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Sample records for myelinated nerve fiber

  1. Evaluation of dermal myelinated nerve fibers in diabetes mellitus

    PubMed Central

    Peltier, Amanda C.; Myers, M. Iliza; Artibee, Kay J.; Hamilton, Audra D.; Yan, Qing; Guo, Jiasong; Shi, Yaping; Wang, Lily; Li, Jun

    2013-01-01

    Skin biopsies have primarily been used to study the non-myelinated nerve fibers of the epidermis in a variety of neuropathies. In the present study, we have expanded the skin biopsy technique to glabrous, non-hairy skin to evaluate myelinated nerve fibers in the most highly prevalent peripheral nerve disease, diabetic polyneuropathy (DPN). Twenty patients with DPN (Type I, n=9; Type II, n=11) and sixteen age-matched healthy controls (ages 29–73) underwent skin biopsy of the index finger, nerve conduction studies, and composite neuropathy scoring. In patients with DPN, we found a statistically significant reduction of both mechanoreceptive Meissner corpuscles (MC) and their afferent myelinated nerve fibers (p=0.01). This myelinated nerve fiber loss was correlated with the decreased amplitudes of sensory/motor responses in nerve conduction studies. This study supports the utilization of skin biopsy to quantitatively evaluate axonal loss of myelinated nerve fibers in patients with DPN. PMID:23781963

  2. Evaluation of dermal myelinated nerve fibers in diabetes mellitus.

    PubMed

    Peltier, Amanda C; Myers, M Iliza; Artibee, Kay J; Hamilton, Audra D; Yan, Qing; Guo, Jiasong; Shi, Yaping; Wang, Lily; Li, Jun

    2013-06-01

    Skin biopsies have primarily been used to study the non-myelinated nerve fibers of the epidermis in a variety of neuropathies. In this study, we have expanded the skin biopsy technique to glabrous, non-hairy skin to evaluate myelinated nerve fibers in the most highly prevalent peripheral nerve disease, diabetic polyneuropathy (DPN). Twenty patients with DPN (Type I, n = 9; Type II, n = 11) and 16 age-matched healthy controls (age 29-73) underwent skin biopsy of the index finger, nerve conduction studies (NCS), and composite neuropathy scoring. In patients with DPN, we found a statistically significant reduction of both mechanoreceptive Meissner corpuscles (MCs) and their afferent myelinated nerve fibers (p = 0.01). This myelinated nerve fiber loss was correlated with the decreased amplitudes of sensory/motor responses in NCS. This study supports the utilization of skin biopsy to quantitatively evaluate axonal loss of myelinated nerve fibers in patients with DPN.

  3. Acquired myelinated nerve fibers in association with optic disk drusen.

    PubMed

    Duval, Renaud; Hammamji, Karim; Aroichane, Maryam; Michaud, Jacques L; Ospina, Luis H

    2010-12-01

    Myelinated retinal nerve fibers are a well-recognized anomaly of the ocular fundus associated with many ocular and systemic conditions. Myelination is almost always congenital and stable, but progression has been documented in rare cases. Optic disk drusen are the result of a degenerative process at the optic nerve head and are often found incidentally on ophthalmologic examination. To our knowledge, optic disk drusen have only been reported once in association with acquired and progressive myelinated retinal nerve fibers. We present 2 such cases and consider the implications for the pathogenesis of myelinated nerve fibers.

  4. Evaluating dermal myelinated nerve fibers in skin biopsy

    PubMed Central

    Myers, M. Iliza; Peltier, Amanda C.; Li, Jun

    2012-01-01

    Although there has been extensive research on small, unmyelinated fibers in the skin, little research has investigated dermal myelinated fibers in comparison. Glabrous, non-hairy skin contains mechanoreceptors that afford a vantage point for observation of myelinated fibers that have previously been seen only with invasively obtained nerve biopsies. This review discusses current morphometric and molecular expression data of normative and pathogenic glabrous skin obtained by various processing and analysis methods for cutaneous myelinated fibers. Recent publications have shed light on the role of glabrous skin biopsy in identifying signs of peripheral neuropathy and as a potential biomarker of distal myelin and mechanoreceptor integrity. The clinical relevance of a better understanding of the role of dermal myelinated nerve terminations in peripheral neuropathy will be addressed in light of recent publications in the growing field of skin biopsy. PMID:23192899

  5. A role for nociceptive, myelinated nerve fibers in itch sensation

    PubMed Central

    Ringkamp, M.; Schepers, R. J.; Shimada, S.G.; Johanek, L.M.; Hartke, T.V.; Borzan, J.; Shim, B.; LaMotte, R.H.; Meyer, R.A.

    2011-01-01

    Despite its clinical importance, the underlying neural mechanisms of itch sensation are poorly understood. In many diseases, pruritus is not effectively treated with antihistamines, indicating the involvement of non-histaminergic mechanisms. To investigate the role of small myelinated afferents in non-histaminergic itch, we tested, in psychophysical studies in humans, the effect of a differential nerve block on itch produced by intradermal insertion of spicules from the pods of a cowhage plant (Mucuna pruriens). Electrophysiological experiments in anesthetized monkey were used to investigate the responsiveness of cutaneous, nociceptive, myelinated afferents to different chemical stimuli (cowhage spicules, histamine, capsaicin). Our results provide several lines of evidence for an important role of myelinated fibers in cowhage-induced itch: 1) a selective conduction block in myelinated fibers substantially reduces itch in a sub-group of subjects with A-fiber dominated itch, 2) the time course of itch sensation differs between subjects with A-fiber versus C-fiber dominated itch, 3) cowhage activates a subpopulation of myelinated and unmyelinated afferents in monkey, 4) the time course of the response to cowhage is different in myelinated and unmyelinated fibers, 5) the time of peak itch sensation for subjects with A-fiber dominated itch matches the time for peak response in myelinated fibers, and 6) the time for peak itch sensation for subjects with C-fiber dominated itch matches the time for the peak response in unmyelinated fibers. These findings demonstrate that activity in nociceptive, myelinated afferents contributes to cowhage-induced sensations, and that non-histaminergic itch is mediated through activity in both unmyelinated and myelinated afferents. PMID:22016517

  6. A role for nociceptive, myelinated nerve fibers in itch sensation.

    PubMed

    Ringkamp, Matthias; Schepers, Raf J; Shimada, Steven G; Johanek, Lisa M; Hartke, Timothy V; Borzan, Jasenka; Shim, Beom; LaMotte, Robert H; Meyer, Richard A

    2011-10-19

    Despite its clinical importance, the underlying neural mechanisms of itch sensation are poorly understood. In many diseases, pruritus is not effectively treated with antihistamines, indicating the involvement of nonhistaminergic mechanisms. To investigate the role of small myelinated afferents in nonhistaminergic itch, we tested, in psychophysical studies in humans, the effect of a differential nerve block on itch produced by intradermal insertion of spicules from the pods of a cowhage plant (Mucuna pruriens). Electrophysiological experiments in anesthetized monkey were used to investigate the responsiveness of cutaneous, nociceptive, myelinated afferents to different chemical stimuli (cowhage spicules, histamine, capsaicin). Our results provide several lines of evidence for an important role of myelinated fibers in cowhage-induced itch: (1) a selective conduction block in myelinated fibers substantially reduces itch in a subgroup of subjects with A-fiber-dominated itch, (2) the time course of itch sensation differs between subjects with A-fiber- versus C-fiber-dominated itch, (3) cowhage activates a subpopulation of myelinated and unmyelinated afferents in monkey, (4) the time course of the response to cowhage is different in myelinated and unmyelinated fibers, (5) the time of peak itch sensation for subjects with A-fiber-dominated itch matches the time for peak response in myelinated fibers, and (6) the time for peak itch sensation for subjects with C-fiber-dominated itch matches the time for the peak response in unmyelinated fibers. These findings demonstrate that activity in nociceptive, myelinated afferents contributes to cowhage-induced sensations, and that nonhistaminergic itch is mediated through activity in both unmyelinated and myelinated afferents.

  7. Generalized cable equation model for myelinated nerve fiber.

    PubMed

    Einziger, Pinchas D; Livshitz, Leonid M; Mizrahi, Joseph

    2005-10-01

    Herein, the well-known cable equation for nonmyelinated axon model is extended analytically for myelinated axon formulation. The myelinated membrane conductivity is represented via the Fourier series expansion. The classical cable equation is thereby modified into a linear second order ordinary differential equation with periodic coefficients, known as Hill's equation. The general internal source response, expressed via repeated convolutions, uniformly converges provided that the entire periodic membrane is passive. The solution can be interpreted as an extended source response in an equivalent nonmyelinated axon (i.e., the response is governed by the classical cable equation). The extended source consists of the original source and a novel activation function, replacing the periodic membrane in the myelinated axon model. Hill's equation is explicitly integrated for the specific choice of piecewise constant membrane conductivity profile, thereby resulting in an explicit closed form expression for the transmembrane potential in terms of trigonometric functions. The Floquet's modes are recognized as the nerve fiber activation modes, which are conventionally associated with the nonlinear Hodgkin-Huxley formulation. They can also be incorporated in our linear model, provided that the periodic membrane point-wise passivity constraint is properly modified. Indeed, the modified condition, enforcing the periodic membrane passivity constraint on the average conductivity only leads, for the first time, to the inclusion of the nerve fiber activation modes in our novel model. The validity of the generalized transmission-line and cable equation models for a myelinated nerve fiber, is verified herein through a rigorous Green's function formulation and numerical simulations for transmembrane potential induced in three-dimensional myelinated cylindrical cell. It is shown that the dominant pole contribution of the exact modal expansion is the transmembrane potential solution of our

  8. CONTINUOUS CONDUCTION OF IMPULSES IN PERIPHERAL MYELINATED NERVE FIBERS

    PubMed Central

    Laporte, Y.

    1951-01-01

    1. Conduction of impulses in peripheral myelinated fibers of a nerve trunk is a continuous process, since with uninjured nerve fibers: (a) within each internodal segment the conduction time increases continuously and linearly with increasing conduction distance; (b) the presence of nodes of Ranvier does not result in any detectable discontinuity in the conduction of the impulse; (c) the ascending phase of the spike always has an S shape and never presents signs of fractionation; (d) the shape and magnitude of the spike are constant at all points of each internodal segment. 2. Records have been presented of the external logitudinal current that flows during propagation of an impulse in undissected single nerve fiber (Fig. 6). 3. Propagation of impulses across a conduction block occurs with a readily demonstrable discontinuity. PMID:14898021

  9. Diffusion of Ions in Myelinated Nerve Fibers

    PubMed Central

    Palti, Y.; Gold, R.; Stämpfli, R.

    1979-01-01

    The diffusion of ions towards or away from the inner side of the nodal membrane in preparations, the cut ends of which are placed in various media, was investigated. The ion concentration changes were calculated by numerical solution of the unidimensional electrodiffusion equation under a variety of media compositions, axoplasmic diffusion coefficients, and internal anionic compositions. The potassium and cesium ion diffusion along the axon towards the node was determined experimentally by two different electrophysiological methods. On the basis of comparison between the experimental data and the computational predictions the axoplasmic potassium ion diffusion coefficient was determined to be almost equal to that in free aqueous solution, while that of cesium ion was close to one half of that in aqueous solution. Utilizing the values of diffusion parameters thus determined, we solved the electrodiffusion equation for a number of common experimental procedures. We found that in short fibers, cut 0.1-0.2 cm at each side of the node, the concentration approached values close to the new steady-state values within 5-30 min. In long fibers (over 1 cm long) steady-state concentrations were obtained only after a few hours. Under some conditions the internal concentrations transiently overshot the steady-state values. The diffusion potentials generated in the system were also evaluated. The ion concentration changes and generation of diffusion potential cannot be prevented by using side pools with cation content identical to that of the axoplasm. PMID:318061

  10. A model of injury potential for myelinated nerve fiber.

    PubMed

    Guang-Hao, Zhang; Xiao-Lin, Huo; Ai-Hua, Wang; Cheng, Zhang; Chang-Zhe, Wu

    2015-01-01

    Excellent models have been described in literatures which related membrane potential to extracellular electric or magnetic stimulation and which described the formation and propagation of action potentials along the axon, for both myelinated and nonmyelinated fibers. There is not, however, an adequate model for nerve injury which allows to compute the distribution of injury potential, a direct current potential difference between intact and injured nerve, because its importance has been ignored in the shadow of the well-known action potential. This paper focus on the injury potential and presents a model of the electrical properties of myelinated nerve which describes the time course of events following injury. The time-varying current and potential at all nodes can be computed from the model, and the factors relate to the amplitude of injury potential can be determined. It is shown that the amplitude of injury potential decreased gradually with injury time, and the recession curve was exponential. Results also showed that the initial amplitude of injury potential is positively related to the grade of injury and fiber diameter. This model explained the mechanism of formation of injury potential and can provide instruction for applied electric field to prevent the formation injury potential.

  11. Ring-shaped myelinated retinal nerve fibers at fovea.

    PubMed

    Ozates, Serdar; Teke, Mehmet Yasin

    2017-07-01

    We aim to report an unusual case of myelinated retinal nerve fibers (MRNFs) at fovea. A 39-year-old woman presented with visual impairment and her visual acuity was 20/80 in the right eye. Ophthalmologic examination revealed MRNF lesions at inferior and superior poles of optic disc in the right eye. Furthermore, a ring-shaped MRNF lesion with feathery edges was observed at fovea. MRNF lesions are rarely seen at macula, and to our knowledge, this is the first report of an MRNF lesion at fovea.

  12. Ring-shaped myelinated retinal nerve fibers at fovea

    PubMed Central

    Ozates, Serdar; Teke, Mehmet Yasin

    2017-01-01

    We aim to report an unusual case of myelinated retinal nerve fibers (MRNFs) at fovea. A 39-year-old woman presented with visual impairment and her visual acuity was 20/80 in the right eye. Ophthalmologic examination revealed MRNF lesions at inferior and superior poles of optic disc in the right eye. Furthermore, a ring-shaped MRNF lesion with feathery edges was observed at fovea. MRNF lesions are rarely seen at macula, and to our knowledge, this is the first report of an MRNF lesion at fovea. PMID:28724828

  13. Statistical physics approach to quantifying differences in myelinated nerve fibers

    NASA Astrophysics Data System (ADS)

    Comin, César H.; Santos, João R.; Corradini, Dario; Morrison, Will; Curme, Chester; Rosene, Douglas L.; Gabrielli, Andrea; da F. Costa, Luciano; Stanley, H. Eugene

    2014-03-01

    We present a new method to quantify differences in myelinated nerve fibers. These differences range from morphologic characteristics of individual fibers to differences in macroscopic properties of collections of fibers. Our method uses statistical physics tools to improve on traditional measures, such as fiber size and packing density. As a case study, we analyze cross-sectional electron micrographs from the fornix of young and old rhesus monkeys using a semi-automatic detection algorithm to identify and characterize myelinated axons. We then apply a feature selection approach to identify the features that best distinguish between the young and old age groups, achieving a maximum accuracy of 94% when assigning samples to their age groups. This analysis shows that the best discrimination is obtained using the combination of two features: the fraction of occupied axon area and the effective local density. The latter is a modified calculation of axon density, which reflects how closely axons are packed. Our feature analysis approach can be applied to characterize differences that result from biological processes such as aging, damage from trauma or disease or developmental differences, as well as differences between anatomical regions such as the fornix and the cingulum bundle or corpus callosum.

  14. Statistical physics approach to quantifying differences in myelinated nerve fibers.

    PubMed

    Comin, César H; Santos, João R; Corradini, Dario; Morrison, Will; Curme, Chester; Rosene, Douglas L; Gabrielli, Andrea; Costa, Luciano da F; Stanley, H Eugene

    2014-03-28

    We present a new method to quantify differences in myelinated nerve fibers. These differences range from morphologic characteristics of individual fibers to differences in macroscopic properties of collections of fibers. Our method uses statistical physics tools to improve on traditional measures, such as fiber size and packing density. As a case study, we analyze cross-sectional electron micrographs from the fornix of young and old rhesus monkeys using a semi-automatic detection algorithm to identify and characterize myelinated axons. We then apply a feature selection approach to identify the features that best distinguish between the young and old age groups, achieving a maximum accuracy of 94% when assigning samples to their age groups. This analysis shows that the best discrimination is obtained using the combination of two features: the fraction of occupied axon area and the effective local density. The latter is a modified calculation of axon density, which reflects how closely axons are packed. Our feature analysis approach can be applied to characterize differences that result from biological processes such as aging, damage from trauma or disease or developmental differences, as well as differences between anatomical regions such as the fornix and the cingulum bundle or corpus callosum.

  15. Myelinated nerve bundles developed on the plano-concave fibers containing nerve conduit.

    PubMed

    Huang, Wei-Chin; Liao, Jiunn-Der; Lin, Chou-Ching K; Ju, Ming-Shaung

    2012-12-01

    Morphologically and chemically modified plano-concave fibers (PCFs) are designed as a unit of guided channels for supporting Schwann cells to facilitate mass transport and promote nerve regeneration. The surface-modified PCFs are imprinted with linearly patterned grooves (LPGs) to guide adherent Schwann cell elongation and axon extension. After being cocultured with PC12 neuron-like cells, Schwann cells differentiate into the myelinated type and interact with PC12 axons. The myelinated axons aggregate as a linear bundle and extend along the direction of LPGs on a PCF. The cross section of a myelin structure is examined using a transmission electron microscope. The PCFs can potentially bridge gaps in injured nerves, improving the therapeutic efficacy of nerve regeneration. Copyright © 2012 Wiley Periodicals, Inc.

  16. The Effects of Normal Aging on Myelinated Nerve Fibers in Monkey Central Nervous System

    PubMed Central

    Peters, Alan

    2009-01-01

    The effects of aging on myelinated nerve fibers of the central nervous system are complex. Many myelinated nerve fibers in white matter degenerate and are lost, leading to some disconnections between various parts of the central nervous system. Other myelinated nerve fibers are affected differently, because only their sheaths degenerate, leaving the axons intact. Such axons are remyelinated by a series of internodes that are much shorter than the original ones and are composed of thinner sheaths. Thus the myelin-forming cells of the central nervous system, the oligodendrocytes, remain active during aging. Indeed, not only do these neuroglial cell remyelinate axons, with age they also continue to add lamellae to the myelin sheaths of intact nerve fibers, so that sheaths become thicker. It is presumed that the degeneration of myelin sheaths is due to the degeneration of the parent oligodendrocyte, and that the production of increased numbers of internodes as a consequence of remyelination requires additional oligodendrocytes. Whether there is a turnover of oligodendrocytes during life has not been studied in primates, but it has been established that over the life span of the monkey, there is a substantial increase in the numbers of oligodendrocytes. While the loss of some myelinated nerve fibers leads to some disconnections, the degeneration of other myelin sheaths and the subsequent remyelination of axons by shorter internodes slow down the rate conduction along nerve fibers. These changes affect the integrity and timing in neuronal circuits, and there is evidence that they contribute to cognitive decline. PMID:19636385

  17. Retinal detachment in a patient with extensive myelinated retinal nerve fibers.

    PubMed

    Chen, Muh-Shy; Ho, Tzyy-Chang; Chang, Ching-Chung; Hou, Ping-Kang

    2007-01-01

    We report extensive myelinated retinal nerve fibers in a 42-year-old patient with retinal detachment. Fundus examination revealed a horseshoe-shaped tear near the temporal edge. Pars plana vitrectomy was performed and firm vitreo-retinal adhesion was noticed in the area of extensive myelinated retinal nerve fibers. Following vitrectomy with silicone oil tamponade, the retina was reattached successfully. In conclusion, retinal detachment may develop in patients with extensive myelinated retinal nerve fibers. Vitrectomy may be performed to treat this condition.

  18. Quantitative analysis of myelinic fibers in human laryngeal nerves according to age.

    PubMed

    Tiago, Romualdo Suzano Louzeiro; Pontes, Paulo Augusto de Lima; Brasil, Osíris de Oliveira Camponês do

    2008-01-01

    To carry out a morphometric analysis of myelinic fibers in laryngeal nerves aiming to identify quantitative changes as a result of aging. Clinical and experimental. A 1cm fragment was collected from the superior laryngeal nerves and recurrent laryngeal nerves taken from twelve male cadavers. The sample was divided into two groups: those aged below 60 years (Adult) and those aged 60 years or more (Elderly). The material was evaluated under light microscopy coupled with an image analysis system. The total number of myelinic fibers from the superior laryngeal nerve was similar in both age groups; there was, however, a trend for a higher number of 1 microm fibers in the adult group (p=0.0744). The adult group had a higher total number of myelinic fibers in the recurrent laryngeal nerve (p=0.0006), and this difference was seen in fibers with diameters between 1-3 microm (p<0.007). The adult group had a higher total number of myelinic fibers in the laryngeal nerves (sum of superior laryngeal nerves and recurrent laryngeal nerves fibers) compared to the elderly group (p<0.0091). The total number of myelinic fibers in laryngeal nerves is higher for the group aged below 60 years.

  19. Aging process of myelinated nerve fibers in the human Lissauer tract.

    PubMed

    Motoura, Hiroyuki; Goto, Noboru; Goto, Jun; Ezure, Hiromitsu; Shibata, Masakazu

    2005-03-01

    We calculated numbers and axonal areas of myelinated nerve fibers in the Lissauer tract of the human lumbar spinal cord (L1) from the viewpoint of the aging process. We examined 20 human spinal cords from 13 males and 7 females, age ranging from 41 to 88 years old. We found that, although the number of nerve fibers showed no significant change in relation to the age of the subject, the axonal area of myelinated nerve fiber in the Lissauer tract did decrease with age.

  20. Structure and function of myelinated nerve fibers in the rabbit eye following ischemia/reperfusion injury.

    PubMed

    Guo, Wenyi; Cringle, Stephen J; Su, Er-Ning; Yu, Paula K; Yu, Xiao-Bo; Sun, Xinghuai; Morgan, William; Yu, Dao-Yi

    2006-02-01

    The rabbit eye presents a valuable model to study the effects of vascular occlusion on the function and structure of myelinated nerve fibers. The rabbit eye has a band of myelinated nerve fibers within the intraocular compartment that are supplied by a narrow band of retinal vasculature. These vessels were transiently occluded ( approximately 8 hours) using laser photocoagulation and the transmission of electrical signals along the nerve fibers was assessed by recording the visual evoked response (VER). Morphological damage was assessed by histological techniques. The ischemic insult produced no permanent change in retinal function as assessed by electroretinography, but the VER was suppressed, indicating failure of nerve fiber transmission. Histologically, the visible damage to the region supported by the retinal vasculature worsened following reperfusion, showing evidence of demyelination and necrosis followed by macrophage responses and gliosis. This rabbit model of ischemia/reperfusion of the retinal vasculature offers a rare opportunity to reliably study the response of myelinated nerve fibers to ischemia/reperfusion insults and has demonstrated the susceptibility of myelinated nerve fibers to such insults.

  1. Effects of limited postnatal ethanol exposure on the development of myelin and nerve fibers in rat optic nerve.

    PubMed

    Phillips, D E

    1989-01-01

    This study was designed to morphologically evaluate the effects of limited postnatal alcohol exposure on the development of myelin and axons in the rat optic nerve. Rat pups were artificially reared on Days 5-18 with a supplemented milk diet fed via a chronic gastrostomy tube. Experimental animals received 4% ethanol in their diet on Days 5-9, otherwise the experimental and control animals received identical diets in identical volumes. Optic nerve tissues were prepared for electron microscopy on Days 10, 16, 22, 29, and 90. The cross-sectional areas of optic nerves were smaller, there were fewer myelinated nerve fibers per unit area, and the progress of myelination was slowed on Day 10 in the ethanol-exposed animals. All of these effects were compensated for at later times. The ratio of myelin thickness to axon diameter was similar in experimental and control animals, indicating that the interaction between axon size and myelin formation was not affected by alcohol. The general distribution of axon sizes was unaffected by ethanol except at 10 days when the largest fibers were smaller. There was no evidence of alcohol-induced degeneration of axons, myelin, or glial structures. Thus, alcohol exposure during myelin development causes a delay in myelin acquisition that is later compensated for.

  2. Study of the Peripheral Nerve Fibers Myelin Structure Changes during Activation of Schwann Cell Acetylcholine Receptors

    PubMed Central

    Verdiyan, Ekaterina E.; Allakhverdiev, Elvin S.; Maksimov, Georgy V.

    2016-01-01

    In the present paper we consider a new type of mechanism by which neurotransmitter acetylcholine (ACh) regulates the properties of peripheral nerve fibers myelin. Our data show the importance of the relationship between the changes in the number of Schwann cell (SC) acetylcholine receptors (AChRs) and the axon excitation (different intervals between action potentials (APs)). Using Raman spectroscopy, an effect of activation of SC AChRs on the myelin membrane fluidity was investigated. It was found, that ACh stimulates an increase in lipid ordering degree of the myelin lipids, thus providing evidence for specific role of the “axon-SC” interactions at the axon excitation. It was proposed, that during the axon excitation, the SC membrane K+- depolarization and the Ca2+—influx led to phospholipase activation or exocytosis of intracellular membrane vesicles and myelin structure reorganization. PMID:27455410

  3. ATP-induced lipid membrane reordering in the myelinated nerve fiber identified using Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Kutuzov, N. P.; Brazhe, A. R.; Yusipovich, A. I.; Maksimov, G. V.; Dracheva, O. E.; Lyaskovskiy, V. L.; Bulygin, F. V.; Rubin, A. B.

    2013-07-01

    We demonstrate a successful application of Raman spectroscopy to the problem of lipid ordering with microscopic resolution in different regions of the myelinated nerve fiber. Simultaneous collection of Raman spectra of lipids and carotenoids has enabled us to characterize membrane fluidity and the degree of lipid ordering based on intensity ratios for the 1527/1160 and 2940/2885 cm-1 bands. We show that the intensity profiles of the major Raman bands vary significantly between the three major regions of myelinated nerve fiber: internode, paranode and the node of Ranvier. Mapping Raman peak intensities over these areas suggested that the carotenoid molecules are localized in the myelin membranes of nerve cells. Paranodal membranes were sensitive to extracellular ATP. ATP solutions (7 mM) influenced the 1527/1160 and 2940/2885 cm-1 intensity ratios. Changes in both carotenoid and lipid Raman spectra were in accord and indicated an increase in lipid ordering degree and decrease in membrane fluidity under ATP administration. The collected data provide evidence for the existence of a regulatory purinergic signaling pathway in the peripheral nervous system.

  4. Myelinated retinal nerve fibers (MRNF) - Dilemmas related to their influence on visual function.

    PubMed

    Grzybowski, Andrzej; Winiarczyk, Iwona

    2015-01-01

    Myelinated nerve fibers (MNF) occur in less than 1% of the population, however, they might be responsible for diagnostic dilemmas in cases with visual loss. The case report of an aged pseudophakic patient with visual deterioration in the right eye and MNF in both eyes is presented. The documentation provided by the patient proved recent several examinations of both fundi, and all of them were described as normal. Physical examination revealed the posterior capsule opacification in the right eye, white lesions on the retina of the right eye around the optic disk, and in the left eye - the peripheral, which could correspond to the myelinated fibers. Although visual field changes and OCTs corresponded to the NMF, it turned out, however, that visual acuity loss was in fact caused by PCO and was reversed by the YAG capsulotomy procedure. This case shows some problems related to MNF diagnosis and evaluation of their influence on visual function.

  5. Age-related morphological regression of myelinated fibers and capillary architecture of distal peripheral nerves in rats.

    PubMed

    Sakita, Masahiro; Murakami, Shinichiro; Fujino, Hidemi

    2016-06-24

    Regression of myelinated peripheral nerve fibers in the lower extremities contributes to sarcopenia and balance dysfunction in normal aging. This subclinical regression of myelinated fibers (MFs) is heavily influenced by alterations in microvasculature, though the mechanism underlying these age-related degenerative phenomena remains unclear. The aim of the present study was to examine age-related regressions in myelinated distal peripheral nerve fibers as well as capillary architecture in rats using both morphological and histochemical methods. MFs were categorized into tertiles of 'large', 'medium', and 'small' sizes based on the distribution of MF diameters. A two-way ANOVA was used to assess effects of fiber size (large/medium/small) and group (young/elderly) on myelin thickness, axon diameter, myelin perimeter, axon perimeter, and G-ratio (axon diameter/fiber diameter). Significant main effects were observed for both MF size and group with respect to all dimensions except for G-ratio. Values for fiber diameter (P < 0.01), myelin thickness (P < 0.01), axon diameter (P < 0.01), myelin perimeter (P < 0.01), and axon perimeter (P < 0.01) were significantly lower than those in the young group. Additionally, mean capillary diameter and number of microvascular branch points were significantly lower in the elderly group than in the young group. The present study demonstrated that spontaneous age-related regression predominantly occurs for all fiber sizes in the distal peripheral nerves and the capillary architecture. The results of the present study further suggest that both the distal MFs and capillaries in the peripheral nerve may simultaneously regress with aging.

  6. The extracellular potential of a myelinated nerve fiber in an unbounded medium and in nerve cuff models.

    PubMed Central

    Struijk, J J

    1997-01-01

    A model is presented for the calculation of single myelinated fiber action potentials in an unbounded homogeneous medium and in nerve cuff electrodes. The model consists of a fiber model, used to calculate the action currents at the nodes of Ranvier, and a cylindrically symmetrical volume conductor model in which the fiber's nodes are represented as point current sources. The extracellular action potentials were shown to remain unchanged if the fiber diameter and the volume conductor geometry are scaled by the same factor (principle of corresponding states), both in an unbounded homogeneous medium and in an inhomogeneous volume conductor. The influence of several cuff electrode parameters, among others, cuff length and cuff diameter, were studied, and the results were compared, where possible, with theoretical and experimental results as reported in the literature. Images FIGURE 2 PMID:9168022

  7. Subtle changes in myelination due to childhood experiences: label-free microscopy to infer nerve fibers morphology and myelination in brain (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Gasecka, Alicja; Tanti, Arnaud; Lutz, Pierre-Eric; Mechawar, Naguib; Cote, Daniel C.

    2017-02-01

    Adverse childhood experiences have lasting detrimental effects on mental health and are strongly associated with impaired cognition and increased risk of developing psychopathologies. Preclinical and neuroimaging studies have suggested that traumatic events during brain development can affect cerebral myelination particularly in areas and tracts implicated in mood and emotion. Although current neuroimaging techniques are quite powerful, they lack the resolution to infer myelin integrity at the cellular level. Recently demonstrated coherent Raman microscopy has accomplished cellular level imaging of myelin sheaths in the nervous system. However, a quantitative morphometric analysis of nerve fibers still remains a challenge. In particular, in brain, where fibres exhibit small diameters and varying local orientation. In this work, we developed an automated myelin identification and analysis method that is capable of providing a complete picture of axonal myelination and morphology in brain samples. This method performs three main procedures 1) detects molecular anisotropy of membrane phospholipids based on polarization resolved coherent Raman microscopy, 2) identifies regions of different molecular organization, 3) calculates morphometric features of myelinated axons (e.g. myelin thickness, g-ratio). We applied this method to monitor white matter areas from suicides adults that suffered from early live adversity and depression compared to depressed suicides adults and psychiatrically healthy controls. We demonstrate that our method allows for the rapid acquisition and automated analysis of neuronal networks morphology and myelination. This is especially useful for clinical and comparative studies, and may greatly enhance the understanding of processes underlying the neurobiological and psychopathological consequences of child abuse.

  8. Clues from Crouzon: Insights into the potential role of growth factors in the pathogenesis of myelinated retinal nerve fibers.

    PubMed

    Garcia, Giancarlo A; Tian, Jack J; Apinyawasisuk, Supanut; Kim, Sarah; Akil, Handan; Sadun, Alfredo A

    2016-12-01

    We present a case of bilateral extensive peripapillary myelinated retinal nerve fibers (MRNF) in an individual with Crouzon syndrome, an inherited form of craniosynostosis caused by overactivation of fibroblast growth factor receptor 2. As a secondary aim, we examine the utility of optical coherence tomography (OCT) angiography for visualization of peripapillary vasculature obscured by myelination on other imaging modalities. A 24-year-old woman with Crouzon syndrome was evaluated for suspected optic neuritis in the right eye. Funduscopic examination and photography revealed the incidental finding of bilateral extensive peripapillary MRNF. OCT angiography provided excellent visualization of peripapillary retinal vessels, which were partially obscured by myelination on other imaging modalities. This association of Crouzon syndrome with bilateral peripapillary MRNF may lend insight into the developmental control of optic nerve myelination, the pathogenesis of MRNF, and the potential role of growth factors in these processes. Further, OCT angiography allowed for excellent blood vessel visualization in this case of MRNF.

  9. Induction of paranodal myelin detachment and sodium channel loss in vivo by Campylobacter jejuni DNA-binding protein from starved cells (C-Dps) in myelinated nerve fibers.

    PubMed

    Piao, Hua; Minohara, Motozumi; Kawamura, Nobutoshi; Li, Wei; Mizunoe, Yoshimitsu; Umehara, Fujio; Goto, Yoshinobu; Kusunoki, Susumu; Matsushita, Takuya; Ikenaka, Kazuhiro; Maejima, Takashi; Nabekura, Jun-ichi; Yamasaki, Ryo; Kira, Jun-ichi

    2010-01-15

    Iba-1-positive macrophages were observed. Thus, we consider that C-Dps damages myelinated nerve fibers, possibly through interference with paranodal sulfatide function, and may contribute to the axonal pathology seen in C. jejuni-related GBS.

  10. Modeling the action-potential-sensitive nonlinear-optical response of myelinated nerve fibers and short-term memory

    NASA Astrophysics Data System (ADS)

    Shneider, M. N.; Voronin, A. A.; Zheltikov, A. M.

    2011-11-01

    The Goldman-Albus treatment of the action-potential dynamics is combined with a phenomenological description of molecular hyperpolarizabilities into a closed-form model of the action-potential-sensitive second-harmonic response of myelinated nerve fibers with nodes of Ranvier. This response is shown to be sensitive to nerve demyelination, thus enabling an optical diagnosis of various demyelinating diseases, including multiple sclerosis. The model is applied to examine the nonlinear-optical response of a three-neuron reverberating circuit—the basic element of short-term memory.

  11. THE MAJORITY OF MYELINATED AND UNMYELINATED SENSORY NERVE FIBERS THAT INNERVATE BONE EXPRESS THE TROPOMYOSIN RECEPTOR KINASE A

    PubMed Central

    Castañeda-Corral, Gabriela; Jimenez-Andrade, Juan M.; Bloom, Aaron P.; Taylor, Reid N.; Mantyh, William G.; Kaczmarska, Magdalena J.; Ghilardi, Joseph R.; Mantyh, Patrick W.

    2011-01-01

    Although skeletal pain is a leading cause of chronic pain and disability, relatively little is known about the specific populations of nerve fibers that innervate the skeleton. Recent studies have reported that therapies blocking nerve growth factor (NGF) or its cognate receptor, tropomyosin receptor kinase A (TrkA) are efficacious in attenuating skeletal pain. A potential factor to consider when assessing the analgesic efficacy of targeting NGF-TrkA signaling in a pain state is the fraction of NGF-responsive TrkA+ nociceptors that innervate the tissue from which the pain is arising, as this innervation and the analgesic efficacy of targeting NGF-TrkA signaling may vary considerably from tissue to tissue. To explore this in the skeleton, tissue slices and whole mount preparations of the normal, adult mouse femur were analyzed using immunohistochemistry and confocal microscopy. Analysis of these preparations revealed that 80% of the unmyelinated/thinly myelinated sensory nerve fibers that express calcitonin gene-related peptide (CGRP) and innervate the periosteum, mineralized bone and bone marrow also express TrkA. Similarly, the majority of myelinated sensory nerve fibers that express neurofilament 200 kDa (NF200) which innervate the periosteum, mineralized bone and bone marrow also co-express TrkA. In the normal femur, the relative density of CGRP+, NF200+ and TrkA+ sensory nerve fibers per unit volume is: periosteum > bone marrow > mineralized bone > cartilage with the respective relative densities being 100: 2: 0.1: 0. The observation that the majority of sensory nerve fibers innervating the skeleton express TrkA+, may in part explain why therapies that block NGF/TrkA pathway are highly efficacious in attenuating skeletal pain. PMID:21277945

  12. PREVALENCE AND ASSOCIATIONS OF MYELINATED RETINAL NERVE FIBERS: Results From the Population-Based Gutenberg Health Study.

    PubMed

    Elbaz, Hisham; Peto, Tunde; Butsch, Christina; Orouji, Elias; Laubert-Reh, Dagmar; Ponto, Katharina A; Binder, Harald; Pfeiffer, Norbert; Mirshahi, Alireza

    2016-12-01

    To determine the prevalence, ocular, and systemic associations of myelinated retinal nerve fibers (MRNF) in a Caucasian cohort. The Gutenberg Health Study (GHS) is a population-based, prospective cohort study encompassing 15,010 subjects in Germany. Gutenberg Health Study participants, aged 35 to 74 years, stratified for gender, decades of age, and residence were examined for ophthalmologic and systemic conditions. Optic disc centered and macular photographs were reviewed for the presence of MRNF. In 25,728 eyes of 12,906 participants (86.0% of the cohort), the prevalence of MRNF was 0.4%. In a binary logistic regression analysis, MRNF was positively associated with history of stroke (OR, 6.8; 95% CI, 2.9-16.1; P < 0.001). Myelinated retinal nerve fibers was not associated with age, sex, cardiovascular conditions other than stroke or ocular parameters, such as refraction, visual acuity, intraocular pressure, or central corneal thickness. This population-based study provides novel data on the prevalence of MRNF in Western Europe. We report a positive association between history of stroke and MRNF. It adds an additional retinal sign for stroke and calls for further studying of the behavior of oligodendrocytes within cerebrovascular diseases.

  13. Action currents, internodal potentials, and extracellular records of myelinated mammalian nerve fibers derived from node potentials.

    PubMed Central

    Marks, W B; Loeb, G E

    1976-01-01

    The potential distribution within the internodal axon of mammalian nerve fibers is derived by applying known node potential waveforms to the ends of an equivalent circuit model of the internode. The complete spatial/temporal profile of action potentials synthesized from the internodal profiles is used to compute the node current waveforn, and the extracellular action potential around fibers captured within a tubular electrode. For amphibia, the results agreed with empirical values. For mammals, the amplitude of the node currents plotted against conduction velocity was fitted by a straight line. The extracellular potential waveform depended on the location of the nodes within the tube. For tubes of length from 2 to 8 internodes, extracellular wave amplitude (mammals) was about one-third of the product of peak node current and tube resistance (center to ends). The extracellular potentials developed by longitudinal and radial currents in an anisotropic medium (fiber bundle) are compared. PMID:1276389

  14. Modeling the Chronic Loss of Optic Nerve Axons and the Effects on the Retinal Nerve Fiber Layer Structure in Primary Disorder of Myelin

    PubMed Central

    Teixeira, Leandro B. C.; Ver Hoeve, James N.; Mayer, Joshua A.; Dubielzig, Richard R.; Smith, Chelsey M.; Radcliff, Abigail B.; Duncan, Ian D.

    2016-01-01

    Purpose We determined whether the chronic lack of optic nerve myelination and subsequent axon loss is associated with optical coherence tomography (OCT) changes in the retinal nerve fiber layer (RNFL), and whether this models what occurs in multiple sclerosis (MS) and confers its use as a surrogate marker for axon degeneration. Methods Using an animal model of Pelizaeus-Merzbacher disease (shp) bilateral longitudinal measurements of the peripapillary RNFL (spectral-domain OCT), electroretinograms (ERG), and visual evoked potentials (VEP) were performed in affected and control animals from 5 months to 2 years and in individual animals at single time points. Light and electron microscopy of the optic nerve and retina and histomorphometric measurements of the RNFL were compared to OCT data. Results Of the shp animals, 17% had an average reduction of OCT RNFL thickness on the superior retinal quadrant compared to controls (P < 0.05). Electroretinograms showed normal photopic A- and B-waves but flash VEPs were disorganized in shp animals. Morphologically, the shp retinas and optic nerves revealed significant RNFL thinning (P < 0.001) without retinal ganglion cell (RGC) loss, decrease total and relative retinal axonal area, and loss of optic nerve axons. There was strong positive correlation between OCT and morphometric RNFL thickness measurements (r = 0.878, P = 0.004). Conclusion The loss of optic nerve axons demonstrated in the shp model resulted in moderate thinning of the RNFL confirmed by OCT and histology. These results indicate that OCT-derived RNFL measurement can be a useful surrogate biomarker of optic nerve axon loss and potentially disease progression in demyelinating diseases. PMID:27654412

  15. [The effect of inhibitors of sodium permeability (novocaine and tetrodotoxin) on the trace depolarization of myelinated nerve fibers].

    PubMed

    Katalymov, L L

    1995-09-01

    Partial block of the sodium permeability by local anesthetics does not induce significant aftereffect of depolarisation in intact Ranvier nodes of the frog isolated myelinated nerve fibres. The sodium current seems to take no part in generation of the depolarisation aftereffect.

  16. Propagation Speed in Myelinated Nerve

    PubMed Central

    Hardy, W. L.

    1973-01-01

    The Hodgkin-Huxley (H.H.) equations modified by Dodge for Rana pipiens myelinated nerve have been solved to determine how well the theory predicts the effects of changes of temperature and [Na+]0 on propagation. Conduction speed θ was found to have an approximately exponential dependence on temperature as was found experimentally, but the theoretical temperature coefficient (Q10) was low; 1.5 compared with the experimental finding of 2.95. θ was found to be a linear function of log ([Na+]0) in contrast to the experimental finding of a square root dependence on [Na+]0. θ is 50% greater at one-fourth normal [Na+]0 than the theory predicts. The difference between the theoretical θ([Na+]0) and the experimental θ([Na+]0) is probably due to an imprecisely known variation of parameters and not to a fundamental inadequacy of the theory. PMID:4542941

  17. Comparable myelinated nerve pathology in feline and human diabetes mellitus.

    PubMed

    Mizisin, Andrew P; Nelson, Richard W; Sturges, B K; Vernau, Karen M; Lecouteur, Richard A; Williams, D Colette; Burgers, Monica L; Shelton, G Diane

    2007-04-01

    The occurrence of diabetic neuropathy in cats provides an opportunity to study the development and treatment of neurological complications not present in diabetic rodent models, where few pathological alterations are evident. The present study further defines pathological alterations in nerve biopsies from 12 cats with spontaneously occurring diabetes mellitus. Peroneal nerve biopsies displayed concurrent injury to both Schwann cells and axons of myelinated fibers that was remarkably similar to that present in human diabetic neuropathy. In addition to demyelination, remyelination (constituting 20-84% of the total myelinated fiber population) was indicated by fibers with inappropriately thin myelin sheaths. Unlike our previous investigations, striking axonal injury was apparent, and consisted of dystrophic accumulations of membranous debris or neurofilaments, as well as degenerative fiber loss resulting in a 50% decrease in myelinated fiber density. In spite of extensive fiber loss, regenerative clusters were apparent, suggesting that axonal regeneration was not completely frustrated. These data highlight the potential utility of feline diabetic neuropathy as a model that faithfully replicates the nerve injury in human diabetes mellitus.

  18. Sensitivity of a frequency-selective electrode based on spatial spectral properties of the extracellular AP of myelinated nerve fibers.

    PubMed

    Rossel, Olivier; Soulier, Fabien; Bernard, Serge; Cathébras, Guy

    2011-01-01

    In the context of functional electrical stimulation, neural recording is one of the main issues. For instance, the control of the limbs in people with motor deficiencies needs information about the muscle lengths and speeds that can be extracted from electroneurograms (ENG) carried on afferent peripheral nerves. The aim of this study is to propose an non-invasive and spatial-selective electrode (because specific informations are carried into different fascicles). To do so, we investigate the spatial properties of an extracellular action potential (AP). This properties are described qualitatively and quantitatively using analytical study on an inhomogeneous an anisotropic nerve model. Then, a spectral analysis on this spatial signal discriminates the different frequency components. Low spatial frequencies represent the global shape of the signal, whereas high frequencies are related to the type of fibers. We show that the latter is rapidly attenuated with the distance and thus, being a local phenomenon, can be used as a selective measurement. Finally, we propose a spatial filtering based on electrode design and an electronic architecture to extract this high frequencies.

  19. Myelin

    MedlinePlus

    ... protein and fatty substances. This myelin sheath allows electrical impulses to transmit quickly and efficiently along the nerve cells. If myelin is damaged, these impulses slow down. This can cause diseases such as multiple sclerosis .

  20. Transverse Magnetic Waves in Myelinated Nerves

    DTIC Science & Technology

    2007-11-02

    IN MYELINATED NERVES M. Mª Villapecellín-Cid1, L. Mª Roa2, and J. Reina-Tosina1 1Área de Teoría de la Señal y Comunicaciones , E.S. de Ingeniería...y Comunicaciones , E.S. de Ingeniería, University of Seville, Seville, Spain Performing Organization Report Number Sponsoring/Monitoring Agency Name(s

  1. Autophagy Is Involved in the Reduction of Myelinating Schwann Cell Cytoplasm during Myelin Maturation of the Peripheral Nerve

    PubMed Central

    Jang, So Young; Shin, Yoon Kyung; Park, So Young; Park, Joo Youn; Rha, Seo-Hee; Kim, Jong Kuk; Lee, Hye Jeong; Park, Hwan Tae

    2015-01-01

    Peripheral nerve myelination involves dynamic changes in Schwann cell morphology and membrane structure. Recent studies have demonstrated that autophagy regulates organelle biogenesis and plasma membrane dynamics. In the present study, we investigated the role of autophagy in the development and differentiation of myelinating Schwann cells during sciatic nerve myelination. Electron microscopy and biochemical assays have shown that Schwann cells remove excess cytoplasmic organelles during myelination through macroautophagy. Inhibition of autophagy via Schwann cell-specific removal of ATG7, an essential molecule for macroautophagy, using a conditional knockout strategy, resulted in abnormally enlarged abaxonal cytoplasm in myelinating Schwann cells that contained a large number of ribosomes and an atypically expanded endoplasmic reticulum. Small fiber hypermyelination and minor anomalous peripheral nerve functions are observed in this mutant. Rapamycin-induced suppression of mTOR activity during the early postnatal period enhanced not only autophagy but also developmental reduction of myelinating Schwann cells cytoplasm in vivo. Together, our findings suggest that autophagy is a regulatory mechanism of Schwann cells structural plasticity during myelination. PMID:25581066

  2. Autophagy is involved in the reduction of myelinating Schwann cell cytoplasm during myelin maturation of the peripheral nerve.

    PubMed

    Jang, So Young; Shin, Yoon Kyung; Park, So Young; Park, Joo Youn; Rha, Seo-Hee; Kim, Jong Kuk; Lee, Hye Jeong; Park, Hwan Tae

    2015-01-01

    Peripheral nerve myelination involves dynamic changes in Schwann cell morphology and membrane structure. Recent studies have demonstrated that autophagy regulates organelle biogenesis and plasma membrane dynamics. In the present study, we investigated the role of autophagy in the development and differentiation of myelinating Schwann cells during sciatic nerve myelination. Electron microscopy and biochemical assays have shown that Schwann cells remove excess cytoplasmic organelles during myelination through macroautophagy. Inhibition of autophagy via Schwann cell-specific removal of ATG7, an essential molecule for macroautophagy, using a conditional knockout strategy, resulted in abnormally enlarged abaxonal cytoplasm in myelinating Schwann cells that contained a large number of ribosomes and an atypically expanded endoplasmic reticulum. Small fiber hypermyelination and minor anomalous peripheral nerve functions are observed in this mutant. Rapamycin-induced suppression of mTOR activity during the early postnatal period enhanced not only autophagy but also developmental reduction of myelinating Schwann cells cytoplasm in vivo. Together, our findings suggest that autophagy is a regulatory mechanism of Schwann cells structural plasticity during myelination.

  3. Dynamic Modulation of Myelination in Response to Visual Stimuli Alters Optic Nerve Conduction Velocity

    PubMed Central

    Etxeberria, Ainhoa; Hokanson, Kenton C.; Dao, Dang Q.; Mayoral, Sonia R.; Mei, Feng; Redmond, Stephanie A.; Ullian, Erik M.

    2016-01-01

    Myelin controls the time required for an action potential to travel from the neuronal soma to the axon terminal, defining the temporal manner in which information is processed within the CNS. The presence of myelin, the internodal length, and the thickness of the myelin sheath are powerful structural factors that control the velocity and fidelity of action potential transmission. Emerging evidence indicates that myelination is sensitive to environmental experience and neuronal activity. Activity-dependent modulation of myelination can dynamically alter action potential conduction properties but direct functional in vivo evidence and characterization of the underlying myelin changes is lacking. We demonstrate that in mice long-term monocular deprivation increases oligodendrogenesis in the retinogeniculate pathway but shortens myelin internode lengths without affecting other structural properties of myelinated fibers. We also demonstrate that genetically attenuating synaptic glutamate neurotransmission from retinal ganglion cells phenocopies the changes observed after monocular deprivation, suggesting that glutamate may constitute a signal for myelin length regulation. Importantly, we demonstrate that visual deprivation and shortened internodes are associated with a significant reduction in nerve conduction velocity in the optic nerve. Our results reveal the importance of sensory input in the building of myelinated fibers and suggest that this activity-dependent alteration of myelination is important for modifying the conductive properties of brain circuits in response to environmental experience. SIGNIFICANCE STATEMENT Oligodendrocyte precursor cells differentiate into mature oligodendrocytes and are capable of ensheathing axons with myelin without molecular cues from neurons. However, this default myelination process can be modulated by changes in neuronal activity. Here, we show, for the first time, that experience-dependent activity modifies the length of myelin

  4. Uncompacted myelin lamellae in peripheral nerve biopsy.

    PubMed

    Vital, Claude; Vital, Anne; Bouillot, Sandrine; Favereaux, Alexandre; Lagueny, Alain; Ferrer, Xavier; Brechenmacher, Christiane; Petry, Klaus G

    2003-01-01

    Since 1979, the authors have studied 49 peripheral nerve biopsies presenting uncompacted myelin lamellae (UML). Based on the ultrastructural pattern of UML they propose a 3-category classification. The first category includes cases displaying regular UML, which was observed in 43 cases; it was more frequent in 9 cases with polyneuropathy organomegaly endocrinopathy m-protein skin changes (POEMS) syndrome as well as in 1 case of Charcot-Marie-Tooth 1B with a novel point mutation in the P0 gene. The second category consists of cases showing irregular UML, observed in 4 cases with IgM monoclonal gammopathy and anti-myelin-associated glycoprotein (MAG) activity. This group included 1 benign case and 3 B-cell malignant lymphomas. The third category is complex UML, which was present in 2 unrelated patients with an Arg 98 His missense mutation in the P0 protein gene. Irregular and complex UML are respectively related to MAG and P0, which play a crucial role in myelin lamellae compaction and adhesion.

  5. Schwann cell autophagy, myelinophagy, initiates myelin clearance from injured nerves

    PubMed Central

    Gomez-Sanchez, Jose A.; Carty, Lucy; Iruarrizaga-Lejarreta, Marta; Palomo-Irigoyen, Marta; Varela-Rey, Marta; Griffith, Megan; Hantke, Janina; Macias-Camara, Nuria; Azkargorta, Mikel; Aurrekoetxea, Igor; De Juan, Virginia Gutiérrez; Jefferies, Harold B.J.; Aspichueta, Patricia; Elortza, Félix; Aransay, Ana M.; Martínez-Chantar, María L.; Baas, Frank; Mato, José M.; Mirsky, Rhona

    2015-01-01

    Although Schwann cell myelin breakdown is the universal outcome of a remarkably wide range of conditions that cause disease or injury to peripheral nerves, the cellular and molecular mechanisms that make Schwann cell–mediated myelin digestion possible have not been established. We report that Schwann cells degrade myelin after injury by a novel form of selective autophagy, myelinophagy. Autophagy was up-regulated by myelinating Schwann cells after nerve injury, myelin debris was present in autophagosomes, and pharmacological and genetic inhibition of autophagy impaired myelin clearance. Myelinophagy was positively regulated by the Schwann cell JNK/c-Jun pathway, a central regulator of the Schwann cell reprogramming induced by nerve injury. We also present evidence that myelinophagy is defective in the injured central nervous system. These results reveal an important role for inductive autophagy during Wallerian degeneration, and point to potential mechanistic targets for accelerating myelin clearance and improving demyelinating disease. PMID:26150392

  6. Early myelin breakdown following sural nerve crush: a freeze-fracture study.

    PubMed

    Martinez, A M; Canavarro, S

    2000-12-01

    In this study we describe the early changes of the myelin sheath following surgical nerve crush. We used the freeze-fracture technique to better evaluate myelin alterations during an early stage of Wallerian degeneration. Rat sural nerves were experimentally crushed and animals were sacrificed by transcardiac perfusion 30 h after surgery. Segments of the nerves were processed for routine transmission electron microscopy and freeze-fracture techniques. Our results show that 30 h after the lesion there was asynchrony in the pattern of Wallerian degeneration, with different nerve fibers exhibiting variable degrees of axon disruption. This was observed by both techniques. Careful examination of several replicas revealed early changes in myelin membranes represented by vacuolization and splitting of consecutive lamellae, rearrangement of intramembranous particles and disappearance of paranodal transverse bands associated or not with retraction of paranodal myelin terminal loops from the axolemma. These alterations are compatible with a direct injury to the myelin sheath following nerve crush. The results are discussed in terms of a similar mechanism underlying both axon and myelin breakdown.

  7. Discrete impulses in ephaptically coupled nerve fibers.

    PubMed

    Maïna, I; Tabi, C B; Ekobena Fouda, H P; Mohamadou, A; Kofané, T C

    2015-04-01

    We exclusively analyze the condition for modulated waves to emerge in two ephaptically coupled nerve fibers. Through the multiple scale expansion, it is shown that a set of coupled cable-like Hodgkin-Huxley equations can be reduced to a single differential-difference nonlinear equation. The standard approach of linear stability analysis of a plane wave is used to predict regions of parameters where nonlinear structures can be observed. Instability features are shown to be importantly controlled not only by the ephaptic coupling parameter, but also by the discreteness parameter. Numerical simulations, to verify our analytical predictions, are performed, and we explore the longtime dynamics of slightly perturbed plane waves in the coupled nerve fibers. On initially exciting only one fiber, quasi-perfect interneuronal communication is discussed along with the possibility of recruiting damaged or non-myelinated nerve fibers, by myelinated ones, into conduction.

  8. Discrete impulses in ephaptically coupled nerve fibers

    NASA Astrophysics Data System (ADS)

    Maïna, I.; Tabi, C. B.; Ekobena Fouda, H. P.; Mohamadou, A.; Kofané, T. C.

    2015-04-01

    We exclusively analyze the condition for modulated waves to emerge in two ephaptically coupled nerve fibers. Through the multiple scale expansion, it is shown that a set of coupled cable-like Hodgkin-Huxley equations can be reduced to a single differential-difference nonlinear equation. The standard approach of linear stability analysis of a plane wave is used to predict regions of parameters where nonlinear structures can be observed. Instability features are shown to be importantly controlled not only by the ephaptic coupling parameter, but also by the discreteness parameter. Numerical simulations, to verify our analytical predictions, are performed, and we explore the longtime dynamics of slightly perturbed plane waves in the coupled nerve fibers. On initially exciting only one fiber, quasi-perfect interneuronal communication is discussed along with the possibility of recruiting damaged or non-myelinated nerve fibers, by myelinated ones, into conduction.

  9. Dynamic Modulation of Myelination in Response to Visual Stimuli Alters Optic Nerve Conduction Velocity.

    PubMed

    Etxeberria, Ainhoa; Hokanson, Kenton C; Dao, Dang Q; Mayoral, Sonia R; Mei, Feng; Redmond, Stephanie A; Ullian, Erik M; Chan, Jonah R

    2016-06-29

    Myelin controls the time required for an action potential to travel from the neuronal soma to the axon terminal, defining the temporal manner in which information is processed within the CNS. The presence of myelin, the internodal length, and the thickness of the myelin sheath are powerful structural factors that control the velocity and fidelity of action potential transmission. Emerging evidence indicates that myelination is sensitive to environmental experience and neuronal activity. Activity-dependent modulation of myelination can dynamically alter action potential conduction properties but direct functional in vivo evidence and characterization of the underlying myelin changes is lacking. We demonstrate that in mice long-term monocular deprivation increases oligodendrogenesis in the retinogeniculate pathway but shortens myelin internode lengths without affecting other structural properties of myelinated fibers. We also demonstrate that genetically attenuating synaptic glutamate neurotransmission from retinal ganglion cells phenocopies the changes observed after monocular deprivation, suggesting that glutamate may constitute a signal for myelin length regulation. Importantly, we demonstrate that visual deprivation and shortened internodes are associated with a significant reduction in nerve conduction velocity in the optic nerve. Our results reveal the importance of sensory input in the building of myelinated fibers and suggest that this activity-dependent alteration of myelination is important for modifying the conductive properties of brain circuits in response to environmental experience. Oligodendrocyte precursor cells differentiate into mature oligodendrocytes and are capable of ensheathing axons with myelin without molecular cues from neurons. However, this default myelination process can be modulated by changes in neuronal activity. Here, we show, for the first time, that experience-dependent activity modifies the length of myelin internodes along axons

  10. Prenatal exposure to low levels of carbon monoxide alters sciatic nerve myelination in rat offspring.

    PubMed

    Carratù, M R; Cagiano, R; Desantis, S; Labate, M; Tattoli, M; Trabace, L; Cuomo, V

    2000-08-25

    Prenatal exposure to low concentrations of carbon monoxide (CO, 75 and 150 ppm from day 0 to day 20 of gestation), resulting in maternal blood HbCO concentrations equivalent to those maintained by human cigarette smokers, leads to subtle myelin alterations in the sciatic nerve of male rat offspring. The rapid growth spurt in pup body weight was related to the period of maximal increase in myelin sheath thickness in both control and CO-exposed animals. A significant reduction in myelin sheath thickness of sciatic nerve fibers, paralleled by changes in the frequency distribution, occurred in both 40- and 90-day-old rats exposed in utero to CO (75 and 150 ppm). Myelin deficit observed in 75 and 150 ppm CO-exposed animals showed up only after the major spurt in myelination but not early during development. The subtle myelin alterations observed in CO-exposed offspring were not accompanied by changes in developmental pattern of axon diameters and did not result in a gross impairment of motor activity. These results suggest that the myelination process is selectively targeted by a prenatal exposure model simulating the CO exposure observed in human cigarette smokers.

  11. Deciphering peripheral nerve myelination by using Schwann cell expression profiling.

    PubMed

    Nagarajan, Rakesh; Le, Nam; Mahoney, Heather; Araki, Toshiyuki; Milbrandt, Jeffrey

    2002-06-25

    Although mutations in multiple genes are associated with inherited demyelinating neuropathies, the molecular components and pathways crucial for myelination remain largely unknown. To approach this question, we performed genome-wide expression analysis in several paradigms where the status of peripheral nerve myelination is dynamically changing. Anchor gene correlation analysis, a form of microarray analysis that integrates functional information, using correlation-based clustering, with a statistically rigorous test, the Westfall and Young step-down algorithm, was applied to this data set. Biological pathways active in myelination, genes encoding proteins involved in myelin synthesis, and genes whose mutation results in myelination defects were identified. Many known genes and previously uncharacterized ESTs not heretofore associated with myelination were also identified. One of these ESTs, MASR (myelin-associated SUR4 protein), encodes a member of the SUR4 family of fatty acid desaturases, enzymes involved in elongation of very long chain fatty acids. Its specific localization in myelinating Schwann cells indicates a crucial role for MASR in normal myelin lipid synthesis.

  12. Molecular architecture of myelinated peripheral nerves is supported by calorie restriction with aging.

    PubMed

    Rangaraju, Sunitha; Hankins, David; Madorsky, Irina; Madorsky, Evgenia; Lee, Wei-Hua; Carter, Christy S; Leeuwenburgh, Christiaan; Notterpek, Lucia

    2009-04-01

    Peripheral nerves from aged animals exhibit features of degeneration, including marked fiber loss, morphological irregularities in myelinated axons and notable reduction in the expression of myelin proteins. To investigate how protein homeostatic mechanisms change with age within the peripheral nervous system, we isolated Schwann cells from the sciatic nerves of young and old rats. The responsiveness of cells from aged nerves to stress stimuli is weakened, which in part may account for the observed age-associated alterations in glial and axonal proteins in vivo. Although calorie restriction is known to slow the aging process in the central nervous system, its influence on peripheral nerves has not been investigated in detail. To determine if dietary restriction is beneficial for peripheral nerve health and glial function, we studied sciatic nerves from rats of four distinct ages (8, 18, 29 and 38 months) kept on an ad libitum (AL) or a 40% calorie restricted diet. Age-associated reduction in the expression of the major myelin proteins and widening of the nodes of Ranvier are attenuated by the dietary intervention, which is paralleled with the maintenance of a differentiated Schwann cell phenotype. The improvements in nerve architecture with diet restriction, in part, are underlined by sustained expression of protein chaperones and markers of the autophagy-lysosomal pathway. Together, the in vitro and in vivo results suggest that there might be an age-limit by which dietary intervention needs to be initiated to elicit a beneficial response on peripheral nerve health.

  13. Perineural hematoma may result in nerve inflammation and myelin damage.

    PubMed

    Steinfeldt, Thorsten; Wiesmann, Thomas; Nimphius, Wilhelm; Cornelius, Valér; Eismann, Daniel; Kratz, Thomas; Hadzic, Admir; Wulf, Hinnerk; Werner, Tilmann

    2014-01-01

    Perineural hematoma may occur during performance of peripheral nerve blocks. The aim of this study was to test the hypothesis that an iatrogenic hematoma in the immediate vicinity of a peripheral nerve may cause histologic evidence of nerve injury. Fifty milliliters of autologous blood was injected adjacent to the right sciatic nerve in 20 anesthetized female pigs. In order to discern between blood-related volume and immune effects, 50 mL of albumin was injected at the same location in an additional 22 pigs. Either blood or albumin was injected in random order. The left sciatic nerve served as a negative control in all animals, that is, either no needle placement or needle placement without injection. After 48 hours, the nerves were resected. The grade of nerve injury was scored from 0 (no injury) to 3 (severe injury) by histologic analysis of myelin tissue and inflammatory cells. Eighty-two nerve specimens were examined. Injury scores were significantly (P < 0.01) higher in the blood injection (n = 20; median [interquartile range] 2 [2-2]) and albumin injection (n = 22, 1 [1-2]) conditions compared with the no needle placement (n = 22, 0 [0-1]) and "dry needle placement" (n = 20, 1 [0-1]) conditions. Widespread inflammatory changes were seen in the blood injection group, in which 15% of nerve specimens showed damage to myelin. Our data suggest that hematoma adjacent to nerve tissue may result in structural nerve injury and inflammatory changes.

  14. Single myelin fiber imaging in living rodents without labeling by deep optical coherence microscopy.

    PubMed

    Ben Arous, Juliette; Binding, Jonas; Léger, Jean-François; Casado, Mariano; Topilko, Piotr; Gigan, Sylvain; Boccara, A Claude; Bourdieu, Laurent

    2011-11-01

    Myelin sheath disruption is responsible for multiple neuropathies in the central and peripheral nervous system. Myelin imaging has thus become an important diagnosis tool. However, in vivo imaging has been limited to either low-resolution techniques unable to resolve individual fibers or to low-penetration imaging of single fibers, which cannot provide quantitative information about large volumes of tissue, as required for diagnostic purposes. Here, we perform myelin imaging without labeling and at micron-scale resolution with >300-μm penetration depth on living rodents. This was achieved with a prototype [termed deep optical coherence microscopy (deep-OCM)] of a high-numerical aperture infrared full-field optical coherence microscope, which includes aberration correction for the compensation of refractive index mismatch and high-frame-rate interferometric measurements. We were able to measure the density of individual myelinated fibers in the rat cortex over a large volume of gray matter. In the peripheral nervous system, deep-OCM allows, after minor surgery, in situ imaging of single myelinated fibers over a large fraction of the sciatic nerve. This allows quantitative comparison of normal and Krox20 mutant mice, in which myelination in the peripheral nervous system is impaired. This opens promising perspectives for myelin chronic imaging in demyelinating diseases and for minimally invasive medical diagnosis.

  15. Single myelin fiber imaging in living rodents without labeling by deep optical coherence microscopy

    NASA Astrophysics Data System (ADS)

    Ben Arous, Juliette; Binding, Jonas; Léger, Jean-François; Casado, Mariano; Topilko, Piotr; Gigan, Sylvain; Claude Boccara, A.; Bourdieu, Laurent

    2011-11-01

    Myelin sheath disruption is responsible for multiple neuropathies in the central and peripheral nervous system. Myelin imaging has thus become an important diagnosis tool. However, in vivo imaging has been limited to either low-resolution techniques unable to resolve individual fibers or to low-penetration imaging of single fibers, which cannot provide quantitative information about large volumes of tissue, as required for diagnostic purposes. Here, we perform myelin imaging without labeling and at micron-scale resolution with >300-μm penetration depth on living rodents. This was achieved with a prototype [termed deep optical coherence microscopy (deep-OCM)] of a high-numerical aperture infrared full-field optical coherence microscope, which includes aberration correction for the compensation of refractive index mismatch and high-frame-rate interferometric measurements. We were able to measure the density of individual myelinated fibers in the rat cortex over a large volume of gray matter. In the peripheral nervous system, deep-OCM allows, after minor surgery, in situ imaging of single myelinated fibers over a large fraction of the sciatic nerve. This allows quantitative comparison of normal and Krox20 mutant mice, in which myelination in the peripheral nervous system is impaired. This opens promising perspectives for myelin chronic imaging in demyelinating diseases and for minimally invasive medical diagnosis.

  16. Accelerated myelination along fiber tracts in patients with hemimegalencephaly.

    PubMed

    Kamiya, Kouhei; Sato, Noriko; Saito, Yuko; Nakata, Yasuhiro; Ito, Kimiteru; Shigemoto, Yoko; Ota, Miho; Sasaki, Masayuki; Ohtomo, Kuni

    2014-07-01

    In infants with hemimegalencephaly, asymmetrical white-matter intensities suggestive of advanced myelination are observed as well as aberrant midsagittal fibers (AMFs) specific to hemimegalencephaly. Also noted are otherwise unreported abnormally enlarged periventricular fibers (APVFs) running anteroposteriorly along the caudate nucleus. This study investigated the degree of myelination and presence of aberrant fibers in hemimegalencephaly through a retrospective review of MRI scans in relation to histopathological findings. MRI scans of 24 infants with hemimegalencephaly (13 boys and 11 girls, 1-9 months old) were evaluated, focusing on the presence and signal intensities of AMFs and APVFs. White-matter signal intensities on T1- and T2-weighted imaging of the cerebral hemisphere were also evaluated and compared with the timetable for normal myelination. Surgical specimens were pathologically examined with Klüver-Barrera staining in four patients. AMFs and APVFs were observed in 18 and nine patients, respectively, while 22 patients had accelerated myelination of the megalencephalic hemisphere that tended to extend along fiber pathways including AMFs and APVFs. In six cases, accelerated myelination even extended into the contralateral hemisphere via the corpus callosum or AMFs. Histopathological analysis identified hypermyelination with disarrayed myelinated fibers corresponding to MRI findings. Accelerated myelination is frequently observed in patients with hemimegalencephaly and tends to extend along fiber pathways, including aberrant or abnormal fibers, as seen in 75% of hemimegalencephaly patients. Accelerated myelination may reflect propagation pathways of abnormal brain activity in such patients. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  17. Deletion of Nrf2 impairs functional recovery, reduces clearance of myelin debris and decreases axonal remyelination after peripheral nerve injury

    PubMed Central

    Zhang, Linxia; Johnson, Delinda; Johnson, Jeffrey A.

    2013-01-01

    Oxidative stress is generated in several peripheral nerve injury models. In response to oxidative stress, the transcription factor Nrf2 is activated to induce expression of antioxidant responsive element (ARE) genes. The role of Nrf2 in peripheral nerve injury has not been studied to date. In this study, we used a sciatic nerve crush model to examine how deletion of Nrf2 affects peripheral nerve degeneration and regeneration. Our study demonstrated that functional recovery in the Nrf2-/- mice were impaired compared to the wild type mice after sciatic nerve crush. Larger myelin debris were present in the distal nerve stump of the Nrf2-/- mice than in the wild type mice. The presence of larger myelin debris in the Nrf2-/- mice coincides with less macrophages accumulation in the distal nerve stump. Less accumulation of macrophages may have contributed to slower clearance of myelin and thus resulted in the presence of larger myelin debris. Meanwhile, axonal regeneration is comparatively lower in the Nrf2-/- mice than in the wild type mice. Even after 3 months post the injury, more thinly myelinated axon fibers were present in the Nrf2-/- mice than in the wild type mice. Taken collectively, these data support the concept of therapeutic intervention with Nrf2 activators following nerve injury. PMID:23328769

  18. Aging and the myelinated fibers in prefrontal cortex and corpus callosum of the monkey.

    PubMed

    Peters, Alan; Sethares, Claire

    2002-01-14

    In the rhesus monkey, the myelin sheaths of nerve fibers in area 46 of prefrontal cortex and in splenium of the corpus callosum show age-related alterations in their structure. The alterations are of four basic types. Most common is splitting of the dense line of myelin sheaths to accommodate electron dense cytoplasm derived from the oligodendroglia. Less common are splits of the intraperiod line to form balloons or blisters that appear to contain fluid, the occurrence of sheaths with redundant myelin, and thick sheaths that are almost completely split so that one set of compact lamellae is surrounded by another set. But despite these alterations in the sheaths, few nerve fibers show axonal degeneration. To quantify the frequency of the age-related alterations in myelin, transversely sectioned nerve fibers from the splenium of the corpus callosum and from the vertical bundles of nerve fibers within area 46 were examined in electron photomicrographs. The material was taken from 19 monkeys, ranging between 5 and 35 years of age. It was found that the frequency of alterations in myelin sheaths from both locations correlates significantly with age. In area 46, the age-related alterations also significantly correlate (P < 0.001) with an overall assessment of impairment in cognition, i.e., the cognitive impairment index, displayed by individual monkeys. The correlation is also significant when only the old monkeys are considered as a group. A similar result was obtained previously in our examination of the effects of age on the myelin sheaths of nerve fibers in primary visual cortex (Peters et al. [2000] J Comp Neurol. 419:364-376). However, in the corpus callosum the myelin alterations correlate significantly with only one component of the cognitive impairment index, namely the delayed nonmatching to sample task with a 2-minute delay. It is proposed that age-related myelin alterations are ubiquitous and that the correlations between their frequency and impairments in

  19. A suspended carbon fiber culture to model myelination by human Schwann cells.

    PubMed

    Merolli, Antonio; Mao, Yong; Kohn, Joachim

    2017-04-01

    Understanding of myelination/remyelination process is essential to guide tissue engineering for nerve regeneration. In vitro models currently used are limited to cell population studies and cannot easily identify individual cell contribution to the process. We established a novel model to study the contribution of human Schwann cells to the myelination process. The model avoids the presence of neurons in culture; Schwann cells respond solely to the biophysical properties of an artificial axon. The model uses a single carbon fiber suspended in culture media far from the floor of the well. The fiber provides an elongated structure of defined diameter with 360-degree of surface available for human Schwann cells to wrap around. This model enabled us to spatially and temporally track the myelination by individual Schwann cells along the fiber. We observed cell attachment, elongation and wrapping over a period of 9 days. Cells remained alive and expressed Myelin Basic Protein and Myelin Associated Glycoprotein as expected. Natural and artificial molecules, and external physical factors (e.g., p atterned electrical impulses), may be tested with this model as possible regulators of myelination.

  20. Running Exercise Reduces Myelinated Fiber Loss in the Dentate Gyrus of the Hippocampus in APP/PS1 Transgenic Mice.

    PubMed

    Chao, Fenglei; Zhang, Lei; Luo, Yanmin; Xiao, Qian; Lv, Fulin; He, Qi; Zhou, Chunni; Zhang, Yi; Jiang, Lin; Jiang, Rong; Gu, Hengwei; Tang, Yong

    2015-01-01

    To investigate the effect of running exercise on myelinated fibers in the dentate gyrus (DG) of the hippocampus during Alzheimer's disease (AD), 6-month-old male APP/PS1 transgenic mice were randomly assigned to control or running groups. The running group mice were subjected to a running protocol for four months. The behaviors of the mice from both group mice were then assessed using the Morris water maze, and the total volume of the DG and the related quantitative parameters with characteristics of the myelinated nerve fiber and the myelin sheath in the DG were investigated using unbiased stereological techniques and electron microscopy. Learning and spatial memory performances were both significantly increased in the running group compared with the control group. There was no significant difference in the gratio of the myelinated axons between the two groups. However, the DG volume, the myelinated fiber length and volume in the DG, and the myelin sheath volume and thickness in the DG were all significantly increased in the running group mice compared with the control group mice. These results indicated that running exercise was able to prevent DG atrophy and delay the progression of the myelinated fiber loss and the demyelination of the myelin sheaths in the DG in an AD mouse model, which may underlie the running-induced improvement in learning and spatial memory. Taken together, these results demonstrated that running exercise could delay the progression of AD.

  1. Contactin orchestrates assembly of the septate-like junctions at the paranode in myelinated peripheral nerve.

    PubMed

    Boyle, M E; Berglund, E O; Murai, K K; Weber, L; Peles, E; Ranscht, B

    2001-05-01

    Rapid nerve impulse conduction depends on specialized membrane domains in myelinated nerve, the node of Ranvier, the paranode, and the myelinated internodal region. We report that GPI-linked contactin enables the formation of the paranodal septate-like axo-glial junctions in myelinated peripheral nerve. Contactin clusters at the paranodal axolemma during Schwann cell myelination. Ablation of contactin in mutant mice disrupts junctional attachment at the paranode and reduces nerve conduction velocity 3-fold. The mutation impedes intracellular transport and surface expression of Caspr and leaves NF155 on apposing paranodal myelin disengaged. The contactin mutation does not affect sodium channel clustering at the nodes of Ranvier but alters the location of the Shaker-type Kv1.1 and Kv1.2 potassium channels. Thus, contactin is a crucial part in the machinery that controls junctional attachment at the paranode and ultimately the physiology of myelinated nerve.

  2. The onset and rate of myelination in six peripheral and autonomic nerves of the rat.

    PubMed Central

    Schäfer, K; Friede, R L

    1988-01-01

    A light and electron microscopic study was carried out of the numbers of myelinated fibres in 6 nerves of the rat for 7 age groups from birth to 73 weeks. The hypoglossal nerve and the mandibular branch of the facial nerve had short and early myelination periods, essentially complete by the second week. The glossopharyngeal nerve and the sympathetic rami communicantes myelinated late and over a protracted period. Myelination of the rami communicantes continued up to 20 weeks, followed by a marked loss of fibres in the 73 week animals. Intercostal and saphenous nerves had intermediary patterns. There was evidence of subpopulations myelinating at different times. Measurements of myelin sheath thickness showed variations of relative sheath thickness with age, between nerves and for subpopulations of nerves. Late myelination corresponded to relatively thin myelin sheaths. Statistical two-stage-density cluster analysis by computer was used for analysing complex fibre populations. The developmental changes of three subpopulations of the intercostal nerve are documented. Nerves also differed in their rates of axon growth. The increment in axon calibre was small and late for sympathetic fibres. Intercostal and facial nerve fibres had rapid axon growth with different growth rates for subpopulations. PMID:3248966

  3. Childhood steroid-responsive acute erythromelalgia with axonal neuropathy of large myelinated fibers: a dysimmune neuropathy?

    PubMed

    Pfund, Zoltan; Stankovics, Jozsef; Decsi, Tamas; Illes, Zsolt

    2009-01-01

    A 12-year-old girl developed acute erythromelalgia of distal extremities. Physical, imaging and laboratory examinations failed to find an infective, systemic autoimmune, metabolic, endocrine, and vascular origin. The severe pain and allodynia indicated small-fiber neuropathy but muscle weakness suggested an involvement of large myelinated nerve fibers. This was confirmed by electrophysiological testing. High-dose then slowly tapered methylprednisolone resulted in rapid remission of painful erythromelalgia and complete electrophysiological recovery. Our case may suggest an additional variant to recently described steroid-responsive erythromelalgia with small-fiber axonopathy and may denote a transitory variant to Guillain-Barré syndrome or chronic dysimmune neuropathies.

  4. Exposure to As, Cd and Pb-mixture impairs myelin and axon development in rat brain, optic nerve and retina.

    PubMed

    Rai, Nagendra Kumar; Ashok, Anushruti; Rai, Asit; Tripathi, Sachin; Nagar, Geet Kumar; Mitra, Kalyan; Bandyopadhyay, Sanghamitra

    2013-12-01

    Arsenic (As), lead (Pb) and cadmium (Cd) are the major metal contaminants of ground water in India. We have reported the toxic effect of their mixture (metal mixture, MM), at human relevant doses, on developing rat astrocytes. Astrocyte damage has been shown to be associated with myelin disintegration in CNS. We, therefore, hypothesized that the MM would perturb myelinating white matter in cerebral cortex, optic nerve (O.N.) and retina. We observed modulation in the levels of myelin and axon proteins, such as myelin basic protein (MBP), proteolipid protein, 2'-, 3'-cyclic-nucleotide-3'-phosphodiesterase, myelin-associated glycoprotein and neurofilament (NF) in the brain of developing rats. Dose and time-dependent synergistic toxic effect was noted. The MBP- and NF-immunolabeling, as well as luxol-fast blue (LFB) staining demonstrated a reduction in the area of intact myelin-fiber, and an increase in vacuolated axons, especially in the corpus-callosum. Transmission electron microscopy (TEM) of O.N. revealed a reduction in myelin thickness and axon-density. The immunolabeling with MBP, NF, and LFB staining in O.N. supported the TEM data. The hematoxylin and eosin staining of retina displayed a decrease in the thickness of nerve-fiber, plexiform-layer, and retinal ganglion cell (RGC) count. Investigating the mechanism revealed a loss in glutamine synthetase activity in the cerebral cortex and O.N., and a fall in the brain derived neurotrophic factor in retina. An enhanced apoptosis in MBP, NF and Brn3b-containing cells justified the diminution in myelinating axons in CNS. Our findings for the first time indicate white matter damage by MM, which may have significance in neurodevelopmental-pediatrics, neurotoxicology and retinal-cell biology.

  5. Histochemical discrimination of fibers in regenerating rat infraorbital nerve

    NASA Technical Reports Server (NTRS)

    Wilke, R. A.; Riley, D. A.; Sanger, J. R.

    1992-01-01

    In rat dorsal root ganglia, histochemical staining of carbonic anhydrase (CA) and cholinesterase (CE) yields a reciprocal pattern of activity: Sensory processes are CA positive and CE negative, whereas motor processes are CA negative and CE positive. In rat infraorbital nerve (a sensory peripheral nerve), we saw extensive CA staining of nearly 100% of the myelinated axons. Although CE reactivity in myelinated axons was extremely rare, we did observe CE staining of unmyelinated autonomic fibers. Four weeks after transection of infraorbital nerves, CA-stained longitudinal sections of the proximal stump demonstrated 3 distinct morphological zones. A fraction of the viable axons retained CA activity to within 2 mm of the distal extent of the stump, and the stain is capable of resolving growth sprouts being regenerated from these fibers. Staining of unmyelinated autonomic fibers in serial sections shows that CE activity was not retained as far distally as is the CA sensory staining.

  6. Histochemical discrimination of fibers in regenerating rat infraorbital nerve

    NASA Technical Reports Server (NTRS)

    Wilke, R. A.; Riley, D. A.; Sanger, J. R.

    1992-01-01

    In rat dorsal root ganglia, histochemical staining of carbonic anhydrase (CA) and cholinesterase (CE) yields a reciprocal pattern of activity: Sensory processes are CA positive and CE negative, whereas motor processes are CA negative and CE positive. In rat infraorbital nerve (a sensory peripheral nerve), we saw extensive CA staining of nearly 100% of the myelinated axons. Although CE reactivity in myelinated axons was extremely rare, we did observe CE staining of unmyelinated autonomic fibers. Four weeks after transection of infraorbital nerves, CA-stained longitudinal sections of the proximal stump demonstrated 3 distinct morphological zones. A fraction of the viable axons retained CA activity to within 2 mm of the distal extent of the stump, and the stain is capable of resolving growth sprouts being regenerated from these fibers. Staining of unmyelinated autonomic fibers in serial sections shows that CE activity was not retained as far distally as is the CA sensory staining.

  7. Short- and long-term effects of combined pre- and postnatal ethanol exposure (three trimester equivalency) on the development of myelin and axons in rat optic nerve.

    PubMed

    Phillips, D E; Krueger, S K; Rydquist, J E

    1991-01-01

    This study evaluated the effects of a combined gestational and 10 day postnatal alcohol exposure (human three trimester equivalency) on the development of myelin and axons in rat optic nerve. Rats were exposed during gestation via liquid diet, then their artificially reared pups were further exposed for 10 postnatal days via an ethanol-containing diet fed by gastrostomy. Control animals from pair-fed dams were artificially reared for 10 days on pair-fed isocaloric diets. Anesthetized animals were perfused with fixative on gestational days (G) 15 and 20 and postnatal days (P) 5, 10, 15, 20, and 90, then optic nerve tissues prepared for electron microscopy. Optic nerve cross-sectional areas were generally less from G20 through P90 in ethanol exposed animals. Counts of the number of myelinated nerve fibers per unit area and of the numbers of fibers in different stages of myelin development revealed that alcohol exposure caused a delay in myelin acquisition at 10 and 15 days that was compensated for at 20 and 90 days. Myelin thickness as a function of axon diameter was decreased in the alcohol exposed animals from 10 through 90 days, indicating a permanent reduction in the relative thickness of myelin. These results show that alcohol exposure for all of gestation and 10 postnatal days in the rat (human three trimester equivalency) causes a permanent reduction in myelin thickness along with a delay in myelin acquisition in the optic nerve. Such alterations in developing and adult myelin could help to explain some of the neurological and visual dysfunctions associated with developmental alcohol exposures.

  8. Myelinated fibers of the mouse spinal cord after a 30-day space flight.

    PubMed

    Povysheva, T V; Rezvyakov, P N; Shaimardanova, G F; Nikolskii, E E; Islamov, R R; Chelyshev, Yu A; Grygoryev, A I

    2016-07-01

    Myelinated fibers and myelin-forming cells in the spinal cord at the L3-L5 level were studied in C57BL/6N mice that had spent 30 days in space. Signs of destruction of myelin in different areas of white matter, reduction of the thickness of myelin sheath and axon diameter, decreased number of myelin-forming cells were detected in "flight" mice. The stay of mice in space during 30 days had a negative impact on the structure of myelinated fibers and caused reduced expression of the markers myelin-forming cells. These findings can complement the pathogenetic picture of the development of hypogravity motor syndrome.

  9. Septin/anillin filaments scaffold central nervous system myelin to accelerate nerve conduction

    PubMed Central

    Patzig, Julia; Erwig, Michelle S; Tenzer, Stefan; Kusch, Kathrin; Dibaj, Payam; Möbius, Wiebke; Goebbels, Sandra; Schaeren-Wiemers, Nicole; Nave, Klaus-Armin; Werner, Hauke B

    2016-01-01

    Myelination of axons facilitates rapid impulse propagation in the nervous system. The axon/myelin-unit becomes impaired in myelin-related disorders and upon normal aging. However, the molecular cause of many pathological features, including the frequently observed myelin outfoldings, remained unknown. Using label-free quantitative proteomics, we find that the presence of myelin outfoldings correlates with a loss of cytoskeletal septins in myelin. Regulated by phosphatidylinositol-(4,5)-bisphosphate (PI(4,5)P2)-levels, myelin septins (SEPT2/SEPT4/SEPT7/SEPT8) and the PI(4,5)P2-adaptor anillin form previously unrecognized filaments that extend longitudinally along myelinated axons. By confocal microscopy and immunogold-electron microscopy, these filaments are localized to the non-compacted adaxonal myelin compartment. Genetic disruption of these filaments in Sept8-mutant mice causes myelin outfoldings as a very specific neuropathology. Septin filaments thus serve an important function in scaffolding the axon/myelin-unit, evidently a late stage of myelin maturation. We propose that pathological or aging-associated diminishment of the septin/anillin-scaffold causes myelin outfoldings that impair the normal nerve conduction velocity. DOI: http://dx.doi.org/10.7554/eLife.17119.001 PMID:27504968

  10. Exposure to As, Cd and Pb-mixture impairs myelin and axon development in rat brain, optic nerve and retina

    SciTech Connect

    Rai, Nagendra Kumar; Ashok, Anushruti; Rai, Asit; Tripathi, Sachin; Nagar, Geet Kumar; Mitra, Kalyan; Bandyopadhyay, Sanghamitra

    2013-12-01

    Arsenic (As), lead (Pb) and cadmium (Cd) are the major metal contaminants of ground water in India. We have reported the toxic effect of their mixture (metal mixture, MM), at human relevant doses, on developing rat astrocytes. Astrocyte damage has been shown to be associated with myelin disintegration in CNS. We, therefore, hypothesized that the MM would perturb myelinating white matter in cerebral cortex, optic nerve (O.N.) and retina. We observed modulation in the levels of myelin and axon proteins, such as myelin basic protein (MBP), proteolipid protein, 2′-, 3′-cyclic-nucleotide-3′-phosphodiesterase, myelin-associated glycoprotein and neurofilament (NF) in the brain of developing rats. Dose and time-dependent synergistic toxic effect was noted. The MBP- and NF-immunolabeling, as well as luxol-fast blue (LFB) staining demonstrated a reduction in the area of intact myelin-fiber, and an increase in vacuolated axons, especially in the corpus-callosum. Transmission electron microscopy (TEM) of O.N. revealed a reduction in myelin thickness and axon-density. The immunolabeling with MBP, NF, and LFB staining in O.N. supported the TEM data. The hematoxylin and eosin staining of retina displayed a decrease in the thickness of nerve-fiber, plexiform-layer, and retinal ganglion cell (RGC) count. Investigating the mechanism revealed a loss in glutamine synthetase activity in the cerebral cortex and O.N., and a fall in the brain derived neurotrophic factor in retina. An enhanced apoptosis in MBP, NF and Brn3b-containing cells justified the diminution in myelinating axons in CNS. Our findings for the first time indicate white matter damage by MM, which may have significance in neurodevelopmental-pediatrics, neurotoxicology and retinal-cell biology. - Highlights: • As, Cd and Pb-mixture, at human relevant dose, demyelinate developing rat CNS. • The attenuation in myelin and axon is synergistic. • The optic nerve and brain demonstrate reduced glutamine synthetase.

  11. RADIOAUTOGRAPHIC STUDIES OF CHOLINE INCORPORATION INTO PERIPHERAL NERVE MYELIN

    PubMed Central

    Hendelman, Walter J.; Bunge, Richard P.

    1969-01-01

    This radioautographic study was designed to localize the cytological sites involved in the incorporation of a lipid precursor into the myelin and the myelin-related cell of the peripheral nervous system. Both myelinating and fully myelinated cultures of rat dorsal root ganglia were exposed to a 30-min pulse of tritiated choline and either fixed immediately or allowed 6 or 48 hr of chase incubation before fixation. After Epon embedding, light and electron microscopic radioautograms were prepared with Ilford L-4 emulsion. Analysis of the pattern of choline incorporation into myelinating cultures indicated that radioactivity appeared all along the length of the internode, without there being a preferential site of initial incorporation. Light microscopic radioautograms of cultures at varying states of maturity were compared in order to determine the relative degree of myelin labeling. This analysis indicated that the myelin-Schwann cell unit in the fully myelinated cultures incorporated choline as actively as did this unit in the myelinating cultures. Because of technical difficulties, it was not possible to determine the precise localization of the incorporated radioactivity within the compact myelin. These data are related to recent biochemical studies indicating that the mature myelin of the central nervous system does incorporate a significant amount of lipid precursor under the appropriate experimental conditions. These observations support the concept that a significant amount of myelin-related metabolic activity occurs in mature tissue; this activity is considered part of an essential and continuous process of myelin maintenance and repair. PMID:5782444

  12. Development of the optic nerve in Xenopus laevis. II. Gliogenesis, myelination and metamorphic remodelling.

    PubMed

    Cima, C; Grant, P

    1982-12-01

    We studied the time of origin, development and location of glial elements in the developing optic nerve of Xenopus with light and electron microscopy. The first cells acting as a primitive glia are ependymal cells lying dorsal to the chiasmatic optic nerve (CON) at Nieuwkoop & Faber (1956) NF stage 39. Later (stage 47/48), immature astrocyte cell bodies migrate from the periphery of the middle optic nerve (MON) into the central fibre mass along cytoplasmic processes extending from the outer glia limitans. Shortly thereafter, oligodendrocyte cell bodies appear in the centre of the fibre mass and myelination begins, first in the middle of the MON, spreading from the centre distally towards the chiasm and proximally to the retina. In late tadpoles myelinated fibres appear first in the CON then in the retinal optic nerve (RON) increasing markedly in juveniles and adults. Segment-specific patterns of glia and myelination appear during optic nerve development. During metamorphic climax, the optic nerve shortens (Cullen & Webster, 1979), a process involving myelin and axon remodelling primarily in the MON. Neither the profound changes during metamorphosis, nor the processes of gliogenesis and myelination significantly alter the underlying chronotopic ordering in the tadpole nerve. In juvenile and adult optic nerves, however, as myelination and gliogenesis increase, and as more axons mature and grow in diameter, the dorsoventral chronotopic arrangement of axons becomes less apparent.

  13. Myelinated mouse nerves studied by X-ray phase contrast zoom tomography.

    PubMed

    Bartels, M; Krenkel, M; Cloetens, P; Möbius, W; Salditt, T

    2015-12-01

    We have used X-ray phase contrast tomography to resolve the structure of uncut, entire myelinated optic, saphenous and sciatic mouse nerves. Intrinsic electron density contrast suffices to identify axonal structures. Specific myelin labeling by an osmium tetroxide stain enables distinction between axon and surrounding myelin sheath. Utilization of spherical wave illumination enables zooming capabilities which enable imaging of entire sciatic internodes as well as identification of sub-structures such as nodes of Ranvier and Schmidt-Lanterman incisures.

  14. Morphology of nerve fiber regeneration along a biodegradable poly (DLLA-epsilon-CL) nerve guide filled with fresh skeletal muscle.

    PubMed

    Varejão, Artur S P; Cabrita, António M; Meek, Marcel F; Fornaro, Michele; Geuna, Stefano; Giacobini-Robecchi, Maria G

    2003-01-01

    Previous morphological and morphometrical studies showed that fresh-skeletal-muscle-enriched vein segments are good conduits for leading peripheral nerve regeneration. In the present study, we investigated the morphological features of peripheral nerve fibers regenerated along a 10-mm-long biodegradable poly (DLLA-epsilon-CL) nerve guide enriched with fresh skeletal muscle, comparing them to nerve fiber regeneration along 10-mm-long phosphate-buffered saline (PBS)-enriched poly (DLLA-epsilon-CL) tubes. Repaired nerves were analyzed at weeks 6 and 24 postoperatively. Structural and ultrastructural observation showed that good nerve fiber regeneration occurred in both PBS-enriched and fresh-skeletal-muscle-enriched nerve guides, and histomorphometrical analysis of regenerated myelinated fibers revealed no statistically significant differences between the two experimental groups at week 24 after surgery. The employment of fresh-muscle-enriched conduits for the repair of nerve defects is critically discussed in the light of these results.

  15. Zebrafish regenerate full thickness optic nerve myelin after demyelination, but this fails with increasing age.

    PubMed

    Münzel, Eva Jolanda; Becker, Catherina G; Becker, Thomas; Williams, Anna

    2014-07-15

    In the human demyelinating central nervous system (CNS) disease multiple sclerosis, remyelination promotes recovery and limits neurodegeneration, but this is inefficient and always ultimately fails. Furthermore, these regenerated myelin sheaths are thinner and shorter than the original, leaving the underlying axons potentially vulnerable. In rodent models, CNS remyelination is more efficient, so that in young animals (but not old) the number of myelinated axons is efficiently restored to normal, but in both young and old rodents, regenerated myelin sheaths are still short and thin. The reasons for these differences in remyelination efficiency, the thinner remyelinated myelin sheaths compared to developmental myelin and the subsequent effect on the underlying axon are unclear. We studied CNS remyelination in the highly regenerative adult zebrafish (Danio rerio), to better understand mechanisms of what we hypothesised would be highly efficient remyelination, and to identify differences to mammalian CNS remyelination, as larval zebrafish are increasingly used for high throughput screens to identify potential drug targets to improve myelination and remyelination. We developed a novel method to induce a focal demyelinating lesion in adult zebrafish optic nerve with no discernible axonal damage, and describe the cellular changes over time. Remyelination is indeed efficient in both young and old adult zebrafish optic nerves, and at 4 weeks after demyelination, the number of myelinated axons is restored to normal, but internode lengths are short. However, unlike in rodents or in humans, in young zebrafish these regenerated myelin sheaths were of normal thickness, whereas in aged zebrafish, they were thin, and remained so even 3 months later. This inability to restore normal myelin thickness in remyelination with age was associated with a reduced macrophage/microglial response. Zebrafish are able to efficiently restore normal thickness myelin around optic nerve axons after

  16. Direct determination of the lamellar structure of peripheral nerve myelin at low resolution (17 A).

    PubMed

    McIntosh, T J; Worthington, C R

    1974-05-01

    New X-ray diffraction data from normal nerve and nerve swollen in glycerol solutions have been recorded. Direct methods of structure analysis have been used in the interpretation of the X-ray data, and the phases of the first five orders of diffraction of peripheral nerve myelin have been uniquely determined. The direct methods include deconvolution of the autocorrelation function, sampling theorem reconstructions, and Fourier synthesis comparisons. Electron density profiles of normal and swollen nerve myelin at a resolution of 17 A together with an electron density scale in electrons per cubic angstrom are presented.

  17. Myelin Abnormalities in the Optic and Sciatic Nerves in Mice With GM1-Gangliosidosis

    PubMed Central

    Heinecke, Karie A.; Luoma, Adrienne; d’Azzo, Alessandra; Kirschner, Daniel A.

    2015-01-01

    GM1-gangliosidosis is a glycosphingolipid lysosomal storage disease involving accumulation of GM1 and its asialo form (GA1) primarily in the brain. Thin-layer chromatography and X-ray diffraction were used to analyze the lipid content/composition and the myelin structure of the optic and sciatic nerves from 7- and 10-month old β-galactosidase (β-gal) +/? and β-gal −/− mice, a model of GM1gangliosidosis. Optic nerve weight was lower in the β-gal −/− mice than in unaffected β-gal +/? mice, but no difference was seen in sciatic nerve weight. The levels of GM1 and GA1 were significantly increased in both the optic nerve and sciatic nerve of the β-gal −/− mice. The content of myelin-enriched cerebrosides, sulfatides, and plasmalogen ethanolamines was significantly lower in optic nerve of β-gal −/− mice than in β-gal +/? mice; however, cholesteryl esters were enriched in the β-gal −/− mice. No major abnormalities in these lipids were detected in the sciatic nerve of the β-gal −/− mice. The abnormalities in GM1 and myelin lipids in optic nerve of β-gal −/− mice correlated with a reduction in the relative amount of myelin and periodicity in fresh nerve. By contrast, the relative amount of myelin and periodicity in the sciatic nerves from control and β-gal −/− mice were indistinguishable, suggesting minimal pathological involvement in sciatic nerve. Our results indicate that the greater neurochemical pathology observed in the optic nerve than in the sciatic nerve of β-gal −/− mice is likely due to the greater glycolipid storage in optic nerve. PMID:25694553

  18. Microanatomy and histological features of central myelin in the root exit zone of facial nerve.

    PubMed

    Yee, Gi-Taek; Yoo, Chan-Jong; Han, Seong-Rok; Choi, Chan-Young

    2014-05-01

    The aim of this study was to evaluate the microanatomy and histological features of the central myelin in the root exit zone of facial nerve. Forty facial nerves with brain stem were obtained from 20 formalin fixed cadavers. Among them 17 facial nerves were ruined during preparation and 23 root entry zone (REZ) of facial nerves could be examined. The length of medial REZ, from detach point of facial nerve at the brain stem to transitional area, and the thickness of glial membrane of central myelin was measured. We cut brain stem along the facial nerve and made a tissue block of facial nerve REZ. Each tissue block was embedded with paraffin and serially sectioned. Slices were stained with hematoxylin and eosin (H&E), periodic acid-Schiff, and glial fibrillary acid protein. Microscopy was used to measure the extent of central myelin and thickness of outer glial membrane of central myelin. Thickness of glial membrane was examined at two different points, the thickest area of proximal and distal REZ. Special stain with PAS and GFAP could be differentiated the central and peripheral myelin of facial nerve. The length of medial REZ was mean 2.6 mm (1.6-3.5 mm). The glial limiting membrane of brain stem is continued to the end of central myelin. We called it glial sheath of REZ. The thickness of glial sheath was mean 66.5 µm (40-110 µm) at proximal REZ and 7.4 µm (5-10 µm) at distal REZ. Medial REZ of facial nerve is mean 2.6 mm in length and covered by glial sheath continued from glial limiting membrane of brain stem. Glial sheath of central myelin tends to become thin toward transitional zone.

  19. Involvement of ADAM10 in axonal outgrowth and myelination of the peripheral nerve.

    PubMed

    Jangouk, Parastoo; Dehmel, Thomas; Meyer Zu Hörste, Gerd; Ludwig, Andreas; Lehmann, Helmar C; Kieseier, Bernd C

    2009-12-01

    The disintegrin and metalloproteinase 10 (ADAM10) is a membrane-anchored metalloproteinase with both proteolytic and disintegrin characteristics. Here, we investigate the expression, regulation, and functional role of ADAM10 in axonal outgrowth and myelination of the peripheral nerve. Expression pattern analysis of 11 ADAM family members in co-cultures of rat dorsal root ganglia (DRG) neurons and Schwann cells (SCs) demonstrated the most pronounced mRNA expression for ADAM10. In further studies, ADAM10 was found to be consistently upregulated in DRG-SC co-cultures before the induction of myelination. Neurons as well as SCs widely expressed ADAM10 at the protein level. In neurons, the expression of ADAM10 was exclusively limited to the axons before the induction of myelination. Inhibition of ADAM10 activity by the hydroxamate-based inhibitors GI254023X and GW280264X resulted in a significant decrease in the mean axonal length. These data suggest that ADAM10 represents a prerequisite for myelination, although its activity is not required during the process of myelination itself as demonstrated by expression analysis of myelin protein zero (P0) and Sudan black staining. Hence, during the process of myelin formation, ADAM10 is highly upregulated and appears to be critically involved in axonal outgrowth that is a requirement for myelination in the peripheral nerve.

  20. Clinical syndromes associated with tomacula or myelin swellings in sural nerve biopsies

    PubMed Central

    Sander, S; Ouvrier, R; McLeod, J; Nicholson, G; Pollard, J

    2000-01-01

    OBJECTIVES—To describe the neuropathological features of clinical syndromes associated with tomacula or focal myelin swellings in sural nerve biospies and to discuss possible common aetiopathological pathways leading to their formation in this group of neuropathies.
METHODS—Fifty two patients with sural nerve biopsies reported to show tomacula or focal myelin swellings were reviewed, light and electron microscopy were performed, and tomacula were analysed on teased fibre studies. Molecular genetic studies were performed on those patients who were available for genetic testing.
RESULTS—Thirty seven patients were diagnosed with hereditary neuropathy with liability to pressure palsies (HNPP), four with hereditary motor and sensory neuropathy type I (HMSN I) or Charcot-Marie-Tooth disease type 1 (CMT1), four with HMSN with myelin outfolding (CMT4B), three with IgM paraproteinemic neuropathy, three with chronic inflammatory demyelinating polyneuropathy (CIDP), and one with HMSN III (CMT3).
CONCLUSIONS—Most of these syndromes were shown to be related to genetic or immunological defects of myelin components such as peripheral myelin protein 22 (PMP22), myelin protein zero (P0), or myelin associated glycoprotein (MAG). These proteins share the HNK-1 epitope which has been implicated in cell adhesion processes. Impaired myelin maintenance may therefore contribute to the formation of tomacula and subsequent demyelination.

 PMID:10727485

  1. Functional and structural properties of ion channels at the nerve terminal depends on compact myelin.

    PubMed

    Berret, Emmanuelle; Kim, Sei Eun; Lee, Seul Yi; Kushmerick, Christopher; Kim, Jun Hee

    2016-10-01

    In the present study, we document the role of compact myelin in regulating the structural and functional properties of ion channels at the nerve terminals, using electrophysiology, dynamic Na(+) imaging and immunohistochemistry. The subcellular segregation of Na(+) channel expression and intracellular Na(+) dynamics at the heminode and terminal was lost in the dysmyelinated axon from Long-Evans shaker rats, which lack compact myelin. In Long-Evans shaker rats, loss of the Nav β4 subunit specifically at the heminode reduced resurgent and persistent Na(+) currents, whereas K(+) channel expression and currents were increased. The results of the present study suggest that there is a specific role for compact myelin in dictating protein expression and function at the axon heminode and in regulating excitability of the nerve terminal. Axon myelination increases the conduction velocity and precision of action potential propagation. Although the negative effects of demyelination are generally attributed to conduction failure, accumulating evidence suggests that myelination also regulates the structural properties and molecular composition of the axonal membrane. In the present study, we investigated how myelination affects ion channel expression and function, particularly at the last axon heminode before the nerve terminal, which regulates the presynaptic excitability of the nerve terminal. We compared the structure and physiology of normal axons and those of the Long-Evans shaker (LES) rat, which lacks compact myelin. The normal segregation of Na(+) channel expression and dynamics at the heminode and terminal was lost in the LES rat. Specifically, NaV -α subunits were dispersed and NaV β4 subunit was absent, whereas the density of K(+) channels was increased at the heminode. Correspondingly, resurgent and persistent Na(+) currents were reduced and K(+) current was increased. Taken together, these data suggest a specific role for compact myelin in the orchestration of

  2. Functional and structural properties of ion channels at the nerve terminal depends on compact myelin

    PubMed Central

    Berret, Emmanuelle; Kim, Sei Eun; Lee, Seul Yi; Kushmerick, Christopher

    2016-01-01

    Key points In the present study, we document the role of compact myelin in regulating the structural and functional properties of ion channels at the nerve terminals, using electrophysiology, dynamic Na+ imaging and immunohistochemistry.The subcellular segregation of Na+ channel expression and intracellular Na+ dynamics at the heminode and terminal was lost in the dysmyelinated axon from Long–Evans shaker rats, which lack compact myelin.In Long–Evans shaker rats, loss of the Navβ4 subunit specifically at the heminode reduced resurgent and persistent Na+ currents, whereas K+ channel expression and currents were increased.The results of the present study suggest that there is a specific role for compact myelin in dictating protein expression and function at the axon heminode and in regulating excitability of the nerve terminal. Abstract Axon myelination increases the conduction velocity and precision of action potential propagation. Although the negative effects of demyelination are generally attributed to conduction failure, accumulating evidence suggests that myelination also regulates the structural properties and molecular composition of the axonal membrane. In the present study, we investigated how myelination affects ion channel expression and function, particularly at the last axon heminode before the nerve terminal, which regulates the presynaptic excitability of the nerve terminal. We compared the structure and physiology of normal axons and those of the Long–Evans shaker (LES) rat, which lacks compact myelin. The normal segregation of Na+ channel expression and dynamics at the heminode and terminal was lost in the LES rat. Specifically, NaV‐α subunits were dispersed and NaVβ4 subunit was absent, whereas the density of K+ channels was increased at the heminode. Correspondingly, resurgent and persistent Na+ currents were reduced and K+ current was increased. Taken together, these data suggest a specific role for compact myelin in the orchestration

  3. Excitation block in a nerve fibre model owing to potassium-dependent changes in myelin resistance

    PubMed Central

    Brazhe, A. R.; Maksimov, G. V.; Mosekilde, E.; Sosnovtseva, O. V.

    2011-01-01

    The myelinated nerve fibre is formed by an axon and Schwann cells or oligodendrocytes that sheath the axon by winding around it in tight myelin layers. Repetitive stimulation of a fibre is known to result in accumulation of extracellular potassium ions, especially between the axon and the myelin. Uptake of potassium leads to Schwann cell swelling and myelin restructuring that impacts the electrical properties of the myelin. In order to further understand the dynamic interaction that takes place between the myelin and the axon, we have modelled submyelin potassium accumulation and related changes in myelin resistance during prolonged high-frequency stimulation. We predict that potassium-mediated decrease in myelin resistance leads to a functional excitation block with various patterns of altered spike trains. The patterns are found to depend on stimulation frequency and amplitude and to range from no block (less than 100 Hz) to a complete block (greater than 500 Hz). The transitional patterns include intermittent periodic block with interleaved spiking and non-spiking intervals of different relative duration as well as an unstable regime with chaotic switching between the spiking and non-spiking states. Intermittent conduction blocks are accompanied by oscillations of extracellular potassium. The mechanism of conductance block based on myelin restructuring complements the already known and modelled block via hyperpolarization mediated by the axonal sodium pump and potassium depolarization. PMID:22419976

  4. Schwann Cell Myelination

    PubMed Central

    Salzer, James L.

    2015-01-01

    Myelinated nerve fibers are essential for the rapid propagation of action potentials by saltatory conduction. They form as the result of reciprocal interactions between axons and Schwann cells. Extrinsic signals from the axon, and the extracellular matrix, drive Schwann cells to adopt a myelinating fate, whereas myelination reorganizes the axon for its role in conduction and is essential for its integrity. Here, we review our current understanding of the development, molecular organization, and function of myelinating Schwann cells. Recent findings into the extrinsic signals that drive Schwann cell myelination, their cognate receptors, and the downstream intracellular signaling pathways they activate will be described. Together, these studies provide important new insights into how these pathways converge to activate the transcriptional cascade of myelination and remodel the actin cytoskeleton that is critical for morphogenesis of the myelin sheath. PMID:26054742

  5. Regulation of Peripheral Nerve Myelin Maintenance by Gene Repression through Polycomb Repressive Complex 2

    PubMed Central

    Ma, Ki H.; Hung, Holly A.; Srinivasan, Rajini; Xie, Huafeng; Orkin, Stuart H.

    2015-01-01

    Myelination of peripheral nerves by Schwann cells requires coordinate regulation of gene repression as well as gene activation. Several chromatin remodeling pathways critical for peripheral nerve myelination have been identified, but the functions of histone methylation in the peripheral nerve have not been elucidated. To determine the role of histone H3 Lys27 methylation, we have generated mice with a Schwann cell-specific knock-out of Eed, which is an essential subunit of the polycomb repressive complex 2 (PRC2) that catalyzes methylation of histone H3 Lys27. Analysis of this mutant revealed no significant effects on early postnatal development of myelin. However, its loss eventually causes progressive hypermyelination of small-diameter axons and apparent fragmentation of Remak bundles. These data identify the PRC2 complex as an epigenomic modulator of mature myelin thickness, which is associated with changes in Akt phosphorylation. Interestingly, we found that Eed inactivation causes derepression of several genes, e.g., Sonic hedgehog (Shh) and Insulin-like growth factor-binding protein 2 (Igfbp2), that become activated after nerve injury, but without activation of a primary regulator of the injury program, c-Jun. Analysis of the activated genes in cultured Schwann cells showed that Igfbp2 regulates Akt activation. Our results identify an epigenomic pathway required for establishing thickness of mature myelin and repressing genes that respond to nerve injury. PMID:26041929

  6. Calibration of the stereological estimation of the number of myelinated axons in the rat sciatic nerve: A multicenter study

    PubMed Central

    Kaplan, S.; Geuna, S.; Ronchi, G.; Ulkay, M.B.; von Bartheld, C.S.

    2010-01-01

    Several sources of variability can affect stereological estimates. Here we measured the impact of potential sources of variability on numerical stereological estimates of myelinated axons in the adult rat sciatic nerve. Besides biological variation, parameters tested included two variations of stereological methods (unbiased counting frame versus 2D-disector), two sampling schemes (few large versus frequent small sampling boxes), and workstations with varying degrees of sophistication. All estimates were validated against exhaustive counts of the same nerve cross sections to obtain calibrated true numbers of myelinated axons (gold standard). In addition, we quantified errors in particle identification by comparing light microscopic and electron microscopic images of selected consecutive sections. Biological variation was 15.6%. There was no significant difference between the two stereological approaches or workstations used, but sampling schemes with few large samples yielded larger differences (20.7%±3.7% SEM) of estimates from true values, while frequent small samples showed significantly smaller differences (12.7%±1.9% SEM). Particle identification was accurate in 94% of cases (range: 89–98%). The most common identification error was due to profiles of Schwann cell nuclei mimicking profiles of small myelinated nerve fibers. We recommend sampling frequent small rather than few large areas, and conclude that workstations with basic stereological equipment are sufficient to obtain accurate estimates. Electron microscopic verification showed that particle misidentification had a surprisingly variable and large impact of up to 11%, corresponding to 2/3 of the biological variation (15.6%). Thus, errors in particle identification require further attention, and we provide a simple nerve fiber recognition test to assist investigators with self-testing and training. PMID:20064555

  7. Brain gangliosides: functional ligands for myelin stability and the control of nerve regeneration.

    PubMed

    Vyas, A A; Schnaar, R L

    2001-07-01

    Gangliosides, sialylated glycosphingolipids which are the predominant glycans on vertebrate nerve cell surfaces, are emerging as components of membrane rafts, where they can mediate important physiological functions. Myelin associated glycoprotein (MAG), a minor constituent of myelin, is a sialic acid binding lectin with two established physiological functions: it is involved in myelin-axon stability and cytoarchitecture, and controls nerve regeneration. MAG is found selectively on the myelin membranes directly apposed to the axon surface, where it has been proposed to mediate myelin-axon interactions. Although the nerve cell surface ligands for MAG remain to be established, evidence supports a functional role for sialylated glycoconjugates. Here we review recent studies that reflect on the role of gangliosides, sialylated glycosphingolipids, as functional MAG ligands. MAG binds to gangliosides with the terminal sequence 'NeuAc alpha 3Gal beta 3GalNAc' which is found on the major nerve gangliosides GD1a and GT1b. Gangliosides lacking that terminus (e.g., GM1 or GD1b), or having any biochemical modification of the terminal NeuAc residue fail to support MAG binding. Genetically engineered mice lacking the GalNAc transferase required for biosynthesis of the 'NeuAc alpha 3Gal beta 3GalNAc' terminus have grossly impaired myelination and progressive neurodegeneration. Notably the MAG level in these animals is dysregulated. Furthermore, removal of NeuAc residues from nerve cells reverses MAG-mediated inhibition of neuritogenesis, and neurons from mice lacking the 'NeuAc alpha 3 Gal beta 3GalNAc' terminus have an attenuated response to MAG. Cross-linking nerve cell surface gangliosides can mimic MAG-mediated inhibition of nerve regeneration. Taken together these observations implicate gangliosides as functional MAG ligands.

  8. Bone Marrow-Derived Mesenchymal Stem Cells Improve Diabetic Neuropathy by Direct Modulation of Both Angiogenesis and Myelination in Peripheral Nerves.

    PubMed

    Han, Ji Woong; Choi, Dabin; Lee, Min Young; Huh, Yang Hoon; Yoon, Young-sup

    2016-01-01

    Recent evidence has suggested that diabetic neuropathy (DN) is pathophysiologically related to both impaired angiogenesis and a deficiency of neurotrophic factors in the nerves. It is widely known that vascular and neural growths are intimately associated. Mesenchymal stem cells (MSCs) promote angiogenesis in ischemic diseases and have neuroprotective effects, particularly on Schwann cells. Accordingly, we investigated whether DN could be improved by local transplantation of MSCs by augmenting angiogenesis and neural regeneration such as remyelination. In sciatic nerves of streptozotocin (STZ)-induced diabetic rats, motor and sensory nerve conduction velocities (NCVs) and capillary density were reduced, and axonal atrophy and demyelination were observed. After injection of bone marrow-derived MSCs (BM-MSCs) into hindlimb muscles, NCVs were restored to near-normal levels. Histological examination demonstrated that injected MSCs were preferentially and durably engrafted in the sciatic nerves, and a portion of the engrafted MSCs were distinctively localized close to vasa nervora of sciatic nerves. Furthermore, vasa nervora increased in density, and the ultrastructure of myelinated fibers in nerves was observed to be restored. Real-time RT-PCR experiments showed that gene expression of multiple factors involved in angiogenesis, neural function, and myelination were increased in the MSC-injected nerves. These findings suggest that MSC transplantation improved DN through direct peripheral nerve angiogenesis, neurotrophic effects, and restoration of myelination.

  9. Bone Marrow-Derived Mesenchymal Stem Cells Improve Diabetic Neuropathy by Direct Modulation of Both Angiogenesis and Myelination in Peripheral Nerves

    PubMed Central

    Han, Ji Woong; Choi, Dabin; Lee, Min Young; Huh, Yang Hoon; Yoon, Young-sup

    2016-01-01

    Recent evidence has suggested that diabetic neuropathy (DN) is pathophysiologically related to both impaired angiogenesis and a deficiency of neurotrophic factors in the nerves. It is widely known that vascular and neural growths are intimately associated. Mesenchymal stem cells (MSCs) promote angiogenesis in ischemic diseases and have neuroprotective effects, particularly on Schwann cells. Accordingly, we investigated whether DN could be improved by local transplantation of MSCs by augmenting angiogenesis and neural regeneration such as remyelination. In sciatic nerves of streptozotocin (STZ)-induced diabetic rats, motor and sensory nerve conduction velocities (NCVs) and capillary density were reduced, and axonal atrophy and demyelination were observed. After injection of bone marrow-derived MSCs (BM-MSCs) into hindlimb muscles, NCVs were restored to near-normal levels. Histological examination demonstrated that injected MSCs were preferentially and durably engrafted in the sciatic nerves, and a portion of the engrafted MSCs were distinctively localized close to vasa nervora of sciatic nerves. Furthermore, vasa nervora increased in density, and the ultrastructure of myelinated fibers in nerves was observed to be restored. Real-time RT-PCR experiments showed that gene expression of multiple factors involved in angiogenesis, neural function, and myelination were increased in the MSC-injected nerves. These findings suggest that MSC transplantation improved DN through direct peripheral nerve angiogenesis, neurotrophic effects, and restoration of myelination. PMID:25975801

  10. A New Method for Automated Identification and Morphometry of Myelinated Fibers Through Light Microscopy Image Analysis.

    PubMed

    Novas, Romulo Bourget; Fazan, Valeria Paula Sassoli; Felipe, Joaquim Cezar

    2016-02-01

    Nerve morphometry is known to produce relevant information for the evaluation of several phenomena, such as nerve repair, regeneration, implant, transplant, aging, and different human neuropathies. Manual morphometry is laborious, tedious, time consuming, and subject to many sources of error. Therefore, in this paper, we propose a new method for the automated morphometry of myelinated fibers in cross-section light microscopy images. Images from the recurrent laryngeal nerve of adult rats and the vestibulocochlear nerve of adult guinea pigs were used herein. The proposed pipeline for fiber segmentation is based on the techniques of competitive clustering and concavity analysis. The evaluation of the proposed method for segmentation of images was done by comparing the automatic segmentation with the manual segmentation. To further evaluate the proposed method considering morphometric features extracted from the segmented images, the distributions of these features were tested for statistical significant difference. The method achieved a high overall sensitivity and very low false-positive rates per image. We detect no statistical difference between the distribution of the features extracted from the manual and the pipeline segmentations. The method presented a good overall performance, showing widespread potential in experimental and clinical settings allowing large-scale image analysis and, thus, leading to more reliable results.

  11. Discrepancies in quantitative assessment of normal and regenerated peripheral nerve fibers between light and electron microscopy.

    PubMed

    Ronchi, Giulia; Jager, Sara Buskbjerg; Vaegter, Christian Bjerggaard; Raimondo, Stefania; Giacobini-Robecchi, Maria Giuseppina; Geuna, Stefano

    2014-09-01

    Quantitative estimation of myelinated nerve fiber number, together with fiber size parameters, is one of the most important tools for nerve regeneration research. In this study we used a design-based stereological method to evaluate the regenerative process in two experimental paradigms: crush injury and autograft repair. Samples were embedded in resin and morphometric counting and measurements were performed using both light and electron microscopes. Results show a significant difference in myelinated fiber number estimation between light and electron microscopes, especially after autograft repair; light microscope significantly underestimates the number of fibers because of the large number of very small axons that can be detected only in electron microscope. The analysis of the size parameters also shows a higher number of small fibers in electron microscopic analysis, especially in regenerated nerves. This comparative study shows that the integration of data obtained in light microscope with those obtained in electron microscope is necessary in revealing very small myelinated fibers that cannot be detected otherwise. Moreover, the difference in the estimation of total number of myelinated fibers between light and electron microscopes must be considered in data analysis to ensure accurate interpretation of the results. © 2014 Peripheral Nerve Society.

  12. Incorporation of fucose and leucine into PNS myelin proteins in nerves undergoing early Wallerian degeneration

    SciTech Connect

    Peterson, R.G.; Baughman, S.; Scheidler, D.M.

    1981-02-01

    The simultaneous incorporation of (/sup 3/H)fucose and (1-/sup 14/C)leucine into normal rat sciatic nerve was examined using an in vitro incubation model. A linear rate of protein precursor uptake was found in purified myelin protein over 1/2-6 hr of incubation utilizing a supplemented medium containing amino acids. This model was then used to examine myelin protein synthesis in nerves undergoing degeneration at 1-4 days following a crush injury. Data showed a statistically significant decrease in the ratio of fucose to leucine at 2, 3, and 4 days of degeneration, which was the consequence of a significant increase in leucine uptake. These results, plus substantial protein recovery in axotomized nerves, are indicative of active synthesis of proteins that purify with myelin during early Wallerian degeneration.

  13. The action of local anesthetics on myelin structure and nerve conduction in toad sciatic nerve.

    PubMed

    Mateu, L; Morán, O; Padrón, R; Borgo, M; Vonasek, E; Márquez, G; Luzzati, V

    1997-06-01

    X-ray scattering and electrophysiological experiments were performed on toad sciatic nerves in the presence of local anesthetics. In vitro experiments were performed on dissected nerves superfused with Ringer's solutions containing procaine, lidocaine, tetracaine, or dibucaine. In vivo experiments were performed on nerves dissected from animals anesthesized by targeted injections of tetracaine-containing solutions. In all cases the anesthetics were found to have the same effects on the x-ray scattering spectra: the intensity ratio of the even-order to the odd-order reflections increases and the lattice parameter increases. These changes are reversible upon removal of the anesthetic. The magnitude of the structural changes varies with the duration of the superfusion and with the nature and concentration of the anesthetic molecule. A striking quantitative correlation was observed between the structural effects and the potency of the anesthetic. Electron density profiles, which hardly showed any structural alteration of the unit membrane, clearly indicated that the anesthetics have the effect of moving the pairs of membranes apart by increasing the thickness of the cytoplasmic space. Electrophysiological measurements performed on the very samples used in the x-ray scattering experiments showed that the amplitude of the compound action potential is affected earlier than the structure of myelin (as revealed by the x-ray scattering experiments), whereas conduction velocity closely follows the structural alterations.

  14. Myelination changes in the rat optic nerve after prenatal exposure to methamphetamine.

    PubMed

    Melo, Pedro; Moreno, Vicente Zanón; Vázquez, Sheila Pons; Pinazo-Durán, Maria Dolores; Tavares, Maria Amélia

    2006-08-23

    The use of psychostimulants during adolescence and early adult life has increased in recent years. It is known that these substances affect the sensory systems, and the optic nerve has been shown to be a target tissue. This work was conducted to evaluate the effects of prenatal exposure to methamphetamine (MA) on the developmental pattern of the rat optic nerve. Pregnant female rats were given 5 mg/kg body weight/day MA, s.c., in 0.9% saline from gestational days 8 to 22. The control group was injected with an isovolumetric dose of 0.9% saline. Animal model parameters, such as gestational body weight evolution, food intake and pups parameters were registered. The offspring were sacrificed at postnatal days (PND) 7, 14 and 21. Morphometric analyses were performed at light and electron microscopic levels on optic nerve cross sections; parameters measured included optic nerve diameter and area, axonal density, total number of axons and myelin thickness. Myelin basic protein (MBP) was measured by western blotting in optic nerve samples at PND14 and PND21. The animal model parameters, such as maternal and pup weight, showed no significant differences between MA and control groups. Optic nerve diameter was smaller at PND7 in the male MA group and in both male and female MA groups at PND21. The mean cross-sectional area was smaller at PND14 in the male MA group and in both male and female groups at PND21. The total number of myelinated axons did not vary between groups at any of the studied ages. The myelin thickness of the axons in MA-treated females was thinner when compared with the respective control group at PND21. No other differences were found concerning myelin thickness. There was a reduction of MBP protein expression in MA-injected females at PND14 and PND21. The combined results suggest that prenatal exposure to MA affects the myelination process.

  15. Exploring the role of nerve growth factor in multiple sclerosis: implications in myelin repair.

    PubMed

    Acosta, C M R; Cortes, C; MacPhee, H; Namaka, M P

    2013-12-01

    Multiple sclerosis (MS) is a chronic disease resulting from targeted destruction of central nervous system (CNS) myelin. MS is suggested to be an autoimmune disease involving the pathogenic activation of CD4(+) T cells by a foreign antigen in the peripheral blood. The activated CD4(+) T cells liberate inflammatory cytokines that facilitate the breakdown of the blood-brain barrier (BBB) promoting their passage into the CNS. Inside the CNS, CD4(+) T cells become re-activated by myelin proteins sharing a similar structure to the foreign antigen that initially triggered the immune response. The CD4(+) T cells continue to liberate inflammatory cytokines, such as tumor necrosis factor α (TNFα), which activates macrophages and antibodies responsible for the phagocytosis of myelin. Acute CNS lesions can be re-myelinated, however, the repair of chronic demyelinating lesions is limited, leading to permanent neurological deficits. Although current MS treatments reduce severity and slow disease progression, they do not directly repair damaged myelin. Henceforth, recent treatment strategies have focused on neurotrophins, such as nerve growth factor (NGF) for myelin repair. NGF promotes axonal regeneration, survival, protection and differentiation of oligodendrocytes (OGs) and facilitates migration and proliferation of oligodendrocyte precursors (OPs) to the sites of myelin damage. NGF also directly regulates key structural proteins that comprise myelin. Interestingly, NGF also induces the production of brain-derived neurotrophic factor (BDNF), another integral neurotrophin involved in myelination. The intricate signaling between neurotrophins and cytokines that governs myelin repair supports the role of NGF as a leading therapeutic candidate in white matter disorders, such as MS.

  16. Axonal Transport and Morphology: How Myelination gets Nerves into Shape

    NASA Astrophysics Data System (ADS)

    Jung, Peter; Zhao, Peng; Monsma, Paula; Brown, Tony

    2011-03-01

    The local caliber of mature axons is largely determined by neurofilament (NF) content. The axoskeleton, mainly consisting of NFs, however, is dynamic. NFs are assembled in the cell body and are transported by molecular motors on microtubule tracks along the axon at a slow rate of fractions of mm per day. We combine live cell fluorescent imaging techniques to access NF transport in myelinated and non-myelinated segments of axons with computational modeling of the active NF flow to show that a), myelination locally slows NF transport rates by regulating duty ratios and b), that the predicted increase in axon caliber agrees well with experiments. This study, for the first time, links NF kinetics directly to axonal morphology, providing a novel conceptual framework for the physical understanding of processes leading to the formation of axonal structures such as the ``Nodes of Ranvier'' as well as abnormal axonal swellings associated with neurodegenerative diseases like Amyotrophic lateral sclerosis (ALS). NSF grants # IOS-0818412(PJ) and IOS-0818653 (AB).

  17. Peripheral Nerve Diffusion Tensor Imaging: Assessment of Axon and Myelin Sheath Integrity.

    PubMed

    Heckel, A; Weiler, M; Xia, A; Ruetters, M; Pham, M; Bendszus, M; Heiland, S; Baeumer, P

    2015-01-01

    To investigate the potential of diffusion tensor imaging (DTI) parameters as in-vivo biomarkers of axon and myelin sheath integrity of the median nerve in the carpal tunnel as validated by correlation with electrophysiology. MRI examinations at 3T including DTI were conducted on wrists in 30 healthy subjects. After manual segmentation of the median nerve quantitative analysis of fractional anisotropy (FA) as well as axial, radial and mean diffusivity (AD, RD, and MD) was carried out. Pairwise Pearson correlations with electrophysiological parameters comprising sensory nerve action potential (SNAP) and compound muscle action potential (CMAP) as markers of axon integrity, and distal motor latency (dml) and sensory nerve conduction velocity (sNCV) as markers of myelin sheath integrity were computed. The significance criterion was set at P=0.05, Bonferroni corrected for multiple comparisons. DTI parameters showed a distinct proximal-to-distal profile with FA, MD, and RD extrema coinciding in the center of the carpal tunnel. AD correlated with CMAP (r=0.50, p=0.04, Bonf. corr.) but not with markers of myelin sheath integrity. RD correlated with sNCV (r=-0.53, p=0.02, Bonf. corr.) but not with markers of axon integrity. FA correlated with dml (r=-0.63, p=0.002, Bonf. corr.) and sNCV (r=0.68, p=0.001, Bonf. corr.) but not with markers of axon integrity. AD reflects axon integrity, while RD (and FA) reflect myelin sheath integrity as validated by correlation with electrophysiology. DTI parameters consistently indicate a slight decrease of structural integrity in the carpal tunnel as a physiological site of median nerve entrapment. DTI is particularly sensitive, since these findings are observed in healthy participants. Our results encourage future studies to evaluate the potential of DTI in differentiating axon from myelin sheath injury in patients with manifest peripheral neuropathies.

  18. Peripheral Nerve Diffusion Tensor Imaging: Assessment of Axon and Myelin Sheath Integrity

    PubMed Central

    Heckel, A.; Weiler, M.; Xia, A.; Ruetters, M.; Pham, M.; Bendszus, M.; Heiland, S.; Baeumer, P.

    2015-01-01

    Purpose To investigate the potential of diffusion tensor imaging (DTI) parameters as in-vivo biomarkers of axon and myelin sheath integrity of the median nerve in the carpal tunnel as validated by correlation with electrophysiology. Methods MRI examinations at 3T including DTI were conducted on wrists in 30 healthy subjects. After manual segmentation of the median nerve quantitative analysis of fractional anisotropy (FA) as well as axial, radial and mean diffusivity (AD, RD, and MD) was carried out. Pairwise Pearson correlations with electrophysiological parameters comprising sensory nerve action potential (SNAP) and compound muscle action potential (CMAP) as markers of axon integrity, and distal motor latency (dml) and sensory nerve conduction velocity (sNCV) as markers of myelin sheath integrity were computed. The significance criterion was set at P=0.05, Bonferroni corrected for multiple comparisons. Results DTI parameters showed a distinct proximal-to-distal profile with FA, MD, and RD extrema coinciding in the center of the carpal tunnel. AD correlated with CMAP (r=0.50, p=0.04, Bonf. corr.) but not with markers of myelin sheath integrity. RD correlated with sNCV (r=-0.53, p=0.02, Bonf. corr.) but not with markers of axon integrity. FA correlated with dml (r=-0.63, p=0.002, Bonf. corr.) and sNCV (r=0.68, p=0.001, Bonf. corr.) but not with markers of axon integrity. Conclusion AD reflects axon integrity, while RD (and FA) reflect myelin sheath integrity as validated by correlation with electrophysiology. DTI parameters consistently indicate a slight decrease of structural integrity in the carpal tunnel as a physiological site of median nerve entrapment. DTI is particularly sensitive, since these findings are observed in healthy participants. Our results encourage future studies to evaluate the potential of DTI in differentiating axon from myelin sheath injury in patients with manifest peripheral neuropathies. PMID:26114630

  19. The Permeability of the Sodium Channel to Metal Cations in Myelinated Nerve

    PubMed Central

    Hille, Bertil

    1972-01-01

    The relative permeability of sodium channels to eight metal cations is studied in myelinated nerve fibers. Ionic currents under voltage-clamp conditions are measured in Na-free solutions containing the test ion. Measured reversal potentials and the Goldman equation are used to calculate the permeability sequence: Na+ ≈ Li+ > Tl+ > K+. The ratio PK/PNa is 1/12. The permeabilities to Rb+, Cs+, Ca++, and Mg++ are too small to measure. The permeability ratios agree with observations on the squid giant axon and show that the reversal potential ENa differs significantly from the Nernst potential for Na+ in normal axons. Opening and closing rates for sodium channels are relatively insensitive to the ionic composition of the bathing medium, implying that gating is a structural property of the channel rather than a result of the movement or accumulation of particular ions around the channel. A previously proposed pore model of the channel accommodates the permeant metal cations in a partly hydrated form. The observed sequence of permeabilities follows the order expected for binding to a high field strength anion in Eisenman's theory of ion exchange equilibria. PMID:5025743

  20. Boric acid reduces axonal and myelin damage in experimental sciatic nerve injury

    PubMed Central

    Kızılay, Zahir; Erken, Haydar Ali; Çetin, Nesibe Kahraman; Aktaş, Serdar; Abas, Burçin İrem; Yılmaz, Ali

    2016-01-01

    The aim of this study was to investigate the effects of boric acid in experimental acute sciatic nerve injury. Twenty-eight adult male rats were randomly divided into four equal groups (n = 7): control (C), boric acid (BA), sciatic nerve injury (I), and sciatic nerve injury + boric acid treatment (BAI). Sciatic nerve injury was generated using a Yasargil aneurysm clip in the groups I and BAI. Boric acid was given four times at 100 mg/kg to rats in the groups BA and BAI after injury (by gavage at 0, 24, 48 and 72 hours) but no injury was made in the group BA. In vivo electrophysiological tests were performed at the end of the day 4 and sciatic nerve tissue samples were taken for histopathological examination. The amplitude of compound action potential, the nerve conduction velocity and the number of axons were significantly lower and the myelin structure was found to be broken in group I compared with those in groups C and BA. However, the amplitude of the compound action potential, the nerve conduction velocity and the number of axons were significantly greater in group BAI than in group I. Moreover, myelin injury was significantly milder and the intensity of nuclear factor kappa B immunostaining was significantly weaker in group BAI than in group I. The results of this study show that administration of boric acid at 100 mg/kg after sciatic nerve injury in rats markedly reduces myelin and axonal injury and improves the electrophysiological function of injured sciatic nerve possibly through alleviating oxidative stress reactions. PMID:27904499

  1. Boric acid reduces axonal and myelin damage in experimental sciatic nerve injury.

    PubMed

    Kızılay, Zahir; Erken, Haydar Ali; Çetin, Nesibe Kahraman; Aktaş, Serdar; Abas, Burçin İrem; Yılmaz, Ali

    2016-10-01

    The aim of this study was to investigate the effects of boric acid in experimental acute sciatic nerve injury. Twenty-eight adult male rats were randomly divided into four equal groups (n = 7): control (C), boric acid (BA), sciatic nerve injury (I), and sciatic nerve injury + boric acid treatment (BAI). Sciatic nerve injury was generated using a Yasargil aneurysm clip in the groups I and BAI. Boric acid was given four times at 100 mg/kg to rats in the groups BA and BAI after injury (by gavage at 0, 24, 48 and 72 hours) but no injury was made in the group BA. In vivo electrophysiological tests were performed at the end of the day 4 and sciatic nerve tissue samples were taken for histopathological examination. The amplitude of compound action potential, the nerve conduction velocity and the number of axons were significantly lower and the myelin structure was found to be broken in group I compared with those in groups C and BA. However, the amplitude of the compound action potential, the nerve conduction velocity and the number of axons were significantly greater in group BAI than in group I. Moreover, myelin injury was significantly milder and the intensity of nuclear factor kappa B immunostaining was significantly weaker in group BAI than in group I. The results of this study show that administration of boric acid at 100 mg/kg after sciatic nerve injury in rats markedly reduces myelin and axonal injury and improves the electrophysiological function of injured sciatic nerve possibly through alleviating oxidative stress reactions.

  2. Raman spectroscopy of nerve fibers. A study of membrane lipids under steady state conditions.

    PubMed Central

    Pézolet, M; Georgescauld, D

    1985-01-01

    The molecular structures of different nerve fibers kept in good physiological conditions were studied by laser Raman spectroscopy. For myelinated nerves like the rat sciatic nerve, the Raman spectrum is dominated by bands due to the lipid component of the myelin sheath. The temperature dependence of these bands does not reveal any thermotropic phase transition between 0 and 40 degrees C. There is, however, with temperature, a linear increase in the intermolecular disorder that is accompanied by an increase in the number of gauche bonds of the phospholipid acyl chains. For unmyelinated nerves such as the lobster leg nerve, the C-H stretching region of the Raman spectrum is covered by bands arising from the protein component of the axoplasm. However, for the garfish olfactory nerve that has a high density of excitable membranes, phospholipid bands are observed and can be used as intrinsic structural probes of the excitable membranes. The relative intensity of these bands is also temperature dependent. PMID:3978206

  3. Vitamin D3 potentiates myelination and recovery after facial nerve injury.

    PubMed

    Montava, Marion; Garcia, Stéphane; Mancini, Julien; Jammes, Yves; Courageot, Joël; Lavieille, Jean-Pierre; Feron, François

    2015-10-01

    Roles of vitamin D on the immune and nervous systems are increasingly recognized. Two previous studies demonstrated that ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3) induced functional recovery and increased myelination in a rat model of peroneal nerve transection. The current report assessed whether cholecalciferol was efficient in repairing transected rabbit facial nerves. Animals were randomized into two groups of rabbits with an unilateral facial nerve surgery: the vitamin D group included animals receiving a weekly oral bolus of vitamin D3 (200 IU/kg/day), from day 1 post-surgery; the control group included animals receiving a weekly oral bolus of vehicle (triglycerides). Contralateral unsectioned facial nerves from all experimental animals were used as controls for the histological study. The facial functional index was measured every week while the inner diameter of myelin sheath and the G ratio were quantified at the end of the 3 month experiment. The current report indicates that cholecalciferol significantly increases functional recovery and myelination, after 12 weeks of treatment. To the best of our knowledge, this is the first study investigating the therapeutic benefit of vitamin D supplementation in an animal model of facial paralysis. It paves further the way for clinical trials based on the administration of this steroid in individuals with injured facial nerves.

  4. Laser interference microscopy: a novel approach to the visualization of structural changes in myelin during the propagation of nerve impulses

    NASA Astrophysics Data System (ADS)

    Yusipovich, A. I.; Cherkashin, A. A.; Verdiyan, E. E.; Sogomonyan, I. A.; Maksimov, G. V.

    2016-08-01

    We used 3D phase images obtained by laser interference microscopy (LIM) for ex vivo evaluation of changes in the structure of myelin during repetitive stimulation. In this work we propose a simple model of myelinated nerve fiber (mNF), which describes phase images as a result of different geometry and membrane-to-cytoplasm ratio in various regions, particularly, the internode and paranodal-nodal-paranodal region, including the node of Ranvier. Application of this model provides clear interpretation of the phase images and also demonstrates that repetitive action potentials are accompanied by structural changes in myelin in the internode and cytoplasmic modification in the node of Ranvier. The first 20 min of stimulation did not induce significant changes in the measured parameters, but then the optical path difference at the periphery of mNF and at the node of Ranvier declined reversibly. We believe that our model is also applicable to other modifications of interference and non-interference imaging.

  5. Myelin-phagocytosing macrophages in isolated sciatic and optic nerves reveal a unique reactive phenotype.

    PubMed

    van Rossum, Denise; Hilbert, Sören; Strassenburg, Silke; Hanisch, Uwe-Karsten; Brück, Wolfgang

    2008-02-01

    Macrophages are key effectors in demyelinating diseases of the central and peripheral nervous system by phagocytosing myelin and releasing immunoregulatory mediators. Here, we report on a distinct, a priori anti-inflammatory reaction of macrophages phagocytosing myelin upon contact with damaged nerve tissue. Macrophages rapidly invaded peripheral (sciatic) and central (optic) nerve tissues in vitro, readily incorporated myelin and expressed high levels of phagocytosis-associated molecules (e.g., Fc and scavenger receptors). In contrast, factors involved in antigen presentation (MHC class-II, CD80, CD86) revealed only a restricted expression. In parallel, a highly ordered appearance of cytokines and chemokines was detected. IL-10, IL-6, CCL22, and CXCL1 were immediately but transiently induced, whereas CCL2, CCL11, and TGFbeta revealed more persisting levels. Such a profile would attract neutrophils, monocytes/macrophages, and Th2 cells as well as bias for a Th2-supporting environment. Importantly, proinflammatory/Th1-supporting factors, such as TNFalpha, IL-12p70, CCL3, and CCL5, were not induced. Still the simultaneous presence of TGFbeta and IL-6 could assist Th17 development, further depending on yet not present IL-23. The release pattern was clearly distinct from reactive phenotypes induced in isolated macrophages and microglia upon treatment with IL-4, IL-13, bacterial lipopolysaccharide, IFNgamma, or purified myelin. Nerve-exposed macrophages thus commit to a unique functional orientation.

  6. Spatial pattern of nerve fiber abnormality indicative of pathologic mechanism.

    PubMed Central

    Dyck, P. J.; Karnes, J.; O'Brien, P.; Nukada, H.; Lais, A.; Low, P.

    1984-01-01

    Estimates of the number, density, and size distribution of myelinated fibers at selected levels of roots, spinal tracts, and sampled levels of peripheral nerves may be used in the detection and characterization of alterations of motor, sensory, and autonomic neurons and their axons with development, aging and disease. Use of imaging techniques, now available, increases the reliability, versatility, and speed of such analysis. In this study, the authors evaluated the spatial pattern of fibers in sampled frames and contour areas of transverse sections of nerve fascicles, utilizing, the coefficient of variation and index of dispersion (ID), the latter extensively employed by plant ecologists. The ID was used for recognization of increased, normal, or decreased variability of density within fascicles, between fascicles, and between nerves in health and in various experimental neuropathies. In addition, various morphometric measurements were made in transverse sections at defined levels along the hind limb nerves of rats in acute and chronic ischemia, after rhizotomy and in galactose neuropathy. These stereomorphometric studies, emphasizing the number, size, shape, and spatial pattern of fibers, revealed differences among experimental neuropathies and may be found to be helpful in the characterization and prediction of pathologic mechanisms in neuropathies of unknown cause. Specifically, these approaches could be used for study of whether fiber loss in human diabetic neuropathy is multifocal and determination of the levels of such losses. PMID:6333825

  7. Differential activation of nerve fibers with magnetic stimulation in humans

    PubMed Central

    Tuday, Eric C; Olree, Kenneth S; Horch, Kenneth W

    2006-01-01

    Background Earlier observations in our lab had indicated that large, time-varying magnetic fields could elicit action potentials that travel in only one direction in at least some of the myelinated axons in peripheral nerves. The objective of this study was to collect quantitative evidence for magnetically induced unidirectional action potentials in peripheral nerves of human subjects. A magnetic coil was maneuvered to a location on the upper arm where physical effects consistent with the creation of unidirectional action potentials were observed. Electromyographic (EMG) and somatosensory evoked potential (SEP) recordings were then made from a total of 20 subjects during stimulation with the magnetic coil. Results The relative amplitudes of the EMG and SEP signals changed oppositely when the current direction in the magnetic coil was reversed. This effect was consistent with current direction in the coil relative to the arm for all subjects. Conclusion A differential evocation of motor and sensory fibers was demonstrated and indicates that it may be possible to induce unidirectional action potentials in myelinated peripheral nerve fibers with magnetic stimulation. PMID:16863593

  8. Sox2 expression in Schwann cells inhibits myelination in vivo and induces influx of macrophages to the nerve.

    PubMed

    Roberts, Sheridan L; Dun, Xin-Peng; Doddrell, Robin D S; Mindos, Thomas; Drake, Louisa K; Onaitis, Mark W; Florio, Francesca; Quattrini, Angelo; Lloyd, Alison C; D'Antonio, Maurizio; Parkinson, David B

    2017-09-01

    Correct myelination is crucial for the function of the peripheral nervous system. Both positive and negative regulators within the axon and Schwann cell function to ensure the correct onset and progression of myelination during both development and following peripheral nerve injury and repair. The Sox2 transcription factor is well known for its roles in the development and maintenance of progenitor and stem cell populations, but has also been proposed in vitro as a negative regulator of myelination in Schwann cells. We wished to test fully whether Sox2 regulates myelination in vivo and show here that, in mice, sustained Sox2 expression in vivo blocks myelination in the peripheral nerves and maintains Schwann cells in a proliferative non-differentiated state, which is also associated with increased inflammation within the nerve. The plasticity of Schwann cells allows them to re-myelinate regenerated axons following injury and we show that re-myelination is also blocked by Sox2 expression in Schwann cells. These findings identify Sox2 as a physiological regulator of Schwann cell myelination in vivo and its potential to play a role in disorders of myelination in the peripheral nervous system. © 2017. Published by The Company of Biologists Ltd.

  9. Cholecalciferol (Vitamin D3) Improves Myelination and Recovery after Nerve Injury

    PubMed Central

    Chabas, Jean-Francois; Stephan, Delphine; Marqueste, Tanguy; Garcia, Stephane; Lavaut, Marie-Noelle; Nguyen, Catherine; Legre, Regis; Khrestchatisky, Michel

    2013-01-01

    Previously, we demonstrated i) that ergocalciferol (vitamin D2) increases axon diameter and potentiates nerve regeneration in a rat model of transected peripheral nerve and ii) that cholecalciferol (vitamin D3) improves breathing and hyper-reflexia in a rat model of paraplegia. However, before bringing this molecule to the clinic, it was of prime importance i) to assess which form – ergocalciferol versus cholecalciferol – and which dose were the most efficient and ii) to identify the molecular pathways activated by this pleiotropic molecule. The rat left peroneal nerve was cut out on a length of 10 mm and autografted in an inverted position. Animals were treated with either cholecalciferol or ergocalciferol, at the dose of 100 or 500 IU/kg/day, or excipient (Vehicle), and compared to unlesioned rats (Control). Functional recovery of hindlimb was measured weekly, during 12 weeks, using the peroneal functional index. Ventilatory, motor and sensitive responses of the regenerated axons were recorded and histological analysis was performed. In parallel, to identify the genes regulated by vitamin D in dorsal root ganglia and/or Schwann cells, we performed an in vitro transcriptome study. We observed that cholecalciferol is more efficient than ergocalciferol and, when delivered at a high dose (500 IU/kg/day), cholecalciferol induces a significant locomotor and electrophysiological recovery. We also demonstrated that cholecalciferol increases i) the number of preserved or newly formed axons in the proximal end, ii) the mean axon diameter in the distal end, and iii) neurite myelination in both distal and proximal ends. Finally, we found a modified expression of several genes involved in axogenesis and myelination, after 24 hours of vitamin supplementation. Our study is the first to demonstrate that vitamin D acts on myelination via the activation of several myelin-associated genes. It paves the way for future randomised controlled clinical trials for peripheral nerve or

  10. Nerve ultrasound findings in neuropathy associated with anti-myelin-associated glycoprotein antibodies.

    PubMed

    Lucchetta, M; Padua, L; Granata, G; Luigetti, M; Campagnolo, M; Dalla Torre, C; Coraci, D; Sabatelli, M; Briani, C

    2015-01-01

    No systematic nerve ultrasound (US) studies on patients with neuropathy and anti-myelin-associated glycoprotein (anti-MAG) antibodies are available. Twenty-eight patients (18 men, 10 women, mean age 69.2 ± 10.9 years; mean disease duration 6.9 years) with anti-MAG neuropathy underwent nerve US. Echotexture, nerve cross-sectional area (CSA) and intra-nerve and inter-nerve CSA variability were assessed. The frequency (number of nerves with enlarged CSA, 'enlarged nerves sum score') and distribution (proximal versus distal, arms versus legs, symmetry) of US abnormalities were considered. Controls included two groups: four patients with immunoglobulin M (IgM) paraproteinaemic neuropathy without anti-MAG antibodies and five with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) associated with IgM paraprotein. In all, 26/28 patients had increased CSA (23 with at least one nerve outside entrapment sites). Intra-nerve CSA variability was abnormal in 21/28 patients (in 14 for increased nerve CSA outside entrapment sites). Inter-nerve CSA variability was abnormal in 16 patients (of whom half for CSA increase out of entrapment sites). The enlarged nerves sum score in anti-MAG neuropathy patients was greater than in MAG-negative paraproteinaemic neuropathies and lower than in CIDP. Intra-nerve variability appeared instead similar in anti-MAG and controls. No correlation was found between US findings and Inflammatory Neuropathy Cause and Treatment Group (INCAT) disability score or disease duration. Amongst the different measures to assess the US pattern (symmetry/asymmetry, proximal/distal distribution and sum score), the enlarged nerves sum score was the most useful for differentiating the three groups of patients with demyelinating neuropathies and may contribute to diagnosis in a typical cases. © 2014 EAN.

  11. Comparison of the fastest regenerating motor and sensory myelinated axons in the same peripheral nerve.

    PubMed

    Moldovan, Mihai; Sørensen, Jesper; Krarup, Christian

    2006-09-01

    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 electrodes. The timing of laminectomy was based on the presence of regenerating fibres along the nerve within the tibial cuff. Stimulation of unlesioned tibial nerves (n = 6) evoked the largest motor response in S1 ventral root and the largest sensory response in L7 dorsal root. Growth rates were compared by mapping the regenerating nerve fibres within the tibial nerve cuff to all ventral or dorsal roots and, regardless of the lesion type, the fastest growth was similar in sensory and motor fibres. Maturation was assessed as recovery of the maximum motor and sensory conduction velocities (CVs) within the tibial nerve cuff. Throughout the observation period the CV was approximately 14% faster in regenerated sensory fibres than in motor fibres in accordance with the difference observed in control nerves. Recovery of amplitude was only partial after section, whereas the root distribution pattern was restored. Our data suggest that the fastest growth and maturation rates that can be achieved during regeneration are similar for motor and sensory myelinated fibres.

  12. Similarities in the surface area/volume ratio in the fibers of the recurrent laryngeal nerve can explain the symmetry in the vocal fold mobility?

    PubMed

    de Campos, Deivis; Xavier, Léder Leal; Goulart, Guilherme Reghelin; Thomaz, Leonardo Dalla Giacomassa Rocha; Malysz, Tais; Jotz, Geraldo Pereira

    2015-12-01

    We demonstrate in this paper that although there are statistical differences for all morphometric data [axon length, axon diameter, myelinated fiber diameter and degree of the myelination (g-Ratio)] between the fibers of recurrent laryngeal nerve right and left, the surface area/volume ratio in the fibers of both nerves is exactly the same (1/1.7). Thereby, this paper presents the hypothesis that this similarity between the nerves can actually trigger a considerable synchrony in mobility of the intrinsic muscles of the larynx that control of the vocal folds.

  13. N,N-diethyldithiocarbamate produces copper accumulation, lipid peroxidation, and myelin injury in rat peripheral nerve.

    PubMed

    Tonkin, Elizabeth G; Valentine, Holly L; Milatovic, Dejan M; Valentine, William M

    2004-09-01

    Previous studies have demonstrated the ability of the dithiocarbamate, disulfiram, to produce a peripheral neuropathy in humans and experimental animals and have also provided evidence that N,N-diethyldithiocarbamate (DEDC) is a proximate toxic species of disulfiram. The ability of DEDC to elevate copper levels in the brain suggests that it may also elevate levels of copper in peripheral nerve, possibly leading to oxidative stress and lipid peroxidation from redox cycling of copper. The study presented here investigates the potential of DEDC to promote copper accumulation and lipid peroxidation in peripheral nerve. Rats were administered either DEDC or deionized water by ip osmotic pumps and fed a normal diet or diet containing elevated copper, and the levels of metals, isoprostanes, and the severity of lesions in peripheral nerve and brain were assessed by ICP-AES/AAS, GC/MS, and light microscopy, respectively. Copper was the only metal that demonstrated any significant compound-related elevations relative to controls, and total copper was increased in both brain and peripheral nerve in animals administered DEDC on both diets. In contrast, lesions and elevated F2-isoprostanes were significantly increased only in peripheral nerve for the rats administered DEDC on both diets. Autometallography staining of peripheral nerve was consistent with increased metal content along the myelin sheath, but in brain, focal densities were observed, and a periportal distribution occurred in liver. These data are consistent with the peripheral nervous system being more sensitive to DEDC-mediated demyelination and demonstrate the ability of DEDC to elevate copper levels in peripheral nerve. Additionally lipid peroxidation appears to either be a contributing event in the development of demyelination, possibly through an increase of redox active copper, or a consequence of the myelin injury.

  14. Endometriosis-associated nerve fibers and pain

    PubMed Central

    Medina, Melissa G.; Lebovic, Dan I.

    2015-01-01

    The assessment and diagnosis of endometriosis remain elusive targets. Patient and medical-related factors add to delays in the detection and treatment. Recently, investigators have revealed specific nerve fibers present in endometriotic tissue, with existing parallels between density and pain severity. The aim of this review is to compile a comprehensive review of existing literature on endometriosis-related nerve fiber detection, and the effects of medical therapy on these neural fibers. We performed a systematic literature-based review using Medline and PubMed of nerve fibers detected in eutopic endometrium, endometriotic lesions, and the peritoneum. Various arrangements of significant medical terms and phrases consisting of endometriosis, pelvic pain, nerve fiber detection/density in endometriosis, and diagnoses methodology, including treatment and detection were applied in the search. Subsequent references used were cross-matched with existing sources to compile all additional similar reports. Similar nerve fibers were detected within lesions, endometrium, and myometrium, though at varying degrees of density. Hormonal therapy is widely used to treat endometriosis and was shown to be related to a reduction in fiber density. A direct result of specific nerve fiber detection within eutopic endometrial layers points to the use of a minimally invasive endometrial biopsy technique in reducing delay in diagnosis and subsequent possible preservation of fertility. PMID:19657753

  15. Endogenous glucocorticoids improve myelination via Schwann cells after peripheral nerve injury: An in vivo study using a crush injury model.

    PubMed

    Morisaki, Shinsuke; Nishi, Mayumi; Fujiwara, Hiroyoshi; Oda, Ryo; Kawata, Mitsuhiro; Kubo, Toshikazu

    2010-06-01

    Glucocorticoids improve the symptoms of peripheral nerve disorders, such as carpal tunnel syndrome and peripheral neuropathy. The effects of glucocorticoids are mainly anti-inflammatory, but the mechanisms of their effects in peripheral nerve disorders remain unclear. Schwann cells of the peripheral nerves express glucocorticoid receptors (GR), and glucocorticoids enhance the rate of myelin formation in vitro. Therefore, it is possible that the clinical improvement of peripheral nerve disorders by glucocorticoids is due, at least in part, to the modulation of myelination. In this study, an adrenalectomy (ADX) was performed, and followed by a daily injection of either low dose (1 mg/kg) or high dose (10 mg/kg) corticosterone (CORT). We then simulated a crush injury of the sciatic nerves. A sham ADX operation, followed by a simulated crush injury, was conducted as a control. Immunohistochemistry showed that the nuclei of in vivo Schwann cells expressed GR and that glucocorticoids impacted the GR immunoreactivity of the Schwann cells. The mRNA and protein expression of myelin basic protein was significantly lower in the animals given ADX with vehicle than in the sham operation group. However, the expression was restored in the low-dose CORT replacement group. Morphological analyses showed that the ADX with vehicle group had a significantly lower myelin thickness than did the low-dose CORT replacement group and the sham operation group. These results suggest that endogenous glucocorticoids have an important role in myelination through the GR in Schwann cells after an in vivo peripheral nerve injury.

  16. Gangliosides are functional nerve cell ligands for myelin-associated glycoprotein (MAG), an inhibitor of nerve regeneration.

    PubMed

    Vyas, Alka A; Patel, Himatkumar V; Fromholt, Susan E; Heffer-Lauc, Marija; Vyas, Kavita A; Dang, Jiyoung; Schachner, Melitta; Schnaar, Ronald L

    2002-06-11

    Myelin-associated glycoprotein (MAG) binds to the nerve cell surface and inhibits nerve regeneration. The nerve cell surface ligand(s) for MAG are not established, although sialic acid-bearing glycans have been implicated. We identify the nerve cell surface gangliosides GD1a and GT1b as specific functional ligands for MAG-mediated inhibition of neurite outgrowth from primary rat cerebellar granule neurons. MAG-mediated neurite outgrowth inhibition is attenuated by (i) neuraminidase treatment of the neurons; (ii) blocking neuronal ganglioside biosynthesis; (iii) genetically modifying the terminal structures of nerve cell surface gangliosides; and (iv) adding highly specific IgG-class antiganglioside mAbs. Furthermore, neurite outgrowth inhibition is mimicked by highly multivalent clustering of GD1a or GT1b by using precomplexed antiganglioside Abs. These data implicate the nerve cell surface gangliosides GD1a and GT1b as functional MAG ligands and suggest that the first step in MAG inhibition is multivalent ganglioside clustering.

  17. Thermally Drawn Fibers as Nerve Guidance Scaffolds

    PubMed Central

    Koppes, Ryan A.; Park, Seongjun; Hood, Tiffany; Jia, Xiaoting; Poorheravi, Negin Abdolrahim; Achyuta, Anilkumar Harapanahalli; Fink, Yoel; Anikeeva, Polina

    2016-01-01

    Synthetic neural scaffolds hold promise to eventually replace nerve autografts for tissue repair following peripheral nerve injury. Despite substantial evidence for the influence of scaffold geometry and dimensions on the rate of axonal growth, systematic evaluation of these parameters remains a challenge due to limitations in materials processing. We have employed fiber drawing to engineer a wide spectrum of polymer-based neural scaffolds with varied geometries and core sizes. Using isolated whole dorsal root ganglia as an in vitro model system we have identified key features enhancing nerve growth within these fiber scaffolds. Our approach enabled straightforward integration of microscopic topography at the scale of nerve fascicles within the scaffold cores, which led to accelerated Schwann cell migration, as well as neurite growth and alignment. Our findings indicate that fiber drawing provides a scalable and versatile strategy for producing nerve guidance channels capable of controlling direction and accelerating the rate of axonal growth. PMID:26717246

  18. Thermally drawn fibers as nerve guidance scaffolds.

    PubMed

    Koppes, Ryan A; Park, Seongjun; Hood, Tiffany; Jia, Xiaoting; Abdolrahim Poorheravi, Negin; Achyuta, Anilkumar Harapanahalli; Fink, Yoel; Anikeeva, Polina

    2016-03-01

    Synthetic neural scaffolds hold promise to eventually replace nerve autografts for tissue repair following peripheral nerve injury. Despite substantial evidence for the influence of scaffold geometry and dimensions on the rate of axonal growth, systematic evaluation of these parameters remains a challenge due to limitations in materials processing. We have employed fiber drawing to engineer a wide spectrum of polymer-based neural scaffolds with varied geometries and core sizes. Using isolated whole dorsal root ganglia as an in vitro model system we have identified key features enhancing nerve growth within these fiber scaffolds. Our approach enabled straightforward integration of microscopic topography at the scale of nerve fascicles within the scaffold cores, which led to accelerated Schwann cell migration, as well as neurite growth and alignment. Our findings indicate that fiber drawing provides a scalable and versatile strategy for producing nerve guidance channels capable of controlling direction and accelerating the rate of axonal growth.

  19. A fiber optic sensor for nerve agent

    NASA Astrophysics Data System (ADS)

    Cordero, Steven R.; Mukamal, Harold; Low, Aaron; Locke, Edward P.; Lieberman, Robert A.

    2006-10-01

    We report advances made on the development of a fiber optic nerve agent sensor having its entire length as the sensing element. The optical fiber is multimode, and consists of a fused-silica core and a nerve agent sensitive cladding. Upon exposure to sarin gas, the cladding changes color, resulting in an alteration of the light intensity throughput. The fiber is mass produced using a conventional fiber optic draw tower. This technology could replace, or be used with, a collection of point-detectors to protect personnel, buildings and perimeters from dangerous chemical attacks.

  20. Changes in myelin sheath thickness and internode geometry in the rabbit phrenic nerve during growth.

    PubMed Central

    Friede, R L; Brzoska, J; Hartmann, U

    1985-01-01

    The rabbit phrenic nerve was studied at seven phases of growth from the newborn to the adult to determine the length of the nerve fibres, the length of the internodes, the fibre calibre, the geometric proportions of the internodes and the thickness of the myelin sheaths. The elongation of the internodes corresponded precisely to the elongation of the nerve, indicating a constant number of approximately 140 internodes per fibre, each internode elongating commensurate with body growth. Internode elongation was accompanied by increases in fibre calibre, but these parameters did not change in precise proportion. The internodes of thick fibres were relatively short for calibre, as defined by the length/diameter quotient. This trend of foreshortening changed during growth. Sheath thickness, defined by the quotient axon diameter/fibre diameter, was determined with a computer-assisted method. Fibres of young rabbits had relatively thin sheaths for axon calibre, compared with adult rabbits. The changes in sheath thickness corresponded to the changes in internode geometry. This was consistent with previous studies showing that elongation or foreshortening of an internode of a given calibre has a slight, but definite effect on the thickness of its myelin sheath. PMID:3870716

  1. Developmental impairment of compound action potential in the optic nerve of myelin mutant taiep rats.

    PubMed

    Roncagliolo, Manuel; Schlageter, Carol; León, Claudia; Couve, Eduardo; Bonansco, Christian; Eguibar, José R

    2006-01-05

    The taiep rat is a myelin mutant with an initial hypomyelination, followed by a progressive demyelination of the CNS. The neurological correlates start with tremor, followed by ataxia, immobility episodes, epilepsy and paralysis. The optic nerve, an easily-isolable central tract fully myelinated by oligodendrocytes, is a suitable preparation to evaluate the developmental impairment of central myelin. We examined the ontogenic development of optic nerve compound action potentials (CAP) throughout the first 6 months of life of control and taiep rats. Control optic nerves (ON) develop CAPs characterized by three waves. Along the first month, the CAPs of taiep rats showed a delayed maturation, with lower amplitudes and longer latencies than controls; at P30, the conduction velocity has only a third of the normal value. Later, as demyelination proceeds, the conduction velocity of taiep ONs begins to decrease and CAPs undergo a gradual temporal dispersion. CAPs of control and taiep showed differences in their pharmacological sensitivity to TEA and 4-AP, two voltage dependent K+ channel-blockers. As compared with TEA, 4-AP induced a significant increase of the amplitudes and a remarkable broadening of CAPs. After P20, unlike controls, the greater sensitivity to 4-AP exhibited by taiep ONs correlates with the detachment and retraction of paranodal loops suggesting that potassium conductances could regulate the excitability as demyelination of CNS axons progresses. It is concluded that the taiep rat, a long-lived mutant, provides a useful model to study the consequences of partial demyelination and the mechanisms by which glial cells regulate the molecular organization and excitability of axonal membranes during development and disease.

  2. Myocilin is involved in NgR1/Lingo-1-mediated oligodendrocyte differentiation and myelination of the optic nerve.

    PubMed

    Kwon, Heung Sun; Nakaya, Naoki; Abu-Asab, Mones; Kim, Hong Sug; Tomarev, Stanislav I

    2014-04-16

    Myocilin is a secreted glycoprotein that belongs to a family of olfactomedin domain-containing proteins. Although myocilin is detected in several ocular and nonocular tissues, the only reported human pathology related to mutations in the MYOCILIN gene is primary open-angle glaucoma. Functions of myocilin are poorly understood. Here we demonstrate that myocilin is a mediator of oligodendrocyte differentiation and is involved in the myelination of the optic nerve in mice. Myocilin is expressed and secreted by optic nerve astrocytes. Differentiation of optic nerve oligodendrocytes is delayed in Myocilin-null mice. Optic nerves of Myocilin-null mice contain reduced levels of several myelin-associated proteins including myelin basic protein, myelin proteolipid protein, and 2'3'-cyclic nucleotide 3'-phosphodiesterase compared with those of wild-type littermates. This leads to reduced myelin sheath thickness of optic nerve axons in Myocilin-null mice compared with wild-type littermates, and this difference is more pronounced at early postnatal stages compared with adult mice. Myocilin also affects differentiation of oligodendrocyte precursors in vitro. Its addition to primary cultures of differentiating oligodendrocyte precursors increases levels of tested markers of oligodendrocyte differentiation and stimulates elongation of oligodendrocyte processes. Myocilin stimulation of oligodendrocyte differentiation occurs through the NgR1/Lingo-1 receptor complex. Myocilin physically interacts with Lingo-1 and may be considered as a Lingo-1 ligand. Myocilin-induced elongation of oligodendrocyte processes may be mediated by activation of FYN and suppression of RhoA GTPase.

  3. Nitrogen Substituent Polarity Influences Dithiocarbamate-Mediated Lipid Oxidation, Nerve Copper Accumulation, and Myelin Injury

    PubMed Central

    Valentine, Holly L.; Viquez, Olga M.; Amarnath, Kalyani; Amarnath, Venkataraman; Zyskowski, Justin; Kassa, Endalkachew N.; Valentine, William M.

    2009-01-01

    Dithiocarbamates have a wide spectrum of applications in industry, agriculture, and medicine, with new applications being investigated. Past studies have suggested that the neurotoxicity of some dithiocarbamates may result from copper accumulation, protein oxidative damage, and lipid oxidation. The polarity of a dithiocarbamate’s nitrogen substituents influences the lipophilicity of the copper complexes it generates and thus potentially determines its ability to promote copper accumulation within nerve and induce myelin injury. In the current study, a series of dithiocarbamate-copper complexes differing in their lipophilicity were evaluated for their relative abilities to promote lipid peroxidation determined by malondialdehyde levels generated in an ethyl arachidonate oil-in-water emulsion. In a second component of this study, rats were exposed to either N,N-diethyldithiocarbamate or sarcosine dithiocarbamate; both generate dithiocarbamate-copper complexes that are lipid and water soluble, respectively. Following the exposures, brain, tibial nerve, spinal cord and liver tissue copper levels were measured by inductively coupled mass spectroscopy to assess the relative abilities of these two dithiocarbamates to promote copper accumulation. Peripheral nerve injury was evaluated using grip strengths, nerve conduction velocities and morphologic changes at the light microscope level. Additionally, the protein expression levels of glutathione transferase alpha and heme-oxygenase-1 in nerve were determined and the quantity of protein carbonyls measured to assess levels of oxidative stress and injury. The data provide evidence that dithiocarbamate-copper complexes are redox active; and that the ability of dithiocarbamate complexes to promote lipid peroxidation is correlated to the lipophilicity of the complex. Consistent with neurotoxicity requiring the formation of a lipid soluble copper complex, significant increases in copper accumulation, oxidative stress and myelin

  4. Nitrogen substituent polarity influences dithiocarbamate-mediated lipid oxidation, nerve copper accumulation, and myelin injury.

    PubMed

    Valentine, Holly L; Viquez, Olga M; Amarnath, Kalyani; Amarnath, Venkataraman; Zyskowski, Justin; Kassa, Endalkachew N; Valentine, William M

    2009-01-01

    Dithiocarbamates have a wide spectrum of applications in industry, agriculture, and medicine, with new applications being investigated. Past studies have suggested that the neurotoxicity of some dithiocarbamates may result from copper accumulation, protein oxidative damage, and lipid oxidation. The polarity of a dithiocarbamate's nitrogen substituents influences the lipophilicity of the copper complexes that it generates and thus potentially determines its ability to promote copper accumulation within nerve and induce myelin injury. In the current study, a series of dithiocarbamate-copper complexes differing in their lipophilicity were evaluated for their relative abilities to promote lipid peroxidation determined by malondialdehyde levels generated in an ethyl arachidonate oil-in-water emulsion. In a second component of this study, rats were exposed to either N,N-diethyldithiocarbamate or sarcosine dithiocarbamate; both generated dithiocarbamate-copper complexes that were lipid- and water-soluble, respectively. Following the exposures, brain, tibial nerve, spinal cord, and liver tissue copper levels were measured by inductively coupled mass spectroscopy to assess the relative abilities of these two dithiocarbamates to promote copper accumulation. Peripheral nerve injury was evaluated using grip strengths, nerve conduction velocities, and morphologic changes at the light microscope level. Additionally, the protein expression levels of glutathione transferase alpha and heme-oxygenase-1 in nerve were determined, and the quantity of protein carbonyls was measured to assess levels of oxidative stress and injury. The data provided evidence that dithiocarbamate-copper complexes are redox active and that the ability of dithiocarbamate complexes to promote lipid peroxidation is correlated to the lipophilicity of the complex. Consistent with neurotoxicity requiring the formation of a lipid-soluble copper complex, significant increases in copper accumulation, oxidative

  5. Schwann cells use TAM receptor-mediated phagocytosis in addition to autophagy to clear myelin in a mouse model of nerve injury

    PubMed Central

    Brosius Lutz, Amanda; Sloan, Steven A.; Carson, Glenn A.; Zhou, Lu; Lovelett, Emilie; Posada, Sean; Zuchero, J. Bradley; Barres, Ben A.

    2017-01-01

    Ineffective myelin debris clearance is a major factor contributing to the poor regenerative ability of the central nervous system. In stark contrast, rapid clearance of myelin debris from the injured peripheral nervous system (PNS) is one of the keys to this system’s remarkable regenerative capacity, but the molecular mechanisms driving PNS myelin clearance are incompletely understood. We set out to discover new pathways of PNS myelin clearance to identify novel strategies for activating myelin clearance in the injured central nervous system, where myelin debris is not cleared efficiently. Here we show that Schwann cells, the myelinating glia of the PNS, collaborate with hematogenous macrophages to clear myelin debris using TAM (Tyro3, Axl, Mer) receptor-mediated phagocytosis as well as autophagy. In a mouse model of PNS nerve crush injury, Schwann cells up-regulate TAM phagocytic receptors Axl and Mertk following PNS injury, and Schwann cells lacking both of these phagocytic receptors exhibit significantly impaired myelin phagocytosis both in vitro and in vivo. Autophagy-deficient Schwann cells also display reductions in myelin clearance after mouse nerve crush injury, as has been recently shown following nerve transection. These findings add a mechanism, Axl/Mertk-mediated myelin clearance, to the repertoire of cellular machinery used to clear myelin in the injured PNS. Given recent evidence that astrocytes express Axl and Mertk and have previously unrecognized phagocytic potential, this pathway may be a promising avenue for activating myelin clearance after CNS injury. PMID:28874532

  6. Anatomy of the retinal nerve fiber layer.

    PubMed

    Radius, R L; de Bruin, J

    1981-11-01

    Anatomy of the retinal nerve fiber layer in rabbit eyes is studied by light microscopy, transmission electron microscopy, and scanning electron microscopy. It is demonstrated that retinal striations noted ophthalmoscopically in these eyes represent individual fiber bundles, Axon bundles are compartmentalized within tissue tunnels comprised of elongated processes of glial cell origin.

  7. Electroactive biodegradable polyurethane significantly enhanced Schwann cells myelin gene expression and neurotrophin secretion for peripheral nerve tissue engineering.

    PubMed

    Wu, Yaobin; Wang, Ling; Guo, Baolin; Shao, Yongpin; Ma, Peter X

    2016-05-01

    Myelination of Schwann cells (SCs) is critical for the success of peripheral nerve regeneration, and biomaterials that can promote SCs' neurotrophin secretion as scaffolds are beneficial for nerve repair. Here we present a biomaterials-approach, specifically, a highly tunable conductive biodegradable flexible polyurethane by polycondensation of poly(glycerol sebacate) and aniline pentamer, to significantly enhance SCs' myelin gene expression and neurotrophin secretion for peripheral nerve tissue engineering. SCs are cultured on these conductive polymer films, and the biocompatibility of these films and their ability to enhance myelin gene expressions and sustained neurotrophin secretion are successfully demonstrated. The mechanism of SCs' neurotrophin secretion on conductive films is demonstrated by investigating the relationship between intracellular Ca(2+) level and SCs' myelination. Furthermore, the neurite growth and elongation of PC12 cells are induced by adding the neurotrophin medium suspension produced from SCs-laden conductive films. These data suggest that these conductive degradable polyurethanes that enhance SCs' myelin gene expressions and sustained neurotrophin secretion perform great potential for nerve regeneration applications.

  8. Altered hippocampal myelinated fiber integrity in a lithium-pilocarpine model of temporal lobe epilepsy: a histopathological and stereological investigation.

    PubMed

    Ye, Yuanzhen; Xiong, Jiajia; Hu, Jun; Kong, Min; Cheng, Li; Chen, Hengsheng; Li, Tingsong; Jiang, Li

    2013-07-19

    The damage of white matter, primarily myelinated fibers, in the central nervous system (CNS) of temporal lobe epilepsy (TLE) patients has been recently reported. However, limited data exist addressing the types of changes that occur to myelinated fibers inside the hippocampus as a result of TLE. The current study was designed to examine this issue in a lithium-pilocarpine rat model. Investigated by electroencephalography (EEG), Gallyas silver staining, immunohistochemistry, western blotting, transmission electron microscopy, and stereological methods, the results showed that hippocampal myelinated fibers of the epilepsy group were degenerated with significantly less myelin basic protein (MBP) expression relative to those of control group rats. Stereological analysis revealed that the total volumes of hippocampal formation, myelinated fibers, and myelin sheaths in the hippocampus of epilepsy group rats were decreased by 20.43%, 49.16%, and 52.60%, respectively. In addition, epilepsy group rats showed significantly greater mean diameters of myelinated fibers and axons, whereas the mean thickness of myelin sheaths was less, especially for small axons with diameters from 0.1 to 0.8µm, compared to control group rats. Finally, the total length of the myelinated fibers in the hippocampus of epilepsy group rats was significantly decreased by 56.92%, compared to that of the control group, with the decreased length most prominent for myelinated fibers with diameters from 0.4 to 0.8µm. This study is the first to provide experimental evidence that the integrity of hippocampal myelinated fibers is negatively affected by inducing epileptic seizures with pilocarpine, which may contribute to the abnormal propagation of epileptic discharge.

  9. Computer simulation of local anesthetic effects using a mathematical model of myelinated nerve.

    PubMed

    Condouris, G A; Goebel, R H; Brady, T

    1976-03-01

    A mathematical model of myelinated axon was programmed for digital computer solution of the consequences of the conduction characteristics when the model membrane was affected by local anesthetics simulated by alteration of the ionic conductance parameter. The effects of tetrodotoxin on impulse conduction were studied in detail by means of a systematic reduction in sodium conductance in 1 to 10 nodes of Ranvier. Rhis technique simulates the method used experimentally and clinically to achieve a conduction block with the circumscribed application of local anesthetics to segments of nerve axons or nerve trunks. The analysis of the tetrodotoxin "dose-response" relationships revealed the fact that the model myelinated axon could support three types of conduction when depressed by this drug. One type of conduction of a subnormal impulse at the nodes of Ranvier; a second is characterized by a form of decremental conduction in which the rate of decrement of the nodal impulse is linear with distance. The third type is a second form of decremental conduction which is exponential in configuration and is seen when the g(Na) at the nodes of Ranvier is reduced to less than 27% of normal. Parallel experiments were performed to simulate the effects of lidocaine and some significant differences were observed. Analysis of the action potentials within the internodel region suggests that, although immune to drug action in the model, the internodal segment affects the generation of action potentials at the nodes. A commentary is presented on the limitations of the model as it reflects known pharmacologic relationships in real myelinated axons.

  10. Myelin ultrastructure of sciatic nerve in rat experimental autoimmune neuritis model and its correlation with associated protein expression

    PubMed Central

    Yuan, Xiao-Jing; Wei, Yu-Jun; Ao, Qiang; Gong, Kai; Wang, Jian-Yong; Sun, Qiang-San; Zhang, Ling; Zheng, Zun-Cheng; Chen, Lin

    2015-01-01

    To explore the relationship of peripheral nerve ultrastructure and its associated protein expression in experimental autoimmune neuritis (EAN). EAN was established in Lewis rats using an emulsified mixture of P0 peptide 180-199, Mycobacterium tuberculosis, and incomplete Freund’s adjuvant. Rats immunized with saline solution were used as a control group. Sciatic nerve ultrastructure and immunofluorescence histopathology were measured at the neuromuscular severity peak on day 18 post-induction. Cell-specific protein markers were used for immunofluorescence histopathology staining to characterize sciatic nerve cells: CD3 (T cell), Iba-1 (microglia), S100 (myelin), and neurofilament 200 (axon). The results showed that swelling of the myelin lamellae, vesicular disorganization, separation of the myelin lamellae, and an attenuation or disappearance of the axon were observed by transmission electron microscopy in the EAN group. CD3 and Iba-1 increased significantly in the structures characterized by separation or swelling of the myelin lamellae, and increased slightly in the structures characterized by vesicular of the myelin lamellae, S100 decreased in the structures characterized by vesicular disorganization or separation of the myelin lamellae. And neurofilament 200 decreased in the structures characterized by separation of the myelin lamellae. Furthermore, we found that Iba1 were positive in the myelin sheath, and overlapped with S100, which significantly indicated that Schwann cells played as macrophage-like cells during the disease progression of ENA. Our findings may be a significant supplement for the knowledge of EAN model, and may offer a novel sight on the treatment of Guillain-Barré syndrome. PMID:26339349

  11. Effects of a 4 month enriched environment on the hippocampus and the myelinated fibers in the hippocampus of middle-aged rats.

    PubMed

    Qiu, Xuan; Huang, Chun-Xia; Lu, Wei; Yang, Shu; Li, Chen; Shi, Xiao-Yan; Chen, Lin; Xiu, Yun; Yang, Jun-Qing; Tang, Yong

    2012-07-17

    An enriched environment has been shown to enhance learning and memory and to induce morphological changes in the hippocampus. In the present study, 14-month (middle-aged) female and male Sprague-Dawley rats were randomly divided into enriched environment (EE) rats and standard environment (SE) rats. EE rats were reared in an enriched environment and SE rats were reared in a standard environment for 4 months. The spatial learning capacity was assessed with Morris water maze. The hippocampus and the myelinated fibers in the rat hippocampus were quantitatively investigated with a transmission electronic microscope technique and stereological methods. The female rats housed in an enriched environment showed improved performance in the Morris water maze. There was no significant difference in the total volume of hippocampus between SE rats and EE rats. The total length and total volume of the myelinated fibers in the hippocampus of the female and male EE rats were significantly increased, respectively, when compared to the female and male SE rats. The increase of the total length of the myelinated nerve fibers in the hippocampus was mainly due to the increase of the myelinated fibers with diameters from 0.5 to 0.9 μm. Our results showed that a 4 month enriched environment had significant effects on the spatial learning capacity and the myelinated fibers in the hippocampus of middle-aged rats. The present study might provide an important theoretical basis for searching for an ethological strategy to delay the progress of brain aging in the future.

  12. Assessment of vascularization and myelination following peripheral nerve repair using angiographic and polarization sensitive optical coherence tomography (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Nam, Ahhyun S.; Chico-Calero, Isabel; Easow, Jeena M.; Villiger, Martin; Welt, Jonathan; Winograd, Jonathan M.; Randolph, Mark A.; Redmond, Robert W.; Vakoc, Benjamin J.

    2017-02-01

    A severe traumatic injury to a peripheral nerve often requires surgical graft repair. However, functional recovery after these surgical repairs is often unsatisfactory. To improve interventional procedures, it is important to understand the regeneration of the nerve grafts. The rodent sciatic nerve is commonly used to investigate these parameters. However, the ability to longitudinally assess the reinnervation of injured nerves are limited, and to our knowledge, no methods currently exist to investigate the timing of the revascularization in functional recovery. In this work, we describe the development and use of angiographic and polarization-sensitive (PS) optical coherence tomography (OCT) to visualize the vascularization, demyelination and remyelination of peripheral nerve healing after crush and transection injuries, and across a variety of graft repair methods. A microscope was customized to provide 3.6 cm fields of view along the nerve axis with a capability to track the nerve height to maintain the nerve within the focal plane. Motion artifact rejection was implemented in the angiography algorithm to reduce degradation by bulk respiratory motion in the hindlimb site. Vectorial birefringence imaging methods were developed to significantly enhance the accuracy of myelination measurements and to discriminate birefringent contributions from the myelin and epineurium. These results demonstrate that the OCT platform has the potential to reveal new insights in preclinical studies and may ultimately provide a means for clinical intra-surgical assessment of peripheral nerve function.

  13. Modelling the effects of electric fields on nerve fibres: influence of the myelin sheath.

    PubMed

    Richardson, A G; McIntyre, C C; Grill, W M

    2000-07-01

    The excitation and conduction properties of computer-based cable models of mammalian motor nerve fibres, incorporating three different myelin representations, are compared. The three myelin representations are a perfectly insulating single cable (model A), a finite impedance single cable (model B) and a finite impedance double cable (model C). Extracellular stimulation of the three models is used to study their strength-duration and current-distance (I-X) relationships, conduction velocity (CV) and action potential shape. All three models have a chronaxie time that is within the experimental range. Models B and C have increased threshold currents compared with model A, but each model has slope to the I-X relationship that matches experimental results. Model B has a CV that matches experimental data, whereas the CV of models A and C are above and below the experimental range, respectively. Model C is able to produce a depolarising afterpotential (DAP), whereas models A and B exhibit hyperpolarising afterpotentials. Models A and B are determined to be the preferred models when low-frequency stimulation (< approximately 25 Hz) is used, owing to their efficiency and accurate excitation and conduction properties. For high frequency stimulation (approximately 25 Hz and greater), model C, with its ability to produce a DAP, is necessary accurately to simulate excitation behaviour.

  14. The recovery heat production in non-myelinated garfish olfactory nerve fibres.

    PubMed Central

    Howarth, J V; Ritchie, J M

    1979-01-01

    1. The recovery heat production of the non-myelinated fibres of garfish olfactory nerve has been measured. 2. At about 20 degrees C the total recovery heat was 381 +/- 26 microcal g-1 impulse-1 at a stimulation frequency of 2 sec-1. 3. The time constant of decay of the recovery heat production after a brief period of stimulation was 78.7 +/- 3.1 sec at about 20 degrees C. 4. Changing the temperature (by +/- 5 degress C) had little effect on the total recovery heat produced. 5. However, lowering the temperature reduced both the rate of rise, and the maximum rate of recovery heat production whereas the time constant of decay was increased. Raising the temperature produced corresponding changes in the opposite direction. 6. the recovery heat production measured in the present experiments is consistent with the previously measured oxygen consumption in the same preparation. PMID:490341

  15. The use of fiber-reinforced scaffolds cocultured with Schwann cells and vascular endothelial cells to repair rabbit sciatic nerve defect with vascularization.

    PubMed

    Gao, Hongyang; You, Yang; Zhang, Guoping; Zhao, Feng; Sha, Ziyi; Shen, Yong

    2013-01-01

    To explore the feasibility of biodegradable fiber-reinforced 3D scaffolds with satisfactory mechanical properties for the repair of long-distance sciatic nerve defect in rabbits and effects of vascularized graft in early stage on the recovery of neurological function, Schwann cells and vascular endothelial cells were cocultured in the fiber-reinforced 3D scaffolds. Experiment group which used prevascularized nerve complex for the repair of sciatic nerve defect and control group which only cultured with Schwann cells were set. The animals in both groups underwent electromyography to show the status of the neurological function recovery at 4, 8, and 16 weeks after the surgery. Sciatic nerve regeneration and myelination were observed under the light microscope and electron microscope. Myelin sheath thickness, axonal diameter, and number of myelinated nerve fiber were quantitatively analyzed using image analysis system. The recovery of foot ulcer, the velocity of nerve conduction, the number of regenerating nerve fiber, and the recovery of ultrastructure were increased in the experimental group than those in the control group. Prevascularized tissue engineered fiber-reinforced 3D scaffolds for the repair of sciatic nerve defects in rabbits can effectively promote the recovery of neurological function.

  16. Order-disorder phenomena in myelinated nerve sheaths: V. Effects of temperature on rat sciatic and optic nerves, and structural differences between the two types of nerve.

    PubMed

    Mateu, L; Luzzati, V; Vonasek, E; Mateu, E; Villegas, G M; Vargas, R

    1995-01-13

    We describe in this work X-ray scattering and electron microscope studies of rat sciatic and optic nerves as a function of temperature. The scattering experiments were analyzed as described in the previous papers of this series: a variety of parameters were determined, some of which characterize the lattice disorder, others the structure of the motif. The main results are the following. All the parameters determined by the X-ray scattering study vary with temperature and the temperature-dependence is specific for the type of nerve (sciatic or optic). Most of the disorder-related parameters display a minimum or a maximum in the vicinity of physiological temperature (38 degrees C in rat); this observation, strongly supported by the electron microscope study, shows that the degree of organization of myelin is highest near physiological temperature. The structure of the motif, as revealed by the electron density profile, is fairly different in the two types of nerves (in contrast with the assumption made by previous workers); the structure also varies with temperature and the temperature-induced alterations are nerve-type specific. In the two types of nerve the thickness of the lipid bilayer varies with temperature as expected for a lipid-containing system with hydrocarbon chains in the disordered conformation. In sciatic nerve the thickness of the (thinner) cytoplasmic polar layer, which is also the layer most affected by lattice disorder in this type of nerve, decreases dramatically with increasing temperature. In optic nerve, in which lattice disorder predominantly affects the extracellular layer, the thickness of both the cytoplasmic and the extracellular layer is barely affected by temperature.

  17. Unmyelinated axons are more vulnerable to degeneration than myelinated axons of the cardiac nerve in Parkinson's disease.

    PubMed

    Orimo, S; Uchihara, T; Kanazawa, T; Itoh, Y; Wakabayashi, K; Kakita, A; Takahashi, H

    2011-12-01

    We recently demonstrated accumulation of α-synuclein aggregates of the cardiac sympathetic nerve in Parkinson's disease (PD) and a possible relationship between degeneration of the cardiac sympathetic nerve and α-synuclein aggregates. The aim of this study is to determine whether there is a difference in the degenerative process between unmyelinated and myelinated axons of the cardiac nerve. We immunohistochemically examined cardiac tissues from four pathologically verified PD patients, nine patients with incidental Lewy body disease (ILBD) and five control subjects, using antibodies against neurofilament, myelin basic protein (MBP) and α-synuclein. First, we counted the number of neurofilament-immunoreactive axons not surrounded by MBP (unmyelinated axons) and those surrounded by MBP (myelinated axons). Next, we counted the number of unmyelinated and myelinated axons with α-synuclein aggregates. (i) The percentage of unmyelinated axons in PD (77.5 ± 9.14%) was significantly lower compared to that in control subjects (92.2 ± 2.40%). (ii) The ratio of unmyelinated axons with α-synuclein aggregates to total axons with α-synuclein aggregates in ILBD ranged from 94.4 to 100 (98.2 ± 2.18%). Among axons with α-synuclein aggregates, unmyelinated axons were the overwhelming majority, comprising 98.2%. These findings suggest that in PD unmyelinated axons are more vulnerable to degeneration than myelinated axons of the cardiac nerve, because α-synuclein aggregates accumulate much more abundantly in unmyelinated axons. © 2011 The Authors. Neuropathology and Applied Neurobiology © 2011 British Neuropathological Society.

  18. Repetitive Adjustment to Estimate the Electric Current Sources in a Nerve Fiber with Magnetic Field Measurement

    NASA Astrophysics Data System (ADS)

    Hayami, Takehito; Mishima, Yukuo; Hiwaki, Osamu

    Magnetic field measuring equipment provides us the way to examine the active position of a peripheral nerve without contact or invasion. To develop a process to estimate the position precisely, simulation study of the magnetic field induced by a myelinated nerve fiber was executed. The electric current sources around the active position of a nerve fiber can be approximated as a pair of electric current dipoles, which represent depolarization and repolarization respectively. Therefore the current sources to estimate from the detected pattern of the magnetic field were modeled as a pair of electric current dipoles. A repetitive adjustment process was proposed as an effective method to find the appropriate positions of the dipoles as the sources of the magnetic fields.

  19. The history of myelin.

    PubMed

    Boullerne, Anne Isabelle

    2016-09-01

    Andreas Vesalius is attributed the discovery of white matter in the 16th century but van Leeuwenhoek is arguably the first to have observed myelinated fibers in 1717. A globular myelin theory followed, claiming all elements of the nervous system except for Fontana's primitive cylinder with outer sheath in 1781. Remak's axon revolution in 1836 relegated myelin to the unknown. Ehrenberg described nerve tubes with double borders in 1833, and Schwann with nuclei in 1839, but the medullary sheath acquired its name of myelin, coined by Virchow, only in 1854. Thanks to Schultze's osmium specific staining in 1865, myelin designates the structure known today. The origin of myelin though was baffling. Only after Ranvier discovered a periodic segmentation, which came to us as nodes of Ranvier, did he venture suggesting in 1872 that the nerve internode was a fatty cell secreting myelin in cytoplasm. Ranvier's hypothesis was met with high skepticism, because nobody could see the cytoplasm, and the term Schwann cell very slowly emerged into the vocabulary with von Lenhossék in 1895. When Cajal finally admitted the concept of Schwann cell internode in 1912, he still firmly believed myelin was secreted by the axon. Del Río-Hortega re-discovered oligodendrocytes in 1919 (after Robertson in 1899) and named them oligodendroglia in 1921, thereby antagonizing Cajal for discovering a second cell type in his invisible third element. Penfield had to come to del Río-Hortega's rescue in 1924 for oligodendrocytes to be accepted. They jointly hypothesized myelin could be made by oligodendrocytes, considered the central equivalent of Schwann cells. Meanwhile myelin birefringence properties observed by Klebs in 1865 then Schmidt in 1924 confirmed its high fatty content, ascertained by biochemistry by Thudichum in 1884. The 20th century saw X-ray diffraction developed by Schmitt, who discovered in 1935 the crystal-like organization of this most peculiar structure, and devised the g

  20. WATER TRANSPORT IN INVERTEBRATE PERIPHERAL NERVE FIBERS

    PubMed Central

    Nevis, Arnold H.

    1958-01-01

    Osmotic and diffusion permeabilities (Pf and Pd) of invertebrate nerve fibers to tritiated water were measured to determine what water flux studies could reveal about "the nerve membrane" and to directly test the possibility of active transport of water into or out of invertebrate nerve fibers. Pf/Pd ratios for lobster walking leg nerve fibers were found to be about 20 ± 7 at 14°C. Pd measurements were made for squid giant axons at 25°C. and found to yield a value of 4 x 10–4 cm.–1 sec.–1. When combined with the data of D. K. Hill for Pf, a Pf/Pd ratio of 21 ± 5 is obtained. These Pf/Pd ratios correspond to "effective pore radii" of about 16 ± 4 angstrom units, according to theories developed by Koefoed-Johnsen and Ussing and independently by Pappenheimer and his colleagues. Variations of water flux ratios with temperatures were studied and apparent activation energies calculated for both diffusion experiments and osmotic filtration experiments using the Arrhenius equation, and found to be close to 3 to 5 cal. per mole of water transferred. Cyanide (5 x 10–3 molar) and iodoacetate (1 x 10–3 molar) poisoned lobster leg nerve fibers showed no appreciable change in diffusion or osmotic filtration water effluxes. Caution in interpreting these proposed channels as simple pores was emphasized, but the possibility that such channels exist and are related to ionic flow is not incompatible with electrophysiological data. PMID:13525675

  1. The history of myelin

    PubMed Central

    Boullerne, Anne Isabelle

    2016-01-01

    Andreas Vesalius is attributed the discovery of white matter in the 16th century but van Leeuwenhoek is arguably the first to have observed myelinated fibers in 1717. A globular myelin theory followed, claiming all elements of the nervous system except for Fontana’s primitive cylinder with outer sheath in 1781. Remak’s axon revolution in 1836 relegated myelin to the unknown. Ehrenberg described nerve tubes with double borders in 1833, and Schwann with nuclei in 1839, but the medullary sheath acquired its name of myelin, coined by Virchow, only in 1854. Thanks to Schultze’s osmium specific staining in 1865, myelin designates the structure known today. The origin of myelin though was baffling. Only after Ranvier discovered a periodic segmentation, which came to us as nodes of Ranvier, did he venture suggesting in 1872 that the nerve internode was a fatty cell secreting myelin in cytoplasm. Ranvier’s hypothesis was met with high skepticism, because nobody could see the cytoplasm, and the term Schwann cell very slowly emerged into the vocabulary with von Lenhossék in 1895. When Cajal finally admitted the concept of Schwann cell internode in 1912, he still firmly believed myelin was secreted by the axon. Del Río-Hortega re-discovered oligodendrocytes in 1919 (after Robertson in 1899) and named them oligodendroglia in 1921, thereby antagonizing Cajal for discovering a second cell type in his invisible third element. Penfield had to come to del Río-Hortega’s rescue in 1924 for oligodendrocytes to be accepted. They jointly hypothesized myelin could be made by oligodendrocytes, considered the central equivalent of Schwann cells. Meanwhile myelin birefringence properties observed by Klebs in 1865 then Schmidt in 1924 confirmed its high fatty content, ascertained by biochemistry by Thudichum in 1884. The 20th century saw X-ray diffraction developed by Schmitt, who discovered in 1935 the crystal-like organization of this most peculiar structure, and devised the g

  2. Innocuous, Not Noxious, Input Activates PKCγ Interneurons of the Spinal Dorsal Horn via Myelinated Afferent Fibers

    PubMed Central

    Braz, Joao M.; Skinner, Kate; Llewellyn-Smith, Ida J.; Basbaum, Allan I.

    2008-01-01

    Protein kinase C γ (PKCγ), which is concentrated in interneurons of the inner part of lamina II of the dorsal horn, has been implicated in injury-induced allodynia, a condition wherein pain is produced by innocuous stimuli. Although it is generally assumed that these interneurons receive input from the nonpeptidergic, IB4-positive subset of nociceptors, the fact that PKCγ cells do not express Fos in response to noxious stimulation suggests otherwise. Here, we demonstrate that the terminal field of the nonpeptidergic population of nociceptors, in fact, lies dorsal to that of PKCγ interneurons. There was also no overlap between the PKCγ-expressing interneurons and the transganglionic tracer wheat germ agglutinin which, after sciatic nerve injection, labels all unmyelinated nociceptors. However, transganglionic transport of the β-subunit of cholera toxin, which marks the medium-diameter and large-diameter myelinated afferents that transmit non-noxious information, revealed extensive overlap with the layer of PKCγ interneurons. Furthermore, expression of a transneuronal tracer in myelinated afferents resulted in labeling of PKCγ interneurons. Light and electron microscopic double labeling further showed that the VGLUT1 subtype of vesicular glutamate transmitter, which is expressed in myelinated afferents, marks synapses that are presynaptic to the PKCγ interneurons. Finally, we demonstrate that a continuous non-noxious input, generated by walking on a rotarod, induces Fos in the PKCγ interneurons. These results establish that PKCγ interneurons are activated by myelinated afferents that respond to innocuous stimuli, which suggests that injury-induced mechanical allodynia is transmitted through a circuit that involves PKCγ interneurons and non-nociceptive, VGLUT1-expressing myelinated primary afferents. PMID:18685019

  3. High concentration of phosphorus is a distinctive feature of myelin. An X-ray elemental microanalysis study using freeze-fracture scanning electron microscopy of rat sciatic nerve.

    PubMed

    Oliveira, Maria João; Águas, Artur P

    2015-07-01

    We have used rat sciatic nerves submitted to freezing and freeze-fracture to determine the elemental composition of small domains of the peripheral nerve studied at high resolution by scanning electron microscopy. We found that myelin of Schwann cells is unique in its high content in phosphorus (P) that was more than 10 times higher than P measured in any other cells. This high concentration in P makes myelin chemistry suitable of monitoring at the subcellular level using the herein described methodology.

  4. Activation of peripheral nerve fibers by electrical stimulation in the sole of the foot

    PubMed Central

    2013-01-01

    Background Human nociceptive withdrawal reflexes (NWR) can be evoked by electrical stimulation applied to the sole of the foot. However, elicitation of NWRs is highly site dependent, and NWRs are especially difficult to elicit at the heel. The aim of the present study was to investigate potential peripheral mechanisms for any site dependent differences in reflex thresholds. Results The first part of the study investigated the neural innervation in different sites of the sole of the foot using two different staining techniques. 1) Staining for the Nav1.7 antigen (small nociceptive fibers) and 2) the Sihler whole nerve technique (myelinated part of the nerve). No differences in innervation densities were found across the sole of the foot using the two staining techniques: Nav1.7 immunochemistry (small nociceptive fibers (1-way ANOVA, NS)) and the Sihler’s method (myelinated nerve fibers (1-way ANOVA, NS)). However, the results indicate that there are no nociceptive intraepidermal nerve fibers (IENFs) innervating the heel. Secondly, mathematical modeling was used to investigate to what degree differences in skin thicknesses affect the activation thresholds of Aδ and Aβ fibers in the sole of the foot. The modeling comprised finite element analysis of the volume conduction combined with a passive model of the activation of branching cutaneous nerve fibers. The model included three different sites in the sole of the foot (forefoot, arch and heel) and three different electrode sizes (diameters: 9.1, 12.9, and 18.3 mm). For each of the 9 combinations of site and electrode size, a total of 3000 Aβ fibers and 300 Aδ fibers was modeled. The computer simulation of the effects of skin thicknesses and innervation densities on thresholds of modeled Aδ and Aβ fibers did not reveal differences in pain and perception thresholds across the foot sole as have been observed experimentally. Instead a lack of IENFs at the heel decreased the electrical activation thresholds

  5. Modification of sodium channels in myelinated nerve by Anemonia sulcata toxin II.

    PubMed

    Ulbricht, W; Schmidtmayer, J

    1981-05-01

    1. Single myelinated nerve fibres of the frog, Rana esculenta, were investigated predominantly in voltage clamp experiments. 2. Sodium current (INa) inactivation was measured in the presence of 10 mM TEA to suppress IK. Inactivation was diphasic but complete in toxin-free solution; it was delayed and became incomplete in Anemonia sulcata toxin II (ATX II) leading to persistent INa flow even during long depolarizations. The effects were reversible. Activation was not affected. 3. The persistent INa component increased with increasing toxin concentration and saturated at ca. 15 microM. The lowest concentration yielding unequivocal effects in the voltage clamp was 0.5 microM. 4. The curve relating the steady-state inactivation parameter, h infinity to the conditioning potential V became non-monotonic in ATX II i.e. dh infinity/dV greater than 0 for V greater than 30 mV. 5. Inactivation could be formally described by a three-state model with two conducting (h2 and h2) and one closed state (x) in the sequence h1 in equilibrium x in equilibrium h2. 6. Ca2+ modifies h2(V) more than h1(V) whose reaction to Ca2+ is similar to h(V) in toxin-free solution. The Ca2+ effect is very rapid and reversible.

  6. Refined distribution of myelinated trigeminal proprioceptive nerve fibres in Mueller's muscle as the mechanoreceptors to induce involuntary reflexive contraction of the levator and frontalis muscles.

    PubMed

    Yuzuriha, Shunsuke; Matsuo, Kiyoshi; Hirasawa, Chihiro; Moriizumi, Tetsuji

    2009-11-01

    Stretching of mechanoreceptors in Mueller's muscle induces reflexive contraction of not only the levator muscle but also the frontalis muscle as two different eyelid-opening muscles. Previously, we reported that fine neural myelinated structures, acting as mechanoreceptors, were found in the proximal Mueller's muscle. Since there is a risk of misunderstanding that the middle and distal Mueller's muscle does not contain mechanoreceptors and can be invalidated or resected, the accurate distribution of myelinated trigeminal proprioceptive nerve fibres as mechanoreceptors in Mueller's muscle was refined horizontally in this study. We explored 10 whole Mueller's muscles between the levator muscle and the tarsus of the upper eyelids obtained from five Japanese cadavers. The specimens were serially sliced along the horizontal plane and stained with HE, S-100 protein to determine the presence of Schwann cells, and smooth muscle actin antibody to determine the presence of Mueller's smooth muscle fibres. Although all myelinated nerve fibres in the intermuscular connective tissues among the sympathetically innervated Mueller's multi-unit smooth muscle fibres may not correspond to the proprioceptive nerve fibres, the nerve bundles consisting of multiple myelinated nerve fibres were well distributed in the proximal Mueller's muscle, and single myelinated nerve fibres were well distributed in the middle and distal Mueller's muscle. We believe that the mechanoreceptors in Mueller's muscle consist of myelinated proprioceptive nerve fibres with nerve endings possibly attached to collagen fibres in the intermuscular connective tissues present among Mueller's smooth muscle fibres. As the myelinated nerve fibres innervate the middle and distal Mueller's muscle to a greater extent than those in the proximal Mueller's muscle, the former may be more important as mechanoreceptors than the latter and should not be invalidated or excised during surgery for treatment of blepharoptosis to

  7. Evidence that contact with connective tissue matrix is required for normal interaction between Schwann cells and nerve fibers

    PubMed Central

    1978-01-01

    Explants of fetal rat sensory ganglia, cultured under conditions allowing axon and Schwann cell outgrowth in the absence of fibroblasts, occasionally develop nerve fascicles that are partially suspended in culture medium above the collagen substrate. In these suspended regions, fascicles are abnormal in that Schwann cells are decreased in number, are confined to occasional clusters along the fascicle, provide ensheathment for only a few axons at the fascicle periphery, and do not form myelin. When these fascicles are presented with a substrate of reconstituted rat-tail collagen, Schwann cell numbers increase, ensheathment of small nerve fibers occurs normally, and larger axons are myelinated. We conclude that, for normal development, Schwann cells require contact with extracellular matrix as well as axons. The Schwann cell abnormalities in suspended fascicles are similar to those observed in nerve roots of dystrophic mice. PMID:701366

  8. The oxygen consumption of mammalian non-myelinated nerve fibres at rest and during activity

    PubMed Central

    Ritchie, J. M.

    1967-01-01

    1. A study has been made of the oxygen consumption of non-myelinated nerve fibres of rabbit desheathed cervical vagus nerves at rest and during activity. 2. The average resting oxygen consumption (Qr) was 0·0924 μmole/g. min at 21° C. Stimulation for 1-3 min at 3/sec caused an extra oxygen consumption (Qs) of 816 p-mole/g.shock. 3. When the frequency of stimulation was increased, to 10/sec and 30/sec, Qs fell. When the frequency was decreased, to 1/sec and 0·3/sec, Qs increased slightly. 4. When the temperature was decreased, Qr fell; when the temperature was increased, Qs also increased. Temperature similarly affected Qs with high frequencies of stimulation, but had relatively little effect on Qs at low frequencies of stimulation. 5. An isolated single shock seemed to produce an increase in oxygen consumption of about 1200 p-mole/g, and this value was largely independent of temperature. 6. When part of the sodium in the Locke solution was replaced by barium, Qr decreased (by 12%) whereas Qs increased (by 87%). 7. Veratrine (1 μg/ml.) increased both Qr (by 142%) and Qs (by 361%). 8. Acetylcholine (1·7 mM) increased Qr (by 32%). 9. When nerves were transferred to potassium-free solutions there was little change in Qr, and Qs fell slightly (by 8%). 10. When the potassium concentration in the Locke solution was increased 4-fold, Qr increased (by 27%). 11. Salicylate (1-10 mM) increased Qr (by 24%) and abolished Qs. 12. When the sodium of Locke solution was replaced by lithium, Qr decreased (by 19%) and Qs was abolished. 13. In sodium-Locke solution ouabain (100 μM) decreased Qr (by 26%) and abolished Qs. In lithium-Locke solution ouabain also decreased Qr (by 28%). 14. All or nearly all of the oxygen consumed at rest or during activity seemed to be used to pump potassium ions into, and sodium ions out of, the axoplasm. 15. The K/O2 ratio during pumping was about 5·0. PMID:6032203

  9. Cranial nerve vascular compression syndromes of the trigeminal, facial and vago-glossopharyngeal nerves: comparative anatomical study of the central myelin portion and transitional zone; correlations with incidences of corresponding hyperactive dysfunctional syndromes.

    PubMed

    Guclu, Bulent; Sindou, Marc; Meyronet, David; Streichenberger, Nathalie; Simon, Emile; Mertens, Patrick

    2011-12-01

    The aim of this study was to evaluate the anatomy of the central myelin portion and the central myelin-peripheral myelin transitional zone of the trigeminal, facial, glossopharyngeal and vagus nerves from fresh cadavers. The aim was also to investigate the relationship between the length and volume of the central myelin portion of these nerves with the incidences of the corresponding cranial dysfunctional syndromes caused by their compression to provide some more insights for a better understanding of mechanisms. The trigeminal, facial, glossopharyngeal and vagus nerves from six fresh cadavers were examined. The length of these nerves from the brainstem to the foramen that they exit were measured. Longitudinal sections were stained and photographed to make measurements. The diameters of the nerves where they exit/enter from/to brainstem, the diameters where the transitional zone begins, the distances to the most distal part of transitional zone from brainstem and depths of the transitional zones were measured. Most importantly, the volume of the central myelin portion of the nerves was calculated. Correlation between length and volume of the central myelin portion of these nerves and the incidences of the corresponding hyperactive dysfunctional syndromes as reported in the literature were studied. The distance of the most distal part of the transitional zone from the brainstem was 4.19  ±  0.81 mm for the trigeminal nerve, 2.86  ±  1.19 mm for the facial nerve, 1.51  ±  0.39 mm for the glossopharyngeal nerve, and 1.63  ±  1.15 mm for the vagus nerve. The volume of central myelin portion was 24.54  ±  9.82 mm(3) in trigeminal nerve; 4.43  ±  2.55 mm(3) in facial nerve; 1.55  ±  1.08 mm(3) in glossopharyngeal nerve; 2.56  ±  1.32 mm(3) in vagus nerve. Correlations (p  < 0.001) have been found between the length or volume of central myelin portions of the trigeminal, facial, glossopharyngeal and vagus nerves and incidences

  10. Ex vivo and in vivo imaging of myelin fibers in mouse brain by coherent anti-Stokes Raman scattering microscopy.

    PubMed

    Fu, Yan; Huff, T Brandon; Wang, Han-Wei; Wang, Haifeng; Cheng, Ji-Xin

    2008-11-24

    Coherent anti-Stokes Raman scattering (CARS) microscopy was applied to image myelinated fibers in different regions of a mouse brain. The CARS signal from the CH2 symmetric stretching vibration allows label-free imaging of myelin sheath with 3D sub-micron resolution. Compared with two-photon excited fluorescence imaging with lipophilic dye labeling, CARS microscopy provides sharper contrast and avoids photobleaching. The CARS signal exhibits excitation polarization dependence which can be eliminated by reconstruction of two complementary images with perpendicular excitation polarizations. The capability of imaging myelinated fibers without exogenous labeling was used to map the whole brain white matter in brain slices and to analyze the microstructural anatomy of brain axons. Quantitative information about fiber volume%, myelin density, and fiber orientations was derived. Combining CARS with two-photon excited fluorescence allowed multimodal imaging of myelinated axons and other cells. Furthermore, in vivo CARS imaging on an upright microscope clearly identified fiber bundles in brain subcortex white matter. These advances open up new opportunities for the study of brain connectivity and neurological disorders.

  11. Quantitative studies of the regeneration of rat myelinated nerve fibres: variations in the number and size of regenerating fibres after repeated localized freezings.

    PubMed Central

    Mira, J C

    1979-01-01

    The number and size of myelinated nerve fibres were determined in the nerve to the medial head of the gastrocnemius muscles of rats whose left sciatic nerve was repeatedly frozen (one to five times at three weekly intervals). The contralateral nerve was used as a control. Results varied according to the number of freezings performed and, for a given number of freezings, according to the period of regeneration. When measurements were completed 1 month after the last of several localized freezings, the number of regenerating myelinated nerve fibres increased regularly up to the third freezing, reaching to about 220% of the control value, but no higher values were recorded after four or five freezings. The nerve fibre distribution was unimodal in all the nerves studied. The mean diameter of all myelinated fibres decreased with the number of freezings from 50% of the control value after the first to 36% after the fifth. When measurements were made 1, 3, 6, 12 and 18 months after the third and final freezing, the number of regenerating myelinated nerve fibres decreased by about 30% between the first and third month and then stabilized at 190% of the control value. Nerve fibre distribution became bimodal from the third month onwards, and the mean diameter of all myelinated fibres increased regularly. However, by the eighteenth month, the size of regenerated myelinated nerve fibres had only reached 70% of the normal contralateral value. Images Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 15 Fig. 16 Fig. 17 Fig. 18 PMID:511774

  12. Computerized enhancement of retinal nerve fiber layer.

    PubMed

    Peli, E; Hedges, T R; Schwartz, B

    1986-04-01

    We investigated a number of image processing techniques for enhancing the retinal nerve fiber layer (NFL) in fundus photographs taken with red-free light. Wedge-type defects within the NFL were enhanced best by contrast enhancement algorithms such as histogram modification and extremum sharpening. Narrow, slitlike NFL defects can be enhanced by directional enhancement techniques. Normal NFL features were enhanced best by high-pass filtering techniques such as homomorphic filtering and adaptive enhancement. The enhanced normal NFL may be useful in the analysis of diffuse NFL loss. All of these successful enhancements of normal and defective features indicate that enhancing fundus photographs with digital image processing techniques should facilitate early detection of optic nerve damage from glaucoma and other diseases.

  13. A reliable in vitro model for studying peripheral nerve myelination in mouse.

    PubMed

    Stettner, Mark; Wolffram, Kathleen; Mausberg, Anne K; Wolf, Christian; Heikaus, Sebastian; Derksen, Angelika; Dehmel, Thomas; Kieseier, Bernd C

    2013-03-30

    The rat dorsal root ganglia (DRG) model is a long-standing in vitro model for analysis of myelination in the peripheral nervous system. For performing systematic, high throughput analysis with transgenic animals, a simplified BL6 mouse protocol is indispensable. Here we present a stable and reliable protocol for myelinating co-cultures producing a high myelin ratio using cells from C57BL/6 mice. As an easy accessible and operable method, Sudan staining proved to be efficient in myelin detection for fixed cultures. Green fatty acid stain turned out to be highly reliable for analysis of the dynamic biological processes of myelination in vital cultures. Once myelinated we were able to induce demyelination by the addition of forskolin into the model system. In addition, we provide an optimised rat DRG protocol with significantly improved myelin ratio and a comparison of the protocols presented. Our results strengthen the value of ex vivo myelination models in neurobiology. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Laminin gamma1 is critical for Schwann cell differentiation, axon myelination, and regeneration in the peripheral nerve.

    PubMed

    Chen, Zu-Lin; Strickland, Sidney

    2003-11-24

    Laminins are heterotrimeric extracellular matrix proteins that regulate cell viability and function. Laminin-2, composed of alpha2, beta1, and gamma1 chains, is a major matrix component of the peripheral nervous system (PNS). To investigate the role of laminin in the PNS, we used the Cre-loxP system to disrupt the laminin gamma1 gene in Schwann cells. These mice have dramatically reduced expression of laminin gamma1 in Schwann cells, which results in a similar reduction in laminin alpha2 and beta1 chains. These mice exhibit motor defects which lead to hind leg paralysis and tremor. During development, Schwann cells that lack laminin gamma1 were present in peripheral nerves, and proliferated and underwent apoptosis similar to control mice. However, they were unable to differentiate and synthesize myelin proteins, and therefore unable to sort and myelinate axons. In mutant mice, after sciatic nerve crush, the axons showed impaired regeneration. These experiments demonstrate that laminin is an essential component for axon myelination and regeneration in the PNS.

  15. Scaling factor relating conduction velocity and diameter for myelinated afferent nerve fibres in the cat hind limb.

    PubMed Central

    Boyd, I A; Kalu, K U

    1979-01-01

    1. Compound action potentials were recorded from certain muscle and cutaneous nerves in normal and chronically de-efferentated hind limbs of cats during stimulation of the appropriate dorsal spinal roots, 2. The peaks for groups I, II and III in the compound action potential were correlated with the corresponding peaks in the fibre-diameter histograms of the same de-efferentated nerve after processing it for light microscopy. 3. The scaling factor (ratio of conduction velocity in m/sec to total diameter in micrometer) was not constant for all sizes of fibre nor did it increase progressively with fibre size. Evidence is presented that a logarithmic relation between conduction velocity and fibre diameter is not appropriate. 4. In muscle nerves the scaling factor for fibres fixed by glutaraldehyde perfusion and embedded in Epon was 5.7 for group I afferent fibres and 4.6 for myelinated fibres in both group II and group III. 5. In cutaneous nerves the scaling factor was 5.6 for large fibres (group I or Abeta) and 4.6 for small fibres (group III or Adelta). 6. The scaling factor for group I fibres is the same as was found previously for alpha-efferent fibres, and that for groups II and III is the same as for gamma-efferent fibres (Boyd & Davey, 1968). 7. The possibility that there is a clear discontinuity in scaling factor between fibres in groups I and alpha, and those in other functional groups, is discussed. 8. It is concluded that there must be some structural feature of alpha and group I fibres which differs from that of smaller myelinated fibres. It is likely that a difference in the relative thickness of the myelin sheath is involved and possibly also in the conductances responsible for generating the action potential. Images Plate 1 PMID:458657

  16. Improved Intraoperative Visualization of Nerves through a Myelin-Binding Fluorophore and Dual-Mode Laparoscopic Imaging.

    PubMed

    Cotero, Victoria E; Kimm, Simon Y; Siclovan, Tiberiu M; Zhang, Rong; Kim, Evgenia M; Matsumoto, Kazuhiro; Gondo, Tatsuo; Scardino, Peter T; Yazdanfar, Siavash; Laudone, Vincent P; Tan Hehir, Cristina A

    2015-01-01

    The ability to visualize and spare nerves during surgery is critical for avoiding chronic morbidity, pain, and loss of function. Visualization of such critical anatomic structures is even more challenging during minimal access procedures because the small incisions limit visibility. In this study, we focus on improving imaging of nerves through the use of a new small molecule fluorophore, GE3126, used in conjunction with our dual-mode (color and fluorescence) laparoscopic imaging instrument. GE3126 has higher aqueous solubility, improved pharmacokinetics, and reduced non-specific adipose tissue fluorescence compared to previous myelin-binding fluorophores. Dosing and kinetics were initially optimized in mice. A non-clinical modified Irwin study in rats, performed to assess the potential of GE3126 to induce nervous system injuries, showed the absence of major adverse reactions. Real-time intraoperative imaging was performed in a porcine model. Compared to white light imaging, nerve visibility was enhanced under fluorescence guidance, especially for small diameter nerves obscured by fascia, blood vessels, or adipose tissue. In the porcine model, nerve visualization was observed rapidly, within 5 to 10 minutes post-intravenous injection and the nerve fluorescence signal was maintained for up to 80 minutes. The use of GE3126, coupled with practical implementation of an imaging instrument may be an important step forward in preventing nerve damage in the operating room.

  17. Improved Intraoperative Visualization of Nerves through a Myelin-Binding Fluorophore and Dual-Mode Laparoscopic Imaging

    PubMed Central

    Cotero, Victoria E.; Kimm, Simon Y.; Siclovan, Tiberiu M.; Zhang, Rong; Kim, Evgenia M.; Matsumoto, Kazuhiro; Gondo, Tatsuo; Scardino, Peter T.; Yazdanfar, Siavash; Laudone, Vincent P.; Tan Hehir, Cristina A.

    2015-01-01

    The ability to visualize and spare nerves during surgery is critical for avoiding chronic morbidity, pain, and loss of function. Visualization of such critical anatomic structures is even more challenging during minimal access procedures because the small incisions limit visibility. In this study, we focus on improving imaging of nerves through the use of a new small molecule fluorophore, GE3126, used in conjunction with our dual-mode (color and fluorescence) laparoscopic imaging instrument. GE3126 has higher aqueous solubility, improved pharmacokinetics, and reduced non-specific adipose tissue fluorescence compared to previous myelin-binding fluorophores. Dosing and kinetics were initially optimized in mice. A non-clinical modified Irwin study in rats, performed to assess the potential of GE3126 to induce nervous system injuries, showed the absence of major adverse reactions. Real-time intraoperative imaging was performed in a porcine model. Compared to white light imaging, nerve visibility was enhanced under fluorescence guidance, especially for small diameter nerves obscured by fascia, blood vessels, or adipose tissue. In the porcine model, nerve visualization was observed rapidly, within 5 to 10 minutes post-intravenous injection and the nerve fluorescence signal was maintained for up to 80 minutes. The use of GE3126, coupled with practical implementation of an imaging instrument may be an important step forward in preventing nerve damage in the operating room. PMID:26076448

  18. Rate of action of Anemonia sulcata toxin II on sodium channels in myelinated nerve fibres.

    PubMed

    Schmidtmayer, J; Stoye-Herzog, M; Ulbricht, W

    1982-10-01

    1. The effect of Anemonia sulcata toxin II (ATX II) on single myelinated nerve fibres of the frog, Rana esculenta, was investigated. 2. ATX II promptly and reversibly increased the duration of action potentials; on applying 9.5 micro M the time, t0.5, to reach half of the final effect was 2.6 s. In the presence of 10 mM tetraethylammonium the duration was very sensitive to ATX II and as little as 10 nM could be detected. 3. The underlying mechanism was a diphasic incomplete inactivation of sodium channels which, at 15 degrees C, caused a sizeable INa to persist after 15 ms depolarization (I15ms). 4. On applying 5 micro M (1.25 micro M) ATX II at ca. 15 degrees C, I15ms developed with a sigmoid time course whose t0.5 was 1.5 s (2.6 s) and on washing declined in a near-exponential fashion with tau off = 6.1 s (6.4 s). Washing after a short (1-2s) application led to a transient considerable increase in I15ms followed by a faster decline with tau'off less than tau off. 5. Cooling decreased the rate of action with a Q10 of 1/tau0.5 = 1.9 and of 1/tau off = 2.0 (between 7 and 14 degrees C). ATX I (up to 15 micro M) was ineffective and did not antagonize ATX II. 6. Both rates of diffusional access and reaction seem to contribute to the rate of action. The results suggest a superficial binding site.

  19. Interactions of guanidinium ions with sodium channels in frog myelinated nerve fibre.

    PubMed Central

    Benoit, E; Dubois, J M

    1987-01-01

    1. The effects of external guanidinium ions on fast and slow inactivating currents flowing through sodium channels of the frog myelinated nerve fibre (Benoit, Corbier & Dubois, 1985) were analysed under voltage-clamp conditions. 2. When external sodium ions were partially replaced by guanidinium ions, the fast inactivating current was preferentially reduced and was absent in a solution containing guanidinium ions as the only external permeant cations. The inactivation time constants of both fast and slow currents were not significantly modified by the replacement of sodium ions by guanidinium ions. 3. Substitution of guanidinium ions for all sodium ions shifted the steady-state inactivation curve of the slow inactivating current towards positive voltages. 4. The voltage dependence of the activation of fast and slow inactivating currents was shifted towards positive voltages by guanidinium ions. Moreover, the activation-voltage curve of the slow inactivating current, which was biphasic under control conditions, was monophasic when guanidinium ions were substituted for all sodium ions. 5. Whereas the slow inactivating current could be carried by guanidinium ions, these cations were not only impermeant through the sodium channels which give rise to the fast inactivating current but also blocked this type of channel with an apparent dissociation constant of 49 mM. 6. It is concluded that guanidinium appears to be an efficient tool for further separating the two types of inactivating current and studying the properties of the slow inactivating current. These results are consistent with the suggestion that there are two types of sodium channels, fast and slow, with guanidinium ions being permeant only through the slow ones. PMID:2451015

  20. In vivo expression of the Arf6 Guanine-nucleotide exchange factor cytohesin-1 in mice exhibits enhanced myelin thickness in nerves.

    PubMed

    Torii, Tomohiro; Miyamoto, Yuki; Onami, Naoko; Tsumura, Hideki; Nemoto, Noriko; Kawahara, Katsumasa; Kato, Minoru; Kotera, Jun; Nakamura, Kazuaki; Tanoue, Akito; Yamauchi, Junji

    2013-10-01

    The myelin sheath consists of a unique multiple layer structure that acts as an insulator between neuronal axons to enhance the propagation of the action potential. In neuropathies such as demyelinating or dismyelinating diseases, chronic demyelination and defective remyelination occur repeatedly, leading to more severe neuropathy. As yet, little is known about the possibility of drug target-specific medicine for such diseases. In the developing peripheral nervous system (PNS), myelin sheaths form as Schwann cells wrap individual axons. It is thought that the development of a drug promoting myelination by Schwann cells would provide effective therapy against peripheral nerve disorders: to test such treatment, genetically modified mice overexpressing the drug target molecules are needed. We previously identified an Arf6 activator, the guanine-nucleotide exchange factor cytohesin-1, as the signaling molecule controlling myelination of peripheral axons by Schwann cells; yet, the important issue of whether cytohesin-1 itself promotes myelin thickness in vivo has remained unclear. Herein, we show that, in mouse PNS nerves, Schwann cell-specific expression of wild-type cytohesin-1 exhibits enhanced myelin thickness. Downstream activation of Arf6 is also seen in these transgenic mice, revealing the involvement of the cytohesin-1 and Arf6 signaling unit in promoting myelination. These results suggest that cytohesin-1 may be a candidate for the basis of a therapy for peripheral neuropathies through its enhancement of myelin thickness.

  1. [Effect of embryonic anlage allografts of the rat spinal cord on growth of regenerating fibers of the recipient nerve].

    PubMed

    Petrova, E S; Isaeva, E N

    2014-01-01

    A comparative study of the effect of tissue and suspension allografts of an embryonic spinal cord on regeneration of nerve fibers of impaired (by application of a ligature) sciatic nerve in rats was conducted. It was demonstrated that unlike tissue grafts that reach a large volume 21 and 60 days after transplantation, suspension grafts do not inhibit the growth of axons of the recipient to the periphery. It was established that introduction of a suspension of dissociated cells of the spinal cord embryonic anlages (but not fragments of these anlages) into the impaired sciatic nerve in rats results in an increase in the amount of myelinated regenerating nerve fibers of the recipient 60 days after the operation.

  2. Identifying motor and sensory myelinated axons in rabbit peripheral nerves by histochemical staining for carbonic anhydrase and cholinesterase activities

    NASA Technical Reports Server (NTRS)

    Riley, Danny A.; Sanger, James R.; Matloub, Hani S.; Yousif, N. John; Bain, James L. W.

    1988-01-01

    Carbonic anhydrase (CA) and cholinesterase (CE) histochemical staining of rabbit spinal nerve roots and dorsal root ganglia demonstrated that among the reactive myeliated axons, with minor exceptions, sensory axons were CA positive and CE negative whereas motor axons were CA negative and CE positive. The high specificity was achieved by adjusting reaction conditions to stain subpopulations of myelinated axons selectively while leaving 50 percent or so unstained. Fixation with glutaraldehyde appeared necessary for achieving selectivity. Following sciatic nerve transection, the reciprocal staining pattern persisted in damaged axons and their regenerating processes which formed neuromas within the proximal nerve stump. Within the neuromas, CA-stained sensory processes were elaborated earlier and in greater numbers than CE-stained regenerating motor processes. The present results indicate that histochemical axon typing can be exploited to reveal heterogeneous responses of motor and sensory axons to injury.

  3. Identifying motor and sensory myelinated axons in rabbit peripheral nerves by histochemical staining for carbonic anhydrase and cholinesterase activities

    NASA Technical Reports Server (NTRS)

    Riley, Danny A.; Sanger, James R.; Matloub, Hani S.; Yousif, N. John; Bain, James L. W.

    1988-01-01

    Carbonic anhydrase (CA) and cholinesterase (CE) histochemical staining of rabbit spinal nerve roots and dorsal root ganglia demonstrated that among the reactive myeliated axons, with minor exceptions, sensory axons were CA positive and CE negative whereas motor axons were CA negative and CE positive. The high specificity was achieved by adjusting reaction conditions to stain subpopulations of myelinated axons selectively while leaving 50 percent or so unstained. Fixation with glutaraldehyde appeared necessary for achieving selectivity. Following sciatic nerve transection, the reciprocal staining pattern persisted in damaged axons and their regenerating processes which formed neuromas within the proximal nerve stump. Within the neuromas, CA-stained sensory processes were elaborated earlier and in greater numbers than CE-stained regenerating motor processes. The present results indicate that histochemical axon typing can be exploited to reveal heterogeneous responses of motor and sensory axons to injury.

  4. Conduction block of mammalian myelinated nerve by local cooling to 15–30°C after a brief heating

    PubMed Central

    Zhang, Zhaocun; Lyon, Timothy D.; Kadow, Brian T.; Shen, Bing; Wang, Jicheng; Lee, Andy; Kang, Audry; Roppolo, James R.; de Groat, William C.

    2016-01-01

    This study aimed at understanding thermal effects on nerve conduction and developing new methods to produce a reversible thermal block of axonal conduction in mammalian myelinated nerves. In 13 cats under α-chloralose anesthesia, conduction block of pudendal nerves (n = 20) by cooling (5–30°C) or heating (42–54°C) a small segment (9 mm) of the nerve was monitored by the urethral striated muscle contractions and increases in intraurethral pressure induced by intermittent (5 s on and 20 s off) electrical stimulation (50 Hz, 0.2 ms) of the nerve. Cold block was observed at 5–15°C while heat block occurred at 50–54°C. A complete cold block up to 10 min was fully reversible, but a complete heat block was only reversible when the heating duration was less than 1.3 ± 0.1 min. A brief (<1 min) reversible complete heat block at 50–54°C or 15 min of nonblock mild heating at 46–48°C significantly increased the cold block temperature to 15–30°C. The effect of heating on cold block fully reversed within ∼40 min. This study discovered a novel method to block mammalian myelinated nerves at 15–30°C, providing the possibility to develop an implantable device to block axonal conduction and treat many chronic disorders. The effect of heating on cold block is of considerable interest because it raises many basic scientific questions that may help reveal the mechanisms underlying cold or heat block of axonal conduction. PMID:26740534

  5. Schwann Cell Glycogen Selectively Supports Myelinated Axon Function

    PubMed Central

    Brown, Angus M; Evans, Richard D; Black, Joel; Ransom, Bruce R

    2012-01-01

    Objectives Interruption of energy supply to peripheral axons is a cause of axon loss. We determined if glycogen was present in mammalian peripheral nerve, and if it supported axon conduction during aglycemia. Methods We used biochemical assay and electron microscopy to determine the presence of glycogen, and electrophysiology to monitor axon function. Results Glycogen was present in sciatic nerve, its concentration varying directly with ambient [glucose]. Electron microscopy detected glycogen granules primarily in myelinating Schwann cell cytoplasm and these diminished after exposure to aglycemia. During aglycemia, conduction failure in large myelinated axons (A fibers) mirrored the time-course of glycogen loss. Latency to CAP failure was directly related to nerve glycogen content at aglycemia onset. Glycogen did not benefit the function of slow-conducting, small diameter unmyelinated axons (C fibers) during aglycemia. Blocking glycogen breakdown pharmacologically accelerated CAP failure during aglycemia in A fibers, but not in C fibers. Lactate was as effective as glucose in supporting sciatic nerve function, and was continuously released into the extracellular space in the presence of glucose and fell rapidly during aglycemia. Interpretation Our findings indicated that glycogen is present in peripheral nerve, primarily in myelinating Schwann cells, and exclusively supports large diameter, myelinated axon conduction during aglycemia. Available evidence suggests that peripheral nerve glycogen breaks down during aglycemia and is passed, probably as lactate, to myelinated axons to support function. Unmyelinated axons are not protected by glycogen and are more vulnerable to dysfunction during periods of hypoglycemia. PMID:23034913

  6. White matter atrophy and myelinated fiber disruption in a rat model of depression.

    PubMed

    Gao, Yuan; Ma, Jing; Tang, Jing; Liang, Xin; Huang, Chun-Xia; Wang, San-Rong; Chen, Lin-Mu; Wang, Fei-Fei; Tan, Chuan-Xue; Chao, Feng-Lei; Zhang, Lei; Qiu, Xuan; Luo, Yan-Min; Xiao, Qian; Du, Lian; Xiao, Qian; Tang, Yong

    2017-06-01

    Brain imaging and postmortem studies have indicated that white matter abnormalities may contribute to the pathology and pathogenesis of depression. However, until now, no study has quantitatively investigated white matter changes in depression in rats. The current study used the chronic unpredictable stress (CUS) model of depression. Body weight and sucrose preference test (SPT) scores were assessed weekly. Upon successfully establishing the CUS animal model, all animals were tested using the SPT and the open field test (OFT). Then, transmission electron microscopy and unbiased stereological methods were used to investigate white matter changes in the rats. Compared with the control group, the body weight and sucrose preference of the CUS rats were significantly decreased (p < .001, p < .001, respectively). In the OFT, the total time spent and the total distance traveled in the inner area by the CUS rats were significantly lower than those of the control group (p = .002, p = .001, respectively). The stereological results revealed that white matter volume, the total volume, and the total length and mean diameter of myelinated fibers in the white matter of the CUS rats were significantly decreased compared to the control rats (p = .042, p = .038, p = .035, p = .019, respectively). The results of this study suggested that white matter atrophy and disruption of myelinated fibers in the white matter may contribute to the pathophysiology underlying depression, which might provide new targets for the development of novel therapeutic interventions for depression.

  7. Normal molecular repair mechanisms in regenerative peripheral nerve interfaces allow recording of early spike activity despite immature myelination.

    PubMed

    Seifert, Jennifer L; Desai, Vidhi; Watson, Robert C; Musa, Tabassum; Kim, Young-tae; Keefer, Edward W; Romero, Mario I

    2012-03-01

    Clinical use of neurally controlled prosthetics has advanced in recent years, but limitations still remain, including lacking fine motor control and sensory feedback. Indwelling multi-electrode arrays, cuff electrodes, and regenerative sieve electrodes have been reported to serve as peripheral neural interfaces, though long-term stability of the nerve-electrode interface has remained a formidable challenge. We recently developed a regenerative multi-electrode interface (REMI) that is able to record neural activity as early as seven days post-implantation. While this activity might represent normal neural depolarization during axonal regrowth, it can also be the result of altered nerve regeneration around the REMI. This study evaluated high-throughput expression levels of 84 genes involved in nerve injury and repair, and the histological changes that occur in parallel to this early neural activity. Animals exhibiting spike activity increased from 29% to 57% from 7 to 14 days following REMI implantation with a corresponding increase in firing rate of 113%. Two weeks after implantation, numbers of neurofilament-positive axons in the control and REMI implanted nerves were comparable, and in both cases the number of myelinated axons was low. During this time, expression levels of genes related to nerve injury and repair were similar in regenerated nerves, both in the presence or absence of the electrode array. Together, these results indicate that the early neural activity is intrinsic to the regenerating axons, and not induced by the REMI neurointerface.

  8. Sera of glaucoma patients show autoantibodies against myelin basic protein and complex autoantibody profiles against human optic nerve antigens.

    PubMed

    Joachim, Stephanie C; Reichelt, Jan; Berneiser, Simone; Pfeiffer, Norbert; Grus, Franz H

    2008-04-01

    The aim of this study was to gain more information about the possible immunological mechanisms in glaucoma. We analyzed the complex autoantibody patterns against human optic nerve antigens in sera of patients with glaucoma and tried to identify important antigens. Sera of 133 patients were included: healthy control subjects (n = 44), primary open-angle glaucoma (n = 44), and normal tension glaucoma patients (n = 45). The sera were tested against Western blots of human optic nerve, and antibody bands were visualized with chloronaphthol. IgG antibody patterns were analyzed by multivariate statistical techniques, and the most significant antigens were identified by mass spectrometry (Maldi-TOFTOF). All subjects, even healthy ones, showed different and complex antibody patterns. Glaucoma groups showed specific up- and down-regulations of antibody reactivities compared to the control group. The multivariate analysis of discriminance found significant differences (P < 0.05) in IgG antibody profiles against human optic nerve antigens between both glaucoma groups and healthy subjects. The identified antigens include: myelin basic protein (up-regulated in the POAG group), glial fibrillary acidic protein (down-regulated in the glaucoma groups), and vimentin (down-regulated in the glaucoma groups in comparison to controls). Using human optic nerve antigen, we were able to demonstrate that complex IgG autoantibody patterns exist in sera of patients with glaucoma. Large correlations between the given and our previous studies using bovine optic nerve antigens could be seen. Furthermore, anti-myelin basic protein antibodies, which can also be detected in patients with multiple sclerosis, were found in sera of glaucoma patients.

  9. Mutation analysis of the nerve specific promoter of the peripheral myelin protein 22 gene in CMT1 disease and HNPP.

    PubMed

    Nelis, E; De Jonghe, P; De Vriendt, E; Patel, P I; Martin, J J; Van Broeckhoven, C

    1998-07-01

    We analysed the nerve specific promoter of the peripheral myelin protein 22 gene (PMP22) in a set of 15 unrelated patients with Charcot-Marie-Tooth type 1 disease (CMT1) and 16 unrelated patients with hereditary neuropathy with liability to pressure palsies (HNPP). In these patients no duplication/deletion nor a mutation in the coding region of the CMT1/ HNPP genes was detected. In one autosomal dominant CMT1 patient, we identified a base change in the non-coding exon 1A of PMP22 which, however, did not cosegregate with the disease in the family. This study indicates that mutations in the nerve specific PMP22 promoter and 5' untranslated exon will not be a common genetic cause of CMT1A and HNPP.

  10. [Nitroxidergic nerve fibers of intracerabral blood vessels].

    PubMed

    Kotsiuba, A E; Kotsiuba, E P; Chertok, V M

    2009-01-01

    Methods of light and electron microscopic histochemistry were applied to study the structure and distribution of NADPH-diaphorase-positive neurons and processes in the parietal area of rat cerebral cortex. It was found that the most of the neurons displayed close connections with the intracerebral vessels. In the cerebral cortex, the smallest distance between the axonal plasma membrane and smooth muscle cells of the intracerebral arteries was found to be no less than 0.3-0.5 microm. Neuronal cell bodies were located in the functionally important areas of the vessels (in the areas of lateral trunk branching and in arteriolar sources), while their processes accompanied the vessels, tightly embracing them with their branches. Quite often, the neurons, the dendrites of which make contacts with the bodies or processes of over- or underlying neurons, sent their nerve fibers to the arteries, veins and capillaries. Thus, nitroxidergic neurons or their groups may control the blood flow in the different areas of vascular bed, performing the functions of the local nerve center.

  11. Concentration of astrocytic filaments at the retinal optic nerve junction is coincident with the absence of intra-retinal myelination: comparative and developmental evidence.

    PubMed

    Morcos, Y; Chan-Ling, T

    2000-09-01

    The structure of the lamina cribrosa (LC) and astrocytic density were examined in various species with and without intra-retinal myelination. Sections of optic nerve from various species were stained with Milligan's trichrome or antibodies to glial fibrillary acidic protein, myelin basic protein (MBP) and antibody O4. Marmoset, flying fox, cat, and sheep, which lack intraretinal myelination, were shown to possess a well-developed LC as well as a marked concentration of astrocytic filaments distal to the LC. Rat and mouse, which lack intraretinal myelination, lacked a well-developed LC but exhibited a marked concentration of astrocytic filaments in this region. Rabbit and chicken, which exhibit intraretinal myelination, lacked both a well-developed LC and a concentration of astrocytes at the retinal optic nerve junction (ROJ). A marked concentration of astrocytes at the ROJ of human fetuses was also apparent at 13 weeks of gestation, prior to myelination of the optic nerve; in contrast, the LC was not fully developed even at birth. This concentration of astrocytes was located distal to O4 and MBP immunoreactivity in human optic nerve, and coincided with the site of initial myelination of ganglion cell axons in marmoset and rat. Myelination proceeded from the chiasm towards the retinal end of the human optic nerve. Moreover, the outer limit of oligodendrocyte precursor cells (OPC) migration into the rabbit retina was restricted by the outer limit of astrocyte spread. These observations indicate that a concentration of astrocytic filaments at the ROJ is coincident with the absence of intraretinal myelination. Differential expression of tenascin-C by astrocytes at the ROJ appears to contribute to the molecular barrier to OPC migration (see Bartsch et al., 1994), while expression of the homedomain protein Vax 1 by glial cells at the optic nerve head appears to inhibit migration of retinal pigment epithelial cells into the optic nerve (see Bertuzzi et al., 1999). These

  12. Decreased Myelinated Fibers in the Hippocampal Dentate Gyrus of the Tg2576 Mouse Model of Alzheimer’s Disease

    PubMed Central

    Lu, Wei; Yang, Shu; Zhang, Lei; Chen, Lin; Chao, Feng-Lei; Luo, Yan-min; Xiao, Qian; Gu, Heng-Wei; Jiang, Rong; Tang, Yong

    2016-01-01

    Alzheimer’s disease (AD), the most common cause of dementia in the elderly, is characterized by deficits in cognition and memory. Although amyloid-β (Aβ) accumulation is known to be the earliest pathological event that triggers subsequent neurodegeneration, how Aβ accumulation causes behavioral deficits remains incompletely understood. In this study, using the Morris water maze test, ELISA and stereological methods, we examined spatial learning and memory performance, the soluble Aβ concentration and the myelination of fibers in the hippocampus of 4-, 6-, 8- and 10-month-old Tg2576 AD model mice. Our results showed that spatial learning and memory performance was significantly impaired in the Tg2576 mice compared to the wild type (WT) controls and that the myelinated fiber length in the hippocampal dentate gyrus (DG) was markedly decreased from 0.33 ± 0.03 km in the WT controls to 0.17 ± 0.02 km in the Tg2576 mice at 10 months of age. However, the concentrations of soluble Aβ40 and Aβ42 were significantly increased as early as 4-6 months of age. The decreased myelinated fiber length in the DG may contribute to the spatial learning and memory deficits of Tg2576 mice. Therefore, we suggest that the significant accumulation of soluble Aβ may serve as a preclinical biomarker for AD diagnosis and that protecting myelinated fibers may represent a novel strategy for delaying the progression of early-stage AD. PMID:26971933

  13. Enriched environment increases myelinated fiber volume and length in brain white matter of 18-month female rats.

    PubMed

    Yang, Shu; Lu, Wei; Zhou, De-shan; Tang, Yong

    2015-04-23

    Cognition and memory decline with normal aging, which could be partly attributed to the degeneration of brain white matter. Previous studies demonstrated that exposure to an enriched environment (EE) could protect cognition and memory from aging. However, if or how EE might affect the brain white matter has not been thoroughly investigated. In the current study, 24 middle-aged (14-month-old) female Sprague -Dawley (SD) rats were randomly assigned to EE or standard environment (SE) for 4 months. At the end of the environment intervention, the Morris water maze tests were performed. Then, 5 rats were randomly selected from each group for stereological assessment of the brain white matter and its myelinated fibers. The results revealed that middle-aged rats living in EE displayed better spatial learning than SE controls. The white matter volume was 124.6 ± 7.8mm(3) in EE rats, which was significantly enlarged compared with 84.8 ± 3.4mm(3) in SE rats. Likewise, the myelinated fiber volume was markedly increased from 56.6 ± 1.7 mm(3) in SE rats to 87.2 ± 9.0mm(3) in EE rats; so was the myelinated fiber length from 83.5 ± 6.6 km in SE rats to 119.0 ± 10.0 km in EE rats. Our data suggested that EE could protect brain white matter and its myelinated fibers of female rats at middle age.

  14. Metanx Alleviates Multiple Manifestations of Peripheral Neuropathy and Increases Intraepidermal Nerve Fiber Density in Zucker Diabetic Fatty Rats

    PubMed Central

    Shevalye, Hanna; Watcho, Pierre; Stavniichuk, Roman; Dyukova, Elena; Lupachyk, Sergey; Obrosova, Irina G.

    2012-01-01

    Metanx is a product containing l-methylfolate, pyridoxal 5′-phosphate, and methylcobalamin for management of endothelial dysfunction. Metanx ingredients counteract endothelial nitric oxide synthase uncoupling and oxidative stress in vascular endothelium and peripheral nerve. This study evaluates Metanx on diabetic peripheral neuropathy in ZDF rats, a model of type 2 diabetes. Metanx was administered to 15-week-old ZDF and ZDF lean rats at either 4.87 mg ⋅ kg−1 ⋅ day−1 (a body weight–based equivalent of human dose) or 24.35 mg ⋅ kg−1 ⋅ day−1 by oral gavage two times a day for 4 weeks. Both doses alleviated hind limb digital sensory, but not sciatic motor, nerve conduction slowing and thermal and mechanical hypoalgesia in the absence of any reduction of hyperglycemia. Low-dose Metanx increased intraepidermal nerve fiber density but did not prevent morphometric changes in distal tibial nerve myelinated fibers. Metanx treatment counteracted endothelial nitric oxide synthase uncoupling, inducible nitric oxide synthase upregulation, and methylglyoxal-derived advanced glycation end product, nitrotyrosine, and nitrite/nitrate accumulation in the peripheral nerve. In conclusion, Metanx, at a body weight–based equivalent of human dose, increased intraepidermal nerve fiber density and improved multiple parameters of peripheral nerve function in ZDF rats. Clinical studies are needed to determine if Metanx finds use in management of diabetic peripheral neuropathy. PMID:22751692

  15. Antibody responses to peptides of peripheral nerve myelin proteins P0 and P2 in patients with inflammatory demyelinating neuropathy

    PubMed Central

    Inglis, H R; Csurhes, P A; McCombe, P A

    2007-01-01

    Background Antibodies with reactivity to peripheral nerve myelin have previously been found in the serum, and bound to peripheral nerves of patients with Guillain–Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Aim To investigate the presence of antibodies reactive to specific peptide sequences within the myelin proteins P0 and P2 in patients with GBS, in patients with CIDP, in healthy controls and in patients with other neuropathies (ON). Methods Blood was obtained from 48 patients with GBS, 36 with CIDP, 48 with ON and 38 controls. ELISA was used to detect antibody responses to peptides of the human peripheral myelin proteins P0 and P2. Blood samples were collected from patients with GBS in early, peak and recovery stages of GBS to analyse antibody levels throughout the course of the disease. Results Significantly increased total IgG levels were found in patients with GBS compared with other groups. A higher percentage of patients with GBS at the peak of disease had antibody reactivity to P214–25 compared with patients with CIDP and control groups. In patients with GBS and CIDP, the percentages of patients with antibody reactivity to P261–70, and peptides derived from P0, were comparable to the control groups. Although some individual patients with GBS had high titres of reactivity to the peptide antigens tested, most patients with GBS and CIDP had levels of antibody similar to controls. Conclusion Our data suggest that increased IgG levels and increased antibody reactivity to P2 14–25 in patients with GBS at the peak of disease may play a contributory role in the disease process in some patients with demyelinating forms of GBS. PMID:17158557

  16. Conductance fluctuations from the inactivation process of sodium channels in myelinated nerve fibres*

    PubMed Central

    Conti, F.; Neumcke, B.; Nonner, W.; Stämpfli, R.

    1980-01-01

    1. Na currents and fluctuations of Na currents were studied under voltage clamp in the same myelinated nerve fibres of Rana esculenta at 13 °C. The results were used to test several kinetic models for the gating process of Na channels. 2. Long voltage pulses, depolarizing the membrane by 16-48 mV from a hyperpolarizing holding level of — 28 mV, were applied in 4 sec intervals. The d.c. and a.c. components of the membrane current were recorded during the last 328 msec of the 473 msec pulses. For each depolarization, ninety-six trials were made with the node in Ringer solution and, again, after adding 300 nm-tetrodotoxin (TTX) in that solution. 3. The TTX-sensitive d.c. component declined during the 328 msec records by 14-51% of its time average. The a.c. component was corrected for this trend by subtracting the first from the second of each pair of subsequent records. The TTX-sensitive part of its variance declined, on the average, in parallel to the current, as if the open probability rather than the conductance of the individual Na channels was reduced by a slow process. 4. Single-channel conductances, γ, were calculated on the assumption that Na channels have only one non-zero conductance and were corrected for the limited band width (5 kHz) of the a.c. records. Values of γ increased slightly (< 30% from 16 to 40 mV), and averaged 8·85 ± 0·7 pS (s.e. of mean, seventeen measurements on ten fibres). This small degree of change in γ suggests that deviations from the all-or-none gating are very small. 5. Power spectral densities of the fluctuations between 3 Hz and 5 kHz were calculated from the trend-free a.c. records and corrected for the TTX-insensitive noise component. Control calculations showed that the only effect of the nonstationarity in the Na current was to enhance the low-frequency points of such spectra by less than 10%. The spectra revealed at least two Lorentzian components with cut-off frequencies in the range expected from the activation and

  17. Shortened internodal length of dermal myelinated nerve fibres in Charcot–Marie-Tooth disease type 1A

    PubMed Central

    Saporta, Mario A.; Katona, Istvan; Lewis, Richard A.; Masse, Stacey; Shy, Michael E.

    2009-01-01

    Charcot–Marie-Tooth disease type 1A is the most common inherited neuropathy and is caused by duplication of chromosome 17p11.2 containing the peripheral myelin protein-22 gene. This disease is characterized by uniform slowing of conduction velocities and secondary axonal loss, which are in contrast with non-uniform slowing of conduction velocities in acquired demyelinating disorders, such as chronic inflammatory demyelinating polyradiculoneuropathy. Mechanisms responsible for the slowed conduction velocities and axonal loss in Charcot–Marie-Tooth disease type 1A are poorly understood, in part because of the difficulty in obtaining nerve samples from patients, due to the invasive nature of nerve biopsies. We have utilized glabrous skin biopsies, a minimally invasive procedure, to evaluate these issues systematically in patients with Charcot–Marie-Tooth disease type 1A (n = 32), chronic inflammatory demyelinating polyradiculoneuropathy (n = 4) and healthy controls (n = 12). Morphology and molecular architecture of dermal myelinated nerve fibres were examined using immunohistochemistry and electron microscopy. Internodal length was uniformly shortened in patients with Charcot–Marie-Tooth disease type 1A, compared with those in normal controls (P < 0.0001). Segmental demyelination was absent in the Charcot–Marie-Tooth disease type 1A group, but identifiable in all patients with chronic inflammatory demyelinating polyradiculoneuropathy. Axonal loss was measurable using the density of Meissner corpuscles and associated with an accumulation of intra-axonal mitochondria. Our study demonstrates that skin biopsy can reveal pathological and molecular architectural changes that distinguish inherited from acquired demyelinating neuropathies. Uniformly shortened internodal length in Charcot–Marie-Tooth disease type 1A suggests a potential developmental defect of internodal lengthening. Intra-axonal accumulation of mitochondria provides new insights into the

  18. What Is the Optimal Value of the g-Ratio for Myelinated Fibers in the Rat CNS? A Theoretical Approach

    PubMed Central

    Chomiak, Taylor; Hu, Bin

    2009-01-01

    Background The biological process underlying axonal myelination is complex and often prone to injury and disease. The ratio of the inner axonal diameter to the total outer diameter or g-ratio is widely utilized as a functional and structural index of optimal axonal myelination. Based on the speed of fiber conduction, Rushton was the first to derive a theoretical estimate of the optimal g-ratio of 0.6 [1]. This theoretical limit nicely explains the experimental data for myelinated axons obtained for some peripheral fibers but appears significantly lower than that found for CNS fibers. This is, however, hardly surprising given that in the CNS, axonal myelination must achieve multiple goals including reducing conduction delays, promoting conduction fidelity, lowering energy costs, and saving space. Methodology/Principal Findings In this study we explore the notion that a balanced set-point can be achieved at a functional level as the micro-structure of individual axons becomes optimized, particularly for the central system where axons tend to be smaller and their myelin sheath thinner. We used an intuitive yet novel theoretical approach based on the fundamental biophysical properties describing axonal structure and function to show that an optimal g-ratio can be defined for the central nervous system (≈0.77). Furthermore, by reducing the influence of volume constraints on structural design by about 40%, this approach can also predict the g-ratio observed in some peripheral fibers (≈0.6). Conclusions/Significance These results support the notion of optimization theory in nervous system design and construction and may also help explain why the central and peripheral systems have evolved different g-ratios as a result of volume constraints. PMID:19915661

  19. Implications of olfactory lamina propria transplantation on hyperreflexia and myelinated fiber regeneration in rats with complete spinal cord transection.

    PubMed

    Centenaro, Lígia Aline; da Cunha Jaeger, Mariane; Ilha, Jocemar; de Souza, Marcelo Alves; Balbinot, Luciane Fachin; do Nascimento, Patrícia Severo; Marcuzzo, Simone; Achaval, Matilde

    2013-02-01

    Transplantation with olfactory ensheathing cells (OECs) has been adopted after several models of spinal cord injury (SCI) with the purpose of creating a favorable environment for the re-growth of injured axons. However, a consensus on the efficacy of this cellular transplantation has yet to be reached. In order to explore alternative parameters that could demonstrate the possible restorative properties of such grafts, the present study investigated the effects of olfactory lamina propria (OLP) transplantation on hyperreflexia and myelinated fiber regeneration in adult rats with complete spinal cord transection. The efficacy of OLP (graft containing OECs) and respiratory lamina propria (RLP, graft without OECs) was tested at different post-injury times (acutely, 2- and 4-week delayed), to establish the optimum period for transplantation. In the therapeutic windows used, OLP and RLP grafts produced no considerable improvements in withdrawal reflex responses or on the low-frequency dependent depression of H-reflex. Both lamina propria grafts produced comparable results for the myelinated fiber density and for the estimated total number of myelinated fibers at the lesion site, indicating that the delayed transplantation approach does not seem to limit the regenerative effects. However, animals transplanted with OLP 2 or 4 weeks after injury exhibit smaller myelin sheath thickness and myelinated fiber area and diameter at the lesion site compared to their respective RLP groups. Despite the ongoing clinical use of OECs, it is important to emphasize the need for more experimental studies to clarify the exact nature of the repair capacity of these grafts in the treatment of SCI.

  20. [Morphometric characterization of the subbasal nerve plexus : Detection and analysis of networks of nerve fibers].

    PubMed

    Winter, K; Scheibe, P; Guthoff, R F; Allgeier, S; Stachs, O

    2017-07-01

    Confocal laser scanning microscopy is a versatile tool in medical research and enables noninvasive in vivo imaging of the corneal subbasal nerve plexus. The aim of this work is to provide a structured overview about the detection and quantification of nerve fibers of the subbasal nerve plexus from images acquired by confocal laser scanning microscopy. Relevant steps are explained and potential factors influencing the quality of the results are pointed out. Information obtained from the quantification of subbasal nerve fiber structure can be potentially used as clinical parameters in the context of diagnostics and therapy control of diabetic neuropathy.

  1. Calculation of action potential propagation in nerve fiber.

    PubMed

    Bogatov, N M; Grigoryan, L R; Ponetaeva, E G; Sinisyn, A S

    2014-05-01

    This article introduces generalization of the action potential spreading model which considers generation of the action potential in each segment of the nerve fiber. Behavior of the impulse signal waveform during the propagation process was analyzed. A mechanism of distributed generation of the charge in nerve fiber results in decrease of phase velocity of signal spreading rate. Amplitude of the action potential decreases and pulse width increases in the action potential propagation process. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Thickness of the retinal nerve fiber layer in primate eyes.

    PubMed

    Radius, R L

    1980-09-01

    Thickness of the retinal nerve fiber layer is studied in the eyes of three primate species. Measurements are made at various points throughout the fundus, including the peripapillary, arcuate, macular (area centralis), equatorial, and peripheral parts of the retina. Anatomic findings are compared with the clinical appearance of retinal light reflexes in these way. It is proposed that the nature of this light reflex is, in part, determined by the thickness of the retinal nerve fiber layer.

  3. Gangliosides and Nogo receptors independently mediate myelin-associated glycoprotein inhibition of neurite outgrowth in different nerve cells.

    PubMed

    Mehta, Niraj R; Lopez, Pablo H H; Vyas, Alka A; Schnaar, Ronald L

    2007-09-21

    In the injured nervous system, myelin-associated glycoprotein (MAG) on residual myelin binds to receptors on axons, inhibits axon outgrowth, and limits functional recovery. Conflicting reports identify gangliosides (GD1a and GT1b) and glycosylphosphatidylinositol-anchored Nogo receptors (NgRs) as exclusive axonal receptors for MAG. We used enzymes and pharmacological agents to distinguish the relative roles of gangliosides and NgRs in MAG-mediated inhibition of neurite outgrowth from three nerve cell types, dorsal root ganglion neurons (DRGNs), cerebellar granule neurons (CGNs), and hippocampal neurons. Primary rat neurons were cultured on control substrata and substrata adsorbed with full-length native MAG extracted from purified myelin. The receptors responsible for MAG inhibition of neurite outgrowth varied with nerve cell type. In DRGNs, most of the MAG inhibition was via NgRs, evidenced by reversal of inhibition by phosphatidylinositol-specific phospholipase C (PI-PLC), which cleaves glycosylphosphatidylinositol anchors, or by NEP1-40, a peptide inhibitor of NgR. A smaller percentage of MAG inhibition of DRGN outgrowth was via gangliosides, evidenced by partial reversal by addition of sialidase to cleave GD1a and GT1b or by P4, an inhibitor of ganglioside biosynthesis. Combining either PI-PLC and sialidase or NEP1-40 and P4 was additive. In contrast to DRGNs, in CGNs MAG inhibition was exclusively via gangliosides, whereas inhibition of hippocampal neuron outgrowth was mostly reversed by sialidase or P4 and only modestly reversed by PI-PLC or NEP1-40 in a non-additive fashion. A soluble proteolytic fragment of native MAG, dMAG, also inhibited neurite outgrowth. In DRGNs, dMAG inhibition was exclusively NgR-dependent, whereas in CGNs it was exclusively ganglioside-dependent. An inhibitor of Rho kinase reversed MAG-mediated inhibition in all nerve cells, whereas a peptide inhibitor of the transducer p75(NTR) had cell-specific effects quantitatively similar to Ng

  4. Polarization and Myelination in Myelinating Glia

    PubMed Central

    Masaki, Toshihiro

    2012-01-01

    Myelinating glia, oligodendrocytes in central nervous system and Schwann cells in peripheral nervous system, form myelin sheath, a multilayered membrane system around axons enabling salutatory nerve impulse conduction and maintaining axonal integrity. Myelin sheath is a polarized structure localized in the axonal side and therefore is supposed to be formed based on the preceding polarization of myelinating glia. Thus, myelination process is closely associated with polarization of myelinating glia. However, cell polarization has been less extensively studied in myelinating glia than other cell types such as epithelial cells. The ultimate goal of this paper is to provide insights for the field of myelination research by applying the information obtained in polarity study in other cell types, especially epithelial cells, to cell polarization of myelinating glia. Thus, in this paper, the main aspects of cell polarization study in general are summarized. Then, they will be compared with polarization in oligodendrocytes. Finally, the achievements obtained in polarization study for epithelial cells, oligodendrocytes, and other types of cells will be translated into polarization/myelination process by Schwann cells. Then, based on this model, the perspectives in the study of Schwann cell polarization/myelination will be discussed. PMID:23326681

  5. Structure-function analysis of protein complexes involved in the molecular architecture of juxtaparanodal regions of myelinated fibers.

    PubMed

    Tzimourakas, Alexandros; Giasemi, Sevasti; Mouratidou, Maria; Karagogeos, Domna

    2007-05-01

    Demyelinating disorders, including multiple sclerosis (MS), are common causes of neurological disability. One critical step towards the management and therapy of demyelinating diseases is to understand the basic functions of myelinating glia and their relationship with axons. Axons and myelinating glia, oligodendrocytes in the central (CNS) and Schwann cells in the peripheral (PNS) nervous systems, reciprocally influence each other's development and trophism. These interactions are critical for the formation of distinct axonal domains in myelinated fibers that ensure the rapid propagation of action potentials. Macromolecular complexes mediating axo-glial interactions in these domains have been identified, consisting of members of the immunoglobulin superfamily (IgSF) of adhesion molecules and the neurexin/NCP superfamily as well as other proteins. We have investigated the molecular details of axo-glial interactions in the juxtaparanodal region of myelinated fibers by utilizing domain-specific GFP constructs and immunoprecipitation assays on transfected cells. We have shown that the immunoglobulin domains of the IgSF member TAG-1/Cnt-2 are necessary and sufficient for the direct, cis interaction of this protein with Caspr2 and potassium channels.

  6. Comparison of the effects of Anemonia toxin II on sodium and gating currents in frog myelinated nerve.

    PubMed

    Neumcke, B; Schwarz, W; Stämpfli, R

    1985-03-28

    Na+ and gating currents were measured in myelinated frog nerve fibres without and in the presence of 7 microM Anemonia toxin II in the extracellular solution. From the experiments, kinetic parameters of Na+ currents and of gating charge displacements during ('on' response) and after ('off' response) depolarizations were determined. The following parallel modifications of Na+ currents and charge displacements by Anemonia toxin II were observed: the toxin reduces the maximum Na+ permeability and the 'on' charge displacement; Na+ activation and 'on' charge displacement become faster; Na+ inactivation and the decline of the 'off' charge displacement with increasing pulse duration (charge immobilization) are prolonged; slow components of 'on' charge displacements are diminished. The observations support the notion that the fast 'on' charge displacement is connected with the process of Na+ activation, while Na+ inactivation is linked to charge immobilization. Our experiments suggest that slow 'on' charge displacements during longer depolarizations are correlated with the process of Na+ inactivation.

  7. Comparison of rabbit facial nerve regeneration in nerve growth factor-containing silicone tubes to that in autologous neural grafts.

    PubMed

    Spector, J G; Lee, P; Derby, A; Roufa, D G

    1995-11-01

    Previous reports suggest that nerve growth factor (NGF) enhanced nerve regeneration in rabbit facial nerves. We compared rabbit facial nerve regeneration in 10-mm silicone tubes prefilled with NGF or cytochrome C (Cyt C), bridging an 8-mm nerve gap, to regeneration of 8-mm autologous nerve grafts. Three weeks following implantation, NGF-treated regenerates exhibited a more mature fascicular organization and more extensive neovascularization than Cyt C-treated controls. Morphometric analysis at the middle of the tube of 3- and 5-week regenerates revealed no significant difference in the mean number of myelinated or unmyelinated axons between NGF- and Cyt C-treated implants. However, when the numbers of myelinated fibers in 5-week regenerates were compared to those in their respective preoperative controls, NGF-treated regenerates had recovered a significantly greater percentage of myelinated axons than Cyt C-treated implants (46% versus 18%, respectively). The number of regenerating myelinated axons in the autologous nerve grafts at 5 weeks was significantly greater than the number of myelinated axons in the silicone tubes. However, in the nerve grafts the majority of the axons were found in the extrafascicular connective tissue (66%). The majority of these myelinated fibers did not find their way into the distal nerve stump. Thus, although the number of regenerating myelinated axons within the nerve grafts is greater than that of axons within silicone tube implants, functional recovery of autologous nerve graft repairs may not be superior to that of intubational repairs.

  8. Olfactory Ensheathing Cells Rescue Optic Nerve Fibers in a Rat Glaucoma Model

    PubMed Central

    Dai, Chao; Khaw, Peng T.; Yin, Zheng Qin; Li, Daqing; Raisman, Geoffrey; Li, Ying

    2012-01-01

    Purpose: To determine if transplantation of olfactory ensheathing cells (OECs) can reduce loss of optic nerve axons after raised intraocular pressure (IOP) in the rat. Methods: OECs cultured from the adult olfactory mucosa were transplanted into the region of the optic disc. The IOP was raised by injection of magnetic microspheres into the anterior chamber. Results: At 4 weeks after raising the IOP, the transplanted OECs had migrated into the dorsal area of the optic nerve head (ONH) where they surrounded the optic nerve fibers with a non-myelinated ensheathment. The mean amount of damage to the ONH astrocytic area in rats was 51.0% compared with 85.8% in those without OEC transplants (P < 0.02) and the mean loss of axons in the optic nerve was 51.0% compared with 80.3% in the absence of OECs (P < 0.01). Conclusions: OECs transplanted into the region of the ONH of the rat can reduce the loss of axons and the damage to ONH astrocytes caused by raised IOP. Translational Relevance: Confirmation of these preliminary experimental data, further understanding of possible mechanisms of axonal protection by OECs, and the longer-term time course of protection could provide a basis for future human clinical trials of autografted OECs, which would be available from autologous nasal epithelial biopsies. PMID:24049703

  9. Olfactory Ensheathing Cells Rescue Optic Nerve Fibers in a Rat Glaucoma Model.

    PubMed

    Dai, Chao; Khaw, Peng T; Yin, Zheng Qin; Li, Daqing; Raisman, Geoffrey; Li, Ying

    2012-01-01

    To determine if transplantation of olfactory ensheathing cells (OECs) can reduce loss of optic nerve axons after raised intraocular pressure (IOP) in the rat. OECs cultured from the adult olfactory mucosa were transplanted into the region of the optic disc. The IOP was raised by injection of magnetic microspheres into the anterior chamber. At 4 weeks after raising the IOP, the transplanted OECs had migrated into the dorsal area of the optic nerve head (ONH) where they surrounded the optic nerve fibers with a non-myelinated ensheathment. The mean amount of damage to the ONH astrocytic area in rats was 51.0% compared with 85.8% in those without OEC transplants (P < 0.02) and the mean loss of axons in the optic nerve was 51.0% compared with 80.3% in the absence of OECs (P < 0.01). OECs transplanted into the region of the ONH of the rat can reduce the loss of axons and the damage to ONH astrocytes caused by raised IOP. Confirmation of these preliminary experimental data, further understanding of possible mechanisms of axonal protection by OECs, and the longer-term time course of protection could provide a basis for future human clinical trials of autografted OECs, which would be available from autologous nasal epithelial biopsies.

  10. Capsaicin Induces Degeneration of Cutaneous Autonomic Nerve Fibers

    PubMed Central

    Gibbons, Christopher H; Wang, Ningshan; Freeman, Roy

    2010-01-01

    Objective To determine the effects of topical application of capsaicin on cutaneous autonomic nerves. Methods Thirty-two healthy subjects underwent occlusive application of 0.1% capsaicin cream (or placebo) for 48 hours. Subjects were followed for 6 months with serial assessments of sudomotor, vasomotor, pilomotor and sensory function with simultaneous assessment of innervation through skin biopsies. Results There were reductions in sudomotor, vasomotor, pilomotor and sensory function in capsaicin- treated subjects (p<0.01 vs. placebo). Sensory function declined more rapidly than autonomic function; reaching a nadir by day 6 while autonomic function reached a nadir by day 16. There were reductions in sudomotor, vasomotor, pilomotor and sensory nerve fiber densities in capsaicin treated subjects (p<0.01 vs. placebo). Intra-epidermal nerve fiber density declined maximally by 6 days while autonomic nerve fiber densities reached maximal degeneration by day 16. Conversely, autonomic nerves generally regenerated more rapidly than sensory nerves, requiring 40–50 days to return to baseline levels while sensory fibers required 140–150 days to return to baseline. Interpretation Topical capsaicin leads to degeneration of sudomotor, vasomotor and pilomotor nerves accompanied by impairment of sudomotor, vasomotor and pilomotor function. These results suggest the susceptibility and/or pathophysiologic mechanisms of nerve damage may differ between autonomic and sensory nerve fibers treated with capsaicin and enhances the capsaicin model for the study of disease modifying agents. The data suggest caution should be taken when topical capsaicin is applied to skin surfaces at risk for ulceration, particularly in neuropathic conditions characterized by sensory and autonomic impairment. PMID:21061393

  11. Direct determination of the lamellar structure of peripheral nerve myelin at moderate resolution (7A).

    PubMed

    Worthington, C R; McIntosh, T J

    1974-10-01

    Low-angle X-ray diffraction patterns have been recorded from normal nerve and nerve swollen in glycerol solutions. The new X-ray data have a resolution of 7 A. Direct methods of structure analysis which include deconvolution of the auto-correlation function and sampling theorem reconstructions have been used in the interpretation of the X-ray data. Phases have been assigned to the first 12 orders of diffraction from normal nerve. Fourier syntheses at a resolution of 7 A are described and an absolute electron density scale is derived. A possible molecular interpretation of the electron density profile is given.

  12. Influence of Breaching the Connective Sheaths of the Donor Nerve on Its Myelinated Sensory Axons and on Their Sprouting into the End-to-Side Coapted Nerve in the Rat

    PubMed Central

    Žele, Tilen; Tomšič, Martin; Sketelj, Janez; Bajrović, Fajko F.

    2012-01-01

    Abstract The influence of breaching the connective sheaths of the donor sural nerve on axonal sprouting into the end-to-side coapted peroneal nerve was examined in the rat. In parallel, the effect of these procedures on the donor nerve was assessed. The sheaths of the donor nerve at the coaptation site were either left completely intact (group A) or they were breached by epineurial sutures (group B), an epineurial window (group C), or a perineurial window (group D). In group A, the compound action potential (CAP) of sensory axons was detected in ∼10% and 40% of the recipient nerves at 4 and 8 weeks, respectively, which was significantly less frequently than in group D at both recovery periods. In addition, the number of myelinated axons in the recipient nerve was significantly larger in group D than in other groups at 4 weeks. At 8 weeks, the number of axons in group A was only ∼15% of the axon numbers in other groups (p<0.05). Focal subepineurial degenerative changes in the donor nerves were only seen after 4 weeks, but not later. The average CAP area and the total number of myelinated axons in the donor nerves were not different among the experimental groups. In conclusion, myelinated sensory axons are able to penetrate the epiperineurium of donor nerves after end-to-side nerve coaption; however, their ingrowth into recipient nerves is significantly enhanced by breaching the epiperineurial sheets at the coaptation site. Breaching does not cause permanent injury to the donor nerve. PMID:22873667

  13. The MMP-9/TIMP-1 axis controls the status of differentiation and function of myelin-forming Schwann cells in nerve regeneration.

    PubMed

    Kim, Youngsoon; Remacle, Albert G; Chernov, Andrei V; Liu, Huaqing; Shubayev, Igor; Lai, Calvin; Dolkas, Jennifer; Shiryaev, Sergey A; Golubkov, Vladislav S; Mizisin, Andrew P; Strongin, Alex Y; Shubayev, Veronica I

    2012-01-01

    Myelinating Schwann cells (mSCs) form myelin in the peripheral nervous system. Because of the works by us and others, matrix metalloproteinase-9 (MMP-9) has recently emerged as an essential component of the Schwann cell signaling network during sciatic nerve regeneration. In the present study, using the genome-wide transcriptional profiling of normal and injured sciatic nerves in mice followed by extensive bioinformatics analyses of the data, we determined that an endogenous, specific MMP-9 inhibitor [tissue inhibitor of metalloproteinases (TIMP)-1] was a top up-regulated gene in the injured nerve. MMP-9 capture followed by gelatin zymography and Western blotting of the isolated samples revealed the presence of the MMP-9/TIMP-1 heterodimers and the activated MMP-9 enzyme in the injured nerve within the first 24 h post-injury. MMP-9 and TIMP-1 co-localized in mSCs. Knockout of the MMP-9 gene in mice resulted in elevated numbers of de-differentiated/immature mSCs in the damaged nerve. Our comparative studies using MMP-9 knockout and wild-type mice documented an aberrantly enhanced proliferative activity and, accordingly, an increased number of post-mitotic Schwann cells, short internodes and additional nodal abnormalities in remyelinated nerves of MMP-9 knockout mice. These data imply that during the first days post-injury MMP-9 exhibits a functionally important anti-mitogenic activity in the wild-type mice. Pharmacological inhibition of MMP activity suppressed the expression of Na(v)1.7/1.8 channels in the crushed nerves. Collectively, our data established an essential role of the MMP-9/TIMP-1 axis in guiding the mSC differentiation and the molecular assembly of myelin domains in the course of the nerve repair process. Our findings of the MMP-dependent regulation of Na(v) channels, which we document here for the first time, provide a basis for therapeutic intervention in sensorimotor pathologies and pain.

  14. Modeling the response of small myelinated axons in a compound nerve to kilohertz frequency signals

    NASA Astrophysics Data System (ADS)

    Pelot, N. A.; Behrend, C. E.; Grill, W. M.

    2017-08-01

    Objective. There is growing interest in electrical neuromodulation of peripheral nerves, particularly autonomic nerves, to treat various diseases. Electrical signals in the kilohertz frequency (KHF) range can produce different responses, including conduction block. For example, EnteroMedics’ vBloc® therapy for obesity delivers 5 kHz stimulation to block the abdominal vagus nerves, but the mechanisms of action are unclear. Approach. We developed a two-part computational model, coupling a 3D finite element model of a cuff electrode around the human abdominal vagus nerve with biophysically-realistic electrical circuit equivalent (cable) model axons (1, 2, and 5.7 µm in diameter). We developed an automated algorithm to classify conduction responses as subthreshold (transmission), KHF-evoked activity (excitation), or block. We quantified neural responses across kilohertz frequencies (5-20 kHz), amplitudes (1-8 mA), and electrode designs. Main results. We found heterogeneous conduction responses across the modeled nerve trunk, both for a given parameter set and across parameter sets, although most suprathreshold responses were excitation, rather than block. The firing patterns were irregular near transmission and block boundaries, but otherwise regular, and mean firing rates varied with electrode-fibre distance. Further, we identified excitation responses at amplitudes above block threshold, termed ‘re-excitation’, arising from action potentials initiated at virtual cathodes. Excitation and block thresholds decreased with smaller electrode-fibre distances, larger fibre diameters, and lower kilohertz frequencies. A point source model predicted a larger fraction of blocked fibres and greater change of threshold with distance as compared to the realistic cuff and nerve model. Significance. Our findings of widespread asynchronous KHF-evoked activity suggest that conduction block in the abdominal vagus nerves is unlikely with current clinical parameters. Our

  15. Modeling the response of small myelinated axons in a compound nerve to kilohertz frequency signals.

    PubMed

    Pelot, N A; Behrend, C E; Grill, W M

    2017-03-31

    There is growing interest in electrical neuromodulation of peripheral nerves, particularly autonomic nerves, to treat various diseases. Electrical signals in the kilohertz frequency (KHF) range can produce different responses, including conduction block. For example, EnteroMedics' vBloc(®) therapy for obesity delivers 5 kHz stimulation to block the abdominal vagus nerves, but the mechanisms of action are unclear. We developed a two-part computational model, coupling a 3D finite element model of a cuff electrode around the human abdominal vagus nerve with biophysically-realistic electrical circuit equivalent (cable) model axons (1, 2, and 5.7 µm in diameter). We developed an automated algorithm to classify conduction responses as subthreshold (transmission), KHF-evoked activity (excitation), or block. We quantified neural responses across kilohertz frequencies (5-20 kHz), amplitudes (1-8 mA), and electrode designs. We found heterogeneous conduction responses across the modeled nerve trunk, both for a given parameter set and across parameter sets, although most suprathreshold responses were excitation, rather than block. The firing patterns were irregular near transmission and block boundaries, but otherwise regular, and mean firing rates varied with electrode-fibre distance. Further, we identified excitation responses at amplitudes above block threshold, termed 're-excitation', arising from action potentials initiated at virtual cathodes. Excitation and block thresholds decreased with smaller electrode-fibre distances, larger fibre diameters, and lower kilohertz frequencies. A point source model predicted a larger fraction of blocked fibres and greater change of threshold with distance as compared to the realistic cuff and nerve model. Our findings of widespread asynchronous KHF-evoked activity suggest that conduction block in the abdominal vagus nerves is unlikely with current clinical parameters. Our results indicate that compound neural or downstream muscle

  16. Molecular characterization of myelin protein zero in Xenopus laevis peripheral nerve

    NASA Astrophysics Data System (ADS)

    Xie, Bo; Luo, Xiaoyang; Zhao, Cheng; Priest, Christina Marie; Chan, Shiu-Yung; O'Connor, Peter B.; Kirschner, Daniel A.; Costello, Catherine E.

    2007-12-01

    Myelin protein zero (P0), a glycosylated single-pass transmembrane protein, is essential in the formation and maintenance of peripheral nervous system (PNS) compact myelin. P0 in Xenopus (xP0) exists primarily as a dimeric form that remains stable after various physical and chemical treatments. In exploring the nature of the interactions underlying the dimer stability, we found that xP0 dimer dissociated into monomer during continuous elution gel electrophoresis and conventional SDS-PAGE, indicating that the dimer is stabilized by non-covalent interactions. Furthermore, as some of the gel-purified monomer re-associated into dimer on SDS-PAGE gels, there is likely a dynamic equilibrium between xP0 dimer and monomer in vivo. Because the carbohydrate and fatty acyl moieties may be crucial for the adhesion role of P0, we used sensitive mass spectrometry approaches to elucidate the detailed N-glycosylation and S-acylation profiles of xP0. Asn92 was determined to be the single, fully-occupied glycosylation site of xP0, and a total of 12 glycans was detected that exhibited new structural features compared with those observed from P0 in other species: (1) the neutral glycans were composed mainly of high mannose and hybrid types; (2) 5 of 12 were acidic glycans, among which three were sialylated and the other two were sulfated; (3) none of the glycans had core fucosylation; and (4) no glucuronic acid, hence no HNK-1 epitope, was detected. The drastically different carbohydrate structures observed here support the concept of the species-specific variation in N-glycosylation of P0. Cys152 was found to be acylated with stearoyl (C18:0), whereas palmitoyl (C16:0) is the corresponding predominant fatty acyl group on P0 from higher vertebrates. We propose that the unique glycosylation and acylation patterns of Xenopus P0 may underlie its unusual dimerization behavior. Our results should shed light on the understanding of the phylogenetic development of P0's adhesion role in PNS

  17. Myelinated sensory and alpha motor axon regeneration in peripheral nerve neuromas

    NASA Technical Reports Server (NTRS)

    Macias, M. Y.; Lehman, C. T.; Sanger, J. R.; Riley, D. A.

    1998-01-01

    Histochemical staining for carbonic anhydrase and cholinesterase (CE) activities was used to analyze sensory and motor axon regeneration, respectively, during neuroma formation in transected and tube-encapsulated peripheral nerves. Median-ulnar and sciatic nerves in the rodent model permitted testing whether a 4 cm greater distance of the motor neuron soma from axotomy site or intrinsic differences between motor and sensory neurons influenced regeneration and neuroma formation 10, 30, and 90 days later. Ventral root radiculotomy confirmed that CE-stained axons were 97% alpha motor axons. Distance significantly delayed axon regeneration. When distance was negligible, sensory axons grew out sooner than motor axons, but motor axons regenerated to a greater quantity. These results indicate regeneration differences between axon subtypes and suggest more extensive branching of motor axons within the neuroma. Thus, both distance from injury site to soma and inherent motor and sensory differences should be considered in peripheral nerve repair strategies.

  18. Myelinated sensory and alpha motor axon regeneration in peripheral nerve neuromas

    NASA Technical Reports Server (NTRS)

    Macias, M. Y.; Lehman, C. T.; Sanger, J. R.; Riley, D. A.

    1998-01-01

    Histochemical staining for carbonic anhydrase and cholinesterase (CE) activities was used to analyze sensory and motor axon regeneration, respectively, during neuroma formation in transected and tube-encapsulated peripheral nerves. Median-ulnar and sciatic nerves in the rodent model permitted testing whether a 4 cm greater distance of the motor neuron soma from axotomy site or intrinsic differences between motor and sensory neurons influenced regeneration and neuroma formation 10, 30, and 90 days later. Ventral root radiculotomy confirmed that CE-stained axons were 97% alpha motor axons. Distance significantly delayed axon regeneration. When distance was negligible, sensory axons grew out sooner than motor axons, but motor axons regenerated to a greater quantity. These results indicate regeneration differences between axon subtypes and suggest more extensive branching of motor axons within the neuroma. Thus, both distance from injury site to soma and inherent motor and sensory differences should be considered in peripheral nerve repair strategies.

  19. Nerve endoneurial microstructure facilitates uniform distribution of regenerative fibers: a post hoc comparison of midgraft nerve fiber densities.

    PubMed

    Johnson, Philip J; Newton, Piyaraj; Hunter, Daniel A; Mackinnon, Susan E

    2011-02-01

    Despite their inferiority to nerve autograft, clinical alternatives are commonly used for reconstruction of peripheral nerve injuries because of their convenient off-the-shelf availability. Previously, our group compared isografts with NeuraGen(®) (Integra, Plainsboro, NJ) nerve guides, which are a commercially available type I collagen conduit and processed rat allografts comparable to Avance(®) (AxoGen, Alachua, FL) human decellularized allograft product. From this study, qualitative observations were made of distinct differences in the pattern of regenerating fibers within conduits, acellular allografts, and isografts. In the current post hoc analysis, these observations were quantified. Using nerve density, we statistically compared the differential pattern of regenerating axon fibers within grafts and conduit. The conduits exhibited a consistent decrease in midgraft density when compared with the isograft and acellularized allografts at two gap lengths (14 mm and 28 mm) and time points (12 and 22 weeks). The decrease in density was accompanied by clustered distribution of nerve fibers in conduits, which contrasted the evenly distributed regeneration seen in processed allografts and isografts. We hypothesize that the lack of endoneurial microstructure of conduits results in the clustering regenerating fibers, and that the presence of microstructure in the acellularized allograft and isografts facilitates even distribution of regenerating fibers. © Thieme Medical Publishers.

  20. Distribution and fine structure of calcitonin gene-related peptide-like immunoreactive nerve fibers in the rat skin.

    PubMed

    Ishida-Yamamoto, A; Senba, E; Tohyama, M

    1989-07-03

    Distribution of calcitonin gene-related peptide-like immunoreactive (CGRPI) nerve fibers and their fine structure were examined in the skin of rat foot pads using immunocytochemistry. The CGRPI fibers formed bundles in the dermis and subcutaneous tissue. Two types of single-stranded CGRPI fibers were seen to leave the fiber bundles: one was located along the blood vessels or around the eccrine sweat glands, while the other entered the epidermis directly or through the Meissner's corpuscles in the dermal papillae. CGRPI fibers in the epidermis were distributed widely and were occasionally associated with Merkel cells. Immunoelectron microscopic study revealed that CGRPI fibers located around blood vessels, sweat glands, epidermal keratinocytes and Merkel cells, or in the Meissner's corpuscles did not form typical synaptic contacts with underlying cells, despite being varicose and filled with vesicles resembling synaptic ones. These findings suggested that the CGRP is released non-synaptically from these terminals to influence diffusely the organs surrounding the terminals. These cutaneous fibers seemed to originate from CGRPI neurons (both small type B cells and large type A cells) in the dorsal root ganglia (DRG), because injection of fast blue dye into the cutaneous nerve resulted in labeling of these CGRPI cells in the DRG and excision of the L3-L6 DRG resulted in the non-detection of cutaneous CGRPI fibers in the foot pads. Analysis of the composition of CGRPI fibers found in the rat skin has revealed that these are mostly unmyelinated. C-type fibers with some of them being thin myelinated fibers. This was true even of CGRPI fibers at the proximal end of peripheral neurites of the DRG.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. Fiber diameter distributions in the chinchilla's ampullary nerves

    NASA Technical Reports Server (NTRS)

    Hoffman, Larry F.; Honrubia, Vicente

    2002-01-01

    A morphometric study of the chinchilla's ampullary nerves was conducted to produce an unbiased accounting of the diameter distribution of their constituent fibers. Diameter analyses were determined from 1 microm plastic-embedded nerve sections taken at a plane immediately proximal to the sensory epithelium. We found these nerves to be composed of 2094+/-573 fibers, having diameters that ranged from 0.5 to 8 microm. The distributions of diameters were positively skewed, where approximately 75% of the fibers were found to have diameters less than 3.5 microm. An analysis of the spatial distribution of diameters within the nerve section revealed that the lateralmost areas of the nerve contained larger fractions of fibers within the smallest diameter quintiles, and the central area harbored greater proportions of the larger diameter quintiles. However, significant fractions of all quintiles were found in all areas. These data were integrated with available data of Fernandez et al. (1998) to produce diameter estimates of calyx, dimorphic, and bouton morphology subpopulations. In view of a general relationship between diameter, innervation locus, and an afferent's physiologic characteristics, these data provide the basis for developing a perspective for the in situ distribution of afferent response dynamics.

  2. Parallel Changes in Structural and Functional Measures of Optic Nerve Myelination after Optic Neuritis

    PubMed Central

    van der Walt, Anneke; Kolbe, Scott; Mitchell, Peter; Wang, Yejun; Butzkueven, Helmut; Egan, Gary; Yiannikas, Con; Graham, Stuart; Kilpatrick, Trevor; Klistorner, Alexander

    2015-01-01

    Introduction Visual evoked potential (VEP) latency prolongation and optic nerve lesion length after acute optic neuritis (ON) corresponds to the degree of demyelination, while subsequent recovery of latency may represent optic nerve remyelination. We aimed to investigate the relationship between multifocal VEP (mfVEP) latency and optic nerve lesion length after acute ON. Methods Thirty acute ON patients were studied at 1,3,6 and 12 months using mfVEP and at 1 and 12 months with optic nerve MRI. LogMAR and low contrast visual acuity were documented. By one month, the mfVEP amplitude had recovered sufficiently for latency to be measured in 23 (76.7%) patients with seven patients having no recordable mfVEP in more than 66% of segments in at least one test. Only data from these 23 patients was analysed further. Results Both latency and lesion length showed significant recovery during the follow-up period. Lesion length and mfVEP latency were highly correlated at 1 (r = 0.94, p = <0.0001) and 12 months (r = 0.75, p < 0.001). Both measures demonstrated a similar trend of recovery. Speed of latency recovery was faster in the early follow-up period while lesion length shortening remained relatively constant. At 1 month, latency delay was worse by 1.76ms for additional 1mm of lesion length while at 12 months, 1mm of lesion length accounted for 1.94ms of latency delay. Conclusion A strong association between two putative measures of demyelination in early and chronic ON was found. Parallel recovery of both measures could reflect optic nerve remyelination. PMID:26020925

  3. Parallel changes in structural and functional measures of optic nerve myelination after optic neuritis.

    PubMed

    van der Walt, Anneke; Kolbe, Scott; Mitchell, Peter; Wang, Yejun; Butzkueven, Helmut; Egan, Gary; Yiannikas, Con; Graham, Stuart; Kilpatrick, Trevor; Klistorner, Alexander

    2015-01-01

    Visual evoked potential (VEP) latency prolongation and optic nerve lesion length after acute optic neuritis (ON) corresponds to the degree of demyelination, while subsequent recovery of latency may represent optic nerve remyelination. We aimed to investigate the relationship between multifocal VEP (mfVEP) latency and optic nerve lesion length after acute ON. Thirty acute ON patients were studied at 1, 3, 6 and 12 months using mfVEP and at 1 and 12 months with optic nerve MRI. LogMAR and low contrast visual acuity were documented. By one month, the mfVEP amplitude had recovered sufficiently for latency to be measured in 23 (76.7%) patients with seven patients having no recordable mfVEP in more than 66% of segments in at least one test. Only data from these 23 patients was analysed further. Both latency and lesion length showed significant recovery during the follow-up period. Lesion length and mfVEP latency were highly correlated at 1 (r = 0.94, p = <0.0001) and 12 months (r = 0.75, p < 0.001). Both measures demonstrated a similar trend of recovery. Speed of latency recovery was faster in the early follow-up period while lesion length shortening remained relatively constant. At 1 month, latency delay was worse by 1.76 ms for additional 1mm of lesion length while at 12 months, 1mm of lesion length accounted for 1.94 ms of latency delay. A strong association between two putative measures of demyelination in early and chronic ON was found. Parallel recovery of both measures could reflect optic nerve remyelination.

  4. Epidermal Nerve Fiber Quantification in Patients With Erythromelalgia.

    PubMed

    Mantyh, William G; Dyck, P James B; Dyck, Peter J; Engelstad, Janean K; Litchy, William J; Sandroni, Paola; Davis, Mark D P

    2016-12-07

    Erythromelalgia is a clinical diagnosis based on intermittent warmth, erythema, and pain in the distal extremities. One problem facing physicians is how to objectively test for this disease. Given that other painful conditions of the distal extremities (ie, neuropathy related to human immunodeficiency virus, diabetes, or Fabry disease) can be evaluated with a skin biopsy to visualize pathologically decreased densities of the small nerve fibers that innervate the epidermis, one hypothesis is that erythromelalgia could similarly be associated with a loss of epidermal nerve fiber density (ENFD). To examine whether erythromelalgia is associated with a structural loss of small fibers using the ENFD technique and to compare this with functional studies of small nerve fibers. In a retrospective study of 52 consecutive patients with erythromelalgia who were seen between September 1, 2010, and September 22, 2015, patients were interviewed and examined and their conditions clinically diagnosed by a board-certified dermatologist at a large tertiary referral center, where ENFD testing became a routine part of evaluating erythromelalgia in 2010. Thus, all 52 consecutive patients were included solely based on their clinical diagnosis of erythromelalgia. For quantification of ENFD, observers were masked to all patient information except for name and clinic number. The hypothesis that patients with erythromelalgia would have decreased ENFD was formulated before data collection. Epidermal nerve fiber density, the primary outcome, is a measurement of the density of small nerve fibers within the epidermis. Secondary measures included functional small fiber evaluation, such as autonomic (heart rate, blood pressure, and sweat testing) and subjective testing of pain. In this cohort study, 52 consecutively seen patients were identified (female, 42 [80%]; median age, 44 years; age range, 13-82 years). Whereas only 5 of 52 patients (10%) had ENFD at or below the fifth percentile of healthy

  5. Autotaxin and lysophosphatidic acid1 receptor-mediated demyelination of dorsal root fibers by sciatic nerve injury and intrathecal lysophosphatidylcholine

    PubMed Central

    2010-01-01

    Background Although neuropathic pain is frequently observed in demyelinating diseases such as Guillain-Barré syndrome and multiple sclerosis, the molecular basis for the relationship between demyelination and neuropathic pain behaviors is poorly understood. Previously, we found that lysophosphatidic acid receptor (LPA1) signaling initiates sciatic nerve injury-induced neuropathic pain and demyelination. Results In the present study, we have demonstrated that sciatic nerve injury induces marked demyelination accompanied by myelin-associated glycoprotein (MAG) down-regulation and damage of Schwann cell partitioning of C-fiber-containing Remak bundles in the sciatic nerve and dorsal root, but not in the spinal nerve. Demyelination, MAG down-regulation and Remak bundle damage in the dorsal root were abolished in LPA1 receptor-deficient (Lpar1-/-) mice, but these alterations were not observed in sciatic nerve. However, LPA-induced demyelination in ex vivo experiments was observed in the sciatic nerve, spinal nerve and dorsal root, all which express LPA1 transcript and protein. Nerve injury-induced dorsal root demyelination was markedly attenuated in mice heterozygous for autotaxin (atx+/-), which converts lysophosphatidylcholine (LPC) to LPA. Although the addition of LPC to ex vivo cultures of dorsal root fibers in the presence of recombinant ATX caused potent demyelination, it had no significant effect in the absence of ATX. On the other hand, intrathecal injection of LPC caused potent dorsal root demyelination, which was markedly attenuated or abolished in atx+/- or Lpar1-/- mice. Conclusions These results suggest that LPA, which is converted from LPC by ATX, activates LPA1 receptors and induces dorsal root demyelination following nerve injury, which causes neuropathic pain. PMID:21062487

  6. Effect of optic nerve sheath fenestration for idiopathic intracranial hypertension on retinal nerve fiber layer thickness.

    PubMed

    Starks, Victoria; Gilliland, Grant; Vrcek, Ivan; Gilliland, Connor

    2016-01-01

    The objective of the study was to evaluate whether optic nerve sheath fenestration in patients with idiopathic intracranial hypertension was associated with improvement in visual field pattern deviation and optical coherence tomography retinal nerve fiber layer thickness.The records of 13 eyes of 11 patients who underwent optic nerve sheath fenestration were reviewed. The subjects were patients of a clinical practice in Dallas, Texas. Charts were reviewed for pre- and postoperative visual field pattern deviation (PD) and retinal nerve fiber layer thickness (RNFL).PD and RNFL significantly improved after surgery. Average PD preoperatively was 8.51 DB and postoperatively was 4.80 DB (p = 0.0002). Average RNFL preoperatively was 113.63 and postoperatively was 102.70 (p = 0.01). The preoperative PD and RNFL did not correlate strongly.Our results demonstrate that PD and RNFL are improved after optic nerve sheath fenestration. The pre- and postoperative RNFL values were compared to the average RNFL value of healthy optic nerves obtained from the literature. Post-ONSF RNFL values were significantly closer to the normal value than preoperative. RNFL is an objective parameter for monitoring the optic nerve after optic nerve sheath fenestration. This study adds to the evidence that OCT RNFL may be an effective monitoring tool for patients with IIH and that it continues to be a useful parameter after ONSF.

  7. Interferon-alpha2b may impair myelinization of rat optic nerve.

    PubMed

    Mehmet, Atila; Yilmaz, Nejat; Zorludemir, Suzan; Güleryüz, Adil; Acoskun, Banu; Haciyakupoglu, Gülhan M

    2006-01-01

    This story investigated the effects of interferon-alpha-2b (IFN-alpha2b) on the optic nerves of 17 adult male Wistar albino rats. Animals were divided into 3 groups: 6 rats (group 1) received 7.5 units (5 mIU/m2) IFN-alpha2b-a normal treatment dose, and 6 (groups 2) received 30.0 units (20 mIU/m2)-a high dose; 5 rats (control group) received 0.5 mL saline. Test substances were delivered by intraperitoneal injection 3 times a week for 3 weeks with animals under inhalation anesthesia. After the rats were sacrificed, their optic nerves were dissected, sectioned, and examined under an electron microscope. The mean thicknesses of the basal membranes of blood vessels were 86.354 nm in the control group, 104.297 nm in group 1, and 140.181 nm in group 2. Basal membrane changes in IFN groups were dose dependent. Mitochondrial swelling, degeneration, increased diameter of vacuoles, and vacuolization in the cytoplasm of oligodendrocytes and astrocytes were also observed. IFN-alpha2b has histopathologic effects on blood vessels and cells of the optic nerve.

  8. Specific Paucity of Unmyelinated C-Fibers in Cutaneous Peripheral Nerves of the African Naked-Mole Rat: Comparative Analysis Using Six Species of Bathyergidae

    PubMed Central

    Smith, Ewan S; Purfürst, Bettina; Grigoryan, Tamara; Park, Thomas J; Bennett, Nigel C; Lewin, Gary R

    2012-01-01

    In mammalian peripheral nerves, unmyelinated C-fibers usually outnumber myelinated A-fibers. By using transmission electron microscopy, we recently showed that the saphenous nerve of the naked mole-rat (Heterocephalus glaber) has a C-fiber deficit manifested as a substantially lower C:A-fiber ratio compared with other mammals. Here we determined the uniqueness of this C-fiber deficit by performing a quantitative anatomical analysis of several peripheral nerves in five further members of the Bathyergidae mole-rat family: silvery (Heliophobius argenteocinereus), giant (Fukomys mechowii), Damaraland (Fukomys damarensis), Mashona (Fukomys darlingi), and Natal (Cryptomys hottentotus natalensis) mole-rats. In the largely cutaneous saphenous and sural nerves, the naked mole-rat had the lowest C:A-fiber ratio (∼1.5:1 compared with ∼3:1), whereas, in nerves innervating both skin and muscle (common peroneal and tibial) or just muscle (lateral/medial gastrocnemius), this pattern was mostly absent. We asked whether lack of hair follicles alone accounts for the C-fiber paucity by using as a model a mouse that loses virtually all its hair as a consequence of conditional deletion of the β-catenin gene in the skin. These β-catenin loss-of function mice (β-cat LOF mice) displayed only a mild decrease in C:A-fiber ratio compared with wild-type mice (4.42 compared with 3.81). We suggest that the selective cutaneous C-fiber deficit in the cutaneous nerves of naked mole-rats is unlikely to be due primarily to lack of skin hair follicles. Possible mechanisms contributing to this unique peripheral nerve anatomy are discussed. J. Comp. Neurol. 520:2785–2803, 2012. © 2012 Wiley Periodicals, Inc. PMID:22528859

  9. Recent advances toward a fiber optic sensor for nerve agent

    NASA Astrophysics Data System (ADS)

    Beshay, Manal; Cordero, Steven R.; Mukamal, Harold; Ruiz, David; Lieberman, Robert A.

    2008-04-01

    We report advances made on the development of a fiber optic nerve agent sensor having its entire length as the sensing element. Upon exposure to sarin gas or its simulant, diisopropyl fluorophosphate, the cladding changes color resulting in an alteration of the light intensity throughput. The optical fiber is multimode and consists of a fused-silica core and a nerve agent sensitive cladding. The absorption characteristics of the cladding affect the fiber's spectral attenuation and limit the length of light guiding fiber that can be deployed continuously. The absorption of the cladding is also dependent on the sensor formulation, which in turn influences the sensitivity of the fiber. In this paper, data related to the trade-off of sensitivity, spectral attenuation, and length of fiber challenged will be reported. The fiber is mass produced using a conventional fiber optic draw tower. This technology could be used to protect human resources and buildings from dangerous chemical attacks, particularly when large areas or perimeters must be covered. It may also be used passively to determine how well such areas have been decontaminated.

  10. Effect of acclimation and fixation temperatures on the number of lamellae and periodicity of myelin in fibres of the optic nerve of goldfish.

    PubMed

    Matheson, D F; Roots, B I

    1988-01-01

    Previous findings from our laboratory have shown that the optic nerves of goldfish acclimated to different temperatures differ considerably in their glycerophospholipid composition. This paper describes changes in the morphology of the nerve with different acclimation and fixation temperatures. Optic nerves of 5 and 25 degrees C acclimated fish were excised and fixed at the temperature of acclimation, or at the reverse temperature, and the morphology observed by electron microscopy. Under all temperature conditions considered there is a statistically significant linear relationship between the radius of the axon and the number of myelin lamellae. However, the temperature of acclimation and fixation both influence the regression coefficients for this relationship, the higher the acclimation temperature the lower the coefficient and the higher the fixation temperature the higher the coefficient. The periodicity of the myelin also alters with these temperatures, being greater in the 25 degrees C fish than in the 5 degrees C ones. Myelin sheath thickness is also significantly greater in the 25 degrees C fish. These results are discussed in relation to observed changes in glycerophospholipid composition and conduction velocities.

  11. Proliferation of Schwann cells in tellurium-induced demyelination in young rats. A radioautographic and teased nerve fiber study.

    PubMed

    Said, G; Duckett, S; Sauron, B

    1981-01-01

    This is a study of DNA synthesis of Schwann cells during the demyelination and the remyelination of peripheral nerves secondary to the intoxication of young rats with tellurium (Te). 3H-thymidine uptake of Schwann cells begins on day 4, reaches a zenith on day 7, and ends before day 20 on the Te diet despite continuation of the diet. The chronology of pathologic events is that myelin breakdown leading to segmental demyelination occurs first, followed within 24--48 h by the appearance of paralysis and by the beginning of DNA synthesis by the Schwann cells. A quantitative study on isolated nerve fiber preparations showed that more Schwann cells are produced than necessary to cope with the remyelination and that only one of four to six Schwann cells present in the demyelinated area at day 12 will participate in the remyelinating process.

  12. Virtual Instrumentation for a Fiber-Optics-Based Artificial Nerve

    NASA Technical Reports Server (NTRS)

    Lyons, Donald R.; Kyaw, Thet Mon; Griffin, DeVon (Technical Monitor)

    2001-01-01

    A LabView-based computer interface for fiber-optic artificial nerves has been devised as a Masters thesis project. This project involves the use of outputs from wavelength multiplexed optical fiber sensors (artificial nerves), which are capable of producing dense optical data outputs for physical measurements. The potential advantages of using optical fiber sensors for sensory function restoration is the fact that well defined WDM-modulated signals can be transmitted to and from the sensing region allowing networked units to replace low-level nerve functions for persons desirous of "intelligent artificial limbs." Various FO sensors can be designed with high sensitivity and the ability to be interfaced with a wide range of devices including miniature shielded electrical conversion units. Our Virtual Instrument (VI) interface software package was developed using LabView's "Laboratory Virtual Instrument Engineering Workbench" package. The virtual instrument has been configured to arrange and encode the data to develop an intelligent response in the form of encoded digitized signal outputs. The architectural layout of our nervous system is such that different touch stimuli from different artificial fiber-optic nerve points correspond to gratings of a distinct resonant wavelength and physical location along the optical fiber. Thus, when an automated, tunable diode laser sends scans, the wavelength spectrum of the artificial nerve, it triggers responses that are encoded with different touch stimuli by way wavelength shifts in the reflected Bragg resonances. The reflected light is detected and a resulting analog signal is fed into ADC1 board and DAQ card. Finally, the software has been written such that the experimenter is able to set the response range during data acquisition.

  13. Regeneration of optic nerve fibers of adult mammals.

    PubMed

    Watanabe, Masami

    2010-09-01

    The pathway from the retina to the brain in mammals provides a well-defined model system for investigation of not only surviving axotomy but also axonal regeneration of injured neurons. Here I introduce our recent works on axonal regeneration in the optic nerve (OpN) of adult cats. Fibers of retinal ganglion cells (RGCs) extend beyond the crush site of OpN with injections of a macrophage stimulator (oxidized galectin-1) or a Rho kinase (ROCK) inhibitor (Y-39983 or Y-27632) while axonal extension is blocked with injection of saline. Elongation of crushed optic fibers, however, is slowed after 2 weeks. Transplantation of peripheral nerve makes RGCs regenerate their transected axons into a graft but regenerated fibers extend only a few mm in the brain. Effectiveness of combination of the drugs and treatments has to be verified in future.

  14. Nitroxidergic nerve fibers of intracerebral vessels.

    PubMed

    Kotsyuba, A E; Kotsyuba, E P; Chertok, V M

    2010-05-01

    Light and electron histochemical methods were used to study the structure and distribution of neurons containing NADPH diaphorase and their processes in the parietal area of the cortex in rats. Most neurons were found to be characterized by tight associations with intracerebral vessels. The smallest distances between the axon plasmalemma and the smooth myocytes of intracerebral arteries in the cerebral cortex were at least 0.3-0.5 microm. Neuron bodies were located at functionally important locations of vessels (sites at which subsidiary vessels branched off, the origins of arterioles), and their processes accompanied vessels, densely entwining the vessels with their branches. Neurons whose dendrites contacted the bodies or process of above- or below-lying neurons often sent nerve conductors to arteries, veins, or capillaries. Thus, nitroxidergic neurons or groups of these neurons may monitor the state of the circulation at different points in the vascular bed, functioning as local nerve centers.

  15. Coding of signals in noise by amphibian auditory nerve fibers.

    PubMed

    Narins, P M

    1987-01-01

    Rate-level (R-L) functions derived for pure-tones and pure-tones in broadband noise were obtained for auditory nerve fibers in the treefrog, Eleutherodactylus coqui. Normalized R-L functions for low-frequency, low-threshold fibers exhibit a horizontal rightward shift in the presence of broadband background noise. The magnitude of this shift is directly proportional to the noise spectrum level, and inversely proportional to the fiber's threshold. R-L functions for mid- and high-frequency fibers also show a horizontal shift, but to a lesser degree, consistent with their elevated thresholds relative to the low-frequency fibers. The implications of these findings for the processing of biologically significant sounds in the high levels of background noise in the animal's natural habitat are considered.

  16. Colchicine reduces myelin thickness and axoplasm volume.

    PubMed

    Hughes, S E; Sloan, H E; Jones, L B; Oakley, B

    1983-06-16

    A Silastic cuff containing either colchicine (1% w/v) or no colchicine was placed around the lingual disorder tympani nerve of the Mongolian gerbil. After 3 days of exposure to colchicine, the mean period of the myelin sheaths was 23% less than the period observed in nerves treated with cuffs lacking colchicine, while the average number of lamellae was unaltered. At the same time colchicine reduced the volume of axoplasm by an average of 19%, an effect which was independent of fiber diameter.

  17. Adult skin-derived precursor Schwann cells exhibit superior myelination and regeneration supportive properties compared to chronically denervated nerve-derived Schwann cells.

    PubMed

    Kumar, Ranjan; Sinha, Sarthak; Hagner, Andrew; Stykel, Morgan; Raharjo, Eko; Singh, Karun K; Midha, Rajiv; Biernaskie, Jeff

    2016-04-01

    Functional outcomes following delayed peripheral nerve repair are poor. Schwann cells (SCs) play key roles in supporting axonal regeneration and remyelination following nerve injury, thus understanding the impact of chronic denervation on SC function is critical toward developing therapies to enhance regeneration. To improve our understanding of SC function following acute versus chronic-denervation, we performed functional assays of SCs from adult rodent sciatic nerve with acute- (Day 5 post) or chronic-denervation (Day 56 post), versus embryonic nerves. We also compared Schwann cells derived from adult skin-derived precursors (aSKP-SCs) as an accessible, autologous alternative to supplement the distal (denervated) nerve. We found that acutely-injured SCs and aSKP-SCs exhibited superior proliferative capacity, promotion of neurite outgrowth and myelination of axons, both in vitro and following transplant into a sciatic nerve crush injury model, while chronically-denervated SCs were severely impaired. Acute injury caused re-activation of transcription factors associated with an immature and pro-myelinating SC state (Oct-6, cJun, Sox2, AP2α, cadherin-19), but was diminished with prolonged denervation in vivo and could not be rescued following expansion in vitro suggesting that this is a permanent deficiency. Interestingly, aSKP-SCs closely resembled acutely injured and embryonic SCs, exhibiting elevated expression of these same transcription factors. In summary, prolonged denervation resulted in SC deficiency in several functional parameters that may contribute to impaired regeneration. In contrast, aSKP-SCs closely resemble the regenerative attributes ascribed to acutely-denervated or embryonic SCs emphasizing their potential as an accessible and autologous source of glia cells to enhance nerve regeneration, particularly following delays to surgical repair.

  18. Small nerve fiber involvement is frequent in X-linked adrenoleukodystrophy.

    PubMed

    Horn, Morten A; Nilsen, Kristian B; Jørum, Ellen; Mellgren, Svein I; Tallaksen, Chantal M E

    2014-05-13

    To investigate the presence of small nerve fiber dysfunction in subjects with X-linked adrenoleukodystrophy. Cross-sectional study in which 11 Norwegian subjects (3 males, 8 females) with X-linked adrenoleukodystrophy, phenotypes ranging from asymptomatic to wheelchair-bound with adrenomyeloneuropathy, were investigated with neurophysiologic studies including EMG, nerve conduction velocities, quantitative sensory testing, tests of autonomic function, and skin biopsy for intraepidermal nerve fiber density measurements. We found small nerve fiber dysfunction in 10 of 11 subjects, increasing with age and more pronounced in males. Low intraepidermal nerve fiber densities were found in 5 of 11 subjects, indicating a loss of thin unmyelinated nerve fibers peripherally. Five of 11 subjects showed small nerve fiber dysfunction despite normal nerve fiber densities, suggesting possible involvement of the spinothalamic tracts. Two subjects showed moderate abnormalities in autonomic function tests. Evidence of small nerve fiber dysfunction was widespread in this cohort of subjects with X-linked adrenoleukodystrophy, with findings indicating loss of peripheral small nerve fibers and possibly also fibers of the spinothalamic tracts. The results support the theory of primary axonal degeneration in adrenomyeloneuropathy. Evidence of nervous system involvement was found in all heterozygotes, with severity increasing with age. Clinicians caring for these patients should be alert to signs of small nerve fiber involvement.

  19. Selectivity of lingual nerve fibers to chemical stimuli

    PubMed Central

    1993-01-01

    The cell bodies of the lingual branch of the trigeminal nerve were localized in the trigeminal ganglion using extracellular recordings together with horseradish peroxidase labeling from the tongue. Individual lingual nerve fibers were characterized with regard to their conduction velocities, receptive fields, and response to thermal, mechanical, and chemical stimuli. Fibers were classified as C, A delta, A beta, cold, and warm. The chemical stimuli included NaCl, KCl, NH4Cl, CaCl2, menthol, nicotine, hexanol, and capsaicin. With increasing salt concentration the latency of the response decreased and the activity increased. The responses elicited by salts (to 2.5 M), but not nonpolar stimuli such as menthol, were reversibly inhibited by 3.5 mM of the tight junction blocker, LaCl3. These data suggest that salts diffuse into stratified squamous epithelia through tight junctions in the stratum corneum and stratum granulosum, whereupon they enter the extracellular space. 11 C fibers were identified and 5 were characterized as polymodal nociceptors. All of the C fibers were activated by one or more of the salts NaCl, KCl, or NH4Cl. Three C fibers were activated by nicotine (1 mM), but none were affected by CaCl2 (1 M), menthol (1 mM), or hexanol (50 mM). However, not all C fibers or even the subpopulation of polymodals were activated by the same salts or by nicotine. Thus, it appears that C fibers display differential responsiveness to chemical stimuli. A delta fibers also showed differential sensitivity to chemicals. Of the 35 characterized A delta mechanoreceptors, 8 responded to NaCl, 9 to KCl, 9 to NH4Cl, 0 to CaCl2, menthol, or hexanol, and 2 to nicotine. 8 of 9 of the cold fibers (characterized as A delta's) responded to menthol, none responded to nicotine, 8 of 16 were inhibited by hexanol, 9 of 19 responded to 2.5 M NH4Cl, 5 of 19 responded to 2.5 M KCl, and 1 of 19 responded to 2.5 M NaCl. In summary, lingual nerve fibers exhibit responsiveness to chemicals

  20. Differential fiber-specific block of nerve conduction in mammalian peripheral nerves using kilohertz electrical stimulation.

    PubMed

    Patel, Yogi A; Butera, Robert J

    2015-06-01

    Kilohertz electrical stimulation (KES) has been shown to induce repeatable and reversible nerve conduction block in animal models. In this study, we characterized the ability of KES stimuli to selectively block specific components of stimulated nerve activity using in vivo preparations of the rat sciatic and vagus nerves. KES stimuli in the frequency range of 5-70 kHz and amplitudes of 0.1-3.0 mA were applied. Compound action potentials were evoked using either electrical or sensory stimulation, and block of components was assessed through direct nerve recordings and muscle force measurements. Distinct observable components of the compound action potential had unique conduction block thresholds as a function of frequency of KES. The fast component, which includes motor activity, had a monotonically increasing block threshold as a function of the KES frequency. The slow component, which includes sensory activity, showed a nonmonotonic block threshold relationship with increasing KES frequency. The distinct trends with frequency of the two components enabled selective block of one component with an appropriate choice of frequency and amplitude. These trends in threshold of the two components were similar when studying electrical stimulation and responses of the sciatic nerve, electrical stimulation and responses of the vagus nerve, and sensorimotor stimulation and responses of the sciatic nerve. This differential blocking effect of KES on specific fibers can extend the applications of KES conduction block to selective block and stimulation of neural signals for neuromodulation as well as selective control of neural circuits underlying sensorimotor function.

  1. Long-term delivery of FGF-6 changes the fiber type and fatigability of muscle reinnervated from embryonic neurons transplanted into adult rat peripheral nerve.

    PubMed

    Grumbles, Robert M; Casella, Gizelda T B; Rudinsky, Michelle J; Wood, Patrick M; Sesodia, Sanjay; Bent, Melissa; Thomas, Christine K

    2007-07-01

    Motoneuron death leads to muscle denervation and atrophy. Transplantation of embryonic neurons into peripheral nerves results in reinnervation and provides a strategy to rescue muscles from atrophy independent of neuron replacement in a damaged or diseased spinal cord. But the count of regenerating axons always exceeds the number of motor units in this model, so target-derived trophic factor levels may limit reinnervation. Our aim was to examine whether long-term infusion of fibroblast growth factor-6 (FGF-6) into denervated medial gastrocnemius muscles improved the function of muscles reinnervated from neurons transplanted into nerve of adult Fischer rats. Factor delivery (10 microg, 4 weeks) began after sciatic nerve transection. After a week of nerve degeneration, 1 million embryonic day 14-15 ventral spinal cord cells were transplanted into the distal tibial stump as a neuron source. Ten weeks later, neurons that expressed motoneuron markers survived in the nerves. More myelinated axons were in nerves to saline-treated muscles than in FGF-6-treated muscles. However, each group showed comparable reductions in muscle fiber atrophy because of reinnervation. Mean reinnervated fiber area was 43%-51% of non-denervated fibers. Denervated fiber area averaged 11%. FGF-6-treated muscles were more fatigable than other reinnervated muscles but had stronger motor units and fewer type I fibers than did saline-treated muscles. FGF-6 thus influenced function by changing the type of fiber reinnervated by transplanted neurons. Deficits in FGF-6 may also contribute to the increase in type I fibers in muscles reinnervated from peripheral axons, suggesting that the effects of FGF-6 on fiber type are independent of the neuron source used for reinnervation.

  2. Modification of sodium inactivation in myelinated nerve by Anemonia toxin II and iodate. Analysis of current fluctuations and current relaxations.

    PubMed

    Neumcke, B; Schwarz, W; Stämpfli, R

    1980-08-04

    (1) Na+ currents and Na+ current fluctuations were measured in single myelinated nerve fibres of Rana esculenta under voltage-clamp conditions. The process of Na+ inactivation was modified by external treatment with 7 microM Anemonia Toxin II or by internal application of 20 or 40 mM IO3(-). (2) At depolarization of 24 and 32 mV the spectral density of Na+ current fluctuations could be described as the sum of two contributions, Sh(f) and Sm(f), representing the spectrum from fluctuations of the inactivation (h) and activation (m) gates, respectively. At higher depolarizations of 40 and 48 mV the low frequency (h) fluctuations could be better fitted by the sum, Sh1(f)+Sh2(f), of two separate Lorentzian functions. (3) The Na+ current and the variance of Na+ current fluctuations between 150 and 450 ms after depolarization are increased by one order of magnitude after application of Anemonia Toxin II or IO3(-). (4) The kinetics of Na+ current inactivation were described as A1 x exp(-t/tau h1) + A2 x exp(-t/tau h2) + B. The constant, tau h1, of fast Na+ inactivation was the same in normal and modified nerve fibres. The slow inactivation time constant, tau h2, increased with increasing depolarizations in modified fibres but decreased under control conditions. In all cases tau h2 showed a similar voltage dependence as the time constant found by fitting the low frequency fluctuations of Na+ current with one Lorentzian function, Sh(f). (5) It is concluded that Anemonia Toxin II and IO3(-) modify a fraction of Na+ channels in an all-or-none manner. A lower limit of the number of modified Na+ channels is estimated from the Na+ current and the variance Na+ current fluctuations. 7 microM external Anemonia Toxin II modifies more than 17% and 20 or 40 mM internal IO3(-) more than 8% of all Na+ channels. The inactivation gates in modified channels experience an electric field different from that in normal fibres.

  3. A dynamic X-ray diffraction study of anaesthesia action. Changes in myelin structure and electrical activity recorded simultaneously from frog sciatic nerves treated with n-alkanes.

    PubMed

    Padrón, R; Mateu, L; Requena, J

    1980-11-04

    Changes induced in the structure and electrical activity of myelin were recorded simultaneously from frog sciatic nerves treated with n-alkanes. The results suggest that the effect of n-alkanes seems to be two-fold: (a) there is an initial reversible phase, in which a significant modification of the X-ray diffraction patterns, concomitant with the continuous fall of the action potential, is observed; (b) there is a final phase which is irreversible. This occurs some time after the complete abolition of the electrical activity. At this stage, further changes of the X-ray diffraction patterns are detected, the most significant of them being in the n-pentane-treated myelin, and consist of an increase in the membrane bilayer thickness.

  4. Secretory leukocyte protease inhibitor reverses inhibition by CNS myelin, promotes regeneration in the optic nerve, and suppresses expression of the TGFβ signaling protein Smad2

    PubMed Central

    Hannila, Sari S.; Siddiq, Mustafa M.; Carmel, Jason B.; Hou, Jianwei; Chaudhry, Nagarathnamma; Bradley, Peter M.J.; Hilaire, Melissa; Richman, Erica L.; Hart, Ronald P.; Filbin, Marie T.

    2013-01-01

    Following CNS injury, axonal regeneration is limited by myelin-associated inhibitors; however, this can be overcome through elevation of intracellular cyclic AMP, as occurs with conditioning lesions of the sciatic nerve. This study reports that expression of secretory leukocyte protease inhibitor (SLPI) is strongly upregulated in response to elevation of cyclic AMP. We also show that SLPI can overcome inhibition by CNS myelin and significantly enhance regeneration of transected retinal ganglion cell axons in rats. Furthermore, regeneration of dorsal column axons does not occur after a conditioning lesion in SLPI null mutant mice, indicating that expression of SLPI is required for the conditioning lesion effect. Mechanistically, we demonstrate that SLPI localizes to the nuclei of neurons, binds to the Smad2 promoter, and reduces levels of Smad2 protein. Adenoviral overexpression of Smad2 also blocked SLPI-induced axonal regeneration. SLPI and Smad2 may therefore represent new targets for therapeutic intervention in CNS injury. PMID:23516280

  5. Electrochemical Skin Conductance Correlates with Skin Nerve Fiber Density

    PubMed Central

    Novak, Peter

    2016-01-01

    Purpose: Electrochemical skin conductance (ESC) using reverse iontophoresis and chronoamperometry has been used to evaluate abnormal function of small fibers. How ESC correlates with loss of small fibers in skin is unclear. Methods: This was a prospective, blinded study. The primary outcome measure was the correlation between ESC at the feet and results of skin biopsies including epidermal nerve fiber density (ENFD) and sweat gland nerve fiber density (SGNFD) at the distal leg. ESC, ENFD, and SGNFD data were normalized by adjusting for weight. The secondary outcome measures were the correlation between ESC and the following variables: quantitative sudomotor axon reflex test (QSART) and symptom scales (neuropathy, pain and autonomic). Results: Eighty-one patients (mean ± sd): age = 53.3 ± 17.3, men/women = 25/56 were enrolled in the study. ESC was reduced in subjects with abnormally low ENFD (ENFD normal/abnormal, ESC = 1.17 ± 0.27/0.87 ± 0.34 μSiemens/kg, p < 0.0008) and abnormally low SGNFD (SGNFD normal/abnormal ESC = 1.09 ± 0.34/0.78 ± 0.3 μSiemens/kg, p < 0.0003). ESC correlated with ENFD (ρ = 0.73, p = 0.0001) and SGNFD (ρ = 0.64, p = 0.0001). ESC did not correlate with symptom scales. Conclusion: ESC is diminished in subjects who have a reduced number of small fibers in the skin and the ESC reduction is proportional to ENFD and SGNFD. ESC can be useful in detecting loss of small nerve fibers. PMID:27605912

  6. Electrochemical Skin Conductance Correlates with Skin Nerve Fiber Density.

    PubMed

    Novak, Peter

    2016-01-01

    Electrochemical skin conductance (ESC) using reverse iontophoresis and chronoamperometry has been used to evaluate abnormal function of small fibers. How ESC correlates with loss of small fibers in skin is unclear. This was a prospective, blinded study. The primary outcome measure was the correlation between ESC at the feet and results of skin biopsies including epidermal nerve fiber density (ENFD) and sweat gland nerve fiber density (SGNFD) at the distal leg. ESC, ENFD, and SGNFD data were normalized by adjusting for weight. The secondary outcome measures were the correlation between ESC and the following variables: quantitative sudomotor axon reflex test (QSART) and symptom scales (neuropathy, pain and autonomic). Eighty-one patients (mean ± sd): age = 53.3 ± 17.3, men/women = 25/56 were enrolled in the study. ESC was reduced in subjects with abnormally low ENFD (ENFD normal/abnormal, ESC = 1.17 ± 0.27/0.87 ± 0.34 μSiemens/kg, p < 0.0008) and abnormally low SGNFD (SGNFD normal/abnormal ESC = 1.09 ± 0.34/0.78 ± 0.3 μSiemens/kg, p < 0.0003). ESC correlated with ENFD (ρ = 0.73, p = 0.0001) and SGNFD (ρ = 0.64, p = 0.0001). ESC did not correlate with symptom scales. ESC is diminished in subjects who have a reduced number of small fibers in the skin and the ESC reduction is proportional to ENFD and SGNFD. ESC can be useful in detecting loss of small nerve fibers.

  7. Damage and repair of the peripheral myelin sheath and node of Ranvier after treatment with trypsin.

    PubMed

    Yu, R C; Bunge, R P

    1975-01-01

    Cultures of whole fetal rat sensory ganglia which had matured and myelinated in culture were treated for 1-3 h with a pulse of 0.2% trypsin. The tissue was observed during the period of treatment and during subsequent weeks using both light and electron microscopy. Within minutes after trypsin addition the matrix of the culture was altered and the nerve fascicles loosened. Progressive changes included the retraction of Schwann cell processes from the nodal region the detachment of the myelin-related paranodal Schwann cell loops from the axon, and lengthening of the nodal region as the axon was bared. The retraction of myelin from nodal stabilized several hours after trypsin withdrawal. Breakdown of the altered myelin segments was rare. There were no discernable changes in neurons or their processes after this exposure to trypsin. The partial repair which occured over a period of several weeks included the reattachment of paranodal Schwann cell loops to the axolemma and the insertion of new myelin segments where a substantial length of axolemma had been bared. The significance of these observations to the characterization of the Schwann cell-axolemmal junctions on myelinated nerve fibers is discussed. The dramatic degree of myelin change that can occur without concomitant myelin breakdown is particularly noted, as is the observation that these altered myelin segments are, in part, repaired.

  8. Evaluation of Retinal Nerve Fiber Layer in Patients with Idiopathic Optic Perineuritis using Optical Coherence Tomography

    PubMed Central

    Byon, Ik Soo; Jung, Jae Ho; Choi, Jae-Hwan; Seo, Je Hyun; Lee, Ji Eun; Choi, Hee-Young

    2015-01-01

    Abstract The aim of this study was to assess the effect of idiopathic Optic perineuritis on the retinal nerve fiber layer, and determine the ability of optical coherence tomography to evaluate retinal nerve fiber loss after idiopathic Optic perineuritis. Four patients were assessed in this study. In all cases, average retinal nerve fiber layer was significantly thinner in the affected eye in comparison with the normal reference value and with the value for the contralateral normal eye at 12 months after the onset of optic perineuritis. Our study revealed that retinal nerve fiber layer loss occurs in idiopathic optic nerve sheath inflammation. PMID:27928329

  9. Mesenchymal Stem Cell Therapy for Nerve Regeneration and Immunomodulation after Composite Tissue Allotransplantation

    DTIC Science & Technology

    2012-02-01

    fiber count, nerve cross-sectional area, myelin thickness , axonal diameter, and fiber diameter. Figure 10: Transverse nerve section stained with...tetroxide, and embedded in resin. Five micrometer thick cross-sections were cut and stained with toluidine blue for examination using light microscopy...image-analysis system linked to morphometric software (Image-Pro Plus, Bethedsda, MD). Using binary image analysis, we will measure the myelinated

  10. Pituitary adenylatecyclase-activating polypeptide-immunoreactive nerve fibers in the rat epiglottis and pharynx.

    PubMed

    Kano, Mitsuhiro; Shimizu, Yoshinaka; Suzuki, Yujiro; Furukawa, Yusuke; Ishida, Hiroko; Oikawa, Miho; Kanetaka, Hiroyasu; Ichikawa, Hiroyuki; Suzuki, Toshihiko

    2011-12-20

    The distribution of pituitary adenylatecyclase-activating polypeptide-immunoreactive (PACAP-IR) nerve fibers was studied in the rat epiglottis and pharynx. PACAP-IR nerve fibers were located beneath the mucous epithelium, and occasionally penetrated the epithelium. These nerve fibers were abundant on the laryngeal side of the epiglottis and in the dorsal and lateral border region between naso-oral and laryngeal parts of the pharynx. PACAP-IR nerve fibers were also detected in taste buds within the epiglottis and pharynx. In addition, many PACAP-IR nerve fibers were found around acinar cells and blood vessels. The double immunofluorescence method demonstrated that distribution of PACAP-IR nerve fibers was similar to that in CGRP-IR nerve fibers in the epithelium and taste bud. However, distributions of PACAP-IR and CGRP-IR nerve fibers innervating mucous glands and blood vessels were different. The retrograde tracing method also demonstrated that PACAP and CGRP were co-expressed by vagal and glossopharyngeal sensory neurons innervating the pharynx. These findings suggest that PACAP-IR nerve fibers in the epithelium and taste bud of the epiglottis and pharynx which originate from the vagal and glossopharyngeal sensory ganglia include nociceptors and chemoreceptors. The origin of PACAP-IR nerve fibers which innervate mucous glands and blood vessels may be the autonomic ganglion. Copyright © 2011 Elsevier GmbH. All rights reserved.

  11. Central projections of auditory nerve fibers in the barn owl.

    PubMed

    Carr, C E; Boudreau, R E

    1991-12-08

    The central projections of the auditory nerve were examined in the barn owl. Each auditory nerve fiber enters the brain and divides to terminate in both the cochlear nucleus angularis and the cochlear nucleus magnocellularis. This division parallels a functional division into intensity and time coding in the auditory system. The lateral branch of the auditory nerve innervates the nucleus angularis and gives rise to a major and a minor terminal field. The terminals range in size and shape from small boutons to large irregular boutons with thorn-like appendages. The medial branch of the auditory nerve conveys phase information to the cells of the nucleus magnocellularis via large axosomatic endings or end bulbs of Held. Each medial branch divides to form 3-6 end bulbs along the rostrocaudal orientation of a single tonotopic band, and each magnocellular neuron receives 1-4 end bulbs. The end bulb envelops the postsynaptic cell body and forms large numbers of synapses. The auditory nerve profiles contain round clear vesicles and form punctate asymmetric synapses on both somatic spines and the cell body.

  12. Reduced neurofilament expression in cutaneous nerve fibers of patients with CMT2E.

    PubMed

    Pisciotta, Chiara; Bai, Yunhong; Brennan, Kathryn M; Wu, Xingyao; Grider, Tiffany; Feely, Shawna; Wang, Suola; Moore, Steven; Siskind, Carly; Gonzalez, Michael; Zuchner, Stephan; Shy, Michael E

    2015-07-21

    To investigate the effects of NEFL Glu396Lys mutation on the expression and assembly of neurofilaments (NFs) in cutaneous nerve fibers of patients with Charcot-Marie-Tooth disease type 2E (CMT2E). A large family with CMT2E underwent clinical, electrophysiologic, and skin biopsy studies. Biopsies were processed by indirect immunofluorescence (IF), electron microscopy (EM), and Western blot analysis. The clinical features demonstrated intrafamilial phenotypic variability, and the electrophysiologic findings revealed nerve conductions that were either slow or in the intermediate range. All patients had reduced or absent compound muscular action potential amplitudes. Skin biopsies showed axons labeled with the axonal markers protein gene product 9.5 and α-tubulin, but not with NFs. The results of Western blot analysis were consistent with those of IF, showing reduced or absent NFs and normal expression of α-tubulin. EM revealed clusters of regenerated fibers, in absence of myelin sheath abnormalities. Both IF and EM failed to show NF aggregates in dermal axons. The morphometric analysis showed a smaller axonal caliber in patients than in controls. The study of the nodal/paranodal architecture demonstrated that sodium channels and Caspr were correctly localized in patients with CMT2E. Decrease in NF abundance may be a pathologic marker of CMT2E. The lack of NF aggregates, consistent with prior studies, suggests that they occur proximally leading to subsequent alterations in the axonal cytoskeleton. The small axonal caliber, along with the normal molecular architecture of nodes and paranodes, explain the reduced velocities detected in patients with CMT2E. Our results also demonstrate that skin biopsy can provide evidence of pathologic and pathogenic abnormalities in patients with CMT2E. © 2015 American Academy of Neurology.

  13. Reduced neurofilament expression in cutaneous nerve fibers of patients with CMT2E

    PubMed Central

    Bai, Yunhong; Brennan, Kathryn M.; Wu, Xingyao; Grider, Tiffany; Feely, Shawna; Wang, Suola; Moore, Steven; Siskind, Carly; Gonzalez, Michael; Zuchner, Stephan; Shy, Michael E.

    2015-01-01

    Objective: To investigate the effects of NEFL Glu396Lys mutation on the expression and assembly of neurofilaments (NFs) in cutaneous nerve fibers of patients with Charcot-Marie-Tooth disease type 2E (CMT2E). Methods: A large family with CMT2E underwent clinical, electrophysiologic, and skin biopsy studies. Biopsies were processed by indirect immunofluorescence (IF), electron microscopy (EM), and Western blot analysis. Results: The clinical features demonstrated intrafamilial phenotypic variability, and the electrophysiologic findings revealed nerve conductions that were either slow or in the intermediate range. All patients had reduced or absent compound muscular action potential amplitudes. Skin biopsies showed axons labeled with the axonal markers protein gene product 9.5 and α-tubulin, but not with NFs. The results of Western blot analysis were consistent with those of IF, showing reduced or absent NFs and normal expression of α-tubulin. EM revealed clusters of regenerated fibers, in absence of myelin sheath abnormalities. Both IF and EM failed to show NF aggregates in dermal axons. The morphometric analysis showed a smaller axonal caliber in patients than in controls. The study of the nodal/paranodal architecture demonstrated that sodium channels and Caspr were correctly localized in patients with CMT2E. Conclusions: Decrease in NF abundance may be a pathologic marker of CMT2E. The lack of NF aggregates, consistent with prior studies, suggests that they occur proximally leading to subsequent alterations in the axonal cytoskeleton. The small axonal caliber, along with the normal molecular architecture of nodes and paranodes, explain the reduced velocities detected in patients with CMT2E. Our results also demonstrate that skin biopsy can provide evidence of pathologic and pathogenic abnormalities in patients with CMT2E. PMID:26109717

  14. Nerve guidance conduits from aligned nanofibers: improvement of nerve regeneration through longitudinal nanogrooves on a fiber surface.

    PubMed

    Huang, Chen; Ouyang, Yuanming; Niu, Haitao; He, Nanfei; Ke, Qinfei; Jin, Xiangyu; Li, Dawei; Fang, Jun; Liu, Wanjun; Fan, Cunyi; Lin, Tong

    2015-04-08

    A novel fibrous conduit consisting of well-aligned nanofibers with longitudinal nanogrooves on the fiber surface was prepared by electrospinning and was subjected to an in vivo nerve regeneration study on rats using a sciatic nerve injury model. For comparison, a fibrous conduit having a similar fiber alignment structure without surface groove and an autograft were also conducted in the same test. The electrophysiological, walking track, gastrocnemius muscle, triple-immunofluorescence, and immunohistological analyses indicated that grooved fibers effectively improved sciatic nerve regeneration. This is mainly attributed to the highly ordered secondary structure formed by surface grooves and an increase in the specific surface area. Fibrous conduits made of longitudinally aligned nanofibers with longitudinal nanogrooves on the fiber surface may offer a new nerve guidance conduit for peripheral nerve repair and regeneration.

  15. Reconstruction of nerve root sheaths for sacral extradural spinal meningeal cysts with spinal nerve root fibers.

    PubMed

    Sun, Jianjun; Wang, Zhenyu; Li, Zhendong; Wu, Haibo; Yen, Ruyu; Zheng, Mei; Chang, Qing; Liu, Isabelle Yisha

    2013-11-01

    This study analyzed the clinical characteristics and outcomes of sacral extradural spinal meningeal cysts with spinal nerve root fibers treated by reconstruction of the nerve root sheaths. The relationships between the cysts and spinal nerve root fibers were examined microscopically, the cysts were partially excised, and the defects were oversewn to reconstruct the nerve root sheaths. The Improved Japanese Orthopedic Association (IJOA) scoring system was used to evaluate preoperative and postoperative neurological function. Thirty-eight patients were included in this study, with a mean age of 41.4 ± 15.57 years. The mean IJOA score was 18.8 ± 1.32 preoperatively and 19.6 ± 0.65 postoperatively, which was a significant difference (t=-3.77, P=0.001). These results indicate a significant improvement in neurological function after surgery. The most significant improvement in neurological function was sensation (z=-2.86, P=0.004), followed by bowel/bladder function (z=-2.31, P=0.02).

  16. Promoting Myelination in an In Vitro Mouse Model of the Peripheral Nerve System: The Effect of Wine Ingredients

    PubMed Central

    Stettner, Mark; Wolffram, Kathleen; Mausberg, Anne K.; Albrecht, Philipp; Derksen, Angelika; Methner, Axel; Dehmel, Thomas; Hartung, Hans-Peter; Dietrich, Helmut; Kieseier, Bernd C.

    2013-01-01

    Protective properties of moderate wine consumption against cancers, cardiovascular, metabolic and degenerative diseases have been reported in various clinical studies. Here, we analysed the effect of red wine (RW) and white wine (WW) on myelination using an in vitro embryonic co-culture mouse model. The total amount of myelin was found to be significantly increased after RW and WW treatment, while only RW significantly increased the number of internodes. Both types of wine increased rat Schwann cell- (rSC) expression of the NAD+-dependent deacetylase sirtuin-two-homolog 2 (Sirt2), a protein known to be involved in myelination. Detailed chemical analysis of RW revealed a broad spectrum of anthocyanins, piceids, and phenolics, including resveratrol (RSV). In our assay system RSV in low concentrations induced myelination. Furthermore RSV raised intracellular glutathione concentrations in rSCs and in co-cultures and therefore augmented antioxidant capacity. We conclude that wine promotes myelination in a rodent in vitro model by controlling intracellular metabolism and SC plasticity. During this process, RSV exhibits protective properties; however, the fostering effect on myelinaton during exposure to wine appears to be a complex interaction of various compounds. PMID:23762469

  17. The distribution of galanin-immunoreactive nerve fibers in the rat pharynx.

    PubMed

    Suzuki, Toshihiko; Sato, Tadasu; Kano, Mitsuhiro; Ichikawa, Hiroyuki

    2013-08-01

    Galanin (GAL) consists of a chain of 29/30 amino acids which is widely distributed in the central and peripheral nervous systems. In this study, the distribution of GAL-immunoreactive (-IR) nerve fibers was examined in the rat pharynx and its adjacent regions. GAL-IR nerve fibers were located beneath the epithelium and taste bud-like structure of the pharynx, epiglottis, soft palate and larynx. These nerve fibers were abundant in the laryngeal part of the pharynx, and were rare in other regions. Mucous glands were mostly devoid of GAL-IR nerve fibers. In the musculature of pharyngeal constrictor muscles, many GAL-IR nerve fibers were also located around small blood vessels. However, intrinsic laryngeal muscles contained only a few GAL-IR nerve fibers. The double immunofluorescence method demonstrated that the distribution pattern of GAL-IR nerve fibers was partly similar to that of calcitonin gene-related peptide-IR nerve fibers in the pharyngeal mucosa and muscles. The present findings suggest that the pharynx is one of main targets of GAL-containing nerves in the upper digestive and respiratory systems. These nerves may have sensory and autonomic origins. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Sex differences in morphometric aspects of the peripheral nerves and related diseases.

    PubMed

    Moriyama, Hiroshi; Hayashi, Shogo; Inoue, Yuriko; Itoh, Masahiro; Otsuka, Naruhito

    2016-07-15

    The elucidation of the relationship between the morphology of the peripheral nerves and the diseases would be valuable in developing new medical treatments on the assumption that characteristics of the peripheral nerves in females are different from those in males. We used 13 kinds of the peripheral nerve. The materials were obtained from 10 Japanese female and male cadavers. We performed a morphometric analysis of nerve fibers. We estimated the total number of myelinated axons, and calculated the average transverse area and average circularity ratio of myelinated axons in the peripheral nerves. There was no statistically significant difference in the total number, average transverse area, or average circularity ratio of myelinated axons between the female and male specimens except for the total number of myelinated axons in the vestibular nerve and the average circularity ratio of myelinated axons in the vagus nerve. The lower number of myelinated axons in the female vestibular nerve may be one of the reasons why vestibular disorders have a female preponderance. Moreover, the higher average circularity ratio of myelinated axons in the male vagus nerve may be one reason why vagus nerve activity to modulate pain has a male preponderance.

  19. Sex differences in morphometric aspects of the peripheral nerves and related diseases

    PubMed Central

    Moriyama, Hiroshi; Hayashi, Shogo; Inoue, Yuriko; Itoh, Masahiro; Otsuka, Naruhito

    2016-01-01

    BACKGROUND: The elucidation of the relationship between the morphology of the peripheral nerves and the diseases would be valuable in developing new medical treatments on the assumption that characteristics of the peripheral nerves in females are different from those in males. METHODS: We used 13 kinds of the peripheral nerve. The materials were obtained from 10 Japanese female and male cadavers. We performed a morphometric analysis of nerve fibers. We estimated the total number of myelinated axons, and calculated the average transverse area and average circularity ratio of myelinated axons in the peripheral nerves. RESULTS: There was no statistically significant difference in the total number, average transverse area, or average circularity ratio of myelinated axons between the female and male specimens except for the total number of myelinated axons in the vestibular nerve and the average circularity ratio of myelinated axons in the vagus nerve. CONCLUSIONS: The lower number of myelinated axons in the female vestibular nerve may be one of the reasons why vestibular disorders have a female preponderance. Moreover, the higher average circularity ratio of myelinated axons in the male vagus nerve may be one reason why vagus nerve activity to modulate pain has a male preponderance. PMID:27589511

  20. [Effect of 2,5-hexanedione on myelin protein zero in sciatic nerve and its antibody in serum of rats at different time points].

    PubMed

    Liu, Qingjun; Zhao, Lei; Duan, Huawei; Dai, Yufei; Niu, Yong; Chen, Hong; Liu, Qing; Bin, Ping; Zheng, Yuxin

    2010-05-01

    To explore the effects of 2,5-hexandione, the metabolite of n-hexane, on the expression of myelin protein zero (P0) in sciatic nerve and on the positive rate of P0 antibody in serum of rats at different time points. Seventy five Wistar rats were divided into five groups and were administrated with 400 mg/kg 2,5-hexanedione per day for 0, 1, 2, 3 and 4 weeks respectively. The P0 expression at different time points was determined with immunohischemistry and the P0 antibody in serum were detected with enzyme-linked immunosorbent assay. With the administration of 2,5-hexandione, the rats gradually showed the signs of peripheral neuropathy. P0 distribution in transverse section of sciatic nerve was different, and the intensity in myelin sheath was higher than that in axon. The expression of P0 in sciatic nerve of rats with 2,5-hexanedione administration for 0 week seemed higher than those of the other time points, and the expression of the P0 showed a decreasing tendency with the time of 2,5-hexanedione administration. The positive rate of P0 antibody in serum of rats administrated with 400 mg/kg 2,5-hexanedione for 0, 1, 2, 3 and 4 weeks were 33.3%, 26.7%, 46.7%, 46.7% and 84.6% respectively. The positive rate of Po antibodies in serum of rats showed an increasing tendency with the time of 2,5-hexanedione administration (chi2 = 11.007, P < 0.05). The P0 in sciatic nerve of rats could be destroyed by 2,5-hexanedione and P0 expression level decreased with the time of 2,5-hexanedione administration. The positive rate of P0 antibody in serum increased with the time of 2,5-hexanedione administration in rats.

  1. Nerve growth factor induces sensitization of nociceptors without evidence for increased intraepidermal nerve fiber density.

    PubMed

    Hirth, Michael; Rukwied, Roman; Gromann, Alois; Turnquist, Brian; Weinkauf, Benjamin; Francke, Klaus; Albrecht, Philip; Rice, Frank; Hägglöf, Björn; Ringkamp, Matthias; Engelhardt, Maren; Schultz, Christian; Schmelz, Martin; Obreja, Otilia

    2013-11-01

    Nerve growth factor (NGF) is involved in the long-term sensitization of nociceptive processing linked to chronic pain. Functional and structural ("sprouting") changes can contribute. Thus, humans report long-lasting hyperalgesia to mechanical and electrical stimulation after intradermal NGF injection and NGF-induced sprouting has been reported to underlie cancer bone pain and visceral pain. Using a human-like animal model we investigated the relationship between the structure and function of unmyelinated porcine nociceptors 3 weeks after intradermal NGF treatment. Axonal and sensory characteristics were studied by in vivo single-fiber electrophysiology and immunohistochemistry. C fibers recorded extracellularly were classified based on mechanical response and activity-dependent slowing (ADS) of conduction velocity. Intraepidermal nerve fiber (IENF) densities were assessed by immunohistochemistry in pigs and in human volunteers using the same NGF model. NGF increased conduction velocity and reduced ADS and propagation failure in mechano-insensitive nociceptors. The proportion of mechano-sensitive C nociceptors within NGF-treated skin areas increased from 45.1% (control) to 71% and their median mechanical thresholds decreased from 40 to 20 mN. After NGF application, the mechanical receptive fields of nociceptors increased from 25 to 43 mm(2). At the structural level, however, IENF density was not increased by NGF. In conclusion, intradermal NGF induces long-lasting axonal and mechanical sensitization in porcine C nociceptors that corresponds to hyperalgesia observed in humans. Sensitization is not accompanied by increased IENF density, suggesting that NGF-induced hyperalgesia might not depend on changes in nerve fiber density but could be linked to the recruitment of previously silent nociceptors. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  2. Increased nerve fibers in placental bed myometrium in women with preeclampsia.

    PubMed

    Fan, Ruijia; Qiu, Lin; Huang, Xiufeng; Chen, Zhengyun; Xu, Hong; Zhou, Caiyun; Zhang, Xinmei

    2011-12-01

    Narrowing of the uterine spiral arterioles below the deciduomyometrial junction is 1 of the key pathophysiological changes in women with preeclampsia. The contribution of pelvic autonomic nerves to decidualization and impaired placentation in preeclampsia is not clear. Placental bed biopsies were obtained from 10 women with preeclampsia and 23 nornotensive women at caesarean section. We stained them with anti-S100 and CD34 antibodies to detect the presence of nerve fibers and blood vessels, respectively. We detected S100-immunoactive nerve fibers in the myometrium but not in the decidua in both groups of women. S100-immunoactive nerve fiber density in the placental bed myometrium was significantly increased in women with preeclampsia compared to normotensive women. There was no clear relationship between the densities of nerve fibers and CD34-positive blood vessels in these biopsies. These results suggest increased nerve fibers in the placental bed myometrium may play a role in the pathogenesis of the preeclampsia.

  3. Reproducibility in Nerve Morphometry: Comparison between Methods and among Observers

    PubMed Central

    Bilego Neto, Antônio Paulo da Costa; Silveira, Fernando Braga Cassiano; Rodrigues da Silva, Greice Anne; Sanada, Luciana Sayuri; Fazan, Valéria Paula Sassoli

    2013-01-01

    We investigated the reproducibility of a semiautomated method (computerized with manual intervention) for nerve morphometry (counting and measuring myelinated fibers) between three observers with different levels of expertise and experience with the method. Comparisons between automatic (fully computerized) and semiautomated morphometric methods performed by the same computer software using the same nerve images were also performed. Sural nerves of normal adult rats were used. Automatic and semiautomated morphometry of the myelinated fibers were made through the computer software KS-400. Semiautomated morphometry was conducted by three independent observers on the same images, using the semiautomated method. Automatic morphometry overestimated the myelin sheath area, thus overestimating the myelinated fiber size and underestimating the axon size. Fiber distributions overestimation was of 0.5 μm. For the semiautomated morphometry, no differences were found between observers for myelinated fiber and axon size distributions. Overestimation of the myelin sheath size of normal fibers by the fully automatic method might have an impact when morphometry is used for diagnostic purposes. We suggest that not only semiautomated morphometry results can be compared between different centers in clinical trials but it can also be performed by more than one investigator in one single experiment, being a reliable and reproducible method. PMID:23841086

  4. Delay-induced destabilization of entrainment of nerve impulses on ephaptically coupled nerve fibers

    NASA Astrophysics Data System (ADS)

    Adhikari, Mohit H.; McIver, John K.; Coutsias, Evangelos A.

    2009-01-01

    We study the effect of delay on the synchronization of two nerve impulses traveling along two ephaptically coupled, unmyelinated nerve fibers. The system is modeled as a pair of delay-coupled Fitzhugh-Nagumo equations. A multiple-scale perturbation approach is used for the analysis of these equations in the limit of weak coupling. In the absence of delay, two pulses with identical speeds are shown to be entrained precisely. However, as the delay is increased beyond a critical value, we show that this precise entrainment becomes unstable. We make quantitative estimates for the actual values of delay at which this can occur in the case of squid giant axons and compare them with the relevant time scales involved.

  5. Peptide Mimetic of the S100A4 Protein Modulates Peripheral Nerve Regeneration and Attenuates the Progression of Neuropathy in Myelin Protein P0 Null Mice

    PubMed Central

    Moldovan, Mihai; Pinchenko, Volodymyr; Dmytriyeva, Oksana; Pankratova, Stanislava; Fugleholm, Kåre; Klingelhofer, Jorg; Bock, Elisabeth; Berezin, Vladimir; Krarup, Christian; Kiryushko, Darya

    2013-01-01

    We recently found that S100A4, a member of the multifunctional S100 protein family, protects neurons in the injured brain and identified two sequence motifs in S100A4 mediating its neurotrophic effect. Synthetic peptides encompassing these motifs stimulated neuritogenesis and survival in vitro and mimicked the S100A4-induced neuroprotection in brain trauma. Here, we investigated a possible function of S100A4 and its mimetics in the pathologies of the peripheral nervous system (PNS). We found that S100A4 was expressed in the injured PNS and that its peptide mimetic (H3) affected the regeneration and survival of myelinated axons. H3 accelerated electrophysiological, behavioral and morphological recovery after sciatic nerve crush while transiently delaying regeneration after sciatic nerve transection and repair. On the basis of the finding that both S100A4 and H3 increased neurite branching in vitro, these effects were attributed to the modulatory effect of H3 on initial axonal sprouting. In contrast to the modest effect of H3 on the time course of regeneration, H3 had a long-term neuroprotective effect in the myelin protein P0 null mice, a model of dysmyelinating neuropathy (Charcot-Marie-Tooth type 1 disease), where the peptide attenuated the deterioration of nerve conduction, demyelination and axonal loss. From these results, S100A4 mimetics emerge as a possible means to enhance axonal sprouting and survival, especially in the context of demyelinating neuropathies with secondary axonal loss, such as Charcot-Marie-Tooth type 1 disease. Moreover, our data suggest that S100A4 is a neuroprotectant in PNS and that other S100 proteins, sharing high homology in the H3 motif, may have important functions in PNS pathologies. PMID:23508572

  6. Changes in the Distribution of Periodontal Nerve Fibers during Dentition Transition in the Cat.

    PubMed

    Miki, Koji; Honma, Shiho; Ebara, Satomi; Kumamoto, Kenzo; Murakami, Shinya; Wakisaka, Satoshi

    2015-01-01

    The periodontal ligament has a rich sensory nerve supply which originates from the trigeminal ganglion and trigeminal mesencephalic nucleus. Although various types of mechanoreceptors have been reported in the periodontal ligament, the Ruffini ending is an essential one. It is unknown whether the distribution of periodontal nerve fibers in deciduous teeth is identical to that in permanent teeth or not. Moreover, morphological changes in the distribution of periodontal nerve fibers during resorption of deciduous teeth and eruption of successional permanent teeth in diphyodont animals have not been reported in detail. Therefore, in this study, we examined changes in the distribution of periodontal nerve fibers in the cat during changes in dentition (i.e., deciduous, mixed and permanent dentition) by immunohistochemistry of protein gene product 9.5. During deciduous dentition, periodontal nerve fibers were concentrated at the apical portion, and sparsely distributed in the periodontal ligament of deciduous molars. During mixed dentition, the periodontal nerve fibers of deciduous molars showed degenerative profiles during resorption. In permanent dentition, the periodontal nerve fibers of permanent premolars, the successors of deciduous molars, increased in number. Similar to permanent premolars, the periodontal nerve fibers of permanent molars, having no predecessors, increased in number, and were densely present in the apical portion. The present results indicate that the distribution of periodontal nerve fibers in deciduous dentition is almost identical to that in permanent dentition although the number of periodontal nerve fibers in deciduous dentition was low. The sparse distribution of periodontal nerve fibers in deciduous dentition agrees with clinical evidence that children are less sensitive to tooth stimulation than adults.

  7. The rabbit brachial plexus as a model for nerve repair surgery--histomorphometric analysis.

    PubMed

    Reichert, Paweł; Kiełbowicz, Zdzisław; DziĘgiel, Piotr; Puła, Bartosz; Kuryszko, Jan; Gosk, Jerzy; Bocheńska, Aneta

    2015-02-01

    One of the most devastating injuries to the upper limb is trauma caused by the avulsion. The anatomical structure of the rabbit's brachial plexus is similar to the human brachial plexus. The aim of our study was to analyze the microanatomy and provide a detailed investigation of the rabbit's brachial plexus. The purpose of our research project was to evaluate the possibility of utilizing rabbit's plexus as a research model in studying brachial plexus injury. Studies included histomorphometric analysis of sampled ventral branches of spinal nerves C5, C6, C7, C8, and Th1, the cranial trunk, the medial part of the caudal trunk, the lateral part of the caudal trunk and peripheral nerve. Horizontal and vertical analysis was done considering following features: the axon diameter, fiber diameter and myelin sheath. The number of axons, nerve area, myelin fiber density and minimal diameter of myelin fiber, minimal axon diameter and myelin area was marked for each element. The changes between ventral branches of spinal nerves C5-Th1, trunks and peripheral nerve in which the myelin sheath, axon diameter and fiber diameter was assessed were statistically significant. It was found that the g-ratio has close value in the brachial plexus as in the peripheral nerve. The peak of these parameters was found in nerve trunks, and then decreased coherently with the nerves travelling peripherally. © 2014 Wiley Periodicals, Inc.

  8. Computer simulation of action potential propagation in septated nerve fibers.

    PubMed

    Barach, J P; Wikswo, J P

    1987-02-01

    The nonlinear, core-conductor model of action potential propagation down axisymmetric nerve fibers is adapted for an implicit, numerical simulation by computer solution of the differential equations. The calculation allows a septum to be inserted in the model fiber; the thin, passive septum is characterized by series resistance Rsz and shunt resistance Rss to the grounded bath. If Rsz is too large or Rss too small, the signal fails to propagate through the septum. Plots of the action potential profiles for various axial positions are obtained and show distortions due to the presence of the septum. A simple linear model, developed from these simulations, relates propagation delay through the septum and the preseptal risetime to Rsz and Rss. This model agrees with the simulations for a wide range of parameters and allows estimation of Rsz and Rss from measured propagation delays at the septum. Plots of the axial current as a function of both time and position demonstrate how the presence of the septum can cause prominent local reversals of the current. This result, not previously described, suggests that extracellular magnetic measurements of cellular action currents could be useful in the biophysical study of septated fibers.

  9. A simple protocol for paraffin-embedded myelin sheath staining with osmium tetroxide for light microscope observation.

    PubMed

    Di Scipio, Federica; Raimondo, Stefania; Tos, Pierluigi; Geuna, Stefano

    2008-07-01

    Experimental investigation of peripheral nerve fiber regeneration is attracting more and more attention among both basic and clinical researchers. Assessment of myelinated nerve fiber morphology is a pillar of peripheral nerve regeneration research. The gold standard for light microscopic imaging of myelinated nerve fibers is toluidine blue staining of resin-embedded semithin sections. However, many researchers are unaware that the dark staining of myelin sheaths typically produced by this procedure is due to osmium tetroxide postfixation and not due to toluidine blue. In this article, we describe a simple pre-embedding protocol for staining myelin sheaths in paraffin-embedded nerve specimens using osmium tetroxide. The method involves immersing the specimen in 2% osmium tetroxide for 2 h after paraformaldehyde fixation, followed by routine dehydration and paraffin embedding. Sections can then be observed directly under the microscope or counterstained using routine histological methods. Particularly good results were obtained with Masson's trichrome counterstain, which permits the imaging of connective structures in nerves that are not detectable in toluidine blue-stained resin sections. Finally, we describe a simple protocol for osmium etching of sections, which makes further immunohistochemical analysis possible on the same specimens. Taken together, our results suggest that the protocol described in this article is a valid alternative to the conventional resin embedding-based protocol: it is much cheaper, can be adopted by any histological laboratory, and allows immunohistochemical analysis to be conducted.

  10. Microvessel basement membrane reduplication is not associated with repeated nerve fiber degeneration and regeneration.

    PubMed

    Baker, M K; Bourque, P; Dyck, P J

    1996-03-01

    To determine whether repeated nerve fiber degeneration and regeneration can induce reduplication of endoneurial microvessel basement membranes (BMs), typical of such conditions as diabetic polyneuropathy, electronmicrographs of endoneurial microvessels of rat peroneal and tibial nerves were studied in repeatedly crushed (10 x) sciatic nerves and compared to microvessels of sham-operated uncrushed nerves. On average, crushed nerves had 2.6, SE +/- 0.1 BMs, whereas control nerves had 2.7, SE +/- 0.1 (P > 0.05). Microvessel cellular components were significantly increased in both number and size in the crushed nerves. These nerves also demonstrated a trend to increased vessel numbers and density. These results are not in keeping with the hypothesis that BM reduplication of endoneurial microvessels is simply due to repeated fiber degeneration and regeneration.

  11. Ultrastructural and cytochemical evidence for single impulse initiation zones in vestibular macular nerve fibers of rat

    NASA Technical Reports Server (NTRS)

    Ross, Muriel D.; Chee, Oliver; Black, Samuel; Cutler, Lynn

    1991-01-01

    Cupric ion-ferricyanide labeling methods and related ferrocyanide-stained tissues were used to locate the characterize, at the ultrastructural level, presumptive impulse initiation zones in the three types of vestibular macular nerve fibers. Large-diameter, M-type vestibular nerve fibers terminate in a calyx at the heminode, and labeling is coextensive with the base of the calyx. Intermediate, M/U-type nerve fibers have short, unmyelinated preterminal segments that sometimes bifurcate intamacularly, and small-diameter, U-type nerve fibers have long, unmyelinated preterminal axons and up to three branches. Preterminals of these nerve fibers display ultrastructural heterogeneity that is correlated with labeling patterns for sodium channels and/or associated polyanionic sites. They have a nodelike ultrastructure and label heavily from near the heminode to the base of the macula. Their intramacular branches, less organized ultrastructurally, label only slightly. Results indicate that vestibular nerve fibers have one impulse initiation zone, located near the heminode, that varies in length according to nerve fiber type. Structural heterogeneity may favor impulse conduction in the central direction, and length of the impulse initiation zone could influence nerve discharge patterns.

  12. Peptide therapy with pentadecapeptide BPC 157 in traumatic nerve injury.

    PubMed

    Gjurasin, Miroslav; Miklic, Pavle; Zupancic, Bozidar; Perovic, Darko; Zarkovic, Kamelija; Brcic, Luka; Kolenc, Danijela; Radic, Bozo; Seiwerth, Sven; Sikiric, Predrag

    2010-02-25

    We focused on the healing of rat transected sciatic nerve and improvement made by stable gastric pentadecapeptide BPC 157 (10 microg, 10ng/kg) applied shortly after injury (i) intraperitoneally/intragastrically/locally, at the site of anastomosis, or after (ii) non-anastomozed nerve tubing (7 mm nerve segment resected) directly into the tube. Improvement was shown clinically (autotomy), microscopically/morphometrically and functionally (EMG, one or two months post-injury, walking recovery (sciatic functional index (SFI)) at weekly intervals). BPC 157-rats exhibited faster axonal regeneration: histomorphometrically (improved presentation of neural fascicles, homogeneous regeneration pattern, increased density and size of regenerative fibers, existence of epineural and perineural regeneration, uniform target orientation of regenerative fibers, and higher proportion of neural vs. connective tissue, all fascicles in each nerve showed increased diameter of myelinated fibers, thickness of myelin sheet, number of myelinated fibers per area and myelinated fibers as a percentage of the nerve transected area and the increased blood vessels presentation), electrophysiologically (increased motor action potentials), functionally (improved SFI), the autotomy absent. Thus, BPC 157 markedly improved rat sciatic nerve healing.

  13. Acute Effect of Pore-Forming Clostridium perfringens ε-Toxin on Compound Action Potentials of Optic Nerve of Mouse.

    PubMed

    Cases, Mercè; Llobet, Artur; Terni, Beatrice; Gómez de Aranda, Inmaculada; Blanch, Marta; Doohan, Briain; Revill, Alexander; Brown, Angus M; Blasi, Juan; Solsona, Carles

    2017-01-01

    ε-Toxin is a pore forming toxin produced by Clostridium perfringens types B and D. It is synthesized as a less active prototoxin form that becomes fully active upon proteolytic activation. The toxin produces highly lethal enterotoxaemia in ruminants, has the ability to cross the blood-brain barrier (BBB) and specifically binds to myelinated fibers. We discovered that the toxin induced a release of ATP from isolated mice optic nerves, which are composed of myelinated fibers that are extended from the central nervous system. We also investigated the effect of the toxin on compound action potentials (CAPs) in isolated mice optic nerves. When nerves were stimulated at 100 Hz during 200 ms, the decrease of the amplitude and the area of the CAPs was attenuated in the presence of ε-toxin. The computational modelling of myelinated fibers of mouse optic nerve revealed that the experimental results can be mimicked by an increase of the conductance of myelin and agrees with the pore forming activity of the toxin which binds to myelin and could drill it by making pores. The intimate ultrastructure of myelin was not modified during the periods of time investigated. In summary, the acute action of the toxin produces a subtle functional impact on the propagation of the nerve action potential in myelinated fibers of the central nervous system with an eventual desynchronization of the information. These results may agree with the hypothesis that the toxin could be an environmental trigger of multiple sclerosis (MS).

  14. A Perturbation Based Decomposition of Compound-Evoked Potentials for Characterization of Nerve Fiber Size Distributions.

    PubMed

    Szlavik, Robert B

    2016-02-01

    The characterization of peripheral nerve fiber distributions, in terms of diameter or velocity, is of clinical significance because information associated with these distributions can be utilized in the differential diagnosis of peripheral neuropathies. Electro-diagnostic techniques can be applied to the investigation of peripheral neuropathies and can yield valuable diagnostic information while being minimally invasive. Nerve conduction velocity studies are single parameter tests that yield no detailed information regarding the characteristics of the population of nerve fibers that contribute to the compound-evoked potential. Decomposition of the compound-evoked potential, such that the velocity or diameter distribution of the contributing nerve fibers may be determined, is necessary if information regarding the population of contributing nerve fibers is to be ascertained from the electro-diagnostic study. In this work, a perturbation-based decomposition of compound-evoked potentials is proposed that facilitates determination of the fiber diameter distribution associated with the compound-evoked potential. The decomposition is based on representing the single fiber-evoked potential, associated with each diameter class, as being perturbed by contributions, of varying degree, from all the other diameter class single fiber-evoked potentials. The resultant estimator of the contributing nerve fiber diameter distribution is valid for relatively large separations in diameter classes. It is also useful in situations where the separation between diameter classes is small and the concomitant single fiber-evoked potentials are not orthogonal.

  15. Holographic Control Of Radial Distribution Of Myelinized Nervous Fiber Refractive Index In Vitality State

    NASA Astrophysics Data System (ADS)

    Antonov I., P.; Goroshkov A., V.; Kalyunov V., N.; Markhvida I., V.; Rubanov A., S.; Tanin L., V.

    1983-12-01

    The role of investigation of peripheral vervous fibers in bitality state is of great importance when elucidating the mechanism of a stimulant low-energy laser radiation influence which is widely applicable, for example, in practice for curing lumbar osteochondros-is (1), trigeminal verve radiculitis, and in developing the processes of transmission and processing of the information required for sustaining organism homeostasis. Using both electrophysiologic and holographic methods simultaneously can increase total information and authenticity of these investigations.

  16. New insights into the signal transmission from taste cells to gustatory nerve fibers.

    PubMed

    Yoshida, Ryusuke; Ninomiya, Yuzo

    2010-01-01

    Taste receptor cells detect chemical compounds in the oral cavity and transfer their messages to gustatory afferent nerve fibers. Considering the coding of taste information, the sensitivity of taste cells and the connection between taste cells and gustatory fibers may be critical in this process. Broadly tuned taste cells and random connections between taste cells and fibers would produce gustatory fibers that have broad sensitivity to multiple taste qualities. Narrowly tuned taste cells and selective connections would yield gustatory nerve fibers that respond to specific taste quality. This review summarizes results showing molecular and morphological aspects of taste bud cells, physiological responses of taste cells, possible connections between taste cells and gustatory fibers, and transmitter release from taste cells, and discusses how taste qualities are encoded among taste bud cells and how taste information is transmitted from taste cells to gustatory nerve fibers. Copyright 2010 Elsevier Inc. All rights reserved.

  17. Immunohistochemical demonstration of enkephalin-containing nerve fibers in guinea pig and rat lungs.

    PubMed

    Shimosegawa, T; Foda, H D; Said, S I

    1989-08-01

    Met-enkephalin (Met-Enk) and Leu-enkephalin (Leu-Enk), the opioid peptides originally isolated from the brain, are believed to act as inhibitory neuromodulators at various synaptic sites. In this immunohistochemical study, we have investigated the localization and distribution of Met- and Leu-Enk immunoreactivities in airways and pulmonary vessels of guinea pigs and rats. Immunoreactivities to both peptides were found in nerve fibers and nerve terminals distributed mainly to the trachea and major bronchi, and were especially prevalent in the smooth muscle layer, in the lamina propria, and around tracheal and bronchial glands, but not in the epithelium. Few immunoreactive nerve fibers were detected in smaller bronchi, bronchioles, and alveoli. Enkephalin-immunoreactive nerve fibers were also localized in the walls of pulmonary and bronchial vessels. Within airway microganglia, immunoreactivity was observed in a few nerve terminals, but not in ganglion cell bodies. Met- and Leu-Enk immunoreactive nerve fibers showed similar distribution patterns, though minor differences were noted between the two species: Enk-immunoreactive nerve fibers in the smooth muscle layer were more abundant in guinea pigs than in rats, whereas those in mucous glands were richer in rats than in guinea pigs. These results document the presence of Met- and Leu-Enk immunoreactivity in nerve fibers supplying guinea pig and rat airways and pulmonary vessels, and provide a morphologic basis for the view that enkephalins are likely neurotransmitters or neuromodulators in the lung.

  18. Altered metabolic incorporation of fucose and leucine into PNS myelin of 25-week-old diabetic (C57BL/Ks (db/db)) mice: effects of untreated diabetes on nerve metabolism

    SciTech Connect

    Chez, M.G.; Peterson, R.G.

    1983-04-01

    Sciatic nerves of 25-week-old genetically diabetic (C57BL/Ks (db/db)) mice and their litter-mate controls were removed, and their metabolic incorporation of (/sup 3/H)fucose and (/sup 14/C)leucine into myelin was studied in vitro. Untreated diabetic animals showed significant increases (p less than 0.05) in the fucose/leucine incorporation into myelin when compared to values found for their litter-mates. These results correlated well with previous experiments performed on alloxan or streptozotocin-diabetic rats and thus show the in vitro incubation procedure to be a good indicator of altered metabolic conditions in peripheral nerves due to diabetes mellitus. The resulting ratio increases seen in diabetic animals is at variance with the decrease in ratios found in animals undergoing typical Wallerian degeneration. These results suggest that different metabolic processes operate in untreated diabetics than in normals or in those undergoing other degenerative nerve processes.

  19. Morphological studies of the vestibular nerve

    NASA Technical Reports Server (NTRS)

    Bergstroem, B.

    1973-01-01

    The anatomy of the intratemporal part of the vestibular nerve in man, and the possible age related degenerative changes in the nerve were studied. The form and structure of the vestibular ganglion was studied with the light microscope. A numerical analysis of the vestibular nerve, and caliber spectra of the myelinated fibers in the vestibular nerve branches were studied in individuals of varying ages. It was found that the peripheral endings of the vestibular nerve form a complicated pattern inside the vestibular sensory epithelia. A detailed description of the sensory cells and their surface organelles is included.

  20. Nerve fiber staining investigations in traumatic and degenerative disc lesions of the wrist.

    PubMed

    Unglaub, Frank; Wolf, Maya B; Dragu, Adrian; Schwarz, Stephan; Kroeber, Markus W; Horch, Raymund E

    2011-05-01

    Traumatic and degenerative disc lesions cause ulnar-sided wrist pain. To date, anatomical investigations of cadaver triangular fibrocartilage discs examining the innervation of the triangular fibrocartilage complex have found no evidence of nerve fibers in the healthy disc. In this study, we immunohistologically investigated biopsies from patients with either central traumatic or degenerative disc lesions, to determine the existence of nerve fibers. We hypothesized that an ingrowth of nerve fibers causes ulnar-sided wrist pain associated with traumatic and degenerative disc lesions. We included 32 patients with a traumatic Palmer 1A lesion and 17 patients with a degenerative Palmer 2C lesion in the study. We obtained a biopsy of each patient and stained the specimen with protein gene product 9.5 for nerve fiber detection. There were no nerve fibers in either traumatic or degenerative disc lesions. In addition, the marginal areas of the biopsies showed no evidence of nerve fibers. Traumatic and degenerative disc lesions show no ingrowth of nerve fibers. Copyright © 2011 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

  1. Study of neuropeptide Y-containing nerve fibers in the human penis.

    PubMed

    Wespes, E; Schiffmann, S; Gilloteaux, J; Schulman, C; Vierendeels, G; Menu, R; Pelletier, G; Vaudry, H; Vanderhaeghen, J J

    1988-10-01

    Neuropeptide Y 1-36 (IR-NPY) immunoreactive nerve-fiber processes have been observed in tunicae of veins and arteries and in smooth muscles of the human penis taken at autopsy or during surgery by use of light- and electron-microscopic immunohistochemical techniques. Numerous IR-NPY nerve fibers were mostly concentrated in the inner part of the adventitia close to the media of the arterial and venous vessels and among the intracavernous smooth muscle cells. IR-NPY nerve fibers were less abundant in veins than in arteries. Positive somata were not observed in the penises. At the ultrastructural level, IR-NPY were localized exclusively in large, dense granules of nerve terminals by means of the postembedding immunogold technique. In the deep dorsal vein, IR-NPY nerve fibers were also located in the media formed by an outer circular and an inner longitudinal layer. In the intracavernous and dorsal arteries, they showed the highest density in the inner part of the adventitia. In the corpora cavernosa and in the corpus spongiosum, IR-NPY nerve processes were intermingled between the smooth-muscle fibers around the sinusoid spaces. IR-NPY nerve fibers were present in the cavernous nerves close to the central arteries. The urethra did not show any IR-NPY-positive nerve fibers. This peculiar distribution of IR-NPY nerve fibers suggested that they could participate in regulating arterial and venous blood flow and intracavernous smooth-muscle tone. NPY may therefore be of importance in some of the mechanisms of penile erection especially during detumescence.

  2. Automatic morphometry of nerve histological sections.

    PubMed

    Romero, E; Cuisenaire, O; Denef, J F; Delbeke, J; Macq, B; Veraart, C

    2000-04-15

    A method for the automatic segmentation, recognition and measurement of neuronal myelinated fibers in nerve histological sections is presented. In this method, the fiber parameters i.e. perimeter, area, position of the fiber and myelin sheath thickness are automatically computed. Obliquity of the sections may be taken into account. First, the image is thresholded to provide a coarse classification between myelin and non-myelin pixels. Next, the resulting binary image is further simplified using connected morphological operators. By applying semantic rules to the zonal graph axon candidates are identified. Those are either isolated or still connected. Then, separation of connected fibers is performed by evaluating myelin sheath thickness around each candidate area with an Euclidean distance transformation. Finally, properties of each detected fiber are computed and false positives are removed. The accuracy of the method is assessed by evaluating missed detection, false positive ratio and comparing the results to the manual procedure with sampling. In the evaluated nerve surface, a 0.9% of false positives was found, along with 6.36% of missed detections. The resulting histograms show strong correlation with those obtained by manual measure. The noise introduced by this method is significantly lower than the intrinsic sampling variability. This automatic method constitutes an original tool for morphometrical analysis.

  3. Evaluation of retinal nerve fiber layer thickness profile in thyroid ophthalmopathy without optic nerve dysfunction.

    PubMed

    Mugdha, Kumari; Kaur, Apjit; Sinha, Neha; Saxena, Sandeep

    2016-01-01

    To evaluate retinal nerve fiber layer (RNFL) thickness profile in patients of thyroid ophthalmopathy with no clinical signs of optic nerve dysfunction. A prospective, case-control, observational study conducted at a tertiary care centre. Inclusion criteria consisted of patients with eyelid retraction in association with any one of: biochemical thyroid dysfunction, exophthalmos, or extraocular muscle involvement; or thyroid dysfunction in association with either exophthalmos or extra-ocular muscle involvement; or a clinical activity score (CAS)>3/7. Two measurements of RNFL thickness were done for each eye, by Cirrus HD-optical coherence tomography 6mo apart. Mean age of the sample was 38.75y (range 13-70y) with 18 males and 22 females. Average RNFL thickness at first visit was 92.06±12.44 µm, significantly lower than control group (101.28±6.64 µm) (P=0.0001). Thickness of inferior quadrant decreased from 118.2±21.27 µm to 115.0±22.27 µm after 6mo (P=0.02). There was no correlation between the change in CAS and RNFL thickness. Decreased RNFL thickness is an important feature of thyroid orbitopathy, which is an inherent outcome of compressive optic neuropathy of any etiology. Subclinical RNFL damage continues in the absence of clinical activity of the disease. RNFL evaluation is essential in Grave's disease and active intervention may be warranted in the presence of significant damage.

  4. Evaluation of retinal nerve fiber layer thickness profile in thyroid ophthalmopathy without optic nerve dysfunction

    PubMed Central

    Mugdha, Kumari; Kaur, Apjit; Sinha, Neha; Saxena, Sandeep

    2016-01-01

    AIM To evaluate retinal nerve fiber layer (RNFL) thickness profile in patients of thyroid ophthalmopathy with no clinical signs of optic nerve dysfunction. METHODS A prospective, case-control, observational study conducted at a tertiary care centre. Inclusion criteria consisted of patients with eyelid retraction in association with any one of: biochemical thyroid dysfunction, exophthalmos, or extraocular muscle involvement; or thyroid dysfunction in association with either exophthalmos or extra-ocular muscle involvement; or a clinical activity score (CAS)>3/7. Two measurements of RNFL thickness were done for each eye, by Cirrus HD-optical coherence tomography 6mo apart. RESULTS Mean age of the sample was 38.75y (range 13-70y) with 18 males and 22 females. Average RNFL thickness at first visit was 92.06±12.44 µm, significantly lower than control group (101.28±6.64 µm) (P=0.0001). Thickness of inferior quadrant decreased from 118.2±21.27 µm to 115.0±22.27 µm after 6mo (P=0.02). There was no correlation between the change in CAS and RNFL thickness. CONCLUSION Decreased RNFL thickness is an important feature of thyroid orbitopathy, which is an inherent outcome of compressive optic neuropathy of any etiology. Subclinical RNFL damage continues in the absence of clinical activity of the disease. RNFL evaluation is essential in Grave's disease and active intervention may be warranted in the presence of significant damage. PMID:27990368

  5. Mechanisms for differential block among single myelinated and non-myelinated axons by procaine

    PubMed Central

    Franz, Donald N.; Perry, Roger S.

    1974-01-01

    1. The differential sensitivity of saphenous nerve fibres in the cat to block by procaine HCl was re-examined by recording identifiable unit action potentials from small nerve filaments. 2. Small myelinated axons were blocked more quickly than large myelinated axons, but this differential effect could not be accounted for by differences in anaesthetic concentration requirements. 3. The onset of block in non-myelinated axons was slower than or equal to that of small myelinated axons depending on anaesthetic concentration. 4. Absolute differential block of non-myelinated and small myelinated axons was obtained by limiting the length of axons exposed to procaine to 2 mm. 5. Differential rates of blocking among myelinated axons appear to depend on differences in the length of axons that must be exposed to blocking concentrations of procaine and to arise from the irregular distribution of such concentrations within an exposed nerve. PMID:4818493

  6. A quantitative study of the facial nerve in mice prenatally exposed to ethanol.

    PubMed

    Komatsu, Suguru; Sasaki, Yasuo; Shiota, Kohei

    2003-03-01

    Pregnant ICR mice were given 20% ethanol intraperitoneally twice on day 13 of gestation and allowed to give birth to offspring. The offspring were killed at 56 days of age and the motor root of their facial nerve was examined histologically and morphometrically. The cross-sectional area of the facial nerve of mice prenatally exposed to ethanol was significantly smaller than that of the control mice. There was no significant difference in the total number of myelinated axons or the mean axonal diameter between control and ethanol-exposed mice, but the mean diameter of myelinated fibers (axon + myelin sheath) and the thickness of myelin sheath were significantly decreased in the treated group. These results suggest that prenatal exposure to ethanol disturbs myelination of the motor root of the facial nerve and may cause permanent neurological effects.

  7. [The changes of the muscular fiber phynotype at different condition of nerve injury].

    PubMed

    Luo, Quan-feng; Qi, Zuo-liang; Wang, Wei; Wang, Xing

    2006-01-01

    To observe the change of the muscular fiber phynotype at different condition of nerve injury. Rabbits were used as an animal model in this study. The trigeminus and facial nerves of the animal were simultaneously severed (group 1) or only the latter was severed (group 2). The morphologic change of the muscular fibers was observed with histochemical methods; the tension of contraction and the threshold value of electrical stimulation were observed with electrical physiological methods. Trigeminus nerve play an important role in delaying muscular atrophy after facial nerve was severed. The atrophy degree of type II a and II b muscular fibers was less in group 2 than that in group 1. The change of type 1 muscular fibers was not affected by trigeminus nerve. New muscular fibers emerged in group 2. The tension of contraction and the threshold value of electrical stimulation were better in group 2 than that of in group 1. Sensory nerve could delay muscle atrophy after denervation. Sensory nerve should be repaired simultaneously when the motor nerve was sutured. The results of this study would facilitate clinical treatment for facial palsy.

  8. Neuroplasticity of Sensory and Sympathetic Nerve Fibers in the Painful Arthritic Joint

    PubMed Central

    Ghilardi, Joseph R.; Freeman, Katie T.; Jimenez-Andrade, Juan M.; Coughlin, Kathleen; Kaczmarska, Magdalena J.; Castaneda-Corral, Gabriela; Bloom, Aaron P.; Kuskowski, Michael A.; Mantyh, Patrick W.

    2012-01-01

    Objective Many forms of arthritis are accompanied by significant chronic joint pain. Here we studied whether there is significant sprouting of sensory and sympathetic nerve fibers in the painful arthritic knee joint and whether nerve growth factor (NGF) drives this pathological reorganization. Methods A painful arthritic knee joint was produced by injection of complete Freund’s adjuvant (CFA) into the knee joint of young adult mice. CFA-injected mice were then treated systemically with vehicle or anti-NGF antibody. Pain behaviors were assessed and at 28 days following the initial CFA injection, the knee joints were processed for immunohistochemistry using antibodies raised against calcitonin gene-related peptide (CGRP; sensory nerve fibers), neurofilament 200 kDa (NF200; sensory nerve fibers), growth associated protein-43 (GAP43; sprouted nerve fibers), tyrosine hydroxylase (TH; sympathetic nerve fibers), CD31 (endothelial cells) or CD68 (monocytes/macrophages). Results In CFA-injected mice, but not vehicle-injected mice, there was a significant increase in the density of CD68+ macrophages, CD31+ blood vessels, CGRP+, NF200+, GAP43+, and TH+ nerve fibers in the synovium as well as joint pain-related behaviors. Administration of anti-NGF reduced these pain-related behaviors and the ectopic sprouting of nerve fibers, but had no significant effect on the increase in density of CD31+ blood vessels or CD68+ macrophages. Conclusions Ectopic sprouting of sensory and sympathetic nerve fibers occurs in the painful arthritic joint and may be involved in the generation and maintenance of arthritic pain. PMID:22246649

  9. Binary imaging analysis for comprehensive quantitative histomorphometry of peripheral nerve.

    PubMed

    Hunter, Daniel A; Moradzadeh, Arash; Whitlock, Elizabeth L; Brenner, Michael J; Myckatyn, Terence M; Wei, Cindy H; Tung, Thomas H H; Mackinnon, Susan E

    2007-10-15

    Quantitative histomorphometry is the current gold standard for objective measurement of nerve architecture and its components. Many methods still in use rely heavily upon manual techniques that are prohibitively time consuming, predisposing to operator fatigue, sampling error, and overall limited reproducibility. More recently, investigators have attempted to combine the speed of automated morphometry with the accuracy of manual and semi-automated methods. Systematic refinements in binary imaging analysis techniques combined with an algorithmic approach allow for more exhaustive characterization of nerve parameters in the surgically relevant injury paradigms of regeneration following crush, transection, and nerve gap injuries. The binary imaging method introduced here uses multiple bitplanes to achieve reproducible, high throughput quantitative assessment of peripheral nerve. Number of myelinated axons, myelinated fiber diameter, myelin thickness, fiber distributions, myelinated fiber density, and neural debris can be quantitatively evaluated with stratification of raw data by nerve component. Results of this semi-automated method are validated by comparing values against those obtained with manual techniques. The use of this approach results in more rapid, accurate, and complete assessment of myelinated axons than manual techniques.

  10. Relationship between myelin sheath diameter and internodal length in axons of the anterior medullary velum of the adult rat.

    PubMed

    Ibrahim, M; Butt, A M; Berry, M

    1995-11-01

    Relations between myelin sheath diameters and internodal lengths were measured in whole mounts of osmium stained intact anterior medullary velum (AMV) from glutaraldehyde perfused adult rats. The AMV is a sheet of CNS tissue which roofs the IVth ventricle and contains fascicles of myelinated fibres which arise mainly from the nucleus of the IVth cranial nerve. These fibers displayed a broad range of myelin sheath external diameters and internodal lengths, from < 1-12 microns and 50-750 microns, respectively. Myelin sheath external diameter was a measurement of the axonal diameter plus the thickness of its myelin sheath, while internodal length was measured as the distance between consecutive nodes. There was a broadly linear relationship between myelin sheath diameters and internodal lengths, with the smaller diameter sheaths tending to have shorter internodes than the larger. However, the correlation was weak and for any given diameter myelin sheaths displayed considerable variation in their internodal lengths. The smallest diameter myelin sheaths, < 4 microns, consistently had shorter internodes than predicted by a linear regression and, in an analysis of consecutive internodes in single fibres, the slope was flattened in fibres with a diameter > 4 microns. Our results indicated that small and large calibre fibres may have different myelin sheath diameter-internodal length interrelations.

  11. Coding of stimulus location and intensity in populations of mechanosensitive nerve fibers of the raccoon: I. Single fiber response properties.

    PubMed

    Ray, R H; Doetsch, G S

    1990-10-01

    The primary aim of this study was to determine and compare the receptive field (RF) characteristics and response properties of single mechanosensitive nerve fibers innervating the glabrous skin of the forepaw and hindpaw of the raccoon. The action potentials of 129 median nerve fibers and 61 posterior tibial nerve fibers were recorded in response to punctate mechanical stimuli varying in location and intensity. The stimuli were delivered to six standard test sites on digit 1 and the contiguous pads of each paw. Attempts were made to classify each fiber according to its rate of adaptation to sustained stimulation; the RF of each fiber was mapped using a standard series of stimulus intensities. The results indicated that the response properties of individual fibers were highly complex and depended on the location and intensity of stimulation. 1) The distributions of absolute threshold were not different for the median or tibial nerve fibers or for different classes of fibers based on adaptation rate. A distal to proximal increase in threshold was found for each paw, suggesting a corresponding gradient of sensitivity across the glabrous skin. 2) Threshold RF areas did not vary across either paw nor did they differ between the two paws. Suprathreshold RFs were quite large relative to expected tactile acuity and displayed complex features. 3) Response properties such as adaptation rate, on- and off-responses, were found to vary with both stimulus location and intensity. It was concluded that the responses of individual nerve fibers could not uniquely encode any stimulus parameter tested, and that the properties of single fibers could not account for apparent differences in tactile acuity across each paw or between the two paws.

  12. Immediate versus delayed primary nerve repair in the rabbit sciatic nerve

    PubMed Central

    Piskin, Ahmet; Altunkaynak, Berrin Zühal; Çιtlak, Atilla; Sezgin, Hicabi; Yazιcι, Ozgür; Kaplan, Süleyman

    2013-01-01

    It is well known that peripheral nerve injury should be treated immediately in the clinic, but in some instances, repair can be delayed. This study investigated the effects of immediate versus delayed (3 days after injury) neurorrhaphy on repair of transected sciatic nerve in New Zealand rabbits using stereological, histomorphological and biomechanical methods. At 8 weeks after immediate and delayed neurorrhaphy, axon number and area in the sciatic nerve, myelin sheath and epineurium thickness, Schwann cell morphology, and the mechanical property of nerve fibers did not differ obviously. These results indicate that delayed neurorrhaphy do not produce any deleterious effect on sciatic nerve repair. PMID:25206663

  13. Effects of metabolic syndrome on the ultrastructure of the femoral nerve in aging rats.

    PubMed

    Rodrigues de Souza, Romeu; Gama, Eliane F; El-Razi Neto, Semaan; Maldonado, Diogo

    2015-10-01

    The aim of the present study was to characterize the morphometry of the femoral nerve in aging rats with metabolic syndrome compared to controls. Systolic blood pressure and fasting plasma glucose were measured, and myelinated and unmyelinated fibers in the femoral nerves were quantitatively assessed under electron microscopy. Aging rats exposed to a regimen of metabolic syndrome developed elevation of plasma glucose concentration, mild hypertension and polyneuropathy characterized by a decrease in myelin fiber area, axon diameter, myelin sheath thickness and myelin fiber loss in the femoral nerve. The histogram of size distribution for myelinated fibers and axons from the aging rats of the control group was bimodal. For aging MS animals, the histogram turned out to be unimodal. The ultrastructure of unmyelinated fibers and of Schwann cells in 18-month-old rats was well preserved. Granules of lipofuscin were seen in unmyelinated fiber axons of 18-month-old rats with MS. The damage percentage of the large myelinated fibers has increased significantly in 18-month-old and 18-month-old (MS) rats in relation to the controls. No significant difference was observed among the groups for the g-ratio. Comparing the three groups, the number of neurotubules and neurofilaments in myelinated fibers of 18-month-old rats with MS was significantly smaller than for the groups of 18-month-old and 14-month-old rats. The overall changes seen in the femoral nerve from aging rats seem minor compared to the changes in the aging rats with MS, suggesting that long-term MS accelerates the progressive modifications in peripheral nerves that develop in old age.

  14. Nerve terminal growth remodels neuromuscular synapses in mice following regeneration of the postsynaptic muscle fiber.

    PubMed

    Li, Yue; Thompson, Wesley J

    2011-09-14

    Muscle fibers degenerate and regenerate in response to contractile damage, during aging, and in various muscle diseases that weaken the fibers. It is known that degeneration and regeneration of the segment of the postsynaptic fiber produces dramatic alterations in the neuromuscular junction (NMJ) that forms on the regenerated fiber, but the mechanisms here are incompletely understood. We have used a laser microbeam to damage the postsynaptic fibers at individual NMJs in the sternomastoid muscle of living young adult mice and then followed the synapses vitally over time using fluorescent proteins expressed in motor neurons and glial cells and staining of postsynaptic acetylcholine receptors. We find, in contrast to previous reports, that the mouse nerve terminal retains contact with the synaptic basal lamina marked by cholinesterase staining even in the absence of the target, showing that this terminal does not require a continuous supply of target-derived molecules for its maintenance. Thus, remodeling of the nerve terminal during the period of target absence does not explain the subsequent changes in the new NMJ. Rather, we see that the synapse becomes altered as the new fiber segment regenerates. Mechanisms for remodeling the synapse include failure of the regenerating muscle fiber to contact the old basal lamina and nerve terminal, growth of the nerve terminal and its glia toward the regenerating fiber, and remodeling of the initial contact as the nerve terminal becomes varicose.

  15. Chemically extracted acellular allogeneic nerve graft combined with ciliary neurotrophic factor promotes sciatic nerve repair

    PubMed Central

    Zhang, Yanru; Zhang, Hui; Katiella, Kaka; Huang, Wenhua

    2014-01-01

    A chemically extracted acellular allogeneic nerve graft can reduce postoperative immune rejection, similar to an autologous nerve graft, and can guide neural regeneration. However, it remains poorly understood whether a chemically extracted acellular allogeneic nerve graft combined with neurotrophic factors provides a good local environment for neural regeneration. This study investigated the repair of injured rat sciatic nerve using a chemically extracted acellular allogeneic nerve graft combined with ciliary neurotrophic factor. An autologous nerve anastomosis group and a chemical acellular allogeneic nerve bridging group were prepared as controls. At 8 weeks after repair, sciatic functional index, evoked potential amplitude of the soleus muscle, triceps wet weight recovery rate, total number of myelinated nerve fibers and myelin sheath thickness were measured. For these indices, values in the three groups showed the autologous nerve anastomosis group > chemically extracted acellular nerve graft + ciliary neurotrophic factor group > chemical acellular allogeneic nerve bridging group. These results suggest that chemically extracted acellular nerve grafts combined with ciliary neurotrophic factor can repair sciatic nerve defects, and that this repair is inferior to autologous nerve anastomosis, but superior to chemically extracted acellular allogeneic nerve bridging alone. PMID:25221592

  16. Human Lymphatic Mesenteric Vessels: Morphology and Possible Function of Aminergic and NPY-ergic Nerve Fibers.

    PubMed

    D'Andrea, Vito; Panarese, Alessandra; Taurone, Samanta; Coppola, Luigi; Cavallotti, Carlo; Artico, Marco

    2015-09-01

    The lymphatic vessels have been studied in different organs from a morphological to a clinical point of view. Nevertheless, the knowledge of the catecholaminergic control of the lymphatic circulation is still incomplete. The aim of this work is to study the presence and distribution of the catecholaminergic and NPY-ergic nerve fibers in the whole wall of the human mesenteric lymphatic vessels in order to obtain knowledge about their morphology and functional significance. The following experimental procedures were performed: 1) drawing of tissue containing lymphatic vessels; 2) cutting of tissue; 3) staining of tissue; 4) staining of nerve fibers; 5) histofluorescence microscopy for the staining of catecholaminergic nerve fibers; 6) staining of neuropeptide Y like-immune reactivity; 7) biochemical assay of proteins; 8) measurement of noradrenaline; 9) quantitative analysis of images; 10) statistical analysis of data. Numerous nerve fibers run in the wall of lymphatic vessels. Many of them are catecholaminergic in nature. Some nerve fibers are NPY-positive. The biochemical results on noradrenaline amounts are in agreement with morphological results on catecholaminergic nerve fibers. Moreover, the morphometric results, obtained by the quantitative analysis of images and the subsequent statistical analysis of data, confirm all our morphological and biochemical data. The knowledge of the physiological or pathological mechanism regulating the functions of the lymphatic system is incomplete. Nevertheless the catecholaminergic nerve fibers of the human mesenteric lymphatic vessels come from the adrenergic periarterial plexuses of the mesenterial arterial bed. NPY-ergic nerve fibers may modulate the microcirculatory mesenterial bed in different pathological conditions.

  17. Automated Measurement of Nerve Fiber Density Using Line Intensity Scan Analysis

    PubMed Central

    Sathyanesan, Aaron; Ogura, Tatsuya; Lin, Weihong

    2012-01-01

    Quantification of nerve fibers in peripheral and central nervous systems is important for the understanding of neuronal function, organization and pathological changes. However, current methods to quantify nerve fibers are resource-intensive and often provide an indirect measurement of nerve fiber density. Here, we describe an automated and efficient method for nerve fiber quantification, which we developed by making use of widely available software and analytical techniques, including Hessian-based feature extraction in NIH ImageJ and line intensity scan analysis. The combined use of these analytical tools through an automated routine enables reliable detection and quantification of nerve fibers from low magnification, non-uniformly labeled epifluorescence images. This allows for time-efficient determination of nerve density and also comparative analysis in large brain structures, such as hippocampus or between various regions of neural circuitry. Using this method, we have obtained accurate measurements of cholinergic fiber density in hippocampus and a large area of cortex in mouse brain sections immunolabeled with an antibody against the vesicular acetylcholine transporter (VAChT). The density values are comparable among animals tested, showing a high degree of reproducibility. Because our method can be performed at relatively low cost and in large tissue sections where nerve fibers can be labeled by various antibodies or visualized by expression of reporter proteins, such as green fluorescent protein in transgenic mice, we expect our method to be broadly useful in both research and clinical investigation. To our knowledge, this is the first method to reliably quantify nerve fibers through a rapid and automated protocol. PMID:22613744

  18. Effects of panretinal laser photocoagulation on the corneal nerve plexus and retinal nerve fiber layer in retinal vein occlusion.

    PubMed

    Bitirgen, Gulfidan; Belviranli, Selman; Malik, Rayaz A; Kerimoglu, Hurkan; Ozkagnici, Ahmet

    2017-08-30

    To determine the effects of panretinal photocoagulation (PRP) on corneal sub-basal nerve plexus (SBNP) and peripapillary retinal nerve fiber layer (RNFL) thickness in patients with unilateral central retinal vein occlusion (CRVO) who had previously undergone PRP treatment. Sixty-four eyes of 32 patients (19 male, 13 female) with unilateral ischemic type CRVO who had undergone PRP treatment at least 6 months previously were included in this cross-sectional study. The laser scanning in vivo corneal confocal microscope was used to determine corneal SBNP parameters. The peripapillary RNFL thickness was assessed with spectral-domain optical coherence tomography. Data obtained from the PRP-treated eyes were compared with those of the fellow unaffected eyes. The mean age of patients was 63.5 ± 10.7 years (range 45-85 years). The mean nerve fiber density (NFD), nerve branch density, and nerve fiber length (NFL) were significantly lower in PRP-treated eyes compared with fellow eyes (p<0.001 for all). Average peripapillary RNFL thickness was significantly lower in PRP-treated eyes than in fellow eyes (p = 0.007). The NFD and NFL showed a modest but significant positive correlation with average peripapillary RNFL thickness (r = 0.310, p = 0.013 and r = 0.272, p = 0.030, respectively). Significant reductions in corneal SBNP parameters and average peripapillary RNFL thickness were observed in the eyes of patients receiving PRP for the treatment of ischemic CRVO.

  19. Effects of dietary sphingomyelin on central nervous system myelination in developing rats.

    PubMed

    Oshida, Kyoichi; Shimizu, Takashi; Takase, Mitsunori; Tamura, Yoshitaka; Shimizu, Toshiaki; Yamashiro, Yuichiro

    2003-04-01

    Human milk contains sphingomyelin (SM) as a major component of the phospholipid fraction. Galactosylceramide (cerebroside), a metabolite of sphingolipids, increases along with CNS myelination, and is generally considered a universal marker of myelination in all vertebrates. l-Cycloserine (LCS) is an inhibitor of serine palmitoyltransferase (SPT), a rate-limiting enzyme for sphingolipid biosynthesis that is reported to show increased activity with development of the rat CNS. The present study examined the effects of dietary SM on CNS myelination during development in LCS-treated rats. From 8 d after birth, Wistar rat pups received a daily s.c. injection (100 mg/kg) of LCS. From 17 d after birth, the animals were fed an 810 mg/100g of bovine SM-supplemented diet (SM-LCS group) or a nonsupplemented diet (LCS group). At 28 d after birth, the animals were killed and subjected to biochemical and morphometric analyses. The myelin dry weight, myelin total lipid content, and cerebroside content were significantly lower in the SM-LCS and LCS groups than in a group not treated with LCS (the non-LCS group). However, these levels were significantly higher in the SM-LCS group than in the LCS group. Morphometric analysis of the optic nerve revealed that the axon diameter, nerve fiber diameter, myelin thickness, and g value (used to compare the relative thickness of myelin sheaths around fibers of different diameter) were significantly lower in the LCS group than in the other groups, but were similar in the SM-LCS and non-LCS groups. These findings suggest that dietary SM contributes to CNS myelination in developing rats with experimental inhibition of SPT activity corrected].

  20. Determination of electrode to nerve fiber distance and nerve conduction velocity through spectral analysis of the extracellular action potentials recorded from earthworm giant fibers.

    PubMed

    Qiao, Shaoyu; Odoemene, Onyekachi; Yoshida, Ken

    2012-08-01

    Microneurography and the use of selective microelectrodes that can resolve single-unit nerve activity have become a tool to understand the coding within the nervous system and a clinical diagnostic tool to assess peripheral neural pathologies. Central to these techniques is the use of the differences in the shape of the extracellular action potential (AP) waveform to identify and discriminate units from one another. Theoretical modeling of the origins of these shape differences has shown that the position of the nerve fiber relative to the electrode and the conduction velocity of the unit contribute to these differences giving rise to the hypothesis that more information about the fiber and its relationship to the electrode could be extracted given further analysis of the AP waveform. This paper addresses this question by exploring the electrical coupling between the electrode and nerve fiber. Idealized models and the literature indicate that two parameters, the electrode-fiber distance and the unit conduction velocity, contribute to the amplitude of the extracellular AP detected by the electrode, which confounds the quantification of coupling using the spike amplitude alone. To resolve this, we develop a method that enables differential quantification of these two parameters using spectral analysis of the single-unit AP waveform and demonstrate that the two parameters could be effectively decoupled in an in vitro earthworm model. The method could open the way forward toward micro-scale in situ monitoring of the interaction of nerve fiber and neural interface.

  1. A polarization measurement method for the quantification of retardation in optic nerve fiber layer

    NASA Astrophysics Data System (ADS)

    Fukuma, Yasufumi; Okazaki, Yoshio; Shioiri, Takashi; Iida, Yukio; Kikuta, Hisao; Ohnuma, Kazuhiko

    2008-02-01

    The thickness measurement of the optic nerve fiber layer is one of the most important evaluations for carrying out glaucoma diagnosis. Because the optic nerve fiber layer has birefringence, the thickness can be measured by illuminating eye optics with circular polarized light and analyzing the elliptical rate of the detected polarized light reflected from the optic nerve fiber layer. In this method, the scattering light from the background and the retardation caused by the cornea disturbs the precise measurement. If the Stokes vector expressing the whole state of polarization can be detected, we can eliminate numerically the influence of the background scattering and of the retardation caused by the cornea. Because the retardation process of the eye optics can be represented by a numerical equation using the retardation matrix of each component and also the nonpolarized background scattering light, it can be calculated by using the Stokes vector. We applied a polarization analysis system that can detect the Stokes vector onto the fundus camera. The polarization analysis system is constructed with a CCD area image sensor, a linear polarizing plate, a micro phase plate array, and a circularly polarized light illumination unit. With this simply constructed system, we can calculate the retardation caused only by the optic nerve fiber layer and it can predict the thickness of the optic nerve fiber layer. We report the method and the results graphically showing the retardation of the optic nerve fiber layer without the retardation of the cornea.

  2. Retinal nerve fiber layer thickness in optic tract syndrome.

    PubMed

    Tatsumi, Yasuko; Kanamori, Akiyasu; Kusuhara, Azusa; Nakanishi, Yoriko; Kusuhara, Sentaro; Nakamura, Makoto

    2005-01-01

    Optic tract syndrome (OTS) is characterized by incongruous homonymous hemianopia and a perpendicular pattern of bilateral optic atrophy due to the optic tract lesion. However, loss of retinal nerve fiber layer thickness (RNFLT) associated with OTS has not been quantitatively assessed. A 20-year-old woman with blunt head trauma showed normal visual acuity, color vision, ocular motility, and intraocular pressure. Because of a relative afferent pupillary defect in her left eye and left-sided homonymous hemianopia, we suspected right-sided optic tract damage, although magnetic resonance imaging detected no intracranial lesion. Using optical coherence tomography (OCT), the RNFLT of this case was measured at 31 months after the trauma and compared with age-matched normal controls (n = 41). Nasal, temporal, superior, and inferior quadrant RNFLT was reduced by 22%, 21%, 5%, and 46% in the right eye and 76%, 64%, 25%, and 27% in the left eye, respectively. The reduction was > 3 x the standard deviation of the normal mean values in the nasal and temporal quadrants of the left eye and in the inferior quadrant of the right eye. OCT can determine the RNFLT reduction corresponding to the characteristic patterns of optic atrophy of OTS. (c) Japanese Ophthalmological Society 2005.

  3. Alpha-synuclein in cutaneous small nerve fibers

    PubMed Central

    Siepmann, Timo; Illigens, Ben Min-Woo; Barlinn, Kristian

    2016-01-01

    Despite progression in the development of pharmacological therapy, treatment of alpha synucleinopathies, such as Parkinson’s disease (PD) and some atypical parkinsonism syndromes, is still challenging. To date, our knowledge of the mechanisms whereby the pathological form of alpha-synuclein causes structural and functional damage to the nervous system is limited and, consequently, there is a lack of specific diagnostic tools to evaluate pathology in these patients and differentiate PD from other neurodegenerative proteinopathies. Recent studies indicated that alpha-synuclein deposition in cutaneous small nerve fibers assessed by skin biopsies might be a valid disease marker of PD and facilitate early differentiation of PD from atypical parkinsonism syndromes. This observation is relevant since early diagnosis may enable timely treatment and improve quality of life. However, challenges include the necessity of standardizing immunohistochemical analysis techniques and the identification of potential distinct patterns of intraneural alpha-synuclein deposition among synucleinopathies. In this perspective, we explore the scientific and clinical opportunities arising from alpha-synuclein assessment using skin biopsies. These include elucidation of the peripheral nervous system pathology of PD and other synucleinopathies, identification of novel targets to study response to neuroprotective treatment, and improvement of clinical management. Furthermore, we discuss future challenges in exploring the diagnostic value of skin biopsy assessment for alpha-synuclein deposition and implementing the technique in clinical practice. PMID:27822045

  4. Retinal Nerve Fiber Layer Thickness in Amblyopic Eyes

    PubMed Central

    Repka, Michael X.; Kraker, Raymond T.; Tamkins, Susanna M.; Suh, Donny W.; Sala, Nicholas A.; Beck, Roy W.

    2010-01-01

    Purpose To compare the peripapillary retinal nerve fiber layer (RNFL) thickness of amblyopic and fellow eyes. We hypothesized that the RNFL of the amblyopic eye might be thinner. Design Prospective cross-sectional observational case series Methods Optical coherence tomography (OCT) of the peripapillary RNFL thickness of amblyopic and fellow eyes was performed in 37 patients age 7 to 12 years (mean 9.2 ± 1.5) with unilateral strabismic, anisometropic or combined mechanism amblyopia enrolled in a randomized treatment trial. Results Mean global RNFL thickness of the amblyopic and fellow eyes was 111.4 microns and 109.6 microns, respectively (mean difference = 1.8 microns thicker in the amblyopic eyes, 95% confidence interval -0.6 to +4.3 microns). The amblyopic eye was 8 or more microns thicker than the fellow eye in 9 patients (24%); the fellow eye was 8 or more microns thicker than the amblyopic eye in 2 patients (5%); and the difference was within test-retest variability (7 microns) in 26 patients (70%). Conclusions Our findings do not indicate that peripapillary RNFL thickness is thinner in eyes with moderate amblyopia compared with their fellow eyes. PMID:19327749

  5. Comparison of probabilistic and deterministic fiber tracking of cranial nerves.

    PubMed

    Zolal, Amir; Sobottka, Stephan B; Podlesek, Dino; Linn, Jennifer; Rieger, Bernhard; Juratli, Tareq A; Schackert, Gabriele; Kitzler, Hagen H

    2017-09-01

    OBJECTIVE The depiction of cranial nerves (CNs) using diffusion tensor imaging (DTI) is of great interest in skull base tumor surgery and DTI used with deterministic tracking methods has been reported previously. However, there are still no good methods usable for the elimination of noise from the resulting depictions. The authors have hypothesized that probabilistic tracking could lead to more accurate results, because it more efficiently extracts information from the underlying data. Moreover, the authors have adapted a previously described technique for noise elimination using gradual threshold increases to probabilistic tracking. To evaluate the utility of this new approach, a comparison is provided with this work between the gradual threshold increase method in probabilistic and deterministic tracking of CNs. METHODS Both tracking methods were used to depict CNs II, III, V, and the VII+VIII bundle. Depiction of 240 CNs was attempted with each of the above methods in 30 healthy subjects, which were obtained from 2 public databases: the Kirby repository (KR) and Human Connectome Project (HCP). Elimination of erroneous fibers was attempted by gradually increasing the respective thresholds (fractional anisotropy [FA] and probabilistic index of connectivity [PICo]). The results were compared with predefined ground truth images based on corresponding anatomical scans. Two label overlap measures (false-positive error and Dice similarity coefficient) were used to evaluate the success of both methods in depicting the CN. Moreover, the differences between these parameters obtained from the KR and HCP (with higher angular resolution) databases were evaluated. Additionally, visualization of 10 CNs in 5 clinical cases was attempted with both methods and evaluated by comparing the depictions with intraoperative findings. RESULTS Maximum Dice similarity coefficients were significantly higher with probabilistic tracking (p < 0.001; Wilcoxon signed-rank test). The false

  6. Molecular Regulators of Nerve Conduction - Lessons from Inherited Neuropathies and Rodent Genetic Models

    PubMed Central

    Li, Jun

    2015-01-01

    Myelinated nerve fibers are highly compartmentalized. Helically wrapped lipoprotein membranes of myelin are integrated with subsets of proteins specifically in each compartment to shape the physiological behavior of these nerve fibers. With the advance of molecular biology and genetics, many functions of these proteins have been revealed over the past decade. In this review, we will first discuss how action potential propagation has been understood by classical electrophysiological studies. In particular, the discussion will be concentrated on how the geometric dimensions of myelinated nerve fibers (such as internodal length and myelin thickness) may affect nerve conduction velocity. This discussion will then extend into how specific myelin proteins may shape these geometric parameters, thereby regulating action potential propagation. For instance, periaxin may specifically affect the internodal length, but not other parameters. In contrast, neuregulin-1 may affect myelin thickness, but not axon diameter or internodal length. Finally, we will discuss how these basic neurobiological observations can be applied to inherited peripheral nerve diseases. PMID:25792482

  7. Uncompacted Myelin Lamellae and Nodal Ion Channel Disruption in POEMS Syndrome.

    PubMed

    Hashimoto, Rina; Koike, Haruki; Takahashi, Mie; Ohyama, Ken; Kawagashira, Yuichi; Iijima, Masahiro; Sobue, Gen

    2015-12-01

    To elucidate the significance of uncompacted myelin lamellae (UML) and ion channel disruption at the nodes of Ranvier in the polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, we evaluated sural nerve biopsy specimens from 33 patients with POEMS syndrome and from 7 control patients. Uncompacted myelin lamellae distribution was assessed by electron microscopy and immunofluorescence microscopy. In the POEMS patient biopsies, UML were seen more frequently in small versus large myelinated fibers. Paranodes and Schmidt-Lanterman incisures, where normal physiologic UM is located, were frequently associated with UM. Widening of the nodes of Ranvier (i.e. segmental demyelination) was not associated with UML. There was axonal hollowing with neurofilament condensation at Schmidt-Lanterman incisures with abnormal UML, suggesting axonal damage at those sites in the POEMS patient biopsies. Myelin sheath irregularity was conspicuous in large myelinated fibers and was associated with abnormally widened bizarrely shaped Schmidt-Lanterman incisures. Indirect immunofluorescent studies revealed abnormalities of sodium (pan sodium) and potassium (KCNQ2) channels, even at nonwidened nodes of Ranvier. Thus, UML was not apparently associated with segmental demyelination but seemed to be associated with axonal damage. These observations suggest that nodal ion channel disruption may be associated with functional deficits in POEMS syndrome patient nerves.

  8. Diagnostic Ability of Retinal Nerve Fiber Layer Thickness Deviation Map for Localized and Diffuse Retinal Nerve Fiber Layer Defects

    PubMed Central

    Shin, Joong Won; Seong, Mincheol; Lee, Jung Wook; Hong, Eun Hee

    2017-01-01

    Purpose. To evaluate the diagnostic ability of the retinal nerve fiber layer (RNFL) deviation map for glaucoma with localized or diffuse RNFL defects. Methods. Eyes of 139 glaucoma patients and 165 healthy subjects were enrolled. All participants were imaged with Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA, USA). A RNFL defect was defined as at least 10 contiguous red (<1% level) superpixels in RNFL deviation map. The area, location, and angular width of RNFL defects were automatically measured. We compared sensitivities, specificities, and area under the receiver operating characteristic curves (AUCs) of RNFL deviation map and circumpapillary RNFL thickness for localized and diffuse RNFL defects. Subgroup analysis was performed according to the severity of glaucoma. Results. For localized defects, the area of RNFL defects (AUC, 0.991; sensitivity, 97%; specificity, 90%) in deviation map showed a higher diagnostic performance (p = 0.002) than the best circumpapillary RNFL parameter (inferior RNFL thickness; AUC, 0.914; sensitivity, 79%; specificity, 92%). For diffuse defects, there was no significant difference between the RNFL deviation map and circumpapillary RNFL parameters. In mild glaucoma with localized defect, RNFL deviation map showed a better diagnostic performance than circumpapillary RNFL measurement. Conclusions. RNFL deviation map is a useful tool for evaluating glaucoma regardless of localized or diffuse defect type and has advantages over circumpapillary RNFL measurement for detecting localized RNFL defects. PMID:28168048

  9. Retinal nerve fiber layer thickness and neuropsychiatric manifestations in systemic lupus erythematosus.

    PubMed

    Shulman, S; Shorer, R; Wollman, J; Dotan, G; Paran, D

    2017-01-01

    Background Cognitive impairment is frequent in systemic lupus erythematosus. Atrophy of the corpus callosum and hippocampus have been reported in patients with systemic lupus erythematosus, and diffusion tensor imaging studies have shown impaired white matter integrity, suggesting that white matter damage in systemic lupus erythematosus may underlie the cognitive impairment as well as other neuropsychiatric systemic lupus erythematosus manifestations. Retinal nerve fiber layer thickness, as assessed by optical coherence tomography, has been suggested as a biomarker for white matter damage in neurologic disorders such as multiple sclerosis, Alzheimer's disease and Parkinson's disease. Retinal nerve fiber layer thinning may occur early, even in patients with mild clinical symptoms. Aim The objective of this study was to assess the association of retinal nerve fiber layer thickness, as a biomarker of white matter damage in systemic lupus erythematosus patients, with neuropsychiatric systemic lupus erythematosus manifestations, including cognitive impairment. Methods Twenty-one consecutive patients with systemic lupus erythematosus underwent neuropsychological testing using a validated computerized battery of tests as well as the Rey-Auditory verbal learning test. All 21 patients, as well as 11 healthy, age matched controls, underwent optical coherence tomography testing to assess retinal nerve fiber layer thickness. Correlations between retinal nerve fiber layer thickness and results in eight cognitive domains assessed by the computerized battery of tests as well as the Rey-Auditory verbal learning test were assessed in patients with systemic lupus erythematosus, with and without neuropsychiatric systemic lupus erythematosus, and compared to retinal nerve fiber layer thickness in healthy controls. Results No statistically significant correlation was found between retinal nerve fiber layer thickness in patients with systemic lupus erythematosus as compared to healthy

  10. Transfer of the extensor indicis proprius branch of posterior interosseous nerve to reconstruct ulnar nerve and median nerve injured proximally: an anatomical study

    PubMed Central

    Wang, Pei-ji; Zhang, Yong; Zhao, Jia-ju; Zhou, Ju-pu; Zuo, Zhi-cheng; Wu, Bing-bing

    2017-01-01

    Proximal or middle lesions of the ulnar or median nerves are responsible for extensive loss of hand motor function. This occurs even when the most meticulous microsurgical techniques or nerve grafts are used. Previous studies had proposed that nerve transfer was more effective than nerve grafting for nerve repair. Our hypothesis is that transfer of the posterior interosseous nerve, which contains mainly motor fibers, to the ulnar or median nerve can innervate the intrinsic muscles of hands. The present study sought to investigate the feasibility of reconstruction of the deep branch of the ulnar nerve and the thenar branch of median nerve by transferring the extensor indicis proprius branch of the posterior interosseous nerve obtained from adult cadavers. The results suggested that the extensor indicis proprius branch of the posterior interosseous nerve had approximately similar diameters and number of fascicles and myelinated nerve fibers to those of the deep branch of ulnar nerve and the thenar branch of the median nerve. These confirm the feasibility of extensor indicis proprius branch of posterior interosseous nerve transfer for reconstruction of the deep branch of the ulnar nerve and the thenar branch of median nerve. This procedure could be a novel and effective method for the functional recovery of the intrinsic muscles of hands after ulnar nerve or median nerve injury. PMID:28250760

  11. FIBER-OPTIC BIOSENSOR FOR DIRECT DETERMINATION OF ORGANOPHOSPHATE NERVE AGENTS. (R823663)

    EPA Science Inventory

    A fiber-optic enzyme biosensor for the direct measurement of organophosphate nerve
    agents was developed. The basic element of this biosensor is organophosphorus hydrolase
    immobilized on a nylon membrane and attached to the common end of a bifurcated optical fiber
    bundle....

  12. FIBER-OPTIC BIOSENSOR FOR DIRECT DETERMINATION OF ORGANOPHOSPHATE NERVE AGENTS. (R823663)

    EPA Science Inventory

    A fiber-optic enzyme biosensor for the direct measurement of organophosphate nerve
    agents was developed. The basic element of this biosensor is organophosphorus hydrolase
    immobilized on a nylon membrane and attached to the common end of a bifurcated optical fiber
    bundle....

  13. Effects of deuterium oxide on the rate and dissociation constants for saxitoxin and tetrodotoxin action. Voltage-clamp studies on frog myelinated nerve

    SciTech Connect

    Hahin, R.; Strichartz, G.

    1981-08-01

    The actions of tetrodotoxin (TTX) and saxitoxin (STX) in normal water and in deuterium oxide (D/sub 20/) have been studied in frog myelinated nerve. Substitution of D/sub 20/ for H/sub 20/ in normal Ringer's solution has no effect on the potency of TTX in blocking action potentials but increases the potency of STX by approximately 50%. Under voltage clamp, the steady-state inhibition of sodium currents by 1 nM STX is doubled in D/sub 20/ as a result of a halving of the rate of dissociation of STX from the sodium channel; the rate of block by STX is not measurably changed by D/sub 20/. Neither steady-state inhibition nor the on- or off-rate constants of TTX are changed by D/sub 20/ substitution. The isotopic effects on STX binding are observed less than 10 min after the toxin has been added to D/sub 20/, thus eliminating the possibility that slow-exchange (t 1/2 greater than 10 h) hydrogen-binding sites on STX are involved. The results are consistent with a hypothesis that attributes receptor-toxin stabilization to isotopic changes of hydrogen bonding; this interpretation suggests that hydrogen bonds contribute more to the binding of STX than to that of TTX at the sodium channel.

  14. Dicer in Schwann cells is required for myelination and axonal integrity.

    PubMed

    Pereira, Jorge A; Baumann, Reto; Norrmén, Camilla; Somandin, Christian; Miehe, Michaela; Jacob, Claire; Lühmann, Tessa; Hall-Bozic, Heike; Mantei, Ned; Meijer, Dies; Suter, Ueli

    2010-05-12

    Dicer is responsible for the generation of mature micro-RNAs (miRNAs) and loading them into RNA-induced silencing complex (RISC). RISC functions as a probe that targets mRNAs leading to translational suppression and mRNA degradation. Schwann cells (SCs) in the peripheral nervous system undergo remarkable differentiation both in morphology and gene expression patterns throughout lineage progression to myelinating and nonmyelinating phenotypes. Gene expression in SCs is particularly tightly regulated and critical for the organism, as highlighted by the fact that a 50% decrease or an increase to 150% of normal gene expression of some myelin proteins, like PMP22, results in peripheral neuropathies. Here, we selectively deleted Dicer and consequently gene expression regulation by mature miRNAs from Mus musculus SCs. Our results show that in the absence of Dicer, most SCs arrest at the promyelinating stage and fail to start forming myelin. At the molecular level, the promyelinating transcription factor Krox20 and several myelin proteins [including myelin associated glycoprotein (MAG) and PMP22] were strongly reduced in mutant sciatic nerves. In contrast, the myelination inhibitors SOX2, Notch1, and Hes1 were increased, providing an additional potential basis for impaired myelination. A minor fraction of SCs, with some peculiar differences between sensory and motor fibers, overcame the myelination block and formed unusually thin myelin, in line with observed impaired neuregulin and AKT signaling. Surprisingly, we also found signs of axonal degeneration in Dicer mutant mice. Thus, our data indicate that miRNAs critically regulate Schwann cell gene expression that is required for myelination and to maintain axons via axon-glia interactions.

  15. The role of the renal afferent and efferent nerve fibers in heart failure

    PubMed Central

    Booth, Lindsea C.; May, Clive N.; Yao, Song T.

    2015-01-01

    Renal nerves contain afferent, sensory and efferent, sympathetic nerve fibers. In heart failure (HF) there is an increase in renal sympathetic nerve activity (RSNA), which can lead to renal vasoconstriction, increased renin release and sodium retention. These changes are thought to contribute to renal dysfunction, which is predictive of poor outcome in patients with HF. In contrast, the role of the renal afferent nerves remains largely unexplored in HF. This is somewhat surprising as there are multiple triggers in HF that have the potential to increase afferent nerve activity, including increased venous pressure and reduced kidney perfusion. Some of the few studies investigating renal afferents in HF have suggested that at least the sympatho-inhibitory reno-renal reflex is blunted. In experimentally induced HF, renal denervation, both surgical and catheter-based, has been associated with some improvements in renal and cardiac function. It remains unknown whether the effects are due to removal of the efferent renal nerve fibers or afferent renal nerve fibers, or a combination of both. Here, we review the effects of HF on renal efferent and afferent nerve function and critically assess the latest evidence supporting renal denervation as a potential treatment in HF. PMID:26483699

  16. The role of the renal afferent and efferent nerve fibers in heart failure.

    PubMed

    Booth, Lindsea C; May, Clive N; Yao, Song T

    2015-01-01

    Renal nerves contain afferent, sensory and efferent, sympathetic nerve fibers. In heart failure (HF) there is an increase in renal sympathetic nerve activity (RSNA), which can lead to renal vasoconstriction, increased renin release and sodium retention. These changes are thought to contribute to renal dysfunction, which is predictive of poor outcome in patients with HF. In contrast, the role of the renal afferent nerves remains largely unexplored in HF. This is somewhat surprising as there are multiple triggers in HF that have the potential to increase afferent nerve activity, including increased venous pressure and reduced kidney perfusion. Some of the few studies investigating renal afferents in HF have suggested that at least the sympatho-inhibitory reno-renal reflex is blunted. In experimentally induced HF, renal denervation, both surgical and catheter-based, has been associated with some improvements in renal and cardiac function. It remains unknown whether the effects are due to removal of the efferent renal nerve fibers or afferent renal nerve fibers, or a combination of both. Here, we review the effects of HF on renal efferent and afferent nerve function and critically assess the latest evidence supporting renal denervation as a potential treatment in HF.

  17. Neura, nerves, nerve fibers, neurofibrils, microtubules: multidimensional routes of pain, pleasure, and voluntary action in images across the ages.

    PubMed

    Frixione, Eugenio

    2013-01-01

    Available records indicate that the human body has always been conceived, in different periods and cultures, as spanned by multiple channels for internal communication and coherent functioning as a unit-"meridians" in treatises of Chinese medicine, metu in Egyptian papyri, srotas in Ayurvedic Indian texts, and neura in the Western scientific heritage from ancient Greece. Unfortunately, the earliest extant figurative depictions of such pathways of general control, complementary to the blood vessels, are late medieval copies of old crude sketches that attempted to show the main anatomico-physiological systems. The scarcity of adequate illustrations was more than compensated in the Renaissance, when the efforts of both artists and anatomists for the first time produced basically correct renditions of the human nervous system and many other bodily structures. As attention was next focused on microscopic structure as a requisite to understand physiological mechanisms, during the Enlightenment the nerves were revealed to consist of numerous thin tubes or fibers aligned in parallel. Improved microscopy techniques in the nineteenth century led to discovering and delineating still finer fibrils coursing along the cores of the nerve fibers themselves. Electron microscopy, developed throughout the twentieth century, recognized some of these fibrils within nerve fibers as being also tubular. All the progressive stages in understanding nerve construction, at increasingly more detailed scales, have been accompanied by technological advances and by debate about the structure and function relationship. And every step has been a source of amazing imagery.

  18. Biomechanics of chiasmal compression: Sensitivity of the mechanical behaviors of nerve fibers to variations in material property and geometry

    NASA Astrophysics Data System (ADS)

    Wang, Xiaofei; Neely, Andrew J.; McIlwaine, Gawn G.; Lueck, Christian J.

    2016-05-01

    The mechanism of bitemporal hemianopia is still unclear. Previous research suggested that the nerve fiber packing pattern may contribute to the selective damage of nasal (crossed) nerve fibers. Numerical models were built using finite element modeling to study the biomechanics of optic nerve fibers. The sensitivity of the mechanical behaviors of the nerve fibers to variations of five parameters in the nerve fiber model were investigated using design of experiments (DOE). Results show that the crossing angle is a very significant factor that affects a wide range of responses of the model. The strain difference between the crossed and the uncrossed nerve fibers may account for the phenomenon of bitemporal hemianopia. This work also highlights the need for more accurate material properties of the tissues in the model and an improved understanding of the microstructure of the optic chiasm.

  19. Reduction in retinal nerve fiber layer thickness in migraine patients.

    PubMed

    Gipponi, Stefano; Scaroni, Niccolò; Venturelli, Elisabetta; Forbice, Eliana; Rao, Renata; Liberini, Paolo; Padovani, Alessandro; Semeraro, Francesco

    2013-06-01

    Migraine is a common disorder and its pathogenesis remains still unclear. Several hypotheses about the mechanisms involved in the pathogenesis of migraine have been proposed, but the issue is still far from being fully clarified. Neurovascular system remains one of the most important mechanisms involved in the pathogenesis of migraine and it could be possible that hypoperfusion might involve other areas besides brain, including the retina. This is, for example, of particular interest in a form of migraine, the retinal migraine, which has been associated with hypoperfusion and vasoconstriction of the retinal vasculature. Although vasoconstriction of cerebral and retinal blood vessels is a transient phenomenon, the chronic nature of the migraine might cause permanent structural abnormalities of the brain and also of the retina. On this basis, a few studies have evaluated whether retina is involved in migraine patients: Tan et al. have not found differences in retinal nerve fiber layer (RNFL) thickness between migraine patients and healthy subjects, while Martinez et al. have shown that RNFL in the temporal retinic quadrant of migraineurs is thinner than in normal people. The aim of our study was to analyze if there are differences in retinal nerve fiber layer thickness between migraine patients and normal subjects by studying 24 consecutive migraine patients who presented at the Headache Center of our Neurological Department. Migraine diagnosis has been made according to the International Classification of Headache disorder (ICHD-II). Patients have been recruited according to strict inclusion criteria; then patients have undergone a complete ophthalmological examination at the Ophthalmological Department. All patients and controls who met the ophthalmological criteria have been examined with ocular coherence tomography spectral domain (OCT-SD) after pupillary dilation. OCT-SD is an optical system designed to acquire the retinal layer images simultaneously with fundus

  20. Retinal nerve fiber bundle tracing and analysis in human eye by polarization sensitive OCT

    PubMed Central

    Sugita, Mitsuro; Pircher, Michael; Zotter, Stefan; Baumann, Bernhard; Roberts, Philipp; Makihira, Tomoyuki; Tomatsu, Nobuhiro; Sato, Makoto; Vass, Clemens; Hitzenberger, Christoph K.

    2015-01-01

    We present a new semi-automatic processing method for retinal nerve fiber bundle tracing based on polarization sensitive optical coherence tomography (PS-OCT) data sets. The method for tracing is based on a nerve fiber orientation map that covers the fovea and optic nerve head (ONH) regions. In order to generate the orientation map, two types of information are used: optic axis orientation based on polarization data, and complementary information obtained from nerve fiber layer (NFL) local thickness variation to reveal fiber bundle structures around the fovea. The corresponding two orientation maps are fused into a combined fiber orientation map. En face maps of NFL retardation, thickness, and unit-depth-retardation (UDR, equivalent to birefringence) are transformed into “along-trace” maps by using the obtained traces of the nerve fiber bundles. The method is demonstrated in the eyes of healthy volunteers, and as an example of further analyses utilizing this method, maps illustrating the gradients of NFL retardation, thickness, and UDR are demonstrated. PMID:25798324

  1. Retinal nerve fiber bundle tracing and analysis in human eye by polarization sensitive OCT.

    PubMed

    Sugita, Mitsuro; Pircher, Michael; Zotter, Stefan; Baumann, Bernhard; Roberts, Philipp; Makihira, Tomoyuki; Tomatsu, Nobuhiro; Sato, Makoto; Vass, Clemens; Hitzenberger, Christoph K

    2015-03-01

    We present a new semi-automatic processing method for retinal nerve fiber bundle tracing based on polarization sensitive optical coherence tomography (PS-OCT) data sets. The method for tracing is based on a nerve fiber orientation map that covers the fovea and optic nerve head (ONH) regions. In order to generate the orientation map, two types of information are used: optic axis orientation based on polarization data, and complementary information obtained from nerve fiber layer (NFL) local thickness variation to reveal fiber bundle structures around the fovea. The corresponding two orientation maps are fused into a combined fiber orientation map. En face maps of NFL retardation, thickness, and unit-depth-retardation (UDR, equivalent to birefringence) are transformed into "along-trace" maps by using the obtained traces of the nerve fiber bundles. The method is demonstrated in the eyes of healthy volunteers, and as an example of further analyses utilizing this method, maps illustrating the gradients of NFL retardation, thickness, and UDR are demonstrated.

  2. Microperimetry of localized retinal nerve fiber layer defects.

    PubMed

    Orzalesi, N; Miglior, S; Lonati, C; Rosetti, L

    1998-03-01

    The aim of this study was to determine the sensitivity of retinal areas involved in a localized retinal nerve fiber layer (RNFL) defect and to assess correlations between microperimetry and the standard full threshold central 30 deg visual field test. Twenty-five patients with focal RNFL defects, evaluated by means of Argon-blue scanning laser ophthalmoscopy (SLO), underwent an automated 30 deg central visual field examination and a microperimetry with SLO. Microperimetry was performed according to standard procedures (infrared laser for fundus imaging; HeNe laser for 10 candles/m2 background illumination, fixation aid and generation of stimuli; manual fundus tracking). The size of stimuli was Goldmann III with 0.1 sec duration. In eyes with focal RNFL defects a deep microperimetric scotoma of at least 5 dB was found in 12 cases and a mild scotoma (1-4 dB) in 13 cases. These scotomas were mainly located throughout the whole defect or grouped in the temporal or nasal sides of the defect and were characterized by sharp and well-defined borders. With automated perimetry, a scotoma, defined by a single point depression of at least 10 dB or a depression of at least 5 dB in two or more contiguous points corresponding to the RNFL, defect, was found in only 14 out of 25 eyes with microperimetric defect. Focal RNFL defects correspond to localized areas of depressed retinal sensitivity as evaluated by microperimetry. The close correspondence between structural and microperimetric findings suggests that, in hypertensive eyes also, localized RNFL defects correspond to visual dysfunction possibly associated with substantial atrophy of ganglion cells.

  3. Methodology for computing white matter nerve fiber orientation in human histological slices

    PubMed Central

    Wisco, Jonathan J.; Hageman, Nathan; Schettler, Stephen P.; Wong, Anita; Vinters, Harry V.; Teng, Chia-Chi; Bangerter, Neal K.

    2016-01-01

    Background The gold standard for mapping nerve fiber orientation in white matter of the human brain is histological analysis through biopsy. Such mappings are a crucial step in validating non-invasive techniques for assessing nerve fiber orientation in the human brain by using diffusion MRI. However, the manual extraction of nerve fiber directions of histological slices is tedious, time consuming, and prone to human error. New Method The presented semi-automated algorithm first creates a binary-segmented mask of the nerve fibers in the histological image, and then extracts an estimate of average directionality of nerve fibers through a Fourier-domain analysis of the masked image. It also generates an uncertainty level for its estimate of average directionality. Results and Comparison with Existing Methods The average orientations of the semi-automatic method were first compared to a qualitative expert opinion based on visual inspection of nerve fibers. A weighted RMS difference between the expert estimate and the algorithmically-determined angle (weighted by expert's confidence in his estimate) was 15.4 degrees, dropping to 9.9 degrees when only cases with an expert confidence level of greater than 50% were included. The algorithmically-determined angles were then compared with angles extracted using a manual segmentation technique, yielding an RMS difference of 11.2 degrees. Conclusion The presented semi-automated method is in good agreement with both qualitative and quantitative manual expert-based approaches for estimating directionality of nerve fibers in white matter from images of stained histological slices of the human brain. PMID:26709015

  4. Methodology for computing white matter nerve fiber orientation in human histological slices.

    PubMed

    Nazaran, Amin; Wisco, Jonathan J; Hageman, Nathan; Schettler, Stephen P; Wong, Anita; Vinters, Harry V; Teng, Chia-Chi; Bangerter, Neal K

    2016-03-01

    The gold standard for mapping nerve fiber orientation in white matter of the human brain is histological analysis through biopsy. Such mappings are a crucial step in validating non-invasive techniques for assessing nerve fiber orientation in the human brain by using diffusion MRI. However, the manual extraction of nerve fiber directions of histological slices is tedious, time consuming, and prone to human error. The presented semi-automated algorithm first creates a binary-segmented mask of the nerve fibers in the histological image, and then extracts an estimate of average directionality of nerve fibers through a Fourier-domain analysis of the masked image. It also generates an uncertainty level for its estimate of average directionality. The average orientations of the semi-automatic method were first compared to a qualitative expert opinion based on visual inspection of nerve fibers. A weighted RMS difference between the expert estimate and the algorithmically determined angle (weighted by expert's confidence in his estimate) was 15.4°, dropping to 9.9° when only cases with an expert confidence level of greater than 50% were included. The algorithmically determined angles were then compared with angles extracted using a manual segmentation technique, yielding an RMS difference of 11.2°. The presented semi-automated method is in good agreement with both qualitative and quantitative manual expert-based approaches for estimating directionality of nerve fibers in white matter from images of stained histological slices of the human brain. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. A 3D Computational Model of Transcutaneous Electrical Nerve Stimulation for Estimating Aβ Tactile Nerve Fiber Excitability

    PubMed Central

    Zhu, Kaihua; Li, Liming; Wei, Xuyong; Sui, Xiaohong

    2017-01-01

    Tactile sensory feedback plays an important role in our daily life. Transcutaneous electrical nerve stimulation (TENS) is widely accepted to produce artificial tactile sensation. To explore the underlying mechanism of tactile sensation under TENS, this paper presented a novel 3D TENS computational model including an active Aβ tactile nerve fiber (TNF) model and a forearm finite element model with the fine-layered skin structure. The conduction velocity vs. fiber diameter and strength-duration relationships in this combined TENS model matched well with experimental data. Based on this validated TENS model, threshold current variation were further investigated under different stimulating electrode sizes with varied fiber diameters. The computational results showed that the threshold current intensity increased with electrode size, and larger nerve fibers were recruited at lower current intensities. These results were comparable to our psychophysical experimental data from six healthy subjects. This novel 3D TENS model would further guide the floorplan of the surface electrodes, and the stimulating paradigms for tactile sensory feedback. PMID:28559787

  6. Relationship Between Optic Nerve Appearance and Retinal Nerve Fiber Layer Thickness as Explored with Spectral Domain Optical Coherence Tomography

    PubMed Central

    Aleman, Tomas S.; Huang, Jiayan; Garrity, Sean T.; Carter, Stuart B.; Aleman, Wendy D.; Ying, Gui-shuang; Tamhankar, Madhura A.

    2014-01-01

    Purpose To study the relationship between the appearance of the optic nerve and the retinal nerve fiber layer (RNFL) thickness determined by spectral domain optical coherence tomography (OCT). Methods Records from patients with spectral domain-OCT imaging in a neuro-ophthalmology practice were reviewed. Eyes with glaucoma/glaucoma suspicion, macular/optic nerve edema, pseudophakia, and with refractive errors > 6D were excluded. Optic nerve appearance by slit lamp biomicroscopy was related to the RNFL thickness by spectral domain-OCT and to visual field results. Results Ninety-one patients (176 eyes; mean age: 49 ± 15 years) were included. Eighty-three eyes (47%) showed optic nerve pallor; 89 eyes (50.6%) showed RNFL thinning (sectoral or average peripapillary). Average peripapillary RNFL thickness in eyes with pallor (mean ± SD = 76 ± 17 μm) was thinner compared to eyes without pallor (91 ± 14 μm, P < 0.001). Optic nerve pallor predicted RNFL thinning with a sensitivity of 69% and a specificity of 75%. Optic nerve appearance predicted RNFL thinning (with a sensitivity and specificity of 81%) when RNFL had thinned by ∼ 40%. Most patients with pallor had RNFL thinning with (66%) or without (25%) visual field loss; the remainder had normal RNFL and fields (5%) or with visual field abnormalities (4%). Conclusions Optic nerve pallor as a predictor of RNFL thinning showed fair sensitivity and specificity, although it is optimally sensitive/specific only when substantial RNFL loss has occurred. Translational Relevance Finding an acceptable relationship between the optic nerve appearance by ophthalmoscopy and spectral domain-OCT RNFL measures will help the clinician's interpretation of the information provided by this technology, which is gaining momentum in neuro-ophthalmic research. PMID:25374773

  7. High-resolution imaging of retinal nerve fiber bundles in glaucoma using adaptive optics scanning laser ophthalmoscopy.

    PubMed

    Takayama, Kohei; Ooto, Sotaro; Hangai, Masanori; Ueda-Arakawa, Naoko; Yoshida, Sachiko; Akagi, Tadamichi; Ikeda, Hanako Ohashi; Nonaka, Atsushi; Hanebuchi, Masaaki; Inoue, Takashi; Yoshimura, Nagahisa

    2013-05-01

    To detect pathologic changes in retinal nerve fiber bundles in glaucomatous eyes seen on images obtained by adaptive optics (AO) scanning laser ophthalmoscopy (AO SLO). Prospective cross-sectional study. Twenty-eight eyes of 28 patients with open-angle glaucoma and 21 normal eyes of 21 volunteer subjects underwent a full ophthalmologic examination, visual field testing using a Humphrey Field Analyzer, fundus photography, red-free SLO imaging, spectral-domain optical coherence tomography, and imaging with an original prototype AO SLO system. The AO SLO images showed many hyperreflective bundles suggesting nerve fiber bundles. In glaucomatous eyes, the nerve fiber bundles were narrower than in normal eyes, and the nerve fiber layer thickness was correlated with the nerve fiber bundle widths on AO SLO (P < .001). In the nerve fiber layer defect area on fundus photography, the nerve fiber bundles on AO SLO were narrower compared with those in normal eyes (P < .001). At 60 degrees on the inferior temporal side of the optic disc, the nerve fiber bundle width was significantly lower, even in areas without nerve fiber layer defect, in eyes with glaucomatous eyes compared with normal eyes (P = .026). The mean deviations of each cluster in visual field testing were correlated with the corresponding nerve fiber bundle widths (P = .017). AO SLO images showed reduced nerve fiber bundle widths both in clinically normal and abnormal areas of glaucomatous eyes, and these abnormalities were associated with visual field defects, suggesting that AO SLO may be useful for detecting early nerve fiber bundle abnormalities associated with loss of visual function. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Intra-epidermal nerve fibers density and nociception in EPO-treated type 1 diabetic rats with peripheral neuropathy.

    PubMed

    Roberto, Bianchi; Raffaella, Lombardi; Carla, Porretta-Serapiglia; Giuseppe, Lauria

    2013-01-01

    Small-diameter nerve fibers, which subserve nociception, can be affected early in peripheral neuropathies, although their injury may not be detectable by routine neurophysiologic tests. On the other hand, skin biopsy has proved to be a reliable tool to examine nonmyelinated nerve fibers, as assessed by the quantification of intra-epidermal nerve fiber (IENF) density not only along with the degenerative process but, noteworthy, IENF density could be very helpful in evaluating drug efficacy such as erythropoietin (EPO) treatment.

  9. Effect of mutated defensin NP-1 on sciatic nerve regeneration after transection--A pivot study.

    PubMed

    Xu, Chungui; Bai, Lili; Chen, Yuhong; Fan, Chengming; Hu, Zanmin; Xu, Hailin; Jiang, Baoguo

    2016-03-23

    Defensins are small cationic peptides that constitute the first line of defense against pathogens and are involved in immune regulation. In this study, their role in peripheral nerve regeneration was investigated. Rat sciatic nerves were transected and the two nerve stumps were bridged by a chitin conduit with a gap of 5mm between the stumps. The animals were injected intramuscularly with mutated rabbit neutrophil peptide 1 (defensin mNP-1), the positive control nerve growth factor (NGF) or the negative control saline, for 7 consecutive days after repair. After 6 weeks, the sciatic functional index (SFI), MNCV (motor nerve conductive velocity) and morphological parameters including myelinated fiber amounts, fiber diameter, axon diameter, myelin thickness and G-ratio were measured. Compared to the SFI of saline group, the NGF and mNP-1 groups had an increase of 18.3% and 18.8%, respectively. The numbers of myelinated fibers in the distal nerve of NGF and mNP-1 groups were 1.45- and 1.32-fold higher than in the saline group. The MNCVs of NGF and mNP-1 groups were 7.3 and 4.4 times of that of saline group. Fiber diameter, axon diameter, myelin thickness and G-ratio in the NGF and mNP-1 groups were also significantly higher than those of saline group. Our results demonstrate that, like NGF, the defensin mNP-1 can promote regeneration after a peripheral nerve cut.

  10. Exposure of rats to a high but not low dose of ethanol during early postnatal life increases the rate of loss of optic nerve axons and decreases the rate of myelination

    PubMed Central

    HARRIS, SIMON J.; WILCE, PETER; BEDI, KULDIP S.

    2000-01-01

    Visual system abnormalities are commonly encountered in the fetal alcohol syndrome although the level of exposure at which they become manifest is uncertain. In this study we have examined the effects of either low (ETLD) or high dose (ETHD) ethanol, given between postnatal days 4–9, on the axons of the rat optic nerve. Rats were exposed to ethanol vapour in a special chamber for a period of 3 h per day during the treatment period. The blood alcohol concentration in the ETLD animals averaged ∼ 171 mg/dl and in the ETHD animals ∼ 430 mg/dl at the end of the treatment on any given day. Groups of 10 and 30-d-old mother-reared control (MRC), separation control (SC), ETLD and ETHD rats were anaesthetised with an intraperitoneal injection of ketamine and xylazine, and killed by intracardiac perfusion with phosphate-buffered glutaraldehyde. In the 10-d-old rat optic nerves there was a total of ∼ 145000–165000 axons in MRC, SC and ETLD animals. About 4% of these fibres were myelinated. The differences between these groups were not statistically significant. However, the 10-d-old ETHD animals had only about 75000 optic nerve axons (P < 0.05) of which about 2.8% were myelinated. By 30 d of age there was a total of between 75000–90000 optic nerve axons, irrespective of the group examined. The proportion of axons which were myelinated at this age was still significantly lower (P < 0.001) in the ETHD animals (∼ 77%) than in the other groups (about 98%). It is concluded that the normal stages of development and maturation of the rat optic nerve axons, as assessed in this study, can be severely compromised by exposure to a relatively high (but not low) dose of ethanol between postnatal d 4 and 9. PMID:11117631

  11. Cornea nerve fiber quantification and construction of phenotypes in patients with fibromyalgia

    PubMed Central

    Oudejans, Linda; He, Xuan; Niesters, Marieke; Dahan, Albert; Brines, Michael; van Velzen, Monique

    2016-01-01

    Cornea confocal microscopy (CCM) is a novel non-invasive method to detect small nerve fiber pathology. CCM generally correlates with outcomes of skin biopsies in patients with small fiber pathology. The aim of this study was to quantify the morphology of small nerve fibers of the cornea of patients with fibromyalgia in terms of density, length and branching and further phenotype these patients using standardized quantitative sensory testing (QST). Small fiber pathology was detected in the cornea of 51% of patients: nerve fiber length was significantly decreased in 44% of patients compared to age- and sex-matched reference values; nerve fiber density and branching were significantly decreased in 10% and 28% of patients. The combination of the CCM parameters and sensory tests for central sensitization, (cold pain threshold, mechanical pain threshold, mechanical pain sensitivity, allodynia and/or windup), yielded four phenotypes of fibromyalgia patients in a subgroup analysis: one group with normal cornea morphology without and with signs of central sensitization, and a group with abnormal cornea morphology parameters without and with signs of central sensitization. In conclusion, half of the tested fibromyalgia population demonstrates signs of small fiber pathology as measured by CCM. The four distinct phenotypes suggest possible differences in disease mechanisms and may require different treatment approaches. PMID:27006259

  12. Sleeve bridging of the rhesus monkey ulnar nerve with muscular branches of the pronator teres: multiple amplification of axonal regeneration

    PubMed Central

    Kou, Yu-hui; Zhang, Pei-xun; Wang, Yan-hua; Chen, Bo; Han, Na; Xue, Feng; Zhang, Hong-bo; Yin, Xiao-feng; Jiang, Bao-guo

    2015-01-01

    Multiple-bud regeneration, i.e., multiple amplification, has been shown to exist in peripheral nerve regeneration. Multiple buds grow towards the distal nerve stump during proximal nerve fiber regeneration. Our previous studies have verified the limit and validity of multiple amplification of peripheral nerve regeneration using small gap sleeve bridging of small donor nerves to repair large receptor nerves in rodents. The present study sought to observe multiple amplification of myelinated nerve fiber regeneration in the primate peripheral nerve. Rhesus monkey models of distal ulnar nerve defects were established and repaired using muscular branches of the right forearm pronator teres. Proximal muscular branches of the pronator teres were sutured into the distal ulnar nerve using the small gap sleeve bridging method. At 6 months after suture, two-finger flexion and mild wrist flexion were restored in the ulnar-sided injured limbs of rhesus monkey. Neurophysiological examination showed that motor nerve conduction velocity reached 22.63 ± 6.34 m/s on the affected side of rhesus monkey. Osmium tetroxide staining demonstrated that the number of myelinated nerve fibers was 1,657 ± 652 in the branches of pronator teres of donor, and 2,661 ± 843 in the repaired ulnar nerve. The rate of multiple amplification of regenerating myelinated nerve fibers was 1.61. These data showed that when muscular branches of the pronator teres were used to repair ulnar nerve in primates, effective regeneration was observed in regenerating nerve fibers, and functions of the injured ulnar nerve were restored to a certain extent. Moreover, multiple amplification was subsequently detected in ulnar nerve axons. PMID:25788920

  13. Coding channels for taste perception: information transmission from taste cells to gustatory nerve fibers.

    PubMed

    Yoshida, Ryusuke; Yasumatsu, Keiko; Shigemura, Noriatsu; Ninomiya, Yuzo

    2006-12-01

    Taste signals are first detected by the taste receptor cells, which are located in taste buds existing in the tongue, soft palate, larynx and epiglottis. Taste receptor cells contact with the chemical compounds in oral cavity through the apical processes which protrude into the taste pore. Interaction between chemical compounds and the taste receptor produces activation of taste receptor cells directly or indirectly. Then the signals are transmitted to gustatory nerve fibers and higher order neurons. A recent study demonstrated many similarities between response properties of taste receptor cells with action potentials and those of the gustatory nerve fibers innervating them, suggesting information derived from receptor cells generating action potentials may form a major component of taste information that is transmitted to gustatory nerve fibers. These findings may also indicate that there is no major modification of taste information sampled by taste receptor cells in synaptic transmission from taste cells to nerve fibers although there is indirect evidence. In the peripheral taste system, gustatory nerve fibers may selectively contact with taste receptor cells that have similar response properties and convey constant taste information to the higher order neurons.

  14. Label-free photoacoustic microscopy of peripheral nerves

    NASA Astrophysics Data System (ADS)

    Matthews, Thomas Paul; Zhang, Chi; Yao, Da-Kang; Maslov, Konstantin; Wang, Lihong V.

    2014-01-01

    Peripheral neuropathy is a common neurological problem that affects millions of people worldwide. Diagnosis and treatment of this condition are often hindered by the difficulties in making objective, noninvasive measurements of nerve fibers. Photoacoustic microscopy (PAM) has the ability to obtain high resolution, specific images of peripheral nerves without exogenous contrast. We demonstrated the first proof-of-concept imaging of peripheral nerves using PAM. As validated by both standard histology and photoacoustic spectroscopy, the origin of photoacoustic signals is myelin, the primary source of lipids in the nerves. An extracted sciatic nerve sandwiched between two layers of chicken tissue was imaged by PAM to mimic the in vivo case. Ordered fibrous structures inside the nerve, caused by the bundles of myelin-coated axons, could be observed clearly. With further technical improvements, PAM can potentially be applied to monitor and diagnose peripheral neuropathies.

  15. Label-free photoacoustic microscopy of peripheral nerves

    PubMed Central

    Matthews, Thomas Paul; Zhang, Chi; Yao, Da-Kang; Maslov, Konstantin; Wang, Lihong V.

    2014-01-01

    Abstract. Peripheral neuropathy is a common neurological problem that affects millions of people worldwide. Diagnosis and treatment of this condition are often hindered by the difficulties in making objective, noninvasive measurements of nerve fibers. Photoacoustic microscopy (PAM) has the ability to obtain high resolution, specific images of peripheral nerves without exogenous contrast. We demonstrated the first proof-of-concept imaging of peripheral nerves using PAM. As validated by both standard histology and photoacoustic spectroscopy, the origin of photoacoustic signals is myelin, the primary source of lipids in the nerves. An extracted sciatic nerve sandwiched between two layers of chicken tissue was imaged by PAM to mimic the in vivo case. Ordered fibrous structures inside the nerve, caused by the bundles of myelin-coated axons, could be observed clearly. With further technical improvements, PAM can potentially be applied to monitor and diagnose peripheral neuropathies. PMID:24395587

  16. Molecular mimicry between Mycobacterium leprae proteins (50S ribosomal protein L2 and Lysyl-tRNA synthetase) and myelin basic protein: a possible mechanism of nerve damage in leprosy.

    PubMed

    Singh, Itu; Yadav, Asha Ram; Mohanty, Keshar Kunja; Katoch, Kiran; Sharma, Prashant; Mishra, Bishal; Bisht, Deepa; Gupta, U D; Sengupta, Utpal

    2015-04-01

    Autoantibodies against various components of host are known to occur in leprosy. Nerve damage is the primary cause of disability associated with leprosy. The aim of this study was to detect the level of autoantibodies and lympho-proliferative response against myelin basic protein (MBP) in leprosy patients (LPs) and their correlation with clinical phenotypes of LPs. Further, probable role of molecular mimicry in nerve damage of LPs was investigated. We observed significantly high level of anti-MBP antibodies in LPs across the spectrum and a positive significant correlation between the level of anti-MBP antibodies and the number of nerves involved in LPs. We report here that 4 B cell epitopes of myelin A1 and Mycobacterium leprae proteins, 50S ribosomal L2 and lysyl tRNA synthetase are cross-reactive. Further, M. leprae sonicated antigen hyperimmunization was responsible for induction of autoantibody response in mice which could be adoptively transferred to naive mice. For the first time our findings suggest the role of molecular mimicry in nerve damage in leprosy. Copyright © 2015 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  17. Myelin structure and composition of myelinated tissue in the African lungfish.

    PubMed

    Kirschner, Daniel A; Karthigesan, Jothie; Bizzozero, Oscar A; Kosaras, Bela; Inouye, Hideyo

    2008-05-01

    To analyze myelin structure and the composition of myelinated tissue in the African lungfish (Protopterus dolloi), we used a combination of ultrastructural and biochemical techniques. Electron microscopy showed typical multilamellar myelin: CNS sheaths abutted one another, and PNS sheaths were separated by endoneurial collagen. The radial component, prominent in CNS myelin of higher vertebrates, was suggested by the pattern of staining but was poorly organized. The lipid and myelin protein compositions of lungfish tissues more closely resembled those of teleost than those of higher vertebrates (frog, mouse). Of particular note, for example, lungfish glycolipids lacked hydroxy fatty acids. Native myelin periodicities from unfixed nerves were in the range of those for higher vertebrates rather than for teleost fish. Lungfish PNS myelin had wider inter-membrane spaces compared with other vertebrates, and lungfish CNS myelin had spaces that were closer in value to those in mammalian than to amphibian or teleost myelins. The membrane lipid bilayer was narrower in lungfish PNS myelin compared to other vertebrates, whereas in the CNS myelin the bilayer was in the typical range. Lungfish PNS myelin showed typical compaction and swelling responses to incubation in acidic or alkaline hypotonic saline. The CNS myelin, by contrast, did not compact in acidic saline but did swell in the alkaline solution. This lability was more similar to that for the higher vertebrates than for teleost.

  18. The origin of the initial heat associated with a single impulse in mammalian non-myelinated nerve fibres

    PubMed Central

    Howarth, J. V.; Keynes, R. D.; Ritchie, J. M.

    1968-01-01

    1. A study has been made of the temperature changes associated with the passage of a single impulse in rabbit desheated vagus nerves. 2. The initial changes consist of an evolution of positive heat followed by a reabsorption of most of it; i.e. there is a phase of positive and a phase of negative heat production. 3. The size of the positive heat, its time of onset, and the time of onset of the negative heat have been measured by an analogue method of analysis. In addition, these parameters, together with the size of the negative heat and the duration of both phases of initial heat, have been studied with the aid of a computer, and also by conventional heat block analysis. 4. At about 5° C the measured positive heat is 7·2 μcal/g. impulse. It starts as soon as the compound action potential reaches the thermopile and lasts for about 107 msec. 5. This positive heat decreases with increasing temperature, the ratio of heat at 4° C to that at 14° C being 1·86. 6. The measured negative heat at about 5° C is 4·9 μcal/g. impulse. It starts 102 msec after the onset of positive heat, and lasts for about 240 msec. 7. When the sodium of Locke solution is replaced by lithium the positive heat is reduced by 19%, but the negative heat is increased by 22%. 8. In potassium-free solutions the positive heat is hardly affected (increase of 5%), but the negative heat is more than doubled. As a result the nerve may become briefly colder than its initial temperature by about 2 μ° C. 9. The effect of sodium-deficient solutions on the positive heat is somewhat variable, but the negative heat is consistently diminished. 10. Replacement of the chloride of Locke solution by sulphate or nitrate has little effect on the positive heat. The negative heat is reduced in size by 26% and in duration by 22%. 11. Replacement of most of the sodium of Locke solution by barium reduces or abolishes the negative heat, and increases the measured size of the positive heat nearly threefold. 12

  19. Multiple sclerosis and optic nerve: an analysis of retinal nerve fiber layer thickness and color Doppler imaging parameters

    PubMed Central

    Akçam, H T; Capraz, I Y; Aktas, Z; Batur Caglayan, H Z; Ozhan Oktar, S; Hasanreisoglu, M; Irkec, C

    2014-01-01

    Purpose To compare both retinal nerve fiber layer thickness and orbital color Doppler ultrasonography parameters in patients with multiple sclerosis (MS) versus healthy controls. Methods This is an observational case–control study. Forty eyes from MS patients and twenty eyes from healthy volunteers were examined. Eyes were classified into three groups as group 1, eyes from MS patients with previous optic neuritis (n=20); group 2, eyes from MS patients without previous optic neuritis (n=20); and group 3, eyes from healthy controls (n=20). Following complete ophthalmologic examination and retinal nerve fiber layer thickness measurement for each group, blood flow velocities of posterior ciliary arteries, central retinal artery, ophthalmic artery, and superior ophthalmic vein were measured. Pourcelot index (resistive index), an indicator of peripheral vascular resistance, was also calculated. The statistical assessment was performed with the assistance of Pearson's Chi-square test, Mann–Whitney U-test, Kruskal–Wallis test, and Spearman's correlation test. Results The studied eyes exposed similar values in terms of intraocular pressure and central corneal thickness, implying no evidence in favor of glaucoma. All nerve fiber layer thickness values, except superior nasal quadrants, in group 1 were found to be significantly thinner than groups 2 and 3. Blood flow velocity and mean resistivity index parameters were similar in all the groups. Conclusions In MS patients, especially with previous optic neuritis, diminished retinal nerve fiber layer thickness was observed. Contrary to several studies in the current literature, no evidence supporting potential vascular origin of ocular involvement in MS was found. PMID:25081285

  20. Intact subepidermal nerve fibers mediate mechanical hypersensitivity via the activation of protein kinase C gamma in spared nerve injury

    PubMed Central

    Ko, Miau-Hwa; Yang, Ming-Ling; Youn, Su-Chung; Tseng, To-Jung

    2016-01-01

    Background Spared nerve injury is an important neuropathic pain model for investigating the role of intact primary afferents in the skin on pain hypersensitivity. However, potential cellular mechanisms remain poorly understood. In phosphoinositide-3 kinase pathway, pyruvate dehydrogenase kinase 1 (PDK1) participates in the regulation of neuronal plasticity for central sensitization. The downstream cascades of PDK1 include: (1) protein kinase C gamma (PKCγ) controls the trafficking and phosphorylation of ionotropic glutamate receptor; (2) protein kinase B (Akt)/the mammalian target of rapamycin (mTOR) signaling is responsible for local protein synthesis. Under these statements, we therefore hypothesized that an increase of PKCγ activation and mTOR-dependent PKCγ synthesis in intact primary afferents after SNI might contribute to pain hypersensitivity. Results The variants of spared nerve injury were performed in Sprague-Dawley rats by transecting any two of the three branches of the sciatic nerve, leaving only one branch intact. Following SNIt (spared tibial branch), mechanical hyperalgesia and mechanical allodynia, but not thermal hyperalgesia, were significantly induced. In the first footpad, normal epidermal innervations were verified by the protein gene product 9.5 (PGP9.5)- and growth-associated protein 43 (GAP43)-immunoreactive (IR) intraepidermal nerve fibers (IENFs) densities. Furthermore, the rapid increases of phospho-PKCγ- and phospho-mTOR-IR subepidermal nerve fibers (SENFs) areas were distinct gathered from the results of PGP9.5-, GAP43-, and neurofilament 200 (NF200)-IR SENFs areas. The efficacy of PKC inhibitor (GF 109203X) or mTOR complex 1 inhibitor (rapamycin) for attenuating mechanical hyperalgesia and mechanical allodynia by intraplantar injection was dose-dependent. Conclusions From results obtained in this study, we strongly recommend that the intact SENFs persistently increase PKCγ activation and mTOR-dependent PKCγ synthesis participate

  1. Brain imaging signatures of the relationship between epidermal nerve fibers and heat pain perception.

    PubMed

    Tseng, Ming-Tsung; Kong, Yazhuo; Chiang, Ming-Chang; Chao, Chi-Chao; Tseng, Wen-Yih I; Hsieh, Sung-Tsang

    2015-11-15

    Although the small-diameter primary afferent fibers in the skin promptly respond to nociceptive stimuli and convey sensory inputs to the central nervous system, the neural signatures that underpin the relationship between cutaneous afferent fibers and pain perception remain elusive. We combined skin biopsy at the lateral aspect of the distal leg, which is used to quantify cutaneous afferent fibers, with fMRI, which is used to assess brain responses and functional connectivity, to investigate the relationship between cutaneous sensory nerves and the corresponding pain perception in the brain after applying heat pain stimulation to the dorsum of the right foot in healthy subjects. During painful stimulation, the degree of cutaneous innervation, as measured by epidermal nerve fiber density, was correlated with individual blood oxygen level-dependent (BOLD) signals of the posterior insular cortex and of the thalamus, periaqueductal gray, and rostral ventromedial medulla. Pain perception was associated with the activation of the anterior insular cortex and with the functional connectivity from the anterior insular cortex to the primary somatosensory cortex during painful stimulation. Most importantly, both epidermal nerve fiber density and activity in the posterior insular cortex showed a positive correlation with the strength of coupling under pain between the anterior insular cortex and the primary somatosensory cortex. Thus, our findings support the notion that the neural circuitry subserving pain perception interacts with the cerebral correlates of peripheral nociceptive fibers, which implicates an indirect role for skin nerves in human pain perception.

  2. Ultrastructural analysis of guided nerve regeneration using progesterone- and pregnenolone-loaded chitosan prostheses.

    PubMed

    Chávez-Delgado, M E; Gomez-Pinedo, U; Feria-Velasco, A; Huerta-Viera, M; Castañeda, S Castro; Toral, F A López-Dellamary; Parducz, A; Anda, S Luquín-De; Mora-Galindo, J; García-Estrada, J

    2005-07-01

    Recently, numerous guide chambers for the treatment of injured nerves made up of different biomaterials have been designed, capable of hosting living cells or carrying neurotrophic or neuroactive substances to be directly released to the injured tissue. In this study, chitosan prostheses containing neurosteroids (progesterone and pregnenolone) were used for bridging a 10-mm gap in the rabbit facial nerve. Gas chromatography was used to quantify neurosteroid content in the prostheses prior to and after subcutaneous implantation at different periods of up to 60 days. The regeneration of the nerve fibers were evaluated at 15 and 45 days after axotomy by means of ultrastructural morphometric analysis. Different nerve fibers regenerative patterns were seen depending the groups studied and the analyzed stages. At 15 days after axotomy, the newly regenerating tissue revealed Schwann cells holding nonmyelinated nerve fiber bundles in an incipient and organized regenerative pattern. At 45 days, the regenerating tissue showed myelinated nerve fibers of different sizes, shapes, and myelin sheath thickness. Although the regeneration of the nerve fibers under neurosteroid treatment showed statistically significant differences in comparison with vehicle regenerated tissue, progesterone-loaded chitosan prostheses produced the best guided nerve regeneration response. These findings indicate that chitosan prostheses allowed regeneration of nerve fibers in their lumen, and when containing neurosteroids produced a faster guided nerve regeneration acting as a long-lasting release delivery vehicle.

  3. Treatment of a patient with small fiber pathology using nerve biopsy and grafting: a case report.

    PubMed

    Peled, Ziv M

    2013-10-01

    Small fiber pathology is a common clinical entity with a variable clinical presentation and etiology. Unfortunately, little has been described regarding its treatment because a majority of cases are idiopathic. Hence, treatment often consists of symptomatic management of pain and autonomic dysfunction. This report describes a patient who was presented with an undiagnosed pain syndrome thought to be affecting nerves within both lower extremities and causing significant pain. A sural nerve biopsy was performed for diagnostic purposes and nerve repair was performed using Avance nerve allograft (AxoGen Inc., Alachua, FL). Light microscopic evaluation was unremarkable, but electron microscopy revealed small fiber pathology. Postoperatively, the patient experienced a complete resolution of her pain on the involved extremity. These results suggest a potential, novel approach for treatment of such cases and possible mechanisms for the patient's clinical improvement are explored. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  4. Fiber-optic-based surface plasmon resonance (SPR) sensors for the detection of toxic nerve agents

    NASA Astrophysics Data System (ADS)

    Prakash, Anna M. C.; Kim, Yoon-Chang; Banerji, Soame; Masson, Jean-Francois; Booksh, Karl S.

    2004-03-01

    Analytical instruments capable of detecting nerve agents in battlefield conditions where speed, accuracy and ease of operation are a must in today's military. Fast detection and decontamination of nerve agents in very low concentrations is the primary focus of our research. The method presented here focuses on optimizing polymer stabilized sensing elements on the surface of SPR fiber-optic probes. A number of polymers & polymer supported metal complexes capable of reversibly binding to the species of interest & which have robust operation in hostile environments are incorporated with the fiber optic sensing elements. An optical technique, such as Surface Plasmon Resonance (SPR), better suited to rapid data collection without sample pretreatment is employed. The approach using polymer-based optical fibers with off-the-shelf SPR system components has been tested for the detection of Pinacolyl methylphosphonate (PMP), a simulant for nerve agent Soman. Surface initiated polymeric sensors have higher sensitivity toward detecting PMP than bulk-polymerized sensors.

  5. The effects of testosterone deficiency on the structural integrity of the penile dorsal nerve in the rat.

    PubMed

    Armagan, A; Hatsushi, K; Toselli, P

    2008-01-01

    Androgens play a vital role in erectile function and are known to have a neuroprotective role in the nervous system. This study investigated, in a rat model, the effects of testosterone deprivation and replacement on the morphology of the dorsal nerve of the rat penis at the light microscopy level. Two weeks after castration, male rats were infused with vehicle alone or 44 mug of testosterone for 2 weeks. Age-matched, sham-operated control animals were used for comparisons. Penile tissue samples were removed for histological analyses. The following parameters were assessed: (1) total myelin sheath thickness; (2) density of nerve fibers; and (3) axon cross-sectional area per nerve fiber. Castration resulted in a significant increase in axon cross-sectional area compared to that of the control and testosterone-treated animals (6.97+/-0.59 microm(2) per fiber in control animals to 14.32+/-0.44 microm(2) per fiber in castrated animals). Qualitatively, there were signs of nerve degeneration, particularly myelin sheath degeneration, in all sample groups. We did not observe statistically significant changes in myelin sheath thickness. There was a trend of reduced nerve density. Nerve degeneration was not quantified since this study was performed at the light microscopic level. This study suggests that testosterone has a neuroprotective role in the nerve fibers of the dorsal nerve and testosterone deficiency may lead to different forms of nerve degeneration resulting in anatomic alterations, thus contributing to erectile dysfunction.

  6. [Morphometry of the recurrent laryngeal nerves of the rat].

    PubMed

    Pascual-Font, A; Merchán, A; Maranillo, E; Brillas, A; Sañudo, J R; Valderrama-Canales, F J

    2006-12-01

    In mammals the recurrent laryngeal nerves are dissimilar in length between both sides. This asymmetry involves different time of arrival of the stimulus to the laryngeal musculature controlled by each nerve. Thus, several explanations have been addressed to elucidate the closest of the glottis at the same time despite the unlike length of the nerves. However, previous works on the topic lack of several important data. The present study compares, in two groups of 10 and 6 rats, the length and the composition of myelinated fibers in the recurrent laryngeal nerves of both sides, by means of light microscopy and a computerized morphometric analysis. The results show a mean difference of 0,84 cm longer the left than the right recurrent laryngeal nerve. No statistical differences were observed in the number of myelinated fibers between both sides. However, the myelinated fibers of the right side were statistically bigger in diameter than the fibers of the left side. The data are discussed in the context of the mechanisms for the compensation of the dissimilar length of both recurrent laryngeal nerves.

  7. Morphologic Characterization of Nerves in Whole-Mount Airway Biopsies

    PubMed Central

    Canning, Brendan J.; Merlo-Pich, Emilio; Woodcock, Ashley A.; Smith, Jaclyn A.

    2015-01-01

    Rationale: Neuroplasticity of bronchopulmonary afferent neurons that respond to mechanical and chemical stimuli may sensitize the cough reflex. Afferent drive in cough is carried by the vagus nerve, and vagal afferent nerve terminals have been well defined in animals. Yet, both unmyelinated C fibers and particularly the morphologically distinct, myelinated, nodose-derived mechanoreceptors described in animals are poorly characterized in humans. To date there are no distinctive molecular markers or detailed morphologies available for human bronchopulmonary afferent nerves. Objectives: Morphologic and neuromolecular characterization of the afferent nerves that are potentially involved in cough in humans. Methods: A whole-mount immunofluorescence approach, rarely used in human lung tissue, was used with antibodies specific to protein gene product 9.5 (PGP9.5) and, for the first time in human lung tissue, 200-kD neurofilament subunit. Measurements and Main Results: We have developed a robust technique to visualize fibers consistent with autonomic and C fibers and pulmonary neuroendocrine cells. A group of morphologically distinct, 200-kD neurofilament-immunopositive myelinated afferent fibers, a subpopulation of which did not express PGP9.5, was also identified. Conclusions: PGP9.5-immunonegative nerves are strikingly similar to myelinated airway afferents, the cough receptor, and smooth muscle–associated airway receptors described in rodents. These have never been described in humans. Full description of human airway nerves is critical to the translation of animal studies to the clinical setting. PMID:25906337

  8. Morphologic Characterization of Nerves in Whole-Mount Airway Biopsies.

    PubMed

    West, Peter W; Canning, Brendan J; Merlo-Pich, Emilio; Woodcock, Ashley A; Smith, Jaclyn A

    2015-07-01

    Neuroplasticity of bronchopulmonary afferent neurons that respond to mechanical and chemical stimuli may sensitize the cough reflex. Afferent drive in cough is carried by the vagus nerve, and vagal afferent nerve terminals have been well defined in animals. Yet, both unmyelinated C fibers and particularly the morphologically distinct, myelinated, nodose-derived mechanoreceptors described in animals are poorly characterized in humans. To date there are no distinctive molecular markers or detailed morphologies available for human bronchopulmonary afferent nerves. Morphologic and neuromolecular characterization of the afferent nerves that are potentially involved in cough in humans. A whole-mount immunofluorescence approach, rarely used in human lung tissue, was used with antibodies specific to protein gene product 9.5 (PGP9.5) and, for the first time in human lung tissue, 200-kD neurofilament subunit. We have developed a robust technique to visualize fibers consistent with autonomic and C fibers and pulmonary neuroendocrine cells. A group of morphologically distinct, 200-kD neurofilament-immunopositive myelinated afferent fibers, a subpopulation of which did not express PGP9.5, was also identified. PGP9.5-immunonegative nerves are strikingly similar to myelinated airway afferents, the cough receptor, and smooth muscle-associated airway receptors described in rodents. These have never been described in humans. Full description of human airway nerves is critical to the translation of animal studies to the clinical setting.

  9. The impairment of small nerve fibers in severe sepsis and septic shock.

    PubMed

    Axer, Hubertus; Grimm, Alexander; Pausch, Christine; Teschner, Ulrike; Zinke, Jan; Eisenach, Sven; Beck, Sindy; Guntinas-Lichius, Orlando; Brunkhorst, Frank M; Witte, Otto W

    2016-03-15

    A decrease of small nerve fibers in skin biopsies during the course of critical illness has been demonstrated recently. However, the diagnostic use of skin biopsies in sepsis and its time course is not known. Patients (n=32) with severe sepsis or septic shock were examined using skin biopsies, neurological examination, nerve conduction studies, and sympathetic skin response in the first week after onset of sepsis, 2 weeks and 4 months later and compared to gender- and age-matched healthy controls. Skin biopsies at the ankle and thigh revealed a significant decrease of intraepidermal nerve fiber density (IENFD) during the first week of sepsis and 2 weeks later. All patients developed critical illness polyneuropathy (CIP) according to electrophysiological criteria and 11 showed IENFD values lower than the 0.05 quantile. Four patients were biopsied after 4 months and still showed decreased IENFD. Results of nerve conduction studies and IENFD did considerably change over time. No differences for survival time between patients with IEFND lower and larger than 3.5 fibers/mm were found. Skin biopsy is able to detect an impairment of small sensory nerve fibers early in the course of sepsis. However, it may not be suited as a prognostic parameter for survival. German Clinical Trials Register, DRKS-ID: DRKS00000642, 12/17/2010.

  10. The touch dome in human skin is supplied by different types of nerve fibers.

    PubMed

    Reinisch, Christina M; Tschachler, Erwin

    2005-07-01

    Receptor end organs and free-nerve endings in the skin are the peripheral sentinels of the sensorial nervous system encoding for touch, temperature, and pain. Using a novel approach to analyze the outermost nerves of the skin, we visualized for the first time the distinct microanatomical structure of the touch dome of human hairy skin. The dermal nerve fibers of this slowly adapting type 1 mechanoreceptor were embedded in dermal protrusions that could be readily discerned by Laminin-5 staining. Concerning the nerves supplying the touch domes, we found, unexpectedly, that besides Abeta-fibers, Adelta- and C-fibers also were regularly present. The epidermis overlying the nerve convolutes showed a distinctive architecture of the rete ridges clearly demarcated from the surroundings and extending over 0.193 +/- 0.138 mm(2) (mean +/- standard deviation). Within this area, 756 +/- 386 Merkel cells/mm(2) (mean +/- standard deviation) were present compared with less than 50/mm(2) outside the touch dome, demonstrating for the first time a highly discontinuous distribution of these cells in nonglabrous skin. Our findings strongly suggest that the receptive qualities of human touch domes exceed mechanosensation, and that they may serve as multifunctional nerve end organs in human skin.

  11. Acquired anhidrosis associated with systemic sarcoidosis: Quantification of nerve fibers around eccrine glands by confocal microscopy.

    PubMed

    Nishida, M; Namiki, T; Sone, Y; Hashimoto, T; Tokoro, S; Hanafusa, T; Yokozeki, H

    2017-08-10

    Neurological disorders can cause hypohidrosis and/or anhidrosis by disturbing either the central or the peripheral nervous systems.(1-3) Although a syringotropic variant of cutaneous sarcoidosis causes dysfunction of sweating, systemic sarcoidosis rarely causes hypohidrosis or anhidrosis.(4,5) Here we present a novel case of an acquired anhidrosis in a patient with systemic sarcoidosis. Furthermore, we developed a novel methodology to quantify nerve fibers around eccrine glands using confocal microscopy and found that nerve fibers around eccrine glands in anhidrotic areas are significantly decreased compared to hidrotic areas. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  12. CAPSAICIN-SENSITIVE SENSORY NERVE FIBERS CONTRIBUTE TO THE GENERATION AND MAINTENANCE OF SKELETAL FRACTURE PAIN

    PubMed Central

    Jimenez-Andrade, Juan Miguel; Bloom, Aaron P.; Mantyh, William G.; Koewler, Nathan J.; Freeman, Katie T.; Delong, David; Ghilardi, Joseph R.; Kuskowski, Michael A.; Mantyh, Patrick W.

    2009-01-01

    Although skeletal pain can have a marked impact on a patient’s functional status and quality of life, relatively little is known about the specific populations of peripheral nerve fibers that drive non-malignant bone pain. In the present report, neonatal male Sprague Dawley rats were treated with capsaicin or vehicle and femoral fracture was produced when the animals were young adults (15–16 weeks old). Capsaicin treatment, but not vehicle, resulted in a significant (>70%) depletion in the density of calcitonin-gene related peptide positive (CGRP+) sensory nerve fibers, but not 200 kD neurofilament H positive (NF200+) sensory nerve fibers in the periosteum. The periosteum is a thin, cellular and fibrous tissue that tightly adheres to the outer surface of all but the articulated surface of bone and appears to play a pivotal role in driving fracture pain. In animals treated with capsaicin, but not vehicle, there was a 50% reduction in the severity, but no change in the time course, of fracture-induced skeletal pain related behaviors as measured by spontaneous flinching, guarding and weight bearing. These results suggest that both capsaicin-sensitive (primarily CGRP+ C-fibers) and capsaicin-insensitive (primarily NF200+ A-delta fibers) sensory nerve fibers participate in driving skeletal fracture pain. Skeletal pain can be a significant impediment to functional recovery following trauma-induced fracture, osteoporosis-induced fracture and orthopedic surgery procedures such as knee and hip replacement. Understanding the specific populations of sensory nerve fibers that need to be targeted to inhibit the generation and maintenance of skeletal pain may allow the development of more specific mechanism-based therapies that can effectively attenuate acute and chronic skeletal pain. PMID:19486928

  13. Stochastic information transfer from cochlear implant electrodes to auditory nerve fibers.

    PubMed

    Gao, Xiao; Grayden, David B; McDonnell, Mark D

    2014-08-01

    Cochlear implants, also called bionic ears, are implanted neural prostheses that can restore lost human hearing function by direct electrical stimulation of auditory nerve fibers. Previously, an information-theoretic framework for numerically estimating the optimal number of electrodes in cochlear implants has been devised. This approach relies on a model of stochastic action potential generation and a discrete memoryless channel model of the interface between the array of electrodes and the auditory nerve fibers. Using these models, the stochastic information transfer from cochlear implant electrodes to auditory nerve fibers is estimated from the mutual information between channel inputs (the locations of electrodes) and channel outputs (the set of electrode-activated nerve fibers). Here we describe a revised model of the channel output in the framework that avoids the side effects caused by an "ambiguity state" in the original model and also makes fewer assumptions about perceptual processing in the brain. A detailed comparison of how different assumptions on fibers and current spread modes impact on the information transfer in the original model and in the revised model is presented. We also mathematically derive an upper bound on the mutual information in the revised model, which becomes tighter as the number of electrodes increases. We found that the revised model leads to a significantly larger maximum mutual information and corresponding number of electrodes compared with the original model and conclude that the assumptions made in this part of the modeling framework are crucial to the model's overall utility.

  14. Stochastic information transfer from cochlear implant electrodes to auditory nerve fibers

    NASA Astrophysics Data System (ADS)

    Gao, Xiao; Grayden, David B.; McDonnell, Mark D.

    2014-08-01

    Cochlear implants, also called bionic ears, are implanted neural prostheses that can restore lost human hearing function by direct electrical stimulation of auditory nerve fibers. Previously, an information-theoretic framework for numerically estimating the optimal number of electrodes in cochlear implants has been devised. This approach relies on a model of stochastic action potential generation and a discrete memoryless channel model of the interface between the array of electrodes and the auditory nerve fibers. Using these models, the stochastic information transfer from cochlear implant electrodes to auditory nerve fibers is estimated from the mutual information between channel inputs (the locations of electrodes) and channel outputs (the set of electrode-activated nerve fibers). Here we describe a revised model of the channel output in the framework that avoids the side effects caused by an "ambiguity state" in the original model and also makes fewer assumptions about perceptual processing in the brain. A detailed comparison of how different assumptions on fibers and current spread modes impact on the information transfer in the original model and in the revised model is presented. We also mathematically derive an upper bound on the mutual information in the revised model, which becomes tighter as the number of electrodes increases. We found that the revised model leads to a significantly larger maximum mutual information and corresponding number of electrodes compared with the original model and conclude that the assumptions made in this part of the modeling framework are crucial to the model's overall utility.

  15. Rat-derived processed nerve allografts support more axon regeneration in rat than human-derived processed nerve xenografts.

    PubMed

    Wood, Matthew D; Kemp, Stephen W P; Liu, Edward H; Szynkaruk, Mark; Gordon, Tessa; Borschel, Gregory H

    2014-04-01

    Processed nerve allografts are increasingly used as "off the shelf" nerve replacements for surgically bridging nerve gaps. Benchmarking the regenerative capacity of a commercially available human-derived nerve or xenograft in a rat nerve injury model would provide a convenient platform for future studies seeking to modify the processed nerve graft. Human and rat processed nerve grafts were used to bridge a 14 mm defect in a Sprague-Dawley rat sciatic nerve. Reversed autografts served as a positive control group. Twelve weeks following surgery, the distal nerve stumps were retrograde labeled and harvested for histology and histomorphometry. The cross-sectional areas of the human- and rat-derived processed nerve grafts were similar. Neuron counts and myelinated axon counts following use of the human-derived processed xenografts were decreased compared with those obtained from both the rat-derived processed nerve allografts and the autografts; the rat-derived processed nerve allografts were statistically equivalent to autografts. Measures of nerve fiber diameter and myelination revealed inferior axon regeneration maturity in both processed nerve grafts compared with autografts. Processed xenografts showed significantly reduced regeneration compared with autografts or processed allografts indicating that cross-species immunological reactions are important considerations in this rat model.

  16. Early detection of nerve fiber loss by corneal confocal microscopy and skin biopsy in recently diagnosed type 2 diabetes.

    PubMed

    Ziegler, Dan; Papanas, Nikolaos; Zhivov, Andrey; Allgeier, Stephan; Winter, Karsten; Ziegler, Iris; Brüggemann, Jutta; Strom, Alexander; Peschel, Sabine; Köhler, Bernd; Stachs, Oliver; Guthoff, Rudolf F; Roden, Michael

    2014-07-01

    We sought to determine whether early nerve damage may be detected by corneal confocal microscopy (CCM), skin biopsy, and neurophysiological tests in 86 recently diagnosed type 2 diabetic patients compared with 48 control subjects. CCM analysis using novel algorithms to reconstruct nerve fiber images was performed for all fibers and major nerve fibers (MNF) only. Intraepidermal nerve fiber density (IENFD) was assessed in skin specimens. Neurophysiological measures included nerve conduction studies (NCS), quantitative sensory testing (QST), and cardiovascular autonomic function tests (AFTs). Compared with control subjects, diabetic patients exhibited significantly reduced corneal nerve fiber length (CNFL-MNF), fiber density (CNFD-MNF), branch density (CNBD-MNF), connecting points (CNCP), IENFD, NCS, QST, and AFTs. CNFD-MNF and IENFD were reduced below the 2.5th percentile in 21% and 14% of the diabetic patients, respectively. However, the vast majority of patients with abnormal CNFD showed concomitantly normal IENFD and vice versa. In conclusion, CCM and skin biopsy both detect nerve fiber loss in recently diagnosed type 2 diabetes, but largely in different patients, suggesting a patchy manifestation pattern of small fiber neuropathy. Concomitant NCS impairment points to an early parallel involvement of small and large fibers, but the precise temporal sequence should be clarified in prospective studies.

  17. Poly(ADP-ribosylation) is present in murine sciatic nerve fibers and is altered in a Charcot-Marie-Tooth-1E neurodegenerative model.

    PubMed

    Lafon Hughes, Laura I; Romeo Cardeillac, Carlos J; Cal Castillo, Karina B; Vilchez Larrea, Salomé C; Sotelo Sosa, José R; Folle Ungo, Gustavo A; Fernández Villamil, Silvia H; Kun González, Alejandra E

    2017-01-01

    ? This question has strong implications in structural cell biology and cell signaling networks. Moreover, if PAR played a stabilizing role, such stabilization could participate in the physiological control of axonal branching. PARP and PAR alterations exist in several neurodegenerative pathologies including Alzheimer's, Parkinson's and Hungtington's diseases. Conversely, PARP inhibition decreases PAR and promotes neurite outgrowth in cortical neurons in vitro. Coherently, the PARP inhibitor XAV939 improves myelination in vitro, ex vivo and in vivo. Until now such results have been interpreted in terms of nuclear PARP activity. Our results indicate for the first time the presence of PARylation in peripheral nerve fibers, in a healthy environment. Besides, we have evidenced a PARylation increase in Tr-J, suggesting that the involvement of cytoplasmic PARPs and PARylation in normal and neurodegenerative conditions should be re-evaluated.

  18. Poly(ADP-ribosylation) is present in murine sciatic nerve fibers and is altered in a Charcot-Marie-Tooth-1E neurodegenerative model

    PubMed Central

    Romeo Cardeillac, Carlos J.; Cal Castillo, Karina B.; Vilchez Larrea, Salomé C.; Sotelo Sosa, José R.; Folle Ungo, Gustavo A.; Fernández Villamil, Silvia H.

    2017-01-01

    stabilizing the AJ-actin complexes? This question has strong implications in structural cell biology and cell signaling networks. Moreover, if PAR played a stabilizing role, such stabilization could participate in the physiological control of axonal branching. PARP and PAR alterations exist in several neurodegenerative pathologies including Alzheimer’s, Parkinson’s and Hungtington’s diseases. Conversely, PARP inhibition decreases PAR and promotes neurite outgrowth in cortical neurons in vitro. Coherently, the PARP inhibitor XAV939 improves myelination in vitro, ex vivo and in vivo. Until now such results have been interpreted in terms of nuclear PARP activity. Our results indicate for the first time the presence of PARylation in peripheral nerve fibers, in a healthy environment. Besides, we have evidenced a PARylation increase in Tr-J, suggesting that the involvement of cytoplasmic PARPs and PARylation in normal and neurodegenerative conditions should be re-evaluated. PMID:28503382

  19. Fibromyalgia Is Correlated with Retinal Nerve Fiber Layer Thinning.

    PubMed

    Garcia-Martin, Elena; Garcia-Campayo, Javier; Puebla-Guedea, Marta; Ascaso, Francisco J; Roca, Miguel; Gutierrez-Ruiz, Fernando; Vilades, Elisa; Polo, Vicente; Larrosa, Jose M; Pablo, Luis E; Satue, Maria

    2016-01-01

    To investigate whether fibromyalgia induces axonal damage in the optic nerve that can be detected using optical coherence tomography (OCT), as the retinal nerve fiber layer (RNFL) is atrophied in patients with fibromyalgia compared with controls. Fibromyalgia patients (n = 116) and age-matched healthy controls (n = 144) were included in this observational and prospective cohort study. All subjects underwent visual acuity measurement and structural analysis of the RNFL using two OCT devices (Cirrus and Spectralis). Fibromyalgia patients were evaluated according to Giesecke's fibromyalgia subgroups, the Fibromyalgia Impact Questionnaire (FIQ), and the European Quality of Life-5 Dimensions (EQ5D) scale. We compared the differences between fibromyalgia patients and controls, and analyzed the correlations between OCT measurements, disease duration, fibromyalgia subgroups, severity, and quality of life. The impact on quality of life in fibromyalgia subgroups and in patients with different disease severity was also analyzed. A significant decrease in the RNFL was detected in fibromyalgia patients compared with controls using the two OCT devices: Cirrus OCT ganglion cell layer analysis registered a significant decrease in the minimum thickness of the inner plexiform layer (74.99±16.63 vs 79.36±3.38 μm, respectively; p = 0.023), nasal inferior, temporal inferior and temporal superior sectors (p = 0.040; 0.011 and 0.046 respectively). The Glaucoma application of the Spectralis OCT revealed thinning in the nasal, temporal inferior and temporal superior sectors (p = 0.009, 0.006, and 0.002 respectively) of fibromyalgia patients and the Axonal application in all sectors, except the nasal superior and temporal sectors. The odds ratio (OR) to estimate the size effect of FM in RNFL thickness was 1.39. RNFL atrophy was detected in patients with FIQ scores <60 (patients in early disease stages) compared with controls in the temporal inferior sector (78.74±17.75 vs 81.65±3.61; p

  20. Fibromyalgia Is Correlated with Retinal Nerve Fiber Layer Thinning

    PubMed Central

    Garcia-Martin, Elena; Garcia-Campayo, Javier; Puebla-Guedea, Marta; Ascaso, Francisco J.; Roca, Miguel; Gutierrez-Ruiz, Fernando; Vilades, Elisa; Polo, Vicente; Larrosa, Jose M.; Pablo, Luis E.; Satue, Maria

    2016-01-01

    Objective To investigate whether fibromyalgia induces axonal damage in the optic nerve that can be detected using optical coherence tomography (OCT), as the retinal nerve fiber layer (RNFL) is atrophied in patients with fibromyalgia compared with controls. Methods Fibromyalgia patients (n = 116) and age-matched healthy controls (n = 144) were included in this observational and prospective cohort study. All subjects underwent visual acuity measurement and structural analysis of the RNFL using two OCT devices (Cirrus and Spectralis). Fibromyalgia patients were evaluated according to Giesecke’s fibromyalgia subgroups, the Fibromyalgia Impact Questionnaire (FIQ), and the European Quality of Life-5 Dimensions (EQ5D) scale. We compared the differences between fibromyalgia patients and controls, and analyzed the correlations between OCT measurements, disease duration, fibromyalgia subgroups, severity, and quality of life. The impact on quality of life in fibromyalgia subgroups and in patients with different disease severity was also analyzed. Results A significant decrease in the RNFL was detected in fibromyalgia patients compared with controls using the two OCT devices: Cirrus OCT ganglion cell layer analysis registered a significant decrease in the minimum thickness of the inner plexiform layer (74.99±16.63 vs 79.36±3.38 μm, respectively; p = 0.023), nasal inferior, temporal inferior and temporal superior sectors (p = 0.040; 0.011 and 0.046 respectively). The Glaucoma application of the Spectralis OCT revealed thinning in the nasal, temporal inferior and temporal superior sectors (p = 0.009, 0.006, and 0.002 respectively) of fibromyalgia patients and the Axonal application in all sectors, except the nasal superior and temporal sectors. The odds ratio (OR) to estimate the size effect of FM in RNFL thickness was 1.39. RNFL atrophy was detected in patients with FIQ scores <60 (patients in early disease stages) compared with controls in the temporal inferior sector (78

  1. Degeneration of auditory nerve fibers in guinea pigs with severe sensorineural hearing loss.

    PubMed

    Kroon, Steven; Ramekers, Dyan; Smeets, Emma M; Hendriksen, Ferry G J; Klis, Sjaak F L; Versnel, Huib

    2017-03-01

    Damage to and loss of the organ of Corti leads to secondary degeneration of the spiral ganglion cell (SGC) somata of the auditory nerve. Extensively examined in animal models, this degeneration process of SGC somata following deafening is well known. However, degeneration of auditory nerve axons, which conduct auditory information towards the brainstem, and its relation to SGC soma degeneration are largely unknown. The consequences of degeneration of the axons are relevant for cochlear implantation, which is applied to a deafened system but depends on the condition of the auditory nerve. We investigated the time sequence of degeneration of myelinated type I axons in deafened guinea pigs. Auditory nerves in six normal-hearing and twelve deafened animals, two, six and fourteen weeks (for each group four) after deafening were histologically analyzed. We developed a semi-automated method for axon counting, which allowed for a relatively large sample size (20% of the total cross-sectional area of the auditory nerve). We observed a substantial loss of auditory nerve area (29%), reduction in axon number (59%) and decrease in axoplasm area (41%) fourteen weeks after deafening compared to normal-hearing controls. The correlation between axonal degeneration and that of the SGC somata in the same cochleas was high, although axonal structures appeared to persist longer than the somata, suggesting a slower degeneration process. In the first two weeks after induction of deafness, the axonal cross-sectional area decreased but the axon number did not. In conclusion, the data strongly suggest that each surviving SGC possesses an axon.

  2. Axotomy of single fluorescent nerve fibers in developing mammalian spinal cord by photoconversion of diaminobenzidine.

    PubMed

    De-Miguel, Francisco F; Muller, Kenneth J; Adams, William B; Nicholls, John G

    2002-05-30

    A technique has been developed for cutting single nerve fibers in mammalian spinal cord. In the presence of diaminobenzidine (DAB), a laser microbeam was applied to carbocyanine (Dil) stained sensory fibers in cultured spinal cords of the newly born opossum Monodelphis domestica. Digital images of fluorescent fibers were acquired with an intensified video CCD-camera coupled to an image processor. Laser illumination of two spots on a fiber in the presence of 3 mg/ml DAB cut it, so that following DAB wash out, Dil fluorescence did not return after the intermediate segment was bleached. In contrast, when a similar procedure was carried out without DAB, fluorescence of the bleached segment was recovered within minutes in darkness, by dye diffusion from adjacent regions of the uncut fiber. After exposure to DAB, through-conduction of compound action potentials continued in undamaged fibers. The DAB reaction product remained as a dark precipitate, helping to localize the lesion sites. By illuminating a continuous series of spots it was possible to cut whole nerve roots. Fluorescent fibers extended across the cut segment 24 h later. With minor modifications, the procedure described here allows a precise lesioning of single fibers within an intact nervous system.

  3. Regional differences in myelination of chick vestibulocochlear ganglion cells.

    PubMed

    Sun, Ying-Jie; Kobayashi, Hiroto; Yoshida, Saori; Shirasawa, Nobuyuki; Naito, Akira

    2013-11-01

    In vertebrates, vestibular and cochlear ganglion (VG and CG, respectively) cells are bipolar neurons with myelinated axons and perikarya. The time course of the myelination of the VG and CG cells during development of chick embryos was investigated. Chick VG and CG from embryonic day at 7-20 (E7-20) were prepared for a transmission electron microscopy, myelin basic protein immunohistochemistry, and real-time quantitative RT-PCR. In the VG cells, myelination was first observed on the peripheral axons of the ampullar nerves at E10, on the utricular and saccular nerves at E12, and on the lagenar and neglecta nerves at E13. In the VG central axons, myelination was first seen on the ampullar nerves at E11, on the utricular and saccular nerves at E13, and on the lagenar nerves at E13. In the CG cells, the myelination was first observed on the peripheral and central axons at E14. In both VG and CG, myelination was observed on the perikarya at E17. These results suggest that the onset of the axonal myelination on the VG cells occurred earlier than that on the CG cells, whereas the perikaryal myelination occurred at about the same time on the both types of ganglion cells. Moreover, the myelination on the ampullar nerves occurred earlier than that on the utricular and saccular nerves. The myelination on the peripheral axons occurred earlier than that on the central axons of the VG cells, whereas that on the central and peripheral axons of the CG cells occurred at about the same time. The regional differences in myelination in relation to the onset of functional activities in the VG and CG cells are discussed. Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved.

  4. Bone marrow mononuclear cells migrate to the demyelinated sciatic nerve and transdifferentiate into Schwann cells after nerve injury: attempt at a peripheral nervous system intrinsic repair mechanism.

    PubMed

    Usach, Vanina; Goitia, Belén; Lavalle, Lucía; Martinez Vivot, Rocío; Setton-Avruj, Patricia

    2011-08-01

    In the present work, we analyzed whether endogenous and/or transplanted bone marrow mononuclear cells (BMMC) migrate spontaneously to the crushed sciatic nerve and whether they transdifferentiate into Schwann cells (SC) in order to help repair the damaged tissue. We also studied both the immunohistochemical evolution of myelin proteins MBP and P(0) and the myelin composition of both the proximal and distal stumps of the crushed sciatic nerve to determine the demyelination-remyelination period. Immunohistochemical analysis of crushed animals showed that the degeneration process consists of loss of nerve fiber integrity accompanied by degradation of myelin basic proteins MBP and P(0) , which is anticipated by protein cluster formation. The remyelination process appears as a recovery in nerve fiber structure as well as in MBP and P(0) immunoreactivity; results obtained studying isolated myelin from the crushed sciatic nerve show a strong correlation between them. As opposed to demyelination, axonal damage is observed for a short period of time and takes place mostly in the crush area and the segments adjacent to the lesion. Evidence of spontaneous migration of endogenous or intravascularly transplanted BMMC (CD34(+) and vimentin(+) ) is found during the demyelination period exclusively to the injured sciatic nerve. Once migration takes place, transdifferentiation to SC is observed. Such migration and transdifferentiation processes might be inferred to constitute a spontaneous repair mechanism after nerve injury. Copyright © 2011 Wiley-Liss, Inc.

  5. Internodal myelin volume and axon surface area. A relationship determining myelin thickness?

    PubMed

    Smith, K J; Blakemore, W F; Murray, J A; Patterson, R C

    1982-08-01

    Internodes from normal, remyelinated and regenerated nerve fibres have been isolated from rat spinal roots and sciatic nerve. The internodes have been examined quantitatively by light and electron microscopy to determine their internodal length, myelin thickness, and the circumference and cross-sectional area of both the axons and fibre. Comparison of these measurements of the axon and myelin sheath has revealed a close relationship between the volume of myelin comprising the internode and the area over which the Schwann cell and axon are in close proximity, i.e. the surface area of the axolemma beneath the internodal myelin sheath. The same relationship described not only the internodes on normal nerve fibres, where internodal length is proportional to axon diameter, but also the short and thinly myelinated internodes formed in the adult animal on remyelinated and on regenerated axons. Examination of data presented by Berthold (1978) revealed that a closely similar relationship is also present in feline nerve fibres. In view of the constancy of the relationship between such different types of internode it is suggested that the regulation of myelin volume, and thereby of myelin thickness, may be mediated via the area of the axolemma or of the Schwann cell membrane beneath the myelin sheath.

  6. Discovering early diabetic neuropathy from epidermal nerve fiber patterns.

    PubMed

    Andersson, Claes; Guttorp, Peter; Särkkä, Aila

    2016-10-30

    Epidermal nerve fibre (ENF) density and morphology are used to study small fibre involvement in diabetic, HIV, chemotherapy induced and other neuropathies. ENF density and summed length of ENFs per epidermal surface area are reduced, and ENFs may appear more clustered within the epidermis in subjects with small fibre neuropathy than in healthy subjects. Therefore, it is important to understand the spatial structure of ENFs. In this paper, we compare the ENF patterns between healthy subjects and subjects suffering from mild diabetic neuropathy. The study is based on suction skin blister specimens from the right foot of 32 healthy subjects and eight subjects with mild diabetic neuropathy. We regard the ENF entry point (location where the trunks of a nerve enters the epidermis) and ENF end point (termination of the nerve fibres) patterns as realizations of spatial point processes, and develop tools that can be used in the analysis and modelling of ENF patterns. We use spatial summary statistics and shift plots and define a new tool, reactive territory, to study the spatial patterns and to compare the patterns of the two groups. We will also introduce a simple model for these data in order to understand the growth process of the nerve fibres. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  7. Reduction in Retinal Nerve Fiber Layer Thickness in Young Adults with Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Emberti Gialloreti, Leonardo; Pardini, Matteo; Benassi, Francesca; Marciano, Sara; Amore, Mario; Mutolo, Maria Giulia; Porfirio, Maria Cristina; Curatolo, Paolo

    2014-01-01

    Recent years have seen an increase in the use of retinal nerve fiber layer (RNFL) evaluation as an easy-to-use, reproducible, proxy-measure of brain structural abnormalities. Here, we evaluated RNFL thickness in a group of subjects with high functioning autism (HFA) or with Asperger Syndrome (AS) to its potential as a tool to study autism…

  8. Dithranol abolishes UCH-L1 immunoreactivity in the nerve fibers of the rat orofacial skin.

    PubMed

    Orojan, Ivan; Szigeti, Csaba; Varszegi, Szilvia; Dobo, Endre; Gulya, Karoly

    2006-11-22

    Dithranol has been used to treat psoriasis for decades. Although its beneficial effect may involve the induction of cutaneous inflammation, and inflammation often leads to damages in nerve fibers, these alterations are not well documented. Therefore, we investigated the effects of dithranol on the immunohistochemical characteristics of the cutaneous nerve fibers in the rat skin. Epidermal nerve fiber staining was achieved with ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) immunohistochemistry in the orofacial skin of control rats, rats treated with (a) dithranol for 5 days, (b) corticosteroid for 5 days following dithranol treatment for 5 days, and (c) corticosteroid for 5 days. The results revealed a complete loss of UCH-L1 immunoreactivity in the dithranol-treated animals. Topical application of corticosteroid onto the inflamed skin for 5 days reversed this effect: the UCH-L1 immunoreactivity was almost completely restored. Steroid treatment for 5 days did not change the appearance of the UCH-L1-immunoreactive nerve fibers. These findings were supported by Western blot analyses. We conclude that dithranol, incidentally similarly to psoriasis, causes inflammation and abolishes UCH-L1 immunoreactivity in the rat orofacial skin in a corticosteroid-reversible manner. This phenomenon may be due to the ability of dithranol to cause oxidative damage to the UCH-L1 protein, and to the antioxidant activity of the corticosteroids countering this effect.

  9. Reduction in Retinal Nerve Fiber Layer Thickness in Young Adults with Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Emberti Gialloreti, Leonardo; Pardini, Matteo; Benassi, Francesca; Marciano, Sara; Amore, Mario; Mutolo, Maria Giulia; Porfirio, Maria Cristina; Curatolo, Paolo

    2014-01-01

    Recent years have seen an increase in the use of retinal nerve fiber layer (RNFL) evaluation as an easy-to-use, reproducible, proxy-measure of brain structural abnormalities. Here, we evaluated RNFL thickness in a group of subjects with high functioning autism (HFA) or with Asperger Syndrome (AS) to its potential as a tool to study autism…

  10. The effects of aminoguanidine, methylprednisolone, and melatonin on nerve recovery in peripheral facial nerve neurorrhaphy.

    PubMed

    Yanilmaz, Muhammed; Akduman, Davut; Sagun, Ömer Faik; Haksever, Mehmet; Yazicilar, Osman; Orhan, Israfil; Akpolat, Nusret; Gök, Uzeyir

    2015-05-01

    The medications may enhance the recovery after nerve paralysis. We aimed to evaluate the effects of aminoguanidine (AG), melatonin, and methylprednisolone on peripheral facial nerve neurorrhaphy. The buccal branch of the facial nerve was transected and autografted in 32 New Zealand rabbits. Subjects were divided into 4 groups equally (AG, melatonin, methylprednisolone, and control). After the medical treatment latency and amplitude were measured with nerve conduction study at 3, 6, and 10 weeks. Then, coapted segments of nerve were examined microscopically. The groups were compared with each other. The latent period was shortened, and the amplitudes were increased in the AG group; the latent period was shortened, and the amplitudes did not show significant change in the melatonin group with the time. There were no significant differences between the amplitudes at 3 to 6 and 3 to 10 weeks in the methylprednisolone group, and the latent period was shortened. There was no significant difference between the amplitude values at 3, 6, and 10 weeks in the control group. In the histological examination, AG had the best influence on preventing myelin degeneration and reducing the accumulation of myelin debris. Considering the increase in collagen fibers, the best results were achieved in the melatonin group. The degree of myelin-axonal degeneration was higher in the methylprednisolone group. The degree of collagen fiber increase, axonal degeneration, myelin degeneration, and the accumulation of myelin debris were detected quite high in the control group. Aminoguanidine and melatonin alone achieved an increase in regeneration after peripheral facial nerve neurorrhaphy, but methylprednisolone did not. The best healing was determined in the AG group.

  11. Exploration of the retinal nerve fiber layer thickness by measurement of the linear dichroism

    NASA Astrophysics Data System (ADS)

    Naoun, Olivier Karim; Dorr, Valérie Louis; Allé, Paul; Sablon, Jean-Christophe; Benoit, Anne-Marie

    2005-11-01

    An electro-optic device mounted on a slit lamp to assess the degree of polarization of a light beam that has double passed through the retina about the optic-nerve head in the living human eye is described. The asymmetric structure of the retinal nerve's fiber layer possesses a linear-form dichroism and will partially polarize an unpolarized light beam that is scattered at the fundus of the eye and has double passed the ocular media (cornea, lens, retina). This partial polarization is a function of the retinal nerve's fiber layer thickness, and its measurement may be used for exploring glaucoma and other retinal neuropathies. Experimental conditions allow us to neglect corneal dichroism. The first clinical measurements show a different degree of polarization between normal and glaucomatous eyes and a good correlation with the results obtained by optical coherence tomography.

  12. Central distribution of nociceptive intradental afferent nerve fibers in the rat.

    PubMed

    Bombardi, C; Chiocchetti, R; Brunetti, O; Grandis, A; Lucchi, M L; Bortolami, R

    2006-08-01

    The central distribution of intradental afferent nerve fibers was investigated by combining electron microscopic observations with a selective method for inducing degeneration of the A delta- and C-type afferent fibers. Degenerating terminals were found on the proprioceptive mesencephalic trigeminal neurons and on dendrites in the neuropil of the trigeminal motor nucleus after application of capsaicin to the rat's lower incisor tooth pulp. The results give anatomical evidence of new sites of central projection of intradental A delta- and C-type fibers whereby the nociceptive information from the tooth pulp can affect jaw muscle activity.

  13. Association of myelinated primary afferents impairment with mechanical allodynia in diabetic peripheral neuropathy: an experimental study in rats.

    PubMed

    Liao, Chenlong; Yang, Min; Zhong, Wenxiang; Liu, Pengfei; Zhang, Wenchuan

    2017-09-08

    To investigate the mechanisms underlying the efficacy of surgical treatment for painful diabetic peripheral neuropathy. Rats were initially divided into 3 groups (I, control rats, II, streptozotocin-induced diabetic rats, III, streptozotocin-induced diabetic rats with latex tube encircling the sciatic nerve without compression). When mechanical allodynia (MA) became stable in the third week, one third of group III rats were sacrificed and the remainder were further divided into subgroups depending on whether the latex tube was removed. Except for some rats in group III, all rats were sacrificed in the fifth week. Morphometric analysis of nerve fibers was performed. Expression level of GABAB receptor protein in spinal dorsal horn was determined. Changes of GABAB receptor within areas of primary afferents central terminal were identified. Chronic nerve compression caused by the interaction of diabetic nerves swelling and the encircling latex tube increased the incidence of MA in diabetic rats, and nerve decompression could ameliorate MA. In diabetic rats with MA, demyelination of myelinated fibers was noted and reduction of GABAB receptor was mainly detected in the area of myelinated afferent central terminals. MA in DPN should be partially attributed to compression impairment of myelinated afferents, supporting the rationale for surgical decompression.

  14. Vasa nervorum in rat major pelvic ganglion are innervated by nitrergic nerve fibers.

    PubMed

    Beetson, Karl A; Smith, Stephanie F; Muneer, Asif; Cameron, Norman E; Cotter, Mary A; Cellek, Selim

    2013-12-01

    The vasa nervorum comprises a network of small diameter blood vessels that provide blood supply to nerves and ganglia. The cell bodies of autonomic nerves innervating the urogenital organs are housed in the major pelvic ganglia (MPG) in rats. The vasa nervorum of rat MPG have not been characterized previously, and it is not known whether these blood vessels are innervated by neuronal nitric oxide synthase (nNOS) containing nitrergic nerves. To characterize the blood vessels in and around the rat MPG and to assess their nitrergic innervation. Characterization of small blood vessels in and around the rat MPG and expression of nNOS in nerve fibers around those blood vessels. MPG were obtained from healthy Sprague Dawley rats, fixed in paraformaldehyde, frozen and sectioned using a cryostat. The blood vessels and their nitrergic innervation were assessed with immunohistochemistry using antibodies against alpha-smooth muscle actin (smooth muscle marker), CD31 (endothelial marker), collagen IV (basal membrane marker) and nNOS. The immunofluorescence was imaged using a laser scanning confocal microscope. The neuronal cell bodies were contained within a capsule in the MPG. Blood vessels were observed within the capsule of the MPG as well as outside the capsule. The blood vessels inside the capsule were CD31-positive capillaries with no smooth muscle staining. Outside the capsule capillaries, arterioles and venules were observed. The extra-capsular arterioles and venules, but not the capillaries were innervated by nNOS-positive nerve fibers. This study, to our knowledge, is the first to demonstrate the blood vessel distribution pattern and their nitrergic innervation in the rat MPG. While similar studies in human pelvic plexus are warranted, these results suggest that the blood flow in the MPG may be regulated by nitrergic nerve fibers and reveal a reciprocal relationship between nerves and blood vessels. © 2013 International Society for Sexual Medicine.

  15. Co-activation of saphenous nerve fibers: a potential therapeutic mechanism of percutaneous tibial nerve stimulation?

    PubMed

    Elder, Christopher W; Yoo, Paul B

    2016-08-01

    Percutaneous tibial nerve stimulation (PTNS) is a minimally invasive and effective treatment for overactive bladder (OAB). However, clinical trials show that positive therapeutic outcomes among patients are difficult to predict (failure rate = 35% to 50%). Inconsistencies in the stimulation amplitudes used clinically and those used in preclinical animal studies led us to hypothesize that OAB therapy involves a secondary bladder-inhibitory pathway. In this paper, we implemented and tested a computer model of the human lower leg that investigated the differential activation of the saphenous nerve (SAFN) and tibial nerve (TN) during percutaneous electrical stimulation. Our preliminary findings show that concomitant activation of SAFN branches occurs during PTNS, which suggests the possibility that the SAFN may influence the clinical outcome of treatment.

  16. Registration of adaptive optics corrected retinal nerve fiber layer (RNFL) images

    PubMed Central

    Ramaswamy, Gomathy; Lombardo, Marco; Devaney, Nicholas

    2014-01-01

    Glaucoma is the leading cause of preventable blindness in the western world. Investigation of high-resolution retinal nerve fiber layer (RNFL) images in patients may lead to new indicators of its onset. Adaptive optics (AO) can provide diffraction-limited images of the retina, providing new opportunities for earlier detection of neuroretinal pathologies. However, precise processing is required to correct for three effects in sequences of AO-assisted, flood-illumination images: uneven illumination, residual image motion and image rotation. This processing can be challenging for images of the RNFL due to their low contrast and lack of clearly noticeable features. Here we develop specific processing techniques and show that their application leads to improved image quality on the nerve fiber bundles. This in turn improves the reliability of measures of fiber texture such as the correlation of Gray-Level Co-occurrence Matrix (GLCM). PMID:24940551

  17. Degradation in the degree of polarization in human retinal nerve fiber layer

    NASA Astrophysics Data System (ADS)

    Yin, Biwei; Wang, Bingqing; Rylander, Henry G.; Milner, Thomas E.

    2014-01-01

    Using a fiber-based swept-source (SS) polarization-sensitive optical coherence tomography (PS-OCT) system, we investigate the degree of polarization (DOP) of light backscattered from the retinal nerve fiber layer (RNFL) in normal human subjects. Algorithms for processing data were developed to analyze the deviation in phase retardation and intensity of backscattered light in directions parallel and perpendicular to the nerve fiber axis (fast and slow axes of RNFL). Considering superior, inferior, and nasal quadrants, we observe the strongest degradation in the DOP with increasing RNFL depth in the temporal quadrant. Retinal ganglion cell axons in normal human subjects are known to have the smallest diameter in the temporal quadrant, and the greater degradation observed in the DOP suggests that higher polarimetric noise may be associated with neural structure in the temporal RNFL. The association between depth degradation in the DOP and RNFL structural properties may broaden the utility of PS-OCT as a functional imaging technique.

  18. Registration of adaptive optics corrected retinal nerve fiber layer (RNFL) images.

    PubMed

    Ramaswamy, Gomathy; Lombardo, Marco; Devaney, Nicholas

    2014-06-01

    Glaucoma is the leading cause of preventable blindness in the western world. Investigation of high-resolution retinal nerve fiber layer (RNFL) images in patients may lead to new indicators of its onset. Adaptive optics (AO) can provide diffraction-limited images of the retina, providing new opportunities for earlier detection of neuroretinal pathologies. However, precise processing is required to correct for three effects in sequences of AO-assisted, flood-illumination images: uneven illumination, residual image motion and image rotation. This processing can be challenging for images of the RNFL due to their low contrast and lack of clearly noticeable features. Here we develop specific processing techniques and show that their application leads to improved image quality on the nerve fiber bundles. This in turn improves the reliability of measures of fiber texture such as the correlation of Gray-Level Co-occurrence Matrix (GLCM).

  19. Central projections of primary vestibular fibers in the bullfrog. II. Nerve branches from individual receptors.

    PubMed

    Suarez, C; Kuruvilla, A; Sitko, S; Schwartz, I R; Honrubia, V

    1985-10-01

    The fibers from the nerves innervating each of the three semicircular canals and the saccule were labeled by injecting horseradish peroxidase extracellularly into these nerves. The projections into the various vestibular nuclei of each receptor were studied in transverse sections of the brain stem throughout the vestibular nuclear area. All five vestibular nuclei receive primary afferents throughout their areas. There are differences in the projection patterns of the canals. In the superior and ventral vestibular nuclei, the location of the projections depends on the crista injected. The anterior canal projects ventrally, the horizontal canal centrally, and the posterior canal more dorsally. Each canal, however, sends fibers to all areas, with overlap of fibers from the different cristae. The cerebellar nucleus receives uniform innervation from the three canals. The medial vestibular nucleus in the rostral and caudal areas receives only thin fibers from each canal, with considerable overlap. The descending nucleus in the rostral and caudal areas receives innervation from the cristae, also with considerable overlap, but with greater intensity in the ventral part of the caudal portion of the nucleus. Each crista sends fibers to the cerebellar granular layer and to the base of the cerebellar Purkinje cell layer. These fibers also innervate the reticular formation below the entry zone of the eighth nerve. The saccule innervates both the dorsal (acoustic) and the ventral nuclei, the latter in the most dorsal position. The innervation of the utricle could be ascertained only in the middle section of the descending and the medial nuclei, an area which does not receive significant innervation from the cristae. Primary afferent fibers course in the vestibular tract, forming a longitudinal bundle lateral to the vestibular nuclei. In the bundle the larger fibers are medially situated.

  20. Three-dimensional morphological characterization of optic nerve fibers by atomic force microscopy and by scanning electron microscopy.

    PubMed

    Melling, Mahmoud; Karimian-Teherani, Daniela; Mostler, Sascha; Hochmeister, Sonja

    2005-08-01

    A comparative study of scanning electron microscopy (SEM) and atomic force microscopy (AFM) imaging of the healthy human optic nerve was carried out to determine the similarities and the differences. In this study we compared the fine optic nerve structures as observed by SEM and AFM. The fibers of the right optic nerve of a 61-year-old man show different arrangements in transverse sections taken from the same individual 5 mm central to the optic canal and 5 mm peripheral to the optic chiasma; this difference can be recognized by light microscopy (LM), SEM, and AFM. AFM revealed such typical optic nerve fibers (taken from a point 5 mm central to the optic canal) with annular and longitudinal orientations, which were not visible by SEM in this form. By contrast, LM and SEM visualized other structures, such as pia mater and optic nerve fibers loosely arranged in bundles, none of which was visualized by AFM. The images, however, taken 5 mm peripheral from the optic chiasma show shapeless nerve fibers having a wavy course. Our results reveal that more detailed information on optic nerve morphology is obtained by exploiting the advantages of both SEM and AFM. These are the first SEM and AFM images of healthy human optic nerve fibers, containing clear representations of the three dimensions of the optic nerve.

  1. Analysis of motor fibers in the communicating branch between the cervical nerves and the spinal accessory nerve to innervate trapezius in the rat.

    PubMed

    Yan, Jun; Hitomi, Jiro

    2006-11-01

    The communicating branch between the ventral rami of cervical nerves and the spinal accessory nerve (SAN) has been reported to also send motor fibers to supply the trapezius. However, the motor fiber type of the communicating branch and its peripheral distribution are still unclear. To determine the fiber elements within the branch and its peripheral distribution of the motor fibers in the trapezius, the anterograde tracing method was used in this study. The results show that a few a motor end plates from the communicating branch were observed on the extrafusal fibers, while in the muscle spindle the motor elements from the communicating branch were distributed to the polar portions of the intrafusal fibers. These results indicated that the motor fibers passing through the communicating branch to supply the trapezius are mainly y motor fibers, with some a motor fibers. Moreover, the a and y motor fibers from the communicating branch were observed in the clavotrapezius, acromiotrapezius and the rostral part of spinotrapezius. These findings also correlate with the clinical observation indicating that even when the spinal accessory nerve is injured, the trapezius is still capable of slight movement.

  2. Taste cell responses in the frog are modulated by parasympathetic efferent nerve fibers.

    PubMed

    Sato, Toshihide; Okada, Yukio; Miyazaki, Toshihiro; Kato, Yuzo; Toda, Kazuo

    2005-11-01

    We studied the anatomical properties of parasympathetic postganglionic neurons in the frog tongue and their modulatory effects on taste cell responses. Most of the parasympathetic ganglion cell bodies in the tongue were found in extremely small nerve bundles running near the fungiform papillae, which originate from the lingual branches of the glossopharyngeal (GP) nerve. The density of parasympathetic postganglionic neurons in the tongue was 8000-11,000/mm(3) of the extremely small nerve bundle. The mean major axis of parasympathetic ganglion cell bodies was 21 microm, and the mean length of parasympathetic postganglionic neurons was 1.45 mm. Electrical stimulation at 30 Hz of either the GP nerve or the papillary nerve produced slow hyperpolarizing potentials (HPs) in taste cells. After nicotinic acetyl choline receptors on the parasympathetic ganglion cells in the tongue had been blocked by intravenous (i.v.) injection of D-tubocurarine (1 mg/kg), stimulation of the GP nerve did not induce any slow HPs in taste cells but that of the papillary nerve did. A further i.v. injection of a substance P NK-1 antagonist, L-703,606, blocked the slow HPs induced by the papillary nerve stimulation. This suggests that the parasympathetic postganglionic efferent fibers innervate taste cells and are related to a generation of the slow HPs and that substance P is released from the parasympathetic postganglionic axon terminals. When the resting membrane potential of a taste cell was hyperpolarized by a prolonged slow HP, the gustatory receptor potentials for NaCl and sugar stimuli were enhanced in amplitude, but those for quinine-HCl and acetic acid stimuli remained unchanged. It is concluded that frog taste cell responses are modulated by activities of parasympathetic postganglionic efferent fibers innervating these cells.

  3. Nerve fibers and endometriotic lesions: partners in crime in inflicting pains in women with endometriosis.

    PubMed

    Yan, Dingmin; Liu, Xishi; Guo, Sun-Wei

    2017-02-01

    One of major objectives in treating endometriosis is to alleviate pain since dysmenorrhea and other types of pain top the list of complaints from women with endometriosis who seek medical attention. Indeed, endometriosis-associated pain (EAP) is the most debilitating of the disease that negatively impacts on the quality of life in affected women, contributing significantly to the burden of disease and adding to the substantial personal and societal costs. Unfortunately, the mechanisms underlying the EAP are still poorly understood. In the last two decades, one active research field in endometriosis is the investigation on the distribution and genesis of nerve fibers in eutopic and ectopic endometrium, and the attempt to use endometrial nerve fiber density for diagnostic purpose. Since EAP presumably starts with the terminal sensory nerves, in or around endometriotic lesions, that transduce noxious mediators to the central nervous system (CNS) which ultimately perceives pain, this field of research holds the promise to elucidate the molecular mechanisms underlying the EAP, thus opening new avenues for novel diagnostics and therapeutics. In this review, we shall first briefly provide some basic facts on nerve fibers, and then provide an overview of some major findings in this filed while also note some conflicting results and expose areas in need of further research. We point out that since recently accumulated evidence suggests that endometriotic lesions are wounds undergoing repeated tissue injury and repair, the relationship between endometriotic lesions and nerve fibers is not simply unidirectional, i.e. lesions promote hyperinnervations. Rather, it is bidirectional, i.e. endometriotic lesions and nerve fibers engage active cross-talks, resulting in the development of endometriosis and pain. That is, nerve fibers and endometriotic lesions are actually partners in crime in inflicting pains in women with endometriosis, aided and abetted possibly by other culprits

  4. Angiotensinergic innervation of the kidney: Localization and relationship with catecholaminergic postganglionic and sensory nerve fibers.

    PubMed

    Bohlender, Jürgen; Pfarrer, Beat; Patil, Jaspal; Nussberger, Jürg; Thalmann, Georg N; Imboden, Hans

    2012-11-01

    We describe an angiotensin (Ang) II-containing innervation of the kidney. Cryosections of rat, pig and human kidneys were investigated for the presence of Ang II-containing nerve fibers using a mouse monoclonal antibody against Ang II (4B3). Co-staining was performed with antibodies against synaptophysin, tyrosine 3-hydroxylase, and dopamine beta-hydroxylase to detect catecholaminergic efferent fibers and against calcitonin gene-related peptide to detect sensory fibers. Tagged secondary antibodies and confocal light or laser scanning microscopy were used for immunofluorescence detection. Ang II-containing nerve fibers were densely present in the renal pelvis, the subepithelial layer of the urothelium, the arterial nervous plexus, and the peritubular interstitium of the cortex and outer medulla. They were infrequent in central veins and the renal capsule and absent within glomeruli and the renal papilla. Ang II-positive fibers represented phenotypic subgroups of catecholaminergic postganglionic or sensory fibers with different morphology and intrarenal distribution compared to their Ang II-negative counterparts. The Ang II-positive postganglionic fibers were thicker, produced typically fusiform varicosities and preferentially innervated the outer medulla and periglomerular arterioles. Ang II-negative sensory fibers were highly varicose, prevailing in the pelvis and scarce in the renal periphery compared to the rarely varicose Ang II-positive fibers. Neurons within renal microganglia displayed angiotensinergic, catecholaminergic, or combined phenotypes. Our results suggest that autonomic fibers may be an independent source of intrarenal Ang II acting as a neuropeptide co-transmitter or neuromodulator. The angiotensinergic renal innervation may play a distinct role in the neuronal control of renal sodium reabsorption, vasomotion and renin secretion.

  5. Three-dimensional Imaging and Analysis of Mitochondria within Human Intraepidermal Nerve Fibers.

    PubMed

    Hamid, Hussein S; Hayes, John M; Feldman, Eva L; Lentz, Stephen I

    2017-09-29

    The goal of this protocol is to study mitochondria within intraepidermal nerve fibers. Therefore, 3D imaging and analysis techniques were developed to isolate nerve-specific mitochondria and evaluate disease-induced alterations of mitochondria in the distal tip of sensory nerves. The protocol combines fluorescence immunohistochemistry, confocal microscopy and 3D image analysis techniques to visualize and quantify nerve-specific mitochondria. Detailed parameters are defined throughout the procedures in order to provide a concrete example of how to use these techniques to isolate nerve-specific mitochondria. Antibodies were used to label nerve and mitochondrial signals within tissue sections of skin punch biopsies, which was followed by indirect immunofluorescence to visualize nerves and mitochondria with a green and red fluorescent signal respectively. Z-series images were acquired with confocal microscopy and 3D analysis software was used to process and analyze the signals. It is not necessary to follow the exact parameters described within, but it is important to be consistent with the ones chosen throughout the staining, acquisition and analysis steps. The strength of this protocol is that it is applicable to a wide variety of circumstances where one fluorescent signal is used to isolate other signals that would otherwise be impossible to study alone.

  6. Functional and structural nerve fiber findings in heterozygote patients with Fabry disease.

    PubMed

    Torvin Møller, Anette; Winther Bach, Flemming; Feldt-Rasmussen, Ulla; Rasmussen, Ase; Hasholt, Lis; Lan, He; Sommer, Claudia; Kølvraa, Steen; Ballegaard, Martin; Staehelin Jensen, Troels

    2009-09-01

    Fabry disease is an X-linked inherited lysosomal disorder with dysfunction of the lysosomal enzyme alpha-galactosidase A causing accumulation of glycolipids in multiple organs including the nervous system. Pain and somatosensory disturbances are prominent manifestations of this disease. Until recently disease manifestations in female carriers of Fabry disease have been questioned. To explore the frequency of symptoms and the functional and structural involvement of the nervous system in female patients we examined the presence of pain, manifestations of peripheral neuropathy and nerve density in skin biopsies in 19 female patients with Fabry disease and 19 sex- and age-matched controls. Diaries, quantitative sensory testing, neurophysiologic tests and skin biopsies were performed. Daily pain was present in 63% of patients, with a median VAS score of 4.0. Tactile detection threshold and pressure pain threshold were lower and cold detection thresholds increased in patients. Sensory nerve action potential amplitude and maximal sensory conduction velocity were not different, whereas there was a highly significant reduction in intraepidermal nerve fiber density. We found no correlation between pain VAS score, quantitative sensory testing and intraepidermal nerve fiber density. Our study demonstrates that careful evaluation of symptoms in female Fabry patients is important as small fiber disease manifestations are present, which in some cases is only detected by skin biopsy.

  7. Relationship between Retinal Nerve Fiber Layer Thickness and Hemoglobin Present in the Optic Nerve Head in Glaucoma

    PubMed Central

    Gonzalez-Hernandez, Marta

    2017-01-01

    Purpose To observe the relationship between topographic hemoglobin levels in the optic nerve head (ONH), the rim thickness (BMO-MRW), and retinal nerve fiber layer (RNFL) thickness. Methods 96 normal eyes and 82 glaucomas were examined using TOP strategy (Octopus 300 perimeter), SPECTRALIS OCT, and Laguna ONhE program which estimates hemoglobin from conventional color photographs (Horus Scope DEC 200 fundus camera). Results The correlation between Laguna ONhE glaucoma discriminant function (GDF) and SPECTRALIS BMO-MRW was R = 0.81 (P < 0.0001), similar to that between the BMO-MRW and BMO-RNFL thicknesses (R = 0.85, P < 0.0001) (P = 0.227 between both R values). GDF correlated well with RNFL thicknesses in the 360 degrees around the nerve, similar to mean perimetric sensitivity (MS) and BMO-MRW. The amount of hemoglobin in the nasal and temporal sectors showed low correlation with superior and inferior RNFL thicknesses. The superotemporal and inferotemporal sectors located on the vertical diameter of the disk showed good intercorrelation but without a clear RNFL topographic relationship. Conclusion GDF showed high correlation with RNFL thickness. Except in the nasal and temporal sectors, ONH hemoglobin correlated well with RNFL thickness. PMID:28660077

  8. Peripapillary Retinal Nerve Fiber Layer Vascular Microcirculation in Glaucoma Using Optical Coherence Tomography–Based Microangiography

    PubMed Central

    Chen, Chieh-Li; Zhang, Anqi; Bojikian, Karine D.; Wen, Joanne C.; Zhang, Qinqin; Xin, Chen; Mudumbai, Raghu C.; Johnstone, Murray A.; Chen, Philip P.; Wang, Ruikang K.

    2016-01-01

    Purpose To investigate the vascular microcirculation changes in the retinal nerve fiber layer (RNFL) in normal, glaucoma suspect, and open-angle glaucoma (OAG) groups using optical coherence tomography–based microangiography (OMAG). Methods One eye from each subject was scanned with a Cirrus HD-OCT 5000–based OMAG prototype system montage scanning protocol centered at the optic nerve head (ONH). Blood flow signals were extracted using OMAG algorithm. Retinal nerve fiber layer vascular microcirculation was measured by calculating the blood flux index and vessel area density within a 1.2-mm width annulus centered at the ONH with exclusion of big retinal vessels. One-way ANOVA were performed to analyze the RNFL microcirculation among groups. Linear-regression models were constructed to analyze the correlation between RNFL microcirculation and clinical parameters. Discrimination capabilities of the flow metrics were assessed with the area under the receiver operating characteristic curve (AROC). Results Twenty normal, 26 glaucoma suspect, and 42 OAG subjects were enrolled. Eyes from OAG subjects and glaucoma suspects showed significantly lower blood flux index compared with normal eyes (P ≤ 0.0015). Retinal nerve fiber layer blood flow metrics showed significant correlations with visual field indices and structural changes in glaucomatous eyes (P ≤ 0.0123). Similar discrimination capability of blood flux index compared with RNFL thickness was found in both disease groups. Conclusions Peripapillary RNFL vascular microcirculation measured as blood flux index by OMAG showed significant differences among OAG, glaucoma suspect, and normal controls and was significantly correlated with functional and structural defects. Retinal nerve fiber layer microcirculation measurement using OMAG may help physicians monitor glaucoma. PMID:27442341

  9. Measurement of the retinal nerve fiber layer thickness in clinical routine.

    PubMed

    Gramer, E; Tausch, M

    1998-04-01

    The possibilities and limitations of methods for indirect and direct nerve fiber layer thickness (NFLT) measurements, and a summary of our own clinical studies using Optic Nerve Head Analyzer (Rodenstock, Munich, Germany) (ONHA), Laser Tomographic Scanner (Heidelberg Engineering, Heidelberg, Germany) (LTS), Heidelberg Retinal Tomograph (Heidelberg Engineering, Heidelberg, Germany) (HRT), Nerve Fiber Analyzer (Laser Diagnostic Technologies, San Diego, CA) (NFA) and Optical Coherence Tomography (OCT), together with the literature of the review period, are highlighted. A retinal hemifield test with the new parameters, retinal asymmetry difference and retinal asymmetry index, is introduced. These relative nerve fiber layer thickness (NFLT) measurement values are found to be independent of age, reference plane, and disc size. This reduces the interindividual variation of the measurements and may improve screening possibilities for glaucoma. The detection probability for nerve fiber bundle defects was found to be stage-dependent using HRT and NFA. For laser polarimetry, a decreasing correlation between NFLT and visual field loss with advanced glaucomatous disease was found. In the lower retina, a 6.9% higher NFLT was evident compared with the upper peripapillary NFLT in healthy eyes using NFA and OCT. This is not in correlation with perimetric retinal sensitivity, which was found to be 3.9% higher in the lower hemifield compared with the upper hemifield. In general, quantitative NFLT measures (HRT, NFA, OCT) were correlated with visual field loss in glaucoma. The interindividual variability of NFLT measurements, among other things, induces limitations on distinguishing beginning glaucoma from normals. Clinical and scientific significance and future directions of NFLT measurements are discussed.

  10. Development of a computer algorithm for feedback controlled electrical nerve fiber stimulation.

    PubMed

    Doruk, R Özgür

    2011-09-01

    The purpose of this research is to develop an algorithm for a feedback controlled local electrical nerve fiber stimulation system which has the purpose to stop the repetitive firing in a particular region of the nervous system. The electrophysiological behavior of the neurons (under electrical currents) is modeled by Hodgkin-Huxley (HH) type nonlinear nerve fiber dynamics. The repetitive firing of in the modeled fiber is due to the deviations in the channel parameters, which is also called as bifurcation in the nonlinear systems theory. A washout filter is augmented to the HH dynamics and then the output of the filter is fed to the external current generator through a linear gain. This gain is computed by linear projective control theory. That is a linear output feedback control technique where the closed loop spectrum of the full state feedback closed loop is partially maintained. By obtaining a spectrum of eigenvalues with completely negative real parts the nerve fibers can be relaxed to the equilibrium point with or without a damped oscillation. The MATLAB script applying the theory of this work is provided at the end of this paper. A MATLAB-Simulink computer simulation is performed in order to verify the algorithm. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  11. Biophysical and functional consequences of receptor-mediated nerve fiber transformation.

    PubMed Central

    Tanelian, D L; Markin, V S

    1997-01-01

    Stimulation of the nervous system by substance P, a G protein-coupled receptor, and subsequent receptor internalization causes dendrites to change their shape from homogeneous cylinders to a heterogeneous string of swollen varicosities (beads) connected by thin segments. In this paper we have analyzed this phenomenon and propose quantitative mechanisms to explain this type of physical shape transformation. We developed a mathematical solution to describe the relationship between the initial radius of a cylindrical nerve fiber and the average radii of the subsequently created varicosities and connecting segments, as well as the periodicity of the varicosities along the nerve fiber. Theoretical predictions are in good agreement with our own and published experimental data from dorsal root ganglion neurons, spinal cord, and brain. Modeling the electrical properties of these beaded fibers has led to an understanding of the functional biophysical consequences of nerve fiber transformation. Several hypotheses for how this shape transformation can be used to process information within the nervous system have been put forth. Images FIGURE 1 FIGURE 6 PMID:9138558

  12. Marked loss of sympathetic nerve fibers in chronic Charcot foot of diabetic origin compared to ankle joint osteoarthritis.

    PubMed

    Koeck, Franz-Xaver; Bobrik, Verena; Fassold, Alexander; Grifka, Joachim; Kessler, Sigurd; Straub, Rainer H

    2009-06-01

    The pathogenesis of Charcot foot is based on three disputed factors: (1) loss of neurotrophic influence, (2) microtraumatic lesions, and (3) neurovascular disturbances. These etiological causes were uncovered by clinicophysiological tests. However, no results of quantitative nerve density studies of sympathetic and sensory substance P-positive (SP+) nerve fibers are available. We studied the density of sympathetic and SP+ nerve fibers in three distinct areas of the tarsus. Fifteen patients with ankle osteoarthritis (OA) and 15 patients with diabetic Charcot foot were included. Patients with OA did not differ from those with Charcot foot in SP+ sensory nerve fiber density. However, at all three areas, the density of sympathetic nerve fibers was significantly lower in patients with Charcot foot compared to OA (p = 0.006). In addition, we found that the sympathetic nerve repellent factor semaphorin 3C was highly expressed in inflamed tissue in Charcot patients. In Charcot foot of diabetic origin a severe loss of sympathetic nerve fibers was observed. These findings in chronically inflamed Charcot foot lend support to the neurovascular theory in the late chronic phase, which probably depends on the inflammatory upregulation of nerve repellent factors.

  13. Quantifying visual pathway axonal and myelin loss in multiple sclerosis and neuromyelitis optica.

    PubMed

    Manogaran, Praveena; Vavasour, Irene M; Lange, Alex P; Zhao, Yinshan; McMullen, Katrina; Rauscher, Alexander; Carruthers, Robert; Li, David K B; Traboulsee, Anthony L; Kolind, Shannon H

    2016-01-01

    The optic nerve is frequently injured in multiple sclerosis and neuromyelitis optica, resulting in visual dysfunction, which may be reflected by measures distant from the site of injury. To determine how retinal nerve fiber layer as a measure of axonal health, and macular volume as a measure of neuronal health are related to changes in myelin water fraction in the optic radiations of multiple sclerosis and neuromyelitis optica participants with and without optic neuritis and compared to healthy controls. 12 healthy controls, 42 multiple sclerosis (16 with optic neuritis), and 10 neuromyelitis optica participants (8 with optic neuritis) were included in this study. Optical coherence tomography assessment involved measurements of the segmented macular layers (total macular, ganglion cell layer, inner plexiform layer, and inner nuclear layer volume) and paripapillary retinal nerve fiber layer thickness. The MRI protocol included a 32-echo T2-relaxation GRASE sequence. Average myelin water fraction values were calculated within the optic radiations as a measure of myelin density. Multiple sclerosis and neuromyelitis optica eyes with optic neuritis history had lower retinal nerve fiber layer thickness, total macular, ganglion cell and inner plexiform layer volumes compared to eyes without optic neuritis history and controls. Inner nuclear layer volume increased in multiple sclerosis with optic neuritis history (mean = 0.99 mm(3), SD = 0.06) compared to those without (mean = 0.97 mm(3), SD = 0.06; p = 0.003). Mean myelin water fraction in the optic radiations was significantly lower in demyelinating diseases (neuromyelitis optica: mean = 0.098, SD = 0.01, multiple sclerosis with optic neuritis history: mean = 0.096, SD = 0.01, multiple sclerosis without optic neuritis history: mean = 0.098, SD = 0.02; F3,55 = 3.35, p = 0.03) compared to controls. Positive correlations between MRI and optical coherence tomography measures were also apparent

  14. Sensory and sympathetic nerve fibers undergo sprouting and neuroma formation in the painful arthritic joint of geriatric mice

    PubMed Central

    2012-01-01

    Introduction Although the prevalence of arthritis dramatically increases with age, the great majority of preclinical studies concerning the mechanisms that drive arthritic joint pain have been performed in young animals. One mechanism hypothesized to contribute to arthritic pain is ectopic nerve sprouting; however, neuroplasticity is generally thought to be greater in young versus old nerves. Here we explore whether sensory and sympathetic nerve fibers can undergo a significant ectopic nerve remodeling in the painful arthritic knee joint of geriatric mice. Methods Vehicle (saline) or complete Freund's adjuvant (CFA) was injected into the knee joint of 27- to 29-month-old female mice. Pain behaviors, macrophage infiltration, neovascularization, and the sprouting of sensory and sympathetic nerve fibers were then assessed 28 days later, when significant knee-joint pain was present. Knee joints were processed for immunohistochemistry by using antibodies raised against CD68 (monocytes/macrophages), PECAM (endothelial cells), calcitonin gene-related peptide (CGRP; sensory nerve fibers), neurofilament 200 kDa (NF200; sensory nerve fibers), tyrosine hydroxylase (TH; sympathetic nerve fibers), and growth-associated protein 43 (GAP43; nerve fibers undergoing sprouting). Results At 4 weeks after initial injection, CFA-injected mice displayed robust pain-related behaviors (which included flinching, guarding, impaired limb use, and reduced weight bearing), whereas animals injected with vehicle alone displayed no significant pain-related behaviors. Similarly, in the CFA-injected knee joint, but not in the vehicle-injected knee joint, a remarkable increase was noted in the number of CD68+ macrophages, density of PECAM+ blood vessels, and density and formation of neuroma-like structures by CGRP+, NF200+, and TH+ nerve fibers in the synovium and periosteum. Conclusions Sensory and sympathetic nerve fibers that innervate the aged knee joint clearly maintain the capacity for robust

  15. High-resolution measurement of electrically-evoked vagus nerve activity in the anesthetized dog

    NASA Astrophysics Data System (ADS)

    Yoo, Paul B.; Lubock, Nathan B.; Hincapie, Juan G.; Ruble, Stephen B.; Hamann, Jason J.; Grill, Warren M.

    2013-04-01

    Objective. Not fully understanding the type of axons activated during vagus nerve stimulation (VNS) is one of several factors that limit the clinical efficacy of VNS therapies. The main goal of this study was to characterize the electrical recruitment of both myelinated and unmyelinated fibers within the cervical vagus nerve. Approach. In anesthetized dogs, recording nerve cuff electrodes were implanted on the vagus nerve following surgical excision of the epineurium. Both the vagal electroneurogram (ENG) and laryngeal muscle activity were recorded in response to stimulation of the right vagus nerve. Main results. Desheathing the nerve significantly increased the signal-to-noise ratio of the ENG by 1.2 to 9.9 dB, depending on the nerve fiber type. Repeated VNS following nerve transection or neuromuscular block (1) enabled the characterization of A-fibers, two sub-types of B-fibers, and unmyelinated C-fibers, (2) confirmed the absence of stimulation-evoked reflex compound nerve action potentials in both the ipsilateral and contralateral vagus nerves, and (3) provided evidence of stimulus spillover into muscle tissue surrounding the stimulating electrode. Significance. Given the anatomical similarities between the canine and human vagus nerves, the results of this study provide a template for better understanding the nerve fiber recruitment patterns associated with VNS therapies.

  16. Small fiber dysfunction predominates in Fabry neuropathy.

    PubMed

    Dütsch, M; Marthol, H; Stemper, B; Brys, M; Haendl, T; Hilz, M J

    2002-12-01

    Fabry disease is an X-linked recessive disease with a reduction of lysosomal alpha galactosidase A and consecutive storage of glycolipids e.g., in the brain, kidney, skin, and nerve fibers. Cardinal neurologic findings are hypohidrosis, painful episodes, and peripheral neuropathy. So far, the neurophysiological findings regarding the extent of large and small fiber dysfunction are contradictory. This study evaluated large and small nerve fiber function in a homogeneous group of Fabry patients. In 24 of 30 Fabry patients with creatinine below 194.7 mmol/L the authors assessed median, ulnar, and peroneal motor conduction velocity (MCV) and median, ulnar, and sural sensory conduction velocity (SCV) nerve conduction to study the function of thickly myelinated nerve fibers. In addition, the authors studied sympathetic skin responses (SSR) at both hands and feet in 24 patients. To evaluate A beta nerve fiber function, the authors determined vibratory detection thresholds (VDT) at the first toe in 30 patients. Function of A delta and C fibers was assessed by quantitative sensory testing of cold detection threshold (CDT) and heat-pain detection thresholds (HPDT). Nerve conduction studies showed significantly decreased amplitudes of MCVs and SCVs in Fabry patients as compared to controls. However, individual results of MCV and SCV studies were only mildly impaired. SSRs were present in all tested patients but SSR amplitudes were significantly decreased in Fabry patients in comparison to controls. VDT, CDT, and HPDT were significantly elevated in Fabry patients as compared to controls. However, only six patients had pathologic VDT, 19 had increased CDT, and 25 had elevated HPDT at a high level of stimulation. In Fabry patients, small fiber dysfunction is more prominent than large fiber dysfunction, confirming previous findings of sural nerve biopsies. The results suggest a higher vulnerability of small-diameter nerve fibers than of the thickly myelinated fibers.

  17. Automatic identification and quantitative morphometry of unstained spinal nerve using molecular hyperspectral imaging technology.

    PubMed

    Li, Qingli; Chen, Zenggan; He, Xiaofu; Wang, Yiting; Liu, Hongying; Xu, Qintong

    2012-12-01

    Quantitative observation of nerve fiber sections is often complemented by morphological analysis in both research and clinical condition. However, existing manual or semi-automated methods are tedious and labour intensive, fully automated morphometry methods are complicated as the information of color or gray images captured by traditional microscopy is limited. Moreover, most of the methods are time-consuming as the nerve sections need to be stained with some reagents before observation. To overcome these shortcomings, a molecular hyperspectral imaging system is developed and used to observe the spinal nerve sections. The molecular hyperspectral images contain both the structural and biochemical information of spinal nerve sections which is very useful for automatic identification and quantitative morphological analysis of nerve fibers. This characteristic makes it possible for researchers to observe the unstained spinal nerve and live cells in their native environment. To evaluate the performance of the new method, the molecular hyperspectral images were captured and the improved spectral angle mapper algorithm was proposed and used to segment the myelin contours. Then the morphological parameters such as myelin thickness and myelin area were calculated and evaluated. With these morphological parameters, the three dimension surface view images were drawn to help the investigators observe spinal nerve at different angles. The experiment results show that the hyperspectral based method has the potential to identify the spinal nerve more accurate than the traditional method as the new method contains both the spectral and spatial information of nerve sections.

  18. Increased severity of inflammation correlates with elevated expression of TRPV1 nerve fibers and nerve growth factor on interstitial cystitis/bladder pain syndrome.

    PubMed

    Liu, Bo-long; Yang, Fei; Zhan, Hai-lun; Feng, Zhi-ying; Zhang, Zhi-gang; Li, Wen-biao; Zhou, Xiang-fu

    2014-01-01

    Although evidence supports a role for inflammation in interstitial cystitis/bladder pain syndrome (IC/BPS), the mechanism remains unknown. We determined whether inflammation causes an elevated expression of nerve growth factor (NGF) and transient receptor potential vanilloid receptor subtype 1 (TRPV1) and correlated them with the symptoms. Bladder biopsies were obtained from 53 IC/BPS patients and 27 controls, and hematoxylin and eosin staining, immunostaining and Western blotting were performed to detect inflammation, TRPV1-immunoreactive and PGP9.5-immunoreactive nerve fibers, and NGF, respectively. Symptoms were assessed using the Pelvic Pain/Urgency/Frequency (PUF) questionnaire and pain visual analogue scale scores. Suburothelial nerve fiber density was quantified and correlated with PUF scores. Increased severity of inflammation was correlated with a higher TRPV1-immunoreactive nerve fiber density (r = 0.4113, p = 0.0024) and higher NGF levels (r = 0.3775, p = 0.0052). Suburothelial TRPV1-immunoreactive nerve fiber density was significantly correlated with pain scores and urgency scores (r = 0.3320, p = 0.0145 and r = 0.3823, p = 0.0039, respectively). PGP9.5-immunoreactive nerve fibers were significantly increased in IC/BPS (p = 0.0193) and had a positive relationship with inflammation severity (r = 0.6138, p < 0.0001). Our study revealed increased severity of inflammation correlated with a higher expression of TRPV1-immunoreactive nerve fibers and NGF in IC/BPS and correlated with clinical symptoms. 2014 S. Karger AG, Basel.

  19. The histology of retinal nerve fiber layer bundles and bundle defects.

    PubMed

    Radius, R L; Anderson, D R

    1979-05-01

    The fiber bundle striations recognized clinically in normal monkey eyes appear to be bundles of axons compartmentalized within glial tunnels formed by Müller's-cell processes, when viewed histologically. The dark boundaries that separate individual bundles are the broadened foot endings of these cells near the inner surface of the retina. Within one week after focal retinal photocoagulation, characteristic fundus changes could be seen in experimental eyes. In histologic sections of the involved retina, there was marked cystic degeneration of the retinal nerve fiber layer. Within one month, atrophy of distal axon segments was complete. With the drop-out of damaged axons and thinning of individual fiber bundles, retinal striations became less prominent. The resulting fundus picture in these experimental eyes is similar to fiber bundle defects that can be seen clinically in various neuro-ophthalmic disorders.

  20. Intraepidermal free nerve fiber endings in the hairless skin of the rat as revealed by the zinc iodide-osmium tetroxide technique.

    PubMed

    Müller, T

    2000-04-01

    The nerve fiber distribution in the epidermis of the hairless rat skin was studied light microscopically by means of zinc iodide-osmium tetroxide staining. Two different morphological types of free nerve fiber endings could be detected: clusters of relatively thick nerve fibers stretched up through the spinous layer up to the granular layer sending off terminal branches. In addition, many solitary thin varicose nerve fibers were seen within the epidermis. The observed discrepancies in nerve fiber diameters appeared to be larger than those reported for human intraepidermal nerve fibers in recent immunohistochemical studies. Moreover, dendritic cells, most probably representing Langerhans cells, could be selectively stained. These cells appeared to be in a close location to thin varicose nerve fibers. Both types of demonstrated free nerve endings have to be functionally connected with different sensoric functions. Possibly, a subpopulation of the thin nerve fibers might possess primarily a nociceptive task, whereas the thick ones have most probably to be regarded as mechanoreceptive. The nerve fibers innervating dendritic cells appear to be identical to the peptidergic ones which may regulate the antigen-presenting capacity of these cells. Due to its selectivity for intraepidermal nerve fibers, the used method might supplement immunohistochemical procedures in a helpful manner.

  1. Innervation of TRPV1-, PGP-, and CGRP-immunoreactive nerve fibers in the subepithelial layer of a whole mount preparation of the rat cornea.

    PubMed

    Hiura, Akio; Nakagawa, Hiroshi

    2012-01-01

    The pattern of innervation of capsaicin receptor, TRPV1-(transient receptor protein vanilloid 1), PGP 9.5-(protein gene product, a marker of peripheral nerve fibers)-, and CGRP (calcitonin gene-related peptide)-immunoreactive (IR) nerve fibers was examined by immunohistological staining of whole mount preparations of the adult rat cornea. The outer corneoscleral limbus toward the central cornea in the subepithelial (stromal) layer was richly innervated by a meshwork of PGP- and CGRP-IR nerve fibers. Sparse innervation was observed in the central cornea, presumably owing to insufficient staining. Dense innervation of TRPV1-IR nerve fibers were demonstrated in addition to innervation of PGP- and CGRP-IR nerve fibers, running from the corneoscleral margin to the central cornea. Although the density of TRPV1-IR nerve fibers appeared to gradually diminish, immunostaining of TRPV1-IR nerve fibers was not as clear as that of PGP- and CGRP-IR nerve fibers. The TRPV1-IR nerve fibers appeared to be thinner than the PGP- and CGRP-IR nerve fibers. The TRPV1-IR leash fibers were observed in the basal epithelial layer, presumably ensuring effective corneal reflex, response to noxious stimuli, and repair of cornea injury.

  2. The cutaneous nerve biopsy: technical aspects, indications, and contribution.

    PubMed

    Mellgren, Svein Ivar; Nolano, Maria; Sommer, Claudia

    2013-01-01

    Skin biopsy with a 3mm disposable circular punch is easy to perform and allows, after proper processing, the visualization of epidermal, dermal, and sweat gland nerve fibers. A technique of sampling the epidermis alone by applying a suction capsule, the "blister" technique, has also been developed. It is most common to stain immunohistochemically for the pan-axonal marker protein gene product 9.5 (PGP 9.5), an ubiquitin C-terminal hydroxylase. The sections are then observed and analyzed with bright-field microscopy or with indirect immunofluorescence with or without confocal microscopy. Most studies report quantification of intraepidermal nerve fiber density displayed in bright-field microscopy. Normative values have been established, particularly from the distal part of the leg, 10cm above the external malleolus. In diabetes mellitus early degeneration of intraepidermal nerve fibers is induced and there is slower regeneration even when there is no evidence of neuropathy. Skin biopsy is of particular value in the diagnosis of small fiber neuropathy when nerve conduction studies are normal. It may also be repeated in order to study the progressive nature of the disease and also has the potential of studying regeneration of nerve fibers and thus the effects of treatment. Inflammatory demyelinating neuropathies may also involve loss of small-diameter nerve fibers and IgM deposits in dermal myelinated nerve fibers in anti-MAG neuropathy. In some cases the presence of vasculitis in skin may indicate a nonsystemic vasculitic neuropathy and in HIV neuropathy intraepidermal nerve fiber density is reduced in a length-dependent manner. In several hereditary neuropathies intraepidermal nerve fiber density may be reduced but other abnormalities can also be demonstrated in dermal myelinated fibers. Some small swellings and varicosities may be present in the distal leg skin biopsy of healthy individuals but large axonal swellings are considered as evidence of a pathological

  3. Anisotropy in the preferred directions and visual field location of directionally-selective optic nerve fibers in the gray squirrel.

    PubMed

    Blakeslee, B; Jacobs, G H; McCourt, M E

    1985-01-01

    Directionally-selective optic nerve fibers in the gray squirrel possess an anisotropic distribution of preferred direction. Similar to the directional anisotropy seen in ground squirrel, the possible role of these units is discussed.

  4. Atrophic nerve fibers in regions of reduced MIBG uptake in doxorubicin cardiomyopathy

    SciTech Connect

    Takano, Hajime; Ozawa Hideyuki; Kobayashi, Isao

    1995-11-01

    A myocardial MIBG-SPECT examination was conducted 2 wk after doxorubicin chemotherapy on a 52-yr-old woman without cardiac symptoms. Despite normal {sup 201}Tl scintigraphy, reduced MIBG uptake was detected in the apical anterior, inferior and lateral segments of the left ventricle. The patient died of congestive heart failure due to doxorubicin-induced cardiomyopathy 10 mo later. At necropsy, the left ventricle was markedly dilated and the apical anterior, inferior and lateral walls were thin, stiff and whitish. Nerve fibers in the apical inferior wall were atrophic and markedly fibrotic where MIBG uptake was most reduced. Nerve fibers in the septum were normal where MIBG uptake had remained normal. The histologic findings correspond with the findings on the MIBG image. MIBG imaging may detect cardiac sympathetic denervation in doxorubicin-induced cardiomyopathy before cardiac symptoms are manifest and cardiac function deteriorates. 5 refs., 2 figs.

  5. Simultaneous degeneration of myenteric plexuses and pelvic parasympathetic colonic nerve in slow transit constipation

    PubMed Central

    Cheng, Zhiqiang; Zhao, Kun; Bi, Dongsong

    2017-01-01

    Abstract Rationale: Slow transit constipation (STC) is a common disease of which the etiology is still not clear. Multiple hypotheses have been proposed to explain STC, including autonomic neuropathy, disorders of the enteric nervous system and so forth. Morphological abnormalities of the enteric nerves of the colon in patients with STC have been extensively reported, while there have been no morphological reports focusing on extrinsic extramural fibers from the pelvic plexus to the distal colon (i.e., pelvic parasympathetic colonic nerve) in patients with STC. Patient concerns: Whether morphological changes of pelvic parasympathetic colonic nerve coexist with abnormalities of the enteric nerves of the colon in the patient with STC. Diagnosis: Slow transit constipation (STC). Interventions: The patient with STC underwent a partial colectomy (sigmoid colon and partial descending colon). The fibers of the myenteric plexuses within the removed colon and the myelinated fibers of the pelvic parasympathetic colonic nerve were observed under optical and electron-microscope. Outcomes: The fibers of the myenteric plexuses showed vacuolated degeneration between the muscularis propria layer under optical microscope. Myelinated fibers of the pelvic parasympathetic colonic nerve showed obvious vacuolated degeneration under electron-microscopic examination. Lessons: Such a simultaneous neuropathy in both myenteric plexuses and extrinsic extramural nerves has not been documented previously. Our finding supports the notion that neuropathy remains the most plausible explanation for STC, in which nerve dysfunction might occur by way of a degenerative process. PMID:28296784

  6. Predominance of synovial sensory nerve fibers in arthrofibrosis following total knee arthroplasty compared to osteoarthritis of the knee.

    PubMed

    Koeck, Franz Xaver; Schmitt, Miriam; Baier, Clemens; Stangl, Hubert; Beckmann, Johannes; Grifka, Joachim; Straub, Rainer H

    2016-02-17

    So far, there exists no golden standard for the treatment of arthrofibrosis (AF) following total knee arthroplasty (TKA). Although pain is a hallmark of AF, nociceptive nerve fibers have never been investigated in affected joint tissue. A total of 24 patients with osteoarthritis (OA) of the knee (n = 12) and post-TKA AF of the knee (n = 12) were included. Along evaluation of typical clinical signs and symptoms by using the Knee Society Clinical Rating System (KSS), the Knee Injury and Osteoarthritis Outcome Score (KOOS), and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC index), the innervation of joint tissue was studied by semiquantitative immunofluorescence of nerve fibers. Patients with AF compared to OA had a lower KSS and lower KOOS. In all compartments (anterior, medial, and lateral recesses), the density of synovial sympathetic nerve fibers was significantly higher in OA compared to AF, which was also true for the density of sensory nerve fibers in the medial and lateral recesses. In synovial tissue of the anterior recess of patients with AF compared to OA, the density of nociceptive sensory nerve fibers was significantly higher relative to sympathetic nerve fibers. This was similarly observed in the neighboring infrapatellar fat pad of the knee. Similar as in many painful musculoskeletal diseases, this study indicates that patients with arthrofibrosis of the knee after TKA demonstrate a preponderance of profibrotic sensory nerve fibers over antifibrotic sympathetic nerve fibers. This could serve as a starting point for AF therapy with specific antifibrotic pain medication or regional anesthetic techniques.

  7. Changes of the different neuropeptide-containing nerve fibers and immunocells in the diabetic rat's alimentary tract.

    PubMed

    Fehér, Erzsébet; Batbayar, Bayarchimeg; Vér, Agota; Zelles, Tivadar

    2006-11-01

    Peripheral neuropathy is a common complication of diabetes mellitus, where neuropeptides and immunocells might play important roles in the pathogenesis of the disease. In this article we have quantified the different neuropeptide-containing nerve fibers and immunocells in the streptozotocin-induced diabetic rat's alimentary tract (tongue, duodenum, colon) using immunohistochemical and immunocytochemical methods. The immunoreactive (IR) nerve fibers were found in all layers of the alimentary tract and their distribution pattern was similar in both control and diabetic groups. Mast cell-nerve fiber contacts were rarely found in the controls. However, after 4 weeks duration of diabetes the number of IR nerve fibers and the immunocompetent cells increased significantly (P < 0.05), and the number of mast cell-nerve fiber contacts was even more significantly increased (P < 0.001). The distance between nerve fibers and immunocells was about 1 mum or even less. Some of the mast cells were degranulated in the vicinity of nerve fibers. No immunocompetent cells were IR for any antisera in the control. However, after the streptozotocin treatment, a large number of the immunocompetent cells showed immunoreactivity for SP and NPY. Counting all immunocompetent cells in whole sections showed that 12.3% of them were IR for SP and 25.4% were IR for NPY. Increased number of SP-containing nerve fibers and immunocells in diabetes mellitus might be the reason for painful neuropathy and might amplify the inflammatory reaction in an axon reflex manner; the released histamine and leukotrienes, cytokines, and chemokines might cause inflammations and lesions of the mucosa.

  8. AXOPLASMIC PROTEINS OF THE SQUID GIANT NERVE FIBER WITH PARTICULAR REFERENCE TO THE FIBROUS PROTEIN

    PubMed Central

    Maxfield, Myles

    1953-01-01

    1. Axoplasm of squid giant nerve fibers is examined with the ultracentrifuge and electrophoresis apparatus and several distinct components demonstrated. 2. One of these components, a protein called axon filaments, is isolated by fractional extraction followed by differential ultracentrifugation and redissolving in glycine solution. Axon filaments are monodisperse by ultracentrifugation. Their physical chemical properties have been studied. 3. The existence of a reversible transformation of axon filaments into a particle of lower molecular weight and lower asymmetry has been demonstrated. PMID:13109156

  9. Nerve fiber outgrowth is increased in the intestinal mucosa of patients with irritable bowel syndrome.

    PubMed

    Dothel, Giovanni; Barbaro, Maria Raffaella; Boudin, Hélène; Vasina, Valentina; Cremon, Cesare; Gargano, Luciana; Bellacosa, Lara; De Giorgio, Roberto; Le Berre-Scoul, Catherine; Aubert, Philippe; Neunlist, Michel; De Ponti, Fabrizio; Stanghellini, Vincenzo; Barbara, Giovanni

    2015-05-01

    Mediators released by the intestinal mucosa of patients with irritable bowel syndrome (IBS) affect the function of enteric and extrinsic sensory nerves, which can contribute to the development of symptoms. Little is known about the effects of mucosal mediators on intestinal neuroplasticity. We investigated how these mediators affect the phenotypes of colonic mucosa nerve fibers, neuron differentiation, and fiber outgrowth. We analyzed mucosal biopsy samples collected from 101 patients with IBS and 23 asymptomatic healthy individuals (controls). We measured levels of neuronal-specific enolase, growth-associated protein 43, nerve growth factor (NGF), and tyrosine kinase receptor A (NTRK1) by immunohistochemistry and enzyme-linked immunosorbent assay. Primary rat enteric neurons and human SH-SY5Y cells were incubated with supernatants from the mucosal biopsies and analyzed by morphometric and polymerase chain reaction analyses. Compared with mucosal tissues of controls, mucosa from patients with IBS had a significant increase in the area of lamina propria occupied by neuronal-specific enolase-positive (57.7% increase) and growth-associated protein 43-positive fibers (56.1% increase) and staining density of NGF (89.3% increase) (P < .05 for all). Levels of NGF protein were also increased in tissues from patients with IBS vs controls (18% increase; P = .16) along with levels of NTRK1 (64% increase; P < .05). Mucosal supernatants from tissues of patients with IBS induced higher levels of neuritogenesis in primary culture of enteric neurons, compared with controls, and more NGF-dependent neuronal sprouting in SH-SY5Y cells. Nerve fiber density and sprouting, as well as expression of NGF and NTRK1, are significantly increased in mucosal tissues of patients with IBS. Mucosal mediators participate to these neuroplastic changes. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

  10. Normal axonal ion channel function in large peripheral nerve fibers following chronic ciguatera sensitization.

    PubMed

    Vucic, Steve; Kiernan, Matthew C

    2008-03-01

    Although the acute clinical effects of ciguatera poisoning, due to ingestion of ciguatoxin, are mediated by activation of transient Na+ channels, the mechanisms underlying ciguatera sensitization remain undefined. Axonal excitability studies were performed by stimulating the median motor and sensory nerves in two patients with ciguatera sensitization. Excitability parameters were all within normal limits, thereby arguing against dysfunction of axonal membrane ion channels in large-diameter fibers in ciguatera sensitization.

  11. Biodegradable magnesium wire promotes regeneration of compressed sciatic nerves.

    PubMed

    Li, Bo-Han; Yang, Ke; Wang, Xiao

    2016-12-01

    Magnesium (Mg) wire has been shown to be biodegradable and have anti-inflammatory properties. It can induce Schwann cells to secrete nerve growth factor and promote the regeneration of nerve axons after central nervous system injury. We hypothesized that biodegradable Mg wire may enhance compressed peripheral nerve regeneration. A rat acute sciatic nerve compression model was made, and AZ31 Mg wire (3 mm diameter; 8 mm length) bridged at both ends of the nerve. Our results demonstrate that sciatic functional index, nerve growth factor, p75 neurotrophin receptor, and tyrosine receptor kinase A mRNA expression are increased by Mg wire in Mg model. The numbers of cross section nerve fibers and regenerating axons were also increased. Sciatic nerve function was improved and the myelinated axon number was increased in injured sciatic nerve following Mg treatment. Immunofluorescence histopathology showed that there were increased vigorous axonal regeneration and myelin sheath coverage in injured sciatic nerve after Mg treatment. Our findings confirm that biodegradable Mg wire can promote the regeneration of acute compressed sciatic nerves.

  12. Biodegradable magnesium wire promotes regeneration of compressed sciatic nerves

    PubMed Central

    Li, Bo-han; Yang, Ke; Wang, Xiao

    2016-01-01

    Magnesium (Mg) wire has been shown to be biodegradable and have anti-inflammatory properties. It can induce Schwann cells to secrete nerve growth factor and promote the regeneration of nerve axons after central nervous system injury. We hypothesized that biodegradable Mg wire may enhance compressed peripheral nerve regeneration. A rat acute sciatic nerve compression model was made, and AZ31 Mg wire (3 mm diameter; 8 mm length) bridged at both ends of the nerve. Our results demonstrate that sciatic functional index, nerve growth factor, p75 neurotrophin receptor, and tyrosine receptor kinase A mRNA expression are increased by Mg wire in Mg model. The numbers of cross section nerve fibers and regenerating axons were also increased. Sciatic nerve function was improved and the myelinated axon number was increased in injured sciatic nerve following Mg treatment. Immunofluorescence histopathology showed that there were increased vigorous axonal regeneration and myelin sheath coverage in injured sciatic nerve after Mg treatment. Our findings confirm that biodegradable Mg wire can promote the regeneration of acute compressed sciatic nerves. PMID:28197200

  13. The "Lillie transition": models of the onset of saltatory conduction in myelinating axons.

    PubMed

    Young, Robert G; Castelfranco, Ann M; Hartline, Daniel K

    2013-06-01

    Almost 90 years ago, Lillie reported that rapid saltatory conduction arose in an iron wire model of nerve impulse propagation when he covered the wire with insulating sections of glass tubing equivalent to myelinated internodes. This led to his suggestion of a similar mechanism explaining rapid conduction in myelinated nerve. In both their evolution and their development, myelinating axons must make a similar transition between continuous and saltatory conduction. Achieving a smooth transition is a potential challenge that we examined in computer models simulating a segmented insulating sheath surrounding an axon having Hodgkin-Huxley squid parameters. With a wide gap under the sheath, conduction was continuous. As the gap was reduced, conduction initially slowed, owing to the increased extra-axonal resistance, then increased (the "rise") up to several times that of the unmyelinated fiber, as saltatory conduction set in. The conduction velocity slowdown was little affected by the number of myelin layers or modest changes in the size of the "node," but strongly affected by the size of the "internode" and axon diameter. The steepness of the rise of rapid conduction was greatly affected by the number of myelin layers and axon diameter, variably affected by internode length and little affected by node length. The transition to saltatory conduction occurred at surprisingly wide gaps and the improvement in conduction speed persisted to surprisingly small gaps. The study demonstrates that the specialized paranodal seals between myelin and axon, and indeed even the clustering of sodium channels at the nodes, are not necessary for saltatory conduction.

  14. [Electroacupuncture promotes the regeneration of different fibers in rat's tibial nerve].

    PubMed

    Kong, T; Fan, T; Han, X; Guo, Z; Lei, L; Zang, J

    1993-01-01

    45 rats (150-200g) were divided into 9 groups. The experimental steps as follows: (1) injured left tibial nerve (group 1-8) and sham operation (group 9); (2) three days after operation, group 1, 3, 5 and 7 were stimulated with electro-acupuncture (EA) in Huantiao (+) and Sanyinjiao (-); (3) according to different survival time (group 1, 2/10 days, group 3, 4/15 days, group 5, 6/20 days, group 7, 8, 9/25 days), 48h before sacrifice, the left femoral nerve was cut, HRP was injected into the hypodermis of paw pad and gastrocnemius; (4) observe HRP labelled cells in the lumber sympathetic ganglia, ganglion spinale (L4-6) and cornu ventrale of spinal cord (L3-S3). EA 7 days, 2-5 labeled cells were only found in ganglion spinales of group 1; EA for 12 days, the more HRP labeled cells were observed in the lumber sympathetic ganglions (mean = 2.6), ganglion spinales (mean = 4.8) and cornu ventrale (mean = 6) of group 3 as compared with group 4 (P < 0.05); 25 days after operation, the quantity of labeled cells in group 8 was close to group 9. (1) EA promote the regeneration of three or more kinds of fibers in tibial nerve; (2) The regeneration velocity of sensory fibers was faster than sympathetic and somatic efferent fibers.

  15. Latency of auditory evoked potential monitoring the effects of general anesthetics on nerve fibers and synapses.

    PubMed

    Huang, Bowan; Liang, Feixue; Zhong, Lei; Lin, Minlin; Yang, Juan; Yan, Linqing; Xiao, Jinfan; Xiao, Zhongju

    2015-08-06

    Auditory evoked potential (AEP) is an effective index for the effects of general anesthetics. However, it's unknown if AEP can differentiate the effects of general anesthetics on nerve fibers and synapses. Presently, we investigated AEP latency and amplitude changes to different acoustic intensities during pentobarbital anesthesia. Latency more regularly changed than amplitude during anesthesia. AEP Latency monotonically decreased with acoustic intensity increase (i.e., latency-intensity curve) and could be fitted to an exponential decay equation, which showed two components, the theoretical minimum latency and stimulus-dependent delay. From the latency-intensity curves, the changes of these two components (∆L and ∆I) were extracted during anesthesia. ∆L and ∆I monitored the effect of pentobarbital on nerve fibers and synapses. Pentobarbital can induce anesthesia, and two side effects, hypoxemia and hypothermia. The hypoxemia was not related with ∆L and ∆I. However, ∆L was changed by the hypothermia, whereas ∆I was changed by the hypothermia and anesthesia. Therefore, we conclude that, AEP latency is superior to amplitude for the effects of general anesthetics, ∆L monitors the effect of hypothermia on nerve fibers, and ∆I monitors a combined effect of anesthesia and hypothermia on synapses. When eliminating the temperature factor, ∆I monitors the anesthesia effect on synapses.

  16. Timing of cochlear responses inferred from frequency-threshold tuning curves of auditory-nerve fibers

    PubMed Central

    Temchin, Andrei N.; Recio-Spinoso, Alberto; Ruggero, Mario A.

    2010-01-01

    Links between frequency tuning and timing were explored in the responses to sound of auditory-nerve fibers. Synthetic transfer functions were constructed by combining filter functions, derived via minimum-phase computations from average frequency-threshold tuning curves of chinchilla auditory-nerve fibers with high spontaneous activity (A. N. Temchin et al., J. Neurophysiol. 100: 2889–2898, 2008), and signal-front delays specified by the latencies of basilar-membrane and auditory-nerve fiber responses to intense clicks (A. N. Temchin et al., J. Neurophysiol. 93: 3635–3648, 2005). The transfer functions predict several features of the phase-frequency curves of cochlear responses to tones, including their shape transitions in the regions with characteristic frequencies of 1 kHz and 3–4 kHz (A. N. Temchin and M. A. Ruggero, JARO 11: 297–318, 2010). The transfer functions also predict the shapes of cochlear impulse responses, including the polarities of their frequency sweeps and their transition at characteristic frequencies around 1 kHz. Predictions are especially accurate for characteristic frequencies < 1 kHz. PMID:20951191

  17. Effects of acoustic trauma on the representation of the vowel "eh" in cat auditory nerve fibers.

    PubMed

    Miller, R L; Schilling, J R; Franck, K R; Young, E D

    1997-06-01

    A population study of cat auditory-nerve fibers was used to characterize the permanent deficits induced by exposure to 110-115 dB SPL, narrow-band noise. Fibers in the region of acoustic trauma (roughly 1-6 kHz) showed a loss of sensitivity at best frequency (BF) of about 50-60 dB and an increased tuning bandwidth. A correlation between weakened two-tone suppression and loss of sensitivity was found for fibers with BFs above 1 kHz. Single-fiber responses to the vowel "eh" were recorded at intensities ranging from near threshold to a maximum of about 110 dB SPL. In normal cochleas, the temporal response patterns show a capture phenomenon, in which the first two formant frequencies dominate the responses at high sound levels among fibers with BFs near the formant frequencies. After acoustic trauma, fibers in the region of threshold shift synchronized to a broad range of the vowel's harmonics and thus did not show capture by the second formant at any sound level used. The broadband nature of this response is consistent with the broadened tuning observed in the damaged fibers, but may also reflect a weakening of compressive nonlinearities responsible for synchrony capture in the normal cochlea.

  18. The human trochlear and abducens nerves at different ages - a morphometric study.

    PubMed

    Ramkumar, Muthu; Sharma, Saroj; Jacob, Tony G; Bhardwaj, Daya N; Nag, Tapas C; Roy, Tara Sankar

    2015-02-01

    The trochlear and abducens nerves (TN and AN) control the movement of the superior oblique and lateral rectus muscles of the eyeball, respectively. Despite their immense clinical and radiological importance no morphometric data was available from a wide spectrum of age groups for comparison with either pathological or other conditions involving these nerves. In the present study, morphometry of the TN and AN was performed on twenty post-mortem samples ranging from 12-90 years of age. The nerve samples were processed for resin embedding and toluidine blue stained thin (1µm) sections were used for estimating the total number of myelinated axons by fractionator and the cross sectional area of the nerve and the axons by point counting methods. We observed that the TN was covered by a well-defined epineurium and had ill-defined fascicles, whereas the AN had multiple fascicles with scanty epineurium. Both nerves contained myelinated and unmyelinated fibers of various sizes intermingled with each other. Out of the four age groups (12-20y, 21-40y, 41-60y and >61y) the younger groups revealed isolated bundles of small thinly myelinated axons. The total number of myelinated fibers in the TN and AN at various ages ranged from 1100-3000 and 1600-7000, respectively. There was no significant change in the cross-sectional area of the nerves or the axonal area of the myelinated nerves across the age groups. However, myelin thickness increased significantly in the AN with aging (one way ANOVA). The present study provides baseline morphometric data on the human TN and AN at various ages.

  19. A nanofibrous PHBV tube with Schwann cell as artificial nerve graft contributing to rat sciatic nerve regeneration across a 30-mm defect bridge.

    PubMed

    Biazar, Esmaeil; Heidari Keshel, Saeed

    2013-02-01

    A nanofibrous PHBV nerve conduit has been used to evaluate its efficiency based on the promotion of nerve regeneration in rats. The designed conduits were investigated by physical, mechanical and microscopic analyses. The conduits were implanted into a 30-mm gap in the sciatic nerves of the rats. Four months after surgery, the regenerated nerves were evaluated by macroscopic assessments and histology. This polymeric conduit had sufficiently high mechanical properties to serve as a nerve guide. The results demonstrated that in the nanofibrous graft with cells, the sciatic nerve trunk had been reconstructed with restoration of nerve continuity and formatted nerve fibers with myelination. For the grafts especially the nanofibrous conduits with cells, muscle cells of gastrocnemius on the operated side were uniform in their size and structures. This study proves the feasibility of artificial conduit with Schwann cells for nerve regeneration by bridging a longer defect in a rat model.

  20. Laminin 211 inhibits protein kinase A in Schwann cells to modulate neuregulin 1 type III-driven myelination

    PubMed Central

    Ghidinelli, Monica; Poitelon, Yannick; Shin, Yoon Kyoung; Ameroso, Dominique; Williamson, Courtney; Ferri, Cinzia; Pellegatta, Marta; Espino, Kevin; Mogha, Amit; Monk, Kelly; Podini, Paola; Taveggia, Carla; Nave, Klaus-Armin; Wrabetz, Lawrence; Park, Hwan Tae

    2017-01-01

    Myelin is required for proper nervous system function. Schwann cells in developing nerves depend on extrinsic signals from the axon and from the extracellular matrix to first sort and ensheathe a single axon and then myelinate it. Neuregulin 1 type III (Nrg1III) and laminin α2β1γ1 (Lm211) are the key axonal and matrix signals, respectively, but how their signaling is integrated and if each molecule controls both axonal sorting and myelination is unclear. Here, we use a series of epistasis experiments to show that Lm211 modulates neuregulin signaling to ensure the correct timing and amount of myelination. Lm211 can inhibit Nrg1III by limiting protein kinase A (PKA) activation, which is required to initiate myelination. We provide evidence that excessive PKA activation amplifies promyelinating signals downstream of neuregulin, including direct activation of the neuregulin receptor ErbB2 and its effector Grb2-Associated Binder-1 (Gab1), thereby elevating the expression of the key transcription factors Oct6 and early growth response protein 2 (Egr2). The inhibitory effect of Lm211 is seen only in fibers of small caliber. These data may explain why hereditary neuropathies associated with decreased laminin function are characterized by focally thick and redundant myelin. PMID:28636612

  1. Laminin 211 inhibits protein kinase A in Schwann cells to modulate neuregulin 1 type III-driven myelination.

    PubMed

    Ghidinelli, Monica; Poitelon, Yannick; Shin, Yoon Kyoung; Ameroso, Dominique; Williamson, Courtney; Ferri, Cinzia; Pellegatta, Marta; Espino, Kevin; Mogha, Amit; Monk, Kelly; Podini, Paola; Taveggia, Carla; Nave, Klaus-Armin; Wrabetz, Lawrence; Park, Hwan Tae; Feltri, Maria Laura

    2017-06-01

    Myelin is required for proper nervous system function. Schwann cells in developing nerves depend on extrinsic signals from the axon and from the extracellular matrix to first sort and ensheathe a single axon and then myelinate it. Neuregulin 1 type III (Nrg1III) and laminin α2β1γ1 (Lm211) are the key axonal and matrix signals, respectively, but how their signaling is integrated and if each molecule controls both axonal sorting and myelination is unclear. Here, we use a series of epistasis experiments to show that Lm211 modulates neuregulin signaling to ensure the correct timing and amount of myelination. Lm211 can inhibit Nrg1III by limiting protein kinase A (PKA) activation, which is required to initiate myelination. We provide evidence that excessive PKA activation amplifies promyelinating signals downstream of neuregulin, including direct activation of the neuregulin receptor ErbB2 and its effector Grb2-Associated Binder-1 (Gab1), thereby elevating the expression of the key transcription factors Oct6 and early growth response protein 2 (Egr2). The inhibitory effect of Lm211 is seen only in fibers of small caliber. These data may explain why hereditary neuropathies associated with decreased laminin function are characterized by focally thick and redundant myelin.

  2. Plasmalogen phospholipids protect internodal myelin from oxidative damage.

    PubMed

    Luoma, Adrienne M; Kuo, Fonghsu; Cakici, Ozgur; Crowther, Michelle N; Denninger, Andrew R; Avila, Robin L; Brites, Pedro; Kirschner, Daniel A

    2015-07-01

    Reactive oxygen species (ROS) are implicated in a range of degenerative conditions, including aging, neurodegenerative diseases, and neurological disorders. Myelin is a lipid-rich multilamellar sheath that facilitates rapid nerve conduction in vertebrates. Given the high energetic demands and low antioxidant capacity of the cells that elaborate the sheaths, myelin is considered intrinsically vulnerable to oxidative damage, raising the question whether additional mechanisms prevent structural damage. We characterized the structural and biochemical basis of ROS-mediated myelin damage in murine tissues from both central nervous system (CNS) and peripheral nervous system (PNS). To determine whether ROS can cause structural damage to the internodal myelin, whole sciatic and optic nerves were incubated ex vivo with a hydroxyl radical-generating system consisting of copper (Cu), hydrogen peroxide (HP), and ortho-phenanthroline (OP). Quantitative assessment of unfixed tissue by X-ray diffraction revealed irreversible compaction of myelin membrane stacking in both sciatic and optic nerves. Incubation in the presence of the hydroxyl radical scavenger sodium formate prevented this damage, implicating hydroxyl radical species. Myelin membranes are particularly enriched in plasmalogens, a class of ether-linked phospholipids proposed to have antioxidant properties. Myelin in sciatic nerve from plasmalogen-deficient (Pex7 knockout) mice was significantly more vulnerable to Cu/OP/HP-mediated ROS-induced compaction than myelin from WT mice. Our results directly support the role of plasmalogens as endogenous antioxidants providing a defense that protects ROS-vulnerable myelin. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Immunodominant fragments of myelin basic protein initiate T cell-dependent pain

    PubMed Central

    2012-01-01

    Background The myelin sheath provides electrical insulation of mechanosensory Aβ-afferent fibers. Myelin-degrading matrix metalloproteinases (MMPs) damage the myelin sheath. The resulting electrical instability of Aβ-fibers is believed to activate the nociceptive circuitry in Aβ-fibers and initiate pain from innocuous tactile stimulation (mechanical allodynia). The precise molecular mechanisms, responsible for the development of this neuropathic pain state after nerve injury (for example, chronic constriction injury, CCI), are not well understood. Methods and results Using mass spectrometry of the whole sciatic nerve proteome followed by bioinformatics analyses, we determined that the pathways, which are classified as the Infectious Disease and T-helper cell signaling, are readily activated in the nerves post-CCI. Inhibition of MMP-9/MMP-2 suppressed CCI-induced mechanical allodynia and concomitant TNF-α and IL-17A expression in nerves. MMP-9 proteolysis of myelin basic protein (MBP) generated the MBP84-104 and MBP68-86 digest peptides, which are prominent immunogenic epitopes. In agreement, the endogenous MBP69-86 epitope co-localized with MHCII and MMP-9 in Schwann cells and along the nodes of Ranvier. Administration of either the MBP84-104 or MBP68-86 peptides into the naïve nerve rapidly produced robust mechanical allodynia with a concomitant increase in T cells and MHCII-reactive cell populations at the injection site. As shown by the genome-wide expression profiling, a single intraneural MBP84-104 injection stimulated the inflammatory, immune cell trafficking, and antigen presentation pathways in the injected naïve nerves and the associated spinal cords. Both MBP84-104-induced mechanical allodynia and characteristic pathway activation were remarkably less prominent in the T cell-deficient athymic nude rats. Conclusions These data implicate MBP as a novel mediator of pain. Furthermore, the action of MMPs expressed within 1 day post-injury is critical

  4. Unmyelinated visceral afferents exhibit frequency dependent action potential broadening while myelinated visceral afferents do not.

    PubMed

    Li, Bai-Yan; Feng, Bin; Tsu, Hwa Y; Schild, John H

    2007-06-21

    Sensory information arising from visceral organ systems is encoded into action potential trains that propagate along afferent fibers to target nuclei in the central nervous system. These information streams range from tight patterns of action potentials that are well synchronized with the sensory transduction event to irregular, patternless discharge with no clear correlation to the sensory input. In general terms these afferent pathways can be divided into unmyelinated and myelinated fiber types. Our laboratory has a long standing interest in the functional differences between these two types of afferents in terms of the preprocessing of sensory information into action potential trains (synchrony, frequency, duration, etc.), the reflexogenic consequences of this sensory input to the central nervous system and the ionic channels that give rise to the electrophysiological properties of these unique cell types. The aim of this study was to determine whether there were any functional differences in the somatic action potential characteristics of unmyelinated and myelinated vagal afferents in response to different rates of sensory nerve stimulation. Our results showed that activity and frequency-dependent widening of the somatic action potential was quite prominent in unmyelinated but not myelinated vagal afferents. Spike broadening often leads to increased influx of Ca(2+) ions that has been associated with a diverse range of modulatory mechanisms both at the cell body and central synaptic terminations (e.g. increased neurotransmitter release.) We conclude that our observations are indicative of fundamentally different mechanisms for neural integration of sensory information arising from unmyelinated and myelinated vagal afferents.

  5. A voltage-controlled capacitive discharge method for electrical activation of peripheral nerves.

    PubMed

    Rosellini, Will M; Yoo, Paul B; Engineer, Navzer; Armstrong, Scott; Weiner, Richard L; Burress, Chester; Cauller, Larry

    2011-01-01

    A voltage-controlled capacitive discharge (VCCD) method was investigated as an alternative to rectangular stimulus pulses currently used in peripheral nerve stimulation therapies.  In two anesthetized Gottingen mini pigs, the threshold (total charge per phase) for evoking a compound nerve action potential (CNAP) was compared between constant current (CC) and VCCD methods. Electrical pulses were applied to the tibial and posterior cutaneous femoralis nerves using standard and modified versions of the Medtronic 3778 Octad.  In contrast to CC stimulation, the combined application of VCCD pulses with a modified Octad resulted in a marked decrease (-73 ± 7.4%) in the stimulation threshold for evoking a CNAP. This was consistent for different myelinated fiber types and locations of stimulation.  The VCCD method provides a highly charge-efficient means of activating myelinated fibers that could potentially be used within a wireless peripheral nerve stimulator system. © 2011 International Neuromodulation Society.

  6. (-)-Epigallocatechin-3-gallate (EGCG) attenuates peripheral nerve degeneration in rat sciatic nerve crush injury.

    PubMed

    Renno, Waleed M; Al-Maghrebi, May; Alshammari, Ahmad; George, Preethi

    2013-02-01

    Recently, we have shown that green tea (GT) consumption improves both reflexes and sensation in unilateral chronic constriction injury to the sciatic nerve. Considering the substantial neuroprotective properties of GT polyphenols, we sought to investigate whether (-)-epigallocatechin-3-gallate (EGCG) could protect the sciatic nerve and improve functional impairments induced by a crushing injury. We also examined whether neuronal cell apoptosis induced by the crushing injury is affected by EGCG treatment. Histological examination of sciatic nerves from EGCG-treated (50mg/kg; i.p.) showed that axonotmized rats had a remarkable axonal and myelin regeneration with significant decrease in the number of myelinated axonal fibers compared to vehicle-treated crush group. Similarly, ultrastructural evaluation of EGCG-treated nerves displayed normal unmyelinated and myelinated axons with regular myelin sheath thickness and normalized appearance of Schmidt-Lantermann clefts. Extracellular matrix displayed normal collagen fibers appearance with distinctively organized distribution similar to sham animals. Analysis of foot position and extensor postural thrust test showed a progressive and faster recovery in the EGCG-treated group compared to vehicle-treated animals. EGCG-treated rats showed significant increase in paw withdrawal thresholds to mechanical stimulation compared to vehicle-treated crush group. EGCG treatment also restored the mRNA expression of Bax, Bcl-2 and survivin but not that of p53 to sham levels on days 3 and 7 post-injury. Our results demonstrate that EGCG treatment enhanced functional recovery, advanced morphological nerve rescue and accelerated nerve regeneration following crush injury partly due to the down regulation of apoptosis related genes.

  7. Early axonal damage and progressive myelin pathology define the kinetics of CNS histopathology in a mouse model of multiple sclerosis.

    PubMed

    Recks, Mascha S; Stormanns, Eva R; Bader, Jonas; Arnhold, Stefan; Addicks, Klaus; Kuerten, Stefanie

    2013-10-01

    Studies of MS histopathology are largely dependent on suitable animal models. While light microscopic analysis gives an overview of tissue pathology, it falls short in evaluating detailed changes in nerve fiber morphology. The ultrastructural data presented here and obtained from studies of myelin oligodendrocyte glycoprotein (MOG):35-55-induced experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice delineate that axonal damage and myelin pathology follow different kinetics in the disease course. While myelin pathology accumulated with disease progression, axonal damage coincided with the initial clinical disease symptoms and remained stable over time. This pattern applied both to irreversible axolysis and early axonal pathology. Notably, these histopathological patterns were reflected by the normal-appearing white matter (NAWM), suggesting that the NAWM is also in an active neurodegenerative state. The data underline the need for neuroprotection in MS and suggest the MOG model as a highly valuable tool for the assessment of different therapeutic strategies.

  8. 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.

    PubMed

    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

  9. SUSTAINED BLOCKADE OF NEUROTROPHIN RECEPTORS TrkA, TrkB AND TrkC REDUCES NON-MALIGNANT SKELETAL PAIN BUT NOT THE MAINTENANCE OF SENSORY AND SYMPATHETIC NERVE FIBERS

    PubMed Central

    Ghilardi, Joseph R.; Freeman, Katie T.; Jimenez-Andrade, Juan M.; Mantyh, William G.; Bloom, Aaron P.; Bouhana, Karyn S.; Trollinger, David; Winkler, James; Lee, Patrice; Andrews, Steven W.; Kuskowski, Michael A.; Mantyh, Patrick W.

    2010-01-01

    Current therapies for treating skeletal pain have significant limitations as available drugs (nonsteroidal anti-inflammatory drugs and opiates) have significant unwanted side effects. Targeting nerve growth factor or it's cognate receptor Tropomysin receptor kinase A (TrkA) has recently become an attractive target for inhibition of adult skeletal pain. Here we explore whether sustained administration of a selective small molecule Trk inhibitor that blocks TrkA, TrkB and TrkC kinase activity with nanomolar affinity reduces skeletal pain while allowing the maintenance of sensory and sympathetic neurons in the adult mouse. Twice-daily administration of a Trk inhibitor was begun 1 day post fracture and within 8 hours of acute administration fracture pain related behaviors were reduced by 50% without significant sedation, weight gain or inhibition of fracture healing. Following administration of the Trk inhibitor for 7 weeks, there was no significant decline in the density of unmyelinated, myelinated sensory or sympathetic nerve fibers, measures of acute thermal pain, acute mechanical pain, or general neuromuscular function. The present results suggest that sustained administration of a peripherally selective TrkA, B & C inhibitor significantly reduces skeletal pain without having any obvious detrimental effects on adult sensory and sympathetic nerve fibers or early fracture healing. As with any potential therapeutic advance, understanding whether the benefits of NGF blockade by ARRY-470 are associated with any risks or unexpected effects will be required to fully appreciate the patient populations that may benefit from this therapy. PMID:20854944

  10. [Expression and dynamics of peptidergic nerve fibers in granulation tissue after distance osteosynthesis].

    PubMed

    Wolf, K; Höcherl, E; Farkas, T; Pfister, C

    2001-10-01

    The transmitters and/or modulators calcitonin gene-related peptide (CGRP), substance P (SP), neuropeptide Y (NPY) and vasointestinal polypeptide (VIP) are supposed to be involved in bone growth, fracture healing and internal remodeling. Immunohistochemical proof of neuropeptide positive fibers in normal bone let us assume that these substances effect the early phase of fracture healing. Exact time of appearance of neuropeptide positive fibers, localisation in the bone, chemospecifity and mode of genesis are unknown so fare. Research was done on a model of distance osteosynthesis of the rabbit tibia. Primary and secondary antibodies were used for indirect immunohistochemical technique. We put more strength on the concrete stereological calculation of length of the nerve fibers than on a conventional statistical evaluation. After histological preparation of tissue specimens from the interfragmental gap and the bone marrow beside the gap the neuropeptides CGRP, SP and NPY were immunohistochemically expressed. Sprouting of CGRP- and SP-positive nerve fibers has its origin in the bone marrow. A vascularisation in the early state of osteoneogenesis after fracture seems impossible without the nerval peptidergic influence and transmission.

  11. Modulation of action potential trains in rabbit saphenous nerve unmyelinated fibers.

    PubMed

    Zhu, Zhi-Ru; Liu, Yi-Hui; Ji, Wei-Gang; Duan, Jian-Hong; Hu, San-Jue

    2013-01-01

    Usually, the main axon is assumed to faithfully conduct action potentials (APs). Recent data have indicated that neural processing can occur along the axonal path. However, the patterns and mechanisms of temporal coding are not clear. In the present study, single fiber recording was used to analyze activity-dependent modulation of AP trains in the main axons of C fibers in the rabbit saphenous nerve. Trains of 5 superthreshold electrical pulses at interstimulus intervals of 20 or 50 ms were applied to the nerve trunk for 200 s. The interspike intervals (ISIs) for these trains were compared to the input interstimulus intervals. Three basic types of C fibers were observed in response to repeated stimuli: first, the ISI between the first and second AP (ISI1-2) of type 1 was longer than the interstimulus interval; second, the ISI1-2 of type 2 showed wavelike fluctuations around the interstimulus interval, and third, the ISI1-2 of type 3 exhibited shorter intervals for a long period. Furthermore, both 4-aminopyridine-sensitive potassium and hyperpolarization-activated cation currents were involved in the modulation of ISI1-2 of train pulses. These data provide new evidence that multiple modes of neural conduction can occur along the main axons of C fibers.

  12. Methods for exploring the morpho-functional relations of the aortic depressor nerve in experimental diabetes.

    PubMed

    do Carmo, Jussara Márcia; Júnior, Rubens Fazan; Salgado, Helio Cesar; Fazan, Valéria Paula Sassoli

    2011-01-30

    The present study investigated morpho-functional relations of the aortic depressor nerve (ADN) 5, 15 and 120 days after the onset of streptozotocin-induced diabetes in rats. Time control animals received vehicle. Under pentobarbital anesthesia, ADN activity was recorded simultaneously with arterial pressure. After the recordings, nerves were prepared for light microscopy study and morphometry. ADN function was accessed by means of pressure-nerve activity curve (fitted by sigmoidal regression) and cross-spectral analysis between mean arterial pressure (MAP) and ADN activity. The relation between morphological (myelinated fibers number and density, total myelin area, total fiber area and percentage of occupancy) and functional (gain, signal/noise relation, frequency) parameters were accessed by linear regression analysis and correlation coefficient calculations. Functional parameters obtained by means of the sigmoidal regression curve as well as by cross-spectral analysis were similar in diabetic and control rats. Morphometric parameters of the ADN were similar between groups 5 days after the onset of diabetes. Average myelin area and myelinated fiber area were significantly smaller on diabetic rats 15 and 120 days after the onset of diabetes, being the myelinated fiber and respective axons area and diameter also smaller on 120 days group. Nevertheless, G ratio (ratio between axon and fiber diameter) was nearly 0.6 and not different between groups or experimental times. No significant relationship between morphological and functional parameters was detected in all experimental groups. The present study suggests that ADN diabetic neuropathy was time-dependent, with damage to myelinated fibers to be the primary event, not evidenced by physiological methods.

  13. Chronic migraine is associated with reduced corneal nerve fiber density and symptoms of dry eye.

    PubMed

    Kinard, Krista I; Smith, A Gordon; Singleton, J Robinson; Lessard, Margaret K; Katz, Bradley J; Warner, Judith E A; Crum, Alison V; Mifflin, Mark D; Brennan, Kevin C; Digre, Kathleen B

    2015-04-01

    We used in vivo corneal confocal microscopy to investigate structural differences in the sub-basal corneal nerve plexus in chronic migraine patients and a normal population. We used a validated questionnaire and tests of lacrimal function to determine the prevalence of dry eye in the same group of chronic migraine patients. Activation of the trigeminal system is involved in migraine. Corneal nociceptive sensation is mediated by trigeminal axons that synapse in the gasserian ganglion and the brainstem, and serve nociceptive, protective, and trophic functions. Noninvasive imaging of the corneal sub-basal nerve plexus is possible with in vivo corneal confocal microscopy. For this case-control study, we recruited chronic migraine patients and compared them with a sex- and age-similar group of control subjects. Patients with peripheral neuropathy, a disease known to be associated with a peripheral neuropathy, or prior corneal or intraocular surgery were excluded. Participants underwent in vivo corneal confocal microscopy using a Heidelberg Retinal Tomography III confocal microscope with a Rostock Cornea Module. Nerve fiber length, nerve branch density, nerve fiber density, and tortuosity coefficient were measured using established methodologies. Migraine participants underwent testing of basal tear production with proparacaine, corneal sensitivity assessment with a cotton-tip applicator, measurement of tear break-up time, and completion of a validated dry eye questionnaire. A total of 19 chronic migraine patients and 30 control participants completed the study. There were no significant differences in age or sex. Nerve fiber density was significantly lower in migraine patients compared with controls (48.4 ± 23.5 vs. 71.0 ± 15.0 fibers/mm2 , P < .001). Nerve fiber length was decreased in the chronic migraine group compared with the control group, but this difference was not statistically significant (21.5 ± 11.8 vs. 26.8 ± 5.9 mm/mm2, P

  14. Somatostatin-immunoreactive nerve cell bodies and fibers in the medulla oblongata et spinalis.

    PubMed

    Forssmann, W G; Burnweit, C; Shehab, T; Triepel, J

    1979-10-01

    Complete serial sectioning of the medulla oblongata in monkey, cat, guinea pig, and japanese dancing mouse and incubation for somatostatin-immunoreaction was carried out. Numerous regions of the medulla oblongata such as the nucleus reticularis gigantocellularis, nucleus cuneatus et gracillis, nucleus raphe magnus, nucleus tractus solitarius, nucleus vestibularis, and parts of the oliva contain dense networks of somatostatin-immunoreactive nerve fibers. Cell bodies were seen in the nucleus reticularis medullae oblongatae. In the spinal cord the sections from each segment were analyzed, showing the highest concentrations of somatostatinergic fibers in the substantia gelantinosa of the columna dorsalis. Cell bodies were seen in the zona intermedia centralis, especially in the upper cervical segments. Many positive fibers were also seen in the entire zona intermedia and the columna ventralis. Especially prominent was the immunoreactivity in the zona intermediolateralis of the thoracic segments and the columna ventralis of the lower lumbar and sacral segments.

  15. Nanofibrous nerve conduits for repair of 30-mm-long sciatic nerve defects

    PubMed Central

    Biazar, Esmaeil; Keshel, Saeed Heidari; Pouya, Majid; Rad, Hadi; Nava, Melody Omrani; Azarbakhsh, Mohammad; Hooshmand, Shirin

    2013-01-01

    It has been confirmed that nanofibrous poly(3-hydroxybutyrate-co-3-hydroxyvalerate) nerve conduit can promote peripheral nerve regeneration in rats. However, its efficiency in repair of over 30-mm-long sciatic nerve defects needs to be assessed. In this study, we used a nanofibrous poly(3-hydroxybutyrate-co-3-hydroxyvalerate) nerve conduit to bridge a 30-mm-long gap in the rat sciatic nerve. At 4 months after nerve conduit implantation, regenerated nerves were cally observed and histologically assessed. In the nanofibrous graft, the rat sciatic nerve trunk had been reconstructed by restoration of nerve continuity and formation of myelinated nerve fiber. There were Schwann cells and glial cells in the regenerated nerves. Masson's trichrome staining showed that there were no pathological changes in the size and structure of gastrocnemius muscle cells on the operated side of rats. These findings suggest that nanofibrous poly(3-hydroxybutyrate-co-3-hydroxyvalerate) nerve conduit is suitable for repair of long-segment sciatic nerve defects. PMID:25206536

  16. Reflectance Spectrum and Birefringence of the Retinal Nerve Fiber Layer With Hypertensive Damage of Axonal Cytoskeleton

    PubMed Central

    Huang, Xiang-Run; Knighton, Robert W.; Spector, Ye Z.; Qiao, Jianzhong; Kong, Wei; Zhao, Qi

    2017-01-01

    Purpose Glaucoma damages the retinal nerve fiber layer (RNFL). This study used precise multimodal image registration to investigate the changes of the RNFL reflectance spectrum and birefringence in nerve fiber bundles with different degrees of axonal damage. Methods The reflectance spectrum of individual nerve fiber bundles in normal rats and rats with experimental glaucoma was measured from 400 to 830 nm and their birefringence was measured at 500 nm. Optical measurements of the same bundles were made at different distances from the optic nerve head (ONH). After the optical measurements, the axonal cytoskeleton of the RNFL was evaluated by confocal microscopy to assess the severity of cytoskeletal change. Results For normal bundles, the shape of the RNFL reflectance spectrum and the value of RNFL birefringence did not change along bundles. In treated retinas, damage to the cytoskeleton varied within and across retinas. The damage in retinal sectors was subjectively graded from normal-looking to severe. Change of spectral shape occurred near the ONH in all sectors studied. This change became more prominent and occurred farther from the ONH with increased damage severity. In contrast, RNFL birefringence did not show change in normal-looking sectors, but decreased in sectors with mild and moderate damage. The birefringence of severely damaged sectors was either within or below the normal range. Conclusions Varying degrees of cytoskeletal damage affect the RNFL reflectance spectrum and birefringence differently, supporting differences in the ultrastructural basis for the two optical properties. Both properties, however, may provide a means to detect disease and to estimate ultrastructural damage of the RNFL in glaucoma. PMID:28395028

  17. A simple method for fabrication of electrospun fibers with controlled degree of alignment having potential for nerve regeneration applications.

    PubMed

    Vimal, Sunil Kumar; Ahamad, Nadim; Katti, Dhirendra S

    2016-06-01

    In peripheral nerve injuries where direct suturing of nerve endings is not feasible, nerve regeneration has been facilitated through the use of artificially aligned fibrous scaffolds that provide directional growth of neurons to bridge the gap. The degree of fiber alignment is crucial and can impact the directionality of cells in a fibrous scaffold. While there have been multiple approaches that have been used for controlling fiber alignment, however, they have been associated with a compromised control on other properties, such as diameter, morphology, curvature, and topology of fibers. Therefore, the present study demonstrates a modified electrospinning set-up, that enabled fabrication of electrospun fibers with controlled degree of alignment from non-aligned (NA), moderately aligned (MA, 75%) to highly aligned (HA, 95%) sub-micron fibers while keeping other physical properties unchanged. The results demonstrate that the aligned fibers (MA and HA) facilitated directional growth of human astrocytoma cells (U373), wherein the aspect ratio of cells was found to increase with an increase in degree of fibers alignment. In contrast to NA and MA fibers, the HA fibers showed improved contact guidance to U373 cells that was demonstrated by a significantly higher cell aspect ratio and nuclear aspect ratio. In conclusion, the present study demonstrated a modified electrospinning setup to fabricate differentially aligned fibrous scaffolds with the HA fibers showing potential for use in neural tissue engineering.

  18. Enkephalin-like immunoreactivity of olivocochlear nerve fibers in cochlea of guinea pig and cat

    PubMed Central

    Fex, Jörgen; Altschuler, Richard A.

    1981-01-01

    The distribution of enkephalin-like immunoreactivity in the cochlea of the guinea pig and cat was studied. Indirect immunofluorescence immunohistochemistry using antisera generated against a methionine enkephalin-bovine thyroglobulin conjugate was applied to surface preparations of the organ of Corti and cryostat sections of the whole of the cochlea. In the cochlear osseous spiral lamina, immunofluorescence was localized to unmyelinated fibers of the intraganglionic spiral bundle. In the organ of Corti, immunofluorescence was localized to a small number of fibers at inner hair cells, the inner spiral bundle, and tunnel spiral bundle, to tunnel crossing fibers at the level of the tunnel floor, to an occasional spiral outer fiber, and to the synaptic region of outer hair cells in the three rows of the basal turn of the cochlea. Less immunofluorescence was found in this region as one progressed towards the apex, with none seen at the apex. At the most apical region the inner spiral bundle became patchy and the tunnel spiral bundle developed arcades. There was no immunofluorescence found in spiral ganglion cells, in auditory nerve fibers, or in the hair cells of the organ of Corti. The findings were the same in cat as in guinea pig, the latter being studied in more detail. It was concluded that efferent, olivocochlear neurons of the cochlea, synapsing predominantly with primary auditory nerve fibers from the inner sensory cells or with the sensory cells, contain enkephalin-like immunoreactivity. Also, the findings indicate that endings of olivocochlear neurons that synapse predominantly with outer hair cells contain enkephalin-like immunoreactivity. It has previously been shown that olivocochlear neurons are likely to be cholinergic. Images PMID:7015329

  19. The organization of taste sensibilities in hamster chorda tympani nerve fibers

    PubMed Central

    Frank, ME; Bieber, SL; Smith, DV

    1988-01-01

    Electrophysiological measurements of nerve impulse frequencies were used to explore the organization of taste sensibilities in single fibers of the hamster chorda tympani nerve. Moderately intense taste solutions that are either very similar or easily discriminated were applied to the anterior lingual surface. 40 response profiles or 13 stimulus activation patterns were considered variables and examined with multivariate statistical techniques. Three kinds of response profiles were seen in fibers that varied in their overall sensitivity to taste solutions. One profile (S) showed selectivity for sweeteners, a second (N) showed selectivity for sodium salts, and a third (H) showed sensitivity to salts, acids, and other compounds. Hierarchical cluster analysis indicated that profiles fell into discrete classes. Responses to many pairs of effective stimuli were covariant across profiles within a class, but some acidic stimuli had more idiosyncratic effects. Factor analysis of profiles identified two common factors, accounting for 77% of the variance. A unipolar factor was identified with the N profile, and a bipolar factor was identified with the S profile and its opposite, the H profile. Three stimulus activation patterns were elicited by taste solutions that varied in intensity of effect. Hierarchical cluster analysis indicated that the patterns fell into discrete classes. Factor analysis of patterns identified three common unipolar factors accounting for 82% of the variance. Eight stimuli (MgSO4, NH4Cl, KCl, citric acid, acetic acid, urea, quinine HCl, HCl) selectively activated fibers with H profiles, three stimuli (fructose, Na saccharin, sucrose) selectively activated fibers with S profiles, and two stimuli (NaNO3, NaCl) activated fibers with N profiles more strongly than fibers with H profiles. Stimuli that evoke different patterns taste distinct to hamsters. Stimuli that evoke the same pattern taste more similar. It was concluded that the hundreds of peripheral

  20. PARP INHIBITION OR GENE DEFICIENCY COUNTERACT INTRAEPIDERMAL NERVE FIBER LOSS AND NEUROPATHIC PAIN IN ADVANCED DIABETIC NEUROPATHY

    PubMed Central

    Obrosova, Irina G.; Xu, Weizheng; Lyzogubov, Valeriy V.; Ilnytska, Olga; Mashtalir, Nazar; Vareniuk, Igor; Pavlov, Ivan A.; Zhang, Jie; Slusher, Barbara; Drel, Viktor R.

    2011-01-01

    Evidence for important role of poly(ADP-ribose) polymerase (PARP) activation in diabetic complications is emerging. This study evaluated the role for PARP in rat and mouse models of advanced diabetic neuropathy. The orally active PARP inhibitor 10-(4-methyl-piperazin-1-ylmethyl)-2H-7-oxa-1,2-diaza-benzo[de]anthracen-3-one(GPI-15427, formulated as mesilate salt, 30 mg kg−1d−1 in the drinking water, for 10 weeks after first 2 weeks without treatment) at least partially prevented PARP activation in peripheral nerve and DRG neurons, as well as thermal hypoalgesia, mechanical hyperalgesia, tactile allodynia, exaggerated response to formalin, and, the most important, intraepidermal nerve fiber degeneration in streptozotocin-diabetic rats. These findings are consistent with the lack of small sensory nerve fiber dysfunction in diabetic PARP−/− mice. Furthermore, whereas diabetic PARP+/+ mice displayed ~ 46% intraepidermal nerve fiber loss, diabetic PARP−/− preserved completely normal intraepidermal nerve fiber density. In conclusion, PARP activation is an important contributor to intraepidermal nerve fiber degeneration and functional changes associated with advanced Type 1 diabetic neuropathy. The results support the rationale for development of potent and low toxic PARP inhibitors and PARP inhibitor-containing combination therapies. PMID:17976390

  1. Periosteum Metabolism and Nerve Fiber Positioning Depend on Interactions between Osteoblasts and Peripheral Innervation in Rat Mandible.

    PubMed

    Mauprivez, Cédric; Bataille, Caroline; Baroukh, Brigitte; Llorens, Annie; Lesieur, Julie; Marie, Pierre J; Saffar, Jean-Louis; Biosse Duplan, Martin; Cherruau, Marc

    2015-01-01

    The sympathetic nervous system controls bone remodeling by regulating bone formation and resorption. How nerves and bone cells influence each other remains elusive. Here we modulated the content or activity of the neuropeptide Vasoactive Intestinal Peptide to investigate nerve-bone cell interplays in the mandible periosteum by assessing factors involved in nerve and bone behaviors. Young adult rats were chemically sympathectomized or treated with Vasoactive Intestinal Peptide or Vasoactive Intestinal Peptide10-28, a receptor antagonist. Sympathectomy depleted the osteogenic layer of the periosteum in neurotrophic proNerve Growth Factor and neurorepulsive semaphorin3a; sensory Calcitonin-Gene Related Peptide-positive fibers invaded this layer physiologically devoid of sensory fibers. In the periosteum non-osteogenic layer, sympathectomy activated mast cells to release mature Nerve Growth Factor while Calcitonin-Gene Related Peptide-positive fibers increased. Vasoactive Intestinal Peptide treatment reversed sympathectomy effects. Treating intact animals with Vasoactive Intestinal Peptide increased proNerve Growth Factor expression and stabilized mast cells. Vasoactive Intestinal Peptide10-28 treatment mimicked sympathectomy effects. Our data suggest that sympathetic Vasoactive Intestinal Peptide modulate the interactions between nervous fibers and bone cells by tuning expressions by osteogenic cells of factors responsible for mandible periosteum maintenance while osteogenic cells keep nervous fibers at a distance from the bone surface.

  2. Periosteum Metabolism and Nerve Fiber Positioning Depend on Interactions between Osteoblasts and Peripheral Innervation in Rat Mandible

    PubMed Central

    Mauprivez, Cédric; Bataille, Caroline; Baroukh, Brigitte; Llorens, Annie; Lesieur, Julie; Marie, Pierre J.; Saffar, Jean-Louis; Biosse Duplan, Martin; Cherruau, Marc

    2015-01-01

    The sympathetic nervous system controls bone remodeling by regulating bone formation and resorption. How nerves and bone cells influence each other remains elusive. Here we modulated the content or activity of the neuropeptide Vasoactive Intestinal Peptide to investigate nerve-bone cell interplays in the mandible periosteum by assessing factors involved in nerve and bone behaviors. Young adult rats were chemically sympathectomized or treated with Vasoactive Intestinal Peptide or Vasoactive Intestinal Peptide10-28, a receptor antagonist. Sympathectomy depleted the osteogenic layer of the periosteum in neurotrophic proNerve Growth Factor and neurorepulsive semaphorin3a; sensory Calcitonin-Gene Related Peptide-positive fibers invaded this layer physiologically devoid of sensory fibers. In the periosteum non-osteogenic layer, sympathectomy activated mast cells to release mature Nerve Growth Factor while Calcitonin-Gene Related Peptide-positive fibers increased. Vasoactive Intestinal Peptide treatment reversed sympathectomy effects. Treating intact animals with Vasoactive Intestinal Peptide increased proNerve Growth Factor expression and stabilized mast cells. Vasoactive Intestinal Peptide10-28 treatment mimicked sympathectomy effects. Our data suggest that sympathetic Vasoactive Intestinal Peptide modulate the interactions between nervous fibers and bone cells by tuning expressions by osteogenic cells of factors responsible for mandible periosteum maintenance while osteogenic cells keep nervous fibers at a distance from the bone surface. PMID:26509533

  3. Employment of the mouse median nerve model for the experimental assessment of peripheral nerve regeneration.

    PubMed

    Tos, P; Ronchi, G; Nicolino, S; Audisio, C; Raimondo, S; Fornaro, M; Battiston, B; Graziani, A; Perroteau, I; Geuna, S

    2008-03-30

    The experimental investigation of nerve regeneration after microsurgical repair is usually carried out in rats, rather than mice, because of the larger sized peripheral nerves. Today however, the availability of genetically modified mice makes the use of this laboratory animal very intriguing for investigating nerve regeneration at a molecular level. In this study we aimed to provide a standardization of the experimental model based on microsurgical direct repair, by 12/0 suture, of the left median nerve in adult male mice. Postoperative recovery was regularly assessed by the grasping test. At day-75 postoperative, regenerated median nerve fibers were analyzed by design-based quantitative morphology and electron microscopy. Yet, sections were immuno-labelled using two axonal antibodies commonly employed for rat nerve fibers. Results indicated that functional recovery begun at day-15 and progressively increased reaching values not significantly different from normal by day-50. Quantitative morphology showed that, at day-75, the number of regenerated nerve fibers was not significantly different in comparison to controls. In contrast, differences were detected in fiber density, mean axon and fiber diameter and myelin thickness which were all significantly lower than controls. Immunohistochemistry showed that axonal markers commonly used for rat nerves studies are effective also for mouse nerves. Similar to the rat, the mouse median nerve model is superior to sciatic nerve model for the minimal impact on animal well-being and the effectiveness of the grasping test for motor function evaluation. The main limitation is the small nerve size which requires advanced microsurgical skills for performing 12/0 epineurial suturing.

  4. β1 integrins are required for normal CNS myelination and promote AKT-dependent myelin outgrowth

    PubMed Central

    Barros, Claudia S.; Nguyen, Tom; Spencer, Kathryn S. R.; Nishiyama, Akiko; Colognato, Holly; Müller, Ulrich

    2009-01-01

    Summary Oligodendrocytes in the central nervous system (CNS) produce myelin sheaths that insulate axons to ensure fast propagation of action potentials. β1 integrins regulate the myelination of peripheral nerves, but their function during the myelination of axonal tracts in the CNS is unclear. Here we show that genetically modified mice lacking β1 integrins in the CNS present a deficit in myelination but no defects in the development of the oligodendroglial lineage. Instead, in vitro data show that β1 integrins regulate the outgrowth of myelin sheaths. Oligodendrocytes derived from mutant mice are unable to efficiently extend myelin sheets and fail to activate AKT (also known as AKT1), a kinase that is crucial for axonal ensheathment. The inhibition of PTEN, a negative regulator of AKT, or the expression of a constitutively active form of AKT restores myelin outgrowth in cultured β1-deficient oligodendrocytes. Our data suggest that β1 integrins play an instructive role in CNS myelination by promoting myelin wrapping in a process that depends on AKT. PMID:19633169