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Sample records for myelinated nerve fiber

  1. Ephaptic coupling of myelinated nerve fibers

    DEFF Research Database (Denmark)

    Binczak, S.; Eilbeck, J. C.; Scott, Alwyn C.

    2001-01-01

    Numerical predictions of a simple myelinated nerve fiber model are compared with theoretical results in the continuum and discrete limits, clarifying the nature of the conduction process on an isolated nerve axon. Since myelinated nerve fibers are often arranged in bundles, this model is used...... to study ephaptic (nonsynaptic) interactions between impulses on parallel fibers, which may play a functional role in neural processing. (C) 2001 Published by Elsevier Science B.V....

  2. Electrophysiological abnormalities associated with extensive myelinated retinal nerve fibers

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    Su Ann Tay

    2012-01-01

    Full Text Available An observational case report of electrophysiological abnormalities in a patient with anisomyopic amblyopia as a result of unilateral extensive myelinated retinal nerve fibers (MNFs is illustrated. The electrophysiological readings revealed an abnormal pattern electroretinogram (PERG but normal full-field electroretinogram readings in the affected eye. The visual-evoked potential was also undetectable in that eye. Our findings suggest that extensive MNFs can be associated with electrophysiological abnormalities, in particular the PERG, which can aid in diagnosing the cause of impaired vision when associated with amblyopia.

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

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    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.

  4. The effects of normal aging on myelinated nerve fibers in monkey central nervous system

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    Alan Peters

    2009-07-01

    Full Text Available 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.

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

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    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.

  6. Association of extensive myelinated nerve fibers and high degree myopia: Case report

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    Elvan Yalcın

    2013-01-01

    Full Text Available Unilateral extensive myelination of the peripapillary nerve fibers may be associated with anisometropic myopia, strabismus, and reduced vision. Myelination of optic nerve fibers terminate at lamina cribrosa. Yet in some patients, myelination progresses into the peripapillary retinal nerve fibers and may affect the visual acuity. In this report, we described 4 patients. All patients presented extensive peripapillary myelinated nerve fibers associated with myopic anisometropia. After routine ophthalmic and orthoptic examinations, all patients underwent treatment for amblyopia through correction with spectacles, contact lenses, and the occlusion of the good eye. Corrected visual acuity improved in 1 patient, but 3 patients had no increase in visual acuity despite treatment with full cycloplegic refraction and appropriate patching. Probably because of structural abnormalies of the macula, visual results are often disappointing with appropriate correction of the refractive error and occlusion.

  7. Corneal Cross-Linking for the Treatment of Keratoconus in a Patient with Ipsilateral Myelinated Retinal Nerve Fiber Layer

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    M. Leozappa

    2011-03-01

    Full Text Available Keratoconus associated with myelinated retinal nerve fibers is not frequent and the relationship between the two pathologies is difficult to explain, therefore studies and further investigation are required. The etiology of each condition may suggest the role of genetic factors. Follow-up is important to evaluate the progression of keratoconus and myelination. Here we describe the unusual coexistence of keratoconus and ipsilateral myelinated retinal nerve fiber layer and, for the first time, the corneal cross-linking treatment in this condition.

  8. Molecular architecture of myelinated nerve fibers: leaky paranodal junctions and paranodal dysmyelination.

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    Rosenbluth, Jack; Mierzwa, Amanda; Shroff, Seema

    2013-12-01

    Myelinated nerve fibers have evolved to optimize signal propagation. Each myelin segment is attached to the axon by the unique paranodal axoglial junction (PNJ), a highly complex structure that serves to define axonal ion channel domains and to direct nodal action currents through adjacent nodes. Surprisingly, this junction does not entirely seal the paranodal myelin sheath to the axon and thus does not entirely isolate the perinodal space from the internodal periaxonal space. Rather the paranode is penetrated by extracellular pathways between the myelin sheath and the axolemma for movement of molecules and the flow of current to and from the internodal axon. This review summarizes past and current studies demonstrating these pathways and considers what functional roles they subserve. In addition, modern genetic engineering methods permit modification of individual PNJ constituents, which provides an opportunity to define their specific functions. One component in particular, the transverse bands, plays a key role in maintaining the structure and function of the PNJ. Loss of transverse bands results not in frank demyelination but rather in subtle dysmyelination, which causes significant functional impairment. The consequences of such subtle defects in the PNJ are considered along with the relevance of these studies to human diseases of myelin.

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

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    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.

  10. 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.

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    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.

  11. Análise quantitativa das fibras mielínicas dos nervos laríngeos em humanos de acordo com a idade Quantitative analysis of myelinic fibers in human laryngeal nerves according to age

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    Romualdo Suzano Louzeiro Tiago

    2008-02-01

    Full Text Available INTRODUÇÃO E OBJETIVO: Realizar análise morfométrica das fibras mielínicas dos nervos laríngeos com a finalidade de verificar modificações quantitativas decorrentes do processo de envelhecimento. FORMA DE ESTUDO: Clínico e experimental. Material e Método: Foi coletado fragmento de 1cm dos nervos laríngeos superiores e nervos laríngeos recorrentes de 12 cadáveres do sexo masculino. A amostra foi dividida em dois grupos: idade inferior a 60 anos (Adulto e idade igual ou superior a 60 anos (Idoso. O material foi avaliado em microscópio de luz acoplado a sistema analisador de imagem. RESULTADOS: O número total de fibras mielínicas do nervo laríngeo superior foi semelhante nos dois grupos etários, mas com tendência para o maior número de fibras de 1µm no grupo adulto (p=0,0744. O grupo adulto apresentou maior número total de fibras mielínicas no nervo laríngeo recorrente (p=0,0006, e esta diferença ocorreu nas fibras com diâmetros de 1-3µm (pINTRODUCTION AND AIM: To carry out a morphometric analysis of myelinic fibers in laryngeal nerves aiming to identify quantitative changes as a result of aging. Study design: Clinical and experimental. MATERIAL AND METHOD: 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. RESULTS: 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 1μm 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 betwee 1-3μm (p<0.007. The adult group had a higher total number of myelinic fibers

  12. Unmyelinated nerve fiber degeneration in chronic inflammatory demyelinating polyneuropathy

    NARCIS (Netherlands)

    Bosboom, WMJ; Van den Berg, LH; Dieks, HJG; Plante, E; Veldman, H; Franssen, H; Wokke, JHJ

    2000-01-01

    To determine whether unmyelinated nerve fibers escape degeneration as one might expect in an immune response exclusively directed at myelin, we performed a morphometric examination of unmyelinated axons and myelinated nerve fibers in sural nerve biopsy specimens of 14 patients with a chronic inflamm

  13. Transverse Magnetic Waves in Myelinated Nerves

    Science.gov (United States)

    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

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

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    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

  15. Purinergic signaling mediated by P2X7 receptors controls myelination in sciatic nerves.

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    Faroni, A; Smith, R J P; Procacci, P; Castelnovo, L F; Puccianti, E; Reid, A J; Magnaghi, V; Verkhratsky, A

    2014-10-01

    Adenosine-5'-triphosphate, the physiological ligand of P2X receptors, is an important factor in peripheral nerve development. P2X7 receptor is expressed in Schwann cells (SCs), but the specific effects of P2X7 purinergic signaling on peripheral nerve development, myelination, and function are largely unknown. In this study, sciatic nerves from P2X7 knockout mice were analyzed for altered expression of myelin-associated proteins and for alterations in nerve morphology. Immunohistochemical analyses revealed that, in the wild-type peripheral nerves, the P2X7 receptor was localized mainly in myelinating SCs, with only a few immunopositive nonmyelinating SCs. Complete absence of P2X7 receptor protein was confirmed in the sciatic nerves of the knockout mice by Western blot and immunohistochemistry. Western blot analysis revealed that expression levels of the myelin proteins protein zero and myelin-associated glycoprotein are reduced in P2X7 knockout nerves. In accordance with the molecular results, transmission electron microscopy analyses revealed that P2X7 knockout nerves possess significantly more unmyelinated axons, contained in a higher number of Remak bundles. The myelinating/nonmyelinating SC ratio was also decreased in knockout mice, and we found a significantly increased number of irregular fibers compared with control nerves. Nevertheless, the myelin thickness in the knockout was unaltered, suggesting a stronger role for P2X7 in determining SC maturation than in myelin formation. In conclusion, we present morphological and molecular evidence of the importance of P2X7 signaling in peripheral nerve maturation and in determining SC commitment to a myelinating phenotype.

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

    Directory of Open Access Journals (Sweden)

    A.M.B. Martinez

    2000-12-01

    Full Text Available 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.

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

    Science.gov (United States)

    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.

  18. The effect of DDT and dieldrin on myelinated nerve fibres

    NARCIS (Netherlands)

    Bercken, J. van den

    1972-01-01

    The effects of the chlorinated hydrocarbon insecticides, DDT and dieldrin, on myelinated nerve fibres of the clawed toad, Xenopus laevis, were studied by recording compound action nerve fibres, and membrane potentials of single nodes of Ranvier. The effect of DDT (5 × 10−4 M) was found to be exclusi

  19. The effect of DDT and dieldrin on myelinated nerve fibres

    NARCIS (Netherlands)

    Bercken, J. van den

    The effects of the chlorinated hydrocarbon insecticides, DDT and dieldrin, on myelinated nerve fibres of the clawed toad, Xenopus laevis, were studied by recording compound action nerve fibres, and membrane potentials of single nodes of Ranvier. The effect of DDT (5 × 10−4 M) was found to be

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

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    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.

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

    Science.gov (United States)

    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.

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

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    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.

  3. Cholecalciferol (vitamin D₃ improves myelination and recovery after nerve injury.

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    Jean-Francois Chabas

    Full Text Available 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

  4. Cholecalciferol (vitamin D₃) improves myelination and recovery after nerve injury.

    Science.gov (United States)

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

    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

  5. Re-innervation patterns by peptidergic Substance-P, non-peptidergic P2X3, and myelinated NF-200 nerve fibers in epidermis and dermis of rats with neuropathic pain

    NARCIS (Netherlands)

    Duraku, Liron S.; Hossaini, Mehdi; Schuettenhelm, Barthold N.; Holstege, Joan C.; Baas, Martijn; Ruigrok, Tom J. H.; Walbeehm, Erik T.

    2013-01-01

    Nerve endings in the epidermis, termed nociceptors, conduct information on noxious stimuli to the central nervous system. The precise role of epidermal nerve fibers in neuropathic pain is however still controversial. Here, we have investigated the re-innervation patterns of epidermal and dermal nerv

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

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    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.

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

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    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.

  8. Re-innervation patterns by peptidergic Substance-P, non-peptidergic P2X3, and myelinated NF-200 nerve fibers in epidermis and dermis of rats with neuropathic pain.

    Science.gov (United States)

    Duraku, Liron S; Hossaini, Mehdi; Schüttenhelm, Barthold N; Holstege, Joan C; Baas, Martijn; Ruigrok, Tom J H; Walbeehm, Erik T

    2013-03-01

    Nerve endings in the epidermis, termed nociceptors, conduct information on noxious stimuli to the central nervous system. The precise role of epidermal nerve fibers in neuropathic pain is however still controversial. Here, we have investigated the re-innervation patterns of epidermal and dermal nerve fibers in a rat neuropathic pain model. After applying the spared nerve injury (SNI) model, we determined the mechanical and thermal withdrawal thresholds in the uninjured lateral (sural) and medial (saphenous) areas of the affected hind paw and investigated the innervations patterns of Substance P (SubP), Neurofilament-200 (NF-200) and P2X3-immunoreactive (IR) nerve fibers in the epidermis and dermis. We found a significant loss in the density of peptidergic (Sub P and NF-200) and non-peptidergic (P2X3) nerve fibers in the center area of the foot sole at 2 weeks postoperatively (PO). The densities of Sub P-IR fibers in the epidermis and upper dermis, and the density of P2X3-IR fibers in the upper dermis were significantly increased at 10 weeks PO as compared to 2 weeks PO, but were still significantly lower than the densities in controls. However, the density of NF-200-IR fibers in the center area reached control levels at 10 weeks PO. No changes were found in the densities of any of the fibers in the medial and lateral parts of the foot sole. The present results suggest that after peripheral nerve injury, specific nerve fibers have different re-innervation patterns in the epidermis and dermis and that they might be involved in the development of neuropathic pain.

  9. Histochemical discrimination of fibers in regenerating rat infraorbital nerve

    Science.gov (United States)

    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.

  10. The application of fuzzy-based methods to central nerve fiber imaging

    DEFF Research Database (Denmark)

    Axer, Hubertus; Jantzen, Jan; Keyserlingk, Diedrich Graf v.

    2003-01-01

    in magnetic resonance images based on the differences in myelin content in various thalamic subnuclei; (2) polarized light for classifying the 3D orientation of the nerve fibers at each point; and (3) confocal laser scanning microscopy (CLSM) for calculating semiquantitative variables for myelin content...

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

    Energy Technology Data Exchange (ETDEWEB)

    Rai, Nagendra Kumar; Ashok, Anushruti [Academy of Scientific and Innovative Research (India); Developmental Toxicology, Council of Scientific and Industrial Research-Indian Institute of Toxicology Research (CSIR-IITR) (India); Rai, Asit; Tripathi, Sachin [Developmental Toxicology, Council of Scientific and Industrial Research-Indian Institute of Toxicology Research (CSIR-IITR) (India); Nagar, Geet Kumar [Endocrinology, CSIR-Central Drug Research Institute (CSIR-CDRI) (India); Mitra, Kalyan [Electron Microscopy Unit, CSIR-CDRI, Lucknow 226001 (India); Bandyopadhyay, Sanghamitra, E-mail: sanghmitra@iitr.res.in [Academy of Scientific and Innovative Research (India); Developmental Toxicology, Council of Scientific and Industrial Research-Indian Institute of Toxicology Research (CSIR-IITR) (India)

    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.

  12. Quantitative Microscopic Analysis of Myelinated Nerve Fibers

    NARCIS (Netherlands)

    Prodanov, D.P.; Feierabend, Hans K.P.; Marani, Enrico; Flynn, Cian E.; Callaghan, Brandon R.

    2010-01-01

    Neuroanatomy is the study of the anatomical organization of the brain. Reciprocal communication between the brain and the cardiovascular system is important in sustaining neurobehavioral states that allow organisms to cope with their environment. Furthermore, in vertebrate animals, the routes that

  13. Quantitative Microscopic Analysis of Myelinated Nerve Fibers

    NARCIS (Netherlands)

    Prodanov, D.P.; Feierabend, Hans K.P.; Marani, Enrico; Costa, A.; Villalba, E.

    2010-01-01

    Horizons in Neuroscience Research presents original research results on the leading edge of neuroscience research. Each article has been carefully selected in an attempt to present substantial research results across a broad spectrum

  14. Support of Nerve Conduction by Respiring Myelin Sheath: Role of Connexons.

    Science.gov (United States)

    Ravera, Silvia; Bartolucci, Martina; Adriano, Enrico; Garbati, Patrizia; Ferrando, Sara; Ramoino, Paola; Calzia, Daniela; Morelli, Alessandro; Balestrino, Maurizio; Panfoli, Isabella

    2016-05-01

    Recently, we have demonstrated that myelin conducts an extramitochondrial oxidative phosphorylation, hypothesizing a novel supportive role for myelin in favor of the axon. We have also hypothesized that the ATP produced in myelin could be transferred thought gap junctions. In this work, by biochemical, immunohistochemical, and electrophysiological techniques, the existence of a connection among myelin to the axon was evaluated, to understand how ATP could be transferred from sheath to the axoplasm. Data confirm a functional expression of oxidative phosphorylation in isolated myelin. Moreover, WB and immunohistochemistry on optic nerve slices show that connexins 32 and 43 are present in myelin and colocalize with myelin basic protein. Interestingly, addition of carbenoxolone or oleamide, two gap junction blockers, causes a decrease in oxidative metabolism in purified myelin, but not in mitochondria. Similar effects were observed on conduction speed in hippocampal Schaffer collateral, in the presence of oleamide. Confocal analysis of optic nerve slices showed that lucifer yellow (that only passes through aqueous pores) signal was found in both the sheath layers and the axoplasma. In the presence of oleamide, but not with oleic acid, signal significantly decreased in the sheath and was lost inside the axon. This suggests the existence of a link among myelin and axons. These results, while supporting the idea that ATP aerobically synthesized in myelin sheath could be transferred to the axoplasm through gap junctions, shed new light on the function of the sheath.

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

    Science.gov (United States)

    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.

  16. GEMSP exerts a myelin-protecting role in the rat optic nerve.

    Science.gov (United States)

    Mangas, Arturo; Vecino, Elena; David Rodríguez, F; Geffard, Michel; Coveñas, Rafael

    2013-11-01

    Chronic experimental autoimmune encephalomyelitis (EAE) was induced in rats to evaluate the potential protective effect of GEMSP, a mixture made up of fatty acids (FA), vitamins, and amino acids or their derivatives, linked to Poly-L-Lysine, on the myelin sheath of the optic nerve. To evaluate the effects of GEMSP on the optic nerve, animals were divided into three experimental groups: (1) EAE rats treated with GEMSP; (2) EAE rats treated with 0.9% NaCl; and (3) control, non-EAE rats. Using electron microscopy, we investigated the possibility that this new drug candidate has a myelin-protective role. A marginally significant reduction in the thickness of the myelin around optic nerve medium-size axons (diameter between 0.8-1.3 μm) was found in EAE rats. Treatment of EAE rats with GEMSP ameliorated myelin damage. Significantly increased myelin thickness was found when animals in groups 2 and 3 were compared. However, the number of myelinated axons studied was not altered in groups 1 or 2 when compared to controls. Our results suggest that in a model of demyelination, GEMSP protects and enhances the formation of the myelin sheath of the optic nerve and therefore could be a potential drug candidate to reduce optic nerve pathogenesis in multiple sclerosis (MS).

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

    DEFF Research Database (Denmark)

    Brazhe, Alexey; Maksimov, G. V.; Mosekilde, Erik;

    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......-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....

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  20. The myelinated fiber loss in the corpus callosum of mouse model of schizophrenia induced by MK-801.

    Science.gov (United States)

    Xiu, Yun; Kong, Xiang-ru; Zhang, Lei; Qiu, Xuan; Gao, Yuan; Huang, Chun-xia; Chao, Feng-lei; Wang, San-rong; Tang, Yong

    2015-04-01

    Previous magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) investigations have shown that the white matter volume and fractional anisotropy (FA) were decreased in schizophrenia (SZ), which indicated impaired white matter integrity in SZ. However, the mechanism underlying these abnormalities has been less studied. The current study was designed to investigate the possible reasons for white matter abnormalities in the mouse model of SZ induced by NMDA receptor antagonist using the unbiased stereological methods and transmission electron microscope technique. We found that the mice treated with MK-801 demonstrated a series of schizophrenia-like behaviors including hyperlocomotor activity and more anxiety. The myelinated fibers in the corpus callosum (CC) of the mice treated with MK-801 were impaired with splitting lamellae of myelin sheaths and segmental demyelination. The CC volume and the total length of the myelinated fibers in the CC of the mice treated with MK-801 were significantly decreased by 9.4% and 16.8% when compared to those of the mice treated with saline. We further found that the loss of the myelinated fibers length was mainly due to the marked loss of the myelinated nerve fibers with the diameter of 0.4-0.5 μm. These results indicated that the splitting myelin sheaths, demyelination and the loss of myelinated fibers with small diameter might provide one of the structural bases for impaired white matter integrity of CC in the mouse model of SZ. These results might also provide a baseline for further studies searching for the treatment of SZ through targeting white matter.

  1. Astrocytes phagocytose focal dystrophies from shortening myelin segments in the optic nerve of Xenopus laevis at metamorphosis.

    Science.gov (United States)

    Mills, Elizabeth A; Davis, Chung-ha O; Bushong, Eric A; Boassa, Daniela; Kim, Keun-Young; Ellisman, Mark H; Marsh-Armstrong, Nicholas

    2015-08-18

    Oligodendrocytes can adapt to increases in axon diameter through the addition of membrane wraps to myelin segments. Here, we report that myelin segments can also decrease their length in response to optic nerve (ON) shortening during Xenopus laevis metamorphic remodeling. EM-based analyses revealed that myelin segment shortening is accomplished by focal myelin-axon detachments and protrusions from otherwise intact myelin segments. Astrocyte processes remove these focal myelin dystrophies using known phagocytic machinery, including the opsonin milk fat globule-EGF factor 8 (Mfge8) and the downstream effector ras-related C3 botulinum toxin substrate 1 (Rac1). By the end of metamorphic nerve shortening, one-quarter of all myelin in the ON is enwrapped or internalized by astrocytes. As opposed to the removal of degenerating myelin by macrophages, which is usually associated with axonal pathologies, astrocytes selectively remove large amounts of myelin without damaging axons during this developmental remodeling event.

  2. Regeneration of unmyelinated and myelinated sensory nerve fibres studied by a retrograde tracer method

    DEFF Research Database (Denmark)

    Lozeron, Pierre; Krarup, Christian; Schmalbruch, Henning

    2004-01-01

    Regeneration of myelinated and unmyelinated sensory nerve fibres after a crush lesion of the rat sciatic nerve was investigated by means of retrograde labelling. The advantage of this method is that the degree of regeneration is estimated on the basis of sensory somata rather than the number...

  3. A note on the mechanism of resistance to anoxia and ischaemia in pathophysiological mammalian myelinated nerve.

    OpenAIRE

    Ritchie, J. M.

    1985-01-01

    Computer simulation of the action potential in myelinated nerve fibres show that the metabolic cost of conduction of an impulse is less than normal in a slightly depolarised fibre. This would account, at least in part, for the greater resistance to ischaemia and anoxia of nerves from diabetics and other pathophysiological conditions.

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

    Science.gov (United States)

    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.

  5. Relationship between genetic expression of BDNF and NRG-1 and myelinated nerve fiber density and cross-sectional area in thoracic sympathetic trunk of palmar hyperhidrosis%手汗症患者胸交感神经干脑源性神经营养因子和神经调节因子-1基因表达与有髓神经纤维密度及横截面积的关系

    Institute of Scientific and Technical Information of China (English)

    罗荣刚; 涂远荣; 李旭; 林敏; 陈剑锋; 邱明链

    2009-01-01

    Objective To investigate the gene expression of brain-derived neurotrophic factor ( BD-NF) and neuregulin-1 (NRG-1) in thoracic sympathetic trunk and their relation to myelinated nerve fiber density and single myelinated nerve fibers cross-sectional area in palmar hyperhidrosis. Methods Fast red-fast green myelin sheath staining was used to show myelinated nerve fibers. Using the micro-image analysis system,30 cases of myelinated nerve fiber density and single myelinated nerve fibers cross-sectional area were observed in T3 thoracic sympathetic trunk of patients with palmar hyperhidrosis. BDNF and NRG-1 gene expression was also analyzed by RT-PCR. Eight cases of non-palmar hyperhidrosis patients served as controls. Results In 33 thoracic sympathetic trunk of patients with palmar hyperhidrosis, myelinated nerve fiber density and single myelinated nerve fibers cross-sectional area were significantly increased as compared with controls (t = 7. 023,P < 0.05 ; t = 7.462, P < 0.05 respectively). The expression of BDNF and NRG-1 in 33 thoracic sympathetic trunk of patients with palmar hyperhidrosis was 1. 176 00 ± 0.028 70,1. 216 10± 0.075 39 respectively, and that in control group was 1. 037 50 ± 0.053 79,1. 042 70 ± 0.043 57 respectively. The former was significantly higher than the latter ( t = 9.940,P < 0.05 ; t = 6. 195. P < 0.05 respectively). Conclusion BDNF and NRG-I gene over expression increased myelinated nerve fiber density and single myelinated nerve fibers cross-sectional area of thoracic sympathetic trunk in patients with palmar hyperhidro-sis. Thus transmission speed and ability of excitatory of thoracic sympathetic nerve were also increased, which may play a role in the pathogenesis of palmar hyperhidrosis.%目的 观察手汗症患者胸交感神经干脑源性神经营养因子(BDNF)和神经调节因子-1(NRG-1)基因表达及对有髓神经纤维密度和单个纤维横截面积的影响,探讨与手汗症发病机制的关系.方法 采用核

  6. Malnutrition and myelin structure: an X-ray scattering study of rat sciatic and optic nerves

    Energy Technology Data Exchange (ETDEWEB)

    Vargas, V.; Vargas, R.; Marquez, G.; Vonasek, E.; Mateu, L. [Dept. de Biologia Estructural, Caracas (Venezuela); Luzzati, V. [Centre de Genetique Moleculaire, CNRS, Gif-sur-Yvette (France); Borges, J. [Servicio de Neurologia, Universidad Central de Venezuela, Caracas (Venezuela)

    2000-07-01

    Taking advantage of the fast and accurate X-ray scattering techniques recently developed in our laboratory, we tackled the study of the structural alterations induced in myelin by malnutrition. Our work was performed on sciatic and optic nerves dissected from rats fed with either a normal or a low-protein caloric diet, as a function of age (from birth to 60 days). By way of electrophysiological controls we also measured (on the sciatic nerves) the height and velocity of the compound action potential. Malnutrition was found to decrease the amount of myelin and to impair the packing order of the membranes in the sheaths. (orig.)

  7. Ultrastructural Alterations of Myelinated Fibers and Oligodendrocytes in the Prefrontal Cortex in Schizophrenia: A Postmortem Morphometric Study

    Directory of Open Access Journals (Sweden)

    Natalya A. Uranova

    2011-01-01

    Full Text Available Schizophrenia is believed to result from altered neuronal connectivity and impaired myelination. However, there are few direct evidence for myelin abnormalities in schizophrenia. We performed electron microscopic study of myelinated fibers and oligodendrocytes and morphometric study of myelinated fibers in the prefrontal cortex in gray and white matters in schizophrenia and normal controls. Six types of abnormal fibers and ultrastructural alterations of oligodendrocytes were found in schizophrenia. No significant group differences in area density of myelinated fibers were found. Frequency of pathological fibers was increased significantly in gray matter in young and elderly schizophrenia patients and in patients with predominantly positive symptoms. In contrast, in white matter, frequency of altered fibers was increased significantly in elderly patients, in patients with predominantly negative symptoms, and correlated with illness duration. Progressive alterations of myelinated fibers in white matter might be followed by alterations of myelinated fibers in gray matter in schizophrenia.

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

    Science.gov (United States)

    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.

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

    Institute of Scientific and Technical Information of China (English)

    Zahir Kzlay; Haydar Ali Erken; Nesibe Kahraman etin; Serdar Akta; Burin rem Abas; Ali Ylmaz

    2016-01-01

    hTe 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 atfer 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 signiifcantly 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 signiifcantly greater in group BAI than in group I. Moreover, myelin injury was signiifcantly milder and the intensity of nuclear factor kappa B immunostaining was signiifcantly weaker in group BAI than in group I. hTe results of this study show that administration of boric acid at 100 mg/kg atfer 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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Olree Kenneth S

    2006-07-01

    Full Text Available Abstract 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.

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

    Science.gov (United States)

    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.

  14. Regeneration of unmyelinated and myelinated sensory nerve fibres studied by a retrograde tracer method

    DEFF Research Database (Denmark)

    Lozeron, Pierre; Krarup, Christian; Schmalbruch, Henning

    2004-01-01

    to large neurons after crush and regeneration than in controls, indicating that regeneration of small neurons was less complete than that of large ones. This contrasted with the fact that unmyelinated axons in the regenerated sural nerve after 74 days were only slightly reduced....... of axons. Axonal counts do not reflect the number of regenerated neurons because of axonal branching and because myelinated axons form unmyelinated sprouts. Two days to 10 weeks after crushing, the distal sural or peroneal nerves were cut and exposed to fluoro-dextran. Large and small dorsal root ganglion...... cells that had been labelled, i.e., that had regenerated axons towards or beyond the injection site, were counted in serial sections. Large and small neurons with presumably myelinated and unmyelinated axons, respectively, were classified by immunostaining for neurofilaments. The axonal growth rate...

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  18. Anatomy of the retinal nerve fiber layer.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  1. GABA and its B-receptor are present at the node of Ranvier in a small population of sensory fibers, implicating a role in myelination

    DEFF Research Database (Denmark)

    Corell, Mikael; Wicher, Grzegorz; Radomska, Katarzyna J

    2015-01-01

    of the GABAB receptor, GABA, and glutamic acid decarboxylase GAD65/67 in both development and injury in fetal dissociated dorsal root ganglia (DRG) cell cultures and in the rat sciatic nerve. We found that GABA, GAD65/67, and the GABAB receptor were expressed in premyelinating and nonmyelinating Schwann cells...... throughout development and after injury. A small population of myelinated sensory fibers displayed all of these molecules at the node of Ranvier, indicating a role in axon-glia communication. Functional studies using GABAB receptor agonists and antagonists were performed in fetal DRG primary cultures...... to study the function of this receptor during development. The results show that GABA, via its B receptor, is involved in the myelination process but not in Schwann cell proliferation. The data from adult nerves suggest additional roles in axon-glia communication after injury....

  2. Effect of nerve growth factor on changes of myelin basic protein and functional repair of peripheral nerve following sciatic nerve injury in rats

    Institute of Scientific and Technical Information of China (English)

    邵阳; 马海涵; 伍亚民; 陈恒胜; 曾琳; 李民; 龙在云; 李应玉; 杨恒文

    2002-01-01

    To investigate the therapeutic effect of nerve growth factor ( NGF ) on changes of myelin basic protein (MBP) and functional repair of sensory and motor nerve following sciatic nerve injury. Methods: The sciatic nerves of rats were injured by sectioning with shaver, and divided into 3 groups: NGF group ( Group A ), group of normal saline solution ( Group B), untreated group (Group C). The time point of observation was at the 4th week after operation. Sensory evoked potential (SEP) and motor evoked potential (MEP) were detected by Model WD-4000 nerve potential working diagnosis system. Immunohistochemical analysis was used for identification of MBP. Results: The latency of SEP in the Group A at the 4th week after operation was shorter than that in the Group B ( P < 0.05). The MEP was elicited in 76 % of the Group A and was higher than that in the Group B. Results of immunohistochemistry showed that there were less MBP-positive cells in the Group A than in the Group B in one and four weeks respectively. Conclusions: NGF can improve the conductive function of injured peripheral nerve and facilitate regeneration of nerve.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  5. The Use of Fiber-Reinforced Scaffolds Cocultured with Schwann Cells and Vascular Endothelial Cells to Repair Rabbit Sciatic Nerve Defect with Vascularization

    Directory of Open Access Journals (Sweden)

    Hongyang Gao

    2013-01-01

    Full Text Available 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.

  6. Neurophysiological studies of thin myelinated (A delta) and unmyelinated (C) fibers: application to peripheral neuropathies.

    Science.gov (United States)

    Santiago, S; Ferrer, T; Espinosa, M L

    2000-02-01

    Dysfunction of small fibers may appear in isolation or associated with large fiber lesions. In some acute neuropathies, such as pandysautonomia, small-fiber impairment is relatively pure but it may also appear in disorders with prominent somatic damage, such as Guillain-Barré syndrome, in which autonomic failure worsens the prognosis. At the present time, chronic idiopathic distal small-fiber neuropathy is diagnosed more frequently, and in some prevalent disorders, such as diabetic or amyloidotic polyneuropathies, small-fiber dysfunction is very noticeable. In pure autonomic failure, a peripheral autonomic failure exists, distinguishing it from multiple-system atrophy. Complex regional pain syndrome is a severe condition in which small fibers are responsible for disabling signs and symptoms, and only instrumental recordings lead to the proper treatment. Standard neurophysiological techniques evaluate large myelinated fibers exclusively. Small-fiber polyneuropathy has been considered as a type of somatic neuropathy, but thin myelinated and unmyelinated fibers are responsible not only for temperature and pain perception but also autonomic function. For instance, full autonomic evaluation is needed in some clinical situations such as autonomic failure in the elderly or orthostatic intolerance syndrome. To evaluate small-fiber impairment we need a battery of sensitive, reproducible, specific and noninvasive tests covering somatic and autonomic systems. In this review, we describe and analyze a number of neurophysiological techniques used to diagnose and characterize small-fiber dysfunction in humans. These include cardiovascular monitoring, sudomotor testing, pupillary responses and quantitative sensory tests, and also to some extent thermography and laser evoked potentials. The use of such techniques has proven useful not only for diagnosis, but also to guide adequate therapy and optimize follow-up.

  7. Human intraretinal myelination: Axon diameters and axon/myelin thickness ratios

    Directory of Open Access Journals (Sweden)

    Thomas FitzGibbon

    2013-01-01

    Full Text Available Purpose: Human intraretinal myelination of ganglion cell axons occurs in about 1% of the population. We examined myelin thickness and axon diameter in human retinal specimens containing myelinated retinal ganglion cell axons. Materials and Methods: Two eyes containing myelinated patches were prepared for electron microscopy. Two areas were examined in one retina and five in the second retina. Measurements were compared to normal retinal and optic nerve samples and the rabbit retina, which normally contains myelinated axons. Measurements were made using a graphics tablet. Results: Mean axon diameter of myelinated axons at all locations were significantly larger than unmyelinated axons (P ≤ 0.01. Myelinated axons within the patches were significantly larger than axons within the optic nerve (P < 0.01. The relationship between axon diameter/fiber diameter (the G-ratio seen in the retinal sites differed from that in the nerve. G-ratios were higher and myelin thickness was positively correlated to axon diameter (P < 0.01 in the retina but negatively correlated to axon diameter in the nerve (P < 0.001. Conclusion: Intraretinally myelinated axons are larger than non-myelinated axons from the same population and suggests that glial cells can induce diameter changes in retinal axons that are not normally myelinated. This effect is more dramatic on intraretinal axons compared with the normal transition zone as axons enter the optic nerve and these changes are abnormal. Whether intraretinal myelin alters axonal conduction velocity or blocks axonal conduction remains to be clarified and these issues may have different clinical outcomes.

  8. 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.

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  11. Evidence for a intimate relationship between mast cells and nerve fibers in the tongue of the frog, Rana esculenta

    Energy Technology Data Exchange (ETDEWEB)

    Chieffi Baccari, Gabriella; Minucci, Sergio [Naples, II Univ. (Italy). Dipt. di Fisiologia Umana e Funzioni Biologiche Integrate `Filippo Bottazzi`

    1997-12-31

    Morphological and ultrastructural association of mast cells and nerve fibers were studied in the tongue of the frog Rana esculenta. The number of mast cells in the tongue (253 {+-} 45 / mm{sup 2}) is far the highest of the frog tissue as far as people know. They are distributed throughout the connective tissue among the muscular fibers, near arterioles and venules but predominantly in close association and within the nerves. They are often embedded in the endoneurium within a nerve bundle near to myelinic or unmyelinic fibers and in membrane-to-membrane contact with axonlike processes. Just for the richness of mast cells, the tongue of the frog could represent an useful model to study the relationship between these cells and the peripheral nervous system.

  12. Axonal plasticity elicits long-term changes in oligodendroglia and myelinated fibers

    DEFF Research Database (Denmark)

    Drøjdahl, Nina; Nielsen, Helle Hvilsted; Gardi, Jonathan E

    2010-01-01

    Axons are linked to induction of myelination during development and to the maintenance of myelin and myelinated tracts in the adult CNS. Currently, it is unknown whether and how axonal plasticity in adult CNS impacts the myelinating cells and their precursors. In this article, we report that newly...

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

    Science.gov (United States)

    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.

  14. Four-month enriched environment prevents myelinated fiber loss in the white matter during normal aging of male rats.

    Science.gov (United States)

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

    2015-01-01

    White matter degenerates with normal aging and accordingly results in declines in multiple brain functions. Previous neuroimaging studies have implied that the white matter is plastic by experiences and contributory to the experience-dependent recovery of brain functions. However, it is not clear how and how far enriched environment (EE) plays a role in the white matter remodeling. Male rats exhibit earlier and severer age-related damages in the white matter and its myelinated fibers than female rats; therefore, in this current study, 24 middle-aged (14-month-old) and 24 old-aged (24-month-old) male SD rats were randomly assigned to an EE or standard environment (SE) for 4 months prior to Morris water maze tests. Five rats from each group were then randomly sampled for stereological assessment of the white matter. Results revealed that EE could somewhat induce improvement of spatial learning and significantly increase the white matter volume, the myelinated fiber volume and the myelinated fiber length during normal aging. The EE-induced improvement of spatial learning ability was significantly correlated with the EE-induced increase of the white matter and its myelinated fibers. We suggested that exposure to an EE could delay the progress of age-related changes in the white matter and the effect could extend to old age.

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

    Science.gov (United States)

    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

  16. Prolonged myelination in human neocortical evolution.

    Science.gov (United States)

    Miller, Daniel J; Duka, Tetyana; Stimpson, Cheryl D; Schapiro, Steven J; Baze, Wallace B; McArthur, Mark J; Fobbs, Archibald J; Sousa, André M M; Sestan, Nenad; Wildman, Derek E; Lipovich, Leonard; Kuzawa, Christopher W; Hof, Patrick R; Sherwood, Chet C

    2012-10-09

    Nerve myelination facilitates saltatory action potential conduction and exhibits spatiotemporal variation during development associated with the acquisition of behavioral and cognitive maturity. Although human cognitive development is unique, it is not known whether the ontogenetic progression of myelination in the human neocortex is evolutionarily exceptional. In this study, we quantified myelinated axon fiber length density and the expression of myelin-related proteins throughout postnatal life in the somatosensory (areas 3b/3a/1/2), motor (area 4), frontopolar (prefrontal area 10), and visual (areas 17/18) neocortex of chimpanzees (N = 20) and humans (N = 33). Our examination revealed that neocortical myelination is developmentally protracted in humans compared with chimpanzees. In chimpanzees, the density of myelinated axons increased steadily until adult-like levels were achieved at approximately the time of sexual maturity. In contrast, humans displayed slower myelination during childhood, characterized by a delayed period of maturation that extended beyond late adolescence. This comparative research contributes evidence crucial to understanding the evolution of human cognition and behavior, which arises from the unfolding of nervous system development within the context of an enriched cultural environment. Perturbations of normal developmental processes and the decreased expression of myelin-related molecules have been related to psychiatric disorders such as schizophrenia. Thus, these species differences suggest that the human-specific shift in the timing of cortical maturation during adolescence may have implications for vulnerability to certain psychiatric disorders.

  17. Effect of acrylamide on the degeneration and regeneration of rat myelinated fiber after sciatic nerve crush injury%丙烯酰胺对小鼠坐骨神经捻挫损伤后有髓纤维变性和再生的影响

    Institute of Scientific and Technical Information of China (English)

    赫秋月; 韩漫夫; 饶明俐

    2005-01-01

    .OBJECTIVE: To observe the effect of acrylamide on the degeneration and regeneration of sciatic nerve medullated fibers following crush injury of C57BL/Ola (Ola) rat and C57BL/6J (6J) rat.DESIGN: Randomized controlled experiment.SETTING: Department of Neurology,Second People's hospital of Shenzhen; Department of Neurology of First hospital of Jilin University MATERIALS: This experiment was carried out in the neurological department in the University of Occupational and Environmental, Japan from January to June 1996. Twelve adult Ola rats and 6J rats were adopted and evenly randomly divided into experimental group and comparison group.METHODS: Rats were subjected to general anaesthesia, and then the proximal section of sciatic nerve was exposed and frustrated with hemostatic forceps for 10 s before suture. Rats in the experimental group were given intraperitoneal injection of acrylamide in a total dosage of 350 mg, which replaced by the same volume of physiological saline in comparison group.At 14 days after sciatic nerve torsion injury, all rats were anaesthetized again and the distal section of sciatic nerve was obtained and cut into slices, meanwhile the cross sectional area, the density and size frequency distribution of medullated fibers, as well as the number of medullated fibers in each nerve were determined.MAIN OUTCOME MEASURES: The density and size frequency distribution of sciatic nerve medullated fibers, as well as the number, the maximum diameter and the mean diameter of medullated fibers in two group of 0la rats and 6J rats.RESULTS: Totally 12 Ola rats and 6J rats entered the result analysis.① No Ola rat displayed Wallerian degeneration; But medullated fiber degeneration and following neonatal small diameter medullated fibers could be observed in 6J rats. ②In the experimental group, the total density of sciatic nerve medullated fibers in 6J rats was lower than that of Ola rat (P < 0.05) ;with the total number of medullated fibers in 6J rats also less than that

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

    Science.gov (United States)

    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.

  19. Neurophysiological approach to disorders of peripheral nerve

    DEFF Research Database (Denmark)

    Crone, Clarissa; Krarup, Christian

    2013-01-01

    Disorders of the peripheral nerve system (PNS) are heterogeneous and may involve motor fibers, sensory fibers, small myelinated and unmyelinated fibers and autonomic nerve fibers, with variable anatomical distribution (single nerves, several different nerves, symmetrical affection of all nerves...... methods including nerve conduction studies and electromyography used in the study of patients suspected of having a neuropathy and the significance of the findings are discussed in detail and more novel and experimental methods are mentioned. Diagnostic considerations are based on a flow chart classifying...

  20. The occurrence of IgM and complement factors along myelin sheaths of peripheral nerves An immunohistochemical study of the Guillain-Barre syndrome : Preliminary communication

    NARCIS (Netherlands)

    Luijten, J.A.F.M.; Baart de la Faille-Kuyper, E.H.

    In nerve biopsies from 4 of 6 patients with the Guillain-Barré syndrome (GBS), IgM and complement factors were found, probably localized along myelin sheaths. The possible significance of this phenomenon has been discussed. No such findings were obtained in control subjects.

  1. The occurrence of IgM and complement factors along myelin sheaths of peripheral nerves An immunohistochemical study of the Guillain-Barre syndrome : Preliminary communication

    NARCIS (Netherlands)

    Luijten, J.A.F.M.; Baart de la Faille-Kuyper, E.H.

    1972-01-01

    In nerve biopsies from 4 of 6 patients with the Guillain-Barré syndrome (GBS), IgM and complement factors were found, probably localized along myelin sheaths. The possible significance of this phenomenon has been discussed. No such findings were obtained in control subjects.

  2. The occurrence of IgM and complement factors along myelin sheaths of peripheral nerves An immunohistochemical study of the Guillain-Barre syndrome : Preliminary communication

    NARCIS (Netherlands)

    Luijten, J.A.F.M.; Baart de la Faille-Kuyper, E.H.

    1972-01-01

    In nerve biopsies from 4 of 6 patients with the Guillain-Barré syndrome (GBS), IgM and complement factors were found, probably localized along myelin sheaths. The possible significance of this phenomenon has been discussed. No such findings were obtained in control subjects.

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

    DEFF Research Database (Denmark)

    Moldovan, Mihai; Sørensen, Jesper; Krarup, Christian

    2006-01-01

    Functional outcome after peripheral nerve regeneration is often poor, particularly involving nerve injuries far from their targets. Comparison of sensory and motor axon regeneration before target reinnervation is not possible in the clinical setting, and previous experimental studies addressing...... the question of differences in growth rates of different nerve fibre populations led to conflicting results. We developed an animal model to compare growth and maturation of the fastest growing sensory and motor fibres within the same mixed nerve after Wallerian degeneration. Regeneration of cat tibial nerve...... after crush (n = 13) and section (n = 7) was monitored for up to 140 days, using implanted cuff electrodes placed around the sciatic and tibial nerves and wire electrodes at plantar muscles. To distinguish between sensory and motor fibres, recordings were carried out from L6-S2 spinal roots using cuff...

  4. Cholesterol and myelin biogenesis.

    Science.gov (United States)

    Saher, Gesine; Simons, Mikael

    2010-01-01

    Myelin consists of several layers of tightly compacted membranes wrapped around axons in the nervous system. The main function of myelin is to provide electrical insulation around the axon to ensure the rapid propagation of nerve conduction. As the myelinating glia terminally differentiates, they begin to produce myelin membranes on a remarkable scale. This membrane is unique in its composition being highly enriched in lipids, in particular galactosylceramide and cholesterol. In this review we will summarize the role of cholesterol in myelin biogenesis in the central and peripheral nervous system.

  5. Membrane properties in small cutaneous nerve fibers in humans

    DEFF Research Database (Denmark)

    Hennings, Kristian; Frahm, Ken Steffen; Petrini, Laura;

    2016-01-01

    than large fibers (rmANOVA, Bonferroni, P=0.006). CONCLUSION: This study is a reliable method to investigate the membrane properties of small cutaneous nerve fibers in humans and may be used in clinical settings as a diagnostic or profiling tool. This article is protected by copyright. All rights...

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    S Torabi

    2014-01-01

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

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

    Science.gov (United States)

    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.

  9. Remodeling of skin nerve fibers during burn wound healing

    Institute of Scientific and Technical Information of China (English)

    Yongqiang Feng; Xia Li; Rui Zhang; Yu Liu; Tingting Leng; Yibing Wang

    2010-01-01

    Burn wound healing involves a complex sequence of processes.Recent studies have revealed that skin reinnervation may have an impact on physiological wound repair.Few studies have addressed the process of reinnervation and morphological changes in regenerated nerve fibers.The regeneration of neurites during full-thickness burn wound healing was determined by immunofluorescent staining using an anti-neurofilament protein monoclonal antibody,and three-dimensional morphology was observed under a laser scanning confocal microscope.Morphology and the volume fraction of collagen and nerve fibers were measured.Skin reinnervation increased during wound healing,peaked during the proliferative scar stage,and then decreased to lower levels during the maturation period.The results from the skin nerve fibers correlated with those from collagen using semi-quantitative analysis.Disintegration and fragmentation were observed frequently in samples from the proliferative stage,and seldom occurred during the maturation stage.There was a remodeling process of regenerated nerve fibers during wound healing,which comprised changed innervation density and topical morphology.The mechanism of remodeling for nerve fibers requires further investigation.

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

    Science.gov (United States)

    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

  11. Normal centrolineal myelination of the callosal splenium reflects the development of the cortical origin and size of its commissural fibers

    Energy Technology Data Exchange (ETDEWEB)

    Whitehead, Matthew T. [University of Tennessee Health Science Center, Department of Radiology, Memphis, TN (United States); Le Bonheur Children' s Hospital, Le Bonheur Neuroscience Institute, Memphis, TN (United States); Children' s National Medical Center, Department of Radiology, Washington, DC (United States); Raju, Anand; Choudhri, Asim F. [University of Tennessee Health Science Center, Department of Radiology, Memphis, TN (United States); Le Bonheur Children' s Hospital, Le Bonheur Neuroscience Institute, Memphis, TN (United States)

    2014-04-15

    Commissural white matter fibers comprising the callosal splenium are diverse. Subsections of the splenium myelinate at different times, in a centrolineal manner. The aims of this study are to depict the normal callosal splenium myelination pattern and to distinguish the transient age-related mid splenium hypointensity from pathology. We reviewed 131 consecutive brain MRIs in patients between ages 3 and 6 months from a single academic children's hospital. Patients that were preterm, hydrocephalic, and/or had volume loss were excluded. Fifty total MR exams that included T1-weighted MR imaging (T1WI), T2-weighted MR imaging (T2WI), and diffusion tensor imaging (DTI) were reviewed. Regions of callosal splenium myelination manifested by T1 and T2 shortening were evaluated. Tractography was performed with seeds placed over the posterior, mid, and anterior splenium to define the origin, destination, and course of traversing fibers. Splenium signal varied significantly from 3 to 6 months, with distinct age-related trends. On T1WI, the splenium was hypointense at 3 months (12/13), centrally hypointense/peripherally hyperintense at 4 months (15/16), and hyperintense at 6 months (10/11). Tractography revealed three distinct white matter tract populations: medial occipital (posterior); precuneus, posterior cingulate, and medial temporal (middle); and postcentral gyri (anterior). Specific commissural fiber components of the splenium myelinate at different times. The transient developmental mid splenium hypointensity on T1WI corresponds to tracts from the associative cortex, principally the precuneus. Heterogeneous splenium signal alteration in patients ages 3-6 months is a normal developmental phenomenon that should not be confused with pathologic lesions. (orig.)

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  14. Effects of normal aging on myelin sheath ultrastructures in the somatic sensorimotor system of rats.

    Science.gov (United States)

    Xie, Fang; Liang, Ping; Fu, Han; Zhang, Jiu-Cong; Chen, Jun

    2014-07-01

    Previous studies have presented qualitative and quantitative data regarding the morphological changes that occur peripherally in myelin sheaths and nerve fibers of rats during their lifespan. However, studies on ultrastructural features of myelinated fibers (MFs) in the central nervous system (CNS) remain limited. In the present study, morphological analyses of the somatic sensorimotor MFs in rats at time‑points between postnatal day 14 and postnatal month (PNM) 26 were conducted using electron microscopy. Significant alterations in the myelin sheath were observed in the sensorimotor system of aging and aged rats, which became aggravated with age. The ultrastructural pattern of myelin lamellae also exhibited age dependence. The transformation of the myelin intraperiod line from complete to incomplete fusion occurred after PNM 5, leading to an expansion of periodicity in myelin lamellae. These pathological changes in the myelin structure occurred very early and showed a significant correlation with age, indicating that myelin was the part of the CNS with the highest susceptibility to the influence of aging, and may be the main target of aging effects. In addition to the myelin breakdown, continued myelin production and remyelination were observed in the aging sensorimotor system, suggesting the presence of endogenous mechanisms of myelin repair.

  15. Epidermal Nerve Fiber Quantification in the Assessment of Diabetic Neuropathy

    Science.gov (United States)

    Beiswenger, Kristina K.; Calcutt, Nigel A.; Mizisin, Andrew P.

    2008-01-01

    Summary Assessment of cutaneous innervation in skin biopsies is emerging as a valuable means of both diagnosing and staging diabetic neuropathy. Immunolabeling, using antibodies to neuronal proteins such as protein gene product 9.5, allows for the visualization and quantification of intraepidermal nerve fibers. Multiple studies have shown reductions in intraepidermal nerve fiber density in skin biopsies from patients with both type 1 and type 2 diabetes. More recent studies have focused on correlating these changes with other measures of diabetic neuropathy. A loss of epidermal innervation similar to that observed in diabetic patients has been observed in rodent models of both type 1 and type 2 diabetes and several therapeutics have been reported to prevent reductions in intraepidermal nerve fiber density in these models. This review discusses the current literature describing diabetes-induced changes in cutaneous innervation in both human and animal models of diabetic neuropathy. PMID:18384843

  16. Simultaneous Quantification of Unmyelinated Nerve Fibers in Sural Nerve and in Skin.

    Science.gov (United States)

    Duchesne, Mathilde; Magy, Laurent; Richard, Laurence; Ingrand, Pierre; Neau, Jean-Philippe; Mathis, Stéphane; Vallat, Jean-Michel

    2016-01-01

    Peripheral polyneuropathies are common and their diagnosis may be challenging. We compared the results from sural-nerve and skin biopsies in 33 patients with a polyneuropathy and neuropathic pain examined in our hospital over a 6-year period. The biopsies were all from the same lower limb of each patient. Intraepidermal nerve fiber (IENF) densities in the skin were determined by fluorescence microscopy; unmyelinated fiber densities in sural-nerve biopsies (UFNB) were determined by electron microscopy. There was no correlation with age or gender in either biopsy type; there was a weak trend to correlation between UFNB density and IENF density, possibly because of the small sample size. The sensitivity of detection of quantitative abnormalities of unmyelinated fibers was better in the skin than in the nerves. Proximal and distal IENF densities were strongly correlated; and counts of UFNB were highly reproducible. Thus, quantification of unmyelinated fibers in sural-nerve and skin biopsies seem to be complementary. Sural-nerve biopsy may be required to confirm a specific diagnosis, to identify lesion mechanisms, and to devise therapeutic strategies, whereas skin biopsy seems to be more efficient in the follow-up of length-dependent polyneuropathies and in the diagnosis of neuropathic pain.

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

    Directory of Open Access Journals (Sweden)

    Anneke van der Walt

    Full Text Available 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.

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

    Science.gov (United States)

    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.

  19. Peptide mimetic of the S100A4 protein modulates peripheral nerve regeneration and attenuates the progression of neuropathy in myelin protein P0 null mice

    DEFF Research Database (Denmark)

    Moldovan, Mihai; Pinchenko, Volodymyr; Dmytriyeva, Oksana

    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 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...

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

    Science.gov (United States)

    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

  1. Spatial clustering analysis in neuroanatomy: Applications of different approaches to motor nerve fiber distribution

    NARCIS (Netherlands)

    Prodanov, Dimiter; Nagelkerke, Nico; Marani, Enrico; Crunelli, V.

    2007-01-01

    Spatial organization of the nerve fibers in the peripheral nerves may be important for the studies of axonal regeneration, the degenerative nerve diseases and the construction of interfaces with peripheral nerves, such as nerve prostheses. Functional topography of motor axons related to the gastrocn

  2. Combination of acellular nerve graft and schwann cells-like cells for rat sciatic nerve regeneration.

    Science.gov (United States)

    Gao, Songtao; Zheng, Yan; Cai, Qiqing; Deng, Zhansheng; Yao, Weitao; Wang, Jiaqiang; Wang, Xin; Zhang, Peng

    2014-01-01

    To investigate the effect of tissue engineering nerve on repair of rat sciatic nerve defect. Forty-five rats with defective sciatic nerve were randomly divided into three groups. Rats in group A were repaired by acellular nerve grafts only. Rats in group B were repaired by tissue engineering nerve. In group C, rats were repaired by autogenous nerve grafts. After six and twelve weeks, sciatic nerve functional index (SFI), neural electrophysiology (NEP), histological and transmission electron microscope observation, recovery ratio of wet weight of gastrocnemius muscle, regenerated myelinated nerve fibers number, nerve fiber diameter, and thickness of the myelin sheath were measured to assess the effect. After six and twelve weeks, the recovery ratio of SFI and wet weight of gastrocnemius muscle, NEP, and the result of regenerated myelinated nerve fibers in groups B and C were superior to that of group A (P 0.05). The tissue engineering nerve composed of acellular allogenic nerve scaffold and Schwann cells-like cells can effectively repair the nerve defect in rats and its effect was similar to that of the autogenous nerve grafts.

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

    Science.gov (United States)

    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. Copyright © 2016. Published by Elsevier Inc.

  4. Gap junction disorders of myelinating cells.

    Science.gov (United States)

    Kleopa, Kleopas A; Orthmann-Murphy, Jennifer; Sargiannidou, Irene

    2010-01-01

    Gap junctions (GJs) are channels that allow the diffusion of ions and small molecules across apposed cell membranes. In peripheral nerves, Schwann cells express the GJ proteins connexin32 (Cx32) and Cx29, which have distinct localizations. Cx32 forms GJs through non-compact myelin areas, whereas Cx29 forms hemichannels in the innermost layers of myelin apposing axonal Shaker-type K+ channels. In the CNS, rodent oligodendrocytes express Cx47, Cx32 and Cx29. Cx47 is expressed by all types of oligodendrocytes both in the white and grey matter and forms GJs on cell bodies and proximal processes, as well as most of the intercellular channels with astrocytes. Cx32 is expressed mostly by white matter oligodendrocytes and is localized in the myelin sheath of large diameter fibers. Cx29, and its human ortholog Cx31.3, appear to be restricted to oligodendrocytes that myelinate small caliber fibers, likely forming hemichannels. The importance of intercellular and intracellular GJs in myelinating cells are demonstrated by human disorders resulting from mutations affecting GJ proteins. The X-linked Charcot Marie Tooth disease (CMT1X) is caused by hundreds of mutations affecting Cx32. Patients with CMT1X present mainly with a progressive peripheral neuropathy, which may be accompanied by CNS myelin dysfunction. Mutations in Cx47 may cause a devastating leukodystrophy called Pelizaeus-Merzbacher-like disease or a milder spastic paraplegia. In addition, CNS demyelination may be caused by defects in genes expressing astrocytic GJ proteins, which are essential for oligodendrocytes. Findings from in vitro and in vivo models of these disorders developed over the last decade indicate that most mutations cause loss of function and an inability of the mutant connexins to form functional GJs. Here we review the clinical, genetic, and neurobiological aspects of GJ disorders affecting the PNS and CNS myelinating cells.

  5. Altered sciatic nerve fiber morphology and endoneural microvessels in mouse models relevant for obesity, peripheral diabetic polyneuropathy, and the metabolic syndrome.

    Science.gov (United States)

    Nowicki, Marcin; Kosacka, Joanna; Serke, Heike; Blüher, Matthias; Spanel-Borowski, Katharina

    2012-01-01

    The morphology of sciatic nerves from leptin-deficient ob/ob mice and leptin receptor-deficient db/db mice, both models for obesity, peripheral diabetic neuropathy, and the metabolic syndrome, has yet to be examined for changes in nerve fibers and in endoneural microvessels. Sciatic nerves from three groups of 4-month-old mice (WT C57BL6, ob/ob, and db/db) were investigated. In ultrathin sections, the thickness of myelin sheaths was significantly reduced in small, medium-sized, and large axons of db/db mice compared with WT mice. In ob/ob mice, only large fibers showed a decrease in myelin sheath thickness. The number of nonmyelinated nerve fibers was lower in ob/ob mice than in the db/db group. A thickened basal lamina of Schwann cells occurred in the ob/ob group only. In contrast, the basement membrane of endoneural microvessels was thickened in both obese groups. For this reason, laminin expression in Western blot analysis was lower in the db/db group than in the ob/ob one. Endoneural microvessels, which had been injected with fluorescein isothiocyanate, depicted signs of vasodilatation in the ob/ob and vasoconstriction in db/db mice. Endoneural vessels displayed two receptors of oxLDL. LOX-1 was strongly expressed in db/db mice, whereas TLR4 was at its maximum in the ob/ob group. We conclude that changes in nerve fibers and in endoneural microvessels are present in sciatic nerve of both mouse models of type 2 diabetes. Upregulation of oxLDL-dependent receptors in endoneural microvessels might be connected to different degrees of oxidative stress in severe diabetic db/db mice and in the mild diabetic ob/ob group.

  6. Neurotrophic Modulation of Myelinated Cutaneous Innervation and Mechanical Sensory Loss in Diabetic Mice

    Science.gov (United States)

    Christianson, Julie A.; Ryals, Janelle M.; Johnson, Megan S.; Dobrowsky, Rick T.; Wright, Douglas E.

    2007-01-01

    Human diabetic patients often lose touch and vibratory sensations, but to date, most studies on diabetes-induced sensory nerve degeneration have focused on epidermal C-fibers. Here, we explored the effects of diabetes on cutaneous myelinated fibers in relation to the behavioral responses to tactile stimuli from diabetic mice. Weekly behavioral testing began prior to STZ administration and continued until 8 weeks, at which time myelinated fiber innervation was examined in the footpad by immunohistochemistry using antiserum to NF-H and MBP. Diabetic mice developed reduced behavioral responses to non-noxious (monofilaments) and noxious (pin prick) stimuli. In addition, diabetic mice displayed a 50% reduction in NF-H-positive myelinated innervation of the dermal footpad compared to non-diabetic mice. To test whether two neurotrophins NGF and/or NT-3 known to support myelinated cutaneous fibers could influence myelinated innervation, diabetic mice were treated intrathecally for two weeks with NGF, NT-3, NGF and NT-3. Neurotrophin-treated mice were then compared to diabetic mice treated with insulin for two weeks. NGF and insulin treatment both increased paw withdrawal to mechanical stimulation in diabetic mice, whereas NT-3 or a combination of NGF and NT-3 failed to alter paw withdrawal responses. Surprisingly, all treatments significantly increased myelinated innervation compared to control-treated diabetic mice, demonstrating that myelinated cutaneous fibers damaged by hyperglycemia respond to intrathecal administration of neurotrophins. Moreover, NT-3 treatment increased epidermal Merkel cell numbers associated with nerve fibers, consistent with increased numbers of NT-3-responsive slowly adapting A-fibers. These studies suggest that myelinated fiber loss may contribute as significantly as unmyelinated epidermal loss in diabetic neuropathy, and the contradiction between neurotrophin-induced increases in dermal innervation and behavior emphasize the need for multiple

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

    Science.gov (United States)

    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 4 microns. Our results indicated that small and large calibre fibres may have different myelin sheath diameter-internodal length interrelations.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  11. Histological observation on acellular nerve grafts co-cultured with Schwann cells for repairing defects of the sciatic nerve

    Institute of Scientific and Technical Information of China (English)

    Xiaohong Sun; Jiangyi Tian; Xiaojie Tong; Xu Zhang; Zheng He

    2006-01-01

    BACKGROUND: Animal experiments and clinical studies about tissue engineering method applied to repair nerve injury mainly focus on seeking ideal artificial nerve grafts, nerve conduit and seed cells. Autologous nerve, allogeneic nerve and xenogeneic nerve are used to bridge nerve defects, it is one of the methods to promote the repair of nerve injury by culturing and growing Schwann cells, which can secrete various neurotrophic factor activities, in the grafts.OBJECTIVE: To observe the effect of acellular nerve grafts co-cultured with Schwann cells in repairing defects of sciatic nerve.DESIGN: An observational comparative study.SETTING: Tissue Engineering Laboratory of China Medical University.MATERIALS: The experiment was carried out in the Tissue Engineering Laboratory of China Medical University between April 2004 and April 2005. Forty neonatal Sprague-Dawley rats of 5-8 days (either males or females) and 24 male Wistar rats of 180-220 g were provided by the experimental animal center of China Medical University.METHODS: ① Culture of Schwann cells: The bilateral sciatic nerves and branchial plexus were isolated from the 40 neonatal SD rats. The sciatic nerves were enzymatically digested with collagenase and dispase, isolatd, purified and cultured with the method of speed-difference adhersion, and identified with the SABC immunohistochemical method. ② Model establishment: In vitro Schwann cells were microinjected into 10-mm long acellular nerve grafts repairing a surgically created gap in the rat sciatic nerve.According to the different grafted methods, the animals were randomly divided into three groups: autografts (n=8), acellular nerve grafts (n=8), or acellular nerve grafts with Schwann cells (n=8). ③ The regenerated nerve fiber number and average diameter of myeline sheath after culture were statistically anlayzed.MAIN OUTCOME MEASURES: ① The regenerated nerve ultrastructure, total number and density of myelinated nerve fibers, and the thickness of

  12. Responses of intact and injured sural nerve fibers to cooling and menthol.

    Science.gov (United States)

    Teliban, Alina; Bartsch, Fabian; Struck, Marek; Baron, Ralf; Jänig, Wilfrid

    2014-05-01

    Intact and injured cutaneous C-fibers in the rat sural nerve are cold sensitive, heat sensitive, and/or mechanosensitive. Cold-sensitive fibers are either low-threshold type 1 cold sensitive or high-threshold type 2 cold sensitive. The hypothesis was tested, in intact and injured afferent nerve fibers, that low-threshold cold-sensitive afferent nerve fibers are activated by the transient receptor potential melastatin 8 (TRPM8) agonist menthol, whereas high-threshold cold-sensitive C-fibers and cold-insensitive afferent nerve fibers are menthol insensitive. In anesthetized rats, activity was recorded from afferent nerve fibers in strands isolated from the sural nerve, which was either intact or crushed 6-12 days before the experiment distal to the recording site. In all, 77 functionally identified afferent C-fibers (30 intact fibers, 47 injured fibers) and 34 functionally characterized A-fibers (11 intact fibers, 23 injured fibers) were tested for their responses to menthol applied to their receptive fields either in the skin (10 or 20%) or in the nerve (4 or 8 mM). Menthol activated all intact (n = 12) and 90% of injured (n = 20/22) type 1 cold-sensitive C-fibers; it activated no intact type 2 cold-sensitive C-fibers (n = 7) and 1/11 injured type 2 cold-sensitive C-fibers. Neither intact nor injured heat- and/or mechanosensitive cold-insensitive C-fibers (n = 25) and almost no A-fibers (n = 2/34) were activated by menthol. These results strongly argue that cutaneous type 1 cold-sensitive afferent fibers are nonnociceptive cold fibers that use the TRPM8 transduction channel.

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

    Science.gov (United States)

    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

  14. Biological conduit small gap sleeve bridging method for peripheral nerve injury: regeneration law of nerve fibers in the conduit

    Directory of Open Access Journals (Sweden)

    Pei-xun Zhang

    2015-01-01

    Full Text Available The clinical effects of 2-mm small gap sleeve bridging of the biological conduit to repair peripheral nerve injury are better than in the traditional epineurium suture, so it is possible to replace the epineurium suture in the treatment of peripheral nerve injury. This study sought to identify the regeneration law of nerve fibers in the biological conduit. A nerve regeneration chamber was constructed in models of sciatic nerve injury using 2-mm small gap sleeve bridging of a biodegradable biological conduit. The results showed that the biological conduit had good histocompatibility. Tissue and cell apoptosis in the conduit apparently lessened, and regenerating nerve fibers were common. The degeneration regeneration law of Schwann cells and axons in the conduit was quite different from that in traditional epineurium suture. During the prime period for nerve fiber regeneration (2-8 weeks, the number of Schwann cells and nerve fibers was higher in both proximal and distal ends, and the effects of the small gap sleeve bridging method were better than those of the traditional epineurium suture. The above results provide an objective and reliable theoretical basis for the clinical application of the biological conduit small gap sleeve bridging method to repair peripheral nerve injury.

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

    Science.gov (United States)

    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

  16. Internal-specific morphological analysis of sciatic nerve fibers in a radiofrequency-induced animal neuropathic pain model.

    Directory of Open Access Journals (Sweden)

    Samjin Choi

    Full Text Available This study investigated the reversible effects of pulsed radiofrequency (PRF treatment at 42 °C on the ultrastructural and biological changes in nerve and collagen fibers in the progression of neuropathic pain after rat sciatic nerve injury. Assessments of morphological changes in the extracellular matrices by atomic force microscopy and hematoxylin-eosin, Masson's trichrome and picrosirius-red staining as well as the expressions of two fibril-forming collagens, types-I and -III, and two inflammatory cytokines, TNF-α and IL-6, were evaluated on day 30 after RF exposure. There were four groups for different RF thermal treatments: no treatment, no current, PRF, and continuous RF (CRF. An RF procedure similar to that used in human clinical trials was used in this study. The CRF treatment at 82 °C led to neural and collagen damage by the permanent blockage of sensory nociceptors. The PRF treatment led to excellent performance and high expandability compared to CRF, with effects including slight damage and swelling of myelinated axons, a slightly decreased amount of collagen fibers, swelling of collagen fibril diameters, decreased immunoreactivity of collagen types-I and -III, presence of newly synthesized collagen, and recovery of inflammatory protein immunoreactivity. These evidence-based findings suggest that PRF-based pain relief is responsible for the temporary blockage of nerve signals as well as the preferential destruction of pain-related principal sensory fibers like the Aδ and C fibers. This suggestion can be supported by the interaction between the PRF-induced electromagnetic field and cell membranes; therefore, PRF treatment provides pain relief while allowing retention of some tactile sensation.

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

    Directory of Open Access Journals (Sweden)

    Koji Miki

    Full Text Available 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.

  18. Peripheral origins and functional characteristics of vibration-sensitive VIIIth nerve fibers in the frog Rana temporaria

    DEFF Research Database (Denmark)

    Jøgensen, Morten Buhl; Christensen-Dalsgaard, Jakob

    1991-01-01

    1) The peripheral origins of vibration-sensitive VIIIth nerve fibers in European grassfrogs (Rana temporaria) were investigated by recording from individual nerve branchlets within the inner ear. Furthermore, the fibers' responses to both pulsed and continuous, dorsoventral, sinusoidal vibrations...

  19. Myelin regeneration: a recapitulation of development?

    Science.gov (United States)

    Fancy, Stephen P J; Chan, Jonah R; Baranzini, Sergio E; Franklin, Robin J M; Rowitch, David H

    2011-01-01

    The developmental process of myelination and the adult regenerative process of remyelination share the common objective of investing nerve axons with myelin sheaths. A central question in myelin biology is the extent to which the mechanisms of these two processes are conserved, a concept encapsulated in the recapitulation hypothesis of remyelination. This question also has relevance for translating myelin biology into a better understanding of and eventual treatments for human myelin disorders. Here we review the current evidence for the recapitulation hypothesis and discuss recent findings in the development and regeneration of myelin in the context of human neurological disease.

  20. Response of feline intradental nerve fibers to tooth cutting by Er:YAG laser.

    Science.gov (United States)

    Chaiyavej, S; Yamamoto, H; Takeda, A; Suda, H

    2000-01-01

    The aim of this study was to investigate the response of intradental A- and C-fibers during tooth cutting by Er:YAG laser. Bipolar electrical stimulation was applied to the cat's canine to identify functional single nerve fibers of the inferior alveolar nerve. The tip of the canine tooth was cut in 0.5-mm steps until the pulp was exposed. Teeth were alternately cut by using Er:YAG laser (50 mJ, 5 pps) and micromotor under water cooling. The nerve response recorded from the single nerve fibers during laser cutting was compared with that during micromotor cutting. All 26 A-fibers responded to laser cutting with high frequency of nerve firings. The nerve firing rate was significantly higher during laser cutting compared with that during micromotor cutting of superficial dentin (Chi(2) test, P or = 0. 05). Nine of 11 C-fibers responded to laser cutting when the deep dentin was cut. Among those nine nerve fibers, three also showed a low frequency response to laser cutting of the superficial dentin. During the tooth cutting, Er:YAG laser was more effective in activating intradental A-fibers compared with micromotor and also caused the activation of intradental C-fibers. Copyright 2000 Wiley-Liss, Inc.

  1. Regenerating nerve fiber innervation of extraocular muscles and motor functional changes following oculomotor nerve injuries at different sites

    Institute of Scientific and Technical Information of China (English)

    Wenchuan Zhang; Massimiliano Visocchi; Eduardo Fernandez; Xuhui Wang; Xinyuan Li; Shiting Li

    2011-01-01

    In the present study, the oculomotor nerves were sectioned at the proximal (subtentorial) and distal (superior orbital fissure) ends and repaired. After 24 weeks, vestibulo-ocular reflex evaluation confirmed that the regenerating nerve fibers following oculomotor nerve injury in the superior orbital fissure had a high level of specificity for innervating extraocular muscles. The level of functional recovery of extraocular muscles in rats in the superior orbital fissure injury group was remarkably superior over that in rats undergoing oculomotor nerve injuries at the proximal end (subtentorium). Horseradish peroxidase retrograde tracing through the right superior rectus muscle showed that the distribution of neurons in the nucleus of the oculomotor nerve was directly associated with the injury site, and that crude fibers were badly damaged. The closer the site of injury of the oculomotor nerve was to the extraocular muscle, the better the recovery of neurological function was. The mechanism may be associated with the aberrant number of regenerated nerve fibers passing through the injury site.

  2. Cholesterol: a novel regulatory role in myelin formation.

    Science.gov (United States)

    Saher, Gesine; Quintes, Susanne; Nave, Klaus-Armin

    2011-02-01

    Myelin consists of tightly compacted membranes that form an insulating sheath around axons. The function of myelin for rapid saltatory nerve conduction is dependent on its unique composition, highly enriched in glycosphingolipids and cholesterol. Cholesterol emerged as the only integral myelin component that is essential and rate limiting for the development of CNS and PNS myelin. Experiments with conditional mouse mutants that lack cholesterol biosynthesis in oligodendrocytes revealed that only minimal changes of the CNS myelin lipid composition are tolerated. In Schwann cells of the PNS, protein trafficking and myelin compaction depend on cholesterol. In this review, the authors summarize the role of cholesterol in myelin biogenesis and myelin disease.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  5. Morphometry of Axons in Optic Nerves of Siamese's Twins

    Institute of Scientific and Technical Information of China (English)

    Xinzu Gu; Zhenping Zhang; Qi Lin; Jiongji Liang; Wenyu Lu; Xiulan Ye; A A Sadun

    2002-01-01

    Purpose: To observe the development of optic nerve, we examined four optic nerves from Siameses Twins by absolute counts of axons.Methods: Mean axon diameter, mean axon density, totally axonal population and optic nerve area were noted for each optic nerve. The mean axon diameter and the mean axon density were compared between paraxial (inner sectors)and cortical (outer sectors)areas of the nerves.Results: More myelinated axons were seen in the inner sectors as compared to the outer sectors(average 11 axons/1 000 μm2 in inner sectors and 34 axons/l 000 μm2 in outer sectors( P=0. 036) . The myelinated fibers were also smaller(63 microns) in the outer sectors as compared to the inner sectors(72 microns) ( P = 0. 001 ). The average cross sectors area for the four 40 week stage optical nerves of Siamese Twins was 3.32 × 103 as compared to 1 million axons for 32-week-old normals.Conclusion: Our finding of fewer axonal number and small myelinated fibers in the Siamese Twins suggests hypoplasia. Myelination was more abnormal in the paraxial optic nerve than that in the peripheral sectors, suggesting anomalous development of optic nerve peripherally and delayed developnent centrally. Axonal density is higher in inner sectors than that in outer sectors, suggesting delayed development of the outer nerve sector.

  6. Simulation of Myelinated Nerve Conduction Block Induced by Electrical Stimulus of Monopolar and Bipolar Electrodes%不同电极电刺激对有髓神经传导阻断影响的仿真研究

    Institute of Scientific and Technical Information of China (English)

    孙晨; 张旭; 任朝晖; 董谦; 崔南

    2011-01-01

    目的 比较双电极双向脉冲刺激和单电极双向脉冲刺激在神经纤维传导阻断中的阻断阈值以及对神经纤维的损伤,并通过该研究为电刺激促进脊髓损伤后下尿路功能重建的动物实验选择最优的刺激模式.方法 以有限长单根有髓神经为研究对象,以两栖动物的有髓神经纤维FrankenhaeuserHuxley(F-H)模型为仿真研究基础.结果 比较了单、双电极在双向对称方波以及双向间歇方波作用下的阻断阈值以及单双电极在同样的刺激条件下(包括刺激波形、频率以及电流强度)产生的离子电流强度大小.结论 双电极的阻断阈值大于单电极的阻断阈值.在相同的刺激条件下,双电极双向脉冲刺激对神经的损伤程度小于单电极双向脉冲刺激.%To compare the thresholds and the degrees of axonal injury caused by the impulse stimulations of monopolar and bipolar electrodes in simulation study of nerve conduction block. This study aimed to find an optimal stimulus pattern for the animal experiment of restoring the normal function of lower urinary tract after spinal cord injury through electrical stimulation. We used the myelinated nerve fiber with limited length as the research object, and the Frankenhaeuser-Huxley ( F - H) model for mammal' s marrow nerve fiber as the basic system. We simulated the symmetry biphasic pulses and intermittent biphasic pulses to compare the block threshold and ionic current intensity generated by monopolar and bipolar electrodes. The simulating results indicated that the conduction block threshold induced by bipolar electrode is higher than that of monopolar electrode, and monopolar electrode caused greater damage to the axon when the other situations were same.

  7. Retinal nerve fiber layer thickness is associated with lesion length in acute optic neuritis

    DEFF Research Database (Denmark)

    Kallenbach, K; Simonsen, Helle Juhl; Sander, B

    2010-01-01

    included 41 patients with unilateral optic neuritis and 19 healthy volunteers. All patients were evaluated and examined within 28 days of onset of symptoms. The peripapillary retinal nerve fiber layer thickness (RNFLT), an objective quantitative measure of optic nerve head edema, was measured by optical...... coherence tomography and the length and location of the inflammatory optic nerve lesion were evaluated using MRI. RESULTS: Ophthalmoscopically, 34% of the patients had papillitis. The retinal nerve fiber layer in affected eyes (mean 123.1 microm) was higher during the acute phase than that of fellow eyes...... (mean 98.1 microm, p eyes (mean 97.1 microm, p

  8. Automatic morphometry of nerve histological sections.

    Science.gov (United States)

    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.

  9. Comparison of Morphometric Aspects of Light and Electron Microscopy of the Hypoglossal Nerve between Young and Aged Male Wistar Rats

    Directory of Open Access Journals (Sweden)

    Mohsen Pourghasem

    2012-01-01

    Full Text Available Objective: Age-related changes occur in many different systems of the body. Many elderlypeople show dysphagia and dysphonia. This research was conducted to evaluatequantitatively the morphometrical changes of the hypoglossal nerve resulting from theaging process in young and aged rats.Materials and Methods: Through an experimental study ten male wistar rats (4 months: 5rats, 24 months: 5 rats were selected randomly from a colony of wistars in the UWC. Aftera fixation process and preparation of samples of the cervical portion of the hypoglossalnerve of these rats, light and electron microscopic imaging were performed. These imageswere evaluated according to the numbers and size of myelinated nerve fibers, nucleoli ofSchwann cells, myelin sheath thickness, axon diameter, and g ratio. All data were analyzedby Mann-Whitney, a non-parametric statistical test.Results: In light microscope, numbers of myelinated nerve fibers, the mean entire nerveperimeters, the mean entire nerve areas and the mean entire nerve diameters in youngand aged rats’ were not significantly different between the two groups.In electron microscope, numbers of myelinated axons, numbers of Schwann cell nucleoliand the mean g ratios of myelinated axon to Schwann cell in young and aged rats werenot significantly different. The myelinated fiber diameters, the myelin sheath thicknesses,myelinated axon diameters and the mean g ratio of axon diameter to myelinated fiberdiameter in young and aged fibers were significantly differentConclusion: The mean g ratio of myelinated nerve fibers of peripheral nerves stabilizes atthe level of 0.6 after maturation and persists without major change during adulthood. Thisratio of axon diameter to fiber diameter (0.6 is optimum for normal conduction velocity ofneural impulses. Our study indicated that the g ratio of myelinated nerve fiber of the hypoglossalnerve decreased prominently in aged rats and can be a cause of impairment innerve function in

  10. Myelin organization in the nodal, paranodal, and juxtaparanodal regions revealed by scanning x-ray microdiffraction.

    Directory of Open Access Journals (Sweden)

    Hideyo Inouye

    Full Text Available X-ray diffraction has provided extensive information about the arrangement of lipids and proteins in multilamellar myelin. This information has been limited to the abundant inter-nodal regions of the sheath because these regions dominate the scattering when x-ray beams of 100 µm diameter or more are used. Here, we used a 1 µm beam, raster-scanned across a single nerve fiber, to obtain detailed information about the molecular architecture in the nodal, paranodal, and juxtaparanodal regions. Orientation of the lamellar membrane stacks and membrane periodicity varied spatially. In the juxtaparanode-internode, 198-202 Å-period membrane arrays oriented normal to the nerve fiber axis predominated, whereas in the paranode-node, 205-208 Å-period arrays oriented along the fiber direction predominated. In parts of the sheath distal to the node, multiple sets of lamellar reflections were observed at angles to one another, suggesting that the myelin multilayers are deformed at the Schmidt-Lanterman incisures. The calculated electron density of myelin in the different regions exhibited membrane bilayer profiles with varied electron densities at the polar head groups, likely due to different amounts of major myelin proteins (P0 glycoprotein and myelin basic protein. Scattering from the center of the nerve fibers, where the x-rays are incident en face (perpendicular to the membrane planes, provided information about the lateral distribution of protein. By underscoring the heterogeneity of membrane packing, microdiffraction analysis suggests a powerful new strategy for understanding the underlying molecular foundation of a broad spectrum of myelinopathies dependent on local specializations of myelin structure in both the PNS and CNS.

  11. Myelin organization in the nodal, paranodal, and juxtaparanodal regions revealed by scanning x-ray microdiffraction.

    Science.gov (United States)

    Inouye, Hideyo; Liu, Jiliang; Makowski, Lee; Palmisano, Marilena; Burghammer, Manfred; Riekel, Christian; Kirschner, Daniel A

    2014-01-01

    X-ray diffraction has provided extensive information about the arrangement of lipids and proteins in multilamellar myelin. This information has been limited to the abundant inter-nodal regions of the sheath because these regions dominate the scattering when x-ray beams of 100 µm diameter or more are used. Here, we used a 1 µm beam, raster-scanned across a single nerve fiber, to obtain detailed information about the molecular architecture in the nodal, paranodal, and juxtaparanodal regions. Orientation of the lamellar membrane stacks and membrane periodicity varied spatially. In the juxtaparanode-internode, 198-202 Å-period membrane arrays oriented normal to the nerve fiber axis predominated, whereas in the paranode-node, 205-208 Å-period arrays oriented along the fiber direction predominated. In parts of the sheath distal to the node, multiple sets of lamellar reflections were observed at angles to one another, suggesting that the myelin multilayers are deformed at the Schmidt-Lanterman incisures. The calculated electron density of myelin in the different regions exhibited membrane bilayer profiles with varied electron densities at the polar head groups, likely due to different amounts of major myelin proteins (P0 glycoprotein and myelin basic protein). Scattering from the center of the nerve fibers, where the x-rays are incident en face (perpendicular) to the membrane planes, provided information about the lateral distribution of protein. By underscoring the heterogeneity of membrane packing, microdiffraction analysis suggests a powerful new strategy for understanding the underlying molecular foundation of a broad spectrum of myelinopathies dependent on local specializations of myelin structure in both the PNS and CNS.

  12. "COMPARISON BETWEEN NUMBER OF NERVE FIBERS IN NORMAL BREAST TISSUE, BENIGN LESIONS AND MALIGNANT BREAST TUMORS"

    Directory of Open Access Journals (Sweden)

    H. Soltanghoraiee

    2004-10-01

    Full Text Available Breast cancer is common and is considered second cause of cancer related mortality in females. Regarding importance of breast cancer, more investigation in this field is recommended. For many years investigators believed that neoplasms were not innervated but new findings have proved otherwise. This descriptive study was carried out to compare number of nerve fibers in benign, malignant and normal breast tissue. Of each group several slides were reviewed and 3608.50 mm2 of malignant tumors (ductal carcinoma, 3641 mm2 of benign tumors (fibroadenoma and 2331.25 mm2 of normal breast tissue (mammoplasty were assessed. Numbers of nerve fibers were compared and a significant increase in nerve fibers was found in malignant tumors compared with benign tumors and normal breast tissue. Accuracy of hematoxylin and eosin method were examined by immunohistochemistry staining (neurofilament method and affirmed. These results reveal that malignant tumors of breast have more nerve fibers than normal breast tissue or benign tumors.

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

    Institute of Scientific and Technical Information of China (English)

    Yanru Zhang; Hui Zhang; Kaka Katiella; Wenhua Huang

    2014-01-01

    A chemically extracted acellular allogeneic nerve graft can reduce postoperative immune re-jection, 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 regenera-tion. 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 anasto-mosis, but superior to chemically extracted acellular allogeneic nerve bridging alone.

  14. Propagation and spatiotemporal summation of electrical pulses in semiconductor nerve fibers

    Science.gov (United States)

    Samardak, A.; Taylor, S.; Nogaret, A.; Hollier, G.; Austin, J.; Ritchie, D. A.

    2007-08-01

    The authors report the propagation and analog summation of electrical impulses in artificial nerve fibers made of submicron p-n wires. These wires model the longitudinal conductivities of K + and Na+ ions inside and outside a nerve capillary as well as the transverse capacitance of the nerve membrane and the nonlinear conductance of its ion channels. They demonstrate the summation and annihilation of electrical impulses at room temperature which form the basis for making spike timing neural networks.

  15. Alpha-synuclein in cutaneous small nerve fibers

    Science.gov (United States)

    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

  16. Tacrolimus reduces scar formation and promotes sciatic nerve regeneration

    Institute of Scientific and Technical Information of China (English)

    Jun Que; Quan Cao; Tao Sui; Shihao Du; Ailiang Zhang; Dechao Kong; Xiaojian Cao

    2012-01-01

    A sciatic nerve transection and repair model was established in Sprague-Dawley rats by transecting the tendon of obturator internus muscle in the greater sciatic foramen and suturing with nylon sutures. The models were treated with tacrolimus gavage (4 mg/kg per day) for 0, 2, 4 and 6 weeks. Specimens were harvested at 6 weeks of intragastric administration. Masson staining revealed that the collagen fiber content and scar area in the nerve anastomosis of the sciatic nerve injury rats were significantly reduced after tacrolimus administration. Hematoxylin-eosin staining showed that tacrolimus significantly increased myelinated nerve fiber density, average axon diameter and myelin sheath thickness. Intragastric administration of tacrolimus also led to a significant increase in the recovery rate of gastrocnemius muscle wet weight and the sciatic functional index after sciatic nerve injury. The above indices were most significantly improved at 6 weeks after of tacrolimus gavage. The myelinated nerve fiber density in the nerve anastomosis and the sciatic nerve functions had a significant negative correlation with the scar area, as detected by Spearman’s rank correlation analysis. These findings indicate that tacrolimus can promote peripheral nerve regeneration and accelerate the recovery of neurological function through the reduction of scar formation.

  17. Contribution of myelunated fibers from spinal L4, L5 and L6 nerves to the sciatic nerve and its main branches in the adult rat Contribución de fibras mielínicas provenientes de los nervios espinales lumbares L4, L5 y L6 al nervio ciático de rata adulta y sus ramas principales

    Directory of Open Access Journals (Sweden)

    Juan D. Robles

    2000-04-01

    Full Text Available The rat sciatic nerve is composed by the L4, L5 and L6 lumbar spinal nerves. However, the contribution in myelinated fibers originating from these nerves along this nervous trunk has not yet been defined. In the present study, the L4, L5 and L4-L5 spinal nerves were selectively transected. After one week the sciatic, tibial, sural and peroneal nerves were dissected. These samples were fixed and processed for optical microscopy, and both degenerated and normal myelinated fibers were counted in toluidine blue-stained semi-thin sections. L4 contributed with myelinated fibers mainly to the peroneal nerve, and L5 to the sciatic, tibial and sural nerves. In general, the contribution of L6 was smaller and variable along the nervous trunk in comparison to the other two spinal branches. Our results give key information for further studies looking to correlate the contribution of spinal nerves making part of the sciatic nerve and its main branches with hind limb function. El nervio ciático de la rata está formado por los nervios espinales (ne lumbares L4, L5 y L6. Sin embargo, aún no se ha definido el aporte en fibras mielínicas de estos nervios espinales a lo largo del tronco nervioso. En este estudio se transectaron selectivamente los NE L4, L5 y L4-L5. Luego de una semana se disecaron los nervios ciático, tibial, sural y peroneal. Estas muestras se fijaron y procesaron para microscopía óptica y a partir de cortes coloreados con azul de toluidina se contaron las fibras mielínicas degeneradas y normales. L4 contribuyó con fibras mielínicas principalmente al nervio peroneal y L5 a los nervios ciático, tibial y sural. En general, el aporte de L6 fue menor y variable a lo largo del tronco nervioso comparado con las otras dos ramas espinales. Nuestros resultados brindan información valiosa para posteriores estudios que busquen correlacionar la contribución de los nervios espinales que componen el ciático y sus ramas principales con la funci

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  20. Wiener-kernel analysis of responses to noise of chinchilla auditory-nerve fibers

    NARCIS (Netherlands)

    Recio-Spinoso, A; Temchin, AN; van Dijk, P; Fan, YH; Ruggero, MA

    2005-01-01

    Responses to broadband Gaussian white noise were recorded in auditory-nerve fibers of deeply anesthetized chinchillas and analyzed by computation of zeroth-, first-, and second-order Wiener kernels. The first- order kernels ( similar to reverse correlations or "revcors") of fibers with characteristi

  1. Peripheral nerves injury of electrophysiology and pathology in MS

    Institute of Scientific and Technical Information of China (English)

    Li runjin; Qian zhimin; Chen ping

    2000-01-01

    OBJECTIVE We report the EMG and pathological features of sural nerve biopsy of 12 patients with MS. The pathological of thesel 1 patients demonstrated demyelination injury of peripheral nerves.METHODS Twelve cases abnomaly are screened with EMG from60 cases MS. Sural nerve biopsy were analyzed by HE AND loyez, and electron microscopy. RESULTS EMG showed slow of MCV in 9 patients and SCV in 7 patients. Myelinated fibers was the presence in 8 sural nerve biopsy patients and most striking demyelinating fibers, regeneration of myelinated fibers. CONCLUSION Ms is characterized by demyelinating disorder limited to the CNS.There are,howeve ,the results of this study sugee that combine with PNS demyelinating injury in MS may be more frequent than is generally assumed.

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

    Science.gov (United States)

    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.

  3. EGFR Activation Mediates Inhibition of Axon Regeneration by Myelin and Chondroitin Sulfate Proteoglycans

    Science.gov (United States)

    Koprivica, Vuk; Cho, Kin-Sang; Park, Jong Bae; Yiu, Glenn; Atwal, Jasvinder; Gore, Bryan; Kim, Jieun A.; Lin, Estelle; Tessier-Lavigne, Marc; Chen, Dong Feng; He, Zhigang

    2005-10-01

    Inhibitory molecules associated with myelin and the glial scar limit axon regeneration in the adult central nervous system (CNS), but the underlying signaling mechanisms of regeneration inhibition are not fully understood. Here, we show that suppressing the kinase function of the epidermal growth factor receptor (EGFR) blocks the activities of both myelin inhibitors and chondroitin sulfate proteoglycans in inhibiting neurite outgrowth. In addition, regeneration inhibitors trigger the phosphorylation of EGFR in a calcium-dependent manner. Local administration of EGFR inhibitors promotes significant regeneration of injured optic nerve fibers, pointing to a promising therapeutic avenue for enhancing axon regeneration after CNS injury.

  4. EFFECTS OF LOCAL NERVE COOLING ON CONDUCTION IN VAGAL FIBERS SHED LIGHT UPON RESPIRATORY REFLEXES IN THE RABBIT

    NARCIS (Netherlands)

    PATBERG, WR; NIJMEIJER, A; VERSPRILLE, A; ZOCK, JP; ZIJLSTRA, WG; Schut, J.K.

    1992-01-01

    In ten vagus nerves the effect of local cooling on the compound action potential was studied in the temperature range of 34 to 0-degrees-C in spontaneously breathing, anaesthetized rabbits. The mean temperature at which the myelinated (A) fibres were completely blocked, was 10.2 +/- 2.4-degrees-C (m

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  8. Alpha-synuclein in cutaneous small nerve fibers

    Directory of Open Access Journals (Sweden)

    Siepmann T

    2016-10-01

    Full Text Available Timo Siepmann,1 Ben Min-Woo Illigens,2 Kristian Barlinn1 1Department of Neurology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; 2Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA Abstract: 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. Keywords: Parkinson’s disease, diagnosis, skin

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

    Science.gov (United States)

    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

  10. Effect of mutated defensin NP-1 on sciatic nerve regeneration after transection--A pivot study.

    Science.gov (United States)

    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.

  11. Cornea nerve fiber quantification and construction of phenotypes in patients with fibromyalgia

    Science.gov (United States)

    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. Large A-fiber activity is required for microglial proliferation and p38 MAPK activation in the spinal cord: different effects of resiniferatoxin and bupivacaine on spinal microglial changes after spared nerve injury

    Directory of Open Access Journals (Sweden)

    Decosterd Isabelle

    2009-09-01

    Full Text Available Abstract Background After peripheral nerve injury, spontaneous ectopic activity arising from the peripheral axons plays an important role in inducing central sensitization and neuropathic pain. Recent evidence indicates that activation of spinal cord microglia also contributes to the development of neuropathic pain. In particular, activation of p38 mitogen-activated protein kinase (MAPK in spinal microglia is required for the development of mechanical allodynia. However, activity-dependent activation of microglia after nerve injury has not been fully addressed. To determine whether spontaneous activity from C- or A-fibers is required for microglial activation, we used resiniferatoxin (RTX to block the conduction of transient receptor potential vanilloid subtype 1 (TRPV1 positive fibers (mostly C- and Aδ-fibers and bupivacaine microspheres to block all fibers of the sciatic nerve in rats before spared nerve injury (SNI, and observed spinal microglial changes 2 days later. Results SNI induced robust mechanical allodynia and p38 activation in spinal microglia. SNI also induced marked cell proliferation in the spinal cord, and all the proliferating cells (BrdU+ were microglia (Iba1+. Bupivacaine induced a complete sensory and motor blockade and also significantly inhibited p38 activation and microglial proliferation in the spinal cord. In contrast, and although it produced an efficient nociceptive block, RTX failed to inhibit p38 activation and microglial proliferation in the spinal cord. Conclusion (1 Blocking peripheral input in TRPV1-positive fibers (presumably C-fibers is not enough to prevent nerve injury-induced spinal microglial activation. (2 Peripheral input from large myelinated fibers is important for microglial activation. (3 Microglial activation is associated with mechanical allodynia.

  13. Label-free photoacoustic microscopy of peripheral nerves

    Science.gov (United States)

    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.

  14. Reduced dermal nerve fiber diameter in skin biopsies of patients with fibromyalgia.

    Science.gov (United States)

    Doppler, Kathrin; Rittner, Heike L; Deckart, Maximiliane; Sommer, Claudia

    2015-11-01

    Recent studies have provided evidence of pathology and functional abnormalities of small nerve fibers as a potential correlate of pain in the fibromyalgia syndrome. Here, we aimed to quantify dermal unmyelinated nerve fiber diameter at the electron microscopic level to find a potential morphological correlate of the functional disturbance. Thirty-two patients with fibromyalgia syndrome, 12 patients with small fiber neuropathy, and 24 healthy controls were prospectively recruited. Skin biopsies of the distal and proximal legs and index finger were taken and processed for immunofluorescence and for electron microscopy. We determined the diameter of small unmyelinated nerve fibers by measuring ten transversely cut axons of each biopsy. The mean axon diameter was reduced in patients with fibromyalgia syndrome compared with patients with small fiber neuropathy and controls (P fibromyalgia. Our study provides further evidence of small fiber pathology in fibromyalgia syndrome and discloses differences compared with small fiber neuropathy, indicating that different pathomechanisms may lead to small fiber loss in the 2 disorders.

  15. Fibromyalgia Is Correlated with Retinal Nerve Fiber Layer Thinning

    Science.gov (United States)

    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 fibromyalgia (FIQ≥60) compared with patients with mild fibromyalgia (FIQfibromyalgia exhibited

  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.

    Science.gov (United States)

    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.

  17. Brain imaging signatures of the relationship between epidermal nerve fibers and heat pain perception.

    Science.gov (United States)

    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.

  18. Ultrastructural analysis of guided nerve regeneration using progesterone- and pregnenolone-loaded chitosan prostheses.

    Science.gov (United States)

    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.

  19. Gamma knife irradiation of injured sciatic nerve induces histological and behavioral improvement in the rat neuropathic pain model.

    Directory of Open Access Journals (Sweden)

    Yuki Yagasaki

    Full Text Available We examined the effects of gamma knife (GK irradiation on injured nerves using a rat partial sciatic nerve ligation (PSL model. GK irradiation was performed at one week after ligation and nerve preparations were made three weeks after ligation. GK irradiation is known to induce immune responses such as glial cell activation in the central nervous system. Thus, we determined the effects of GK irradiation on macrophages using immunoblot and histochemical analyses. Expression of Iba-1 protein, a macrophage marker, was further increased in GK-treated injured nerves as compared with non-irradiated injured nerves. Immunohistochemical study of Iba-1 in GK-irradiated injured sciatic nerves demonstrated Iba-1 positive macrophage accumulation to be enhanced in areas distal to the ligation point. In the same area, myelin debris was also more efficiently removed by GK-irradiation. Myelin debris clearance by macrophages is thought to contribute to a permissive environment for axon growth. In the immunoblot study, GK irradiation significantly increased expressions of βIII-tubulin protein and myelin protein zero, which are markers of axon regeneration and re-myelination, respectively. Toluidine blue staining revealed the re-myelinated fiber diameter to be larger at proximal sites and that the re-myelinated fiber number was increased at distal sites in GK-irradiated injured nerves as compared with non-irradiated injured nerves. These results suggest that GK irradiation of injured nerves facilitates regeneration and re-myelination. In a behavior study, early alleviation of allodynia was observed with GK irradiation in PSL rats. When GK-induced alleviation of allodynia was initially detected, the expression of glial cell line-derived neurotrophic factor (GDNF, a potent analgesic factor, was significantly increased by GK irradiation. These results suggested that GK irradiation alleviates allodynia via increased GDNF. This study provides novel evidence that GK

  20. Acquired anhidrosis associated with systemic sarcoidosis: Quantification of nerve fibers around eccrine glands by confocal microscopy.

    Science.gov (United States)

    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.

  1. Retinal nerve fiber layer thickness is associated with lesion length in acute optic neuritis

    DEFF Research Database (Denmark)

    Kallenbach, K; Simonsen, Helle Juhl; Sander, B;

    2010-01-01

    BACKGROUND: Acute optic neuritis occurs with and without papillitis. The presence of papillitis has previously been thought to imply an anterior location of the neuritis, but imaging studies seeking to test this hypothesis have been inconclusive. METHODS: This prospective observational cohort study...... included 41 patients with unilateral optic neuritis and 19 healthy volunteers. All patients were evaluated and examined within 28 days of onset of symptoms. The peripapillary retinal nerve fiber layer thickness (RNFLT), an objective quantitative measure of optic nerve head edema, was measured by optical...... in the development of optic nerve head edema in optic neuritis....

  2. 大鼠坐骨神经髓鞘相关蛋白随年龄的变化%Change of myelin-associated protein expressions in rat sciatic nerves with age

    Institute of Scientific and Technical Information of China (English)

    张琦; 王彩萍; 蒋蔚; 蒋茂荣; 丁妹; 丁斐

    2013-01-01

    目的:研究大鼠坐骨神经髓鞘相关蛋白随年龄的变化及与髓鞘板层数之间的相互关系.方法:SD大鼠分别于饲养1周、1月、3月、9月、15月和21月后取坐骨神经,利用透射电镜观察计数髓鞘板层;采用免疫印迹检测髓鞘相关蛋白—髓鞘碱性蛋白(MBP)、髓鞘相关糖蛋白(MAG)和P0蛋白(P0)的表达变化,并分析与板层数之间的相关性;采用荧光免疫组织化学显色观察MBP的表达变化.结果:透射电镜观察显示,大鼠坐骨神经髓鞘板层数从1周到15月逐渐增加,直到21月无显著变化.免疫印迹显示,MBP的表达随年龄增长而增加,21月时达到高峰,与髓鞘板层数呈正性直线相关;MAG在出生后1周表达最高,而P0在1月时达峰值,后皆随年龄增加而下降,MAG与髓鞘板层数呈负性直线相关,而P0与髓鞘板层数之间呈非直线相关.荧光免疫组织化学显色显示,随着年龄增长,MBP在大鼠坐骨神经的髓鞘表达的荧光强度逐渐增强.结论:大鼠坐骨神经髓鞘相关蛋白随年龄改变呈现不同的表达模式,并与髓鞘板层数之间存在一定相关性.%Objective:To investigate the changes of myelin-associated proteins in myelin of rat sciatic nerves with age,as well as the relationships between the protein expressions and morphology changes.Methods:Sparague-Dawley (SD) rats were randomly divided into 6 distinct age groups:1-week,1-,3-,9-,15-and 21-month age groups.The number of myelin sheath lamellae of the sciatic nerve was counted with electron micrographs.Western blotting was performed to examine the changes of protein expression levels of myelin-associated proteins in rat sciatic nerves,such as myelin basic protein (MBP),myelinassociated glycoprotein (MAG) and myelin protein zero (P0).And fluorescent immunohistochemistry was performed to observe the change of MBP in the sciatic nerve.The relationships between myelin sheath lamellae and the expression of myelin

  3. The Association between Serum Cytokines and Damage to Large and Small Nerve Fibers in Diabetic Peripheral Neuropathy

    Directory of Open Access Journals (Sweden)

    Francesca Magrinelli

    2015-01-01

    Full Text Available Diabetic peripheral neuropathy (DPN is a frequent complication of type 2 diabetes mellitus (DM and may involve small and large peripheral nerve fibers. Recent evidence suggests a role of cytokines in DPN. The paper is aimed at exploring whether the serum concentration of cytokines is associated with small and large nerve fiber function and with neuropathic pain (NP. We recruited a group of 32 type 2 DM patients who underwent serum cytokines (TNF-α, IL-2, IL-4, IL-6, and IL-10 dosage as well as electrodiagnostic and quantitative sensory testing (QST assessment to explore damage to large and small nerve fibers. Raised serum levels of IL-6 and IL-10 correlated with markers of large nerve fiber sensory and motor axonal damage. Raised IL-10 serum level was associated with signs of motor nerve demyelination. No differences were found in pain characteristics and electrodiagnostic and QST markers of small nerve fiber function in relation to cytokines serum levels. IL-6 and IL-10 serum levels were associated with large nerve fiber damage but not to small fibers function or NP. IL-6 and IL-10 cytokines might play a role in the pathogenesis of nerve fiber damage or represent a compensatory or neuroprotective mechanism.

  4. Rat-derived processed nerve allografts support more axon regeneration in rat than human-derived processed nerve xenografts.

    Science.gov (United States)

    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. Copyright © 2013 Wiley Periodicals, Inc.

  5. Schwann cell myelination requires Dynein function

    Directory of Open Access Journals (Sweden)

    Langworthy Melissa M

    2012-11-01

    Full Text Available Abstract Background Interaction of Schwann cells with axons triggers signal transduction that drives expression of Pou3f1 and Egr2 transcription factors, which in turn promote myelination. Signal transduction appears to be mediated, at least in part, by cyclic adenosine monophosphate (cAMP because elevation of cAMP levels can stimulate myelination in the absence of axon contact. The mechanisms by which the myelinating signal is conveyed remain unclear. Results By analyzing mutations that disrupt myelination in zebrafish, we learned that Dynein cytoplasmic 1 heavy chain 1 (Dync1h1, which functions as a motor for intracellular molecular trafficking, is required for peripheral myelination. In dync1h1 mutants, Schwann cell progenitors migrated to peripheral nerves but then failed to express Pou3f1 and Egr2 or make myelin membrane. Genetic mosaic experiments revealed that robust Myelin Basic Protein expression required Dync1h1 function within both Schwann cells and axons. Finally, treatment of dync1h1 mutants with a drug to elevate cAMP levels stimulated myelin gene expression. Conclusion Dync1h1 is required for retrograde transport in axons and mutations of Dync1h1 have been implicated in axon disease. Our data now provide evidence that Dync1h1 is also required for efficient myelination of peripheral axons by Schwann cells, perhaps by facilitating signal transduction necessary for myelination.

  6. Galectin-4, a novel neuronal regulator of myelination

    NARCIS (Netherlands)

    Stancic, Mirjana; Slijepcevic, Davor; Nomden, Anita; Vos, Michel J.; De Jonge, Jenny C.; Sikkema, Arend H.; Gabius, Hans-J.; Hoekstra, Dick; Baron, Wia

    2012-01-01

    Myelination of axons by oligodendrocytes (OLGs) is essential for proper saltatory nerve conduction, i.e., rapid transmission of nerve impulses. Among others, extracellular matrix (ECM) molecules, neuronal signaling, and axonal adhesion regulate the biogenesis and maintenance of myelin membranes, dri

  7. 面神经修复中再生室内髓鞘碱性蛋白的作用初探%Preliminary study of the facial nerve regeneration in the chamber: the influence of myelin basic protein

    Institute of Scientific and Technical Information of China (English)

    骆文龙; 林代诚; 李永懋

    2001-01-01

    Objective To study the role of exogenous myelin basic protein(MBP) in neural repairment. Methods Adult New Zealand rabbits were employed in vivo preparation. A 12 μL nerve growth chamber was created by suturing the proximal and distal stumps of a transected facial never (FN) trunk into a tube. The regenerated nerves within the chambers were dissected and fixed for histological studies with light microscope at 4,6 and 8 weeks respectively following the surgery. Results Morphological analysis of nerves showed no difference between the MBP and control group in the size of the regeneration FN within the chambers, diameters of myelinated axons, thickness of myelin sheath and number of myelin axons grew into the distal end of chamber at 4 weeks. At 6 and 8 weeks after operation, the MBP group showed a more mature-appearance regenerative nerve comparing to control group. Especially, the enhancement of maturation in the regeneration axons was very noticeable at 6 weeks. Conclusion The study showed that pharmacological administration of exogenous MBP within a chamber at the time of entubational nerve repair enhances regeneration of myelinated axons across the sectioned ends of FN.%目的探讨外源性髓鞘碱性蛋白(myelin basic protein, MBP)在家兔面神经再生室修复中的作用。方法将33只家兔横断的面神经干近、远端缝于硅胶管壁上,形成约12 μL大小的神经再生室。一侧为实验组,将MBP注入再生室内;对侧为对照组不注任何物质。分别在术后4、6、8周处死动物, 切取标本,在光镜下行组织形态学观察。结果形态学分析表明术后4周2组再生室内再生面神经的有髓轴突直径、髓鞘厚度及长入再生室远端有髓轴突数差异无显著性 (P>0.05),随着时间的延长(术后6、8周),MBP组较对照组再生面神经显得更为成熟,6周时再生轴突成熟程度差异更明显。结论 MBP有促进家兔面神经再生修复的作用,但

  8. CHANGES OF THE THICKNESS OF RETINA NERVE FIBER LAYER IN ALZHEIMER’S DISEASE

    Institute of Scientific and Technical Information of China (English)

    陈燕; 孙悦

    2013-01-01

    <正>Objective To determine the changes of retina nerve fiber thickness with optical coherence tomography(OCT) in Alzheimer’s disease(AD) patients.Methods OCT was used to measure the thickness of retinal nerve fiber layer(RNFL) from 38 AD patients and 26 healthy age-matched controls.The corrected visual acuity and intraocular pressure were measured and the dilated fundus examinations were also performed in those subjects.Results Compared with healthy age-matched controls,the RNFL thickness of AD patients(95.40±29.45) were much thinner than the controls(105.91±29.87)(P <().05),especially in superior quadrant,while no difference was found in the other retinal area.Conclusion Retinal nerve degeneration may be present in the retina of AD patients and this degeneration is likely localized preferentially to the superior quadrant.

  9. Exploration of the retinal nerve fiber layer thickness by measurement of the linear dichroism

    Science.gov (United States)

    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.

  10. Temporal retinal nerve fiber loss in patients with spinocerebellar ataxia type 1.

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    Sarah Stricker

    Full Text Available BACKGROUND: Autosomal dominant spinocerebellar ataxia type 1 is an adult onset progressive disorder with well characterized neurodegeneration in the cerebellum and brainstem. Beyond brain atrophy, few data exist concerning retinal and optic nerve involvement. OBJECTIVE: To evaluate retinal changes in SCA1 patients compared to age and gender matched healthy controls. METHODOLOGY/PRINCIPAL FINDINGS: Nine patients with SCA1 were prospectively recruited from the ataxia clinic and were compared to nine age and gender matched healthy controls. Both cohorts received assessment of visually evoked potentials and eye examination by optical coherence tomography to determine retinal nerve fiber layer thickness and total macular volume. While no differences were found in visually evoked potentials, SCA1 patients showed a significant reduction of mean retinal nerve fiber layer thickness (RNFLT compared to healthy controls (84±13 µm vs. 97±8 µm, p = 0.004. Temporal areas showed the most prominent RNFLT reduction with high statistical significances (temporal-inferior: p<0.001, temporal: p<0.001, temporal-superior: p = 0.005 whereas RNFLT in nasal areas was in the range of the control group. From six SCA1 patients an additional macular scan was obtained. The comparison to the corresponding healthy control showed a slight but not significant reduction in TMV (8.22±0.68 mm(3 vs. 8.61±0.41 mm(3, p = 0.15. CONCLUSION: In SCA1 patients, we found evidence for degeneration of retinal nerve fibers. The temporal focus of the observed retinal nerve fiber layer reduction suggests an involvement of the papillo-macular bundle which resembles pathology found in toxic or mitochondrial optic nerve disease such as Leber's hereditary optic neuropathy (LHON or dominant optic atrophy (DOA.

  11. Sound and vibration sensitivity of VIIIth nerve fibers in the grassfrog, Rana temporaria

    DEFF Research Database (Denmark)

    Christensen-Dalsgaard, J; Jørgensen, M B

    1996-01-01

    , the animals were stimulated with dorso-ventral vibrations, and the sound-induced vertical vibrations in the setup could be canceled by emitting vibrations in antiphase from the vibration exciter. All low-frequency fibers responded to both sound and vibration with sound thresholds from 23 dB SPL and vibration......We have studied the sound and vibration sensitivity of 164 amphibian papilla fibers in the VIIIth nerve of the grassfrog, Rana temporaria. The VIIIth nerve was exposed using a dorsal approach. The frogs were placed in a natural sitting posture and stimulated by free-field sound. Furthermore...... thresholds from 0.02 cm/s2. The sound and vibration sensitivity was compared for each fiber using the offset between the rate-level curves for sound and vibration stimulation as a measure of relative vibration sensitivity. When measured in this way relative vibration sensitivity decreases with frequency from...

  12. Registration of adaptive optics corrected retinal nerve fiber layer (RNFL) images.

    Science.gov (United States)

    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).

  13. Study of nerve fibers nature reinforcing duodenal contractions by electrical stimulation of sympathetic nerve

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    Sveshnikov D.S.

    2011-09-01

    Full Text Available The subject of the article is to investigate the mechanism of increased reactions by electrical stimulation of the sympathetic nerve. Materials and methods: Experiments on dogs have shown that stimulant reactions during blockade of a-adrenergic by phentolamine and (3-adrenergic receptors with propranolol were completely eliminated by lizer-gol —the blocker of 5-HT12-receptors. Results: Infusion of lizergol did not influence on duodenal motor activity and the function of the vagus nerve. Conclusion: Effector neuron is found out to be serotonergic and its action is provided by 5-HT1 2 receptors

  14. Analysis of motor fibers in the communicating branch between the cervical nerves and the spinal accessory nerve to innervate trapezius in the rat.

    Science.gov (United States)

    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.

  15. Use of Corneal Confocal Microscopy to Evaluate Small Nerve Fibers in Patients With Human Immunodeficiency Virus.

    Science.gov (United States)

    Kemp, Harriet I; Petropoulos, Ioannis N; Rice, Andrew S C; Vollert, Jan; Maier, Christoph; Sturm, Dietrich; Schargus, Marc; Peto, Tunde; Hau, Scott; Chopra, Reena; Malik, Rayaz A

    2017-07-01

    Objective quantification of small fiber neuropathy in patients with human immunodeficiency virus (HIV)-associated sensory neuropathy (HIV-SN) is difficult but needed for diagnosis and monitoring. In vivo corneal confocal microscopy (IVCCM) can quantify small fiber damage. To establish whether IVCCM can identify an abnormality in corneal nerve fibers and Langerhans cells in patients with and without HIV-SN. This prospective, cross-sectional cohort study was conducted between July 24, 2015, and September 17, 2015. Twenty patients who were HIV positive were recruited from adult outpatient clinics at Chelsea and Westminster Hospital NHS Foundation Trust in England. These patients underwent IVCCM at Moorfields Eye Hospital NHS Foundation Trust in London, England, and the IVCCM images were analyzed at Weill Cornell Medicine-Qatar in Ar-Rayyan, Qatar. Patients were given a structured clinical examination and completed validated symptom questionnaires and the Clinical HIV-Associated Neuropathy Tool. Results from patients with HIV were compared with the results of the age- and sex-matched healthy control participants (n = 20). All participants were classified into 3 groups: controls, patients with HIV but without SN, and patients with HIV-SN. Comparison of corneal nerve fiber density, corneal nerve branch density, corneal nerve fiber length, corneal nerve fiber tortuosity, and corneal Langerhans cell density between healthy controls and patients with HIV with and without SN. All 40 participants were male, and most (≥70%) self-identified as white. Of the 20 patients with HIV, 14 (70%) had HIV-SN. This group was older (mean [SD] age, 57.7 [7.75] years) than the group without HIV-SN (mean [SD] age, 42.3 [7.26] years) and the controls (mean [SD] age, 53.8 [10.5] years). Corneal nerve fiber density was reduced in patients with HIV compared with the controls (26.7/mm2 vs 38.6/mm2; median difference, -10.37; 95.09% CI, -14.27 to -6.25; P < .001) and in patients with HIV

  16. Three-dimensional Imaging and Analysis of Mitochondria within Human Intraepidermal Nerve Fibers.

    Science.gov (United States)

    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.

  17. Evidence of sympathetic fibers in the male rat pelvic nerve by gross anatomy, retrograde labeling and high resolution autoradiographic study.

    Science.gov (United States)

    Giuliano, F; Facchinetti, P; Bernabé, J; Benoit, G; Calas, A; Rampin, O

    1997-12-01

    Several arguments exist in various animal species and man for the presence of a sympathetic component in the pelvic nerve, classically regarded as parasympathetic. We tested this hypothesis in the male rat. Nerve bundles issued from the sacral region of the paravertebral sympathetic chain and reaching the S1 spinal nerve were identified. Neurons in the sacral parasympathetic nucleus of the L6-S1 spinal cord and in the L2-S1 paravertebral sympathetic chain were retrogradely labeled from the pelvic nerve. Radioautography evidenced labeling of unmyelinated fibers in the pelvic nerve following in vitro incubation with 3H-noradrenaline. A population of sympathetic fibers issued from the lumbosacral sympathetic chain exists in the pelvic nerve of the male rat. This qualitative study provides a morphological basis to uncover the role of the sympathetic outflow present in the pelvic nerve.

  18. PUNICA GRANATUM ATTENUATES SCIATIC NERVE LIGATION INDUCED-NEUROPATHIC PAIN

    Directory of Open Access Journals (Sweden)

    Ramica Sharma et al.

    2012-02-01

    Full Text Available The study has been designed to investigate the effect of aqueous extract of rind of Punica granatum in sciatic nerve ligation induced-neuropathic pain in rats. Surgical procedure was performed with sciatic nerve ligation to develop neuropathic pain in rats. The development of neuropathic pain was assessed by employing behaviour parameters such as hyperalgesia and allodynia. Further, the functionality of sciatic nerve was assessed using the histopathological study of myelinated and unmyelinated fibers in sciatic nerve. Moreover, the oxidative stress was assessed by estimating serum thiobarbituric acid reactive substances (TBARS, catalase, glutathione and tissue TBARS and Superoxide dismutase (SOD. Rats exposed to sciatic nerve ligation produced marked increase in oxidative stress, which was assessed in terms of TBARS and SOD along with decrease in the level of catalase and glutathione. Moreover, it develops neuropathic pain by impairing the normal functions of myelinated and unmyelinated fibers in sciatic nerve. Treatment with aqueous extract of Punica granatum extract (100mg/kg, p.o markedly prevented sciatic nerve ligation-induced neuropathy and oxidative stress by increasing the pain threshold, by improving the functionality of sciatic nerve, by decreasing serum and tissue TBARS and tissue SOD, by increasing levels of serum glutathione and catalase. It may be concluded that Punica granatum extract reduced the oxidative stress via inhibiting p38MAPK and alleviates neuropathic symptoms and consequently improved the functionality of sciatic nerve and prevents sciatic nerve ligation–induced neuropathic pain.

  19. Marked loss of sympathetic nerve fibers in chronic Charcot foot of diabetic origin compared to ankle joint osteoarthritis.

    Science.gov (United States)

    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.

  20. Galanin - Immunoreactive Nerve Fibers in the Mucosal Layer of the Canine Gastrointestinal Tract During Inflammatory Bowel Disease

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    Rychlik Andrzej

    2015-04-01

    Full Text Available The effect of inflammatory bowel disease (IBD on the density of galanin - immunoreactive (GAL-IR nerve fibers was determined in the mucosa of canine duodenum, jejunum, and descending colon. Fiber density was evaluated by a single immunofluorescence method in biopsy specimens obtained from healthy dogs and patients with variable severity of the disease. The density of GAL-IR nerve fibers was determined by the semi-quantitative method by counting fibers in the field of view (0.l mm2. Fiber density was higher in dogs with moderate and severe IBD than in healthy animals. The results of the study suggest that GAL present in intestinal nerve fibers could play a role in the pathogenesis and development of canine IBD.

  1. Quantifying visual pathway axonal and myelin loss in multiple sclerosis and neuromyelitis optica.

    Science.gov (United States)

    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

  2. High-resolution measurement of electrically-evoked vagus nerve activity in the anesthetized dog

    Science.gov (United States)

    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.

  3. The histology of retinal nerve fiber layer bundles and bundle defects.

    Science.gov (United States)

    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.

  4. Innervation of TRPV1-, PGP-, and CGRP-immunoreactive nerve fibers in the subepithelial layer of a whole mount preparation of the rat cornea.

    Science.gov (United States)

    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.

  5. Partial epineural burying of nerve grafts with different sizes next to or distant from neurorrhaphy?s site: histological and electrophysiological studies in rat sciatic nerves

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    Cunha Marco Túlio Rodrigues da

    2001-01-01

    Full Text Available The aim of the present study was to compare and correlate histologically and electromyographically the effects of partial epineural burying of sural nerve segments in sectioned and sutured rat sciatic nerves. Sixty adult male Wistar rats were operated on 3 groups: Group 1, sural nerve graft, 9mm long, placed next to neurorrhaphy; Group 2, sural nerve graft, 9mm long, buryied 10mm distant from neurorrhaphy; Group 3, sural nerve graft, 18mm long, set next to neurorrhaphy. The morphological features were examined at light microscope after 3 months in 45 rats. The elements observed were: vascularization, vacuoles in nerve fibers, mastocytes and inflammatory infiltrate. The morphometry was made after 6 months in 15 rats from Group 1, 2 and 3, measuring external nerve fiber diameters and counting myelinated nerve fibers/mm². The electrophysiological study was perfomed after 6 months, registering maximum amplitude and frequency of EMG pontentials, at rest, in extensor digitorum longus muscle. Group 3 rats presented sciatic nerves better conserved morphologically and mean external nerve fiber diameters greater than those from Groups 1 and 2. There were no significant differences in density of nerve fibers/mm², and in the electrophysiological study in rats from Group 1, 2 and 3. The epineural burying of sural nerve grafts with greater length and placed next to the neurorrhaphy?s site had a significantly better regeneration of the histological features than the smaller ones distant from neurorrhaphy.

  6. Non-thermal influence of a weak microwave on nerve fiber activity

    CERN Document Server

    Shneider, M N

    2014-01-01

    This paper presents a short selective review of the non-thermal weak microwave field impact on a nerve fiber. The published results of recent experiments are reviewed and analyzed. The theory of the authors is presented, according to which there are strongly pronounced resonances in the range of about 30-300 GHz associated with the excitation of ultrasonic vibrations in the membrane as a result of interactions with the microwave radiation. These forced vibrations create acoustic pressure, which may lead to the redistribution of the protein transmembrane channels, thus changing the threshold of the action potential excitation in the axons of the neural network. The problem of surface charge on the bilayer lipid membrane of the nerve fiber is discussed. Various experiments for observing the effects considered are also discussed.

  7. Functional and structural nerve fiber findings in heterozygote patients with Fabry disease

    DEFF Research Database (Denmark)

    Møller, Anette Torvin; Bach, Flemming Winther; Feldt-Rasmussen, Ulla;

    2009-01-01

    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...

  8. Predominance of synovial sensory nerve fibers in arthrofibrosis following total knee arthroplasty compared to osteoarthritis of the knee.

    Science.gov (United States)

    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.

  9. Retinal nerve fiber layer thickness and visual hallucinations in Parkinson's Disease.

    Science.gov (United States)

    Lee, Jee-Young; Kim, Jae Min; Ahn, Jeeyun; Kim, Han-Joon; Jeon, Beom S; Kim, Tae Wan

    2014-01-01

    Defective visual information processing from both central and peripheral pathways is one of the suggested mechanisms of visual hallucination in Parkinson's disease (PD). To investigate the role of retinal thinning for visual hallucination in PD, we conducted a case-control study using spectral domain optical coherence tomography. We examined a representative sample of 61 patients with PD and 30 healthy controls who had no history of ophthalmic diseases. General ophthalmologic examinations and optical coherence tomography scans were performed in each participant. Total macular thickness and the thickness of each retinal layer on horizontal scans through the fovea were compared between the groups. In a comparison between patients with PD and healthy controls, there was significant parafoveal inner nuclear layer thinning, whereas other retinal layers, including the retinal nerve fiber layer, as well as total macular thicknesses were not different. In terms of visual hallucinations among the PD subgroups, only retinal nerve fiber layer thickness differed significantly, whereas total macular thickness and the thickness of other retinal layers did not differ. The retinal nerve fiber layer was thinnest in the group that had hallucinations without dementia, followed by the group that had hallucinations with dementia, and the group that had no hallucinations and no dementia. General ophthalmologic examinations did not reveal any significant correlation with hallucinations. There were no significant correlations between retinal thicknesses and duration or severity of PD and medication dosages. The results indicate that retinal nerve fiber layer thinning may be related to visual hallucination in nondemented patients with PD. Replication studies as well as further studies to elucidate the mechanism of thinning are warranted.

  10. Normal axonal ion channel function in large peripheral nerve fibers following chronic ciguatera sensitization.

    Science.gov (United States)

    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. Nerve fiber outgrowth is increased in the intestinal mucosa of patients with irritable bowel syndrome.

    Science.gov (United States)

    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.

  12. Reproducibility of peripapillary retinal nerve fiber layer thickness measurements using Spectral Domain OCT in Brazilian patients

    Directory of Open Access Journals (Sweden)

    Daniela Araújo Toscano

    2012-10-01

    Full Text Available PURPOSE: To evaluate the reproducibility of peripapillary retinal nerve fiber layer (RNFL thickness measurements in normal eyes and eyes with glaucoma using spectral domain optical coherence tomography (SDOCT. METHODS: One eye of 79 normal and 72 glaucoma patients was analyzed. All patients underwent a complete ophthalmological examination, including visual acuity testing; intraocular pressure, slit-lamp examination, indirect ophthalmoscopy; and the glaucoma group underwent achromatic perimetry with the 24-2 SITA Fast Humphrey Field Analyzer. All patients' eyes were scanned using the spectral domain optical coherence tomography - Spectralis® and one of them was chosen randomly. Three consecutive circular B-scan centered at the optic disc were performed in one visit. RESULTS: The intraclass correlation coefficient (ICC, coefficient of variation and test-retest variability for the mean retinal nerve fiber layer thickness were respectively: 0.94, 2.56% and 4.85 µm for the normal group and 0.93, 4.65% and 6.61 µm for the glaucomatous group. The intraclass correlation coefficient for retinal nerve fiber layer thickness in all quadrants were all excellent in both groups, with the superior quadrant having the highest ICCs (0.964 in glaucomatous eyes and nasal quadrant measurements having the lowest (0.800, but still excellent in eyes without glaucoma. The coefficient of variation was between 2.56% - 8.74% and between 4.65% - 11.44% in normal and glaucomatous group respectively. The test-retest variability was between 4.85 µm and 11.51 µm in the normal group and between 6.61 µm and 14.24 µm in the glaucomatous group. The measurements in glaucomatous eyes were more variable than normal eyes. CONCLUSIONS: Spectral domain optical coherence tomography showed excellent reproducibility with regard to retinal nerve fiber layer thickness measurements in normal and glaucomatous eyes.

  13. Latency of auditory evoked potential monitoring the effects of general anesthetics on nerve fibers and synapses

    OpenAIRE

    Bowan Huang; Feixue Liang; Lei Zhong; Minlin Lin; Juan Yang; Linqing Yan; Jinfan Xiao; Zhongju Xiao

    2015-01-01

    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 curv...

  14. Biodegradable magnesium wire promotes regeneration of compressed sciatic nerves.

    Science.gov (United States)

    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.

  15. Hirschsprung's disease: Is there a relationship between mast cells and nerve fibers?

    Institute of Scientific and Technical Information of China (English)

    Amit Kumar Yadav; Kiran Mishra; Anup Mohta; Sarla Agarwal

    2009-01-01

    AIM:To define the topography of mast cells and their numbers in cases of Hirschsprung's disease (HD) and non-HD, assess neural hypertrophy using imaging software and to study the relationship between mast cells and nerve fibers. METHODS:HE stained sections of 32 cases of chronic constipation in the age group of 0-14 years were reviewed for ganglion cells. AChE staining was performed on frozen sections of colonic and rectal biopsies. Based on their findings cases were divided into HD and non-HD and mast cells stained by toluidine blue were evaluated. Image analysis by computerized software was applied to S-100 stained sections for assessment of neural hypertrophy. RESULTS:Difference between number of mast cells in HD group (mean = 36.44) and in non-HD group (mean = 14.79) was statistically significant. Image analysis morphometry on S-100 stained sections served as a useful adjunct. The difference between number, size, and perimeter of the nerve fibers between HD and non-HD group was statistically significant. CONCLUSION:Mast cells are significantly increased in HD and their base line values are much higher in Indian children than that reported in Western literature. Their role in HD needs further research. Morphometry of S-100 stained nerve fibers is a useful adjunct to conventional methods for diagnosis of HD.

  16. Hypertension-induced peripheral neuropathy and the combined effects of hypertension and diabetes on nerve structure and function in rats.

    Science.gov (United States)

    Gregory, Joshua A; Jolivalt, Corinne G; Goor, Jared; Mizisin, Andrew P; Calcutt, Nigel A

    2012-10-01

    Diabetic neuropathy includes damage to neurons, Schwann cells and blood vessels. Rodent models of diabetes do not adequately replicate all pathological features of diabetic neuropathy, particularly Schwann cell damage. We, therefore, tested the hypothesis that combining hypertension, a risk factor for neuropathy in diabetic patients, with insulin-deficient diabetes produces a more pertinent model of peripheral neuropathy. Behavioral, physiological and structural indices of neuropathy were measured for up to 6 months in spontaneously hypertensive and age-matched normotensive rats with or without concurrent streptozotocin-induced diabetes. Hypertensive rats developed nerve ischemia, thermal hyperalgesia, nerve conduction slowing and axonal atrophy. Thinly myelinated fibers with supernumerary Schwann cells indicative of cycles of demyelination and remyelination were also identified along with reduced nerve levels of myelin basic protein. Similar disorders were noted in streptozotocin-diabetic rats, except that thinly myelinated fibers were not observed and expression of myelin basic protein was normal. Superimposing diabetes on hypertension compounded disorders of nerve blood flow, conduction slowing and axonal atrophy and increased the incidence of thinly myelinated fibers. Rats with combined insulinopenia, hyperglycemia and hypertension provide a model for diabetic neuropathy that offers an opportunity to study mechanisms of Schwann cell pathology and suggests that hypertension may contribute to the etiology of diabetic neuropathy.

  17. The aqueous layers within the myelin sheath modulate the membrane properties of simulated hereditary demyelinating neuropathies.

    Science.gov (United States)

    Stephanova, D I; Krustev, S M; Daskalova, M

    2011-03-01

    To expand our studies on the mechanisms underlying the clinical decline of the nerve excitability properties in patients with hereditary demyelinating neuropathies, the contribution of myelin sheath aqueous layers on multiple membrane properties of simulated fiber demyelinations is investigated. Three progressively greater degrees of internodal systematic demyelinations (two mild and one severe termed as ISD1, ISD2 and ISD3, respectively) without/with aqueous layers are simulated using our previous multi-layered model of human motor nerve fiber. The calculated multiple membrane excitability properties are as follows: potentials (intracellular action, electrotonic), strength-duration time constants, rheobasic currents and recovery cycles. They reflect the propagating, accommodative and adaptive processes in the fibers. The results show that all membrane properties, except for the strength-duration time constants and refractoriness, worsen when the myelin lamellae and their corresponding aqueous layers are uniformly reduced along the fiber length. The effect of the aqueous layers is significantly higher on the accommodative and adaptive processes than on the propagating processes in the fibers. Our multi-layered model better approximated some of the functional deficits documented for axons of patients with Charcot-Marie-Tooth disease type 1A. The study provides new and important information on the mechanisms underlying the pathophysiology of hereditary demyelinating neuropathies.

  18. Human amniotic epithelial cells express specific markers of nerve cells and migrate along the nerve fibers in the corpus callosum

    Institute of Scientific and Technical Information of China (English)

    Zhiyuan Wu; Guozhen Hui; Yi Lu; Tianjin Liu; Qin Huang; Lihe Guo

    2012-01-01

    Human amniotic epithelial cells were isolated from a piece of fresh amnion. Using immunocytochemical methods, we investigated the expression of neuronal phenotypes (microtubule-associated protein-2, glial fibrillary acidic protein and nestin) in human amniotic epithelial cells. The conditioned medium of human amniotic epithelial cells promoted the growth and proliferation of rat glial cells cultured in vitro, and this effect was dose-dependent. Human amniotic epithelial cells were further transplanted into the corpus striatum of healthy adult rats and the grafted cells could integrate with the host and migrate 1-2 mm along the nerve fibers in corpus callosum. Our experimental findings indicate that human amniotic epithelial cells may be a new kind of seed cells for use in neurograft.

  19. Immunodominant fragments of myelin basic protein initiate T cell-dependent pain

    Directory of Open Access Journals (Sweden)

    Liu Huaqing

    2012-06-01

    Full Text Available Abstract 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

  20. A simple method for fabrication of electrospun fibers with controlled degree of alignment having potential for nerve regeneration applications

    Energy Technology Data Exchange (ETDEWEB)

    Vimal, Sunil Kumar; Ahamad, Nadim; Katti, Dhirendra S., E-mail: dsk@iitk.ac.in

    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. - Highlights: • Modified electrospinning set-up for fabrication of fibers with controlled alignment • Three parameter-based control on the degree of alignment of fibers • The aligned fibers enhanced cell elongation and cell-cell contact. • The aligned fibers show potential for use in nerve regeneration.

  1. Myelin architecture: zippering membranes tightly together.

    Science.gov (United States)

    Bakhti, Mostafa; Aggarwal, Shweta; Simons, Mikael

    2014-04-01

    Rapid nerve conduction requires the coating of axons by a tightly packed multilayered myelin membrane. In the central nervous system, myelin is formed from cellular processes that extend from oligodendrocytes and wrap in a spiral fashion around an axon, resulting in the close apposition of adjacent myelin membrane bilayers. In this review, we discuss the physical principles underlying the zippering of the plasma membrane of oligodendrocytes at the cytoplasmic and extracellular leaflet. We propose that the interaction of the myelin basic protein with the cytoplasmic leaflet of the myelin bilayer triggers its polymerization into a fibrous network that drives membrane zippering and protein extrusion. In contrast, the adhesion of the extracellular surfaces of myelin requires the down-regulation of repulsive components of the glycocalyx, in order to uncover weak and unspecific attractive forces that bring the extracellular surfaces into close contact. Unveiling the mechanisms of myelin membrane assembly at the cytoplasmic and extracelluar sites may help to understand how the myelin bilayers are disrupted and destabilized in the different demyelinating diseases.

  2. Unmyelinated visceral afferents exhibit frequency dependent action potential broadening while myelinated visceral afferents do not.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2015-02-20

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

  4. Modulation of action potential trains in rabbit saphenous nerve unmyelinated fibers.

    Science.gov (United States)

    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.

  5. [Expression and dynamics of peptidergic nerve fibers in granulation tissue after distance osteosynthesis].

    Science.gov (United States)

    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.

  6. Evaluation of peripheral compression and auditory nerve fiber intensity coding using auditory steady-state responses

    DEFF Research Database (Denmark)

    Encina Llamas, Gerard; M. Harte, James; Epp, Bastian

    2015-01-01

    cause auditory nerve fiber (ANF) deafferentation in predominantly low-spontaneous rate (SR) fibers. In the present study, auditory steadystate response (ASSR) level growth functions were measured to evaluate the applicability of ASSR to assess compression and the ability to code intensity fluctuations...... at high stimulus levels. Level growth functions were measured in normal-hearing adults at stimulus levels ranging from 20 to 90 dB SPL. To evaluate compression, ASSR were measured for multiple carrier frequencies simultaneously. To evaluate intensity coding at high intensities, ASSR were measured using....... The results indicate that the slope of the ASSR level growth function can be used to estimate peripheral compression simultaneously at four frequencies below 60 dB SPL, while the slope above 60 dB SPL may provide information about the integrity of intensity coding of low-SR fibers....

  7. Somatostatin-immunoreactive nerve cell bodies and fibers in the medulla oblongata et spinalis.

    Science.gov (United States)

    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.

  8. Nanofibrous nerve conduits for repair of 30-mm-long sciatic nerve defects*

    Institute of Scientific and Technical Information of China (English)

    Esmaeil Biazar; Saeed Heidari Keshel; Majid Pouya; Hadi Rad; Melody Omrani Nava; Mohammad Azarbakhsh; Shirin Hooshmand

    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 macroscopi-cal y observed and histological y 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 cel s and glial cel s in the regenerated nerves. Masson’s trichrome staining showed that there were no pathological changes in the size and structure of gastrocnemius muscle cel s 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.

  9. Periosteum Metabolism and Nerve Fiber Positioning Depend on Interactions between Osteoblasts and Peripheral Innervation in Rat Mandible.

    Directory of Open Access Journals (Sweden)

    Cédric Mauprivez

    Full Text Available 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.

  10. Periosteum Metabolism and Nerve Fiber Positioning Depend on Interactions between Osteoblasts and Peripheral Innervation in Rat Mandible.

    Science.gov (United States)

    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.

  11. PARP INHIBITION OR GENE DEFICIENCY COUNTERACT INTRAEPIDERMAL NERVE FIBER LOSS AND NEUROPATHIC PAIN IN ADVANCED DIABETIC NEUROPATHY

    Science.gov (United States)

    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

  12. A role of peripheral myelin protein 2 in lipid homeostasis of myelinating Schwann cells.

    Science.gov (United States)

    Zenker, Jennifer; Stettner, Mark; Ruskamo, Salla; Domènech-Estévez, Enric; Baloui, Hasna; Médard, Jean-Jacques; Verheijen, Mark H G; Brouwers, Jos F; Kursula, Petri; Kieseier, Bernd C; Chrast, Roman

    2014-09-01

    Peripheral myelin protein 2 (Pmp2, P2 or Fabp8), a member of the fatty acid binding protein family, was originally described together with myelin basic protein (Mbp or P1) and myelin protein zero (Mpz or P0) as one of the most abundant myelin proteins in the peripheral nervous system (PNS). Although Pmp2 is predominantly expressed in myelinated Schwann cells, its role in glia is currently unknown. To study its function in PNS biology, we have generated a complete Pmp2 knockout mouse (Pmp2(-/-) ). Comprehensive characterization of Pmp2(-/-) mice revealed a temporary reduction in their motor nerve conduction velocity (MNCV). While this change was not accompanied by any defects in general myelin structure, we detected transitory alterations in the myelin lipid profile of Pmp2(-/-) mice. It was previously proposed that Pmp2 and Mbp have comparable functions in the PNS suggesting that the presence of Mbp can partially mask the Pmp2(-/-) phenotype. Indeed, we found that Mbp lacking Shi(-/-) mice, similar to Pmp2(-/-) animals, have preserved myelin structure and reduced MNCV, but this phenotype was not aggravated in Pmp2(-/-) /Shi(-/-) mutants indicating that Pmp2 and Mbp do not substitute each other's functions in the PNS. These data, together with our observation that Pmp2 binds and transports fatty acids to membranes, uncover a role for Pmp2 in lipid homeostasis of myelinating Schwann cells.

  13. Survey of Nerve Fiber Layer Thickness in Anisometropic and Strabismic Amblyopia

    Directory of Open Access Journals (Sweden)

    Reza Soltani Moghaddam

    2017-02-01

    Full Text Available . To investigate the effect of anisometropic and strabismic amblyopia on the nerve fiber layer thickness. This cross-sectional study was done on 54 amblyopic subjects, equally in both strabismic and anisometropic groups. The thickness otonerve fiber layer measured in superior, inferior, nasal, temporal quadrants and as a whole in both eyes of both groups. The means of thickness were compared in amblyopic and sound eyes. In strabismus group, the average nerve fiber layer thickness of the sound eye , in superior, inferior, nasal and temporal quadrants and as a whole were 113.23±14, 117.37±25, 68.96±6, 69.55±14 and 93.40±8 microns respectively. In amblyopic eyes of the same group, these measurements were 103.11±18, 67.74±11, and 69.59±16 and 89.59±12 microns in superior, inferior, nasal, temporal quadrants and as whole respectively. In anisometropic groups, the sound eye measurements were as 130.96±22, 129.07±29, 80.62±12, and 83.88±20 and 107.7±13 microns in superior, inferior, nasal and temporal quadrants and as a whole orderly. In amblyopic eyes of this group the mean thicknesses were 115.63±29, 133.15±25, 78.8±15, 80.2±16 and 109.17±21 microns in superior, inferior, nasal, temporal quadrants and as a whole respectively. Statistically, there were no significant differences between amblyopic and sound eyes (P>0.5. Our study did not support any significant change in a nerve fiber layer thickness of amblyopic patients; however, decreased thickness in superior and nasal quadrants of strabismic amblyopia and except inferior quadrant and as a whole. These measurements may be a clue for management and prognosis of amblyopia in old age.

  14. Survey of Nerve Fiber Layer Thickness in Anisometropic and Strabismic Amblyopia.

    Science.gov (United States)

    Soltani Moghaddam, Reza; Medghalchi, Abdolreza; Alizadeh, Yousef

    2017-01-01

    . To investigate the effect of anisometropic and strabismic amblyopia on the nerve fiber layer thickness. This cross-sectional study was done on 54 amblyopic subjects, equally in both strabismic and anisometropic groups. The thickness otonerve fiber layer measured in superior, inferior, nasal, temporal quadrants and as a whole in both eyes of both groups. The means of thickness were compared in amblyopic and sound eyes. In strabismus group, the average nerve fiber layer thickness of the sound eye , in superior, inferior, nasal and temporal quadrants and as a whole were 113.23±14, 117.37±25, 68.96±6, 69.55±14 and 93.40±8 microns respectively. In amblyopic eyes of the same group, these measurements were 103.11±18, 67.74±11, and 69.59±16 and 89.59±12 microns in superior, inferior, nasal, temporal quadrants and as whole respectively. In anisometropic groups, the sound eye measurements were as 130.96±22, 129.07±29, 80.62±12, and 83.88±20 and 107.7±13 microns in superior, inferior, nasal and temporal quadrants and as a whole orderly. In amblyopic eyes of this group the mean thicknesses were 115.63±29, 133.15±25, 78.8±15, 80.2±16 and 109.17±21 microns in superior, inferior, nasal, temporal quadrants and as a whole respectively. Statistically, there were no significant differences between amblyopic and sound eyes (P>0.5). Our study did not support any significant change in a nerve fiber layer thickness of amblyopic patients; however, decreased thickness in superior and nasal quadrants of strabismic amblyopia and except inferior quadrant and as a whole. These measurements may be a clue for management and prognosis of amblyopia in old age.

  15. Synergistic effects of ultrashort wave and bone marrow stromal cells on nerve regeneration with acellular nerve allografts.

    Science.gov (United States)

    Pang, Chao-Jian; Tong, Lei; Ji, Li-Li; Wang, Zhen-Yu; Zhang, Xu; Gao, Hai; Jia, Hua; Zhang, Li-Xin; Tong, Xiao-Jie

    2013-10-01

    Acellular nerve allografts (ANA) possess bioactivity and neurite promoting factors in nerve tissue engineering. Previously we reported that low dose ultrashort wave (USW) radiation could enhance the rate and quality of peripheral nerve regeneration with ANA repairing sciatic nerve defects. Meanwhile, ANA implanted with bone marrow stromal cells (BMSCs) exhibited a similar result. Thus, it is interesting to know whether it might yield a synergistic effect when USW radiation is combined with BMSCs-laden ANA. Here we investigated the effectiveness of ANA seeded with BMSCs, combined with USW therapy on repairing peripheral nerve injuries. Adult male Wistar rats were randomly divided into four groups: Dulbecco's modified Eagle's medium (DMEM) control group, BMSCs-laden group, ultrashort wave (USW) group and BMSC + USW group. The regenerated nerves were assayed morphologically and functionally, and growth-promoting factors in the regenerated tissues following USW administration or BMSCs integration were also detected. The results indicated that the combination therapy caused much better beneficial effects evidenced by increased myelinated nerve fiber number, myelin sheath thickness, axon diameter, sciatic function index, nerve conduction velocity, and restoration rate of tibialis anterior wet weight. Moreover, the mRNA levels of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) in the spinal cord and muscles were elevated significantly. In conclusion, we found a synergistic effect of USW radiation and BMSCs treatment on peripheral nerve regeneration, which may help establish novel strategies for repairing peripheral nerve defects. Copyright © 2013 Wiley Periodicals, Inc.

  16. Pulp nerve fibers distribution of human carious teeth: An immunohistochemical study

    Directory of Open Access Journals (Sweden)

    Tetiana Haniastuti

    2010-12-01

    Full Text Available Background: Human dental pulp is richly innervated by trigeminal afferent axons that subserve nociceptive function. Accordingly, they respond to stimuli that induce injury to the pulp tissue. An injury to the nerve terminals and other tissue components in the pulp stimulate metabolic activation of the neurons in the trigeminal ganglion which result in morphological changes in the peripheral nerve terminals. Purpose: The aim of the study was to observe caries-related changes in the distribution of human pulpal nerve. Methods: Under informed consents, 15 third molars with caries at various stages of decay and 5 intact third molars were extracted because of orthodontic or therapeutic reasons. All samples were observed by micro-computed tomography to confirm the lesion condition 3-dimensionally, before decalcifying with 10% EDTA solution (pH 7.4. The specimens were then processed for immunohistochemistry using anti-protein gene products (PGP 9.5, a specific marker for the nerve fiber. Results: In normal intact teeth, PGP 9.5 immunoreactive nerve fibers were seen concentrated beneath the odontoblast cell layer. Nerve fibers exhibited an increased density along the pulp-dentin border corresponding to the carious lesions. Conclusion: Neural density increases throughout the pulp chamber with the progression of caries. The activity and pathogenicity of the lesion as well as caries depth, might influence the degree of neural sprouting.Latar belakang: Pulpa gigi manusia diinervasi oleh serabut saraf trigeminal yang berespon terhadap stimuli penyebab perlukaan dengan menimbulkan rasa sakit. Perlukaan pada akhiran saraf dan komponen lain dari pulpa akan menstimulasi aktivasi metabolik dari neuron pada ganglion trigeminal sehingga mengakibatkan perubahan morfologi pada akhiran saraf perifer. Tujuan: Penelitian ini bertujuan untuk mengamati perubahan distribusi saraf pada pulpa gigi manusia yang disebabkan oleh proses karies. Metode: Penelitian ini menggunakan

  17. Topiramate improves neurovascular function, epidermal nerve fiber morphology, and metabolism in patients with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Boyd A

    2010-12-01

    Full Text Available Amanda L Boyd, Patricia M Barlow, Gary L Pittenger, Kathryn F Simmons, Aaron I VinikDepartment of Internal Medicine, Eastern Virginia Medical School, Norfolk, VA, USAPurpose: To assess the effects of topiramate on C-fiber function, nerve fiber morphology, and metabolism (including insulin sensitivity, obesity, and dyslipidemia in type 2 diabetes.Patients and methods: We conducted an 18-week, open-label trial treating patients with topiramate. Twenty subjects with type 2 diabetes and neuropathy (61.5 ± 1.29 years; 15 male, 5 female were enrolled and completed the trial. Neuropathy was evaluated by total neuropathy scores, nerve conduction studies, quantitative sensory tests, laser Doppler skin blood flow, and intraepidermal nerve fibers in skin biopsies.Results: Topiramate treatment improved symptoms compatible with C-fiber dysfunction. Weight, blood pressure, and hemoglobin A1c also improved. Laser Doppler skin blood flow improved significantly after 12 weeks of treatment, but returned to baseline at 18 weeks. After 18 weeks of treatment there was a significant increase in intraepidermal nerve fiber length at the forearm, thigh, and proximal leg. Intraepidermal nerve fiber density was significantly increased by topiramate in the proximal leg.Conclusion: This study is the first to demonstrate that it is possible to induce skin intraepidermal nerve fiber regeneration accompanied by enhancement of neurovascular function, translating into improved symptoms as well as sensory nerve function. The simultaneous improvement of selective metabolic indices may play a role in this effect, but this remains to be determined.Keywords: diabetic neuropathy, skin blood flow, skin biopsy, diabetes

  18. Functionalized Cellulose: PET Polymer Fibers with Zeolites for Detoxification Against Nerve Agents%Functionalized Cellulose:PET Polymer Fibers with Zeolites for Detoxification Against Nerve Agents

    Institute of Scientific and Technical Information of China (English)

    Agarwal Satya R; Sundarrajan Subramanian; Ramakrishna Seeram

    2012-01-01

    Presently activated carbon is used as an adsorptive material for chemical and biological warfare agents.It possess excellent surface properties such as large surface area,fire-resistance and plenty availability,but has disadvantages such as its heavy weight,low breathability (after adsorption of moisture) and disposal.In this paper,we propose to utilize novel electrospun polymeric nanostructures having zeolites as catalyst materials.In this respective,the electrospun polymer nanofibers would serve as the best possible substitutes to activated carbon based protective clothing applications.This is the first in the literature that reports the integration of these types of catalysts with nanofiberous membranes.Electrospinning of cellulose/polyethylene terephthalate (PET) blend nanofibers has been carried out.Zeolite catalysts (Linde Type A and Mordenite) for the detoxification of nerve agent stimulant-paraoxon,were prepared due to their relative simplicity of synthesis.The catalysts were then coated onto nanofiber membranes and their morphology was confirmed using SEM.This is the first report on the coating of nanofibers with zeolites and their successful demonstration against nerve agent stimulant.The UV absorption spectra clearly show the detoxification ability of the functionalized fibers and their potential to be used in textiles for protection and decontamination.

  19. Self-Segregation of Myelin Membrane Lipids in Model Membranes

    NARCIS (Netherlands)

    Yurlova, Larisa; Kahya, Nicoletta; Aggarwal, Shweta; Kaiser, Hermann-Josef; Chiantia, Salvatore; Bakhti, Mostafa; Pewzner-Jung, Yael; Ben-David, Oshrit; Futerman, Anthony H.; Bruegger, Britta; Simons, Mikael

    2011-01-01

    Rapid conduction of nerve impulses requires coating of axons by myelin sheaths, which are multilamellar, lipid-rich membranes produced by oligodendrocytes in the central nervous system. To act as an insulator, myelin has to form a stable and firm membrane structure. In this study, we have analyzed t

  20. FK506-loaded chitosan conduit promotes the regeneration of injured sciatic nerves in the rat through the upregulation of brain-derived neurotrophic factor and TrkB.

    Science.gov (United States)

    Zhao, Jia; Zheng, Xifu; Fu, Chongyang; Qu, Wei; Wei, Guoqiang; Zhang, Weiguo

    2014-09-15

    FK506 has been shown to exert neurotrophic and neuroprotective effects, but its long-term application for nerve regeneration is limited. This study evaluated the potential application of a novel FK506-loaded chitosan conduit for peripheral nerve repair, and explored the underlying mechanism. A sciatic nerve injury model was created in male Wistar rats, which were then randomly divided into three treatment groups (n=40, each): chitosan-only, chitosan+FK506 injection, and FK506-loaded chitosan. We found significant recovery of normal morphology of sciatic nerves and higher density of myelinated nerve fibers in rats treated with FK506-loaded chitosan. Similarly, the total number of myelinated nerve fibers, myelin sheath thickness, and axon diameters were significantly higher in this group compared with the others, and the compound muscle action potentials and motor nerve conduction velocity values of sciatic nerves were significantly higher. BDNF and TrkB levels in motor neurons were highest in rats treated with FK506-loaded chitosan. In conclusion, FK506-loaded chitosan promoted peripheral nerve repair and regeneration in a rat model of sciatic nerve injury. These effects are correlated with increased BDNF and TrkB expression in motor neurons.

  1. A simple model of radial nerve injury in the rhesus monkey to evaluate peripheral nerve repair

    Institute of Scientific and Technical Information of China (English)

    Dong Wang; Qingtang Zhu; Xijun Huang; Guo Fu; Liqiang Gu; Xiaolin Liu; Honggang Wang; Jun Hu; Jianhua Yi; Xiaofeng Niu

    2014-01-01

    Current research on bone marrow stem cell transplantation and autologous or xenogenic nerve transplantation for peripheral nerve regeneration has mainly focused on the repair of peripher-al nerve defects in rodents. In this study, we established a standardized experimental model of radial nerve defects in primates and evaluated the effect of repair on peripheral nerve injury. We repaired 2.5-cm lesions in the radial nerve of rhesus monkeys by transplantation of autografts, acellular allografts, or acellular allografts seeded with autologous bone marrow stem cells. Five months after surgery, regenerated nerve tissue was assessed for function, electrophysiology, and histomorphometry. Postoperative functional recovery was evaluated by the wrist-extension test. Compared with the simple autografts, the acellular allografts and allografts seeded with bone marrow stem cells facilitated remarkable recovery of the wrist-extension functions in the rhesus monkeys. This functional improvement was coupled with radial nerve distal axon growth, a higher percentage of neuron survival, increased nerve fiber density and diameter, increased myelin sheath thickness, and increased nerve conduction velocities and peak amplitudes of compound motor action potentials. Furthermore, the quality of nerve regeneration in the bone marrow stem cells-laden allografts group was comparable to that achieved with autografts. The wrist-extension test is a simple behavioral method for objective quantification of peripheral nerve regeneration.

  2. Sympathetic nerve fibers sprout into rat odontoblast layer, but not into dentinal tubules, in response to cavity preparation.

    Science.gov (United States)

    Shimeno, Yoichi; Sugawara, Yumiko; Iikubo, Masahiro; Shoji, Noriaki; Sasano, Takashi

    2008-04-11

    This study was designed to determine if sympathetic nerve fibers exist in dentinal tubules in rat normal dental pulp, and if they sprout into the dentinal tubules in response to artificial cavity preparation in dentin. Sympathetic nerve fibers in rat molar dental pulp were labeled using an anterograde axonal transport technique involving injection of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) into the superior cervical ganglion (SCG). They were then observed using light and electron microscopes. In normal dental pulp (control), scattered WGA-HRP reaction products were observed in unmyelinated nerve endings in the odontoblast layer and subodontoblastic region. In injured pulp 3 weeks after cavity preparation, reaction products were about 1.8-times more plentiful in the above areas (versus control pulp). However, no labeled nerve fibers were observed in the dentinal tubules in either control or injured dental pulp. These results indicate that although sympathetic nerve fibers do indeed sprout in rat dental pulp in response to cavity preparation, they do not penetrate into the dentinal tubules in which postganglionic nerve endings derived from the SCG were not originally present.

  3. On the Myelin-Axon Interaction : Structural Studies of Myelin-Associated Glycoprotein, Olfactomedin-1 and the Nogo Receptor

    NARCIS (Netherlands)

    Pronker, M.F.

    2017-01-01

    In most parts of the body, nerves regenerate after injury. However, in the brain and spinal cord regeneration is very limited. One of the causes for this lack of regeneration is the presence of myelin proteins that inhibit outgrowth of neuronal projections. Three myelin-associated inhibitors of

  4. Dopamine release from serotonergic nerve fibers is reduced in L-DOPA-induced dyskinesia

    Science.gov (United States)

    Nevalainen, Nina; af Bjerkén, Sara; Lundblad, Martin; Gerhardt, Greg A.; Strömberg, Ingrid

    2011-01-01

    L-DOPA (3,4-dihydroxyphenyl-L-alanine) is the most commonly used treatment for symptomatic control in patients with Parkinson’s disease. Unfortunately, most patients develop severe side effects, such as dyskinesia, upon chronic L-DOPA treatment. The patophysiology of dyskinesia is unclear, however, involvement of serotonergic nerve fibers in converting L-DOPA to dopamine has been suggested. Therefore, potassium-evoked dopamine release was studied after local application of L-DOPA in the striata of normal, dopamine- and dopamine/serotonin-lesioned L-DOPA naïve, and dopamine-denervated chronically L-DOPA-treated dyskinetic rats using in vivo chronoamperometry. The results revealed that local L-DOPA administration into normal and intact hemisphere of dopamine-lesioned L-DOPA naïve animals significantly increased the potassium-evoked dopamine release. L-DOPA application also increased the dopamine peak amplitude in the dopamine-depleted L-DOPA naïve striatum, although these dopamine levels were several-folds lower than in the normal striatum, while no increased dopamine release was found in the dopamine/serotonin-denervated striatum. In dyskinetic animals, local L-DOPA application did not affect the dopamine release, resulting in significantly attenuated dopamine levels compared to those measured in L-DOPA naïve dopamine-denervated striatum. To conclude, L-DOPA is most likely converted to dopamine in serotonergic nerve fibers in the dopamine-depleted striatum, but the dopamine release is several-fold lower than in normal striatum. Furthermore, L-DOPA loading does not increase the dopamine release in dyskinetic animals as found in L-DOPA naïve animals, despite similar density of serotonergic innervation. Thus, the dopamine overflow produced from the serotonergic nerve fibers appears not to be the major cause of dyskinetic behavior. PMID:21534956

  5. Clinical analysis of retinal nerve fiber layer thickness and macular fovea in hyperopia children with anisometropia amblyopia

    Directory of Open Access Journals (Sweden)

    Fei-Fei Li

    2017-10-01

    Full Text Available AIM:To analyze the clinical significance of axial length, diopter and retinal nerve fiber layer thickness in hyperopia children with anisometropia amblyopia. METHODS: From January 2015 to January 2017 in our hospital for treatment, 103 cases, all unilateral, were diagnosed as hyperopia anisometropia amblyopia. The eyes with amblyopia were as experimental group(103 eyes, another normal eye as control group(103 eyes. We took the detection with axial length, refraction, foveal thickness, corrected visual acuity, diopter and the average thickness of retinal nerve fiber layer. RESULTS: Differences in axial length and diopter and corrected visual acuity were statistically significant between the two groups(PP>0.05. There was statistical significance difference on the foveal thickness(PP>0.05. The positive correlation between diopter with nerve fiber layer thickness of foveal and around the optic disc were no statistically significant difference(P>0.05. CONCLUSION: Retinal thickness of the fovea in the eye with hyperopic anisometropia amblyopia were thicker than those in normal eyes; the nerve fiber layer of around the optic disc was not significantly different between the amblyopic eyes and contralateral eyes. The refraction and axial length had no significant correlation with optic nerve fiber layer and macular foveal thickness.

  6. MR tractography; Visualization of structure of nerve fiber system from diffusion weighted images with maximum intensity projection method

    Energy Technology Data Exchange (ETDEWEB)

    Kinosada, Yasutomi; Okuda, Yasuyuki (Mie Univ., Tsu (Japan). School of Medicine); Ono, Mototsugu (and others)

    1993-02-01

    We developed a new noninvasive technique to visualize the anatomical structure of the nerve fiber system in vivo, and named this technique magnetic resonance (MR) tractography and the acquired image an MR tractogram. MR tractography has two steps. One is to obtain diffusion-weighted images sensitized along axes appropriate for depicting the intended nerve fibers with anisotropic water diffusion MR imaging. The other is to extract the anatomical structure of the nerve fiber system from a series of diffusion-weighted images by the maximum intensity projection method. To examine the clinical usefulness of the proposed technique, many contiguous, thin (3 mm) coronal two-dimensional sections of the brain were acquired sequentially in normal volunteers and selected patients with paralyses, on a 1.5 Tesla MR system (Signa, GE) with an ECG-gated Stejskal-Tanner pulse sequence. The structure of the nerve fiber system of normal volunteers was almost the same as the anatomy. The tractograms of patients with paralyses clearly showed the degeneration of nerve fibers and were correlated with clinical symptoms. MR tractography showed great promise for the study of neuroanatomy and neuroradiology. (author).

  7. Increased axonal regeneration and swellings in intraepidermal nerve fibers characterize painful phenotypes of diabetic neuropathy

    OpenAIRE

    Cheng, H.T.; Dauch, J.R.; Porzio, M.T.; Yanik, B.M.; Hsieh, W; Smith, A.G.; Singleton, J.R.; Feldman, E.L.

    2013-01-01

    We examined changes in intraepidermal nerve fibers (IENFs) to differentiate patients with diabetic neuropathy (DN) and neuropathic pain (DN-P) from those with DN without pain (DN-NOP). Punch skin biopsies were collected from the proximal thigh (PT) and distal leg (DL) of normal subjects (NS), patients with type 2 diabetes without evidence of DN (DM), or DN-P and DN-NOP patients. Protein gene product 9.5 (PGP) immunohistochemistry was used to quantify total IENF, and growth associated protein ...

  8. Vagus Nerve and Vagus Nerve Stimulation, a Comprehensive Review: Part I.

    Science.gov (United States)

    Yuan, Hsiangkuo; Silberstein, Stephen D

    2016-01-01

    The vagus nerve (VN), the "great wondering protector" of the body, comprises an intricate neuro-endocrine-immune network that maintains homeostasis. With reciprocal neural connections to multiple brain regions, the VN serves as a control center that integrates interoceptive information and responds with appropriate adaptive modulatory feedbacks. While most VN fibers are unmyelinated C-fibers from the visceral organs, myelinated A- and B-fiber play an important role in somatic sensory, motor, and parasympathetic innervation. VN fibers are primarily cholinergic but other noncholinergic nonadrenergic neurotransmitters are also involved. VN has four vagal nuclei that provide critical controls to the cardiovascular, respiratory, and alimentary systems. Latest studies revealed that VN is also involved in inflammation, mood, and pain regulation, all of which can be potentially modulated by vagus nerve stimulation (VNS). With a broad vagal neural network, VNS may exert a neuromodulatory effect to activate certain innate "protective" pathways for restoring health.

  9. Rabbit facial nerve regeneration in NGF-containing silastic tubes.

    Science.gov (United States)

    Spector, J G; Lee, P; Derby, A; Frierdich, G E; Neises, G; Roufa, D G

    1993-05-01

    Previous reports suggest that exogenous nerve growth factor (NGF) enhanced nerve regeneration in rabbit facial nerves. Rabbit facial nerve regeneration in 10-mm Silastic tubes prefilled with NGF was compared to cytochrome C (Cyt. C), bridging an 8-mm nerve gap. Three weeks following implantation, NGF-treated regenerates exhibited a more mature fascicular organization and more extensive neovascularization than cytochrome-C-treated controls. Morphometric analysis at the midtube of 3- and 5-week regenerates revealed no significant difference in the mean number of myelinated or unmyelinated axons between NGF- and cytochrome-C-treated implants. However, when the number of myelinated fibers in 5-week regenerates were compared to their respective preoperative controls, NGF-treated regenerates had recovered a significantly greater percentage of myelinated axons than cytochrome-C--treated implants (46% vs. 18%, respectively). In addition, NGF-containing chambers reinnervated a higher percentage of myelinated axons in the distal transected neural stumps (49% vs. 34%). Behavioral and electrophysiologic studies demonstrated spontaneous and induced activities in the target muscles when approximately one third of the myelinated axons were recovered in the midchamber (1280 axons). Horseradish peroxidase (HRP) studies demonstrated retrograde axonal transport to the midchamber and proximal transected neural stump. PC12 bioassay demonstrated persistent NGF activity in the intrachamber fluids at 3 (5:1 dilution) and 5 (2:1 dilution) weeks of entubation. Electrophysiologic tests demonstrated a slow conduction velocity of a propagated electrical impulse (43.5 m/s-1 vs. 67 m/s-1) and shallow wide compound action potential. In wider defects (15-mm chambers) and longer entubation periods (7 weeks), no regeneration or NGF activity was seen. Therefore, exogenous NGF provides an early but limited neurotrophic effect on the regeneration of the rabbit buccal division of the facial nerve and a

  10. Pharmacological switch in Aβ-fiber stimulation-induced spinal transmission in mice with partial sciatic nerve injury

    Directory of Open Access Journals (Sweden)

    Ma Lin

    2008-07-01

    Full Text Available Abstract Background We have previously demonstrated that different spinal transmissions are involved in the nociceptive behavior caused by electrical stimulation of Aβ-, Aδ- or C-fibers using a Neurometer® in naïve mice. In this study, we attempted to pharmacologically characterize the alteration in spinal transmission induced by partial sciatic nerve injury in terms of nociceptive behavior and phosphorylation of extracellular signal-regulated kinase (pERK in the spinal dorsal horn. Results Aβ-fiber responses (2000-Hz, which were selectively blocked by the AMPA/kainate antagonist CNQX in naïve mice, were hypersensitized but blocked by the NMDA receptor antagonists MK-801 and AP-5 in injured mice in an electrical stimulation-induced paw withdrawal (EPW test. Although Aδ-fiber responses (250-Hz were also hypersensitized by nerve injury, there was no change in the pharmacological characteristics of Aδ-fiber responses through NMDA receptors. On the contrary, C-fiber responses (5-Hz were hyposensitized by nerve injury. Moreover, Aδ- and C-, but not Aβ-fiber stimulations significantly increased the number of pERK-positive neurons in the superficial spinal dorsal horns of naïve mice, and corresponding antagonists used in the EPW test inhibited this increase. In mice with nerve injury, Aβ- as well as Aδ-fiber stimulations significantly increased the number of pERK-positive neurons in the superficial spinal dorsal horn, whereas C-fiber stimulation decreased this number. The nerve injury-specific pERK increase induced by Aβ-stimulation was inhibited by MK-801 and AP-5, but not by CNQX. However, Aβ- and Aδ-stimulations did not affect the number or size of pERK-positive neurons in the dorsal root ganglion, whereas C-fiber-stimulation selectively decreased the number of pERK-positive neurons. Conclusion These results suggest that Aβ-fiber perception is newly transmitted to spinal neurons, which originally receive only Aδ- and C-fiber

  11. Development and evaluation of spatial point process models for epidermal nerve fibers.

    Science.gov (United States)

    Olsbo, Viktor; Myllymäki, Mari; Waller, Lance A; Särkkä, Aila

    2013-06-01

    We propose two spatial point process models for the spatial structure of epidermal nerve fibers (ENFs) across human skin. The models derive from two point processes, Φb and Φe, describing the locations of the base and end points of the fibers. Each point of Φe (the end point process) is connected to a unique point in Φb (the base point process). In the first model, both Φe and Φb are Poisson processes, yielding a null model of uniform coverage of the skin by end points and general baseline results and reference values for moments of key physiologic indicators. The second model provides a mechanistic model to generate end points for each base, and we model the branching structure more directly by defining Φe as a cluster process conditioned on the realization of Φb as its parent points. In both cases, we derive distributional properties for observable quantities of direct interest to neurologists such as the number of fibers per base, and the direction and range of fibers on the skin. We contrast both models by fitting them to data from skin blister biopsy images of ENFs and provide inference regarding physiological properties of ENFs.

  12. Collateral development and spinal motor reorganization after nerve injury and repair.

    Science.gov (United States)

    Yu, Youlai; Zhang, Peixun; Han, Na; Kou, Yuhui; Yin, Xiaofeng; Jiang, Baoguo

    2016-01-01

    Functional recovery is often unsatisfactory after severe extended nerve defects or proximal nerve trunks injuries repaired by traditional repair methods, as the long regeneration distance for the regenerated axons to reinnervate their original target end-organs. The proximal nerve stump can regenerate with many collaterals that reinnervate the distal stump after peripheral nerve injury, it may be possible to use nearby fewer nerve fibers to repair more nerve fibers at the distal end to shorten the regenerating distance. In this study, the proximal peroneal nerve was used to repair both the distal peroneal and tibial nerve. The number and location of motor neurons in spinal cord as well as functional and morphological recovery were assessed at 2 months, 4 months and 8 months after nerve repair, respectively. Projections from the intact peroneal and tibial nerves were also studied in normal animals. The changes of motor neurons were assessed using the retrograde neurotracers FG and DiI to backlabel motor neurons that regenerate axons into two different pathways. To evaluate the functional recovery, the muscle forces and sciatic function index were examined. The muscles and myelinated axons were assessed using electrophysiology and histology. The results showed that all labeled motor neurons after nerve repair were always confined within the normal peroneal nerve pool and nearly all the distribution of motor neurons labeled via distal different nerves was disorganized as compared to normal group. However, there was a significant decline in the number of double labeled motor neurons and an obvious improvement with respect to the functional and morphological recovery between 2 and 8 months. In addition, the tibial/peroneal motor neuron number ratio at different times was 2.11±0.05, 2.13±0.08, 2.09±0.12, respectively, and was close to normal group (2.21±0.09). Quantitative analysis showed no significant morphological differences between myelinated nerve fibers

  13. Evaluation of retinal nerve fiber layer thickness measurement following laser in situ keratomileusis using scanning laser polarimetry

    Directory of Open Access Journals (Sweden)

    Dada Tanuj

    2007-01-01

    Full Text Available Aim: To evaluate the effect of laser-assisted in situ keratomileusis (LASIK on the measurement of retinal nerve fiber layer thickness by scanning laser polarimetry using customized corneal compensation in myopes. Materials and Methods: Scanning laser polarimetry was performed on 54 eyes of 54 healthy patients with myopia using the glaucoma diagnostics variable corneal compensation (GDx VCC instrument (Laser Diagnostic Technologies, San Diego, California before and a week after LASIK. The various parameters were compared using the Student′s t test. Results: No statistically significant change was observed in any of the retinal nerve fiber layer parameters before and after LASIK. Conclusions: While the measurement of retinal nerve fiber layer thickness by scanning laser polarimetry is affected by anterior segment birefringent properties and LASIK would be expected to produce changes in the same, customized corneal compensation using the GDx VCC seems to adequately compensate for these changes.

  14. The border between the central and the peripheral nervous system in the cat cochlear nerve: a light and scanning electron microscopical study.

    Science.gov (United States)

    Osen, Kirsten K; Furness, David N; Hackney, Carole M

    2011-07-01

    The transition between the central (CNS) and peripheral nervous system (PNS) in cranial and spinal nerve roots, referred to here as the CNS-PNS border, is of relevance to nerve root disorders and factors that affect peripheral-central regeneration. Here, this border is described in the cat cochlear nerve using light microscopical sections, and scanning electron microscopy of the CNS-PNS interfaces exposed by fracture of the nerve either prior to or following critical point drying. The CNS-PNS border represents an abrupt change in type of myelin, supporting elements, and vascularization. Because central myelin is formed by oligodendrocytes and peripheral myelin by Schwann cells, the myelinated fibers are as a rule equipped with a node of Ranvier at the border passage. The border is shallower and smoother in cat cochlear nerve than expected from other nerves, and the borderline nodes are largely in register. The loose endoneurial connective tissue of the PNS compartment is closed at the border by a compact glial membrane, the mantle zone, of the CNS compartment. The mantle zone is penetrated by the nerve fibers, but is otherwise composed of astrocytes and their interwoven processes like the external limiting membrane of the brain surface with which it is continuous. The distal surface of the mantle zone is covered by a fenestrated basal lamina. Only occasional vessels traverse the border. From an anatomical point of view, the border might be expected to be a weak point along the cochlear nerve and thus vulnerable to trauma. In mature animals, the CNS-PNS border presents a barrier to regrowth of regenerating nerve fibers and to invasion of the CNS by Schwann cells. An understanding of this region in the cochlear nerve is therefore relevant to head injuries that lead to hearing loss, to surgery on acoustic Schwannomas, and to the possibility of cochlear nerve regeneration.

  15. Stimulation of adult oligodendrogenesis by myelin-specific T cells

    DEFF Research Database (Denmark)

    Hvilsted Nielsen, Helle; Toft-Hansen, Henrik; Lambertsen, Kate Lykke

    2011-01-01

    investigated the effect of myelin-specific T cells on oligodendrocyte formation at sites of axonal damage in the mouse hippocampal dentate gyrus. Infiltrating T cells specific for myelin proteolipid protein stimulated proliferation of chondroitin sulfate NG2-expressing oligodendrocyte precursor cells early...... of calretinergic associational/commissural fibers within the dentate gyrus. These results have implications for the perception of MS pathogenesis because they show that infiltrating myelin-specific T cells can stimulate oligodendrogenesis in the adult central nervous system....

  16. Evoked bioelectrical activity of efferent fibers of the sciatic nerve of white rats in experimental menopause

    Directory of Open Access Journals (Sweden)

    Rodinsky A.G.

    2016-03-01

    Full Text Available The aim of our work was analysis of the bioelectrical activity of efferent fibers of the sciatic nerve in experimental menopause condition. Experiments were performed on 25 female white rats, divided into experimental and control groups. Menopause was modeled by total ovariohysterectomy. In 120 days after modeling we had recorded evoked action potentials of fibers of isolated ventral root L5 induced by stimulation of sciatic nerve with rectangular pulses. Threshold, chronaxia, latency, amplitude and duration of the action potential (AP were analysed. Refractory phenomenon was investigated by applying paired stimuli at intervals of 2 to 20 ms. In the context of long-term hypoestrogenemy threshold of AP appearance was 55,32±7,69%, chronaxy – 115,09±2,67%, latent period – 112,62±1,74% as compared with the control animals (p<0.01. In conditions of paired stimuli applying the amplitude of response to the testing stimulus in animals with ovariohysterectomy at intervals 3 and 4 ms was 61,25±36,45% and 53,48±18,64% (p<0.05 respectively.

  17. Thin-fiber mechanoreceptors reflexly increase renal sympathetic nerve activity during static contraction.

    Science.gov (United States)

    Kim, Jong Kyung; Hayes, Shawn G; Kindig, Angela E; Kaufman, Marc P

    2007-02-01

    The renal vasoconstriction induced by the sympathetic outflow during exercise serves to direct blood flow from the kidney toward the exercising muscles. The renal circulation seems to be particularly important in this regard, because it receives a substantial part of the cardiac output, which in resting humans has been estimated to be 20%. The role of group III mechanoreceptors in causing the reflex renal sympathetic response to static contraction remains an open question. To shed some light on this question, we recorded the renal sympathetic nerve responses to static contraction before and after injection of gadolinium into the arterial supply of the statically contracting triceps surae muscles of decerebrate unanesthetized and chloralose-anesthetized cats. Gadolinium has been shown to be a selective blocker of mechanogated channels in thin-fiber muscle afferents, which comprise the afferent arm of the exercise pressor reflex arc. In decerebrate (n = 15) and chloralose-anesthetized (n = 12) cats, we found that gadolinium (10 mM; 1 ml) significantly attenuated the renal sympathetic nerve and pressor responses to static contraction (60 s) after a latent period of 60 min; both responses recovered after a latent period of 120 min. We conclude that thin-fiber mechanoreceptors supplying contracting muscle are involved in some of the renal vasoconstriction evoked by the exercise pressor reflex.

  18. The Effects of Smoking on Anterior Segment Parameters, Retinal Nerve Fiber Layer, and Pupillary Functions

    Directory of Open Access Journals (Sweden)

    Bengü Ekinci Köktekir

    2014-01-01

    Full Text Available Objectives: To evaluate the alterations in the anterior segment parameters, retinal nerve fiber layer, and pupillary functions in smokers. Materials and Methods: In this case-control study, 45 eyes of 45 smokers and 45 eyes of 45 non-smoker control subjects were evaluated. All patients underwent measurement of anterior segment parameters with optical low coherence reflectometry (OLCR, mesopic and photopic pupillary diameter with an aberrometer device, retinal nerve fiber layer thickness with optical coherence tomography, and dry-eye assessment with Schirmer’s test. The results were compared with independent t-test by SPSS 16.0 Inc., and a p-value lower than 0.05 was determined as significant. Results: There was a significant difference between both groups in terms of mesopic pupil diameters that were measured with both OLCR and aberrometer device (p=0.03 and 0.02, respectively. Schirmer scores were also significantly decreased in smokers (p=0.001. The other measured parameters demonstrated no difference between smokers and non-smokers (p>0.05 for all. Conclusion: Smoking may affect pupillary functions, especially the mesopic pupillary diameter, and may cause a deficiency in pupil response under dark circumstances. (Turk J Ophthalmol 2014; 44: 11-4

  19. Tracking Epidermal Nerve Fiber Changes in Asian Macaques: Tools and Techniques for Quantitative Assessment.

    Science.gov (United States)

    Mangus, Lisa M; Dorsey, Jamie L; Weinberg, Rachel L; Ebenezer, Gigi J; Hauer, Peter; Laast, Victoria A; Mankowski, Joseph L

    2016-08-01

    Quantitative assessment of epidermal nerve fibers (ENFs) has become a widely used clinical tool for the diagnosis of small fiber neuropathies such as diabetic neuropathy and human immunodeficiency virus-associated sensory neuropathy (HIV-SN). To model and investigate the pathogenesis of HIV-SN using simian immunodeficiency virus (SIV)-infected Asian macaques, we adapted the skin biopsy and immunostaining techniques currently employed in human patients and then developed two unbiased image analysis techniques for quantifying ENF in macaque footpad skin. This report provides detailed descriptions of these tools and techniques for ENF assessment in macaques and outlines important experimental considerations that we have identified in the course of our long-term studies. Although initially developed for studies of HIV-SN in the SIV-infected macaque model, these methods could be readily translated to a range of studies involving peripheral nerve degeneration and neurotoxicity in nonhuman primates as well as preclinical investigations of agents aimed at neuroprotection and regeneration.

  20. Evaluating Glaucomatous Retinal Nerve Fiber Damage by GDx VCC Polarimetry in Taiwan Chinese Population

    Science.gov (United States)

    Chen, Hsin-Yi; Huang, Mei-Ling; Huang, Wei-Cheng

    2010-01-01

    Purpose To study the capability of scanning laser polarimetry with variable corneal compensation (GDx VCC) to detect differences in retinal nerve fiber layer thickness between normal and glaucomatous eyes in a Taiwan Chinese population. Methods This study included 44 normal eyes and 107 glaucomatous eyes. The glaucomatous eyes were divided into three subgroups on the basis of its visual field defects (early, moderate, severe). Each subject underwent a GDx-VCC exam and visual field testing. The area under the receiver-operating characteristic curve (AROC) of each relevant parameter was used to differentiate normal from each glaucoma subgroup, respectively. The correlation between visual field index and each parameter was evaluated for the eyes in the glaucoma group. Results For normal vs. early glaucoma, the parameter with the best AROC was Nerve fiber indicator (NFI) (0.942). For normal vs. moderate glaucoma, the parameter showing the best AROC was NFI (0.985). For normal vs. severe glaucoma, the parameter that had the best AROC was NFI (1.000). For early vs. moderate glaucoma, the parameter with the best AROC was NFI (0.732). For moderate vs. severe, the parameter showing the best AROC was temporal-superior-nasal-inferior-temporal average (0.652). For early vs. severe, the parameter with the best AROC was NFI (0.852). Conclusions GDx-VCC-measured parameters may serve as a useful tool to distinguish normal from glaucomatous eyes; in particular, NFI turned out to be the best discriminating parameter.

  1. Sound and vibration sensitivity of VIIIth nerve fibers in the grassfrog, Rana temporaria.

    Science.gov (United States)

    Christensen-Dalsgaard, J; Jørgensen, M B

    1996-10-01

    We have studied the sound and vibration sensitivity of 164 amphibian papilla fibers in the VIIIth nerve of the grassfrog, Rana temporaria. The VIIIth nerve was exposed using a dorsal approach. The frogs were placed in a natural sitting posture and stimulated by free-field sound. Furthermore, the animals were stimulated with dorso-ventral vibrations, and the sound-induced vertical vibrations in the setup could be canceled by emitting vibrations in antiphase from the vibration exciter. All low-frequency fibers responded to both sound and vibration with sound thresholds from 23 dB SPL and vibration thresholds from 0.02 cm/s2. The sound and vibration sensitivity was compared for each fiber using the offset between the rate-level curves for sound and vibration stimulation as a measure of relative vibration sensitivity. When measured in this way relative vibration sensitivity decreases with frequency from 42 dB at 100 Hz to 25 dB at 400 Hz. Since sound thresholds decrease from 72 dB SPL at 100 Hz to 50 dB SPL at 400 Hz the decrease in relative vibration sensitivity reflects an increase in sound sensitivity with frequency, probably due to enhanced tympanic sensitivity at higher frequencies. In contrast, absolute vibration sensitivity is constant in most of the frequency range studied. Only small effects result from the cancellation of sound-induced vibrations. The reason for this probably is that the maximal induced vibrations in the present setup are 6-10 dB below the fibers' vibration threshold at the threshold for sound. However, these results are only valid for the present physical configuration of the setup and the high vibration-sensitivities of the fibers warrant caution whenever the auditory fibers are stimulated with free-field sound. Thus, the experiments suggest that the low-frequency sound sensitivity is not caused by sound-induced vertical vibrations. Instead, the low-frequency sound sensitivity is either tympanic or mediated through bone conduction or sound

  2. Use of retinal nerve fiber layer birefringence as an addition to absorption in retinal scanning for biometric purposes

    Science.gov (United States)

    Agopov, Mikael; Gramatikov, Boris I.; Wu, Yi-Kai; Irsch, Kristina; Guyton, David L.

    2008-03-01

    We built a device sensitive to the birefringence of the retinal nerve fiber layer for biometric purposes. A circle of 20° diameter on the retina was scanned around the optic disk with a spot of light from a 785 nm laser diode. The nonbirefringent blood vessels indenting or displacing the retinal nerve fiber layer were seen as “blips” in the measured birefringence-derived signal. For comparison, the reflection-absorption signature of the blood vessel pattern in the scanned circle was also measured. The birefringence-derived signal proved to add useful information to the reflectance-absorption signature for retinal biometric scanning.

  3. No change in total length of white matter fibers in Alzheimer's disease

    DEFF Research Database (Denmark)

    Jorgensen, A.M.; Marner, L.; Pakkenberg, B.

    2008-01-01

    White matter changes have been reported as part of Alzheimer dementia. To investigate this, the total subcortical myelinated nerve fiber length was estimated in postmortem brains from eight females (age 79-88 years) with severe Alzheimer's disease (AD) and compared with brains from 10 female...

  4. Relationship between birefringence and neurotubule density in the primate retinal nerve fiber layer

    Science.gov (United States)

    Aranibar, R. G.; Kemp, N. J.; Dwelle, J. C.; Byers, S. E.; Markey, M. K.; Milner, T. E.; Rylander, H. G.

    2007-02-01

    The relationship between retinal nerve fiber layer (RNFL) birefringence (Δn) and neurotubule density (NTD, retinal ganglion cell (RGC) neurotubules per unit RNFL area) was investigated by correlating measurements of these two parameters in 1 eye of a healthy cynomolgus monkey. Phase retardation per unit depth (PR/UD, proportional to Δn) was measured at 5.6-15 ° intervals around the optic nerve head (ONH) with an enhanced polarization-sensitive optical coherence tomography (EPS-OCT) instrument. Transverse tissue sections containing 3 RGC nerve fiber bundles from each peripapillary RNFL octant were imaged with a transmission electron microscope (TEM). Morphological measurements taken in TEM images were used by a novel algorithm to estimate NTD. Registered PR/UD and NTD data were then correlated using single- and multi-level models, yielding correlation coefficients in the range 0.49 = 80%), NTD measurements in at least 16, rather than 8, RNFL sectors were needed. Interestingly, a single-level correlation coefficient of r = 0.81 (P = 0.01) was calculated between octant-averaged PR/UD and RGC axoplasmic area (A x, axon area less non-cytoskeletal organelle area) mode. A x represents a RGC axon's neurotubule-inhabitable area. Intuitively, a strong relationship should exist between A x and neurotubule number if neurotubules provide the primary structural support for RGC axons and structural requirements are the same in all RGC axons. If this relationship exists, error resulting from NTD estimation methods or preservation artifacts may have caused lower observed correlations of PR/UD with NTD than with A x mode, and more accurate methods of measuring in vivo NTD may be required to determine an accurate relationship between RNFL birefringence and NTD.

  5. Effects of nerve growth factor delivery via a gel to inferior alveolar nerve in mandibular distraction osteogenesis.

    Science.gov (United States)

    Wang, Lei; Cao, Jian; Lei, De-lin; Cheng, Xiao-bing; Yang, Yao-wu; Hou, Rui; Zhao, Ying-hua; Cui, Fu-zhai

    2009-11-01

    Inferior alveolar nerve (IAN) injury is a concern in mandible distraction osteogenesis (DO). We have previously demonstrated that repeated local injections of human nerve growth factor beta (NGF-beta) have significantly enhanced the histologic recovery of the IAN in a rabbit model of DO. This study was to further test the effect of a single injection of human NGF-beta delivered via a collagen/nanohydroxyapatite/kappa-carrageenan gel to the recovery of the IAN in DO. Rabbits underwent mandibular DO at a rate of 0.75 mm/12 h for 6 days. At the end of the distraction period, injections were performed near the IAN percutaneously as follows: group 1, human NGF-beta in the gel; group 2, human NGF-beta in saline; group 3, the gel alone; and group 4, saline alone. At 14 days after the end of distraction, IAN histologic findings and histomorphometric parameters were evaluated. Histologically, there were less myelin debris and more abundant regenerating nerve fibers in group 1 than the other groups. Both the myelinated fiber density and the myelinated axon area in group 1 were significantly higher than groups 3 and 4 (P NGF-beta in the gel leads to a better acceleration of the IAN injury recovery over the saline delivery. It provides a possible way to enhance the recovery of nerve injuries in craniofacial DO clinically.

  6. NKCC1 Activation Is Required for Myelinated Sensory Neurons Regeneration through JNK-Dependent Pathway.

    Science.gov (United States)

    Mòdol, Laura; Santos, Daniel; Cobianchi, Stefano; González-Pérez, Francisco; López-Alvarez, Víctor; Navarro, Xavier

    2015-05-13

    After peripheral nerve injury, axons are able to regenerate, although specific sensory reinnervation and functional recovery are usually worse for large myelinated than for small sensory axons. The mechanisms that mediate the regeneration of different sensory neuron subpopulations are poorly known. The Na(+)-K(+)-Cl(-) cotransporter 1 (NKCC1) is particularly relevant in setting the intracellular chloride concentration. After axotomy, increased NKCC1 phosphorylation has been reported to be important for neurite outgrowth of sensory neurons; however, the mechanisms underlying its effects are still unknown. In the present study we used in vitro and in vivo models to assess the differential effects of blocking NKCC1 activity on the regeneration of different types of dorsal root ganglia (DRGs) neurons after sciatic nerve injury in the rat. We observed that blocking NKCC1 activity by bumetanide administration induces a selective effect on neurite outgrowth and regeneration of myelinated fibers without affecting unmyelinated DRG neurons. To further study the mechanism underlying NKCC1 effects, we also assessed the changes in mitogen-activated protein kinase (MAPK) signaling under NKCC1 modulation. The inhibition of NKCC1 activity in vitro and in vivo modified pJNK1/2/3 expression in DRG neurons. Together, our study identifies a mechanism selectively contributing to myelinated axon regeneration, and point out the role of Cl(-) modulation in DRG neuron regeneration and in the activation of MAPKs, particularly those belonging to the JNK family. Copyright © 2015 the authors 0270-6474/15/357414-14$15.00/0.

  7. Morphometric analysis of the phrenic nerve in male and female Wistar-Kyoto (WKY and spontaneously hypertensive rats (SHR

    Directory of Open Access Journals (Sweden)

    A.R. Rodrigues

    2011-06-01

    Full Text Available Ventilatory differences between rat strains and genders have been described but the morphology of the phrenic nerve has not been investigated in spontaneously hypertensive (SHR and normotensive Wistar-Kyoto (WKY rats. A descriptive and morphometric study of the phrenic nerves of male (N = 8 and female (N = 9 SHR, and male (N = 5 and female (N = 6 WKY is presented. After arterial pressure and heart rate recordings, the phrenic nerves of 20-week-old animals were prepared for epoxy resin embedding and light microscopy. Morphometric analysis performed with the aid of computer software that took into consideration the fascicle area and diameter, as well as myelinated fiber profile and Schwann cell nucleus number per area. Phrenic nerves were generally larger in males than in females on both strains but larger in WKY compared to SHR for both genders. Myelinated fiber numbers (male SHR = 228 ± 13; female SHR = 258 ± 4; male WKY = 382 ± 23; female WKY = 442 ± 11 for proximal right segments and density (N/mm²; male SHR = 7048 ± 537; female SHR = 10355 ± 359; male WKY = 9457 ± 1437; female WKY = 14351 ± 1448 for proximal right segments were significantly larger in females of both groups and remarkably larger in WKY than SHR for both genders. Strain and gender differences in phrenic nerve myelinated fiber number are described for the first time in this experimental model of hypertension, indicating the need for thorough functional studies of this nerve in male and female SHR.

  8. Structural and dynamical properties of reconstituted myelin sheaths in the presence of myelin proteins MBP and P2 studied by neutron scattering.

    Science.gov (United States)

    Knoll, Wiebke; Peters, Judith; Kursula, Petri; Gerelli, Yuri; Ollivier, Jacques; Demé, Bruno; Telling, Mark; Kemner, Ewout; Natali, Francesca

    2014-01-21

    The myelin sheath is a tightly packed, multilayered membrane structure wrapped around selected nerve axons in the central and the peripheral nervous system. Because of its electrical insulation of the axons, which allows fast, saltatory nerve impulse conduction, myelin is crucial for the proper functioning of the vertebrate nervous system. A subset of myelin-specific proteins is well-defined, but their influence on membrane dynamics, i.e. myelin stability, has not yet been explored in detail. We investigated the structure and the dynamics of reconstituted myelin membranes on a pico- to nanosecond timescale, influenced by myelin basic protein (MBP) and myelin protein 2 (P2), using neutron diffraction and quasi-elastic neutron scattering. A model for the scattering function describing molecular lipid motions is suggested. Although dynamical properties are not affected significantly by MBP and P2 proteins, they act in a highly synergistic manner influencing the membrane structure.

  9. Challenges for Nerve Repair Using Chitosan-Siloxane Hybrid Porous Scaffolds

    Directory of Open Access Journals (Sweden)

    Yuki Shirosaki

    2014-01-01

    Full Text Available The treatment of peripheral nerve injuries remains one of the greatest challenges of neurosurgery, as functional recover is rarely satisfactory in these patients. Recently, biodegradable nerve guides have shown great potential for enhancing nerve regeneration. A major advantage of these nerve guides is that no foreign material remains after the device has fulfilled its task, which spares a second surgical intervention. Recently, we studied peripheral nerve regeneration using chitosan-γ-glycidoxypropyltrimethoxysilane (chitosan-GPTMS porous hybrid membranes. In our studies, these porous membranes significantly improved nerve fiber regeneration and functional recovery in rat models of axonotmetic and neurotmetic sciatic nerve injuries. In particular, the number of regenerated myelinated nerve fibers and myelin thickness were significantly higher in rat treated with chitosan porous hybrid membranes, whether or not they were used in combination with mesenchymal stem cells isolated from the Wharton’s jelly of the umbilical cord. In this review, we describe our findings on the use of chitosan-GPTMS hybrids for nerve regeneration.

  10. Development of rat tibia innervation: colocalization of autonomic nerve fiber markers with growth-associated protein 43.

    Science.gov (United States)

    Gajda, Mariusz; Litwin, Jan A; Tabarowski, Zbigniew; Zagólski, Olaf; Cichocki, Tadeusz; Timmermans, Jean-Pierre; Adriaensen, Dirk

    2010-01-01

    Development of autonomic innervation of the tibia was investigated in rat fetuses on gestational days (GD) 17-21 and in juvenile animals on postnatal days (PD) 1-28. Double immunofluorescence combined with confocal microscopy was applied to study colocalization of neuronal growth- associated protein 43 (GAP-43) and panneuronal marker protein gene product 9.5 (PGP) with markers of the autonomic nervous system: neuropeptide Y (NPY) and dopamine beta-hydroxylase (DbetaH) for adrenergic, as well as vasoactive intestinal polypeptide (VIP) and vesicular acetylcholine transporter (VAChT) for cholinergic fibers. The first GAP-43-immunoreactive (GAP-IR) nerve fibers were seen on GD17 in the perichondrium of the proximal epiphysis. Further GAP- and PGP-IR innervation appeared in the perichondrium/periosteum of the diaphysis and in the distal epiphysis (GD19), then in the bone marrow and in the intercondylar eminence (GD21). On PD1, NPY-IR and DbetaH-IR fibers appeared within the diaphyseal periosteum and on PD4 within the bone marrow. From PD14, GAP-43 immunoreactivity of NPY-positive fibers decreased. From PD7 on, NPY-IR fibers were observed in cartilage canals of both epiphyses and in the intercondylar eminence. In secondary ossification centers, NPY-IR fibers were seen from PD10, and in the bone marrow of the epiphyses from PD14. First VIP-IR and VAChT-IR fibers were observed on PD4 within the periosteum, bone marrow and patellar ligament. From PD10 on, VIP-positive fibers were seen in the intercondylar eminence, and from PD14 in secondary ossification centers. GAP-43 proved to be superior to PGP 9.5 as marker of growing nerve fibers, mostly due to its earlier appearance. The presence of specific nerve fibers may suggest possible involvement of autonomic innervation in regulation of bone development.

  11. Prevalence of Split Nerve Fiber Layer Bundles in Healthy People Imaged with Spectral Domain Optical Coherence Tomography

    Directory of Open Access Journals (Sweden)

    Sirel Gür Güngör

    2016-12-01

    Full Text Available Objectives: The presence of retinal nerve fiber layer (RNFL split bundles was recently described in normal eyes scanned using scanning laser polarimetry and by histologic studies. Split bundles may resemble RNFL loss in healthy eyes. The aim of our study was to determine the prevalence of nerve fiber layer split bundles in healthy people. Materials and Methods: We imaged 718 eyes of 359 healthy persons with the spectral domain optical coherence tomography in this cross-sectional study. All eyes had intraocular pressure of 21 mmHg or less, normal appearance of the optic nerve head, and normal visual fields (Humphrey Field Analyzer 24-2 full threshold program. In our study, a bundle was defined as ‘split’ when there is localized defect not resembling a wedge defect in the RNFL deviation map with a symmetrically divided RNFL appearance on the RNFL thickness map. The classification was performed by two independent observers who used an identical set of reference examples to standardize the classification. Results: Inter-observer consensus was reached in all cases. Bilateral superior split bundles were seen in 19 cases (5.29% and unilateral superior split was observed in 15 cases (4.16%. In 325 cases (90.52% there was no split bundle. Conclusion: Split nerve fiber layer bundles, in contrast to single nerve fiber layer bundles, are not common findings in healthy eyes. In eyes with normal optic disc appearance, especially when a superior RNFL defect is observed in RNFL deviation map, the RNLF thickness map and graphs should also be examined for split nerve fiber layer bundles.

  12. Diffusion tensor imaging-based fiber tracking for prediction of the position of the facial nerve in relation to large vestibular schwannomas.

    Science.gov (United States)

    Gerganov, Venelin M; Giordano, Mario; Samii, Madjid; Samii, Amir

    2011-12-01

    The reliable preoperative visualization of facial nerve location in relation to vestibular schwannoma (VS) would allow surgeons to plan tumor removal accordingly and may increase the safety of surgery. In this prospective study, the authors attempted to validate the reliability of facial nerve diffusion tensor (DT) imaging-based fiber tracking in a series of patients with large VSs. Furthermore, the authors evaluated the potential of this visualization technique to predict the morphological shape of the facial nerve (tumor compression-related flattening of the nerve). Diffusion tensor imaging and anatomical images (constructive interference in steady state) were acquired in a series of 22 consecutive patients with large VSs and postprocessed with navigational software to obtain facial nerve fiber tracking. The location of the cerebellopontine angle (CPA) part of the nerve in relation to the tumor was recorded during surgery by the surgeon, who was blinded to the results of the fiber tracking. A correlative analysis was performed of the imaging-based location of the nerve compared with its in situ position in relation to the VS. Fibers corresponding to the anatomical location and course of the facial nerve from the brainstem to the internal auditory meatus were identified with the DT imaging-based fiber tracking technique in all 22 cases. The location of the CPA segment of the facial nerve in relation to the VS determined during surgery corresponded to the location of the fibers, predicted by the DT imaging-based fiber tracking, in 20 (90.9%) of the 22 patients. No DT imaging-based fiber tracking correlates were found with the 2 morphological types of the nerve (compact or flat). The current study of patients with large VSs has shown that the position of the facial nerve in relation to the tumor can be predicted reliably (in 91%) using DT imaging-based fiber tracking. These are preliminary results that need further verification in a larger series.

  13. Sleeve bridging of the rhesus monkey ulnar nerve with muscular branches of the pronator teres:multiple ampliifcation of axonal regeneration

    Institute of Scientific and Technical Information of China (English)

    Yu-hui Kou; Pei-xun Zhang; Yan-hua Wang; Bo Chen; Na Han; Feng Xue; Hong-bo Zhang; Xiao-feng Yin; Bao-guo Jiang

    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 ifber regeneration. Our previous studies have veriifed the limit and validity of multiple ampli-ifcation 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 ampli-ifcation of myelinated nerve ifber 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 su-tured into the distal ulnar nerve using the small gap sleeve bridging method. At 6 months after suture, two-ifnger lfexion and mild wrist lfexion were restored in the ulnar-sided injured limbs of rhesus monkey. Neurophysiological examination showed that motor nerve conduction veloc-ity 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 ampliifcation of regenerating myelinated nerve ifbers 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 ifbers, and functions of the injured ulnar nerve were restored to a certain extent. Moreover, multiple ampliifcation was subsequently detected in ulnar nerve axons.

  14. Optimal myelin elongation relies on YAP activation by axonal growth and inhibition by Crb3/Hippo pathway

    Science.gov (United States)

    Fernando, Ruani N.; Cotter, Laurent; Perrin-Tricaud, Claire; Berthelot, Jade; Bartolami, Sylvain; Pereira, Jorge A.; Gonzalez, Sergio; Suter, Ueli; Tricaud, Nicolas

    2016-01-01

    Fast nerve conduction relies on successive myelin segments that electrically isolate axons. Segment geometry—diameter and length—is critical for the optimization of nerve conduction and the molecular mechanisms allowing this optimized geometry are partially known. We show here that peripheral myelin elongation is dynamically regulated by stimulation of YAP (Yes-associated protein) transcription cofactor activity during axonal elongation and limited by inhibition of YAP activity via the Hippo pathway. YAP promotes myelin and non-myelin genes transcription while the polarity protein Crb3, localized at the tips of the myelin sheath, activates the Hippo pathway to temper YAP activity, therefore allowing for optimal myelin growth. Dystrophic Dy2j/2j mice mimicking human peripheral neuropathy with reduced internodal lengths have decreased nuclear YAP which, when corrected, leads to longer internodes. These data show a novel mechanism controlling myelin growth and nerve conduction, and provide a molecular ground for disease with short myelin segments. PMID:27435623

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

    Science.gov (United States)

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

    2013-01-01

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

  16. Effect of surface pore structure of nerve guide conduit on peripheral nerve regeneration.

    Science.gov (United States)

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

    2013-03-01

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

  17. Effects of multiple intravitreal anti-VEGF injections on retinal nerve fiber layer and intraocular pressure: a comparative clinical study

    Institute of Scientific and Technical Information of China (English)

    Franck; Amouyal; Danièle; Denis; Frédéric; Matonti

    2014-01-01

    Dear Sir,Ifound the article by Sobac1etal[1]very interesting.The authors concluded that repeated intravitreal injection(IVI)of ranibizumab or bevacizumab didn’t seem have adverse effects on retinal nerve fiber layer(RNFL)thickness in wet age-related macular degeneration(AMD)patients.

  18. A Model of Electrically Stimulated Auditory Nerve Fiber Responses with Peripheral and Central Sites of Spike Generation

    DEFF Research Database (Denmark)

    Joshi, Suyash Narendra; Dau, Torsten; Epp, Bastian

    2017-01-01

    A computational model of cat auditory nerve fiber (ANF) responses to electrical stimulation is presented. The model assumes that (1) there exist at least two sites of spike generation along the ANF and (2) both an anodic (positive) and a cathodic (negative) charge in isolation can evoke a spike. ...

  19. Retinal nerve fiber layer thickness in subgroups of multiple sclerosis, measured by optical coherence tomography and scanning laser polarimetry

    NARCIS (Netherlands)

    T.A.M. Siepman (Theodora); M. Wefers Bettink-Remeijer (Marijke); R.Q. Hintzen (Rogier)

    2010-01-01

    textabstractOptical coherence tomography (OCT) and scanning laser polarimetry (GDx ECC) are non-invasive methods used to assess retinal nerve fiber layer (RNFL) thickness, which may be a reliable tool used to monitor axonal loss in multiple sclerosis (MS). The objectives of this study are (1) to com

  20. Utilization of scanning laser ophthalmoscopy in laser-induced bilateral human retinal nerve fiber layer damage

    Science.gov (United States)

    Zwick, Harry; Gagliano, Donald A.; Ruiz, S.; Stuck, Bruce E.

    1995-05-01

    In this paper, we describe a military laser accident case where bilateral Q-switched laser exposure resulted in bilateral macular damage with immediate visual acuity loss in one eye (OS) and delayed visual acuity loss in the other exposed eye (OD), where retinal damage appeared more parafoveal. At 6 weeks post exposure, OS had recovered to 20/17 and OD had dropped to 20/100 Snellen activity. Retinal nerve fiber damage was observed in both eyes at this time. Contrast sensitivity measurements made in OS were suppressed across all spatial frequencies, even though Snellen acuity measured in the normal range. More severe high spatial frequency loss in contrast was measured in the right eye as well as low spatial frequency loss. Both OS and OD revealed a parafoveal preferred retinal locus with scanning laser ophthalmoscopy contrast sensitivity measurements, suggesting parafoveal retinal compensatory processes.

  1. The Effect of Pseudoexfoliation Syndrome on the Retinal Nerve Fiber Layer and Choroid Thickness.

    Science.gov (United States)

    Demircan, Süleyman; Yılmaz, Uğur; Küçük, Erkut; Ulusoy, M Döndü; Ataş, Mustafa; Gülhan, Ahmet; Zararsız, Gökmen

    2017-01-01

    To investigate thickness of the retinal nerve fiber layer (RNFL) and choroid thickness in patients with pseudoexfoliation syndrome (PEX) and pseudoexfoliation glaucoma (PXG) compared to healthy volunteers. This cross-sectional, prospective study included 43 patients with PXG, 45 patients with PEX syndrome, and 48 healthy volunteers. The RNFL and macular thickness were analyzed with standard OCT protocol while choroidal thickness was analyzed with EDI protocol in all subjects. The RNFL thickness was higher in the PEX and control groups compared to the PXG group (pchoroid thickness was significantly higher in the control group compared to the PXG and PEX groups (pchoroid circulation by accumulating in choroid vessels. The thinner choroid in the PXG group suggests that ischemia affects the duration of PEX and has a role in the development of glaucoma.

  2. Somatic modulation of spinal reflex bladder activity mediated by nociceptive bladder afferent nerve fibers in cats.

    Science.gov (United States)

    Xiao, Zhiying; Rogers, Marc J; Shen, Bing; Wang, Jicheng; Schwen, Zeyad; Roppolo, James R; de Groat, William C; Tai, Changfeng

    2014-09-15

    The goal of the present study was to determine if supraspinal pathways are necessary for inhibition of bladder reflex activity induced by activation of somatic afferents in the pudendal or tibial nerve. Cats anesthetized with α-chloralose were studied after acute spinal cord transection at the thoracic T9/T10 level. Dilute (0.25%) acetic acid was used to irritate the bladder, activate nociceptive afferent C-fibers, and trigger spinal reflex bladder contractions (amplitude: 19.3 ± 2.9 cmH2O). Hexamethonium (a ganglionic blocker, intravenously) significantly (P irritation. Understanding the sites of action for PNS or TNS inhibition is important for the clinical application of pudendal or tibial neuromodulation to treat bladder dysfunctions. Copyright © 2014 the American Physiological Society.

  3. Chemoattractive capacity of different lengths of nerve fragments bridging regeneration chambers for the repair of sciatic nerve defects

    Institute of Scientific and Technical Information of China (English)

    Jiren Zhang; Yubo Wang; Jincheng Zhang

    2012-01-01

    A preliminary study by our research group showed that 6-mm-long regeneration chamber bridging is equivalent to autologous nerve transplantation for the repair of 12-mm nerve defects.In this study,we compared the efficacy of different lengths (6,8,10 mm) of nerve fragments bridging 6-mm regeneration chambers for the repair of 12-mm-long nerve defects.At 16 weeks after the regeneration chamber was implanted,the number,diameter and myelin sheath thickness of the regenerated nerve fibers,as well as the conduction velocity of the sciatic nerve and gastrocnemius muscle wet weight ratio,were similar to that observed with autologous nerve transplantation.Our results demonstrate that 6-,8-and 10-mm-long nerve fragments bridging 6-mm regeneration chambers effectively repair 12-mm-long nerve defects.Because the chemoattractive capacity is not affected by the length of the nerve fragment,we suggest adopting 6-mm-long nerve fragments for the repair of peripheral nerve defects.

  4. In-vivo imaging of retinal nerve fiber layer vasculature: imaging – histology comparison

    Directory of Open Access Journals (Sweden)

    Libby Richard T

    2009-08-01

    Full Text Available Abstract Background Although it has been suggested that alterations of nerve fiber layer vasculature may be involved in the etiology of eye diseases, including glaucoma, it has not been possible to examine this vasculature in-vivo. This report describes a novel imaging method, fluorescence adaptive optics (FAO scanning laser ophthalmoscopy (SLO, that makes possible for the first time in-vivo imaging of this vasculature in the living macaque, comparing in-vivo and ex-vivo imaging of this vascular bed. Methods We injected sodium fluorescein intravenously in two macaque monkeys while imaging the retina with an FAO-SLO. An argon laser provided the 488 nm excitation source for fluorescence imaging. Reflectance images, obtained simultaneously with near infrared light, permitted precise surface registration of individual frames of the fluorescence imaging. In-vivo imaging was then compared to ex-vivo confocal microscopy of the same tissue. Results Superficial focus (innermost retina at all depths within the NFL revealed a vasculature with extremely long capillaries, thin walls, little variation in caliber and parallel-linked structure oriented parallel to the NFL axons, typical of the radial peripapillary capillaries (RPCs. However, at a deeper focus beneath the NFL, (toward outer retina the polygonal pattern typical of the ganglion cell layer (inner and outer retinal vasculature was seen. These distinguishing patterns were also seen on histological examination of the same retinas. Furthermore, the thickness of the RPC beds and the caliber of individual RPCs determined by imaging closely matched that measured in histological sections. Conclusion This robust method demonstrates in-vivo, high-resolution, confocal imaging of the vasculature through the full thickness of the NFL in the living macaque, in precise agreement with histology. FAO provides a new tool to examine possible primary or secondary role of the nerve fiber layer vasculature in retinal

  5. Peripapillary retinal nerve fiber layer changes in preclinical diabetic retinopathy: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Xiaofei Chen

    Full Text Available Diabetic retinopathy is a microvascular neurodegenerative disorder in diabetic patients. Peripapillary retinal nerve fiber layer changes have been described in patients with preclinical diabetic retinopathy, but study results have been inconsistent.To assess changes in peripapillary retinal nerve fiber layer thickness in diabetic patients with preclinical diabetic retinopathy.A literature search was conducted through PubMed, EMBASE, Web of Science and Cochrane Library. Case-control studies on RNFL thickness in preclinical diabetic retinopathy patients and healthy controls were retrieved. A meta-analysis of weighted mean difference and a sensitivity analysis were performed using RevMan 5.2 software.Thirteen case-control studies containing 668 diabetic patients and 556 healthy controls were selected. Peripapillary RNFL thickness was significantly reduced in patients with preclinical diabetic retinopathy compared to healthy controls in studies applying Optical Coherence Tomography (-2.88 μm, 95%CI: -4.44 to -1.32, P = 0.0003 and in studies applying Scanning Laser Polarimeter (-4.21 μm, 95%CI: -6.45 to -1.97, P = 0.0002. Reduction of RNFL thickness was significant in the superior quadrant (-3.79 μm, 95%CI: -7.08 to -0.50, P = 0.02, the inferior quadrant (-2.99 μm, 95%CI: -5.44 to -0.54, P = 0.02 and the nasal quadrant (-2.88 μm, 95%CI: -4.93 to -0.82, P = 0.006, but was not significant in the temporal quadrant (-1.22 μm, 95%CI: -3.21 to 0.76, P = 0.23, in diabetic patients.Peripapillary RNFL thickness was significantly decreased in preclinical diabetic retinopathy patients compared to healthy control. Neurodegenerative changes due to preclinical diabetic retinopathy need more attention.

  6. Scanning Laser Polarimetry and Optical Coherence Tomography for Detection of Retinal Nerve Fiber Layer Defects

    Science.gov (United States)

    Oh, Jong-Hyun

    2009-01-01

    Purpose To compare the ability of scanning laser polarimetry with variable corneal compensation (GDx-VCC) and Stratus optical coherence tomography (OCT) to detect photographic retinal nerve fiber layer (RNFL) defects. Methods This retrospective cross-sectional study included 45 eyes of 45 consecutive glaucoma patients with RNFL defects in red-free fundus photographs. The superior and inferior temporal quadrants in each eye were included for data analysis separately. The location and presence of RNFL defects seen in red-free fundus photographs were compared with those seen in GDx-VCC deviation maps and OCT RNFL analysis maps for each quadrant. Results Of the 90 quadrants (45 eyes), 31 (34%) had no apparent RNFL defects, 29 (32%) had focal RNFL defects, and 30 (33%) had diffuse RNFL defects in red-free fundus photographs. The highest agreement between GDx-VCC and red-free photography was 73% when we defined GDx-VCC RNFL defects as a cluster of three or more color-coded squares (p<5%) along the traveling line of the retinal nerve fiber in the GDx-VCC deviation map (kappa value, 0.388; 95% confidence interval (CI), 0.195 to 0.582). The highest agreement between OCT and red-free photography was 85% (kappa value, 0.666; 95% CI, 0.506 to 0.825) when a value of 5% outside the normal limit for the OCT analysis map was used as a cut-off value for OCT RNFL defects. Conclusions According to the kappa values, the agreement between GDx-VCC deviation maps and red-free photography was poor, whereas the agreement between OCT analysis maps and red-free photography was good. PMID:19794943

  7. Imaging retinal nerve fiber bundles using optical coherence tomography with adaptive optics.

    Science.gov (United States)

    Kocaoglu, Omer P; Cense, Barry; Jonnal, Ravi S; Wang, Qiang; Lee, Sangyeol; Gao, Weihua; Miller, Donald T

    2011-08-15

    Early detection of axonal tissue loss in retinal nerve fiber layer (RNFL) is critical for effective treatment and management of diseases such as glaucoma. This study aims to evaluate the capability of ultrahigh-resolution optical coherence tomography with adaptive optics (UHR-AO-OCT) for imaging the RNFL axonal bundles (RNFBs) with 3×3×3μm(3) resolution in the eye. We used a research-grade UHR-AO-OCT system to acquire 3°×3° volumes in four normal subjects and one subject with an arcuate retinal nerve fiber layer defect (n=5; 29-62years). Cross section (B-scans) and en face (C-scan) slices extracted from the volumes were used to assess visibility and size distribution of individual RNFBs. In one subject, we reimaged the same RNFBs twice over a 7month interval and compared bundle width and thickness between the two imaging sessions. Lastly we compared images of an arcuate RNFL defect acquired with UHR-AO-OCT and commercial OCT (Heidelberg Spectralis). Individual RNFBs were distinguishable in all subjects at 3° retinal eccentricity in both cross-sectional and en face views (width: 30-50μm, thickness: 10-15μm). At 6° retinal eccentricity, RNFBs were distinguishable in three of the five subjects in both views (width: 30-45μm, thickness: 20-40μm). Width and thickness RNFB measurements taken 7months apart were strongly correlated (p<0.0005). Mean difference and standard deviation of the differences between the two measurement sessions were -0.1±4.0μm (width) and 0.3±1.5μm (thickness). UHR-AO-OCT outperformed commercial OCT in terms of clarity of the microscopic retina. To our knowledge, these are the first measurements of RNFB cross section reported in the living human eye.

  8. Scanning laser polarimetry and optical coherence tomography for detection of retinal nerve fiber layer defects.

    Science.gov (United States)

    Oh, Jong-Hyun; Kim, Yong Yeon

    2009-09-01

    To compare the ability of scanning laser polarimetry with variable corneal compensation (GDx-VCC) and Stratus optical coherence tomography (OCT) to detect photographic retinal nerve fiber layer (RNFL) defects. This retrospective cross-sectional study included 45 eyes of 45 consecutive glaucoma patients with RNFL defects in red-free fundus photographs. The superior and inferior temporal quadrants in each eye were included for data analysis separately. The location and presence of RNFL defects seen in red-free fundus photographs were compared with those seen in GDx-VCC deviation maps and OCT RNFL analysis maps for each quadrant. Of the 90 quadrants (45 eyes), 31 (34%) had no apparent RNFL defects, 29 (32%) had focal RNFL defects, and 30 (33%) had diffuse RNFL defects in red-free fundus photographs. The highest agreement between GDx-VCC and red-free photography was 73% when we defined GDx-VCC RNFL defects as a cluster of three or more color-coded squares (p<5%) along the traveling line of the retinal nerve fiber in the GDx-VCC deviation map (kappa value, 0.388; 95% confidence interval (CI), 0.195 to 0.582). The highest agreement between OCT and red-free photography was 85% (kappa value, 0.666; 95% CI, 0.506 to 0.825) when a value of 5% outside the normal limit for the OCT analysis map was used as a cut-off value for OCT RNFL defects. According to the kappa values, the agreement between GDx-VCC deviation maps and red-free photography was poor, whereas the agreement between OCT analysis maps and red-free photography was good.

  9. Retinal nerve fiber layer measurements by scanning laser polarimetry with enhanced corneal compensation in healthy subjects.

    Science.gov (United States)

    Rao, Harsha L; Venkatesh, Chirravuri R; Vidyasagar, Kelli; Yadav, Ravi K; Addepalli, Uday K; Jude, Aarthi; Senthil, Sirisha; Garudadri, Chandra S

    2014-12-01

    To evaluate the (i) effects of biological (age and axial length) and instrument-related [typical scan score (TSS) and corneal birefringence] parameters on the retinal nerve fiber layer (RNFL) measurements and (ii) repeatability of RNFL measurements with the enhanced corneal compensation (ECC) protocol of scanning laser polarimetry (SLP) in healthy subjects. In a cross-sectional study, 140 eyes of 73 healthy subjects underwent RNFL imaging with the ECC protocol of SLP. Linear mixed modeling methods were used to evaluate the effects of age, axial length, TSS, and corneal birefringence on RNFL measurements. One randomly selected eye of 48 subjects from the cohort underwent 3 serial scans during the same session to determine the repeatability. Age significantly influenced all RNFL measurements. RNFL measurements decreased by 1 µm for every decade increase in age. TSS affected the overall average RNFL measurement (β=-0.62, P=0.003), whereas residual anterior segment retardance affected the superior quadrant measurement (β=1.14, P=0.01). Axial length and corneal birefringence measurements did not influence RNFL measurements. Repeatability, as assessed by the coefficient of variation, ranged between 1.7% for the overall average RNFL measurement and 11.4% for th nerve fiber indicator. Age significantly affected all RNFL measurements with the ECC protocol of SLP, whereas TSS and residual anterior segment retardance affected the overall average and the superior average RNFL measurements, respectively. Axial length and corneal birefringence measurements did not influence any RNFL measurements. RNFL measurements had good intrasession repeatability. These results are important while evaluating the change in structural measurements over time in glaucoma patients.

  10. Differential sensitivity of myosin-heavy-chain-typed fibers to distinct aggregates of nerve-mediated activation.

    Science.gov (United States)

    Dunn, S E; Michel, R N

    1999-02-01

    We studied the regulatory effects of nerve-mediated activity on the early expression of embryonic and adult myosin heavy chains (MHC) within inactive though still innervated rat plantaris and soleus muscle fibers. To this end, we stimulated motor nerves that were quiescent following treatment with tetrodotoxin (TTX) with paradigms designed to partition the influence of neural activation frequency and assessed the selective expression and accumulation of MHCs within muscle fibers using an array of specific antibodies. We show rapid de novo expression of IIx MHC within select soleus fibers in response to high-frequency activation for more than 0.01% of daily time. High-frequency aggregates were also the most effective in preventing the TTX-induced reexpression of embryonic MHCs within specific fibers. Only configurations that included high-frequency trains for more than 0.01% of daily time or combined with 10 Hz stimulation preserved the size of select fibers, used as a measure of the net cellular content of MHC. The effectiveness of this preservation varied according to the muscle type and MHC expressed, and, in a subset of fibers, was influenced by contractile loading status. Our results demonstrate that distinct subsets of MHC-typed fibers are differentially sensitive to the neural activation cues mediating the cellular expression of these proteins.

  11. In vivo quantitative evaluation of the rat retinal nerve fiber layer with optical coherence tomography.

    Science.gov (United States)

    Nagata, Atsushi; Higashide, Tomomi; Ohkubo, Shinji; Takeda, Hisashi; Sugiyama, Kazuhisa

    2009-06-01

    To determine whether optical coherence tomography (OCT) is useful for quantitative evaluation of the thickness of the rat retinal nerve fiber layer (RNFL) in an optic nerve crush model. An OCT system was developed with a modified commercial time-domain OCT and a superluminescent diode with a bandwidth of 150 nm. Optical components were optimized to acquire rat retinal images. The right optic nerve was crushed intraorbitally with a clip. The left eye served as the untreated control. Circumpapillary OCT scans with a circle diameter of 500 microm centered on the optic disc were performed before and 1, 2, and 4 weeks after the crush. Repeatability and reproducibility of RNFL thickness measurements were evaluated. The RNFL thicknesses at 400, 500, and 600 microm from the center of the optic disc determined by linear vertical OCT scans were compared with thicknesses in retinal sections. The mean RNFL thicknesses in circumpapillary OCT scans were 27.9 +/- 1.8, 29.2 +/- 2.4, 19.9 +/- 2.3, and 4.5 +/- 3.6 microm before and 1, 2, and 4 weeks after the crush, respectively. RNFL thickness was unchanged 1 week after the crush, but then decreased significantly and progressively after the second week (P < 0.01). Coefficients of repeatability and reproducibility were less than 10% except for the crushed eyes at 4 weeks. RNFL thicknesses in OCT images correlated significantly with thicknesses determined histologically (r = 0.90, P < 0.001). OCT is a useful and valuable tool for quantitative evaluation of rat RNFL thickness.

  12. Changes across time in the temporal responses of auditory nerve fibers stimulated by electric pulse trains.

    Science.gov (United States)

    Miller, Charles A; Hu, Ning; Zhang, Fawen; Robinson, Barbara K; Abbas, Paul J

    2008-03-01

    Most auditory prostheses use modulated electric pulse trains to excite the auditory nerve. There are, however, scant data regarding the effects of pulse trains on auditory nerve fiber (ANF) responses across the duration of such stimuli. We examined how temporal ANF properties changed with level and pulse rate across 300-ms pulse trains. Four measures were examined: (1) first-spike latency, (2) interspike interval (ISI), (3) vector strength (VS), and (4) Fano factor (FF, an index of the temporal variability of responsiveness). Data were obtained using 250-, 1,000-, and 5,000-pulse/s stimuli. First-spike latency decreased with increasing spike rate, with relatively small decrements observed for 5,000-pulse/s trains, presumably reflecting integration. ISIs to low-rate (250 pulse/s) trains were strongly locked to the stimuli, whereas ISIs evoked with 5,000-pulse/s trains were dominated by refractory and adaptation effects. Across time, VS decreased for low-rate trains but not for 5,000-pulse/s stimuli. At relatively high spike rates (>200 spike/s), VS values for 5,000-pulse/s trains were lower than those obtained with 250-pulse/s stimuli (even after accounting for the smaller periods of the 5,000-pulse/s stimuli), indicating a desynchronizing effect of high-rate stimuli. FF measures also indicated a desynchronizing effect of high-rate trains. Across a wide range of response rates, FF underwent relatively fast increases (i.e., within 100 ms) for 5,000-pulse/s stimuli. With a few exceptions, ISI, VS, and FF measures approached asymptotic values within the 300-ms duration of the low- and high-rate trains. These findings may have implications for designs of cochlear implant stimulus protocols, understanding electrically evoked compound action potentials, and interpretation of neural measures obtained at central nuclei, which depend on understanding the output of the auditory nerve.

  13. Optical coherence tomography evaluation of retinal nerve fiber layer in longitudinally extensive transverse myelitis

    Directory of Open Access Journals (Sweden)

    Frederico C. Moura

    2011-02-01

    Full Text Available OBJECTIVE: To compare optical coherence tomography (OCT measurements on the retinal nerve fiber layer (RNFL of healthy controls and patients with longitudinally extensive transverse myelitis (LETM without previous optic neuritis. METHOD: Twenty-six eyes from 26 patients with LETM and 26 control eyes were subjected to automated perimetry and OCT for comparison of RNFL measurements. RESULTS: The mean deviation values from perimetry were significantly lower in patients with LETM than in controls (p<0.0001. RNFL measurements in the nasal quadrant and in the 3-o'clock segment were significantly smaller in LETM eyes than in controls. (p=0.04 and p=0.006, respectively. No significantly differences in other RNFL measurements were found. CONCLUSION: Patients with LETM may present localized RNFL loss, particularly on the nasal side of the optic disc, associated with slight visual field defects, even in the absence of previous episodes of optic neuritis. These findings emphasize the fact that patients with LETM may experience attacks of subclinical optic nerve damage.

  14. Effect of Media Opacity on Retinal Nerve Fiber Layer Thickness Measurements by Optical Coherence Tomography

    Directory of Open Access Journals (Sweden)

    Dae Woong Lee

    2010-01-01

    Full Text Available Purpose: To assess the effect of ocular media opacity on retinal nerve fiber layer (RNFL thickness measurements by optical coherence tomography (OCT. Methods: In this prospective, non-randomized clinical study, ocular examinations and OCT measurements were performed on 77 cataract patients, 80 laser refractive surgery patients and 90 patients whose signal strength on OCT was different on two consecutive measurements. None of the eyes had preexisting retinal or optic nerve pathology, including glaucoma. Cataracts were classified according to the Lens Opacity Classification System III (LOCS III. All eyes were scanned with the Stratus OCT using the Fast RNFL program before and three months after surgery. Internal fixation was used during scanning and all eyes underwent circular scans around the optic disc with a diameter of 3.4 mm. Results: Average RNFL thickness, quadrant thickness and signal strength significantly increased after cataract surgery (P<0.05. Cortical and posterior subcapsular cataracts, but not nuclear cataracts, had a significant influence on RNFL thickness measurements (P<0.05. There was no significant difference between OCT parameters before and after laser refractive surgery. In eyes for which different signal strengths were observed, significantly larger RNFL thickness values were obtained on scans with higher signal strengths. Conclusion: OCT parameters are affected by ocular media opacity because of changes in signal strength; cortical cataracts have the most significant effect followed by posterior subcapsular opacities. Laser refractive procedures do not seem to affect OCT parameters significantly.

  15. The Retinal Nerve Fiber Layer Defects in Patients with Anterior Ischemic Optic Neuropathy

    Institute of Scientific and Technical Information of China (English)

    HaiLu; QiZang

    1995-01-01

    Purpose:To demonstrate the effects of optic nerve ischemia on retinal nerve fiber layer(RNFL)and the associated visual dysfunction.Methods:23patients(25eyes)wits anterior ischemic optic neuropathy(AION)un derwent fundus fluorescein angiography(FFA),and then red-foree light pic-tures were taken via SE-40exceiter filter.All pictures were printed for RNAFL analysis,Humphrey central field analysis was conducted.All dataobtained fromFFA and visual field defects were analysed statistically.Results:The RNFL defects and the corresponding visual field edfects were pre-sented in 23of 25eyes(92%),The optic disc filling defects,RNAL edfects and visual field defects were found to be highly correspondent to each other.The RNFL defects were mainly the local losses of RNFL which were correspondent to the ischemic regions.Conclusion:The poor optic disc filling or ischemia can result in the RNFL defects which cause the associated visual dysfunction.Because RNFLdefects are irrever-siable changes,the potential values in predicting the prognosis of visual field de-fects caused by RNFL damages were suggested.Eye Science1995;11:165-167.

  16. Detection of retinal nerve fiber layer defects on retinal fundus images for early diagnosis of glaucoma

    Science.gov (United States)

    Muramatsu, Chisako; Hayashi, Yoshinori; Sawada, Akira; Hatanaka, Yuji; Hara, Takeshi; Yamamoto, Tetsuya; Fujita, Hiroshi

    2010-01-01

    Retinal nerve fiber layer defect (NFLD) is a major sign of glaucoma, which is the second leading cause of blindness in the world. Early detection of NFLDs is critical for improved prognosis of this progressive, blinding disease. We have investigated a computerized scheme for detection of NFLDs on retinal fundus images. In this study, 162 images, including 81 images with 99 NFLDs, were used. After major blood vessels were removed, the images were transformed so that the curved paths of retinal nerves become approximately straight on the basis of ellipses, and the Gabor filters were applied for enhancement of NFLDs. Bandlike regions darker than the surrounding pixels were detected as candidates of NFLDs. For each candidate, image features were determined and the likelihood of a true NFLD was determined by using the linear discriminant analysis and an artificial neural network (ANN). The sensitivity for detecting the NFLDs was 91% at 1.0 false positive per image by using the ANN. The proposed computerized system for the detection of NFLDs can be useful to physicians in the diagnosis of glaucoma in a mass screening.

  17. Insulin influenced expression of myelin proteins in diabetic peripheral neuropathy.

    Science.gov (United States)

    Rachana, Kuruvanthe S; Manu, Mallahalli S; Advirao, Gopal M

    2016-08-26

    Diabetic peripheral neuropathy (DPN) is one of the downstream complications of diabetes. This complication is caused by the deficiency of insulin action and subsequent hyperglycemia, but the details of their pathogenesis remain unclear. Hence, it is of critical importance to understand how such hormonal variation affects the expression of myelin proteins such as myelin basic protein (MBP) and myelin associated glycoprotein (MAG) in the peripheral nerve. An earlier report from our lab has demonstrated the expression of insulin receptors (IR) in Schwann cells (SCs) of sciatic nerve. To assess the neurotrophic role of insulin in diabetic neuropathy, we studied the expression of these myelin proteins under control, DPN and insulin treated DPN subjects at developmental stages. Further, the expression of these myelin proteins was correlated with the expression of insulin receptor. Expression of myelin proteins was significantly reduced in the diabetic model compared to normal, and upregulated in insulin treated diabetic rats. Similarly, an in vitro study was also carried out in SCs grown at high glucose and insulin treated conditions. The expression pattern of myelin proteins in SCs was comparable to that of in vivo samples. In addition, quantitative study of myelin genes by real time PCR has also showed the significant expression pattern change in the insulin treated and non-treated DPN subjects. Taken together, these results corroborate the critical importance of insulin as a neurotrophic factor in demyelinized neurons in diabetic neuropathy.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-02-20

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

  19. A schwannoma of the S1 dural sleeve was resected while the intact nerve fibers were preserved using a microscope. Report of a case with early MRI findings.

    Science.gov (United States)

    Kobayashi, S; Uchida, K; Kokubo, Y; Yayama, T; Nakajima, H; Inukai, T; Nomura, E; Baba, H

    2007-04-01

    In this report, we describe a small schwannoma of the dural sleeve and mention that it is often difficult to differentiate this tumor from lumbar disc herniation, especially a sequestered hernia, or a discal cyst. Gadolinium-enhanced MR images were a useful preoperative examination modality for differentiating this lesion from other diseases. Microscopically, the intradural tumor was successfully removed. The dura mater of the S1 nerve root was opened microsurgically, allowing the nerve fibers involved in the tumor to be identified. The involved fibers were cut around the tumor, and the lesion was resected while the intact nerve fibers were preserved. Based on histological examination of the resected specimen, the tumor was diagnosed as a schwannoma with multilocular cystic degeneration. Microsurgery allowed the tumor to be removed with minimal impairment from cutting of nerve fibers in the nerve root.

  20. Sox10 Expression in Goldfish Retina and Optic Nerve Head in Controls and after the Application of Two Different Lesion Paradigms

    Science.gov (United States)

    Parrilla, Marta; León-Lobera, Fernando; Lillo, Concepción; Arévalo, Rosario; Aijón, José; Lara, Juan Manuel; Velasco, Almudena

    2016-01-01

    The mammalian central nervous system (CNS) is unable to regenerate. In contrast, the CNS of fish, including the visual system, is able to regenerate after damage. Moreover, the fish visual system grows continuously throughout the life of the animal, and it is therefore an excellent model to analyze processes of myelination and re-myelination after an injury. Here we analyze Sox10+ oligodendrocytes in the goldfish retina and optic nerve in controls and after two kinds of injuries: cryolesion of the peripheral growing zone and crushing of the optic nerve. We also analyze changes in a major component of myelin, myelin basic protein (MBP), as a marker for myelinated axons. Our results show that Sox10+ oligodendrocytes are located in the retinal nerve fiber layer and along the whole length of the optic nerve. MBP was found to occupy a similar location, although its loose appearance in the retina differed from the highly organized MBP+ axon bundles in the optic nerve. After optic nerve crushing, the number of Sox10+ cells decreased in the crushed area and in the optic nerve head. Consistent with this, myelination was highly reduced in both areas. In contrast, after cryolesion we did not find changes in the Sox10+ population, although we did detect some MBP- degenerating areas. We show that these modifications in Sox10+ oligodendrocytes are consistent with their role in oligodendrocyte identity, maintenance and survival, and we propose the optic nerve head as an excellent area for research aimed at better understanding of de- and remyelination processes. PMID:27149509

  1. Sox10 Expression in Goldfish Retina and Optic Nerve Head in Controls and after the Application of Two Different Lesion Paradigms.

    Directory of Open Access Journals (Sweden)

    Marta Parrilla

    Full Text Available The mammalian central nervous system (CNS is unable to regenerate. In contrast, the CNS of fish, including the visual system, is able to regenerate after damage. Moreover, the fish visual system grows continuously throughout the life of the animal, and it is therefore an excellent model to analyze processes of myelination and re-myelination after an injury. Here we analyze Sox10+ oligodendrocytes in the goldfish retina and optic nerve in controls and after two kinds of injuries: cryolesion of the peripheral growing zone and crushing of the optic nerve. We also analyze changes in a major component of myelin, myelin basic protein (MBP, as a marker for myelinated axons. Our results show that Sox10+ oligodendrocytes are located in the retinal nerve fiber layer and along the whole length of the optic nerve. MBP was found to occupy a similar location, although its loose appearance in the retina differed from the highly organized MBP+ axon bundles in the optic nerve. After optic nerve crushing, the number of Sox10+ cells decreased in the crushed area and in the optic nerve head. Consistent with this, myelination was highly reduced in both areas. In contrast, after cryolesion we did not find changes in the Sox10+ population, although we did detect some MBP- degenerating areas. We show that these modifications in Sox10+ oligodendrocytes are consistent with their role in oligodendrocyte identity, maintenance and survival, and we propose the optic nerve head as an excellent area for research aimed at better understanding of de- and remyelination processes.

  2. Stretch-induced nerve injury: a proposed technique for the study of nerve regeneration and evaluation of the influence of gabapentin on this model

    Directory of Open Access Journals (Sweden)

    J.A. Machado

    2013-11-01

    Full Text Available The rat models currently employed for studies of nerve regeneration present distinct disadvantages. We propose a new technique of stretch-induced nerve injury, used here to evaluate the influence of gabapentin (GBP on nerve regeneration. Male Wistar rats (300 g; n=36 underwent surgery and exposure of the median nerve in the right forelimbs, either with or without nerve injury. The technique was performed using distal and proximal clamps separated by a distance of 2 cm and a sliding distance of 3 mm. The nerve was compressed and stretched for 5 s until the bands of Fontana disappeared. The animals were evaluated in relation to functional, biochemical and histological parameters. Stretching of the median nerve led to complete loss of motor function up to 12 days after the lesion (P<0.001, compared to non-injured nerves, as assessed in the grasping test. Grasping force in the nerve-injured animals did not return to control values up to 30 days after surgery (P<0.05. Nerve injury also caused an increase in the time of sensory recovery, as well as in the electrical and mechanical stimulation tests. Treatment of the animals with GBP promoted an improvement in the morphometric analysis of median nerve cross-sections compared with the operated vehicle group, as observed in the area of myelinated fibers or connective tissue (P<0.001, in the density of myelinated fibers/mm2 (P<0.05 and in the degeneration fragments (P<0.01. Stretch-induced nerve injury seems to be a simple and relevant model for evaluating nerve regeneration.

  3. Peripheral nerve injury and TRPV1-expressing primary afferent C-fibers cause opening of the blood-brain barrier

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    Salter Michael W

    2010-11-01

    Full Text Available Abstract Background The blood-brain barrier (BBB plays the crucial role of limiting exposure of the central nervous system (CNS to damaging molecules and cells. Dysfunction of the BBB is critical in a broad range of CNS disorders including neurodegeneration, inflammatory or traumatic injury to the CNS, and stroke. In peripheral tissues, the vascular-tissue permeability is normally greater than BBB permeability, but vascular leakage can be induced by efferent discharge activity in primary sensory neurons leading to plasma extravasation into the extravascular space. Whether discharge activity of sensory afferents entering the CNS may open the BBB or blood-spinal cord barrier (BSCB remains an open question. Results Here we show that peripheral nerve injury (PNI produced by either sciatic nerve constriction or transecting two of its main branches causes an increase in BSCB permeability, as assessed by using Evans Blue dye or horseradish peroxidase. The increase in BSCB permeability was not observed 6 hours after the PNI but was apparent 24 hours after the injury. The increase in BSCB permeability was transient, peaking about 24-48 hrs after PNI with BSCB integrity returning to normal levels by 7 days. The increase in BSCB permeability was prevented by administering the local anaesthetic lidocaine at the site of the nerve injury. BSCB permeability was also increased 24 hours after electrical stimulation of the sciatic nerve at intensity sufficient to activate C-fibers, but not when A-fibers only were activated. Likewise, BSCB permeability increased following application of capsaicin to the nerve. The increase in permeability caused by C-fiber stimulation or by PNI was not anatomically limited to the site of central termination of primary afferents from the sciatic nerve in the lumbar cord, but rather extended throughout the spinal cord and into the brain. Conclusions We have discovered that injury to a peripheral nerve and electrical stimulation of C-fibers

  4. Synergistic motor nerve fiber transfer between different nerves through the use of end-to-side coaptation.

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    Schmidhammer, R; Nógrádi, A; Szabó, A; Redl, H; Hausner, T; van der Nest, D G; Millesi, H

    2009-06-01

    End-to-end nerve repair is a widely used and successful experimental microsurgical technique via which a denervated nerve stump is supplied with reinnervating motor or sensory axons. On the other hand, questions are still raised as concerns the reliability and usefulness of the end-to-side coaptation technique. This study had the aim of the reinnervation of the denervated forearm flexor muscles in baboons through the use of an end-to-side coaptation technique and the synergistic action of the radial nerve. The median and ulnar nerves were transected, and the motor branch of the radial nerve supplying the extensor carpi radialis muscles (MBECR) was used as an axon donor for the denervated superficial forearm flexors. A nerve graft was connected to the axon donor nerve through end-to-side coaptation, while at the other end of the graft an end-to-end connection was established so as to reinnervate the motor branch of the forearm flexors. Electrophysiological investigations and functional tests indicated successful reinnervation of the forearm flexors and recovery of the flexor function. The axon counts in the nerve segments proximal (1038+/-172 S.E.M.) and distal (1050+/-116 S.E.M.) to the end-to-side coaptation site and in the nerve graft revealed that motor axon collaterals were given to the graft without the loss or appreciable misdirection of the axons in the MBECR nerve distal to the coaptation site. The nerve graft was found to contain varying, but satisfactory numbers of axons (269+/-59 S.E.M.) which induced morphological reinnervation of the end-plates in the flexor muscles. Accordingly, we have provided evidence that end-to-side coaptation can be a useful technique when no free donor nerve is available. This technique is able to induce limited, but still useful reinnervation for the flexor muscles, thereby producing a synergistic action of the flexor and extensor muscles which allows the hand to achieve a basic gripping function.

  5. [Peripheral nerve disease associated with acute renal failure due to bromate poisoning].

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    Deshimaru, M; Miyagawa, T; Sumiyoshi, S; Nomura, Y

    1976-08-01

    A case of 21 year old male with neuropathy caused by renal insufficiency was present. He had taken bromate (mixed powder of potassium bromate and sodium bromate) for the purpose of suicide and suffered from acute renal insufficiency and hard of hearing. Renal dysfunction improved gradually by peritoneal dialysis and hemodialysis. However, on the 32th day after the onset, burning pain appeared in the bilateral feets. Following this, he began to complain of the disturbances of superficial and deep sensory below the ankle jerks and the weakness of his toes. Considering the clinical features, we supposed that the disturbance of the peripheral nerve was caused by uremia due to taking bromate. N. suralis was biopsied on the 80th day after the onset and examined electron microscopically. Electroscopical findings was as follows. Degeneration of the Schwann cells and irregularity or destruction of the myelin sheaths were observed. The axoplasm of the myelinated nerve fiber were relatively preserved as compared with the changes of the myelin sheaths. In the unmyelinated nerve fibers, cavity formations were observed. The findings of regeneration were not observed. From the electron microscopical findings, we speculate that the changes of the Schwann cells and the myelin sheaths are primary resulting from the disturbance of the metabolism of the Schwann cells. We speculate that anemia and hypoproteinemia caused by bromate disturbed regeneration.

  6. Post-evaluation of the neurophaties treatment post-trauma with therapeutic laser. Model in sciatic nerve of frog

    Science.gov (United States)

    Escobar, Antonio S.; Ocampo, Arcelia F. M.; Hernández, María G. H.; Jasso, José L. C.; Lira, Maricela O. F.; Flores, Mariana A.; Balderrama, Vicente L.

    2010-05-01

    The purpose of this study was to evaluate the compound nerve action potential amplitude and latency measured to determine the degree of myelination and the number of fibers stimulated in a model of stimulated frog sciatic nerve laser at 810 nm as perioperative treatment after injury. It used 30 bullfrogs (Rana catesbeiana) to obtain 60 sciatic nerves forming four groups, groups 1 and 2 worked with nerves in vitro, were dissected in humid chambers for placing isolated organ, was recorded on compound nerve action potential, the second group laser was applied at 24, 48, 72, 96 and 120 hours and at the same time were placed in 10% formalin. Groups 3 and 4 are worked in vivo localizing the nerve and causing damage through compression, occurred over the compound nerve action potential to assess the degree of myelination and the number of fibers stimulated, the group 4 was applied to 810 nm laser (500 Hz, 10 J, 200 mW) after injury, after 48 hours, three frogs were sacrificed by introducing the nerves in 10% formalin. The latency recorded by stimulating the sciatic nerve of frog to 0.5 mA and 100 ms in groups 1 and 2 show significant differences (p000), as to the extent, if any statistically significant difference. (p<0.001 and p<0.000). The laser produces a favorable response in the treatment of paresthesia (post-traumatic neuropathy).

  7. Origin and endpoint of the olfactory nerve fibers: as described by Santiago Ramón y Cajal.

    Science.gov (United States)

    Levine, Catherine; Marcillo, Alexander

    2008-07-01

    In the late Nineteenth Century, Santiago Ramón y Cajal was able to reproduce an exceptional illustration of the Olfactory Nerve pathway and its myriad of cells, by using the Golgi Method. Dr. Cajal focused intense study on the histology of the nervous system and published a treatise on the olfactory nerve fibers and the distinct peripheral origin and central nervous system endpoint of this unique pathway. The original title of this work is "Origen y terminación de las fibras nerviosas olfatorias" published in 1890. As the original publication is in Spanish, here we provide an English translation allowing present-day English speakers to read these writings. Cajal followed the trajectory of the olfactory nerve fibers as they transitioned between the peripheral and central nervous system and was able to assert that these fibers were not continuous from the olfactory bulb to the bipolar cells that relinquish into the olfactory epithelium, but that the olfactory system was made up of various cell types each having distinct morphologies and functions. This may very well be the first definitive description of the olfactory receptor neurons and the first illustrations of the continuity of these cells throughout the olfactory pathway. These meticulous histological preparations were created by first using Camillo Golgi's potassium dichromate and silver nitrate impregnation method known as "reazione nera" or "black reaction," where nerve cells, nerve fibers, and neuroglia could be visualized. This study exhibits the structural and functional organization of the mammalian fila olfactoria as it was investigated in centuries past.

  8. Structural insight into the function of myelin basic protein as a ligand for integrin αMβ2

    DEFF Research Database (Denmark)

    Stapulionis, Romualdas; Oliveira, Cristiano; Gjelstrup, Mikkel Carstensen

    2008-01-01

    Multiple sclerosis (MS) is an inflammatory disease where phagocytic cells infiltrate the nerve tissue and act as terminal agents in destruction of the myelin sheath. However, the mechanism that triggers the ability of these cells to recognize myelin remains obscure. We show that myelin basic...

  9. Transcriptional Expression of Myelin Basic Protein in Oligodendrocytes Depends on Functional Syntaxin 4 : a Potential Correlation with Autocrine Signaling

    NARCIS (Netherlands)

    Bijlard, Marjolein; Klunder, Lammert; de Jonge, Jenny C.; Nomden, Anita; Tyagi, Sanjay; de Vries, Hans; Hoekstra, Dick; Baron, Wia

    2015-01-01

    Myelination of axons by oligodendrocytes is essential for saltatory nerve conduction. To form myelin membranes, a coordinated synthesis and subsequent polarized transport of myelin components are necessary. Here, we show that as part of the mechanism to establish membrane polarity, oligodendrocytes

  10. Myelin membrane assembly is driven by a phase transition of myelin basic proteins into a cohesive protein meshwork.

    Directory of Open Access Journals (Sweden)

    Shweta Aggarwal

    Full Text Available Rapid conduction of nerve impulses requires coating of axons by myelin. To function as an electrical insulator, myelin is generated as a tightly packed, lipid-rich multilayered membrane sheath. Knowledge about the mechanisms that govern myelin membrane biogenesis is required to understand myelin disassembly as it occurs in diseases such as multiple sclerosis. Here, we show that myelin basic protein drives myelin biogenesis using weak forces arising from its inherent capacity to phase separate. The association of myelin basic protein molecules to the inner leaflet of the membrane bilayer induces a phase transition into a cohesive mesh-like protein network. The formation of this protein network shares features with amyloid fibril formation. The process is driven by phenylalanine-mediated hydrophobic and amyloid-like interactions that provide the molecular basis for protein extrusion and myelin membrane zippering. These findings uncover a physicochemical mechanism of how a cytosolic protein regulates the morphology of a complex membrane architecture. These results provide a key mechanism in myelin membrane biogenesis with implications for disabling demyelinating diseases of the central nervous system.

  11. Myelin membrane assembly is driven by a phase transition of myelin basic proteins into a cohesive protein meshwork.

    Science.gov (United States)

    Aggarwal, Shweta; Snaidero, Nicolas; Pähler, Gesa; Frey, Steffen; Sánchez, Paula; Zweckstetter, Markus; Janshoff, Andreas; Schneider, Anja; Weil, Marie-Theres; Schaap, Iwan A T; Görlich, Dirk; Simons, Mikael

    2013-01-01

    Rapid conduction of nerve impulses requires coating of axons by myelin. To function as an electrical insulator, myelin is generated as a tightly packed, lipid-rich multilayered membrane sheath. Knowledge about the mechanisms that govern myelin membrane biogenesis is required to understand myelin disassembly as it occurs in diseases such as multiple sclerosis. Here, we show that myelin basic protein drives myelin biogenesis using weak forces arising from its inherent capacity to phase separate. The association of myelin basic protein molecules to the inner leaflet of the membrane bilayer induces a phase transition into a cohesive mesh-like protein network. The formation of this protein network shares features with amyloid fibril formation. The process is driven by phenylalanine-mediated hydrophobic and amyloid-like interactions that provide the molecular basis for protein extrusion and myelin membrane zippering. These findings uncover a physicochemical mechanism of how a cytosolic protein regulates the morphology of a complex membrane architecture. These results provide a key mechanism in myelin membrane biogenesis with implications for disabling demyelinating diseases of the central nervous system.

  12. Sensory nerve conduction and nociception in the equine lower forelimb during perineural bupivacaine infusion along the palmar nerves

    Science.gov (United States)

    Zarucco, Laura; Driessen, Bernd; Scandella, Massimiliano; Cozzi, Francesca; Cantile, Carlo

    2010-01-01

    The purpose of this investigation was to study lateral palmar nerve (LPN) and medial palmar nerve (MPN) morphology and determine nociception and sensory nerve conduction velocity (SNCV) following placement of continuous peripheral nerve block (CPNB) catheters along LPN and MPN with subsequent bupivacaine (BUP) infusion. Myelinated nerve fiber distribution in LPN and MPN was examined after harvesting nerve specimens in 3 anesthetized horses and processing them for morphometric analysis. In 5 sedated horses, CPNB catheters were placed along each PN in both forelimbs. Horses then received in one forelimb 3 mL 0.125% BUP containing epinephrine 1:200 000 and 0.04% NaHCO3 per catheter site followed by 2 mL/h infusion over a 6-day period, while in the other forelimb equal amounts of saline (SAL) solution were administered. The hoof withdrawal response (HWR) threshold during pressure loading of the area above the dorsal coronary band was determined daily in both forelimbs. On day 6 SNCV was measured under general anesthesia of horses in each limb’s LPN and MPN to detect nerve injury, followed by CPNB catheter removal. The SNCV was also recorded in 2 anesthetized non-instrumented horses (sham controls). In both LPN and MPN myelinated fiber distributions were bimodal. The fraction of large fibers (>7 μm) was greater in the MPN than LPN (P < 0.05). Presence of CPNB catheters and SAL administration did neither affect measured HWR thresholds nor SNCVs, whereas BUP infusion suppressed HWRs. In conclusion, CPNB with 0.125% BUP provides pronounced analgesia by inhibiting sensory nerve conduction in the distal equine forelimb. PMID:21197231

  13. Effects of tacrolimus (FK506) on sciatic nerve regeneration in rats

    Institute of Scientific and Technical Information of China (English)

    Weiguo Zhang; Decheng Lü; Shouyu Wang; Chongyang Fu

    2009-01-01

    BACKGROUND: Tacrolimus (FK506) protects peripheral nerves located in damaged regions by inhibiting T lymphocyte proliferation and activation.OBJECTIVE: To evaluate the effect of FK506 on promoting regeneration of rat sciatic nerve. DESIGN, TIME AND SETTING: A randomized, controlled, animal study was performed at the Laboratory of the Department of Orthopedic Surgery, Dalian Medical University, China, from September 2007 to September 2008.MATERIALS: A total of 60 adult, male, Sprague-Dawley rats were equally and randomly divided into model, local administration and systemic administration groups. All rats received a neurotomy of bilateral sciatic nerves to establish models of nerve regeneration chambers. The powder and injection of FK506 were supplied by Fujisawa Pharmaceutical, Japan.METHODS: The regeneration chambers of the model group were infused with 0.2 mL saline. The systemic group were injected with 0.2 mL saline, followed by daily subcutaneous injections of FK506 (1 mg/kg), for 14 days. The local administration group was infused with 0.2 mL FK506 (1 μg/mL).MAIN OUTCOME MEASURES: Local immune response was observed using hematoxylin-eosin staining. Myelinated nerve fiber number, myelin sheath and nerve fiber thickness were observed using toluidine blue staining. Wet weight of gastrocnemius was evaluated. Compound muscle action potential amplitude, latency, and conduction time were recorded, and motor nerve conduction velocity was calculated using electrophysiology.RESULTS: The total number of myeiinated nerve fibers in the local and systemic administration groups was significantly higher than in the model group. The density of myelinated nerve fibers, myelin sheath thickness and mean axon diameter were significantly increased in the systemic administration group compared with the model group (P < 0.05). Lymphocyte infiltration was decreased in the local and systemic administration groups compared with the model group. The wet weight of rat gastrocnemius in

  14. Nogo-A and myelin-associated glycoprotein differently regulate oligodendrocyte maturation and myelin formation.

    Science.gov (United States)

    Pernet, Vincent; Joly, Sandrine; Christ, Franziska; Dimou, Leda; Schwab, Martin E

    2008-07-16

    Nogo-A is one of the most potent oligodendrocyte-derived inhibitors for axonal regrowth in the injured adult CNS. However, the physiological function of Nogo-A in development and in healthy oligodendrocytes is still unknown. In the present study, we investigated the role of Nogo-A for myelin formation in the developing optic nerve. By quantitative real-time PCR, we found that the expression of Nogo-A increased faster in differentiating oligodendrocytes than that of the major myelin proteins MBP (myelin basic protein), PLP (proteolipid protein)/DM20, and CNP (2',3'-cyclic nucleotide 3'-phosphodiesterase). The analysis of optic nerves and cerebella of mice deficient for Nogo-A (Nogo-A(-/-)) revealed a marked delay of oligodendrocyte differentiation, myelin sheath formation, and axonal caliber growth within the first postnatal month. The combined deletion of Nogo-A and MAG caused a more severe transient hypomyelination. In contrast to MAG(-/-) mice, Nogo-A(-/-) mutants did not present abnormalities in the structure of myelin sheaths and Ranvier nodes. The common binding protein for Nogo-A and MAG, NgR1, was exclusively upregulated in MAG(-/-) animals, whereas the level of Lingo-1, a coreceptor, remained unchanged. Together, our results demonstrate that Nogo-A and MAG are differently involved in oligodendrocyte maturation in vivo, and suggest that Nogo-A may influence also remyelination in pathological conditions such as multiple sclerosis.

  15. Structural Transition in Myelin Membrane as Initiator of Multiple Sclerosis.

    Science.gov (United States)

    Shaharabani, Rona; Ram-On, Maor; Avinery, Ram; Aharoni, Rina; Arnon, Ruth; Talmon, Yeshayahu; Beck, Roy

    2016-09-21

    In demyelinating diseases such as multiple sclerosis, disrupted myelin structures impair the functional role of the sheath as an insulating layer for proper nerve conduction. Though the etiology and recovery pathways remain unclear, in vivo studies show alterations in the lipid and the adhesive protein (myelin basic protein, MBP) composition. We find that in vitro cytoplasmic myelin membranes with modified lipid composition and low MBP concentration, as in demyelinating disease, show structural instabilities and pathological phase transition from a lamellar to inverted hexagonal, which involve enhanced local curvature. Similar curvatures are also found in vivo in diseased myelin sheaths. In addition, MBP dimers form a correlated mesh-like network within the inner membrane space, only in the vicinity of native lipid composition. These findings delineate the distinct functional roles of dominant constituents in cytoplasmic myelin sheaths, and shed new light on mechanisms disrupting lipid-protein complexes in the diseased state.

  16. Molecular evolution of myelin basic protein, an abundant structural myelin component.

    Science.gov (United States)

    Nawaz, Schanila; Schweitzer, Jörn; Jahn, Olaf; Werner, Hauke B

    2013-08-01

    Rapid nerve conduction in jawed vertebrates is facilitated by the myelination of axons, which evolved in ancient cartilaginous fish. We aim to understand the coevolution of myelin and the major myelin proteins. We found that myelin basic protein (MBP) derived from living cartilaginous fish (sharks and rays) associated with the plasma membrane of glial cells similar to the phosphatidylinositol (4,5)-bisphosphate (PIP₂)-binding marker PH-PLCδ1, and that ionomycin-induced PIP₂-hydrolysis led to its cellular redistribution. We identified two paralogous mbp genes in multiple teleost species, consistent with a genome duplication at the root of the teleost clade. Zebrafish mbpb is organized in a complex transcription unit together with the unrelated gene-of-the-oligodendrocyte-lineage (golli) while mbpa does not encode GOLLI. Moreover, the embryonic expression of mbpa and mbpb differed, indicating functional specialization after duplication. However, both mbpa and mbpb-mRNAs were detected in mature oligodendrocytes and Schwann cells, MBPa and MBPb were mass spectrometrically identified in zebrafish myelin, both associated with the plasma membrane via PIP₂, and the ratio of nonsynonymous to synonymous nucleotide-substitution rates (Ka/Ks) was low. Together, this indicates selective pressure to conserve many aspects of the cellular expression and function of MBP across vertebrate species. We propose that the PIP₂-binding function of MBP is evolutionarily old and that its emergence in ancient gnathostomata provided glial cells with the competence to myelinate.

  17. Myelin, myelin-related disorders, and psychosis.

    Science.gov (United States)

    Mighdoll, Michelle I; Tao, Ran; Kleinman, Joel E; Hyde, Thomas M

    2015-01-01

    The neuropathological basis of schizophrenia and related psychoses remains elusive despite intensive scientific investigation. Symptoms of psychosis have been reported in a number of conditions where normal myelin development is interrupted. The nature, location, and timing of white matter pathology seem to be key factors in the development of psychosis, especially during the critical adolescent period of association area myelination. Numerous lines of evidence implicate myelin and oligodendrocyte function as critical processes that could affect neuronal connectivity, which has been implicated as a central abnormality in schizophrenia. Phenocopies of schizophrenia with a known pathological basis involving demyelination or dysmyelination may offer insights into the biology of schizophrenia itself. This article reviews the pathological changes in white matter of patients with schizophrenia, as well as demyelinating diseases associated with psychosis. In an attempt to understand the potential role of dysmyelination in schizophrenia, we outline the evidence from a number of both clinically-based and post-mortem studies that provide evidence that OMR genes are genetically associated with increased risk for schizophrenia. To further understand the implication of white matter dysfunction and dysmyelination in schizophrenia, we examine diffusion tensor imaging (DTI), which has shown volumetric and microstructural white matter differences in patients with schizophrenia. While classical clinical-neuropathological correlations have established that disruption in myelination can produce a high fidelity phenocopy of psychosis similar to schizophrenia, the role of dysmyelination in schizophrenia remains controversial.

  18. Does the addition of a nerve wrap to a motor nerve repair affect motor outcomes?

    Science.gov (United States)

    Lee, Joo-Yup; Parisi, Thomas J; Friedrich, Patricia F; Bishop, Allen T; Shin, Alexander Y

    2014-10-01

    The purpose of this study was to evaluate the effect of wrapping bioabsorbable nerve conduit around primary suture repair on motor nerve regeneration in a rat model. Forty rats were randomly divided into two experimental groups according to the type of repair of the rat sciatic nerve: group I had primary suture repair; group II had primary suture repair and bioabsorbable collagen nerve conduit (NeuraGen® 1.5 mm, Integra LifeSciences Corp., Plainsboro, NJ) wrapped around the repair. At 12 weeks, no significant differences in the percentage of recovery between the two groups were observed with respect to compound muscle action potentials, isometric muscle force, and muscle weight (P = 0.816, P = 0.698, P = 0.861, respectively). Histomorphometric analysis as compared to the non-operative sites was also not significantly different between the two groups in terms of number of myelinated axons, myelinated fiber area, and nerve fiber density (P = 0.368, P = 0.968, P = 0.071, respectively). Perineural scar tissue formation was greater in primary suture repair group (0.36 ± 0.15) than in primary repair plus conduit wrapping group (0.17 ± 0.08). This difference was statistically significant (P decrease perineural scar tissue formation. Although the scar-decreasing effect of bioabsorbable nerve wrap does not translate into better motor nerve recovery in this study, it might have an effect on the functional outcome in humans where scar formation is much more evident than in rats.

  19. Innervation of the Human Cavum Conchae and Auditory Canal: Anatomical Basis for Transcutaneous Auricular Nerve Stimulation

    Science.gov (United States)

    Bermejo, P.; López, M.; Larraya, I.; Chamorro, J.; Cobo, J. L.; Ordóñez, S.

    2017-01-01

    The innocuous transcutaneous stimulation of nerves supplying the outer ear has been demonstrated to be as effective as the invasive direct stimulation of the vagus nerve for the treatment of some neurological and nonneurological disturbances. Thus, the precise knowledge of external ear innervation is of maximal interest for the design of transcutaneous auricular nerve stimulation devices. We analyzed eleven outer ears, and the innervation was assessed by Masson's trichrome staining, immunohistochemistry, or immunofluorescence (neurofilaments, S100 protein, and myelin-basic protein). In both the cavum conchae and the auditory canal, nerve profiles were identified between the cartilage and the skin and out of the cartilage. The density of nerves and of myelinated nerve fibers was higher out of the cartilage and in the auditory canal with respect to the cavum conchae. Moreover, the nerves were more numerous in the superior and posterior-inferior than in the anterior-inferior segments of the auditory canal. The present study established a precise nerve map of the human cavum conchae and the cartilaginous segment of the auditory canal demonstrating regional differences in the pattern of innervation of the human outer ear. These results may provide additional neuroanatomical basis for the accurate design of auricular transcutaneous nerve stimulation devices.

  20. Regeneration of peripheral nerve fibres following Haloxon-induced degeneration

    Directory of Open Access Journals (Sweden)

    Maria Veronica de Souza

    1996-12-01

    Full Text Available Delayed neurotoxicity has been associated with organophosphorus poisoning for years. In order to study such condition in sheep, 11 animals were given either one or two high doses of Haloxon. Exposed sheep were observed daily and between 16 and 25 days after administration neurological signs as incoordination and ataxia were detected in six of them. Biopsies of tibial and laryngeal nerves were performed as soon as neurotoxicity was diagnosed, and after death fragments of selected nerves were collected together with CNS tissues for light and electron microscopy and teased fiber studies. Laryngeal, tibial and sciatic nerves showed the most pronouced changes, consisting chiefly of wallerian degeneration that was seen either as a single fiber or as a complete fascicle feature. Exams performed after death clearly showed regenerating fascicles with axonal sprouts growing within a Schwann cell old basal lamina, and some thinly myelinated axonal sprouts.

  1. The phylogeny of invertebrates and the evolution of myelin.

    Science.gov (United States)

    Roots, Betty I

    2008-05-01

    Current concepts of invertebrate phylogeny are reviewed. Annelida and Arthropoda, previously regarded as closely related, are now placed in separate clades. Myelin, a sheath of multiple layers of membranes around nerve axons, is found in members of the Annelida, Arthropoda and Chordata. The structure, composition and function of the sheaths in Annelida and Arthropoda are examined and evidence for the separate evolutionary origins of myelin in the three clades is presented. That myelin has arisen independently at least three times, namely in Annelids, Arthropodas and Chordates, provides a remarkable example of convergent evolution.

  2. Auditory brainstem responses predict auditory nerve fiber thresholds and frequency selectivity in hearing impaired chinchillas.

    Science.gov (United States)

    Henry, Kenneth S; Kale, Sushrut; Scheidt, Ryan E; Heinz, Michael G

    2011-10-01

    Noninvasive auditory brainstem responses (ABRs) are commonly used to assess cochlear pathology in both clinical and research environments. In the current study, we evaluated the relationship between ABR characteristics and more direct measures of cochlear function. We recorded ABRs and auditory nerve (AN) single-unit responses in seven chinchillas with noise-induced hearing loss. ABRs were recorded for 1-8 kHz tone burst stimuli both before and several weeks after 4 h of exposure to a 115 dB SPL, 50 Hz band of noise with a center frequency of 2 kHz. Shifts in ABR characteristics (threshold, wave I amplitude, and wave I latency) following hearing loss were compared to AN-fiber tuning curve properties (threshold and frequency selectivity) in the same animals. As expected, noise exposure generally resulted in an increase in ABR threshold and decrease in wave I amplitude at equal SPL. Wave I amplitude at equal sensation level (SL), however, was similar before and after noise exposure. In addition, noise exposure resulted in decreases in ABR wave I latency at equal SL and, to a lesser extent, at equal SPL. The shifts in ABR characteristics were significantly related to AN-fiber tuning curve properties in the same animal at the same frequency. Larger shifts in ABR thresholds and ABR wave I amplitude at equal SPL were associated with greater AN threshold elevation. Larger reductions in ABR wave I latency at equal SL, on the other hand, were associated with greater loss of AN frequency selectivity. This result is consistent with linear systems theory, which predicts shorter time delays for broader peripheral frequency tuning. Taken together with other studies, our results affirm that ABR thresholds and wave I amplitude provide useful estimates of cochlear sensitivity. Furthermore, comparisons of ABR wave I latency to normative data at the same SL may prove useful for detecting and characterizing loss of cochlear frequency selectivity.

  3. YAP/TAZ initiate and maintain Schwann cell myelination

    Science.gov (United States)

    Grove, Matthew; Kim, Hyukmin; Santerre, Maryline; Krupka, Alexander J; Han, Seung Baek; Zhai, Jinbin; Cho, Jennifer Y; Park, Raehee; Harris, Michele; Kim, Seonhee; Sawaya, Bassel E; Kang, Shin H; Barbe, Mary F; Cho, Seo-Hee; Lemay, Michel A; Son, Young-Jin

    2017-01-01

    Nuclear exclusion of the transcriptional regulators and potent oncoproteins, YAP/TAZ, is considered necessary for adult tissue homeostasis. Here we show that nuclear YAP/TAZ are essential regulators of peripheral nerve development and myelin maintenance. To proliferate, developing Schwann cells (SCs) require YAP/TAZ to enter S-phase and, without them, fail to generate sufficient SCs for timely axon sorting. To differentiate, SCs require YAP/TAZ to upregulate Krox20 and, without them, completely fail to myelinate, resulting in severe peripheral neuropathy. Remarkably, in adulthood, nuclear YAP/TAZ are selectively expressed by myelinating SCs, and conditional ablation results in severe peripheral demyelination and mouse death. YAP/TAZ regulate both developmental and adult myelination by driving TEAD1 to activate Krox20. Therefore, YAP/TAZ are crucial for SCs to myelinate developing nerve and to maintain myelinated nerve in adulthood. Our study also provides a new insight into the role of nuclear YAP/TAZ in homeostatic maintenance of an adult tissue. DOI: http://dx.doi.org/10.7554/eLife.20982.001 PMID:28124973

  4. YAP/TAZ initiate and maintain Schwann cell myelination.

    Science.gov (United States)

    Grove, Matthew; Kim, Hyukmin; Santerre, Maryline; Krupka, Alexander J; Han, Seung Baek; Zhai, Jinbin; Cho, Jennifer Y; Park, Raehee; Harris, Michele; Kim, Seonhee; Sawaya, Bassel E; Kang, Shin H; Barbe, Mary F; Cho, Seo-Hee; Lemay, Michel A; Son, Young-Jin

    2017-01-26

    Nuclear exclusion of the transcriptional regulators and potent oncoproteins, YAP/TAZ, is considered necessary for adult tissue homeostasis. Here we show that nuclear YAP/TAZ are essential regulators of peripheral nerve development and myelin maintenance. To proliferate, developing Schwann cells (SCs) require YAP/TAZ to enter S-phase and, without them, fail to generate sufficient SCs for timely axon sorting. To differentiate, SCs require YAP/TAZ to upregulate Krox20 and, without them, completely fail to myelinate, resulting in severe peripheral neuropathy. Remarkably, in adulthood, nuclear YAP/TAZ are selectively expressed by myelinating SCs, and conditional ablation results in severe peripheral demyelination and mouse death. YAP/TAZ regulate both developmental and adult myelination by driving TEAD1 to activate Krox20. Therefore, YAP/TAZ are crucial for SCs to myelinate developing nerve and to maintain myelinated nerve in adulthood. Our study also provides a new insight into the role of nuclear YAP/TAZ in homeostatic maintenance of an adult tissue.

  5. Diffusion tensor imaging with quantitative evaluation and fiber tractography of lumbar nerve roots in sciatica

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Yin; Zong, Min; Xu, Xiaoquan; Zou, Yuefen; Feng, Yang; Liu, Wei; Wang, Chuanbing; Wang, Dehang, E-mail: njmu_wangdehang@126.com

    2015-04-15

    Highlights: •In the present study, we first elected ROIs corresponding to the proximal, medial, and distal levels of the lumbar foraminal zone. •The ROC analysis for FA values of distal nerves indicated a high level of reliability in the diagnosis of sciatica. •The declining trend of FA values from proximal to distal along the nerve tract may correlate with the disparity of axonal regeneration at different levels. •DTI is able to quantitatively evaluate compressed nerve roots and has a higher sensitivity and specificity for diagnosing sciatica than conventional MR imaging. •DTT enables visualization of abnormal nerve tracts, providing vivid anatomic information and probable localization of nerve compression. -- Abstract: Objective: To quantitatively evaluate nerve roots by measuring fractional anisotropy (FA) values in healthy volunteers and sciatica patients, visualize nerve roots by tractography, and compare the diagnostic efficacy between conventional magnetic resonance imaging (MRI) and DTI. Materials and methods: Seventy-five sciatica patients and thirty-six healthy volunteers underwent MR imaging using DTI. FA values for L5–S1 lumbar nerve roots were calculated at three levels from DTI images. Tractography was performed on L3–S1 nerve roots. ROC analysis was performed for FA values. Results: The lumbar nerve roots were visualized and FA values were calculated in all subjects. FA values decreased in compressed nerve roots and declined from proximal to distal along the compressed nerve tracts. Mean FA values were more sensitive and specific than MR imaging for differentiating compressed nerve roots, especially in the far lateral zone at distal nerves. Conclusions: DTI can quantitatively evaluate compressed nerve roots, and DTT enables visualization of abnormal nerve tracts, providing vivid anatomic information and localization of probable nerve compression. DTI has great potential utility for evaluating lumbar nerve compression in sciatica.

  6. Human myelin proteome and comparative analysis with mouse myelin

    OpenAIRE

    Ishii, Akihiro; Dutta, Ranjan; Wark, Greg M.; Hwang, Sun-Il; Han, David K.; Trapp, Bruce D.; Pfeiffer, Steven E.; Bansal, Rashmi

    2009-01-01

    Myelin, formed by oligodendrocytes (OLs) in the CNS, is critical for axonal functions, and its damage leads to debilitating neurological disorders such as multiple sclerosis. Understanding the molecular mechanisms of myelination and the pathogenesis of human myelin disease has been limited partly by the relative lack of identification and functional characterization of the repertoire of human myelin proteins. Here, we present a large-scale analysis of the myelin proteome, using the shotgun ap...

  7. Changes in retinal nerve fiber layer thickness after spinal surgery in the prone position: a prospective study

    Directory of Open Access Journals (Sweden)

    Baran Gencer

    2015-02-01

    Full Text Available BACKGROUND AND OBJECTIVES: Changes in ocular perfusion play an important role in the pathogenesis of ischemic optic neuropathy. Ocular perfusion pressure is equal to mean arterial pressure minus intraocular pressure. The aim of this study was to evaluate the changes in the intraocular pressure and the retinal nerve fiber layer thickness in patients undergoing spinal surgery in the prone position. METHODS: This prospective study included 30 patients undergoing spinal surgery. Retinal nerve fiber layer thickness were measured one day before and after the surgery by using optical coherence tomography. Intraocular pressure was measured by tonopen six times at different position and time-duration: supine position (baseline; 10 min after intubation (Supine 1; 10 (Prone 1, 60 (Prone 2, 120 (Prone 3 min after prone position; and just after postoperative supine position (Supine 2. RESULTS: Our study involved 10 male and 20 female patients with the median age of 57 years. When postoperative retinal nerve fiber layer thickness measurements were compared with preoperative values, a statistically significant thinning was observed in inferior and nasal quadrants (p = 0.009 and p = 0.003, respectively. We observed a statistically significant intraocular pressure decrease in Supine 1 and an increase in both Prone 2 and Prone 3 when compared to the baseline. Mean arterial pressure and ocular perfusion pressure were found to be significantly lower in Prone 1, Prone 2 and Prone 3, when compared with the baseline. CONCLUSIONS: Our study has shown increase in intraocular pressure during spinal surgery in prone position. A statistically significant retinal nerve fiber layer thickness thinning was seen in inferior and nasal quadrants one day after the spinal surgery.

  8. Paradoxical thinning of the retinal nerve fiber layer after reversal of cupping: A case report of primary infantile glaucoma

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    Ta Chen Chang

    2016-01-01

    Full Text Available The circumpapillary retinal nerve fiber layer (RNFL thickness was assessed by spectral domain optical coherent tomography (SD-OCT before and after surgical reduction of intraocular pressure in an eye with primary infantile glaucoma. In this case, a postoperative reduction of cupping and a subsequent increase in neuroretinal rim area is associated with a paradoxical thinning of the RNFL. This is the first-known characterization of cupping reversal using SD-OCT.

  9. Human primordial germ cells migrate along nerve fibers and Schwann cells from the dorsal hind gut mesentery to the gonadal ridge

    DEFF Research Database (Denmark)

    Møllgård, Kjeld; Jespersen, Åse; Lutterodt, Melissa Catherine

    2010-01-01

    The aim of this study was to investigate the spatiotemporal development of autonomic nerve fibers and primordial germ cells (PGCs) along their migratory route from the dorsal mesentery to the gonadal ridges in human embryos using immunohistochemical markers and electron microscopy. Autonomic nerve...

  10. Clinicopathological Features and Immunohistochemical Alterations of Keratinocyte Proliferation, Melanocyte Density, Smooth Muscle Hyperplasia and Nerve Fiber Distribution in Becker's Nevus

    Science.gov (United States)

    Sheng, Ping; Cheng, Yun-Long; Cai, Chuan-Chuan; Guo, Wei-Jin; Zhou, Ying; Shi, Ge

    2016-01-01

    Background Although Becker's nevus (BN) is a relatively common disease, the systematic studies of clinicopathological and immunohistochemical results are poorly reported. Objective To investigate the clinicopathological features and immunohistochemical alterations of keratinocyte proliferation, melanocyte density, smooth muscle hyperplasia and nerve fiber distribution in BN. Methods Clinical and pathological data were collected in 60 newly-diagnosed BN cases. Immunohistochemical stain of Ki-67, Melan-A, keratin 15, smooth muscle actin and protein gene product 9.5 was performed in 21 cases. Results The median diagnostic and onset age was 17 and 12 years, respectively. Skin lesions usually appeared on the upper trunk and upper limbs. The pathological features included the rete ridge elongation and fusion and basal hyperpigmentation. Epidermal Ki-67, Melan-A and keratin 15 expression and dermal nerve fiber length were significantly higher in lesional and perilesional skin than in normal skin (p<0.05~0.01), while smooth muscle actin expression was upregulated only in skin lesion (p<0.05). Conclusion Although the clinical diagnosis of BN is often straightforward, histopathology is helpful to differentiate from other pigmentary disorders. The hyperproliferation of keratinocytes, melanocytes, arrector pili muscle and dermal nerve fibers could be involved in the pathogenesis of BN. PMID:27904268

  11. TACE (ADAM17) inhibits Schwann cell myelination.

    Science.gov (United States)

    La Marca, Rosa; Cerri, Federica; Horiuchi, Keisuke; Bachi, Angela; Feltri, M Laura; Wrabetz, Lawrence; Blobel, Carl P; Quattrini, Angelo; Salzer, James L; Taveggia, Carla

    2011-06-12

    Tumor necrosis factor-α-converting enzyme (TACE; also known as ADAM17) is a proteolytic sheddase that is responsible for the cleavage of several membrane-bound molecules. We report that TACE cleaves neuregulin-1 (NRG1) type III in the epidermal growth factor domain, probably inactivating it (as assessed by deficient activation of the phosphatidylinositol-3-OH kinase pathway), and thereby negatively regulating peripheral nervous system (PNS) myelination. Lentivirus-mediated knockdown of TACE in vitro in dorsal root ganglia neurons accelerates the onset of myelination and results in hypermyelination. In agreement, motor neurons of conditional knockout mice lacking TACE specifically in these cells are significantly hypermyelinated, and small-caliber fibers are aberrantly myelinated. Further, reduced TACE activity rescues hypomyelination in NRG1 type III haploinsufficient mice in vivo. We also show that the inhibitory effect of TACE is neuron-autonomous, as Schwann cells lacking TACE elaborate myelin of normal thickness. Thus, TACE is a modulator of NRG1 type III activity and is a negative regulator of myelination in the PNS.

  12. Macular and peripapillary retinal nerve fiber layer thickness in children with hyperopic anisometropic amblyopia

    Directory of Open Access Journals (Sweden)

    Shuang-Qing Wu

    2013-02-01

    Full Text Available AIM:To compare the retinal nerve fiber layer (RNFL thickness and macular thickness in the amblyopic eye with that in the sound eye of children with hyperopic anisometropic amblyopia using optical coherence tomography (OCT.METHODS: A prospective, nonrandom, intraindividual comparative cohort study includes 72 children with hyperopic anisometropic amblyopia in a single center. Macular thickness, macular foveola thickness, and peripapillary RNFL thickness were compared between the amblyopia eyes and the contralateral sound eyes.RESULTS:There were 38 male and 34 female patients, with a mean age as 9.7±1.9 years (range, 5–16 years. Hyperopic was +3.62±1.16D (range +2.00D to +6.50D in the amblyopic eyes, which was significantly higher in the control eyes with +0.76±0.90D (range 0D to +2.00D (P P = 0.02. The mean macular foveola thickness was significantly thicker in the amblyopic eyes than the contralateral sound eyes (181.4±14.2µm vs 175.2±13.3µm, P CONCLUSION:Eyes with hyperopic anisometropic amblyopia are found thicker macular foveola and peripapillary RNFL than the contralateral eyes in children.

  13. Macular and retinal nerve fiber thickness in recovered and persistent amblyopia.

    Science.gov (United States)

    Yassin, Sanaa A; Al-Tamimi, Elham R; Al-Hassan, Sultan

    2015-12-01

    The aim of this study was to investigate the presence of increased macular or retinal nerve fiber layer thickness (RNFLT) in amblyopic eyes, find if the increased macular or RNFLT is related to the lack of response in amblyopic eyes, and to explore whether the increased central macular thickness (CMT) in amblyopic eyes is purely related to the hyperopia. This is a prospective descriptive study. CMT and peripapillary RNFLT were measured by spectral-domain optical coherence tomography to evaluate 60 patients with unilateral-treated amblyopia (median age 11.00 year). Patients were divided into two groups: 33 patients in recovered amblyopia group and 27 patients in persistent amblyopia group. The mean CMT in the recovered group was 247.31 (±23.4) versus 246.8 (±32.7) µm (p = 0.95) for the persistent group. The mean peripapillary RNFLT was 99.13 (±12.1) versus 99.9 (±14.9) µm (p = 0.85) for the persistent group. In anisometropic amblyopia, there was no significant difference in CMT and RNFLT in either group. Also there was no relation between the type of refractive error and CMT or RNFLT. There was no significant difference in CMT and RNFLT in amblyopic eyes for both the recovered amblyopia group and the persistent amblyopia group to explain the lack of response in persistent amblyopic eyes. Additionally there was no relation between the type of refractive error and CMT or peripapillary RNFLT.

  14. Effects of Electrode Position on Spatiotemporal Auditory Nerve Fiber Responses: A 3D Computational Model Study

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    Soojin Kang

    2015-01-01

    Full Text Available A cochlear implant (CI is an auditory prosthesis that enables hearing by providing electrical stimuli through an electrode array. It has been previously established that the electrode position can influence CI performance. Thus, electrode position should be considered in order to achieve better CI results. This paper describes how the electrode position influences the auditory nerve fiber (ANF response to either a single pulse or low- (250 pulses/s and high-rate (5,000 pulses/s pulse-trains using a computational model. The field potential in the cochlea was calculated using a three-dimensional finite-element model, and the ANF response was simulated using a biophysical ANF model. The effects were evaluated in terms of the dynamic range, stochasticity, and spike excitation pattern. The relative spread, threshold, jitter, and initiated node were analyzed for single-pulse response; and the dynamic range, threshold, initiated node, and interspike interval were analyzed for pulse-train stimuli responses. Electrode position was found to significantly affect the spatiotemporal pattern of the ANF response, and this effect was significantly dependent on the stimulus rate. We believe that these modeling results can provide guidance regarding perimodiolar and lateral insertion of CIs in clinical settings and help understand CI performance.

  15. Evaluation of peripapillary choroidal and retinal nerve fiber layer thickness in eyes with tilted optic disc

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    Muammer Ozcımen

    2014-12-01

    Full Text Available Purpose: This study was performed to evaluate the retinal nerve fiber layer (RNFL and peripapillary choroidal thickness in eyes with tilted optic disc in order to identify characteristic RNFL and peripapillary choroid patterns verified by optical coherence tomography (OCT. Methods: Twenty-nine eyes of 29 patients with tilted optic discs were studied with spectral-domain (SD-OCT and compared with age and sex-matched control subjects in a prospective design. The imaging of RNFL was performed using circular scans of a diameter of 3.4 mm around the optic disc using OCT. For measurements of peripapillary choroidal thickness, the standar d protocol for RNFL assessment was performed. Results: SD-OCT indicated significantly lower superotemporal (p<0.001, superonasal (p=0.001, and global (p=0.005 RNFL thicknesses in the tilted disc group than those of the control group. Peripapillary choroid was significantly thicker at the site of the elevated rim of eyes with tilted disc (p<0.001. Conclusion: This study demonstrated a clinical characterization of the main tilted disc morphologies that may be helpful in differentiating a tilted disc from other altered disc morphologies. Further studies are recommended to study the comparison between glaucoma and tilted disc groups.

  16. Specific Location of Disc Hemorrhage is Linked to Nerve Fiber Layer Defects.

    Science.gov (United States)

    Yoo, Young Cheol; Kim, Joon Mo; Park, Han Seok; Yoo, Chungkwon; Shim, Seong Hee; Won, Yu Sam; Park, Ki Ho; Chang, Robert T

    2017-06-01

    To investigate the relationship between retinal nerve fiber layer (RNFL) defects and the quadrant and proximal location of disc hemorrhages (DHs) in a large population examined for health screening. A total of 168,044 subjects older than 20 years underwent a single screening ophthalmic examination with color fundus photography as part of a comprehensive health screening program. The presence and location of DHs and RNFL defects were assessed. The DH locations were defined according to the quadrant location (inferotemporal, superotemporal, inferonasal, or superonasal) and the most proximal end of DHs relative to the disc center (cup base, cup margin, disc rim, or extrapapillary region). Using these two location descriptors as independent variables, a logistic regression analysis was conducted to explore the effects of DH location on RNFL defects. Two hundred twenty-six eyes had DH and 120 (53.1%) of them had RNFL defects. After adjusting for proximal location, DHs located in the inferotemporal quadrant accompanied RFNL defects 12 times more frequently than those in the superonasal quadrant (odds ratio [OR], 11.81; P = .004). Conversely, after adjusting for quadrant location, the ORs for an associated RNFL defect were 3.73 (P locations, DHs were identified most frequently in the inferotemporal quadrant and outside the disc, respectively. Some DH locations, such as the inferotemporal quadrant and the cup margin, were associated with RNFL defects, whereas others were not.

  17. The association of Helicobacter pylori with choroidal and retinal nerve fiber layer thickness.

    Science.gov (United States)

    Can, Mehmet Erol; Kaplan, Fatma Efe; Uzel, Mehmet Murat; Kiziltoprak, Hasan; Ergun, Mustafa Cagri; Koc, Mustafa; Simsek, Gülcin

    2017-08-05

    To investigate the effect of Helicobacter pylori (H. pylori) infection on choroidal thickness (CT) and retinal nerve fiber layer thickness (RNFLT). The study included 25 patients with H. pylori infection and 25 healthy individuals as the control group. Helicobacter pylori patients were classified as the pre-treatment (Group 1; n: 25) and the post-treatment (Group 2; n: 25). RNFLT and CT were measured before and after treatment of H. pylori infection, using enhanced depth imaging (EDI) spectral-domain optical coherence tomography (Spectralis, Heidelberg Engineering, Heidelberg, Germany). The axial length and intraocular pressure were also measured. The mean subfoveal CT was 320.96 ± 29.15 μm in Group 1 and 287.48 ± 49.17 in the control group (p = 0.007), while the mean subfoveal CT did not show any difference between Group 2 and the control group (p > 0.05). No statistically significant difference was determined between the H. pylori patients and the control group in respect of RNFLT values (p > 0.05). CT increases during H. pylori infection and returns to the normal range within 6 weeks of treatment. RNFLT does not show any change during H. pylori infection. The data related to the subfoveal CT may be useful in understanding the pathogenesis of central serous chorioretinopathy developing in H. pylori patients.

  18. Perimetric and retinal nerve fiber layer findings in patients with Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    Tsironi Evangelia E

    2012-10-01

    Full Text Available Abstract Background Visual dysfunction is common in Parkinson’s disease (PD. It remains, however, unknown whether it is related to structural alterations of the retina. The aim of this study is to compare visual field (VF findings and circumpapillary retinal nerve fiber layer (RNFL thickness in a series of PD patients and normal controls, in order to assess possible retinal anatomical changes and/or functional damage associated with PD. Methods PD patients and controls were recruited and underwent VF testing with static automated perimetry and RNFL examination with optical coherence tomography (OCT. Cognitive performance using Mini Mental State Examination (MMSE, PD staging using modified Hoehn and Yahr (H-Y scale and duration of the disease was recorded in PD patients. Results One randomly selected eye from each of 24 patients and 24 age-matched controls was included. OCT RNFL thickness analysis revealed no difference in the inferior, superior, nasal or temporal sectors between the groups. The average peripapillary RNFL was also similar in the two groups. However, perimetric indices of generalized sensitivity loss (mean deviation and localized scotomas (pattern standard deviation were worse in patients with PD compared to controls (p  Conclusion PD patients may demonstrate glaucomatous-like perimetric defects even in the absence of decreased RNFL thickness.

  19. Retinal nerve fiber layer and ganglion cell complex thickness in patients with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Mehmet Demir

    2014-01-01

    Full Text Available Aim: The aim of the following study is to evaluate the retinal nerve fiber layer (RNFL and ganglion cell complex (GCC thickness in patients with type 2 diabetes mellitus (DM. Materials and Methods: Average, inferior, and superior values of RNFL and GCC thickness were measured in 123 patients using spectral domain optical coherence tomography. The values of participants with DM were compared to controls. Diabetic patients were collected in Groups 1, 2 and 3. Group 1 = 33 participants who had no diabetic retinopathy (DR; Group 2 = 30 participants who had mild nonproliferative DR and Group 3 = 30 participants who had moderate non-proliferative DR. The 30 healthy participants collected in Group 4. Analysis of variance test and a multiple linear regression analysis were used for statistical analysis. Results: The values of RNFL and GCC in the type 2 diabetes were thinner than controls, but this difference was not statistically significant. Conclusions: This study showed that there is a nonsignificant loss of RNFL and GCC in patients with type 2 diabetes.

  20. Detection of retinal nerve fiber layer defects in retinal fundus images using Gabor filtering

    Science.gov (United States)

    Hayashi, Yoshinori; Nakagawa, Toshiaki; Hatanaka, Yuji; Aoyama, Akira; Kakogawa, Masakatsu; Hara, Takeshi; Fujita, Hiroshi; Yamamoto, Tetsuya

    2007-03-01

    Retinal nerve fiber layer defect (NFLD) is one of the most important findings for the diagnosis of glaucoma reported by ophthalmologists. However, such changes could be overlooked, especially in mass screenings, because ophthalmologists have limited time to search for a number of different changes for the diagnosis of various diseases such as diabetes, hypertension and glaucoma. Therefore, the use of a computer-aided detection (CAD) system can improve the results of diagnosis. In this work, a technique for the detection of NFLDs in retinal fundus images is proposed. In the preprocessing step, blood vessels are "erased" from the original retinal fundus image by using morphological filtering. The preprocessed image is then transformed into a rectangular array. NFLD regions are observed as vertical dark bands in the transformed image. Gabor filtering is then applied to enhance the vertical dark bands. False positives (FPs) are reduced by a rule-based method which uses the information of the location and the width of each candidate region. The detected regions are back-transformed into the original configuration. In this preliminary study, 71% of NFLD regions are detected with average number of FPs of 3.2 per image. In conclusion, we have developed a technique for the detection of NFLDs in retinal fundus images. Promising results have been obtained in this initial study.

  1. Rates of progressive retinal nerve fiber layer loss in glaucoma measured by scanning laser polarimetry.

    Science.gov (United States)

    Medeiros, Felipe A; Zangwill, Linda M; Alencar, Luciana M; Sample, Pamela A; Weinreb, Robert N

    2010-06-01

    To evaluate rates of change measured with scanning laser polarimetry with enhanced corneal compensation (GDx ECC) and compare them to those measured using the variable corneal compensation (GDx VCC) method in a cohort of glaucoma patients and individuals suspected of having the disease followed over time. Observational cohort study. The study included 213 eyes of 213 patients with an average follow-up time of 4.5 years. Images were obtained annually with the GDx ECC and VCC, along with optic disc stereophotographs and standard automated perimetry (SAP) visual fields. Progression was determined by the Guided Progression Analysis software for SAP and by masked assessment of stereophotographs by expert graders. Joint linear mixed-effects models were used to evaluate rates of change in GDx measurements and their relationship with disease progression. Thirty-three patients (15%) showed progression over time on visual fields and/or stereophotographs. Mean rates of average retinal nerve fiber layer (RNFL) thickness change measured by the GDx ECC were significantly different in progressors versus nonprogressors (-1.24 microm/year vs -0.34 microm/year; P polarimetry. Copyright 2010 Elsevier Inc. All rights reserved.

  2. Low-intensity ultrasound for regeneration of injured peripheral nerve

    Institute of Scientific and Technical Information of China (English)

    Wei Zhou; Wenzhi Chen; Kun Zhou; Zhibiao Wang

    2006-01-01

    application for total 8 weeks.At various stages after operation,the sciatic nerve function index(SFI).the sensory nerve conduction velocity and its histology were detected.Rats in the control received a sham exposure.MAIN OUTCOME MEASURES:SFI;sensory nerve conduction velocity;density of myelinated nerve fiber;velocity of nerve regeneration;histological examination.RESULTS: Among 64 Wistar rats, 2 were lost during the experiment and another 2 were supplied. ①Histological examination:Two weeks after treatment,degeneration of axis-cylinder and myelin sheath was obvious in treatment group as compared with that in control group. Within 4-8 weeks after treatment.regeneration of axis-cylinder and myelin sheath of nerve fiber was superior in treatment group to that in control group.At 8 weeks after treatment,axis-cylinder and myelin sheath in treatment group were closed to normal value.Quantity of nerve fiber was less in control group than that in treatment group and the arrangement was disorder.At 2,4 and 6 weeks after treatment,proliferation of Schwann cells was superior in treatment group to that in control group.At 6 and 8 weeks after treatment,proliferation of fiber tissue in nerve was severer in control group than that in treatment group.②SFI:At 4.6 and 8 weeks after treatment.SFI was higher in treatment group than that in control group(t=8.00,12.41m15.13,P<0.01).③Sensory nerve conduction velocity:At 2,4,6 and 8 weeks after treatment,sensory nerve conduction velocity was faster in treatment group than that in control group(t=11.74,10.81,3.51,P<0.01).④Density of myelinated nerve fiber:At 2,4,6 and 8 weeks after treatment,density of myelinated nerve fiber was higher in treatment group than that in control group(t=2.16,P<0.05;t=3.29,3.52,3.23,P<0.01).⑤Velocity of nerve regeneration:Velocity of nerve regeneration was(1.50+0.08)mm/d and(1.22±0.10)mm/d of treatment group and control group.respectively. This suggested that velocity of nerve regeneration was faster

  3. Isoflurane depresses hippocampal CA1 glutamate nerve terminals without inhibiting fiber volleys

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    MacIver M Bruce

    2006-01-01

    Full Text Available Abstract Background Anesthetic-induced CNS depression is thought to involve reduction of glutamate release from nerve terminals. Recent studies suggest that isoflurane reduces glutamate release by block of Na channels. To further investigate this question we examined the actions of isoflurane, TTX, extracellular Ca2+, CNQX and stimulus voltage (stim on glutamate-mediated transmission at hippocampal excitatory synapses. EPSPs were recorded from CA1 neurons in rat hippocampal brain slices in response to Schaffer-collateral fiber stimulation. Results Isoflurane (350 μM; 1 MAC reversibly depressed EPSP amplitudes by ~60% while facilitation increased ~20%. Consistent with previous studies, these results indicate a presynaptic site of action that involves reduced excitation-release coupling. EPSPs were depressed to comparable levels by TTX (60 nM or lowered stim, but facilitation was not changed, indicating a simple failure of axonal conduction. Similarly, partial antagonism of postsynaptic glutamate receptors with CNQX (10 μM depressed EPSP amplitudes with no change in facilitation. However, EPSP depression by low external Ca2+ (0.8 mM was accompanied by an increase in facilitation comparable to isoflurane. Isoflurane depression of EPSP amplitudes could also be partly reversed by high external Ca2+ (4 mM that also decreased facilitation. Isoflurane or low Ca2+ markedly reduced the slopes of fiber volley (FV-EPSP input-output curves, consistent with little or no effect on FVs. By contrast, TTX didn't alter the FV-EPSP curve slope, indicating that EPSP depression resulted from FV depression. FVs were remarkably resistant to isoflurane. Somatic spike currents were unaffected by 350 μM (1 MAC isoflurane as well. The EC50 for isoflurane depression of FVs was ~2.8 mM (12 vol. %; 8 MAC. Conclusion Isoflurane appears to depress CA1 synapses at presynaptic sites downstream from Na channels, as evident by the increased facilitation that accompanies EPSP

  4. Raman spectroscopy of non-penetrating peripheral nerve damage in swine: a tool for spectral pathology of nerves

    Science.gov (United States)

    Cilwa, Katherine E.; Slaughter, Tiffani; Elster, Eric A.; Forsberg, Jonathan A.; Crane, Nicole J.

    2015-03-01

    Over 30% of combat injuries involve peripheral nerve injury compared to only 3% in civilian trauma. In fact, nerve dysfunction is the second leading cause of long-term disability in injured service members and is present in 37% of upper limb injuries with disability. Identification and assessment of non-penetrating nerve injury in trauma patients could improve outcome and aid in therapeutic monitoring. We report the use of Raman spectroscopy as a noninvasive, non-destructive method for detection of nerve degeneration in intact nerves due to non-penetrating trauma. Nerve trauma was induced via compression and ischemia/reperfusion injury using a combat relevant swine tourniquet model (>3 hours ischemia). Control animals did not undergo compression/ischemia. Seven days post-operatively, sciatic and femoral nerves were harvested and fixed in formalin. Raman spectra of intact, peripheral nerves were collected using a fiber-optic probe with 3 mm diameter spot size and 785 nm excitation. Data was preprocessed, including fluorescence background subtraction, and Raman spectroscopic metrics were determined using custom peak fitting MATLAB scripts. The abilities of bivariate and multivariate analysis methods to predict tissue state based on Raman spectroscopic metrics are compared. Injured nerves exhibited changes in Raman metrics indicative of 45% decreased myelin content and structural damage (pdetect nerve degeneration associated with non-penetrating injury, relevant to neurapraxic and axonotmetic injuries; future experiments will further explore the clinical utility of Raman spectroscopy to recognize neural injury.

  5. Use of Natural Neural Scaffolds Consisting of Engineered Vascular Endothelial Growth Factor Immobilized on Ordered Collagen Fibers Filled in a Collagen Tube for Peripheral Nerve Regeneration in Rats

    Directory of Open Access Journals (Sweden)

    Fukai Ma

    2014-10-01

    Full Text Available The search for effective strategies for peripheral nerve regeneration has attracted much attention in recent years. In this study, ordered collagen fibers were used as intraluminal fibers after nerve injury in rats. Vascular endothelial growth factor (VEGF plays an important role in nerve regeneration, but its very fast initial burst of activity within a short time has largely limited its clinical use. For the stable binding of VEGF to ordered collagen fibers, we fused a collagen-binding domain (CBD to VEGF through recombinant DNA technology. Then, we filled the ordered collagen fibers-CBD-VEGF targeting delivery system in a collagen tube to construct natural neural scaffolds, which were then used to bridge transected nerve stumps in a rat sciatic nerve transection model. After transplantation, the natural neural scaffolds showed minimal foreign body reactions and good integration into the host tissue. Oriented collagen fibers in the collagen tube could guide regenerating axons in an oriented manner to the distal, degenerating nerve segment, maximizing the chance of target reinnervation. Functional and histological analyses indicated that the recovery of nerve function in the natural neural scaffolds-treated group was superior to the other grafted groups. The guiding of oriented axonal regeneration and effective delivery systems surmounting the otherwise rapid and short-lived diffusion of growth factors in body fluids are two important strategies in promoting peripheral nerve regeneration. The natural neural scaffolds described take advantage of these two aspects and may produce synergistic effects. These properties qualified the artificial nerve conduits as a putative candidate system for the fabrication of peripheral nerve reconstruction devices.

  6. Use of natural neural scaffolds consisting of engineered vascular endothelial growth factor immobilized on ordered collagen fibers filled in a collagen tube for peripheral nerve regeneration in rats.

    Science.gov (United States)

    Ma, Fukai; Xiao, Zhifeng; Meng, Danqing; Hou, Xianglin; Zhu, Jianhong; Dai, Jianwu; Xu, Ruxiang

    2014-10-15

    The search for effective strategies for peripheral nerve regeneration has attracted much attention in recent years. In this study, ordered collagen fibers were used as intraluminal fibers after nerve injury in rats. Vascular endothelial growth factor (VEGF) plays an important role in nerve regeneration, but its very fast initial burst of activity within a short time has largely limited its clinical use. For the stable binding of VEGF to ordered collagen fibers, we fused a collagen-binding domain (CBD) to VEGF through recombinant DNA technology. Then, we filled the ordered collagen fibers-CBD-VEGF targeting delivery system in a collagen tube to construct natural neural scaffolds, which were then used to bridge transected nerve stumps in a rat sciatic nerve transection model. After transplantation, the natural neural scaffolds showed minimal foreign body reactions and good integration into the host tissue. Oriented collagen fibers in the collagen tube could guide regenerating axons in an oriented manner to the distal, degenerating nerve segment, maximizing the chance of target reinnervation. Functional and histological analyses indicated that the recovery of nerve function in the natural neural scaffolds-treated group was superior to the other grafted groups. The guiding of oriented axonal regeneration and effective delivery systems surmounting the otherwise rapid and short-lived diffusion of growth factors in body fluids are two important strategies in promoting peripheral nerve regeneration. The natural neural scaffolds described take advantage of these two aspects and may produce synergistic effects. These properties qualified the artificial nerve conduits as a putative candidate system for the fabrication of peripheral nerve reconstruction devices.

  7. High Spatial Resolution Imaging Mass Spectrometry of Human Optic Nerve Lipids and Proteins

    Science.gov (United States)

    Anderson, David M. G.; Spraggins, Jeffrey M.; Rose, Kristie L.; Schey, Kevin L.

    2015-06-01

    The human optic nerve carries signals from the retina to the visual cortex of the brain. Each optic nerve is comprised of approximately one million nerve fibers that are organized into bundles of 800-1200 fibers surrounded by connective tissue and supportive glial cells. Damage to the optic nerve contributes to a number of blinding diseases including: glaucoma, neuromyelitis optica, optic neuritis, and neurofibromatosis; however, the molecular mechanisms of optic nerve damage and death are incompletely understood. Herein we present high spatial resolution MALDI imaging mass spectrometry (IMS) analysis of lipids and proteins to define the molecular anatomy of the human optic nerve. The localization of a number of lipids was observed in discrete anatomical regions corresponding to myelinated and unmyelinated nerve regions as well as to supporting connective tissue, glial cells, and blood vessels. A protein fragment from vimentin, a known intermediate filament marker for astrocytes, was observed surrounding nerved fiber bundles in the lamina cribrosa region. S100B was also found in supporting glial cell regions in the prelaminar region, and the hemoglobin alpha subunit was observed in blood vessel areas. The molecular anatomy of the optic nerve defined by MALDI IMS provides a firm foundation to study biochemical changes in blinding human diseases.

  8. Construction of a three-dimensional bionic nerve conduit containing two neurotrophic factors with separate delivery systems for the repair of sciatic nerve defects

    Institute of Scientific and Technical Information of China (English)

    Zhiyue Li; Qun Zhao; Ran Bi; Yong Zhuang; Siyin Feng

    2011-01-01

    Previous studies of nerve conduits have investigated numerous properties, such as conduit luminal structure and neurotrophic factor incorporation, for the regeneration of nerve defects. The present study used a poly(lactic-co-glycolic acid) (PLGA) copolymer to construct a three-dimensional (3D) bionic nerve conduit, with two channels and multiple microtubule lumens, and incorporating two neurotrophic factors, each with their own delivery system, as a novel environment for peripheral nerve regeneration. The efficacy of this conduit in repairing a 1.5 cm sciatic nerve defect was compared with PLGA-alone and PLGA-microfilament conduits, and autologous nerve transplantation. Results showed that compared with the other groups, the 3D bionic nerve conduit had the fastest nerve conduction velocity, largest electromyogram amplitude, and shortest electromyogram latency. In addition, the nerve fiber density, myelin sheath thickness and axon diameter were significantly increased, and the recovery rate of the triceps surae muscle wet weight was lowest. These findings suggest that 3D bionic nerve conduits can provide a suitable microenvironment for peripheral nerve regeneration to efficiently repair sciatic nerve defects.

  9. Restorative effect and mechanism of mecobalamin on sciatic nerve crush injury in mice.

    Science.gov (United States)

    Gan, Lin; Qian, Minquan; Shi, Keqin; Chen, Gang; Gu, Yanglin; Du, Wei; Zhu, Guoxing

    2014-11-15

    Mecobalamin, a form of vitamin B12 containing a central metal element (cobalt), is one of the most important mediators of nervous system function. In the clinic, it is often used to accelerate recovery of peripheral nerves, but its molecular mechanism remains unclear. In the present study, we performed sciatic nerve crush injury in mice, followed by daily intraperitoneal administration of mecobalamin (65 μg/kg or 130 μg/kg) or saline (negative control). Walking track analysis, histomorphological examination, and quantitative real-time PCR showed that mecobalamin significantly improved functional recovery of the sciatic nerve, thickened the myelin sheath in myelinated nerve fibers, and increased the cross-sectional area of target muscle cells. Furthermore, mecobalamin upregulated mRNA expression of growth associated protein 43 in nerve tissue ipsilateral to the injury, and of neurotrophic factors (nerve growth factor, brain-derived nerve growth factor and ciliary neurotrophic factor) in the L4-6 dorsal root ganglia. Our findings indicate that the molecular mechanism underlying the therapeutic effect of mecobalamin after sciatic nerve injury involves the upregulation of multiple neurotrophic factor genes.

  10. The Multiple Silicone Tube Device, “Tubes within a Tube,” for Multiplication in Nerve Reconstruction

    Directory of Open Access Journals (Sweden)

    Fredrik Johansson

    2014-01-01

    Full Text Available Multiple nerve branches were created during the regeneration procedure after a nerve injury and such multiple branches are suggested to be used to control, for example, prosthesis with many degrees of freedom. Transected rat sciatic nerve stumps were inserted into a nine mm long silicone tube, which contained four, five mm long, smaller tubes, thus leaving a five mm gap for regenerating nerve fibers. Six weeks later, several new nerve structures were formed not only in the four smaller tubes, but also in the spaces in-between. The 7–9 new continuous nerve structures, which were isolated as individual free nerves after removal of the tubes, were delineated by a perineurium and contained both myelinated and unmyelinated nerve fibers as well as blood vessels. Stimulation of the proximal nerve elicited contractions in distal muscles. Thin metal electrodes, inserted initially into the smaller tubes in some experiments, became embedded in the new nerve structures and when stimulated contractions of the distal muscles were observed. The “tubes within a tube” technique, creating multiple new nerves from a single “mother” nerve, can be used to record multiple signals for prosthetic device control or as sources for supply of multiple denervated targets.

  11. Directionality of auditory nerve fiber responses to pure tone stimuli in the grassfrog, Rana temporaria. I. Spike rate responses

    DEFF Research Database (Denmark)

    Jørgensen, M B; Christensen-Dalsgaard, J

    1997-01-01

    We studied the directionality of spike rate responses of auditory nerve fibers of the grassfrog, Rana temporaria, to pure tone stimuli. All auditory fibers showed spike rate directionality. The strongest directionality was seen at low frequencies (200-400 Hz), where the spike rate could change by...

  12. Arrest of Myelination and Reduced Axon Growth when Schwann Cells Lack mTOR

    OpenAIRE

    Sherman, Diane L; Krols, Michiel; Wu, Lai-Man N; Grove, Matthew; Nave, Klaus-Armin; Gangloff, Yann-Gaël; Brophy, Peter J.

    2012-01-01

    In developing peripheral nerves differentiating Schwann cells sort individual axons from bundles and ensheath them to generate multiple layers of myelin. In recent years there has been an increasing understanding of the extracellular and intracellular factors that initiate and stimulate Schwann cell myelination together with a growing appreciation of some of the signalling pathways involved. However, our knowledge of how Schwann cell growth is regulated during myelination is still incomplete....

  13. Functional recovery of sciatic nerve through inside-out vein graft in rats

    Institute of Scientific and Technical Information of China (English)

    Rahim Mohammadi; Saeed Azizi; Nowruz Delirezh; Rahim Hobbenaghi; Keyvan Amini

    2011-01-01

    Objective: Present study aimed at further comprehensive functional, histomorphometrical and immunohistochemical assessment of peripheral nerve regeneration using rat sciatic nerve transection model.Methods: The 10-mm rat sciatic nerve gap was created in rats. In control group nerve stumps were sutured to adjacent muscle and in treatment group the gap was bridged using an inside-out vein graft. In sham-operated group the nerve was manipulated and left intact. All animals underwent walking track analysis test 4, 8, and 12 weeks after surgery.Subsequently, muscle mass measurement was performed to assess reenervation, histological examination to observe the sciatic nerve regeneration morphologically and immunohistochemistry to detect Schwann cells using anti S-100. Results were analyzed using a factorial ANOVA with two between-subjects factors. Bonferroni test for pairwise comparisons was used to examine the effect of treatments.Results: Functional analysis ofmyelinated nerve fibers showed that nerve function improved significantly in the time course in treatment group. However, quantitative morphometrical analysis of myelinated nerve fibers showed that there was no significant difference between 8 and 12 weeks in treatment group. Muscle weight ratio was bigger and weight loss of the gastrocnemius muscle was ameliorated by inside-out vein grafting. The position of positive immunohistochemical reactions further implied that regenerated axons and Schwann cell-like cells existed after vein grafting was performed, and was accompanied by the process of myelination and structural recovery of regenerated nerves.Conclusion: Functional analysis of peripheral nerve repair is far more reliable than quantitative morphometrical analysis

  14. Diffusion tensor imaging and fiber tractography of the median nerve at 1.5T: optimization of b value

    Energy Technology Data Exchange (ETDEWEB)

    Andreisek, Gustav [University of Toronto, Division of Musculoskeletal Imaging, Department of Medical Imaging, Mount Sinai Hospital and the University Health Network, Toronto, Ontario (Canada); University Hospital Zuerich, Institute of Diagnostic Radiology, Zuerich (Switzerland); White, Lawrence M. [University of Toronto, Division of Musculoskeletal Imaging, Department of Medical Imaging, Mount Sinai Hospital and the University Health Network, Toronto, Ontario (Canada); Kassner, Andrea [University of Toronto, Department of Medical Imaging, University Health Network, Toronto (Canada); Tomlinson, George [Toronto General Hospital, Division of Clinical Decision-Making and Health Care, Department of Public Health Sciences, University of Toronto, Toronto, Ontario (Canada); Sussman, Marshall S. [University of Toronto, Department of Medical Imaging, Toronto General Hospital, Toronto (Canada)

    2009-01-15

    The objective of this study was to systematically assess the optimal b value for diffusion tensor imaging and fiber tractography of the median nerve at 1.5 T. This is a prospective study which was carried out with institutional review board approval and written informed consent from the study subjects. Fifteen healthy volunteers (seven men, eight women; mean age, 31.2 years) underwent diffusion tensor imaging of the wrist. A single-shot spin-echo-based echo-planar imaging sequence (TR/TE, 7000/103 ms) was performed in each subject at eight different b values ranging from 325 to 1,550 s/mm{sup 2}. Number and length of reconstructed fiber tracts, fiber density index (FDi), fractional anisotropy (FA), and apparent diffusion coefficient (ADC) were calculated for the median nerve. Signal-to-noise ratio (SNR) was also calculated for each acquisition. The overall image quality was assessed by two readers in consensus by ranking representative fiber tract images for each subject using a scale range from 1 to 8 (1 = best to 8 = worst image quality). Longest fibers were observed for b values between 675 and 1,025 s/mm{sup 2}. Maximum FDi was found at b values of 1,025 s/mm{sup 2}. FA was between 0.5 and 0.6 for all b values. ADC gradually decreased from 1.44 x 10{sup -3} to 0.92 x 10{sup -3} mm{sup 2}/s with increasing b values. Maximum SNR {+-} standard deviation (175.4 {+-} 72.6) was observed at the lowest b value and decreased with increasing b values. SNR at b values of 1,025 s/mm{sup 2} was 48.5% of the maximum SNR. Optimal fiber tract image quality was found for b values of 1,025 s/mm{sup 2}. The optimal b value for diffusion tensor imaging and fiber tractography of the median nerve at 1.5 T was 1,025 s/mm{sup 2}. (orig.)

  15. Arrest of myelination and reduced axon growth when Schwann cells lack mTOR.

    Science.gov (United States)

    Sherman, Diane L; Krols, Michiel; Wu, Lai-Man N; Grove, Matthew; Nave, Klaus-Armin; Gangloff, Yann-Gaël; Brophy, Peter J

    2012-02-01

    In developing peripheral nerves, differentiating Schwann cells sort individual axons from bundles and ensheath them to generate multiple layers of myelin. In recent years, there has been an increased understanding of the extracellular and intracellular factors that initiate and stimulate Schwann cell myelination, together with a growing appreciation of some of the signaling pathways involved. However, our knowledge of how Schwann cell growth is regulated during myelination is still incomplete. The mammalian target of rapamycin (mTOR) is a core kinase in two major complexes, mTORC1 and mTORC2, that regulate cell growth and differentiation in a variety of mammalian cells. Here we show that elimination of mTOR from murine Schwann cells prevented neither radial sorting nor the initiation of myelination. However, normal postnatal growth of myelinating Schwann cells, both radially and longitudinally, was highly retarded. The myelin sheath in the mutant was much thinner than normal; nevertheless, sheath thickness relative to axon diameter (g-ratio) remained constant in both wild-type and mutant nerves from P14 to P90. Although axon diameters were normal in the mutant at the initiation of myelination, further growth as myelination proceeded was retarded, and this was associated with reduced phosphorylation of neurofilaments. Consistent with thinner axonal diameters and internodal lengths, conduction velocities in mutant quadriceps nerves were also reduced. These data establish a critical role for mTOR signaling in both the longitudinal and radial growth of the myelinating Schwann cell.

  16. Relationship between Plasma Homocysteine Level and Glaucomatous Retinal Nerve Fiber Layer Defect.

    Science.gov (United States)

    Lee, Jae Yeun; Kim, Joon Mo; Kim, In Tae; Yoo, Chung Kwon; Won, Yu Sam; Kim, Jung Hoon; Kwon, Hyun Seok; Park, Ki Ho

    2017-06-01

    To investigate the association between plasma homocysteine levels and glaucomatous retinal nerve fiber layer (RNFL) defect in South Korean population. This retrospective cross-sectional study included subjects who underwent screening at Kangbuk Samsung Hospital Health Screening Center between August 2012 and July 2013. Subjects underwent physical examination and provided samples for laboratory analysis of homocysteine. Subjects were divided equally into four quartiles (Qs) based on plasma homocysteine level. Digital fundus photographs of both eyes were obtained. Determination of glaucomatous disc appearance was based on criteria set forth by the International Society of Geographical and Epidemiological Ophthalmology and based on the appearance of the RNFL and optic disc. Multivariate logistic regression models were used to define elevated glaucoma risk with P < 0.2 on univariate analysis. A total of 78,049 subjects were included; 76,093 subjects were male, and 1956 subjects were female. When analyzed by gender, the mean homocysteine level in the male group with glaucomatous RNFL defects (11.05 ± 3.80 µmol/L) was higher than those without RNFL defects (10.81 ± 4.12 µmol/L (P = 0.000, χ(2) test). Upon multifactorial logistic regression analysis adjusted for age, gender, creatinine, diabetes mellitus, hypertension, and hyperlipidemia, glaucomatous RNFL defects had a significant correlation with plasma homocysteine level. Based on the Q2 level, the odds ratio (OR) of Q3 was 1.267, while the OR of Q4 was 1.285 (95% CI = 1.067-1.505, 1.081-1.529, respectively, P for trend = 0.001). Our results suggest that homocysteine level is associated with the presence of glaucomatous RNFL defects.

  17. A Phenomenological Model of the Electrically Stimulated Auditory Nerve Fiber: Temporal and Biphasic Response Properties.

    Science.gov (United States)

    Horne, Colin D F; Sumner, Christian J; Seeber, Bernhard U

    2016-01-01

    We present a phenomenological model of electrically stimulated auditory nerve fibers (ANFs). The model reproduces the probabilistic and temporal properties of the ANF response to both monophasic and biphasic stimuli, in isolation. The main contribution of the model lies in its ability to reproduce statistics of the ANF response (mean latency, jitter, and firing probability) under both monophasic and cathodic-anodic biphasic stimulation, without changing the model's parameters. The response statistics of the model depend on stimulus level and duration of the stimulating pulse, reproducing trends observed in the ANF. In the case of biphasic stimulation, the model reproduces the effects of pseudomonophasic pulse shapes and also the dependence on the interphase gap (IPG) of the stimulus pulse, an effect that is quantitatively reproduced. The model is fitted to ANF data using a procedure that uniquely determines each model parameter. It is thus possible to rapidly parameterize a large population of neurons to reproduce a given set of response statistic distributions. Our work extends the stochastic leaky integrate and fire (SLIF) neuron, a well-studied phenomenological model of the electrically stimulated neuron. We extend the SLIF neuron so as to produce a realistic latency distribution by delaying the moment of spiking. During this delay, spiking may be abolished by anodic current. By this means, the probability of the model neuron responding to a stimulus is reduced when a trailing phase of opposite polarity is introduced. By introducing a minimum wait period that must elapse before a spike may be emitted, the model is able to reproduce the differences in the threshold level observed in the ANF for monophasic and biphasic stimuli. Thus, the ANF response to a large variety of pulse shapes are reproduced correctly by this model.

  18. Reproducibility of retinal nerve fiber layer measurements across the glaucoma spectrum using optical coherence tomography

    Directory of Open Access Journals (Sweden)

    Jayesh Vazirani

    2015-01-01

    Full Text Available Purpose: The purpose was to determine intra-session and inter-session reproducibility of retinal nerve fiber layer (RNFL thickness measurements with the spectral-domain Cirrus optical coherence tomography (OCT ® (SD-OCT in normal and glaucomatous eyes, including a subset of advanced glaucoma. Materials and Methods: RNFL measurements of 40 eyes of 40 normal subjects and 40 eyes of 40 glaucomatous patients including 14 with advanced glaucoma were obtained on the Cirrus OCT ® (Carl Zeiss Meditec, Dublin, CA, USA five times on 1-day (intra-session and on five separate days (inter-session. Intraclass correlation coefficient (ICC, coefficient of variation (COV, and test-retest variability (TRT values were calculated for mean and quadrant RNFL in each group separately. Reproducibility values were correlated with age and stage of glaucoma. Results: For intra-session reproducibility, the ICC, COV, and TRT values for mean RNFL thickness in normal eyes were 0.993, 1.96%, and 4.02 µm, respectively, 0.996, 2.39%, and 3.84 µm in glaucomatous eyes, and 0.996, 2.41%, and 3.70 µm in advanced glaucoma. The corresponding inter-session values in normal eyes were 0.992, 2.16%, and 4.09 µm, 0.995, 2.62%, and 3.98 µm in glaucoma and 0.990, 2.70%, and 4.16 µm in advanced glaucoma. The mean RNFL thickness measurements were the most reproducible while the temporal quadrant had the lowest reproducibility values in all groups. There was no correlation between reproducibility and age or mean deviation on visual fields. Conclusions: Peripapillary RNFL thickness measurements using Cirrus OCT ® demonstrated excellent reproducibility in normal and glaucomatous eyes, including eyes with advanced glaucoma. Mean RNFL thickness measurements appear to be the most reproducible and probably represent the best parameter to use for longitudinal follow-up.

  19. Retinal nerve fiber layer thickness in normal Indian pediatric population measured with optical coherence tomography

    Directory of Open Access Journals (Sweden)

    Neelam Pawar

    2014-01-01

    Full Text Available Purpose: To measure the peripapillary retinal nerve fiber layer (RNFL thickness in normal Indian pediatric population. Subjects and Methods: 120 normal Indian children ages 5-17 years presenting to the Pediatric Clinic were included in this observational cross-sectional study. RNFL thickness was measured with stratus optical coherence tomography (OCT. Children with strabismus or amblyopia, with neurological, metabolic, vascular, or other disorders and those with abnormal optic discs were excluded. One eye of each subject was randomly selected for statistical analysis. The effect of age, refraction and gender on RNFL thickness was investigated statistically. Result: OCT measurements were obtained in 120 of 130 (92.3% subjects. Mean age was 10.8 ± 3.24 years (range 5-17. Average RNFL thickness was (± SD 106.11 ± 9.5 μm (range 82.26-146.25. The RNFL was thickest inferiorly (134.10 ± 16.16 μm and superiorly (133.44 ± 15.50 μm, thinner nasally (84.26 ± 16.43 μm, and thinnest temporally (70.72 ± 14.80 μm. In univariate regression analysis, age had no statistical significant effect on RNFL thickness (P = 0.7249 and refraction had a significant effect on RNFL thickness (P = 0.0008. Conclusion: OCT can be used to measure RNFL thickness in children. Refraction had an effect on RNFL thickness. In normal children, variation in RNFL thickness is large. The normative data provided by this study may assist in identifying changes in RNFL thickness in Indian children.

  20. Additive diagnostic role of imaging in glaucoma: optical coherence tomography and retinal nerve fiber layer photography.

    Science.gov (United States)

    Kim, Ko Eun; Kim, Seok Hwan; Oh, Sohee; Jeoung, Jin Wook; Suh, Min Hee; Seo, Je Hyun; Kim, Martha; Park, Ki Ho; Kim, Dong Myung

    2014-11-20

    To investigate the additive diagnostic role of spectral-domain optical coherence tomography (SD-OCT) and red-free retinal nerve fiber layer photography (RNFLP) in making clinical glaucoma diagnosis. Four diagnostic combination sets, including the most recent image from each measurement of 196 glaucoma eyes (including the 44 preperimetric glaucoma eyes) and 101 healthy eyes, were prepared: (1) stereo disc photography and Humphrey visual field (SH), (2) SH and SD-OCT (SHO), (3) SH and RNFLP (SHR), and (4) SHR and SD-OCT (SHRO). Each randomly sorted set was serially presented at 1-month intervals to five glaucoma specialists who were asked to evaluate them in a subjective and independent manner. The specialists' glaucoma-diagnostic performances based on the sets were then compared. For each specialist, adding SD-OCT to SH or SHR increased the glaucoma-diagnostic sensitivity but not to a level of statistical significance. For one specialist, adding RNFLP to SH significantly increased the sensitivity. Each specialist showed a high level of specificity regardless of the diagnostic set. The overall sensitivity of all specialists' assessments was significantly increased by adding RNFLP or the combination of SD-OCT and RNFLP to SH (P < 0.001); however, adding SD-OCT to SH or SHR did not significantly increase the sensitivity. A similar relationship was noted also for the preperimetric glaucoma subgroup. In contrast to RNFLP, SD-OCT did not significantly enhance the diagnostic accuracy of detecting glaucoma or even of preperimetric glaucoma. Our results suggest that, at least for glaucoma specialists, the additive diagnostic role of OCT is limited. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  1. Microcystic Inner Nuclear Layer Changes and Retinal Nerve Fiber Layer Defects in Eyes with Glaucoma.

    Directory of Open Access Journals (Sweden)

    Tomoko Hasegawa

    Full Text Available To examine microcystic inner nuclear layer (INL changes in glaucomatous eyes and to determine associated factors.Retrospective, cross-sectional, observational study.Two hundred seventeen eyes of 133 patients with primary open angle glaucoma (POAG, 41 eyes of 32 patients with preperimetric glaucoma and 181 normal eyes of 117 subjects were ultimately included. Microcystic INL lesions were examined with infrared fundus images and with 19 vertical spectral domain optical coherence tomography (SD-OCT images in the macular area.Microcystic INL changes were observed in 6.0% of eyes with POAG, but none of the normal eyes or eyes with preperimetric glaucoma showed microcystic INL changes. The proportion of eyes with advanced glaucoma was significantly larger (P = 0.013 in eyes with microcystic lesions than without. The visual field mean deviation (MD slope was also significantly worse (P = 0.027 in eyes with microcystic lesions. No significant differences were observed in age, sex, refraction, axial length, intraocular pressure, or MD value between eyes with and without microcystic INL lesions. In several cases, microcystic INL lesions occurred along with glaucomatous visual field progression. The retinal nerve fiber layer (RNFL thickness (P = 0.013 and ganglion cell layer (GCL + inner plexiform layer thickness (P = 0.023 were significantly lower in areas with microcystic lesions than without. The INL was also significantly thicker (P = 0.002 in areas with microcystic lesions.Microcystic INL lesions in glaucomatous eyes are closely associated with RNFL and GCL thinning and correlated with worse MD slope. These INL lesions may indicate focal and progressive damage in glaucoma.

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

    Science.gov (United States)

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

    2013-02-01

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

  3. KV1 channels identified in rodent myelinated axons, linked to Cx29 in innermost myelin: support for electrically active myelin in mammalian saltatory conduction.

    Science.gov (United States)

    Rash, John E; Vanderpool, Kimberly G; Yasumura, Thomas; Hickman, Jordan; Beatty, Jonathan T; Nagy, James I

    2016-04-01

    Saltatory conduction in mammalian myelinated axons was thought to be well understood before recent discoveries revealed unexpected subcellular distributions and molecular identities of the K(+)-conductance pathways that provide for rapid axonal repolarization. In this study, we visualize, identify, localize, quantify, and ultrastructurally characterize axonal KV1.1/KV1.2 channels in sciatic nerves of rodents. With the use of light microscopic immunocytochemistry and freeze-fracture replica immunogold labeling electron microscopy, KV1.1/KV1.2 channels are localized to three anatomically and compositionally distinct domains in the internodal axolemmas of large myelinated axons, where they form densely packed "rosettes" of 9-nm intramembrane particles. These axolemmal KV1.1/KV1.2 rosettes are precisely aligned with and ultrastructurally coupled to connexin29 (Cx29) channels, also in matching rosettes, in the surrounding juxtaparanodal myelin collars and along the inner mesaxon. As >98% of transmembrane proteins large enough to represent ion channels in these specialized domains, ∼500,000 KV1.1/KV1.2 channels define the paired juxtaparanodal regions as exclusive membrane domains for the voltage-gated K(+)conductance that underlies rapid axonal repolarization in mammals. The 1:1 molecular linkage of KV1 channels to Cx29 channels in the apposed juxtaparanodal collars, plus their linkage to an additional 250,000-400,000 Cx29 channels along each inner mesaxon in every large-diameter myelinated axon examined, supports previously proposed K(+)conductance directly from juxtaparanodal axoplasm into juxtaparanodal myeloplasm in mammalian axons. With neither Cx29 protein nor myelin rosettes detectable in frog myelinated axons, these data showing axon-to-myelin linkage by abundant KV1/Cx29 channels in rodent axons support renewed consideration of an electrically active role for myelin in increasing both saltatory conduction velocity and maximum propagation frequency in

  4. Chitosan-cross-linked nanofibrous PHBV nerve guide for rat sciatic nerve regeneration across a defect bridge.

    Science.gov (United States)

    Biazar, Esmaeil; Keshel, Saeed Heidari

    2013-01-01

    The aim of this study was to produce a chitosan-cross-linked nanofibrous biodegradable poly (3-hydroxybutyrate-co-3-hydroxyvalerate) nerve conduit. The artificial nerve scaffold designed by electrospinning method and cross-linked with chitosan by chemical method. Afterwards, the scaffolds were evaluated by microscopic, physical, and mechanical analyses and cell culture assays with Schwann cells. The conduits were implanted into a 10 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 good mechanical properties to serve as a nerve guide. Cellular experiments showed a better cell adhesion, growth, and proliferation inside the cross-linked nanofibrous scaffolds compared with un-cross-linked ones, also Schwann cells well attached on chitosan-cross-linked nanofibrous surface. The in vivo results demonstrated that in the nanofibrous graft, the sciatic nerve trunk had been reconstructed with restoration of nerve continuity and formatted nerve fibers with myelination. This neural conduit appears to have the right organization for testing in vivo nerve tissue engineering studies.

  5. Changes in microtubule stability and density in myelin-deficient shiverer mouse CNS axons

    Science.gov (United States)

    Kirkpatrick, L. L.; Witt, A. S.; Payne, H. R.; Shine, H. D.; Brady, S. T.

    2001-01-01

    Altered axon-Schwann cell interactions in PNS myelin-deficient Trembler mice result in changed axonal transport rates, neurofilament and microtubule-associated protein phosphorylation, neurofilament density, and microtubule stability. To determine whether PNS and CNS myelination have equivalent effects on axons, neurofilaments, and microtubules in CNS, myelin-deficient shiverer axons were examined. The genetic defect in shiverer is a deletion in the myelin basic protein (MBP) gene, an essential component of CNS myelin. As a result, shiverer mice have little or no compact CNS myelin. Slow axonal transport rates in shiverer CNS axons were significantly increased, in contrast to the slowing in demyelinated PNS nerves. Even more striking were substantial changes in the composition and properties of microtubules in shiverer CNS axons. The density of axonal microtubules is increased, reflecting increased expression of tubulin in shiverer, and the stability of microtubules is drastically reduced in shiverer axons. Shiverer transgenic mice with two copies of a wild-type myelin basic protein transgene have an intermediate level of compact myelin, making it possible to determine whether the actual level of compact myelin is an important regulator of axonal microtubules. Both increased microtubule density and reduced microtubule stability were still observed in transgenic mouse nerves, indicating that signals beyond synaptogenesis and the mere presence of compact myelin are required for normal regulation of the axonal microtubule cytoskeleton.

  6. Inherited and acquired disorders of myelin: The underlying myelin pathology.

    Science.gov (United States)

    Duncan, Ian D; Radcliff, Abigail B

    2016-09-01

    Remyelination is a major therapeutic goal in human myelin disorders, serving to restore function to demyelinated axons and providing neuroprotection. The target disorders that might be amenable to the promotion of this repair process are diverse and increasing in number. They range primarily from those of genetic, inflammatory to toxic origin. In order to apply remyelinating strategies to these disorders, it is essential to know whether the myelin damage results from a primary attack on myelin or the oligodendrocyte or both, and whether indeed these lead to myelin breakdown and demyelination. In some disorders, myelin sheath abnormalities are prominent but demyelination does not occur. This review explores the range of human and animal disorders where myelin pathology exists and focusses on defining the myelin changes in each and their cause, to help define whether they are targets for myelin repair therapy.

  7. Methods of peripheral nerve tissue preparation for second harmonic generation imaging of collagen fibers.

    Science.gov (United States)

    Vijayaraghavan, Surabhi; Huq, Rumana; Hausman, Michael R

    2014-03-15

    Second harmonic generation (SHG) imaging of the peripheral nerve using multi-photon microscopy is a novel technique with little documentation. It affords the significant possibility of non-destructive imaging of internal nerve anatomy. The nature of nerve tissue, especially its size and viscoelastic properties, present special challenges for microscopy. While nerves are under an innate in situ strain, they retract once dissected, thus distorting microscopic structure. The challenge is to preserve the nerve in its natural strain range to obtain images that most truly reveal its structure. This study examined backscattered SHG images of rat median nerve prepared by several different methods to compare image quality and content. Nerve segments were fixed under strained (constant load or length) and unstrained conditions and imaged as whole nerve as well as plastic (methyl methacrylate) and paraffin embedded sections. These were tested for optimal excitation wavelength, quantitative image contrast, and overall quality. Root mean squared (RMS) contrast proved to be a reliable measure of the level of image contrast perceived by eye. We concluded that images obtained from tissue sections (plastic and paraffin) provided the most accurate and revealing SHG images of peripheral nerve structure. Removing the embedding material prior to imaging significantly improved image quality. Optimal excitation wavelengths were consistent regardless of the preparation method. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. GABA and its B-receptor are present at the node of Ranvier in a small population of sensory fibers, implicating a role in myelination

    DEFF Research Database (Denmark)

    Corell, Mikael; Wicher, Grzegorz; Radomska, Katarzyna J;

    2015-01-01

    of the GABAB receptor, GABA, and glutamic acid decarboxylase GAD65/67 in both development and injury in fetal dissociated dorsal root ganglia (DRG) cell cultures and in the rat sciatic nerve. We found that GABA, GAD65/67, and the GABAB receptor were expressed in premyelinating and nonmyelinating Schwann cells...

  9. Visualization of nerve fiber orientation in gross histological sections of the human brain.

    Science.gov (United States)

    Axer, H; Berks, G; Keyserlingk, D G

    2000-12-01

    Diffusion weighted magnetic resonance imaging (DWMRI) allows visualization of the orientation of the nervous fibers in the living brain. For comparison, a method was developed to examine the orientation of fibers in histological sections of the human brain. Serial sections through the entire human brain were analyzed regarding fiber orientation using polarized light. Direction of fibers in the cutting plane was obtained by measuring the azimuth with the lowest intensity value at each point, and inclination of fibers in the section was evaluated using fuzzy logic approximations. Direction and inclination of fibers revealing their three-dimensional orientation were visualized by colored arrows mapped into the images. Using this procedure, various fiber tracts were identified (pyramidal tract, radiatio optica, radiatio acustica, arcuate fascicle, and 11 more). Intermingled fibers could be separated from each other. The orientation of the fiber tracts derived from polarized light microscopy was validated by confocal laser scanning microscopy in a defined volume of the internal capsule, where the fiber orientation was studied in four human brains. The polarization method visualizes the high degree of intermingled fiber bundles in the brain, so that distinct fiber pathways cannot be understood as solid, compact tracts: Neighbouring bundles of fibers can belong to different systems of fibers distinguishable by their orientation.

  10. Expression of myelin basic protein in rat optic nerve with experimental allergic encephalomyelitis%实验性变态反应性脑脊髓炎大鼠视神经内髓鞘碱性蛋白表达的变化

    Institute of Scientific and Technical Information of China (English)

    曹小鹏; 高晓唯; 曹芃; 雷英; 刘李平

    2012-01-01

    of neural fiber was found at 12 days,and changes of cellular structure,edema of neural shaft bunch were observed at 18 days.However,the abnormal cells were significantly less 25 days following the immune.Immunochemistry showed that the MBP was expressed mainly in the myelination of optic nerve fibers.The numbers of positive cells for MBP were (115.75±26.49)cells/5 fields at the 12th day,showing a significant lowing in comparison with (167.44±22.49)cells/5 fields of control group (t=4.537,P<0.05 ).The positive cells were lest at the 18th day with the values ( 75.57 ± 34.54) cells/5 fields ( t =6.362,P<0.01 ).At the 25th day,positive cells increased to ( 117.63 ± 13.78) cells/5 fields,which still was lower than those of the control group ( t =4.068,P<0.05 ).Western blot assay illuminated that with the prolong of immune time,MBP/β-actin ratio in optic nerve was gradually reduced and followed the same pattern at the 12th day( t =4.639,P<0.05 ).At 18 days after immune in comparison with the control group,the expression of MBP/β-actin ratio in optic nerve was the least (t=8.427,P<0.01). Conclusions MBP can be degraded in rat optic nerve.This is a further evidence that optic neuritis is a severe demyelination disease.It is clearly related to MS.

  11. Effect of Delayed Peripheral Nerve Repair on Nerve Regeneration, Schwann Cell Function and Target Muscle Recovery

    Science.gov (United States)

    Jonsson, Samuel; Wiberg, Rebecca; McGrath, Aleksandra M.; Novikov, Lev N.; Wiberg, Mikael; Novikova, Liudmila N.; Kingham, Paul J.

    2013-01-01

    Despite advances in surgical techniques for peripheral nerve repair, functional restitution remains incomplete. The timing of surgery is one factor influencing the extent of recovery but it is not yet clearly defined how long a delay may be tolerated before repair becomes futile. In this study, rats underwent sciatic nerve transection before immediate (0) or 1, 3, or 6 months delayed repair with a nerve graft. Regeneration of spinal motoneurons, 13 weeks after nerve repair, was assessed using retrograde labeling. Nerve tissue was also collected from the proximal and distal stumps and from the nerve graft, together with the medial gastrocnemius (MG) muscles. A dramatic decline in the number of regenerating motoneurons and myelinated axons in the distal nerve stump was observed in the 3- and 6-months delayed groups. After 3 months delay, the axonal number in the proximal stump increased 2–3 folds, accompanied by a smaller axonal area. RT-PCR of distal nerve segments revealed a decline in Schwann cells (SC) markers, most notably in the 3 and 6 month delayed repair samples. There was also a progressive increase in fibrosis and proteoglycan scar markers in the distal nerve with increased delayed repair time. The yield of SC isolated from the distal nerve segments progressively fell with increased delay in repair time but cultured SC from all groups proliferated at similar rates. MG muscle at 3- and 6-months delay repair showed a significant decline in weight (61% and 27% compared with contra-lateral side). Muscle fiber atrophy and changes to neuromuscular junctions were observed with increased delayed repair time suggestive of progressively impaired reinnervation. This study demonstrates that one of the main limiting factors for nerve regeneration after delayed repair is the distal stump. The critical time point after which the outcome of regeneration becomes too poor appears to be 3-months. PMID:23409189

  12. Evaluation of retinal nerve fiber layer thickness parameters in myopic population using scanning laser polarimetry (GDxVCC).

    Science.gov (United States)

    Dada, Tanuj; Aggarwal, A; Bali, S J; Sharma, A; Shah, B M; Angmo, D; Panda, A

    2013-01-01

    Myopia presents a significant challenge to the ophthalmologist as myopic discs are often large, tilted, with deep cups and have a thinner neuroretinal rim all of which may mimic glaucomatous optic nerve head changes causing an error in diagnosis. To evaluate the retinal fiber layer (RNFL) thickness in low, moderate and high myopia using scanning laser polarimetry with variable corneal compensation (GDxVCC). One hundred eyes of 100 emmetropes, 30 eyes of low myopes (0 to - 4 D spherical equivalent(SE), 45 eyes with moderate myopia (- 4 to - 8D SE), and 30 eyes with high myopia (- 8 to - 15D SE) were subjected to retinal nerve fiber layer assessment using the scanning laser polarimetry (GDxVCC) in all subjects using the standard protocol. Subjects with IOP > 21 mm Hg, optic nerve head or visual field changes suggestive of glaucoma were excluded from the study. The major outcome parameters were temporal-superior-nasal-inferiortemporal (TSNIT) average, the superior and inferior average and the nerve fibre indicator (NFI). The TSNIT average (p = 0.009), superior (p = 0.001) and inferior average (p = 0.008) were significantly lower; the NFI was higher (P less than 0.001) in moderate myopes as compared to that in emmetropes. In high myopia the RNFL showed supranormal values; the TSNIT average, superior and inferior average was significantly higher(p less than 0.001) as compared to that in emmetropes. The RNFL measurements on scanning laser polarimetry are affected by the myopic refractive error. Moderate myopes show a significant thinning of the RNFL. In high myopia due to peripapillary chorioretinal atrophy and contribution of scleral birefringence, the RNFL values are abnormally high. These findings need to be taken into account while assessing and monitoring glaucoma damage in moderate to high myopes on GDxVCC. © NEPjOPH.

  13. Creation of highly aligned electrospun poly-L-lactic acid fibers for nerve regeneration applications

    Science.gov (United States)

    Wang, Han Bing; Mullins, Michael E.; Cregg, Jared M.; Hurtado, Andres; Oudega, Martin; Trombley, Matthew T.; Gilbert, Ryan J.

    2009-02-01

    Aligned, electrospun polymer fibers have shown considerable promise in directing regenerating axons in vitro and in vivo. However, in several studies, final electrospinning parameters are presented for producing aligned fiber scaffolds, and alignment where minimal fiber crossing occurs is not achieved. Highly aligned species are necessary for neural tissue engineering applications to ensure that axonal extension occurs through a regenerating environment efficiently. Axonal outgrowth on fibers that deviate from the natural axis of growth may delay axonal extension from one end of a scaffold to the other. Therefore, producing aligned fiber scaffolds with little fiber crossing is essential. In this study, the contributions of four electrospinning parameters (collection disk rotation speed, needle size, needle tip shape and syringe pump flow rate) were investigated thoroughly with the goal of finding parameters to obtain highly aligned electrospun fibers made from poly-L-lactic acid (PLLA). Using an 8 wt% PLLA solution in chloroform, a collection disk rotation speed of 1000 revolutions per minute (rpm), a 22 gauge, sharp-tip needle and a syringe pump rate of 2 ml h-1 produced highly aligned fiber (1.2-1.6 µm in diameter) scaffolds verified using a fast Fourier transform and a fiber alignment quantification technique. Additionally, the application of an insulating sheath around the needle tip improved the rate of fiber deposition (electrospinning efficiency). Optimized scaffolds were then evaluated in vitro using embryonic stage nine (E9) chick dorsal root ganglia (DRGs) and rat Schwann cells (SCs). To demonstrate the importance of creating highly aligned scaffolds to direct neurite outgrowth, scaffolds were created that contained crossing fibers. Neurites on these scaffolds were directed down the axis of the aligned fibers, but neurites also grew along the crossed fibers. At times, these crossed fibers even stopped further axonal extension. Highly aligned PLLA fibers

  14. [CHANGES OF THE SUPERFICIAL PERONEAL NERVE IN RELATION TO THE FREQUENCY OF HIGH-FRACTIONAL AUTODISTRACTION IN ORTHOPEDIC LENGTHENING OF THE TIBIA IN DOGS WITH A DAILY RATE OF 3 mm].

    Science.gov (United States)

    Varsegova, T N; Shchudlo, N A; Shchudlo, M M; Yemanov, A A

    2015-01-01

    The experiments on the elongation of the tibia in 18 dogs were performed for 10 days using the Ilizarov apparatus with an automatic drive providing the pace of 3 mm/day for 120 moves (group 1) and 180 moves (group 2). The impact of fractionation of distraction on the structure of the peroneal nerve was estimated. In group 1, perineurium micro-injuries and endoneural blood vessel destruction were detected. In group 2, perineurium preserved its integrity and fine-lamellar structure, endoneural blood vessels were also preserved, however, the decrease in the total area of nerve fiber bundles was more pronounced. Morphometric analysis of the preserved myelinated nerve fibers 60 days after the cessation of distraction indicated less marked axonal atrophy and better myelination in group 2.

  15. Distribution of serotonergic and dopaminergic nerve fibers in the salivary gland complex of the cockroach Periplaneta americana

    Directory of Open Access Journals (Sweden)

    Kühnel Dana

    2002-06-01

    Full Text Available Abstract Background The cockroach salivary gland consists of secretory acini with peripheral ion-transporting cells and central protein-producing cells, an extensive duct system, and a pair of reservoirs. Salivation is controled by serotonergic and dopaminergic innervation. Serotonin stimulates the secretion of a protein-rich saliva, dopamine causes the production of a saliva without proteins. These findings suggest a model in which serotonin acts on the central cells and possibly other cell types, and dopamine acts selectively on the ion-transporting cells. To examine this model, we have analyzed the spatial relationship of dopaminergic and serotonergic nerve fibers to the various cell types. Results The acinar tissue is entangled in a meshwork of serotonergic and dopaminergic varicose fibers. Dopaminergic fibers reside only at the surface of the acini next to the peripheral cells. Serotonergic fibers invade the acini and form a dense network between central cells. Salivary duct segments close to the acini are locally associated with dopaminergic and serotonergic fibers, whereas duct segments further downstream have only dopaminergic fibers on their surface and within the epithelium. In addition, the reservoirs have both a dopaminergic and a serotonergic innervation. Conclusion Our results suggest that dopamine is released on the acinar surface, close to peripheral cells, and along the entire duct system. Serotonin is probably released close to peripheral and central cells, and at initial segments of the duct system. Moreover, the presence of serotonergic and dopaminergic fiber terminals on the reservoir indicates that the functions of this structure are also regulated by dopamine and serotonin.

  16. HISTOMORPHOMETRIC CHARACTERISTICS AND PATHOGENIC MECHANISM OF PERONEAL NERVE NEUROPATHY IN EXPERIMENTAL FRACTIONAL LOWER LEG LENGTHENING

    Directory of Open Access Journals (Sweden)

    T. N. Varsegova

    2016-01-01

    Full Text Available Purpose – to study histomorphometric characteristics and pathogenic mechanism of peroneal nerve neuropathy in experimental lower leg lengthening by one millimeter per day in four increments. Methods. The authors performed lengthening of lower leg in 12 adult mongrel dogs at 14-15% of initial length by Ilizarov technique. 28 days after the leg distraction, 30 days after its fixation in the device and 30 days after the Ilizarov fixator dismounting the authors withdrew the animals from the experiment. Peroneal nerve portions were examined using light microscopy, histomorphometry of the full-color images of the giant epoxy semifine sections stained with methylene blue and diamond fuchsin. Results. Planimetric investigation demonstrated 15% decrease (p<0.05 in the total area of nerve fiber bundles after distraction confirming transverse contraction of intrafascicular content. Fibrosis, increased cellularity of epineurium as well as the decrease in adipocyte number and size was observed in result of distraction and fixation. Neuropathy of the peroneal nerve was observed in one of the 12 animals – more than 80% of myelinated fibers demonstrated destructive changes, the large arteries of epineurium demonstrated obliterated lumina, part of arteries had necrobiotic changes in the cellular elements of the walls. In the remaining animals the proportion of the transformed myelinated fibers in the experiment time frame amounted to 6.0±1.4%, 4.3±1.3% and 4.2±0.4% (normally: 1.9±0.3%, no marked vascular damage was observed, the number of epineural vascular modules increased up to 6.0±1.5 (contralaterally – up to 4.0±1.6, the number of endoneural microvessels was increased at 35.5%, 10.9% and 38.9% (p<0.05 in respect of intact norm (141.8±8.7 per 1 mm2. Reduced proportion of capillaries with open lumina confirmed vasomotion disorder. The changes analysis in the distribution of myelinated fibers by diameter and mean size indicates the distinct axonal

  17. Neutron scattering from myelin revisited: bilayer asymmetry and water-exchange kinetics

    Energy Technology Data Exchange (ETDEWEB)

    Denninger, Andrew R. [Boston College, Chestnut Hill, MA 02467 (United States); Demé, Bruno; Cristiglio, Viviana [Institut Laue–Langevin (ILL), CS 20156, F-38042 Grenoble CEDEX 9 (France); LeDuc, Géraldine [European Synchrotron Radiation Facility (ESRF), CS 40220, F-38043 Grenoble CEDEX 9 (France); Feller, W. Bruce [NOVA Scientific Inc., Sturbridge, MA 01566 (United States); Kirschner, Daniel A., E-mail: kirschnd@bc.edu [Boston College, Chestnut Hill, MA 02467 (United States)

    2014-12-01

    The structure of internodal myelin in the rodent central and peripheral nervous systems has been determined using neutron diffraction. The kinetics of water exchange in these tissues is also described. Rapid nerve conduction in the central and peripheral nervous systems (CNS and PNS, respectively) of higher vertebrates is brought about by the ensheathment of axons with myelin, a lipid-rich, multilamellar assembly of membranes. The ability of myelin to electrically insulate depends on the regular stacking of these plasma membranes and on the presence of a number of specialized membrane-protein assemblies in the sheath, including the radial component, Schmidt–Lanterman incisures and the axo–glial junctions of the paranodal loops. The disruption of this fine-structure is the basis for many demyelinating neuropathies in the CNS and PNS. Understanding the processes that govern myelin biogenesis, maintenance and destabilization requires knowledge of myelin structure; however, the tight packing of internodal myelin and the complexity of its junctional specializations make myelin a challenging target for comprehensive structural analysis. This paper describes an examination of myelin from the CNS and PNS using neutron diffraction. This investigation revealed the dimensions of the bilayers and aqueous spaces of myelin, asymmetry between the cytoplasmic and extracellular leaflets of the membrane, and the distribution of water and exchangeable hydrogen in internodal multilamellar myelin. It also uncovered differences between CNS and PNS myelin in their water-exchange kinetics.

  18. Findings of Optical Coherence Tomography of Retinal Nerve Fiber Layer in Two Common Types of Multiple Sclerosis.

    Science.gov (United States)

    Yousefipour, Gholamali; Hashemzahi, Zabihollah; Yasemi, Masood; Jahani, Pegah

    2016-06-01

    Multiple sclerosis (MS) is the most prevalent disease caused by the inflammatory demyelinating process that causes progressive nervous system degeneration over the time. Optical Coherence Tomography (OCT) is a non-invasive optical imaging technology, which can measure the thickness of retinal nerve fiber layer as well as the diameter of the macula. The purpose of the study is evaluation OCT findings in two common types of multiple sclerosis. For doing the cross-sectional study, 63 patients with two prevalent types of multiple sclerosis (35 patients with Relapse Remitting Multiple Sclerosis (RRMS) and 28 patients with Secondary Progressive Multiple Sclerosis (SPMS) were evaluated for 6 months. Exclusion criteria of the study were a history of optic neuritis, suffering from diabetes mellitus, hypertension, ocular disease, and the presence of other neurologic degenerative diseases. Then, the thickness of retinal nerve fiber layer (RNFL), as well as thickness and volume of the macula, were measured in the patients using OCT technology. The disability rate of patients was evaluated according to Expanded Disability Status Scale (EDSS). Finally, data was analyzed by means of SPSS software. Overall, 35 patients with RRMS (with mean age of 32.37+10.01, average disease period of 3.81+3.42 and mean EDSS of 1.84+0.45) and 28 patients with SPMS (with mean age of 39.21+9.33, average disease period of 11.32+5.87 and mean EDSS of 5.12+1.46) were assessed and compared in terms of retinal nerve fiber layer and size and thickness of macula. In all of these sections, the thicknesses were smaller in SPMS patients than patients with RRMS. But, there was a significant difference in total thickness (81.82µm versus 96.03µm with P=0.04) and thickness of temporal sector (54.5 µm versus 69.34 µm with P=0.04) of retinal nerve fiber layer and macular size at the superior sector of external ring (1.48 mm³ versus 1.58 mm³ with P=0.03), and nasal sector of external ring surrounding macula (1

  19. Findings of Optical Coherence Tomography of Retinal Nerve Fiber Layer in Two Common Types of Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Gholamali Yousefipour

    2016-06-01

    Full Text Available Multiple sclerosis (MS is the most prevalent disease caused by the inflammatory demyelinating process that causes progressive nervous system degeneration over the time. Optical Coherence Tomography (OCT is a non-invasive optical imaging technology, which can measure the thickness of retinal nerve fiber layer as well as the diameter of the macula. The purpose of the study is evaluation OCT findings in two common types of multiple sclerosis. For doing the cross-sectional study, 63 patients with two prevalent types of multiple sclerosis (35 patients with Relapse Remitting Multiple Sclerosis (RRMS and 28 patients with Secondary Progressive Multiple Sclerosis (SPMS were evaluated for 6 months. Exclusion criteria of the study were a history of optic neuritis, suffering from diabetes mellitus, hypertension, ocular disease, and the presence of other neurologic degenerative diseases. Then, the thickness of retinal nerve fiber layer (RNFL, as well as thickness and volume of the macula, were measured in the patients using OCT technology. The disability rate of patients was evaluated according to Expanded Disability Status Scale (EDSS. Finally, data was analyzed by means of SPSS software. Overall, 35 patients with RRMS (with mean age of 32.37+10.01, average disease period of 3.81+3.42 and mean EDSS of 1.84+0.45 and 28 patients with SPMS (with mean age of 39.21+9.33, average disease period of 11.32+5.87 and mean EDSS of 5.12+1.46 were assessed and compared in terms of retinal nerve fiber layer and size and thickness of macula. In all of these sections, the thicknesses were smaller in SPMS patients than patients with RRMS. But, there was a significant difference in total thickness (81.82µm versus 96.03µm with P=0.04 and thickness of temporal sector (54.5 µm versus 69.34 µm with P=0.04 of retinal nerve fiber layer and macular size at the superior sector of external ring (1.48 mm³ versus 1.58 mm³ with P=0.03, and nasal sector of external ring surrounding

  20. Retinal Nerve Fiber Layer May Be Better Preserved in MOG-IgG versus AQP4-IgG Optic Neuritis: A Cohort Study

    Science.gov (United States)

    Chodick, Gabriel; Bialer, Omer; Marignier, Romain; Bach, Michael; Hellmann, Mark Andrew

    2017-01-01

    Background Optic neuritis (ON) in patients with anti-myelin oligodendrocyte glycoprotein (MOG)-IgG antibodies has been associated with a better clinical outcome than anti-aquaporin 4 (AQP4)- IgG ON. Average retinal nerve fiber layer thickness (RNFL) correlates with visual outcome after ON. Objectives The aim of this study was to examine whether anti-MOG-IgG ON is associated with better average RNFL compared to anti-AQP4-IgG ON, and whether this corresponds with a better visual outcome. Methods A retrospective study was done in a consecutive cohort of patients following anti-AQP4-IgG and anti-MOG-IgG ON. A generalized estimating equation (GEE) models analysis was used to compare average RNFL outcomes in ON eyes of patients with MOG-IgG to AQP4-IgG-positive patients, after adjusting for the number of ON events. The final mean visual field defect and visual acuity were compared between ON eyes of MOG-IgG and AQP4-IgG-positive patients. A correlation between average RNFL and visual function was performed in all study eyes. Results Sixteen patients were analyzed; ten AQP4-IgG-positive and six MOG-IgG-positive. The six patients with MOG-IgG had ten ON events with disc edema, five of which were bilateral. In the AQP4-IgG-positive ON events, 1/10 patients had disc edema. Final average RNFL was significantly better in eyes following MOG-IgG-ON (75.33μm), compared to 63.63μm in AQP4-IgG-ON, after adjusting for the number of ON attacks (GEE, p = 0.023). Mean visual field defects were significantly smaller (GEE, p = 0.046) among MOG-IgG positive ON eyes compared to AQP-IgG positive ON eyes, but last visual acuity did not differ between the groups (GEE, p = 0.153). Among all eyes, average RNFL positively correlated with mean visual field defect (GEE, p = 0.00015) and negatively correlated with final visual acuity (GEE, p = 0.00005). Conclusions Following ON, RNFL is better preserved in eyes of patients with MOG-IgG antibodies compared to those with AQP4-IgG antibodies

  1. Raman spectroscopic detection of peripheral nerves towards nerve-sparing surgery

    Science.gov (United States)

    Minamikawa, Takeo; Harada, Yoshinori; Takamatsu, Tetsuro

    2017-02-01

    The peripheral nervous system plays an important role in motility, sensory, and autonomic functions of the human body. Preservation of peripheral nerves in surgery, namely nerve-sparing surgery, is now promising technique to avoid functional deficits of the limbs and organs following surgery as an aspect of the improvement of quality of life of patients. Detection of peripheral nerves including myelinated and unmyelinated nerves is required for the nerve-sparing surgery; however, conventional nerve identification scheme is sometimes difficult to identify peripheral nerves due to similarity of shape and color to non-nerve tissues or its limited application to only motor peripheral nerves. To overcome these issues, we proposed a label-free detection technique of peripheral nerves by means of Raman spectroscopy. We found several fingerprints of peripheral myelinated and unmyelinated nerves by employing a modified principal component analysis of typical spectra including myelinated nerve, unmyelinated nerve, and adjacent tissues. We finally realized the sensitivity of 94.2% and the selectivity of 92.0% for peripheral nerves including myelinated and unmyelinated nerves against adjacent tissues. Although further development of an intraoperative Raman spectroscopy system is required for clinical use, our proposed approach will serve as a unique and powerful tool for peripheral nerve detection for nerve-sparing surgery in the future.

  2. The Study of Retinal Nerve Fiber Layer Thickness of Normal Eyes Using Scanning Laser Polarimetry

    Institute of Scientific and Technical Information of China (English)

    Xing Liu; Jingjing Huang; Jian Ge; Yunlan Ling; Xiaoping Zheng

    2006-01-01

    Purpoe: To evaluate retinal nerve fiber layer (RNFL) thickness measurements in local normal Chinese subjects of different age groups and analyse the correlation of RNFL thickness with age using scanning laser polarimetry (SLP, GDxVCC). To assess the reproducibility of RNFL thickness measurement with GDxVCC.Methods: The RNFL thickness of 67 normal subjects (123 eyes) were measured by GDxVCC. The average TSNIT parameters were calculated. The differences of RNFL thickness between sex, right and left eyes, superior and inferior were compared. The relationship between RNFL thickness and age was analyzed with correlation analysis and linear regression analysis. The intraclass correlation coefficients (ICC) of three images in every eye were calculated.Results: The average peripapillary RNFL thickness at the superior, inferior and whole ellipse regions in 123 eyes of 67 normal subjects were (70.30±6.76)μm, (67.35±6.77) μm and (56.87±4.53) μm, respectively. The average TNSIT standard deviation was 23.68±4.61 and the average inter-eye symmetric value was 0.86±0.11. There were significant difference of RNFL thickness between superior and inferior (t=4.952,P <0.001 ). There were significant difference of inferior RNFL thickness and TNSIT standard deviation between right and left eyes (P=0.005 and 0.002),while not significant difference of superior RNFL thickness and whole mean RNFL thickness between right and left eye (P=0.086 and 0.529). There was no significant difference in TSNIT parameters between different genders. There was a slight negative correlation average RNFL thickness in superior sector with age (decreased approximately 0.15 microns per year,P=0.047) in the subjects aged below 60 years old. The ICC values of RNFL thickness were >0.8 in superior, inferior and global.Conclusions: The RNFL thickness can be measured accurately by GDxVCC and the reproducibility of RNFL thickness measurement by GDxVCC is good. There was a slight negative correlation between

  3. Peripapillary retinal nerve fiber layer thickness in patients with iron deficiency anemia

    Science.gov (United States)

    Cikmazkara, Ipek; Ugurlu, Seyda Karadeniz

    2016-01-01

    Purpose: To evaluate the effect of iron deficiency anemia (IDA) on peripapillary retinal nerve fiber layer (RNFL) thickness with optical coherence tomography (OCT). Materials and Methods: 102 female patients who had IDA (hemoglobin <12 g/dl, serum transferrin saturation <15%, serum iron <50 μg/dl, and serum ferritin <15 μg/dl) were enrolled in the study. Optic disc and RNFL parameters obtained by Cirrus high-definition OCT 4000 were compared with those of 49 age and sex-matched nonanemic individuals. The time between blood analysis and OCT measurements was 3.14 ± 5.6 (range, 0–28) days in the anemia group, and 3.5 ± 6.7 (range, 0–27) days in the control group (P = 0.76). Results: Average ages of 102 patients and 49 control subjects were 35.76 ± 10.112 (range, 18–66) years, and 36.08 ± 8.416 (range, 19–57) years (P = 0.850), respectively. The average RNFL thickness was 94.67 ± 9.380 in the anemia group, and 100.22 ± 9.12 in the control group (P = 0.001). Temporal, nasal, and lower quadrant average RNFL thicknesses of IDA group were thinner than the control group (P = 0.001, P = 0.013, P = 0.008). Upper quadrant RNFL thicknesses in IDA and control groups were similar. Correlation analysis revealed positive correlation between mean RNFL thickness and hemoglobin (r = 0.273), iron (r = 0.177), ferritin (r = 0.163), and transferrin saturations (r = 0.185), while a negative correlation was found between total iron binding capacity (r = −0.199) and mean RNFL thickness. Conclusions: Peripapillary RNFL thickness measured by OCT is thinner in adult female patients with IDA. It may have a significant influence on the management of many disorders such as glaucoma and neuro-ophthalmological diseases. PMID:27146929

  4. What is myelin?

    Science.gov (United States)

    Hartline, Daniel K

    2008-05-01

    The evolution of a character is better appreciated if examples of convergent emergence of the same character are available for comparison. Three instances are known among invertebrates of the evolution of axonal sheaths possessing the functional properties and many of the structural properties of vertebrate myelin. Comparison of these invertebrate myelins raises the question of what structural features must a sheath possess in order to produce the two principal functional characteristics of impulse speed enhancement and energy savings. This essay reviews the features recognized by early workers as pertaining to myelin in vertebrate and invertebrate alike: osmiophilia, negative birefringence and saltatory conduction. It then examines common features revealed by the advent of electron microscopy: multiplicity of lipid membranes, condensation of those membranes, specialized marginal seals, and nodes. Next it examines the robustness of these features as essential components of a speed-enhancing sheath. Features that are not entirely essential for speed enhancement include membrane compaction, spiral wrapping of layers, glial cell involvement, non-active axonal membrane, and even nodes and perinodal sealing. This permissiveness is discussed in relation to the possible evolutionary origin of myelin.

  5. Comparison of histopathological effects of perineural administration of bupivacaine and bupivacaine-dexmedetomidine in rat sciatic nerve.

    Science.gov (United States)

    Memari, Elham; Hosseinian, Mohammad-Ali; Mirkheshti, Ali; Arhami-Dolatabadi, Ali; Mirabotalebi, Mojtaba; Khandaghy, Mohsen; Daneshbod, Yahya; Alizadeh, Leila; Shirian, Sadegh

    2016-11-01

    Injection of a variety of drugs such as local anesthetics (LAs) for peripheral nerve block has been shown to cause damage to peripheral nerves. Bupivacaine is a local anesthetic widely used in surgical procedures. The aim of this study was to evaluate the neurotoxicity of LAs including Bupivacaine and dexmedetomidine (DEX)-Bupivacaine on sciatic nerve tissue at histopathological level. In addition, we investigated whether perineural administration of DEX can attenuate Bupivacaine-induced neurotoxicity. Twenty adult Sprague Dawley rats received unilateral sciatic nerve blocks with either 0.2ml of 0.5% bupivacaine (n=8) or 0.5% bupivacaine plus 0.005% DEX (n=8) or normal saline (0.9%, as control group) (n=4) in the left hind extremity. Sciatic nerves were harvested at 14days post-injection and analyzed for nerve damage using ultrastructure and histopathologic analysis. Histopathology of sciatic nerve at day 14 post-injection showed a variable degree of neuronal injury associated with perineural inflammation in each treatment group and was classified as none or mild, intermediate or severe. Administration of both LAs resulted in a significant decrease in the total number of myelinated fibers per nerve (95% CI for group difference: Bupivacaine, P=0.001, DEX-Bupivacaine, P=0.036) compared to the saline control group. Animals that received these perineural local anesthetics (LAs) injections showed increased severity of injury compared to the control group. Animals in the DEX-Bupivacaine group had higher perineural inflammation and nerve damage than those of the saline control group and less than those of the Bupivacaine group at day 14 post-injection. Quantitatively, average total nerve fiber per nerve and average myelinated nerve fiber density in the injured region of the Bupivacaine-treated group was less than that of the DEX-Bupivacaine-treated group. LAs injection into the nerve causes peripheral nerve damage and remains an important clinical danger. Bupivacaine is

  6. Association of Electroencephalography (EEG) Power Spectra with Corneal Nerve Fiber Injury in Retinoblastoma Patients.

    Science.gov (United States)

    Liu, Jianliang; Sun, Juanjuan; Diao, Yumei; Deng, Aijun

    2016-09-04

    BACKGROUND In our clinical experience we discovered that EEG band power may be correlated with corneal nerve injury in retinoblastoma patients. This study aimed to investigate biomarkers obtained from electroencephalography (EEG) recordings to reflect corneal nerve injury in retinoblastoma patients. MATERIAL AND METHODS Our study included 20 retinoblastoma patients treated at the Department of Ophthalmology, Affiliated Hospital of Weifang Medical University between 2010 and 2014. Twenty normal individuals were included in the control group. EEG activity was recorded continuously with 32 electrodes using standard EEG electrode placement for detecting EEG power. A cornea confocal microscope was used to examine corneal nerve injury in retinoblastoma patients and normal individuals. Spearman rank correlation analysis was used to analyze the correlation between corneal nerve injury and EEG power changes. The sensitivity and specificity of changed EEG power in diagnosis of corneal nerve injury were also analyzed. RESULTS The predominantly slow EEG oscillations changed gradually into faster waves in retinoblastoma patients. The EEG pattern in retinoblastoma patients was characterized by a distinct increase of delta (PEEG spectra power and negatively correlated with theta EEG spectra power. The diagnostic sensitivity and specificity by compounding in the series were 60% and 67%, respectively. CONCLUSIONS Changes in delta and theta of EEG appear to be associated with occurrence of corneal nerve injury. Useful information can be provided for evaluating corneal nerve damage in retinoblastoma patients through analyzing EEG power bands.

  7. Collagen scaffolds modified with CNTF and bFGF promote facial nerve regeneration in minipigs.

    Science.gov (United States)

    Cui, Yi; Lu, Chao; Meng, Danqing; Xiao, Zhifeng; Hou, Xianglin; Ding, Wenyong; Kou, Depeng; Yao, Yao; Chen, Bing; Zhang, Zhen; Li, Jiayin; Pan, Juli; Dai, Jianwu

    2014-09-01

    Most experiments of peripheral nerve repair after injury have been conducted in the rodent model but the translation of findings from rodent studies to clinical practice is needed partly because the nerve regeneration must occur over much longer distances in humans than in rodents. The reconstruction of long distance nerve injuries still represents a great challenge to surgeons who is engaged in peripheral nerve surgery. Here we used the functional nerve conduit (collagen scaffolds incorporated with neurocytokines CNTF and bFGF) to bridge a 35 mm long facial nerve gap in minipig models. At 6 months after surgery, electrophysiology assessment and histological examination were conducted to evaluate the regeneration of peripheral facial nerves. Based on functional and histological observations, the results indicated that the functional collagen scaffolds promoted nerve reconstruction. The number and arrangement of regenerated nerve fibers, myelination, and nerve function reconstruction was better in the CNTF + bFGF conduit group than the single factor CNTF or bFGF conduit group. The functional composite conduit, which exhibited favorable mechanical properties, may promote facial nerve regeneration in minipigs effectively. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Ultrastructural changes in the optic nerve and capillary vessels during early stages of optic nerve injury

    Institute of Scientific and Technical Information of China (English)

    Xuehong Ju; Xiuyun Li; Xiaoshuang Li; Hongtao Tang; Hongguo Liu

    2008-01-01

    BACKGROUND: Capillaries are the only blood supply for optic nerves, which makes the system more vulnerable to impaired blood circulation. OBJECTIVE: To observe the ultrastructural changes in the optic nerves and capillaries in rabbits following intracanalicular segment injury to the optic nerve. DESIGN, TIME AND SETTING: Comparative, observational, pathological morphology was performed at the Department of Anatomy, Weifang Medical College from September to November 2007. MATERIALS: Models of intracanalicular segment injury to the optic nerve were induced in the right eye of thirty healthy, adult rabbits by a flee-falling metal cylinder. The H-7500 transmission electron microscope was provided by Hitachi, Japan. METHODS: All rabbits were randomly assigned into experimental (n = 25) and control (n = 5) groups. Optic nerve specimens were obtained from the experimental group at 0.5, 6, 12, 48, and 96 hours, respectively, following injury. Uitrastructural changes to the optic nerves and their capillaries were observed by electron microscopy. Optic nerve injury was not established in the control group, but optic nerve specimens were collected similarly to the experimental group. MAIN OUTCOME MEASURES: Ultrastructural changes in the injured optic nerves and their capillaries. RESULTS: Thirty rabbits were included in the final analysis. In the control group, cross-sections of the optic nerves exhibited varied thicknesses with regularly arranged fibers. The axons appeared to be smooth with condensed myelin sheaths and oval mitochondria. The microtubules and mierofilaments were clearly seen. The lumens of the capillaries were regular with densely arranged endothelial cells and visible mitochondria. In the experimental group, 30 minutes after injury to the optic nerves, swollen axons, sparse myelin sheath, disordered microtubules and microfilaments, swollen mitochondria, and a decreased number of pinocytosis vesicles and microfilaments in endothelial cells of the capillaries

  9. Nociceptive and Neuronal Evaluation of the Sciatic Nerve of Wistar Rats Subjected to Compression Injury and Treated with Resistive Exercise

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    Juliana Sobral Antunes

    2016-01-01

    Full Text Available Background. To investigate the climb stairs resistance exercise on nociception and axonal regeneration in the sciatic nerve of rats. Methods. 24 Wistar rats were divided: control group (CG—no injury, exercise group (EG—no injury with physical exercise, lesion group (LG—injury, but without exercise, and treated group (LEG—injury and physical exercise. LG and LEG were subjected to sciatic nerve compression with hemostat. From the 3rd day after injury began treatment with exercise, and after 22 days occurs the removal of a nerve fragment for morphological analysis. Results. Regarding allodynia, CG obtained values less than EG (p=0.012 and larger than LG and LEG (p<0.001. Histological results showed that CG and EG had normal appearance, as LG and LEG showed up with large amounts of inflammatory infiltration, degeneration and disruption of nerve fibers, and reduction of the myelin sheath; however LEG presented some regenerated fibers. From the morphometric data there were significant differences, for nerve fiber diameter, comparing CG with LG and LEG and comparing axon diameter and the thickness of the myelin of the CG to others. Conclusion. Climb stairs resistance exercise was not effective to speed up the regenerative process of axons.

  10. Fast negative feedback enables mammalian auditory nerve fibers to encode a wide dynamic range of sound intensities.

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    Mark Ospeck

    Full Text Available Mammalian auditory nerve fibers (ANF are remarkable for being able to encode a 40 dB, or hundred fold, range of sound pressure levels into their firing rate. Most of the fibers are very sensitive and raise their quiescent spike rate by a small amount for a faint sound at auditory threshold. Then as the sound intensity is increased, they slowly increase their spike rate, with some fibers going up as high as ∼300 Hz. In this way mammals are able to combine sensitivity and wide dynamic range. They are also able to discern sounds embedded within background noise. ANF receive efferent feedback, which suggests that the fibers are readjusted according to the background noise in order to maximize the information content of their auditory spike trains. Inner hair cells activate currents in the unmyelinated distal dendrites of ANF where sound intensity is rate-coded into action potentials. We model this spike generator compartment as an attenuator that employs fast negative feedback. Input current induces rapid and proportional leak currents. This way ANF are able to have a linear frequency to input current (f-I curve that has a wide dynamic range. The ANF spike generator remains very sensitive to threshold currents, but efferent feedback is able to lower its gain in response to noise.

  11. Effects of subcutaneous implant of peripheral nerve allograft on the regeneration of defected sciatic nerve

    Institute of Scientific and Technical Information of China (English)

    Mingtang Gao; Dianming Jiang; Hong An

    2006-01-01

    structure of epineurium was in integrity and there were no obvious differences in perineurium and endonurium between two groups. A large number of myelinated nerve fibers and a few unmyelinated nerve fibers regenerated. The structure of myelin sheath was in integrity. ③The number and size of regenerated axons of anastomosis of proximal and distal sciatic nerve had no significant difference 14 weeks after grafting [(575.500±7.495) vs(585.700±11.172) axons/visual field; (389.300±49.073) vs (407.600±0.283)axons/visual field;(6 423.830±119.911)vs (6 695.36±84.287) μm2/visual field; (5 980.110±74.572) vs(5 980.110±74.572) μm2/visual field] (P > 0.05). ④ Neuroelectrophysiological examination showed that there were no significant differences in motor nerve evoked potential latent period[(1.420±0.346)vs (1.237±0.250) ms] , motor nerve conduction velocity [(12.120±0.906) vs(13.020±0.599) m/s]and latent period of sciatic nerve [(0.500±0.380)vs (1.250±1.067) mV] of rats between two groups (P > 0.05).CONCLUSION: Although subcutaneous implant of peripheral nerve allograft has some inflammatory reactions, no obvious rejection is found. Repair results of two groups show that subcutaneous implant of allograft can promote nerve regeneration, which is similar to autologous nerve grafting.

  12. Nerve growth factor combined with an epineural conduit for bridging a short nerve gap (10 mm). A study in rabbits.

    Science.gov (United States)

    Barmpitsioti, Antonia; Konofaos, Petros; Ignatiadis, Ioannis; Papalois, Apostolos; Zoubos, Aristides B; Soucacos, Panagiotis N

    2011-10-01

    The purpose of this study was to evaluate the effect of direct administration of nerve growth factor (NGF) into an epineural conduit across a short nerve gap (10 mm) in a rabbit sciatic nerve model. The animals were divided into two groups. In group 1, n = 6, a 10-mm defect was created in the sciatic nerve and bridged with an epineural flap. A dose of 1 μg of NGF was locally administered daily for the first 21 days. NGF administration was made inside the epineural flap using a silicone reservoir connected to a silicone tube. In group 2, n = 6, the 10-mm defect was bridged with a nerve graft. This group did not receive any further treatment. At 13 weeks, all animals, before euthanasia, underwent electromyography (EMG) studies and then specimen sent for histology morphometric analysis. NGF administration ensured a significantly increased average number of myelinated axons per μm(2) (P = 0.028) and promoted fiber maturation (P = 0.031) and better EMG results (P = 0.046 for latency P = 0.048 for amplitude), compared with the control group. Although nerve grafts remain the gold standard for peripheral nerve repair, NGF-treated epineural conduits represent a good alternative, particularly when an unfavorable environment for nerve grafts is present.

  13. Endurance training induces structural and morphoquantitative changes in rat vagus nerve

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    Eduardo Pianca

    2015-10-01

    Full Text Available ABSTRACTIntroduction:Many nervous system tissues and cells suffers positive changes when faced to exercise training. However, data on vagus nerve adaptation from exercise-induced study is absent.Objective:To analyze the effect of an endurance training on the vagus nerve morphology of rats.Methods:Wistar rats (6 months of age were divided into two groups: control group (CG, n=8, and aerobic trained group (AT, n=8. AT was submitted to a treadmill training program of five times per week during 12 weeks. The maximum speed stipulated in the training protocol corresponded to 60% of the mean maximum intensity achieved by the group in the test of maximum effort.Results:Twelve weeks of treadmill training resulted in left ventricular hypertrophy in the AT group com-pared to CG. There was a significant increase in the area of both the myelinated and unmyelinated axons, and in the area of myelin sheath with training. The number of neurotubules and neurofilaments in myelinated fibers of aerobic trained group was significantly greater than CG (p≤0.05.Conclusion:Endurance training promoted significant increase in morphometric parameters of the vagus nerve in the same way it affect somatic nerves.

  14. Interspecies variation in axon-myelin relationships.

    Science.gov (United States)

    Fraher, J P; O'Sullivan, A W

    2000-01-01

    The primary objective of this paper was to determine the extent and nature of interspecies differences in axon calibre and myelin sheath thickness and in the various relationships between these. Morphometric analysis of the axon perimeter-myelin sheath thickness relationship was performed on an equivalent nerve fibre population in a mammal, the rat, a bird, the chicken, an amphibian, the frog, a bony fish, the trout, and a cartilaginous fish, the dogfish. The abducent nerve was studied. It is especially suitable for this purpose because its fibres are closely similar in type and in peripheral distribution across the species studied. The relationship differed substantially between species. Differences were present in its setting, as described by the positions of the scatterplots, in the g ratio and in the regression and correlation data relating the parameters. Both parameters were markedly larger in the fish species than in all of the others. In addition, in rat, chicken, frog and trout, where large and small fibre classes could be differentiated clearly, the setting of the relationship between the two parameters was different for the two classes. In the main, variation in each of the parameters was greater between than within species. The larger fibres in the fish species were closely similar in axon perimeter and sheath thickness despite their long evolutionary separation. From this study and from others in the series, it may be concluded that there is no fixed or constant relationship between axon calibre and the thickness of the surrounding myelin sheath. Each nerve tends to have its own particular relationship and this differs between species.

  15. Effect of Refractive Correction Error on Retinal Nerve Fiber Layer Thickness: A Spectralis Optical Coherence Tomography Study

    Science.gov (United States)

    Ma, Xiaoli; Chen, Yutong; Liu, Xianjie; Ning, Hong

    2016-01-01

    Background Identifying and assessing retinal nerve fiber layer defects are important for diagnosing and managing glaucoma. We aimed to investigate the effect of refractive correction error on retinal nerve fiber layer (RNFL) thickness measured with Spectralis spectral-domain optical coherence tomography (SD-OCT). Material/Methods We included 68 participants: 32 healthy (normal) and 36 glaucoma patients. RNFL thickness was measured using Spectralis SD-OCT circular scan. Measurements were made with a refractive correction of the spherical equivalent (SE), the SE+2.00D and the SE–2.00D. Results Average RNFL thickness was significantly higher in the normal group (105.88±10.47 μm) than in the glaucoma group (67.67±17.27 μm, Prefractive correction error significantly affected measurements of average (Prefractive correction error significantly increased average (Prefractive correction. However, −2.00D of refractive correction error did not significantly affect RNFL thickness measurements in either group. Conclusions Positive defocus error significantly affects RNFL thickness measurements made by the Spectralis SD-OCT. Negative defocus error did not affect RNFL measurement examined. Careful correction of refractive error is necessary to obtain accurate baseline and follow-up RNFL thickness measurements in healthy and glaucomatous eyes. PMID:28030536

  16. The Influence of Low Doses of Zearalenone on Distribution of Selected Active Substances in Nerve Fibers Within the Circular Muscle Layer of Porcine Ileum.

    Science.gov (United States)

    Gonkowski, Sławomir; Obremski, Kazimierz; Calka, Jaroslaw

    2015-08-01

    The aim of this study was to investigate, whether low doses (25 % of no observable adverse effect levels values) of zearalenone (ZEN) can affect the expression of active substances in nerve fibers in the muscular layer of porcine ileum. The study was performed on ten immature pigs divided into two groups: experimental group (n = 5), where zearalenone (10 μg/kg body weight) was given for 42 days, and control animals (n = 5), where placebo was administered. Fragments of ileum of all animals were processed for single-labelling immunofluorescence technique using the antibodies against vasoactive intestinal peptide, neuronal form of nitric oxide synthase, cocaine and amphetamine regulatory peptide, galanin, pituitary adenylate cyclase-activating peptide-27 and substance P. The number of nerve fibers immunoreactive to particular substances was evaluated by the counting of nerves per observation field (0.1 mm(2)). Low doses of zearalenone caused the clear changes in the expression of substances studied. The number of nerve fibers immunoreactive to the majority of substances increased in experimental animals. The exception was only galanin, the expression of which was less after administration of zearalenone. The obtained results for the first time show that even low doses of zearalenone can affect the nerve fibers in the digestive tract.

  17. Neuropeptide Y as a presynaptic modulator of norepinephrine release from the sympathetic nerve fibers in the pig pineal gland.

    Science.gov (United States)

    Ziółkowska, N; Lewczuk, B; Przybylska-Gornowicz, B

    2015-01-01

    Norepinephrine (NE) released from the sympathetic nerve endings is the main neurotransmitter controlling melatonin synthesis in the mammalian pineal gland. Although neuropeptide Y (NPY) co-exists with NE in the pineal sympathetic nerve fibers it also occurs in a population of non-adrenergic nerve fibers located in this gland. The role of NPY in pineal physiology is still enigmatic. The present study characterizes the effect of NPY on the depolarization-evoked 3H-NE release from the pig pineal explants. The explants of the pig pineal gland were loaded with 3H-NE in the presence of pargyline and superfused with Tyrode medium. They were exposed twice to the modified Tyrode medium containing 60 mM of K+ to evoke the 3H-NE release via depolarization. NPY, specific agonists of Y1- and Y2- receptors and pharmacologically active ligands of α2-adrenoceptors were added to the medium before and during the second depolarization. The radioactivity was measured in medium fractions collected every 2 minutes during the superfusion. NPY (0.1-10 μM) significantly decreased the depolarization-induced 3H-NE release. Similar effect was observed after the treatment with Y2-agonist: NPY13-36, but not with Y1-agonist: [Leu31,Pro34]-NPY. The tritium overflow was lower in the explants exposed to the 5 μM NPY and 1 μM rauwolscine than to rauwolscine only. The effects of 5 μM NPY and 0.05 μM UK 14,304 on the depolarization-evoked 3H-NE release were additive. The results show that NPY is involved in the regulation of NE release from the sympathetic terminals in the pig pineal gland, inhibiting this process via Y2-receptors.

  18. Formation of compact myelin is required for maturation of the axonal cytoskeleton

    Science.gov (United States)

    Brady, S. T.; Witt, A. S.; Kirkpatrick, L. L.; de Waegh, S. M.; Readhead, C.; Tu, P. H.; Lee, V. M.

    1999-01-01

    Although traditional roles ascribed to myelinating glial cells are structural and supportive, the importance of compact myelin for proper functioning of the nervous system can be inferred from mutations in myelin proteins and neuropathologies associated with loss of myelin. Myelinating Schwann cells are known to affect local properties of peripheral axons (de Waegh et al., 1992), but little is known about effects of oligodendrocytes on CNS axons. The shiverer mutant mouse has a deletion in the myelin basic protein gene that eliminates compact myelin in the CNS. In shiverer mice, both local axonal features like phosphorylation of cytoskeletal proteins and neuronal perikaryon functions like cytoskeletal gene expression are altered. This leads to changes in the organization and composition of the axonal cytoskeleton in shiverer unmyelinated axons relative to age-matched wild-type myelinated fibers, although connectivity and patterns of neuronal activity are comparable. Remarkably, transgenic shiverer mice with thin myelin sheaths display an intermediate phenotype indicating that CNS neurons are sensitive to myelin sheath thickness. These results indicate that formation of a normal compact myelin sheath is required for normal maturation of the neuronal cytoskeleton in large CNS neurons.

  19. Spider silk constructs enhance axonal regeneration and remyelination in long nerve defects in sheep.

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    Christine Radtke

    Full Text Available BACKGROUND: Surgical reapposition of peripheral nerve results in some axonal regeneration and functional recovery, but the clinical outcome in long distance nerve defects is disappointing and research continues to utilize further interventional approaches to optimize functional recovery. We describe the use of nerve constructs consisting of decellularized vein grafts filled with spider silk fibers as a guiding material to bridge a 6.0 cm tibial nerve defect in adult sheep. METHODOLOGY/PRINCIPAL FINDINGS: The nerve constructs were compared to autologous nerve grafts. Regeneration was evaluated for clinical, electrophysiological and histological outcome. Electrophysiological recordings were obtained at 6 months and 10 months post surgery in each group. Ten months later, the nerves were removed and prepared for immunostaining, electrophysiological and electron microscopy. Immunostaining for sodium channel (NaV 1.6 was used to define nodes of Ranvier on regenerated axons in combination with anti-S100 and neurofilament. Anti-S100 was used to identify Schwann cells. Axons regenerated through the constructs and were myelinated indicating migration of Schwann cells into the constructs. Nodes of Ranvier between myelin segments were observed and identified by intense sodium channel (NaV 1.6 staining on the regenerated axons. There was no significant difference in electrophysiological results between control autologous experimental and construct implantation indicating that our construct are an effective alternative to autologous nerve transplantation. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that spider silk enhances Schwann cell migration, axonal regrowth and remyelination including electrophysiological recovery in a long-distance peripheral nerve gap model resulting in functional recovery. This improvement in nerve regeneration could have significant clinical implications for reconstructive nerve surgery.

  20. Spider Silk Constructs Enhance Axonal Regeneration and Remyelination in Long Nerve Defects in Sheep

    Science.gov (United States)

    Radtke, Christine; Allmeling, Christina; Waldmann, Karl-Heinz; Reimers, Kerstin; Thies, Kerstin; Schenk, Henning C.; Hillmer, Anja; Guggenheim, Merlin; Brandes, Gudrun; Vogt, Peter M.

    2011-01-01

    Background Surgical reapposition of peripheral nerve results in some axonal regeneration and functional recovery, but the clinical outcome in long distance nerve defects is disappointing and research continues to utilize further interventional approaches to optimize functional recovery. We describe the use of nerve constructs consisting of decellularized vein grafts filled with spider silk fibers as a guiding material to bridge a 6.0 cm tibial nerve defect in adult sheep. Methodology/Principal Findings The nerve constructs were compared to autologous nerve grafts. Regeneration was evaluated for clinical, electrophysiological and histological outcome. Electrophysiological recordings were obtained at 6 months and 10 months post surgery in each group. Ten months later, the nerves were removed and prepared for immunostaining, electrophysiological and electron microscopy. Immunostaining for sodium channel (NaV 1.6) was used to define nodes of Ranvier on regenerated axons in combination with anti-S100 and neurofilament. Anti-S100 was used to identify Schwann cells. Axons regenerated through the constructs and were myelinated indicating migration of Schwann cells into the constructs. Nodes of Ranvier between myelin segments were observed and identified by intense sodium channel (NaV 1.6) staining on the regenerated axons. There was no significant difference in electrophysiological results between control autologous experimental and construct implantation indicating that our construct are an effective alternative to autologous nerve transplantation. Conclusions/Significance This study demonstrates that spider silk enhances Schwann cell migration, axonal regrowth and remyelination including electrophysiological recovery in a long-distance peripheral nerve gap model resulting in functional recovery. This improvement in nerve regeneration could have significant clinical implications for reconstructive nerve surgery. PMID:21364921

  1. Transcriptional upregulation of myelin components in spontaneous myelin basic protein-deficient mice.

    Science.gov (United States)

    Staats, Kim A; Pombal, Diana; Schönefeldt, Susann; Van Helleputte, Lawrence; Maurin, Hervé; Dresselaers, Tom; Govaerts, Kristof; Himmelreich, Uwe; Van Leuven, Fred; Van Den Bosch, Ludo; Dooley, James; Humblet-Baron, Stephanie; Liston, Adrian

    2015-05-01

    Myelin is essential for efficient signal transduction in the nervous system comprising of multiple proteins. The intricacies of the regulation of the formation of myelin, and its components, are not fully understood. Here, we describe the characterization of a novel myelin basic protein (Mbp) mutant mouse, mbp(jive), which spontaneously occurred in our mouse colony. These mice displayed the onset of a shaking gait before 3 weeks of age and seizure onset before 2 months of age. Due to a progressive increase of seizure intensity, mbp(jive) mice experienced premature lethality at around 3 months of age. Mbp mRNA transcript or protein was undetectable and, accordingly, genetic analysis demonstrated a homozygous loss of exons 3 to 6 of Mbp. Peripheral nerve conductance was mostly unimpaired. Additionally, we observed grave structural changes in white matter predominant structures were detected by T1, T2 and diffusion weighted magnetic resonance imaging. We additionally observed that Mbp-deficiency results in an upregulation of Qkl, Mag and Cnp, suggestive of a regulatory feedback mechanism whereby compensatory increases in Qkl have downstream effects on Mag and Cnp. Further research will clarify the role and specifications of this myelin feedback loop, as well as determine its potential role in therapeutic strategies for demyelinating disorders.

  2. Optic Nerve Head and Retinal Nerve Fiber Layer Analysis in Ocular Hypertension and Early-Stage Glucoma Using Spectral-Domain Optical Coherence Tomography Copernicus

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    Nilgün Solmaz

    2014-01-01

    Full Text Available Objectives: Evaluation of structural alterations of the optic nerve head (ONH and the retinal nerve fiber layer (RNFL in patients with ocular hypertension (OHT and early-stage glaucoma and assessment of the discriminatory diagnostic performance of spectral-domain optical coherence tomography (SD-OCT Copernicus (Optopol Technology S.A.. Materials and Methods: This study included 59 eyes of a total of 59 patients, 29 of whom were diagnosed with OHT (Group 1 and 30 with early-stage glaucoma (Group 2. The differentiation of early-stage glaucoma and OHT was carried out on the basis of standard achromatic visual field test results. Analysis of the ONH and RNFL thickness of all cases was made using SD-OCT. Group 1 and Group 2 were compared with respect to the ONH parameters and RNFL thickness. The diagnostic sensitivity of the OCT parameters was evaluated by the area under the receiver operating characteristics curves (AUC. Results: The average, superior, inferior, and nasal RNFL thicknesses in early-stage glaucoma cases were approximately 10% (12-14 µm less compared to the OHT eyes, with differences being highly significant (p≤0.001. However, there was no statistically significant difference in the temporal RNFL thicknesses. The most sensitive parameter in the early diagnosis of glaucoma was average RNFL thickness corresponding to AUC: 0.852, followed by AUC: 0.816 and AUC: 0.773 values in superior and inferior RNFL thickness, respectively. In localized RNFL defects, the highest sensitivity corresponded to superior and superonasal quadrants (ACU: 0.805 and ACU: 0.781, respectively. There were not any statistically significant differences between the ONH morphological parameters of the two groups. Conclusion: RNFL analysis obtained using SD-OCT Copernicus is able to discriminate early-stage glaucoma eyes from those with OHT. However, ONH morphological parameters do not have the same diagnostic sensitivity. Turk J Ophthalmol 2014; 44: 35-41

  3. Spectral domain optical coherence tomography in glaucoma: qualitative and quantitative analysis of the optic nerve head and retinal nerve fiber layer (an AOS thesis).

    Science.gov (United States)

    Chen, Teresa C

    2009-12-01

    To demonstrate that video-rate spectral domain optical coherence tomography (SDOCT) can qualitatively and quantitatively evaluate optic nerve head (ONH) and retinal nerve fiber layer (RNFL) glaucomatous structural changes. To correlate quantitative SDOCT parameters with disc photography and visual fields. SDOCT images from 4 glaucoma eyes (4 patients) with varying stages of open-angle glaucoma (ie, early, moderate, late) were qualitatively contrasted with 2 age-matched normal eyes (2 patients). Of 61 other consecutive patients recruited in an institutional setting, 53 eyes (33 patients) met inclusion/exclusion criteria for quantitative studies. Images were obtained using two experimental SDOCT systems, one utilizing a superluminescent diode and the other a titanium:sapphire laser source, with axial resolutions of about 6 microm and 3 microm, respectively. Classic glaucomatous ONH and RNFL structural changes were seen in SDOCT images. An SDOCT reference plane 139 microm above the retinal pigment epithelium yielded cup-disc ratios that best correlated with masked physician disc photography cup-disc ratio assessments. The minimum distance band, a novel SDOCT neuroretinal rim parameter, showed good correlation with physician cup-disc ratio assessments, visual field mean deviation, and pattern standard deviation (P values range, .0003-.024). RNFL and retinal thickness maps correlated well with disc photography and visual field testing. To our knowledge, this thesis presents the first comprehensive qualitative and quantitative evaluation of SDOCT images of the ONH and RNFL in glaucoma. This pilot study provides basis for developing more automated quantitative SDOCT-specific glaucoma algorithms needed for future prospective multicenter national trials.

  4. Spectral Domain Optical Coherence Tomography in Glaucoma: Qualitative and Quantitative Analysis of the Optic Nerve Head and Retinal Nerve Fiber Layer (An AOS Thesis)

    Science.gov (United States)

    Chen, Teresa C.

    2009-01-01

    Purpose: To demonstrate that video-rate spectral domain optical coherence tomography (SDOCT) can qualitatively and quantitatively evaluate optic nerve head (ONH) and retinal nerve fiber layer (RNFL) glaucomatous structural changes. To correlate quantitative SDOCT parameters with disc photography and visual fields. Methods: SDOCT images from 4 glaucoma eyes (4 patients) with varying stages of open-angle glaucoma (ie, early, moderate, late) were qualitatively contrasted with 2 age-matched normal eyes (2 patients). Of 61 other consecutive patients recruited in an institutional setting, 53 eyes (33 patients) met inclusion/exclusion criteria for quantitative studies. Images were obtained using two experimental SDOCT systems, one utilizing a superluminescent diode and the other a titanium:sapphire laser source, with axial resolutions of about 6 μm and 3 μm, respectively. Results: Classic glaucomatous ONH and RNFL structural changes were seen in SDOCT images. An SDOCT reference plane 139 μm above the retinal pigment epithelium yielded cup-disc ratios that best correlated with masked physician disc photography cup-disc ratio assessments. The minimum distance band, a novel SDOCT neuroretinal rim parameter, showed good correlation with physician cup-disc ratio assessments, visual field mean deviation, and pattern standard deviation (P values range, .0003–.024). RNFL and retinal thickness maps correlated well with disc photography and visual field testing. Conclusions: To our knowledge, this thesis presents the first comprehensive qualitative and quantitative evaluation of SDOCT images of the ONH and RNFL in glaucoma. This pilot study provides basis for developing more automated quantitative SDOCT-specific glaucoma algorithms needed for future prospective multicenter national trials. PMID:20126502

  5. Hunting for origins of migraine pain: cluster analysis of spontaneous and capsaicin-induced firing in meningeal trigeminal nerve fibers

    Directory of Open Access Journals (Sweden)

    Andrei eZakharov

    2015-07-01

    Full Text Available Trigeminal nerves in meninges are implicated in generation of nociceptive firing underlying migraine pain. However, the neurochemical mechanisms of nociceptive firing in meningeal trigeminal nerves are little understood. In this study, using suction electrode recordings from peripheral branches of the trigeminal nerve in isolated rat meninges, we analyzed spontaneous and capsaicin-induced orthodromic spiking activity. In control, biphasic single spikes with variable amplitude and shapes were observed. Application of the TRPV1 agonist capsaicin to meninges dramatically increased firing whereas the amplitudes and shapes of spikes remained essentially unchanged. This effect was antagonized by the specific TRPV1 antagonist capsazepine. Using the clustering approach, several groups of uniform spikes (clusters were identified. The clustering approach combined with capsaicin application allowed us to detect and to distinguish ‘responder’ (65% from ‘non-responder’ clusters (35%. Notably, responders fired spikes at frequencies exceeding 10 Hz, high enough to provide postsynaptic temporal summation of excitation at spinal cord level. Almost all spikes were suppressed by TTX suggesting an involvement of the TTX-sensitive sodium channels in nociceptive signaling at the peripheral branches of trigeminal neurons. Our analysis also identified transient (desensitizing and long-lasting (slowly desensitizing, responses to the continuous application of capsaicin. Thus, the persistent activation of nociceptors in capsaicin-sensitive nerve fibers shown here may be involved in trigeminal pain signaling and plasticity along with the release of migraine-related neuropeptides from TRPV1 positive neurons. Furthermore, cluster analysis could be widely used to characterize the temporal and neurochemical profiles of other pain transducers likely implicated in migraine.

  6. Automatic estimation of retinal nerve fiber bundle orientation in SD-OCT images using a structure-oriented smoothing filter

    Science.gov (United States)

    Ghafaryasl, Babak; Baart, Robert; de Boer, Johannes F.; Vermeer, Koenraad A.; van Vliet, Lucas J.

    2017-02-01

    Optical coherence tomography (OCT) yields high-resolution, three-dimensional images of the retina. A better understanding of retinal nerve fiber bundle (RNFB) trajectories in combination with visual field data may be used for future diagnosis and monitoring of glaucoma. However, manual tracing of these bundles is a tedious task. In this work, we present an automatic technique to estimate the orientation of RNFBs from volumetric OCT scans. Our method consists of several steps, starting from automatic segmentation of the RNFL. Then, a stack of en face images around the posterior nerve fiber layer interface was extracted. The image showing the best visibility of RNFB trajectories was selected for further processing. After denoising the selected en face image, a semblance structure-oriented filter was applied to probe the strength of local linear structure in a discrete set of orientations creating an orientation space. Gaussian filtering along the orientation axis in this space is used to find the dominant orientation. Next, a confidence map was created to supplement the estimated orientation. This confidence map was used as pixel weight in normalized convolution to regularize the semblance filter response after which a new orientation estimate can be obtained. Finally, after several iterations an orientation field corresponding to the strongest local orientation was obtained. The RNFB orientations of six macular scans from three subjects were estimated. For all scans, visual inspection shows a good agreement between the estimated orientation fields and the RNFB trajectories in the en face images. Additionally, a good correlation between the orientation fields of two scans of the same subject was observed. Our method was also applied to a larger field of view around the macula. Manual tracing of the RNFB trajectories shows a good agreement with the automatically obtained streamlines obtained by fiber tracking.

  7. Perivascular nerve fiber α-synuclein regulates contractility of mouse aorta: a link to autonomic dysfunction in Parkinson's disease.

    Science.gov (United States)

    Marrachelli, Vannina G; Miranda, Francisco J; Alabadí, José A; Milán, Miguel; Cano-Jaimez, Marifé; Kirstein, Martina; Alborch, Enrique; Fariñas, Isabel; Pérez-Sánchez, Francisco

    2010-07-01

    Parkinson's disease and other neurodegenerative disorders associated to changes in alpha-synuclein often result in autonomic dysfunction, most of the time accompanied by abundant expression of this synaptic protein in peripheral autonomic neurons. Given that expression of alpha-synuclein in vascular elements has been previously reported, the present study was undertaken to determine whether alpha-synuclein directly participates in the regulation of vascular responsiveness. We detected by immunohistochemistry perivascular nerve fibers containing alpha-synuclein in the aorta of mice while aortic endothelial cells and muscular fibers themselves did not exhibit detectable levels of this protein. To assess the effect of alpha-synuclein on vascular reactivity, aortic ring preparations obtained from alpha-synuclein-deficient knockout mice and from transgenic mice overexpressing human wild-type alpha-synuclein under the control of the tyrosine hydroxylase-promoter were mounted and equilibrated in organ baths for isometric tension recording. Lack of alpha-synuclein did not modify the relaxant responses to the endothelium-dependent (acetylcholine) and -independent (sodium nitroprusside) vasodilators, but resulted in a greater than normal norepinephrine-induced vasoconstriction along with a lowered response to dopamine, suggesting potential presynaptic changes in dopamine and norepinephrine releases in knockout mice. Overexpression of alpha-synuclein in TH-positive fibers resulted in complex abnormal responses, characterized by lowered acetylcholine-induced relaxation and lowered norepinephrin-induced contraction. Taken together, our data show for the first time that alpha-synuclein is present in sympathetic fibers supplying the murine aorta and provide evidence that changes in alpha-synuclein levels in perivascular fibers play a physiological role in the regulation of vascular function.

  8. Basic response characteristics of auditory nerve fibers in the grassfrog (Rana temporaria)

    DEFF Research Database (Denmark)

    Christensen-Dalsgaard, J; Jørgensen, M B; Kanneworff, M

    1998-01-01

    -excitatory suppression (PS) of their spontaneous activity. The duration of PS increased with sound level, also in fibers showing a decrease in firing rate at high intensities. Most fibers showing one-tone suppression did not show PS at their best suppression frequencies. Strong suppression was observed also in very...... important. Udgivelsesdato: 1998-May...

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

    Science.gov (United States)

    Gordon, Tessa; Gordon, Karen

    2010-01-01

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

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

    Science.gov (United States)

    Gordon, Tessa; Gordon, Karen

    2010-01-01

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

  11. Glycans of myelin proteins.

    Science.gov (United States)

    Sedzik, Jan; Jastrzebski, Jan Pawel; Grandis, Marina

    2015-01-01

    Human P0 is the main myelin glycoprotein of the peripheral nervous system. It can bind six different glycans, all linked to Asn(93) , the unique glycosylation site. Other myelin glycoproteins, also with a single glycosylation site (PMP22 at Asn(36) , MOG at Asn(31) ), bind only one glycan. The MAG has 10 glycosylation sites; the glycoprotein OMgp has 11 glycosylation sites. Aside from P0, no comprehensive data are available on other myelin glycoproteins. Here we review and analyze all published data on the physicochemical structure of the glycans linked to P0, PMP22, MOG, and MAG. Most data concern bovine P0, whose glycan moieties have an MW ranging from 1,294.56 Da (GP3) to 2,279.94 Da (GP5). The pI of glycosylated P0 protein varies from pH 9.32 to 9.46. The most charged glycan is MS2 containing three sulfate groups and one glucuronic acid; whereas the least charged one is the BA2 residue. All glycans contain one fucose and one galactose. The most mannose rich are the glycans MS2 and GP4, each of them has four mannoses; OPPE1 contains five N-acetylglucosamines and one sulfated glucuronic acid; GP4 contains one sialic acid. Furthermore, human P0 variants causing both gain and loss of glycosylation have been described and cause peripheral neuropathies with variable clinical severity. In particular, the substitution T(95) →M is a very common in Europe and is associated with a late-onset axonal neuropathy. Although peripheral myelin is made up largely of glycoproteins, mutations altering glycosylation have been described only in P0. This attractive avenue of research requires further study.

  12. The Effect of Electrospun Gelatin Fibers Alignment on Schwann Cell and Axon Behavior and Organization in the Perspective of Artificial Nerve Design.

    Science.gov (United States)

    Gnavi, Sara; Fornasari, Benedetta Elena; Tonda-Turo, Chiara; Laurano, Rossella; Zanetti, Marco; Ciardelli, Gianluca; Geuna, Stefano

    2015-01-01

    Electrospun fibrous substrates mimicking extracellular matrices can be prepared by electrospinning, yielding aligned fibrous matrices as internal fillers to manufacture artificial nerves. Gelatin aligned nano-fibers were prepared by electrospinning after tuning the collector rotation speed. The effect of alignment on cell adhesion and proliferation was tested in vitro using primary cultures, the Schwann cell line, RT4-D6P2T, and the sensory neuron-like cell line, 50B11. Cell adhesion and proliferation were assessed by quantifying at several time-points. Aligned nano-fibers reduced adhesion and proliferation rate compared with random fibers. Schwann cell morphology and organization were investigated by immunostaining of the cytoskeleton. Cells were elongated with their longitudinal body parallel to the aligned fibers. B5011 neuron-like cells were aligned and had parallel axon growth when cultured on the aligned gelatin fibers. The data show that the alignment of electrospun gelatin fibers can modulate Schwann cells and axon organization in vitro, suggesting that this substrate shows promise as an internal filler for the design of artificial nerves for peripheral nerve reconstruction.

  13. Akt Regulates Axon Wrapping and Myelin Sheath Thickness in the PNS

    Science.gov (United States)

    Baloui, Hasna; Meng, Xiaosong; Zhang, Yanqing; Deinhardt, Katrin; Dupree, Jeff L.; Einheber, Steven; Chrast, Roman

    2016-01-01

    The signaling pathways that regulate myelination in the PNS remain poorly understood. Phosphatidylinositol-4,5-bisphosphate 3-kinase 1A, activated in Schwann cells by neuregulin and the extracellular matrix, has an essential role in the early events of myelination. Akt/PKB, a key effector of phosphatidylinositol-4,5-bisphosphate 3-kinase 1A, was previously implicated in CNS, but not PNS myelination. Here we demonstrate that Akt plays a crucial role in axon ensheathment and in the regulation of myelin sheath thickness in the PNS. Pharmacological inhibition of Akt in DRG neuron-Schwann cell cocultures dramatically decreased MBP and P0 levels and myelin sheath formation without affecting expression of Krox20/Egr2, a key transcriptional regulator of myelination. Conversely, expression of an activated form of Akt in purified Schwann cells increased expression of myelin proteins, but not Krox20/Egr2, and the levels of activated Rac1. Transgenic mice expressing a membrane-targeted, activated form of Akt under control of the 2′,3′-cyclic nucleotide 3′-phosphodiesterase promoter, exhibited thicker PNS and CNS myelin sheaths, and PNS myelin abnormalities, such as tomacula and myelin infoldings/outfoldings, centered around the paranodes and Schmidt Lanterman incisures. These effects were corrected by rapamycin treatment in vivo. Importantly, Akt activity in the transgenic mice did not induce myelination of nonmyelinating Schwann cells in the sympathetic trunk or Remak fibers of the dorsal roots, although, in those structures, they wrapped membranes redundantly around axons. Together, our data indicate that Akt is crucial for PNS myelination driving axonal wrapping by unmyelinated and myelinated Schwann cells and enhancing myelin protein synthesis in myelinating Schwann cells. SIGNIFICANCE STATEMENT Although the role of the key serine/threonine kinase Akt in promoting CNS myelination has been demonstrated, its role in the PNS has not been established and remains

  14. Sciatic nerve regeneration in rats subjected to ketogenic diet.

    Science.gov (United States)

    Liśkiewicz, Arkadiusz; Właszczuk, Adam; Gendosz, Daria; Larysz-Brysz, Magdalena; Kapustka, Bartosz; Łączyński, Mariusz; Lewin-Kowalik, Joanna; Jędrzejowska-Szypułka, Halina

    2016-01-01

    Ketogenic diet (KD) is a high-fat-content diet with insufficiency of carbohydrates that induces ketogenesis. Besides its anticonvulsant properties, many studies have shown its neuroprotective effect in central nervous system, but its influence on peripheral nervous system has not been studied yet. We examined the influence of KD on regeneration of peripheral nerves in adult rats. Fifty one rats were divided into three experimental (n = 15) and one control (n = 6) groups. Right sciatic nerve was crushed and animals were kept on standard (ST group) or ketogenic diet, the latter was introduced 3 weeks before (KDB group) or on the day of surgery (KDA group). Functional (CatWalk) tests were performed once a week, and morphometric (fiber density, axon diameter, and myelin thickness) analysis of the nerves was made after 6 weeks. Body weight and blood ketone bodies level were estimated at the beginning and the end of experiment. Functional analysis showed no differences between groups. Morphometric evaluation showed most similarities to the healthy (uncrushed) nerves in KDB group. Nerves in ST group differed mostly from all other groups. Ketone bodies were elevated in both KD groups, while post-surgery animals' body weight was lower as compared to ST group. Regeneration of sciatic nerves was improved in KD - preconditioned rats. These results suggest a neuroprotective effect of KD on peripheral nerves.

  15. Optical coherence tomography, scanning laser polarimetry and confocal scanning laser ophthalmoscopy in retinal nerve fiber layer measurements of glaucoma patients.

    Science.gov (United States)

    Fanihagh, Farsad; Kremmer, Stephan; Anastassiou, Gerasimos; Schallenberg, Maurice

    2015-01-01

    To determine the correlations and strength of association between different imaging systems in analyzing the retinal nerve fiber layer (RNFL) of glaucoma patients: optical coherence tomography (OCT), scanning laser polarimetry (SLP) and confocal scanning laser ophthalmoscopy (CSLO). 114 eyes of patients with moderate open angle glaucoma underwent spectral domain OCT (Topcon SD-OCT 2000 and Zeiss Cirrus HD-OCT), SLP (GDx VCC and GDx Pro) and CSLO (Heidelberg Retina Tomograph, HRT 3). Correlation coefficients were calculated between the structural parameters yielded by these examinations. The quantitative relationship between the measured RNFL thickness globally and for the four regions (superior, inferior, nasal, temporal) were evaluated with different regression models for all used imaging systems. The strongest correlation of RNFL measurements was found between devices using the same technology like GDx VCC and GDx Pro as well as Topcon OCT and Cirrus OCT. In glaucoma patients, the strongest associations (R²) were found between RNFL measurements of the two optical coherence tomography devices Topcon OCT and Cirrus OCT (R² = 0.513) and between GDx VCC and GDx Pro (R² = 0.451). The results of the OCTs and GDX Pro also had a strong quantitative relationship (Topcon OCT R² = 0.339 and Cirrus OCT R² = 0.347). GDx VCC and the OCTs showed a mild to moderate association (Topcon OCT R² = 0.207 and Cirrus OCT R² = 0.258). The confocal scanning laser ophthalmoscopy (HRT 3) had the lowest association to all other devices (Topcon OCT R² = 0.254, Cirrus OCT R² = 0.158, GDx Pro R² = 0.086 and GDx VCC R² = 0.1). The measurements of the RNFL in glaucoma patients reveal a high correlation of OCT and GDx devices because OCTs can measure all major retinal layers and SLP can detect nerve fibers allowing a comparison between the results of this devices. However, CSLO by means of HRT topography can only measure height values of the retinal surface but it cannot distinguish

  16. [A pharmacological analysis of the central control of the preganglionic sympathetic neurons during stimulation of the afferent nerve fibers of the digestive tract].

    Science.gov (United States)

    Itina, L V; Posniak, V A

    1995-12-01

    In acute experiments on cats, effect of adrenergic brain neurons on impulse activity of preganglionic fibers of the left splanchnic nerve was studied. Afferent fibers of nerves innervating the stomach, duodenum, ileum and ileocecal angle were electrically stimulated. Phenoxybenzamine, obsidan, amizyl, iprazid, nuredal, dalargine, and morphine were used for pharmacological analysis. Nerves, stimulation at 20 Hz of different segments of the digestive tract was accompanied by different inhibition of preganglionic neurons. Sympathetic-stimulating effects were observed more frequently at 5 Hz stimulation. After vagotomy, alpha- and beta-adrenoreceptor block, central cholinoreceptor and monoamine oxidase (MAO) block, and after dalargine (0.1 and 0.01 mg/kg) nerves stimulation at 20 Hz was followed by sympathetic-stimulating effect. A weak regulatory effect of morphine (1 and 10 mg/kg) on ileal nerve stimulation effects was shown. It is suggested that excitation from afferent neurons of the vagus is transmitted to central cholinergic neurons which, in their turn, excite adrenergic neurons of the brain, and the latter inhibit impulsation of preganglionic fibers. MAO block increased the balance of excitatory effect of serotonin on spinal reflexes. Morphine and dalargine intracentrally may block adrenergic and cholinergic transmissions, as well as decrease the release of substance P from afferent neurons. Their regulatory action is revealed when different frequencies of stimulation are used.

  17. Cervical vagus nerve stimulation augments spontaneous discharge in second- and higher-order sensory neurons in the rat nucleus of the solitary tract.

    Science.gov (United States)

    Beaumont, Eric; Campbell, Regenia P; Andresen, Michael C; Scofield, Stephanie; Singh, Krishna; Libbus, Imad; KenKnight, Bruce H; Snyder, Logan; Cantrell, Nathan

    2017-08-01

    Vagus nerve stimulation (VNS) currently treats patients with drug-resistant epilepsy, depression, and heart failure. The mild intensities used in chronic VNS suggest that primary visceral afferents and central nervous system activation are involved. Here, we measured the activity of neurons in the nucleus of the solitary tract (NTS) in anesthetized rats using clinically styled VNS. Our chief findings indicate that VNS at threshold bradycardic intensity activated NTS neuron discharge in one-third of NTS neurons. This VNS directly activated only myelinated vagal afferents projecting to second-order NTS neurons. Most VNS-induced activity in NTS, however, was unsynchronized to vagal stimuli. Thus, VNS activated unsynchronized activity in NTS neurons that were second order to vagal afferent C-fibers as well as higher-order NTS neurons only polysynaptically activated by the vagus. Overall, cardiovascular-sensitive and -insensitive NTS neurons were similarly activated by VNS: 3/4 neurons with monosynaptic vagal A-fiber afferents, 6/42 neurons with monosynaptic vagal C-fiber afferents, and 16/21 polysynaptic NTS neurons. Provocatively, vagal A-fibers indirectly activated C-fiber neurons during VNS. Elevated spontaneous spiking was quantitatively much higher than synchronized activity and extended well into the periods of nonstimulation. Surprisingly, many polysynaptic NTS neurons responded to half the bradycardic intensity used in clinical studies, indicating that a subset of myelinated vagal afferents is sufficient to evoke VNS indirect activation. Our study uncovered a myelinated vagal afferent drive that indirectly activates NTS neurons and thus central pathways beyond NTS and support reconsideration of brain contributions of vagal afferents underpinning of therapeutic impacts.NEW & NOTEWORTHY Acute vagus nerve stimulation elevated activity in neurons located in the medial nucleus of the solitary tract. Such stimuli directly activated only myelinated vagal afferents but

  18. Role of capsaicin-sensitive nerve fibers in uterine contractility in the rat.

    Science.gov (United States)

    Klukovits, Anna; Gaspar, Robert; Santha, Peter; Jancso, Gabor; Falkay, George

    2004-01-01

    The possible participation of capsaicin-sensitive sensory nerves in the modulation of neurogenic contractions was studied in nonpregnant and term pregnant rat uteri. Neurogenic contractions were elicited by electric field stimulation (40 V, 1-70 Hz, 0.6 msec) in intact uteri and uteri that were previously exposed to capsaicin in vitro. In capsaicin pretreated preparations obtained both from nonpregnant and term pregnant rats, a dose-dependent increase in the amplitude of uterine contractions was detected. Prior systemic treatment of the rats with capsaicin (130 mg/kg, s.c.) abolished the effect of in vitro capsaicin administration on the amplitude of neurogenic contractions. Use of a specific antagonist of calcitonin gene-related peptide revealed that depletion of this peptide, which normally elicits uterine smooth muscle relaxation, may be responsible for the increased responsiveness of the uterus to low-frequency stimulation. Experiments on the localization of calcitonin gene-related peptide in uterine tissue specimens exposed to capsaicin revealed dose-dependent depletion of calcitonin-gene related peptide-immunoreactive nerves innervating blood vessels and the myometrium. The findings indicate that capsaicin-sensitive afferent nerves, by the release of sensory neuropeptides, significantly contribute to the modulation of uterine contractility both in nonpregnant and term pregnant rats. It is suggested that uterine sensory nerve activation may be part of a trigger mechanism leading to preterm contractions evoked by, for example, inflammation.

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

    Science.gov (United States)

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

  20. Spatiotemporal dynamics of re-innervation and hyperinnervation patterns by uninjured CGRP fibers in the rat foot sole epidermis after nerve injury.

    Science.gov (United States)

    Duraku, Liron S; Hossaini, Mehdi; Hoendervangers, Sieske; Falke, Lukas L; Kambiz, Shoista; Mudera, Vivek C; Holstege, Joan C; Walbeehm, Erik T; Ruigrok, Tom J H

    2012-08-30

    The epidermis is innervated by fine nerve endings that are important in mediating nociceptive stimuli. However, their precise role in neuropathic pain is still controversial. Here, we have studied the role of epidermal peptidergic nociceptive fibers that are located adjacent to injured fibers in a rat model of neuropathic pain. Using the Spared Nerve Injury (SNI) model, which involves complete transections of the tibial and common peroneal nerve while sparing the sural and saphenous branches, mechanical hypersensitivity was induced of the uninjured lateral (sural) and medial (saphenous) area of the foot sole. At different time points, a complete foot sole biopsy was taken from the injured paw and processed for Calcitonin Gene-Related Peptide (CGRP) immunohistochemistry. Subsequently, a novel 2D-reconstruction model depicting the density of CGRP fibers was made to evaluate the course of denervation and re-innervation by uninjured CGRP fibers. The results show an increased density of uninjured CGRP-IR epidermal fibers on the lateral and medial side after a SNI procedure at 5 and 10 weeks. Furthermore, although in control animals the density of epidermal CGRP-IR fibers in the footpads was lower compared to the surrounding skin of the foot, 10 weeks after the SNI procedure, the initially denervated footpads displayed a hyper-innervation. These data support the idea that uninjured fibers may play a considerable role in development and maintenance of neuropathic pain and that it is important to take larger biopsies to test the relationship between innervation of injured and uninjured nerve areas.

  1. Spatiotemporal dynamics of re-innervation and hyperinnervation patterns by uninjured CGRP fibers in the rat foot sole epidermis after nerve injury

    Directory of Open Access Journals (Sweden)

    Duraku Liron S

    2012-08-01

    Full Text Available Abstract The epidermis is innervated by fine nerve endings that are important in mediating nociceptive stimuli. However, their precise role in neuropathic pain is still controversial. Here, we have studied the role of epidermal peptidergic nociceptive fibers that are located adjacent to injured fibers in a rat model of neuropathic pain. Using the Spared Nerve Injury (SNI model, which involves complete transections of the tibial and common peroneal nerve while sparing the sural and saphenous branches, mechanical hypersensitivity was induced of the uninjured lateral (sural and medial (saphenous area of the foot sole. At different time points, a complete foot sole biopsy was taken from the injured paw and processed for Calcitonin Gene-Related Peptide (CGRP immunohistochemistry. Subsequently, a novel 2D-reconstruction model depicting the density of CGRP fibers was made to evaluate the course of denervation and re-innervation by uninjured CGRP fibers. The results show an increased density of uninjured CGRP-IR epidermal fibers on the lateral and medial side after a SNI procedure at 5 and 10 weeks. Furthermore, although in control animals the density of epidermal CGRP-IR fibers in the footpads was lower compared to the surrounding skin of the foot, 10 weeks after the SNI procedure, the initially denervated footpads displayed a hyper-innervation. These data support the idea that uninjured fibers may play a considerable role in development and maintenance of neuropathic pain and that it is important to take larger biopsies to test the relationship between innervation of injured and uninjured nerve areas.

  2. Directionality of auditory nerve fiber responses to pure tone stimuli in the grassfrog, Rana temporaria. II. Spike timing

    DEFF Research Database (Denmark)

    Jørgensen, M B; Christensen-Dalsgaard, J

    1997-01-01

    We studied the directionality of spike timing in the responses of single auditory nerve fibers of the grass frog, Rana temporaria, to tone burst stimulation. Both the latency of the first spike after stimulus onset and the preferred firing phase during the stimulus were studied. In addition, the ...

  3. Wiener kernels of chinchilla auditory-nerve fibers : Verification using responses to tones, clicks, and noise and comparison with basilar-membrane vibrations

    NARCIS (Netherlands)

    Temchin, AN; Recio-Spinoso, A; van Dijk, P; Ruggero, MA

    2005-01-01

    Responses to tones, clicks, and noise were recorded from chinchilla auditory-nerve fibers (ANFs). The responses to noise were analyzed by computing the zeroth-, first-, and second-order Wiener kernels (h(0), h(1), and h(2)). The h(1) s correctly predicted the frequency tuning and phases of responses

  4. Colocalization of APC and PSD-95 in the nerve fiber as well as in the post-synapse of matured neurons.

    Science.gov (United States)

    Onouchi, Takanori; Takamori, Nobutaka; Senda, Takao

    2012-06-01

    Adenomatous polyposis coli protein (APC) is highly expressed in the nervous tissue, but its function there is not yet known. We previously found that the microtubule-bundling activity of APC is stimulated by its interaction with PSD-95, a neuronal scaffolding protein, in cultured COS-7 cells. In the present study, we investigated the distribution and localization of the intrinsic APC and PSD-95 in both cultured rat hippocampal neurons and in the rat cerebellum by immunofluorescence and immunoelectron microscopy. In cultured neurons, most of the PSD-95 immunofluorescence puncta were colocalized with APC, and the APC and PSD-95 immunogolds were colocalized in the nerve fibers as well as in the postsynaptic site, but not in the presynaptic site. In the molecular layer of the rat cerebellum, colocalization of APC and PSD-95 was also detected in the nerve fibers and the postsynaptic site, but not in the presynaptic site. Based on these results, we conclude that APC and PSD-95 colocalize and bind to form a protein complex in nerve fibers as well as in postsynaptic sites in matured neurons, suggesting the involvement of the APC/PSD-95 complex in the microtubule functions within the nerve fibers and the synapse functions at the postsynaptic site.

  5. Long-term result of guided nerve regeneration with an inert microporous polytetrafluoroethylene conduit

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Objective: To evaluate the long-term outcome of Polytetrafluoroethylene (PTFE) conduit in nerve repair and to provide more evidence in view of its potential application to achieve a satisfactory functional recovery in clinical settings. Methods: Thirty-six Wistar rats had their right sciatic nerve transected and were repaired with either conventional microsuture technique (Control group, n=18) or a PTFE conduit with a gap of 5 mm left between the nerve stumps (PTFE group, n=18). At 6 and 9 months after the operation, electrophysiological assessment and measurement of gastrocnemius muscle weight were conducted and morphology of the regenerated nerves were studied with image analysis. Results: At 6 months postoperatively, the nerve conduction velocity recovered to 60.86% and 54.36% (P>0.05), and the gastrocnemius muscle weight recovered to 50.89% and 46.11% (P>0.05) in the Control group and the PTFE group respectively. At 9 months postoperatively, the recovery rate was 65.99% and 58.79% for NCV (P>0.05), and 52.56% and 47.89% for gastrocnemius muscle weight (P>0.05) in the Control group and the PTFE group respectively. Regenerated nerve fibers in the PTFE group had a regular round shape with no fragmentation, wrinkling or splitting of the myelin sheath. Image analysis revealed that the ratio of the myelin area to the total fiber area was larger at 9 months than at 6 months in both groups (P<0.01). Conclusions: Microporous PTFE conduit may be an alternative for nerve repair allowing of guided nerve regeneration and functional recovery with no obvious adverse effect at long-term.

  6. Depth-sensing nano-indentation on a myelinated axon at various stages

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Wei-Chin; Liao, Jiunn-Der [Department of Materials Science and Engineering, National Cheng Kung University, 1 University Road, Tainan 70101, Taiwan (China); Lin, Chou-Ching K [Department of Neurology, National Cheng Kung University, 1 University Road, Tainan 70101, Taiwan (China); Ju, Ming-Shaung, E-mail: jdliao@mail.ncku.edu.tw [Department of Mechanical Engineering, National Cheng Kung University, 1 University Road, Tainan 70101, Taiwan (China)

    2011-07-08

    A nano-mechanical characterization of a multi-layered myelin sheath structure, which enfolds an axon and plays a critical role in the transmission of nerve impulses, is conducted. Schwann cells co-cultured in vitro with PC12 cells for various co-culture times are differentiated to form a myelinated axon, which is then observed using a transmission electron microscope. Three major myelination stages, with distinct structural characteristics and thicknesses around the axon, can be produced by varying the co-culture time. A dynamic contact module and continuous depth-sensing nano-indentation are used on the myelinated structure to obtain the load-on-sample versus measured displacement curve of a multi-layered myelin sheath, which is used to determine the work required for the nano-indentation tip to penetrate the myelin sheath. By analyzing the harmonic contact stiffness versus the measured displacement profile, the results can be used to estimate the three stages of the multi-layered structure on a myelinated axon. The method can also be used to evaluate the development stages of myelination or demyelination during nerve regeneration.

  7. Mass Potentials Recorded at the Round Window Enable the Detection of Low Spontaneous Rate Fibers in Gerbil Auditory Nerve

    Science.gov (United States)

    Batrel, Charlène; Huet, Antoine; Hasselmann, Florian; Wang, Jing; Desmadryl, Gilles; Nouvian, Régis

    2017-01-01

    Auditory nerve fibers (ANFs) transmit acoustic information from the sensory hair cells to the cochlear nuclei. In experimental and clinical audiology, probing the whole ANF population remains a difficult task, as the ANFs differ greatly in their threshold and onset response to sound. Thus, low spontaneous rate (SR) fibers, which have rather higher thresholds, delay and larger jitter in their first spike latency are not detectable in the far-field compound action potential of the auditory nerve. Here, we developed a new protocol of acoustic stimulation together with electrophysiological signal processing to track the steady state activity of ANFs. Mass potentials at the round window were recorded in response to repetitive 300-ms bursts of 1/3 octave band noise centered on a frequency probe. Analysis was assessed during the last 200-ms of the response to capture the steady-state response of ANFs. To eliminate the microphonic component reflecting the sensory cells activity, repetitive pairs of sounds of opposite polarities were used. The spectral analysis was calculated on the average of two consecutive responses, and the neural gain was calculated by dividing point-by-point the spectrum to sound over unstimulated condition. In response to low-sound-level stimulation, neural gain predominated in the low-frequency cochlear regions, while a second component of responses centered on higher cochlear frequency regions appeared beyond 30 dB SPL. At 60 dB SPL, neural gain showed a bimodal shape, with a notch near 5.6 kHz. In addition to correlate with the functional mapping of ANFs along the tonotopic axis, the deletion of low-SR fibers leads to a reduction in the high-frequency response, where the low-SR fibers are preferentially located. Thus, mass potentials at the round window may provide a useful tool to probe the SR-based distribution of ANFs in humans and in other species in which direct single-unit recordings are difficult to achieve or not feasible. PMID:28085968

  8. Fibered fluorescence microscopy (FFM) of intra epidermal nerve fibers--translational marker for peripheral neuropathies in preclinical research: processing and analysis of the data

    Science.gov (United States)

    Cornelissen, Frans; De Backer, Steve; Lemeire, Jan; Torfs, Berf; Nuydens, Rony; Meert, Theo; Schelkens, Peter; Scheunders, Paul

    2008-08-01

    Peripheral neuropathy can be caused by diabetes or AIDS or be a side-effect of chemotherapy. Fibered Fluorescence Microscopy (FFM) is a recently developed imaging modality using a fiber optic probe connected to a laser scanning unit. It allows for in-vivo scanning of small animal subjects by moving the probe along the tissue surface. In preclinical research, FFM enables non-invasive, longitudinal in vivo assessment of intra epidermal nerve fibre density in various models for peripheral neuropathies. By moving the probe, FFM allows visualization of larger surfaces, since, during the movement, images are continuously captured, allowing to acquire an area larger then the field of view of the probe. For analysis purposes, we need to obtain a single static image from the multiple overlapping frames. We introduce a mosaicing procedure for this kind of video sequence. Construction of mosaic images with sub-pixel alignment is indispensable and must be integrated into a global consistent image aligning. An additional motivation for the mosaicing is the use of overlapping redundant information to improve the signal to noise ratio of the acquisition, because the individual frames tend to have both high noise levels and intensity inhomogeneities. For longitudinal analysis, mosaics captured at different times must be aligned as well. For alignment, global correlation-based matching is compared with interest point matching. Use of algorithms working on multiple CPU's (parallel processor/cluster/grid) is imperative for use in a screening model.

  9. Effect of cataract surgery on retinal nerve fiber layer thickness parameters using scanning laser polarimetry (GDxVCC

    Directory of Open Access Journals (Sweden)

    Dada Tanuj

    2010-01-01

    Full Text Available Purpose: To study the effect of cataract extraction on the retinal nerve fiber layer (RNFL thickness, and assessment by scanning laser polarimetry (SLP, with variable corneal compensation (GDx VCC, at the glaucoma service of a tertiary care center in North India. Materials and Methods: Thirty-two eyes of 32 subjects were enrolled in the study. The subjects underwent RNFL analysis by SLP (GDx VCC before undergoing phacoemulsification cataract extraction with intraocular lens (IOL implantation (Acrysof SA 60 AT four weeks following cataract surgery. The RNFL thickness parameters evaluated both before and after surgery included temporal, superior, nasal, inferior, temporal (TSNIT average, superior average, inferior average, and nerve fiber index (NFI. Results: The mean age of subjects was 57.6 ± 11.7 years (18 males, 14 females. Mean TSNIT average thickness (μm pre- and post-cataract surgery was 49.2 ± 14.1 and 56.5 ± 7.6 ( P = 0.001. There was a statistically significant increase in RNFL thickness parameters (TSNIT average, superior average, and inferior average and decrease in NFI post-cataract surgery as compared to the baseline values. Mean NFI pre- and post-cataract surgery was 41.3 ± 15.3 and 21.6 ± 11.8 ( P = 0.001. Conclusions: Measurement of RNFL thickness parameters by scanning laser polarimetry is significantly altered following cataract surgery. Post the cataract surgery, a new baseline needs to be established for assessing the longitudinal follow-up of a glaucoma patient. The presence of cataract may lead to an underestimation of the RNFL thickness, and this should be taken into account when analyzing progression in a glaucoma patient.

  10. Correlation between peripapillary retinal nerve fiber layer thickness and fundus autofluorescence in primary open-angle glaucoma

    Directory of Open Access Journals (Sweden)

    Reznicek L

    2013-09-01

    Full Text Available Lukas Reznicek,* Florian Seidensticker,* Thomas Mann, Irene Hübert, Alexandra Buerger, Christos Haritoglou, Aljoscha S Neubauer, Anselm Kampik, Christoph Hirneiss, Marcus Kernt Department of Ophthalmology, Ludwig-Maximilians-University, Munich, Germany *These authors contributed equally to this work Purpose: To investigate the relationship between retinal nerve fiber layer (RNFL thickness and retinal pigment epithelium alterations in patients with advanced glaucomatous visual field defects. Methods: A consecutive, prospective series of 82 study eyes with primary open-angle glaucoma and advanced glaucomatous visual field defects were included in this study. All study participants underwent a full ophthalmic examination followed by visual field testing with standard automated perimetry as well as spectral-domain optical coherence tomography (SD-OCT for peripapillary RNFL thickness and Optos wide-field fundus autofluorescence (FAF images. A pattern grid with corresponding locations between functional visual field sectors and structural peripapillary RNFL thickness was aligned to the FAF images at corresponding location. Mean FAF intensity (range: 0 = black and 255 = white of each evaluated sector (superotemporal, temporal, inferotemporal, inferonasal, nasal, superonasal was correlated with the corresponding peripapillary RNFL thickness obtained with SD-OCT. Results: Correlation analyses between sectoral RNFL thickness and standardized FAF intensity in the corresponding topographic retina segments revealed partly significant correlations with correlation coefficients ranging between 0.004 and 0.376 and were statistically significant in the temporal inferior central field (r = 0.324, P = 0.036 and the nasal field (r = 0.376, P = 0.014. Conclusion: Retinal pigment epithelium abnormalities correlate with corresponding peripapillary RNFL damage, especially in the temporal inferior sector of patients with advanced glaucomatous visual field defects. A

  11. Effect of cataract surgery on retinal nerve fiber layer thickness parameters using scanning laser polarimetry (GDxVCC).

    Science.gov (United States)

    Dada, Tanuj; Behera, Geeta; Agarwal, Anand; Kumar, Sanjeev; Sihota, Ramanjit; Panda, Anita

    2010-01-01

    To study the effect of cataract extraction on the retinal nerve fiber layer (RNFL) thickness, and assessment by scanning laser polarimetry (SLP), with variable corneal compensation (GDx VCC), at the glaucoma service of a tertiary care center in North India. Thirty-two eyes of 32 subjects were enrolled in the study. The subjects underwent RNFL analysis by SLP (GDx VCC) before undergoing phacoemulsification cataract extraction with intraocular lens (IOL) implantation (Acrysof SA 60 AT) four weeks following cataract surgery. The RNFL thickness parameters evaluated both before and after surgery included temporal, superior, nasal, inferior, temporal (TSNIT) average, superior average, inferior average, and nerve fiber index (NFI). The mean age of subjects was 57.6 +/- 11.7 years (18 males, 14 females). Mean TSNIT average thickness (microm) pre- and post-cataract surgery was 49.2 +/- 14.1 and 56.5 +/- 7.6 ( P = 0.001). There was a statistically significant increase in RNFL thickness parameters (TSNIT average, superior average, and inferior average) and decrease in NFI post-cataract surgery as compared to the baseline values. Mean NFI pre- and post-cataract surgery was 41.3 +/- 15.3 and 21.6 +/- 11.8 ( P = 0.001). Measurement of RNFL thickness parameters by scanning laser polarimetry is significantly altered following cataract surgery. Post the cataract surgery, a new baseline needs to be established for assessing the longitudinal follow-up of a glaucoma patient. The presence of cataract may lead to an underestimation of the RNFL thickness, and this should be taken into account when analyzing progression in a glaucoma patient.

  12. Late changes in human sural nerves in Minamata disease and in nerves of rats with experimental organic mercury poisoning.

    Science.gov (United States)

    Miyakawa, T; Murayama, E; Sumiyoshi, S; Deshimaru, M; Fujimoto, T

    1976-06-15

    The sural nerves of 2 human cases with Minamata disease and poisoned rats were examined histopathologically. Both showed similar findings: the myelinated nerve fibres were decreased in number, but small myelinated nerve fibres were increased: The latter were irregular in shape and their Schwann cells showed regressive changes, with high electron density of the cytoplasms and many glycogen granules. Onion bulb formation was not found. According to fibre diameter histograms, the ratio of small myelinated nerve fibres of 2-5 mum showed a high percentage. A large number of the small myelinated nerve fibres were presumed to be regenerated nerve fibres. These findings are different from other peripheral neuropathies and may be characteristics of the late changes of the sural nerve induced by organic mercury compound.

  13. A rapid and versatile method for the isolation, purification and cryogenic storage of Schwann cells from adult rodent nerves.

    Science.gov (United States)

    Andersen, Natalia D; Srinivas, Shruthi; Piñero, Gonzalo; Monje, Paula V

    2016-08-23

    We herein developed a protocol for the rapid procurement of adult nerve-derived Schwann cells (SCs) that was optimized to implement an immediate enzymatic dissociation of fresh nerve tissue while maintaining high cell viability, improving yields and minimizing fibroblast and myelin contamination. This protocol introduces: (1) an efficient method for enzymatic cell release immediately after removal of the epineurium and extensive teasing of the nerve fibers; (2) an adaptable drop-plating method for selective cell attachment, removal of myelin debris, and expansion of the initial SC population in chemically defined medium; (3) a magnetic-activated cell sorting purification protocol for rapid and effective fibroblast elimination; and (4) an optional step of cryopreservation for the storage of the excess of cells. Highly proliferative SC cultures devoid of myelin and fibroblast growth were obtained within three days of nerve processing. Characterization of the initial, expanded, and cryopreserved cell products confirmed maintenance of SC identity, viability and growth rates throughout the process. Most importantly, SCs retained their sensitivity to mitogens and potential for differentiation even after cryopreservation. To conclude, this easy-to-implement and clinically relevant protocol allows for the preparation of expandable homogeneous SC cultures while minimizing time, manipulation of the cells, and exposure to culture variables.

  14. Stromal vascular fraction combined with silicone rubber chamber improves sciatic nerve regeneration in diabetes

    Institute of Scientific and Technical Information of China (English)

    Rahim Mohammadi; Negin Sanaei; Sima Ahsan; Masoume Masoumi-Verki; Fatemeh Khadir; Aram Mokarizadeh

    2015-01-01

    Purpose:To study the effects of transplantation of characterized uncultured stromal vascular fraction (SVF) on sciatic nerve regeneration.Methods:A 10-mm sciatic nerve defect was bridged using a silicone conduit filled with SVF.In control group,silicone conduit was filled with phosphate-buffered saline alone.In sham-operated group,the sciatic nerve was only exposed and manipulated.The regenerated nerve fibers were studied 8 and 12 weeks after surgery.Results:Behavioral and functional studies confirmed faster recovery of regenerated axons in SVF transplanted animals than in control group (p < 0.05).Gastrocnemius muscle mass in SVF transplanted animal was found to be significantly more than that in control group.Morphometric indices of the regenerated fibers showed the number and diameter of the myelinated fibers to be significantly higher in SVF transplanted animals than in control group.In immunohistochemistry,the location of reactions to S-100 in SVF transplanted animals was clearly more positive than that in control group.Conclusion:SVF transplantation combined with silicone conduit could be considered as a readily accessible source of stromal cells that improves functional recovery of sciatic nerve.It may have clinical implications for the surgical management of acute diabetic patients after facial nerve transection.

  15. Protective effect of mulberry flavonoids on sciatic nerve in alloxan-induced diabetic rats

    Directory of Open Access Journals (Sweden)

    Ma Song-Tao

    2014-12-01

    Full Text Available Mulberry leaves (Morus alba L. are a traditional Chinese medicine for blood serum glucose reduction. This study evaluated the protective effects of mulberry flavonoids on sciatic nerve in alloxan-induced diabetic rats. In this study, 80 Sprague-Dawley rats were divided into five groups: A (control, B (diabetic treated with saline, C-D (diabetic treated with 0.3, 0.1 g/kg mulberry flavonoids once a day for 8 weeks and E (diabetic treated with 0.3 mg/kg methycobal. The diabetic condition was induced by intraperitoneal injection of 200 mg/kg alloxan dissolved in saline. At the end of the experimental period, blood, and tissue samples were obtained for biochemical and histopathological investigation. Treatment with 0.3 g/kg mulberry flavonoids significantly inhibited the elevated serum glucose (P< 0.01. The increased myelin sheath area (P< 0.01, myelinated fiber cross-sectional area and extramedullary fiber number (P< 0.05 were also reduced in alloxan-induced rats treated with 0.3 g/kg mulberry flavonoids. 0.3 g/kg mulberry flavonoids also markedly decreased onion-bulb type myelin destruction and degenerative changes of mitochondria and Schwann cells. These findings demonstrate that mulberry flavonoids may improve the recovery of a severe peripheral nerve injury in alloxan-induced diabetic rats and is likely to be useful as a potential treatment on peripheral neuropathy (PN in diabetic rats.

  16. Detection of retinal nerve fiber layer defects in Alzheimer‘s disease using SD-OCT

    Directory of Open Access Journals (Sweden)

    Robert eKromer

    2014-02-01

    Full Text Available Introduction:To examine the clinical value of spectral-domain optical coherence tomography (Spectralis OCT to detect retinal nerve fibre layer defects in patients with clinically defined Alzheimer‘s disease (AD.Material and Methods:This cross-sectional study included 22 patients with AD (mean age: 75.9 ± 6.1 years and 22 healthy age- and sex-matched controls. Neuro-ophthalmologic examinations and a series of high-resolution OCT examinations of the peripapillary retinal nerve fibre layer (RNFL thickness using the Spectralis 3.5-mm circle scan protocol with ART-Modus and eye tracking were obtained, and compared to age- and sex-matched healthy control subjects.Results:Patients with AD showed a significant decrease in RNFL thickness in the nasal superior sector compared to the control group (101.0 ± 18.18 µm vs. 122.8 ± 28.08 µm; p

  17. Polylactic-co-glycolic acid microspheres containing three neurotrophic factors promote sciatic nerve repair after injury

    Directory of Open Access Journals (Sweden)

    Qun Zhao

    2015-01-01

    Full Text Available A variety of neurotrophic factors have been shown to repair the damaged peripheral nerve. However, in clinical practice, nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor are all peptides or proteins that may be rapidly deactivated at the focal injury site; their local effective concentration time following a single medication cannot meet the required time for spinal axons to regenerate and cross the glial scar. In this study, we produced polymer sustained-release microspheres based on the polylactic-co-glycolic acid copolymer; the microspheres at 300-μm diameter contained nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor. Six microspheres were longitudinally implanted into the sciatic nerve at the anastomosis site, serving as the experimental group; while the sciatic nerve in the control group was subjected to the end-to-end anastomosis using 10/0 suture thread. At 6 weeks after implantation, the lower limb activity, weight of triceps surae muscle, sciatic nerve conduction velocity and the maximum amplitude were obviously better in the experimental group than in the control group. Compared with the control group, more regenerating nerve fibers were observed and distributed in a dense and ordered manner with thicker myelin sheaths in the experimental group. More angiogenesis was also visible. Experimental findings indicate that polylactic-co-glycolic acid composite microspheres containing nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor can promote the restoration of sciatic nerve in rats after injury.

  18. Polylactic-co-glycolic acid microspheres containing three neurotrophic factors promote sciatic nerve repair after injury.

    Science.gov (United States)

    Zhao, Qun; Li, Zhi-Yue; Zhang, Ze-Peng; Mo, Zhou-Yun; Chen, Shi-Jie; Xiang, Si-Yu; Zhang, Qing-Shan; Xue, Min

    2015-09-01

    A variety of neurotrophic factors have been shown to repair the damaged peripheral nerve. However, in clinical practice, nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor are all peptides or proteins that may be rapidly deactivated at the focal injury site; their local effective concentration time following a single medication cannot meet the required time for spinal axons to regenerate and cross the glial scar. In this study, we produced polymer sustained-release microspheres based on the polylactic-co-glycolic acid copolymer; the microspheres at 300-μm diameter contained nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor. Six microspheres were longitudinally implanted into the sciatic nerve at the anastomosis site, serving as the experimental group; while the sciatic nerve in the control group was subjected to the end-to-end anastomosis using 10/0 suture thread. At 6 weeks after implantation, the lower limb activity, weight of triceps surae muscle, sciatic nerve conduction velocity and the maximum amplitude were obviously better in the experimental group than in the control group. Compared with the control group, more regenerating nerve fibers were observed and distributed in a dense and ordered manner with thicker myelin sheaths in the experimental group. More angiogenesis was also visible. Experimental findings indicate that polylactic-co-glycolic acid composite microspheres containing nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor can promote the restoration of sciatic nerve in rats after injury.

  19. Effect of growth hormone-releasing peptide on ardiac cholinergic nerve fiber density distribution in a rat model of heart failure

    Institute of Scientific and Technical Information of China (English)

    Guozhong Tian; Xiuqin Ni; Yong Zhao; Jia Feng; Yanjun Li; Zhenya Zhong; Shuling Bai

    2009-01-01

    BACKGROUND: Changes in the cardiac autonomic nerve are considered to be important factors in the mechanisms of heart failure. It is possible to reduce or slow down nerve degeneration and necrosis, provided that patients take effective neuroprotectants during the early stages of heart failure. Moreover, it is possible to relieve the pathological process and reduce the risk of death.OBJECTIVE: To study the effect of growth hormone releasing peptide (GHRP) on cardiac cholinergic nerve fiber density distribution in a rat model of heart failure, and verify whether GHRP can ameliorate denervation.DESIGN, TIME AND SETTING: A randomized controlled study was performed at the Key Laboratory of Anatomy, Harbin Medical University, between June and October 2009.MATERIALS: Fifty adult, healthy, female, Wistar rats, weighing (200±20) g, were randomly divided into GHRP (n=30), model (n=10), and sham operation (n=10) groups. GHRP-2 was made in Shanghai, China (batch No. z071212-03).METHODS: Acute myocardial infarction was established by ligating the left anterior descending coronary artery in the GHRP and model groups. Five weeks later, myocardial function was detected using color ultrasound electrocardiograph. Ejection fraction < 60% was considered to be a successful marker of chronic heart failure models. However, the left anterior descending coronary artery was not ligated in the sham operation group. The GHRP group was injected with 100μg/kg GHRP-2, and the other two groups were injected with the same volume of physiological saline, once per day.MAIN OUTCOME MEASURES: After 4 weeks, pathological changes in cardiac cholinergic nerve fibers were detected under optic microscopy following hematoxylin/eosin staining. In addition, density distribution was measured using a multi-function color pathological image system.RESULTS: In the sham operation group, myocardial cells were regular, uniformly stained, and no inflammatory cells were present. In the model group, myocardial cells

  20. Cervical vagus and sympathetic trunk and fiber components of external laryngeal nerve: comparative anatomy between human and dog%人与狗迷走/交感干的比较解剖及其喉上神经外支纤维成分

    Institute of Scientific and Technical Information of China (English)

    许士叶; 董剑平; 孙善全; Kannaiyan Vijesh Ramnarayan; Joyeeta Sengupta

    2012-01-01

    目的 对人与狗的颈段迷走/交感干进行比较解剖,并鉴定狗的喉上神经外支的纤维成分.方法 随机解剖经福尔马林固定的成年人尸体颈部(n=50)及狗的颈部(n=10),暴露其颈交感干与喉上神经及其外支间的交通;并取狗的喉上神经外支,甲醛固定,明胶包埋,恒冷切片后用Kamovsky AchE组化方法染色并观察.结果 狗的迷走神经结状神经节与颈上神经节完全或部分融合,迷走神经干与交感神经干完全或部分融合为迷走-交感干;而人的结状神经节与颈上神经节互相分离;颈上神经节与喉上神经及其分支之间存在交通,其中颈上神经节与喉上神经外支相交通者占86%.AchE染色显示:狗的喉上神经外支含AchE阳性有髓神经纤维、AchE阴性有髓神经纤维和AchE阳性无髓神经纤维. 结论 喉上神经外支呈袢状,而非干式,含躯体运动、交感神经节后及躯体感觉纤维,因此喉上神经外支为一混合神经.%Objective To compare the differences of cervical vagus and sympathetic trunks between human being and dog, and identify the fiber components of the dog external laryngeal nerve (ELN). Methods SO adult human cadavers fixed with formalin and 10 fresh dog cadavers were randomly used. The superior laryngeal nerve and its branches, superior cervical sympathetic ganglion (SCSG) and nodose ganglion (NG) were exposed. The communications between the cervical sympathetic trunk and the superior laryngeal nerve (SLN) were identified. The tissues from ELN and NG together with a branch from dog SCSG were taken for AchE activity analysis. Results In dog, the nodosum of vagus and the SCSG were completely or partially fused. In human being, the nodosum of vagus and SCSG separated, and in the most cases (86%) the SCSG connected with the ELN. The AchE staining demonstrated the presence of three different types of fibers in dog ELN: AchE-positive myelinated fibers, AchE-negative myelinated fibers and Ach

  1. Lipid membrane association of myelin proteins and peptide segments studied by oriented and synchrotron radiation circular dichroism spectroscopy.

    Science.gov (United States)

    Muruganandam, Gopinath; Bürck, Jochen; Ulrich, Anne S; Kursula, Inari; Kursula, Petri

    2013-12-01

    Myelin-specific proteins are either integral or peripheral membrane proteins that, in complex with lipids, constitute a multilayered proteolipid membrane system, the myelin sheath. The myelin sheath surrounds the axons of nerves and enables rapid conduction of axonal impulses. Myelin proteins interact intimately with the lipid bilayer and play crucial roles in the assembly, function, and stability of the myelin sheath. Although myelin proteins have been investigated for decades, their structural properties upon membrane surface binding are still largely unknown. In this study, we have used simplified model systems consisting of synthetic peptides and membrane mimics, such as detergent micelles and/or lipid vesicles, to probe the conformation of peptides using synchrotron radiation circular dichroism spectroscopy (SRCD). Additionally, oriented circular dichroism spectroscopy (OCD) was employed to examine the orientation of myelin peptides in macroscopically aligned lipid bilayers. Various representative peptides from the myelin basic protein (MBP), P0, myelin/oligodencrocyte glycoprotein, and connexin32 (cx32) were studied. A helical peptide from the central immunodominant epitope of MBP showed a highly tilted orientation with respect to the membrane surface, whereas the N-terminal cytoplasmic segment of cx32 folded into a helical structure that was only slightly tilted. The folding of full-length myelin basic protein was, furthermore, studied in a bicelle environment. Our results provide information on the conformation and membrane alignment of important membrane-binding peptides in a membrane-mimicking environment, giving novel insights into the mechanisms of membrane binding and stacking by myelin proteins.

  2. Schwann cell myelination requires integration of laminin activities.

    Science.gov (United States)

    McKee, Karen K; Yang, Dong-Hua; Patel, Rajesh; Chen, Zu-Lin; Strickland, Sidney; Takagi, Junichi; Sekiguchi, Kiyotoshi; Yurchenco, Peter D

    2012-10-01

    Laminins promote early stages of peripheral nerve myelination by assembling basement membranes (BMs) on Schwann cell surfaces, leading to activation of β1 integrins and other receptors. The BM composition, structural bonds and ligands needed to mediate this process, however, are not well understood. Mice hypomorphic for laminin γ1-subunit expression that assembled endoneurial BMs with reduced component density exhibited an axonal sorting defect with amyelination but normal Schwann cell proliferation, the latter unlike the null. To identify the basis for this, and to dissect participating laminin interactions, LAMC1 gene-inactivated dorsal root ganglia were treated with recombinant laminin-211 and -111 lacking different architecture-forming and receptor-binding activities, to induce myelination. Myelin-wrapping of axons by Schwann cells was found to require higher laminin concentrations than either proliferation or axonal ensheathment. Laminins that were unable to polymerize through deletions that removed critical N-terminal (LN) domains, or that lacked cell-adhesive globular (LG) domains, caused reduced BMs and almost no myelination. Laminins engineered to bind weakly to α6β1 and/or α7β1 integrins through their LG domains, even though they could effectively assemble BMs, decreased myelination. Proliferation depended upon both integrin binding to LG domains and polymerization. Collectively these findings reveal that laminins integrate scaffold-forming and cell-adhesion activities to assemble an endoneurial BM, with myelination and proliferation requiring additional α6β1/α7β1-laminin LG domain interactions, and that a high BM ligand/structural density is needed for efficient myelination.

  3. Nerve growth factor and injured peripheral nerve regeneration

    Institute of Scientific and Technical Information of China (English)

    Endong Shi; Bingchen Wang; Qingshan Sun

    2008-01-01

    Nerve growth factor (NGF) exhibits many biological activities, such as supply of nutrients, neuroprotection, and the generation and rehabilitation of injured nerves. The neuroprotective and neurotrophic qualities of NGF are generally recognized. NGF may enhance axonal regeneration and myelination of peripheral nerves, as well as cooperatively promote functional recovery of injured nerves and limbs. The clinical efficacy of NGF and its therapeutic potentials are reviewed here. This paper also reviews the latest NGF research developments for repairing injured peripheral nerve, thereby providing scientific evidence for the appropriate clinical application of NGF.

  4. The mechanism of astragaloside IV promoting sciatic nerve regeneration

    Institute of Scientific and Technical Information of China (English)

    Xiaohong Zhang; Jiajun Chen

    2013-01-01

    3-O-beta-D-xylopyranosyl-6-O-beta-D-glucopyranosyl-cycloastragenol (astragaloside IV), the main active component of the traditional Chinese medicine astragalus membranaceus, has been shown to be neuroprotective. This study investigated whether astragaloside IV could promote the repair of injured sciatic nerve. Denervated sciatic nerve of mice was subjected to anastomosis. The mice were intraperitoneal y injected with 10, 5, 2.5 mg/kg astragaloside IV per day for 8 consecutive days. Western blot assay and real-time PCR results demonstrated that growth-associated protein-43 ex-pression was upregulated in mouse spinal cord segments L 4–6 after intervention with 10, 5, 2.5 mg/kg astragaloside IV per day in a dose-dependent manner. Luxol fast blue staining and elec-trophysiological detection suggested that astragaloside IV elevated the number and diameter of myelinated nerve fibers, and simultaneously increased motor nerve conduction velocity and action potential amplitude in the sciatic nerve of mice. These results indicated that astragaloside IV con-tributed to sciatic nerve regeneration and functional recovery in mice. The mechanism underlying this effect may be associated with the upregulation of growth-associated protein-43 expression.

  5. Differentiation of nerve fibers storing CGRP and CGRP receptors in the peripheral trigeminovascular system

    DEFF Research Database (Denmark)

    Eftekhari, Sajedeh; Warfvinge, Karin; Blixt, Frank W;

    2013-01-01

    Primary headaches such as migraine are postulated to involve the activation of sensory trigeminal pain neurons that innervate intracranial blood vessels and the dura mater. It is suggested that local activation of these sensory nerves may involve dural mast cells as one factor in local inflammation......, causing sensitization of meningeal nociceptors. Immunofluorescence was used to study the detailed distribution of calcitonin gene-related peptide (CGRP) and its receptor components calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1) in whole-mount rat dura mater...

  6. Neutron scattering studies on protein dynamics using the human myelin peripheral membrane protein P2

    Directory of Open Access Journals (Sweden)

    Laulumaa Saara

    2015-01-01

    Full Text Available Myelin is a multilayered proteolipid membrane structure surrounding selected axons in the vertebrate nervous system, which allows the rapid saltatory conduction of nerve impulses. Deficits in myelin formation and maintenance may lead to chronic neurological disease. P2 is an abundant myelin protein from peripheral nerves, binding between two apposing lipid bilayers. We studied the dynamics of the human myelin protein P2 and its mutated P38G variant in hydrated powders using elastic incoherent neutron scattering. The local harmonic vibrations at low temperatures were very similar for both samples, but the mutant protein had increased flexibility and softness close to physiological temperatures. The results indicate that a drastic mutation of proline to glycine at a functional site can affect protein dynamics, and in the case of P2, they may explain functional differences between the two proteins.

  7. Neutron scattering studies on protein dynamics using the human myelin peripheral membrane protein P2

    Science.gov (United States)

    Laulumaa, Saara; Kursula, Petri; Natali, Francesca

    2015-01-01

    Myelin is a multilayered proteolipid membrane structure surrounding selected axons in the vertebrate nervous system, which allows the rapid saltatory conduction of nerve impulses. Deficits in myelin formation and maintenance may lead to chronic neurological disease. P2 is an abundant myelin protein from peripheral nerves, binding between two apposing lipid bilayers. We studied the dynamics of the human myelin protein P2 and its mutated P38G variant in hydrated powders using elastic incoherent neutron scattering. The local harmonic vibrations at low temperatures were very similar for both samples, but the mutant protein had increased flexibility and softness close to physiological temperatures. The results indicate that a drastic mutation of proline to glycine at a functional site can affect protein dynamics, and in the case of P2, they may explain functional differences between the two proteins.

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

    DEFF Research Database (Denmark)

    Pereira, Jorge A.; Baumann, Reto; Norrmén, Camilla

    2010-01-01

    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...... 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......, 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....

  9. Oligodendrocyte, Astrocyte, and Microglia Crosstalk in Myelin Development, Damage, and Repair

    Science.gov (United States)

    Domingues, Helena S.; Portugal, Camila C.; Socodato, Renato; Relvas, João B.

    2016-01-01

    Oligodendrocytes are the myelinating glia of the central nervous system. Myelination of axons allows rapid saltatory conduction of nerve impulses and contributes to axonal integrity. Devastating neurological deficits caused by demyelinating diseases, such as multiple sclerosis, illustrate well the importance of the process. In this review, we focus on the positive and negative interactions between oligodendrocytes, astrocytes, and microglia during developmental myelination and remyelination. Even though many lines of evidence support a crucial role for glia crosstalk during these processes, the nature of such interactions is often neglected when designing therapeutics for repair of demyelinated lesions. Understanding the cellular and molecular mechanisms underlying glial cell communication and how they influence oligodendrocyte differentiation and myelination is fundamental to uncover novel therapeutic strategies for myelin repair. PMID:27551677

  10. Pulsed electrical stimulation protects neurons in the dorsal root and anterior horn of the spinal cord after peripheral nerve injury.

    Science.gov (United States)

    Pei, Bao-An; Zi, Jin-Hua; Wu, Li-Sheng; Zhang, Cun-Hua; Chen, Yun-Zhen

    2015-10-01

    Most studies on peripheral nerve injury have focused on repair at the site of injury, but very few have examined the effects of repair strategies on the more proximal neuronal cell bodies. In this study, an approximately 10-mm-long nerve segment from the ischial tuberosity in the rat was transected and its proximal and distal ends were inverted and sutured. The spinal cord was subjected to pulsed electrical stimulation at T10 and L3, at a current of 6.5 mA and a stimulation frequency of 15 Hz, 15 minutes per session, twice a day for 56 days. After pulsed electrical stimulation, the number of neurons in the dorsal root ganglion and anterior horn was increased in rats with sciatic nerve injury. The number of myelinated nerve fibers was increased in the sciatic nerve. The ultrastructure of neurons in the dorsal root ganglion and spinal cord was noticeably improved. Conduction velocity of the sciatic nerve was also increased. These results show that pulsed electrical stimulation protects sensory neurons in the dorsal root ganglia as well as motor neurons in the anterior horn of the spinal cord after peripheral nerve injury, and that it promotes the regeneration of peripheral nerve fibers.

  11. Effects of locally applied nerve growth factor to the inferior alveolar nerve histology in a rabbit model of mandibular distraction osteogenesis.

    Science.gov (United States)

    Wang, L; Zhao, Y; Cheng, X; Yang, Y; Liu, G; Ma, Q; Shang, H; Tian, L; Lei, D

    2009-01-01

    Distraction osteogenesis (DO) is widely used in deformities and defects of the craniofacial bone. Accelerating inferior alveolar nerve (IAN) recovery would aid the process. Nerve growth factor (NGF) plays a vital role in peripheral nerve regeneration. In this study, the ability of locally applied human NGF beta (hNGFbeta) to enhance the morphological recovery of the IAN in a rabbit model of mandibular DO was studied. Rabbits underwent bilateral DO with a rate of 0.5mm per 12h. Two doses of 40 microg hNGFbeta in buffer were injected into callus at the beginning the of consolidation time. The contralateral side received injections of placebo. Rabbits were killed at 14 and 28 days. IAN specimens were subjected to histological and histomorphometric analysis. In both 14 and 28 days consolidation experiments, nerve histological analysis showed less degeneration and more regeneration in nerve fibers on the hNGFbeta treated side than the control side. Histomorphometric analysis showed that the myelinated fiber density on the hNGFbeta treated side was significantly higher than on the control side (p<0.01). The data indicate that locally applied hNGFbeta can accelerate the morphological recovery of the IAN and may play a role in reducing nerve injury in mandibular DO clinically.

  12. Constituent ratio of motor fibers from the C5-C7 spinal nerves in the radial nerve is greater in pup rats than in adult rats.

    Science.gov (United States)

    Nie, Mingbo; Chen, Liang; Gu, Yudong

    2012-06-01

    Clinically, injuries of C5-C7 of the brachial plexus cause falling of the wrist and fingers in infants but not in adults unless 4 consecutive spinal nerves are injured. The purpose of this study was to compare the constituent difference of spinal nerves in the radial nerve between pup and adult rats.A group of 16 pup rats and a group of 16 adult rats were each divided into 2 groups of 8 (P1 and A1 groups, C5-C6 were divided; P2 and A2 groups, C5-C7 were divided]). A nerve conduction study and histological examination were performed to evaluate radial nerve innervation to the extensor digitorum communis muscle after dividing the spinal nerves. Retrograde tracing with 5% cholera toxin B for anterior horn motoneurons of the spinal cord innervating the radial nerve was performed in 8 pup rats and 8 adult rats. Results showed that the division of C5-C7 caused more significant damage to radial nerve innervation to the extensor digitorum communis in pups than in adults, although the division of C5-C6 did not. In pups, the percentages (median with interquartile) of anterior horn motoneurons of the spinal cord innervating the radial nerve were 36.4 (28.3-38.5) in C5-C6, 28.1 (24.5-32.5) in C7, and 37.5 (36.5-39.3) in C8-T1. In adults, they were 24.2 (23.6-27.8) in C5-C6, 21.8 (19.5-26.3) in C7, and 50.7 (48.7-55.5) C8-T1.This study implies that C7 innervation in the radial nerve in humans may be more critical to the function of this nerve in infants than in adults.

  13. The Expanded Bead Size of Corneal C-Nerve Fibers Visualized by Corneal Confocal Microscopy Is Associated with Slow Conduction Velocity of the Peripheral Nerves in Patients with Type 2 Diabetes Mellitus

    Science.gov (United States)

    2016-01-01

    This study aims to establish the corneal nerve fiber (CNF) morphological alterations in a large cohort of type 2 diabetic patients and to investigate the association between the bead size, a novel parameter representing composite of accumulated mitochondria, glycogen particles, and vesicles in CNF, and the neurophysiological dysfunctions of the peripheral nerves. 162 type 2 diabetic patients and 45 healthy control subjects were studied in detail with a battery of clinical and neurological examinations and corneal confocal microscopy. Compared with controls, patients had abnormal CNF parameters. In particular the patients had reduced density and length of CNF and beading frequency and increased bead size. Alterations in CNF parameters were significant even in patients without neuropathy. The HbA1c levels were tightly associated with the bead size, which was inversely related to the motor and sensory nerve conduction velocity (NCV) and to the distal latency period of the median nerve positively. The CNF density and length positively correlated with the NCV and amplitude. The hyperglycemia-induced expansion of beads in CNF might be a predictor of slow NCV in peripheral nerves in type 2 diabetic patients. PMID:27563679

  14. Evaluation of changes in retinal nerve fiber layer thickness and visual functions in cases of optic neuritis and multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Rohit Saxena

    2013-01-01

    Full Text Available Context: Retinal nerve fiber layer (RNFL thinning has been demonstrated in cases of optic neuritis (ON and multiple sclerosis (MS in Caucasian eyes, but no definite RNFL loss pattern or association with visual functions is known in Indian eyes. Aim : To evaluate RNFL thickness in cases of ON and MS, and to correlate it with visual function changes in Indian patients. Settings and Design: Cross-sectional case-control study at a tertiary level institution . Materials and Methods: Cases consisted of patients of (i typical ON without a recent episode (n = 30:39 ON eyes and 21 fellow eyes, (ii MS without ON (n = 15;30 eyes while the controls were age-matched (n = 15; 30 eyes. RNFL thickness was measured using the Stratus 3 °CT. The visual functions tested included the best-corrected visual acuity (BCVA, contrast sensitivity, stereopsis, visual evoked responses, and visual fields. Statistical analysis used: Intergroup analysis was done using ANOVA and Pearson′s correlation coefficient used for associations. Results: RNFL thickness was reduced significantly in the ON and MS patients compared to the controls (P-0.001. Maximum loss is in the temporal quadrant. Lower visual function scores are associated with reduced average overall RNFL thickness. In ON group, RNFL thinning is associated with severe visual field defects while contrast sensitivity has strongest correlation with RNFL in the MS group. Conclusions:RNFL thickness is reduced in ON and MS cases in a pattern similar to Caucasians and is associated with the magnitude of impairment of other visual parameters. Contrast sensitivity and stereoacuity are useful tests to identify subclinical optic nerve involvement in multiple sclerosis.

  15. Retinal nerve fiber layer thickness of middle aged or elderly people measured by 3D optical coherence tomography

    Directory of Open Access Journals (Sweden)

    Li Li

    2015-11-01

    Full Text Available AIM: To build the reference values of normal eye retinal nerve fiber layer(RNFLthickness on middle aged people between 40~69 years old, and infer the baseline data for early diagnosis of glaucoma. METHODS:A total of 180 eyes from 90 healthy subjects(age ranged from 40~69 years oldwere recruited for this study. Topcon 3D optical coherence tomography(OCT-2000(Ver 8.0was used to measure RNFL thickness. Each subject was performed circular scans around the optic nerve with a circle size of 3.4mm. Clock-hour, quadrant and total average RNFL thicknesses were recorded. The data was analyzed with SPSS statistical. The relationship between age, gender and laterality was analyzed, and the reference value for normal eye RNFL thickness parameters was obtained, RESULTS:Normal RNFL thickness distribution was bimodal curve type in 40~69 year-old middle aged or elderly people. RNFL thickness was decreased for temporal quadrant, followed by nasal, superior, inferior. RNFL thickness at 10 o'clock, 5 o'clock, 6 o'clock, superior got thinner with age prolong. Except 10 o'clock(PP>0.05. The RNFL thickness at 11 o'clock was associated with different gender. the RNFL thickness at 11 o'clock, 12 o'clock, 1 o'clock, 4 o'clock, superior, nasal was associated with different eyes, the differe