inhibition of NGF-induced activation of FYN, YES, RAS, and ERK and inhibited neurite outgrowth, NGF-stimulated integrin-directed migration and blocked the NGF-induced conversion of GDP-RAC to its GTP-bound active state. CSK overexpression markedly augmented the activation state of AKT following NGF stimulation. In contrast, kinase-dead CSK augmented the activation of FYN, RAS, and ERK and increased neurite outgrowth. These data suggest a distinct requirement for CSK in the regulation of NGF/TrkA activation of RAS, RAC, ERK, and AKT via the differential control of SFKs in the orchestration of neuronal differentiation

  17. Differential effects of the steaming time and frequency for manufactured red Liriope platyphylla on nerve growth factor secretion ability, nerve growth factor receptor signaling pathway and regulation of calcium concentration.

    Science.gov (United States)

    Choi, Sun Il; Goo, Jun Seo; Kim, Ji Eun; Nam, So Hee; Hwang, In Sik; Lee, Hye Ryun; Lee, Young Ju; Son, Hong Joo; Lee, Hee Seob; Lee, Jong Sup; Kim, Hak Jin; Hwang, Dae Youn

    2012-11-01

    The herb Liriope platyphylla (LP) has been considered to have curative properties for diabetes, asthma and neurodegenerative disorders. To examine the effects of steaming time and frequency of manufactured red LP (RLP) on the nerve growth factor (NGF) secretion ability and NGF receptor signaling pathway, the NGF concentration, cell differentiation, NGF signaling pathway and calcium concentration were analyzed in neuronal cells treated with several types of LPs manufactured under different conditions. The maximum NGF secretion was observed in B35 cells treated with 50 µg/ml LP extract steamed for 9 h (9-SLP) and with two repeated steps (3 h steaming and 24 h air-dried) carried out 7 times (7-SALP). No significant changes in viability were detected in any of the cells treated with the various LPs, with the exception of 0-SLP and 0-SALP. In addition, PC12 cell differentiation was induced by treatment with the NGF-containing conditional medium (CM) collected from the RLP-treated cells. The levels of TrkA and extracellular signal-regulated kinase (ERK) phosphorylation in the high affinity NGF receptor signaling pathway were significantly higher in the cells treated with 3-SLP or 1-SALP/3-SALP CM compared with those treated with the vehicle CM. In the low affinity NGF receptor pathway, the expression levels of most components were higher in the 9-, 15- and 24-SALP CM-treated cells compared with the vehicle CM-treated cells. However, this level was significantly altered in cells treated with 3-SALP CM. Furthermore, an examination of the RLP function on calcium regulation revealed that only the LP- or RLP-treated cells exhibited changes in intracellular and extracellular calcium levels. RLP induced a significant decrease in the intracellular calcium levels and an increase in the extracellular calcium levels. These results suggest the possibility that steaming-processed LP may aid in the relief of neurodegenerative diseases through the NGF secretion ability and NGF

  18. Swimming: Effects on Stress Urinary Incontinence and the Expression of Nerve Growth Factor in Rats Following Transabdominal Urethrolysis

    Directory of Open Access Journals (Sweden)

    Il Gyu Ko

    2011-06-01

    Full Text Available PurposeStress urinary incontinence (SUI commonly occurs in women, and it has an enormous impact on quality of life. Surgery, drugs, and exercise have been recommended for the treatment of this disease. Among these, exercise is known to be effective for the relief of symptoms of SUI; however, the efficacy and underlying mechanisms of the effect of exercise on SUI are poorly understood. We investigated the effect of swimming the symptom of SUI in relation to the expression of nerve growth factor (NGF in rats.MethodsTransabdominal urethrolysis was used to induce SUI, in Sprague-Dawley rats. The experimental groups were divided into the following three groups: sham-operation group, transabdominal urethrolysis-induced group, and transabdominal urethrolysis-induced and swimming group. The rats in the swimming group were forced to swim for 30 minutes once daily starting 2 weeks after SUI induction and continuing for 4 weeks. For this study, determination of abdominal leak point pressure and immunohistochemistry for NGF in the urethra and in the neuronal voiding centers (medial preoptic nucleus [MPA], ventrolateral periaqueductal gray [vlPAG], pontine micturition center [PMC], and spinal cord [L4-L5] were performed.ResultsTransabdominal urethrolysis significantly reduced the abdominal leak point pressure, thereby contributing to the induction of SUI. Abdominal leak point pressure, however, was significantly improved by swimming. The expression of NGF in the urethra and in the neuronal voiding centers (MPA, vlPAG, PMC, and L4-L5 relating to micturition was enhanced by the induction of SUI. Swimming, however, significantly suppressed SUI-induced NGF expression.ConclusionsSwimming alleviated symptoms of transabdominal urethrolysis-induced SUI, as assessed by an increase in abdominal leak point pressure. The underlying mechanisms of these effects of swimming might be ascribed to the inhibitory effect of swimming on NGF expression.

  19. QTL replication and targeted association highlight the nerve growth factor gene for nonverbal communication deficits in autism spectrum disorders.

    Science.gov (United States)

    Lu, A T-H; Yoon, J; Geschwind, D H; Cantor, R M

    2013-02-01

    Autism Spectrum Disorder (ASD) has a heterogeneous etiology that is genetically complex. It is defined by deficits in communication and social skills and the presence of restricted and repetitive behaviors. Genetic analyses of heritable quantitative traits that correlate with ASD may reduce heterogeneity. With this in mind, deficits in nonverbal communication (NVC) were quantified based on items from the Autism Diagnostic Interview Revised. Our previous analysis of 228 families from the Autism Genetics Research Exchange (AGRE) repository reported 5 potential quantitative trait loci (QTL). Here we report an NVC QTL replication study in an independent sample of 213 AGRE families. One QTL was replicated (Panalysis of 476 haplotype blocks with 708 AGRE families using the Family Based Association Test (FBAT). Blocks in two QTL genes were associated with NVC with a P-value of 0.001. Three associated haplotype blocks were intronic to the Nerve Growth Factor (NGF) gene (P=0.001, 0.001, 0.002), and one was intronic to KCND3 (P=0.001). Individual haplotypes within the associated blocks drove the associations (0.003, 0.0004 and 0.0002) for NGF and 0.0001 for KCND3. Using the same methods, these genes were tested for association with NVC in an independent sample of 1517 families from an Autism Genome Project (AGP). NVC was associated with a haplotype in an adjacent NGF block (P=0.0005) and one 46 kb away from the associated block in KCND3 (0.008). These analyses illustrate the value of QTL and targeted association studies for genetically complex disorders such as ASD. NGF is a promising risk gene for NVC deficits.

  20. Quotient normed cones

    Indian Academy of Sciences (India)

    general setting of the space CL(X, Y ) of all continuous linear mappings from a normed cone (X, p) to a normed cone (Y, q), extending several well-known results related to open continuous linear mappings between normed linear spaces. Keywords. Normed cone; extended quasi-metric; continuous linear mapping; bicom-.

  1. Comparison of the Regenerative Effects of Platelet-Rich Fibrin and Plasma Rich in Growth Factors on Injured Peripheral Nerve: An Experimental Study.

    Science.gov (United States)

    Torul, Damla; Bereket, Mehmet Cihan; Onger, Mehmet Emin; Altun, Gamze

    2018-04-20

    The aim of this study was to investigate the effects of platelet-rich fibrin (PRF) and plasma rich in growth factors (PRGF) on peripheral nerve injury in the early period of healing. Thirty Wistar albino rats were used in this study. Rats were divided into control (C), damaged (D), PRF, and PRGF groups. The left sciatic nerves of each group were identified as group C. Crush-type injury was performed on the right sciatic nerves of the D, PRF, and PRGF groups. In the PRF and PRGF groups, blood 2 mL was obtained to prepare the PRF and PRGF and the biomaterials were applied to the injured nerve area. After 8 weeks, functional, electrophysiologic, and stereological evaluations were performed. For the electrophysiologic evaluation, the latency and amplitude values in the D, PRF, and PRGF groups were significantly lower than those in the C group (P > .05). According to the sciatic functional index result, there were significant differences between groups D and PRF and between groups D and PRGF (P = .000). For the stereological evaluations, although no significant difference was observed between the PRGF and C groups (P > .05), a significant difference was observed among the D, PRF, and PRGF groups for myelinated axon number. There were significant differences between groups D and PRF and between groups D and PRGF for axon area (P = .021 and .001, respectively). No significant difference was observed among the D, PRF, and PRGF groups for myelin sheath thickness and ratio of axon area to myelin sheath thickness (P > .05). The results of this study suggest that PRGF increases nerve regeneration in the early period of healing and that the limited early action of PRF should be re-evaluated in the late period. Copyright © 2018 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  2. Cerebrolysin modulates pronerve growth factor/nerve growth factor ratio and ameliorates the cholinergic deficit in a transgenic model of Alzheimer's disease.

    Science.gov (United States)

    Ubhi, Kiren; Rockenstein, Edward; Vazquez-Roque, Ruben; Mante, Michael; Inglis, Chandra; Patrick, Christina; Adame, Anthony; Fahnestock, Margaret; Doppler, Edith; Novak, Philip; Moessler, Herbert; Masliah, Eliezer

    2013-02-01

    Alzheimer's disease (AD) is characterized by degeneration of neocortex, limbic system, and basal forebrain, accompanied by accumulation of amyloid-β and tangle formation. Cerebrolysin (CBL), a peptide mixture with neurotrophic-like effects, is reported to improve cognition and activities of daily living in patients with AD. Likewise, CBL reduces synaptic and behavioral deficits in transgenic (tg) mice overexpressing the human amyloid precursor protein (hAPP). The neuroprotective effects of CBL may involve multiple mechanisms, including signaling regulation, control of APP metabolism, and expression of neurotrophic factors. We investigate the effects of CBL in the hAPP tg model of AD on levels of neurotrophic factors, including pro-nerve growth factor (NGF), NGF, brain-derived neurotrophic factor (BDNF), neurotropin (NT)-3, NT4, and ciliary neurotrophic factor (CNTF). Immunoblot analysis demonstrated that levels of pro-NGF were increased in saline-treated hAPP tg mice. In contrast, CBL-treated hAPP tg mice showed levels of pro-NGF comparable to control and increased levels of mature NGF. Consistently with these results, immunohistochemical analysis demonstrated increased NGF immunoreactivity in the hippocampus of CBL-treated hAPP tg mice. Protein levels of other neurotrophic factors, including BDNF, NT3, NT4, and CNTF, were unchanged. mRNA levels of NGF and other neurotrophins were also unchanged. Analysis of neurotrophin receptors showed preservation of the levels of TrKA and p75(NTR) immunoreactivity per cell in the nucleus basalis. Cholinergic cells in the nucleus basalis were reduced in the saline-treated hAPP tg mice, and treatment with CBL reduced these cholinergic deficits. These results suggest that the neurotrophic effects of CBL might involve modulation of the pro-NGF/NGF balance and a concomitant protection of cholinergic neurons. Copyright © 2012 Wiley Periodicals, Inc.

  3. The beneficial effect of genetically engineered Schwann cells with enhanced motility in peripheral nerve regeneration: review.

    Science.gov (United States)

    Gravvanis, A I; Lavdas, A A; Papalois, A; Tsoutsos, D A; Matsas, R

    2007-01-01

    The importance of Schwann cells in promoting nerve regeneration across a conduit has been extensively reported in the literature, and Schwann cell motility has been acknowledged as a prerequisite for myelination of the peripheral nervous system during regeneration after injury. Review of recent literature and retrospective analysis of our studies with genetically modified Schwann Cells with increased motility in order to identify the underlying mechanism of action and outline the future trends in peripheral nerve repair. Schwann cell transduction with the pREV-retrovirus, for expression of Sialyl-Transferase-X, resulting in conferring Polysialyl-residues (PSA) on NCAM, increases their motility in-vitro and ensures nerve regeneration through silicone tubes after end-to-side neurorraphy in the rat sciatic nerve model, thus significantly promoting fiber maturation and functional outcome. An artificial nerve graft consisting of a type I collagen tube lined with the genetically modified Schwann cells with increased motility, used to bridge a defect in end-to-end fashion in the rat sciatic nerve model, was shown to promote nerve regeneration to a level equal to that of a nerve autograft. The use of genetically engineered Schwann cells with enhanced motility for grafting endoneural tubes promotes axonal regeneration, by virtue of the interaction of the transplanted cells with regenerating axonal growth cones as well as via the recruitment of endogenous Schwann cells. It is envisaged that mixed populations of Schwann cells, expressing PSA and one or more trophic factors, might further enhance the regenerating and remyelinating potential of the lesioned nerves.

  4. Pharmacokinetics and biodistribution of a radioiodine labeled peptidomimetic ligand for high-affinity nerve growth factor receptors

    Energy Technology Data Exchange (ETDEWEB)

    Jung, K. H.; Kim, D. H.; Paik, J. Y.; Koh, B. H.; Bae, J. S.; Choe, Y. S.; Lee, K. H.; Kim, B. T. [Samsung Medical Center, Seoul (Korea, Republic of)

    2005-07-01

    Some of the obstacles for the clinical application of whole nerve growth factor (NGF) may be overcome by utilizing small molecule mimetics. We thus investigated the in vivo pharmacokinetics and biodistribution of a small cyclic peptide derived from NGF-[C(92-96)] with high receptor binding affinity. I-125 C(92-96) was labeled with the Bolton-Hunter method, and binding to TrkA/IgG chimeric protein was confirmed on a polyacrylamide gel after cross-linking. Pharmacokinetic analysis was performed in normal ICR mice intravenously injected with 0.5 MBq I-125 C(92-96) containing varying doses of C(92-96). Biodistribution studies were done at 6 h after injection. Cross-linkage analysis confirmed binding of I-125 C(92-96) to the high affinity NGF receptor, TrkA. Intravenously injected I-125 C(92-96) was cleared from the blood in a biexponential manner with an early T1/2{alpha} of 5.2 min and late T1/2{beta} of 121.3 min. Log blood-concentration decreased over time with a k-slope of 0.0025, clearance of 11.8{+-}0.5 ml/min, T1/2 of 4.1{+-}0.4 hr, and volume of distribution of 69.7{+-}4.6 ml. The pattern of elimination from the blood remained essentially unchanged regardless of the dose of added C(92-96), with dose-proportionate increases in AUCs and peak concentrations consistent with linear pharmacokinetics. Biodistribution studies demonstrated high kidney activity suggesting renal excretion of I-125 C(92-96). There were moderate levels of accumulation in the spleen, lungs and liver, followed by the myocardium and skeletal muscle, whereas brain uptake was low (< 0.2 %ID/gm). Intravenously administered C(92-96) follows linear pharmacokinetics, and is cleared from the circulation at a rate comparable to whole NGF despite its substantially smaller size. Although intravenous C(92-96) does not adequately reach brain tissue, clinically relevant doses can achieve major organ accumulation levels that may be sufficient to elicit biologic responses through NGF receptors.

  5. Pharmacokinetics and biodistribution of a radioiodine labeled peptidomimetic ligand for high-affinity nerve growth factor receptors

    International Nuclear Information System (INIS)

    Jung, K. H.; Kim, D. H.; Paik, J. Y.; Koh, B. H.; Bae, J. S.; Choe, Y. S.; Lee, K. H.; Kim, B. T.

    2005-01-01

    Some of the obstacles for the clinical application of whole nerve growth factor (NGF) may be overcome by utilizing small molecule mimetics. We thus investigated the in vivo pharmacokinetics and biodistribution of a small cyclic peptide derived from NGF-[C(92-96)] with high receptor binding affinity. I-125 C(92-96) was labeled with the Bolton-Hunter method, and binding to TrkA/IgG chimeric protein was confirmed on a polyacrylamide gel after cross-linking. Pharmacokinetic analysis was performed in normal ICR mice intravenously injected with 0.5 MBq I-125 C(92-96) containing varying doses of C(92-96). Biodistribution studies were done at 6 h after injection. Cross-linkage analysis confirmed binding of I-125 C(92-96) to the high affinity NGF receptor, TrkA. Intravenously injected I-125 C(92-96) was cleared from the blood in a biexponential manner with an early T1/2α of 5.2 min and late T1/2β of 121.3 min. Log blood-concentration decreased over time with a k-slope of 0.0025, clearance of 11.8±0.5 ml/min, T1/2 of 4.1±0.4 hr, and volume of distribution of 69.7±4.6 ml. The pattern of elimination from the blood remained essentially unchanged regardless of the dose of added C(92-96), with dose-proportionate increases in AUCs and peak concentrations consistent with linear pharmacokinetics. Biodistribution studies demonstrated high kidney activity suggesting renal excretion of I-125 C(92-96). There were moderate levels of accumulation in the spleen, lungs and liver, followed by the myocardium and skeletal muscle, whereas brain uptake was low (< 0.2 %ID/gm). Intravenously administered C(92-96) follows linear pharmacokinetics, and is cleared from the circulation at a rate comparable to whole NGF despite its substantially smaller size. Although intravenous C(92-96) does not adequately reach brain tissue, clinically relevant doses can achieve major organ accumulation levels that may be sufficient to elicit biologic responses through NGF receptors

  6. Activation of transglutaminase 2 by nerve growth factor in differentiating neuroblastoma cells: A role in cell survival and neurite outgrowth.

    Science.gov (United States)

    Algarni, Alanood S; Hargreaves, Alan J; Dickenson, John M

    2018-02-05

    NGF (nerve growth factor) and tissue transglutaminase (TG2) play important roles in neurite outgrowth and modulation of neuronal cell survival. In this study, we investigated the regulation of TG2 transamidase activity by NGF in retinoic acid-induced differentiating mouse N2a and human SH-SY5Y neuroblastoma cells. TG2 transamidase activity was determined using an amine incorporation and a peptide cross linking assay. In situ TG2 activity was assessed by visualising the incorporation of biotin-X-cadaverine using confocal microscopy. The role of TG2 in NGF-induced cytoprotection and neurite outgrowth was investigated by monitoring hypoxia-induced cell death and appearance of axonal-like processes, respectively. The amine incorporation and protein crosslinking activity of TG2 increased in a time and concentration-dependent manner following stimulation with NGF in N2a and SH-SY5Y cells. NGF mediated increases in TG2 activity were abolished by the TG2 inhibitors Z-DON (Z-ZON-Val-Pro-Leu-OMe; Benzyloxycarbonyl-(6-Diazo-5-oxonorleucinyl)-l-valinyl-l-prolinyl-l-leucinmethylester) and R283 (1,3,dimethyl-2[2-oxo-propyl]thio)imidazole chloride) and by pharmacological inhibition of extracellular signal-regulated kinases 1 and 2 (ERK1/2), protein kinase B (PKB) and protein kinase C (PKC), and removal of extracellular Ca 2+ . Fluorescence microscopy demonstrated NGF induced in situ TG2 activity. TG2 inhibition blocked NGF-induced attenuation of hypoxia-induced cell death and neurite outgrowth in both cell lines. Together, these results demonstrate that NGF stimulates TG2 transamidase activity via a ERK1/2, PKB and PKC-dependent pathway in differentiating mouse N2a and human SH-SY5Y neuroblastoma cells. Furthermore, NGF-induced cytoprotection and neurite outgrowth are dependent upon TG2. These results suggest a novel and important role of TG2 in the cellular functions of NGF. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Thyroid hormone modulates the development of cholinergic terminal fields in the rat forebrain: relation to nerve growth factor receptor.

    Science.gov (United States)

    Oh, J D; Butcher, L L; Woolf, N J

    1991-04-24

    Hyperthyroidism, induced in rat pups by the daily intraperitoneal administration of 1 microgram/g body weight triiodothyronine, facilitated the development of ChAT fiber plexuses in brain regions innervated by basal forebrain cholinergic neurons, leading to an earlier and increased expression of cholinergic markers in those fibers in the cortex, hippocampus and amygdala. A similar enhancement was seen in the caudate-putamen complex. This histochemical profile was correlated with an accelerated appearance of ChAT-positive telencephalic puncta, as well as with a larger total number of cholinergic terminals expressed, which persisted throughout the eight postnatal week, the longest time examined in the present study. Hypothyroidism was produced in rat pups by adding 0.5% propylthiouracil to the dams' diet beginning the day after birth. This dietary manipulation resulted in the diminished expression of ChAT in forebrain fibers and terminals. Hypothyroid treatment also reduced the quantity of ChAT puncta present during postnatal weeks 2 and 3, and, from week 4 and continuing through week 6, the number of ChAT-positive terminals in the telencephalic regions examined was actually less than the amount extant during the former developmental epoch. Immunostaining for nerve growth factor receptor (NGF-R), which is associated almost exclusively with ChAT-positive somata and fibers in the basal forebrain, demonstrated a different time course of postnatal development. Forebrain fibers and terminals demonstrating NGF-R were maximally visualized 1 week postnatally, a time at which these same neuronal elements evinced minimal ChAT-like immunopositivity. Thereafter and correlated with increased immunoreactivity for ChAT, fine details of NGF-R stained fibers were observed less frequently. Although propylthiouracil administration decreased NGF-R immunodensity, no alteration in the development of that receptor was observed as a function of triiodothyronine treatment. Cholinergic

  8. Nerve growth factor-inducible large external (NILE) glycoprotein: studies of a central and peripheral neuronal marker.

    Science.gov (United States)

    Salton, S R; Richter-Landsberg, C; Greene, L A; Shelanski, M L

    1983-03-01

    The PC12 clone of pheochromocytoma cells undergoes neuronal differentiation in the presence of nerve growth factor (NGF). Concomitant with this is a significant induction in the incorporation of radiolabeled fucose or glucosamine into a 230,000-dalton cell surface glycoprotein named the NGF-Inducible Large External, or NILE, glycoprotein (GP) (McGuire, J. C., L. A. Greene, and A. V. Furano (1978) Cell 15: 357-365). In the current studies NILE GP was purified from PC12 cells using wheat germ agglutinin-agarose affinity chromatography and SDS-polyacrylamide gel electrophoresis (PAGE). Polyclonal antisera were raised against purified NILE GP and were found to selectively immunoprecipitate a single 230,000-dalton protein from detergent extracts of PC12 cells metabolically labeled with either [3H]fucose, [3H]glucosamine, or [35S]methionine. These antisera stained the surfaces of PC12 cells by indirect immunofluorescence and were cytotoxic to PC12 cells in the presence of complement. Limited treatment of PC12 cells with either trypsin or pronase produced a fucosylated 90,000-dalton immunoreactive fragment of NILE GP which remained in the membrane. Using quantitative immunoelectrophoresis, the action of NGF on NILE GP was represent an increase in the amount of protein, rather than a selective increase in carbohydrate incorporation. Immunofluorescent staining of primary cell cultures and tissue whole mounts revealed that immunologically cross-reactive NILE GP appears to be expressed on the cell surfaces (somas and neurites) of most if not all peripheral and central neurons examined. Immunoprecipitation of radiolabeled cultures showed that the cross-reactive material had an apparent molecular weight by SDS-PAGE of 225,000 to 230,000 in the peripheral nervous system and 200,000 to 210,000 in the central nervous system. NILE-cross-reactive material was also found to a small extent on Schwann cell surfaces, but not at all on a variety of other cell types. These results suggest

  9. Serum cytokines, T lymphocyte subsets and STAT3 function in patients with herpes zoster as well as the intervention effect of mouse nerve growth factor

    Directory of Open Access Journals (Sweden)

    Yun Xu

    2016-07-01

    Full Text Available Objective: To assess the levels of serum cytokines, T lymphocyte subsets and STAT3 in patients with herpes zoster as well as the intervention effect of mouse nerve growth factor. Methods: A total of 102 patients with herpes zoster were selected as observation group and received mouse nerve growth factor intervention, and 100 cases of normal people who received physical examination in our hospital during the same period as the healthy control group. The levels of serum Th1/Th2 cytokines, IgG subclass and complements and T lymphocyte subsets as well as STAT3 function of observation group before and after treatment and healthy control group were detected. Results: Serum IL-2 and γ-IFN levels of observation group after treatment were higher than those before treatment while IL-4, IL-5, IL-10 and TNF-α毩 levels were lower than those before treatment (P<0.05; serum IgG1, IgG3, IgG4, C3 and C4 values of observation group after treatment were higher than those before treatment while IgG2 value was lower than that before treatment (P<0.05; CD3, CD4 and CD4/CD8 levels of observation group after treatment were higher than those before treatment while CD8 level was lower than that before treatment (P<0.05; STAT3, p-STAT3 and JAK2 expression levels of observation group after treatment were lower than those before treatment (P<0.05. Conclusions: There are abnormal immune system and STAT3 signaling pathway function in patients with herpes zoster, and mouse nerve growth factor intervention can restore multisystem balance and accelerate disease rehabilitation, and has positive clinical significance.

  10. Effects of insulin-like growth factor-I and platelet-rich plasma on sciatic nerve crush injury in a rat model.

    Science.gov (United States)

    Emel, Erhan; Ergün, Selma Sönmez; Kotan, Dilcan; Gürsoy, Esra Başar; Parman, Yeşim; Zengin, Asli; Nurten, Asiye

    2011-02-01

    Local administration of insulin-like growth factor-I (IGF-I) has been shown to increase the rate of axon regeneration in crush-injured and freeze-injured rat sciatic nerves. Local administration of platelet-rich plasma (PRP) has been also shown to have a measurable effect on facial nerve regeneration after transection in a rat model. The objective of the study was to compare the effects of locally administered IGF-I and PRP on the parameters of the Sciatic Function Index (SFI), sensory function (SF), axon count, and myelin thickness/axon diameter ratio (G-ratio) in a rat model of crush-injured sciatic nerves. The right sciatic nerve of Wistar albino rats (24 animals) was crushed using a Yasargil-Phynox aneurysm clip for 45 minutes. All animals were randomly divided into 3 groups: Group 1 (control group) was treated with saline, Group 2 was treated with IGF-I, and Group 3 was treated with PRP. Injections were performed using the tissue expander's injection port with a connecting tube directed at the crush-injured site. Functional recovery was assessed with improvement in the SFI. Recovery of sensory function was using the pinch test. Histopathological examination was performed 3 months after the injury. The SFI showed an improved functional recovery in the IGF-I-treated animals (Group 2) compared with the saline-treated animals (Group 1) 30 days after the injury. In IGF-I-treated rats, sensory function returned to the baseline level significantly faster than in saline-treated and PRP-treated rats as shown in values between SF-2 and SF-7. The G-ratios were found to be significantly higher in both experimental groups than in the control group. This study suggests that the application of IGF-I to the crush-injured site may expedite the functional recovery of paralyzed muscle by increasing the rate of axon regeneration.

  11. Berkeley Lighting Cone

    Energy Technology Data Exchange (ETDEWEB)

    Lask, Kathleen [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Gadgil, Ashok [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2016-10-24

    A lighting cone is a simple metal cone placed on the fuel bed of a stove during ignition to act as a chimney, increasing the draft through the fuel bed. Many stoves tend to be difficult to light due to poor draft through the fuel bed, so lighting cones are used in various parts of the world as an inexpensive accessory to help with ignition.

  12. Terminal nerve: cranial nerve zero

    Directory of Open Access Journals (Sweden)

    Jorge Eduardo Duque Parra

    2006-12-01

    Full Text Available It has been stated, in different types of texts, that there are only twelve pairs of cranial nerves. Such texts exclude the existence of another cranial pair, the terminal nerve or even cranial zero. This paper considers the mentioned nerve like a cranial pair, specifying both its connections and its functional role in the migration of liberating neurons of the gonadotropic hormone (Gn RH. In this paper is also stated the hypothesis of the phylogenetic existence of a cerebral sector and a common nerve that integrates the terminal nerve with the olfactory nerves and the vomeronasals nerves which seem to carry out the odors detection function as well as in the food search, pheromone detection and nasal vascular regulation.

  13. A Comparison Study of Growth Factor Expression following Treatment with Transcutaneous Electrical Nerve Stimulation, Saline Solution, Povidone-Iodine, and Lavender Oil in Wounds Healing

    Directory of Open Access Journals (Sweden)

    Adalet Koca Kutlu

    2013-01-01

    Full Text Available This study compared the effects of transcutaneous electrical nerve stimulation (TENS, saline solution (SS, povidone-iodine (PI, and lavender oil (Lavandula angustifolia through expression of growth factors in a rat model of wound healing. Six experimental groups were established, each containing 8 rats: a healthy group with no incision wounds, an incision-control group, an incision and TENS group, an incision and SS group, an incision and PI group, and an incision and lavender oil group. Experiments continued for 5 days, after which the skin in the excision area was removed. Tissue concentrations of epidermal growth factor (EGF and platelet-derived growth factor (PDGF-A were measured using enzyme-linked immunosorbent assay (ELISA. Tissue expressions of EGF, PDGF-A, and fibroblast growth factor (FGF-2 were determined using immunohistochemistry. Wound closure progressed more rapidly in the TENS and lavender oil groups than in the control and other study groups. In particular, PDGF-A expressions in the dermis and EGF expression in the epidermis were significantly intense in the TENS group (P<0.05. In addition, ELISA levels of growth factors such as PDGF-A and EGF were significantly higher in TENS group compared to the control group (P<0.05. These immunohistochemical and ELISA results suggest that TENS may improve wound healing through increasing growth factors in the dermis and epidermis more than other topical applications.

  14. Rescuing apoptotic neurons in Alzheimer’s disease using wheat germ agglutinin-conjugated and cardiolipin-conjugated liposomes with encapsulated nerve growth factor and curcumin

    Directory of Open Access Journals (Sweden)

    Kuo YC

    2015-04-01

    Full Text Available Yung-Chih Kuo, Ching-Chun Lin Department of Chemical Engineering, National Chung Cheng University, Chia-Yi, Taiwan, Republic of China Abstract: Liposomes with cardiolipin (CL and wheat germ agglutinin (WGA were developed to permeate the blood–brain barrier and treat Alzheimer’s disease. WGA-conjugated and CL-incorporated liposomes (WGA-CL-liposomes were used to transport nerve growth factor (NGF and curcumin (CUR across a monolayer of human brain-microvascular endothelial cells regulated by human astrocytes and to protect SK-N-MC cells against apoptosis induced by ß-amyloid1–42 (Aß1–42 fibrils. An increase in the CL mole percentage in lipids increased the liposomal diameter, absolute zeta potential value, entrapment efficiency of NGF and CUR, release of NGF, biocompatibility, and viability of SK-N-MC cells with Aß1–42, but decreased the atomic ratio of nitrogen to phosphorus and release of CUR. In addition, an increase in the WGA concentration for grafting enhanced the liposomal diameter, atomic ratio of nitrogen to phosphorus, and permeability of NGF and CUR across the blood–brain barrier, but reduced the absolute zeta potential value and biocompatibility. WGA-CL-liposomes carrying NGF and CUR could be promising colloidal delivery carriers for future clinical application in targeting the blood–brain barrier and inhibiting neurotoxicity. Keywords: Alzheimer’s disease, nerve growth factor, curcumin, wheat germ agglutinin, cardiolipin, liposome

  15. Plasma microinstabilities driven by loss-cone distributions

    International Nuclear Information System (INIS)

    Summers, D.; Thorne, R.M.

    1995-01-01

    Electromagnetic and electrostatic instabilities driven by loss-cone particle distributions have been invoked to explain a variety of plasma phenomena observed in space and in the laboratory. In this paper we analyse how the loss-cone feature (as determined by the loss-cone index or indices) influences the growth of such instabilities in a fully ionized, homogeneous, hot plasma in a uniform magnetic field. Specifically, we consider three loss-cone distributions: a generalized Lorentzian (kappa) loss-cone distribution, the Dory-Guest-Harris distribution and the Ashour-Abdalla-Kennel distribution (involving a subtracted Maxwellian). Our findings are common to all three distributions. We find that, for parallel propagation, electromagnetic instabilities are only affected by the loss-cone indices in terms of their occurrence in the temperature anisotropy. However, for oblique propagation, even including propagation at small angles to the ambient magnetic field, the loss-cone indices do independently affect the growth of instabilities for electromagnetic waves, in contrast to certain claims in the literature. For electrostatic waves such that 1/2(κ perpendicular to ρ L σ 2 L σ is the Larmor radius for particle species σ, we find that the loss-cone indices only enter the dispersion equation via the temperature anisotropy, and so in this case the loss-cone feature and perpendicular effective thermal speed do not independently affect wave growth. (Author)

  16. APP overexpression prevents neuropathic pain and motoneuron death after peripheral nerve injury in mice.

    Science.gov (United States)

    Kotulska, Katarzyna; Larysz-Brysz, Magdalena; LePecheur, Marie; Marcol, Wiesław; Lewin-Kowalik, Joanna; Paly, Evelyn; London, Jacqueline

    2010-03-16

    Despite general capacity of peripheral nervous system to regenerate, peripheral nerve injury is often followed by incomplete recovery of function and sometimes burdened by neuropathic pain. Amyloid precursor protein (APP) was suggested to play a role in neuronal growth, however, its role in peripheral nerve repair was not studied. The aim of this study was to examine the role of APP overexpression in peripheral nerve regeneration and neuropathic pain-related behavior in mice. Sciatic nerves of APP overexpressing and FVB/N wild-type mice were transected and immediately resutured. Evaluation of motor and sensory function and autotomy was carried out during 4-week follow up. We found no autotomy behavior as well as less significant atrophy of denervated muscles in APP overexpressing animals when compared to wild-type ones. Sciatic nerve function index outcome did not differ between groups. Histological evaluation revealed that the intensity of regeneration features, including GAP-43-positive growth cones and Schwann cells number in the distal stump of the transected nerve, was also similar in both groups. However, the regenerating fibers were organized more chaotically in wild-type mice and neuromas were much more often seen in this group. The number of macrophages infiltrating the injury site was significantly higher in control group. The number of surviving motoneurons was higher in transgenic mice than in control animals. Taken together, our findings suggest that APP overexpression is beneficial for nerve regeneration processes due to better organization of regenerating fibers, increased survival of motoneurons after autotomy and prevention of neuropathic pain. Copyright 2009 Elsevier Inc. All rights reserved.

  17. In vitro and in vivo gene therapy with CMV vector-mediated presumed dog beta-nerve growth factor in pyridoxine-induced neuropathy dogs.

    Science.gov (United States)

    Chung, Jin Young; Choi, Jung Hoon; Shin, Il Seob; Choi, Eun Wha; Hwang, Cheol Yong; Lee, Sang Koo; Youn, Hwa Young

    2008-12-01

    Due to the therapeutic potential of gene therapy for neuronal injury, many studies of neurotrophic factors, vectors, and animal models have been performed. The presumed dog beta-nerve growth factor (pdbeta-NGF) was generated and cloned and its expression was confirmed in CHO cells. The recombinant pdbeta-NGF protein reacted with a human beta-NGF antibody and showed bioactivity in PC12 cells. The pdbeta-NGF was shown to have similar bioactivity to the dog beta-NGF. The recombinant pdbeta-NGF plasmid was administrated into the intrathecal space in the gene therapy group. Twenty-four hours after the vector inoculation, the gene therapy group and the positive control group were intoxicated with excess pyridoxine for seven days. Each morning throughout the test period, the dogs' body weight was taken and postural reaction assessments were made. Electrophysiological recordings were performed twice, once before the experiment and once after the test period. After the experimental period, histological analysis was performed. Dogs in the gene therapy group had no weight change and were normal in postural reaction assessments. Electrophysiological recordings were also normal for the gene therapy group. Histological analysis showed that neither the axons nor the myelin of the dorsal funiculus of L4 were severely damaged in the gene therapy group. In addition, the dorsal root ganglia of L4 and the peripheral nerves (sciatic nerve) did not experience severe degenerative changes in the gene therapy group. This study is the first to show the protective effect of NGF gene therapy in a dog model.

  18. Lysine-doped polypyrrole/spider silk protein/poly(l-lactic) acid containing nerve growth factor composite fibers for neural application.

    Science.gov (United States)

    Zhang, Hong; Wang, Kefeng; Xing, Yiming; Yu, Qiaozhen

    2015-11-01

    Lysine-doped polypyrrole (PPy)/regenerated spider silk protein (RSSP)/poly(l-lactic) acid (PLLA)/nerve growth factor (NGF) (L-PRPN) composite scaffold was fabricated by co-axial electrospraying and electrospinning. This L-PRPN composite scaffold had a structure of microfibers with a core-shell structure as the stems and nanofibers as branches. Assessment in vitro demonstrated that the L-PRPN composite micro/nano-fibrous scaffold could maintain integrated structure for at least 4months and the pH value of PBS at about 7.28. It had good biocompatibility and cell adhesion and relatively stable conductivity. PC 12 cells cultured on this scaffold, anisotropic cell-neurite-cell-neurite or neurite-neurite sheets were formed after being cultured for 6days. Evaluations in vivo also showed that L-PRPN composite fibrous conduit was effective at bridging 2.0cm sciatic nerve gap in adult rat within 10months. This conduit and electrical stimulation (ES) through it promoted Schwann cell migration and axonal regrowth. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Ulnar nerve dysfunction

    Science.gov (United States)

    Neuropathy - ulnar nerve; Ulnar nerve palsy; Mononeuropathy; Cubital tunnel syndrome ... Damage to one nerve group, such as the ulnar nerve, is called mononeuropathy . Mononeuropathy means there is damage to a single nerve. Both ...

  20. Radial nerve dysfunction

    Science.gov (United States)

    Neuropathy - radial nerve; Radial nerve palsy; Mononeuropathy ... Damage to one nerve group, such as the radial nerve, is called mononeuropathy . Mononeuropathy means there is damage to a single nerve. Both ...

  1. Intrapontine malignant nerve sheath tumor

    DEFF Research Database (Denmark)

    Kozić, Dusko; Nagulić, Mirjana; Samardzić, Miroslav

    2008-01-01

    . On pathological examination, the neoplasm appeared to be an intrapontine nerve sheath tumor originating most likely from the intrapontine segment of one of the cranial nerve fibres. The tumor showed exophytic growth, with consequent spread to adjacent subaracnoid space. MR spectroscopy revealed the presence......The primary source of malignant intracerebral nerve sheath tumors is still unclear We report the imaging and MR spectroscopic findings in a 39-year-old man with a very rare brain stem tumor MR examination revealed the presence of intraaxial brain stem tumor with a partial exophytic growth...

  2. HemoHIM improves ovarian morphology and decreases expression of nerve growth factor in rats with steroid-induced polycystic ovaries.

    Science.gov (United States)

    Kim, Sung Ho; Lee, Hae June; Kim, Joong Sun; Moon, Changjong; Kim, Jong Choon; Bae, Chun Sik; Park, Hae Ran; Jung, Uhee; Jo, Sung Kee

    2009-12-01

    Estradiol valerate (EV)-induced polycystic ovaries (PCOs) in rats cause the anovulation and cystic ovarian morphology. We investigated whether treatment with HemoHIM influences the ovarian morphology and the expression of nerve growth factor (NGF) in an EV-induced PCO rat model. PCO was induced by a single intramuscular injection of EV (4 mg, dissolved in sesame oil) in adult cycling rats. HemoHIM was either administered orally (100 mg/kg of body weight/day) for 35 consecutive days or injected intraperitoneally (50 mg/kg of body weight) every other day after EV injection. Ovarian morphology was almost normalized, and NGF was normalized in the PCO + HemoHIM group. HemoHIM lowered the high numbers of antral follicles and increased the number of corpora lutea in PCOs. The results are consistent with a beneficial effect of HemoHIM in the prevention and treatment of PCO syndrome.

  3. Influence of nerve growth factor on developing dorso-medial and ventro-lateral neurons of chick and mouse trigeminal ganglia.

    Science.gov (United States)

    Davies, A; Lumsden, A

    1983-01-01

    Trigeminal ganglia have been removed from five, six, seven and eight day chick embryos and explants of the dorso-medial (DM) and ventro-lateral (VL) parts of the maxillomandibular lobe were grown in tissue culture. Quantitative methods were used to assess the influence of nerve growth factor (NGF) on fiber outgrowth from these explants. At all ages outgrowth from DM explants was significantly greater than from VL explants, the difference being most pronounced between the extreme DM and VL poles of the maxillomandibular lobe. These observations are interpreted as indicating the existence of two distinct populations of neurons in terms of their response to NGF rather than the consequence of the asynchronous differentiation and maturation of the VL and DM neurons. A similar study of 10, 11 and 12 day embryonic mouse trigeminal ganglia revealed no significant difference in neurite outgrowth between DM and VL regions grown in the presence or absence of NGF. Copyright © 1983. Published by Elsevier Ltd.

  4. Demonstration of immunochemical identity between the nerve growth factor-inducible large external (NILE) glycoprotein and the cell adhesion molecule L1

    DEFF Research Database (Denmark)

    Bock, E; Richter-Landsberg, C; Faissner, A

    1985-01-01

    The nerve growth factor-inducible large external (NILE) glycoprotein and the neural cell adhesion molecule L1 were shown to be immunochemically identical. Immunoprecipitation with L1 and NILE antibodies of [3H]fucose-labeled material from culture supernatants and detergent extracts of NGF......-treated rat PC12 pheochromocytoma cells yielded comigrating bands by SDS-PAGE. NILE antibodies reacted with immunopurified L1 antigen, but not with N-CAM and other L2 epitope-bearing glycoproteins from adult mouse brain. Finally, by sequential immunoprecipitation from detergent extracts of [35S......]methionine-labeled early post-natal cerebellar cell cultures or [3H]fucose-labeled NGF-treated PC12 cells, all immunoreactivity for NILE antibody could be removed by pre-clearing with L1 antibody and vice versa....

  5. Glucose, other secretagogues, and nerve growth factor stimulate mitogen-activated protein kinase in the insulin-secreting beta-cell line, INS-1

    DEFF Research Database (Denmark)

    Frödin, M; Sekine, N; Roche, E

    1995-01-01

    The signaling pathways whereby glucose and hormonal secretagogues regulate insulin-secretory function, gene transcription, and proliferation of pancreatic beta-cells are not well defined. We show that in the glucose-responsive beta-cell line INS-1, major secretagogue-stimulated signaling pathways...... converge to activate 44-kDa mitogen-activated protein (MAP) kinase. Thus, glucose-induced insulin secretion was found to be associated with a small stimulatory effect on 44-kDa MAP kinase, which was synergistically enhanced by increased levels of intracellular cAMP and by the hormonal secretagogues......-1. Phorbol ester, an activator of protein kinase C, stimulated 44-kDa MAP kinase by both Ca(2+)-dependent and -independent pathways. Nerve growth factor, independently of changes in cytosolic Ca2+, efficiently stimulated 44-kDa MAP kinase without causing insulin release, indicating that activation...

  6. Nerve Cross-Bridging to Enhance Nerve Regeneration in a Rat Model of Delayed Nerve Repair

    Science.gov (United States)

    2015-01-01

    There are currently no available options to promote nerve regeneration through chronically denervated distal nerve stumps. Here we used a rat model of delayed nerve repair asking of prior insertion of side-to-side cross-bridges between a donor tibial (TIB) nerve and a recipient denervated common peroneal (CP) nerve stump ameliorates poor nerve regeneration. First, numbers of retrogradely-labelled TIB neurons that grew axons into the nerve stump within three months, increased with the size of the perineurial windows opened in the TIB and CP nerves. Equal numbers of donor TIB axons regenerated into CP stumps either side of the cross-bridges, not being affected by target neurotrophic effects, or by removing the perineurium to insert 5-9 cross-bridges. Second, CP nerve stumps were coapted three months after inserting 0-9 cross-bridges and the number of 1) CP neurons that regenerated their axons within three months or 2) CP motor nerves that reinnervated the extensor digitorum longus (EDL) muscle within five months was determined by counting and motor unit number estimation (MUNE), respectively. We found that three but not more cross-bridges promoted the regeneration of axons and reinnervation of EDL muscle by all the CP motoneurons as compared to only 33% regenerating their axons when no cross-bridges were inserted. The same 3-fold increase in sensory nerve regeneration was found. In conclusion, side-to-side cross-bridges ameliorate poor regeneration after delayed nerve repair possibly by sustaining the growth-permissive state of denervated nerve stumps. Such autografts may be used in human repair surgery to improve outcomes after unavoidable delays. PMID:26016986

  7. An anatomical study of porcine peripheral nerve and its potential use in nerve tissue engineering

    Science.gov (United States)

    Zilic, Leyla; Garner, Philippa E; Yu, Tong; Roman, Sabiniano; Haycock, John W; Wilshaw, Stacy-Paul

    2015-01-01

    Current nerve tissue engineering applications are adopting xenogeneic nerve tissue as potential nerve grafts to help aid nerve regeneration. However, there is little literature that describes the exact location, anatomy and physiology of these nerves to highlight their potential as a donor graft. The aim of this study was to identify and characterise the structural and extracellular matrix (ECM) components of porcine peripheral nerves in the hind leg. Methods included the dissection of porcine nerves, localisation, characterisation and quantification of the ECM components and identification of nerve cells. Results showed a noticeable variance between porcine and rat nerve (a commonly studied species) in terms of fascicle number. The study also revealed that when porcine peripheral nerves branch, a decrease in fascicle number and size was evident. Porcine ECM and nerve fascicles were found to be predominately comprised of collagen together with glycosaminoglycans, laminin and fibronectin. Immunolabelling for nerve growth factor receptor p75 also revealed the localisation of Schwann cells around and inside the fascicles. In conclusion, it is shown that porcine peripheral nerves possess a microstructure similar to that found in rat, and is not dissimilar to human. This finding could extend to the suggestion that due to the similarities in anatomy to human nerve, porcine nerves may have utility as a nerve graft providing guidance and support to regenerating axons. PMID:26200940

  8. Progress in light cone physics

    International Nuclear Information System (INIS)

    Preparata, G.

    1973-01-01

    A very brief review is given of the progress made in the physics of the light cone in the past year. Included are the light cone expansion, gauge invariance and the consequences of precocious scaling near threshold, the light cone description of the muon pair experiment, light cone expansions, and the assessment and exploitation of analyticity properties in both mass and energy of light cone amplitudes. (U.S.)

  9. Activation of phosphatidylinositol-3 kinase by nerve growth factor involves indirect coupling of the trk proto-oncogene with src homology 2 domains.

    Science.gov (United States)

    Ohmichi, M; Decker, S J; Saltiel, A R

    1992-10-01

    Growth factor receptor tyrosine kinases can form stable associations with intracellular proteins that contain src homology (SH) 2 domains, including the p85 regulatory subunit of phosphatidylinositol (PI)-3 kinase. The activation of this enzyme by growth factors is evaluated in PC12 pheochromocytoma cells and NIH 3T3 fibroblasts expressing the pp140c-trk nerve growth factor (NGF) receptor (3T3-c-trk). NGF causes the rapid stimulation of PI-3 kinase activity detected in anti-phosphotyrosine, but not in anti-trk, immunoprecipitates. This effect coincides with the tyrosine phosphorylation of two proteins, with molecular masses of of 100 kd and 110 kd, that coimmunoprecipitate with p85. Similar phosphorylation patterns are induced when an immobilized fusion protein containing the amino-terminal SH2 domain of p85 is used to precipitate tyrosine-phosphorylated proteins. Thus, although NGF produces the rapid activation of PI-3 kinase through a mechanism that involves tyrosine phosphorylation, there is no evidence for tyrosine phosphorylation of p85, or for its ligand-dependent association with the NGF receptor. Perhaps another phosphoprotein may link the NGF receptor to this enzyme.

  10. Promoting neuroregeneration by applying dynamic magnetic fields to a novel nanomedicine: Superparamagnetic iron oxide (SPIO)-gold nanoparticles bounded with nerve growth factor (NGF).

    Science.gov (United States)

    Yuan, Muzhaozi; Wang, Ya; Qin, Yi-Xian

    2018-04-05

    Neuroregeneration imposes a significant challenge in neuroscience for treating neurodegenerative diseases. The objective of this study is to evaluate the hypothesis that the nerve growth factor (NGF) functionalized superparamagnetic iron oxide (SPIO)-gold (Au) nanomedicine can stimulate the neuron growth and differentiation under external magnetic fields (MFs), and dynamic MFs outperform their static counterparts. The SPIO-Au core-shell nanoparticles (NPs) (Diameter: 20.8 nm) possessed advantages such as uniform quasi-spherical shapes, narrow size distribution, excellent stabilities, and low toxicity (viability >96% for 5 days). NGF functionalization has enhanced the cellular uptake. The promotion of neuronal growth and orientation using NGF functionalized SPIO-Au NPs, driven by both the static and dynamic MFs, were revealed experimentally on PC-12 cells and theoretically on a cytoskeletal force model. More importantly, dynamic MFs via rotation performed better than the static ones, i.e., the cellular differentiation ratio increased 58%; the neurite length elongation increased 63%. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Cones for dental radiography

    Energy Technology Data Exchange (ETDEWEB)

    Butler, M J [National Radiological Protection Board, Harwell (UK)

    1977-04-01

    Dental radiographic techniques are summarized. The advantages and disadvantages of the use of both the conventional plastic pointer cone and the open-ended cylinders or divergent cones favoured both by the ICRP (Protection against Ionizing Radiation from External Sources, Oxford, Pergamon Press, 1973, ICRP Publication 15), and in the Code of Practice for the Protection of Persons against Ionizing Radiation arising from Medical and Dental Use (1972, 3rd edition, London, HMSO) are discussed. The use of the word 'should' in these recommendations to signify a desirable requirement, not an essential one, is noted. This wording is currently of interest both nationally and internationally in relation to regulations, standards and notes for guidance. The National Radiological Protection Board (NRPB) has been reviewing the position, and has concluded that open-ended cones have disadvantages which may sometimes outweigh their advantages. Although open-ended cones are preferable under some circumstances, the recommendation that they should be used ought not to be followed without an understanding of the issues involved. The hazards associated with the use of interchangeable cones are considered. The NRPB now proposes that the requirement for the replacement of pointer cones (for both new and existing equipment) should be withdrawn.

  12. Structure of the gene encoding VGF, a nervous system-specific mRNA that is rapidly and selectively induced by nerve growth factor in PC12 cells.

    Science.gov (United States)

    Salton, S R; Fischberg, D J; Dong, K W

    1991-05-01

    Nerve growth factor (NGF) plays a critical role in the development and survival of neurons in the peripheral nervous system. Following treatment with NGF but not epidermal growth factor, rat pheochromocytoma (PC12) cells undergo neural differentiation. We have cloned a nervous system-specific mRNA, NGF33.1, that is rapidly and relatively selectively induced by treatment of PC12 cells with NGF and basic fibroblast growth factor in comparison with epidermal growth factor. Analysis of the nucleic acid and predicted amino acid sequences of the NGF33.1 cDNA clone suggested that this clone corresponded to the NGF-inducible mRNA called VGF (A. Levi, J. D. Eldridge, and B. M. Paterson, Science 229:393-395, 1985; R. Possenti, J. D. Eldridge, B. M. Paterson, A. Grasso, and A. Levi, EMBO J. 8:2217-2223, 1989). We have used the NGF33.1 cDNA clone to isolate and characterize the VGF gene, and in this paper we report the complete sequence of the VGF gene, including 853 bases of 5' flank revealed TATAA and CCAAT elements, several GC boxes, and a consensus cyclic AMP response element-binding protein binding site. The VGF promoter contains sequences homologous to other NGF-inducible, neuronal promoters. We further show that VGF mRNA is induced in PC12 cells to a greater extent by depolarization and by phorbol-12-myristate-13-acetate treatment than by 8-bromo-cyclic AMP treatment. By Northern (RNA) and RNase protection analysis, VGF mRNA is detectable in embryonic and postnatal central and peripheral nervous tissues but not in a number of nonneural tissues. In the cascade of events which ultimately leads to the neural differentiation of NGF-treated PC12 cells, the VGF gene encodes the most rapidly and selectively regulated, nervous-system specific mRNA yet identified.

  13. Low-Intensity Pulsed Ultrasound Enhances Nerve Growth Factor-Induced Neurite Outgrowth through Mechanotransduction-Mediated ERK1/2-CREB-Trx-1 Signaling.

    Science.gov (United States)

    Zhao, Lu; Feng, Yi; Hu, Hong; Shi, Aiwei; Zhang, Lei; Wan, Mingxi

    2016-12-01

    Enhancing the action of nerve growth factor (NGF) is a potential therapeutic approach to neural regeneration. To facilitate neural regeneration, we investigated whether combining low-intensity pulsed ultrasound (LIPUS) and NGF could promote neurite outgrowth, an essential process in neural regeneration. In the present study, PC12 cells were subjected to a combination of LIPUS (1 MHz, 30 or 50 mW/cm 2 , 20% duty cycle and 100-Hz pulse repetition frequency, 10 min every other day) and NGF (50 ng/mL) treatment, and then neurite outgrowth was compared. Our findings indicated that the combined treatment with LIPUS (50 mW/cm 2 ) and NGF (50 ng/mL) promotes neurite outgrowth that is comparable to that achieved by NGF (100 ng/mL) treatment alone. LIPUS significantly increased NGF-induced neurite length, but not neurite branching. These effects were attributed to the enhancing effects of LIPUS on NGF-induced phosphorylation of ERK1/2 and CREB and the expression of thioredoxin (Trx-1). Furthermore, blockage of stretch-activated ion channels with Gd 3+ suppressed the stimulating effects of LIPUS on NGF-induced neurite outgrowth and the downstream signaling activation. Taken together, our findings suggest that LIPUS enhances NGF-induced neurite outgrowth through mechanotransduction-mediated signaling of the ERK1/2-CREB-Trx-1 pathway. The combination of LIPUS and NGF could potentially be used for the treatment of nerve injury and neurodegenerative diseases. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  14. Effect of dietary γ-aminobutyric acid on the nerve growth factor and the choline acetyltransferase in the cerebral cortex and hippocampus of ovariectomized female rats.

    Science.gov (United States)

    Tujioka, Kazuyo; Thanapreedawat, Panicha; Yamada, Takashi; Yokogoshi, Hidehiko; Horie, Kenji; Kim, Mujo; Tsutsui, Kazumi; Hayase, Kazutoshi

    2014-01-01

    The brain protein synthesis and the plasma concentration of growth hormone (GH) is sensitive to the dietary γ-aminobutyric acid (GABA) in ovariectomized female rats; however, the role of dietary GABA on biomarkers including nerve growth factor (NGF) and choline acetyltransferase for the function of cholinergic neurons remains unknown in ovariectomized female rats. The purpose of this study was to determine whether the dietary GABA affects the concentration and mRNA level of NGF, and the activity of choline acetyltransferase in the brains of ovariectomized female rats. Experiments were done on two groups of 24-wk-old ovariectomized female rats given 0 or 0.5% GABA added to a 20% casein diet. The concentrations of NGF and activities of choline acetyltransferase in the cerebral cortex and hippocampus, and mRNA level of NGF in the hippocampus increased significantly with the 20% casein+0.5% GABA compared with the 20% casein diet alone. In the hippocampus, the mRNA level of NGF significantly correlated with the NGF concentration (r=0.714, pGABA to ovariectomized female rats is likely to control the mRNA level and concentration of NGF and cause an increase in the activity of choline acetyltransferase in the brains.

  15. Surface microstructures on planar substrates and textile fibers guide neurite outgrowth: a scaffold solution to push limits of critical nerve defect regeneration?

    Directory of Open Access Journals (Sweden)

    Stefan Weigel

    Full Text Available The treatment of critical size peripheral nerve defects represents one of the most serious problems in neurosurgery. If the gap size exceeds a certain limit, healing can't be achieved. Connection mismatching may further reduce the clinical success. The present study investigates how far specific surface structures support neurite outgrowth and by that may represent one possibility to push distance limits that can be bridged. For this purpose, growth cone displacement of fluorescent embryonic chicken spinal cord neurons was monitored using time-lapse video. In a first series of experiments, parallel patterns of polyimide ridges of different geometry were created on planar silicon oxide surfaces. These channel-like structures were evaluated with and without amorphous hydrogenated carbon (a-C:H coating. In a next step, structured and unstructured textile fibers were investigated. All planar surface materials (polyimide, silicon oxide and a-C:H proved to be biocompatible, i.e. had no adverse effect on nerve cultures and supported neurite outgrowth. Mean growth cone migration velocity measured on 5 minute base was marginally affected by surface structuring. However, surface structure variability, i.e. ridge height, width and inter-ridge spacing, significantly enhanced the resulting net velocity by guiding the growth cone movement. Ridge height and inter-ridge distance affected the frequency of neurites crossing over ridges. Of the evaluated dimensions ridge height, width, and inter-ridge distance of respectively 3, 10, and 10 µm maximally supported net axon growth. Comparable artificial grooves, fabricated onto the surface of PET fibers by using an excimer laser, showed similar positive effects. Our data may help to further optimize surface characteristics of artificial nerve conduits and bioelectronic interfaces.

  16. CONE BIOPSY IN PREGNANCY*

    African Journals Online (AJOL)

    1 Mei 1971. S.-A. TYDSKRIF VIR OBSTETRIE EN GINEKOLOGIE. CONE BIOPSY ... of the abnormal cervix in pregnancy is also no longer in question following the .... the concept of cancer prophylaxis to the majority of women, many of whom ...

  17. Recurrent abnormalities in conifer cones and the evolutionary origins of flower-like structures.

    Science.gov (United States)

    Rudall, Paula J; Hilton, Jason; Vergara-Silva, Francisco; Bateman, Richard M

    2011-03-01

    Conifer cones are reproductive structures that are typically of restricted growth and either exclusively pollen-bearing (male) or exclusively ovule-bearing (female). Here, we review two common spontaneous developmental abnormalities of conifer cones: proliferated cones, in which the apex grows vegetatively, and bisexual cones, which possess both male and female structures. Emerging developmental genetic data, combined with evidence from comparative morphology, ontogeny and palaeobotany, provide new insights into the evolution of both cones and flowers, and prompt novel strategies for understanding seed-plant evolution. Copyright © 2010 Elsevier Ltd. All rights reserved.

  18. The effects of different combinations of perceptual-motor exercises, music, and vitamin D supplementation on the nerve growth factor in children with high-functioning autism.

    Science.gov (United States)

    Moradi, Hadi; Sohrabi, Mehdi; Taheri, Hamidreza; Khodashenas, Ezzat; Movahedi, Ahmadreza

    2018-05-01

    The present study investigated the effects of different combinations of perceptual-motor exercises, music, and Vitamin D consumption on the nerve growth factor (NGF) in children with high-functioning autism. 48 children with autism, aged between six and nine years, were divided into four groups: Group A- perceptual-motor activities along with music (n = 12); Group B-Vitamin D supplementation (n = 12); Group C-perceptual-motor activities along with music and Vitamin D (n = 12); and Group D-control (n = 12). Participants' blood NGF level was measured before and after the intervention. The results showed a significant improvement in the NGF levels in Groups B and C due to the interventions. Also, in Group A, the NGF levels increased compared to Group D, although this increase was not significant. In addition, the intake of Vitamin D along with perceptual-motor exercises resulted in a significant increase in the levels of NGF compared to Groups A, B and D. These findings suggest that perceptual-motor exercises along with music as well as taking Vitamin D may provide two appropriate interventions for improving NGF in children with autism. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. Impairment of the nerve growth factor pathway driving amyloid accumulation in cholinergic neurons: the incipit of the Alzheimer′s disease story?

    Directory of Open Access Journals (Sweden)

    Viviana Triaca

    2016-01-01

    Full Text Available The current idea behind brain pathology is that disease is initiated by mild disturbances of common physiological processes. Overtime, the disruption of the neuronal homeostasis will determine irreversible degeneration and neuronal apoptosis. This could be also true in the case of nerve growth factor (NGF alterations in sporadic Alzheimer′s disease (AD, an age-related pathology characterized by cholinergic loss, amyloid plaques and neurofibrillary tangles. In fact, the pathway activated by NGF, a key neurotrophin for the metabolism of basal forebrain cholinergic neurons (BFCN, is one of the first homeostatic systems affected in prodromal AD. NGF signaling dysfunctions have been thought for decades to occur in AD late stages, as a mere consequence of amyloid-driven disruption of the retrograde axonal transport of neurotrophins to BFCN. Nowadays, a wealth of knowledge is potentially opening a new scenario: NGF signaling impairment occurs at the onset of AD and correlates better than amyloid load with cognitive decline. The recent acceleration in the characterization of anatomical, functional and molecular profiles of early AD is aimed at maximizing the efficacy of existing treatments and setting novel therapies. Accordingly, the elucidation of the molecular events underlying APP metabolism regulation by the NGF pathway in the septo-hippocampal system is crucial for the identification of new target molecules to slow and eventually halt mild cognitive impairment (MCI and its progression toward AD.

  20. Potentiation of nerve growth factor-induced neurite outgrowth in PC12 cells by ifenprodil: the role of sigma-1 and IP3 receptors.

    Directory of Open Access Journals (Sweden)

    Tamaki Ishima

    Full Text Available In addition to both the α1 adrenergic receptor and N-methyl-D-aspartate (NMDA receptor antagonists, ifenprodil binds to the sigma receptor subtypes 1 and 2. In this study, we examined the effects of ifenprodil on nerve growth factor (NGF-induced neurite outgrowth in PC12 cells. Ifenprodil significantly potentiated NGF-induced neurite outgrowth, in a concentration-dependent manner. In contrast, the α1 adrenergic receptor antagonist, prazosin and the NMDA receptor NR2B antagonist, Ro 25-6981 did not alter NGF-induced neurite outgrowth. Potentiation of NGF-induced neurite outgrowth mediated by ifenprodil was significantly antagonized by co-administration of the selective sigma-1 receptor antagonist, NE-100, but not the sigma-2 receptor antagonist, SM-21. Similarly, ifenprodil enhanced NGF-induced neurite outgrowth was again significantly reduced by the inositol 1,4,5-triphosphate (IP(3 receptor antagonists, xestospongin C and 2-aminoethoxydiphenyl borate (2-APB treatment. Furthermore, BAPTA-AM, a chelator of intracellular Ca(2+, blocked the effects of ifenprodil on NGF-induced neurite outgrowth, indicating the role of intracellular Ca(2+ in the neurite outgrowth. These findings suggest that activation at sigma-1 receptors and subsequent interaction with IP(3 receptors may mediate the pharmacological effects of ifenprodil on neurite outgrowth.

  1. Expression of Nerve Growth Factor (NGF and Its Receptors TrkA and p75 in the Reproductive Organs of Laying Hens

    Directory of Open Access Journals (Sweden)

    PU Shaoxia

    2016-03-01

    Full Text Available Abstract In order to investigate the expression levels of nerve growth factor (NGF and its receptors (TrkA and p75 in prehierarchical follicles and oviducts of hens, five 130-day-old laying hens were examined by immunohistochemistry and RT-PCR analysis. NGF and its receptors were expressed in theca cells and granulosa cells of prehierarchical follicles, and they were also expressed in the epithelial cells of oviducts. The expression of the genes NGF, TrkA and p75 were significantly different in prehierarchical follicles (p<0.05 or p<0.01, and NGF and TrkA gene expression was significantly different in different parts of oviduct (p<0.05 or p<0.01. The expression of NGF and p75 mRNA levels was highest in large white follicle (LWF, as well as the expression of TrkA in small yellow follicle (SYF. In the oviduct, the expression of NGF was the highest in infundibulum, and lowest in isthmus. These results suggest that NGF may play an important role in the regulation of hen reproduction.

  2. Asarone from Acori Tatarinowii Rhizoma Potentiates the Nerve Growth Factor-Induced Neuronal Differentiation in Cultured PC12 Cells: A Signaling Mediated by Protein Kinase A.

    Directory of Open Access Journals (Sweden)

    Kelly Y C Lam

    Full Text Available Acori Tatarinowii Rhizoma (ATR, the rhizome of Acorus tatarinowii Schott, is being used clinically to treat neurological disorders. The volatile oil of ATR is being considered as an active ingredient. Here, α-asarone and β-asarone, accounting about 95% of ATR oil, were evaluated for its function in stimulating neurogenesis. In cultured PC12 cells, application of ATR volatile oil, α-asarone or β-asarone, stimulated the expression of neurofilaments, a bio-marker for neurite outgrowth, in a concentration-dependent manner. The co-treatment of ATR volatile oil, α-asarone or β-asarone, with low concentration of nerve growth factor (NGF potentiated the NGF-induced neuronal differentiation in cultured PC12 cells. In addition, application of protein kinase A inhibitors, H89 and KT5720, in cultures blocked the ATR-induced neurofilament expression, as well as the phosphorylation of cAMP-responsive element binding protein (CREB. In the potentiation of NGF-induced signaling in cultured PC12 cells, α-asarone and β-asarone showed synergistic effects. These results proposed the neurite-promoting asarone, or ATR volatile oil, could be useful in finding potential drugs for treating various neurodegenerative diseases, in which neurotrophin deficiency is normally involved.

  3. Serum brain-derived neurotrophic factor, glial-derived neurotrophic factor, nerve growth factor, and neurotrophin-3 levels in children with attention-deficit/hyperactivity disorder.

    Science.gov (United States)

    Bilgiç, Ayhan; Toker, Aysun; Işık, Ümit; Kılınç, İbrahim

    2017-03-01

    It has been suggested that neurotrophins are involved in the etiopathogenesis of attention-deficit/hyperactivity disorder (ADHD). This study aimed to investigate whether there are differences in serum brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), nerve growth factor (NGF), and neurotrophin-3 (NTF3) levels between children with ADHD and healthy controls. A total of 110 treatment-naive children with the combined presentation of ADHD and 44 healthy controls aged 8-18 years were enrolled in this study. The severity of ADHD symptoms was determined by scores on the Conners' Parent Rating Scale-Revised Short and Conners' Teacher Rating Scale-Revised Short. The severity of depression and anxiety symptoms of the children were evaluated by the self-report inventories. Serum levels of neurotrophins were measured using commercial enzyme-linked immunosorbent assay kits. The multivariate analysis of covariance (MANCOVA) revealed a significant main effect of groups in the levels of serum neurotrophins, an effect that was independent of age, sex, and the severity of the depression and anxiety. The analysis of covariance (ANCOVA) indicated that the mean serum GDNF and NTF3 levels of ADHD patients were significantly higher than that of controls. However, serum BDNF and NGF levels did not show any significant differences between groups. No correlations between the levels of serum neurotrophins and the severity of ADHD were observed. These results suggest that elevated serum GDNF and NTF3 levels may be related to ADHD in children.

  4. Nerve growth factor affects [sup 11]C-nicotine binding, blood flow, EEG, and verbal episodic memory in an Alzheimer patient; Case report

    Energy Technology Data Exchange (ETDEWEB)

    Olson, L [Dept. of Histology and Neurobiology, Karolinska Inst., Stockholm (Sweden); Nordberg, A [Dept. of Pharmacology, Biomedical Center, Uppsala Univ., Uppsala (Sweden); Holst, H von [Dept. of Neurosurgery, Karolinska Hospital, Stockholm (Sweden); and others

    1992-01-01

    Based on animal research suggesting that nerve growth factor (NGF) can stimulate central cholinergic neurons, the known losses of cholinergic innervation of the cortices in Alzheimer's disease (AD), and our experience of infusing NGF to support adrenal grafts in parkinsonian patients, we have initiated clinical trials of NGF infusions into the brain of patients with AD. Here we report a follow-up of our first case, a 69-year-old woman, with symptoms of dementia since 8 years. Intraventricular infusion of 6.6 mg NGF during three months resulted in a marked transient increase in uptake and binding of [sup 11]C-nicotine in frontal and temporal cortex and a persistent increase in cortical blood flow as measured by PET as well as progressive decreases of slow wave EEG activity. After one month of NGF, tests of verbal episodic memory were improved whereas other cognitive tests were not. No adverse effects could be ascribed to the NGF infusion. Taken together, the results of this case study indicate that NGF may counteract cholinergic deficits in AD, and suggest that further clinical trials of NGF infusion in AD are warranted. (authors).

  5. Combined intranasal nerve growth factor and ventricle neural stem cell grafts prolong survival and improve disease outcome in amyotrophic lateral sclerosis transgenic mice.

    Science.gov (United States)

    Zhong, Shi-Jiang; Gong, Yan-Hua; Lin, Yan-Chen

    2017-08-24

    Amyotrophic lateral sclerosis (ALS) is a fatal disease that selectively involves motor neurons. Neurotrophic factor supplementation and neural stem cell (NSC) alternative therapy have been used to treat ALS. The two approaches can affect each other in their pathways of action, and there is a possibility for synergism. However, to date, there have been no studies demonstrating the effects of combined therapy in the treatment of ALS. In this study, for the first time, we adopted a method involving the intranasal administration of nerve growth factor combined with lateral ventricle NSC transplantation using G93A-SOD1 transgenic mice as experimental subjects to explore the treatment effect of this combined therapy in ALS. We discover that the combined therapy increase the quantity of TrkA receptors, broaden the migration of exogenous NSCs, further promote active proliferation in neurogenic regions of the brain and enhance the preservation of motor neurons in the spinal cord. Regarding physical activity, the combined therapy improved motor functions, further postponed ALS onset and extended the survival time of the mice. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Effects of hyperbaric oxygen and nerve growth factor on the long-term neural behavior of neonatal rats with hypoxic ischemic brain damage.

    Science.gov (United States)

    Wei, Lixia; Ren, Qing; Zhang, Yongjun; Wang, Jiwen

    2017-04-01

    To evaluate the effects of HBO (Hyperbaric oxygen) and NGF (Nerve growth factor) on the long-term neural behavior of neonatal rats with HIBD (Neonatal hypoxic ischemic brain damage). The HIBD model was produced by ligating the right common carotid artery of 7 days old SD (Sprague-Dawley) rats followed by 8% O2 + 92% N2 for 2h. Totally 40 rats were randomly divided into 5 groups including sham-operated group, HIBD control group, HBO treated group, NGF treated group and NGF + HBO treated group. The learning and memory ability of these rats was evaluated by Morris water maze at 30 days after birth, and sensory motor function was assessed by experiments of foot error and limb placement at 42 days after birth. The escape latency of HBO treated group, NGF treated group and NGF + HBO treated group was shorter than that of HIBD control group (pmemory ability and sensory motor function in neonatal rats after hypoxic ischemic brain damage.

  7. Effects of huperzine A on secretion of nerve growth factor in cultured rat cortical astrocytes and neurite outgrowth in rat PC12 cells.

    Science.gov (United States)

    Tang, Li-li; Wang, Rui; Tang, Xi-can

    2005-06-01

    To study the effects of huperzine A (HupA) on neuritogenic activity and the expression of nerve growth factor (NGF). After being treated with 10 micromol/L HupA, neurite outgrowth of PC12 cells was observed and counted under phase-contrast microscopy. Mitogenic activity was assayed by [3H]thymidine incorporation. Cell cytotoxicity was evaluated by lactate dehydrogenase (LDH) release. AChE activity, mRNA and protein expression were measured by the Ellman method, RT-PCR, and Western blot, respectively. NGF mRNA and protein levels were determined by RT-PCR and ELISA assays. Treatment of PC12 cells with 10 micromol/L HupA for 48 h markedly increased the number of neurite-bearing cells, but caused no significant alteration in cell viability or other signs of cytotoxicity. In addition to inhibiting AChE activity, 10 micromol/L HupA also increased the mRNA and protein levels of this enzyme. In addition, following 2 h exposure of the astrocytes to 10 micromol/L HupA, there was a significant up-regulation of mRNA for NGF and P75 low-affinity NGF receptor. The protein level of NGF was also increased after 24 h treatment with HupA. Our findings demonstrate for the first time that HupA has a direct or indirect neurotrophic activity, which might be beneficial in treatment of neurodegenerative disorders such as Alzheimer disease.

  8. Role of brain-derived neurotrophic factor and nerve growth factor in the regulation of Neuropeptide W in vitro and in vivo.

    Science.gov (United States)

    Wang, Rikang; Yan, Fengxia; Liao, Rifang; Wan, Pei; Little, Peter J; Zheng, Wenhua

    2017-05-15

    Nerve growth factor (NGF) and Brain-derived neurotrophic factor (BDNF) are neurotrophic factors involved in the growth, survival and functioning of neurons. In addition, a possible role of neurotrophins, particularly BDNF, in HPA axis hyperactivation has recently been proposed. Neuropeptide W (NPW) is an endogenous peptide ligand for the GPR7 and GPR8 and a stress mediator in the hypothalamus. It activates the HPA axis by working on hypothalamic corticotrophin-releasing hormone (CRH). No information is available about the interrelationships between neurotrophines like NGF/BDNF and NPW. We studied the effect and underlying mechanisms of NGF/BDNF on the production of NPW in PC12 cells and hypothalamus. NGF time- and concentration-dependently stimulated the expression of NPW in PC12 cells. The effect of NGF was blocked by the inhibition of PI3K/Akt signal pathway with specific inhibitors for PI3K or AktsiRNA for Akt while inhibition of ERK pathway had no effect. Moreover, BDNF concentration-dependently induced the expression of NPW mRNA and decreased the expression of NPY mRNA in primary cultured hypothalamic neurons which was also blocked by a PI3K kinase inhibitor. Finally, in vivo study showed that exogenous BDNF injected icv increased NPW production in the hypothalamus and this effect was reversed by a PI3 kinase inhibitor. These results and the fact that BDNF was able to stimulate the expression of CRH demonstrated that neurotrophines can modulate the expression of NPW in neuronal cells via the PI3K/Akt pathway and suggest that BDNF might be involved in functions of the HPA axis, at least in part by modulating the expression of NPW/NPY and CRH. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Nerve growth factor alters microtubule targeting agent-induced neurotransmitter release but not MTA-induced neurite retraction in sensory neurons.

    Science.gov (United States)

    Pittman, Sherry K; Gracias, Neilia G; Fehrenbacher, Jill C

    2016-05-01

    Peripheral neuropathy is a dose-limiting side effect of anticancer treatment with the microtubule-targeted agents (MTAs), paclitaxel and epothilone B (EpoB); however, the mechanisms by which the MTAs alter neuronal function and morphology are unknown. We previously demonstrated that paclitaxel alters neuronal sensitivity, in vitro, in the presence of nerve growth factor (NGF). Evidence in the literature suggests that NGF may modulate the neurotoxic effects of paclitaxel. Here, we examine whether NGF modulates changes in neuronal sensitivity and morphology induced by paclitaxel and EpoB. Neuronal sensitivity was assessed using the stimulated release of calcitonin gene-related peptide (CGRP), whereas morphology of established neurites was evaluated using a high content screening system. Dorsal root ganglion cultures, maintained in the absence or presence of NGF, were treated from day 7 to day 12 in culture with paclitaxel (300nM) or EpoB (30nM). Following treatment, the release of CGRP was stimulated using capsaicin or high extracellular potassium. In the presence of NGF, EpoB mimicked the effects of paclitaxel: capsaicin-stimulated release was attenuated, potassium-stimulated release was slightly enhanced and the total peptide content was unchanged. In the absence of NGF, both paclitaxel and EpoB decreased capsaicin- and potassium-stimulated release and the total peptide content, suggesting that NGF may reverse MTA-induced hyposensitivity. Paclitaxel and EpoB both decreased neurite length and branching, and this attenuation was unaffected by NGF in the growth media. These differential effects of NGF on neuronal sensitivity and morphology suggest that neurite retraction is not a causative factor to alter neuronal sensitivity. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Neural stem cells enhance nerve regeneration after sciatic nerve injury in rats.

    Science.gov (United States)

    Xu, Lin; Zhou, Shuai; Feng, Guo-Ying; Zhang, Lu-Ping; Zhao, Dong-Mei; Sun, Yi; Liu, Qian; Huang, Fei

    2012-10-01

    With the development of tissue engineering and the shortage of autologous nerve grafts in nerve reconstruction, cell transplantation in a conduit is an alternative strategy to improve nerve regeneration. The present study evaluated the effects and mechanism of brain-derived neural stem cells (NSCs) on sciatic nerve injury in rats. At the transection of the sciatic nerve, a 10-mm gap between the nerve stumps was bridged with a silicon conduit filled with 5 × 10(5) NSCs. In control experiments, the conduit was filled with nerve growth factor (NGF) or normal saline (NS). The functional and morphological properties of regenerated nerves were investigated, and expression of hepatocyte growth factor (HGF) and NGF was measured. One week later, there was no connection through the conduit. Four or eight weeks later, fibrous connections were evident between the proximal and distal segments. Motor function was revealed by measurement of the sciatic functional index (SFI) and sciatic nerve conduction velocity (NCV). Functional recovery in the NSC and NGF groups was significantly more advanced than that in the NS group. NSCs showed significant improvement in axon myelination of the regenerated nerves. Expression of NGF and HGF in the injured sciatic nerve was significantly lower in the NS group than in the NSCs and NGF groups. These results and other advantages of NSCs, such as ease of harvest and relative abundance, suggest that NSCs could be used clinically to enhance peripheral nerve repair.

  11. Ejecta evolution during cone impact

    KAUST Repository

    Marston, Jeremy

    2014-07-07

    We present findings from an experimental investigation into the impact of solid cone-shaped bodies onto liquid pools. Using a variety of cone angles and liquid physical properties, we show that the ejecta formed during the impact exhibits self-similarity for all impact speeds for very low surface tension liquids, whilst for high-surface tension liquids similarity is only achieved at high impact speeds. We find that the ejecta tip can detach from the cone and that this phenomenon can be attributed to the air entrainment phenomenon. We analyse of a range of cone angles, including some ogive cones, and impact speeds in terms of the spatiotemporal evolution of the ejecta tip. Using superhydrophobic cones, we also examine the entry of cones which entrain an air layer.

  12. Cone Algorithm of Spinning Vehicles under Dynamic Coning Environment

    Directory of Open Access Journals (Sweden)

    Shuang-biao Zhang

    2015-01-01

    Full Text Available Due to the fact that attitude error of vehicles has an intense trend of divergence when vehicles undergo worsening coning environment, in this paper, the model of dynamic coning environment is derived firstly. Then, through investigation of the effect on Euler attitude algorithm for the equivalency of traditional attitude algorithm, it is found that attitude error is actually the roll angle error including drifting error and oscillating error, which is induced directly by dynamic coning environment and further affects the pitch angle and yaw angle through transferring. Based on definition of the cone frame and cone attitude, a cone algorithm is proposed by rotation relationship to calculate cone attitude, and the relationship between cone attitude and Euler attitude of spinning vehicle is established. Through numerical simulations with different conditions of dynamic coning environment, it is shown that the induced error of Euler attitude fluctuates by the variation of precession and nutation, especially by that of nutation, and the oscillating frequency of roll angle error is twice that of pitch angle error and yaw angle error. In addition, the rotation angle is more competent to describe the spinning process of vehicles under coning environment than Euler angle gamma, and the real pitch angle and yaw angle are calculated finally.

  13. The effect of antenatal depression and selective serotonin reuptake inhibitor treatment on nerve growth factor signaling in human placenta.

    Directory of Open Access Journals (Sweden)

    Helena Kaihola

    Full Text Available Depressive symptoms during pregnancy are common and may have impact on the developing child. Selective serotonin reuptake inhibitors (SSRIs are the most prescribed antidepressant treatment, but unfortunately, these treatments can also negatively affect the behavioral development and health of a child during pregnancy. In addition, serotonin (5-HT exerts neurotrophic actions with thus far not fully known effects in the offspring. The neurotrophic growth factor (NGF is involved in neuronal cell survival and differentiation, and altered placenta levels have been found to increase the risk for pregnancy complications, similar to those found in women treated with SSRIs. We therefore investigated whether the NGF signaling pathway was altered in the placenta from women treated with SSRIs (n = 12 and compared them with placenta from depressed (n = 12 and healthy mothers (n = 12. Results from immunohistochemical stainings revealed that placental NGF protein levels of SSRI-treated women were increased in both trophoblasts and endothelial cells compared with depressed and control women. In addition, downstream of the NGF receptor TrkA, increased levels of the signaling proteins ROCK2 and phosphorylated Raf-1 were found in stromal cells and a tendency towards increased levels of ROCK2 in trophoblasts and endothelial cells in SSRI-treated women when compared to healthy controls. SSRI-treated women also displayed increased levels of phosphorylated ROCK2 in all placental cell types studied in comparison with depressed and control women. Interestingly, in placental endothelial cells from depressed women, NGF levels were significantly lower compared to control women, but ROCK2 levels were increased compared with control and SSRI-treated women. Taken together, these results show that the NGF signaling and downstream pathways in the placenta are affected by SSRI treatment and/or antenatal depression. This might lead to an altered placental function, although the

  14. Nuclear-Encoded Mitochondrial mRNAs: A Powerful Force in Axonal Growth and Development.

    Science.gov (United States)

    Gale, Jenna R; Aschrafi, Armaz; Gioio, Anthony E; Kaplan, Barry B

    2018-04-01

    Axons, their growth cones, and synaptic nerve terminals are neuronal subcompartments that have high energetic needs. As such, they are enriched in mitochondria, which supply the ATP necessary to meet these demands. To date, a heterogeneous population of nuclear-encoded mitochondrial mRNAs has been identified in distal axons and growth cones. Accumulating evidence suggests that the local translation of these mRNAs is required for mitochondrial maintenance and axonal viability. Here, we review evidence that suggests a critical role for axonal translation of nuclear-encoded mitochondrial mRNAs in axonal growth and development. Additionally, we explore the role that site-specific translation at the mitochondria itself may play in this process. Finally, we briefly review the clinical implications of dysregulation of local translation of mitochondrial-related mRNAs in neurodevelopmental disorders.

  15. Light cone thermodynamics

    Science.gov (United States)

    De Lorenzo, Tommaso; Perez, Alejandro

    2018-02-01

    We show that null surfaces defined by the outgoing and infalling wave fronts emanating from and arriving at a sphere in Minkowski spacetime have thermodynamical properties that are in strict formal correspondence with those of black hole horizons in curved spacetimes. Such null surfaces, made of pieces of light cones, are bifurcate conformal Killing horizons for suitable conformally stationary observers. They can be extremal and nonextremal depending on the radius of the shining sphere. Such conformal Killing horizons have a constant light cone (conformal) temperature, given by the standard expression in terms of the generalization of surface gravity for conformal Killing horizons. Exchanges of conformally invariant energy across the horizon are described by a first law where entropy changes are given by 1 /(4 ℓp2) of the changes of a geometric quantity with the meaning of horizon area in a suitable conformal frame. These conformal horizons satisfy the zeroth to the third laws of thermodynamics in an appropriate way. In the extremal case they become light cones associated with a single event; these have vanishing temperature as well as vanishing entropy.

  16. Cone rod dystrophies

    Science.gov (United States)

    Hamel, Christian P

    2007-01-01

    Cone rod dystrophies (CRDs) (prevalence 1/40,000) are inherited retinal dystrophies that belong to the group of pigmentary retinopathies. CRDs are characterized by retinal pigment deposits visible on fundus examination, predominantly localized to the macular region. In contrast to typical retinitis pigmentosa (RP), also called the rod cone dystrophies (RCDs) resulting from the primary loss in rod photoreceptors and later followed by the secondary loss in cone photoreceptors, CRDs reflect the opposite sequence of events. CRD is characterized by primary cone involvement, or, sometimes, by concomitant loss of both cones and rods that explains the predominant symptoms of CRDs: decreased visual acuity, color vision defects, photoaversion and decreased sensitivity in the central visual field, later followed by progressive loss in peripheral vision and night blindness. The clinical course of CRDs is generally more severe and rapid than that of RCDs, leading to earlier legal blindness and disability. At end stage, however, CRDs do not differ from RCDs. CRDs are most frequently non syndromic, but they may also be part of several syndromes, such as Bardet Biedl syndrome and Spinocerebellar Ataxia Type 7 (SCA7). Non syndromic CRDs are genetically heterogeneous (ten cloned genes and three loci have been identified so far). The four major causative genes involved in the pathogenesis of CRDs are ABCA4 (which causes Stargardt disease and also 30 to 60% of autosomal recessive CRDs), CRX and GUCY2D (which are responsible for many reported cases of autosomal dominant CRDs), and RPGR (which causes about 2/3 of X-linked RP and also an undetermined percentage of X-linked CRDs). It is likely that highly deleterious mutations in genes that otherwise cause RP or macular dystrophy may also lead to CRDs. The diagnosis of CRDs is based on clinical history, fundus examination and electroretinogram. Molecular diagnosis can be made for some genes, genetic counseling is always advised. Currently

  17. Cone rod dystrophies

    Directory of Open Access Journals (Sweden)

    Hamel Christian P

    2007-02-01

    Full Text Available Abstract Cone rod dystrophies (CRDs (prevalence 1/40,000 are inherited retinal dystrophies that belong to the group of pigmentary retinopathies. CRDs are characterized by retinal pigment deposits visible on fundus examination, predominantly localized to the macular region. In contrast to typical retinitis pigmentosa (RP, also called the rod cone dystrophies (RCDs resulting from the primary loss in rod photoreceptors and later followed by the secondary loss in cone photoreceptors, CRDs reflect the opposite sequence of events. CRD is characterized by primary cone involvement, or, sometimes, by concomitant loss of both cones and rods that explains the predominant symptoms of CRDs: decreased visual acuity, color vision defects, photoaversion and decreased sensitivity in the central visual field, later followed by progressive loss in peripheral vision and night blindness. The clinical course of CRDs is generally more severe and rapid than that of RCDs, leading to earlier legal blindness and disability. At end stage, however, CRDs do not differ from RCDs. CRDs are most frequently non syndromic, but they may also be part of several syndromes, such as Bardet Biedl syndrome and Spinocerebellar Ataxia Type 7 (SCA7. Non syndromic CRDs are genetically heterogeneous (ten cloned genes and three loci have been identified so far. The four major causative genes involved in the pathogenesis of CRDs are ABCA4 (which causes Stargardt disease and also 30 to 60% of autosomal recessive CRDs, CRX and GUCY2D (which are responsible for many reported cases of autosomal dominant CRDs, and RPGR (which causes about 2/3 of X-linked RP and also an undetermined percentage of X-linked CRDs. It is likely that highly deleterious mutations in genes that otherwise cause RP or macular dystrophy may also lead to CRDs. The diagnosis of CRDs is based on clinical history, fundus examination and electroretinogram. Molecular diagnosis can be made for some genes, genetic counseling is

  18. Molecular evolution of vertebrate neurotrophins: co-option of the highly conserved nerve growth factor gene into the advanced snake venom arsenalf.

    Science.gov (United States)

    Sunagar, Kartik; Fry, Bryan Grieg; Jackson, Timothy N W; Casewell, Nicholas R; Undheim, Eivind A B; Vidal, Nicolas; Ali, Syed A; King, Glenn F; Vasudevan, Karthikeyan; Vasconcelos, Vitor; Antunes, Agostinho

    2013-01-01

    Neurotrophins are a diverse class of structurally related proteins, essential for neuronal development, survival, plasticity and regeneration. They are characterized by major family members, such as the nerve growth factors (NGF), brain-derived neurotrophic factors (BDNF) and neurotrophin-3 (NT-3), which have been demonstrated here to lack coding sequence variations and follow the regime of negative selection, highlighting their extremely important conserved role in vertebrate homeostasis. However, in stark contrast, venom NGF secreted as part of the chemical arsenal of the venomous advanced snake family Elapidae (and to a lesser extent Viperidae) have characteristics consistent with the typical accelerated molecular evolution of venom components. This includes a rapid rate of diversification under the significant influence of positive-selection, with the majority of positively-selected sites found in the secreted β-polypeptide chain (74%) and on the molecular surface of the protein (92%), while the core structural and functional residues remain highly constrained. Such focal mutagenesis generates active residues on the toxin molecular surface, which are capable of interacting with novel biological targets in prey to induce a myriad of pharmacological effects. We propose that caenophidian NGFs could participate in prey-envenoming by causing a massive release of chemical mediators from mast cells to mount inflammatory reactions and increase vascular permeability, thereby aiding the spread of other toxins and/or by acting as proapoptotic factors. Despite their presence in reptilian venom having been known for over 60 years, this is the first evidence that venom-secreted NGF follows the molecular evolutionary pattern of other venom components, and thus likely participates in prey-envenomation.

  19. Effects of varying doses of β-nerve growth factor on the timing of ovulation, plasma progesterone concentration and corpus luteum size in female alpacas (Vicugna pacos).

    Science.gov (United States)

    Stuart, C C; Vaughan, J L; Kershaw-Young, C M; Wilkinson, J; Bathgate, R; de Graaf, S P

    2015-11-01

    Ovulation in camelids is induced by the seminal plasma protein ovulation-inducing factor (OIF), recently identified as β-nerve growth factor (β-NGF). The present study measured the total protein concentration in alpaca seminal plasma using a bicinchoninic acid (BCA) protein quantification assay and found it to be 22.2±2.0mgmL(-1). To measure the effects of varying doses of β-NGF on the incidence and timing of ovulation, corpus luteum (CL) size and plasma progesterone concentration, 24 female alpacas were synchronised and treated with either: (1) 1mL 0.9% saline (n=5); (2) 4µg buserelin (n=5); (3) 1mg β-NGF protein (n=5); (4) 0.1mg β-NGF (n=5); or (5) 0.01mg β-NGF (n=4). Females were examined by transrectal ultrasonography at 1-2-h intervals between 20 and 45h after treatment or until ovulation occurred, as well as on Day 8 to observe the size of the CL, at which time blood was collected to measure plasma progesterone concentrations. Ovulation was detected in 0/5, 5/5, 5/5, 3/5 and 0/4 female alpacas treated with saline, buserelin, 1, 0.1 and 0.01mg β-NGF, respectively. Mean ovulation interval (P=0.76), CL diameter (P=0.96) and plasma progesterone concentration (P=0.96) did not differ between treatments. Mean ovulation interval overall was 26.2±1.0h. In conclusion, buserelin and 1mg β-NGF are equally effective at inducing ovulation in female alpacas, but at doses ≤0.1mg, β-NGF is not a reliable method for the induction of ovulation.

  20. Molecular Evolution of Vertebrate Neurotrophins: Co-Option of the Highly Conserved Nerve Growth Factor Gene into the Advanced Snake Venom Arsenalf

    Science.gov (United States)

    Sunagar, Kartik; Fry, Bryan Grieg; Jackson, Timothy N. W.; Casewell, Nicholas R.; Undheim, Eivind A. B.; Vidal, Nicolas; Ali, Syed A.; King, Glenn F.; Vasudevan, Karthikeyan; Vasconcelos, Vitor; Antunes, Agostinho

    2013-01-01

    Neurotrophins are a diverse class of structurally related proteins, essential for neuronal development, survival, plasticity and regeneration. They are characterized by major family members, such as the nerve growth factors (NGF), brain-derived neurotrophic factors (BDNF) and neurotrophin-3 (NT-3), which have been demonstrated here to lack coding sequence variations and follow the regime of negative selection, highlighting their extremely important conserved role in vertebrate homeostasis. However, in stark contrast, venom NGF secreted as part of the chemical arsenal of the venomous advanced snake family Elapidae (and to a lesser extent Viperidae) have characteristics consistent with the typical accelerated molecular evolution of venom components. This includes a rapid rate of diversification under the significant influence of positive-selection, with the majority of positively-selected sites found in the secreted β-polypeptide chain (74%) and on the molecular surface of the protein (92%), while the core structural and functional residues remain highly constrained. Such focal mutagenesis generates active residues on the toxin molecular surface, which are capable of interacting with novel biological targets in prey to induce a myriad of pharmacological effects. We propose that caenophidian NGFs could participate in prey-envenoming by causing a massive release of chemical mediators from mast cells to mount inflammatory reactions and increase vascular permeability, thereby aiding the spread of other toxins and/or by acting as proapoptotic factors. Despite their presence in reptilian venom having been known for over 60 years, this is the first evidence that venom-secreted NGF follows the molecular evolutionary pattern of other venom components, and thus likely participates in prey-envenomation. PMID:24312363

  1. Intra-articular nerve growth factor regulates development, but not maintenance, of injury-induced facet joint pain & spinal neuronal hypersensitivity.

    Science.gov (United States)

    Kras, J V; Kartha, S; Winkelstein, B A

    2015-11-01

    The objective of the current study is to define whether intra-articular nerve growth factor (NGF), an inflammatory mediator that contributes to osteoarthritic pain, is necessary and sufficient for the development or maintenance of injury-induced facet joint pain and its concomitant spinal neuronal hyperexcitability. Male Holtzman rats underwent painful cervical facet joint distraction (FJD) or sham procedures. Mechanical hyperalgesia was assessed in the forepaws, and NGF expression was quantified in the C6/C7 facet joint. An anti-NGF antibody was administered intra-articularly in additional rats immediately or 1 day following facet distraction or sham procedures to block intra-articular NGF and test its contribution to initiation and/or maintenance of facet joint pain and spinal neuronal hyperexcitability. NGF was injected into the bilateral C6/C7 facet joints in separate rats to determine if NGF alone is sufficient to induce these behavioral and neuronal responses. NGF expression increases in the cervical facet joint in association with behavioral sensitivity after that joint's mechanical injury. Intra-articular application of anti-NGF immediately after a joint distraction prevents the development of both injury-induced pain and hyperexcitability of spinal neurons. Yet, intra-articular anti-NGF applied after pain has developed does not attenuate either behavioral or neuronal hyperexcitability. Intra-articular NGF administered to the facet in naïve rats also induces behavioral hypersensitivity and spinal neuronal hyperexcitability. Findings demonstrate that NGF in the facet joint contributes to the development of injury-induced joint pain. Localized blocking of NGF signaling in the joint may provide potential treatment for joint pain. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  2. Decrease of urinary nerve growth factor but not brain-derived neurotrophic factor in patients with interstitial cystitis/bladder pain syndrome treated with hyaluronic acid.

    Directory of Open Access Journals (Sweden)

    Yuan-Hong Jiang

    Full Text Available To investigate urinary nerve growth factor (NGF and brain-derived neurotrophic factor (BDNF levels in interstitial cystitis/bladder pain syndrome (IC/BPS patients after hyaluronic acid (HA therapy.Thirty-three patients with IC/BPS were prospectively studied; a group of 45 age-matched healthy subjects served as controls. All IC/BPS patients received nine intravesical HA instillations during the 6-month treatment regimen. Urine samples were collected for measuring urinary NGF and BDNF levels at baseline and 2 weeks after the last HA treatment. The clinical parameters including visual analog scale (VAS of pain, daily frequency nocturia episodes, functional bladder capacity (FBC and global response assessment (GRA were recorded. Urinary NGF and BDNF levels were compared between IC/BPS patients and controls at baseline and after HA treatment.Urinary NGF, NGF/Cr, BDNF, and BDNF/Cr levels were significantly higher in IC/BPS patients compared to controls. Both NGF and NGF/Cr levels significantly decreased after HA treatment. Urinary NGF and NGF/Cr levels significantly decreased in the responders with a VAS pain reduction by 2 (both p < 0.05 and the GRA improved by 2 (both p < 0.05, but not in non-responders. Urinary BDNF and BDNF/Cr did not decrease in responders or non-responders after HA therapy.Urinary NGF, but not BDNF, levels decreased significantly after HA therapy; both of these factors remained higher than in controls even after HA treatment. HA had a beneficial effect on IC/BPS, but it was limited. The reduction of urinary NGF levels was significant in responders, with a reduction of pain and improved GRA.

  3. Molecular evolution of vertebrate neurotrophins: co-option of the highly conserved nerve growth factor gene into the advanced snake venom arsenalf.

    Directory of Open Access Journals (Sweden)

    Kartik Sunagar

    Full Text Available Neurotrophins are a diverse class of structurally related proteins, essential for neuronal development, survival, plasticity and regeneration. They are characterized by major family members, such as the nerve growth factors (NGF, brain-derived neurotrophic factors (BDNF and neurotrophin-3 (NT-3, which have been demonstrated here to lack coding sequence variations and follow the regime of negative selection, highlighting their extremely important conserved role in vertebrate homeostasis. However, in stark contrast, venom NGF secreted as part of the chemical arsenal of the venomous advanced snake family Elapidae (and to a lesser extent Viperidae have characteristics consistent with the typical accelerated molecular evolution of venom components. This includes a rapid rate of diversification under the significant influence of positive-selection, with the majority of positively-selected sites found in the secreted β-polypeptide chain (74% and on the molecular surface of the protein (92%, while the core structural and functional residues remain highly constrained. Such focal mutagenesis generates active residues on the toxin molecular surface, which are capable of interacting with novel biological targets in prey to induce a myriad of pharmacological effects. We propose that caenophidian NGFs could participate in prey-envenoming by causing a massive release of chemical mediators from mast cells to mount inflammatory reactions and increase vascular permeability, thereby aiding the spread of other toxins and/or by acting as proapoptotic factors. Despite their presence in reptilian venom having been known for over 60 years, this is the first evidence that venom-secreted NGF follows the molecular evolutionary pattern of other venom components, and thus likely participates in prey-envenomation.

  4. Development of an imaging mitigation strategy for patient enrolment in the tanezumab nerve growth factor inhibitor (NGF-ab) program with a focus on eligibility assessment.

    Science.gov (United States)

    Roemer, Frank W; Miller, Colin G; West, Christine R; Brown, Mark T; Sherlock, Sarah P; Kompel, Andrew J; Diaz, Luis; Galante, Nicholas; Crema, Michel D; Guermazi, Ali

    2017-12-01

    Nerve growth factor antibodies (NGF-ab) have shown promising analgesic efficacy. Aim was to describe reader training efforts and present reliability data focusing on radiographic eligibility in the tanezumab program. A multi-step process was used for reader calibration and reliability testing. First, a reference standard set of cases was created and diagnostic performance was evaluated. A second exercise focused on agreement of ordinal assessment (Kellgren-Lawrence grading) of radiographic osteoarthritis. Subsequently, 11 readers were trained and read a test set of 100 cases focused on eligibility assessments. Additional reliability testing and calibration of five core readers assessing eligibility of 30 cases was performed 3 and 6 months after study start. Sensitivity for the reference standard readings ranged from 0.50 to 0.90 and specificity from 0.40 to 0.83. Overall agreement for Kellgren-Lawrence grading ranged from 71.4% to 82.9%. For the 11 reader exercise, in 76% of cases at least 8 of 11 readers agreed on eligibility status. For the reliability testing 3 months after study start, in 80.0% of cases at least 4 of 5 readers agreed on eligibility with a κ = 0.43 (95% CI: 0.32-0.54). For the reliability testing after 6 months, in 83.3% of cases at least 4 of 5 readers agreed on eligibility with a κ = 0.52 (95% CI: 0.41-0.63). After intense efforts spent in the development of an imaging program for an NGF-ab clinical program, the achieved reliability for eligibility assessment is substantial but not perfect. Ongoing efforts of calibration prior to including additional readers to the program and during study conduct between current readers will be needed to ensure agreement on potential adverse events and radiographic disease severity. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Nerve growth factor induced changes in the Golgi apparatus of PC-12 rat pheochromocytoma cells as studied by ligand endocytosis, cytochemical and morphometric methods.

    Science.gov (United States)

    Hickey, W F; Stieber, A; Hogue-Angeletti, R; Gonatas, J; GOnatas, N K

    1983-10-01

    Cells of the PC-12 rat pheochromocytoma cell line respond to nerve growth factor (NGF) by sprouting neurites and biochemically differentiating into sympathetic ganglion-like cells. NGF-stimulated ('differentiated') and unstimulated ('undifferentiated') cells were studied by cytochemical techniques for the localization of the enzymes acid phosphatase (ACPase) and thiamine pyrophosphatase (TPPase), and by a morphometric analysis of the distribution of endocytosed wheat-germ agglutinin labelled with horseradish peroxidase (WGA-HRP). Both cytochemical stains showed the enzymes to be distributed in lysosomes and certain cisternae of the Golgi apparatus in both NGF stimulated and unstimulated cells. ACPase was not confined to GERL (Golgi-endoplasmic reticulum-lysosome) as in certain other cells. The morphometric studies demonstrated that the reaction product of the internalized WGA-HRP occupied 4.7% of the cytoplasmic area in unstimulated cells and 4.5% in NGF-stimulated ones. Despite this similarity, the distribution of the WGA-HRP among the studied intracellular compartments in these two cell groups varied. In the NGF-stimulated cells 3.3% of the WGA-HRP reaction product was found in the innermost Golgi cisterna(e) while in unstimulated cells only 0.3% was seen in this compartment. Similarly, 4.3% of the WGA-HRP stain was found in small vesicles at the 'trans' aspect of the Golgi apparatus in stimulated cells, when only 0.3% of the stain occupied this compartment in 'undifferentiated' cells. The morphometric analysis also revealed that when the PC-12 cells were stimulated with NGF, the Golgi apparatus increased in area by approximately 70%. These findings are consistent with the hypothesis that NGF induced differentiation of PC-12 cells is coupled with enhanced endocytosis of WGA and probably of its 'receptor' to the innermost Golgi cisterna(e) and the closely associated vesicles.

  6. Effects of perinatal hypo- and hyperthyroidism on the levels of nerve growth factor and its low-affinity receptor in cerebellum.

    Science.gov (United States)

    Figueiredo, B C; Otten, U; Strauss, S; Volk, B; Maysinger, D

    1993-04-16

    Deficits or excesses of thyroid hormones during critical periods of mammalian cerebellar development can lead to profound biochemical and morphological abnormalities in this system. The goal of this study was to investigate the effects of perinatal hypo- and hyperthyroidism on the ontogeny of nerve growth factor (NGF) and its low-affinity receptor (p75NGFR) in the rat cerebellum. The concentration of NGF and of p75NGFR immunoreactivity (IR) were measured, several days after birth, in cerebella of rats which had received propylthiouracil (PTU) or thyroxine. NGF concentration was markedly enhanced only on postnatal day 2 (P2) in hyperthyroid rats, whereas in hypothyroid (PTU-treated) rats NGF values were similar to age-matched controls. These observations suggest that thyroid hormone affects NGF synthesis during early periods of cerebellar development. In Purkinje cells of control animals, p75NGFR IR peaked at P10. In hypothyroid rats, the expression of p75NGFR was retarded, peaking at P15, whereas in hyperthyroid rats it was advanced, peaking at P8. The increased p75NGFR IR found in Purkinje cell bodies and the delayed disappearance of p75NGFR IR from the external granular layer of hypothyroid rats suggest different roles for thyroid hormone in the developing cerebellum. We conclude that p75NGFR and NGF are independently regulated by thyroid hormone during critical periods of cerebellar development. The effect of thyroid hormone deficiency on p75NGFR content in Purkinje cells may involve complex mechanisms such as impaired efficiency of axonal transport.

  7. Effect of 8 weeks resistance training on plasma levels of nerve growth factor and interlukin-6 in female patients with multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Mehrzad Moghadasi

    2015-07-01

    Full Text Available Background: In recent years, evidence from a number of studies has suggested that exercise is a safe and efficient way to induce improvements in a number of physiological functions in multiple sclerosis (MS patients, but the effects of exercise on nerve growth factor (NGF and interlukin-6 (IL-6 in these patients are not well known. Thus, the purpose of this study was to evaluate the effect of 8 weeks resistance training on plasma NGF and IL-6 in female patients with MS. Materials and methods: Thirty two female MS patients with 32.4±5.5 years of old, and expanded disability status scale (EDSS 0-4.5, participated in this study. The subjects were randomly assigned to control group (n=13 and training group (n=14. Subjects in training group performed selected upper and lower extremities resistance training with weight-training equipment and rubber bands 3 days a week for 8 weeks. Body composition parameters, NGF and IL-6 levels were measured before and after the intervention. Results: The results showed that body weight, body mass index, body fat mass and EDSS were decreased significantly after 8 weeks in training group compared to control group (P<0.05. Also, no significant differences were seen after the intervention in NGF and IL-6 between the training and control groups. Conclusion: The results suggest resistance training with specific intensity and duration utilized in this study improves EDSS in female patients with MS but it has no effecting on NGF and IL-6 in these patients.

  8. Effects of chronic alcohol consumption, withdrawal and nerve growth factor on neuropeptide Y expression and cholinergic innervation of the rat dentate hilus.

    Science.gov (United States)

    Pereira, Pedro A; Rocha, João P; Cardoso, Armando; Vilela, Manuel; Sousa, Sérgio; Madeira, M Dulce

    2016-05-01

    Several studies have demonstrated the vulnerability of the hippocampal formation (HF) to chronic alcohol consumption and withdrawal. Among the brain systems that appear to be particularly vulnerable to the effects of these conditions are the neuropeptide Y (NPY)-ergic and the cholinergic systems. Because these two systems seem to closely interact in the HF, we sought to study the effects of chronic alcohol consumption (6months) and subsequent withdrawal (2months) on the expression of NPY and on the cholinergic innervation of the rat dentate hilus. As such, we have estimated the areal density and the somatic volume of NPY-immunoreactive neurons, and the density of the cholinergic varicosities. In addition, because alcohol consumption and withdrawal are associated with impaired nerve growth factor (NGF) trophic support and the administration of exogenous NGF alters the effects of those conditions on various cholinergic markers, we have also estimated the same morphological parameters in withdrawn rats infused intracerebroventricularly with NGF. NPY expression increased after withdrawal and returned to control values after NGF treatment. Conversely, the somatic volume of these neurons did not differ among all groups. On other hand, the expression of vesicular acetylcholine transporter (VAChT) was reduced by 24% in ethanol-treated rats and by 46% in withdrawn rats. The administration of NGF to withdrawn rats increased the VAChT expression to values above control levels. These results show that the effects of prolonged alcohol intake and protracted withdrawal on the hilar NPY expression differ from those induced by shorter exposures to ethanol and by abrupt withdrawal. They also suggest that the normalizing effect of NGF on NPY expression might rely on the NGF-induced improvement of cholinergic neurotransmission in the dentate hilus. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Evolution of an Astrocytic Hamartoma of the Optic Nerve Head in a Patient with Retinitis Pigmentosa – Photographic Documentation over 2 Years of Follow-Up

    Science.gov (United States)

    Loukianou, Eleni; Kisma, Nacima; Pal, Bishwanathan

    2011-01-01

    Aim To report photographically the evolution of an astrocytic hamartoma of the left optic nerve head over a 2-year follow-up in a patient with retinitis pigmentosa. Methods A 14-year-old boy was seen in the medical retina clinic with a 3-year history of night blindness. Best corrected visual acuity was 6/18 in both eyes. Colour vision was normal in both eyes and confrontation fields showed peripheral constriction. Fundus examination revealed bone spicule pigmentary changes at the retinal mid periphery typical of retinitis pigmentosa and superficial globules at the margins of both optic nerve heads. Electrodiagnostic tests confirmed moderately severe rod cone dystrophy with macular involvement bilaterally. Results Two years later, the ocular examination was unchanged except for the appearance of the optic nerve head lesion in the left eye. There was an increase in the size of the lesion which was diagnosed as an astrocytic hamartoma. Further investigations were recommended to exclude neurofibromatosis and tuberous sclerosis. Conclusion Astrocytic hamartomas of the optic nerve head and optic nerve head drusen have both been described in patients with retinitis pigmentosa. They can be a diagnostic dilemma although drusen are more common (10%). To differentiate these two entities it is very important to document any growth during the follow-up period which is suggestive of astrocytic hamartoma rather than optic disc drusen. PMID:21347192

  10. Evolution of an Astrocytic Hamartoma of the Optic Nerve Head in a Patient with Retinitis Pigmentosa - Photographic Documentation over 2 Years of Follow-Up.

    Science.gov (United States)

    Loukianou, Eleni; Kisma, Nacima; Pal, Bishwanathan

    2011-02-02

    To report photographically the evolution of an astrocytic hamartoma of the left optic nerve head over a 2-year follow-up in a patient with retinitis pigmentosa. A 14-year-old boy was seen in the medical retina clinic with a 3-year history of night blindness. Best corrected visual acuity was 6/18 in both eyes. Colour vision was normal in both eyes and confrontation fields showed peripheral constriction. Fundus examination revealed bone spicule pigmentary changes at the retinal mid periphery typical of retinitis pigmentosa and superficial globules at the margins of both optic nerve heads. Electrodiagnostic tests confirmed moderately severe rod cone dystrophy with macular involvement bilaterally. Two years later, the ocular examination was unchanged except for the appearance of the optic nerve head lesion in the left eye. There was an increase in the size of the lesion which was diagnosed as an astrocytic hamartoma. Further investigations were recommended to exclude neurofibromatosis and tuberous sclerosis. Astrocytic hamartomas of the optic nerve head and optic nerve head drusen have both been described in patients with retinitis pigmentosa. They can be a diagnostic dilemma although drusen are more common (10%). To differentiate these two entities it is very important to document any growth during the follow-up period which is suggestive of astrocytic hamartoma rather than optic disc drusen.

  11. Evolution of an Astrocytic Hamartoma of the Optic Nerve Head in a Patient with Retinitis Pigmentosa – Photographic Documentation over 2 Years of Follow-Up

    Directory of Open Access Journals (Sweden)

    Eleni Loukianou

    2011-02-01

    Full Text Available Aim: To report photographically the evolution of an astrocytic hamartoma of the left optic nerve head over a 2-year follow-up in a patient with retinitis pigmentosa. Methods: A 14-year-old boy was seen in the medical retina clinic with a 3-year history of night blindness. Best corrected visual acuity was 6/18 in both eyes. Colour vision was normal in both eyes and confrontation fields showed peripheral constriction. Fundus examination revealed bone spicule pigmentary changes at the retinal mid periphery typical of retinitis pigmentosa and superficial globules at the margins of both optic nerve heads. Electrodiagnostic tests confirmed moderately severe rod cone dystrophy with macular involvement bilaterally. Results: Two years later, the ocular examination was unchanged except for the appearance of the optic nerve head lesion in the left eye. There was an increase in the size of the lesion which was diagnosed as an astrocytic hamartoma. Further investigations were recommended to exclude neurofibromatosis and tuberous sclerosis. Conclusion: Astrocytic hamartomas of the optic nerve head and optic nerve head drusen have both been described in patients with retinitis pigmentosa. They can be a diagnostic dilemma although drusen are more common (10%. To differentiate these two entities it is very important to document any growth during the follow-up period which is suggestive of astrocytic hamartoma rather than optic disc drusen.

  12. Optic Nerve Disorders

    Science.gov (United States)

    The optic nerve is a bundle of more than 1 million nerve fibers that carry visual messages. You have one connecting ... retina) to your brain. Damage to an optic nerve can cause vision loss. The type of vision ...

  13. Optic Nerve Imaging

    Science.gov (United States)

    ... News About Us Donate In This Section Optic Nerve Imaging email Send this article to a friend ... measurements of nerve fiber damage (or loss). The Nerve Fiber Analyzer (GDx) uses laser light to measure ...

  14. Femoral nerve damage (image)

    Science.gov (United States)

    The femoral nerve is located in the leg and supplies the muscles that assist help straighten the leg. It supplies sensation ... leg. One risk of damage to the femoral nerve is pelvic fracture. Symptoms of femoral nerve damage ...

  15. Ulnar nerve damage (image)

    Science.gov (United States)

    The ulnar nerve originates from the brachial plexus and travels down arm. The nerve is commonly injured at the elbow because of elbow fracture or dislocation. The ulnar nerve is near the surface of the body where ...

  16. Steroid-induced polycystic ovaries in rats: effect of electro-acupuncture on concentrations of endothelin-1 and nerve growth factor (NGF, and expression of NGF mRNA in the ovaries, the adrenal glands, and the central nervous system

    Directory of Open Access Journals (Sweden)

    Aloe Luigi

    2003-04-01

    Full Text Available Abstract Previous studies on the effect of repeated electro-acupuncture (EA treatments in rats with steriod-induced polycystic ovaries (PCO, EA has been shown to modulate nerve growth factor (NGF concentration in the ovaries as well as corticotropin releasing factor (CRF in the median eminence (ME. In the present study we tested the hypothesis that repeated EA treatments modulates sympathetic nerve activity in rats with PCO. This was done by analysing endothelin-1 (ET-1, a potent vasoconstrictor involved in ovarian functions, as well as NGF and NGF mRNA expression involved in the pathophysiological process underlying steroid-induced PCO. The main result in the present study was that concentrations of ET-1 in the ovaries were significantly lower in the PCO group receiving EA compared with the healthy control group (p p p p

  17. Null cone superspace supergravity

    International Nuclear Information System (INIS)

    Downes-Martin, S.G.

    1980-03-01

    The null cone formalism is used to derive a 2(N-1) parameter family of constraints for O(N) extended superspace supergravity. The invariance groups of these constraints is analysed and is found to be [subgroup U submanifold] contains GL(4,R) for N = 1, the submanifold being eliminated for N > 1. The invariance group defines non-Weyl rotations on the superbein which combine to form Weyl transformations on the supertangent space metric. The invariance of the supergravity Lagrangian under these transformations is discussed. (Auth.)

  18. The holographic entropy cone

    Energy Technology Data Exchange (ETDEWEB)

    Bao, Ning [Institute for Quantum Information and Matter, California Institute of Technology,Pasadena, CA 91125 (United States); Walter Burke Institute for Theoretical Physics, California Institute of Technology,452-48, Pasadena, CA 91125 (United States); Nezami, Sepehr [Stanford Institute for Theoretical Physics, Stanford University,Stanford, CA 94305 (United States); Ooguri, Hirosi [Walter Burke Institute for Theoretical Physics, California Institute of Technology,452-48, Pasadena, CA 91125 (United States); Kavli Institute for the Physics and Mathematics of the Universe, University of Tokyo,Kashiwa 277-8583 (Japan); Stoica, Bogdan [Walter Burke Institute for Theoretical Physics, California Institute of Technology,452-48, Pasadena, CA 91125 (United States); Sully, James [Theory Group, SLAC National Accelerator Laboratory, Stanford University,Menlo Park, CA 94025 (United States); Walter, Michael [Stanford Institute for Theoretical Physics, Stanford University,Stanford, CA 94305 (United States)

    2015-09-21

    We initiate a systematic enumeration and classification of entropy inequalities satisfied by the Ryu-Takayanagi formula for conformal field theory states with smooth holographic dual geometries. For 2, 3, and 4 regions, we prove that the strong subadditivity and the monogamy of mutual information give the complete set of inequalities. This is in contrast to the situation for generic quantum systems, where a complete set of entropy inequalities is not known for 4 or more regions. We also find an infinite new family of inequalities applicable to 5 or more regions. The set of all holographic entropy inequalities bounds the phase space of Ryu-Takayanagi entropies, defining the holographic entropy cone. We characterize this entropy cone by reducing geometries to minimal graph models that encode the possible cutting and gluing relations of minimal surfaces. We find that, for a fixed number of regions, there are only finitely many independent entropy inequalities. To establish new holographic entropy inequalities, we introduce a combinatorial proof technique that may also be of independent interest in Riemannian geometry and graph theory.

  19. The holographic entropy cone

    International Nuclear Information System (INIS)

    Bao, Ning; Nezami, Sepehr; Ooguri, Hirosi; Stoica, Bogdan; Sully, James; Walter, Michael

    2015-01-01

    We initiate a systematic enumeration and classification of entropy inequalities satisfied by the Ryu-Takayanagi formula for conformal field theory states with smooth holographic dual geometries. For 2, 3, and 4 regions, we prove that the strong subadditivity and the monogamy of mutual information give the complete set of inequalities. This is in contrast to the situation for generic quantum systems, where a complete set of entropy inequalities is not known for 4 or more regions. We also find an infinite new family of inequalities applicable to 5 or more regions. The set of all holographic entropy inequalities bounds the phase space of Ryu-Takayanagi entropies, defining the holographic entropy cone. We characterize this entropy cone by reducing geometries to minimal graph models that encode the possible cutting and gluing relations of minimal surfaces. We find that, for a fixed number of regions, there are only finitely many independent entropy inequalities. To establish new holographic entropy inequalities, we introduce a combinatorial proof technique that may also be of independent interest in Riemannian geometry and graph theory.

  20. Review on resonance cone fields

    International Nuclear Information System (INIS)

    Ohnuma, Toshiro.

    1980-02-01

    Resonance cone fields and lower hybrid heating are reviewed in this report. The resonance cone fields were reported by Fisher and Gould, and they proposed the use of the measurement of resonance cones and structure as a diagnostic tool to determine the plasma density and electron temperature in magnetoplasma. After the resonance cone, a wave-like disturbance persists. Ohnuma et al. have measured bending, reflection and ducting of resonance cones in detail. The thermal modes in inhomogeneous magnetoplasma were seen. The reflection of thermal mode near an electron plasma frequency layer and an insulating plate has been observed. The non-linear effects of resonance cones is reported. Monochromatic electron beam produces the noise of broad band whistler mode. Lower hybrid waves have been the subject of propagation from the edge of plasma to the lower hybrid layer. Linear lower hybrid waves were studied. The lower hybrid and ion acoustic waves radiated from a point source were observed. The parametric decay of finite-extent, cold electron plasma waves was studied. The lower hybrid cone radiated from a point source going along magnetic field lines was observed. Several experimental data on the lower hybrid heating in tokamak devices have been reported. The theories on resonance cones and lower hybrid waves are introduced in this report. (Kato, T.)

  1. Plate Tearing by a Cone

    DEFF Research Database (Denmark)

    Simonsen, Bo Cerup

    1997-01-01

    The present paper is concerned with steady-state plate tearing by a cone. This is a scenario where a cone is forced through a ductile metal plate with a constant lateral tip penetration in a motion in the plane of the plate. The considered process could be an idealisaton of the damage, which...... as for the out-of-plane reaction force....

  2. Pro region engineering of nerve growth factor by deep mutational scanning enables a yeast platform for conformational epitope mapping of anti-NGF monoclonal antibodies.

    Science.gov (United States)

    Medina-Cucurella, Angélica V; Zhu, Yaqi; Bowen, Scott J; Bergeron, Lisa M; Whitehead, Timothy A

    2018-04-12

    Nerve growth factor (NGF) plays a central role in multiple chronic pain conditions. As such, anti-NGF monoclonal antibodies (mAbs) that function by antagonizing NGF downstream signaling are leading drug candidates for non-opioid pain relief. To evaluate anti-canine NGF (cNGF) mAbs we sought a yeast surface display platform of cNGF. Both mature cNGF and pro-cNGF displayed on the yeast surface but bound conformationally sensitive mAbs at most 2.5-fold in mean fluorescence intensity above background, suggesting that cNGF was mostly misfolded. To improve the amount of folded, displayed cNGF, we used comprehensive mutagenesis, FACS, and deep sequencing to identify point mutants in the pro-region of canine NGF that properly enhance the folded protein displayed on the yeast surface. Out of 1,737 tested single point mutants in the pro region, 49 increased the amount of NGF recognized by conformationally sensitive mAbs. These gain-of-function mutations cluster around residues A-61-P-26. Gain-of-function mutants were additive, and a construct containing three mutations increased amount of folded cNGF to 23- fold above background. Using this new cNGF construct, fine conformational epitopes for tanezumab and three anti-cNGF mAbs were evaluated. The epitope revealed by the yeast experiments largely overlapped with the tanezumab epitope previously determined by X-ray crystallography. The other mAbs showed site-specific differences with tanezumab. As the number of binding epitopes of functionally neutralizing anti-NGF mAbs on NGF are limited, subtle differences in the individual interacting residues on NGF that bind each mAb contribute to the understanding of each antibody and variations in its neutralizing activity. These results demonstrate the potential of deep sequencing-guided protein engineering to improve the production of folded surface-displayed protein, and the resulting cNGF construct provides a platform to map conformational epitopes for other anti-neurotrophin m

  3. QCD on the light cone

    International Nuclear Information System (INIS)

    Brodsky, S.J.

    1992-09-01

    The quantization of gauge theory at fixed light-cone time τ = t - z/c provides new perspectives for solving non-perturbative problems in quantum chromodynamics. The light-cone Fock state expansion provides both a precise definition of the relativistic wavefunctions of hadrons as bound-states of quarks and gluons and a general calculus for predicting QCD processes at the amplitude level. Applications to exclusive processes and weak decay amplitudes are discussed. The problem of computing the hadronic spectrum and the corresponding light-cone wavefunctions of QCD in one space and one time dimension has been successfully reduced to the diagonalization of a discrete representation of the light-cone Hamiltonian. The problems confronting the solution of gauge theories in 3 + 1 dimensions in the light-cone quantization formalism,, including zero modes and non-perturbative renormalization, are reviewed

  4. Microvascular Cranial Nerve Palsy

    Science.gov (United States)

    ... Español Eye Health / Eye Health A-Z Microvascular Cranial Nerve Palsy Sections What Is Microvascular Cranial Nerve Palsy? ... Microvascular Cranial Nerve Palsy Treatment What Is Microvascular Cranial Nerve Palsy? Leer en Español: ¿Qué es una parálisis ...

  5. Ordered cones and approximation

    CERN Document Server

    Keimel, Klaus

    1992-01-01

    This book presents a unified approach to Korovkin-type approximation theorems. It includes classical material on the approximation of real-valuedfunctions as well as recent and new results on set-valued functions and stochastic processes, and on weighted approximation. The results are notonly of qualitative nature, but include quantitative bounds on the order of approximation. The book is addressed to researchers in functional analysis and approximation theory as well as to those that want to applythese methods in other fields. It is largely self- contained, but the readershould have a solid background in abstract functional analysis. The unified approach is based on a new notion of locally convex ordered cones that are not embeddable in vector spaces but allow Hahn-Banach type separation and extension theorems. This concept seems to be of independent interest.

  6. Effects of early cone collection and artificial ripening on white spruce and red pine germination

    Energy Technology Data Exchange (ETDEWEB)

    Winston, D.A.; Haddon, B.D.

    1981-12-01

    Two experiments were conducted at the Petawawa National Forestry Institute. Chalk River, Ontario in 1978 to test the feasibility of early cone collection and to determine the optimum conditions for the artificial ripening of white spruce and red pine cones. Cones were collected at periodic intervals, commencing 7 weeks before natural cone ripeness, and stored under four storage conditions and three storage periods. White spruce cones collected August 1, 4 weeks before natural seed dispersal, and stored on open, screened trays for 12 weeks at 5 degrees Celcius and 75-95% relative humidity yielded seeds of high germinability. Seeds extracted from cones immediately after this collection failed to germinate. Cold storage of white spruce cones at 5 degrees Celcius for as little as 4 weeks eliminated dormancy and the subsequent need for seed stratification after extraction. Good germination of red pine seeds was obtained from cones collected August 16, 7 weeks before natural seed dispersal, and stored on screened trays in a well-ventilated, unheated building, for 4 weeks. Completion of embryo growth must be attained before artificial ripening can be successfully applied; it may be used as an index for commencement of cone collections provided subsequent cone handling includes artificial ripening. (Refs. 39).

  7. Cone and Seed Maturation of Southern Pines

    Science.gov (United States)

    James P. Barnett

    1976-01-01

    If slightly reduced yields and viability are acceptable, loblolly and slash cone collections can begin 2 to 3 weeks before maturity if the cones are stored before processing. Longleaf(P. palestris Mill.) pine cones should be collected only when mature, as storage decreased germination of seeds from immature cones. Biochemical analyses to determine reducing sugar...

  8. Nerves Regulate Cardiomyocyte Proliferation and Heart Regeneration.

    Science.gov (United States)

    Mahmoud, Ahmed I; O'Meara, Caitlin C; Gemberling, Matthew; Zhao, Long; Bryant, Donald M; Zheng, Ruimao; Gannon, Joseph B; Cai, Lei; Choi, Wen-Yee; Egnaczyk, Gregory F; Burns, Caroline E; Burns, C Geoffrey; MacRae, Calum A; Poss, Kenneth D; Lee, Richard T

    2015-08-24

    Some organisms, such as adult zebrafish and newborn mice, have the capacity to regenerate heart tissue following injury. Unraveling the mechanisms of heart regeneration is fundamental to understanding why regeneration fails in adult humans. Numerous studies have revealed that nerves are crucial for organ regeneration, thus we aimed to determine whether nerves guide heart regeneration. Here, we show using transgenic zebrafish that inhibition of cardiac innervation leads to reduction of myocyte proliferation following injury. Specifically, pharmacological inhibition of cholinergic nerve function reduces cardiomyocyte proliferation in the injured hearts of both zebrafish and neonatal mice. Direct mechanical denervation impairs heart regeneration in neonatal mice, which was rescued by the administration of neuregulin 1 (NRG1) and nerve growth factor (NGF) recombinant proteins. Transcriptional analysis of mechanically denervated hearts revealed a blunted inflammatory and immune response following injury. These findings demonstrate that nerve function is required for both zebrafish and mouse heart regeneration. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. [Brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) blood levels in patients with acute carbon monoxide poisoning - a preliminary observations].

    Science.gov (United States)

    Ciszowski, Krzysztof; Gomółka, Ewa; Gawlikowski, Tomasz; Szpak, Dorota; Potoczek, Anna; Boba, Magdalena

    Neurotrophins are the family of proteins which stimulate and regulate the process of neurogenesis. Several factors belong to the family, mainly nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT 3), and neurotrophin-4/5 (NT-4/5). Acute poisoning with carbon monoxide (CO), which usually is accompanied by neurologic symptoms, can potentially change the secretion profile of neurotrophins. Aim of the study. The main goal of the study is to assess the changes of NGF and BDNF plasma levels during an acute phase of CO poisoning as well as immediately after recovery. Additionally, the relationship among neurotrophin levels and selected aspects of clinical course of CO poisoning were studied. The study group consisted of 18 patients (mean age: 31.8±10.3 years) hospitalized in Toxicology Department of University Hospital in Cracow because of acute CO poisoning. There were 10 women (mean age: 30.2±6.9 years) and 8 men (mean age 33.9±13.7 years) in the group. The levels of NGF and BDNF were evaluated using immunoenzymatic method (ELISA) in plasma samples taken thrice in each patient. The sample 1. was taken during hospital admission, the sample 2. about 12-36 hours after admission, and the sample 3. just before the hospital discharging (usually, on the 3rd-4th day). The clinical data were collected from patients’ anamnesis, physical examination and neuropsychological evaluation. The statistical analysis were performed using tools comprised in STATISTICA 12.0 PL (StatSoft Polska, Cracow, Poland) software. The majority of NGF plasma levels were less than 14 pg/mL (values below the limit of quantification), contrary to the sole case of 34.3 pg/mL. BDNF plasma levels ranged from 4.8 ng/mL to above 48 ng/mL, i.e. they were higher than the upper limit of measurement range for the plasma dilution which had been used. The comparison of NGF and BDNF plasma levels in the study group with their analogues in healthy volunteers taken from the

  10. Effect of Surface Pore Structure of Nerve Guide Conduit on Peripheral Nerve Regeneration

    Science.gov (United States)

    Oh, Se Heang; Kim, Jin Rae; Kwon, Gu Birm; Namgung, Uk; Song, Kyu Sang

    2013-01-01

    Polycaprolactone (PCL)/Pluronic F127 nerve guide conduits (NGCs) with different surface pore structures (nano-porous inner surface vs. micro-porous inner surface) but similar physical and chemical properties were fabricated by rolling the opposite side of asymmetrically porous PCL/F127 membranes. The effect of the pore structure on peripheral nerve regeneration through the NGCs was investigated using a sciatic nerve defect model of rats. The nerve fibers and tissues were shown to have regenerated along the longitudinal direction through the NGC with a nano-porous inner surface (Nanopore NGC), while they grew toward the porous wall of the NGC with a micro-porous inner surface (Micropore NGC) and, thus, their growth was restricted when compared with the Nanopore NGC, as investigated by immunohistochemical evaluations (by fluorescence microscopy with anti-neurofilament staining and Hoechst staining for growth pattern of nerve fibers), histological evaluations (by light microscopy with Meyer's modified trichrome staining and Toluidine blue staining and transmission electron microscopy for the regeneration of axon and myelin sheath), and FluoroGold retrograde tracing (for reconnection between proximal and distal stumps). The effect of nerve growth factor (NGF) immobilized on the pore surfaces of the NGCs on nerve regeneration was not so significant when compared with NGCs not containing immobilized NGF. The NGC system with different surface pore structures but the same chemical/physical properties seems to be a good tool that is used for elucidating the surface pore effect of NGCs on nerve regeneration. PMID:22871377

  11. 3D printing strategies for peripheral nerve regeneration.

    Science.gov (United States)

    Petcu, Eugen B; Midha, Rajiv; McColl, Erin; Popa-Wagner, Aurel; Chirila, Traian V; Dalton, Paul D

    2018-03-23

    After many decades of biomaterials research for peripheral nerve regeneration, a clinical product (the nerve guide), is emerging as a proven alternative for relatively short injury gaps. This review identifies aspects where 3D printing can assist in improving long-distance nerve guide regeneration strategies. These include (1) 3D printing of the customizable nerve guides, (2) fabrication of scaffolds that fill nerve guides, (3) 3D bioprinting of cells within a matrix/bioink into the nerve guide lumen and the (4) establishment of growth factor gradients along the length a nerve guide. The improving resolution of 3D printing technologies will be an important factor for peripheral nerve regeneration, as fascicular-like guiding structures provide one path to improved nerve guidance. The capability of 3D printing to manufacture complex structures from patient data based on existing medical imaging technologies is an exciting aspect that could eventually be applied to treating peripheral nerve injury. Ultimately, the goal of 3D printing in peripheral nerve regeneration is the automated fabrication, potentially customized for the patient, of structures within the nerve guide that significantly outperform the nerve autograft over large gap injuries.

  12. The vestibulocochlear nerve (VIII).

    Science.gov (United States)

    Benoudiba, F; Toulgoat, F; Sarrazin, J-L

    2013-10-01

    The vestibulocochlear nerve (8th cranial nerve) is a sensory nerve. It is made up of two nerves, the cochlear, which transmits sound and the vestibular which controls balance. It is an intracranial nerve which runs from the sensory receptors in the internal ear to the brain stem nuclei and finally to the auditory areas: the post-central gyrus and superior temporal auditory cortex. The most common lesions responsible for damage to VIII are vestibular Schwannomas. This report reviews the anatomy and various investigations of the nerve. Copyright © 2013. Published by Elsevier Masson SAS.

  13. Plate Tearing by a Cone

    DEFF Research Database (Denmark)

    Simonsen, Bo Cerup

    1998-01-01

    The present paper is concerned with steady-state plate tearing by a cone. This is a scenario where a cone is forced through a ductile metal plate with a constant lateral tip penetration in a motion in the plane of the plate. The considered process could be an idealisation of the damage, which...... as for the out-of-plane reaction force. (C) 1998 Elsevier Science Ltd. All rights reserved....

  14. Loss-cone-driven ion cyclotron waves in the magnetosphere

    International Nuclear Information System (INIS)

    Denton, R.E.; Hudson, M.K.; Roth, I.

    1992-01-01

    The theoretical properties of linear ion cyclotron waves propagating in the magnetosphere at arbitrary angles to the background magnetic field are explored. It is found that in some cases the linear wave growth of modes with oblique propagation can dominate that of the parallel propagating electromagnetic ion cyclotron (EMIC) wave. In particular, when the hot ring current protons have a loss cone and their temperature anisotropy A ≡ T perpendicular /T parallel - 1 is reduced, the parallel propagating EMIC wave becomes stable, while the obliquely propagating loss-cone-driven mode persists. The growth rate of the loss-cone-driven model depends strongly on the depth of the loss cone. Unlike the parallel propagating EMIC wave, it can be unstable with A = 0. Other conditions that favor the loss-cone-driven mode in comparison to the parallel mode are stronger background magnetic field, lower density of cold hydrogen, and a lower temperature for the hot anisotropic component of hydrogen. A simple analytical theory is presented which explains the scaling of the growth rate of the oblique mode with respect to various parameters. The loss-cone-driven mode is an electromagnetic mode which is preferentially nearly linearly polarized. It is nearly electrostatic in the sense that the wave electric field is aligned with the perpendicular (to B 0 ) component of the wave vector k and k perpendicular > k parallel . Since the electric and magnetic wave fields are perpendicular to B 0 , they would be difficult to distinguish from those of a linearly polarized parallel propagating electromagnetic wave with the same k parallel

  15. Light cone approach

    International Nuclear Information System (INIS)

    Brodsky, Stan

    1993-01-01

    One of the most challenging problems in theoretical high energy physics is to compute the bound state structure of the proton and other hadrons from quantum chromodynamics (QCD), the field theory of quarks and gluons. The goal is not only to calculate the spectrum of hadrons masses from first principles, but also to derive the momentum and spin distributions of the quarks and gluons which control high energy hadron interactions. One approach to these difficult calculations is to simulate QCD on an artificial lattice. Recently, several new methods based on ''light-cone'' quantization have been proposed as alternatives to lattice theory for solving non-perturbative problems in QCD and other field theories. The basic idea is a generalization of Heisenberg's pioneer matrix formulation of quantum mechanics: if one could numerically diagonalize the matrix of the Hamiltonian representing the underlying QCD interaction, then the resulting eigenvalues would give the hadron spectrum, while the corresponding eigenstates would describe each hadron in terms of its quark and gluon degrees of freedom

  16. Radial nerve dysfunction (image)

    Science.gov (United States)

    The radial nerve travels down the arm and supplies movement to the triceps muscle at the back of the upper arm. ... the wrist and hand. The usual causes of nerve dysfunction are direct trauma, prolonged pressure on the ...

  17. Degenerative Nerve Diseases

    Science.gov (United States)

    Degenerative nerve diseases affect many of your body's activities, such as balance, movement, talking, breathing, and heart function. Many ... viruses. Sometimes the cause is not known. Degenerative nerve diseases include Alzheimer's disease Amyotrophic lateral sclerosis Friedreich's ...

  18. Nerve conduction velocity

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003927.htm Nerve conduction velocity To use the sharing features on this page, please enable JavaScript. Nerve conduction velocity (NCV) is a test to see ...

  19. Distal median nerve dysfunction

    Science.gov (United States)

    ... later on. Inflammation of the tendons ( tendonitis ) or joints ( arthritis ) can also put pressure on the nerve. ... how fast electrical signals move through a nerve Neuromuscular ultrasound to view problems with the muscles and ...

  20. Large Extremity Peripheral Nerve Repair

    Science.gov (United States)

    2016-12-01

    LM, de Crombrugghe B. Some recent advances in the chemistry and biology of trans- forming growth factor-beta. J Cell Biol 1987;105:1039e45. 12. Hao Y...SUPPLEMENTARY NOTES 14. ABSTRACT In current war trauma, 20-30% of all extremity injuries and >80% of penetrating injuries being associated with peripheral nerve...through both axonal advance and in revascularization of the graft following placement. We are confident that this technology may allow us to

  1. Foveal cone spacing and cone photopigment density difference: objective measurements in the same subjects.

    Science.gov (United States)

    Marcos, S; Tornow, R P; Elsner, A E; Navarro, R

    1997-07-01

    Foveal cone spacing was measured in vivo using an objective technique: ocular speckle interferometry. Cone packing density was computed from cone spacing data. Foveal cone photopigment density difference was measured in the same subjects using retinal densitometry with a scanning laser ophthalmoscope. Both the cone packing density and cone photopigment density difference decreased sharply with increasing retinal eccentricity. From the comparison of both sets of measurements, the computed amounts of photopigment per cone increased slightly with increasing retinal eccentricity. Consistent with previous results, decreases in cone outer segment length are over-compensated by an increase in the outer segment area, at least in retinal eccentricities up to 1 deg.

  2. Optic Nerve Pit

    Science.gov (United States)

    ... Conditions Frequently Asked Questions Español Condiciones Chinese Conditions Optic Nerve Pit What is optic nerve pit? An optic nerve pit is a ... may be seen in both eyes. How is optic pit diagnosed? If the pit is not affecting ...

  3. Diagnostic nerve ultrasonography

    International Nuclear Information System (INIS)

    Baeumer, T.; Grimm, A.; Schelle, T.

    2017-01-01

    For the diagnostics of nerve lesions an imaging method is necessary to visualize peripheral nerves and their surrounding structures for an etiological classification. Clinical neurological and electrophysiological investigations provide functional information about nerve lesions. The information provided by a standard magnetic resonance imaging (MRI) examination is inadequate for peripheral nerve diagnostics; however, MRI neurography is suitable but on the other hand a resource and time-consuming method. Using ultrasonography for peripheral nerve diagnostics. With ultrasonography reliable diagnostics of entrapment neuropathies and traumatic nerve lesions are possible. The use of ultrasonography for neuropathies shows that a differentiation between different forms is possible. Nerve ultrasonography is an established diagnostic tool. In addition to the clinical examination and clinical electrophysiology, structural information can be obtained, which results in a clear improvement in the diagnostics. Ultrasonography has become an integral part of the diagnostic work-up of peripheral nerve lesions in neurophysiological departments. Nerve ultrasonography is recommended for the diagnostic work-up of peripheral nerve lesions in addition to clinical and electrophysiological investigations. It should be used in the clinical work-up of entrapment neuropathies, traumatic nerve lesions and spacy-occupying lesions of nerves. (orig.) [de

  4. The challenges and beauty of peripheral nerve regrowth.

    Science.gov (United States)

    Zochodne, Douglas W

    2012-03-01

    This review provides an overview of selected aspects of peripheral nerve regeneration and potential avenues to explore therapeutically. The overall coordinated and orchestrated pattern of recovery from peripheral nerve injury has a beauty of execution and progress that rivals all other forms of neurobiology. It involves changes at the level of the perikaryon, coordination with important peripheral glial partners, the Schwann cells, a controlled inflammatory response, and growth that overcomes surprising intrinsic roadblocks. Both regenerative axon growth and collateral sprouting encompass fascinating aspects of this story. Better understanding of peripheral nerve regeneration may also lead to enhanced central nervous system recovery. © 2012 Peripheral Nerve Society.

  5. Intraoperative cranial nerve monitoring.

    Science.gov (United States)

    Harper, C Michel

    2004-03-01

    The purpose of intraoperative monitoring is to preserve function and prevent injury to the nervous system at a time when clinical examination is not possible. Cranial nerves are delicate structures and are susceptible to damage by mechanical trauma or ischemia during intracranial and extracranial surgery. A number of reliable electrodiagnostic techniques, including nerve conduction studies, electromyography, and the recording of evoked potentials have been adapted to the study of cranial nerve function during surgery. A growing body of evidence supports the utility of intraoperative monitoring of cranial nerve nerves during selected surgical procedures.

  6. Axotomy induces MHC class I antigen expression on rat nerve cells

    DEFF Research Database (Denmark)

    Maehlen, J; Schröder, H D; Klareskog, L

    1988-01-01

    Immunomorphological staining demonstrates that class I major histocompatibility complex (MHC)-coded antigen expression can be selectively induced on otherwise class I-negative rat nerve cells by peripheral axotomy. Induction of class I as well as class II antigen expression was simultaneously seen...... on non-neural cells in the immediate vicinity of the injured nerve cells. As nerve regeneration after axotomy includes growth of new nerve cell processes and formation of new nerve cell contacts, the present findings raise the question of a role for MHC-coded molecules in cell-cell interactions during...... nerve cell growth....

  7. Optic nerve oxygenation

    DEFF Research Database (Denmark)

    Stefánsson, Einar; Pedersen, Daniella Bach; Jensen, Peter Koch

    2005-01-01

    The oxygen tension of the optic nerve is regulated by the intraocular pressure and systemic blood pressure, the resistance in the blood vessels and oxygen consumption of the tissue. The oxygen tension is autoregulated and moderate changes in intraocular pressure or blood pressure do not affect...... the optic nerve oxygen tension. If the intraocular pressure is increased above 40 mmHg or the ocular perfusion pressure decreased below 50 mmHg the autoregulation is overwhelmed and the optic nerve becomes hypoxic. A disturbance in oxidative metabolism in the cytochromes of the optic nerve can be seen...... at similar levels of perfusion pressure. The levels of perfusion pressure that lead to optic nerve hypoxia in the laboratory correspond remarkably well to the levels that increase the risk of glaucomatous optic nerve atrophy in human glaucoma patients. The risk for progressive optic nerve atrophy in human...

  8. Traumatic facial nerve neuroma with facial palsy presenting in infancy.

    Science.gov (United States)

    Clark, James H; Burger, Peter C; Boahene, Derek Kofi; Niparko, John K

    2010-07-01

    To describe the management of traumatic neuroma of the facial nerve in a child and literature review. Sixteen-month-old male subject. Radiological imaging and surgery. Facial nerve function. The patient presented at 16 months with a right facial palsy and was found to have a right facial nerve traumatic neuroma. A transmastoid, middle fossa resection of the right facial nerve lesion was undertaken with a successful facial nerve-to-hypoglossal nerve anastomosis. The facial palsy improved postoperatively. A traumatic neuroma should be considered in an infant who presents with facial palsy, even in the absence of an obvious history of trauma. The treatment of such lesion is complex in any age group but especially in young children. Symptoms, age, lesion size, growth rate, and facial nerve function determine the appropriate management.

  9. Testicular atrophy and loss of nerve growth factor-immunoreactive germ cell line in rats exposed to n-hexane and a protective effect of simultaneous exposure to toluene or xylene

    Energy Technology Data Exchange (ETDEWEB)

    Nylen, P; Johnson, A C; Hoeglund, G; Ebendal, T; Eriksdotter-Nilsson, M; Henschen, A; Olson, L; Hansson, T; Kronevi, T; Kvist, U

    1989-07-01

    Testicular and germ cell line morphology in rats were studied 2 weeks, 10 months and 14 months after cessation of a 61-day inhalation exposure to 1000 ppm n-hexane. Androgen biosynthetic capacity of testis, testosterone blood concentration, vas deferens morphology and noradrenaline (NA) concentration, epididymal sperm morphology, and fertility were also studied. Severe testicular atrophy involving the seminiferous tubules with loss of the nerve growth factor (NGF) immunoreactive germ cell line was found. Total loss of the germ cell line was found in a fraction of animals up to 14 months post-exposure, indicating permanent testicular damage. No impairment of androgen synthesis or androgen dependent accessory organs was observed. Simultaneous administration of 1000 ppm n-hexane and 1000 ppm toluene, or 1000 ppm n-hexane and 1000 ppm xylene, did not cause germ cell line alterations or testicular atrophy. Toluene and xylene were thus found to protect from n-hexane induced testicular atrophy. (orig.).

  10. Cone-Beam Computed Tomography Evaluation of Mental Foramen Variations: A Preliminary Study

    International Nuclear Information System (INIS)

    Sheikhi, Mahnaz; Karbasi Kheir, Mitra; Hekmatian, Ehsan

    2015-01-01

    Background. Mental foramen is important in surgical operations of premolars because it transfers the mental nerves and vessels. This study evaluated the variations of mental foramen by cone-beam computed tomography among a selected Iranian population. Materials and Methods. A total number of 180 cone-beam computed tomography projections were analyzed in terms of shape, size, direction, and horizontal and vertical positions of mental foramen in the right and left sides. Results. The most common shape was oval, opening direction was posterior-superior, horizontal position was in line with second premolar, and vertical position was apical to the adjacent dental root. The mean of foremen diameter was 3.59 mm. Conclusion. In addition to the most common types of mental foramen, other variations exist, too. Hence, it reflects the significance of preoperative radiographic examinations, especially 3-dimensional images to prevent nerve damage

  11. MiR-203 involves in neuropathic pain development and represses Rap1a expression in nerve growth factor differentiated neuronal PC12 cells.

    Science.gov (United States)

    Li, Haixia; Huang, Yuguang; Ma, Chao; Yu, Xuerong; Zhang, Zhiyong; Shen, Le

    2015-01-01

    Although microRNAs (miRNAs) have been shown to play a role in numerous biological processes, their function in neuropathic pain is not clear. The rat bilateral sciatic nerve chronic constriction injury (bCCI) is an established model of neuropathic pain, so we examined miRNA expression and function in the spinal dorsal horn in bCCI rats. Microarray and real-time polymerase chain reaction were used to examine the expression of miRNA in nerve system of bCCI rats, and the targets of miRNA were predicted by bioinformatic approaches. The function of specific miRNA was estimated through the methods of gene engineering. This study revealed substantially (∼10-fold) decreased miR-203 expression in the spinal dorsal horns but not the dorsal root ganglions, hippocampus, or anterior cingulate cortexes of bCCI rats. Rap1a protein expression was upregulated in bCCI rat spinal dorsal horns. We further verified that miR-203 directly targeted the 3'-untranslated region of the rap1a gene, thereby decreasing rap1a protein expression in neuron-like cells. Rap1a has diverse neuronal functions and their perturbation is responsible for several mental disorders. For example, Rap1a/MEK/ERK is involved in peripheral sensitization. These data suggest a potential role for miR-203 in regulating neuropathic pain development, and Rap1a is a validated target gene in vitro. Results from our study and others indicate the possibility that Rap1a may be involved in pain. We hope that these results can provide support for future research into miR-203 in gene therapy for neuropathic pain.

  12. Imaging the trigeminal nerve

    International Nuclear Information System (INIS)

    Borges, Alexandra; Casselman, Jan

    2010-01-01

    Of all cranial nerves, the trigeminal nerve is the largest and the most widely distributed in the supra-hyoid neck. It provides sensory input from the face and motor innervation to the muscles of mastication. In order to adequately image the full course of the trigeminal nerve and its main branches a detailed knowledge of neuroanatomy and imaging technique is required. Although the main trunk of the trigeminal nerve is consistently seen on conventional brain studies, high-resolution tailored imaging is mandatory to depict smaller nerve branches and subtle pathologic processes. Increasing developments in imaging technique made possible isotropic sub-milimetric images and curved reconstructions of cranial nerves and their branches and led to an increasing recognition of symptomatic trigeminal neuropathies. Whereas MRI has a higher diagnostic yield in patients with trigeminal neuropathy, CT is still required to demonstrate the bony anatomy of the skull base and is the modality of choice in the context of traumatic injury to the nerve. Imaging of the trigeminal nerve is particularly cumbersome as its long course from the brainstem nuclei to the peripheral branches and its rich anastomotic network impede, in most cases, a topographic approach. Therefore, except in cases of classic trigeminal neuralgia, in which imaging studies can be tailored to the root entry zone, the full course of the trigeminal nerve has to be imaged. This article provides an update in the most recent advances on MR imaging technique and a segmental imaging approach to the most common pathologic processes affecting the trigeminal nerve.

  13. Imaging the trigeminal nerve

    Energy Technology Data Exchange (ETDEWEB)

    Borges, Alexandra [Radiology Department, Instituto Portugues de Oncologia Francisco Gentil, Centro de Lisboa, Rua Prof. Lima Basto, 1093, Lisboa (Portugal)], E-mail: borgalexandra@gmail.com; Casselman, Jan [Department of Radiology, A. Z. St Jan Brugge and A. Z. St Augustinus Antwerpen Hospitals (Belgium)

    2010-05-15

    Of all cranial nerves, the trigeminal nerve is the largest and the most widely distributed in the supra-hyoid neck. It provides sensory input from the face and motor innervation to the muscles of mastication. In order to adequately image the full course of the trigeminal nerve and its main branches a detailed knowledge of neuroanatomy and imaging technique is required. Although the main trunk of the trigeminal nerve is consistently seen on conventional brain studies, high-resolution tailored imaging is mandatory to depict smaller nerve branches and subtle pathologic processes. Increasing developments in imaging technique made possible isotropic sub-milimetric images and curved reconstructions of cranial nerves and their branches and led to an increasing recognition of symptomatic trigeminal neuropathies. Whereas MRI has a higher diagnostic yield in patients with trigeminal neuropathy, CT is still required to demonstrate the bony anatomy of the skull base and is the modality of choice in the context of traumatic injury to the nerve. Imaging of the trigeminal nerve is particularly cumbersome as its long course from the brainstem nuclei to the peripheral branches and its rich anastomotic network impede, in most cases, a topographic approach. Therefore, except in cases of classic trigeminal neuralgia, in which imaging studies can be tailored to the root entry zone, the full course of the trigeminal nerve has to be imaged. This article provides an update in the most recent advances on MR imaging technique and a segmental imaging approach to the most common pathologic processes affecting the trigeminal nerve.

  14. Side-To-Side Nerve Bridges Support Donor Axon Regeneration Into Chronically Denervated Nerves and Are Associated With Characteristic Changes in Schwann Cell Phenotype.

    Science.gov (United States)

    Hendry, J Michael; Alvarez-Veronesi, M Cecilia; Snyder-Warwick, Alison; Gordon, Tessa; Borschel, Gregory H

    2015-11-01

    Chronic denervation resulting from long nerve regeneration times and distances contributes greatly to suboptimal outcomes following nerve injuries. Recent studies showed that multiple nerve grafts inserted between an intact donor nerve and a denervated distal recipient nerve stump (termed "side-to-side nerve bridges") enhanced regeneration after delayed nerve repair. To examine the cellular aspects of axon growth across these bridges to explore the "protective" mechanism of donor axons on chronically denervated Schwann cells. In Sprague Dawley rats, 3 side-to-side nerve bridges were placed over a 10-mm distance between an intact donor tibial (TIB) nerve and a recipient denervated common peroneal (CP) distal nerve stump. Green fluorescent protein-expressing TIB axons grew across the bridges and were counted in cross section after 4 weeks. Immunofluorescent axons and Schwann cells were imaged over a 4-month period. Denervated Schwann cells dedifferentiated to a proliferative, nonmyelinating phenotype within the bridges and the recipient denervated CP nerve stump. As donor TIB axons grew across the 3 side-to-side nerve bridges and into the denervated CP nerve, the Schwann cells redifferentiated to the myelinating phenotype. Bridge placement led to an increased mass of hind limb anterior compartment muscles after 4 months of denervation compared with muscles whose CP nerve was not "protected" by bridges. This study describes patterns of donor axon regeneration and myelination in the denervated recipient nerve stump and supports a mechanism where these donor axons sustain a proregenerative state to prevent deterioration in the face of chronic denervation.

  15. DOS cones along atomic chains

    Science.gov (United States)

    Kwapiński, Tomasz

    2017-03-01

    The electron transport properties of a linear atomic chain are studied theoretically within the tight-binding Hamiltonian and the Green’s function method. Variations of the local density of states (DOS) along the chain are investigated. They are crucial in scanning tunnelling experiments and give important insight into the electron transport mechanism and charge distribution inside chains. It is found that depending on the chain parity the local DOS at the Fermi level can form cone-like structures (DOS cones) along the chain. The general condition for the local DOS oscillations is obtained and the linear behaviour of the local density function is confirmed analytically. DOS cones are characterized by a linear decay towards the chain which is in contrast to the propagation properties of charge density waves, end states and Friedel oscillations in one-dimensional systems. We find that DOS cones can appear due to non-resonant electron transport, the spin-orbit scattering or for chains fabricated on a substrate with localized electrons. It is also shown that for imperfect chains (e.g. with a reduced coupling strength between two neighboring sites) a diamond-like structure of the local DOS along the chain appears.

  16. DOS cones along atomic chains

    International Nuclear Information System (INIS)

    Kwapiński, Tomasz

    2017-01-01

    The electron transport properties of a linear atomic chain are studied theoretically within the tight-binding Hamiltonian and the Green’s function method. Variations of the local density of states (DOS) along the chain are investigated. They are crucial in scanning tunnelling experiments and give important insight into the electron transport mechanism and charge distribution inside chains. It is found that depending on the chain parity the local DOS at the Fermi level can form cone-like structures (DOS cones) along the chain. The general condition for the local DOS oscillations is obtained and the linear behaviour of the local density function is confirmed analytically. DOS cones are characterized by a linear decay towards the chain which is in contrast to the propagation properties of charge density waves, end states and Friedel oscillations in one-dimensional systems. We find that DOS cones can appear due to non-resonant electron transport, the spin–orbit scattering or for chains fabricated on a substrate with localized electrons. It is also shown that for imperfect chains (e.g. with a reduced coupling strength between two neighboring sites) a diamond-like structure of the local DOS along the chain appears. (paper)

  17. Ejecta evolution during cone impact

    KAUST Repository

    Marston, Jeremy; Thoroddsen, Sigurdur T

    2014-01-01

    -similarity for all impact speeds for very low surface tension liquids, whilst for high-surface tension liquids similarity is only achieved at high impact speeds. We find that the ejecta tip can detach from the cone and that this phenomenon can be attributed

  18. A biosynthetic nerve guide conduit based on silk/SWNT/fibronectin nanocomposite for peripheral nerve regeneration.

    Directory of Open Access Journals (Sweden)

    Fatemeh Mottaghitalab

    Full Text Available As a contribution to the functionality of nerve guide conduits (NGCs in nerve tissue engineering, here we report a conduit processing technique through introduction and evaluation of topographical, physical and chemical cues. Porous structure of NGCs based on freeze-dried silk/single walled carbon nanotubes (SF/SWNTs has shown a uniform chemical and physical structure with suitable electrical conductivity. Moreover, fibronectin (FN containing nanofibers within the structure of SF/SWNT conduits produced through electrospinning process have shown aligned fashion with appropriate porosity and diameter. Moreover, fibronectin remained its bioactivity and influenced the adhesion and growth of U373 cell lines. The conduits were then implanted to 10 mm left sciatic nerve defects in rats. The histological assessment has shown that nerve regeneration has taken places in proximal region of implanted nerve after 5 weeks following surgery. Furthermore, nerve conduction velocities (NCV and more myelinated axons were observed in SF/SWNT and SF/SWNT/FN groups after 5 weeks post implantation, indicating a functional recovery for the injured nerves. With immunohistochemistry, the higher S-100 expression of Schwann cells in SF/SWNT/FN conduits in comparison to other groups was confirmed. In conclusion, an oriented conduit of biocompatible SF/SWNT/FN has been fabricated with acceptable structure that is particularly applicable in nerve grafts.

  19. Trends in the design of nerve guidance channels in peripheral nerve tissue engineering.

    Science.gov (United States)

    Chiono, Valeria; Tonda-Turo, Chiara

    2015-08-01

    The current trend of peripheral nerve tissue engineering is the design of advanced nerve guidance channels (NGCs) acting as physical guidance for regeneration of nerves across lesions. NGCs should present multifunctional properties aiming to direct the sprouting of axons from the proximal nerve end, to concentrate growth factors secreted by the injured nerve ends, and to reduce the ingrowth of scar tissue into the injury site. A critical aspect in the design of NGCs is conferring them the ability to provide topographic, chemotactic and haptotactic cues that lead to functional nerve regeneration thus increasing the axon growth rate and avoiding or minimizing end-organ (e.g. muscle) atrophy. The present work reviews the recent state of the art in NGCs engineering and defines the external guide and internal fillers structural and compositional requirements that should be satisfied to improve nerve regeneration, especially in the case of large gaps (>2 cm). Techniques for NGCs fabrication were described highlighting the innovative approaches direct to enhance the regeneration of axon stumps compared to current clinical treatments. Furthermore, the possibility to apply stem cells as internal cues to the NGCs was discussed focusing on scaffold properties necessary to ensure cell survival. Finally, the optimized features for NGCs design were summarized showing as multifunctional cues are needed to produce NGCs having improved results in clinics. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Conjoined lumbosacral nerve roots

    International Nuclear Information System (INIS)

    Kyoshima, Kazumitsu; Nishiura, Iwao; Koyama, Tsunemaro

    1986-01-01

    Several kinds of the lumbosacral nerve root anomalies have already been recognized, and the conjoined nerve roots is the most common among them. It does not make symptoms by itself, but if there is a causation of neural entrapment, for example, disc herniation, lateral recessus stenosis, spondylolisthesis, etc., so called ''biradicular syndrome'' should occur. Anomalies of the lumbosacral nerve roots, if not properly recognized, may lead to injury of these nerves during operation of the lumbar spine. Recently, the chance of finding these anomalous roots has been increased more and more with the use of metrizamide myelography and metrizamide CT, because of the improvement of the opacification of nerve roots. We describe the findings of the anomalous roots as revealed by these two methods. They demonstrate two nerve roots running parallel and the asymmetrical wide root sleeve. Under such circumstances, it is important to distinguish the anomalous roots from the normal ventral and dorsal roots. (author)

  1. Hanford waste tank cone penetrometer

    International Nuclear Information System (INIS)

    Seda, R.Y.

    1995-12-01

    A new tool is being developed to characterize tank waste at the Hanford Reservation. This tool, known as the cone penetrometer, is capable of obtaining chemical and physical properties in situ. For the past 50 years, this tool has been used extensively in soil applications and now has been modified for usage in Hanford Underground Storage tanks. These modifications include development of new ''waste'' data models as well as hardware design changes to accommodate the hazardous and radioactive environment of the tanks. The modified cone penetrometer is scheduled to be deployed at Hanford by Fall 1996. At Hanford, the cone penetrometer will be used as an instrumented pipe which measures chemical and physical properties as it pushes through tank waste. Physical data, such as tank waste stratification and mechanical properties, is obtained through three sensors measuring tip pressure, sleeve friction and pore pressure. Chemical data, such as chemical speciation, is measured using a Raman spectroscopy sensor. The sensor package contains other instrumentation as well, including a tip and side temperature sensor, tank bottom detection and an inclinometer. Once the cone penetrometer has reached the bottom of the tank, a moisture probe will be inserted into the pipe. This probe is used to measure waste moisture content, water level, waste surface moisture and tank temperature. This paper discusses the development of this new measurement system. Data from the cone penetrometer will aid in the selection of sampling tools, waste tank retrieval process, and addressing various tank safety issues. This paper will explore various waste models as well as the challenges associated with tank environment

  2. [Facial nerve neurinomas].

    Science.gov (United States)

    Sokołowski, Jacek; Bartoszewicz, Robert; Morawski, Krzysztof; Jamróz, Barbara; Niemczyk, Kazimierz

    2013-01-01

    Evaluation of diagnostic, surgical technique, treatment results facial nerve neurinomas and its comparison with literature was the main purpose of this study. Seven cases of patients (2005-2011) with facial nerve schwannomas were included to retrospective analysis in the Department of Otolaryngology, Medical University of Warsaw. All patients were assessed with history of the disease, physical examination, hearing tests, computed tomography and/or magnetic resonance imaging, electronystagmography. Cases were observed in the direction of potential complications and recurrences. Neurinoma of the facial nerve occurred in the vertical segment (n=2), facial nerve geniculum (n=1) and the internal auditory canal (n=4). The symptoms observed in patients were analyzed: facial nerve paresis (n=3), hearing loss (n=2), dizziness (n=1). Magnetic resonance imaging and computed tomography allowed to confirm the presence of the tumor and to assess its staging. Schwannoma of the facial nerve has been surgically removed using the middle fossa approach (n=5) and by antromastoidectomy (n=2). Anatomical continuity of the facial nerve was achieved in 3 cases. In the twelve months after surgery, facial nerve paresis was rated at level II-III° HB. There was no recurrence of the tumor in radiological observation. Facial nerve neurinoma is a rare tumor. Currently surgical techniques allow in most cases, the radical removing of the lesion and reconstruction of the VII nerve function. The rate of recurrence is low. A tumor of the facial nerve should be considered in the differential diagnosis of nerve VII paresis. Copyright © 2013 Polish Otorhinolaryngology - Head and Neck Surgery Society. Published by Elsevier Urban & Partner Sp. z.o.o. All rights reserved.

  3. Growth

    Science.gov (United States)

    John R. Jones; George A. Schier

    1985-01-01

    This chapter considers aspen growth as a process, and discusses some characteristics of the growth and development of trees and stands. For the most part, factors affecting growth are discussed elsewhere, particularly in the GENETICS AND VARIATION chapter and in chapters in PART 11. ECOLOGY. Aspen growth as it relates to wood production is examined in the WOOD RESOURCE...

  4. Novel drug delivering conduit for peripheral nerve regeneration

    Science.gov (United States)

    Labroo, Pratima; Shea, Jill; Edwards, Kyle; Ho, Scott; Davis, Brett; Sant, Himanshu; Goodwin, Isak; Gale, Bruce; Agarwal, Jay

    2017-12-01

    Objective. This paper describes the design of a novel drug delivery apparatus integrated with a poly lactic-co-glycolic acid (PLGA) based nerve guide conduit for controlled local delivery of nerve growth factor (NGF) and application in peripheral nerve gap injury. Approach. An NGF dosage curve was acquired to determine the minimum in vitro concentration for optimal neurite outgrowth of dorsal root ganglion (DRG) cells; PLGA based drug delivery devices were then designed and tested in vitro and in vivo across 15 mm rat sciatic nerve gap injury model. Main results. The drug delivery nerve guide was able to release NGF for 28 d at concentrations (0.1-10 ng ml-1) that were shown to enhance DRG neurite growth. Furthermore, the released NGF was bioactive and able to enhance DRG neurite growth. Following these tests, optimized NGF-releasing nerve conduits were implanted across 15 mm sciatic nerve gaps in a rat model, where they demonstrated significant myelination and muscle innervation in vivo as compared to empty nerve conduits (p  design process and provides increased versatility for releasing a variety of different growth factors. This innovative device has the potential for broad applicability and allows for easier customization to change the type of drugs and dosage of individual drugs without devising a completely new biomaterial-drug conjugate each time.

  5. Enhancing Peripheral Nerve Regeneration with a Novel Drug-Delivering Nerve Conduit

    Science.gov (United States)

    2015-10-01

    our novel nerve conduit. 15. SUBJECT TERMS 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE...growth in dorsal root ganglion ( DRG ) cell culture Tasks/Subtasks: 1. In Vitro NGF/GNDF release kinetics experiments.......................... (Gale...Axonal growth of DRGs ................................................................ (Terry, Shea) (11-18months) Progress: We have started these

  6. Intratemporal and extratemporal facial nerve schwannoma: CT and MRI findings

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Keum Won [Pohang Medical Center, Pohang (Korea, Republic of); Lee, Ho Kyu; Shin, Ji Hoon; Choi, Choong Gon; Suh, Dae Chul [Asan Medical Center, Ulsan Univ. College of Medicine, Seoul (Korea, Republic of); Cheong, Hae Kwan [Dongguk Univ. College of Medicine, Seoul (Korea, Republic of)

    2001-05-01

    To analyze the characteristics of CT and MRI findings of facial nerve schwannoma in ten patients. Ten patients with pathologically confirmed facial nerve schwannoma, underwent physical and radilolgic examination. The latter involved MRI in all ten and CT scanning in six. We analyzed the location (epicenter), extent and number of involved segments of tumors, tuumor morphology, and changes in adjacent bony structures. The major symptoms of facial nerve schwannoma were facial nerve paralysis in seven cases and hearing loss in six. Epicenters were detected at the intraparotid portion in five cases, the intracanalicular portion in two, the cisternal portion in one, and the intratemporal portion in two. The segment most frequently involved was the mastoid (n=6), followed by the parotid (n=5), intracanalicular (n=4), cisternal (n=2), the labyrinthine/geniculate ganglion (n=2) and the tympanic segment (n=1). Tumors affected two segments of the facial nerve in eight cases, only one segment in one, and four continuous segments in one. Morphologically, tumors were ice-cream cone shaped in the cisternal segment tumor (1/1), cone shaped in intracanalicular tumors (2/2), oval shaped in geniculate ganglion tumors (1/1), club shaped in intraparotid tumors (5/5) and bead shaped in the diffuse-type tumor (1/1). Changes in adjacent bony structures involved widening of the stylomastoid foramen in intraparotid tumors (5/5), widening of the internal auditary canal in intracanalicular and cisternal tumors (3/3), bony erosion of the geniculate fossa in geniculate ganglion tumors (2/2), and widening of the facial nerve canal in intratemporal and intraparotid tumors (6/6). The characteristic location, shape and change in adjacent bony structures revealed by facial schwannomas on CT and MR examination lead to correct diagnosis.

  7. Intratemporal and extratemporal facial nerve schwannoma: CT and MRI findings

    International Nuclear Information System (INIS)

    Kim, Keum Won; Lee, Ho Kyu; Shin, Ji Hoon; Choi, Choong Gon; Suh, Dae Chul; Cheong, Hae Kwan

    2001-01-01

    To analyze the characteristics of CT and MRI findings of facial nerve schwannoma in ten patients. Ten patients with pathologically confirmed facial nerve schwannoma, underwent physical and radilolgic examination. The latter involved MRI in all ten and CT scanning in six. We analyzed the location (epicenter), extent and number of involved segments of tumors, tuumor morphology, and changes in adjacent bony structures. The major symptoms of facial nerve schwannoma were facial nerve paralysis in seven cases and hearing loss in six. Epicenters were detected at the intraparotid portion in five cases, the intracanalicular portion in two, the cisternal portion in one, and the intratemporal portion in two. The segment most frequently involved was the mastoid (n=6), followed by the parotid (n=5), intracanalicular (n=4), cisternal (n=2), the labyrinthine/geniculate ganglion (n=2) and the tympanic segment (n=1). Tumors affected two segments of the facial nerve in eight cases, only one segment in one, and four continuous segments in one. Morphologically, tumors were ice-cream cone shaped in the cisternal segment tumor (1/1), cone shaped in intracanalicular tumors (2/2), oval shaped in geniculate ganglion tumors (1/1), club shaped in intraparotid tumors (5/5) and bead shaped in the diffuse-type tumor (1/1). Changes in adjacent bony structures involved widening of the stylomastoid foramen in intraparotid tumors (5/5), widening of the internal auditary canal in intracanalicular and cisternal tumors (3/3), bony erosion of the geniculate fossa in geniculate ganglion tumors (2/2), and widening of the facial nerve canal in intratemporal and intraparotid tumors (6/6). The characteristic location, shape and change in adjacent bony structures revealed by facial schwannomas on CT and MR examination lead to correct diagnosis

  8. Overexpression of copper/zinc-superoxide dismutase in transgenic mice markedly impairs regeneration and increases development of neuropathic pain after sciatic nerve injury.

    Science.gov (United States)

    Kotulska, Katarzyna; LePecheur, Marie; Marcol, Wiesław; Lewin-Kowalik, Joanna; Larysz-Brysz, Magdalena; Paly, Evelyn; Matuszek, Iwona; London, Jacqueline

    2006-10-01

    Despite the general capacity of peripheral nervous system to regenerate, peripheral nerve injury is often followed by incomplete recovery of function, sometimes with the burden of neuropathic pain. The mechanisms of both regeneration and nociception have not been clarified, but it is known that inflammatory reactions are involved. Cu/Zn-superoxide dismutase (SOD1) is an important scavenger protein that acts against oxidative stress. It has been shown to play an important role in apoptosis and inflammation. The aim of this study was to examine the role of SOD1 overexpression in peripheral nerve regeneration and neuropathic pain-related behavior in mice. Sciatic nerves of SOD1-overexpressing and FVB/N wild type-mice were transected and immediately resutured. Evaluation of motor and sensory function and autotomy was carried out during 4 weeks of followup. We found markedly worse sciatic function index outcome as well as more significant atrophy of denervated muscles in SOD1-overexpressing animals compared with wild type. Autotomy was markedly worse in SOD1 transgenic mice than in wild-type animals. Histological evaluation revealed that the intensity of regeneration features, including numbers of GAP-43-positive growth cones, Schwann cells, and macrophages in the distal stump of the transected nerve, was also decreased in transgenic mice. Neuroma formation at the injury site was significantly more prominent in this group. Taken together, our findings suggest that SOD1 overexpression is deleterious for nerve regeneration processes and aggravates neuropathic pain-like state in mice. This can be at least partially ascribed to disturbed inflammatory reactions at the injury site. Copyright 2006 Wiley-Liss, Inc.

  9. Communication between radial nerve and medial cutaneous nerve of forearm

    Directory of Open Access Journals (Sweden)

    R R Marathe

    2010-01-01

    Full Text Available Radial nerve is usually a branch of the posterior cord of the brachial plexus. It innervates triceps, anconeous, brachialis, brachioradialis, extensor carpi radialis longus muscles and gives the posterior cutaneous nerve of the arm, lower lateral cutaneous nerve of arm, posterior cutaneous nerve of forearm; without exhibiting any communication with the medial cutaneous nerve of forearm or any other nerve. We report communication between the radial nerve and medial cutaneous nerve of forearm on the left side in a 58-year-old male cadaver. The right sided structures were found to be normal. Neurosurgeons should keep such variations in mind while performing the surgeries of axilla and upper arm.

  10. Engineering a multimodal nerve conduit for repair of injured peripheral nerve

    Science.gov (United States)

    Quigley, A. F.; Bulluss, K. J.; Kyratzis, I. L. B.; Gilmore, K.; Mysore, T.; Schirmer, K. S. U.; Kennedy, E. L.; O'Shea, M.; Truong, Y. B.; Edwards, S. L.; Peeters, G.; Herwig, P.; Razal, J. M.; Campbell, T. E.; Lowes, K. N.; Higgins, M. J.; Moulton, S. E.; Murphy, M. A.; Cook, M. J.; Clark, G. M.; Wallace, G. G.; Kapsa, R. M. I.

    2013-02-01

    Injury to nerve tissue in the peripheral nervous system (PNS) results in long-term impairment of limb function, dysaesthesia and pain, often with associated psychological effects. Whilst minor injuries can be left to regenerate without intervention and short gaps up to 2 cm can be sutured, larger or more severe injuries commonly require autogenous nerve grafts harvested from elsewhere in the body (usually sensory nerves). Functional recovery is often suboptimal and associated with loss of sensation from the tissue innervated by the harvested nerve. The challenges that persist with nerve repair have resulted in development of nerve guides or conduits from non-neural biological tissues and various polymers to improve the prognosis for the repair of damaged nerves in the PNS. This study describes the design and fabrication of a multimodal controlled pore size nerve regeneration conduit using polylactic acid (PLA) and (PLA):poly(lactic-co-glycolic) acid (PLGA) fibers within a neurotrophin-enriched alginate hydrogel. The nerve repair conduit design consists of two types of PLGA fibers selected specifically for promotion of axonal outgrowth and Schwann cell growth (75:25 for axons; 85:15 for Schwann cells). These aligned fibers are contained within the lumen of a knitted PLA sheath coated with electrospun PLA nanofibers to control pore size. The PLGA guidance fibers within the nerve repair conduit lumen are supported within an alginate hydrogel impregnated with neurotrophic factors (NT-3 or BDNF with LIF, SMDF and MGF-1) to provide neuroprotection, stimulation of axonal growth and Schwann cell migration. The conduit was used to promote repair of transected sciatic nerve in rats over a period of 4 weeks. Over this period, it was observed that over-grooming and self-mutilation (autotomy) of the limb implanted with the conduit was significantly reduced in rats implanted with the full-configuration conduit compared to rats implanted with conduits containing only an alginate

  11. NMNAT1 variants cause cone and cone-rod dystrophy.

    Science.gov (United States)

    Nash, Benjamin M; Symes, Richard; Goel, Himanshu; Dinger, Marcel E; Bennetts, Bruce; Grigg, John R; Jamieson, Robyn V

    2018-03-01

    Cone and cone-rod dystrophies (CD and CRD, respectively) are degenerative retinal diseases that predominantly affect the cone photoreceptors. The underlying disease gene is not known in approximately 75% of autosomal recessive cases. Variants in NMNAT1 cause a severe, early-onset retinal dystrophy called Leber congenital amaurosis (LCA). We report two patients where clinical phenotyping indicated diagnoses of CD and CRD, respectively. NMNAT1 variants were identified, with Case 1 showing an extremely rare homozygous variant c.[271G > A] p.(Glu91Lys) and Case 2 compound heterozygous variants c.[53 A > G];[769G > A] p.(Asn18Ser);(Glu257Lys). The detailed variant analysis, in combination with the observation of an associated macular atrophy phenotype, indicated that these variants were disease-causing. This report demonstrates that the variants in NMNAT1 may cause CD or CRD associated with macular atrophy. Genetic investigations of the patients with CD or CRD should include NMNAT1 in the genes examined.

  12. Silk fibroin enhances peripheral nerve regeneration by improving vascularization within nerve conduits.

    Science.gov (United States)

    Wang, Chunyang; Jia, Yachao; Yang, Weichao; Zhang, Cheng; Zhang, Kuihua; Chai, Yimin

    2018-07-01

    Silk fibroin (SF)-based nerve conduits have been widely used to bridge peripheral nerve defects. Our previous study showed that nerve regeneration in a SF-blended poly (l-lactide-co-ɛ-caprolactone) [P(LLA-CL)] nerve conduit is better than that in a P(LLA-CL) conduit. However, the involved mechanisms remain unclarified. Because angiogenesis within a nerve conduit plays an important role in nerve regeneration, vascularization of SF/P(LLA-CL) and P(LLA-CL) conduits was compared both in vitro and in vivo. In the present study, we observed that SF/P(LLA-CL) nanofibers significantly promoted fibroblast proliferation, and vascular endothelial growth factor secreted by fibroblasts seeded in SF/P(LLA-CL) nanofibers was more than seven-fold higher than that in P(LLA-CL) nanofibers. Conditioned medium of fibroblasts in the SF/P(LLA-CL) group stimulated more human umbilical vein endothelial cells (HUVEC) to form capillary-like networks and promoted faster HUVEC migration. The two kinds of nerve conduits were used to bridge 10-mm-length nerve defects in rats. At 3 weeks of reparation, the blood vessel area in the SF/P(LLA-CL) group was significantly larger than that in the P(LLA-CL) group. More regenerated axons and Schwann cells were also observed in the SF/P(LLA-CL) group, which was consistent with the results of blood vessels. Collectively, our data revealed that the SF/P(LLA-CL) nerve conduit enhances peripheral nerve regeneration by improving angiogenesis within the conduit. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2070-2077, 2018. © 2018 Wiley Periodicals, Inc.

  13. Recovery of whisking function promoted by manual stimulation of the vibrissal muscles after facial nerve injury requires insulin-like growth factor 1 (IGF-1).

    Science.gov (United States)

    Kiryakova, S; Söhnchen, J; Grosheva, M; Schuetz, U; Marinova, Ts; Dzhupanova, R; Sinis, N; Hübbers, C U; Skouras, E; Ankerne, J; Fries, J W U; Irintchev, A; Dunlop, S A; Angelov, D N

    2010-04-01

    Recently, we showed that manual stimulation (MS) of denervated vibrissal muscles enhanced functional recovery following facial nerve cut and suture (FFA) by reducing poly-innervation at the neuro-muscular junctions (NMJ). Although the cellular correlates of poly-innervation are established, with terminal Schwann cells (TSC) processes attracting axon sprouts to "bridge" adjacent NMJ, molecular correlates are poorly understood. Since quantitative RT-PCR revealed a rapid increase of IGF-1 mRNA in denervated muscles, we examined the effect of daily MS for 2 months after FFA in IGF-1(+/-) heterozygous mice; controls were wild-type (WT) littermates including intact animals. We quantified vibrissal motor performance and the percentage of NMJ bridged by S100-positive TSC. There were no differences between intact WT and IGF-1(+/-) mice for vibrissal whisking amplitude (48 degrees and 49 degrees ) or the percentage of bridged NMJ (0%). After FFA and handling alone (i.e. no MS) in WT animals, vibrissal whisking amplitude was reduced (60% lower than intact) and the percentage of bridged NMJ increased (42% more than intact). MS improved both the amplitude of vibrissal whisking (not significantly different from intact) and the percentage of bridged NMJ (12% more than intact). After FFA and handling in IGF-1(+/-) mice, the pattern was similar (whisking amplitude 57% lower than intact; proportion of bridged NMJ 42% more than intact). However, MS did not improve outcome (whisking amplitude 47% lower than intact; proportion of bridged NMJ 40% more than intact). We conclude that IGF-I is required to mediate the effects of MS on target muscle reinnervation and recovery of whisking function. Copyright 2010 Elsevier Inc. All rights reserved.

  14. Isolated optic nerve pseudotumour

    International Nuclear Information System (INIS)

    Patankar, T.; Prasad, S.; Krishnan, A.; Laxminarayan, R.

    2000-01-01

    Isolated optic nerve involvement by the idiopathic inflammatory process is a rare finding and very few reports are available. Here a case of an isolated optic nerve inflammatory pseudotumour presenting with gradually progressive unilateral loss of vision is described. It showed dramatic response to a trial of steroids and its differential diagnoses are discussed. Copyright (1999) Blackwell Science Pty Ltd

  15. Axillary nerve dysfunction

    Science.gov (United States)

    ... changes in sensation or movement No history of injury to the area No signs of nerve damage These medicines reduce swelling and pressure on the nerve. They may be injected directly into the area or taken by mouth. Other medicines include: Over-the-counter pain ...

  16. Tibial nerve (image)

    Science.gov (United States)

    ... nerve is commonly injured by fractures or other injury to the back of the knee or the lower leg. It may be affected by systemic diseases such as diabetes mellitus. The nerve can also be damaged by pressure from a tumor, abscess, or bleeding into the ...

  17. Ultrasound diagnosis of postoperative complications of nerve repair.

    Science.gov (United States)

    Fantoni, Caterina; Erra, Carmen; Fernandez Marquez, Eduardo Marcos; Ortensi, Andrea; Faiola, Andrea; Coraci, Daniele; Piccinini, Giulia; Padua, Luca

    2018-05-03

    Peripheral nerve injuries often undergo surgical repair, but poor postoperative functional recovery is frequently observed. We describe four cases of traumatic nerve lesions in whom postoperative recovery was prevented by complications such as detachment of nerve sutures or neuroma growth. To the best of our knowledge no similar cases have been reported in literature so far. It is important an early diagnosis of such condition because it prevents recovery and delays re-intervention, which should be performed before complete muscle denervation and atrophy. Nerve ultrasound is a valuable tool in traumatic nerve injury and has proven to be useful in postoperative follow-up, especially in diagnosing surgical complications such as detachment of nerve direct sutures. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. [Experimental studies for the improvement of facial nerve regeneration].

    Science.gov (United States)

    Guntinas-Lichius, O; Angelov, D N

    2008-02-01

    Using a combination of the following, it is possible to investigate procedures to improve the morphological and functional regeneration of the facial nerve in animal models: 1) retrograde fluorescence tracing to analyse collateral axonal sprouting and the selectivity of reinnervation of the mimic musculature, 2) immunohistochemistry to analyse both the terminal axonal sprouting in the muscles and the axon reaction within the nucleus of the facial nerve, the peripheral nerve, and its environment, and 3) digital motion analysis of the muscles. To obtain good functional facial nerve regeneration, a reduction of terminal sprouting in the mimic musculature seems to be more important than a reduction of collateral sprouting at the lesion site. Promising strategies include acceleration of nerve regeneration, forced induced use of the paralysed face, mechanical stimulation of the face, and transplantation of nerve-growth-promoting olfactory epithelium at the lesion site.

  19. Photocrosslinkable Gelatin/Tropoelastin Hydrogel Adhesives for Peripheral Nerve Repair.

    Science.gov (United States)

    Soucy, Jonathan R; Shirzaei Sani, Ehsan; Portillo Lara, Roberto; Diaz, David; Dias, Felipe; Weiss, Anthony S; Koppes, Abigail N; Koppes, Ryan A; Annabi, Nasim

    2018-05-09

    Suturing peripheral nerve transections is the predominant therapeutic strategy for nerve repair. However, the use of sutures leads to scar tissue formation, hinders nerve regeneration, and prevents functional recovery. Fibrin-based adhesives have been widely used for nerve reconstruction, but their limited adhesive and mechanical strength and inability to promote nerve regeneration hamper their utility as a stand-alone intervention. To overcome these challenges, we engineered composite hydrogels that are neurosupportive and possess strong tissue adhesion. These composites were synthesized by photocrosslinking two naturally derived polymers, gelatin-methacryloyl (GelMA) and methacryloyl-substituted tropoelastin (MeTro). The engineered materials exhibited tunable mechanical properties by varying the GelMA/MeTro ratio. In addition, GelMA/MeTro hydrogels exhibited 15-fold higher adhesive strength to nerve tissue ex vivo compared to fibrin control. Furthermore, the composites were shown to support Schwann cell (SC) viability and proliferation, as well as neurite extension and glial cell participation in vitro, which are essential cellular components for nerve regeneration. Finally, subcutaneously implanted GelMA/MeTro hydrogels exhibited slower degradation in vivo compared with pure GelMA, indicating its potential to support the growth of slowly regenerating nerves. Thus, GelMA/MeTro composites may be used as clinically relevant biomaterials to regenerate nerves and reduce the need for microsurgical suturing during nerve reconstruction.

  20. Polyhedral combinatorics of UPGMA cones

    OpenAIRE

    Davidson, Ruth; Sullivant, Seth

    2013-01-01

    Distance-based methods such as UPGMA (Unweighted Pair Group Method with Arithmetic Mean) continue to play a significant role in phylogenetic research. We use polyhedral combinatorics to analyze the natural subdivision of the positive orthant induced by classifying the input vectors according to tree topologies returned by the algorithm. The partition lattice informs the study of UPGMA trees. We give a closed form for the extreme rays of UPGMA cones on n taxa, and compute the normalized volume...

  1. Liouville action in cone gauge

    International Nuclear Information System (INIS)

    Zamolodchikov, A.B.

    1989-01-01

    The effective action of the conformally invariant field theory in the curved background space is considered in the light cone gauge. The effective potential in the classical background stress is defined as the Legendre transform of the Liouville action. This potential is tightly connected with the sl(2) current algebra. The series of the covariant differential operators is constructed and the anomalies of their determinants are reduced to this effective potential. 7 refs

  2. Cardiac cone-beam CT

    International Nuclear Information System (INIS)

    Manzke, Robert

    2005-01-01

    This doctoral thesis addresses imaging of the heart with retrospectively gated helical cone-beam computed tomography (CT). A thorough review of the CT reconstruction literature is presented in combination with a historic overview of cardiac CT imaging and a brief introduction to other cardiac imaging modalities. The thesis includes a comprehensive chapter about the theory of CT reconstruction, familiarizing the reader with the problem of cone-beam reconstruction. The anatomic and dynamic properties of the heart are outlined and techniques to derive the gating information are reviewed. With the extended cardiac reconstruction (ECR) framework, a new approach is presented for the heart-rate-adaptive gated helical cardiac cone-beam CT reconstruction. Reconstruction assessment criteria such as the temporal resolution, the homogeneity in terms of the cardiac phase, and the smoothness at cycle-to-cycle transitions are developed. Several reconstruction optimization approaches are described: An approach for the heart-rate-adaptive optimization of the temporal resolution is presented. Streak artifacts at cycle-to-cycle transitions can be minimized by using an improved cardiac weighting scheme. The optimal quiescent cardiac phase for the reconstruction can be determined automatically with the motion map technique. Results for all optimization procedures applied to ECR are presented and discussed based on patient and phantom data. The ECR algorithm is analyzed for larger detector arrays of future cone-beam systems throughout an extensive simulation study based on a four-dimensional cardiac CT phantom. The results of the scientific work are summarized and an outlook proposing future directions is given. The presented thesis is available for public download at www.cardiac-ct.net

  3. Prescriptionless light-cone integrals

    International Nuclear Information System (INIS)

    Suzuki, A.T.; Schmidt, A.G.M.

    2000-01-01

    Perturbative quantum gauge field theory as seen within the perspective of physical gauge choices such as the light-cone gauge entails the emergence of troublesome poles of the type (k.n) -α in the Feynman integrals. These come from the boson field propagator, where α=1,2,.. and n μ is the external arbitrary four-vector that defines the gauge properly. This becomes an additional hurdle in the computation of Feynman diagrams, since any graph containing internal boson lines will inevitably produce integrands with denominators bearing the characteristic gauge-fixing factor. How one deals with them has been the subject of research over decades, and several prescriptions have been suggested and tried in the course of time, with failures and successes. However, a more recent development at this fronteer which applies the negative dimensional technique to compute light-cone Feynman integrals shows that we can altogether dispense with prescriptions to perform the calculations. An additional bonus comes to us attached to this new technique, in that not only it renders the light-cone prescriptionless but, by the very nature of it, it can also dispense with decomposition formulas or partial fractioning tricks used in the standard approach to separate pole products of the type (k.n) -α [(k-p).n] -β (β=1,2,..). In this work we demonstrate how all this can be done. (orig.)

  4. Light-cone quantization of quantum chromodynamics

    International Nuclear Information System (INIS)

    Brodsky, S.J.; Pauli, H.C.

    1991-06-01

    We discuss the light-cone quantization of gauge theories from two perspectives: as a calculational tool for representing hadrons as QCD bound-states of relativistic quarks and gluons, and also as a novel method for simulating quantum field theory on a computer. The light-cone Fock state expansion of wavefunctions at fixed light cone time provides a precise definition of the parton model and a general calculus for hadronic matrix elements. We present several new applications of light-cone Fock methods, including calculations of exclusive weak decays of heavy hadrons, and intrinsic heavy-quark contributions to structure functions. A general nonperturbative method for numerically solving quantum field theories, ''discretized light-cone quantization,'' is outlined and applied to several gauge theories, including QCD in one space and one time dimension, and quantum electrodynamics in physical space-time at large coupling strength. The DLCQ method is invariant under the large class of light-cone Lorentz transformations, and it can be formulated such at ultraviolet regularization is independent of the momentum space discretization. Both the bound-state spectrum and the corresponding relativistic light-cone wavefunctions can be obtained by matrix diagonalization and related techniques. We also discuss the construction of the light-cone Fock basis, the structure of the light-cone vacuum, and outline the renormalization techniques required for solving gauge theories within the light-cone Hamiltonian formalism

  5. Light-cone quantization of quantum chromodynamics

    Energy Technology Data Exchange (ETDEWEB)

    Brodsky, S.J. (Stanford Linear Accelerator Center, Menlo Park, CA (USA)); Pauli, H.C. (Max-Planck-Institut fuer Kernphysik, Heidelberg (Germany, F.R.))

    1991-06-01

    We discuss the light-cone quantization of gauge theories from two perspectives: as a calculational tool for representing hadrons as QCD bound-states of relativistic quarks and gluons, and also as a novel method for simulating quantum field theory on a computer. The light-cone Fock state expansion of wavefunctions at fixed light cone time provides a precise definition of the parton model and a general calculus for hadronic matrix elements. We present several new applications of light-cone Fock methods, including calculations of exclusive weak decays of heavy hadrons, and intrinsic heavy-quark contributions to structure functions. A general nonperturbative method for numerically solving quantum field theories, discretized light-cone quantization,'' is outlined and applied to several gauge theories, including QCD in one space and one time dimension, and quantum electrodynamics in physical space-time at large coupling strength. The DLCQ method is invariant under the large class of light-cone Lorentz transformations, and it can be formulated such at ultraviolet regularization is independent of the momentum space discretization. Both the bound-state spectrum and the corresponding relativistic light-cone wavefunctions can be obtained by matrix diagonalization and related techniques. We also discuss the construction of the light-cone Fock basis, the structure of the light-cone vacuum, and outline the renormalization techniques required for solving gauge theories within the light-cone Hamiltonian formalism.

  6. Geomorphometric variability of "monogenetic" volcanic cones: Evidence from Mauna Kea, Lanzarote and experimental cones

    Science.gov (United States)

    Kervyn, M.; Ernst, G. G. J.; Carracedo, J.-C.; Jacobs, P.

    2012-01-01

    Volcanic cones are the most common volcanic constructs on Earth. Their shape can be quantified using two morphometric ratios: the crater/cone base ratio (W cr/W co) and the cone height/width ratio (H co/W co). The average values for these ratios obtained over entire cone fields have been explained by the repose angle of loose granular material (i.e. scoria) controlling cone slopes. The observed variability in these ratios between individual cones has been attributed to the effect of erosional processes or contrasting eruptive conditions on cone morphometry. Using a GIS-based approach, high spatial resolution Digital Elevation Models and airphotos, two new geomorphometry datasets for cone fields at Mauna Kea (Hawaii, USA) and Lanzarote (Canary Islands, Spain) are extracted and analyzed here. The key observation in these datasets is the great variability in morphometric ratios, even for simple-shape and well-preserved cones. Simple analog experiments are presented to analyze factors influencing the morphometric ratios. The formation of a crater is simulated within an analog cone (i.e. a sand pile) by opening a drainage conduit at the cone base. Results from experiments show that variability in the morphometric ratios can be attributed to variations in the width, height and horizontal offset of the drainage point relative to the cone symmetry axis, to the dip of the underlying slope or to the influence of a small proportion of fine cohesive material. GIS analysis and analog experiments, together with specific examples of cones documented in the field, suggest that the morphometric ratios for well-preserved volcanic cones are controlled by a combination of 1) the intrinsic cone material properties, 2) time-dependent eruption conditions, 3) the local setting, and 4) the method used to estimate the cone height. Implications for interpreting cone morphometry solely as either an age or as an eruption condition indicator are highlighted.

  7. Use of Synthetic Nerve Grafts to Restore Cavernous Nerve Function Following Prostate Cancer Surgery: In Vitro and In Vivo Studies

    National Research Council Canada - National Science Library

    Konety, Badrinath R

    2006-01-01

    .... Schwann cell and neurona stem cells en neurite growth are being investigated. Tubulized sheets of the polymer with and without those factors/cells have been used to microsurgically replace resected cavernous nerve...

  8. Malignant peripheral nerve sheath tumor of the oculomotor nerve

    DEFF Research Database (Denmark)

    Kozic, D; Nagulic, M; Ostojic, J

    2006-01-01

    We present the short-term follow-up magnetic resonance (MR) studies and 1H-MR spectroscopy in a child with malignant peripheral nerve sheath tumor of the oculomotor nerve associated with other less aggressive cranial nerve schwannomas. The tumor revealed perineural extension and diffuse nerve...

  9. Drug Delivery for Peripheral Nerve Regeneration

    Science.gov (United States)

    2015-11-01

    enhancement in dorsal root ganglion ( DRG ) cells with the released drug. In the first year of this 18 month project we have completed device fabrication of...the nerve guide conduit and drug delivery reservoir. We were able to release NGF at a concentration that enhancing DRG nerve growth in vitro. We next...KrF excimer laser system (Optec) and with diameters larger than 100μm using the VLS3.60 CO2 system (Universal Laser Systems )) (Figure 3). The laser

  10. g-Weak Contraction in Ordered Cone Rectangular Metric Spaces

    Directory of Open Access Journals (Sweden)

    S. K. Malhotra

    2013-01-01

    Full Text Available We prove some common fixed-point theorems for the ordered g-weak contractions in cone rectangular metric spaces without assuming the normality of cone. Our results generalize some recent results from cone metric and cone rectangular metric spaces into ordered cone rectangular metric spaces. Examples are provided which illustrate the results.

  11. Construction of nerve guide conduits from cellulose/soy protein composite membranes combined with Schwann cells and pyrroloquinoline quinone for the repair of peripheral nerve defect.

    Science.gov (United States)

    Luo, Lihua; Gan, Li; Liu, Yongming; Tian, Weiqun; Tong, Zan; Wang, Xiong; Huselstein, Celine; Chen, Yun

    2015-02-20

    Regeneration and functional reconstruction of peripheral nerve defects remained a significant clinical challenge. Nerve guide conduits, with seed cells or neurotrophic factors (NTFs), had been widely used to improve the repair and regeneration of injured peripheral nerve. Pyrroloquinoline quinone (PQQ) was an antioxidant that can stimulate nerve growth factors (NGFs) synthesis and accelerate the Schwann cells (SCs) proliferation and growth. In present study, three kinds of nerve guide conduits were constructed: one from cellulose/SPI hollow tube (CSC), another from CSC combined with SCs (CSSC), and the third one from CSSC combined with PQQ (CSSPC), respectively. And then they were applied to bridge and repair the sciatic nerve defect in rats, using autograft as control. Effects of different nerve guide conduits on the nerve regeneration were comparatively evaluated by general analysis, sciatic function index (SFI) and histological analysis (HE and TEM). Newly-formed regenerative nerve fibers were observed and running through the transparent nerve guide conduits 12 weeks after surgery. SFI results indicated that the reconstruction of motor function in CSSPC group was better than that in CSSC and CSC groups. HE images from the cross-sections and longitudinal-sections of the harvested regenerative nerve indicated that regenerative nerve fibers had been formed and accompanied with new blood vessels and matrix materials in the conduits. TEM images also showed that lots of fresh myelinated and non-myelinated nerve fibers had been formed. Parts of vacuolar, swollen and abnormal axons occurred in CSC and CSSC groups, while the vacuolization and swell of axons was the least serious in CSSPC group. These results indicated that CSSPC group had the most ability to repair and reconstruct the nerve structure and functions due to the comprehensive contributions from hollow CSC tube, SCs and PQQ. As a result, the CSSPC may have the potential for the applications as nerve guide

  12. Nanofiber Nerve Guide for Peripheral Nerve Repair and Regeneration

    Science.gov (United States)

    2016-04-01

    1 Award Number: W81XWH-11-2-0047 TITLE: Nanofiber Nerve Guide for Peripheral Nerve Repair and Regeneration PRINCIPAL INVESTIGATOR: Ahmet Höke...TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-11-2-0047 Nanofiber nerve guide for peripheral nerve repair and regeneration 5b. GRANT NUMBER...goal of this collaborative research project was to develop next generation engineered nerve guide conduits (NGCs) with aligned nanofibers and

  13. Augmenting nerve regeneration with electrical stimulation.

    Science.gov (United States)

    Gordon, T; Brushart, T M; Chan, K M

    2008-12-01

    Poor functional recovery after peripheral nerve injury is generally attributed to irreversible target atrophy. In rats, we addressed the functional outcomes of prolonged neuronal separation from targets (chronic axotomy for up to 1 year) and atrophy of Schwann cells (SCs) in distal nerve stumps, and whether electrical stimulation (ES) accelerates axon regeneration. In carpal tunnel syndrome (CTS) patients with severe axon degeneration and release surgery, we asked whether ES accelerates muscle reinnervation. Reinnervated motor unit (MUs) and regenerating neuron numbers were counted electrophysiologically and with dye-labeling after chronic axotomy, chronic SC denervation and after immediate nerve repair with and without trains of 20 Hz ES for 1 hour to 2 weeks in rats and in CTS patients. Chronic axotomy reduced regenerative capacity to 67% and was alleviated by exogenous growth factors. Reduced regeneration to approximately 10% by SC denervation atrophy was ameliorated by forskolin and transforming growth factor-beta SC reactivation. ES (1 h) accelerated axon outgrowth across the suture site in association with elevated neuronal neurotrophic factor and receptors and in patients, promoted the full reinnervation of thenar muscles in contrast to a non-significant increase in MU numbers in the control group. The rate limiting process of axon outgrowth, progressive deterioration of both neuronal growth capacity and SC support, but not irreversible target atrophy, account for observed poor functional recovery after nerve injury. Brief ES accelerates axon outgrowth and target muscle reinnervation in animals and humans, opening the way to future clinical application to promote functional recovery.

  14. Excess of nerve growth factor in the ovary causes a polycystic ovary-like syndrome in mice, which closely resembles both reproductive and metabolic aspects of the human syndrome.

    Science.gov (United States)

    Wilson, Jenny L; Chen, Weiyi; Dissen, Gregory A; Ojeda, Sergio R; Cowley, Michael A; Garcia-Rudaz, Cecilia; Enriori, Pablo J

    2014-11-01

    Polycystic ovarian syndrome (PCOS), the most common female endocrine disorder of unknown etiology, is characterized by reproductive abnormalities and associated metabolic conditions comprising insulin resistance, type 2 diabetes mellitus, and dyslipidemia. We previously reported that transgenic overexpression of nerve growth factor (NGF), a marker of sympathetic hyperactivity, directed to the ovary by the mouse 17α-hydroxylase/C17-20 lyase promoter (17NF mice), results in ovarian abnormalities similar to those seen in PCOS women. To investigate whether ovarian overproduction of NGF also induces common metabolic alterations of PCOS, we assessed glucose homeostasis by glucose tolerance test, plasma insulin levels, and body composition by dual-energy x-ray absorptiometry scan in young female 17NF mice and wild-type mice. 17NF mice exhibited increased body weight and alterations in body fat distribution with a greater accumulation of visceral fat compared with sc fat (P ovary may suffice to cause both reproductive and metabolic alterations characteristic of PCOS and support the hypothesis that sympathetic hyperactivity may contribute to the development and/or progression of PCOS.

  15. Construction of nerve guide conduits from cellulose/soy protein composite membranes combined with Schwann cells and pyrroloquinoline quinone for the repair of peripheral nerve defect

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Lihua [Department of Biomedical Engineering, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Center of Molecular Medicine, School of Medicine, Hubei University of Arts and Sciences, Xiangyang 441053 (China); Gan, Li; Liu, Yongming; Tian, Weiqun; Tong, Zan [Department of Biomedical Engineering, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Wang, Xiong; Huselstein, Celine [Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), UMR 7365 CNRS – Université de Lorraine, Biopôle, 54500 Vandoeuvre-lès-Nancy (France); Chen, Yun, E-mail: yunchen@whu.edu.cn [Department of Biomedical Engineering, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China)

    2015-02-20

    Regeneration and functional reconstruction of peripheral nerve defects remained a significant clinical challenge. Nerve guide conduits, with seed cells or neurotrophic factors (NTFs), had been widely used to improve the repair and regeneration of injured peripheral nerve. Pyrroloquinoline quinone (PQQ) was an antioxidant that can stimulate nerve growth factors (NGFs) synthesis and accelerate the Schwann cells (SCs) proliferation and growth. In present study, three kinds of nerve guide conduits were constructed: one from cellulose/SPI hollow tube (CSC), another from CSC combined with SCs (CSSC), and the third one from CSSC combined with PQQ (CSSPC), respectively. And then they were applied to bridge and repair the sciatic nerve defect in rats, using autograft as control. Effects of different nerve guide conduits on the nerve regeneration were comparatively evaluated by general analysis, sciatic function index (SFI) and histological analysis (HE and TEM). Newly-formed regenerative nerve fibers were observed and running through the transparent nerve guide conduits 12 weeks after surgery. SFI results indicated that the reconstruction of motor function in CSSPC group was better than that in CSSC and CSC groups. HE images from the cross-sections and longitudinal-sections of the harvested regenerative nerve indicated that regenerative nerve fibers had been formed and accompanied with new blood vessels and matrix materials in the conduits. TEM images also showed that lots of fresh myelinated and non-myelinated nerve fibers had been formed. Parts of vacuolar, swollen and abnormal axons occurred in CSC and CSSC groups, while the vacuolization and swell of axons was the least serious in CSSPC group. These results indicated that CSSPC group had the most ability to repair and reconstruct the nerve structure and functions due to the comprehensive contributions from hollow CSC tube, SCs and PQQ. As a result, the CSSPC may have the potential for the applications as nerve guide

  16. Diabetic Nerve Problems

    Science.gov (United States)

    ... at the wrong times. This damage is called diabetic neuropathy. Over half of people with diabetes get ... you change positions quickly Your doctor will diagnose diabetic neuropathy with a physical exam and nerve tests. ...

  17. Diabetes and nerve damage

    Science.gov (United States)

    Diabetic neuropathy; Diabetes - neuropathy; Diabetes - peripheral neuropathy ... In people with diabetes, the body's nerves can be damaged by decreased blood flow and a high blood sugar level. This condition is ...

  18. Tumors of peripheral nerves

    International Nuclear Information System (INIS)

    Ho, Michael; Lutz, Amelie M.

    2017-01-01

    Differentiation between malignant and benign tumors of peripheral nerves in the early stages is challenging; however, due to the unfavorable prognosis of malignant tumors early identification is required. To show the possibilities for detection, differential diagnosis and clinical management of peripheral nerve tumors by imaging appearance in magnetic resonance (MR) neurography. Review of current literature available in PubMed and MEDLINE, supplemented by the authors' own observations in clinical practice. Although not pathognomonic, several imaging features have been reported for a differentiation between distinct peripheral nerve tumors. The use of MR neurography enables detection and initial differential diagnosis in tumors of peripheral nerves. Furthermore, it plays an important role in clinical follow-up, targeted biopsy and surgical planning. (orig.) [de

  19. Energy integration in south cone

    International Nuclear Information System (INIS)

    Ribeiro, M.A.K.

    1990-01-01

    The economic development of a geo-political region is directly related to the energy resources available to its productive system. The analysis carried out in this paper focus a region limited by Paraguay, Uruguay, the Argentina north and the Brazilian south, the core of the so called South Cone. The region has a diversified energy matrix that assures strong connections between the countries. The main resources available are hydroelectric but the approach gives a strong emphasis in coal and natural gas. The outlined model of a self sustained development of the region can be used as the foundation of the independent economic development of South America. (author)

  20. Seawave Slot-Cone Generator

    DEFF Research Database (Denmark)

    Vicinanza, Diego; Margheritini, Lucia; Contestabile, Pasquale

    2009-01-01

    This paper discusses a new type of Wave Energy Converter (WEC) named Seawave Slot-Cone Generator (SSG). The SSG is a WEC of the overtopping type. The structure consists of a number of reservoirs one on the top of each others above the mean water level in which the water of incoming waves is store...... on sloping walls constituting the structure. The research is intended to be of direct use to engineers analyzing design and stability of this peculiar kind of coastal structure....

  1. Optic nerve oxygen tension

    DEFF Research Database (Denmark)

    la Cour, M; Kiilgaard, Jens Folke; Eysteinsson, T

    2000-01-01

    To investigate the influence of acute changes in intraocular pressure on the oxygen tension in the vicinity of the optic nerve head under control conditions and after intravenous administration of 500 mg of the carbonic anhydrase inhibitor dorzolamide.......To investigate the influence of acute changes in intraocular pressure on the oxygen tension in the vicinity of the optic nerve head under control conditions and after intravenous administration of 500 mg of the carbonic anhydrase inhibitor dorzolamide....

  2. Primary nerve grafting: A study of revascularization.

    Science.gov (United States)

    Chalfoun, Charbel; Scholz, Thomas; Cole, Matthew D; Steward, Earl; Vanderkam, Victoria; Evans, Gregory R D

    2003-01-01

    It was the purpose of this study to evaluate the revascularization of primary nerve repair and grafts using orthogonal polarization spectral (OPS) (Cytometrix, Inc.) imaging, a novel method for real-time evaluation of microcirculatory blood flow. Twenty male Sprague Dawley rats (250 g) were anesthetized with vaporized halothane and surgically prepared for common peroneal nerve resection. Group I animals (n = 10) underwent primary neurorraphy following transection, utilizing a microsurgical technique with 10-0 nylon suture. Group II (n = 10) animals had a 7-mm segment of nerve excised, reversed, and subsequently replaced as a nerve graft under similar techniques. All animals were evaluated using the OPS imaging system on three portions (proximal, transection site/graft, and distal) of the nerve following repair or grafting. Reevaluation of 5 animals randomly selected from each group using the OPS imaging system was again performed on days 14 and 28 following microsurgical repair/grafting. Values were determined by percent change in vascularity of the common peroneal nerve at 0 hr following surgery. Real-time evaluation of blood flow was utilized as an additional objective criterion. Percent vascularity in group I and II animals increased from baseline in all segments at day 14. By day 28, vascularity in nerves of group I rats decreased in all segments to values below baseline, with the exception of the transection site, which remained at a higher value than obtained directly after surgical repair. In group II animals, vascularity remained above baseline in all segments except the distal segment, which returned to vascularity levels similar to those at 0 hr. Further, occlusion of the vessels demonstrated in the graft and distal segments following initial transection appeared to be corrected. This study suggests that revascularization may occur via bidirectional inosculation with favored proximal vascular growth advancement. The use of real-time imaging offers a

  3. End-to-side neurorrhaphy repairs peripheral nerve injury: sensory nerve induces motor nerve regeneration.

    Science.gov (United States)

    Yu, Qing; Zhang, She-Hong; Wang, Tao; Peng, Feng; Han, Dong; Gu, Yu-Dong

    2017-10-01

    End-to-side neurorrhaphy is an option in the treatment of the long segment defects of a nerve. It involves suturing the distal stump of the disconnected nerve (recipient nerve) to the side of the intimate adjacent nerve (donor nerve). However, the motor-sensory specificity after end-to-side neurorrhaphy remains unclear. This study sought to evaluate whether cutaneous sensory nerve regeneration induces motor nerves after end-to-side neurorrhaphy. Thirty rats were randomized into three groups: (1) end-to-side neurorrhaphy using the ulnar nerve (mixed sensory and motor) as the donor nerve and the cutaneous antebrachii medialis nerve as the recipient nerve; (2) the sham group: ulnar nerve and cutaneous antebrachii medialis nerve were just exposed; and (3) the transected nerve group: cutaneous antebrachii medialis nerve was transected and the stumps were turned over and tied. At 5 months, acetylcholinesterase staining results showed that 34% ± 16% of the myelinated axons were stained in the end-to-side group, and none of the myelinated axons were stained in either the sham or transected nerve groups. Retrograde fluorescent tracing of spinal motor neurons and dorsal root ganglion showed the proportion of motor neurons from the cutaneous antebrachii medialis nerve of the end-to-side group was 21% ± 5%. In contrast, no motor neurons from the cutaneous antebrachii medialis nerve of the sham group and transected nerve group were found in the spinal cord segment. These results confirmed that motor neuron regeneration occurred after cutaneous nerve end-to-side neurorrhaphy.

  4. Cone calorimeter tests of wood composites

    Science.gov (United States)

    Robert H. White; Kuma Sumathipala

    2013-01-01

    The cone calorimeter is widely used for the determination of the heat release rate (HRR) of building products and other materials. As part of an effort to increase the availability of cone calorimeter data on wood products, the U.S. Forest Products Laboratory and the American Wood Council conducted this study on composite wood products in cooperation with the Composite...

  5. Cone Penetrometer N Factor Determination Testing Results

    Energy Technology Data Exchange (ETDEWEB)

    Follett, Jordan R.

    2014-03-05

    This document contains the results of testing activities to determine the empirical 'N Factor' for the cone penetrometer in kaolin clay simulant. The N Factor is used to releate resistance measurements taken with the cone penetrometer to shear strength.

  6. Cone penetrometer demonstration standard startup review checklist

    International Nuclear Information System (INIS)

    KRIEG, S.A.

    1998-01-01

    Startup readiness for the Cone Penetrometer Demonstration in AX Tank Farm will be verified through the application of a Standard Startup Review Checklist. This is a listing of those items essential to demonstrating readiness to start the Cone Penetrometer Demonstration in AX Tank Farm

  7. Gradual nerve elongation affects nerve cell bodies and neuro-muscular junctions.

    Science.gov (United States)

    Kazuo Ikeda, K I; Masaki Matsuda, M M; Daisuke Yamauchi, D Y; Katsuro Tomita, K T; Shigenori Tanaka, S T

    2005-07-01

    The purpose of this study is to clarify the reactions of the neuro-muscular junction and nerve cell body to gradual nerve elongation. The sciatic nerves of Japanese white rabbits were lengthened by 30 mm in increments of 0.8 mm/day, 2.0 mm/day and 4.0 mm/day. A scanning electron microscopic examination showed no degenerative change at the neuro-muscular junction, even eight weeks after elongation in the 4-mm group. Hence, neuro-muscular junction is not critical for predicting damage from gradual nerve elongation. There were no axon reaction cells in the 0.8-mm group, a small amount in the 2-mm group, and a large amount in the 4-mm group. The rate of growth associated protein-43 positive nerve cells was significant in the 4-mm group. Hence, the safe speed for nerve cells appeared to be 0.8-mm/day, critical speed to be 2.0-mm/day, and dangerous speed to be 4.0-mm/day in this elongation model.

  8. Regeneration of Optic Nerve

    Directory of Open Access Journals (Sweden)

    Kwok-Fai So

    2011-05-01

    Full Text Available The optic nerve is part of the central nervous system (CNS and has a structure similar to other CNS tracts. The axons that form the optic nerve originate in the ganglion cell layer of the retina and extend through the optic tract. As a tissue, the optic nerve has the same organization as the white matter of the brain in regard to its glia. There are three types of glial cells: Oligodendrocytes, astrocytes, and microglia. Little structural and functional regeneration of the CNS takes place spontaneously following injury in adult mammals. In contrast, the ability of the mammalian peripheral nervous system (PNS to regenerate axons after injury is well documented. A number of factors are involved in the lack of CNS regeneration, including: (i the response of neuronal cell bodies against the damage; (ii myelin-mediated inhibition by oligodendrocytes; (iii glial scarring, by astrocytes; (iv macrophage infiltration; and (v insufficient trophic factor support. The fundamental difference in the regenerative capacity between CNS and PNS neuronal cell bodies has been the subject of intensive research. In the CNS the target normally conveys a retrograde trophic signal to the cell body. CNS neurons die because of trophic deprivation. Damage to the optic nerve disconnects the neuronal cell body from its target-derived trophic peptides, leading to the death of retinal ganglion cells. Furthermore, the axontomized neurons become less responsive to the peptide trophic signals they do receive. On the other hand, adult PNS neurons are intrinsically responsive to neurotrophic factors and do not lose trophic responsiveness after axotomy. In this talk different strategies to promote optic-nerve regeneration in adult mammals are reviewed. Much work is still needed to resolve many issues. This is a very important area of neuroregeneration and neuroprotection, as currently there is no cure after traumatic optic nerve injury or retinal disease such as glaucoma, which

  9. Double Dirac cones in phononic crystals

    KAUST Repository

    Li, Yan

    2014-07-07

    A double Dirac cone is realized at the center of the Brillouin zone of a two-dimensional phononic crystal (PC) consisting of a triangular array of core-shell-structure cylinders in water. The double Dirac cone is induced by the accidental degeneracy of two double-degenerate Bloch states. Using a perturbation method, we demonstrate that the double Dirac cone is composed of two identical and overlapping Dirac cones whose linear slopes can also be accurately predicted from the method. Because the double Dirac cone occurs at a relatively low frequency, a slab of the PC can be mapped onto a slab of zero refractive index material by using a standard retrieval method. Total transmission without phase change and energy tunneling at the double Dirac point frequency are unambiguously demonstrated by two examples. Potential applications can be expected in diverse fields such as acoustic wave manipulations and energy flow control.

  10. Double Dirac cones in phononic crystals

    KAUST Repository

    Li, Yan; Wu, Ying; Mei, Jun

    2014-01-01

    A double Dirac cone is realized at the center of the Brillouin zone of a two-dimensional phononic crystal (PC) consisting of a triangular array of core-shell-structure cylinders in water. The double Dirac cone is induced by the accidental degeneracy of two double-degenerate Bloch states. Using a perturbation method, we demonstrate that the double Dirac cone is composed of two identical and overlapping Dirac cones whose linear slopes can also be accurately predicted from the method. Because the double Dirac cone occurs at a relatively low frequency, a slab of the PC can be mapped onto a slab of zero refractive index material by using a standard retrieval method. Total transmission without phase change and energy tunneling at the double Dirac point frequency are unambiguously demonstrated by two examples. Potential applications can be expected in diverse fields such as acoustic wave manipulations and energy flow control.

  11. Acellular Nerve Allografts in Peripheral Nerve Regeneration: A Comparative Study

    Science.gov (United States)

    Moore, Amy M.; MacEwan, Matthew; Santosa, Katherine B.; Chenard, Kristofer E.; Ray, Wilson Z.; Hunter, Daniel A.; Mackinnon, Susan E.; Johnson, Philip J.

    2011-01-01

    Background Processed nerve allografts offer a promising alternative to nerve autografts in the surgical management of peripheral nerve injuries where short deficits exist. Methods Three established models of acellular nerve allograft (cold-preserved, detergent-processed, and AxoGen® -processed nerve allografts) were compared to nerve isografts and silicone nerve guidance conduits in a 14 mm rat sciatic nerve defect. Results All acellular nerve grafts were superior to silicone nerve conduits in support of nerve regeneration. Detergent-processed allografts were similar to isografts at 6 weeks post-operatively, while AxoGen®-processed and cold-preserved allografts supported significantly fewer regenerating nerve fibers. Measurement of muscle force confirmed that detergent-processed allografts promoted isograft-equivalent levels of motor recovery 16 weeks post-operatively. All acellular allografts promoted greater amounts of motor recovery compared to silicone conduits. Conclusions These findings provide evidence that differential processing for removal of cellular constituents in preparing acellular nerve allografts affects recovery in vivo. PMID:21660979

  12. Neuromuscular ultrasound of cranial nerves.

    Science.gov (United States)

    Tawfik, Eman A; Walker, Francis O; Cartwright, Michael S

    2015-04-01

    Ultrasound of cranial nerves is a novel subdomain of neuromuscular ultrasound (NMUS) which may provide additional value in the assessment of cranial nerves in different neuromuscular disorders. Whilst NMUS of peripheral nerves has been studied, NMUS of cranial nerves is considered in its initial stage of research, thus, there is a need to summarize the research results achieved to date. Detailed scanning protocols, which assist in mastery of the techniques, are briefly mentioned in the few reference textbooks available in the field. This review article focuses on ultrasound scanning techniques of the 4 accessible cranial nerves: optic, facial, vagus and spinal accessory nerves. The relevant literatures and potential future applications are discussed.

  13. Regulation of semaphorin III/collapsin-1 gene expression during peripheral nerve regeneration

    NARCIS (Netherlands)

    Pasterkamp, R Jeroen; Giger, Roman J; Verhaagen, J

    1998-01-01

    The competence of neurons to regenerate depends on their ability to initiate a program of gene expression supporting growth and on the growth-permissive properties of glial cells in the distal stump of the injured nerve. Most studies on intrinsic molecular mechanisms governing peripheral nerve

  14. Chitin biological absorbable catheters bridging sural nerve grafts transplanted into sciatic nerve defects promote nerve regeneration.

    Science.gov (United States)

    Wang, Zhi-Yong; Wang, Jian-Wei; Qin, Li-Hua; Zhang, Wei-Guang; Zhang, Pei-Xun; Jiang, Bao-Guo

    2018-06-01

    To investigate the efficacy of chitin biological absorbable catheters in a rat model of autologous nerve transplantation. A segment of sciatic nerve was removed to produce a sciatic nerve defect, and the sural nerve was cut from the ipsilateral leg and used as a graft to bridge the defect, with or without use of a chitin biological absorbable catheter surrounding the graft. The number and morphology of regenerating myelinated fibers, nerve conduction velocity, nerve function index, triceps surae muscle morphology, and sensory function were evaluated at 9 and 12 months after surgery. All of the above parameters were improved in rats in which the nerve graft was bridged with chitin biological absorbable catheters compared with rats without catheters. The results of this study indicate that use of chitin biological absorbable catheters to surround sural nerve grafts bridging sciatic nerve defects promotes recovery of structural, motor, and sensory function and improves muscle fiber morphology. © 2018 John Wiley & Sons Ltd.

  15. ZnO twin-cones: synthesis, photoluminescence, and catalytic decomposition of ammonium perchlorate.

    Science.gov (United States)

    Sun, Xuefei; Qiu, Xiaoqing; Li, Liping; Li, Guangshe

    2008-05-19

    ZnO twin-cones, a new member to the ZnO family, were prepared directly by a solvothermal method using a mixed solution of zinc nitrate and ethanol. The reaction and growth mechanisms of ZnO twin-cones were investigated by X-ray diffraction, UV-visible spectra, infrared and ion trap mass spectra, and transmission electron microscopy. All as-prepared ZnO cones consisted of tiny single crystals with lengths of several micrometers. With prolonging of the reaction time from 1.5 h to 7 days, the twin-cone shape did not change at all, while the lattice parameters increased slightly and the emission peak of photoluminescence shifted from the green region to the near orange region. ZnO twin-cones are also explored as an additive to promote the thermal decomposition of ammonium perchlorate. The variations of photoluminescence spectra and catalytic roles in ammonium perchlorate decomposition were discussed in terms of the defect structure of ZnO twin-cones.

  16. 142 Key words: Brachialis, radial nerve, musculocutaneous nerve.

    African Journals Online (AJOL)

    AWORI KIRSTEEN

    The innervation of brachialis muscle by the musculocutaneous nerve has been described as either type I or type II and the main trunk to this muscle is rarely absent. The contribution .... brachialis muscle by fiber analysis of supply nerves].

  17. Nerve conduction and excitability studies in peripheral nerve disorders

    DEFF Research Database (Denmark)

    Krarup, Christian; Moldovan, Mihai

    2009-01-01

    counterparts in the peripheral nervous system, in some instances without peripheral nervous system symptoms. Both hereditary and acquired demyelinating neuropathies have been studied and the effects on nerve pathophysiology have been compared with degeneration and regeneration of axons. SUMMARY: Excitability......PURPOSE OF REVIEW: The review is aimed at providing information about the role of nerve excitability studies in peripheral nerve disorders. It has been known for many years that the insight into peripheral nerve pathophysiology provided by conventional nerve conduction studies is limited. Nerve...... excitability studies are relatively novel but are acquiring an increasingly important role in the study of peripheral nerves. RECENT FINDINGS: By measuring responses in nerve that are related to nodal function (strength-duration time constant, rheobase and recovery cycle) and internodal function (threshold...

  18. The southern cone petroleum market

    International Nuclear Information System (INIS)

    Pisani, W.

    1992-01-01

    The Argentine oil sector has been moving strongly toward complete deregulation since 1989. Price controls on byproducts has been lifted, old petroleum contracts became into concessions, and the state oil company, YPF, is under process of privatization. In this context, the international companies scouting for opportunities can find an important menu of potential investments But here remain some problems connected with this deregulation, too. The lack of a reference crude and product market price is one of them. This paper focuses how to overcome this trouble with the establishment of an institutional market for crude and products, not only for Argentina but also for the entire Southern Cone Region (Argentina, Bolivia, Brazil, Chile, Paraguay and Uruguay), inquiring into the benefits of its creation

  19. [Nerve growth factor and the physiology of pain: the relationships among interoception, sympathetic neurons and the emotional response indicated by the molecular pathophysiology of congenital insensitivity to pain with anhidrosis].

    Science.gov (United States)

    Indo, Yasuhiro

    2015-05-01

    Nerve growth factor (NGF) is a neurotrophic factor essential for the survival and maintenance of neurons. Congenital insensitivity to pain with anhidrosis (CIPA) is caused by loss-of-function mutations in NTRK1, which encodes a receptor tyrosine kinase, TrkA, for NGF. Mutations in NTRK1 cause the selective loss of NGF-dependent neurons, including both NGF-dependent primary afferents and sympathetic postganglionic neurons, in otherwise intact systems. The NGF-dependent primary afferents are thinly myelinated AΔ or unmyelinated C-fibers that are dependent on the NGF-TrkA system during development. NGF-dependent primary afferents are not only nociceptive neurons that transmit pain and temperature sensation, but also are polymodal receptors that play essential roles for interoception by monitoring various changes in the physiological status of all tissues in the body. In addition, they contribute to various inflammatory processes in acute, chronic and allergic inflammation. Together with sympathetic postganglionic neurons, they maintain the homeostasis of the body and emotional responses via interactions with the brain, immune and endocrine systems. Pain is closely related to emotions that accompany physical responses induced by systemic activation of the sympathetic nervous system. In contrast to a negative image of emotions in daily life, Antonio Damasio proposed the 'Somatic Marker Hypothesis', wherein emotions play critical roles in the decision-making and reasoning processes. According to this hypothesis, reciprocal communication between the brain and the body-proper are essential for emotional responses. Using the pathophysiology of CIPA as a foundation, this article suggests that NGF-dependent neurons constitute a part of the neuronal network required for homeostasis and emotional responses, and indicates that this network plays important roles in mediating the reciprocal communication between the brain and the body-proper.

  20. Nerve growth factor (NGF) immunoreactive neurons in the juvenile rat hippocampus: response to acute and long-term high-light open-field (HL-OF) or forced swim (FS) stress stimulation.

    Science.gov (United States)

    Badowska-Szalewska, E; Spodnik, E; Ludkiewicz, B; Klejbor, I; Moryś, J

    2011-12-29

    This study aimed at examining and comparing the influence of two different stress stimuli on the density (number of cells/mm²) of nerve growth factor (NGF) containing neurons in the hippocampal CA1 and CA3 pyramidal cell layers and the dentate gyrus (DG) granule cell layer in juvenile rats (P28; P-postnatal day). The high-light open-field (HL-OF) test and forced swim (FS) test were employed to investigate the effects of a single, 15-min acute exposure and repeated (15 min daily for 21 days) long-term exposure to stress. In order to detect NGF-ir neurons, immunohistochemical (-ir) techniques were used. In comparison with nonstressed animals, acute and long-term HL-OF or FS stimulation resulted in a marked increase (P<0.001) in the density of NGF-ir containing cells in all the hippocampal structures. The frequency of stress application (acute vs. long-term), however, did not have a substantial impact on the studied parameter, with the exception of the CA3 sector, where a decreased density (P<0.001) of NGF-ir neurons was observed after long-term exposure to FS. It may be concluded that a rise in the density of NGF-ir neurons in the juvenile rat hippocampus after exposure to HL-OF or FS stressors could have affected the activity of the hypothalamic-pituitary-adrenocortical (HPA) stress axis. Prolonged HL-OF or FS stress was probably aggravating enough not to trigger the habituation process. The type of stressor applied (HL-OF vs. FS) was not essentially a factor determining the density of NGF-ir cells in the hippocampus. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

  1. Cranial nerve palsies

    International Nuclear Information System (INIS)

    Ruggieri, P.; Adelizzi, J.; Modic, M.T.; Ross, J.S.; Tkach, J.; Masaryk, T.J.

    1990-01-01

    This paper evaluates the utility of multiplanar reconstructions (MPRs) of three-dimensional (3D) MR angiography data sets in the examination of patients with cranial nerve palsies. The authors hypothesis was that 3D data could be reformatted to highlight the intricate spatial relationships of vessels to adjacent neural tissues by taking advantage of the high vessel-parenchyma contrast in high-resolution 3D time-of-flight sequences. Twenty patients with cranial nerve palsies and 10 asymptomatic patients were examined with coronal T1-weighted and axial T2-weighted imaging plus a gadolinium-enhanced 3D MRA sequence (40/7/15 degrees, axial 60-mm volume, 0.9-mm isotropic resolution). Cranial nerves II-VIII were subsequently evaluated on axial and reformatted coronal and/or sagittal images

  2. Dirac cones in isogonal hexagonal metallic structures

    Science.gov (United States)

    Wang, Kang

    2018-03-01

    A honeycomb hexagonal metallic lattice is equivalent to a triangular atomic one and cannot create Dirac cones in its electromagnetic wave spectrum. We study in this work the low-frequency electromagnetic band structures in isogonal hexagonal metallic lattices that are directly related to the honeycomb one and show that such structures can create Dirac cones. The band formation can be described by a tight-binding model that allows investigating, in terms of correlations between local resonance modes, the condition for the Dirac cones and the consequence of the third structure tile sustaining an extra resonance mode in the unit cell that induces band shifts and thus nonlinear deformation of the Dirac cones following the wave vectors departing from the Dirac points. We show further that, under structure deformation, the deformations of the Dirac cones result from two different correlation mechanisms, both reinforced by the lattice's metallic nature, which directly affects the resonance mode correlations. The isogonal structures provide new degrees of freedom for tuning the Dirac cones, allowing adjustment of the cone shape by modulating the structure tiles at the local scale without modifying the lattice periodicity and symmetry.

  3. Lower cranial nerves.

    Science.gov (United States)

    Soldatos, Theodoros; Batra, Kiran; Blitz, Ari M; Chhabra, Avneesh

    2014-02-01

    Imaging evaluation of cranial neuropathies requires thorough knowledge of the anatomic, physiologic, and pathologic features of the cranial nerves, as well as detailed clinical information, which is necessary for tailoring the examinations, locating the abnormalities, and interpreting the imaging findings. This article provides clinical, anatomic, and radiological information on lower (7th to 12th) cranial nerves, along with high-resolution magnetic resonance images as a guide for optimal imaging technique, so as to improve the diagnosis of cranial neuropathy. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Tumors of the optic nerve

    DEFF Research Database (Denmark)

    Lindegaard, Jens; Heegaard, Steffen

    2009-01-01

    A variety of lesions may involve the optic nerve. Mainly, these lesions are inflammatory or vascular lesions that rarely necessitate surgery but may induce significant visual morbidity. Orbital tumors may induce proptosis, visual loss, relative afferent pupillary defect, disc edema and optic...... atrophy, but less than one-tenth of these tumors are confined to the optic nerve or its sheaths. No signs or symptoms are pathognomonic for tumors of the optic nerve. The tumors of the optic nerve may originate from the optic nerve itself (primary tumors) as a proliferation of cells normally present...... in the nerve (e.g., astrocytes and meningothelial cells). The optic nerve may also be invaded from tumors originating elsewhere (secondary tumors), invading the nerve from adjacent structures (e.g., choroidal melanoma and retinoblastoma) or from distant sites (e.g., lymphocytic infiltration and distant...

  5. Cone penetrometer moisture probe acceptance test report

    International Nuclear Information System (INIS)

    Barnes, G.A.

    1996-01-01

    This Acceptance Test Report (ATR) documents the results of WHC-SD-WM-ATP-146 (Prototype Cone Penetrometer Moisture Probe Acceptance Test Procedure) and WHC-SD-WM-ATP-145 (Cone Penetrometer Moisture Probe Acceptance Test Procedure). The master copy of WHC-SD-WM-ATP-145 can be found in Appendix A and the master copy of WHC-SD-WM-ATP-146 can be found in Appendix B. Also included with this report is a matrix showing design criteria of the cone penetrometer moisture probe and the verification method used (Appendix C)

  6. Demise of light cone field theory

    International Nuclear Information System (INIS)

    Hagen, C.R.

    1977-01-01

    It is shown that the massive spin one-half field is noncovariant in two dimensional light cone coordinates. It is shown that spin one-half is noncovariant in four dimensions as well. It is concluded that since the case of the spin one-half field is an absolute necessity if one is to build a world containing fermions. It seems safe to infer that light cone quantization cannot be useful in the quark binding problem as currently conceived. It is suggested that further work on light cone quantization be focused solely upon the questions of consistency as discussed rather than on applications to model building. 9 references

  7. Time development of drift wave with loss-cone in an inhomogeneous low β plasma

    International Nuclear Information System (INIS)

    Pandey, R.P.; Sharan, R.R.; Prasad, Ramesh; Mishra, S.P.; Tiwari, M.S.

    1995-01-01

    Using particle aspect analysis, a generalized dispersion relation for the time-dependent electrostatic drift waves propagating through inhomogeneous low β magnetoplasma (β being the ratio of plasma pressure to the magnetic pressure) has been derived in the presence of the loss-cone distribution index (J). The dispersion characteristics and time-dependent growth/damping rates of the wave have been computed. The distribution index seems to modify the dispersion characteristics and hence the growth rate. The computed growth rate is time-dependent, increasing with the increase of time, while the growth rate decreases with the increase of the loss-cone distribution index. In the case when growth rate increasing sufficiently with time, becomes comparable to the real frequency of the wave, the present linear theory loses its validity. The applicability of the result for the space plasma has been indicated particularly for the parameters suited to plasmapause region. (author). 30 refs., 5 figs

  8. Correlation Between Cone Penetration Rate And Measured Cone Penetration Parameters In Silty Soils

    DEFF Research Database (Denmark)

    Poulsen, Rikke; Nielsen, Benjaminn Nordahl; Ibsen, Lars Bo

    2013-01-01

    This paper shows, how a change in cone penetration rate affects the cone penetration measurements, hence the cone resistance, pore pressure, and sleeve friction in silty soil. The standard rate of penetration is 20 mm/s, and it is generally accepted that undrained penetration occurs in clay while...... drained penetration occurs in sand. When lowering the penetration rate, the soil pore water starts to dissipate and a change in the drainage condition is seen. In intermediate soils such as silty soils, the standard cone penetration rate may result in a drainage condition that could be undrained......, partially or fully drained. However, lowering the penetration rate in silty soils has a great significance because of the soil permeability, and only a small change in penetration rate will result in changed cone penetration measurements. In this paper, analyses will be done on data from 15 field cone...

  9. Anatomy of the trigeminal nerve

    NARCIS (Netherlands)

    van Eijden, T.M.G.J.; Langenbach, G.E.J.; Baart, J.A.; Brand, H.S.

    2017-01-01

    The trigeminal nerve is the fifth cranial nerve (n. V), which plays an important role in the innervation of the head and neck area, together with other cranial and spinal nerves. Knowledge of the nerve’s anatomy is very important for the correct application of local anaesthetics.

  10. Imaging the ocular motor nerves.

    NARCIS (Netherlands)

    Ferreira, T.; Verbist, B.M.; Buchem, M. van; Osch, T. van; Webb, A.

    2010-01-01

    The ocular motor nerves (OMNs) comprise the oculomotor, trochlear and the abducens nerves. According to their course, they are divided into four or five anatomic segments: intra-axial, cisternal, cavernous and intra-orbital and, for the abducens nerve, an additional interdural segment. Magnetic

  11. Neural stem cells promote nerve regeneration through IL12-induced Schwann cell differentiation.

    Science.gov (United States)

    Lee, Don-Ching; Chen, Jong-Hang; Hsu, Tai-Yu; Chang, Li-Hsun; Chang, Hsu; Chi, Ya-Hui; Chiu, Ing-Ming

    2017-03-01

    Regeneration of injured peripheral nerves is a slow, complicated process that could be improved by implantation of neural stem cells (NSCs) or nerve conduit. Implantation of NSCs along with conduits promotes the regeneration of damaged nerve, likely because (i) conduit supports and guides axonal growth from one nerve stump to the other, while preventing fibrous tissue ingrowth and retaining neurotrophic factors; and (ii) implanted NSCs differentiate into Schwann cells and maintain a growth factor enriched microenvironment, which promotes nerve regeneration. In this study, we identified IL12p80 (homodimer of IL12p40) in the cell extracts of implanted nerve conduit combined with NSCs by using protein antibody array and Western blotting. Levels of IL12p80 in these conduits are 1.6-fold higher than those in conduits without NSCs. In the sciatic nerve injury mouse model, implantation of NSCs combined with nerve conduit and IL12p80 improves motor recovery and increases the diameter up to 4.5-fold, at the medial site of the regenerated nerve. In vitro study further revealed that IL12p80 stimulates the Schwann cell differentiation of mouse NSCs through the phosphorylation of signal transducer and activator of transcription 3 (Stat3). These results suggest that IL12p80 can trigger Schwann cell differentiation of mouse NSCs through Stat3 phosphorylation and enhance the functional recovery and the diameter of regenerated nerves in a mouse sciatic nerve injury model. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Optic nerve oxygen tension

    DEFF Research Database (Denmark)

    Kiilgaard, Jens Folke; Pedersen, D B; Eysteinsson, T

    2004-01-01

    The authors have previously reported that carbonic anhydrase inhibitors such as acetazolamide and dorzolamide raise optic nerve oxygen tension (ONPO(2)) in pigs. The purpose of the present study was to investigate whether timolol, which belongs to another group of glaucoma drugs called beta...

  13. Mach cones in space and laboratory dusty magnetoplasmas

    International Nuclear Information System (INIS)

    Mamun, A.A.; Shukla, P.K

    2004-07-01

    We present a rigorous theoretical investigation on the possibility for the formation of Mach cones in both space and laboratory dusty magnetoplasmas. We find the parametric regimes for which different types of Mach cones, such as dust acoustic Mach cones, dust magneto-acoustic Mach cones, oscillonic Mach cones, etc. are formed in space and laboratory dusty magnetoplasmas. We also identify the basic features of such different classes of Mach cones (viz. dust- acoustic, dust magneto-acoustic, oscillonic Mach cones, etc.), and clearly explain how they are relevant to space and laboratory dusty manetoplasmas. (author)

  14. Accessory mental foramen: A rare anatomical variation detected by cone-beam computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Torres, Marianna Guanaes Gomes; De Faro Valverde, Ludmila; Vidal, Manuela Torres Andion; Crusoe-Rebello, Ieda Margarida [Dept. of Oral Radiology, School of Dentistry, Federal University of Bahia, Salvador (Brazil)

    2015-03-15

    The mental foramen is a bilateral opening in the vestibular portion of the mandible through which nerve endings, such as the mental nerve, emerge. In general, the mental foramen is located between the lower premolars. This region is a common area for the placement of dental implants. It is very important to identify anatomical variations in presurgical imaging exams since damage to neurovascular bundles may have a direct influence on treatment success. In the hemimandible, the mental foramen normally appears as a single structure, but there are some rare reports on the presence and number of anatomical variations; these variations may include accessory foramina. The present report describes the presence of accessory mental foramina in the right mandible, as detected by cone-beam computed tomography before dental implant placement.

  15. Assessment of nerve regeneration across nerve allografts treated with tacrolimus.

    Science.gov (United States)

    Haisheng, Han; Songjie, Zuo; Xin, Li

    2008-01-01

    Although regeneration of nerve allotransplant is a major concern in the clinic, there have been few papers quantitatively assessing functional recovery of animals' nerve allografts in the long term. In this study, functional recovery, histopathological study, and immunohistochemistry changes of rat nerve allograft with FK506 were investigated up to 12 weeks without slaughtering. C57 and SD rats were used for transplantation. The donor's nerve was sliced and transplanted into the recipient. The sciatic nerve was epineurally sutured with 10-0 nylon. In total, 30 models of transplantation were performed and divided into 3 groups that were either treated with FK506 or not. Functional recovery of the grafted nerve was serially assessed by the pin click test, walking track analysis and electrophysiological evaluations. A histopathological study and immunohistochemistry study were done in the all of the models. Nerve allografts treated with FK506 have no immune rejection through 12 weeks. Sensibility had similarly improved in both isografts and allografts. There has been no difference in each graft. Walk track analysis demonstrates significant recovery of motor function of the nerve graft. No histological results of difference were found up to 12 weeks in each graft. In the rodent nerve graft model, FK506 prevented nerve allograft rejection across a major histocompatibility barrier. Sensory recovery seems to be superior to motor function. Nerve isograft and allograft treated with FK506 have no significant difference in function recovery, histopathological result, and immunohistochemistry changes.

  16. Genetics Home Reference: cone-rod dystrophy

    Science.gov (United States)

    ... common cause of autosomal recessive cone-rod dystrophy , accounting for 30 to 60 percent of cases. At ... dystrophy play essential roles in the structure and function of specialized light receptor cells (photoreceptors) in the ...

  17. Perturbation theory in light-cone gauge

    International Nuclear Information System (INIS)

    Vianello, Eliana

    2000-01-01

    Perturbation calculations are presented for the light-cone gauge Schwinger model. Eigenstates can be calculated perturbatively but the perturbation theory is nonstandard. We hope to extend the work to QCD 2 to resolve some outstanding issues in those theories

  18. Modified superstring in light cone gauge

    International Nuclear Information System (INIS)

    Kamimura, Kiyoshi; Tatewaki, Machiko.

    1988-01-01

    We analyze the covariant superstring theory proposed by Siegel in light cone gauge. The physical states are the direct product of those of Green-Schwarz Superstring and the additional internal space spanned by light cone spinors. At clasical level, there is no difference among observables in Siegel's modified Superstring theory (SMST) and Green-Schwarz's one (GSST). However SMST can not be quantized with additional constraints as the physical state conditions. (author)

  19. Biocompatibility of Different Nerve Tubes

    Science.gov (United States)

    Stang, Felix; Keilhoff, Gerburg; Fansa, Hisham

    2009-01-01

    Bridging nerve gaps with suitable grafts is a major clinical problem. The autologous nerve graft is considered to be the gold standard, providing the best functional results; however, donor site morbidity is still a major disadvantage. Various attempts have been made to overcome the problems of autologous nerve grafts with artificial nerve tubes, which are “ready-to-use” in almost every situation. A wide range of materials have been used in animal models but only few have been applied to date clinically, where biocompatibility is an inevitable prerequisite. This review gives an idea about artificial nerve tubes with special focus on their biocompatibility in animals and humans.

  20. Pathology of the vestibulocochlear nerve

    Energy Technology Data Exchange (ETDEWEB)

    De Foer, Bert [Department of Radiology, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail: bert.defoer@GZA.be; Kenis, Christoph [Department of Radiology, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail: christophkenis@hotmail.com; Van Melkebeke, Deborah [Department of Neurology, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail: Deborah.vanmelkebeke@Ugent.be; Vercruysse, Jean-Philippe [University Department of ENT, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail: jphver@yahoo.com; Somers, Thomas [University Department of ENT, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail: Thomas.somers@GZA.be; Pouillon, Marc [Department of Radiology, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail: marc.pouillon@GZA.be; Offeciers, Erwin [University Department of ENT, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium)], E-mail: Erwin.offeciers@GZA.be; Casselman, Jan W. [Department of Radiology, AZ Sint-Jan AV Hospital, Ruddershove 10, Bruges (Belgium); Consultant Radiologist, Sint-Augustinus Hospital, Oosterveldlaan 24, 2610 Wilrijk (Belgium); Academic Consultent, University of Ghent (Belgium)], E-mail: jan.casselman@azbrugge.be

    2010-05-15

    There is a large scala of pathology affecting the vestibulocochlear nerve. Magnetic resonance imaging is the method of choice for the investigation of pathology of the vestibulocochlear nerve. Congenital pathology mainly consists of agenesis or hypoplasia of the vestibulocochlear nerve. Tumoral pathology affecting the vestibulocochlear nerve is most frequently located in the internal auditory canal or cerebellopontine angle. Schwannoma of the vestibulocochlear nerve is the most frequently found tumoral lesion followed by meningeoma, arachnoid cyst and epidermoid cyst. The most frequently encountered pathologies as well as some more rare entities are discussed in this chapter.

  1. Pathology of the vestibulocochlear nerve

    International Nuclear Information System (INIS)

    De Foer, Bert; Kenis, Christoph; Van Melkebeke, Deborah; Vercruysse, Jean-Philippe; Somers, Thomas; Pouillon, Marc; Offeciers, Erwin; Casselman, Jan W.

    2010-01-01

    There is a large scala of pathology affecting the vestibulocochlear nerve. Magnetic resonance imaging is the method of choice for the investigation of pathology of the vestibulocochlear nerve. Congenital pathology mainly consists of agenesis or hypoplasia of the vestibulocochlear nerve. Tumoral pathology affecting the vestibulocochlear nerve is most frequently located in the internal auditory canal or cerebellopontine angle. Schwannoma of the vestibulocochlear nerve is the most frequently found tumoral lesion followed by meningeoma, arachnoid cyst and epidermoid cyst. The most frequently encountered pathologies as well as some more rare entities are discussed in this chapter.

  2. Evaluation of the relationship between mandibular third molar and mandibular canal by different algorithms of cone-beam computed tomography.

    Science.gov (United States)

    Mehdizadeh, Mojdeh; Ahmadi, Navid; Jamshidi, Mahsa

    2014-11-01

    Exact location of the inferior alveolar nerve (IAN) bundle is very important. The aim of this study is to evaluate the relationship between the mandibular third molar and the mandibular canal by cone-beam computed tomography. This was a cross-sectional study with convenience sampling. 94 mandibular CBCTs performed with CSANEX 3D machine (Soredex, Finland) and 3D system chosen. Vertical and horizontal relationship between the mandibular canal and the third molar depicted by 3D, panoramic reformat view of CBCT and cross-sectional view. Cross-sectional view was our gold standard and other view evaluated by it. There were significant differences between the vertical and horizontal relation of nerve and tooth in all views (p < 0.001). The results showed differences in the position of the inferior alveolar nerve with different views of CBCT, so CBCT images are not quite reliable and have possibility of error.

  3. Design of a trichromatic cone array.

    Directory of Open Access Journals (Sweden)

    Patrick Garrigan

    2010-02-01

    Full Text Available Cones with peak sensitivity to light at long (L, medium (M and short (S wavelengths are unequal in number on the human retina: S cones are rare (<10% while increasing in fraction from center to periphery, and the L/M cone proportions are highly variable between individuals. What optical properties of the eye, and statistical properties of natural scenes, might drive this organization? We found that the spatial-chromatic structure of natural scenes was largely symmetric between the L, M and S sensitivity bands. Given this symmetry, short wavelength attenuation by ocular media gave L/M cones a modest signal-to-noise advantage, which was amplified, especially in the denser central retina, by long-wavelength accommodation of the lens. Meanwhile, total information represented by the cone mosaic remained relatively insensitive to L/M proportions. Thus, the observed cone array design along with a long-wavelength accommodated lens provides a selective advantage: it is maximally informative.

  4. Chloride currents in cones modify feedback from horizontal cells to cones in goldfish retina

    Science.gov (United States)

    Endeman, Duco; Fahrenfort, Iris; Sjoerdsma, Trijntje; Steijaert, Marvin; ten Eikelder, Huub; Kamermans, Maarten

    2012-01-01

    In neuronal systems, excitation and inhibition must be well balanced to ensure reliable information transfer. The cone/horizontal cell (HC) interaction in the retina is an example of this. Because natural scenes encompass an enormous intensity range both in temporal and spatial domains, the balance between excitation and inhibition in the outer retina needs to be adaptable. How this is achieved is unknown. Using electrophysiological techniques in the isolated retina of the goldfish, it was found that opening Ca2+-dependent Cl− channels in recorded cones reduced the size of feedback responses measured in both cones and HCs. Furthermore, we show that cones express Cl− channels that are gated by GABA released from HCs. Similar to activation of ICl(Ca), opening of these GABA-gated Cl− channels reduced the size of light-induced feedback responses both in cones and HCs. Conversely, application of picrotoxin, a blocker of GABAA and GABAC receptors, had the opposite effect. In addition, reducing GABA release from HCs by blocking GABA transporters also led to an increase in the size of feedback. Because the independent manipulation of Ca2+-dependent Cl− currents in individual cones yielded results comparable to bath-applied GABA, it was concluded that activation of either Cl− current by itself is sufficient to reduce the size of HC feedback. However, additional effects of GABA on outer retinal processing cannot be excluded. These results can be accounted for by an ephaptic feedback model in which a cone Cl− current shunts the current flow in the synaptic cleft. The Ca2+-dependent Cl− current might be essential to set the initial balance between the feedforward and the feedback signals active in the cone HC synapse. It prevents that strong feedback from HCs to cones flood the cone with Ca2+. Modulation of the feedback strength by GABA might play a role during light/dark adaptation, adjusting the amount of negative feedback to the signal to noise ratio of the

  5. [Effect of "Xingnao Kaiqiao Zhenfa" (Acupuncture Technique for Restoring Consciousness) Combined with Rehabilitation Training on Nerve Repair and Expression of Growth-associated Protein-43 of Peri-ischemic Cortex in Ischemic Stroke Rats].

    Science.gov (United States)

    Xu, Lei; Yan, Xing-Zhou; Li, Zhen-Yu; Cao, Xiao-Fang; Wang, Min

    2017-06-25

    To observe the effect of "Xingnao Kaiqiao Zhenfa" (acupuncture technique for restoring consciousness) combined with enriched rehabilitation training on motor function and expression of growth-associated protein-43 (GAP-43) of peri-ischemic cortex in ischemic stroke rats, so as to investigate its mechanism underlying improvement of ischemic stroke. SD rats were randomly divided into sham operation, model, rehabilitation and comprehensive rehabilitation groups, which were further divided into 3 time-points:7, 14 and 21 d ( n =6 in each). Cerebral ischemia(CI) model was established by occlusion of the middle cerebral artery with heat-coagulation. The rehabilitation group was treated by enriched rehabilitation training, once a day. The comprehensive rehabilitation group was treated by acupuncture combined with enriched rehabilitation training. Acupuncture was applied to bilateral "Neiguan"(PC 6) and "Shuigou"(GV 26) for 30 min, once a day. The neurological function score, balance-beam walking test and rotating-rod walking test were evaluated at the end of the corresponding treatment time. The expression of GAP-43 in peri-ischemic cortex was detected by immunohistochemistry. In comparison with the sham operation group, the scores of neurological function, beam walking test and rotating-rod walking test were significantly higher in the model group ( P beam walking and rotating-rod walking tests in the rehabilitation group compared with the model group on day 7 ( P >0.05). Compared with the model group at the other time points, the scores of neurological function, balance-beam walking test and rotating-rod walking test were significantly lower in the rehabilitation and comprehensive rehabilitation groups ( P beam walking test and rotating-rod walking test were significantly lower in the comprehensive rehabilitation group ( P <0.05). In comparison with the sham operation group, the number of GAP-43 positive cells of peri-ischemic cortex was significantly higher in the

  6. Vascularized nerve grafts for lower extremity nerve reconstruction.

    Science.gov (United States)

    Terzis, Julia K; Kostopoulos, Vasileios K

    2010-02-01

    Vascularized nerve grafts (VNG) were introduced in 1976 but since then, there have been no reports of their usage in lower extremity reconstruction systematically. The factors influencing outcomes as well as a comparison with conventional nerve grafts will be presented.Since 1981, 14 lower extremity nerve injuries in 12 patients have been reconstructed with VNG. Common peroneal nerve was injured in 12 and posterior tibial nerve in 5 patients. The level of the injury was at the knee or thigh. Twelve sural nerves were used as VNG with or without concomitant vascularized posterior calf fascia.All patients regained improved sensibility and adequate posterior tibial nerve function. For common peroneal nerve reconstructions, all patients with denervation time less than 6 months regained muscle strength of grade at least 4, even when long grafts were used for defects of 20 cm or more. Late cases, yielded inadequate muscle function even with the use of VNG.Denervation time of 6 months or less was critical for reconstruction with vascularized nerve graft. Not only the results were statistically significant compared with late cases, but also all early operated patients achieved excellent results. VNG are strongly recommended in traction avulsion injuries of the lower extremity with lengthy nerve damage.

  7. Comparison of the fastest regenerating motor and sensory myelinated axons in the same peripheral nerve

    DEFF Research Database (Denmark)

    Moldovan, Mihai; Sørensen, Jesper; Krarup, Christian

    2006-01-01

    Functional outcome after peripheral nerve regeneration is often poor, particularly involving nerve injuries far from their targets. Comparison of sensory and motor axon regeneration before target reinnervation is not possible in the clinical setting, and previous experimental studies addressing...... the question of differences in growth rates of different nerve fibre populations led to conflicting results. We developed an animal model to compare growth and maturation of the fastest growing sensory and motor fibres within the same mixed nerve after Wallerian degeneration. Regeneration of cat tibial nerve...... after crush (n = 13) and section (n = 7) was monitored for up to 140 days, using implanted cuff electrodes placed around the sciatic and tibial nerves and wire electrodes at plantar muscles. To distinguish between sensory and motor fibres, recordings were carried out from L6-S2 spinal roots using cuff...

  8. Spectral characteristics of light sources for S-cone stimulation.

    Science.gov (United States)

    Schlegelmilch, F; Nolte, R; Schellhorn, K; Husar, P; Henning, G; Tornow, R P

    2002-11-01

    Electrophysiological investigations of the short-wavelength sensitive pathway of the human eye require the use of a suitable light source as a S-cone stimulator. Different light sources with their spectral distribution properties were investigated and compared with the ideal S-cone stimulator. First, the theoretical background of the calculation of relative cone energy absorption from the spectral distribution function of the light source is summarized. From the results of the calculation, the photometric properties of the ideal S-cone stimulator will be derived. The calculation procedure was applied to virtual light sources (computer generated spectral distribution functions with different medium wavelengths and spectrum widths) and to real light sources (blue and green light emitting diodes, blue phosphor of CRT-monitor, multimedia projector, LCD monitor and notebook display). The calculated relative cone absorbencies are compared to the conditions of an ideal S-cone stimulator. Monochromatic light sources with wavelengths of less than 456 nm are close to the conditions of an ideal S-cone stimulator. Spectrum widths up to 21 nm do not affect the S-cone activation significantly (S-cone activation change < 0.2%). Blue light emitting diodes with peak wavelength at 448 nm and spectrum bandwidth of 25 nm are very useful for S-cone stimulation (S-cone activation approximately 95%). A suitable display for S-cone stimulation is the Trinitron computer monitor (S-cone activation approximately 87%). The multimedia projector has a S-cone activation up to 91%, but their spectral distribution properties depends on the selected intensity. LCD monitor and notebook displays have a lower S-cone activation (< or = 74%). Carefully selecting the blue light source for S-cone stimulation can reduce the unwanted L-and M-cone activation down to 4% for M-cones and 1.5% for L-cones.

  9. Releasing 'brakes' to nerve regeneration: intrinsic molecular targets.

    Science.gov (United States)

    Krishnan, Anand; Duraikannu, Arul; Zochodne, Douglas W

    2016-02-01

    Restoring critical neuronal architecture after peripheral nerve injury is challenging. Although immediate regenerative responses to peripheral axon injury involve the synthesis of regeneration-associated proteins in neurons and Schwann cells, an unfavorable balance between growth facilitatory and growth inhibitory signaling impairs the growth continuum of injured peripheral nerves. Molecules involved with the signaling network of tumor suppressors play crucial roles in shifting the balance between growth and restraint during axon regeneration. An understanding of the molecular framework of tumor suppressor molecules in injured neurons and its impact on stage-specific regeneration events may expose therapeutic intervention points. In this review we discuss how signaling networks of the specific tumor suppressors PTEN, Rb1, p53, p27 and p21 are altered in injured peripheral nerves and how this impacts peripheral nerve regeneration. Insights into the roles and importance of these pathways may open new avenues for improving the neurological deficits associated with nerve injury. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  10. Electrical Stimulation to Enhance Axon Regeneration After Peripheral Nerve Injuries in Animal Models and Humans.

    Science.gov (United States)

    Gordon, Tessa

    2016-04-01

    Injured peripheral nerves regenerate their lost axons but functional recovery in humans is frequently disappointing. This is so particularly when injuries require regeneration over long distances and/or over long time periods. Fat replacement of chronically denervated muscles, a commonly accepted explanation, does not account for poor functional recovery. Rather, the basis for the poor nerve regeneration is the transient expression of growth-associated genes that accounts for declining regenerative capacity of neurons and the regenerative support of Schwann cells over time. Brief low-frequency electrical stimulation accelerates motor and sensory axon outgrowth across injury sites that, even after delayed surgical repair of injured nerves in animal models and patients, enhances nerve regeneration and target reinnervation. The stimulation elevates neuronal cyclic adenosine monophosphate and, in turn, the expression of neurotrophic factors and other growth-associated genes, including cytoskeletal proteins. Electrical stimulation of denervated muscles immediately after nerve transection and surgical repair also accelerates muscle reinnervation but, at this time, how the daily requirement of long-duration electrical pulses can be delivered to muscles remains a practical issue prior to translation to patients. Finally, the technique of inserting autologous nerve grafts that bridge between a donor nerve and an adjacent recipient denervated nerve stump significantly improves nerve regeneration after delayed nerve repair, the donor nerves sustaining the capacity of the denervated Schwann cells to support nerve regeneration. These reviewed methods to promote nerve regeneration and, in turn, to enhance functional recovery after nerve injury and surgical repair are sufficiently promising for early translation to the clinic.

  11. Injectable systems and implantable conduits for peripheral nerve repair

    International Nuclear Information System (INIS)

    Lin, Yen-Chih; Marra, Kacey G

    2012-01-01

    Acute sensory problems following peripheral nerve injury include pain and loss of sensation. Approximately 360 000 people in the United States suffer from upper extremity paralytic syndromes every year. Restoration of sufficient functional recovery after long-gap peripheral nerve damage remains a clinical challenge. Potential nerve repair therapies have increased in the past decade as the field of tissue engineering expands. The following review describes the use of biomaterials in nerve tissue engineering. Namely, the use of both synthetic and natural biomaterials, including non-degradable and degradable nerve grafts, is addressed. The enhancement of axonal regeneration can be achieved by further modification of the nerve guides. These approaches include injectable hydrogel fillers, controlled drug delivery systems, and cell incorporation. Hydrogels are a class of liquid–gel biomaterials with high water content. Injectable and gelling hydrogels can serve as growth factor delivery vehicles and cell carriers for tissue engineering applications. While natural hydrogels and polymers are suitable for short gap nerve repair, the use of polymers for relatively long gaps remains a clinical challenge. (paper)

  12. Clinical Course, Genetic Etiology, and Visual Outcome in Cone and Cone-Rod Dystrophy

    NARCIS (Netherlands)

    Thiadens, Alberta A. H. J.; Phan, T. My Lan; Zekveld-Vroon, Renate C.; Leroy, Bart P.; van den Born, L. Ingeborgh; Hoyng, Carel B.; Klaver, Caroline C. W.; Roosing, Susanne; Pott, Jan-Willem R.; van Schooneveld, Mary J.; van Moll-Ramirez, Norka; van Genderen, Maria M.; Boon, Camiel J. F.; den Hollander, Anneke I.; Bergen, Arthur A. B.; De Baere, Elfride; Cremers, Frans P. M.; Lotery, Andrew J.

    Objective: To evaluate the clinical course, genetic etiology, and visual prognosis in patients with cone dystrophy (CD) and cone-rod dystrophy (CRD). Design: Clinic-based, longitudinal, multicenter study. Participants: Consecutive probands with CD (N = 98), CRD (N = 83), and affected relatives (N =

  13. Optic nerve hypoplasia

    Directory of Open Access Journals (Sweden)

    Savleen Kaur

    2013-01-01

    Full Text Available Optic nerve hypoplasia (ONH is a congenital anomaly of the optic disc that might result in moderate to severe vision loss in children. With a vast number of cases now being reported, the rarity of ONH is obviously now refuted. The major aspects of ophthalmic evaluation of an infant with possible ONH are visual assessment, fundus examination, and visual electrophysiology. Characteristically, the disc is small, there is a peripapillary double-ring sign, vascular tortuosity, and thinning of the nerve fiber layer. A patient with ONH should be assessed for presence of neurologic, radiologic, and endocrine associations. There may be maternal associations like premature births, fetal alcohol syndrome, maternal diabetes. Systemic associations in the child include endocrine abnormalities, developmental delay, cerebral palsy, and seizures. Besides the hypoplastic optic nerve and chiasm, neuroimaging shows abnormalities in ventricles or white- or gray-matter development, septo-optic dysplasia, hydrocephalus, and corpus callosum abnormalities. There is a greater incidence of clinical neurologic abnormalities in patients with bilateral ONH (65% than patients with unilateral ONH. We present a review on the available literature on the same to urge caution in our clinical practice when dealing with patients with ONH. Fundus photography, ocular coherence tomography, visual field testing, color vision evaluation, neuroimaging, endocrinology consultation with or without genetic testing are helpful in the diagnosis and management of ONH. (Method of search: MEDLINE, PUBMED.

  14. Sensation, mechanoreceptor, and nerve fiber function after nerve regeneration

    DEFF Research Database (Denmark)

    Krarup, Christian; Rosén, Birgitta; Boeckstyns, Michel

    2017-01-01

    Objective: Sensation is essential for recovery after peripheral nerve injury. However, the relationship between sensory modalities and function of regenerated fibers is uncertain. We have investigated the relationships between touch threshold, tactile gnosis, and mechanoreceptor and sensory fiber...... function after nerve regeneration. Methods: Twenty-one median or ulnar nerve lesions were repaired by a collagen nerve conduit or direct suture. Quantitative sensory hand function and sensory conduction studies by near-nerve technique, including tactile stimulation of mechanoreceptors, were followed for 2...... years, and results were compared to noninjured hands. Results: At both repair methods, touch thresholds at the finger tips recovered to 81 ± 3% and tactile gnosis only to 20 ± 4% (p nerve action potentials (SNAPs) remained dispersed and areas recovered to 23 ± 2...

  15. Electrophysiology of Cranial Nerve Testing: Spinal Accessory and Hypoglossal Nerves.

    Science.gov (United States)

    Stino, Amro M; Smith, Benn E

    2018-01-01

    Multiple techniques have been developed for the electrodiagnostic evaluation of cranial nerves XI and XII. Each of these carries both benefits and limitations, with more techniques and data being available in the literature for spinal accessory than hypoglossal nerve evaluation. Spinal accessory and hypoglossal neuropathy are relatively uncommon cranial mononeuropathies that may be evaluated in the outpatient electrodiagnostic laboratory setting. A review of available literature using PubMed was conducted regarding electrodiagnostic technique in the evaluation of spinal accessory and hypoglossal nerves searching for both routine nerve conduction studies and repetitive nerve conduction studies. The review provided herein provides a resource by which clinical neurophysiologists may develop and implement clinical and research protocols for the evaluation of both of these lower cranial nerves in the outpatient setting.

  16. Resveratrol Promotes Nerve Regeneration via Activation of p300 Acetyltransferase-Mediated VEGF Signaling in a Rat Model of Sciatic Nerve Crush Injury.

    Science.gov (United States)

    Ding, Zhuofeng; Cao, Jiawei; Shen, Yu; Zou, Yu; Yang, Xin; Zhou, Wen; Guo, Qulian; Huang, Changsheng

    2018-01-01

    Peripheral nerve injuries are generally associated with incomplete restoration of motor function. The slow rate of nerve regeneration after injury may account for this. Although many benefits of resveratrol have been shown in the nervous system, it is not clear whether resveratrol could promote fast nerve regeneration and motor repair after peripheral nerve injury. This study showed that the motor deficits caused by sciatic nerve crush injury were alleviated by daily systematic resveratrol treatment within 10 days. Resveratrol increased the number of axons in the distal part of the injured nerve, indicating enhanced nerve regeneration. In the affected ventral spinal cord, resveratrol enhanced the expression of several vascular endothelial growth factor family proteins (VEGFs) and increased the phosphorylation of p300 through Akt signaling, indicating activation of p300 acetyltransferase. Inactivation of p300 acetyltransferase reversed the resveratrol-induced expression of VEGFs and motor repair in rats that had undergone sciatic nerve crush injury. The above results indicated that daily systematic resveratrol treatment promoted nerve regeneration and led to rapid motor repair. Resveratrol activated p300 acetyltransferase-mediated VEGF signaling in the affected ventral spinal cord, which may have thus contributed to the acceleration of nerve regeneration and motor repair.

  17. Applied electric field enhances DRG neurite growth: influence of stimulation media, surface coating and growth supplements

    Science.gov (United States)

    Wood, Matthew D.; Willits, Rebecca Kuntz

    2009-08-01

    Electrical therapies have been found to aid repair of nerve injuries and have been shown to increase and direct neurite outgrowth during stimulation. This enhanced neural growth existed even after the electric field (EF) or stimulation was removed, but the factors that may influence the enhanced growth, such as stimulation media or surface coating, have not been fully investigated. This study characterized neurite outgrowth and branching under various conditions: EF magnitude and application time, ECM surface coating, medium during EF application and growth supplements. A uniform, low-magnitude EF (24 or 44 V m-1) was applied to dissociated chick embryo dorsal root ganglia seeded on collagen or laminin-coated surfaces. During the growth period, cells were either exposed to NGF or N2, and during stimulation cells were exposed to either unsupplemented media (Ca2+) or PBS (no Ca2+). Parallel controls for each experiment included cells exposed to the chamber with no stimulation and cells remaining outside the chamber. After brief electrical stimulation (10 min), neurite length significantly increased 24 h after application for all conditions studied. Of particular interest, increased stimulation time (10-100 min) further enhanced neurite length on laminin but not on collagen surfaces. Neurite branching was not affected by stimulation on any surface, and no preferential growth of neurites was noted after stimulation. Overall, the results of this report suggest that short-duration electric stimulation is sufficient to enhance neurite length under a variety of conditions. While further data are needed to fully elucidate a mechanism for this increased growth, these data suggest that one focus of those investigations should be the interaction between the growth cone and the substrata.

  18. Multiple dendrochronological responses to the eruption of Cinder Cone, Lassen Volcanic National Park, California

    Science.gov (United States)

    Sheppard, P.R.; Ort, M.H.; Anderson, K.C.; Clynne, M.A.; May, E.M.

    2009-01-01

    Two dendrochronological properties – ring width and ring chemistry – were investigated in trees near Cinder Cone in Lassen Volcanic National Park, northeastern California, for the purpose of re-evaluating the date of its eruption. Cinder Cone is thought to have erupted in AD 1666 based on ring-width evidence, but interpreting ring-width changes alone is not straightforward because many forest disturbances can cause changes in ring width. Old Jeffrey pines growing in Cinder Cone tephra and elsewhere for control comparison were sampled. Trees growing in tephra show synchronous ring-width changes at AD 1666, but this ring-width signal could be considered ambiguous for dating the eruption because changes in ring width can be caused by other events. Trees growing in tephra also show changes in ring phosphorus, sulfur, and sodium during the late 1660s, but inter-tree variability in dendrochemical signals makes dating the eruption from ring chemistry alone difficult. The combination of dendrochemistry and ring-width signals improves confidence in dating the eruption of Cinder Cone over the analysis of just one ring-growth property. These results are similar to another case study using dendrochronology of ring width and ring chemistry at Parícutin, Michoacán, Mexico, a cinder cone that erupted beginning in 1943. In both cases, combining analysis with ring width and ring chemistry improved confidence in the dendro-dating of the eruptions.

  19. Fundamental harmonic electron cyclotron emission for hot, loss-cone type distributions

    International Nuclear Information System (INIS)

    Bornatici, M.; Ruffina, U.; Westerhof, E.

    1988-01-01

    Electron cyclotron emission (ECE) is an important diagnostic tool for the study of hot plasmas. ECE can be used not only to measure the electron temperature but also to obtain information about non-thermal characteristics of the electron distribution function. One such a nonthermal characteristic is a loss-cone anisotropy. Loss-cone anisotropy can give rise to unstable growth of electro-magnetic waves around the harmonics of the electron cyclotron resonance and to increased emissivity of electron cyclotron waves. In case of high electron temperatures, also the dispersion properties of the extraordinary (X-) mode arond the fundamental electron cyclotron resonance are changed due to loss-cone anisotropy. The consequences of these dispersion properties for the emissivity of the fundamental harmonic X-mode are analyzed for perpendicular propagation. The emissivity, is calculated for two types of distribution functions having a loss-cone anisotropy. These distribution functions are a relativistic Dory-Guest-Harris type distribution function and modified relativistic Maxwellian distribution having a loss-cone with rounded edges (author). 9 refs.; 2 figs

  20. Nerves and nerve endings in the skin of tropical cattle.

    Science.gov (United States)

    Amakiri, S F; Ozoya, S E; Ogunnaike, P O

    1978-01-01

    The nerves and nerve endings in the skin of tropical cattle were studied using histological and histochemical techniques. Many nerve trunks and fibres were present in the reticular and papillary dermis in both hairy and non-hairy skin sites. In non-hairy skin locations such as the muzzle and lower lip, encapsulated endings akin to Krause and Ruffini end bulbs, which arise from myelinated nerve trunks situated lower down the dermis were observed at the upper papillary layer level. Some fibre trunks seen at this level extended upwards to terminate within dermal papillae as bulb-shaped longitudinally lamellated Pacinian-type endings, while other onion-shaped lamellated nerve structures were located either within dermal papillae or near the dermo-epidermal area. Intraepidermal free-ending nerve fibres, appearing non-myelinated were observed in areas with thick epidermis. Intraepidermal free-ending nerve fibres, appearing non-myelinated were observed in areas with thick epidermis. On hairy skin sites, however, organized nerve endings or intraepidermal nerve endings were not readily identifiable.

  1. Electrophysiology of Cranial Nerve Testing: Cranial Nerves IX and X.

    Science.gov (United States)

    Martinez, Alberto R M; Martins, Melina P; Moreira, Ana Lucila; Martins, Carlos R; Kimaid, Paulo A T; França, Marcondes C

    2018-01-01

    The cranial nerves IX and X emerge from medulla oblongata and have motor, sensory, and parasympathetic functions. Some of these are amenable to neurophysiological assessment. It is often hard to separate the individual contribution of each nerve; in fact, some of the techniques are indeed a composite functional measure of both nerves. The main methods are the evaluation of the swallowing function (combined IX and X), laryngeal electromyogram (predominant motor vagal function), and heart rate variability (predominant parasympathetic vagal function). This review describes, therefore, the techniques that best evaluate the major symptoms presented in IX and X cranial nerve disturbance: dysphagia, dysphonia, and autonomic parasympathetic dysfunction.

  2. Transplantation of bone-marrow-derived cells into a nerve guide resulted in transdifferentiation into Schwann cells and effective regeneration of transected mouse sciatic nerve.

    Science.gov (United States)

    Pereira Lopes, Fátima Rosalina; Frattini, Flávia; Marques, Suelen Adriani; Almeida, Fernanda Martins de; de Moura Campos, Lenira Camargo; Langone, Francesco; Lora, Silvano; Borojevic, Radovan; Martinez, Ana Maria Blanco

    2010-10-01

    Peripheral nerves possess the capacity of self-regeneration after traumatic injury. Nevertheless, the functional outcome after peripheral-nerve regeneration is often poor, especially if the nerve injuries occur far from their targets. Aiming to optimize axon regeneration, we grafted bone-marrow-derived cells (BMDCs) into a collagen-tube nerve guide after transection of the mouse sciatic nerve. The control group received only the culture medium. Motor function was tested at 2, 4, and 6 weeks after surgery, using the sciatic functional index (SFI), and showed that functional recovery was significantly improved in animals that received the cell grafts. After 6 weeks, the mice were anesthetized, perfused transcardially, and the sciatic nerves were dissected and processed for transmission electron microscopy and light microscopy. The proximal and distal segments of the nerves were compared, to address the question of improvement in growth rate; the results revealed a maintenance and increase of nerve regeneration for both myelinated and non-myelinated fibers in distal segments of the experimental group. Also, quantitative analysis of the distal region of the regenerating nerves showed that the numbers of myelinated fibers, Schwann cells (SCs) and g-ratio were significantly increased in the experimental group compared to the control group. The transdifferentiation of BMDCs into Schwann cells was confirmed by double labeling with S100/and Hoechst staining. Our data suggest that BMDCs transplanted into a nerve guide can differentiate into SCs, and improve the growth rate of nerve fibers and motor function in a transected sciatic-nerve model.

  3. Strain engineering of Dirac cones in graphyne

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Gaoxue; Kumar, Ashok; Pandey, Ravindra, E-mail: pandey@mtu.edu [Department of Physics, Michigan Technological University, Houghton, Michigan 49931 (United States); Si, Mingsu [Key Laboratory for Magnetism and Magnetic Materials of the Ministry of Education, Lanzhou University, Lanzhou 730000 (China)

    2014-05-26

    6,6,12-graphyne, one of the two-dimensional carbon allotropes with the rectangular lattice structure, has two kinds of non-equivalent anisotropic Dirac cones in the first Brillouin zone. We show that Dirac cones can be tuned independently by the uniaxial compressive strain applied to graphyne, which induces n-type and p-type self-doping effect, by shifting the energy of the Dirac cones in the opposite directions. On the other hand, application of the tensile strain results into a transition from gapless to finite gap system for the monolayer. For the AB-stacked bilayer, the results predict tunability of Dirac-cones by in-plane strains as well as the strain applied perpendicular to the plane. The group velocities of the Dirac cones show enhancement in the resistance anisotropy for bilayer relative to the case of monolayer. Such tunable and direction-dependent electronic properties predicted for 6,6,12-graphyne make it to be competitive for the next-generation electronic devices at nanoscale.

  4. CRALBP supports the mammalian retinal visual cycle and cone vision

    OpenAIRE

    Xue, Yunlu; Shen, Susan Q.; Jui, Jonathan; Rupp, Alan C.; Byrne, Leah C.; Hattar, Samer; Flannery, John G.; Corbo, Joseph C.; Kefalov, Vladimir J.

    2015-01-01

    Mutations in the cellular retinaldehyde-binding protein (CRALBP, encoded by RLBP1) can lead to severe cone photoreceptor-mediated vision loss in patients. It is not known how CRALBP supports cone function or how altered CRALBP leads to cone dysfunction. Here, we determined that deletion of Rlbp1 in mice impairs the retinal visual cycle. Mice lacking CRALBP exhibited M-opsin mislocalization, M-cone loss, and impaired cone-driven visual behavior and light responses. Additionally, M-cone dark ad...

  5. Evaluation of Optic Canal and Surrounding Structures Using Cone Beam Computed Tomography: Considerations for Maxillofacial Surgery.

    Science.gov (United States)

    Sinanoglu, Alper; Orhan, Kaan; Kursun, Sebnem; Inceoglu, Beste; Oztas, Bengi

    2016-07-01

    The optic canal connects the anterior cranial fossa and the orbit and maintains the optic nerve and the ophthalmic artery. Within the extent of the surgical approach of the region, risk of iatrogenic injury of the neural and vascular structures increases. The aim of this retrospective morphometric study is to investigate the radiological anatomy of orbita, optic canal, and its surrounding using cone beam computed tomography (CBCT) scans in a group of Turkish population.Cone beam computed tomography images of a total of 182 patients were evaluated by 2 observers. Anatomical parameters regarding optic canal and orbita were measured for all patients from axial, sagittal, and three-dimensional reconstructed images. To assess intraobserver reliability, the Wilcoxon matched-pairs test was used. Pearson χ test and Student t test were performed for statistical analysis of differences, sex, localization, and measurements (P  0.05). The orbita width and height were larger for the males than females (P  0.05). Examination CBCT scans revealed that the shape of the optic canal was 70% funnel and 28% Hourglass shape, 2% amorph type round.These results provide detailed knowledge of the anatomical characteristics in the orbital area which may be of assistance for surgeons preoperatively. Cone beam computed tomography scans can be an alternative modality for multislice computed tomography with submillimeter resolution and lower dose in preoperative imaging of the orbit.

  6. Facial nerve function after vestibular schwannoma surgery following failed conservative management

    DEFF Research Database (Denmark)

    Kaltoft, Mikkel; Stangerup, Sven-Eric; Cayé-Thomasen, Per

    2012-01-01

    the risk of impaired facial nerve function post-surgery. OBJECTIVE:: To compare facial nerve function in patients operated soon after diagnosis with patients allocated to conservative management, and the subgroup of these who later had surgery due to tumor growth. METHODS:: 1378 consecutive patients...... patients had normal facial nerve function at the end of observation. Good facial nerve outcome was found in 87 % of patients operated at diagnosis, and in 84 % of patients operated after established tumor growth. For the subgroup of small extrameatal tumors this difference was significant. Pooling all...... to preservation of the facial nerve function. Tumor growth during observation is found in only a minor proportion of the patients, and in these cases surgery or irradiation should be performed immediately....

  7. Continuous growth of the motor system in the axolotl

    International Nuclear Information System (INIS)

    Holder, N.; Clarke, J.D.; Stephens, N.; Wilson, S.W.; Orsi, C.; Bloomer, T.; Tonge, D.A.

    1991-01-01

    During growth of the axolotl, motor neurons, and muscle fibres are added to the motor system. By double labelling neurons with tritiated thymidine and retrogradely transported HRP, we show that some motor neurons are born at postembryonic stages. Further analysis of motor neurons with the aid of HRP reveals this population of newly born cells relatively frequently in small (5-7 cm long) axolotls, but only rarely in large (7-13 cm long) axolotls. Evidence is presented that suggests that these immature cells are in the process of migrating from close to the ependyma out to the ventral horn. HRP transport also reveals growth cones of advancing axons within spinal nerves in animals up to 6 cm in length. Cell counts by light and electron microscopic methods show that muscle fibres are generated throughout larval life in the iliotibialis, a typical limb muscle. This analysis provides data consistent with the notion that new muscle fibres are added from a localised growth zone situated at the superficial edge of the muscle. These results are discussed in terms of the correlation between continuous growth of the motor system and the ability of the axolotl to functionally repair lesions to the peripheral nervous system

  8. Respiratory correlated cone beam CT

    International Nuclear Information System (INIS)

    Sonke, Jan-Jakob; Zijp, Lambert; Remeijer, Peter; Herk, Marcel van

    2005-01-01

    A cone beam computed tomography (CBCT) scanner integrated with a linear accelerator is a powerful tool for image guided radiotherapy. Respiratory motion, however, induces artifacts in CBCT, while the respiratory correlated procedures, developed to reduce motion artifacts in axial and helical CT are not suitable for such CBCT scanners. We have developed an alternative respiratory correlated procedure for CBCT and evaluated its performance. This respiratory correlated CBCT procedure consists of retrospective sorting in projection space, yielding subsets of projections that each corresponds to a certain breathing phase. Subsequently, these subsets are reconstructed into a four-dimensional (4D) CBCT dataset. The breathing signal, required for respiratory correlation, was directly extracted from the 2D projection data, removing the need for an additional respiratory monitor system. Due to the reduced number of projections per phase, the contrast-to-noise ratio in a 4D scan reduced by a factor 2.6-3.7 compared to a 3D scan based on all projections. Projection data of a spherical phantom moving with a 3 and 5 s period with and without simulated breathing irregularities were acquired and reconstructed into 3D and 4D CBCT datasets. The positional deviations of the phantoms center of gravity between 4D CBCT and fluoroscopy were small: 0.13±0.09 mm for the regular motion and 0.39±0.24 mm for the irregular motion. Motion artifacts, clearly present in the 3D CBCT datasets, were substantially reduced in the 4D datasets, even in the presence of breathing irregularities, such that the shape of the moving structures could be identified more accurately. Moreover, the 4D CBCT dataset provided information on the 3D trajectory of the moving structures, absent in the 3D data. Considerable breathing irregularities, however, substantially reduces the image quality. Data presented for three different lung cancer patients were in line with the results obtained from the phantom study. In

  9. The role of great auricular-facial nerve neurorrhaphy in facial nerve damage

    OpenAIRE

    Sun, Yan; Liu, Limei; Han, Yuechen; Xu, Lei; Zhang, Daogong; Wang, Haibo

    2015-01-01

    Background: Facial nerve is easy to be damaged, and there are many reconstructive methods for facial nerve reconstructive, such as facial nerve end to end anastomosis, the great auricular nerve graft, the sural nerve graft, or hypoglossal-facial nerve anastomosis. However, there is still little study about great auricular-facial nerve neurorrhaphy. The aim of the present study was to identify the role of great auricular-facial nerve neurorrhaphy and the mechanism. Methods: Rat models of facia...

  10. [Imaging anatomy of cranial nerves].

    Science.gov (United States)

    Hermier, M; Leal, P R L; Salaris, S F; Froment, J-C; Sindou, M

    2009-04-01

    Knowledge of the anatomy of the cranial nerves is mandatory for optimal radiological exploration and interpretation of the images in normal and pathological conditions. CT is the method of choice for the study of the skull base and its foramina. MRI explores the cranial nerves and their vascular relationships precisely. Because of their small size, it is essential to obtain images with high spatial resolution. The MRI sequences optimize contrast between nerves and surrounding structures (cerebrospinal fluid, fat, bone structures and vessels). This chapter discusses the radiological anatomy of the cranial nerves.

  11. Autonomic nerve-sparing surgery with preoperative or intraoperative radiotherapy for advanced lower rectal cancer

    International Nuclear Information System (INIS)

    Saito, Norio; Ono, Masato; Sugifuji, Masanori; Kawashima, Kiyotaka; Arai, Tatsuo; Koda, Keishi; Takiguchi, Nobuhiro; Oda, Kenji; Nakajima, Nobuyuki

    2000-01-01

    Autonomic-nerve-sparing surgery was performed for advanced lower rectal cancer, and the results in patients who had undergone preoperative irradiation plus chemotherapy (RCT group) and intraoperative irradiation (IORT group) were compared. The autonomic nerves of 76 of the 84 patients in the RCT group were conserved. The radiation dose was 42.6 Gy, and surgery was performed 2 weeks after the irradiation. Their curability was A. Urinary function was maintained. The results for sexual function were better in the cases in which the autonomic nerves were completely conserved. The 5-year cumulative survival rate was 84.1%. The local recurrence rate was 7.9% and was no higher after treatment by the conventional method. The autonomic nerves of all 61 patients in the IORT group, were conserved. Patients were irradiated with 15 Gy (5 MeV) to the pelvic nerve plexuses and peripheral region with a cone 4 cm in diameter. Irradiation depth was estimated to be approximately 15 mm. The results for urinary function and sexual function were equivalent to those in the RCT group. The 5-year cumulative survival rate was 79%. The local recurrence rate was 9.8%. The autonomic nerve conservation rate was increased in both groups but the results in terms of QOL, such as sexual function, were inadequate. Further development and improvement of treatment methods for advanced lower rectal cancer are needed. (K.H.)

  12. Identification of adequate vehicles to carry nerve regeneration inducers using tubulisation.

    Science.gov (United States)

    do Nascimento-Elias, Adriana Helena; Fresnesdas, Bruno César; Schiavoni, Maria Cristina Lopes; de Almeida, Natália Fernanda Gaspar; Santos, Ana Paula; de Oliveira Ramos, Jean; Junior, Wilson Marques; Barreira, Amilton Antunes

    2012-08-14

    Axonal regeneration depends on many factors, such as the type of injury and repair, age, distance from the cell body and distance of the denervated muscle, loss of surrounding tissue and the type of injured nerve. Experimental models use tubulisation with a silicone tube to research regenerative factors and substances to induce regeneration. Agarose, collagen and DMEM (Dulbecco's modified Eagle's medium) can be used as vehicles. In this study, we compared the ability of these vehicles to induce rat sciatic nerve regeneration with the intent of finding the least active or inert substance. The experiment used 47 female Wistar rats, which were divided into four experimental groups (agarose 4%, agarose 0.4%, collagen, DMEM) and one normal control group. The right sciatic nerve was exposed, and an incision was made that created a 10 mm gap between the distal and proximal stumps. A silicone tube was grafted onto each stump, and the tubes were filled with the respective media. After 70 days, the sciatic nerve was removed. We evaluated the formation of a regeneration cable, nerve fibre growth, and the functional viability of the regenerated fibres. Comparison among the three vehicles showed that 0.4% agarose gels had almost no effect on provoking the regeneration of peripheral nerves and that 4% agarose gels completely prevented fibre growth. The others substances were associated with profuse nerve fibre growth. In the appropriate concentration, agarose gel may be an important vehicle for testing factors that induce regeneration without interfering with nerve growth.

  13. A rare case of diaphragmatic paralysis due to isolated phrenic nerve ...

    African Journals Online (AJOL)

    2008-11-04

    Nov 4, 2008 ... Isolated phrenic nerve palsy is a rare condition resulting from birth injury, with many possible complications such as diaphragmatic paralysis, pulmonary infection, chronic lung disease, growth failure and even death.1-3 I report a case of neonatal isolated phrenic nerve palsy in an infant delivered.

  14. Characterization of a chondroitin sulfate hydrogel for nerve root regeneration

    Science.gov (United States)

    Conovaloff, Aaron; Panitch, Alyssa

    2011-10-01

    Brachial plexus injury is a serious medical problem that affects many patients annually, with most cases involving damage to the nerve roots. Therefore, a chondroitin sulfate hydrogel was designed to both serve as a scaffold for regenerating root neurons and deliver neurotrophic signals. Capillary electrophoresis showed that chondroitin sulfate has a dissociation constant in the micromolar range with several common neurotrophins, and this was determined to be approximately tenfold stronger than with heparin. It was also revealed that nerve growth factor exhibits a slightly stronger affinity for hyaluronic acid than for chondroitin sulfate. However, E8 chick dorsal root ganglia cultured in the presence of nerve growth factor revealed that ganglia cultured in chondroitin sulfate scaffolds showed more robust growth than those cultured in control gels of hyaluronic acid. It is hypothesized that, despite the stronger affinity of nerve growth factor for hyaluronic acid, chondroitin sulfate serves as a better scaffold for neurite outgrowth, possibly due to inhibition of growth by hyaluronic acid chains.

  15. Understanding the cone scale in Cupressaceae: insights from seed-cone teratology in Glyptostrobus pensilis.

    Science.gov (United States)

    Dörken, Veit Martin; Rudall, Paula J

    2018-01-01

    Both wild-type and teratological seed cones are described in the monoecious conifer Glyptostrobus pensilis and compared with those of other Cupressaceae sensu lato and other conifers. Some Cupressaceae apparently possess a proliferation of axillary structures in their cone scales. In our interpretation, in Glyptostrobus each bract of both typical and atypical seed cones bears two descending accessory shoots, interpreted here as seed scales (ovuliferous scales). The primary seed scale is fertile and forms the ovules, the second is sterile and forms characteristic tooth-like structures. The bract and the two axillary seed scales are each supplied with a single distinct vascular bundle that enters the cone axis as a separate strand; this vasculature also characterises the descending accessory short shoots in the vegetative parts of the crown. In wild-type seed cones, the fertile seed scale is reduced to its ovules, and the ovules are always axillary. In contrast, the ovules of some of the teratological seed cones examined were located at the centre of the cone scale. An additional tissue found on the upper surface of the sterile lower seed scale is here interpreted as the axis of the fertile seed scale. Thus, the central position of the ovules can be explained by recaulescent fusion of the upper fertile and lower sterile seed scales. In several teratological cone scales, the ovules were enveloped by an additional sterile tissue that is uniseriate and represents an epidermal outgrowth of the fertile seed scale. Close to the ovules, the epidermis was detached from lower tissue and surrounded the ovule completely, except at the micropyle. These teratological features are potentially significant in understanding seed-cone homologies among extant conifers.

  16. Understanding the cone scale in Cupressaceae: insights from seed-cone teratology in Glyptostrobus pensilis

    Directory of Open Access Journals (Sweden)

    Veit Martin Dörken

    2018-06-01

    Full Text Available Both wild-type and teratological seed cones are described in the monoecious conifer Glyptostrobus pensilis and compared with those of other Cupressaceae sensu lato and other conifers. Some Cupressaceae apparently possess a proliferation of axillary structures in their cone scales. In our interpretation, in Glyptostrobus each bract of both typical and atypical seed cones bears two descending accessory shoots, interpreted here as seed scales (ovuliferous scales. The primary seed scale is fertile and forms the ovules, the second is sterile and forms characteristic tooth-like structures. The bract and the two axillary seed scales are each supplied with a single distinct vascular bundle that enters the cone axis as a separate strand; this vasculature also characterises the descending accessory short shoots in the vegetative parts of the crown. In wild-type seed cones, the fertile seed scale is reduced to its ovules, and the ovules are always axillary. In contrast, the ovules of some of the teratological seed cones examined were located at the centre of the cone scale. An additional tissue found on the upper surface of the sterile lower seed scale is here interpreted as the axis of the fertile seed scale. Thus, the central position of the ovules can be explained by recaulescent fusion of the upper fertile and lower sterile seed scales. In several teratological cone scales, the ovules were enveloped by an additional sterile tissue that is uniseriate and represents an epidermal outgrowth of the fertile seed scale. Close to the ovules, the epidermis was detached from lower tissue and surrounded the ovule completely, except at the micropyle. These teratological features are potentially significant in understanding seed-cone homologies among extant conifers.

  17. Resonance in a Cone-Topped Tube

    Directory of Open Access Journals (Sweden)

    Angus Cheng-Huan Chia

    2011-06-01

    Full Text Available The relationship between ratio of the upper opening diameter of a cone-topped cylinder to the cylinder diameter,and the ratio of the length of the air column to resonant period was examined. Plastic cones with upper openings ranging from 1.3 cm to 3.6 cm and tuning forks with frequencies ranging from 261.6 Hz to 523.3 Hz were used. The transition from a standing wave in a cylindrical column to a Helmholtz-type resonance in a resonant cavity with a narrow opening was observed.

  18. Cone-based Electrical Resistivity Tomography

    Science.gov (United States)

    Pidlisecky, A.; Knight, R.; Haber, E.

    2005-05-01

    Determining the 3D spatial distribution of subsurface properties is a critical part of managing the clean-up of contaminated sites. Most standard hydrologic methods sample small regions immediately adjacent to wells or testing devices. This provides data which are not representative of the entire region of interest. Furthermore, at many contaminated sites invasive methods are not acceptable, due to the risks associated with contacting and spreading the contaminants. To address these issues, we have developed a minimally invasive technology that provides information about the 3D distribution of electrical conductivity. This new technique, cone-based electrical resistivity tomography (C-bert), involves placing several permanent current electrodes in the subsurface and using electrodes mounted on a cone penetrometer to measure the resultant potential field while advancing the cone into the subsurface. In addition to potential field measurements, we obtain the standard suite of cone-penetration measurements, including high resolution resistivity logs; these data can then be used to constrain the inversion of the potential field data. A major challenge of working with these data is that the cone penetrometer is highly conductive, and thus presents a large local perturbation around the measurement location. As the cone is very small (approximately 30mm in diameter) with respect to the total model space, explicitly modeling the cone is computationally demanding. We developed a method for solving the forward model that reduces computational time by an order of magnitude. This solution method, iteratively determined boundary conditions, makes it possible to correct for the cone effect before inversion of the data. Results from synthetic experiments suggest that the C-bert method of data acquisition can result in high quality electrical conductivity images of the subsurface. We tested the practicality of this technique by performing a field test of the C-bert system to image

  19. Use of cone beam computed tomography in implant dentistry: current concepts, indications and limitations for clinical practice and research.

    Science.gov (United States)

    Bornstein, Michael M; Horner, Keith; Jacobs, Reinhilde

    2017-02-01

    Diagnostic radiology is an essential component of treatment planning in the field of implant dentistry. This narrative review will present current concepts for the use of cone beam computed tomography imaging, before and after implant placement, in daily clinical practice and research. Guidelines for the selection of three-dimensional imaging will be discussed, and limitations will be highlighted. Current concepts of radiation dose optimization, including novel imaging modalities using low-dose protocols, will be presented. For preoperative cross-sectional imaging, data are still not available which demonstrate that cone beam computed tomography results in fewer intraoperative complications such as nerve damage or bleeding incidents, or that implants inserted using preoperative cone beam computed tomography data sets for planning purposes will exhibit higher survival or success rates. The use of cone beam computed tomography following the insertion of dental implants should be restricted to specific postoperative complications, such as damage of neurovascular structures or postoperative infections in relation to the maxillary sinus. Regarding peri-implantitis, the diagnosis and severity of the disease should be evaluated primarily based on clinical parameters and on radiological findings based on periapical radiographs (two dimensional). The use of cone beam computed tomography scans in clinical research might not yield any evident beneficial effect for the patient included. As many of the cone beam computed tomography scans performed for research have no direct therapeutic consequence, dose optimization measures should be implemented by using appropriate exposure parameters and by reducing the field of view to the actual region of interest. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Transient femoral nerve palsy following ilioinguinal nerve block for ...

    African Journals Online (AJOL)

    Nigerian Journal of Surgery ... Background: Elective inguinal hernia repair in young fit patients is preferably done under ilioinguinal nerve block anesthesia in the ambulatory setting to improve ... Conclusion: TFNP is a rare complication of ilioinguinal nerve block which delays patient discharge postambulatory hernioplasty.

  1. Critical condition for the transformation from Taylor cone to cone-jet

    International Nuclear Information System (INIS)

    Wei Cheng; Zhao Yang; Gang Tie-Qiang; Chen Li-Jie

    2014-01-01

    An energy method is proposed to investigate the critical transformation condition from a Taylor cone to a cone-jet. Based on the kinetic theorem, the system power allocation and the electrohydrodynamics stability are discussed. The numerical results indicate that the energy of the liquid cone tip experiences a maximum value during the transformation. With the proposed jetting energy, we give the critical transformation condition under which the derivative of jetting energy with respect to the surface area is greater than or equal to the energy required to form a unit of new liquid surface

  2. Functional and Physical Outcomes following Use of a Flexible CO2 Laser Fiber and Bipolar Electrocautery in Close Proximity to the Rat Sciatic Nerve with Correlation to an In Vitro Thermal Profile Model

    Directory of Open Access Journals (Sweden)

    A. M. Robinson

    2015-01-01

    Full Text Available This study compared functional and physical collateral damage to a nerve when operating a Codman MALIS Bipolar Electrosurgical System CMC-III or a CO2 laser coupled to a laser, with correlation to an in vitro model of heating profiles created by the devices in thermochromic ink agarose. Functional damage of the rat sciatic nerve after operating the MALIS or CO2 laser at various power settings and proximities to the nerve was measured by electrically evoked nerve action potentials, and histology of the nerve was used to assess physical damage. Thermochromic ink dissolved in agarose was used to model the spatial and temporal profile of the collateral heating zone of the electrosurgical system and the laser ablation cone. We found that this laser can be operated at 2 W directly above the nerve with minimal damage, while power settings of 5 W and 10 W resulted in acute functional and physical nerve damage, correlating with the maximal heating cone in the thermochromic ink model. MALIS settings up to 40 (11 W did not result in major functional or physical nerve damage until the nerve was between the forceps tips, correlating with the hottest zone, localized discretely between the tips.

  3. Jordan's algebra of a facially homogeneous autopolar cone

    International Nuclear Information System (INIS)

    Bellissard, Jean; Iochum, Bruno

    1979-01-01

    It is shown that a Jordan-Banach algebra with predual may be canonically associated with a facially homogeneous autopolar cone. This construction generalizes the case where a trace vector exists in the cone [fr

  4. Electrophysiology of Cranial Nerve Testing: Trigeminal and Facial Nerves.

    Science.gov (United States)

    Muzyka, Iryna M; Estephan, Bachir

    2018-01-01

    The clinical examination of the trigeminal and facial nerves provides significant diagnostic value, especially in the localization of lesions in disorders affecting the central and/or peripheral nervous system. The electrodiagnostic evaluation of these nerves and their pathways adds further accuracy and reliability to the diagnostic investigation and the localization process, especially when different testing methods are combined based on the clinical presentation and the electrophysiological findings. The diagnostic uniqueness of the trigeminal and facial nerves is their connectivity and their coparticipation in reflexes commonly used in clinical practice, namely the blink and corneal reflexes. The other reflexes used in the diagnostic process and lesion localization are very nerve specific and add more diagnostic yield to the workup of certain disorders of the nervous system. This article provides a review of commonly used electrodiagnostic studies and techniques in the evaluation and lesion localization of cranial nerves V and VII.

  5. Receptivity of Hypersonic Boundary Layers over Straight and Flared Cones

    Science.gov (United States)

    Balakumar, Ponnampalam; Kegerise, Michael A.

    2010-01-01

    The effects of adverse pressure gradients on the receptivity and stability of hypersonic boundary layers were numerically investigated. Simulations were performed for boundary layer flows over a straight cone and two flared cones. The steady and the unsteady flow fields were obtained by solving the two-dimensional Navier-Stokes equations in axi-symmetric coordinates using the 5th order accurate weighted essentially non-oscillatory (WENO) scheme for space discretization and using third-order total-variation-diminishing (TVD) Runge-Kutta scheme for time integration. The mean boundary layer profiles were analyzed using local stability and non-local parabolized stability equations (PSE) methods. After the most amplified disturbances were identified, two-dimensional plane acoustic waves were introduced at the outer boundary of the computational domain and time accurate simulations were performed. The adverse pressure gradient was found to affect the boundary layer stability in two important ways. Firstly, the frequency of the most amplified second-mode disturbance was increased relative to the zero pressure gradient case. Secondly, the amplification of first- and second-mode disturbances was increased. Although an adverse pressure gradient enhances instability wave growth rates, small nose-tip bluntness was found to delay transition due to the low receptivity coefficient and the resulting weak initial amplitude of the instability waves. The computed and measured amplitude-frequency spectrums in all three cases agree very well in terms of frequency and the shape except for the amplitude.

  6. Side Effects: Nerve Problems (Peripheral Neuropathy)

    Science.gov (United States)

    Nerve problems, such as peripheral neuropathy, can be caused by cancer treatment. Learn about signs and symptoms of nerve changes. Find out how to prevent or manage nerve problems during cancer treatment.

  7. Integrity of the cone photoreceptor mosaic in oligocone trichromacy

    DEFF Research Database (Denmark)

    Michaelides, Michel; Rha, Jungtae; Dees, Elise W

    2011-01-01

    Oligocone trichromacy (OT) is an unusual cone dysfunction syndrome characterized by reduced visual acuity, mild photophobia, reduced amplitude of the cone electroretinogram with normal rod responses, normal fundus appearance, and normal or near-normal color vision. It has been proposed that these...... that these patients have a reduced number of normal functioning cones (oligocone). This paper has sought to evaluate the integrity of the cone photoreceptor mosaic in four patients previously described as having OT....

  8. Multimodal imaging in neurofibromatosis type 1-associated nerve sheath tumors

    International Nuclear Information System (INIS)

    Salamon, J.; Adam, G.; Mautner, V.F.; Derlin, T.

    2015-01-01

    Neurofibromatosis type 1 (NF1) is a neurogenetic disorder. Individuals with NF1 may develop a variety of benign and malignant tumors of which peripheral nerve sheath tumors represent the most frequent entity. Plexiform neurofibromas may demonstrate a locally destructive growth pattern, may cause severe symptoms and may undergo malignant transformation into malignant peripheral nerve sheath tumors (MPNSTs). Whole-body magnetic resonance imaging (MRI) represents the reference standard for detection of soft tissue tumors in NF1. It allows for identification of individuals with plexiform neurofibromas, for assessment of local tumor extent, and for evaluation of whole-body tumor burden on T2-weighted imaging. Multiparametric MRI may provide a comprehensive characterization of different tissue properties of peripheral nerve sheath tumors, and may identify parameters associated with malignant transformation. Due to the absence of any radiation exposure, whole-body MRI may be used for serial follow-up of individuals with plexiform neurofibromas. 18 F-fluorodeoxyglucose positron-emission-tomography (FDG PET/CT) allows a highly sensitive and specific detection of MPNST, and should be used in case of potential malignant transformation of a peripheral nerve sheath tumor. PET/CT provides a sensitive whole-body tumor staging. The use of contrast-enhanced CT for diagnosis of peripheral nerve sheath tumors is limited to special indications. To obtain the most precise readings, optimized examination protocols and dedicated radiologists and nuclear medicine physicians familiar with the complex and variable morphologies of peripheral nerve sheath tumors are required.

  9. Caenorhabditis elegans VEM-1, a novel membrane protein, regulates the guidance of ventral nerve cord-associated axons.

    Science.gov (United States)

    Runko, Erik; Kaprielian, Zaven

    2004-10-13

    In the developing CNS, pathfinding growth cones use intermediate target- and pioneer axon-associated guidance cues to navigate along stereotypical trajectories. We previously showed that the novel membrane-associated protein Vema is localized to the floor plate and the optic chiasm, intermediate targets located at the ventral midline of the spinal cord and diencephalon in the developing rodent CNS, respectively. Here, we report that the Caenorhabditis elegans ortholog of vema, vem-1, is expressed by the AVG pioneer midline neuron and by several neurons that extend longitudinally projecting axons into the ventral nerve cord (VNC). In vem-1 mutants and vem-1 (RNAi) animals, a subset of posteriorly projecting interneuron axons either fail to extend ventrally to the VNC and, instead, assume aberrant lateral positions or are inappropriately located in the left tract of the VNC. In addition, ventral motor neuron axons exhibit pathfinding errors within the VNC and along the dorsoventral body axis. The conserved UNC-40/DCC and SAX-3-/Robo receptors mediate signaling events that regulate axon guidance in a wide variety of systems. Double-mutant analyses reveal that vem-1 genetically interacts with unc-40 and is likely to function in parallel with sax-3 to regulate the guidance of a subset of VNC-associated interneuron and motor neuron axons. Consistent with these genetic data, we also show that VEM-1 is capable of physically interacting with UNC-40 but not SAX-3.

  10. Anastomotic stoma coated with chitosan film as a betamethasone dipropionate carrier for peripheral nerve regeneration

    Directory of Open Access Journals (Sweden)

    Ping Yao

    2018-01-01

    Full Text Available Scar hyperplasia at the suture site is an important reason for hindering the repair effect of peripheral nerve injury anastomosis. To address this issue, two repair methods are often used. Biological agents are used to block nerve sutures and the surrounding tissue to achieve physical anti-adhesion effects. Another agent is glucocorticosteroid, which can prevent scar growth by inhibiting inflammation. However, the overall effect of promoting regeneration of the injured nerve is not satisfactory. In this regard, we envision that these two methods can be combined and lead to shared understanding for achieving improved nerve repair. In this study, the right tibial nerve was transected 1 cm above the knee to establish a rat tibial nerve injury model. The incision was directly sutured after nerve transection. The anastomotic stoma was coated with 0.5 × 0.5 cm2 chitosan sheets with betamethasone dipropionate. At 12 weeks after injury, compared with the control and poly (D, L-lactic acid groups, chitosan-betamethasone dipropionate film slowly degraded with the shape of the membrane still intact. Further, scar hyperplasia and the degree of adhesion at anastomotic stoma were obviously reduced, while the regenerated nerve fiber structure was complete and arranged in a good order in model rats. Electrophysiological study showed enhanced compound muscle action potential. Our results confirm that chitosan-betamethasone dipropionate film can effectively prevent local scar hyperplasia after tibial nerve repair and promote nerve regeneration.

  11. Diagnostic nerve ultrasonography; Diagnostische Nervensonographie

    Energy Technology Data Exchange (ETDEWEB)

    Baeumer, T. [Universitaet zu Luebeck CBBM, Haus 66, Institut fuer Neurogenetik, Luebeck (Germany); Grimm, A. [Universitaetsklinikum Tuebingen, Klinik und Poliklinik fuer Neurologie, Tuebingen (Germany); Schelle, T. [Staedtisches Klinikum Dessau, Neurologische Klinik, Dessau (Germany)

    2017-03-15

    For the diagnostics of nerve lesions an imaging method is necessary to visualize peripheral nerves and their surrounding structures for an etiological classification. Clinical neurological and electrophysiological investigations provide functional information about nerve lesions. The information provided by a standard magnetic resonance imaging (MRI) examination is inadequate for peripheral nerve diagnostics; however, MRI neurography is suitable but on the other hand a resource and time-consuming method. Using ultrasonography for peripheral nerve diagnostics. With ultrasonography reliable diagnostics of entrapment neuropathies and traumatic nerve lesions are possible. The use of ultrasonography for neuropathies shows that a differentiation between different forms is possible. Nerve ultrasonography is an established diagnostic tool. In addition to the clinical examination and clinical electrophysiology, structural information can be obtained, which results in a clear improvement in the diagnostics. Ultrasonography has become an integral part of the diagnostic work-up of peripheral nerve lesions in neurophysiological departments. Nerve ultrasonography is recommended for the diagnostic work-up of peripheral nerve lesions in addition to clinical and electrophysiological investigations. It should be used in the clinical work-up of entrapment neuropathies, traumatic nerve lesions and spacy-occupying lesions of nerves. (orig.) [German] Fuer die Diagnostik von Nervenlaesionen ist ein bildgebendes Verfahren zur Darstellung des peripheren Nervs und seiner ihn umgebenden Strukturen fuer eine aetiologische Einordnung erforderlich. Mit der klinisch-neurologischen Untersuchung und Elektrophysiologie ist eine funktionelle Aussage ueber die Nervenlaesion moeglich. In der Standard-MRT-Untersuchung wird der periphere Nerv nur unzureichend gut dargestellt. Die MRT-Neurographie ist ein sehr gutes, aber auch zeit- und ressourcenintensives Verfahren. Nutzung des Ultraschalls fuer die

  12. Peripheral nerve conduits: technology update

    Science.gov (United States)

    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

  13. Analog Experiment for rootless cone eruption

    Science.gov (United States)

    Noguchi, R.; Hamada, A.; Suzuki, A.; Kurita, K.

    2017-09-01

    Rootless cone is a unique geomorphological landmark to specify igneous origin of investigated terrane, which is formed by magma-water interaction. To understand its formation mechanism we conducted analog experiment for heat-induced vesiculation by using hot syrup and sodium bicarbonate solution.

  14. Chloride equilibrium potential in salamander cones

    Directory of Open Access Journals (Sweden)

    Bryson Eric J

    2004-12-01

    Full Text Available Abstract Background GABAergic inhibition and effects of intracellular chloride ions on calcium channel activity have been proposed to regulate neurotransmission from photoreceptors. To assess the impact of these and other chloride-dependent mechanisms on release from cones, the chloride equilibrium potential (ECl was determined in red-sensitive, large single cones from the tiger salamander retinal slice. Results Whole cell recordings were done using gramicidin perforated patch techniques to maintain endogenous Cl- levels. Membrane potentials were corrected for liquid junction potentials. Cone resting potentials were found to average -46 mV. To measure ECl, we applied long depolarizing steps to activate the calcium-activated chloride current (ICl(Ca and then determined the reversal potential for the current component that was inhibited by the Cl- channel blocker, niflumic acid. With this method, ECl was found to average -46 mV. In a complementary approach, we used a Cl-sensitive dye, MEQ, to measure the Cl- flux produced by depolarization with elevated concentrations of K+. The membrane potentials produced by the various high K+ solutions were measured in separate current clamp experiments. Consistent with electrophysiological experiments, MEQ fluorescence measurements indicated that ECl was below -36 mV. Conclusions The results of this study indicate that ECl is close to the dark resting potential. This will minimize the impact of chloride-dependent presynaptic mechanisms in cone terminals involving GABAa receptors, glutamate transporters and ICl(Ca.

  15. Cone beam computed tomography in veterinary dentistry

    NARCIS (Netherlands)

    van Thielen, B.; Siguenza, F.; Hassan, B.

    2012-01-01

    The purpose of this study was to assess the feasibility of cone beam computed tomography (CBCT) in imaging dogs and cats for diagnostic dental veterinary applications. CBCT scans of heads of six dogs and two cats were made. Dental panoramic and multi-planar reformatted (MPR) para-sagittal

  16. Neural tissue engineering options for peripheral nerve regeneration.

    Science.gov (United States)

    Gu, Xiaosong; Ding, Fei; Williams, David F

    2014-08-01

    Tissue engineered nerve grafts (TENGs) have emerged as a potential alternative to autologous nerve grafts, the gold standard for peripheral nerve repair. Typically, TENGs are composed of a biomaterial-based template that incorporates biochemical cues. A number of TENGs have been used experimentally to bridge long peripheral nerve gaps in various animal models, where the desired outcome is nerve tissue regeneration and functional recovery. So far, the translation of TENGs to the clinic for use in humans has met with a certain degree of success. In order to optimize the TENG design and further approach the matching of TENGs with autologous nerve grafts, many new cues, beyond the traditional ones, will have to be integrated into TENGs. Furthermore, there is a strong requirement for monitoring the real-time dynamic information related to the construction of TENGs. The aim of this opinion paper is to specifically and critically describe the latest advances in the field of neural tissue engineering for peripheral nerve regeneration. Here we delineate new attempts in the design of template (or scaffold) materials, especially in the context of biocompatibility, the choice and handling of support cells, and growth factor release systems. We further discuss the significance of RNAi for peripheral nerve regeneration, anticipate the potential application of RNAi reagents for TENGs, and speculate on the possible contributions of additional elements, including angiogenesis, electrical stimulation, molecular inflammatory mediators, bioactive peptides, antioxidant reagents, and cultured biological constructs, to TENGs. Finally, we consider that a diverse array of physicochemical and biological cues must be orchestrated within a TENG to create a self-consistent coordinated system with a close proximity to the regenerative microenvironment of the peripheral nervous system. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Case of Unilateral Peripheral Cone Dysfunction

    Directory of Open Access Journals (Sweden)

    Yujin Mochizuki

    2012-05-01

    Full Text Available Purpose: Peripheral cone dystrophy is a subgroup of cone dystrophy, and only 4 cases have been reported. We present a patient with unilateral peripheral cone dysfunction and report the functional changes determined by electrophysiological tests and ultrastructural changes determined by spectral domain optical coherence tomography (SD-OCT. Case: A 34-year-old woman complained of blurred vision in both eyes. Our examination showed that her visual acuity was 0.05 OD and 0.2 OS. A relative afferent pupillary defect was present in her right eye. The results of slit-lamp examination, ophthalmoscopy, and fluorescein angiography were normal except for pallor of the right optic disc. SD-OCT showed a diffuse thinning of the retina in the posterior pole of the right eye. A severe constriction of the visual fields was found in both eyes but more in the right eye. The photopic full-field electroretinograms (ERGs were reduced in the right eye but normal in the left eye. The multifocal ERGs were severely reduced throughout the visual field except in the central area of the right eye. The multifocal ERGs from the left eye were normal. The pattern visual evoked responses were within the normal range in both eyes. She had a 5-year history of sniffing paint thinner. Results: Although the visual dysfunction was initially suspected to be due to psychological problems from the results of subjective tests, objective tests indicated a peripheral cone dysfunction in the right eye. The pathophysiological mechanism and the relationship with thinner sniffing were not determined. Conclusions: Our findings indicate that peripheral cone dysfunction can occur unilaterally. Electrophysiology and SD-OCT are valuable tests to perform to determine the pathogenesis of unusual ocular findings objectively.

  18. Sustained Local Release of NGF from a Chitosan-Sericin Composite Scaffold for Treating Chronic Nerve Compression.

    Science.gov (United States)

    Zhang, Lei; Yang, Wen; Tao, Kaixiong; Song, Yu; Xie, Hongjian; Wang, Jian; Li, Xiaolin; Shuai, Xiaoming; Gao, Jinbo; Chang, Panpan; Wang, Guobin; Wang, Zheng; Wang, Lin

    2017-02-01

    Chronic nerve compression (CNC), a common form of peripheral nerve injury, always leads to chronic peripheral nerve pain and dysfunction. Current available treatments for CNC are ineffective as they usually aim to alleviate symptoms at the acute phase with limited capability toward restoring injured nerve function. New approaches for effective recovery of CNC injury are highly desired. Here we report for the first time a tissue-engineered approach for the repair of CNC. A genipin cross-linked chitosan-sericin 3D scaffold for delivering nerve growth factor (NGF) was designed and fabricated. This scaffold combines the advantages of both chitosan and sericin, such as high porosity, adjustable mechanical properties and swelling ratios, the ability of supporting Schwann cells growth, and improving nerve regeneration. The degradation products of the composite scaffold upregulate the mRNA levels of the genes important for facilitating nerve function recovery, including glial-derived neurotrophic factor (GDNF), early growth response 2 (EGR2), and neural cell adhesion molecule (NCAM) in Schwann cells, while down-regulating two inflammatory genes' mRNA levels in macrophages, tumor necrosis factor alpha (TNF-α), and interleukin-1 beta (IL-1β). Importantly, our tissue-engineered strategy achieves significant nerve functional recovery in a preclinical CNC animal model by decreasing neuralgia, improving nerve conduction velocity (NCV), accelerating microstructure restoration, and attenuating gastrocnemius muscles dystrophy. Together, this work suggests a promising clinical alternative for treating chronic peripheral nerve compression injury.

  19. Nonlinear interactions of focused resonance cone fields with plasmas

    International Nuclear Information System (INIS)

    Stenzel, R.L.; Gekelman, W.

    1977-01-01

    A simple yet novel rf exciter structure has been developed for generating remotely intense rf fields in a magnetoplasma. It is a circular line source of radius R in a plane perpendicularB 0 driven with an rf signal at ω 0 E/sub rf/ 2 /nkT/sub e/>0.2, a strong density depression in the focal region (deltan/n>40%) is observed. The density perturbation modifies the cone angle and field distribution. This nonlinear interaction leads to a rapid growth of ion acoustic wave turbulence and a corresponding random rf field distribution in a broadened focal region. The development of the interaction is mapped in space and time

  20. The role of neurotrophic factors in nerve regeneration.

    Science.gov (United States)

    Gordon, Tessa

    2009-02-01

    This review considers the 2 sources of neurotrophic factors in the peripheral nervous system (PNS), the neurons and the nonneuronal cells in the denervated distal nerve stumps, and their role in axon regeneration. Morphological assessment of regenerative success in response to administration of exogenous growth factors after nerve injury and repair has indicated a role of the endogenous neurotrophic factors from Schwann cells in the distal nerve stump. However, the increased number of axons may reflect more neurons regenerating their axons and/or increased numbers of axon sprouts from the same number of neurons. Using fluorescent dyes to count neurons that regenerated their axons across a suture site and into distal nerve stumps, brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF) were found not to increase the number of neurons that regenerated their axons after immediate nerve repair. Nevertheless, the factors did reverse the deleterious effect of delayed nerve repair, indicating that the axons that regenerate into the distal nerve stump normally have access to sufficient levels of endogenous neurotrophic factors to sustain their regeneration, while neurons that do not have access to these factors require exogenous factors to sustain axon regeneration. Neurons upregulate neurotrophic factors after axotomy. The upregulation is normally slow, beginning after 7 days and occurring in association with a protracted period of axonal regeneration in which axons grow out from the proximal nerve stump across a suture site over a period of 1 month in rodents. This staggered axon regeneration across the suture site is accelerated by a 1-hour period of low-frequency electrical stimulation that simultaneously accelerates the expression of BDNF and its trkB receptor in the neurons. Elevation of the level of BDNF after 2 days to > 3 times that found in unstimulated neurons was accompanied by elevation of the level of cAMP and followed by

  1. Sensory nerve function and auto-mutilation after reconstruction of various gap lengths with nerve guides and autologous nerve grafts

    NARCIS (Netherlands)

    den Dunnen, WFA; Meek, MF

    The aim of this study was to evaluate sensory nerve recovery and auto-mutilation after reconstruction of various lengths of nerve gaps in the sciatic nerve of the rat, using different techniques. Group 4, in which the longest nerve gap (15 mm) was reconstructed with a thin-walled

  2. CRALBP supports the mammalian retinal visual cycle and cone vision.

    Science.gov (United States)

    Xue, Yunlu; Shen, Susan Q; Jui, Jonathan; Rupp, Alan C; Byrne, Leah C; Hattar, Samer; Flannery, John G; Corbo, Joseph C; Kefalov, Vladimir J

    2015-02-01

    Mutations in the cellular retinaldehyde-binding protein (CRALBP, encoded by RLBP1) can lead to severe cone photoreceptor-mediated vision loss in patients. It is not known how CRALBP supports cone function or how altered CRALBP leads to cone dysfunction. Here, we determined that deletion of Rlbp1 in mice impairs the retinal visual cycle. Mice lacking CRALBP exhibited M-opsin mislocalization, M-cone loss, and impaired cone-driven visual behavior and light responses. Additionally, M-cone dark adaptation was largely suppressed in CRALBP-deficient animals. While rearing CRALBP-deficient mice in the dark prevented the deterioration of cone function, it did not rescue cone dark adaptation. Adeno-associated virus-mediated restoration of CRALBP expression specifically in Müller cells, but not retinal pigment epithelial (RPE) cells, rescued the retinal visual cycle and M-cone sensitivity in knockout mice. Our results identify Müller cell CRALBP as a key component of the retinal visual cycle and demonstrate that this pathway is important for maintaining normal cone-driven vision and accelerating cone dark adaptation.

  3. Use of RI-cone penetrometer in clay foundations

    International Nuclear Information System (INIS)

    Mimura, Mamoru; Shibata, Toru; Shrivastava, A.K.

    1993-01-01

    RI cone penetrometer tests are carried out at four different sites. The foundation grounds discussed here mainly consist of clayey materials. The measured results by RI cone penetrometers are shown for Kyobashi, Hachirougata, Kurihama and Kinkai Bay site. According to comparison of water content and density profiles by RI cone measurement with the conventional testing results, RI cone penetrometers are proved to be versatile tools for site investigation. Settlement assessment by RI cone penetrometer is also discussed by exemplifying the embankment at Kinkai Bay site. Elasto-vis-coplastic finite element analysis correspondingly performed strongly supports the RI cone based assessment. Repeated use of RI cone penetrometer with the advance of construction enables us to assess the consolidation process of the clay foundation. (author)

  4. Tenascin-C in peripheral nerve morphogenesis.

    Science.gov (United States)

    Chiquet, M; Wehrle-Haller, B

    1994-01-01

    The extracellular matrix (ECM) molecule tenascin/cytotactin (TN-C) is expressed at a high level by satellite (glial precursor) cells in developing peripheral nerves of the chick embryo; synthesis of its mRNA peaks at the time period when axonal growth is maximal. When offered as a substrate in vitro, TN-C mediates neurite outgrowth by both motor and sensory neurons. The ability to grow neurites on TN-C is developmentally regulated: sensory neurons from 4-day chick embryos (the stage at which peripheral nerves start to develop) grow immediately and rapidly, whereas neurons from older embryos respond with a long delay. A TN-C domain responsible for this activity is located within the C-terminal (distal) portion of TN-C subunits. Integrin receptors seem to be involved on peripheral neurites because their growth on TN-C is completely blocked by antibodies to beta 1 integrins. In striking contrast to neuronal processes, nerve satellite cells can attach to a TN-C substrate but are completely inhibited in their migratory activity. Artificial substrate borders between tenascin and fibronectin or laminin act as selective barriers that allow neurites to pass while holding up satellite cells. The repulsive action of TN-C on satellite cells is similar to that observed for other cell types and is likely to be mediated by additional TN-C domains. In view of these data, it is surprising that mice seem to develop normally without a functional TN-C gene. TN-C is likely to be redundant, that is, its dual action on cell adhesion is shared by other molecules.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Microsurgical reconstruction of large nerve defects using autologous nerve grafts.

    Science.gov (United States)

    Daoutis, N K; Gerostathopoulos, N E; Efstathopoulos, D G; Misitizis, D P; Bouchlis, G N; Anagnostou, S K

    1994-01-01

    Between 1986 and 1993, 643 patients with peripheral nerve trauma were treated in our clinic. Primary neurorraphy was performed in 431 of these patients and nerve grafting in 212 patients. We present the functional results after nerve grafting in 93 patients with large nerve defects who were followed for more than 2 years. Evaluation of function was based on the Medical Research Council (MRC) classification for motor and sensory recovery. Factors affecting functional outcome, such as age of the patient, denervation time, length of the defect, and level of the injury were noted. Good results according to the MRC classification were obtained in the majority of cases, although function remained less than that of the uninjured side.

  6. Electrophysiology of Extraocular Cranial Nerves: Oculomotor, Trochlear, and Abducens Nerve.

    Science.gov (United States)

    Hariharan, Praveen; Balzer, Jeffery R; Anetakis, Katherine; Crammond, Donald J; Thirumala, Parthasarathy D

    2018-01-01

    The utility of extraocular cranial nerve electrophysiologic recordings lies primarily in the operating room during skull base surgeries. Surgical manipulation during skull base surgeries poses a risk of injury to multiple cranial nerves, including those innervating extraocular muscles. Because tumors distort normal anatomic relationships, it becomes particularly challenging to identify cranial nerve structures. Studies have reported the benefits of using intraoperative spontaneous electromyographic recordings and compound muscle action potentials evoked by electrical stimulation in preventing postoperative neurologic deficits. Apart from surgical applications, electromyography of extraocular muscles has also been used to guide botulinum toxin injections in patients with strabismus and as an adjuvant diagnostic test in myasthenia gravis. In this article, we briefly review the rationale, current available techniques to monitor extraocular cranial nerves, technical difficulties, clinical and surgical applications, as well as future directions for research.

  7. Assessment of Rod, Cone, and Intrinsically Photosensitive Retinal Ganglion Cell Contributions to the Canine Chromatic Pupillary Response.

    Science.gov (United States)

    Yeh, Connie Y; Koehl, Kristin L; Harman, Christine D; Iwabe, Simone; Guzman, José M; Petersen-Jones, Simon M; Kardon, Randy H; Komáromy, András M

    2017-01-01

    The purpose of this study was to evaluate a chromatic pupillometry protocol for specific functional assessment of rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs) in dogs. Chromatic pupillometry was tested and compared in 37 dogs in different stages of primary loss of rod, cone, and combined rod/cone and optic nerve function, and in 5 wild-type (WT) dogs. Eyes were stimulated with 1-s flashes of dim (1 cd/m2) and bright (400 cd/m2) blue light (for scotopic conditions) or bright red (400 cd/m2) light with 25-cd/m2 blue background (for photopic conditions). Canine retinal melanopsin/Opn4 was cloned, and its expression was evaluated using real-time quantitative reverse transcription-PCR and immunohistochemistry. Mean ± SD percentage of pupil constriction amplitudes induced by scotopic dim blue (scDB), scotopic bright blue (scBB), and photopic bright red (phBR) lights in WT dogs were 21.3% ± 10.6%, 50.0% ± 17.5%, and 19.4% ± 7.4%, respectively. Melanopsin-mediated responses to scBB persisted for several minutes (7.7 ± 4.6 min) after stimulus offset. In dogs with inherited retinal degeneration, loss of rod function resulted in absent scDB responses, followed by decreased phBR responses with disease progression and loss of cone function. Primary loss of cone function abolished phBR responses but preserved those responses to blue light (scDB and scBB). Although melanopsin/Opn4 expression was diminished with retinal degeneration, melanopsin-expressing ipRGCs were identified for the first time in both WT and degenerated canine retinas. Pupil responses elicited by light stimuli of different colors and intensities allowed differential functional assessment of canine rods, cones, and ipRGCs. Chromatic pupillometry offers an effective tool for diagnosing retinal and optic nerve diseases.

  8. Fibrin matrices with affinity-based delivery systems and neurotrophic factors promote functional nerve regeneration.

    Science.gov (United States)

    Wood, Matthew D; MacEwan, Matthew R; French, Alexander R; Moore, Amy M; Hunter, Daniel A; Mackinnon, Susan E; Moran, Daniel W; Borschel, Gregory H; Sakiyama-Elbert, Shelly E

    2010-08-15

    Glial-derived neurotrophic factor (GDNF) and nerve growth factor (NGF) have both been shown to enhance peripheral nerve regeneration following injury and target different neuronal populations. The delivery of either growth factor at the site of injury may, therefore, result in quantitative differences in motor nerve regeneration and functional recovery. In this study we evaluated the effect of affinity-based delivery of GDNF or NGF from fibrin-filled nerve guidance conduits (NGCs) on motor nerve regeneration and functional recovery in a 13 mm rat sciatic nerve defect. Seven experimental groups were evaluated consisting of GDNF or NGF and the affinity-based delivery system (DS) within NGCs, control groups excluding the DS and/or growth factor, and nerve isografts. Groups with growth factor in the conduit demonstrated equivalent or superior performance in behavioral tests and relative muscle mass measurements compared to isografts at 12 weeks. Additionally, groups with GDNF demonstrated greater specific twitch and tetanic force production in extensor digitorum longus (EDL) muscle than the isograft control, while groups with NGF produced demonstrated similar force production compared to the isograft control. Assessment of motor axon regeneration by retrograde labeling further revealed that the number of ventral horn neurons regenerating across NGCs containing GDNF and NGF DS was similar to the isograft group and these counts were greater than the groups without growth factor. Overall, the GDNF DS group demonstrated superior functional recovery and equivalent motor nerve regeneration compared to the isograft control, suggesting it has potential as a treatment for motor nerve injury.

  9. POROSITY OF THE WALL OF A NEUROLAC (R) NERVE CONDUIT HAMPERS NERVE REGENERATION

    NARCIS (Netherlands)

    Meek, Marcel F.; Den Dunnen, Wilfred F. A.

    2009-01-01

    One way to improve nerve regeneration and bridge longer nerve gaps may be the use of semipermeable/porous conduits. With porosity less biomaterial is used for the nerve conduit. We evaluated the short-term effects of porous Neurolac (R) nerve conduits for in vivo peripheral nerve regeneration. In 10

  10. Poly(DL-lactide-epsilon-caprolactone) nerve guides perform better than autologous nerve grafts

    NARCIS (Netherlands)

    DenDunnen, WFA; VanderLei, B; Schakenraad, JM; Stokroos, [No Value; Blaauw, E; Pennings, AJ; Robinson, PH; Bartels, H.

    1996-01-01

    The aim of this study was to compare the speed and quality of nerve regeneration after reconstruction using a biodegradable nerve guide or an autologous nerve graft. We evaluated nerve regeneration using light microscopy, transmission electron microscopy and morphometric analysis. Nerve regeneration

  11. Scaffoldless tissue-engineered nerve conduit promotes peripheral nerve regeneration and functional recovery after tibial nerve injury in rats

    Institute of Scientific and Technical Information of China (English)

    Aaron M. Adams; Keith W. VanDusen; Tatiana Y. Kostrominova; Jacob P. Mertens; Lisa M. Larkin

    2017-01-01

    Damage to peripheral nerve tissue may cause loss of function in both the nerve and the targeted muscles it innervates. This study compared the repair capability of engineered nerve conduit (ENC), engineered fibroblast conduit (EFC), and autograft in a 10-mm tibial nerve gap. ENCs were fabricated utilizing primary fibroblasts and the nerve cells of rats on embryonic day 15 (E15). EFCs were fabricated utilizing primary fi-broblasts only. Following a 12-week recovery, nerve repair was assessed by measuring contractile properties in the medial gastrocnemius muscle, distal motor nerve conduction velocity in the lateral gastrocnemius, and histology of muscle and nerve. The autografts, ENCs and EFCs reestablished 96%, 87% and 84% of native distal motor nerve conduction velocity in the lateral gastrocnemius, 100%, 44% and 44% of native specific force of medical gastrocnemius, and 63%, 61% and 67% of native medial gastrocnemius mass, re-spectively. Histology of the repaired nerve revealed large axons in the autograft, larger but fewer axons in the ENC repair, and many smaller axons in the EFC repair. Muscle histology revealed similar muscle fiber cross-sectional areas among autograft, ENC and EFC repairs. In conclusion, both ENCs and EFCs promot-ed nerve regeneration in a 10-mm tibial nerve gap repair, suggesting that the E15 rat nerve cells may not be necessary for nerve regeneration, and EFC alone can suffice for peripheral nerve injury repair.

  12. On Krasnoselskii's Cone Fixed Point Theorem

    Directory of Open Access Journals (Sweden)

    Man Kam Kwong

    2008-04-01

    Full Text Available In recent years, the Krasnoselskii fixed point theorem for cone maps and its many generalizations have been successfully applied to establish the existence of multiple solutions in the study of boundary value problems of various types. In the first part of this paper, we revisit the Krasnoselskii theorem, in a more topological perspective, and show that it can be deduced in an elementary way from the classical Brouwer-Schauder theorem. This viewpoint also leads to a topology-theoretic generalization of the theorem. In the second part of the paper, we extend the cone theorem in a different direction using the notion of retraction and show that a stronger form of the often cited Leggett-Williams theorem is a special case of this extension.

  13. Basic principle of cone beam computed tomography

    International Nuclear Information System (INIS)

    Choi, Yong Suk; Kim, Gyu Tae; Hwang, Eui Hwan

    2006-01-01

    The use of computed tomography for dental procedures has increased recently. Cone beam computed tomography(CBCT) systems have been designed for imaging hard tissues of the dentomaxillofacial region. CBCT is capable of providing high resolution in images of high diagnostic quality. This technology allows for 3-dimensional representation of the dentomaxillofacial skeleton with minimal distortion, but at lower equipment cost, simpler image acquisition and lower patient dose. Because this technology produces images with isotropic sub-millimeter spatial resolution, it is ideally suited for dedicated dentomaxillofacial imaging. In this paper, we provide a brief overview of cone beam scanning technology and compare it with the fan beam scanning used in conventional CT and the basic principles of currently available CBCT systems

  14. Bilateral absence of musculocutaneous nerve

    Directory of Open Access Journals (Sweden)

    Mathada V Ravishankar

    2012-01-01

    Full Text Available Brachial plexus is an important group of spinal nerve plexus that supplies the muscles of the upper limb via the ventral rami of the Cervical 5 - Thoracic 1 fibers of the spinal nerves. It is not uncommon to notice the variations during cadaveric dissections in many regions of the body, at different levels, such as, roots, trunks, division, cords, communications, and branches as reported in the literature. Although the nerve supply of the body musculature takes place in the fetal life itself, its course, branching pattern, innervations, and communication can show variable patterns as the fetal development progresses. One such anomaly was noticed during our routine cadaveric dissection in the Department of Anatomy, Jawaharlal Nehru Medical College, Belgaum, showing bilateral absence of the musculocutaneous nerve, which obviously drew the attention of the students of medicine, physiotherapy, and learning clinicians as well.

  15. Imaging of the facial nerve

    Energy Technology Data Exchange (ETDEWEB)

    Veillon, F. [Service de Radiologie I, Hopital de Hautepierre, 67098 Strasbourg Cedex (France)], E-mail: Francis.Veillon@chru-strasbourg.fr; Ramos-Taboada, L.; Abu-Eid, M. [Service de Radiologie I, Hopital de Hautepierre, 67098 Strasbourg Cedex (France); Charpiot, A. [Service d' ORL, Hopital de Hautepierre, 67098 Strasbourg Cedex (France); Riehm, S. [Service de Radiologie I, Hopital de Hautepierre, 67098 Strasbourg Cedex (France)

    2010-05-15

    The facial nerve is responsible for the motor innervation of the face. It has a visceral motor function (lacrimal, submandibular, sublingual glands and secretion of the nose); it conveys a great part of the taste fibers, participates to the general sensory of the auricle (skin of the concha) and the wall of the external auditory meatus. The facial mimic, production of tears, nasal flow and salivation all depend on the facial nerve. In order to image the facial nerve it is mandatory to be knowledgeable about its normal anatomy including the course of its efferent and afferent fibers and about relevant technical considerations regarding CT and MR to be able to achieve high-resolution images of the nerve.

  16. Hadronic wavefunctions in light-cone quantization

    International Nuclear Information System (INIS)

    Hyer, T.

    1994-05-01

    The analysis of light-cone wavefunctions seems the most promising theoretical approach to a detailed understanding of the structure of relativistic bound states, particularly hadrons. However, there are numerous complications in this approach. Most importantly, the light-cone approach sacrifices manifest rotational invariance in exchange for the elimination of negative-energy states. The requirement of rotational invariance of the full theory places important constraints on proposed light-cone wavefunctions, whether they are modelled or extracted from some numerical procedure. A formulation of the consequences of the hidden rotational symmetry has been sought for some time; it is presented in Chapter 2. In lattice gauge theory or heavy-quark effective theory, much of the focus is on the extraction of numerical values of operators which are related to the hadronic wavefunction. These operators are to some extent interdependent, with relations induced by fundamental constraints on the underlying wavefunction. The consequences of the requirement of unitarity are explored in Chapter 3, and are found to have startling phenomenological relevance. To test model light-cone wavefunctions, experimental predictions must be made. The reliability of perturbative QCD as a tool for making such predictions has been questioned. In Chapter 4, the author presents a computation of the rates for nucleon-antinucleon annihilation, improving the reliability of the perturbative computation by taking into account the Sudakov suppression of exclusive processes at large transverse impact parameter. In Chapter 5, he develops the analysis of semiexclusive production. This work focuses on processes in which a single isolated meson is produced perturbatively and recoils against a wide hadronizing system. At energies above about 10 GeV, semiexclusive processes are shown to be the most sensitive experimental probes of hadronic structure

  17. Development of a Motorized Digital Cone Penetrometer

    OpenAIRE

    Chung, Sun–Ok; Cho, Jin–Woong; Yamakawa, Takeo; 山川, 武夫

    2012-01-01

    Quantification and management of variability in soil strength, or soil compaction, is an important issue in countries such as Korea and Japan where typical field sizes are small, but tractor mounted on–the–go sensors that have been developed in USA and European countries are not practical. Therefore, hand–operated digital penetrometers have been widely used in Asian countries, but maintaining standard penetration rate and angle would be difficult. In this study, a motorized digital cone penet...

  18. Evidence for a systemic regulation of neurotrophin synthesis in response to peripheral nerve injury.

    Science.gov (United States)

    Shakhbazau, Antos; Martinez, Jose A; Xu, Qing-Gui; Kawasoe, Jean; van Minnen, Jan; Midha, Rajiv

    2012-08-01

    Up-regulation of neurotrophin synthesis is an important mechanism of peripheral nerve regeneration after injury. Neurotrophin expression is regulated by a complex series of events including cell interactions and multiple molecular stimuli. We have studied neurotrophin synthesis at 2 weeks time-point in a transvertebral model of unilateral or bilateral transection of sciatic nerve in rats. We have found that unilateral sciatic nerve transection results in the elevation of nerve growth factor (NGF) and NT-3, but not glial cell-line derived neurotrophic factor or brain-derived neural factor, in the uninjured nerve on the contralateral side, commonly considered as a control. Bilateral transection further increased NGF but not other neurotrophins in the nerve segment distal to the transection site, as compared to the unilateral injury. To further investigate the distinct role of NGF in regeneration and its potential for peripheral nerve repair, we transduced isogeneic Schwann cells with NGF-encoding lentivirus and transplanted the over-expressing cells into the distal segment of a transected nerve. Axonal regeneration was studied at 2 weeks time-point using pan-neuronal marker NF-200 and found to directly correlate with NGF levels in the regenerating nerve. © 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry.

  19. Stereotactic radiotherapy using Novalis for skull base metastases developing with cranial nerve symptoms.

    Science.gov (United States)

    Mori, Yoshimasa; Hashizume, Chisa; Kobayashi, Tatsuya; Shibamoto, Yuta; Kosaki, Katsura; Nagai, Aiko

    2010-06-01

    Skull base metastases are challenging situations because they often involve critical structures such as cranial nerves. We evaluated the role of stereotactic radiotherapy (SRT) which can give high doses to the tumors sparing normal structures. We treated 11 cases of skull base metastases from other visceral carcinomas. They had neurological symptoms due to cranial nerve involvement including optic nerve (3 patients), oculomotor (3), trigeminal (6), abducens (1), facial (4), acoustic (1), and lower cranial nerves (1). The interval between the onset of cranial nerve symptoms and Novalis SRT was 1 week to 7 months. Eleven tumors of 8-112 ml in volume were treated by Novalis SRT with 30-50 Gy in 10-14 fractions. The tumors were covered by 90-95% isodose. Imaging and clinical follow-up has been obtained in all 11 patients for 5-36 months after SRT. Seven patients among 11 died from primary carcinoma or other visceral metastases 9-36 months after Novalis SRT. All 11 metastatic tumors were locally controlled until the end of the follow-up time or patient death, though retreatment for re-growth was done in 1 patient. In 10 of 11 patients, cranial nerve deficits were improved completely or partially. In some patients, the cranial nerve symptoms were relieved even during the period of fractionated SRT. Novalis SRT is thought to be safe and effective treatment for skull base metastases with involvement of cranial nerves and it may improve cranial nerve symptoms quickly.

  20. Variability of silver fir (Abies alba Mill. cones – variability of cone parameters

    Directory of Open Access Journals (Sweden)

    Aniszewska Monika

    2016-09-01

    Full Text Available This study aimed at determining the shape of closed silver fir cones from the Jawor Forest District (Wroclaw, based purely on measurements of their length and thickness. Using these two parameters, the most accurate estimations were achieved with a fourth-degree polynomial fitting function. We then calculated the cones’ surface area and volume in three different ways: 1 Using the fourth-degree polynomial shape estimation, 2 Introducing indicators of compliance (k1, k2, k3 to calculate the volume and then comparing it to its actual value as measured in a pitcher filled with water, 3 Comparing the surface area of the cones as calculated with the polynomial function to the value obtained from ratios of indicators of compliance (ratios k4 and k5. We found that the calculated surface area and volume were substantially higher than the corresponding measured values. Test values of cone volume and surface area as calculated by our model were 8% and 5% lower, respectively, compared to direct measurements. We also determined the fir cones apparent density to be 0.8 g·cm-3on average. The gathered data on cone surface area, volume and bulk density is a valuable tool for optimizing the thermal peeling process in mill cabinets to acquire high quality seeds.

  1. The NLO jet vertex in the small-cone approximation for kt and cone algorithms

    International Nuclear Information System (INIS)

    Colferai, D.; Niccoli, A.

    2015-01-01

    We determine the jet vertex for Mueller-Navelet jets and forward jets in the small-cone approximation for two particular choices of jet algoritms: the kt algorithm and the cone algorithm. These choices are motivated by the extensive use of such algorithms in the phenomenology of jets. The differences with the original calculations of the small-cone jet vertex by Ivanov and Papa, which is found to be equivalent to a formerly algorithm proposed by Furman, are shown at both analytic and numerical level, and turn out to be sizeable. A detailed numerical study of the error introduced by the small-cone approximation is also presented, for various observables of phenomenological interest. For values of the jet “radius” R=0.5, the use of the small-cone approximation amounts to an error of about 5% at the level of cross section, while it reduces to less than 2% for ratios of distributions such as those involved in the measure of the azimuthal decorrelation of dijets.

  2. The NLO jet vertex in the small-cone approximation for kt and cone algorithms

    Energy Technology Data Exchange (ETDEWEB)

    Colferai, D.; Niccoli, A. [Dipartimento di Fisica e Astronomia, Università di Firenze and INFN, Sezione di Firenze, 50019 Sesto Fiorentino (Italy)

    2015-04-15

    We determine the jet vertex for Mueller-Navelet jets and forward jets in the small-cone approximation for two particular choices of jet algoritms: the kt algorithm and the cone algorithm. These choices are motivated by the extensive use of such algorithms in the phenomenology of jets. The differences with the original calculations of the small-cone jet vertex by Ivanov and Papa, which is found to be equivalent to a formerly algorithm proposed by Furman, are shown at both analytic and numerical level, and turn out to be sizeable. A detailed numerical study of the error introduced by the small-cone approximation is also presented, for various observables of phenomenological interest. For values of the jet “radius” R=0.5, the use of the small-cone approximation amounts to an error of about 5% at the level of cross section, while it reduces to less than 2% for ratios of distributions such as those involved in the measure of the azimuthal decorrelation of dijets.

  3. Large Extremity Peripheral Nerve Repair

    Science.gov (United States)

    2016-12-01

    These antimicrobial peptides are implicated in the resistance of epithelial surfaces to microbial colonisation and have been shown to be upregulated...be equivalent to standard autograft repair in rodent models. Outcomes have now been validated in a large animal (swine) model with 5 cm ulnar nerve...Goals of the Project Task 1– Determine mechanical properties, seal strength and resistance to biodegradation of candidate photochemical nerve wrap

  4. Outcome of different facial nerve reconstruction techniques

    OpenAIRE

    Mohamed, Aboshanif; Omi, Eigo; Honda, Kohei; Suzuki, Shinsuke; Ishikawa, Kazuo

    2016-01-01

    Abstract Introduction: There is no technique of facial nerve reconstruction that guarantees facial function recovery up to grade III. Objective: To evaluate the efficacy and safety of different facial nerve reconstruction techniques. Methods: Facial nerve reconstruction was performed in 22 patients (facial nerve interpositional graft in 11 patients and hypoglossal-facial nerve transfer in another 11 patients). All patients had facial function House-Brackmann (HB) grade VI, either caused by...

  5. Neurophysiological approach to disorders of peripheral nerve

    DEFF Research Database (Denmark)

    Crone, Clarissa; Krarup, Christian

    2013-01-01

    Disorders of the peripheral nerve system (PNS) are heterogeneous and may involve motor fibers, sensory fibers, small myelinated and unmyelinated fibers and autonomic nerve fibers, with variable anatomical distribution (single nerves, several different nerves, symmetrical affection of all nerves......, plexus, or root lesions). Furthermore pathological processes may result in either demyelination, axonal degeneration or both. In order to reach an exact diagnosis of any neuropathy electrophysiological studies are crucial to obtain information about these variables. Conventional electrophysiological...

  6. Optic nerve invasion of uveal melanoma

    DEFF Research Database (Denmark)

    Lindegaard, Jens; Isager, Peter; Prause, Jan Ulrik

    2007-01-01

    in Denmark between 1942 and 2001 were reviewed (n=157). Histopathological characteristics and depth of optic nerve invasion were recorded. The material was compared with a control material from the same period consisting of 85 cases randomly drawn from all choroidal/ciliary body melanomas without optic nerve...... juxtapapillary tumors invading the optic nerve because of simple proximity to the nerve. A neurotropic subtype invades the optic nerve and retina in a diffuse fashion unrelated to tumor size or location. Udgivelsesdato: 2007-Jan...

  7. Cranial nerve monitoring during subpial dissection in temporomesial surgery.

    Science.gov (United States)

    Ortler, Martin; Fiegele, Thomas; Walser, Gerald; Trinka, Eugen; Eisner, Wilhelm

    2011-06-01

    Cranial nerves (CNs) crossing between the brainstem and skull base at the level of the tentorial hiatus may be at risk in temporomesial surgery involving subpial dissection and/or tumorous growth leading to distorted anatomy. We aimed to identify the surgical steps most likely to result in CN damage in this type of surgery. Electromyographic responses obtained with standard neuromonitoring techniques and a continuous free-running EMG were graded as either contact activity or pathological spontaneous activity (PSA) during subpial resection of temporomesial structures in 16 selective amygdalohippocampectomy cases. Integrity of peripheral motor axons was tested by transpial/transarachnoidal electrical stimulation while recording compound muscle action potentials from distal muscle(s). Continuous EMG showed pathological activity in five (31.2%) patients. Nine events with PSA (slight activity, n = 8; strong temporary activity, n = 1) were recorded. The oculomotor nerve was involved three times, the trochlear nerve twice, the facial nerve once, and all monitored nerves on three occasions. Surgical maneuvers associated with PSA were the resection of deep parts of the hippocampus and parahippocampal gyrus (CN IV, twice; CN III, once), lining with or removing cotton patties from the resection cavity (III, twice; all channels, once) and indirect exertion of tension on the intact pia/arachnoid of the uncal region while mobilizing the hippocampus and parahippocampal gyrus en bloc (all channels, once; III, once). CMAPs were observed at 0.3 mA in two patients and at 0.6 mA in one patient, and without registering the exact amount of intensity in three patients. The most dangerous steps leading to cranial nerve damage during mesial temporal lobe surgery are the final stages of the intervention while the resection is being completed in the deep posterior part and the resection cavity is being lined with patties. Distant traction may act on nerves crossing the tentorial

  8. A novel method of lengthening the accessory nerve for direct coaptation during nerve repair and nerve transfer procedures.

    Science.gov (United States)

    Tubbs, R Shane; Maldonado, Andrés A; Stoves, Yolanda; Fries, Fabian N; Li, Rong; Loukas, Marios; Oskouian, Rod J; Spinner, Robert J

    2018-01-01

    OBJECTIVE The accessory nerve is frequently repaired or used for nerve transfer. The length of accessory nerve available is often insufficient or marginal (under tension) for allowing direct coaptation during nerve repair or nerve transfer (neurotization), necessitating an interpositional graft. An attractive maneuver would facilitate lengthening of the accessory nerve for direct coaptation. The aim of the present study was to identify an anatomical method for such lengthening. METHODS In 20 adult cadavers, the C-2 or C-3 connections to the accessory nerve were identified medial to the sternocleidomastoid (SCM) muscle and the anatomy of the accessory nerve/cervical nerve fibers within the SCM was documented. The cervical nerve connections were cut. Lengths of the accessory nerve were measured. Samples of the cut C-2 and C-3 nerves were examined using immunohistochemistry. RESULTS The anatomy and adjacent neural connections within the SCM are complicated. However, after the accessory nerve was "detethered" from within the SCM and following transection, the additional length of the accessory nerve increased from a mean of 6 cm to a mean of 10.5 cm (increase of 4.5 cm) after cutting the C-2 connections, and from a mean of 6 cm to a mean length of 9 cm (increase of 3.5 cm) after cutting the C-3 connections. The additional length of accessory nerve even allowed direct repair of an infraclavicular target (i.e., the proximal musculocutaneous nerve). The cervical nerve connections were shown not to contain motor fibers. CONCLUSIONS An additional length of the accessory nerve made available in the posterior cervical triangle can facilitate direct repair or neurotization procedures, thus eliminating the need for an interpositional nerve graft, decreasing the time/distance for regeneration and potentially improving clinical outcomes.

  9. Unilateral traumatic oculomotor nerve paralysis

    International Nuclear Information System (INIS)

    Asari, Syoji; Satoh, Toru; Yamamoto, Yuji

    1982-01-01

    The present authors report a case of unilateral traumatic oculomotor nerve paralysis which shows interesting CT findings which suggest its mechanism. A 60-year-old woman was admitted to our hospital with a cerebral concussion soon after a traffic accident. A CT scan was performed soon after admission. A high-density spot was noted at the medial aspect of the left cerebral peduncle, where the oculomotor nerve emerged from the midbrain, and an irregular, slender, high-density area was delineated in the right dorsolateral surface of the midbrain. Although the right hemiparesis had already improved by the next morning, the function of the left oculomotor nerve has been completely disturbed for the three months since the injury. In our case, it is speculated that an avulsion of the left oculomotor nerve rootlet occurred at the time of impact as the mechanism of the oculomotor nerve paralysis. A CT taken soon after the head injury showed a high-density spot; this was considered to be a hemorrhage occurring because of the avulsion of the nerve rootlet at the medial surface of the cerebral peduncle. (J.P.N.)

  10. The First Experience of Triple Nerve Transfer in Proximal Radial Nerve Palsy.

    Science.gov (United States)

    Emamhadi, Mohammadreza; Andalib, Sasan

    2018-01-01

    Injury to distal portion of posterior cord of brachial plexus leads to palsy of radial and axillary nerves. Symptoms are usually motor deficits of the deltoid muscle; triceps brachii muscle; and extensor muscles of the wrist, thumb, and fingers. Tendon transfers, nerve grafts, and nerve transfers are options for surgical treatment of proximal radial nerve palsy to restore some motor functions. Tendon transfer is painful, requires a long immobilization, and decreases donor muscle strength; nevertheless, nerve transfer produces promising outcomes. We present a patient with proximal radial nerve palsy following a blunt injury undergoing triple nerve transfer. The patient was involved in a motorcycle accident with complete palsy of the radial and axillary nerves. After 6 months, on admission, he showed spontaneous recovery of axillary nerve palsy, but radial nerve palsy remained. We performed triple nerve transfer, fascicle of ulnar nerve to long head of the triceps branch of radial nerve, flexor digitorum superficialis branch of median nerve to extensor carpi radialis brevis branch of radial nerve, and flexor carpi radialis branch of median nerve to posterior interosseous nerve, for restoration of elbow, wrist, and finger extensions, respectively. Our experience confirmed functional elbow, wrist, and finger extensions in the patient. Triple nerve transfer restores functions of the upper limb in patients with debilitating radial nerve palsy after blunt injuries. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Microfasciculation: a morphological pattern in leprosy nerve damage.

    Science.gov (United States)

    Antunes, Sérgio L G; Medeiros, Mildred F; Corte-Real, Suzana; Jardim, Márcia R; Nery, José A da Costa; Hacker, Mariana A V B; Valentim, Vânia da Costa; Amadeu, Thaís Porto; Sarno, Euzenir N

    2011-01-01

    To study Microfasciculation, a perineurial response found in neuropathies, emphasizing its frequency, detailed morphological characteristics and biological significance in pure neural leprosy (PNL), post-treatment leprosy neuropathy (PTLN) and non-leprosy neuropathies (NLN). Morphological characteristics of microfascicles were examined via histological staining methods, immunohistochemical expression of neural markers and transmission electronmicroscopy. The detection of microfasciculation in 18 nerve biopsy specimens [12 PNL, six PTLN but not in the NLN group, was associated strongly with perineurial damage and the presence of a multibacillary inflammatory process in the nerves, particularly in the perineurium. Immunoreactivity to anti-S100 protein, anti-neurofilament, anti-nerve growth receptor and anti-myelin basic protein immunoreactivity was found within microfascicles. Ultrastructural examination of three biopsies showed that fibroblast-perineurial cells were devoid of basement membrane despite perineurial-like NGFr immunoreactivity. Morphological evidence demonstrated that multipotent pericytes from inflammation-activated microvessels could be the origin of fibroblast-perineurial cells. A microfasciculation pattern was found in 10% of leprosy-affected nerves. The microfascicles were composed predominantly of unmyelinated fibres and denervated Schwann cells (SCs) surrounded by fibroblast-perineurial cells. This pattern was found more frequently in leprosy nerves with acid-fast bacilli (AFB) and perineurial damage while undergoing an inflammatory process. Further experimental studies are necessary to elucidate microfascicle formation. © 2011 Blackwell Publishing Limited.

  12. Generation of three-dimensional prototype models based on cone beam computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Lambrecht, J.T.; Berndt, D.C.; Zehnder, M. [University of Basel, Department of Oral Surgery, University Hospital for Oral Surgery, Oral Radiology and Oral Medicine, Basel (Switzerland); Schumacher, R. [University of Applied Sciences Northwestern Switzerland, School of Life Sciences, Institute for Medical and Analytical Technologies, Muttenz (Switzerland)

    2009-03-15

    The purpose of this study was to generate three-dimensional models based on digital volumetric data that can be used in basic and advanced education. Four sets of digital volumetric data were established by cone beam computed tomography (CBCT) (Accuitomo, J. Morita, Kyoto, Japan). Datasets were exported as Dicom formats and imported into Mimics and Magic software programs to separate the different tissues such as nerve, tooth and bone. These data were transferred to a Polyjet 3D Printing machine (Eden 330, Object, Israel) to generate the models. Three-dimensional prototype models of certain limited anatomical structures as acquired volumetrically were fabricated. Generating three-dimensional models based on CBCT datasets is possible. Automated routine fabrication of these models, with the given infrastructure, is too time-consuming and therefore too expensive. (orig.)

  13. Generation of three-dimensional prototype models based on cone beam computed tomography

    International Nuclear Information System (INIS)

    Lambrecht, J.T.; Berndt, D.C.; Zehnder, M.; Schumacher, R.

    2009-01-01

    The purpose of this study was to generate three-dimensional models based on digital volumetric data that can be used in basic and advanced education. Four sets of digital volumetric data were established by cone beam computed tomography (CBCT) (Accuitomo, J. Morita, Kyoto, Japan). Datasets were exported as Dicom formats and imported into Mimics and Magic software programs to separate the different tissues such as nerve, tooth and bone. These data were transferred to a Polyjet 3D Printing machine (Eden 330, Object, Israel) to generate the models. Three-dimensional prototype models of certain limited anatomical structures as acquired volumetrically were fabricated. Generating three-dimensional models based on CBCT datasets is possible. Automated routine fabrication of these models, with the given infrastructure, is too time-consuming and therefore too expensive. (orig.)

  14. Light-cone observables and gauge-invariance in the geodesic light-cone formalism

    Energy Technology Data Exchange (ETDEWEB)

    Scaccabarozzi, Fulvio; Yoo, Jaiyul, E-mail: fulvio@physik.uzh.ch, E-mail: jyoo@physik.uzh.ch [Center for Theoretical Astrophysics and Cosmology, Institute for Computational Science, University of Zürich, Winterthurerstrasse 190, CH-8057, Zürich (Switzerland)

    2017-06-01

    The remarkable properties of the geodesic light-cone (GLC) coordinates allow analytic expressions for the light-cone observables, providing a new non-perturbative way for calculating the effects of inhomogeneities in our Universe. However, the gauge-invariance of these expressions in the GLC formalism has not been shown explicitly. Here we provide this missing part of the GLC formalism by proving the gauge-invariance of the GLC expressions for the light-cone observables, such as the observed redshift, the luminosity distance, and the physical area and volume of the observed sources. Our study provides a new insight on the properties of the GLC coordinates and it complements the previous work by the GLC collaboration, leading to a comprehensive description of light propagation in the GLC representation.

  15. A cone-beam reconstruction algorithm using shift-variant filtering and cone-beam backprojection

    International Nuclear Information System (INIS)

    Defrise, M.; Clack, R.

    1994-01-01

    An exact inversion formula written in the form of shift-variant filtered-backprojection (FBP) is given for reconstruction from cone-beam data taken from any orbit satisfying Tuy's sufficiency conditions. The method is based on a result of Grangeat, involving the derivative of the three-dimensional (3-D) Radon transform, but unlike Grangeat's algorithm, no 3D rebinning step is required. Data redundancy, which occurs when several cone-beam projections supply the same values in the Radon domain, is handled using an elegant weighting function and without discarding data. The algorithm is expressed in a convenient cone-beam detector reference frame, and a specific example for the case of a dual orthogonal circular orbit is presented. When the method is applied to a single circular orbit, it is shown to be equivalent to the well-known algorithm of Feldkamp et al

  16. The Role of Nerve Exploration in Supracondylar Humerus Fracture in Children with Nerve Injury

    Directory of Open Access Journals (Sweden)

    Anuar RIM

    2015-11-01

    Full Text Available The supracondylar humerus fracture (SCHF in children is common and can be complicated with nerve injury either primarily immediate post-trauma or secondarily posttreatment. The concept of neurapraxic nerve injury makes most surgeons choose to ‘watch and see’ the nerve recovery before deciding second surgery if the nerve does not recover. We report three cases of nerve injury in SCHF, all of which underwent nerve exploration for different reasons. Early reduction in the Casualty is important to release the nerve tension before transferring the patient to the operation room. If close reduction fails, we proceed to explore the nerve together with open reduction of the fracture. In iatrogenic nerve injury, we recommend nerve exploration to determine the surgical procedure that is causing the injury. Primary nerve exploration will allow early assessment of the injured nerve and minimize subsequent surgery.

  17. Delayed peripheral nerve repair: methods, including surgical ?cross-bridging? to promote nerve regeneration

    OpenAIRE

    Gordon, Tessa; Eva, Placheta; Borschel, Gregory H.

    2015-01-01

    Despite the capacity of Schwann cells to support peripheral nerve regeneration, functional recovery after nerve injuries is frequently poor, especially for proximal injuries that require regenerating axons to grow over long distances to reinnervate distal targets. Nerve transfers, where small fascicles from an adjacent intact nerve are coapted to the nerve stump of a nearby denervated muscle, allow for functional return but at the expense of reduced numbers of innervating nerves. A 1-hour per...

  18. Techniques for optimizing nanotips derived from frozen taylor cones

    Science.gov (United States)

    Hirsch, Gregory

    2017-12-05

    Optimization techniques are disclosed for producing sharp and stable tips/nanotips relying on liquid Taylor cones created from electrically conductive materials with high melting points. A wire substrate of such a material with a preform end in the shape of a regular or concave cone, is first melted with a focused laser beam. Under the influence of a high positive potential, a Taylor cone in a liquid/molten state is formed at that end. The cone is then quenched upon cessation of the laser power, thus freezing the Taylor cone. The tip of the frozen Taylor cone is reheated by the laser to allow its precise localized melting and shaping. Tips thus obtained yield desirable end-forms suitable as electron field emission sources for a variety of applications. In-situ regeneration of the tip is readily accomplished. These tips can also be employed as regenerable bright ion sources using field ionization/desorption of introduced chemical species.

  19. Phrenic nerve transfer to the musculocutaneous nerve for the repair of brachial plexus injury: electrophysiological characteristics

    Directory of Open Access Journals (Sweden)

    Ying Liu

    2015-01-01

    Full Text Available Phrenic nerve transfer is a major dynamic treatment used to repair brachial plexus root avulsion. We analyzed 72 relevant articles on phrenic nerve transfer to repair injured brachial plexus that were indexed by Science Citation Index. The keywords searched were brachial plexus injury, phrenic nerve, repair, surgery, protection, nerve transfer, and nerve graft. In addition, we performed neurophysiological analysis of the preoperative condition and prognosis of 10 patients undergoing ipsilateral phrenic nerve transfer to the musculocutaneous nerve in our hospital from 2008 to 201 3 and observed the electromyograms of the biceps brachii and motor conduction function of the musculocutaneous nerve. Clinically, approximately 28% of patients had brachial plexus injury combined with phrenic nerve injury, and injured phrenic nerve cannot be used as a nerve graft. After phrenic nerve transfer to the musculocutaneous nerve, the regenerated potentials first appeared at 3 months. Recovery of motor unit action potential occurred 6 months later and became more apparent at 12 months. The percent of patients recovering ′excellent′ and ′good′ muscle strength in the biceps brachii was 80% after 18 months. At 12 months after surgery, motor nerve conduction potential appeared in the musculocutaneous nerve in seven cases. These data suggest that preoperative evaluation of phrenic nerve function may help identify the most appropriate nerve graft in patients with an injured brachial plexus. The functional recovery of a transplanted nerve can be dynamically observed after the surgery.

  20. Phrenic nerve transfer to the musculocutaneous nerve for the repair of brachial plexus injury: electrophysiological characteristics.

    Science.gov (United States)

    Liu, Ying; Xu, Xun-Cheng; Zou, Yi; Li, Su-Rong; Zhang, Bin; Wang, Yue

    2015-02-01

    Phrenic nerve transfer is a major dynamic treatment used to repair brachial plexus root avulsion. We analyzed 72 relevant articles on phrenic nerve transfer to repair injured brachial plexus that were indexed by Science Citation Index. The keywords searched were brachial plexus injury, phrenic nerve, repair, surgery, protection, nerve transfer, and nerve graft. In addition, we performed neurophysiological analysis of the preoperative condition and prognosis of 10 patients undergoing ipsilateral phrenic nerve transfer to the musculocutaneous nerve in our hospital from 2008 to 201 3 and observed the electromyograms of the biceps brachii and motor conduction function of the musculocutaneous nerve. Clinically, approximately 28% of patients had brachial plexus injury combined with phrenic nerve injury, and injured phrenic nerve cannot be used as a nerve graft. After phrenic nerve transfer to the musculocutaneous nerve, the regenerated potentials first appeared at 3 months. Recovery of motor unit action potential occurred 6 months later and became more apparent at 12 months. The percent of patients recovering 'excellent' and 'good' muscle strength in the biceps brachii was 80% after 18 months. At 12 months after surgery, motor nerve conduction potential appeared in the musculocutaneous nerve in seven cases. These data suggest that preoperative evaluation of phrenic nerve function may help identify the most appropriate nerve graft in patients with an injured brachial plexus. The functional recovery of a transplanted nerve can be dynamically observed after the surgery.

  1. JWFront: Wavefronts and Light Cones for Kerr Spacetimes

    Science.gov (United States)

    Frutos Alfaro, Francisco; Grave, Frank; Müller, Thomas; Adis, Daria

    2015-04-01

    JWFront visualizes wavefronts and light cones in general relativity. The interactive front-end allows users to enter the initial position values and choose the values for mass and angular momentum per unit mass. The wavefront animations are available in 2D and 3D; the light cones are visualized using the coordinate systems (t, x, y) or (t, z, x). JWFront can be easily modified to simulate wavefronts and light cones for other spacetime by providing the Christoffel symbols in the program.

  2. Preparation of Au cone for fast ignition target

    International Nuclear Information System (INIS)

    Du Kai; Zhou Lan; Zhang Lin; Wan Xiaobo; Xiao Jiang

    2005-01-01

    Cone-shell target is typically used for the fast ignition experiments of inertial confinement fusion. In order to fabricate cone-shell target the Au cones with different angles were produced by electroplating and precise machining. The Au electroplating process was introduced in the paper, and the dependence of coating quality on the parameters, such as composition, temperature, pH of electroplating bath, current density and tip effect, were discussed. (author)

  3. Feedback-induced glutamate spillover enhances negative feedback from horizontal cells to cones

    NARCIS (Netherlands)

    Vroman, Rozan; Kamermans, M.

    2015-01-01

    KEY POINTS: In the retina, horizontal cells feed back negatively to cone photoreceptors. Glutamate released from cones can spill over to neighbouring cones. Here we show that cone glutamate release induced by negative feedback can also spill over to neighbouring cones. This glutamate activates the

  4. Feedback-induced glutamate spillover enhances negative feedback from horizontal cells to cones

    NARCIS (Netherlands)

    Vroman, Rozan; Kamermans, Maarten

    2015-01-01

    In the retina, horizontal cells feed back negatively to cone photoreceptors. Glutamate released from cones can spill over to neighbouring cones. Here we show that cone glutamate release induced by negative feedback can also spill over to neighbouring cones. This glutamate activates the glutamate

  5. Synergistic effect of nisin and cone essential oil of Metasequoia glyptostroboides Miki ex Hu against Listeria monocytogenes in milk samples.

    Science.gov (United States)

    Yoon, Jung In; Bajpai, Vivek K; Kang, Sun Chul

    2011-01-01

    This study was undertaken to evaluate the effect of nisin and cone essential oil of Metasequoia glyptostroboides against Listeria monocytogenes ATCC 19116 inoculated in whole (8%), low (1%) and skim (no fat content) milks. Essential oil at the concentrations of 2% and 5% revealed strong antilisterial effect against L. monocytogenes ATCC 19116 in all categories of milks. Nisin at the concentrations of 250 and 500 IU/ml displayed a remarkable antilisterial effect as compared to the control group. Also, the synergistic combinations of cone essential oil (1% and 2%) and nisin (62.5, 125, 250 and 500 IU/ml) had a remarkable antilisterial activity in all categories of whole, low and skim milks after 14 days. Results of this study indicate that the cone essential oil of M. glyptostroboides might be a useful candidate for using in food industry to control the growth of pathogenic microorganisms. Copyright © 2010 Elsevier Ltd. All rights reserved.

  6. Identifying Dirac cones in carbon allotropes with square symmetry

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jinying [College of Chemistry and Molecular Engineering, Peking University, Beijing 100871 (China); Huang, Huaqing; Duan, Wenhui [Department of Physics, Tsinghua University, Beijing 100084 (China); Liu, Zhirong, E-mail: LiuZhiRong@pku.edu.cn [College of Chemistry and Molecular Engineering, Peking University, Beijing 100871 (China); State Key Laboratory for Structural Chemistry of Unstable and Stable Species and Beijing National Laboratory for Molecular Sciences (BNLMS), Peking University, Beijing 100871 (China)

    2013-11-14

    A theoretical study is conducted to search for Dirac cones in two-dimensional carbon allotropes with square symmetry. By enumerating the carbon atoms in a unit cell up to 12, an allotrope with octatomic rings is recognized to possess Dirac cones under a simple tight-binding approach. The obtained Dirac cones are accompanied by flat bands at the Fermi level, and the resulting massless Dirac-Weyl fermions are chiral particles with a pseudospin of S = 1, rather than the conventional S = 1/2 of graphene. The spin-1 Dirac cones are also predicted to exist in hexagonal graphene antidot lattices.

  7. Integrity of the cone photoreceptor mosaic in oligocone trichromacy

    DEFF Research Database (Denmark)

    Michaelides, Michel; Rha, Jungtae; Dees, Elise W

    2011-01-01

    Oligocone trichromacy (OT) is an unusual cone dysfunction syndrome characterized by reduced visual acuity, mild photophobia, reduced amplitude of the cone electroretinogram with normal rod responses, normal fundus appearance, and normal or near-normal color vision. It has been proposed that these......Oligocone trichromacy (OT) is an unusual cone dysfunction syndrome characterized by reduced visual acuity, mild photophobia, reduced amplitude of the cone electroretinogram with normal rod responses, normal fundus appearance, and normal or near-normal color vision. It has been proposed...

  8. Conical Refraction: new observations and a dual cone model.

    Science.gov (United States)

    Sokolovskii, G S; Carnegie, D J; Kalkandjiev, T K; Rafailov, E U

    2013-05-06

    We propose a paraxial dual-cone model of conical refraction involving the interference of two cones of light behind the exit face of the crystal. The supporting experiment is based on beam selecting elements breaking down the conically refracted beam into two separate hollow cones which are symmetrical with one another. The shape of these cones of light is a product of a 'competition' between the divergence caused by the conical refraction and the convergence due to the focusing by the lens. The developed mathematical description of the conical refraction demonstrates an excellent agreement with experiment.

  9. In vivo testing of a 3D bifurcating microchannel scaffold inducing separation of regenerating axon bundles in peripheral nerves

    NARCIS (Netherlands)

    Stoyanova, II; Wezel, R.J.A. van; Rutten, W.L.C.

    2013-01-01

    Artificial nerve guidance channels enhance the regenerative effectiveness in an injured peripheral nerve but the existing design so far has been limited to basic straight tubes simply guiding the growth to bridge the gap. Hence, one of the goals in development of more effective neuroprostheses is to

  10. Cone photoreceptor structure in patients with x-linked cone dysfunction and red-green color vision deficiency

    DEFF Research Database (Denmark)

    Patterson, Emily J.; Wilk, Melissa; Langlo, Christopher S.

    2016-01-01

    encoded by exon 4, and two with a novel insertion in exon 2. Foveal cone structure and retinal thickness was disrupted to a variable degree, even among related individuals with the same L/M array. CONCLUSIONS. Our findings provide a direct link between disruption of the cone mosaic and L/ M opsin variants......PURPOSE. Mutations in the coding sequence of the L and M opsin genes are often associated with X-linked cone dysfunction (such as Bornholm Eye Disease, BED), though the exact color vision phenotype associated with these disorders is variable. We examined individuals with L/ M opsin gene mutations...... to clarify the link between color vision deficiency and cone dysfunction.  METHODS. We recruited 17 males for imaging. The thickness and integrity of the photoreceptor layers were evaluated using spectral-domain optical coherence tomography. Cone density was measured using high-resolution images of the cone...

  11. Imaging the ocular motor nerves

    Energy Technology Data Exchange (ETDEWEB)

    Ferreira, Teresa [Department of Radiology, Leiden University Medical Center (Netherlands)], E-mail: T.A.Ferreira@lumc.nl; Verbist, Berit [Department of Radiology, Leiden University Medical Center (Netherlands)], E-mail: B.M.Verbist@lumc.nl; Buchem, Mark van [Department of Radiology, Leiden University Medical Center (Netherlands)], E-mail: M.A.van_Buchem@lumc.nl; Osch, Thijs van [C.J. Gorter for High-Field MRI, Department of Radiology, Leiden University Medical Center (Netherlands)], E-mail: M.J.P.van_Osch@lumc.nl; Webb, Andrew [C.J. Gorter for High-Field MRI, Department of Radiology, Leiden University Medical Center (Netherlands)], E-mail: A.Webb@lumc.nl

    2010-05-15

    The ocular motor nerves (OMNs) comprise the oculomotor, trochlear and the abducens nerves. According to their course, they are divided into four or five anatomic segments: intra-axial, cisternal, cavernous and intra-orbital and, for the abducens nerve, an additional interdural segment. Magnetic resonance imaging is the imaging method of choice in the evaluation of the normal and pathologic ocular motor nerves. CT still plays a limited but important role in the evaluation of the intraosseous portions at the skull base and bony foramina. We describe for each segment of these cranial nerves, the normal anatomy, the most appropriate image sequences and planes, their imaging appearance and pathologic conditions. Magnetic resonance imaging with high magnetic fields is a developing and promising technique. We describe our initial experience with a Phillips 7.0 T MRI scanner in the evaluation of the brainstem segments of the OMNs. As imaging becomes more refined, an understanding of the detailed anatomy is increasingly necessary, as the demand on radiology to diagnose smaller lesions also increases.

  12. Electrodiagnosis and nerve conduction studies.

    Science.gov (United States)

    Posuniak, E A

    1984-08-01

    The use of electrodiagnostic techniques in evaluation of complaints in the lower extremities provides an objective method of assessment. A basic understanding of principles of neurophysiology, EMG and NCV methodology, and neuropathology of peripheral nerves greatly enhances physical diagnosis and improves the state of the art in treatment of the lower extremity, especially foot and ankle injuries. Familiarity with the method of reporting electrodiagnostic studies and appreciation of the electromyographer's interpretation of the EMG/NCV studies also reflects an enhanced fund of knowledge, skills, and attitudes as pertains to one's level of professional expertise. Information regarding the etiology of positive sharp waves, fibrillation potentials, fasciculation, and normal motor action potentials and conduction studies serves as a sound basis for the appreciation of the categories of nerve injury. Competence in understanding the degree of axonal or myelin function or dysfunction in a nerve improve one's effectiveness not only in medical/surgical treatment but in prognostication of recovery of function. A review of the entrapment syndromes in the lower extremity with emphasis on tarsal tunnel syndrome summarizes the most common nerve entrapments germane to the practice of podiatry. With regard to tarsal tunnel syndrome, the earliest electrodiagnostic study to suggest compression was reported to be the EMG of the foot and leg muscles, even before prolonged nerve latency was noted.

  13. Peripheral nerve injury induces glial activation in primary motor cortex

    Directory of Open Access Journals (Sweden)

    Julieta Troncoso

    2015-02-01

    Full Text Available Preliminary evidence suggests that peripheral facial nerve injuries are associated with sensorimotor cortex reorganization. We have characterized facial nerve lesion-induced structural changes in primary motor cortex layer 5 pyramidal neurons and their relationship with glial cell density using a rodent facial paralysis model. First, we used adult transgenic mice expressing green fluorescent protein in microglia and yellow fluorescent protein in pyramidal neurons which were subjected to either unilateral lesion of the facial nerve or sham surgery. Two-photon excitation microscopy was then used for evaluating both layer 5 pyramidal neurons and microglia in vibrissal primary motor cortex (vM1. It was found that facial nerve lesion induced long-lasting changes in dendritic morphology of vM1 layer 5 pyramidal neurons and in their surrounding microglia. Pyramidal cells’ dendritic arborization underwent overall shrinkage and transient spine pruning. Moreover, microglial cell density surrounding vM1 layer 5 pyramidal neurons was significantly increased with morphological bias towards the activated phenotype. Additionally, we induced facial nerve lesion in Wistar rats to evaluate the degree and extension of