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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...

  2. Evaluation of dermal myelinated nerve fibers in diabetes mellitus

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

    2013-01-01

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

  3. Morphometric analysis of the diameter and g-ratio of the myelinated nerve fibers of the human sciatic nerve during the aging process.

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    Ugrenović, Sladjana; Jovanović, Ivan; Vasović, Ljiljana; Kundalić, Braca; Čukuranović, Rade; Stefanović, Vladisav

    2016-06-01

    Myelinated nerve fibers suffer from different degrees of atrophy with age. The success of subsequent regeneration varies. The aim of this research was to analyze myelinated fibers of the human sciatic nerve during the aging process. Morphometric analysis was performed on 17 cases with an age range from 9 to 93 years. The outer and inner diameter of 100 randomly selected nerve fibers was measured in each of the cases evaluated, and the g-ratio (axonal diameter/outer diameter of the whole nerve fiber) of each was calculated. Scatter plots of the diameters and g-ratios of the analyzed fibers were then analyzed. Nerve fibers of each case were classified into three groups according to the g-ratio values: group I (g-ratio lower than 0.6), group II (g-ratio from 0.6 to 0.7) and group III (g-ratio higher than 0.7). Afterwards, nerve fibers of group II were further classified into small and large subgroups. The percentages of each group of nerve fibers were computed for each case and these values were used for correlational and bivariate linear regression analysis. The percentage of myelinated nerve fibers with large diameter and optimal g-ratio of the sciatic nerve declines significantly with age. This is accompanied by a simultaneous significant increase in the percentage of small myelinated fibers with g-ratio values close to 1 that occupy the upper left quadrant of the scatter plot. It can be concluded that aging of the sciatic nerve is associated with significant atrophy of large myelinated fibers. Additionally, a significant increase in regenerated nerve fibers with thinner myelin sheath is observed with age, which, together with the large myelinated fiber atrophy, might be the cause of the age-related decline in conduction velocity. A better understanding of the changes in aging peripheral nerves might improve interpretation of their pathological changes, as well as comprehension of their regeneration in individuals of different age.

  4. Electron microscopic study of the myelinated nerve fibres and the perineurial cell basement membrane in the diabetic human peripheral nerves

    International Nuclear Information System (INIS)

    ElBarrany, Wagih G.; Hamdy, Raid M.; AlHayani, Abdulmonem A.; Jalalah, Sawsan M.

    2009-01-01

    To study the quantitative and ultrastructural changes in myelinated nerve fibers and the basement membranes of the perineurial cells in diabetic nerves. The study was performed at the Department of Anatomy, Faculty of Medicine, King Abdul-Aziz University, Jeddah, Saudi Arabia from 2003 to 2005. Human sural nerves were obtained from 15 lower limbs and 5 diabetic nerve biopsies. The total mean and density of myelinated nerve fibers per fascicle were calculated, with density of microtubules and mitochondria in the axoplasm. The number of the perineurial cell basement membrane layers was counted, and thickness of the basement membrane was measured. Among the 15 diabetic and 5 normal human sural nerves, the average diameters, number and surface area of myelinated nerve fibers and axonal microtubules density were found to be less in diabetic nerves. Mitochondrial density was higher in diabetic axons. Thickness of the perineurial cell basement membrane had a greater mean, but the number of perineurial cell layers was less than that of the diabetic group. The inner cellular layer of the perineurium of the diabetic nerves contained large vacuoles containing electron-dense degenerated myelin. A few specimens showed degenerated myelinated nerve fibers, while others showed recovering ones. Retracted axoplasms were encountered with albumin extravasation. Diabetes caused an increase in perineurial permeability. The diabetic sural nerve showed marked decrease in the myelinated nerve fibres, increase degenerated mitochondria, and decreased microtubules. (author)

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

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    Martinez A.M.B.

    2000-01-01

    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.

  6. 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.

  7. Myelination and nodal formation of regenerated peripheral nerve fibers following transplantation of acutely prepared olfactory ensheathing cells

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    Dombrowski, Mary A.; Sasaki, Masanori; Lankford, Karen L.; Kocsis, Jeffery D.; Radtke, Christine

    2009-01-01

    Transplantation of olfactory ensheathing cells (OECs) into injured spinal cord results in improved functional outcome. Mechanisms suggested to account for this functional improvement include axonal regeneration, remyelination and neuroprotection. OECs transplanted into transected peripheral nerve have been shown to modify peripheral axonal regeneration and functional outcome. However, little is known of the detailed integration of OECs at the transplantation site in peripheral nerve. To address this issue cells populations enriched in OECs were isolated from the olfactory bulbs of adult green fluorescent protein (GFP)-expressing transgenic rats and transplanted into a sciatic nerve crush lesion which transects all axons. Five weeks to six months after transplantation the nerves were studied histologically. GFP-expressing OECs survived in the lesion and distributed longitudinally across the lesion zone. The internodal regions of individual teased fibers distal to the transection site were characterized by GFP expression in the cytoplasmic and nuclear compartments of cells surrounding the axons. Immuno-electron microscopy for GFP indicated that the transplanted OECs formed peripheral type myelin. Immunostaining for sodium channel and Caspr revealed a high density of Nav1.6 at the newly formed nodes of Ranvier which were flanked by paranodal Caspr staining. These results indicate that transplanted OECs extensively integrate into transected peripheral nerve and form myelin on regenerated peripheral nerve fibers, and that nodes of Ranvier of these axons display proper sodium channel organization. PMID:17112480

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

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    So Young Jang

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

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

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    Ekaterina E Verdiyan

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

  10. 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.

  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. Histological methods for assessing myelin sheaths and axons in human nerve trunks.

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    Miko, T L; Gschmeissner, S E

    1994-03-01

    Although there are many histological techniques for assessing myelin sheaths and axons in paraffin embedded or frozen sections of the peripheral nervous system, modern approaches usually use plastic embedded material. Although plastic embedding is superior for small cutaneous branches, this method has limited value for histological assessment of nerve trunks. We report three methods which together yield a comprehensive approach for thorough and detailed investigation of human nerve trunks. The rapid osmication method permitted assessment of myelinated nerve fibers from frozen sections at operation, thus providing the surgeon with guidance on the extent of nerve resection. The modification presented here resulted in permanent slides, allowing comparison of results with those of the other two procedures. The new osmium-hematoxylin technique could be performed on paraffin embedded nerves. Paraffin, unlike plastic, permitted the study of the whole cross sectional area of the nerve in single sections. Moreover, the sharp image of the myelin permitted computerized morphometry. The significantly modified axonal silver impregnation technique was performed on frozen sections mounted on glass slides, as opposed to the time-consuming impregnation of free-floating sections. The latter technique had a high success rate and permitted semiquantitative assessment of axons in nerve trunks. These methods can be performed in any routine histology laboratory and resulted in greater accuracy compared to conventional methods.

  13. DC-Evoked Modulation of Excitability of Myelinated Nerve Fibers and Their Terminal Branches; Differences in Sustained Effects of DC.

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    Kaczmarek, Dominik; Jankowska, Elzbieta

    2018-03-15

    Direct current (DC) evokes long-lasting changes in neuronal networks both presynaptically and postsynaptically and different mechanisms were proposed to be involved in them. Different mechanisms were also suggested to account for the different dynamics of presynaptic DC actions on myelinated nerve fibers stimulated before they entered the spinal gray matter and on their terminal branches. The aim of the present study was to examine whether these different dynamics might be related to differences in the involvement of K + channels. To this end, we compared effects of the K + channel blocker 4-amino-pyridine (4-AP) on DC-evoked changes in the excitability of afferent fibers stimulated within the dorsal columns (epidurally) and within their projection areas in the dorsal horn and motor nuclei (intraspinally). 4-AP was applied systemically in deeply anesthetized rats. DC-evoked increases in the excitability of epidurally stimulated afferent nerve fibers, and increases in field potentials evoked by these fibers, were not affected by 4-AP. In contrast, sustained decreases rather than increases in the excitability of intraspinally stimulated terminal nerve branches were evoked by local application of DC in conjunction with 4-AP. The study leads to the conclusion that 4-AP-sensitive K + channels contribute to the sustained DC-evoked post-polarization increases in the excitability at the level of terminal branches of nerve fibers but not of the nodes of Ranvier nor within the juxta-paranodal regions where other mechanisms would be involved in inducing the sustained DC-evoked changes. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

  14. 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.

  15. 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.

  16. Schwann Cell Glycogen Selectively Supports Myelinated Axon Function

    Science.gov (United States)

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

    2012-01-01

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

  17. The human dorsal spinocerebellar tract: myelinated fiber spectrum and fiber density in controls, autosomal dominant spinocerebellar atrophy, Huntington's chorea, radiation myelopathy, and diseases with peripheral sensory nerve involvement

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    Ringelstein, E.B.; Schroeder, J.M.

    1982-01-01

    The human dorsal spinocerebellar tract (DSCT) was evaluated morphometrically in 14 control cases of different age and sex using semithin sections of epon-embedded cross sections from the C3, T5, and T10 segments of the spinal cord. A bimodal fiber spectrum was revealed with one peak at 2-3 microns, and a second, broader peak at about 6-8 microns. Fiber density at C3 was 11,188 fibers/mm2 and at T5, 11,156 fibers/mm2. Regression analysis relating fiber density to age disclosed a highly significant loss of myelinated fibers at T5 amounting to about 2.5% per decade. A severe reduction of fiber density and a distinct change in the fiber spectrum with predominant loss of large myelinated fibers were noted in a case of autosomal dominant spinocerebellar atrophy with late onset, and, to a lesser degree, in a case of Huntington's chorea. A subtotal loss of fibers with a persistent normal distribution of fiber sizes was observed rostral to a focus of severe radiation myelopathy, indicating Wallerian degeneration of large numbers of fibers, and a reduction of fiber diameters caudal to the lesion, suggesting retrograde fiber change. By contrast, no primary or transneural changes in the DSCT were detected in six cases of long-term alcoholism, carcinomatous sensory neuropathy, and neurofibromatosis in spite of the involvement of numerous nerve roots.

  18. Automated characterization of nerve fibers labeled fluorescently: determination of size, class and spatial distribution.

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    Prodanov, Dimiter; Feirabend, Hans K P

    2008-10-03

    Morphological classification of nerve fibers could help interpret the assessment of neural regeneration and the understanding of selectivity of nerve stimulation. Specific populations of myelinated nerve fibers can be investigated by retrograde tracing from a muscle followed by microscopic measurements of the labeled fibers at different anatomical levels. Gastrocnemius muscles of adult rats were injected with the retrograde tracer Fluoro-Gold. After a survival period of 3 days, cross-sections of spinal cords, ventral roots, sciatic, and tibial nerves were collected and imaged on a fluorescence microscope. Nerve fibers were classified using a variation-based criterion acting on the distribution of their equivalent diameters. The same criterion was used to classify the labeled axons using the size of the fluorescent marker. Measurements of the axons were paired to those of the entire fibers (axons+myelin sheaths) in order to establish the correspondence between so-established axonal and fiber classifications. It was found that nerve fibers in L6 ventral roots could be classified into four populations comprising two classes of Aalpha (denoted Aalpha1 and Aalpha2), Agamma, and an additional class of Agammaalpha fibers. Cut-off borders between Agamma and Agammaalpha fiber classes were estimated to be 5.00+/-0.09 microm (SEM); between Agammaalpha and Aalpha1 fiber classes to be 6.86+/-0.11 microm (SEM); and between Aalpha1 and Aalpha2 fiber classes to be 8.66+/-0.16 microm (SEM). Topographical maps of the nerve fibers that innervate the gastrocnemius muscles were constructed per fiber class for the spinal root L6. The major advantage of the presented approach consists of the combined indirect classification of nerve fiber types and the construction of topographical maps of so-identified fiber classes.

  19. 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 [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.

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

    International Nuclear Information System (INIS)

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

    2013-01-01

    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.

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

    OpenAIRE

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

    2015-01-01

    Nerve morphometry is known to produce relevant information for the evaluation of several phenomena, such as nerve repair, regeneration, implant, transplant, aging, and different human neuropathies. Manual morphometry is laborious, tedious, time consuming, and subject to many sources of error. Therefore, in this paper, we propose a new method for the automated morphometry of myelinated fibers in cross-section light microscopy images. Images from the recurrent laryngeal nerve of adult rats and ...

  2. Noninvasive Evaluation of Nerve Conduction in Small Diameter Fibers in the Rat

    OpenAIRE

    Elena G. Zotova; Joseph C. Arezzo

    2013-01-01

    A novel noninvasive technique was applied to measure velocity within slow conducting axons in the distal extreme of the sciatic nerve (i.e., digital nerve) in a rat model. The technique is based on the extraction of rectified multiple unit activity (MUA) from in vivo whole nerve compound responses. This method reliably identifies compound action potentials in thinly myelinated fibers conducting at a range of 9–18 m/s ( axons), as well as in a subgroup of unmyelinated C fibers conducting at ap...

  3. NON-INVASIVE EVALUATION OF NERVE CONDUCTION IN SMALL DIAMETER FIBERS IN THE RAT

    OpenAIRE

    Zotova, Elena G.; Arezzo, Joseph C.

    2013-01-01

    A novel non-invasive technique was applied to measure velocity within slow conducting axons in the distal extreme of the sciatic nerve (i.e., digital nerve) in a rat model. The technique is based on the extraction of rectified multiple unit activity (MUA) from in vivo whole nerve compound responses. This method reliably identifies compound action potentials in thinly myelinated fibers conducting at a range of 9-18 m/s (Aδ axons), as well as in a subgroup of unmylinated C fibers conducting at ...

  4. Selective Fiber Degeneration in the Peripheral Nerve of a Patient With Severe Complex Regional Pain Syndrome

    Directory of Open Access Journals (Sweden)

    Adrien Yvon

    2018-04-01

    Full Text Available Aims: Complex regional pain syndrome (CRPS is characterized by chronic debilitating pain disproportional to the inciting event and accompanied by motor, sensory, and autonomic disturbances. The pathophysiology of CRPS remains elusive. An exceptional case of severe CRPS leading to forearm amputation provided the opportunity to examine nerve histopathological features of the peripheral nerves.Methods: A 35-year-old female developed CRPS secondary to low voltage electrical injury. The CRPS was refractory to medical therapy and led to functional loss of the forelimb, repeated cutaneous wound infections leading to hospitalization. Specifically, the patient had exhausted a targeted conservative pain management programme prior to forearm amputation. Radial, median, and ulnar nerve specimens were obtained from the amputated limb and analyzed by light and transmission electron microscopy (TEM.Results: All samples showed features of selective myelinated nerve fiber degeneration (47–58% of fibers on electron microscopy. Degenerating myelinated fibers were significantly larger than healthy fibers (p < 0.05, and corresponded to the larger Aα fibers (motor/proprioception whilst smaller Aδ (pain/temperature fibers were spared. Groups of small unmyelinated C fibers (Remak bundles also showed evidence of degeneration in all samples.Conclusions: We are the first to show large fiber degeneration in CRPS using TEM. Degeneration of Aα fibers may lead to an imbalance in nerve signaling, inappropriately triggering the smaller healthy Aδ fibers, which transmit pain and temperature. These findings suggest peripheral nerve degeneration may play a key role in CRPS. Improved knowledge of pathogenesis will help develop more targeted treatments.

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

    NARCIS (Netherlands)

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

    2015-01-01

    Although Schwann cell myelin breakdown is the universal outcome of a remarkably wide range of conditions that cause disease or injury to peripheral nerves, the cellular and molecular mechanisms that make Schwann cell-mediated myelin digestion possible have not been established. We report that

  6. 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

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

    Directory of Open Access Journals (Sweden)

    Zahir Kizilay

    2016-01-01

    Full Text Available 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.

  8. Ultrastructural changes of compressed lumbar ventral nerve roots following decompression

    International Nuclear Information System (INIS)

    El-Barrany, Wagih G.; Hamdy, Raid M.; Al-Hayani, Abdulmonem A.; Jalalah, Sawsan M.; Al-Sayyad, Mohammad J.

    2006-01-01

    To study whether there will be permanent lumbar nerve rot scanning or degeneration secondary to continuous compression followed by decompression on the nerve roots, which can account for postlaminectomy leg weakness or back pain. The study was performed at the Department of Anatomy, Faulty of Medicine, king Abdulaziz University, Jeddah, Kingdom of Saudi Arabia during 2003-2005. Twenty-six adult male New Zealand rabbits were used in the present study. The ventral roots of the left fourth lumbar nerve were clamped for 2 weeks then decompression was allowed by removal of the clips. The left ventral roots of the fourth lumbar nerve were excised for electron microscopic study. One week after nerve root decompression, the ventral root peripheral to the site of compression showed signs of Wallerian degeneration together with signs of regeneration. Schwann cells and myelinated nerve fibers showed severe degenerative changes. Two weeks after decompression, the endoneurium of the ventral root showed extensive edema with an increase in the regenerating myelinated and unmyentilated nerve fibers, and fibroblasts proliferation. Three weeks after decompression, the endoneurium showed an increase in the regenerating myelinated and unmyelinated nerve fibers with diminution of the endoneurial edema, and number of macrophages and an increase in collagen fibrils. Five and 6 weeks after decompression, the endoneurium showed marked diminution of the edema, macrophages, mast cells and fibroblasts. The enoneurium was filed of myelinated and unmyelinated nerve fibers and collagen fibrils. Decompression of the compressed roots of a spinal nerve is followed by regeneration of the nerve fibers and nerve and nerve recovery without endoneurial scarring. (author)

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

    Directory of Open Access Journals (Sweden)

    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

  10. Neurophysiological approach to disorders of peripheral nerve

    DEFF Research Database (Denmark)

    Crone, Clarissa; Krarup, Christian

    2013-01-01

    Disorders of the peripheral nerve system (PNS) are heterogeneous and may involve motor fibers, sensory fibers, small myelinated and unmyelinated fibers and autonomic nerve fibers, with variable anatomical distribution (single nerves, several different nerves, symmetrical affection of all nerves......, plexus, or root lesions). Furthermore pathological processes may result in either demyelination, axonal degeneration or both. In order to reach an exact diagnosis of any neuropathy electrophysiological studies are crucial to obtain information about these variables. Conventional electrophysiological...

  11. 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

    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......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...... 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...

  12. 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...... and in human dural vessels. The relative distributions of CGRP, CLR, and RAMP1 were evaluated with respect to each other and in relationship to mast cells, myelin, substance P, neuronal nitric oxide synthase, pituitary adenylate cyclase-activating polypeptide, and vasoactive intestinal peptide. CGRP expression...... was found in thin unmyelinated fibers, whereas CLR and RAMP1 were expressed in thicker myelinated fibers coexpressed with an A-fiber marker. CLR and RAMP1 immunoreactivity colocalized with mast cell tryptase in rodent; however, expression of both receptor components was not observed in human mast cells...

  13. Transverse Magnetic Waves in Myelinated Nerves

    Science.gov (United States)

    2001-10-25

    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...Element Number Author(s) Project Number Task Number Work Unit Number Performing Organization Name(s) and Address(es) Área de Teoría de la Señal...y Comunicaciones , E.S. de Ingeniería, University of Seville, Seville, Spain Performing Organization Report Number Sponsoring/Monitoring Agency Name(s

  14. NON-INVASIVE EVALUATION OF NERVE CONDUCTION IN SMALL DIAMETER FIBERS IN THE RAT.

    Science.gov (United States)

    Zotova, Elena G; Arezzo, Joseph C

    2013-01-01

    A novel non-invasive technique was applied to measure velocity within slow conducting axons in the distal extreme of the sciatic nerve (i.e., digital nerve) in a rat model. The technique is based on the extraction of rectified multiple unit activity (MUA) from in vivo whole nerve compound responses. This method reliably identifies compound action potentials in thinly myelinated fibers conducting at a range of 9-18 m/s (Aδ axons), as well as in a subgroup of unmylinated C fibers conducting at approximately 1-2 m/s. The sensitivity of the method to C-fiber conduction was confirmed by the progressive decrement of the responses in the 1-2 m/s range over a 20-day period following the topical application of capsaicin (ANOVA p <0.03). Increasing the frequency of applied repetitive stimulation over a range of 0.75 Hz to 6.0 Hz produced slowing of conduction and a significant decrease in the magnitude of the compound C-fiber response (ANOVA p <0.01). This technique offers a unique opportunity for the non-invasive, repeatable, and quantitative assessment of velocity in the subsets of Aδ and C fibers in parallel with evaluation of fast nerve conduction.

  15. 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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Splanchnic preganglionic neurons in man. III. Morphometry of myelinated fibers of rami communicantes.

    Science.gov (United States)

    Low, P A; Dyck, P J

    1978-01-01

    The myelinated fiber (MF) composition of T6-T8 Rami Communicantes were obtained in 9 healthy persons of various ages. The textbook picture that distal rami (DR) contain all of the myelinated fibers and therefore are white, while proximal rami (PR) contain none of them and therefore are grey must be modified. We found that DR usually contained abundant MFs and that PR concordance was found between segmental numbers of intermediolateral nuclei cytons, ventral root small myelinated fibers (SMFs), and rami total small MFs to suggest that both rami probably contain the distal myelinated axons of preganglionic autonomic fibers. Finally, there was an attrition of total MFs of rami with age, similar to what we had previously found for ILC cytons and for root SMFs. The decrease in number of pre-ganglionic autonomic neurons with age is thought to be of sufficient magnitude to account for the dysautonomia of the elderly.

  17. 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.

  18. 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`

    1998-12-31

    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.

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

    Science.gov (United States)

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

    2016-02-01

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

  20. A Laminin-2, Dystroglycan, Utrophin Axis is Required for Compartmentalization and Elongation of Myelin Segments

    OpenAIRE

    Court, Felipe A.; Hewitt, Jane E.; Davies, Kay; Patton, Bruce L.; Uncini, Antonino; Wrabetz, Lawrence; Feltri, M. Laura

    2009-01-01

    Animal and plant cells compartmentalize to perform morphogenetic functions. Compartmentalization of myelin-forming Schwann cells may favor elongation of myelin segments to the size required for efficient conduction of nerve impulses. Compartments in myelinated fibers were described by Ramon-y-Cajal and depend on periaxin, mutated in the hereditary neuropathy Charcot-Marie-Tooth 4F. Lack of periaxin in mice causes loss of compartments, formation of short myelin segments (internodes) and reduce...

  1. Short-term observations of the regenerative potential of injured proximal sensory nerves crossed with distal motor nerves

    Directory of Open Access Journals (Sweden)

    Xiu-xiu Zhang

    2017-01-01

    Full Text Available Motor nerves and sensory nerves conduct signals in different directions and function in different ways. In the surgical treatment of peripheral nerve injuries, the best prognosis is obtained by keeping the motor and sensory nerves separated and repairing the nerves using the suture method. However, the clinical consequences of connections between sensory and motor nerves currently remain unknown. In this study, we analyzed the anatomical structure of the rat femoral nerve, and observed the motor and sensory branches of the femoral nerve in the quadriceps femoris. After ligation of the nerves, the proximal end of the sensory nerve was connected with the distal end of the motor nerve, followed by observation of the changes in the newly-formed regenerated nerve fibers. Acetylcholinesterase staining was used to distinguish between the myelinated and unmyelinated motor and sensory nerves. Denervated muscle and newly formed nerves were compared in terms of morphology, electrophysiology and histochemistry. At 8 weeks after connection, no motor nerve fibers were observed on either side of the nerve conduit and the number of nerve fibers increased at the proximal end. The proportion of newly-formed motor and sensory fibers was different on both sides of the conduit. The area occupied by autonomic nerves in the proximal regenerative nerve was limited, but no distinct myelin sheath was visible in the distal nerve. These results confirm that sensory and motor nerves cannot be effectively connected. Moreover, the change of target organ at the distal end affects the type of nerves at the proximal end.

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

    Science.gov (United States)

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

    2011-12-01

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

  3. 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

  4. Transplantation of bone-marrow-derived cells into a nerve guide resulted in transdifferentiation into Schwann cells and effective regeneration of transected mouse sciatic nerve.

    Science.gov (United States)

    Pereira Lopes, Fátima Rosalina; Frattini, Flávia; Marques, Suelen Adriani; Almeida, Fernanda Martins de; de Moura Campos, Lenira Camargo; Langone, Francesco; Lora, Silvano; Borojevic, Radovan; Martinez, Ana Maria Blanco

    2010-10-01

    Peripheral nerves possess the capacity of self-regeneration after traumatic injury. Nevertheless, the functional outcome after peripheral-nerve regeneration is often poor, especially if the nerve injuries occur far from their targets. Aiming to optimize axon regeneration, we grafted bone-marrow-derived cells (BMDCs) into a collagen-tube nerve guide after transection of the mouse sciatic nerve. The control group received only the culture medium. Motor function was tested at 2, 4, and 6 weeks after surgery, using the sciatic functional index (SFI), and showed that functional recovery was significantly improved in animals that received the cell grafts. After 6 weeks, the mice were anesthetized, perfused transcardially, and the sciatic nerves were dissected and processed for transmission electron microscopy and light microscopy. The proximal and distal segments of the nerves were compared, to address the question of improvement in growth rate; the results revealed a maintenance and increase of nerve regeneration for both myelinated and non-myelinated fibers in distal segments of the experimental group. Also, quantitative analysis of the distal region of the regenerating nerves showed that the numbers of myelinated fibers, Schwann cells (SCs) and g-ratio were significantly increased in the experimental group compared to the control group. The transdifferentiation of BMDCs into Schwann cells was confirmed by double labeling with S100/and Hoechst staining. Our data suggest that BMDCs transplanted into a nerve guide can differentiate into SCs, and improve the growth rate of nerve fibers and motor function in a transected sciatic-nerve model.

  5. Miconazole enhances nerve regeneration and functional recovery after sciatic nerve crush injury.

    Science.gov (United States)

    Lin, Tao; Qiu, Shuai; Yan, Liwei; Zhu, Shuang; Zheng, Canbin; Zhu, Qingtang; Liu, Xiaolin

    2018-05-01

    Improving axonal outgrowth and remyelination is crucial for peripheral nerve regeneration. Miconazole appears to enhance remyelination in the central nervous system. In this study we assess the effect of miconazole on axonal regeneration using a sciatic nerve crush injury model in rats. Fifty Sprague-Dawley rats were divided into control and miconazole groups. Nerve regeneration and myelination were determined using histological and electrophysiological assessment. Evaluation of sensory and motor recovery was performed using the pinprick assay and sciatic functional index. The Cell Counting Kit-8 assay and Western blotting were used to assess the proliferation and neurotrophic expression of RSC 96 Schwann cells. Miconazole promoted axonal regrowth, increased myelinated nerve fibers, improved sensory recovery and walking behavior, enhanced stimulated amplitude and nerve conduction velocity, and elevated proliferation and neurotrophic expression of RSC 96 Schwann cells. Miconazole was beneficial for nerve regeneration and functional recovery after peripheral nerve injury. Muscle Nerve 57: 821-828, 2018. © 2017 Wiley Periodicals, Inc.

  6. Demyelinating polyneuropathy with focally folded myelin sheaths in a family of Miniature Schnauzer dogs.

    Science.gov (United States)

    Vanhaesebrouck, An E; Couturier, Jérôme; Cauzinille, Laurent; Mizisin, Andrew P; Shelton, G Diane; Granger, Nicolas

    2008-12-15

    A spontaneous demyelinating polyneuropathy in two young Miniature Schnauzer dogs was characterized clinically, electrophysiologically and histopathologically. Both dogs were related and a third dog, belonging to the same family, had similar clinical signs. On presentation, clinical signs were restricted to respiratory dysfunction. Electrophysiological tests showed a dramatic decrease in both motor and sensory nerve conduction velocities. Microscopic examination of peripheral nerve biopsies (light and electron microscopy, teased nerve fibers), showed that this neuropathy was characterized by segmental demyelination and focally folded myelin sheaths. Various clinical syndromes associated with tomacula or focal thickening of the myelin sheath of the peripheral nerves have been described in humans and shown to be caused by gene mutations affecting the myelin proteins, such as the hereditary neuropathy with liability to pressure palsies or the demyelinating forms of Charcot-Marie-Tooth disease. In animals, a tomaculous neuropathy has been reported in cattle and chickens but not in carnivores. Here we report a demyelinating peripheral neuropathy with tomacula in two Miniature Schnauzer dogs.

  7. [Morphology research of the rat sciatic nerve bridged by collage-heparin sulfate scaffold].

    Science.gov (United States)

    Wang, Shu-sen; Hu, Yun-yu; Luo, Zhuo-jing; Chen, Liang-wei; Liu, Hui-ling; Meng, Guo-lin; Lü, Rong; Xu, Xin-zhi

    2005-04-15

    To observe the treating effect of collage-heparin sulfate after the 10 mm rat sciatic nerve defect was bridged by it. A new kind of nervous tissue engineering scaffold was produced by freeze-drying technique from collagen-heparin sulfate. Thirty-two SD rats were randomly divided into A, B, C and D groups. Sciatic nerve defect in group A was bridged by collagen-heparin sulfate. In group B, sciatic nerve was bridged by auto-nerve transplantation. Group C was the blank control group. Animals in group D were normal. And 10 mm sciatic nerve defect was bridged in the experiment. Thirty-six weeks after the operation, the experimental animals were detected by HRP labeled retrograde trace, HE staining, toluidine staining, silvering staining, S100, GAP-43 and NF immunohistological staining, MBP immunofluorescence staining and transmission electron microscope to observe the nerve regeneration inducing effect of this new scaffold. Nine months after operation, the collage-heparin sulfate scaffold was replaced by newly regenerated nerve. The number of HRP labeled spinal cord anterior horn cells and the area of sensation nerve fiber at the posterior horn were similar with that was repaired by auto-nerve. GAP-43, NF and S100 labeled regenerated nerve fiber had passed the total scaffold and entered the distal terminal. The regenerated nerve fibers were paralleled, lineage arranged, coincide with the prearranged regenerating "channel" in the collagen-heparin sulfate scaffold. MBP immunofluorescence staining also proved that the newly regenerated nerve fiber could be ensheathed. In the experimental group, the area of myelinated nerve fiber and the thickness of the myelin sheath had no obvious difference with that of the group repaired by auto-nerve, except that the density of the regenerated myelinated sheath fiber was lower than that of the control group. Nervous tissue engineering scaffold produced by collagen-heparin sulfate can guide the regeneration of nerve fibers. The nerve

  8. 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

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

    Science.gov (United States)

    Liu, Huaqing; Shiryaev, Sergey A; Chernov, Andrei V; Kim, Youngsoon; Shubayev, Igor; Remacle, Albert G; Baranovskaya, Svetlana; Golubkov, Vladislav S; Strongin, Alex Y; Shubayev, Veronica I

    2012-06-07

    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. 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. These data implicate MBP as a novel mediator of pain. Furthermore, the action of MMPs expressed within 1 day post-injury is critical to the generation of tactile allodynia

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

    International Nuclear Information System (INIS)

    Vargas, V.; Vargas, R.; Marquez, G.; Vonasek, E.; Mateu, L.; Luzzati, V.; Borges, J.

    2000-01-01

    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.)

  11. After Nerve Injury, Lineage Tracing Shows That Myelin and Remak Schwann Cells Elongate Extensively and Branch to Form Repair Schwann Cells, Which Shorten Radically on Remyelination.

    Science.gov (United States)

    Gomez-Sanchez, Jose A; Pilch, Kjara S; van der Lans, Milou; Fazal, Shaline V; Benito, Cristina; Wagstaff, Laura J; Mirsky, Rhona; Jessen, Kristjan R

    2017-09-13

    There is consensus that, distal to peripheral nerve injury, myelin and Remak cells reorganize to form cellular columns, Bungner's bands, which are indispensable for regeneration. However, knowledge of the structure of these regeneration tracks has not advanced for decades and the structure of the cells that form them, denervated or repair Schwann cells, remains obscure. Furthermore, the origin of these cells from myelin and Remak cells and their ability to give rise to myelin cells after regeneration has not been demonstrated directly, although these conversions are believed to be central to nerve repair. Using genetic lineage-tracing and scanning-block face electron microscopy, we show that injury of sciatic nerves from mice of either sex triggers extensive and unexpected Schwann cell elongation and branching to form long, parallel processes. Repair cells are 2- to 3-fold longer than myelin and Remak cells and 7- to 10-fold longer than immature Schwann cells. Remarkably, when repair cells transit back to myelinating cells, they shorten ∼7-fold to generate the typically short internodes of regenerated nerves. The present experiments define novel morphological transitions in injured nerves and show that repair Schwann cells have a cell-type-specific structure that differentiates them from other cells in the Schwann cell lineage. They also provide the first direct evidence using genetic lineage tracing for two basic assumptions in Schwann cell biology: that myelin and Remak cells generate the elongated cells that build Bungner bands in injured nerves and that such cells can transform to myelin cells after regeneration. SIGNIFICANCE STATEMENT After injury to peripheral nerves, the myelin and Remak Schwann cells distal to the injury site reorganize and modify their properties to form cells that support the survival of injured neurons, promote axon growth, remove myelin-associated growth inhibitors, and guide regenerating axons to their targets. We show that the

  12. Chitin biological absorbable catheters bridging sural nerve grafts transplanted into sciatic nerve defects promote nerve regeneration.

    Science.gov (United States)

    Wang, Zhi-Yong; Wang, Jian-Wei; Qin, Li-Hua; Zhang, Wei-Guang; Zhang, Pei-Xun; Jiang, Bao-Guo

    2018-06-01

    To investigate the efficacy of chitin biological absorbable catheters in a rat model of autologous nerve transplantation. A segment of sciatic nerve was removed to produce a sciatic nerve defect, and the sural nerve was cut from the ipsilateral leg and used as a graft to bridge the defect, with or without use of a chitin biological absorbable catheter surrounding the graft. The number and morphology of regenerating myelinated fibers, nerve conduction velocity, nerve function index, triceps surae muscle morphology, and sensory function were evaluated at 9 and 12 months after surgery. All of the above parameters were improved in rats in which the nerve graft was bridged with chitin biological absorbable catheters compared with rats without catheters. The results of this study indicate that use of chitin biological absorbable catheters to surround sural nerve grafts bridging sciatic nerve defects promotes recovery of structural, motor, and sensory function and improves muscle fiber morphology. © 2018 John Wiley & Sons Ltd.

  13. The longitudinal epineural incision and complete nerve transection method for modeling sciatic nerve injury

    Directory of Open Access Journals (Sweden)

    Xing-long Cheng

    2015-01-01

    Full Text Available Injury severity, operative technique and nerve regeneration are important factors to consider when constructing a model of peripheral nerve injury. Here, we present a novel peripheral nerve injury model and compare it with the complete sciatic nerve transection method. In the experimental group, under a microscope, a 3-mm longitudinal incision was made in the epineurium of the sciatic nerve to reveal the nerve fibers, which were then transected. The small, longitudinal incision in the epineurium was then sutured closed, requiring no stump anastomosis. In the control group, the sciatic nerve was completely transected, and the epineurium was repaired by anastomosis. At 2 and 4 weeks after surgery, Wallerian degeneration was observed in both groups. In the experimental group, at 8 and 12 weeks after surgery, distinct medullary nerve fibers and axons were observed in the injured sciatic nerve. Regular, dense myelin sheaths were visible, as well as some scarring. By 12 weeks, the myelin sheaths were normal and intact, and a tight lamellar structure was observed. Functionally, limb movement and nerve conduction recovered in the injured region between 4 and 12 weeks. The present results demonstrate that longitudinal epineural incision with nerve transection can stably replicate a model of Sunderland grade IV peripheral nerve injury. Compared with the complete sciatic nerve transection model, our method reduced the difficulties of micromanipulation and surgery time, and resulted in good stump restoration, nerve regeneration, and functional recovery.

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

    Directory of Open Access Journals (Sweden)

    Yu-hui Kou

    2015-01-01

    Full Text Available Multiple-bud regeneration, i.e., multiple amplification, has been shown to exist in peripheral nerve regeneration. Multiple buds grow towards the distal nerve stump during proximal nerve fiber regeneration. Our previous studies have verified the limit and validity of multiple amplification of peripheral nerve regeneration using small gap sleeve bridging of small donor nerves to repair large receptor nerves in rodents. The present study sought to observe multiple amplification of myelinated nerve fiber regeneration in the primate peripheral nerve. Rhesus monkey models of distal ulnar nerve defects were established and repaired using muscular branches of the right forearm pronator teres. Proximal muscular branches of the pronator teres were sutured into the distal ulnar nerve using the small gap sleeve bridging method. At 6 months after suture, two-finger flexion and mild wrist flexion were restored in the ulnar-sided injured limbs of rhesus monkey. Neurophysiological examination showed that motor nerve conduction velocity reached 22.63 ± 6.34 m/s on the affected side of rhesus monkey. Osmium tetroxide staining demonstrated that the number of myelinated nerve fibers was 1,657 ± 652 in the branches of pronator teres of donor, and 2,661 ± 843 in the repaired ulnar nerve. The rate of multiple amplification of regenerating myelinated nerve fibers was 1.61. These data showed that when muscular branches of the pronator teres were used to repair ulnar nerve in primates, effective regeneration was observed in regenerating nerve fibers, and functions of the injured ulnar nerve were restored to a certain extent. Moreover, multiple amplification was subsequently detected in ulnar nerve axons.

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

    Science.gov (United States)

    Kou, Yu-Hui; Zhang, Pei-Xun; Wang, Yan-Hua; Chen, Bo; Han, Na; Xue, Feng; Zhang, Hong-Bo; Yin, Xiao-Feng; Jiang, Bao-Guo

    2015-01-01

    Multiple-bud regeneration, i.e., multiple amplification, has been shown to exist in peripheral nerve regeneration. Multiple buds grow towards the distal nerve stump during proximal nerve fiber regeneration. Our previous studies have verified the limit and validity of multiple amplification of peripheral nerve regeneration using small gap sleeve bridging of small donor nerves to repair large receptor nerves in rodents. The present study sought to observe multiple amplification of myelinated nerve fiber regeneration in the primate peripheral nerve. Rhesus monkey models of distal ulnar nerve defects were established and repaired using muscular branches of the right forearm pronator teres. Proximal muscular branches of the pronator teres were sutured into the distal ulnar nerve using the small gap sleeve bridging method. At 6 months after suture, two-finger flexion and mild wrist flexion were restored in the ulnar-sided injured limbs of rhesus monkey. Neurophysiological examination showed that motor nerve conduction velocity reached 22.63 ± 6.34 m/s on the affected side of rhesus monkey. Osmium tetroxide staining demonstrated that the number of myelinated nerve fibers was 1,657 ± 652 in the branches of pronator teres of donor, and 2,661 ± 843 in the repaired ulnar nerve. The rate of multiple amplification of regenerating myelinated nerve fibers was 1.61. These data showed that when muscular branches of the pronator teres were used to repair ulnar nerve in primates, effective regeneration was observed in regenerating nerve fibers, and functions of the injured ulnar nerve were restored to a certain extent. Moreover, multiple amplification was subsequently detected in ulnar nerve axons.

  16. 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

  17. Simulation of multipolar fiber selective neural stimulation using intrafascicular electrodes

    NARCIS (Netherlands)

    Meier, J.H.; Meier, Jan H.; Rutten, Wim; Zoutman, Arne E.; Boom, H.B.K.; Bergveld, Piet

    1992-01-01

    A realistic, quantitative model for the excitation of myelinated nerve fibers by intrafascicular electrodes is presented. It predicts the stimulatory regions of any configuration of any number of electrodes, positioned anywhere inside the fascicle. The model has two parts. First, the nerve fiber is

  18. Nerve endings in the heart of teleosts.

    Science.gov (United States)

    Kumar, S

    1979-01-01

    The nerve endings in the heart of fishes were studied using silver impregnation techniques. The heart chambers are profusely innervated by the sympathetic, parasympathetic (vagal) and postganglionic fibers of the intracardiac ganglia situated at the sinuatrial and the atrioventricular junctions. The plexuses are composed of medullated and nonmedullated fibers. The nerve fibers generally end freely and are slightly branched or unbranched terminations of myelinated and unmyelinated fibers. Moreover, a few nerve fibers end redundant in the form of end-rings, bulb-like, bush-like, club-shaped end end-coil like structures. The complex unencapsulated types of endings are also found in the myocardium of the atrium and the ventricle. The encapsulated endings (Vater-Pacinian; Krause end-bulb) could not be observed.

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

    Science.gov (United States)

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

    2011-02-06

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

  20. 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.

  1. 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)

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

    2012-08-15

    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. Copyright © 2012 Wiley Periodicals, Inc.

  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

    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...

  3. Sensation, mechanoreceptor, and nerve fiber function after nerve regeneration

    DEFF Research Database (Denmark)

    Krarup, Christian; Rosén, Birgitta; Boeckstyns, Michel

    2017-01-01

    Objective: Sensation is essential for recovery after peripheral nerve injury. However, the relationship between sensory modalities and function of regenerated fibers is uncertain. We have investigated the relationships between touch threshold, tactile gnosis, and mechanoreceptor and sensory fiber...... function after nerve regeneration. Methods: Twenty-one median or ulnar nerve lesions were repaired by a collagen nerve conduit or direct suture. Quantitative sensory hand function and sensory conduction studies by near-nerve technique, including tactile stimulation of mechanoreceptors, were followed for 2...... years, and results were compared to noninjured hands. Results: At both repair methods, touch thresholds at the finger tips recovered to 81 ± 3% and tactile gnosis only to 20 ± 4% (p nerve action potentials (SNAPs) remained dispersed and areas recovered to 23 ± 2...

  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. 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

    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.......The γ-aminobutyric acid (GABA) type B receptor has been implicated in glial cell development in the peripheral nervous system (PNS), although the exact function of GABA signaling is not known. To investigate GABA and its B receptor in PNS development and degeneration, we studied the expression...

  6. Functional and structural microanatomy of the fetal sciatic nerve.

    Science.gov (United States)

    Creze, Maud; Zaitouna, Mazen; Krystel, Nyangoh Timoh; Diallo, Djibril; Lebacle, Cédric; Bellin, Marie-France; Ducreux, Denis; Benoit, Gérard; Bessede, Thomas

    2017-10-01

    The ultrastructure of a nerve has implications for surgical nerve repair. The aim of our study was to characterize the fascicular versus fibrillar anatomy and the autonomic versus somatic nature of the fetal sciatic nerve (SN). Immunohistochemistry for vesicular acetylcholine transporter, tyrosine hydroxylase, and peripheral myelin protein 22 was performed to identify cholinergic, adrenergic, and somatic axons, respectively, in the human fetal SN. Two-dimensional (2D) analysis and 3D reconstructions were performed. The fetal SN is composed of one-third stromal tissue and two-thirds neural tissue. Autonomic fibers are predominant over somatic fibers within the neural tissue. The distribution of somatic fibers is initially random, but then become topographically organized after intra- and interfascicular rearrangements have occurred within the nerve. The fetal model presents limitations but enables illustration of the nature of the nerve fibers and the 3D fascicular anatomy of the SN. Muscle Nerve 56: 787-796, 2017. © 2017 Wiley Periodicals, Inc.

  7. 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.

  8. A Novel Approach for Studying the Physiology and Pathophysiology of Myelinated and Non-Myelinated Axons in the CNS White Matter.

    Directory of Open Access Journals (Sweden)

    Lijun Li

    Full Text Available Advances in brain connectomics set the need for detailed knowledge of functional properties of myelinated and non-myelinated (if present axons in specific white matter pathways. The corpus callosum (CC, a major white matter structure interconnecting brain hemispheres, is extensively used for studying CNS axonal function. Unlike another widely used CNS white matter preparation, the optic nerve where all axons are myelinated, the CC contains also a large population of non-myelinated axons, making it particularly useful for studying both types of axons. Electrophysiological studies of optic nerve use suction electrodes on nerve ends to stimulate and record compound action potentials (CAPs that adequately represent its axonal population, whereas CC studies use microelectrodes (MEs, recording from a limited area within the CC. Here we introduce a novel robust isolated "whole" CC preparation comparable to optic nerve. Unlike ME recordings where the CC CAP peaks representing myelinated and non-myelinated axons vary broadly in size, "whole" CC CAPs show stable reproducible ratios of these two main peaks, and also reveal a third peak, suggesting a distinct group of smaller caliber non-myelinated axons. We provide detailed characterization of "whole" CC CAPs and conduction velocities of myelinated and non-myelinated axons along the rostro-caudal axis of CC body and show advantages of this preparation for comparing axonal function in wild type and dysmyelinated shiverer mice, studying the effects of temperature dependence, bath-applied drugs and ischemia modeled by oxygen-glucose deprivation. Due to the isolation from gray matter, our approach allows for studying CC axonal function without possible "contamination" by reverberating signals from gray matter. Our analysis of "whole" CC CAPs revealed higher complexity of myelinated and non-myelinated axonal populations, not noticed earlier. This preparation may have a broad range of applications as a robust

  9. 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.

  10. Characterization of nerve and microvessel damage and recovery in type 1 diabetic mice after permanent femoral artery ligation.

    Science.gov (United States)

    Lozeron, Pierre; Mantsounga, Chris S; Broqueres-You, Dong; Dohan, Anthony; Polivka, Marc; Deroide, Nicolas; Silvestre, Jean-Sébastien; Kubis, Nathalie; Lévy, Bernard I

    2015-09-01

    Neuropathy is the most common complication of the peripheral nervous system during the progression of diabetes. The pathophysiology is unclear but may involve microangiopathy, reduced endoneurial blood flow, and tissue ischemia. We used a mouse model of type 1 diabetes to study parallel alterations of nerves and microvessels following tissue ischemia. We designed an easily reproducible model of ischemic neuropathy induced by irreversible ligation of the femoral artery. We studied the evolution of behavioral function, epineurial and endoneurial vessel impairment, and large nerve myelinated fiber as well as small cutaneous unmyelinated fiber impairment for 1 month following the onset of ischemia. We observed a more severe hindlimb dysfunction and delayed recovery in diabetic animals. This was associated with reduced density of large arteries in the hindlimb and reduced sciatic nerve epineurial blood flow. A reduction in sciatic nerve endoneurial capillary density was also observed, associated with a reduction in small unmyelinated epidermal fiber number and large myelinated sciatic nerve fiber dysfunction. Moreover, vascular recovery was delayed, and nerve dysfunction was still present in diabetic animals at day 28. This easily reproducible model provides clear insight into the evolution over time of the impact of ischemia on nerve and microvessel homeostasis in the setting of diabetes. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  11. Promoting peripheral myelin repair.

    Science.gov (United States)

    Zhou, Ye; Notterpek, Lucia

    2016-09-01

    Compared to the central nervous system (CNS), peripheral nerves have a remarkable ability to regenerate and remyelinate. This regenerative capacity to a large extent is dependent on and supported by Schwann cells, the myelin-forming glial cells of the peripheral nervous system (PNS). In a variety of paradigms, Schwann cells are critical in the removal of the degenerated tissue, which is followed by remyelination of newly-regenerated axons. This unique plasticity of Schwann cells has been the target of myelin repair strategies in acute injuries and chronic diseases, such as hereditary demyelinating neuropathies. In one approach, the endogenous regenerative capacity of Schwann cells is enhanced through interventions such as exercise, electrical stimulation or pharmacological means. Alternatively, Schwann cells derived from healthy nerves, or engineered from different tissue sources have been transplanted into the PNS to support remyelination. These transplant approaches can then be further enhanced by exercise and/or electrical stimulation, as well as by the inclusion of biomaterial engineered to support glial cell viability and neurite extension. Advances in our basic understanding of peripheral nerve biology, as well as biomaterial engineering, will further improve the functional repair of myelinated peripheral nerves. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. 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.

  13. Adipose-derived mesenchymal stem cells accelerate nerve regeneration and functional recovery in a rat model of recurrent laryngeal nerve injury

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    Yun Li

    2017-01-01

    Full Text Available Medialization thyroplasty or injection laryngoplasty for unilateral vocal fold paralysis cannot restore mobility of the vocal fold. Recent studies have shown that transplantation of mesenchymal stem cells is effective in the repair of nerve injuries. This study investigated whether adipose-derived stem cell transplantation could repair recurrent laryngeal nerve injury. Rat models of recurrent laryngeal nerve injury were established by crushing with micro forceps. Adipose-derived mesenchymal stem cells (ADSCs; 8 × 105 or differentiated Schwann-like adipose-derived mesenchymal stem cells (dADSCs; 8 × 105 or extracellular matrix were injected at the site of injury. At 2, 4 and 6 weeks post-surgery, a higher density of myelinated nerve fiber, thicker myelin sheath, improved vocal fold movement, better recovery of nerve conduction capacity and reduced thyroarytenoid muscle atrophy were found in ADSCs and dADSCs groups compared with the extracellular matrix group. The effects were more pronounced in the ADSCs group than in the dADSCs group. These experimental results indicated that ADSCs transplantation could be an early interventional strategy to promote regeneration after recurrent laryngeal nerve injury.

  14. Peripheral myelin protein 22 alters membrane architecture

    Science.gov (United States)

    Mittendorf, Kathleen F.; Marinko, Justin T.; Hampton, Cheri M.; Ke, Zunlong; Hadziselimovic, Arina; Schlebach, Jonathan P.; Law, Cheryl L.; Li, Jun; Wright, Elizabeth R.; Sanders, Charles R.; Ohi, Melanie D.

    2017-01-01

    Peripheral myelin protein 22 (PMP22) is highly expressed in myelinating Schwann cells of the peripheral nervous system. PMP22 genetic alterations cause the most common forms of Charcot-Marie-Tooth disease (CMTD), which is characterized by severe dysmyelination in the peripheral nerves. However, the functions of PMP22 in Schwann cell membranes remain unclear. We demonstrate that reconstitution of purified PMP22 into lipid vesicles results in the formation of compressed and cylindrically wrapped protein-lipid vesicles that share common organizational traits with compact myelin of peripheral nerves in vivo. The formation of these myelin-like assemblies depends on the lipid-to-PMP22 ratio, as well as on the PMP22 extracellular loops. Formation of the myelin-like assemblies is disrupted by a CMTD-causing mutation. This study provides both a biochemical assay for PMP22 function and evidence that PMP22 directly contributes to membrane organization in compact myelin. PMID:28695207

  15. Myelin injury in the central nervous system and Alzheimer's diseases.

    Science.gov (United States)

    Wang, Sha-Sha; Zhang, Zhao; Zhu, Tian-Bi; Chu, Shi-Feng; He, Wen-Bin; Chen, Nai-Hong

    2018-05-03

    Myelin is a membrane wrapped around the axon of the nerve cell, which is composed of the mature oligodendrocytes. The role of myelin is to insulate and prevent the nerve electrical impulses from the axon of the neurons to the axons of the other neurons, which is essential for the proper functioning of the nervous system. Minor changes in myelin thickness could lead to substantial changes in conduction speed and may thus alter neural circuit function. Demyelination is the myelin damage, which characterized by the loss of nerve sheath and the relative fatigue of the neuronal sheath and axon. Studies have shown that myelin injury may be closely related to neurodegenerative diseases and may be an early diagnostic criteria and therapeutic target. Thus this review summarizes the recent result of pathologic effect and signal pathways of myelin injury in neurodegenerative diseases, especially the Alzheimer's disease to provide new and effective therapeutic targets. Copyright © 2018. Published by Elsevier Inc.

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

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    Hernán Hurtado

    2000-04-01

    Full Text Available 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 función de la extremidad inferior. 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

  17. Short-term low-frequency electrical stimulation enhanced remyelination of injured peripheral nerves by inducing the promyelination effect of brain-derived neurotrophic factor on Schwann cell polarization.

    Science.gov (United States)

    Wan, Lidan; Xia, Rong; Ding, Wenlong

    2010-09-01

    Electrical stimulation (ES) has been found to aid repair of nerve injuries and have been shown to increase and direct neurite outgrowth during stimulation. However, the effect of ES on peripheral remyelination after nerve damage has been investigated less well, and the mechanism underlying its action remains unclear. In the present study, the crush-injured sciatic nerves in rats were subjected to 1 hr of continuous ES (20 Hz, 100 microsec, 3 V). Electron microscopy and nerve morphometry were performed to investigate the extent of regenerated nerve myelination. The expression profiles of P0, Par-3, and brain-derived neurotrophic factor (BDNF) in the injuried sciatic nerves and in the dorsal root ganglion neuron/Schwann cell cocultures were examined by Western blotting. Par-3 localization in the sciatic nerves was determined by immunohistochemistry to demonstrate Schwann cell polarization during myelination. We reported that 20-Hz ES increased the number of myelinated fibers and the thickness myelin sheath at 4 and 8 weeks postinjury. P0 level in the ES-treated groups, both in vitro and in vivo, was enhanced compared with the controls. The earlier peak of Par-3 in the ES-treated groups indicated an earlier initiation of Schwann cell myelination. Additionally, ES significantly elevated BDNF expression in nerve tissues and in cocultures. ES on the site of nerve injury potentiates axonal regrowth and myelin maturation during peripheral nerve regeneration. Furthermore, the therapeutic actions of ES on myelination are mediated via enhanced BDNF signals, which drive the promyelination effect on Schwann cells at the onset of myelination.

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

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    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.

  19. MORPHOLOGICAL ADJUSTMENTS OF THE RADIAL NERVE ARE INTENSITY-DEPENDENT

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    Patrícia Oliva Carbone

    Full Text Available ABSTRACT Introduction: Peripheral nerve adaptation is critical for strength gains. However, information about intensity effects on nerve morphology is scarce. Objective: To compare the effects of different intensities of resistance training on radial nerve structures. Methods: Rats were divided into three groups: control (GC, training with 50% (GF1 and training 75% (GF2 of the animal’s body weight. The morphological analysis of the nerve was done by light and transmission electron microscopy. One-way ANOVA and the Tukey’s post hoc test were applied and the significance level was set at p≤0.05. Results: Training groups had an increase of strength compared to GC (p≤0.05. All measured nerve components (mean area and diameter of myelin fibers and axons, mean area and thickness of the myelin sheath, and of neurofilaments and microtubules were higher in GF2 compared to the other (p≤0.05. Conclusion: Results demonstrated greater morphological changes on radial nerve after heavier loads. This can be important for rehabilitation therapies, training, and progression.

  20. N,N-diethyldithiocarbamate promotes oxidative stress prior to myelin structural changes and increases myelin copper content

    International Nuclear Information System (INIS)

    Viquez, Olga M.; Lai, Barry; Ahn, Jae Hee; Does, Mark D.; Valentine, Holly L.; Valentine, William M.

    2009-01-01

    Dithiocarbamates are a commercially important class of compounds that can produce peripheral neuropathy in humans and experimental animals. Previous studies have supported a requirement for copper accumulation and enhanced lipid peroxidation in dithiocarbamate-mediated myelinopathy. The study presented here extends previous investigations in two areas. Firstly, although total copper levels have been shown to increase within the nerve it has not been determined whether copper is increased within the myelin compartment, the primary site of lesion development. Therefore, the distribution of copper in sciatic nerve was characterized using synchrotron X-ray fluorescence microscopy to determine whether the neurotoxic dithiocarbamate, N,N-diethyldithiocarbamate, increases copper levels in myelin. Secondly, because lipid peroxidation is an ongoing process in normal nerve and the levels of lipid peroxidation products produced by dithiocarbamate exposure demonstrated an unusual cumulative dose response in previous studies the biological impact of dithiocarbamate-mediated lipid peroxidation was evaluated. Experiments were performed to determine whether dithiocarbamate-mediated lipid peroxidation products elicit an antioxidant response through measuring the protein expression levels of three enzymes, superoxide dismutase 1, heme oxygenase 1, and glutathione transferase α, that are linked to the antioxidant response element promoter. To establish the potential of oxidative injury to contribute to myelin injury the temporal relationship of the antioxidant response to myelin injury was determined. Myelin structure in peripheral nerve was assessed using multi-exponential transverse relaxation measurements (MET 2 ) as a function of exposure duration, and the temporal relationship of protein expression changes relative to the onset of changes in myelin integrity were determined. Initial assessments were also performed to explore the potential contribution of dithiocarbamate

  1. 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

  2. The effect of methylprednisolone on facial nerve paralysis with different etiologies.

    Science.gov (United States)

    Yildirim, Mehmet Akif; Karlidag, Turgut; Akpolat, Nusret; Kaygusuz, Irfan; Keles, Erol; Yalcin, Sinasi; Akyigit, Abdulvahap

    2015-05-01

    The objective of this study was to evaluate the effectiveness of methylprednisolone (MP) in models of facial nerve paralysis obtained by nerve section, compression, or inoculation with herpes simplex virus (HSV). Experimental controlled animal study. Tertiary referral center. A total of 30 female New Zealand rabbits weighing 1200-3000 g were used for the study. They were randomly assigned to one of 6 groups of 5 animals each. A nerve section injury was realized in Groups 1a (section and MP) and 1b (section, control) rabbits. A compression-type injury was inflicted to rabbits in Groups 2a (compression and MP) and 2b (compression, control). As for animals in Groups 3a (Type 1 HSV and MP) and 3b (Type 1 HSV, controls), facial nerve paralysis resulting from viral infection was obtained. Animals in the 3 treatment groups, designated with the letter "a", were administered MP, 1 mg/kg/d, whereas those in control groups "b" received 1 mL normal saline, both during 3 weeks. All subjects were followed up for 2 months. At the end of this period, all animals had the buccal branch of the facial nerve excised on the operated side. Semi-thin sections of these specimens were evaluated under light microscopy for the following: perineural fibrosis, increase in collagen fibers, myelin degeneration, axonal degeneration, Schwann cell proliferation, and edema. No significant difference was observed (P > 0.05) between the MP treatment group and the control group with regard to perineural fibrosis, increase in collagen fibers, myelin degeneration, axonal degeneration, edema, or Schwann cell proliferation. In the group with a compressive lesion (Group 2), controls were no different from MP-treated animals as to perineural fibrosis, increase in collagen fibers, or Schwann cell proliferation, whereas axonal degeneration, myelin degeneration, and edema were significantly higher (P facial nerve palsy, we may say that this drug was without effect on nerve healing in paralysis due to nerve

  3. What is the optimal value of the g-ratio for myelinated fibers in the rat CNS? A theoretical approach.

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    Taylor Chomiak

    2009-11-01

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

  4. What is the optimal value of the g-ratio for myelinated fibers in the rat CNS? A theoretical approach.

    Science.gov (United States)

    Chomiak, Taylor; Hu, Bin

    2009-11-13

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

  5. Response properties of the refractory auditory nerve fiber.

    Science.gov (United States)

    Miller, C A; Abbas, P J; Robinson, B K

    2001-09-01

    The refractory characteristics of auditory nerve fibers limit their ability to accurately encode temporal information. Therefore, they are relevant to the design of cochlear prostheses. It is also possible that the refractory property could be exploited by prosthetic devices to improve information transfer, as refractoriness may enhance the nerve's stochastic properties. Furthermore, refractory data are needed for the development of accurate computational models of auditory nerve fibers. We applied a two-pulse forward-masking paradigm to a feline model of the human auditory nerve to assess refractory properties of single fibers. Each fiber was driven to refractoriness by a single (masker) current pulse delivered intracochlearly. Properties of firing efficiency, latency, jitter, spike amplitude, and relative spread (a measure of dynamic range and stochasticity) were examined by exciting fibers with a second (probe) pulse and systematically varying the masker-probe interval (MPI). Responses to monophasic cathodic current pulses were analyzed. We estimated the mean absolute refractory period to be about 330 micros and the mean recovery time constant to be about 410 micros. A significant proportion of fibers (13 of 34) responded to the probe pulse with MPIs as short as 500 micros. Spike amplitude decreased with decreasing MPI, a finding relevant to the development of computational nerve-fiber models, interpretation of gross evoked potentials, and models of more central neural processing. A small mean decrement in spike jitter was noted at small MPI values. Some trends (such as spike latency-vs-MPI) varied across fibers, suggesting that sites of excitation varied across fibers. Relative spread was found to increase with decreasing MPI values, providing direct evidence that stochastic properties of fibers are altered under conditions of refractoriness.

  6. Nerves and nerve endings in the skin of tropical cattle.

    Science.gov (United States)

    Amakiri, S F; Ozoya, S E; Ogunnaike, P O

    1978-01-01

    The nerves and nerve endings in the skin of tropical cattle were studied using histological and histochemical techniques. Many nerve trunks and fibres were present in the reticular and papillary dermis in both hairy and non-hairy skin sites. In non-hairy skin locations such as the muzzle and lower lip, encapsulated endings akin to Krause and Ruffini end bulbs, which arise from myelinated nerve trunks situated lower down the dermis were observed at the upper papillary layer level. Some fibre trunks seen at this level extended upwards to terminate within dermal papillae as bulb-shaped longitudinally lamellated Pacinian-type endings, while other onion-shaped lamellated nerve structures were located either within dermal papillae or near the dermo-epidermal area. Intraepidermal free-ending nerve fibres, appearing non-myelinated were observed in areas with thick epidermis. Intraepidermal free-ending nerve fibres, appearing non-myelinated were observed in areas with thick epidermis. On hairy skin sites, however, organized nerve endings or intraepidermal nerve endings were not readily identifiable.

  7. Curcumin accelerates the repair of sciatic nerve injury in rats through reducing Schwann cells apoptosis and promoting myelinization.

    Science.gov (United States)

    Zhao, Zhiwei; Li, Xiaoling; Li, Qing

    2017-08-01

    Schwann cells (SCs) play an indispensable role in the repair and regeneration of injured peripheral nerve. Curcumin can reduce SCs apoptosis, and promote the regeneration and functional recovery of injured peripheral nerves. However, the corresponding mechanisms are not clear. The article was aimed to explore the effect and corresponding mechanisms of curcumin on the repair of sciatic nerve injury in rats. After surgery induced sciatic nerve injury, the model rats were divided into three groups and treated with curcumin, curcumin+PD98059 and curcumin+IGF-1 respectively for 4days. The phosphorylation of Erk1/2 and Akt, and the expression of LC3-II, Beclin 1 and p62 were measured using western blotting. After treatment for 60days, myelination of the injured sciatic nerve was evaluated by MBP immunohistochemical staining and the expression of PMP22, Fibrin and S100 were determined using qRT-PCR and western blotting. In vitro, RSC96 cells were starved for 12h to induce autophagy, and received DMSO, curcumin, PD98059+curcumin, IGF-1+curcumin and BFA1 respectively. The phosphorylation of Erk1/2、Akt and the expression of LC3-II, Beclin 1, p62, PMP22, Fibrin and S100 were measured using western blotting, and the cell apoptosis was detected by flow cytometry. Curcumin could promote injury-induced cell autophagy, remyelination and axon regeneration in sciatic nerve of rats. In vitro, curcumin could accelerate cell autophagy through regulating autophagy related Erk1/2 and Akt pathway, prevent cell apoptosis and promote expression of PMP22 and S100, and reduced deposition of Fibrin in cultured RSC96 SCs. Curcumin could accelerate injured sciatic nerve repair in rats through reducing SCs apoptosis and promoting myelinization. Copyright © 2017. Published by Elsevier Masson SAS.

  8. 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.

  9. 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.

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

    Science.gov (United States)

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

    2016-01-01

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

  11. 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.

  12. [Experimental study on regeneration of sciatic nerve injury with physical therapy].

    Science.gov (United States)

    Zhao, Juan; Yu, Hong; Xu, Yiming; Bai, Yuehong

    2011-01-01

    Peripheral nerve injury is a common clinical disease, to study the effects of the physical therapy on the regeneration of the injured sciatic nerve, and provide a reference for clinical treatment. Sixty-four female adult Wistar rats (weighing 252-365 g) were chosen and randomly divided into 4 groups (n = 16): group A, group B, group C, and group D. The experimental model of sciatic nerve defect was established by crushing the right sciatic nerve in groups B, C, and D; group A served as the control group without crushing. At 2 days after injury, no treatment was given in group B, electrical stimulation in group C, and combined physical therapies (decimeter and infrared ray) in group D. At 0, 7, 14, and 30 days after treatment, the sciatic nerve function index (SFI) and the motor nerve conduction velocity (MNCV) were measured, and morphological and transmission electron microscopy (TEM) examinations were done; at 30 days after treatment, the morphological evaluation analysis of axons was performed. At 0 and 7 days after treatment, the SFI values of groups B, C, and D were significantly higher than that of group A (P 0.05) at 30 days; whereas the SFI values of groups B and C decreased, showing significant difference when compared with the value of group A (P 0.05). At 0 and 7 days, only collagen and lipid were observed by TEM; at 14 and 30 days, many Schwann cells and perineurial cells in regeneration axon were observed in groups B, C, and D, especially in group D. Automated image analysis of axons showed that there was no significant difference in the number of myelinated nerve fibers, axon diameter, and myelin sheath thickness between group D and group A (P > 0.05), and the number of myelinated nerve fibers and axon diameter of group D were significantly higher than those of groups B and C (P < 0.05). Physical therapy can improve the regeneration of the injured sciatic nerve of rats.

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

    OpenAIRE

    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 fiber regeneration. Our previous studies have verified the limit and validity of multiple amplification of peripheral nerve regeneration using small gap sleeve bridging of small donor nerves to repair large receptor nerves in rodents. The present study sought to observe multiple amplification of myelinated ne...

  14. Remarkable Stability of Myelinating Oligodendrocytes in Mice

    Directory of Open Access Journals (Sweden)

    Richa B. Tripathi

    2017-10-01

    Full Text Available New myelin-forming oligodendrocytes (OLs are generated in the mouse central nervous system during adulthood. These adult-born OLs might augment the existing population, contributing to neural plasticity, or else replace OLs that die in use (turnover. To distinguish between these alternatives, we induced genetic labeling of mature myelinating OLs in young adult mice and tracked their subsequent survival. OL survival rates were region dependent, being higher in corpus callosum (∼90% survival over 20 months and motor cortex (∼70% survival than in corticospinal tract or optic nerve (50%–60% survival. Survival rates over the first 8 months were 90%–100% in all regions except the optic nerve. In the corpus callosum, new OLs accumulate during young adulthood and are therefore likely to participate in adaptive myelination. We also found that the number of myelin internodes maintained by individual cortical OLs is stable for at least 8 months but declines ∼12% in the following year.

  15. 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.

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

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    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

  17. Neuronal Regulation of Schwann Cell Mitochondrial Ca(2+) Signaling during Myelination.

    Science.gov (United States)

    Ino, Daisuke; Sagara, Hiroshi; Suzuki, Junji; Kanemaru, Kazunori; Okubo, Yohei; Iino, Masamitsu

    2015-09-29

    Schwann cells (SCs) myelinate peripheral neurons to promote the rapid conduction of action potentials, and the process of myelination is known to be regulated by signals from axons to SCs. Given that SC mitochondria are one of the potential regulators of myelination, we investigated whether SC mitochondria are regulated by axonal signaling. Here, we show a purinergic mechanism that sends information from neurons to SC mitochondria during myelination. Our results show that electrical stimulation of rat sciatic nerve increases extracellular ATP levels enough to activate purinergic receptors. Indeed, electrical stimulation of sciatic nerves induces Ca(2+) increases in the cytosol and the mitochondrial matrix of surrounding SCs via purinergic receptor activation. Chronic suppression of this pathway during active myelination suppressed the longitudinal and radial development of myelinating SCs and caused hypomyelination. These results demonstrate a neuron-to-SC mitochondria signaling, which is likely to have an important role in proper myelination. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Neuronal Regulation of Schwann Cell Mitochondrial Ca2+ Signaling during Myelination

    Directory of Open Access Journals (Sweden)

    Daisuke Ino

    2015-09-01

    Full Text Available Schwann cells (SCs myelinate peripheral neurons to promote the rapid conduction of action potentials, and the process of myelination is known to be regulated by signals from axons to SCs. Given that SC mitochondria are one of the potential regulators of myelination, we investigated whether SC mitochondria are regulated by axonal signaling. Here, we show a purinergic mechanism that sends information from neurons to SC mitochondria during myelination. Our results show that electrical stimulation of rat sciatic nerve increases extracellular ATP levels enough to activate purinergic receptors. Indeed, electrical stimulation of sciatic nerves induces Ca2+ increases in the cytosol and the mitochondrial matrix of surrounding SCs via purinergic receptor activation. Chronic suppression of this pathway during active myelination suppressed the longitudinal and radial development of myelinating SCs and caused hypomyelination. These results demonstrate a neuron-to-SC mitochondria signaling, which is likely to have an important role in proper myelination.

  19. Alterations of sympathetic nerve fibers in avascular necrosis of femoral head.

    Science.gov (United States)

    Li, Deqiang; Liu, Peilai; Zhang, Yuankai; Li, Ming

    2015-01-01

    Avascular necrosis of the femoral head (ANFH) was mainly due to alterations of bone vascularity. And noradrenaline (NA), as the neurotransmitter of the sympathetic nervous system (SNS), leads to the vasoconstriction by activating its α-Receptor. This study was to explore the nerve fiber density of the femoral head in the rabbit model of ANFH. Twenty New Zealand white rabbits were used in this study. The rabbit model of ANFH was established by the injection of methylprednisolone acetate. The nerve fiber density and distribution in the femoral head was determined using an Olympus BH2 microscope. Significant fewer sympathetic nerve fibers was found in the ANFH intertrochanteric bone samples (P = 0.036) with osteonecrosis. The number of sympathetic nerve fibers was compared between the two groups. And less sympathetic nerve fibers were found in later stage ANFH samples in comparison with those of early stages. ANFH might be preceded by an inflammatory reaction, and an inflammatory response might lead to arthritic changes in tissue samples, which in turn reduces the number of sympathetic nerve fibers.

  20. 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. (pparesthesia (post-traumatic neuropathy).

  1. Diagnostic capability of optic nerve head rim width and retinal nerve fiber thickness in open-angle glaucoma.

    Science.gov (United States)

    Di Staso, Silvio; Agnifili, Luca; Di Staso, Federico; Climastone, Hilary; Ciancaglini, Marco; Scuderi, Gian Luca

    2018-03-01

    This study was performed to test the diagnostic capability of the minimum rim width compared to peripapillary retinal nerve fiber layer thickness in patients with glaucoma. A case control, observer masked study, was conducted. Minimum rim width and retinal nerve fiber layer thickness were assessed using the patient-specific axis traced between fovea-to-Bruch's membrane opening center axis. For both minimum rim width and retinal nerve fiber layer thickness, the regionalization in six sectors (nasal, superior-nasal, superior-temporal, temporal, inferior-temporal, and inferior-nasal) was analyzed. Eyes with at least one sector with value below the 5% or 1% normative limit of the optical coherence tomography normative database were classified as glaucomatous. The area under the receiver operator characteristic curve, the accuracy, sensitivity, specificity, and predictive positive and negative values were calculated for both minimum rim width and retinal nerve fiber layer thickness. A total of 118 eyes of 118 Caucasian subjects (80 eyes with open-angle glaucoma and 38 control eyes) were enrolled in the study. Accuracy, sensitivity, and specificity were 79.7%, 77.5%, and 84.2%, respectively, for minimum rim width and 84.7%, 82.5%, and 89.5% for retinal nerve fiber layer thickness. The positive predictive values were 0.91% and 0.94% for minimum rim width and retinal nerve fiber layer thickness, respectively, whereas the negative predictive values were 0.64% and 0.70%. The area under the receiver operator characteristic curve was 0.892 for minimum rim width and 0.938 for retinal nerve fiber layer thickness. Our results indicated that the sector analysis based on Bruch's membrane opening and fovea to disk alignment is able to detect glaucomatous defects, and that Bruch's membrane opening minimum rim width and retinal nerve fiber layer thickness showed equivalent diagnostic ability.

  2. Depth-sensing nano-indentation on a myelinated axon at various stages

    International Nuclear Information System (INIS)

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

    2011-01-01

    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.

  3. A novel approach to 32-channel peripheral nervous system myelin imaging in vivo, with single axon resolution.

    Science.gov (United States)

    Grochmal, Joey; Teo, Wulin; Gambhir, Hardeep; Kumar, Ranjan; Stratton, Jo Anne; Dhaliwal, Raveena; Brideau, Craig; Biernaskie, Jeff; Stys, Peter K; Midha, Rajiv

    2018-01-19

    OBJECTIVE Intravital spectral imaging of the large, deeply situated nerves in the rat peripheral nervous system (PNS) has not been well described. Here, the authors have developed a highly stable platform for performing imaging of the tibial nerve in live rodents, thus allowing the capture of high-resolution, high-magnification spectral images requiring long acquisition times. By further exploiting the qualities of the topically applied myelin dye Nile red, this technique is capable of visualizing the detailed microenvironment of peripheral nerve demyelination injury and recovery, while allowing us to obtain images of exogenous Schwann cell myelination in a living animal. METHODS The authors caused doxorubicin-induced focal demyelination in the tibial nerves of 25 Thy-1 GFP rats, of which 2 subsets (n = 10 each) received either BFP-labeled SKP-SCs or SCs to the zone of injury. Prior to acquiring images of myelin recovery in these nerves, a tibial nerve window was constructed using a silicone hemitube, a fast drying silicone polymer, and a small coverslip. This construct was then affixed to a 3D-printed nerve stage, which in turn was affixed to an external fixation/microscope stage device. Myelin visualization was facilitated by the topical application of Nile red. RESULTS The authors reliably demonstrated intravital peripheral nerve myelin imaging with micron-level resolution and magnification, and minimal movement artifact. The detailed microenvironment of nerve remyelination can be vividly observed, while exogenously applied Schwann cells and skin-derived precursor Schwann cells can be seen myelinating axons. CONCLUSIONS Topically applied Nile red enables intravital study of myelin in the living rat PNS. Furthermore, the use of a tibial nerve window facilitates stable intravital peripheral nerve imaging, making possible high-definition spectral imaging with long acquisition times.

  4. 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

  5. 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

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

    International Nuclear Information System (INIS)

    Escobar, Antonio S.; Ocampo, Arcelia F. M.; Hernandez, Maria G. H.; Jasso, Jose L. C.; Lira, Maricela O. F.; Flores, Mariana A.; Balderrama, Vicente L.

    2010-01-01

    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 (p 000), 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. 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.

  8. Pure neuritic leprosy: Resolving diagnostic issues in acid fast bacilli (AFB)-negative nerve biopsies: A single centre experience from South India.

    Science.gov (United States)

    Hui, Monalisa; Uppin, Megha S; Challa, Sundaram; Meena, A K; Kaul, Subhash

    2015-01-01

    Demonstration of lepra bacilli is essential for definite or unequivocal diagnosis of pure neuritic leprosy (PNL) on nerve biopsy. However, nerves always do not show bacilli owing to the changes of previous therapy or due to low bacillary load in tuberculoid forms. In absence of granuloma or lepra bacilli, other morphologic changes in endoneurium and perineurium can be of help in making a probable diagnosis of PNL and treating the patient with multidrug therapy. Forty-six biopsies of PNL were retrospectively reviewed and histologic findings were compared with 25 biopsies of non leprosy neuropathies (NLN) including vasculitic neuropathy and chronic inflammatory demyelinating polyneuropathy (CIDP). The distribution of endoneurial infiltrate and fibrosis, perineurial thickening, and myelin abnormalities were compared between PNL and NLN biopsies and analyzed by Chi-square test. Out of 46 PNL casses, 24 (52.17 %) biopsies were negative for acid fast bacilli (AFB). In these cases, the features which favor a diagnosis of AFB-negative PNL were endoneurial infiltrate (51.1%), endoneurial fibrosis (54.2%), perineurial thickening (70.8%), and reduced number of myelinated nerve fibers (75%). Nerve biopsy is an efficient tool to diagnose PNL and differentiate it from other causes of NLN. In absence of AFB, the diagnosis of PNL is challenging. In this article, we have satisfactorily evaluated the various hisopthological features and found that endoneurial inflammation, dense fibrosis, and reduction in the number of myelinated nerve fibers are strong supportive indicators of PNL regardless of AFB positivity.

  9. Nerve Fiber Flux Analysis Using Wide-Field Swept-Source Optical Coherence Tomography.

    Science.gov (United States)

    Tan, Ou; Liu, Liang; Liu, Li; Huang, David

    2018-02-01

    To devise a method to quantify nerve fibers over their arcuate courses over an extended peripapillary area using optical coherence tomography (OCT). Participants were imaged with 8 × 8-mm volumetric OCT scans centered at the optic disc. A new quantity, nerve fiber flux (NFF), represents the cross-sectional area transected perpendicular to the nerve fibers. The peripapillary area was divided into 64 tracks with equal flux. An iterative algorithm traced the trajectory of the tracks assuming that the relative distribution of the NFF was conserved with compensation for fiber connections to ganglion cells on the macular side. Average trajectory was averaged from normal eyes and use to calculate the NFF maps for glaucomatous eyes. The NFF maps were divided into eight sectors that correspond to visual field regions. There were 24 healthy and 10 glaucomatous eyes enrolled. The algorithm converged on similar patterns of NFL tracks for all healthy eyes. In glaucomatous eyes, NFF correlated with visual field sensitivity in the arcuate sectors (Spearman ρ = 0.53-0.62). Focal nerve fiber loss in glaucomatous eyes appeared as uniform tracks of NFF defects that followed the expected arcuate fiber trajectory. Using an algorithm based on the conservation of flux, we derived nerve fiber trajectories in the peripapillary area. The NFF map is useful for the visualization of focal defects and quantification of sector nerve fiber loss from wide-area volumetric OCT scans. NFF provides a cumulative measure of volumetric loss along nerve fiber tracks and could improve the detection of focal glaucoma damage.

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

    Science.gov (United States)

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

    2013-02-01

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

  11. Maternal exposure to hexachlorophene targets intermediate-stage progenitor cells of the hippocampal neurogenesis in rat offspring via dysfunction of cholinergic inputs by myelin vacuolation

    International Nuclear Information System (INIS)

    Itahashi, Megu; Abe, Hajime; Tanaka, Takeshi; Mizukami, Sayaka; Kimura, Masayuki; Yoshida, Toshinori; Shibutani, Makoto

    2015-01-01

    Highlights: • The effect of maternal exposure to HCP on rat hippocampal neurogenesis was examined. • HCP induces myelin vacuolation of nerve tracts in the septal–hippocampal pathway. • Myelin changes suppress Chrnb2-mediated cholinergic inputs to the dentate gyrus. • SGZ apoptosis occurs via the mitochondrial pathway and targets type-2b cells. • Dysfunction of cholinergic inputs is related to type-2b SGZ cell apoptosis. - Abstract: Hexachlorophene (HCP) is known to induce myelin vacuolation corresponding to intramyelinic edema of nerve fibers in the central and peripheral nervous system in animals. This study investigated the effect of maternal exposure to HCP on hippocampal neurogenesis in rat offspring using pregnant rats supplemented with 0 (controls), 100, or 300 ppm HCP in the diet from gestational day 6 to day 21 after delivery. On postnatal day (PND) 21, the numbers of T box brain 2 + progenitor cells and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling + apoptotic cells in the hippocampal subgranular zone (SGZ) decreased in female offspring at 300 ppm, which was accompanied by myelin vacuolation and punctate tubulin beta-3 chain staining of nerve fibers in the hippocampal fimbria. In addition, transcript levels of the cholinergic receptor, nicotinic beta 2 (Chrnb2) and B-cell CLL/lymphoma 2 (Bcl2) decreased in the dentate gyrus. HCP-exposure did not alter the numbers of SGZ proliferating cells and reelin- or calcium-binding protein-expressing γ-aminobutyric acid (GABA)-ergic interneuron subpopulations in the dentate hilus on PND 21 and PND 77. Although some myelin vacuolation remained, all other changes observed in HCP-exposed offspring on PND 21 disappeared on PND 77. These results suggest that maternal HCP exposure reversibly decreases type-2b intermediate-stage progenitor cells via the mitochondrial apoptotic pathway in offspring hippocampal neurogenesis at 300 ppm HCP. Neurogenesis may be affected by dysfunction

  12. Structure and function of the contactin-associated protein family in myelinated axons and their relationship with nerve diseases

    Institute of Scientific and Technical Information of China (English)

    Yan Zou; De-en Xu; Wei-feng Zhang; Hai-ying Liu; Xia Li; Xing Zhang; Xiao-fang Ma; Yang Sun; Shi-yi Jiang; Quan-hong Ma

    2017-01-01

    The contactin-associated protein (Caspr) family participates in nerve excitation and conduction, and neurotransmitter release in myelinated axons. We analyzed the structures and functions of the Caspr family–CNTNAP1 (Caspr1), CNTNAP2 (Caspr2), CNTNAP3 (Caspr3), CNTNAP4 (Caspr4) and CNTNAP5 (Caspr5), Caspr1–5 is not only involved in the formation of myelinated axons, but also participates in maintaining the stability of adjacent connections. Caspr1 participates in the formation, differentiation, and proliferation of neurons and astrocytes, and in motor control and cognitive function. We also analyzed the relationship between the Caspr family and neurodegenerative diseases, multiple sclerosis, and autoimmune encephalitis. However, the effects of Caspr on disease course and prognosis remain poorly understood. The effects of Caspr on disease diagnosis and treatment need further investigation.

  13. 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

    2017-11-01

    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

  14. 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.

  15. 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.

  16. 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...

  17. Myelin repair by Schwann cells in the regenerating goldfish visual pathway: regional patterns revealed by X-irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Nona, S.N.; Stafford, C.A.; Cronly-Dillon, J.R. (Manchester Univ. (United Kingdom). Inst. of Science and Technology); Duncan, A. (Guy' s Hospital, London (United Kingdom). Dept. of Anatomy); Scholes, J. (University Coll., London (United Kingdom))

    1994-07-01

    In the regenerating goldfish optic nerves, Schwann cells of unknown origin reliably infiltrate the lesion site forming a band of peripheral-type myelinating tissue by 1-2 months, sharply demarcated form the adjacent new CNS myelin. To investigate this effect, we have interfered with cell proliferation by locally X-irradiating the fish visual pathway 24 h after the lesion. As assayed by immunohistochemistry and EM, irradiation retards until 6 months formation of new myelin by Schwann cells at the lesion site, and virtually abolishes oligodendrocyte myelination distally, but has little or no effect on nerve fibre regrowth. Optic nerve astrocyte processes normally fail to re-infiltrate the lesion, but re-occupy it after irradiation, suggesting that they are normally excluded by early cell proliferation at this site. Moreover, scattered myelinating Schwann cells also appear in the oligodendrocyte-depleted distal optic nerve after irradiation, although only as far as the optic tract. (Author).

  18. Influence of oculomotor nerve afferents on central endings of primary trigeminal fibers.

    Science.gov (United States)

    Manni, E; Bortolami, R; Pettorossi, V E; Lucchi, M L; Callegari, E; Draicchio, F

    1987-12-01

    Painful fibers running in the third nerve and originating from the ophthalmic trigeminal area send their central projections at level of substantia gelatinosa of nucleus caudalis trigemini. The central endings of these fibers form axoaxonic synapses with trigeminal fibers entering the brain stem through the trigeminal root. The effect of electrical stimulation of the third nerve central stump on the central endings of trigeminal afferent fibers consists in an increased excitability, possibly resulting in a presynaptic inhibition. This inhibitory influence is due to both direct and indirect connections of the third nerve afferent fibers with the trigeminal ones.

  19. 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.

  20. Transfer of obturator nerve for femoral nerve injury: an experiment study in rats.

    Science.gov (United States)

    Meng, Depeng; Zhou, Jun; Lin, Yaofa; Xie, Zheng; Chen, Huihao; Yu, Ronghua; Lin, Haodong; Hou, Chunlin

    2018-07-01

    Quadriceps palsy is mainly caused by proximal lesions in the femoral nerve. The obturator nerve has been previously used to repair the femoral nerve, although only a few reports have described the procedure, and the outcomes have varied. In the present study, we aimed to confirm the feasibility and effectiveness of this treatment in a rodent model using the randomized control method. Sixty Sprague-Dawley rats were randomized into two groups: the experimental group, wherein rats underwent femoral neurectomy and obturator nerve transfer to the femoral nerve motor branch; and the control group, wherein rats underwent femoral neurectomy without nerve transfer. Functional outcomes were measured using the BBB score, muscle mass, and histological assessment. At 12 and 16 weeks postoperatively, the rats in the experimental group exhibited recovery to a stronger stretch force of the knee and higher BBB score, as compared to the control group (p nerve with myelinated and unmyelinated fibers was observed in the experimental group. No significant differences were observed between groups at 8 weeks postoperatively (p > 0.05). Obturator nerve transfer for repairing femoral nerve injury was feasible and effective in a rat model, and can hence be considered as an option for the treatment of femoral nerve injury.

  1. 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

  2. Measurement and simulation of unmyelinated nerve electrostimulation: Lumbricus terrestris experiment and numerical model.

    Science.gov (United States)

    Šarolić, A; Živković, Z; Reilly, J P

    2016-06-21

    The electrostimulation excitation threshold of a nerve depends on temporal and frequency parameters of the stimulus. These dependences were investigated in terms of: (1) strength-duration (SD) curve for a single monophasic rectangular pulse, and (2) frequency dependence of the excitation threshold for a continuous sinusoidal current. Experiments were performed on the single-axon measurement setup based on Lumbricus terrestris having unmyelinated nerve fibers. The simulations were performed using the well-established SENN model for a myelinated nerve. Although the unmyelinated experimental model differs from the myelinated simulation model, both refer to a single axon. Thus we hypothesized that the dependence on temporal and frequency parameters should be very similar. The comparison was made possible by normalizing each set of results to the SD time constant and the rheobase current of each model, yielding the curves that show the temporal and frequency dependencies regardless of the model differences. The results reasonably agree, suggesting that this experimental setup and method of comparison with SENN model can be used for further studies of waveform effect on nerve excitability, including unmyelinated neurons.

  3. Structure and function of the contactin-associated protein family in myelinated axons and their relationship with nerve diseases

    Directory of Open Access Journals (Sweden)

    Yan Zou

    2017-01-01

    Full Text Available The contactin-associated protein (Caspr family participates in nerve excitation and conduction, and neurotransmitter release in myelinated axons. We analyzed the structures and functions of the Caspr family–CNTNAP1 (Caspr1, CNTNAP2 (Caspr2, CNTNAP3 (Caspr3, CNTNAP4 (Caspr4 and CNTNAP5 (Caspr5, Caspr1–5 is not only involved in the formation of myelinated axons, but also participates in maintaining the stability of adjacent connections. Caspr1 participates in the formation, differentiation, and proliferation of neurons and astrocytes, and in motor control and cognitive function. We also analyzed the relationship between the Caspr family and neurodegenerative diseases, multiple sclerosis, and autoimmune encephalitis. However, the effects of Caspr on disease course and prognosis remain poorly understood. The effects of Caspr on disease diagnosis and treatment need further investigation.

  4. 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.

  5. Optic Nerve Head and Retinal Nerve Fiber Layer Differences Between Caribbean Black and African American Patients as Measured by Spectral Domain OCT.

    Science.gov (United States)

    Rao, Rohini; Dhrami-Gavazi, Elona; Al-Aswad, Lama; Ciarleglio, Adam; Cioffi, George A; Blumberg, Dana M

    2015-01-01

    There are well-established differences in optic nerve morphology between patients of African and European descent. Spectral domain optical coherence tomography (OCT) scanning has demonstrated these differences with respect to optic disc area (DA), average cup-disc ratio, cup volume, and nerve fiber layer thickness. However, the term "African descent" describes a heterogenous group with considerable variability. This study evaluates differences in optic nerve and retinal nerve fiber layer (RNFL) parameters as measured by Cirrus HD-OCT between Caribbean black and African American patients. A total of 25 African American subjects and 25 Caribbean black subjects with normal ocular examinations were consecutively recruited to this study. All patients received imaging of the optic nerve and nerve fiber layer with Cirrus HD-OCT. Optic nerve and RNFL parameters were evaluated for statistically significant differences using a t test. A mixed effect model for correlated data was then created to adjust outcome variables for (1) repeated measures and (2) optic nerve size. Two one-sided t tests were then utilized to determine equivalence. After adjustment for DA, RNFL thickness, cup volume, DA, inferior nerve fiber layer, and vertical cup-disc ratio demonstrated statistically significant equivalence between the 2 groups (P value fiber layer quadrant was significantly different between the 2 groups and may merit further investigation. Findings of this study suggest that optic nerve and RNFL morphology is markedly similar between Caribbean blacks and African Americans once adjusted for optic nerve size but cannot be considered equivalent in all measures, particularly in the superior nerve fiber layer.

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

    Science.gov (United States)

    Takayama, Kohei; Ooto, Sotaro; Hangai, Masanori; Ueda-Arakawa, Naoko; Yoshida, Sachiko; Akagi, Tadamichi; Ikeda, Hanako Ohashi; Nonaka, Atsushi; Hanebuchi, Masaaki; Inoue, Takashi; Yoshimura, Nagahisa

    2013-05-01

    To detect pathologic changes in retinal nerve fiber bundles in glaucomatous eyes seen on images obtained by adaptive optics (AO) scanning laser ophthalmoscopy (AO SLO). Prospective cross-sectional study. Twenty-eight eyes of 28 patients with open-angle glaucoma and 21 normal eyes of 21 volunteer subjects underwent a full ophthalmologic examination, visual field testing using a Humphrey Field Analyzer, fundus photography, red-free SLO imaging, spectral-domain optical coherence tomography, and imaging with an original prototype AO SLO system. The AO SLO images showed many hyperreflective bundles suggesting nerve fiber bundles. In glaucomatous eyes, the nerve fiber bundles were narrower than in normal eyes, and the nerve fiber layer thickness was correlated with the nerve fiber bundle widths on AO SLO (P fiber layer defect area on fundus photography, the nerve fiber bundles on AO SLO were narrower compared with those in normal eyes (P optic disc, the nerve fiber bundle width was significantly lower, even in areas without nerve fiber layer defect, in eyes with glaucomatous eyes compared with normal eyes (P = .026). The mean deviations of each cluster in visual field testing were correlated with the corresponding nerve fiber bundle widths (P = .017). AO SLO images showed reduced nerve fiber bundle widths both in clinically normal and abnormal areas of glaucomatous eyes, and these abnormalities were associated with visual field defects, suggesting that AO SLO may be useful for detecting early nerve fiber bundle abnormalities associated with loss of visual function. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. 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.

  8. Evaluation of neuroprotection by melatonin against adverse effects of prenatal exposure to a nonsteroidal anti-inflammatory drug during peripheral nerve development.

    Science.gov (United States)

    Keskin, Ilknur; Kaplan, Suleyman; Kalkan, Serpil; Sutcu, Mustafa; Ulkay, M Basak; Esener, O Burak

    2015-04-01

    The potential ability of melatonin to protect against impairment of the fetal peripheral nerve system due to maternal consumption of diclofenac sodium (DS) was investigated. Eighty-four pregnant rats were divided into seven groups: control (CONT), saline administered (PS), DS administered (DS), DS with low-dose melatonin administered (DS+MLT10), DS with high-dose melatonin administered (DS+MLT50), low-dose melatonin administered (MLT10), and high-dose melatonin administered (MLT50). After the pregnancy, six male newborn rats from each group were sacrificed at 4 and 20 weeks of age. Their right sciatic nerves were harvested, and nerve fibers were evaluated using stereological techniques. Mean numbers of myelinated axons, axon cross-section areas and the mean thickness of the myelin sheet were estimated. Four-week-old prenatally DS-exposed rats had significantly fewer axons, a smaller myelinated axonal area, and a thinner myelin sheath compared to CONT group (pmelatonin at both doses significantly increased axon numbers, only a high dose of melatonin increased the diameter of those axons (pmelatonin prophylaxis can prevent these effects. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. 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.)

  10. Expression patterns and role of PTEN in rat peripheral nerve development and injury.

    Science.gov (United States)

    Chen, Hui; Xiang, Jianping; Wu, Junxia; He, Bo; Lin, Tao; Zhu, Qingtang; Liu, Xiaolin; Zheng, Canbin

    2018-05-29

    Studies have suggested that phosphatase and tensin homolog (PTEN) plays an important role in neuroprotection and neuronal regeneration. To better understand the potential role of PTEN with respect to peripheral nerve development and injury, we investigated the expression pattern of PTEN at different stages of rat peripheral nerve development and injury and subsequently assessed the effect of pharmacological inhibition of PTEN using bpV(pic) on axonal regeneration in a rat sciatic nerve crush injury model. During the early stages of development, PTEN exhibits low expression in neuronal cell bodies and axons. From embryonic day (E) 18.5 and postnatal day (P)5 to adult, PTEN protein becomes more detectable, with high expression in the dorsal root ganglia (DRG) and axons. PTEN expression is inhibited in peripheral nerves, preceding myelination during neuronal development and remyelination after acute nerve injury. Low PTEN expression after nerve injury promotes Akt/mammalian target of rapamycin (mTOR) signaling pathway activity. In vivo pharmacological inhibition of PTEN using bpV(pic) promoted axonal regrowth, increased the number of myelinated nerve fibers, improved locomotive recovery and enhanced the amplitude response and nerve conduction velocity following stimulation in a rat sciatic nerve crush injury model. Thus, we suggest that PTEN may play potential roles in peripheral nerve development and regeneration and that inhibition of PTEN expression is beneficial for nerve regeneration and functional recovery after peripheral nerve injury. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Adaptive myelination from fish to man.

    Science.gov (United States)

    Baraban, Marion; Mensch, Sigrid; Lyons, David A

    2016-06-15

    Myelinated axons with nodes of Ranvier are an evolutionary elaboration common to essentially all jawed vertebrates. Myelin made by Schwann cells in our peripheral nervous system and oligodendrocytes in our central nervous system has been long known to facilitate rapid energy efficient nerve impulse propagation. However, it is now also clear, particularly in the central nervous system, that myelin is not a simple static insulator but that it is dynamically regulated throughout development and life. New myelin sheaths can be made by newly differentiating oligodendrocytes, and mature myelin sheaths can be stimulated to grow again in the adult. Furthermore, numerous studies in models from fish to man indicate that neuronal activity can affect distinct stages of oligodendrocyte development and the process of myelination itself. This begs questions as to how these effects of activity are mediated at a cellular and molecular level and whether activity-driven adaptive myelination is a feature common to all myelinated axons, or indeed all oligodendrocytes, or is specific to cells or circuits with particular functions. Here we review the recent literature on this topic, elaborate on the key outstanding questions in the field, and look forward to future studies that incorporate investigations in systems from fish to man that will provide further insight into this fundamental aspect of nervous system plasticity. This article is part of a Special Issue entitled SI: Myelin Evolution. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  12. 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.

  13. 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...... formed axonal sprouts are able to induce a protracted myelination response in adult CNS. We show that newly formed axonal sprouts, induced by lesion of the entorhino-hippocampal perforant pathway, have the ability to induce a myelination response in stratum radiatum and lucidum CA3. The lesion resulted...... in significant recruitment of newly formed myelinating cells, documented by incorporation of the proliferation marker bromodeoxyuridine into chondroitin sulphate NG2 expressing cells in stratum radiatum and lucidum CA3 early after lesion, and the occurrence of a 28% increase in the number of oligodendrocytes...

  14. A multiparametric assay for quantitative nerve regeneration evaluation

    OpenAIRE

    Weyn, Barbara; Van Remoortere, M; Nuydens, R; Meert, Theo; Van de Wouwer, G

    2005-01-01

    We introduce an assay for the semi-automated quantification of nerve regeneration by image analysis. Digital images of histological sections of regenerated nerves are recorded using an automated inverted microscope and merged into high-resolution mosaic images representing the entire nerve. These are analysed by a dedicated image-processing package that computes nerve-specific features (e.g. nerve area, fibre count, myelinated area) and fibre-specific features (area, perimeter, myelin sheet t...

  15. A novel rat model of brachial plexus injury with nerve root stumps.

    Science.gov (United States)

    Fang, Jintao; Yang, Jiantao; Yang, Yi; Li, Liang; Qin, Bengang; He, Wenting; Yan, Liwei; Chen, Gang; Tu, Zhehui; Liu, Xiaolin; Gu, Liqiang

    2018-02-01

    The C5-C6 nerve roots are usually spared from avulsion after brachial plexus injury (BPI) and thus can be used as donors for nerve grafting. To date, there are no appropriate animal models to evaluate spared nerve root stumps. Hence, the aim of this study was to establish and evaluate a rat model with spared nerve root stumps in BPI. In rupture group, the proximal parts of C5-T1 nerve roots were held with the surrounding muscles and the distal parts were pulled by a sudden force after the brachial plexus was fully exposed, and the results were compared with those of sham group. To validate the model, the lengths of C5-T1 spared nerve root stumps were measured and the histologies of the shortest one and the corresponding spinal cord were evaluated. C5 nerve root stump was found to be the shortest. Histology findings demonstrated that the nerve fibers became more irregular and the continuity decreased; numbers and diameters of myelinated axons and thickness of myelin sheaths significantly decreased over time. The survival of motoneurons was reduced, and the death of motoneurons may be related to the apoptotic process. Our model could successfully create BPI model with nerve root stumps by traction, which could simulate injury mechanisms. While other models involve root avulsion or rupturing by distal nerve transection. This model would be suitable for evaluating nerve root stumps and testing new therapeutic strategies for neuroprotection through nerve root stumps in the future. Copyright © 2017. Published by Elsevier B.V.

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

    International Nuclear Information System (INIS)

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

    1983-01-01

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

  17. Myelin-associated proteins labelled by slow axonal transport

    International Nuclear Information System (INIS)

    Giorgi, P.P.; DuBois, H.

    1981-01-01

    This paper deals with the problem of protein metabolism and provides evidence that the neuronal contribution to myelin metabolism may be restricted to lipids only. On the other hand this line of research led to the partial characterization of a group of neuronal proteins probably involved in axo-glial interactions subserving the onset of myelination and the structural maintenance of the mature myelin sheath. Intraocular injection of radioactive amino acids allows the study of the anterograde transport of labelled proteins along retinofugal fibres which are well myelinated. Myelin extracted from the optic nerve and tract under these conditions also contains labelled proteins. Three hypotheses are available to explain this phenomenon. To offer an explanation for this phenomenon the work was planned as follows. a) Characterization of the spatio-temporal pattern of labelling of myelin, in order to define the experimental conditions (survival time and region of the optic pathway to be studied) necessary to obtain maximal labelling. b) Characterization (by gel electrophoresis) of the myelin-associated proteins which become labelled by axonal transport, in order to work on a consistent pattern of labelling. c) Investigation of the possible mechanism responsible for the labelling of myelin-associated proteins. (Auth.)

  18. Determination of Nerve Fiber Diameter Distribution From Compound Action Potential: A Continuous Approach.

    Science.gov (United States)

    Un, M Kerem; Kaghazchi, Hamed

    2018-01-01

    When a signal is initiated in the nerve, it is transmitted along each nerve fiber via an action potential (called single fiber action potential (SFAP)) which travels with a velocity that is related with the diameter of the fiber. The additive superposition of SFAPs constitutes the compound action potential (CAP) of the nerve. The fiber diameter distribution (FDD) in the nerve can be computed from the CAP data by solving an inverse problem. This is usually achieved by dividing the fibers into a finite number of diameter groups and solve a corresponding linear system to optimize FDD. However, number of fibers in a nerve can be measured sometimes in thousands and it is possible to assume a continuous distribution for the fiber diameters which leads to a gradient optimization problem. In this paper, we have evaluated this continuous approach to the solution of the inverse problem. We have utilized an analytical function for SFAP and an assumed a polynomial form for FDD. The inverse problem involves the optimization of polynomial coefficients to obtain the best estimate for the FDD. We have observed that an eighth order polynomial for FDD can capture both unimodal and bimodal fiber distributions present in vivo, even in case of noisy CAP data. The assumed FDD distribution regularizes the ill-conditioned inverse problem and produces good results.

  19. Retinal nerve fiber layer assessment by scanning laser polarimetry and standardized photography

    NARCIS (Netherlands)

    Niessen, A. G.; van den Berg, T. J.; Langerhorst, C. T.; Greve, E. L.

    1996-01-01

    To determine whether, in a clinical setting, scanning laser polarimetry and retinal nerve fiber layer photography provide equivalent information on the retinal nerve fiber layer. We prospectively studied 60 patients with glaucoma or ocular hypertension and 24 healthy subjects. With scanning laser

  20. 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…

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

    Science.gov (United States)

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

    2017-10-01

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

  2. 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

    2016-03-23

    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.

  3. Electrical stimulation enhanced remyelination of injured sciatic nerves by increasing neurotrophins.

    Science.gov (United States)

    Wan, L D; Xia, R; Ding, W L

    2010-09-01

    Previous studies have demonstrated that electrical stimulation (ES) enhances axonal regeneration following central and peripheral nerve injury. However, the effect of ES on peripheral remyelination after nerve damage has been investigated less, and the mechanism underlying its action remains unclear. In the present study, neuron/Schwann cell (SC) co-cultures in vitro and crush-injured sciatic nerves in rats were subjected to 1 h of continuous ES (20 Hz, 100 micros, 3 V). Electron microscopy and nerve morphometry were performed to investigate the extent of regenerated nerve myelination. The expression profiles of P0, Par-3 and brain-derived neurotrophic factor (BDNF) in vitro and in vivo were examined by western blotting. We reported that 20 Hz ES increased the number of regenerated and myelinated axons at 4 and 8 weeks after injury. P0 level in the ES-treated groups, as well as myelin sheath thickness, were enhanced compared with the controls. The earlier peak Par-3 in the ES-treated groups indicated earlier initiation of SC myelination. Moreover, the similar results were achieved in the cell co-culture. Additionally, brief ES significantly elevated BDNF expression in co-cultured cells and nerve tissues. In conclusion, ES of the site of nerve injury potentiates axonal regrowth and myelin maturation during peripheral nerve regeneration. Further, the therapeutic actions of ES on myelination that is mediated via enhanced BDNF signals, which driving the promyelination effect on SCs at the onset of myelination. Copyright (c) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

  4. Avaliação morfométrica de fibras nervosas do nervo ulnar após reparação cirúrgica com auto-enxerto e prótese tubular em cães

    Directory of Open Access Journals (Sweden)

    Ângelo João Stopiglia

    1998-01-01

    Full Text Available The purpose of this study was to evaluate, by morphometric analysis, the regenerated nerve fibers of dogs, after 26 weeks of observation, in gaps of the ulnar nerves substituted by allografts and tubular prosthesis of silicone. The ulnar nerves of four dogs were processed for electron microscopic evaluation. Six fields, with 1750 µm², for each dog and each procedure, were photographed at 1880x. A morphometric computer based analysis (Sigma Scan - Jandel Co., USA resulted in the following numbers (average numbers in micrometers. 1. ulnar nerve with tubular prosthesis- a: myelinated fiber diameter-5.12 ± 1.67. b: myelinated axon diameter: 4.08 ± 1.52. c: myelin sheath thickness-0.52 ± 0.18. d: unmyelinated axon diameter: 0.98 ± 0.37. 2. ulnar nerve with allograft- a: myelinated fiber diameter: 6.04 ± 2.27. b: myelinated axon diameter: 4.59 ± 1.95. c: myelin sheath thickness: 0.72 ± 0.23. d: unmyelinated axon diameter: 0.96 ± 0.40. The morphometric analysis after 26 weeks of nerve repair didn’t show a significant difference between the two surgical procedures.

  5. Role of Demyelination Efficiency within Acellular Nerve Scaffolds during Nerve Regeneration across Peripheral Defects

    Directory of Open Access Journals (Sweden)

    Meiqin Cai

    2017-01-01

    Full Text Available Hudson’s optimized chemical processing method is the most commonly used chemical method to prepare acellular nerve scaffolds for the reconstruction of large peripheral nerve defects. However, residual myelin attached to the basal laminar tube has been observed in acellular nerve scaffolds prepared using Hudson’s method. Here, we describe a novel method of producing acellular nerve scaffolds that eliminates residual myelin more effectively than Hudson’s method through the use of various detergent combinations of sulfobetaine-10, sulfobetaine-16, Triton X-200, sodium deoxycholate, and peracetic acid. In addition, the efficacy of this new scaffold in repairing a 1.5 cm defect in the sciatic nerve of rats was examined. The modified method produced a higher degree of demyelination than Hudson’s method, resulting in a minor host immune response in vivo and providing an improved environment for nerve regeneration and, consequently, better functional recovery. A morphological study showed that the number of regenerated axons in the modified group and Hudson group did not differ. However, the autograft and modified groups were more similar in myelin sheath regeneration than the autograft and Hudson groups. These results suggest that the modified method for producing a demyelinated acellular scaffold may aid functional recovery in general after nerve defects.

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

    Science.gov (United States)

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

    2015-09-01

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

  7. Functional recovery of denervated skeletal muscle with sensory or mixed nerve protection: a pilot study.

    Directory of Open Access Journals (Sweden)

    Qing Tian Li

    Full Text Available Functional recovery is usually poor following peripheral nerve injury when reinnervation is delayed. Early innervation by sensory nerve has been indicated to prevent atrophy of the denervated muscle. It is hypothesized that early protection with sensory axons is adequate to improve functional recovery of skeletal muscle following prolonged denervation of mixed nerve injury. In this study, four groups of rats received surgical denervation of the tibial nerve. The proximal and distal stumps of the tibial nerve were ligated in all animals except for those in the immediate repair group. The experimental groups underwent denervation with nerve protection of peroneal nerve (mixed protection or sural nerve (sensory protection. The experimental and unprotected groups had a stage II surgery in which the trimmed proximal and distal tibial nerve stumps were sutured together. After 3 months of recovery, electrophysiological, histological and morphometric parameters were assessed. It was detected that the significant muscle atrophy and a good preserved structure of the muscle were observed in the unprotected and protective experimental groups, respectively. Significantly fewer numbers of regenerated myelinated axons were observed in the sensory-protected group. Enhanced recovery in the mixed protection group was indicated by the results of the muscle contraction force tests, regenerated myelinated fiber, and the results of the histological analysis. Our results suggest that early axons protection by mixed nerve may complement sensory axons which are required for promoting functional recovery of the denervated muscle natively innervated by mixed nerve.

  8. Ultrastructural relationships between the receptor nerve fiber and surrounding lamellae in Krause end-bulbs.

    Science.gov (United States)

    Spassova, I

    1981-01-01

    The ultrastructural relationship between the receptor nerve fiber and the surrounding lamellae in Krause end-bulbs was discussed. Many sites of specialized junctions of symmetrical or asymmetrical type along the receptor nerve fiber and the surrounding lamellae were found. In addition, in close vicinity to them, spine-like digitations of the receptor nerve fiber, filled mainly with small clear vesicles, were observed. Mitochondrion-like cholinesterase-positive structures bulging in some cytoplasmic lamellae were also found. It is suggested that a functional link might exist between the specialized junctions, digitations and mitochrondrion-like structures in the transformation of external mechanical stimuli into nerve impulses.

  9. 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.

  10. 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. Copyright © 2015 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  11. Comparisons of retinal nerve fiber layer thickness changes after macular hole surgery

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    Nelson Chamma Capelanes

    Full Text Available ABSTRACT Purpose: To compare postoperative changes in retinal nerve fiber layer thickness in patients with macular holes treated with vitrectomy with Brilliant Blue-assisted internal limiting membrane peeling. Methods: Twenty-two eyes of 20 patients with macular holes were studied. Each eye was selected to undergo Brilliant Blue-assisted internal limiting membrane peeling. The circumferential retinal nerve fiber layer thickness was determined using spectral domain optical coherence tomography preoperatively and 2 months postoperatively. Mean overall and sectoral retinal nerve fiber layer thicknesses were obtained for each patient. Results: There was no statistically significant difference (p≥0.05 between the pre- and post-treatment measurements in relation to each CFN variable, i.e., on average, pre-treatment measures were the same as post-treatment measures. Furthermore, despite the differences between the pre- and post-treatment measures always being positive (pre-post >0, they are not statistically significant. Conclusions: This study showed no significant decrease in retinal nerve fiber layer thickness measurements after macular holes surgery, regardless of age or sex.

  12. 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. PMID:26483699

  13. An autologously generated platelet-rich plasma suturable membrane may enhance peripheral nerve regeneration after neurorraphy in an acute injury model of sciatic nerve neurotmesis.

    Science.gov (United States)

    Giannessi, Elisabetta; Coli, Alessandra; Stornelli, Maria Rita; Miragliotta, Vincenzo; Pirone, Andrea; Lenzi, Carla; Burchielli, Silvia; Vozzi, Giovanni; De Maria, Carmelo; Giorgetti, Margherita

    2014-11-01

    The aim of this study was to investigate the ability of suturable platelet-rich plasma (PRP) membrane to promote peripheral nerve regeneration after neurotmesis and neurorraphy. A total of 36 rats were used: 32 animals underwent surgery and were split in two groups. An interim sacrifice was performed at 6 weeks postsurgery and final sacrifice at 12 weeks; four animals did not sustain nerve injury and served as control. Clinical, electromyographic (EMG), gross, and histological changes were assessed. The EMG signal was evaluated for its amplitude and frequency spectrum. Number of regenerating fibers, their diameter, and myelin thickness were histologically analyzed. Both EMG parameters showed a significant (p neurorraphy improves the nerve regeneration process in a rat sciatic nerve model. The use of PRP as a suturable membrane could perform an action not only as a source of bioactive proteins but also as a nerve guide to hold the scar reaction and thus improve axonal regeneration. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  14. Peripapillary retinal nerve fiber layer and choroidal thickness in cirrhosis patients

    Directory of Open Access Journals (Sweden)

    M.Orcun Akdemir

    2015-12-01

    Full Text Available ABSTRACT Purpose: To evaluate the effect of cirrhosis on peripapillary retinal nerve fiber layer and choroidal thickness with enhanced depth imaging optical coherence tomography. Methods: This cross sectional, single center study was undertaken at Bulent Ecevit University Ophthalmology department with the participation of internal medicine, Gastroenterology department. Patients who were treated with the diagnosis of cirrhosis (n=75 were examined in the ophthalmology clinic. Age and sex matched patients (n=50 who were healthy and met the inclusion, exclusion criteria were included in the study. Complete ophthalmological examination included visual acuity with Snellen chart, intraocular pressure measurement with applanation tonometry, biomicroscopy of anterior and posterior segments, gonioscopy, axial length measurement, visual field examination, peripapillary retinal nerve fiber layer, central macular and subfoveal choroidal thickness measurements. Results: The difference between intraocular pressure values was not statistically significant between cirrhosis and control group (p=0.843. However, mean peripapillary retinal nerve fiber layer thickness was significantly thinner in cirrhosis group in all regions (p<0.001 and subfoveal choroidal thickness was significantly thinner in cirrhosis group also (p<0.001. Moreover, central macular thickness of cirrhosis group was significantly thicker than the control group (p=0.001. Conclusion: Peripapillary retinal nerve fiber layer and subfoveal choroidal thickness was significantly thinner in cirrhosis patients.

  15. Myelination competent conditionally immortalized mouse Schwann cells

    NARCIS (Netherlands)

    Saavedra, José T.; Wolterman, Ruud A.; Baas, Frank; ten Asbroek, Anneloor L. M. A.

    2008-01-01

    Numerous mouse myelin mutants are available to analyze the biology of the peripheral nervous system related to health and disease in vivo. However, robust in vitro biochemical characterizations of players in peripheral nerve processes are still not possible due to the limited growth capacities of

  16. Functional recovery of regenerating motor axons is delayed in mice heterozygously deficient for the myelin protein P(0) gene

    DEFF Research Database (Denmark)

    Rosberg, Mette Romer; Alvarez, Susana; Krarup, Christian

    2013-01-01

    Mice with a heterozygous knock-out of the myelin protein P0 gene (P0+/-) develop a neuropathy similar to human Charcot-Marie-Tooth disease. They are indistinguishable from wild-types (WT) at birth and develop a slowly progressing demyelinating neuropathy. The aim of this study was to investigate...... whether the regeneration capacity of early symptomatic P0+/- is impaired as compared to age matched WT. Right sciatic nerves were lesioned at the thigh in 7-8 months old mice. Tibial motor axons at ankle were investigated by conventional motor conduction studies and axon excitability studies using...... threshold tracking. To evaluate regeneration we monitored the recovery of motor function after crush, and then compared the fiber distribution by histology. The overall motor performance was investigated using Rotor-Rod. P0+/- had reduced compound motor action potential amplitudes and thinner myelinated...

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

    Directory of Open Access Journals (Sweden)

    Ryan L Wood

    2018-01-01

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

  18. Morphology of Donor and Recipient Nerves Utilised in Nerve Transfers to Restore Upper Limb Function in Cervical Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    Aurora Messina

    2016-09-01

    Full Text Available Loss of hand function after cervical spinal cord injury (SCI impacts heavily on independence. Multiple nerve transfer surgery has been applied successfully after cervical SCI to restore critical arm and hand functions, and the outcome depends on nerve integrity. Nerve integrity is assessed indirectly using muscle strength testing and intramuscular electromyography, but these measures cannot show the manifestation that SCI has on the peripheral nerves. We directly assessed the morphology of nerves biopsied at the time of surgery, from three patients within 18 months post injury. Our objective was to document their morphologic features. Donor nerves included teres minor, posterior axillary, brachialis, extensor carpi radialis brevis and supinator. Recipient nerves included triceps, posterior interosseus (PIN and anterior interosseus nerves (AIN. They were fixed in glutaraldehyde, processed and embedded in Araldite Epon for light microscopy. Eighty percent of nerves showed abnormalities. Most common were myelin thickening and folding, demyelination, inflammation and a reduction of large myelinated axon density. Others were a thickened perineurium, oedematous endoneurium and Renaut bodies. Significantly, very thinly myelinated axons and groups of unmyelinated axons were observed indicating regenerative efforts. Abnormalities exist in both donor and recipient nerves and they differ in appearance and aetiology. The abnormalities observed may be preventable or reversible.

  19. 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.

  20. 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.

  1. Aspectos morfométricos do nervo hipoglosso humano em adultos e idosos Morphometric aspects of the human hypoglossal nerve in adults and the elderly

    Directory of Open Access Journals (Sweden)

    Romualdo Suzano Louzeiro Tiago

    2005-10-01

    Full Text Available OBJETIVO: Realizar análise morfométrica das fibras mielínicas do nervo hipoglosso direito, em dois grupos etários, com a finalidade de verificar modificações quantitativas decorrentes do processo de envelhecimento. FORMA DE ESTUDO: anatômico. MATERIAL E MÉTODO: Foi coletado fragmento de 1cm do nervo hipoglosso direito de 12 cadáveres do sexo masculino, sem antecedentes para doenças como diabetes, alcoolismo e neoplasia maligna. A amostra foi dividida em dois grupos: grupo adulto (idade inferior a 60 anos, composto por seis cadáveres; grupo idoso (idade igual ou superior a 60 anos, composto por seis cadáveres. O material foi fixado em solução contendo 2,5% de glutaraldeído e 2% de paraformaldeído; pós-fixado em tetróxido de ósmio 2%; desidratado em concentrações crescentes de etanol e incluído em resina epóxi. Cortes semifinos de 0,3¼m de espessura foram obtidos, corados com azul de toluidina a 1% e avaliados em microscópio de luz acoplado a sistema analisador de imagens. Os seguintes dados morfométricos foram quantificados: área de secção transversal intraperineural, número e o diâmetro das fibras mielínicas. RESULTADOS: A área intraperineural do nervo hipoglosso foi semelhante nos dois grupos etários (p=0,8691. A média da área no grupo adulto foi de 1,697 mm2, e no grupo idoso foi de 1,649 mm2. O número total de fibras mielínicas do nervo hipoglosso foi semelhante nos dois grupos etários (p=0,9018. O grupo adulto apresentou média de 10.286 ± 2308 fibras mielínicas e o grupo idoso apresentou média de 10.141 ± 1590 fibras mielínicas. Foi observada distribuição bimodal das fibras mielínicas, com pico acentuado nas fibras de 9¼m e outro menor nas fibras de 2¼m. CONCLUSÃO: A área intraperineural e o número total de fibras mielínicas do nervo hipoglosso direito é semelhante nos dois grupos etários.AIM: Perform a morphometric analysis of the myelinic fibers of the right hypoglossal nerve, in two

  2. Schwann cell-derived Apolipoprotein D controls the dynamics of post-injury myelin recognition and degradation

    Directory of Open Access Journals (Sweden)

    Nadia eGarcía-Mateo

    2014-11-01

    Full Text Available Management of lipids, particularly signaling lipids that control neuroinflammation, is crucial for the regeneration capability of a damaged nervous system. Knowledge of pro- and anti-inflammatory signals after nervous system injury is extensive, most of them being proteins acting through well-known receptors and intracellular cascades. However, the role of lipid binding extracellular proteins able to modify the fate of lipids released after injury is not well understood.Apolipoprotein D (ApoD is an extracellular lipid binding protein of the Lipocalin family induced upon nervous system injury. Our previous study shows that axon regeneration is delayed without ApoD, and suggests its participation in early events during Wallerian degeneration. Here we demonstrate that ApoD is expressed by myelinating and non-myelinating Schwann cells and is induced early upon nerve injury. We show that ApoD, known to bind arachidonic acid (AA, also interacts with lysophosphatidylcholine (LPC in vitro. We use an in vivo model of nerve crush injury, a nerve explant injury model, and cultured macrophages exposed to purified myelin, to uncover that: (i ApoD regulates denervated Schwann cell-macrophage signaling, dampening MCP1- and Tnf-dependent macrophage recruitment and activation upon injury; (ii ApoD controls the over-expression of the phagocytosis activator Galectin-3 by infiltrated macrophages; (iii ApoD controls the basal and injury-triggered levels of LPC and AA; (iv ApoD modifies the dynamics of myelin-macrophage interaction, favoring the initiation of phagocytosis and promoting myelin degradation.Regulation of macrophage behaviour by Schwann-derived ApoD is therefore a key mechanism conditioning nerve injury resolution. These results place ApoD as a lipid binding protein controlling the signals exchanged between glia, neurons and blood-borne cells during nerve recovery after injury, and open the possibility for a therapeutic use of ApoD as a regeneration

  3. [Changes in facial nerve function, morphology and neurotrophic factor III expression following three types of facial nerve injury].

    Science.gov (United States)

    Zhang, Lili; Wang, Haibo; Fan, Zhaomin; Han, Yuechen; Xu, Lei; Zhang, Haiyan

    2011-01-01

    To study the changes in facial nerve function, morphology and neurotrophic factor III (NT-3) expression following three types of facial nerve injury. Changes in facial nerve function (in terms of blink reflex (BF), vibrissae movement (VM) and position of nasal tip) were assessed in 45 rats in response to three types of facial nerve injury: partial section of the extratemporal segment (group one), partial section of the facial canal segment (group two) and complete transection of the facial canal segment lesion (group three). All facial nerves specimen were then cut into two parts at the site of the lesion after being taken from the lesion site on 1st, 7th, 21st post-surgery-days (PSD). Changes of morphology and NT-3 expression were evaluated using the improved trichrome stain and immunohistochemistry techniques ,respectively. Changes in facial nerve function: In group 1, all animals had no blink reflex (BF) and weak vibrissae movement (VM) at the 1st PSD; The blink reflex in 80% of the rats recovered partly and the vibrissae movement in 40% of the rats returned to normal at the 7th PSD; The facial nerve function in 600 of the rats was almost normal at the 21st PSD. In group 2, all left facial nerve paralyzed at the 1st PSD; The blink reflex partly recovered in 40% of the rats and the vibrissae movement was weak in 80% of the rats at the 7th PSD; 8000 of the rats'BF were almost normal and 40% of the rats' VM completely recovered at the 21st PSD. In group 3, The recovery couldn't happen at anytime. Changes in morphology: In group 1, the size of nerve fiber differed in facial canal segment and some of myelin sheath and axons degenerated at the 7th PSD; The fibres' degeneration turned into regeneration at the 21st PSD; In group 2, the morphologic changes in this group were familiar with the group 1 while the degenerated fibers were more and dispersed in transection at the 7th PSD; Regeneration of nerve fibers happened at the 21st PSD. In group 3, most of the fibers

  4. Local delivery of glial cell line-derived neurotrophic factor improves facial nerve regeneration after late repair.

    Science.gov (United States)

    Barras, Florian M; Kuntzer, Thierry; Zurn, Anne D; Pasche, Philippe

    2009-05-01

    Facial nerve regeneration is limited in some clinical situations: in long grafts, by aged patients, and when the delay between nerve lesion and repair is prolonged. This deficient regeneration is due to the limited number of regenerating nerve fibers, their immaturity and the unresponsiveness of Schwann cells after a long period of denervation. This study proposes to apply glial cell line-derived neurotrophic factor (GDNF) on facial nerve grafts via nerve guidance channels to improve the regeneration. Two situations were evaluated: immediate and delayed grafts (repair 7 months after the lesion). Each group contained three subgroups: a) graft without channel, b) graft with a channel without neurotrophic factor; and c) graft with a GDNF-releasing channel. A functional analysis was performed with clinical observation of facial nerve function, and nerve conduction study at 6 weeks. Histological analysis was performed with the count of number of myelinated fibers within the graft, and distally to the graft. Central evaluation was assessed with Fluoro-Ruby retrograde labeling and Nissl staining. This study showed that GDNF allowed an increase in the number and the maturation of nerve fibers, as well as the number of retrogradely labeled neurons in delayed anastomoses. On the contrary, after immediate repair, the regenerated nerves in the presence of GDNF showed inferior results compared to the other groups. GDNF is a potent neurotrophic factor to improve facial nerve regeneration in grafts performed several months after the nerve lesion. However, GDNF should not be used for immediate repair, as it possibly inhibits the nerve regeneration.

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

    NARCIS (Netherlands)

    Crunelli, V.; Prodanov, D.P.; Nagelkerke, Nico; Marani, Enrico

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  7. On the nature of the afferent fibers of oculomotor nerve.

    Science.gov (United States)

    Manni, E; Draicchio, F; Pettorossi, V E; Carobi, C; Grassi, S; Bortolami, R; Lucchi, M L

    1989-03-01

    The oculogyric nerves contain afferent fibers originating from the ophthalmic territory, the somata of which are located in the ipsilateral semilunar ganglion. These primary sensory neurons project to the Subnucleus Gelatinosus of the Nucleus Caudalis Trigemini, where they make presynaptic contact with the central endings of the primary trigeminal afferents running in the fifth cranial nerve. After complete section of the trigeminal root, the antidromic volleys elicited in the trunk of the third cranial nerve by stimulating SG of NCT consisted of two waves belonging to the A delta and C groups. The area of both components of the antidromic volleys decreased both after bradykinin and hystamine injection into the corresponding cutaneous region and after thermic stimulation of the ipsilateral trigeminal ophthalmic territory. The reduction of such potentials can be explained in terms of collision between the antidromic volleys and those elicited orthodromically by chemical and thermic stimulation. Also, capsaicin applied on the nerve induced an immediate increase, followed by a long lasting decrease, of orthodromic evoked response area. These findings bring further support to the nociceptive nature of the afferent fibers running into the oculomotor nerve.

  8. 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

    . Uptake of potassium leads to Schwann cell swelling and myelin restructuring that impacts the electrical properties of the myelin. In order to further understand the dynamic interaction that takes place between the myelin and the axon, we have modelled submyelin potassium accumulation and related changes...... in myelin resistance during prolonged high-frequency stimulation. We predict that potassium-mediated decrease in myelin resistance leads to a functional excitation block with various patterns of altered spike trains. The patterns are found to depend on stimulation frequency and amplitude and to range from...

  9. Bone marrow-derived mesenchymal stem cells versus adipose-derived mesenchymal stem cells for peripheral nerve regeneration

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    Marcela Fernandes

    2018-01-01

    Full Text Available Studies have confirmed that bone marrow-derived mesenchymal stem cells (MSCs can be used for treatment of several nervous system diseases. However, isolation of bone marrow-derived MSCs (BMSCs is an invasive and painful process and the yield is very low. Therefore, there is a need to search for other alterative stem cell sources. Adipose-derived MSCs (ADSCs have phenotypic and gene expression profiles similar to those of BMSCs. The production of ADSCs is greater than that of BMSCs, and ADSCs proliferate faster than BMSCs. To compare the effects of venous grafts containing BMSCs or ADSCs on sciatic nerve injury, in this study, rats were randomly divided into four groups: sham (only sciatic nerve exposed, Matrigel (MG; sciatic nerve injury + intravenous transplantation of MG vehicle, ADSCs (sciatic nerve injury + intravenous MG containing ADSCs, and BMSCs (sciatic nerve injury + intravenous MG containing BMSCs groups. Sciatic functional index was calculated to evaluate the function of injured sciatic nerve. Morphologic characteristics of nerves distal to the lesion were observed by toluidine blue staining. Spinal motor neurons labeled with Fluoro-Gold were quantitatively assessed. Compared with sham-operated rats, sciatic functional index was lower, the density of small-diameter fibers was significantly increased, and the number of motor neurons significantly decreased in rats with sciatic nerve injury. Neither ADSCs nor BMSCs significantly improved the sciatic nerve function of rats with sciatic nerve injury, increased fiber density, fiber diameters, axonal diameters, myelin sheath thickness, and G ratios (axonal diameter/fiber diameter ratios in the sciatic nerve distal to the lesion site. There was no significant difference in the number of spinal motor neurons among ADSCs, BMSCs and MG groups. These results suggest that neither BMSCs nor ADSCs provide satisfactory results for peripheral nerve repair when using MG as the conductor for

  10. Energy-optimal electrical excitation of nerve fibers.

    Science.gov (United States)

    Jezernik, Saso; Morari, Manfred

    2005-04-01

    We derive, based on an analytical nerve membrane model and optimal control theory of dynamical systems, an energy-optimal stimulation current waveform for electrical excitation of nerve fibers. Optimal stimulation waveforms for nonleaky and leaky membranes are calculated. The case with a leaky membrane is a realistic case. Finally, we compare the waveforms and energies necessary for excitation of a leaky membrane in the case where the stimulation waveform is a square-wave current pulse, and in the case of energy-optimal stimulation. The optimal stimulation waveform is an exponentially rising waveform and necessitates considerably less energy to excite the nerve than a square-wave pulse (especially true for larger pulse durations). The described theoretical results can lead to drastically increased battery lifetime and/or decreased energy transmission requirements for implanted biomedical systems.

  11. Promoting peripheral myelin repair

    OpenAIRE

    Zhou, Ye; Notterpek, Lucia

    2016-01-01

    Compared to the central nervous system (CNS), peripheral nerves have a remarkable ability to regenerate and remyelinate. This regenerative capacity to a large extent is dependent on and supported by Schwann cells, the myelin-forming glial cells of the peripheral nervous system (PNS). In a variety of paradigms, Schwann cells are critical in the removal of the degenerated tissue, which is followed by remyelination of newly-regenerated axons. This unique plasticity of Schwann cells has been the ...

  12. 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.

  13. HLA-DR-expressing cells and T-lymphocytes in sural nerve biopsies

    DEFF Research Database (Denmark)

    Schrøder, H D; Olsson, T; Solders, G

    1988-01-01

    was confirmed. HLA-DR expression was found in all biopsies and thus was not restricted to any particular type of neuropathy. The HLA-DR expression appeared to correlate with severity and activity of the neuropathy. HLA-DR-expressing macrophages wrapping myelinated fibers were prominent in primary demyelinating......Thirty-five sural nerve biopsies were stained immunohistochemically for HLA-DR antigen. HLA-DR was expressed on nonmyelinating Schwann cells, macrophages, vascular endothelium, and perineurium. By means of double immunofluorescence staining the identity of the HLA-DR presenting structures...

  14. A mathematical description of nerve fiber bundle trajectories and their variability in the human retina

    NARCIS (Netherlands)

    Jansonius, N. M.; Nevalainen, J.; Selig, B.; Zangwill, L. M.; Sample, P. A.; Budde, W. M.; Jonas, J. B.; Lagreze, W. A.; Airaksinen, P. J.; Vonthein, R.; Levin, L. A.; Paetzold, J.; Schiefer, U.

    2009-01-01

    We developed a mathematical model wherein retinal nerve fiber trajectories can be described and the corresponding inter-subject variability analyzed. The model was based on traced nerve fiber bundle trajectories extracted from 55 fundus photographs of 55 human subjects. The model resembled the

  15. Staining Methods for Normal and Regenerative Myelin in the Nervous System.

    Science.gov (United States)

    Carriel, Víctor; Campos, Antonio; Alaminos, Miguel; Raimondo, Stefania; Geuna, Stefano

    2017-01-01

    Histochemical techniques enable the specific identification of myelin by light microscopy. Here we describe three histochemical methods for the staining of myelin suitable for formalin-fixed and paraffin-embedded materials. The first method is conventional luxol fast blue (LFB) method which stains myelin in blue and Nissl bodies and mast cells in purple. The second method is a LBF-based method called MCOLL, which specifically stains the myelin as well the collagen fibers and cells, giving an integrated overview of the histology and myelin content of the tissue. Finally, we describe the osmium tetroxide method, which consist in the osmication of previously fixed tissues. Osmication is performed prior the embedding of tissues in paraffin giving a permanent positive reaction for myelin as well as other lipids present in the tissue.

  16. Phrenic nerves and diaphragms in sudden infant death syndrome.

    Science.gov (United States)

    Weis, J; Weber, U; Schröder, J M; Lemke, R; Althoff, H

    1998-01-30

    Disturbances of the respiratory system may be an important factor in the cascade of events leading to sudden infant death syndrome (SIDS). Even though the diaphragm is the major respiratory muscle in infants, little is known about alterations of this muscle and of the phrenic nerve in SIDS. In the present study, diaphragms and phrenic nerves of 24 SIDS infants and seven controls were analyzed. Morphometric analysis revealed only slightly larger cross sectional areas of phrenic nerve axons but no increase in myelin sheath thickness in SIDS cases. However, in one SIDS case, myelinated nerve fibre density was severely reduced. Using electron microscopy, several nerve fibres of SIDS infants showed focal accumulations of neurofilaments. Muscle fibre diameters in SIDS diaphragms were significantly larger compared to controls (P fibre ruptures and contracture bands were found. These prominent nonspecific ultrastructural alterations should advise caution in the interpretation of morphometric data. Thus, in some cases exemplified by one case of the present series, decreased density of phrenic nerve myelinated axons might contribute to SIDS. Still, the present results indicate that development of phrenic nerves and diaphragms is not delayed in most SIDS infants.

  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. Pre-differentiation of mesenchymal stromal cells in combination with a microstructured nerve guide supports peripheral nerve regeneration in the rat sciatic nerve model.

    Science.gov (United States)

    Boecker, Arne Hendrik; van Neerven, Sabien Geraldine Antonia; Scheffel, Juliane; Tank, Julian; Altinova, Haktan; Seidensticker, Katrin; Deumens, Ronald; Tolba, Rene; Weis, Joachim; Brook, Gary Anthony; Pallua, Norbert; Bozkurt, Ahmet

    2016-02-01

    Many bioartificial nerve guides have been investigated pre-clinically for their nerve regeneration-supporting function, often in comparison to autologous nerve transplantation, which is still regarded as the current clinical gold standard. Enrichment of these scaffolds with cells intended to support axonal regeneration has been explored as a strategy to boost axonal regeneration across these nerve guides Ansselin et al. (1998). In the present study, 20 mm rat sciatic nerve defects were implanted with a cell-seeded microstructured collagen nerve guide (Perimaix) or an autologous nerve graft. Under the influence of seeded, pre-differentiated mesenchymal stromal cells, axons regenerated well into the Perimaix nerve guide. Myelination-related parameters, like myelin sheath thickness, benefitted from an additional seeding with pre-differentiated mesenchymal stromal cells. Furthermore, both the number of retrogradely labelled sensory neurons and the axon density within the implant were elevated in the cell-seeded scaffold group with pre-differentiated mesenchymal stromal cells. However, a pre-differentiation had no influence on functional recovery. An additional cell seeding of the Perimaix nerve guide with mesenchymal stromal cells led to an extent of functional recovery, independent of the differentiation status, similar to autologous nerve transplantation. These findings encourage further investigations on pre-differentiated mesenchymal stromal cells as a cellular support for peripheral nerve regeneration. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  19. Axonal and glial currents activated during the post-tetanic hyperpolarization in non-myelinated nerve.

    Science.gov (United States)

    Robert, A; Jirounek, P

    1998-07-01

    Changes in membrane potential and potassium concentration in the extracellular space ([K+]e) of rabbit vagus nerve were measured simultaneously during electrical activity and during the period of recovery using a modified sucrose-gap method and potassium-sensitive microelectrodes. After stimulation for 15 s at 15 Hz the main activity-induced increase in [K+]e reached 16.9 mM. This increase in [K+]e was paralleled by a depolarization of the preparation. The period of activity was followed by a post-tetanic hyperpolarization (PTH) lasting tens of seconds, generated by the axonal electrogenic Na+-K+ pump and to a lesser extent by the pump of the surrounding Schwann cells. The amplitude of the PTH dramatically increased in experiments in which inward currents were blocked by removal of Cl– or after application of Cs+ or Ba2+, indicating that under normal conditions the current generated by the Na+-K+ pump is strongly short-circuited. A pharmacological and kinetic study showed that these currents are: (1) the hyperpolarization-activated current I h, and (2) the inwardly rectifying I KIR current. The results show that the latter originates from Schwann cells. Our data indicate that in non-myelinated nerves there is a subtle association of inward ionic channels which (1) helps the cell to maintain an optimal membrane potential after a period of activity, and (2) contributes to the removal of excess K+ from the extracellular space.

  20. A role for myelin-associated peroxisomes in maintaining paranodal loops and axonal integrity.

    Science.gov (United States)

    Kassmann, Celia M; Quintes, Susanne; Rietdorf, Jens; Möbius, Wiebke; Sereda, Michael Werner; Nientiedt, Tobias; Saher, Gesine; Baes, Myriam; Nave, Klaus-Armin

    2011-07-21

    Demyelinating diseases of the nervous system cause axon loss but the underlying mechanisms are not well understood. Here we show by confocal and electron microscopy that in myelin-forming glia peroxisomes are associated with myelin membranes. When peroxisome biogenesis is experimentally perturbed in Pex5 conditional mouse mutants, myelination by Schwann cells appears initially normal. However, in nerves of older mice paranodal loops become physically unstable and develop swellings filled with vesicles and electron-dense material. This novel model of a demyelinating neuropathy demonstrates that peroxisomes serve an important function in the peripheral myelin compartment, required for long-term axonal integrity. Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  1. Radiofrequency neurolysis in a clinical model. Neuropathological correlation

    International Nuclear Information System (INIS)

    Smith, H.P.; McWhorter, J.M.; Challa, V.R.

    1981-01-01

    Reports differ on which nerve fibers are affected by radiofrequency lesions made in peripheral nerves, some stating that primarily the myelinated delta and unmyelinated C fibers are destroyed, others stating that the destruction affects all sizes of nerve fibers and both myelinated and unmyelinated fibers. This study was designed to confirm one of those two findings, and to study the role that different temperatures might play in determining which fibers are affected. Radiofrequency lesions (85 degrees C for 2 minutes) were made in dogs by placing a temperature-monitored electrode into the lumber intervertebral foramina. The dogs were killed at intervals up to 6 weeks after rhizotomy, and the lesions were studied by light and electron microscopy. In all lesions, there was a total loss of unmyelinated fibers and a nearly total loss of myelinated fibers. In other dogs, 2-minute lesions were made at 45 degrees, 55 degrees, 65 degrees, and 75 degrees C, and the lesions examined 1 week later. Again, all sizes and all types of fibers were destroyed

  2. Bone Marrow-Derived, Neural-Like Cells Have the Characteristics of Neurons to Protect the Peripheral Nerve in Microenvironment

    Directory of Open Access Journals (Sweden)

    Shi-lei Guo

    2015-01-01

    Full Text Available Effective repair of peripheral nerve defects is difficult because of the slow growth of new axonal growth. We propose that “neural-like cells” may be useful for the protection of peripheral nerve destructions. Such cells should prolong the time for the disintegration of spinal nerves, reduce lesions, and improve recovery. But the mechanism of neural-like cells in the peripheral nerve is still unclear. In this study, bone marrow-derived neural-like cells were used as seed cells. The cells were injected into the distal end of severed rabbit peripheral nerves that were no longer integrated with the central nervous system. Electromyography (EMG, immunohistochemistry, and transmission electron microscopy (TEM were employed to analyze the development of the cells in the peripheral nerve environment. The CMAP amplitude appeared during the 5th week following surgery, at which time morphological characteristics of myelinated nerve fiber formation were observed. Bone marrow-derived neural-like cells could protect the disintegration and destruction of the injured peripheral nerve.

  3. Nerve Regenerative Effects of GABA-B Ligands in a Model of Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Valerio Magnaghi

    2014-01-01

    Full Text Available Neuropathic pain arises as a direct consequence of a lesion or disease affecting the peripheral somatosensory system. It may be associated with allodynia and increased pain sensitivity. Few studies correlated neuropathic pain with nerve morphology and myelin proteins expression. Our aim was to test if neuropathic pain is related to nerve degeneration, speculating whether the modulation of peripheral GABA-B receptors may promote nerve regeneration and decrease neuropathic pain. We used the partial sciatic ligation- (PSL- induced neuropathic model. The biochemical, morphological, and behavioural outcomes of sciatic nerve were analysed following GABA-B ligands treatments. Simultaneous 7-days coadministration of baclofen (10 mg/kg and CGP56433 (3 mg/kg alters tactile hypersensitivity. Concomitantly, specific changes of peripheral nerve morphology, nerve structure, and myelin proteins (P0 and PMP22 expression were observed. Nerve macrophage recruitment decreased and step coordination was improved. The PSL-induced changes in nociception correlate with altered nerve morphology and myelin protein expression. Peripheral synergic effects, via GABA-B receptor activation, promote nerve regeneration and likely ameliorate neuropathic pain.

  4. Enhancement of Median Nerve Regeneration by Mesenchymal Stem Cells Engraftment in an Absorbable Conduit: Improvement of Peripheral Nerve Morphology with Enlargement of Somatosensory Cortical Representation.

    Directory of Open Access Journals (Sweden)

    Julia Teixeira Oliveira

    2014-10-01

    Full Text Available We studied the morphology and the cortical representation of the median nerve (MN, 10 weeks after a transection immediately followed by treatment with tubulization using a polycaprolactone (PCL conduit with or without bone marrow-derived mesenchymal stem cell (MSC transplant. In order to characterize the cutaneous representation of MN inputs in primary somatosensory cortex (S1, electrophysiological cortical mapping of the somatosensory representation of the forepaw and adjacent body parts was performed after acute lesion of all brachial plexus nerves, except for the MN. This was performed in ten adult male Wistar rats randomly assigned in 3 groups: MN Intact (n=4, PCL-Only (n=3 and PCL+MSC (n=3. Ten weeks before mapping procedures in animals from PCL-Only and PCL+MSC groups, animal were subjected to MN transection with removal of a 4-mm-long segment, immediately followed by suturing a PCL conduit to the nerve stumps with (PCL+MSC group or without (PCL-Only group injection of MSC into the conduit. After mapping the representation of the MN in S1, animals had a segment of the regenerated nerve processed for light and transmission electron microscopy. For histomorphometric analysis of the nerve segment, sample size was increased to 5 animals per experimental group. The PCL+MSC group presented a higher number of myelinated fibers and a larger cortical representation of MN inputs in S1 (3,383±390 fibers; 2.3 mm2, respectively than the PCL-Only group (2,226±575 fibers; 1.6 mm2. In conclusion, MSC-based therapy associated with PCL conduits can improve MN regeneration. This treatment seems to rescue the nerve representation in S1, thus minimizing the stabilization of new representations of adjacent body parts in regions previously responsive to the MN.

  5. Local Xenotransplantation of Bone Marrow Derived Mast Cells (BMMCs) Improves Functional Recovery of Transected Sciatic Nerve in Cat: A Novel Approach in Cell Therapy.

    Science.gov (United States)

    Mohammadi, Rahim; Anousheh, Dana; Alaei, Mohammad-Hazhir; Nikpasand, Amin; Rostami, Hawdam; Shahrooz, Rasoul

    2018-04-01

    To determine the effects of bone marrow derived mast cells (BMMCs) on functional recovery of transected sciatic nerve in animal model of cat. A 20-mm sciatic nerve defect was bridged using a silicone nerve guide filled with BMMCs in BMMC group. In Sham-surgery group (SHAM), the sciatic nerve was only exposed and manipulated. In control group (SILOCONE) the gap was repaired with a silicone nerve guide and both ends were sealed using sterile Vaseline to avoid leakage and the nerve guide was filled with 100 μL of phosphate-buffered saline alone. In cell treated group ([SILOCONE/BMMC) the nerve guide was filled with 100 μL BMMCs (2× 106 cells/100 μL). The regenerated nerve fibers were studied, biomechanically, histologically and immunohiscochemically 6 months later. Biomechanical studies confirmed faster recovery of regenerated axons in BMMCs transplanted animals compared to control group ( p <0.05). Morphometric indices of the regenerated fibers showed that the number and diameter of the myelinated fibers were significantly higher in BMMCs transplanted animals than in control group ( p <0.05). In immunohistochemistry, location of reactions to S-100 in BMMCs transplanted animals was clearly more positive than that in control group. BMMCs xenotransplantation could be considered as a readily accessible source of cells that could improve recovery of transected sciatic nerve.

  6. Nerve fibers and menstrual cycle in peritoneal endometriosis.

    Science.gov (United States)

    Wang, Guoyun; Tokushige, Natsuko; Fraser, Ian S

    2011-06-30

    There was no difference in the density of nerve fibers across the menstrual cycle in peritoneal endometriotic lesions. These findings may explain why patients with peritoneal endometriosis often have painful symptoms throughout the menstrual cycle. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  7. Subtle paranodal injury slows impulse conduction in a mathematical model of myelinated axons.

    Directory of Open Access Journals (Sweden)

    Charles F Babbs

    Full Text Available This study explores in detail the functional consequences of subtle retraction and detachment of myelin around the nodes of Ranvier following mild-to-moderate crush or stretch mediated injury. An equivalent electrical circuit model for a series of equally spaced nodes of Ranvier was created incorporating extracellular and axonal resistances, paranodal resistances, nodal capacitances, time varying sodium and potassium currents, and realistic resting and threshold membrane potentials in a myelinated axon segment of 21 successive nodes. Differential equations describing membrane potentials at each nodal region were solved numerically. Subtle injury was simulated by increasing the width of exposed nodal membrane in nodes 8 through 20 of the model. Such injury diminishes action potential amplitude and slows conduction velocity from 19.1 m/sec in the normal region to 7.8 m/sec in the crushed region. Detachment of paranodal myelin, exposing juxtaparanodal potassium channels, decreases conduction velocity further to 6.6 m/sec, an effect that is partially reversible with potassium ion channel blockade. Conduction velocity decreases as node width increases or as paranodal resistance falls. The calculated changes in conduction velocity with subtle paranodal injury agree with experimental observations. Nodes of Ranvier are highly effective but somewhat fragile devices for increasing nerve conduction velocity and decreasing reaction time in vertebrate animals. Their fundamental design limitation is that even small mechanical retractions of myelin from very narrow nodes or slight loosening of paranodal myelin, which are difficult to notice at the light microscopic level of observation, can cause large changes in myelinated nerve conduction velocity.

  8. Delayed nerve stimulation promotes axon-protective neurofilament phosphorylation, accelerates immune cell clearance and enhances remyelination in vivo in focally demyelinated nerves.

    Directory of Open Access Journals (Sweden)

    Nikki A McLean

    Full Text Available Rapid and efficient axon remyelination aids in restoring strong electrochemical communication with end organs and in preventing axonal degeneration often observed in demyelinating neuropathies. The signals from axons that can trigger more effective remyelination in vivo are still being elucidated. Here we report the remarkable effect of delayed brief electrical nerve stimulation (ES; 1 hour @ 20 Hz 5 days post-demyelination on ensuing reparative events in a focally demyelinated adult rat peripheral nerve. ES impacted many parameters underlying successful remyelination. It effected increased neurofilament expression and phosphorylation, both implicated in axon protection. ES increased expression of myelin basic protein (MBP and promoted node of Ranvier re-organization, both of which coincided with the early reappearance of remyelinated axons, effects not observed at the same time points in non-stimulated demyelinated nerves. The improved ES-associated remyelination was accompanied by enhanced clearance of ED-1 positive macrophages and attenuation of glial fibrillary acidic protein expression in accompanying Schwann cells, suggesting a more rapid clearance of myelin debris and return of Schwann cells to a nonreactive myelinating state. These benefits of ES correlated with increased levels of brain derived neurotrophic factor (BDNF in the acute demyelination zone, a key molecule in the initiation of the myelination program. In conclusion, the tremendous impact of delayed brief nerve stimulation on enhancement of the innate capacity of a focally demyelinated nerve to successfully remyelinate identifies manipulation of this axis as a novel therapeutic target for demyelinating pathologies.

  9. Delayed nerve stimulation promotes axon-protective neurofilament phosphorylation, accelerates immune cell clearance and enhances remyelination in vivo in focally demyelinated nerves.

    Science.gov (United States)

    McLean, Nikki A; Popescu, Bogdan F; Gordon, Tessa; Zochodne, Douglas W; Verge, Valerie M K

    2014-01-01

    Rapid and efficient axon remyelination aids in restoring strong electrochemical communication with end organs and in preventing axonal degeneration often observed in demyelinating neuropathies. The signals from axons that can trigger more effective remyelination in vivo are still being elucidated. Here we report the remarkable effect of delayed brief electrical nerve stimulation (ES; 1 hour @ 20 Hz 5 days post-demyelination) on ensuing reparative events in a focally demyelinated adult rat peripheral nerve. ES impacted many parameters underlying successful remyelination. It effected increased neurofilament expression and phosphorylation, both implicated in axon protection. ES increased expression of myelin basic protein (MBP) and promoted node of Ranvier re-organization, both of which coincided with the early reappearance of remyelinated axons, effects not observed at the same time points in non-stimulated demyelinated nerves. The improved ES-associated remyelination was accompanied by enhanced clearance of ED-1 positive macrophages and attenuation of glial fibrillary acidic protein expression in accompanying Schwann cells, suggesting a more rapid clearance of myelin debris and return of Schwann cells to a nonreactive myelinating state. These benefits of ES correlated with increased levels of brain derived neurotrophic factor (BDNF) in the acute demyelination zone, a key molecule in the initiation of the myelination program. In conclusion, the tremendous impact of delayed brief nerve stimulation on enhancement of the innate capacity of a focally demyelinated nerve to successfully remyelinate identifies manipulation of this axis as a novel therapeutic target for demyelinating pathologies.

  10. 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.

  11. Local translation in primary afferent fibers regulates nociception.

    Directory of Open Access Journals (Sweden)

    Lydia Jiménez-Díaz

    2008-04-01

    Full Text Available Recent studies have demonstrated the importance of local protein synthesis for neuronal plasticity. In particular, local mRNA translation through the mammalian target of rapamycin (mTOR has been shown to play a key role in regulating dendrite excitability and modulating long-term synaptic plasticity associated with learning and memory. There is also increased evidence to suggest that intact adult mammalian axons have a functional requirement for local protein synthesis in vivo. Here we show that the translational machinery is present in some myelinated sensory fibers and that active mTOR-dependent pathways participate in maintaining the sensitivity of a subpopulation of fast-conducting nociceptors in vivo. Phosphorylated mTOR together with other downstream components of the translational machinery were localized to a subset of myelinated sensory fibers in rat cutaneous tissue. We then showed with electromyographic studies that the mTOR inhibitor rapamycin reduced the sensitivity of a population of myelinated nociceptors known to be important for the increased mechanical sensitivity that follows injury. Behavioural studies confirmed that local treatment with rapamycin significantly attenuated persistent pain that follows tissue injury, but not acute pain. Specifically, we found that rapamycin blunted the heightened response to mechanical stimulation that develops around a site of injury and reduced the long-term mechanical hypersensitivity that follows partial peripheral nerve damage--a widely used model of chronic pain. Our results show that the sensitivity of a subset of sensory fibers is maintained by ongoing mTOR-mediated local protein synthesis and uncover a novel target for the control of long-term pain states.

  12. Nano-scale Biophysical and Structural Investigations on Intact and Neuropathic Nerve Fibers by Simultaneous Combination of Atomic Force and Confocal Microscopy

    Directory of Open Access Journals (Sweden)

    Gonzalo Rosso

    2017-08-01

    Full Text Available The links between neuropathies of the peripheral nervous system (PNS, including Charcot-Marie-Tooth1A and hereditary neuropathy with liability to pressure palsies, and impaired biomechanical and structural integrity of PNS nerves remain poorly understood despite the medical urgency. Here, we present a protocol describing simultaneous structural and biomechanical integrity investigations on isolated nerve fibers, the building blocks of nerves. Nerve fibers are prepared from nerves harvested from wild-type and exemplary PNS neuropathy mouse models. The basic principle of the designed experimental approach is based on the simultaneous combination of atomic force microscopy (AFM and confocal microscopy. AFM is used to visualize the surface structure of nerve fibers at nano-scale resolution. The simultaneous combination of AFM and confocal microscopy is used to perform biomechanical, structural, and functional integrity measurements at nano- to micro-scale. Isolation of sciatic nerves and subsequent teasing of nerve fibers take ~45 min. Teased fibers can be maintained at 37°C in a culture medium and kept viable for up to 6 h allowing considerable time for all measurements which require 3–4 h. The approach is designed to be widely applicable for nerve fibers from mice of any PNS neuropathy. It can be extended to human nerve biopsies.

  13. Occurrence of substance P-like immunoreactive nerve fibers in Krause corpuscles of the dog's tongue.

    Science.gov (United States)

    Ichikawa, H; Nishikawa, S; Wakisaka, S; Matsuo, S; Takano, Y; Akai, M

    1988-01-01

    Substance P-like immunoreactive (SPLI) nerve fibers were demonstrated in the Krause corpuscles of the dog's tongue using the indirect immunofluorescence method and cholinesterase histochemistry. SPLI nerve fibers were often in contact with Krause end bulbs and occasionally entered them. From this result it was suggested that substance P might be involved in sensory mechanism of the Krause apparatus.

  14. Effects of Schwann cell alignment along the oriented electrospun chitosan nanofibers on nerve regeneration.

    Science.gov (United States)

    Wang, Wei; Itoh, Soichiro; Konno, Katsumi; Kikkawa, Takeshi; Ichinose, Shizuko; Sakai, Katsuyoshi; Ohkuma, Tsuneo; Watabe, Kazuhiko

    2009-12-15

    We have constructed a chitosan nonwoven nanofiber mesh tube consisting of oriented fibers by the electrospinning method. The efficacy of oriented nanofibers on Schwann cell alignment and positive effect of this tube on peripheral nerve regeneration were confirmed. The physical properties of the chitosan nanofiber mesh sheets prepared by electrospinning with or without fiber orientation were characterized. Then, immortalized Schwann cells were cultured on these sheets. Furthermore, the chitosan nanofiber mesh tubes with or without orientation, and bilayered chitosan mesh tube with an inner layer of oriented nanofibers and an outer layer of randomized nanofibers were bridgegrafted into rat sciatic nerve defect. As a result of fiber orientation, the tensile strength along the axis of the sheet increased. Because Schwann cells aligned along the nanofibers, oriented fibrous sheets could exhibit a Schwann cell column. Functional recovery and electrophysiological recovery occurred in time in the oriented group as well as in the bilayered group, and approximately matched those in the isograft. Furthermore, histological analysis revealed that the sprouting of myelinated axons occurred vigorously followed by axonal maturation in the isograft, oriented, and bilayered group in the order. The oriented chitosan nanofiber mesh tube may be a promising substitute for autogenous nerve graft.

  15. Influence of myelin proteins on the structure and dynamics of a model membrane with emphasis on the low temperature regime

    Energy Technology Data Exchange (ETDEWEB)

    Knoll, W. [University Joseph Fourier, UFR PhiTEM, Grenoble (France); Institut Laue–Langevin, Grenoble (France); Peters, J. [University Joseph Fourier, UFR PhiTEM, Grenoble (France); Institut Laue–Langevin, Grenoble (France); Institut de Biologie Structurale, Grenoble (France); Kursula, P. [University of Oulu, Oulu (Finland); CSSB–HZI, DESY, Hamburg (Germany); Gerelli, Y. [Institut Laue–Langevin, Grenoble (France); Natali, F., E-mail: natali@ill.fr [Institut Laue–Langevin, Grenoble (France); CNR–IOM–OGG, c/o Institut Laue–Langevin, Grenoble (France)

    2014-11-28

    Myelin is an insulating, multi-lamellar membrane structure wrapped around selected nerve axons. Increasing the speed of nerve impulses, it is crucial for the proper functioning of the vertebrate nervous system. Human neurodegenerative diseases, such as multiple sclerosis, are linked to damage to the myelin sheath through demyelination. Myelin exhibits a well defined subset of myelin-specific proteins, whose influence on membrane dynamics, i.e., myelin flexibility and stability, has not yet been explored in detail. In a first paper [W. Knoll, J. Peters, P. Kursula, Y. Gerelli, J. Ollivier, B. Demé, M. Telling, E. Kemner, and F. Natali, Soft Matter 10, 519 (2014)] we were able to spotlight, through neutron scattering experiments, the role of peripheral nervous system myelin proteins on membrane stability at room temperature. In particular, the myelin basic protein and peripheral myelin protein 2 were found to synergistically influence the membrane structure while keeping almost unchanged the membrane mobility. Further insight is provided by this work, in which we particularly address the investigation of the membrane flexibility in the low temperature regime. We evidence a different behavior suggesting that the proton dynamics is reduced by the addition of the myelin basic protein accompanied by negligible membrane structural changes. Moreover, we address the importance of correct sample preparation and characterization for the success of the experiment and for the reliability of the obtained results.

  16. Analysis of White Matter Damage in Patients with Multiple Sclerosis via a Novel In Vivo MR Method for Measuring Myelin, Axons, and G-Ratio.

    Science.gov (United States)

    Hagiwara, A; Hori, M; Yokoyama, K; Nakazawa, M; Ueda, R; Horita, M; Andica, C; Abe, O; Aoki, S

    2017-10-01

    Myelin and axon volume fractions can now be estimated via MR imaging in vivo, as can the g-ratio, which equals the ratio of the inner to the outer diameter of a nerve fiber. The purpose of this study was to evaluate WM damage in patients with MS via this novel MR imaging technique. Twenty patients with relapsing-remitting MS with a combined total of 149 chronic plaques were analyzed. Myelin volume fraction was calculated based on simultaneous tissue relaxometry. Intracellular and CSF compartment volume fractions were quantified via neurite orientation dispersion and density imaging. Axon volume fraction and g-ratio were calculated by combining these measurements. Myelin and axon volume fractions and g-ratio were measured in plaques, periplaque WM, and normal-appearing WM. All metrics differed significantly across the 3 groups ( P ratio between periplaque WM and normal-appearing WM). Those in plaques differed most from those in normal-appearing WM. The percentage changes in plaque and periplaque WM metrics relative to normal-appearing WM were significantly larger in absolute value for myelin volume fraction than for axon volume fraction and g-ratio ( P ratio may potentially be useful for evaluating WM damage in patients with MS. © 2017 by American Journal of Neuroradiology.

  17. Sensory and motor neuropathy in a Border Collie.

    Science.gov (United States)

    Harkin, Kenneth R; Cash, Walter C; Shelton, G Diane

    2005-10-15

    A 5-month-old female Border Collie was evaluated because of progressive hind limb ataxia. The predominant clinical findings suggested a sensory neuropathy. Sensory nerve conduction velocity was absent in the tibial, common peroneal, and radial nerves and was decreased in the ulnar nerve; motor nerve conduction velocity was decreased in the tibial, common peroneal, and ulnar nerves. Histologic examination of nerve biopsy specimens revealed considerable nerve fiber depletion; some tissue sections had myelin ovoids, foamy macrophages, and axonal degeneration in remaining fibers. Marked depletion of most myelinated fibers within the peroneal nerve (a mixed sensory and motor nerve) supported the electrodiagnostic findings indicative of sensorimotor neuropathy. Progressive deterioration in motor function occurred over the following 19 months until the dog was euthanatized. A hereditary link was not established, but a littermate was similarly affected. The hereditary characteristic of this disease requires further investigation.

  18. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Scanning laser polarimetry retinal nerve fiber layer thickness measurements after LASIK.

    Science.gov (United States)

    Zangwill, Linda M; Abunto, Teresa; Bowd, Christopher; Angeles, Raymund; Schanzlin, David J; Weinreb, Robert N

    2005-02-01

    To compare retinal nerve fiber layer (RNFL) thickness measurements before and after LASIK. Cohort study. Twenty participants undergoing LASIK and 14 normal controls. Retinal nerve fiber layer thickness was measured before LASIK and approximately 3 months after surgery in one eye each of 20 patients using a scanning laser polarimeter (GDx Nerve Fiber Analyzer) with fixed corneal compensation (FCC), one with variable corneal compensation (GDx VCC), and optical coherence tomography (OCT). Fourteen normal controls also were tested at baseline and approximately 3 months later. Retinal nerve fiber layer thicknesses measured with the GDx FCC, GDx VCC, and OCT. At baseline, mean (95% confidence interval [CI]) RNFL thicknesses for the GDx FCC, GDx VCC, and OCT were 78.1 microm (72.2-83.9), 54.3 microm (52.7-56.0), and 96.8 microm (93.2-100.5), respectively. In both LASIK and control groups, there were no significant changes between baseline and follow-up examinations in GDx VCC and OCT RNFL thickness measurements globally or in the superior and inferior quadrants (mean change, FCC measurements between baseline and follow-up. In LASIK patients, significant reductions were observed in GDx FCC RNFL measurements. Average absolute values of the mean (95% CI) change in thickness were 12.4 microm (7.7-17.2), 15.3 microm (9.6-20.9), and 12.9 microm (7.6-18.1) for GDx FCC RNFL measurements superiorly, inferiorly, and globally, respectively (all Ps FCC RNFL thickness measurements after LASIK is a measurement artifact and is most likely due to erroneous compensation for corneal birefringence. With scanning laser polarimetry, it is mandatory to compensate individually for change in corneal birefringence after LASIK to ensure accurate RNFL assessment.

  20. Crystal structure of the extracellular domain of human myelin protein zero

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Zhigang; Wang, Yong; Yedidi, Ravikiran S.; Brunzelle, Joseph S.; Kovari, Iulia A.; Sohi, Jasloveleen; Kamholz, John; Kovari, Ladislau C. (WSU-MED); (NWU)

    2012-03-27

    Charcot-Marie-Tooth disease (CMT), a hereditary motor and sensory neuropathy, is the most common genetic neuropathy with an incidence of 1 in 2600. Several forms of CMT have been identified arising from different genomic abnormalities such as CMT1 including CMT1A, CMT1B, and CMTX. CMT1 with associated peripheral nervous system (PNS) demyelination, the most frequent diagnosis, demonstrates slowed nerve conduction velocities and segmental demyelination upon nerve biopsy. One of its subtypes, CMT1A, presents a 1.5-Mb duplication in the p11-p12 region of the human chromosome 17 which encodes peripheral myelin protein 22 (PMP22). CMT1B, a less common form, arises from the mutations in the myelin protein zero (MPZ) gene on chromosome 1, region q22-q23, which encodes the major structural component of the peripheral myelin. A rare type of CMT1 has been found recently and is caused by point mutations in early growth response gene 2 (EGR2), encoding a zinc finger transcription factor in Schwann cells. In addition, CMTX, an X-linked form of CMT, arises from a mutation in the connexin-32 gene. Myelin protein zero, associated with CMT1B, is a transmembrane protein of 219 amino acid residues. Human MPZ consists of three domains: 125 residues constitute the glycosylated immunoglobulin-like extracellular domain; 27 residues span the membrane; and 67 residues comprise the highly basic intracellular domain. MPZ makes up approximately 50% of the protein content of myelin, and is expressed predominantly in Schwann cells, the myelinating cell of the PNS. Myelin protein zero, a homophilic adhesion molecule, is a member of the immunoglobulin super-family and is essential for normal myelin structure and function. In addition, MPZ knockout mice displayed abnormal myelin that severely affects the myelination pathway, and overexpression of MPZ causes congenital hypomyelination of peripheral nerves. Myelin protein zero mutations account for {approx}5% of patients with CMT. To date, over 125

  1. Effect of duration and severity of migraine on retinal nerve fiber layer, ganglion cell layer, and choroidal thickness.

    Science.gov (United States)

    Abdellatif, Mona K; Fouad, Mohamed M

    2018-03-01

    To investigate the factors in migraine that have the highest significance on retinal and choroidal layers' thickness. Ninety patients with migraine and 40 age-matched healthy participants were enrolled in this observational, cross-sectional study. After full ophthalmological examination, spectral domain-optical coherence tomography was done for all patients measuring the thickness of ganglion cell layer and retinal nerve fiber layer. Enhanced depth imaging technique was used to measure the choroidal thickness. There was significant thinning in the superior and inferior ganglion cell layers, all retinal nerve fiber layer quadrants, and all choroidal quadrants (except for the central subfield) in migraineurs compared to controls. The duration of migraine was significantly correlated with ganglion cell layer, retinal nerve fiber layer, and all choroidal quadrants, while the severity of migraine was significantly correlated with ganglion cell layer and retinal nerve fiber layer only. Multiregression analysis showed that the duration of migraine is the most important determinant factor of the superior retinal nerve fiber layer quadrant (β = -0.375, p = 0.001) and in all the choroidal quadrants (β = -0.531, -0.692, -0.503, -0.461, -0.564, respectively, p  layer quadrants (β = -0.256, -0.335, -0.308; p  = 0.036, 0.005, 0.009, respectively) and the inferior ganglion cell layer hemisphere (β = -0.377 and p = 0.001). Ganglion cell layer, retinal nerve fiber layer, and choroidal thickness are significantly thinner in patients with migraine. The severity of migraine has more significant influence in the thinning of ganglion cell layer and retinal nerve fiber layer, while the duration of the disease affected the choroidal thickness more.

  2. Serotonin Immunoreactive Cells and Nerve Fibers in the Mucosa of ...

    African Journals Online (AJOL)

    hydroxytryptamine) immunoreactivity in the pyloric mucosa of the rat stomach. The immunoreactive elements included the endocrine cells, mast cells and mucosal nerve fibers in the lamina propria. The immunopositive endocrine cells were oval in ...

  3. 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......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...

  4. Nanoscale Correlated Disorder in Out-of-Equilibrium Myelin Ultrastructure.

    Science.gov (United States)

    Campi, Gaetano; Di Gioacchino, Michael; Poccia, Nicola; Ricci, Alessandro; Burghammer, Manfred; Ciasca, Gabriele; Bianconi, Antonio

    2018-01-23

    Ultrastructural fluctuations at nanoscale are fundamental to assess properties and functionalities of advanced out-of-equilibrium materials. We have taken myelin as a model of supramolecular assembly in out-of-equilibrium living matter. Myelin sheath is a simple stable multilamellar structure of high relevance and impact in biomedicine. Although it is known that myelin has a quasi-crystalline ultrastructure, there is no information on its fluctuations at nanoscale in different states due to limitations of the available standard techniques. To overcome these limitations, we have used scanning micro X-ray diffraction, which is a unique non-invasive probe of both reciprocal and real space to visualize statistical fluctuations of myelin order of the sciatic nerve of Xenopus laevis. The results show that the ultrastructure period of the myelin is stabilized by large anticorrelated fluctuations at nanoscale, between hydrophobic and hydrophilic layers. The ratio between the total thickness of hydrophilic and hydrophobic layers defines the conformational parameter, which describes the different states of myelin. Our key result is that myelin in its out-of-equilibrium functional state fluctuates point-to-point between different conformations showing a correlated disorder described by a Levy distribution. As the system approaches the thermodynamic equilibrium in an aged state, the disorder loses its correlation degree and the structural fluctuation distribution changes to Gaussian. In a denatured state at low pH, it changes to a completely disordered stage. Our results aim to clarify the degradation mechanism in biological systems by associating these states with ultrastructural dynamic fluctuations at nanoscale.

  5. 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

    protein (MBP), a major autoantigen in MS, is a potent and specific ligand for the integrin αMβ2 (Mac-1, CD11b/CD18) expressed mainly on phagocytic cells. MBP undergoes a dramatic conformational change when liberated from the lipid-rich environment of the myelin sheath. The MS drug glatiramer acetate......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...

  6. A pilot study to evaluate the clinical relevance of endometriosis-associated nerve fibers in peritoneal endometriotic lesions.

    Science.gov (United States)

    Mechsner, Sylvia; Kaiser, Andrea; Kopf, Andreas; Gericke, Christine; Ebert, Andreas; Bartley, Julia

    2009-12-01

    To investigate the clinical relevance of endometriosis-associated nerve fibers in the development of endometriosis-associated symptoms. Prospective nonrandomized study. University hospital endometriosis center. Fifty-one premenopausal patients underwent surgical laparoscopy because of chronic pelvic pain, dysmenorrhea, or for ovarian cysts. Endometriosis was diagnosed in 44 patients. The preoperative and postoperative pain scores were determined using a standardized questionnaire with a visual analogue scale from 1-10. Patients with peritoneal endometriosis were divided into two groups depending on their preoperative pain score: group A with a pain score of at least 3 or more and group B with a pain score of 2 or less. Patients without peritoneal endometriosis were classified as group C and patients without endometriosis were classified as group D. Immunohistochemical analysis of neurofilament and protein gene product 9.5 were used for nerve fiber detection. Occurrence of endometriosis-associated nerve fibers was correlated with the severity of pelvic pain and/or dysmenorrhea. Peritoneal endometriosis-associated nerve fibers were found significantly more frequently in group A than in group B (82.6% vs. 33.3%). The present study suggests that the presence of endometriosis-associated nerve fibers in the peritoneum is important for the development of endometriosis-associated pelvic pain and dysmenorrhea.

  7. 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.

  8. Functional role of peripheral opioid receptors in the regulation of cardiac spinal afferent nerve activity during myocardial ischemia

    Science.gov (United States)

    Longhurst, John C.

    2013-01-01

    Thinly myelinated Aδ-fiber and unmyelinated C-fiber cardiac sympathetic (spinal) sensory nerve fibers are activated during myocardial ischemia to transmit the sensation of angina pectoris. Although recent observations showed that myocardial ischemia increases the concentrations of opioid peptides and that the stimulation of peripheral opioid receptors inhibits chemically induced visceral and somatic nociception, the role of opioids in cardiac spinal afferent signaling during myocardial ischemia has not been studied. The present study tested the hypothesis that peripheral opioid receptors modulate cardiac spinal afferent nerve activity during myocardial ischemia by suppressing the responses of cardiac afferent nerve to ischemic mediators like bradykinin and extracellular ATP. The nerve activity of single unit cardiac afferents was recorded from the left sympathetic chain (T2–T5) in anesthetized cats. Forty-three ischemically sensitive afferent nerves (conduction velocity: 0.32–3.90 m/s) with receptive fields in the left and right ventricles were identified. The responses of these afferent nerves to repeat ischemia or ischemic mediators were further studied in the following protocols. First, epicardial administration of naloxone (8 μmol), a nonselective opioid receptor antagonist, enhanced the responses of eight cardiac afferent nerves to recurrent myocardial ischemia by 62%, whereas epicardial application of vehicle (PBS) did not alter the responses of seven other cardiac afferent nerves to ischemia. Second, naloxone applied to the epicardial surface facilitated the responses of seven cardiac afferent nerves to epicardial ATP by 76%. Third, administration of naloxone enhanced the responses of seven other afferent nerves to bradykinin by 85%. In contrast, in the absence of naloxone, cardiac afferent nerves consistently responded to repeated application of ATP (n = 7) or bradykinin (n = 7). These data suggest that peripheral opioid peptides suppress the

  9. Role of Schwann cells in the regeneration of penile and peripheral nerves

    Directory of Open Access Journals (Sweden)

    Lin Wang

    2015-01-01

    Full Text Available Schwann cells (SCs are the principal glia of the peripheral nervous system. The end point of SC development is the formation of myelinating and nonmyelinating cells which ensheath large and small diameter axons, respectively. They play an important role in axon regeneration after injury, including cavernous nerve injury that leads to erectile dysfunction (ED. Despite improvement in radical prostatectomy surgical techniques, many patients still suffer from ED postoperatively as surgical trauma causes traction injuries and local inflammatory changes in the neuronal microenvironment of the autonomic fibers innervating the penis resulting in pathophysiological alterations in the end organ. The aim of this review is to summarize contemporary evidence regarding: (1 the origin and development of SCs in the peripheral and penile nerve system; (2 Wallerian degeneration and SC plastic change following peripheral and penile nerve injury; (3 how SCs promote peripheral and penile nerve regeneration by secreting neurotrophic factors; (4 and strategies targeting SCs to accelerate peripheral nerve regeneration. We searched PubMed for articles related to these topics in both animal models and human research and found numerous studies suggesting that SCs could be a novel target for treatment of nerve injury-induced ED.

  10. 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).

  11. 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.

  12. 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

    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....

  13. Cytoskeletal Linker Protein Dystonin Is Not Critical to Terminal Oligodendrocyte Differentiation or CNS Myelination.

    Directory of Open Access Journals (Sweden)

    Samantha F Kornfeld

    Full Text Available Oligodendrocyte differentiation and central nervous system myelination require massive reorganization of the oligodendrocyte cytoskeleton. Loss of specific actin- and tubulin-organizing factors can lead to impaired morphological and/or molecular differentiation of oligodendrocytes, resulting in a subsequent loss of myelination. Dystonin is a cytoskeletal linker protein with both actin- and tubulin-binding domains. Loss of function of this protein results in a sensory neuropathy called Hereditary Sensory Autonomic Neuropathy VI in humans and dystonia musculorum in mice. This disease presents with severe ataxia, dystonic muscle and is ultimately fatal early in life. While loss of the neuronal isoforms of dystonin primarily leads to sensory neuron degeneration, it has also been shown that peripheral myelination is compromised due to intrinsic Schwann cell differentiation abnormalities. The role of this cytoskeletal linker in oligodendrocytes, however, remains unclear. We sought to determine the effects of the loss of neuronal dystonin on oligodendrocyte differentiation and central myelination. To address this, primary oligodendrocytes were isolated from a severe model of dystonia musculorum, Dstdt-27J, and assessed for morphological and molecular differentiation capacity. No defects could be discerned in the differentiation of Dstdt-27J oligodendrocytes relative to oligodendrocytes from wild-type littermates. Survival was also compared between Dstdt-27J and wild-type oligodendrocytes, revealing no significant difference. Using a recently developed migration assay, we further analysed the ability of primary oligodendrocyte progenitor cell motility, and found that Dstdt-27J oligodendrocyte progenitor cells were able to migrate normally. Finally, in vivo analysis of oligodendrocyte myelination was done in phenotype-stage optic nerve, cerebral cortex and spinal cord. The density of myelinated axons and g-ratios of Dstdt-27J optic nerves was normal, as

  14. Effect of diabetic retinopathy and panretinal photocoagulation on retinal nerve fiber layer and optic nerve appearance.

    Science.gov (United States)

    Lim, Michele C; Tanimoto, Suzana A; Furlani, Bruno A; Lum, Brent; Pinto, Luciano M; Eliason, David; Prata, Tiago S; Brandt, James D; Morse, Lawrence S; Park, Susanna S; Melo, Luiz A S

    2009-07-01

    To determine if panretinal photocoagulation (PRP) alters retinal nerve fiber layer (RNFL) thickness and optic nerve appearance. Patients with diabetes who did and did not undergo PRP and nondiabetic control subjects were enrolled in a prospective study. Participants underwent optical coherence tomography of the peripapillary retina and optic nerve. Stereoscopic optic nerve photographs were graded in a masked fashion. Ninety-four eyes of 48 healthy individuals, 89 eyes of 55 diabetic patients who did not undergo PRP, and 37 eyes of 24 subjects with diabetes who underwent PRP were included in this study. Eyes that had been treated with PRP had thinner peripapillary RNFL compared with the other groups; this was statistically significantly different in the inferior (P = .004) and nasal (P = .003) regions. Optic nerve cupping did not increase with severity of disease classification, but the proportion of optic nerves graded as suspicious for glaucoma or as having nonglaucomatous optic neuropathy did (P = .008). These grading categories were associated with thinner RNFL measurements. Diabetic eyes that have been treated with PRP have thinner RNFL than nondiabetic eyes. Optic nerves in eyes treated with PRP are more likely to be graded as abnormal, but their appearance is not necessarily glaucomatous and may be related to thinning of the RNFL.

  15. 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.

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

    Science.gov (United States)

    Frixione, Eugenio

    2013-01-01

    Available records indicate that the human body has always been conceived, in different periods and cultures, as spanned by multiple channels for internal communication and coherent functioning as a unit-"meridians" in treatises of Chinese medicine, metu in Egyptian papyri, srotas in Ayurvedic Indian texts, and neura in the Western scientific heritage from ancient Greece. Unfortunately, the earliest extant figurative depictions of such pathways of general control, complementary to the blood vessels, are late medieval copies of old crude sketches that attempted to show the main anatomico-physiological systems. The scarcity of adequate illustrations was more than compensated in the Renaissance, when the efforts of both artists and anatomists for the first time produced basically correct renditions of the human nervous system and many other bodily structures. As attention was next focused on microscopic structure as a requisite to understand physiological mechanisms, during the Enlightenment the nerves were revealed to consist of numerous thin tubes or fibers aligned in parallel. Improved microscopy techniques in the nineteenth century led to discovering and delineating still finer fibrils coursing along the cores of the nerve fibers themselves. Electron microscopy, developed throughout the twentieth century, recognized some of these fibrils within nerve fibers as being also tubular. All the progressive stages in understanding nerve construction, at increasingly more detailed scales, have been accompanied by technological advances and by debate about the structure and function relationship. And every step has been a source of amazing imagery. © 2013 Elsevier B.V. All rights reserved.

  17. [Ultrastructural changes of myelinated fibers in the brain in continuous and attack-like paranoid schizophrenia].

    Science.gov (United States)

    Uranova, N A; Kolomeets, N S; Vikhreva, O V; Zimina, I S; Rakhmanova, V I; Orlovskaya, D D

    Previously the authors have reported the ultrastructural pathology of myelinated fibers (MF) in the brain in schizophrenia. The aim of the present study was to compare the effect of disease course on ultrastructural changes of MF. Postmortem electron microscopic morphometric study of MF was performed in the prefrontal cortex, caudate nucleus and hippocampus in 19 cases of paranoid schizophrenia. Fourteen cases of continuous schizophrenia, 5 cases of attack-like schizophrenia and 25 normal matched control cases were studied. The proportion (percentage) of pathological MF was estimated in the prefrontal cortex, layer 5, CA3 area of hippocampus, pyramidal layer, and in the head of the caudate nucleus. The percentage of MF having axonal atrophy and swelling of periaxonal oligodendrocyte process was significantly higher in both continuous and attack-like schizophrenia in all brain structures studied as compared to the control group. In the hippocampus and caudate nucleus, this parameter was increased significantly in attack-like schizophrenia as compared to continuous schizophrenia. In the prefrontal cortex. The percentage of the pathological MF having signs of deformation and destruction of myelin sheaths increased significantly only in continuous schizophrenia as compared to the control group. MF pathology is similar in attack-like and continuous paranoid schizophrenia but differ by the degree of severity of pathological MF. Abnormalities in MF contribute to the disconnectivity between the prefrontal cortex, caudate nucleus and hippocampus.

  18. Diffusion tensor imaging for nerve fiber bundles in the brain stem and spinocerebellar degeneration

    International Nuclear Information System (INIS)

    Honma, Tsuguo

    2009-01-01

    Diffusion tensor imaging (DTI) can create an image of the anisotropic nature of diffusion and express it quantitatively. Nerve fibers have a large anisotropic diffusion, and it is possible to obtain images of the nerve fiber bundle. The purpose of this study is to observe the nerve fiber bundles in the brain stem using DTI and study its potential for diagnosing the type of spinocerebellar degeneration (SCD). Fractional anisotropy (FA) maps and 3D-tractography images were obtained for 41 subjects with no brain stem abnormalities. We created an apparent diffusion coefficient (ADC) map and an FA map using DTI for 16 subjects in the disease group (11 with hereditary SCD and 5 with non-hereditary SCD) and 25 in the control group. The diffusion value of the pons and middle cerebellar peduncle was measured using ADC, and the degree of anisotropic diffusion was measured using FA. The pyramidal tract, superior cerebellar peduncle, and inferior cerebellar peduncle were clearly demonstrated for all cases. ADC for the middle cerebellar peduncle in spinocerebellar ataxin (SCA)1 was significantly higher, similar to that for the pons in dentatorubro-pallidoluysian atrophy (DRPLA). In MSA-C, ADC for both the pons and middle cerebellar peduncle was significantly elevated and FA was significantly decreased. There were no significant changes in SCA3. We could observe the nerve fiber bundles in the brain stem using DTI. FA and ADC measurements with DTI can aid in diagnosing the type of SCD. (author)

  19. A multiparametric assay for quantitative nerve regeneration evaluation.

    Science.gov (United States)

    Weyn, B; van Remoortere, M; Nuydens, R; Meert, T; van de Wouwer, G

    2005-08-01

    We introduce an assay for the semi-automated quantification of nerve regeneration by image analysis. Digital images of histological sections of regenerated nerves are recorded using an automated inverted microscope and merged into high-resolution mosaic images representing the entire nerve. These are analysed by a dedicated image-processing package that computes nerve-specific features (e.g. nerve area, fibre count, myelinated area) and fibre-specific features (area, perimeter, myelin sheet thickness). The assay's performance and correlation of the automatically computed data with visually obtained data are determined on a set of 140 semithin sections from the distal part of a rat tibial nerve from four different experimental treatment groups (control, sham, sutured, cut) taken at seven different time points after surgery. Results show a high correlation between the manually and automatically derived data, and a high discriminative power towards treatment. Extra value is added by the large feature set. In conclusion, the assay is fast and offers data that currently can be obtained only by a combination of laborious and time-consuming tests.

  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. Technique Selectively Represses Immune System

    Science.gov (United States)

    ... Research Matters December 3, 2012 Technique Selectively Represses Immune System Myelin (green) encases and protects nerve fibers (brown). A new technique prevents the immune system from attacking myelin in a mouse model of ...

  2. 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

    were studied. 2) Vibration-sensitive fibers were found in both the anterior and posterior branch of the VIIIth nerve. 3) No vibration-sensitive fibers were found in the lagenar nerve. 4) The vibration-sensitive fibers in the posterior branch probably innervated the amphibian papilla and many...... of these fibers also responded to low-frequency sound. 5) The vibration-sensitive fibers in the anterior branch probably innervated the sacculus and the utriculus. 6) Hence, the grassfrog has at least two, and probably three, vibration-sensitive organs in the inner ear. 7) All fibers had V-shaped vibrational...... tuning curves. In the posterior branch best frequencies (BFs) ranged from 10 to 300 Hz, in the anterior branch from 10 to 100 Hz. In the posterior branch spike-rate thresholds at BF ranged from 0.04 to 1.28 cm/s2, in the anterior branch from 0.02 to 1.28 cm/s2. All fibers showed strong synchronization...

  3. 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.

  4. Optic Nerve Imaging

    Science.gov (United States)

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

  5. Taste bud-derived BDNF maintains innervation of a subset of TrkB-expressing gustatory nerve fibers.

    Science.gov (United States)

    Tang, Tao; Rios-Pilier, Jennifer; Krimm, Robin

    2017-07-01

    Taste receptor cells transduce different types of taste stimuli and transmit this information to gustatory neurons that carry it to the brain. Taste receptor cells turn over continuously in adulthood, requiring constant new innervation from nerve fibers. Therefore, the maintenance of innervation to taste buds is an active process mediated by many factors, including brain-derived neurotrophic factor (BDNF). Specifically, 40% of taste bud innervation is lost when Bdnf is removed during adulthood. Here we speculated that not all gustatory nerve fibers express the BDNF receptor, TrkB, resulting in subsets of neurons that vary in their response to BDNF. However, it is also possible that the partial loss of innervation occurred because the Bdnf gene was not effectively removed. To test these possibilities, we first determined that not all gustatory nerve fibers express the TrkB receptor in adult mice. We then verified the efficiency of Bdnf removal specifically in taste buds of K14-CreER:Bdnf mice and found that Bdnf expression was reduced to 1%, indicating efficient Bdnf gene recombination. BDNF removal resulted in a 55% loss of TrkB-expressing nerve fibers, which was greater than the loss of P2X3-positive fibers (39%), likely because taste buds were innervated by P2X3+/TrkB- fibers that were unaffected by BDNF removal. We conclude that gustatory innervation consists of both TrkB-positive and TrkB-negative taste fibers and that BDNF is specifically important for maintaining TrkB-positive innervation to taste buds. In addition, although taste bud size was not affected by inducible Bdnf removal, the expression of the γ subunit of the ENaC channel was reduced. So, BDNF may regulate expression of some molecular components of taste transduction pathways. Copyright © 2017. Published by Elsevier Inc.

  6. 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

    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......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...

  7. Myelination and myelin disorders

    International Nuclear Information System (INIS)

    Knaap, M.S. van der.

    1991-01-01

    The first part of this thesis contains the results of a study into the capabilities of MR in the assessment of normal cerebral development. The process of normal myelination under the age of 1 year is divided into stages with specific MRI characteristics. An indication of normal age limits for each stage is given. The relationships between changes in signal intensities and biochemical background, and between progress of myelination and psychomotor development are discussed. The latter in the light of a study performed in hydrocephalic children, prior to and repeatedly after shunt implantation. Normal changes in 1 H and 31 P spectra of the brain in infants and children are described. The relationship between observed spectral changes and cerebral maturational processes is discussed. The second part deals with assessment of myelin disorders with MRI. Basic information about demyelinating disorders and biochemical background are reviewed. A new classification of myelin disorders, underlying the development of an MRI pattern recognition scheme, is proposed based on the most recent scientific developments. Common histological characteristics are described for all main categories of myelin disorders. Extensive information is presented about MRI patterns of abnormalities in patients in whom the disease is predominantly or exclusively located in the white matter. On the basis of the data of these patients a global MRI pattern recognition scheme has been developed covering all white matter disorders that were encountered. Also an example of an in-depth pattern recognition in a circumscribed category of disorders is presented. Finally a study of MRS in demyelinating disorders as opposed to neuronal disorders is described. While MRI provides information about the extent of the process of demyelination and about the disease category, MRS turns out to provide information about the severity of the demyelination and of the concomitant neuronal damage. (H.W.). 725 refs.; 53 figs

  8. COMPARISON OF HEMATOXYLIN AND EOSIN STAINING WITH AND WITHOUT PRE TREATMENT WITH MARCHI’S SOLUTION ON NERVE SAMPLES FOR NERVE DEGENERATION AND REGENERATION STUDIES

    Directory of Open Access Journals (Sweden)

    Malik Abu Rafee

    2017-12-01

    Full Text Available The study was conducted on four healthy guinea pigs (Cavia porcellus of either sex in which the nerve was identified and subjected to crush injury with the tip (3mm of a curved hemostatic forceps. 30 days after the injury nerve samples were collected and subjected to Hematoxylin and Eosin staining with or without pretreatment with Marchi’s solution. The routine Hematoxylin and Eosin (H&E stained all neural elements in various intensities of pink and in purple and the degenerative changes were seen as vacuoles ranging from vacuolated foci- containing eosinophilic material and associated with a distorted cell nucleus to larger, multilocular, linear array of compartmentalized digestion chambers supposed to contain myelin debris .The myelin on the other hand appeared as empty zones in H&E staining. Combining Marchi’s and H & E procedures revealed the presence black aggregates/ deposits in the vacuoles and digestion chambers. This method confirmed the presence of degenerated myelin inside the vacuoles and digestion chambers and thus may allow better analysis of nerve damage and regeneration.

  9. Investigation of interactions in a biological membrane using structure factor/pair correlation function approach: a first communication on nerve myelin

    International Nuclear Information System (INIS)

    Gbordzoe, M.K.

    1984-09-01

    Interactions in biological and artificial membranes have been studied by applying mostly the methods of biochemical analysis and determination of thermodynamic parameters related to phase transition phenomena. Structure factor, obtained by measuring scattered intensity from small-angle X-ray or neutron scattering experiments, has been used mainly for determining electron density distribution. Drawing upon the experience of the theory of liquids, where Johnson and March (1963) and Johnson, Hutchinson and March (1964) first established the possibility of deriving interparticle potential from experimental measurement of structure factor, it is suggested that structure factor/distance correlation function approach, can be a useful method for studying interactions between various membrane components. Preliminary experimental data presented for nerve myelin are to demonstrate the possibility of studying interactions from the distance correlation function of a membrane pair. (author)

  10. Deficiency in monocarboxylate transporter 1 (MCT1) in mice delays regeneration of peripheral nerves following sciatic nerve crush

    KAUST Repository

    Morrison, Brett M.; Tsingalia, Akivaga; Vidensky, Svetlana; Lee, Youngjin; Jin, Lin; Farah, Mohamed H.; Lengacher, Sylvain; Magistretti, Pierre J.; Pellerin, Luc; Rothsteinb, Jeffrey D.

    2015-01-01

    Peripheral nerve regeneration following injury occurs spontaneously, but many of the processes require metabolic energy. The mechanism of energy supply to axons has not previously been determined. In the central nervous system, monocarboxylate transporter 1 (MCT1), expressed in oligodendroglia, is critical for supplying lactate or other energy metabolites to axons. In the current study, MCT1 is shown to localize within the peripheral nervous system to perineurial cells, dorsal root ganglion neurons, and Schwann cells by MCT1 immunofluorescence in wild-type mice and tdTomato fluorescence in MCT1 BAC reporter mice. To investigate whether MCT1 is necessary for peripheral nerve regeneration, sciatic nerves of MCT1 heterozygous mice are crushed and peripheral nerve regeneration was quantified electrophysiologically and anatomically. Compound muscle action potential (CMAP) recovery is delayed from a median of 21. days in wild-type mice to greater than 38. days in MCT1 heterozygote mice. In fact, half of the MCT1 heterozygote mice have no recovery of CMAP at 42. days, while all of the wild-type mice recovered. In addition, muscle fibers remain 40% more atrophic and neuromuscular junctions 40% more denervated at 42. days post-crush in the MCT1 heterozygote mice than wild-type mice. The delay in nerve regeneration is not only in motor axons, as the number of regenerated axons in the sural sensory nerve of MCT1 heterozygote mice at 4. weeks and tibial mixed sensory and motor nerve at 3. weeks is also significantly reduced compared to wild-type mice. This delay in regeneration may be partly due to failed Schwann cell function, as there is reduced early phagocytosis of myelin debris and remyelination of axon segments. These data for the first time demonstrate that MCT1 is critical for regeneration of both sensory and motor axons in mice following sciatic nerve crush.

  11. Repair of facial nerve defects with decellularized artery allografts containing autologous adipose-derived stem cells in a rat model.

    Science.gov (United States)

    Sun, Fei; Zhou, Ke; Mi, Wen-Juan; Qiu, Jian-Hua

    2011-07-20

    The purpose of this study was to investigate the effects of a decellularized artery allograft containing autologous adipose-derived stem cells (ADSCs) on an 8-mm facial nerve branch lesion in a rat model. At 8 weeks postoperatively, functional evaluation of unilateral vibrissae movements, morphological analysis of regenerated nerve segments and retrograde labeling of facial motoneurons were all analyzed. Better regenerative outcomes associated with functional improvement, great axonal growth, and improved target reinnervation were achieved in the artery-ADSCs group (2), whereas the cut nerves sutured with artery conduits alone (group 1) achieved inferior restoration. Furthermore, transected nerves repaired with nerve autografts (group 3) resulted in significant recovery of whisking, maturation of myelinated fibers and increased number of labeled facial neurons, and the latter two parameters were significantly different from those of group 2. Collectively, though our combined use of a decellularized artery allograft with autologous ADSCs achieved regenerative outcomes inferior to a nerve autograft, it certainly showed a beneficial effect on promoting nerve regeneration and thus represents an alternative approach for the reconstruction of peripheral facial nerve defects. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  12. Chronic migraine is associated with reduced corneal nerve fiber density and symptoms of dry eye.

    Science.gov (United States)

    Kinard, Krista I; Smith, A Gordon; Singleton, J Robinson; Lessard, Margaret K; Katz, Bradley J; Warner, Judith E A; Crum, Alison V; Mifflin, Mark D; Brennan, Kevin C; Digre, Kathleen B

    2015-04-01

    We used in vivo corneal confocal microscopy to investigate structural differences in the sub-basal corneal nerve plexus in chronic migraine patients and a normal population. We used a validated questionnaire and tests of lacrimal function to determine the prevalence of dry eye in the same group of chronic migraine patients. Activation of the trigeminal system is involved in migraine. Corneal nociceptive sensation is mediated by trigeminal axons that synapse in the gasserian ganglion and the brainstem, and serve nociceptive, protective, and trophic functions. Noninvasive imaging of the corneal sub-basal nerve plexus is possible with in vivo corneal confocal microscopy. For this case-control study, we recruited chronic migraine patients and compared them with a sex- and age-similar group of control subjects. Patients with peripheral neuropathy, a disease known to be associated with a peripheral neuropathy, or prior corneal or intraocular surgery were excluded. Participants underwent in vivo corneal confocal microscopy using a Heidelberg Retinal Tomography III confocal microscope with a Rostock Cornea Module. Nerve fiber length, nerve branch density, nerve fiber density, and tortuosity coefficient were measured using established methodologies. Migraine participants underwent testing of basal tear production with proparacaine, corneal sensitivity assessment with a cotton-tip applicator, measurement of tear break-up time, and completion of a validated dry eye questionnaire. A total of 19 chronic migraine patients and 30 control participants completed the study. There were no significant differences in age or sex. Nerve fiber density was significantly lower in migraine patients compared with controls (48.4 ± 23.5 vs. 71.0 ± 15.0 fibers/mm2 , P dry eye syndrome. We found that in the sample used in this study, the presence of structural changes in nociceptive corneal axons lends further support to the hypothesis that the trigeminal system plays a critical role

  13. Allograft pretreatment for the repair of sciatic nerve defects: green tea polyphenols versus radiation

    Directory of Open Access Journals (Sweden)

    Sheng-hu Zhou

    2015-01-01

    Full Text Available Pretreatment of nerve allografts by exposure to irradiation or green tea polyphenols can eliminate neuroimmunogenicity, inhibit early immunological rejection, encourage nerve regeneration and functional recovery, improve tissue preservation, and minimize postoperative infection. In the present study, we investigate which intervention achieves better results. We produced a 1.0 cm sciatic nerve defect in rats, and divided the rats into four treatment groups: autograft, fresh nerve allograft, green tea polyphenol-pretreated (1 mg/mL, 4°C nerve allograft, and irradiation-pretreated nerve allograft (26.39 Gy/min for 12 hours; total 19 kGy. The animals were observed, and sciatic nerve electrophysiology, histology, and transmission electron microscopy were carried out at 6 and 12 weeks after grafting. The circumference and structure of the transplanted nerve in rats that received autografts or green tea polyphenol-pretreated nerve allografts were similar to those of the host sciatic nerve. Compared with the groups that received fresh or irradiation-pretreated nerve allografts, motor nerve conduction velocity in the autograft and fresh nerve allograft groups was greater, more neurites grew into the allografts, Schwann cell proliferation was evident, and a large number of new blood vessels was observed; in addition, massive myelinated nerve fibers formed, and abundant microfilaments and microtubules were present in the axoplasm. Our findings indicate that nerve allografts pretreated by green tea polyphenols are equivalent to transplanting autologous nerves in the repair of sciatic nerve defects, and promote nerve regeneration. Pretreatment using green tea polyphenols is better than pretreatment with irradiation

  14. Renal hemodynamic effects of activation of specific renal sympathetic nerve fiber groups.

    Science.gov (United States)

    DiBona, G F; Sawin, L L

    1999-02-01

    To examine the effect of activation of a unique population of renal sympathetic nerve fibers on renal blood flow (RBF) dynamics, anesthetized rats were instrumented with a renal sympathetic nerve activity (RSNA) recording electrode and an electromagnetic flow probe on the ipsilateral renal artery. Peripheral thermal receptor stimulation (external heat) was used to activate a unique population of renal sympathetic nerve fibers and to increase total RSNA. Total RSNA was reflexly increased to the same degree with somatic receptor stimulation (tail compression). Arterial pressure and heart rate were increased by both stimuli. Total RSNA was increased to the same degree by both stimuli but external heat produced a greater renal vasoconstrictor response than tail compression. Whereas both stimuli increased spectral density power of RSNA at both cardiac and respiratory frequencies, modulation of RBF variability by fluctuations of RSNA was small at these frequencies, with values for the normalized transfer gain being approximately 0.1 at >0.5 Hz. During tail compression coherent oscillations of RSNA and RBF were found at 0.3-0.4 Hz with normalized transfer gain of 0.33 +/- 0.02. During external heat coherent oscillations of RSNA and RBF were found at both 0.2 and 0.3-0.4 Hz with normalized transfer gains of 0. 63 +/- 0.05 at 0.2 Hz and 0.53 +/- 0.04 to 0.36 +/- 0.02 at 0.3-0.4 Hz. Renal denervation eliminated the oscillations in RBF at both 0.2 and 0.3-0.4 Hz. These findings indicate that despite similar increases in total RSNA, external heat results in a greater renal vasoconstrictor response than tail compression due to the activation of a unique population of renal sympathetic nerve fibers with different frequency-response characteristics of the renal vasculature.

  15. Morphological Changes and Immunohistochemical Expression of RAGE and its Ligands in the Sciatic Nerve of Hyperglycemic Pig (Sus Scrofa

    Directory of Open Access Journals (Sweden)

    Judyta K. Juranek

    2010-09-01

    Full Text Available The aim of our project was to study the effect of streptozotocin (STZ—induced hyperglycemia on sciatic nerve morphology, blood plasma markers and immunohistochemical expression of RAGE (the Receptor for Advanced Glycation End-products, and its ligands—S100B and Carboxymethyl Lysine (CML-advanced glycation endproduct (AGE in the laboratory pig. Six months after STZ—injections, blood plasma measurements, morphometric analysis of sciatic nerve fiber density, immunofluorescent distribution of potential molecular neuropathy contributors, ELISA measurement of plasma AGE level and HPLC analysis of sciatic nerve levels of one of the pre-AGE and the glycolysis intermediate products—methyl-glyoxal (MG were performed. The results of our study revealed that STZ—injected animals displayed elevated levels of plasma glucose, gamma glutamyl transferase (GGT and triglycerides. The sciatic nerve of STZ-injected pigs revealed significantly lower numbers of small-diameter myelinated fibers, higher immunoreactivity for RAGE and S100B and increased levels of MG as compared to control animals. Our results correspond to clinical findings in human patients with hyperglycemia/diabetes-evoked peripheral neuropathy and suggest that the domestic pig may be a suitable large animal model for the study of mechanisms underlying hyperglycemia-induced neurological complications in the peripheral nerve and may serve as a relevant model for the pre-clinical assessment of candidate drugs in neuropathy.

  16. Morphological Changes and Immunohistochemical Expression of RAGE and its Ligands in the Sciatic Nerve of Hyperglycemic Pig (Sus Scrofa

    Directory of Open Access Journals (Sweden)

    Judyta K. Juranek

    2010-01-01

    Full Text Available The aim of our project was to study the effect of streptozotocin (STZ–-induced hyperglycemia on sciatic nerve morphology, blood plasma markers and immunohistochemical expression of RAGE (the Receptor for Advanced Glycation End-products, and its ligands–-S100B and Carboxymethyl Lysine (CML-advanced glycation endproduct (AGE in the laboratory pig. Six months after STZ–-injections, blood plasma measurements, morphometric analysis of sciatic nerve fiber density, immunofluorescent distribution of potential molecular neuropathy contributors, ELISA measurement of plasma AGE level and HPLC analysis of sciatic nerve levels of one of the pre-AGE and the glycolysis intermediate products–-methylglyoxal (MG were performed. The results of our study revealed that STZ–-injected animals displayed elevated levels of plasma glucose, gamma glutamyl transferase (GGT and triglycerides. The sciatic nerve of STZ-injected pigs revealed significantly lower numbers of small-diameter myelinated fibers, higher immunoreactivity for RAGE and S100B and increased levels of MG as compared to control animals. Our results correspond to clinical findings in human patients with hyperglycemia/diabetes-evoked peripheral neuropathy and suggest that the domestic pig may be a suitable large animal model for the study of mechanisms underlying hyperglycemia-induced neurological complications in the peripheral nerve and may serve as a relevant model for the pre-clinical assessment of candidate drugs in neuropathy.

  17. Effect of anti-GM2 antibodies on rat sciatic nerve: electrophysiological and morphological study.

    Science.gov (United States)

    Ortiz, Nicolau; Sabaté, M Mar; Garcia, Neus; Santafe, Manel M; Lanuza, M Angel; Tomàs, Marta; Tomàs, Josep

    2009-03-31

    We found that a monoclonal human IgM anti-GM2 was fixed in rat sciatic axons and Schwann cells and was able to activate human complement. The passive transfer of IgM and complement in sciatic nerves can induce an acute alteration in nerve conduction. When the transfer of IgM plus complement was repeated for 10 days, the compound action motor potential amplitude was very low and the morphological study showed axons and myelin damage. Without human complement, IgM can only slightly disorganize the myelin by separating some layers, probably by interfering with the functional role of gangliosides in the myelin package.

  18. 17β-Estradiol Promotes Schwann Cell Proliferation and Differentiation, Accelerating Early Remyelination in a Mouse Peripheral Nerve Injury Model

    Directory of Open Access Journals (Sweden)

    Yan Chen

    2016-01-01

    Full Text Available Estrogen induces oligodendrocyte remyelination in response to demyelination in the central nervous system. Our objective was to determine the effects of 17β-estradiol (E2 on Schwann cell function and peripheral nerve remyelination after injury. Adult male C57BL/6J mice were used to prepare the sciatic nerve transection injury model and were randomly categorized into control and E2 groups. To study myelination in vitro, dorsal root ganglion (DRG explant culture was prepared using 13.5-day-old mouse embryos. Primary Schwann cells were isolated from the sciatic nerves of 1- to 3-day-old Sprague–Dawley rats. Immunostaining for myelin basic protein (MBP expression and toluidine blue staining for myelin sheaths demonstrated that E2 treatment accelerates early remyelination in the “nerve bridge” region between the proximal and distal stumps of the transection injury site in the mouse sciatic nerve. The 5-bromo-2′-deoxyuridine incorporation assay revealed that E2 promotes Schwann cell proliferation in the bridge region and in the primary culture, which is blocked using AKT inhibitor MK2206. The in vitro myelination in the DRG explant culture determined showed that the MBP expression in the E2-treated group is higher than that in the control group. These results show that E2 promotes Schwann cell proliferation and myelination depending on AKT activation.

  19. 17β-Estradiol Promotes Schwann Cell Proliferation and Differentiation, Accelerating Early Remyelination in a Mouse Peripheral Nerve Injury Model

    Science.gov (United States)

    Chen, Yan; Guo, Wenjie; Li, Wenjuan; Cheng, Meng; Hu, Ying; Xu, Wenming

    2016-01-01

    Estrogen induces oligodendrocyte remyelination in response to demyelination in the central nervous system. Our objective was to determine the effects of 17β-estradiol (E2) on Schwann cell function and peripheral nerve remyelination after injury. Adult male C57BL/6J mice were used to prepare the sciatic nerve transection injury model and were randomly categorized into control and E2 groups. To study myelination in vitro, dorsal root ganglion (DRG) explant culture was prepared using 13.5-day-old mouse embryos. Primary Schwann cells were isolated from the sciatic nerves of 1- to 3-day-old Sprague–Dawley rats. Immunostaining for myelin basic protein (MBP) expression and toluidine blue staining for myelin sheaths demonstrated that E2 treatment accelerates early remyelination in the “nerve bridge” region between the proximal and distal stumps of the transection injury site in the mouse sciatic nerve. The 5-bromo-2′-deoxyuridine incorporation assay revealed that E2 promotes Schwann cell proliferation in the bridge region and in the primary culture, which is blocked using AKT inhibitor MK2206. The in vitro myelination in the DRG explant culture determined showed that the MBP expression in the E2-treated group is higher than that in the control group. These results show that E2 promotes Schwann cell proliferation and myelination depending on AKT activation. PMID:27872858

  20. Direct visualization of membrane architecture of myelinating cells in transgenic mice expressing membrane-anchored EGFP.

    Science.gov (United States)

    Deng, Yaqi; Kim, BongWoo; He, Xuelian; Kim, Sunja; Lu, Changqing; Wang, Haibo; Cho, Ssang-Goo; Hou, Yiping; Li, Jianrong; Zhao, Xianghui; Lu, Q Richard

    2014-04-01

    Myelinogenesis is a complex process that involves substantial and dynamic changes in plasma membrane architecture and myelin interaction with axons. Highly ramified processes of oligodendrocytes in the central nervous system (CNS) make axonal contact and then extrapolate to wrap around axons and form multilayer compact myelin sheathes. Currently, the mechanisms governing myelin sheath assembly and axon selection by myelinating cells are not fully understood. Here, we generated a transgenic mouse line expressing the membrane-anchored green fluorescent protein (mEGFP) in myelinating cells, which allow live imaging of details of myelinogenesis and cellular behaviors in the nervous systems. mEGFP expression is driven by the promoter of 2'-3'-cyclic nucleotide 3'-phosphodiesterase (CNP) that is expressed in the myelinating cell lineage. Robust mEGFP signals appear in the membrane processes of oligodendrocytes in the CNS and Schwann cells in the peripheral nervous system (PNS), wherein mEGFP expression defines the inner layers of myelin sheaths and Schmidt-Lanterman incisures in adult sciatic nerves. In addition, mEGFP expression can be used to track the extent of remyelination after demyelinating injury in a toxin-induced demyelination animal model. Taken together, the membrane-anchored mEGFP expression in the new transgenic line would facilitate direct visualization of dynamic myelin membrane formation and assembly during development and process remodeling during remyelination after various demyelinating injuries.

  1. Correlation between local glaucomatous visual field defects and loss of nerve fiber layer thickness measured with polarimetry and spectral domain OCT.

    Science.gov (United States)

    Horn, Folkert K; Mardin, Christian Y; Laemmer, Robert; Baleanu, Delia; Juenemann, Anselm M; Kruse, Friedrich E; Tornow, Ralf P

    2009-05-01

    To study the correlation between local perimetric field defects and glaucoma-induced thickness reduction of the nerve layer measured in the peripapillary area with scanning laser polarimetry (SLP) and spectral domain optical coherence tomography (SOCT) and to compare the results with those of a theoretical model. The thickness of the retinal nerve fiber layer was determined in 32 sectors (11.25 degrees each) by using SLP with variable cornea compensation (GDxVCC; Laser Diagnostics, San Diego, CA) and the newly introduced high-resolution SOCT (Spectralis; Heidelberg Engineering, Heidelberg, Germany). Eighty-eight healthy subjects served as control subjects, to determine the thickness deviation in patients with glaucoma. The relationship between glaucomatous nerve fiber reduction and visual field losses was calculated in six nerve fiber bundle-related areas. Sixty-four patients at different stages of open-angle glaucoma and 26 patients with ocular hypertension underwent perimetry (Octopus G1; Haag-Streit, Köniz, Switzerland) and measurements with the two morphometric techniques. Sector-shaped analyses between local perimetric losses and reduction of the retinal nerve fiber layer thickness showed a significant association for corresponding areas except for the central visual field in SLP. Correlation coefficients were highest in the area of the nasal inferior visual field (SOCT, -0.81; SLP, -0.57). A linear model describes the association between structural and functional damage. Localized perimetric defects can be explained by reduced nerve fiber layer thickness. The data indicate that the present SOCT is useful for determining the functional-structural relationship in peripapillary areas and that association between perimetric defects and corresponding nerve fiber losses is stronger for SOCT than for the present SLP. (ClinicalTrials.gov number, NCT00494923.).

  2. Stabilization, Rolling, and Addition of Other Extracellular Matrix Proteins to Collagen Hydrogels Improve Regeneration in Chitosan Guides for Long Peripheral Nerve Gaps in Rats.

    Science.gov (United States)

    Gonzalez-Perez, Francisco; Cobianchi, Stefano; Heimann, Claudia; Phillips, James B; Udina, Esther; Navarro, Xavier

    2017-03-01

    Autograft is still the gold standard technique for the repair of long peripheral nerve injuries. The addition of biologically active scaffolds into the lumen of conduits to mimic the endoneurium of peripheral nerves may increase the final outcome of artificial nerve devices. Furthermore, the control of the orientation of the collagen fibers may provide some longitudinal guidance architecture providing a higher level of mesoscale tissue structure. To evaluate the regenerative capabilities of chitosan conduits enriched with extracellular matrix-based scaffolds to bridge a critical gap of 15 mm in the rat sciatic nerve. The right sciatic nerve of female Wistar Hannover rats was repaired with chitosan tubes functionalized with extracellular matrix-based scaffolds fully hydrated or stabilized and rolled to bridge a 15 mm nerve gap. Recovery was evaluated by means of electrophysiology and algesimetry tests and histological analysis 4 months after injury. Stabilized constructs enhanced the success of regeneration compared with fully hydrated scaffolds. Moreover, fibronectin-enriched scaffolds increased muscle reinnervation and number of myelinated fibers compared with laminin-enriched constructs. A mixed combination of collagen and fibronectin may be a promising internal filler for neural conduits for the repair of peripheral nerve injuries, and their stabilization may increase the quality of regeneration over long gaps. Copyright © 2017 by the Congress of Neurological Surgeons

  3. Fish oil supplementation prevents diabetes-induced nerve conduction velocity and neuroanatomical changes in rats.

    Science.gov (United States)

    Gerbi, A; Maixent, J M; Ansaldi, J L; Pierlovisi, M; Coste, T; Pelissier, J F; Vague, P; Raccah, D

    1999-01-01

    Diabetic neuropathy has been associated with a decrease in nerve conduction velocity, Na,K-ATPase activity and characteristic histological damage of the sciatic nerve. The aim of this study was to evaluate the potential effect of a dietary supplementation with fish oil [(n-3) fatty acids] on the sciatic nerve of diabetic rats. Diabetes was induced by intravenous streptozotocin injection. Diabetic animals (n = 20) were fed a nonpurified diet supplemented with either olive oil (DO) or fish oil (DM), and control animals (n = 10) were fed a nonpurified diet supplemented with olive oil at a daily dose of 0.5 g/kg by gavage for 8 wk. Nerves were characterized by their conduction velocity, morphometric analysis and membrane Na, K-ATPase activity. Nerve conduction velocity, as well as Na,K-ATPase activity, was improved by fish oil treatment. A correlation was found between these two variables (R = 0.999, P < 0.05). Moreover, a preventive effect of fish oil was observed on nerve histological damage [endoneurial edema, axonal degeneration (by 10-15%) with demyelination]. Moreover, the normal bimodal distribution of the internal diameter of myelinated fibers was absent in the DO group and was restored in the DM group. These data suggest that fish oil therapy may be effective in the prevention of diabetic neuropathy.

  4. A standardized method to create peripheral nerve injury in dogs using an automatic non-serrated forceps

    Institute of Scientific and Technical Information of China (English)

    Xuhui Wang; Shiting Li; Liang Wan; Xinyuan Li; Youqiang Meng; Ningxi Zhu; Min Yang; Baohui Feng; Wenchuan Zhang; Shugan Zhu

    2012-01-01

    This study describes a method that not only generates an automatic and standardized crush injury in the skull base, but also provides investigators with the option to choose from a range of varying pressure levels. We designed an automatic, non-serrated forceps that exerts a varying force of 0 to 100 g and lasts for a defined period of 0 to 60 seconds. This device was then used to generate a crush injury to the right oculomotor nerve of dogs with a force of 10 g for 15 seconds, resulting in a deficit in the pupil-light reflex and ptosis. Further testing of our model with Toluidine-blue staining demonstrated that, at 2 weeks post-surgery disordered oculomotor nerve fibers, axonal loss, and a thinner than normal myelin sheath were visible. Electrophysiological examination showed occasional spontaneous potentials. Together, these data verified that the model for oculomotor nerve injury was successful, and that the forceps we designed can be used to establish standard mechanical injury models of peripheral nerves.

  5. 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...... arrive at the gonadal ridge between 29 and 33 days pc. In conclusion, our data suggest that PGCs in human embryos preferentially migrate along autonomic nerve fibers from the dorsal mesentery to the developing gonad where they are delivered via a fine nerve plexus....

  6. 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

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

    Science.gov (United States)

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

    2015-11-01

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

  8. MR neurography of the median nerve at 3.0 T: Optimization of diffusion tensor imaging and fiber tractography

    International Nuclear Information System (INIS)

    Guggenberger, Roman; Eppenberger, Patrick; Markovic, Daniel; Nanz, Daniel; Chhabra, Avneesh; Pruessmann, Klaas P.; Andreisek, Gustav

    2012-01-01

    Objectives: The purpose of this study was to systematically assess the optimal b-value and reconstruction parameters for DTI and fiber tractography of the median nerve at 3.0 T. Methods: Local ethical board approved study with 45 healthy volunteers (15 men, 30 women; mean age, 41 ± 3.4 years) who underwent DTI of the right wrist at 3.0 T. A single-shot echo-planar-imaging sequence (TR/TE 10123/40 ms) was acquired at four different b-values (800, 1000, 1200, and 1400 s/mm 2 ). Two independent readers performed post processing and fiber-tractography. Fractional anisotropy (FA) maps were calculated. Fiber tracts of the median nerve were generated using four different algorithms containing different FA thresholds and different angulation tolerances. Data were evaluated quantitatively and qualitatively. Results: Tracking algorithms using a minimum FA threshold of 0.2 and a maximum angulation of 10° were significantly better than other algorithms. Fiber tractography generated significantly longer fibers in DTI acquisitions with higher b-values (1200 and 1400 s/mm 2 versus 800 s/mm 2 ; p 2 (p 2 for DTI of the median nerve at 3.0 T. Optimal reconstruction parameters for fiber tractography should encompass a minimum FA threshold of 0.2 and a maximum angulation tolerance of 10.

  9. Is it necessary to use the entire root as a donor when transferring contralateral C7 nerve to repair median nerve?

    Science.gov (United States)

    Gao, Kai-Ming; Lao, Jie; Guan, Wen-Jie; Hu, Jing-Jing

    2018-01-01

    If a partial contralateral C 7 nerve is transferred to a recipient injured nerve, results are not satisfactory. However, if an entire contralateral C 7 nerve is used to repair two nerves, both recipient nerves show good recovery. These findings seem contradictory, as the above two methods use the same donor nerve, only the cutting method of the contralateral C 7 nerve is different. To verify whether this can actually result in different repair effects, we divided rats with right total brachial plexus injury into three groups. In the entire root group, the entire contralateral C 7 root was transected and transferred to the median nerve of the affected limb. In the posterior division group, only the posterior division of the contralateral C 7 root was transected and transferred to the median nerve. In the entire root + posterior division group, the entire contralateral C 7 root was transected but only the posterior division was transferred to the median nerve. After neurectomy, the median nerve was repaired on the affected side in the three groups. At 8, 12, and 16 weeks postoperatively, electrophysiological examination showed that maximum amplitude, latency, muscle tetanic contraction force, and muscle fiber cross-sectional area of the flexor digitorum superficialis muscle were significantly better in the entire root and entire root + posterior division groups than in the posterior division group. No significant difference was found between the entire root and entire root + posterior division groups. Counts of myelinated axons in the median nerve were greater in the entire root group than in the entire root + posterior division group, which were greater than the posterior division group. We conclude that for the same recipient nerve, harvesting of the entire contralateral C 7 root achieved significantly better recovery than partial harvesting, even if only part of the entire root was used for transfer. This result indicates that the entire root should be used as a

  10. Networks of myelin covariance.

    Science.gov (United States)

    Melie-Garcia, Lester; Slater, David; Ruef, Anne; Sanabria-Diaz, Gretel; Preisig, Martin; Kherif, Ferath; Draganski, Bogdan; Lutti, Antoine

    2018-04-01

    Networks of anatomical covariance have been widely used to study connectivity patterns in both normal and pathological brains based on the concurrent changes of morphometric measures (i.e., cortical thickness) between brain structures across subjects (Evans, ). However, the existence of networks of microstructural changes within brain tissue has been largely unexplored so far. In this article, we studied in vivo the concurrent myelination processes among brain anatomical structures that gathered together emerge to form nonrandom networks. We name these "networks of myelin covariance" (Myelin-Nets). The Myelin-Nets were built from quantitative Magnetization Transfer data-an in-vivo magnetic resonance imaging (MRI) marker of myelin content. The synchronicity of the variations in myelin content between anatomical regions was measured by computing the Pearson's correlation coefficient. We were especially interested in elucidating the effect of age on the topological organization of the Myelin-Nets. We therefore selected two age groups: Young-Age (20-31 years old) and Old-Age (60-71 years old) and a pool of participants from 48 to 87 years old for a Myelin-Nets aging trajectory study. We found that the topological organization of the Myelin-Nets is strongly shaped by aging processes. The global myelin correlation strength, between homologous regions and locally in different brain lobes, showed a significant dependence on age. Interestingly, we also showed that the aging process modulates the resilience of the Myelin-Nets to damage of principal network structures. In summary, this work sheds light on the organizational principles driving myelination and myelin degeneration in brain gray matter and how such patterns are modulated by aging. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

  11. Schwann cell-mediated delivery of glial cell line-derived neurotrophic factor restores erectile function after cavernous nerve injury.

    Science.gov (United States)

    May, Florian; Buchner, Alexander; Schlenker, Boris; Gratzke, Christian; Arndt, Christian; Stief, Christian; Weidner, Norbert; Matiasek, Kaspar

    2013-03-01

    To evaluate the time-course of functional recovery after cavernous nerve injury using glial cell line-derived neurotrophic factor-transduced Schwann cell-seeded silicon tubes. Sections of the cavernous nerves were excised bilaterally (5 mm), followed by immediate bilateral surgical repair. A total of 20 study nerves per group were reconstructed by interposition of empty silicon tubes and silicon tubes seeded with either glial cell line-derived neurotrophic factor-overexpressing or green fluorescent protein-expressing Schwann cells. Control groups were either sham-operated or received bilateral nerve transection without nerve reconstruction. Erectile function was evaluated by relaparotomy, electrical nerve stimulation and intracavernous pressure recording after 2, 4, 6, 8 and 10 weeks. The animals underwent re-exploration only once, and were killed afterwards. The nerve grafts were investigated for the maturation state of regenerating nerve fibers and the fascular composition. Recovery of erectile function took at least 4 weeks in the current model. Glial cell line-derived neurotrophic factor-transduced Schwann cell grafts restored erectile function better than green fluorescent protein-transduced controls and unseeded conduits. Glial cell line-derived neurotrophic factor-transduced grafts promoted an intact erectile response (4/4) at 4, 6, 8 and 10 weeks that was overall significantly superior to negative controls (P cell line-derived neurotrophic factor-transduced grafts compared with negative controls (P = 0.018) and unseeded tubes (P = 0.034). Return of function was associated with the electron microscopic evidence of preganglionic myelinated nerve fibers and postganglionic unmyelinated axons. Schwann cell-mediated delivery of glial cell line-derived neurotrophic factor presents a viable approach for the treatment of erectile dysfunction after cavernous nerve injury. © 2013 The Japanese Urological Association.

  12. Effects of cholinergic compounds on the axon-Schwann cell relationship in the squid nerve fiber.

    Science.gov (United States)

    Villegas, J

    1975-04-01

    The effects of acetylcholine, carbamylcholine, D-tubocurarine, eserine, and alpha-bungarotoxin on the Schwann cell electrical potential of resting and stimulated squid nerve fibers were studied. Acetylcholine (10-7 M) and barbamylcholine (10-6 M) induce a prolonged hyper polarization in the Schwann cells of the unstimulated nerve fiber. In the presence of carbamylcholine (10-6 M) the behavior of the Schwann cell membrane to changes in the external potassium concentration approximates the behavior of an ideal potassium electrode. D-Tubocurarine (10-9 M) blocks the hyperpolarizing effects of nerve impulse trains and carbamylcholine (10-6 M), whereas at the same concentration eserine prolongs the Schwann cell hyperpolarizations induced by axon stimulation or by acetylcholine (10-7 M). alpha-Bungarotoxin (10-9M) also blocks the hyperpolarizing effect of nerve impulse trains and of carbamylcholine. D-Tubocurarine (10-5M) protects the Schwann cells against the irreversible action of alpha-bungarotoxin. These results show the existence of acetylcholine receptors in the Schwann cell membrane. Preliminary measurements of the binding of 125I-alpha bungarotoxin to the plasma membranes isolated from squid nerves also indicate the presence of acetylcholine receptors. These findings support the involvement of cholinergic mechanisms in the axon-Schwann cell relationship previously described.

  13. Na(v)1.8 channelopathy in mutant mice deficient for myelin protein zero is detrimental to motor axons

    DEFF Research Database (Denmark)

    Moldovan, Mihai; Alvarez Herrero, Susana; Pinchenko, Volodymyr

    2011-01-01

    Myelin protein zero mutations were found to produce Charcot-Marie-Tooth disease phenotypes with various degrees of myelin impairment and axonal loss, ranging from the mild 'demyelinating' adult form to severe and early onset forms. Protein zero deficient homozygous mice ( ) show a severe and prog......Myelin protein zero mutations were found to produce Charcot-Marie-Tooth disease phenotypes with various degrees of myelin impairment and axonal loss, ranging from the mild 'demyelinating' adult form to severe and early onset forms. Protein zero deficient homozygous mice ( ) show a severe...... and progressive dysmyelinating neuropathy from birth with compromised myelin compaction, hypomyelination and distal axonal degeneration. A previous study using immunofluorescence showed that motor nerves deficient of myelin protein zero upregulate the Na(V)1.8 voltage gated sodium channel isoform, which...... is normally present only in restricted populations of sensory axons. The aim of this study was to investigate the function of motor axons in protein zero-deficient mice with particular emphasis on ectopic Na(V)1.8 voltage gated sodium channel. We combined 'threshold tracking' excitability studies...

  14. Myelin down-regulates myelin phagocytosis by microglia and macrophages through interactions between CD47 on myelin and SIRPα (signal regulatory protein-α on phagocytes

    Directory of Open Access Journals (Sweden)

    Reichert Fanny

    2011-03-01

    Full Text Available Abstract Background Traumatic injury to axons produces breakdown of axons and myelin at the site of the lesion and then further distal to this where Wallerian degeneration develops. The rapid removal of degenerated myelin by phagocytosis is advantageous for repair since molecules in myelin impede regeneration of severed axons. Thus, revealing mechanisms that regulate myelin phagocytosis by macrophages and microglia is important. We hypothesize that myelin regulates its own phagocytosis by simultaneous activation and down-regulation of microglial and macrophage responses. Activation follows myelin binding to receptors that mediate its phagocytosis (e.g. complement receptor-3, which has been previously studied. Down-regulation, which we test here, follows binding of myelin CD47 to the immune inhibitory receptor SIRPα (signal regulatory protein-α on macrophages and microglia. Methods CD47 and SIRPα expression was studied by confocal immunofluorescence microscopy, and myelin phagocytosis by ELISA. Results We first document that myelin, oligodendrocytes and Schwann cells express CD47 without SIRPα and further confirm that microglia and macrophages express both CD47 and SIRPα. Thus, CD47 on myelin can bind to and subsequently activate SIRPα on phagocytes, a prerequisite for CD47/SIRPα-dependent down-regulation of CD47+/+ myelin phagocytosis by itself. We then demonstrate that phagocytosis of CD47+/+ myelin is augmented when binding between myelin CD47 and SIRPα on phagocytes is blocked by mAbs against CD47 and SIRPα, indicating that down-regulation of phagocytosis indeed depends on CD47-SIRPα binding. Further, phagocytosis in serum-free medium of CD47+/+ myelin is augmented after knocking down SIRPα levels (SIRPα-KD in phagocytes by lentiviral infection with SIRPα-shRNA, whereas phagocytosis of myelin that lacks CD47 (CD47-/- is not. Thus, myelin CD47 produces SIRPα-dependent down-regulation of CD47+/+ myelin phagocytosis in phagocytes

  15. Epitope diversity of N-glycans from bovine peripheral myelin glycoprotein P0 revealed by mass spectrometry and nano probe magic angle spinning 1H NMR spectroscopy

    NARCIS (Netherlands)

    Vliegenthart, J.F.G.; Gutiérrez Gallego, R.; Jiménez Blanco, J.L.; Thijssen-van Zuylen, C.W.E.M.; Gotfredsen, C.H.; Voshol, H.; Duus, J.Ø.; Schachner, M.

    2001-01-01

    The carbohydrate structures present on the glycoproteins in the central and peripheral nerve systems are essential in many cell adhesion processes. The P0 glycoprotein, expressed by myelinating Schwann cells, plays an important role during the formation and maintenance of myelin, and it is the most

  16. Resistance wheel exercise from mid-life has minimal effect on sciatic nerves from old mice in which sarcopenia was prevented.

    Science.gov (United States)

    Krishnan, Vidya S; White, Zoe; Terrill, Jessica R; Hodgetts, Stuart I; Fitzgerald, Melinda; Shavlakadze, Tea; Harvey, Alan R; Grounds, Miranda D

    2017-10-01

    The ability of resistance exercise, initiated from mid-life, to prevent age-related changes in old sciatic nerves, was investigated in male and female C57BL/6J mice. Aging is associated with cellular changes in old sciatic nerves and also loss of skeletal muscle mass and function (sarcopenia). Mature adult mice aged 15 months (M) were subjected to increasing voluntary resistance wheel exercise (RWE) over a period of 8 M until 23 M of age. This prevented sarcopenia in the old 23 M aged male and female mice. Nerves of control sedentary (SED) males at 3, 15 and 23 M of age, showed a decrease in the myelinated axon numbers at 15 and 23 M, a decreased g-ratio and a significantly increased proportion of myelinated nerves containing electron-dense aggregates at 23 M. Myelinated axon and nerve diameter, and axonal area, were increased at 15 M compared with 3 and 23 M. Exercise increased myelinated nerve profiles containing aggregates at 23 M. S100 protein, detected with immunoblotting was increased in sciatic nerves of 23 M old SED females, but not males, compared with 15 M, with no effect of exercise. Other neuronal proteins showed no significant alterations with age, gender or exercise. Overall the RWE had no cellular impact on the aging nerves, apart from an increased number of old nerves containing aggregates. Thus the relationship between cellular changes in aging nerves, and their sustained capacity for stimulation of old skeletal muscles to help maintain healthy muscle mass in response to exercise remains unclear.

  17. 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

  18. Retinal nerve fiber and optic disc morphology using spectral-domain optical coherence tomography in scleroderma patients.

    Science.gov (United States)

    Sahin-Atik, Sevinc; Koc, Feray; Akin-Sari, Sirin; Ozmen, Mustafa

    2017-05-11

    To evaluate the optic nerve head parameters and peripapillary retinal nerve fiber layer using spectral-domain optical coherence tomography (SD-OCT) in a systemic sclerosis (SSc) cohort and age-matched controls to determine whether SSc patients have an increased risk of normal-tension glaucoma (NTG). We examined 30 patients (3 male, 27 female) with SSc and 28 age- and sex-matched controls. Retinal nerve fiber and optic disc morphology were evaluated using Cirrus SD-OCT. Optic disc morphology measurements including disc area, rim area, average and vertical cup/disc (C/D) ratio, and cup volume were not significantly different between the study groups. The average and 4-quadrant retinal nerve fiber layer (RNFL) measurements of the C/D >0.3 subgroups were not significantly different in the patients and controls. These values were also similar for the C/D >0.5 subgroups except that the average inferior quadrant RNFL thickness of the right eyes in the patient subgroup was significantly thinner than in the control subgroup (p<0.05). Our SSc cohort had relatively shorter disease duration but increased prevalence of early glaucomatous damage signs. Our findings indicate that SSc is a risk factor for developing normal-tension glaucoma. Further studies combined with visual field evaluation are necessary to identify the long-term glaucomatous effects of SSc.

  19. Surgical Anatomy of the Radial Nerve at the Elbow and in the Forearm: Anatomical Basis for Intraplexus Nerve Transfer to Reconstruct Thumb and Finger Extension in C7 - T1 Brachial Plexus Palsy.

    Science.gov (United States)

    Zhang, Lei; Dong, Zhen; Zhang, Chun-Lin; Gu, Yu-Dong

    2016-11-01

    Background  C7 - T1 palsy results in complete loss of finger motion and poses a surgical challenge. This study investigated the anatomy of the radial nerve in the elbow and forearm and the feasibility of intraplexus nerve transfer to restore thumb and finger extension. Methods  The radial nerves were dissected in 28 formalin-fixed upper extremities. Branching pattern, length, diameter, and number of myelinated fibers were recorded. Results  Commonly, the branching pattern (from proximal to distal) was to the brachioradialis, extensor carpi radialis longus, superficial sensory proximal to the lateral epicondyle, extensor carpi radialis brevis, supinator, extensor digitorum communis, extensor digiti minimi, extensor carpi ulnaris, abductor pollicis longus, extensor pollicis brevis, extensor pollicis longus, and extensor indicis distal to the lateral epicondyle. Conclusions  Branches to the brachioradialis, extensor carpi radialis longus, and supinator can be transferred to the posterior interosseous nerve to restore hand movement in patients with C7 - T1 brachial plexus palsies; the supinator branch is probably the best choice in this regard. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  20. Development of a mouse model of neuropathic pain following photochemically induced ischemia in the sciatic nerve.

    Science.gov (United States)

    Hao, J X; Blakeman, K H; Yu, W; Hultenby, K; Xu, X J; Wiesenfeld-Hallin, Z

    2000-05-01

    A mouse model of neuropathic pain was developed by a photochemically induced ischemic nerve injury in normal male C57/BL6 mice. The ischemia was induced by unilateral irradiation of the sciatic nerve with an argon ion laser after intravenous administration of a photosensitizing dye, erythrosin B. The nerve injury resulted in a significant decrease in withdrawal threshold of the hindpaws to mechanical stimulation with von Frey hairs, as well as increased responsiveness to cold and heat stimulation. The mice, however, did not exhibit overt spontaneous pain-like behaviors. The evoked pain-related behaviors were observed bilaterally, although the ipsilateral changes were greater than on the contralateral side. The extent and time course of the behavioral changes were related to the duration of laser irradiation, with 1-min exposure producing the most consistent effect. Morphological examination at the light microscopic level revealed partial demyelination and axonal degeneration of the large myelinated fibers at the epicenter of the lesion 1 week postirradiation. The extent of the damage was correlated with the duration of irradiation. Injury and loss of unmyelinated fibers were also observed at the electronmicroscopic level. We conclude that an intravascular photochemical reaction leading to ischemia results in graded damage to the sciatic nerve in mice. Moreover, the nerve injury is associated with the development of abnormal pain-related behaviors. Both the behavioral and the morphological changes are correlated with the duration of irradiation. These results establish a mouse model of partial nerve injury with neuropathic pain-like behaviors which may be useful in studies using genetically modified mice. Copyright 2000 Academic Press.

  1. Optical coherence tomography in retinitis pigmentosa: reproducibility and capacity to detect macular and retinal nerve fiber layer thickness alterations.

    Science.gov (United States)

    Garcia-Martin, Elena; Pinilla, Isabel; Sancho, Eva; Almarcegui, Carmen; Dolz, Isabel; Rodriguez-Mena, Diego; Fuertes, Isabel; Cuenca, Nicolas

    2012-09-01

    To evaluate the ability of time-domain and Fourier-domain optical coherence tomographies (OCTs) to detect macular and retinal nerve fiber layer atrophies in retinitis pigmentosa (RP). To test the intrasession reproducibility using three OCT instruments (Stratus, Cirrus, and Spectralis). Eighty eyes of 80 subjects (40 RP patients and 40 healthy subjects) underwent a visual field examination, together with 3 macular scans and 3 optic disk evaluations by the same experienced examiner using 3 OCT instruments. Differences between healthy and RP eyes were compared. The relationship between measurements with each OCT instrument was evaluated. Repeatability was studied by intraclass correlation coefficients and coefficients of variation. Macular and retinal nerve fiber layer atrophies were detected in RP patients for all OCT parameters. Macular and retinal nerve fiber layer thicknesses, as determined by the different OCTs, were correlated but significantly different (P < 0.05). Reproducibility was moderately high using Stratus, good using Cirrus and Spectralis, and excellent using the Tru-track technology of Spectralis. In RP eyes, measurements showed higher variability compared with healthy eyes. Differences in thickness measurements existed between OCT instruments, despite there being a high degree of correlation. Fourier-domain OCT can be considered a valid and repeatability technique to detect retinal nerve fiber layer atrophy in RP patients.

  2. Retinal nerve fiber layer thickness map determined from optical coherence tomography images

    NARCIS (Netherlands)

    Mujat, M.; Chan, R. C.; Cense, B.; Park, B.H.; Joo, C.; Akkin, T.; Chen, TC; de Boer, JF

    2005-01-01

    We introduce a method to determine the retinal nerve fiber layer (RNFL) thickness in OCT images based on anisotropic noise suppression and deformable splines. Spectral-Domain Optical Coherence Tomography (SDOCT) data was acquired at 29 kHz A-line rate with a depth resolution of 2.6 mum and a depth

  3. A quantitative evaluation of gross versus histologic neuroma formation in a rabbit forelimb amputation model: potential implications for the operative treatment and study of neuromas

    Directory of Open Access Journals (Sweden)

    Kuiken Todd A

    2011-10-01

    Full Text Available Abstract Background Surgical treatment of neuromas involves excision of neuromas proximally to the level of grossly "normal" fascicles; however, proximal changes at the axonal level may have both functional and therapeutic implications with regard to amputated nerves. In order to better understand the retrograde "zone of injury" that occurs after nerve transection, we investigated the gross and histologic changes in transected nerves using a rabbit forelimb amputation model. Methods Four New Zealand White rabbits underwent a forelimb amputation with transection and preservation of the median, radial, and ulnar nerves. After 8 weeks, serial sections of the amputated nerves were then obtained in a distal-to-proximal direction toward the brachial plexus. Quantitative histomorphometric analysis was performed on all nerve specimens. Results All nerves demonstrated statistically significant increases in nerve cross-sectional area between treatment and control limbs at the distal nerve end, but these differences were not observed 10 mm more proximal to the neuroma bulb. At the axonal level, an increased number of myelinated fibers were seen at the distal end of all amputated nerves. The number of myelinated fibers progressively decreased in proximal sections, normalizing at 15 mm proximally, or the level of the brachial plexus. The cross-sectional area of myelinated fibers was significantly decreased in all sections of the treatment nerves, indicating that atrophic axonal changes proceed proximally at least to the level of the brachial plexus. Conclusions Morphologic changes at the axonal level extend beyond the region of gross neuroma formation in a distal-to-proximal fashion after nerve transection. This discrepancy between gross and histologic neuromas signifies the need for improved standardization among neuroma models, while also providing a fresh perspective on how we should view neuromas during peripheral nerve surgery.

  4. Relationship of distraction rate with inferior alveolar nerve degeneration-regeneration shift

    Directory of Open Access Journals (Sweden)

    Ying-hua Zhao

    2018-01-01

    Full Text Available Distraction osteogenesis is an important technique for the treatment of maxillofacial abnormities and defects. However, distraction osteogenesis may cause the injury of the inferior alveolar nerve. The relationship between distraction rate and nerve degeneration-regeneration shift remains poorly understood. In this study, 24 rabbits were randomly divided into four groups. To establish the rabbit mandibular distraction osteogenesis model, the mandibles of rabbits in distraction osteogenesis groups were subjected to continuous osteogenesis distraction at a rate of 1.0, 1.5 and 2.0 mm/d, respectively, by controlling rounds of screwing each day in the distractors. In the sham group, mandible osteotomy was performed without distraction. Pin-prick test with a 10 g blunt pin on the labium, histological and histomorphometric analyses with methylene blue staining, Bodian's silver staining, transmission electron microscopy and myelinated fiber density of inferior alveolar nerve cross-sections were performed to assess inferior alveolar nerve conditions. At 28 days after model establishment, in the pin-prick test, the inferior alveolar nerve showed no response in the labium to a pin pricks in the 2 mm/d group, indicating a severe dysfunction. Histological and histomorphometric analyses indicated that the inferior alveolar nerve suffered more degeneration and injuries at a high distraction rate (2 mm/d. Importantly, the nerve regeneration, indicated by newborn Schwann cells and axons, was more abundant in 1.0 and 1.5 mm/d groups than in 2.0 mm/d group. We concluded that the distraction rate was strongly associated with the inferior alveolar nerve function, and the distraction rates of 1.0 and 1.5 mm/d had regenerative effects on the inferior alveolar nerve. This study provides an experimental basis for the relationship between distraction rate and nerve degeneration-regeneration shift during distraction osteogenesis, and may facilitate reducing nerve

  5. Retinal Nerve Fiber Layer Protrusion Associated with Tilted Optic Discs.

    Science.gov (United States)

    Chiang, Jaclyn; Yapp, Michael; Ly, Angelica; Hennessy, Michael P; Kalloniatis, Michael; Zangerl, Barbara

    2018-03-01

    This study resulted in the identification of an optic nerve head (ONH) feature associated with tilted optic discs, which might potentially contribute to ONH pathologies. Knowledge of such findings will enhance clinical insights and drive future opportunities to understand disease processes related to tilted optic discs. The aim of this study was to identify novel retinal nerve fiber layer (RNFL) anomalies by evaluating tilted optic discs using optical coherence tomography. An observed retinal nerve fiber protrusion was further investigated for association with other morphological or functional parameters. A retrospective review of 400 randomly selected adult patients with ONH examinations was conducted in a referral-only, diagnostic imaging center. After excluding other ONH pathologies, 215 patients were enrolled and evaluated for optic disc tilt and/or torsion. Gross anatomical ONH features, including size and rim or parapapillary region elevation, were assessed with stereoscopic fundus photography. Optical coherence tomography provided detailed morphological information of individual retinal layers. Statistical analysis was applied to identify significant changes between individual patient cohorts. A dome-shaped hyperreflective RNFL bulge, protruding into the neurosensory retina at the optic disc margins, was identified in 17 eyes with tilted optic discs. Available follow-up data were inconclusive regarding natural changes with this ONH feature. This RNFL herniation was significantly correlated with smaller than average optic disc size (P = .005), congenital disc tilt (P optic discs, which has not previously been assessed as an independent ONH structure. The feature is predominantly related to congenital crowded, small optic discs and variable between patients. This study is an important first step to elucidate diagnostic capabilities of tilted disc morphological changes and understanding associated functional deficits.

  6. Variations in retinal nerve fiber layer measurements on optical coherence tomography after implantation of trifocal intraocular lens.

    Science.gov (United States)

    García-Bella, Javier; Martínez de la Casa, José M; Talavero González, Paula; Fernández-Vigo, José I; Valcarce Rial, Laura; García-Feijóo, Julián

    2018-01-01

    To establish the changes produced after implantation of a trifocal intraocular lens (IOL) on retinal nerve fiber layer measurements performed with Fourier-domain optical coherence tomography (OCT). This prospective study included 100 eyes of 50 patients with bilateral cataract in surgical range, no other associated ocular involvement, refractive errors between +5 and -5 spherical diopters, and less than 1.5 D of corneal astigmatism. The eyes were operated by phacoemulsification with implantation of 2 different trifocal IOLs (FineVision and AT LISA tri 839MP) in randomized equal groups. Cirrus OCT and Spectralis OCT were performed before surgery and 3 months later. Both analyzed the thickness of the nerve fiber layer and thickness divided by quadrants (6 in case of Spectralis and 4 in case of Cirrus HD). The mean age of patients was 67.5 ± 5.8 years. The global nerve fiber layer thickness measured with Spectralis OCT was 96.77 μm before surgery and 99.55 μm after. With Cirrus OCT, the global thickness was 85.29 μm before surgery and 89.77 μm after. Statistically significant differences in global thickness measurements between preimplantation and postimplantation of the IOL were found with both OCT in the 2 groups. Statistically significant differences were also found in temporal and superior quadrants. The implantation of a diffractive trifocal IOL alters the results of the optic nerve fiber layer on Fourier-domain OCT in these patients, which should be taken into account in the posterior study of these patients.

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

    OpenAIRE

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

    2001-01-01

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

  8. Split bundle detection in polarimetric images of the human retinal nerve fiber layer

    NARCIS (Netherlands)

    Vermeer, K. A.; Reus, N. J.; Vos, F. M.; Lemij, H. G.; Vossepoel, A. M.

    2007-01-01

    One method for assessing pathological retinal nerve fiber layer (NFL) appearance is by comparing the NFL to normative values, derived from healthy subjects. These normative values will be more specific when normal physiological differences are taken into account. One common variation is a split

  9. Inhibition of KLF7-Targeting MicroRNA 146b Promotes Sciatic Nerve Regeneration.

    Science.gov (United States)

    Li, Wen-Yuan; Zhang, Wei-Ting; Cheng, Yong-Xia; Liu, Yan-Cui; Zhai, Feng-Guo; Sun, Ping; Li, Hui-Ting; Deng, Ling-Xiao; Zhu, Xiao-Feng; Wang, Ying

    2018-06-01

    A previous study has indicated that Krüppel-like factor 7 (KLF7), a transcription factor that stimulates Schwann cell (SC) proliferation and axonal regeneration after peripheral nerve injury, is a promising therapeutic transcription factor in nerve injury. We aimed to identify whether inhibition of microRNA-146b (miR-146b) affected SC proliferation, migration, and myelinated axon regeneration following sciatic nerve injury by regulating its direct target KLF7. SCs were transfected with miRNA lentivirus, miRNA inhibitor lentivirus, or KLF7 siRNA lentivirus in vitro. The expression of miR146b and KLF7, as well as SC proliferation and migration, were subsequently evaluated. In vivo, an acellular nerve allograft (ANA) followed by injection of GFP control vector or a lentiviral vector encoding an miR-146b inhibitor was used to assess the repair potential in a model of sciatic nerve gap. miR-146b directly targeted KLF7 by binding to the 3'-UTR, suppressing KLF7. Up-regulation of miR-146b and KLF7 knockdown significantly reduced the proliferation and migration of SCs, whereas silencing miR-146b resulted in increased proliferation and migration. KLF7 protein was localized in SCs in which miR-146b was expressed in vivo. Similarly, 4 weeks after the ANA, anti-miR-146b increased KLF7 and its target gene nerve growth factor cascade, promoting axonal outgrowth. Closer analysis revealed improved nerve conduction and sciatic function index score, and enhanced expression of neurofilaments, P0 (anti-peripheral myelin), and myelinated axon regeneration. Our findings provide new insight into the regulation of KLF7 by miR-146b during peripheral nerve regeneration and suggest a potential therapeutic strategy for peripheral nerve injury.

  10. Biosynthesis of fatty acids and cholesterol in squid giant nerve fiber

    International Nuclear Information System (INIS)

    Tanaka, T.; Kishimoto, Y.; Gould, R.M.

    1987-01-01

    The giant nerve fiber of squid 3 (loligo pealel) was incubated with [1- 14 C]acetate and ( 3 H)myristate. Fifty-five percent of the radioactivity incorporated from acetate was recovered in fatty acid methyl esters (FAME). The FAME was fractionated by AgNO 3 -impregnated TLC plate; and 52%, 31%, 0.3%, 5%, and 11% of the radioactivity was recovered in spots associated with saturated, monoenes, dienes, trienes, and polyenes, respectively. The saturated FAME was further fractionated by reverse-phase HPLC; and 4, 47, 1, and 48% of the radioactivity was recovered in 14:0, 16:0, 17:0, and 18:0, respectively. Most radioactivity from polyenes migrated to the spot containing saturated FAME, after catalytical hydrogenation. Cholesterol was isolated and converted to dibromoderivative and the derivative was recrystallized. No radioactivity was found in purified dibromocholesterol. Nearly all radioactivity from myristate-labeled tissue was recovered in saturated FAME. Reverse-phase HPLC showed that 71%, 25%, and 3% of radioactivity was associated with 14:0, 16:0, and 18:0, respectively. These results indicate that the squid giant nerve fibers can synthesize fatty acids by de novo and also by chain elongation and desaturation, though at a slower rate

  11. Quantitative analysis of the myelin g-ratio from electron microscopy images of the macaque corpus callosum

    Directory of Open Access Journals (Sweden)

    Nikola Stikov

    2015-09-01

    Full Text Available We provide a detailed morphometric analysis of eight transmission electron micrographs (TEMs obtained from the corpus callosum of one cynomolgus macaque. The raw TEM images are included in the article, along with the distributions of the axon caliber and the myelin g-ratio in each image. The distributions are analyzed to determine the relationship between axon caliber and g-ratio, and compared against the aggregate metrics (myelin volume fraction, fiber volume fraction, and the aggregate g-ratio, as defined in the accompanying research article entitled ‘In vivo histology of the myelin g-ratio with magnetic resonance imaging’ (Stikov et al., NeuroImage, 2015.

  12. 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

  13. 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

  14. Nerve fiber layer (NFL) degeneration associated with acute q-switched laser exposure in the nonhuman primate

    Science.gov (United States)

    Zwick, Harry; Zuclich, Joseph A.; Stuck, Bruce E.; Gagliano, Donald A.; Lund, David J.; Glickman, Randolph D.

    1995-01-01

    We have evaluated acute laser retinal exposure in non-human primates using a Rodenstock scanning laser ophthalmoscope (SLO) equipped with spectral imaging laser sources at 488, 514, 633, and 780 nm. Confocal spectral imaging at each laser wavelength allowed evaluation of the image plane from deep within the retinal vascular layer to the more superficial nerve fiber layer in the presence and absence of the short wavelength absorption of the macular pigment. SLO angiography included both fluorescein and indocyanine green procedures to assess the extent of damage to the sensory retina, the retinal pigment epithelium (RPE), and the choroidal vasculature. All laser exposures in this experiment were from a Q-switched Neodymium laser source at an exposure level sufficient to produce vitreous hemorrhage. Confocal imaging of the nerve fiber layer revealed discrete optic nerve sector defects between the lesion site and the macula (retrograde degeneration) as well as between the lesion site and the optic disk (Wallerian degeneration). In multiple hemorrhagic exposures, lesions placed progressively distant from the macula or overlapping the macula formed bridging scars visible at deep retinal levels. Angiography revealed blood flow disturbance at the retina as well as at the choroidal vascular level. These data suggest that acute parafoveal laser retinal injury can involve both direct full thickness damage to the sensory and non-sensory retina and remote nerve fiber degeneration. Such injury has serious functional implications for both central and peripheral visual function.

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

    Directory of Open Access Journals (Sweden)

    Crutcher Keith A

    2001-05-01

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

  16. Morphometric analysis of the fiber populations of the rat sciatic nerve, its spinal roots, and its major branches

    NARCIS (Netherlands)

    Prodanov, D.P.; Feierabend, H.K.P.

    2007-01-01

    Correspondence between the nerve composition and the functional characteristics of its fiber populations is not always evident. To investigate such correspondence and to give a systematic picture of the morphology of the rat hind limb nerves, extensive morphometric study was performed on the sciatic

  17. 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.

  18. Deficiency of a membrane skeletal protein, 4.1G, results in myelin abnormalities in the peripheral nervous system.

    Science.gov (United States)

    Saitoh, Yurika; Ohno, Nobuhiko; Yamauchi, Junji; Sakamoto, Takeharu; Terada, Nobuo

    2017-12-01

    We previously demonstrated that a membrane skeletal molecular complex, 4.1G-membrane palmitoylated protein 6 (MPP6)-cell adhesion molecule 4, is incorporated in Schwann cells in the peripheral nervous system (PNS). In this study, we evaluated motor activity and myelin ultrastructures in 4.1G-deficient (-/-) mice. When suspended by the tail, aged 4.1G -/- mice displayed spastic leg extension, especially after overwork. Motor-conduction velocity in 4.1G -/- mice was slower than that in wild-type mice. Using electron microscopy, 4.1G -/- mice exhibited myelin abnormalities: myelin was thicker in internodes, and attachment of myelin tips was distorted in some paranodes. In addition, we found a novel function of 4.1G for sorting a scaffold protein, Lin7, due to disappearance of the immunolocalization and reduction of the production of Lin7c and Lin7a in 4.1G -/- sciatic nerves, as well as the interaction of MPP6 and Lin7 with immunoprecipitation. Thus, we herein propose 4.1G functions as a signal for proper formation of myelin in PNS.

  19. Phosphorylation of myelin basic proteins and its relevance to myelin biogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Ulmer, J.B.

    1985-01-01

    Age-related differences in the in vivo incorporation of (32-P) into mouse myelin basic proteins (MBPs) of the central nervous system were observed. The resulting specific radioactivity (S.A.) of the MBPs appeared to be related to the S.A. of the acid-soluble pool of phosphates of myelin. In development, MBPs were phosphorylated in vivo prior to the onset of myelination in the brain, indicating that MBPs are phosphorylated prior to their deposition in the myelin sheath. The incorporation of (32-P) into MBPs and the turnover rates of MBP phosphates were studied in vivo in developmentally-related myelin compartments. The results suggest that there are two separate events in MBP phosphorylation and that the turnover rates of the MBP phosphates derived from these two events are different. A model for MBP phosphorylation, that could explain in these observations, is postulated and discussed in the light of existing information.

  20. Acceleration of Regeneration of Large-Gap Peripheral Nerve Injuries Using Acellular Nerve Allografts plus amniotic Fluid Derived Stem Cells (AFS)

    Science.gov (United States)

    2017-09-01

    cells (AFS) to promote and accelerate nerve regeneration . The presence of the AFS will provide support for the regenerating axons without the...plus AFS cells . Cross sections of the distal part of the regenerated nerves were evaluated by light and electronic microscopy. ANA plus AFS group...and myelin thickness in ANA plus AFS cells treated group (Figure 2.1.1), indicating enhanced regenerating ability of the axons. Neuromuscular

  1. The Changes in Rats with Sciatic Nerve Crush Injury Supplemented with Evening Primrose Oil: Behavioural, Morphologic, and Morphometric Analysis

    Directory of Open Access Journals (Sweden)

    Danial Ramli

    2017-01-01

    Full Text Available Nerve crush injuries are commonly used models for axonotmesis to examine peripheral nerve regeneration. As evening primrose oil (EPO is rich in omega-6 essential fatty acid component and gamma-linolenic acid, studies have shown the potential role of EPO in myelination. Seventy-two healthy adult Sprague-Dawley rats were classified into three groups: normal group, control group, and experimental group. The result indicates that there was significant difference in toe-spreading reflex between the normal and the control groups (1.9±0.031, p<0.05 and the normal and the EPO groups (0.4±0.031, p<0.05 and significant difference between EPO and the control groups (1.5±0.031, p<0.05. Regeneration of axons and myelin in nerve fibre in the EPO-treated group developed better and faster than in the control group. In the control group, the shape of the axon was irregular with a thinner myelin sheath. In the experimental group, the shape of the axons, the thickness of the myelin sheath, and the diameter of the axons were almost the same as in the normal group. In conclusion, EPO supplementation may be beneficial as a therapeutic option for disturbances of nerve interaction.

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

    NARCIS (Netherlands)

    Zenker, J.; Stettner, M.; Ruskamo, S.; Domenech-Estevez, E.; Baloui, H.; Medard, J.J.; Verheijen, M.H.G.; Brouwers, J.F.; Kursula, P.; Kieseier, B.C.; Chrast, R.

    2014-01-01

    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

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

    NARCIS (Netherlands)

    Zenker, Jennifer; ruskamo, salla; domenech-estevez, Enric; medard, jean-jacques; Verheijen, M.H.; Brouwers, Jos|info:eu-repo/dai/nl/173812694; Kursula, Petri; kieseier, bernd; Chrast, Roman

    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

  4. Resetting translational homeostasis restores myelination in Charcot-Marie-Tooth disease type 1B mice.

    Science.gov (United States)

    D'Antonio, Maurizio; Musner, Nicolò; Scapin, Cristina; Ungaro, Daniela; Del Carro, Ubaldo; Ron, David; Feltri, M Laura; Wrabetz, Lawrence

    2013-04-08

    P0 glycoprotein is an abundant product of terminal differentiation in myelinating Schwann cells. The mutant P0S63del causes Charcot-Marie-Tooth 1B neuropathy in humans, and a very similar demyelinating neuropathy in transgenic mice. P0S63del is retained in the endoplasmic reticulum of Schwann cells, where it promotes unfolded protein stress and elicits an unfolded protein response (UPR) associated with translational attenuation. Ablation of Chop, a UPR mediator, from S63del mice completely rescues their motor deficit and reduces active demyelination by half. Here, we show that Gadd34 is a detrimental effector of CHOP that reactivates translation too aggressively in myelinating Schwann cells. Genetic or pharmacological limitation of Gadd34 function moderates translational reactivation, improves myelination in S63del nerves, and reduces accumulation of P0S63del in the ER. Resetting translational homeostasis may provide a therapeutic strategy in tissues impaired by misfolded proteins that are synthesized during terminal differentiation.

  5. 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.

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

    Science.gov (United States)

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

    2012-04-15

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

  7. 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

  8. Degeneration and regeneration of motor and sensory nerves: a stereological study of crush lesions in rat facial and mental nerves

    DEFF Research Database (Denmark)

    Barghash, Ziad; Larsen, Jytte Overgaard; Al-Bishri, Awad

    2013-01-01

    The aim of this study was to evaluate the degeneration and regeneration of a sensory nerve and a motor nerve at the histological level after a crush injury. Twenty-five female Wistar rats had their mental nerve and the buccal branch of their facial nerve compressed unilaterally against a glass rod...... for 30 s. Specimens of the compressed nerves and the corresponding control nerves were dissected at 3, 7, and 19 days after surgery. Nerve cross-sections were stained with osmium tetroxide and toluidine blue and analysed using two-dimensional stereology. We found differences between the two nerves both...... in the normal anatomy and in the regenerative pattern. The mental nerve had a larger cross-sectional area including all tissue components. The mental nerve had a larger volume fraction of myelinated axons and a correspondingly smaller volume fraction of endoneurium. No differences were observed...

  9. Neurotoxocarosis alters myelin protein gene transcription and expression.

    Science.gov (United States)

    Heuer, Lea; Beyerbach, Martin; Lühder, Fred; Beineke, Andreas; Strube, Christina

    2015-06-01

    Neurotoxocarosis is an infection of the central nervous system caused by migrating larvae of the common dog and cat roundworms (Toxocara canis and Toxocara cati), which are zoonotic agents. As these parasites are prevalent worldwide and neuropathological and molecular investigations on neurotoxocarosis are scare, this study aims to characterise nerve fibre demyelination associated with neurotoxocarosis on a molecular level. Transcription of eight myelin-associated genes (Cnp, Mag, Mbp, Mog, Mrf-1, Nogo-A, Plp1, Olig2) was determined in the mouse model during six time points of the chronic phase of infection using qRT-PCR. Expression of selected proteins was analysed by Western blotting or immunohistochemistry. Additionally, demyelination and neuronal damage were investigated histologically. Significant differences (p ≤ 0.05) between transcription rates of T. canis-infected and uninfected control mice were detected for all analysed genes while T. cati affected five of eight investigated genes. Interestingly, 2', 3 ´-cyclic nucleotide 3'-phosphodiesterase (Cnp) and myelin oligodendrocyte glycoprotein (Mog) were upregulated in both T. canis- and T. cati-infected mice preceding demyelination. Later, CNPase expression was additionally enhanced. As expected, myelin basic protein (Mbp) was downregulated in cerebra and cerebella of T. canis-infected mice when severe demyelination was present 120 days post infectionem (dpi). The transcriptional pattern observed in the present study appears to reflect direct traumatic and hypoxic effects of larval migration as well as secondary processes including host immune reactions, demyelination and attempts to remyelinate damaged areas.

  10. The formation of lipid droplets favors intracellular Mycobacterium leprae survival in SW-10, non-myelinating Schwann cells.

    Science.gov (United States)

    Jin, Song-Hyo; An, Sung-Kwan; Lee, Seong-Beom

    2017-06-01

    Leprosy is a chronic infectious disease that is caused by the obligate intracellular pathogen Mycobacterium leprae (M.leprae), which is the leading cause of all non-traumatic peripheral neuropathies worldwide. Although both myelinating and non-myelinating Schwann cells are infected by M.leprae in patients with lepromatous leprosy, M.leprae preferentially invades the non-myelinating Schwann cells. However, the effect of M.leprae infection on non-myelinating Schwann cells has not been elucidated. Lipid droplets (LDs) are found in M.leprae-infected Schwann cells in the nerve biopsies of lepromatous leprosy patients. M.leprae-induced LD formation favors intracellular M.leprae survival in primary Schwann cells and in a myelinating Schwann cell line referred to as ST88-14. In the current study, we initially characterized SW-10 cells and investigated the effects of LDs on M.leprae-infected SW-10 cells, which are non-myelinating Schwann cells. SW-10 cells express S100, a marker for cells from the neural crest, and NGFR p75, a marker for immature or non-myelinating Schwann cells. SW-10 cells, however, do not express myelin basic protein (MBP), a marker for myelinating Schwann cells, and myelin protein zero (MPZ), a marker for precursor, immature, or myelinating Schwann cells, all of which suggests that SW-10 cells are non-myelinating Schwann cells. In addition, SW-10 cells have phagocytic activity and can be infected with M. leprae. Infection with M. leprae induces the formation of LDs. Furthermore, inhibiting the formation of M. leprae-induced LD enhances the maturation of phagosomes containing live M.leprae and decreases the ATP content in the M. leprae found in SW-10 cells. These facts suggest that LD formation by M. leprae favors intracellular M. leprae survival in SW-10 cells, which leads to the logical conclusion that M.leprae-infected SW-10 cells can be a new model for investigating the interaction of M.leprae with non-myelinating Schwann cells.

  11. Localization of substance P, calcitonin gene related peptide and galanin in the nerve fibers of porcine cystic ovaries

    Directory of Open Access Journals (Sweden)

    Mariusz Majewski

    2012-01-01

    Full Text Available In a previous study, we showed that both the noradrenergic and cholinergic component of ovarian innervation is markedly changed in porcine cystic ovaries. The present study is aimed at elucidating the distribution pattern of substance P- (SP, calcitonin gene related peptide CGRP- and/or galanin (GAL-containing nerve fibers within porcine cystic ovaries. The status polycysticus was induced by dexamethasone phosphate disodium salt i.m. injections performed from the 7th until the 21st day of the first studied estrous cycle. During the same period of time, gilts of the control group received saline. All animals were slaughtered on the expected 11th day of the second studied estrous cycle, and their ovaries were collected. When compared to control gonad, a distinct difference in the distribution pattern and the density of SP-, CGRP- and/or GAL-immunoreactive (GAL-IR nerve fibers was observed. Thus, unlike in the control gonad, SP- and/or CGRP-IR perivascular nerve fibers were found to supply medullar blood vessels of polycystic ovary. Furthermore, the number of GAL-IR nerve fibers contributing to the ground plexus in polycystic ovaries was higher than that observed in the control gonads. Thus, as may be judged from the profound changes in the distribution pattern of differently chemically coded afferent terminals within polycystic gonads, it appears possible that neuropeptides released from these terminals may take part in the etiopathogenesis of this disorder. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 4, pp. 622–630

  12. Peripheral Nerve Regeneration by Secretomes of Stem Cells from Human Exfoliated Deciduous Teeth.

    Science.gov (United States)

    Sugimura-Wakayama, Yukiko; Katagiri, Wataru; Osugi, Masashi; Kawai, Takamasa; Ogata, Kenichi; Sakaguchi, Kohei; Hibi, Hideharu

    2015-11-15

    Peripheral nerve regeneration across nerve gaps is often suboptimal, with poor functional recovery. Stem cell transplantation-based regenerative therapy is a promising approach for axon regeneration and functional recovery of peripheral nerve injury; however, the mechanisms remain controversial and unclear. Recent studies suggest that transplanted stem cells promote tissue regeneration through a paracrine mechanism. We investigated the effects of conditioned media derived from stem cells from human exfoliated deciduous teeth (SHED-CM) on peripheral nerve regeneration. In vitro, SHED-CM-treated Schwann cells exhibited significantly increased proliferation, migration, and the expression of neuron-, extracellular matrix (ECM)-, and angiogenesis-related genes. SHED-CM stimulated neuritogenesis of dorsal root ganglia and increased cell viability. Similarly, SHED-CM enhanced tube formation in an angiogenesis assay. In vivo, a 10-mm rat sciatic nerve gap model was bridged by silicon conduits containing SHED-CM or serum-free Dulbecco's modified Eagle's medium. Light and electron microscopy confirmed that the number of myelinated axons and axon-to-fiber ratio (G-ratio) were significantly higher in the SHED-CM group at 12 weeks after nerve transection surgery. The sciatic functional index (SFI) and gastrocnemius (target muscle) wet weight ratio demonstrated functional recovery. Increased compound muscle action potentials and increased SFI in the SHED-CM group suggested sciatic nerve reinnervation of the target muscle and improved functional recovery. We also observed reduced muscle atrophy in the SHED-CM group. Thus, SHEDs may secrete various trophic factors that enhance peripheral nerve regeneration through multiple mechanisms. SHED-CM may therefore provide a novel therapy that creates a more desirable extracellular microenvironment for peripheral nerve regeneration.

  13. Effects of intraoperative irradiation (IORT) and intraoperative hyperthermia (IOHT) on canine sciatic nerve: histopathological and morphometric studies

    International Nuclear Information System (INIS)

    Vujaskovic, Zeljko; Powers, Barbara E.; Paardekoper, Gabriel; Gillette, Sharon M.; Gillette, Edward L.; Colacchio, Thomas A.

    1999-01-01

    Purpose/Objective: Peripheral neuropathies have emerged as the major dose-limiting complication reported after intraoperative radiation therapy (IORT). The combination of IORT with hyperthermia may further increase the risk of peripheral nerve injury. The objective of this study was to evaluate histopathological and histomorphometric changes in the sciatic nerve of dogs, after IORT with or without hyperthermia treatment. Methods and Materials: Young adult beagle dogs were randomized into five groups of 3-5 dogs each to receive IORT doses of 16, 20, 24, 28, or 32 Gy. Six groups of 4-5 dogs each received IORT doses of 12, 16, 20, 24, or 28 Gy simultaneously with 44 deg. C of intraoperative hyperthermia (IOHT) for 60 min. One group of dogs acted as hyperthermia-alone controls. Two years after the treatment, dogs were euthanized, and histopathological and morphometric analyses were performed. Results: Qualitative histological analysis showed prominant changes such as focal necrosis, mineralization, fibrosis, and severe fiber loss in dogs which received combined treatment. Histomorphometric results showed a significantly higher decrease in axon and myelin and small blood vessels, with a corresponding increase in connective tissue in dogs receiving IORT plus hyperthermia treatment. The effective dose for 50% of nerve fiber loss (ED 50 ) in dogs exposed to IORT only was 25.3 Gy. The ED 50 for nerve fiber loss in dogs exposed to IORT combined with IOHT was 14.8 Gy. The thermal enhancement ratio (TER) was 1.7. Conclusion: The probability of developing peripheral neuropathies in a large animal model is higher when IORT is combined with IOHT, when compared to IORT application alone. To minimize the risk of peripheral neuropathy, clinical treatment protocols for the combination of IORT and hyperthermia should not assume a thermal enhancement ratio (TER) to be lower than 1.5

  14. Altered protein phosphorylation in sciatic nerve from rats with streptozocin-induced diabetes

    International Nuclear Information System (INIS)

    Schrama, L.H.; Berti-Mattera, L.N.; Eichberg, J.

    1987-01-01

    The effect of experimental diabetes on the phosphorylation of proteins in the rat sciatic nerve was studied. Nerves from animals made diabetic with streptozocin were incubated in vitro with [ 32 P]orthophosphate and divided into segments from the proximal to the distal end, and proteins from each segment were then separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The principal labeled species were the major myelin proteins, P0, and the basic proteins. After 6 wk of diabetes, the incorporation of isotope into these proteins rose as a function of distance along the nerve in a proximal to distal direction and was significantly higher at the distal end compared with incorporation into nerves from age-matched controls. The overall level of isotope uptake was similar in nerves from diabetic animals and weight-matched controls. The distribution of 32 P among proteins also differed in diabetic nerve compared with both control groups in that P0 and the small basic protein accounted for a greater proportion of total label incorporated along the entire length of nerve. In contrast to intact nerve, there was no significant difference in protein phosphorylation when homogenates from normal and diabetic nerve were incubated with [ 32 P]-gamma-ATP. The results suggest that abnormal protein phosphorylation, particularly of myelin proteins, is a feature of experimental diabetic neuropathy and that the changes are most pronounced in the distal portion of the nerve

  15. Peripheral neuropathy in type A Niemann-Pick disease. A morphological study.

    Science.gov (United States)

    Landrieu, P; Saïd, G

    1984-01-01

    A black boy had a severe neuropathic form of Niemann-Pick disease (NPD) with a pronounced sphingomyelinase deficiency in the fibroblasts. Nerve conduction velocities were diminished, and a nerve biopsy was performed. Isolated fibers showed segmental demyelination and numerous dense bodies in the Schwann cells (SC). Electron microscopy revealed two categories of inclusions: the first was made up of lysosomal inclusions usually described in NPD. The second comprised myelin inclusions--sometimes still connected to the original myelin sheath--indicating severe myelinopathy. Both myelin debris and NPD inclusions were found in axoplasms and probably came from SC cytoplasm through axolemma lesions. NPD is a unique example of myelinopathy due to sphingomyelinase deficiency.

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

    Science.gov (United States)

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

    2007-01-01

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

  17. Optic Nerve Disorders

    Science.gov (United States)

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

  18. Evaluation of myelination and myelination disorders with turbo inversion recovery magnetic resonance imaging

    International Nuclear Information System (INIS)

    Daldrup, H.E.; Schuierer, G.; Link, T.M.; Moeller, H.; Bick, U.; Peters, P.E.; Kurlemann, G.

    1997-01-01

    The aim of our work was to determine the efficacy of turbo inversion recovery spin echo (TIRSE) pulse sequences in differentiating patients with normal and abnormal myelination. Twenty neurological normal children (aged 5 months to 12 years) as well as 65 children presenting clinically with neurologic developmental deficits (aged 2 months to 10 years) were examined using TIRSE, T1-weighted SE, and T2-weighted turbo SE pulse sequences. Contrast-to-noise-ratio (CNR) between myelinated white and gray matter was compared for the different pulse sequences. In addition, two readers analyzed all images qualitatively by consensus. The CNR values were significantly higher on TIRSE images as compared with conventional images (p < 0.05). Forty-two neurologically abnormal patients displayed a normal myelination on all sequences, whereas 23 showed an abnormal myelination. The TIRSE sequence provided a sensitive and specific depiction of an abnormal myelination in all of these patients. The TIRSE sequence provided additional information to conventional pulse sequences in determining myelination disorders in children, especially in children older than 2 years. (orig.)

  19. Effect of neurotrophic factor, MDP, on rats’ nerve regeneration

    Directory of Open Access Journals (Sweden)

    A.A. Fornazari

    2011-04-01

    Full Text Available Our objective was to determine the immune-modulating effects of the neurotrophic factor N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP on median nerve regeneration in rats. We used male Wistar rats (120-140 days of age, weighing 250-332 g and compared the results of three different techniques of nerve repair: 1 epineural neurorrhaphy using sutures alone (group S - 10 rats, 2 epineural neurorrhaphy using sutures plus fibrin tissue adhesive (FTA; group SF - 20 rats, and 3 sutures plus FTA, with MDP added to the FTA (group SFM - 20 rats. Functional assessments using the grasp test were performed weekly for 12 weeks to identify recovery of flexor muscle function in the fingers secondary to median nerve regeneration. Histological analysis was also utilized. The total number and diameter of myelinated fibers were determined in each proximal and distal nerve segment. Two indices, reported as percentage, were calculated from these parameters, namely, the regeneration index and the diameter change index. By the 8th week, superiority of group SFM over group S became apparent in the grasping test (P = 0.005. By the 12th week, rats that had received MDP were superior in the grasping test compared to both group S (P < 0.001 and group SF (P = 0.001. Moreover, group SF was better in the grasping test than group S (P = 0.014. However, no significant differences between groups were identified by histological analysis. In the present study, rats that had received MDP obtained better function, in the absence of any significant histological differences.

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

    Science.gov (United States)

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

    2012-10-01

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

  1. Long-lasting increase in axonal excitability after epidurally applied DC.

    Science.gov (United States)

    Jankowska, Elzbieta; Kaczmarek, Dominik; Bolzoni, Francesco; Hammar, Ingela

    2017-08-01

    Effects of direct current (DC) on nerve fibers have primarily been investigated during or just after DC application. However, locally applied cathodal DC was recently demonstrated to increase the excitability of intraspinal preterminal axonal branches for >1 h. The aim of this study was therefore to investigate whether DC evokes a similarly long-lasting increase in the excitability of myelinated axons within the dorsal columns. The excitability of dorsal column fibers stimulated epidurally was monitored by recording compound action potentials in peripheral nerves in acute experiments in deeply anesthetized rats. The results show that 1 ) cathodal polarization (0.8-1.0 µA) results in a severalfold increase in the number of epidurally activated fibers and 2 ) the increase in the excitability appears within seconds, 3 ) lasts for >1 h, and 4 ) is activity independent, as it does not require fiber stimulation during the polarization. These features demonstrate an unexplored form of plasticity of myelinated fibers and indicate the conditions under which it develops. They also suggest that therapeutic effects of epidural stimulation may be significantly enhanced if it is combined with DC polarization. In particular, by using DC to increase the number of fibers activated by low-intensity epidural stimuli, the low clinical tolerance to higher stimulus intensities might be overcome. The activity independence of long-lasting DC effects would also allow the use of only brief periods of DC polarization preceding epidural stimulation to increase the effect. NEW & NOTEWORTHY The study indicates a new form of plasticity of myelinated fibers. The differences in time course of DC-evoked increases in the excitability of myelinated nerve fibers in the dorsal columns and in preterminal axonal branches suggest that distinct mechanisms are involved in them. The results show that combining epidural stimulation and transspinal DC polarization may dramatically improve their outcome and

  2. Treatment with acetyl-L-carnitine exerts a neuroprotective effect in the sciatic nerve following loose ligation: a functional and microanatomical study

    Directory of Open Access Journals (Sweden)

    Daniele Tomassoni

    2018-01-01

    Full Text Available Peripheral neuropathies are chronic painful syndromes characterized by allodynia, hyperalgesia and altered nerve functionality. Nerve tissue degeneration represents the microanatomical correlate of peripheral neuropathies. Aimed to improve the therapeutic possibilities, this study investigated the hypersensitivity and the neuromorphological alterations related to the loose ligation of the sciatic nerve in rats. Effects elicited by treatment with acetyl-L-carnitine (ALCAR in comparison to gabapentin were assessed. Axonal injury, reduction of myelin deposition and accumulation of inflammatory cells were detected in damaged nerve. A decrease of phosphorylated 200-kDa neurofilament (NFP immunoreactivity and a redistribution in small clusters of myelin basic like-protein (MBP were observed in ipsilateral nerves. Treatment with ALCAR (100 mg/kg intraperitoneally - i.p. and gabapentin (70 mg/kg i.p. administered bis in die for 14 days induced a significant pain relieving effect. ALCAR, but not gabapentin, significantly countered neuromorphological changes and increased axonal NFP immunoreactivity. These findings indicate that both ALCAR and gabapentin significantly decreased the hypersensitivity related to neuropathic lesions. The observation of the positive ALCAR effect on axonal and myelin sheath alterations in damaged nerve supports its use as neurorestorative agent against neuropathies through mechanism(s consistent to those focused in this study.

  3. [Progression of nerve fiber layer defects in retrobulbar optic neuritis by the macular ganglion cell complex].

    Science.gov (United States)

    Hong, D; Bosc, C; Chiambaretta, F

    2017-11-01

    Recent studies with SD OCT had shown early axonal damage to the macular ganglion cell complex (which consists of the three innermost layers of the retina: Inner Plexiform Layer [IPL], Ganglion Cell Layer [GCL], Retinal Nerve Fibre layer [RNFL]) in optic nerve pathology. Retrobulbar optic neuritis (RBON), occurring frequently in demyelinating diseases, leads to atrophy of the optic nerve fibers at the level of the ganglion cell axons, previously described in the literature. The goal of this study is to evaluate the progression of optic nerve fiber defects and macular ganglion cell complex defects with the SPECTRALIS OCT via a reproducible method by calculating a mean thickness in each quadrant after an episode of retrobulbar optic neuritis. This is a prospective monocentric observational study including 8 patients at the Clermont-Ferrand university medical center. All patients underwent ocular examination with macular and disc OCT analysis and a Goldmann visual field at the time of inclusion (onset or recurrence of RBON), at 3 months and at 6 months. Patients were 40-years-old on average at the time of inclusion. After 6 months of follow-up, there was progression of the atrophy of the macular ganglion cell complex in the affected eye on (11.5% or 11μm) predominantly inferonasally (13.9% or 16μm) and superonasally (12.9% or 14μm) while the other eye remained stable. The decrease in thickness occurred mainly in the most internal 3 layers of the retina. On average, the loss in thickness of the peripapillary RNFL was predominantly inferotemporal (24.9% or 39μm) and superotemporal (21.8% or 28μm). In 3 months of progression, the loss of optic nerve fibers is already seen on macular and disc OCT after an episode of RBON, especially in inferior quadrants in spite of the improvement in the Goldmann visual field and visual acuity. Segmentation by quadrant was used here to compare the progression of the defect by region compared to the fovea in a global and reproducible

  4. 142 Key words: Brachialis, radial nerve, musculocutaneous nerve.

    African Journals Online (AJOL)

    AWORI KIRSTEEN

    The innervation of brachialis muscle by the musculocutaneous nerve has been described as either type I or type II and the main trunk to this muscle is rarely absent. The contribution .... brachialis muscle by fiber analysis of supply nerves].

  5. Topographical distribution of pinprick and warmth thresholds to CO2 laser stimulation on the human skin

    DEFF Research Database (Denmark)

    Agostino, R.; Cruccu, G.; Iannetti, G.

    2000-01-01

    nociceptors, the fibers which convey pinprick sensation, are more dense at proximal than at distal body sites. This finding adds information to skin biopsy studies of epidermal free nerve endings which showed a similar gradient, but could not differentiate small myelinated from unmyelinated fiber afferents...

  6. Proliferation of Schwann cells induced by axolemmal and myelin membranes

    International Nuclear Information System (INIS)

    Dinneen, M.

    1985-01-01

    Purified Schwann Cells were cultured from neonatal rat sciatic nerve using a modification of the method of Brockes. Schwann cells and contaminating fibroblasts were unambiguously identified using fluorescent antibodies of 2'3' cyclic nucleotide 3'-phosphodiesterase and the thy 1.1 antigen respectively. The Schwann cells were quiescent unless challenged with mitogens. They proliferated rapidly in response to the soluble mitogen, cholera toxin, or to membrane fractions from rat CNS or PNS, prepared by the method of DeVries. Mitogenic activity was present in both axolemmal and myelin enriched fractions and promoted a 10-15 fold increase in the rate of 3 H-thymidine uptake. The axolemmal mitogen was sensitive to heat (80 0 C for 10 minutes), trypsin digestion (0.05% x 30 mins) or to treatment with endoglycosidase D, suggesting that it could be a glycoprotein. Fifty percent of the axolemmal mitogenic activity was solubilized in 1% octyl-glucoside. The solubilized material, however, was very unstable and further purification was not possible. The myelin associated mitogenic activity was markedly different. It was resistant to freeze thaw cycles, trypsin digestion of endoglycosidase treatment and the activity was actually enhanced by heating at 100 0 C for two hours. It is proposed that the axolemmal activity is responsible for Schwann cell proliferation during development and that the myelin associated activity promotes Schwann cell proliferation during Wallerian degeneration

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

    Science.gov (United States)

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

    2017-09-01

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

  8. Long-Chain Omega-3 Fatty Acids Supplementation Accelerates Nerve Regeneration and Prevents Neuropathic Pain Behavior in Mice

    Directory of Open Access Journals (Sweden)

    Rafaela V. Silva

    2017-10-01

    Full Text Available Fish oil (FO is the main source of long chain omega-3 polyunsaturated fatty acids (ω-3 PUFAs, which display relevant analgesic and anti-inflammatory properties. Peripheral nerve injury is driven by degeneration, neuroinflammation, and neuronal plasticity which results in neuropathic pain (NP symptoms such as allodynia and hyperalgesia. We tested the preventive effect of an EPA/DHA-concentrate fish oil (CFO on NP development and regenerative features. Swiss mice received daily oral treatment with CFO 4.6 or 2.3 g/kg for 10 days after NP was induced by partial sciatic nerve ligation. Mechanical allodynia and thermal hypernociception were assessed 5 days after injury. CFO 2.3 g/kg significantly prevented mechanical and thermal sensitization, reduced TNF levels in the spinal cord, sciatic MPO activity, and ATF-3 expression on DRG cells. CFO improved Sciatic Functional Index (SFI as well as electrophysiological recordings, corroborating the increased GAP43 expression and total number of myelinated fibers observed in sciatic nerve. No locomotor activity impairment was observed in CFO treated groups. These results point to the regenerative and possibly protective properties of a combined EPA and DHA oral administration after peripheral nerve injury, as well as its anti-neuroinflammatory activity, evidencing ω-3 PUFAs promising therapeutic outcomes for NP treatment.

  9. BDNF-hypersecreting human umbilical cord blood mesenchymal stem cells promote erectile function in a rat model of cavernous nerve electrocautery injury.

    Science.gov (United States)

    Song, Lujie; Zhu, Jianqiang; Zhang, Xiong; Cui, Zhiqiang; Fu, Qiang; Huang, Jianwen; Lu, Hongkai

    2016-01-01

    Erectile dysfunction (ED) continues to be a significant problem for men following radical prostatectomy. We hypothesize that intracavernous injection of BDNF-hypersecreting human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) can ameliorate ED in a rat model of cavernous nerve electrocautery injury (CNEI). Forty-two male Sprague-Dawley rats were randomly divided into four groups: sham + PBS (n = 6), CNEI + PBS (n = 12), CNEI + hUCB-MSCs (n = 12) and CNEI + BDNF-hUCB-MSCs (n = 12). At day 28 post-surgery, erectile function was examined and specimens were harvested for histology. Immunofluorescence staining, Masson's trichrome staining and transmission electron microscopy were performed to determine the structural changes in corpus cavernosum. Cells that are injected into penis were labeled by BrdU and tracked by immunofluorescence staining. Three days post-surgery, the concentration of BDNF protein in penile tissues was measured by Western blotting. Rats intracavernosally injected with BDNF-hUCB-MSCs showed the most significant improvement in the ratio of maximal ICP to MAP (ICP/MAP). Histological examinations showed moderate recovery of nNOS-positive nerve fibers, ratio of smooth muscle to collagen and smooth muscle content in the CNEI + hUCB-MSCs group and remarkable recovery in the CNEI + BDNF-hUCB-MSCs group compared to the CNEI + PBS group. By TEM examination, atrophy of myelinated and non-myelinated nerve fibers was noted in CNEI + PBS group and significant recovery was observed in two treated groups. There were more BrdU-positive cells in the BDNF-hUCB-MSCs group than in the hUCB-MSCs group both in the penis and in the MPG. Three days post-surgery, the concentration of BDNF protein in penile tissues in BDNF-hUCB-MSCs group was much higher than in other groups. Intracavernous injection of BDNF-hypersecreting hUCB-MSCs can enhance the recovery of erectile function, promote the CNs regeneration and inhibit corpus cavernosum fibrosis after CNEI in a rat

  10. 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......Responses to free-field sound of 401 fibers from the VIIIth nerve of the grassfrog, Rana temporaria, are described. The spontaneous activities of the fibers ranged from 0 to 75 spikes/s, showing only weak correlation with frequency or sensitivity of the fibers. The highest spontaneous activities...... were approximately twice as high as reported previously for frogs. Best frequencies ranged from 100 to 1600 Hz and thresholds ranged from 21 to 80 dB SPL. The median dynamic range was 20 dB and the slopes of the rate-level curves ranged from 5 to 20 spikes/(s-dB). Most of the units showed post...

  11. Expression analysis of the N-Myc downstream-regulated gene 1 indicates that myelinating Schwann cells are the primary disease target in hereditary motor and sensory neuropathy-Lom.

    Science.gov (United States)

    Berger, Philipp; Sirkowski, Erich E; Scherer, Steven S; Suter, Ueli

    2004-11-01

    Mutations in the gene encoding N-myc downstream-regulated gene-1 (NDRG1) lead to truncations of the encoded protein and are associated with an autosomal recessive demyelinating neuropathy--hereditary motor and sensory neuropathy-Lom. NDRG1 protein is highly expressed in peripheral nerve and is localized in the cytoplasm of myelinating Schwann cells, including the paranodes and Schmidt-Lanterman incisures. In contrast, sensory and motor neurons as well as their axons lack NDRG1. NDRG1 mRNA levels in developing and injured adult sciatic nerves parallel those of myelin-related genes, indicating that the expression of NDRG1 in myelinating Schwann cells is regulated by axonal interactions. Oligodendrocytes also express NDRG1, and the subtle CNS deficits of affected patients may result from a lack of NDRG1 in these cells. Our data predict that the loss of NDRG1 leads to a Schwann cell autonomous phenotype resulting in demyelination, with secondary axonal loss.

  12. Anatomical feasibility of vagus nerve esophageal branch transfer to the phrenic nerve☆

    Science.gov (United States)

    Wang, Ce; Liu, Jun; Yuan, Wen; Zhou, Xuhui; Wang, Xinwei; Xu, Peng; Chen, Jian; Wu, Guoxin; Shi, Sheng

    2012-01-01

    This study measured the vagus and phrenic nerves from 12 adult cadavers. We found that the width and thickness of the vagus and phrenic nerves were different in the chest. The distance from the point of the vagus nerve and phrenic nerve on the plane of the inferior border of portal pulmonary arteries (T point) was approximately 7 cm to the diaphragm and was approximately 10 cm to the clavicle level. The number of motor fibers in the vagus nerves was 1 716 ± 362, and the number of nerve fibers was 4 473 ± 653. The number of motor fibers in the phrenic nerves ranged from 3 078 ± 684 to 4 794 ± 638, and the number of nerve fibers ranged from 3 437 ± 642 to 5 071 ± 723. No significant difference was found in the total number of nerve fibers. The results suggest that width, thickness, and total number of nerve fibers are similar between the vagus and phrenic nerves, but the number of motor fibers is different between them. PMID:25745467

  13. Retinal Nerve Fiber Layer Converges More Convexly on Normal Smaller Optic Nerve Head.

    Science.gov (United States)

    Jung, Kyoung In; Shin, Jeong Ah; Park, Hae-Young Lopilly; Park, Chan Kee

    2015-08-01

    To investigate retinal nerve fiber layer (RNFL) configuration in the optic nerve head (ONH) and peripapillary area according to disc size and to determine whether it explains cup discrepancy among eyes with different disc sizes. Horizontal and vertical RNFL curvature and mean thickness were measured using confocal scanning laser ophthalmoscopy (Heidelberg Retina Tomograph) in 63 normal subjects grouped by disc size. Average and quadrant RNFL thickness, disc size, average cup-to-disc ratio (CDR), and convergence angle at the optic disc were also measured using Cirrus HD-optical coherence tomography. The relationships between disc size and RNFL curvature, thickness, angle at optic disc, and CDR were evaluated. RNFL curvature and convergence angle reflects convexity "on" and "into" the optic disc, respectively. CDR was smaller for small discs and was positively correlated with disc size (Poptic disc were positively correlated with disc size (POptic disc area was negatively correlated with mean RNFL thickness at the optic disc margin measured by HRT (P=0.002), but not in the peripapillary area by optical coherence tomography. Using imaging techniques, we demonstrated that the shape of the RNFLs converging "on" and entering "into" the optic disc was more convex for small optic discs compared with large discs. A low CDR for small discs could be mediated by these RNFL profiles at the ONH, which may guide the clinical evaluation of glaucomatous ONH damage.

  14. Bony fish myelin: evidence for common major structural glycoproteins in central and peripheral myelin of trout.

    Science.gov (United States)

    Jeserich, G; Waehneldt, T V

    1986-02-01

    Peripheral nervous system (PNS) myelin from the rainbow trout (Salmo gairdneri) banded at a density of 0.38 M sucrose. The main myelin proteins consisted of (1) two basic proteins, BPa and BPb (11,500 and 13,000 MW, similar to those of trout central nervous system (CNS) myelin proteins BP1 and BP2), and (2) two glycosylated components, IPb (24,400 MW) and IPc (26,200 MW). IPc comigrated with trout CNS myelin protein IP2 in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, whereas trout CNS myelin protein IP1 had a lower molecular weight (23,000). Following two-dimensional separation, however, both IPb and IPc from PNS showed two components; the more acidic component of IPc comigrated with IP2 from CNS. PNS tissue autolysis led to the formation of IPa (20,000 MW), consisting of two components in isoelectric focusing of which again the more acidic one comigrated with the CNS autolysis product IP0. Limited enzymatic digestion of isolated IP proteins from PNS and CNS led to closely similar degradation patterns, being most pronounced in the case of IP2 and IPc. Immunoblotting revealed that all IP components from trout PNS and CNS myelins reacted with antibodies to trout IP1 (CNS) and bovine P0 protein (PNS) whereas antibodies to rat PLP (CNS) were entirely unreactive. All BP components from trout PNS and CNS myelins bound to antibodies against human myelin basic protein. On the basis of these studies trout PNS and CNS myelins contain at least one common IP glycoprotein, whereas other members of the IP myelin protein family appear closely related. In the CNS myelin of trout the IP components appear to replace PLP.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Terminal changes in hereditary sensory and autonomic neuropathy: a long-term follow-up of a sporadic case.

    Science.gov (United States)

    Lee, Sang-Soo; Lee, Sung-Hyun; Han, Seol-Heui

    2003-07-01

    We describe terminal changes in a long-term follow-up of a 51-year-old man with sporadic hereditary sensory and autonomic neuropathy (HSAN). From the age of 15 years onwards, he suffered from multiple painless ulcers of his feet and fingers, necessitating amputation. Neurological studies revealed almost complete sensory loss affecting all modalities in the upper and lower limbs, minimal involvement of motor fibers, and areflexia. A neurophysiological abnormality involved an absence of sensory action potentials with relatively normal motor nerve conduction velocities. Biopsy of the sural nerve showed almost total loss of myelinated fibers with a mild decrease in unmyelinated fibers. Despite the late onset of the disease, the progressive course, and the lancinating pain, the terminal features of this patient, which involved a selective loss of myelinated fibers and widespread sensory loss, seem to be symptomatic of HSAN II, the progressive form of autosomal recessive sensory neuropathy, and emphasize the clinical heterogeneity of HSAN.

  16. Non-Invasive Study of Nerve Fibres using Laser Interference Microscopy

    DEFF Research Database (Denmark)

    Brazhe, A. R.; Brazhe, N. A.; Rodionova, N. N.

    2008-01-01

    This paper presents the results of a laser interference microscopy study of the morphology and dynamical properties of myelinated nerve fibres. We describe the principles of operation of the phase-modulated laser interference microscope and show how this novel technique allows us to obtain...... information non-invasively about the internal structure of different regions of a nerve fibre. We also analyse the temporal variations in the internal optical properties in order to detect the rhythmic activity in the nerve fibre at different time scales and to shed light on the underlying biological...

  17. Cholesterol in myelin biogenesis and hypomyelinating disorders.

    Science.gov (United States)

    Saher, Gesine; Stumpf, Sina Kristin

    2015-08-01

    The largest pool of free cholesterol in mammals resides in myelin membranes. Myelin facilitates rapid saltatory impulse propagation by electrical insulation of axons. This function is achieved by ensheathing axons with a tightly compacted stack of membranes. Cholesterol influences myelination at many steps, from the differentiation of myelinating glial cells, over the process of myelin membrane biogenesis, to the functionality of mature myelin. Cholesterol emerged as the only integral myelin component that is essential and rate-limiting for the development of myelin in the central and peripheral nervous system. Moreover, disorders that interfere with sterol synthesis or intracellular trafficking of cholesterol and other lipids cause hypomyelination and neurodegeneration. This review summarizes recent results on the roles of cholesterol in CNS myelin biogenesis in normal development and under different pathological conditions. This article is part of a Special Issue entitled Brain Lipids. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Networks of myelin covariance

    Science.gov (United States)

    Slater, David; Ruef, Anne; Sanabria‐Diaz, Gretel; Preisig, Martin; Kherif, Ferath; Draganski, Bogdan; Lutti, Antoine

    2017-01-01

    Abstract Networks of anatomical covariance have been widely used to study connectivity patterns in both normal and pathological brains based on the concurrent changes of morphometric measures (i.e., cortical thickness) between brain structures across subjects (Evans, 2013). However, the existence of networks of microstructural changes within brain tissue has been largely unexplored so far. In this article, we studied in vivo the concurrent myelination processes among brain anatomical structures that gathered together emerge to form nonrandom networks. We name these “networks of myelin covariance” (Myelin‐Nets). The Myelin‐Nets were built from quantitative Magnetization Transfer data—an in‐vivo magnetic resonance imaging (MRI) marker of myelin content. The synchronicity of the variations in myelin content between anatomical regions was measured by computing the Pearson's correlation coefficient. We were especially interested in elucidating the effect of age on the topological organization of the Myelin‐Nets. We therefore selected two age groups: Young‐Age (20–31 years old) and Old‐Age (60–71 years old) and a pool of participants from 48 to 87 years old for a Myelin‐Nets aging trajectory study. We found that the topological organization of the Myelin‐Nets is strongly shaped by aging processes. The global myelin correlation strength, between homologous regions and locally in different brain lobes, showed a significant dependence on age. Interestingly, we also showed that the aging process modulates the resilience of the Myelin‐Nets to damage of principal network structures. In summary, this work sheds light on the organizational principles driving myelination and myelin degeneration in brain gray matter and how such patterns are modulated by aging. PMID:29271053

  19. Cutaneous somatic and autonomic nerve TDP-43 deposition in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Ren, Yuting; Liu, Wenxiu; Li, Yifan; Sun, Bo; Li, Yanran; Yang, Fei; Wang, Hongfen; Li, Mao; Cui, Fang; Huang, Xusheng

    2018-05-26

    To evaluate the involvement of the sensory and autonomic nervous system in amyotrophic lateral sclerosis (ALS) and to determine whether TDP-43/pTDP-43 deposits in skin nerve fibers signify a valuable biomarker for ALS. Eighteen patients with ALS and 18 age- and sex-matched control subjects underwent physical examinations, in addition to donating skin biopsies from the distal leg. The density of epidermal, Meissner's corpuscle (MC), sudomotor, and pilomotor nerve fibers were measured. Confocal microscopy was used to determine the cutaneous somatic and autonomic nerve fiber density and TDP-43/pTDP-43 deposition. Intraepidermal nerve fiber density (IENFD) was reduced in individuals with ALS (P nerve fiber density (SGNFD) (P nerve fiber density (PNFD) (P nerve fibers may indicate an important role in the underlying pathogenesis of ALS. This observation might be used as a potential biomarker for diagnosing ALS.

  20. The influence of botulinum toxin type A (BTX) on the immunohistochemical characteristics of noradrenergic and cholinergic nerve fibers supplying the porcine urinary bladder wall.

    Science.gov (United States)

    Lepiarczyk, E; Bossowska, A; Kaleczyc, J; Majewski, M

    2011-01-01

    Botulinum toxin (BTX) belongs to a family of neurotoxins which strongly influence the function of autonomic neurons supplying the urinary bladder. Accordingly, BTX has been used as an effective drug in experimental therapies of a range of neurogenic bladder disorders. However, there is no detailed information dealing with the influence of BTX on the morphological and chemical properties of nerve fibres supplying the urinary bladder wall. Therefore, the present study investigated, using double-labeling immunohistochemistry, the distribution, relative frequency and chemical coding of cholinergic and noradrenergic nerve fibers supplying the wall of the urinary bladder in normal female pigs (n = 6) and in the pigs (n = 6) after intravesical BTX injections. In the pigs injected with BTX, the number of adrenergic (DbetaH-positive) nerve fibers distributed in the bladder wall (urothelium, submucosa and muscle coat) was distinctly higher while the number of cholinergic (VAChT-positive) nerve terminals was lower than that found in the control animals. Moreover, the injections of BTX resulted in some changes dealing with the chemical coding of the adrenergic nerve fibers. In contrast to the normal pigs, in BTX injected animals the number of DbetaH/NPY- or DbetaH/CGRP-positive axons was higher in the muscle coat, and some fibres distributed in the urothelium and submucosa expressed immunoreactivity to CGRP. The results obtained suggest that the therapeutic effects of BTX on the urinary bladder might be dependent on changes in the distribution and chemical coding of nerve fibers supplying this organ.

  1. Reduction in Retinal Nerve Fiber Layer Thickness in Young Adults with Autism Spectrum Disorders

    Science.gov (United States)

    Emberti Gialloreti, Leonardo; Pardini, Matteo; Benassi, Francesca; Marciano, Sara; Amore, Mario; Mutolo, Maria Giulia; Porfirio, Maria Cristina; Curatolo, Paolo

    2014-01-01

    Recent years have seen an increase in the use of retinal nerve fiber layer (RNFL) evaluation as an easy-to-use, reproducible, proxy-measure of brain structural abnormalities. Here, we evaluated RNFL thickness in a group of subjects with high functioning autism (HFA) or with Asperger Syndrome (AS) to its potential as a tool to study autism…

  2. Nerve conduction in relation to vibration exposure - a non-positive cohort study

    Directory of Open Access Journals (Sweden)

    Nilsson Tohr

    2010-07-01

    distal neuropathy of the large myelinated fibers in a cohort of male office and manual workers.

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

    Science.gov (United States)

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

    2014-04-01

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

  4. Long-Standing Motor and Sensory Recovery following Acute Fibrin Sealant Based Neonatal Sciatic Nerve Repair

    Directory of Open Access Journals (Sweden)

    Natalia Perussi Biscola

    2016-01-01

    Full Text Available Brachial plexus lesion results in loss of motor and sensory function, being more harmful in the neonate. Therefore, this study evaluated neuroprotection and regeneration after neonatal peripheral nerve coaptation with fibrin sealant. Thus, P2 neonatal Lewis rats were divided into three groups: AX: sciatic nerve axotomy (SNA without treatment; AX+FS: SNA followed by end-to-end coaptation with fibrin sealant derived from snake venom; AX+CFS: SNA followed by end-to-end coaptation with commercial fibrin sealant. Results were analyzed 4, 8, and 12 weeks after lesion. Astrogliosis, microglial reaction, and synapse preservation were evaluated by immunohistochemistry. Neuronal survival, axonal regeneration, and ultrastructural changes at ventral spinal cord were also investigated. Sensory-motor recovery was behaviorally studied. Coaptation preserved synaptic covering on lesioned motoneurons and led to neuronal survival. Reactive gliosis and microglial reaction decreased in the same groups (AX+FS, AX+CFS at 4 weeks. Regarding axonal regeneration, coaptation allowed recovery of greater number of myelinated fibers, with improved morphometric parameters. Preservation of inhibitory synaptic terminals was accompanied by significant improvement in the motor as well as in the nociceptive recovery. Overall, the present data suggest that acute repair of neonatal peripheral nerves with fibrin sealant results in neuroprotection and regeneration of motor and sensory axons.

  5. A novel method of lengthening the accessory nerve for direct coaptation during nerve repair and nerve transfer procedures.

    Science.gov (United States)

    Tubbs, R Shane; Maldonado, Andrés A; Stoves, Yolanda; Fries, Fabian N; Li, Rong; Loukas, Marios; Oskouian, Rod J; Spinner, Robert J

    2018-01-01

    OBJECTIVE The accessory nerve is frequently repaired or used for nerve transfer. The length of accessory nerve available is often insufficient or marginal (under tension) for allowing direct coaptation during nerve repair or nerve transfer (neurotization), necessitating an interpositional graft. An attractive maneuver would facilitate lengthening of the accessory nerve for direct coaptation. The aim of the present study was to identify an anatomical method for such lengthening. METHODS In 20 adult cadavers, the C-2 or C-3 connections to the accessory nerve were identified medial to the sternocleidomastoid (SCM) muscle and the anatomy of the accessory nerve/cervical nerve fibers within the SCM was documented. The cervical nerve connections were cut. Lengths of the accessory nerve were measured. Samples of the cut C-2 and C-3 nerves were examined using immunohistochemistry. RESULTS The anatomy and adjacent neural connections within the SCM are complicated. However, after the accessory nerve was "detethered" from within the SCM and following transection, the additional length of the accessory nerve increased from a mean of 6 cm to a mean of 10.5 cm (increase of 4.5 cm) after cutting the C-2 connections, and from a mean of 6 cm to a mean length of 9 cm (increase of 3.5 cm) after cutting the C-3 connections. The additional length of accessory nerve even allowed direct repair of an infraclavicular target (i.e., the proximal musculocutaneous nerve). The cervical nerve connections were shown not to contain motor fibers. CONCLUSIONS An additional length of the accessory nerve made available in the posterior cervical triangle can facilitate direct repair or neurotization procedures, thus eliminating the need for an interpositional nerve graft, decreasing the time/distance for regeneration and potentially improving clinical outcomes.

  6. Tissue-engineered spiral nerve guidance conduit for peripheral nerve regeneration.

    Science.gov (United States)

    Chang, Wei; Shah, Munish B; Lee, Paul; Yu, Xiaojun

    2018-06-01

    Recently in peripheral nerve regeneration, preclinical studies have shown that the use of nerve guidance conduits (NGCs) with multiple longitudinally channels and intra-luminal topography enhance the functional outcomes when bridging a nerve gap caused by traumatic injury. These features not only provide guidance cues for regenerating nerve, but also become the essential approaches for developing a novel NGC. In this study, a novel spiral NGC with aligned nanofibers and wrapped with an outer nanofibrous tube was first developed and investigated. Using the common rat sciatic 10-mm nerve defect model, the in vivo study showed that a novel spiral NGC (with and without inner nanofibers) increased the successful rate of nerve regeneration after 6 weeks recovery. Substantial improvements in nerve regeneration were achieved by combining the spiral NGC with inner nanofibers and outer nanofibrous tube, based on the results of walking track analysis, electrophysiology, nerve histological assessment, and gastrocnemius muscle measurement. This demonstrated that the novel spiral NGC with inner aligned nanofibers and wrapped with an outer nanofibrous tube provided a better environment for peripheral nerve regeneration than standard tubular NGCs. Results from this study will benefit for future NGC design to optimize tissue-engineering strategies for peripheral nerve regeneration. We developed a novel spiral nerve guidance conduit (NGC) with coated aligned nanofibers. The spiral structure increases surface area by 4.5 fold relative to a tubular NGC. Furthermore, the aligned nanofibers was coated on the spiral walls, providing cues for guiding neurite extension. Finally, the outside of spiral NGC was wrapped with randomly nanofibers to enhance mechanical strength that can stabilize the spiral NGC. Our nerve histological data have shown that the spiral NGC had 50% more myelinated axons than a tubular structure for nerve regeneration across a 10 mm gap in a rat sciatic nerve

  7. Magnetic resonance imaging and myelin

    International Nuclear Information System (INIS)

    Adamsbaum, C.; Andre, C.; Rolland, Y.

    1995-01-01

    Postnatal development of the brain is characterized by growth and by myelination. Myelination of the brain normally extends from birth until about two years of age. MRI changes corresponding to the various myelination stages are due mainly to changes in the water content of the cerebral parenchyma. Myelination kinetics follow a fairly precise timetable, with variations across areas of the brain. Abnormalities of white matter are responsible for relatively stereotyped, nonspecific manifestations, which are mainly due to an increase in the amount of water contained in diseased white matter, whatever the cause of the disorder. Interpretation is based on the location, distribution, and progression of lesions. (authors). 7 refs., 5 figs

  8. In vivo assessment of peripheral nerve regeneration by diffusion tensor imaging.

    Science.gov (United States)

    Morisaki, Shinsuke; Kawai, Yuko; Umeda, Masahiro; Nishi, Mayumi; Oda, Ryo; Fujiwara, Hiroyoshi; Yamada, Kei; Higuchi, Toshihiro; Tanaka, Chuzo; Kawata, Mitsuhiro; Kubo, Toshikazu

    2011-03-01

    To evaluate the sensitivity of diffusion tensor imaging (DTI) in assessing peripheral nerve regeneration in vivo. We assessed the changes in the DTI parameters and histological analyses after nerve injury to examine degeneration and regeneration in the rat sciatic nerves. For magnetic resonance imaging (MRI), 16 rats were randomly divided into two groups: group P (permanently crushed; n = 7) and group T (temporally crushed; n = 9). Serial MRI of the right leg was performed before the operation, and then performed at the timepoints of 1, 2, 3, and 4 weeks after the crush injury. The changes in fractional anisotropy (FA), axial diffusivity (λ(∥)), and radial diffusivity (λ(⟂)) were quantified. For histological analyses, the number of axons and the myelinated axon areas were quantified. Decreased FA and increased λ(⟂) were observed in the degenerative phase, and increased FA and decreased λ(⟂) were observed in the regenerative phase. The changes in FA and λ(⟂) were strongly correlated with histological changes, including axonal and myelin regeneration. DTI parameters, especially λ(⟂) , can be good indicators for peripheral nerve regeneration and can be applied as noninvasive diagnostic tools for a variety of neurological diseases. Copyright © 2011 Wiley-Liss, Inc.

  9. Recovery of the sub-basal nerve plexus and superficial nerve terminals after corneal epithelial injury in mice.

    Science.gov (United States)

    Downie, Laura E; Naranjo Golborne, Cecilia; Chen, Merry; Ho, Ngoc; Hoac, Cam; Liyanapathirana, Dasun; Luo, Carol; Wu, Ruo Bing; Chinnery, Holly R

    2018-06-01

    Our aim was to compare regeneration of the sub-basal nerve plexus (SBNP) and superficial nerve terminals (SNT) following corneal epithelial injury. We also sought to compare agreement when quantifying nerve parameters using different image analysis techniques. Anesthetized, female C57BL/6 mice received central 1-mm corneal epithelial abrasions. Four-weeks post-injury, eyes were enucleated and processed for PGP9.5 to visualize the corneal nerves using wholemount immunofluorescence staining and confocal microscopy. The percentage area of the SBNP and SNT were quantified using: ImageJ automated thresholds, ImageJ manual thresholds and manual tracings in NeuronJ. Nerve sum length was quantified using NeuronJ and Imaris. Agreement between methods was considered with Bland-Altman analyses. Four-weeks post-injury, the sum length of nerve fibers in the SBNP, but not the SNT, was reduced compared with naïve eyes. In the periphery, but not central cornea, of both naïve and injured eyes, nerve fiber lengths in the SBNP and SNT were strongly correlated. For quantifying SBNP nerve axon area, all image analysis methods were highly correlated. In the SNT, there was poor correlation between manual methods and auto-thresholding, with a trend towards underestimating nerve fiber area using auto-thresholding when higher proportions of nerve fibers were present. In conclusion, four weeks after superficial corneal injury, there is differential recovery of epithelial nerve axons; SBNP sum length is reduced, however the sum length of SNTs is similar to naïve eyes. Care should be taken when selecting image analysis methods to compare nerve parameters in different depths of the corneal epithelium due to differences in background autofluorescence. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2016-06-01

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

  11. Hypoxia-induced increases in serotonin-immunoreactive nerve fibers in the medulla oblongata of the rat.

    Science.gov (United States)

    Morinaga, Ryosuke; Nakamuta, Nobuaki; Yamamoto, Yoshio

    2016-10-01

    Hypoxia induces respiratory responses in mammals and serotonergic neurons in the medulla oblongata participate in respiratory control. However, the morphological changes in serotonergic neurons induced by hypoxia have not yet been examined and respiratory controls of serotonergic neurons have not been clarified. We herein investigated the distribution of immunoreactivity for serotonin (5-hydroxytryptamine; 5-HT) in the medulla oblongata of control rats and rats exposed to 1-6h of hypoxia (10% O 2 ). We also examined the medulla oblongata by multiple immunofluorescence labeling for 5-HT, neurokinin 1 receptors (NK1R), a marker for some respiratory neurons in the pre-Bötzinger complex (PBC), and dopamine β-hydroxylase (DBH), a marker for catecholaminergic neurons. The number of 5-HT-immunoreactive nerve cell bodies in the raphe nuclei was higher in rats exposed to hypoxia than in control rats. The number of 5-HT-immunoreactive nerve fibers significantly increased in the rostral ventrolateral medulla of rats exposed to 1-6h of hypoxia, caudal ventrolateral medulla of rats exposed to 2-6h of hypoxia, and lateral part of the nucleus of the solitary tract and dorsal motor nucleus of the vagus nerve of rats exposed to 1-2h of hypoxia. Multiple immunofluorescence labeling showed that 5-HT-immunoreactive nerve fibers were close to NK1R-immunoreactive neurons in ventrolateral medulla and to DBH-immunoreactive neurons in the medulla. These results suggest that serotonergic neurons partly regulate respiratory control under hypoxic conditions by modulating the activity of NK1R-expressing and catecholaminergic neurons. Copyright © 2016 Elsevier GmbH. All rights reserved.

  12. [Glaucoma and optic nerve drusen: Limitations of optic nerve head OCT].

    Science.gov (United States)

    Poli, M; Colange, J; Goutagny, B; Sellem, E

    2017-09-01

    Optic nerve head drusen are congenital calcium deposits located in the prelaminar section of the optic nerve head. Their association with visual field defects has been classically described, but the diagnosis of glaucoma is not easy in these cases of altered optic nerve head anatomy. We describe the case of a 67-year-old man with optic nerve head drusen complicated by glaucoma, which was confirmed by visual field and OCT examination of the peripapillary retinal nerve fiber layer (RNFL), but the measurement of the minimum distance between the Bruch membrane opening and the internal limiting membrane (minimum rim width, BMO-MRW) by OCT was normal. OCT of the BMO-MRW is a new diagnostic tool for glaucoma. Superficial optic nerve head drusen, which are found between the internal limiting membrane and the Bruch's membrane opening, overestimate the value of this parameter. BMO-MRW measurement is not adapted to cases of optic nerve head drusen and can cause false-negative results for this parameter, and the diagnosis of glaucoma in this case should be based on other parameters such as the presence of a fascicular defect in the retinal nerve fibers, RNFL or macular ganglion cell complex thinning, as well as visual field data. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  13. 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. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Atomic resolution view into the structure–function relationships of the human myelin peripheral membrane protein P2

    Energy Technology Data Exchange (ETDEWEB)

    Ruskamo, Salla [University of Oulu, Oulu (Finland); University of Oulu, Oulu (Finland); Yadav, Ravi P. [Banaras Hindu University, Varanasi (India); Helmholtz Centre for Infection Research (CSSB-HZI), German Electron Synchrotron (DESY), Hamburg (Germany); Sharma, Satyan; Lehtimäki, Mari [University of Oulu, Oulu (Finland); University of Oulu, Oulu (Finland); Laulumaa, Saara [University of Oulu, Oulu (Finland); University of Oulu, Oulu (Finland); Helmholtz Centre for Infection Research (CSSB-HZI), German Electron Synchrotron (DESY), Hamburg (Germany); Aggarwal, Shweta; Simons, Mikael [Max Planck Institute for Experimental Medicine, Göttingen (Germany); Bürck, Jochen; Ulrich, Anne S. [Karlsruhe Institute for Technology (KIT), Karlsruhe (Germany); Juffer, André H. [University of Oulu, Oulu (Finland); University of Oulu, Oulu (Finland); Kursula, Inari [University of Oulu, Oulu (Finland); Helmholtz Centre for Infection Research (CSSB-HZI), German Electron Synchrotron (DESY), Hamburg (Germany); Kursula, Petri, E-mail: petri.kursula@oulu.fi [University of Oulu, Oulu (Finland); University of Oulu, Oulu (Finland); Helmholtz Centre for Infection Research (CSSB-HZI), German Electron Synchrotron (DESY), Hamburg (Germany); University of Hamburg, Hamburg (Germany)

    2014-01-01

    The structure of the human myelin peripheral membrane protein P2 has been refined at 0.93 Å resolution. In combination with functional experiments in vitro, in vivo and in silico, the fine details of the structure–function relationships in P2 are emerging. P2 is a fatty acid-binding protein expressed in vertebrate peripheral nerve myelin, where it may function in bilayer stacking and lipid transport. P2 binds to phospholipid membranes through its positively charged surface and a hydrophobic tip, and accommodates fatty acids inside its barrel structure. The structure of human P2 refined at the ultrahigh resolution of 0.93 Å allows detailed structural analyses, including the full organization of an internal hydrogen-bonding network. The orientation of the bound fatty-acid carboxyl group is linked to the protonation states of two coordinating arginine residues. An anion-binding site in the portal region is suggested to be relevant for membrane interactions and conformational changes. When bound to membrane multilayers, P2 has a preferred orientation and is stabilized, and the repeat distance indicates a single layer of P2 between membranes. Simulations show the formation of a double bilayer in the presence of P2, and in cultured cells wild-type P2 induces membrane-domain formation. Here, the most accurate structural and functional view to date on P2, a major component of peripheral nerve myelin, is presented, showing how it can interact with two membranes simultaneously while going through conformational changes at its portal region enabling ligand transfer.

  15. White Matter Fiber-based Analysis of T1w/T2w Ratio Map.

    Science.gov (United States)

    Chen, Haiwei; Budin, Francois; Noel, Jean; Prieto, Juan Carlos; Gilmore, John; Rasmussen, Jerod; Wadhwa, Pathik D; Entringer, Sonja; Buss, Claudia; Styner, Martin

    2017-02-01

    To develop, test, evaluate and apply a novel tool for the white matter fiber-based analysis of T1w/T2w ratio maps quantifying myelin content. The cerebral white matter in the human brain develops from a mostly non-myelinated state to a nearly fully mature white matter myelination within the first few years of life. High resolution T1w/T2w ratio maps are believed to be effective in quantitatively estimating myelin content on a voxel-wise basis. We propose the use of a fiber-tract-based analysis of such T1w/T2w ratio data, as it allows us to separate fiber bundles that a common regional analysis imprecisely groups together, and to associate effects to specific tracts rather than large, broad regions. We developed an intuitive, open source tool to facilitate such fiber-based studies of T1w/T2w ratio maps. Via its Graphical User Interface (GUI) the tool is accessible to non-technical users. The framework uses calibrated T1w/T2w ratio maps and a prior fiber atlas as an input to generate profiles of T1w/T2w values. The resulting fiber profiles are used in a statistical analysis that performs along-tract functional statistical analysis. We applied this approach to a preliminary study of early brain development in neonates. We developed an open-source tool for the fiber based analysis of T1w/T2w ratio maps and tested it in a study of brain development.

  16. White matter fiber-based analysis of T1w/T2w ratio map

    Science.gov (United States)

    Chen, Haiwei; Budin, Francois; Noel, Jean; Prieto, Juan Carlos; Gilmore, John; Rasmussen, Jerod; Wadhwa, Pathik D.; Entringer, Sonja; Buss, Claudia; Styner, Martin

    2017-02-01

    Purpose: To develop, test, evaluate and apply a novel tool for the white matter fiber-based analysis of T1w/T2w ratio maps quantifying myelin content. Background: The cerebral white matter in the human brain develops from a mostly non-myelinated state to a nearly fully mature white matter myelination within the first few years of life. High resolution T1w/T2w ratio maps are believed to be effective in quantitatively estimating myelin content on a voxel-wise basis. We propose the use of a fiber-tract-based analysis of such T1w/T2w ratio data, as it allows us to separate fiber bundles that a common regional analysis imprecisely groups together, and to associate effects to specific tracts rather than large, broad regions. Methods: We developed an intuitive, open source tool to facilitate such fiber-based studies of T1w/T2w ratio maps. Via its Graphical User Interface (GUI) the tool is accessible to non-technical users. The framework uses calibrated T1w/T2w ratio maps and a prior fiber atlas as an input to generate profiles of T1w/T2w values. The resulting fiber profiles are used in a statistical analysis that performs along-tract functional statistical analysis. We applied this approach to a preliminary study of early brain development in neonates. Results: We developed an open-source tool for the fiber based analysis of T1w/T2w ratio maps and tested it in a study of brain development.

  17. Quantifying Demyelination in NK venom treated nerve using its electric circuit model.

    Science.gov (United States)

    Das, H K; Das, D; Doley, R; Sahu, P P

    2016-03-02

    Reduction of myelin in peripheral nerve causes critical demyelinating diseases such as chronic inflammatory demyelinating polyneuropathy, Guillain-Barre syndrome, etc. Clinical monitoring of these diseases requires rapid and non-invasive quantification of demyelination. Here we have developed formulation of nerve conduction velocity (NCV) in terms of demyelination considering electric circuit model of a nerve having bundle of axons for its quantification from NCV measurements. This approach has been validated and demonstrated with toad nerve model treated with crude Naja kaouthia (NK) venom and also shows the effect of Phospholipase A2 and three finger neurotoxin from NK-venom on peripheral nerve. This opens future scope for non-invasive clinical measurement of demyelination.

  18. Quantifying Demyelination in NK venom treated nerve using its electric circuit model

    Science.gov (United States)

    Das, H. K.; Das, D.; Doley, R.; Sahu, P. P.

    2016-03-01

    Reduction of myelin in peripheral nerve causes critical demyelinating diseases such as chronic inflammatory demyelinating polyneuropathy, Guillain-Barre syndrome, etc. Clinical monitoring of these diseases requires rapid and non-invasive quantification of demyelination. Here we have developed formulation of nerve conduction velocity (NCV) in terms of demyelination considering electric circuit model of a nerve having bundle of axons for its quantification from NCV measurements. This approach has been validated and demonstrated with toad nerve model treated with crude Naja kaouthia (NK) venom and also shows the effect of Phospholipase A2 and three finger neurotoxin from NK-venom on peripheral nerve. This opens future scope for non-invasive clinical measurement of demyelination.

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

    Directory of Open Access Journals (Sweden)

    Fatemeh Mottaghitalab

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

  20. The nerve endings of the acetabular labrum.

    Science.gov (United States)

    Kim, Y T; Azuma, H

    1995-11-01

    The nerve endings of the human acetabular labrum were investigated. Twenty-three acetabular labra were obtained from 24 fresh human cadavers, stained with Suzuki's silver impregnation and an immunohistochemical technique for neurogenic specific protein S-100, and examined by light and electron microscopy. Ramified free nerve endings were seen in all specimens by silver staining, and also were observed by the immunohistochemical technique for S-100 protein. Sensory nerve end organs, such as a Vater-Pacini corpuscle, Golgi-Mazzoni corpuscle, Ruffini corpuscle, and articular corpuscle (Krause corpuscle), were observed by silver staining. Collagen fibers were scattered sparsely in the superficial layer of the labrum, and nerve endings were observed mostly in this region. Collagen fibers were sparse, and nerve endings also were observed in some regions among the collagen fiber bundles in the inner layer. Innervation of the acetabular labrum was confirmed in this study, suggesting that nerve endings in the labrum may be involved in nociceptive and proprioceptive mechanisms.

  1. Acute sciatic nerve crush injuries in rabbits: MRI and pathological comparative study

    International Nuclear Information System (INIS)

    Li Xinchun; Chen Jianyu; Wang Xinlu; Shen Jun; Liu Qingyu; Liang Biling

    2004-01-01

    Objective: Simulating injury mechanism in human peripheral nerve, acute sciatic nerve crush injuries model was produced in rabbits to investigate the relationship between the manifestations of MRI and pathology in order to provide the information for clinical therapy and operative plan. Methods: Thirty-two adult rabbits were randomly divided into two groups: group A (n=16) and B (n=16). In group A, the left sciatic nerves were crushed with a stress of 3.61 kg; In group B, with a stress of 10.50 kg. 4 time intervals in each group were observed in 1, 2, 4, and 8 weeks, respectively, and each time interval contained 4 rabbits. Left sciatic nerves were served as injured sides, right sciatic nerves were regarded as control sides. MRI was performed at different time interval after crush injury. Then the nerves were examined pathologically. Results: There were no obvious changes on T 1 WI in injured sides, but the injured distal segment of sciatic nerve thickened and twisted, showing high signal intensity on 3D T 2 WI, T 2 WI/SPIR, B-FFE, and T 2 WI/STIR. MRI could show abnormality of 30 sciatic nerves, the correct diagnostic rate was 93.75% and false negative rate was 6.25%. The distal sciatic nerve/muscle signal intensity ratio (SIR) of the injured sides was significantly higher than that of the control sides (P 0.05). SIR in injured side increased at 1 week, reached the peak at 2 weeks, at this time, nerve axons disappeared and lots of myelin degenerated, abduction function disappeared. SIR decreased during 4-8 weeks, the myelin sheath breakdown and Schwann cell proliferated obviously, and abduction functions were observed. The control sciatic nerves showed no abnormality in MRI and pathology. Conclusion: MRI can make the diagnosis of crush injury of sciatic nerve, and dynamic SIR measurement of nerve injury correlates well with the pathological and functional recovery process. MRI is an effective method to monitor degeneration, regeneration, and prognosis after

  2. The Role of Neurotrophic Factors Conjugated to Iron Oxide Nanoparticles in Peripheral Nerve Regeneration: In Vitro Studies

    Directory of Open Access Journals (Sweden)

    Ofra Ziv-Polat

    2014-01-01

    Full Text Available Local delivery of neurotrophic factors is a pillar of neural repair strategies in the peripheral nervous system. The main disadvantage of the free growth factors is their short half-life of few minutes. In order to prolong their activity, we have conjugated to iron oxide nanoparticles three neurotrophic factors: nerve growth factor (βNGF, glial cell-derived neurotrophic factor (GDNF, and basic fibroblast growth factor (FGF-2. Comparative stability studies of free versus conjugated factors revealed that the conjugated neurotrophic factors were significantly more stable in tissue cultures and in medium at 37°C. The biological effects of free versus conjugated neurotrophic factors were examined on organotypic dorsal root ganglion (DRG cultures performed in NVR-Gel, composed mainly of hyaluronic acid and laminin. Results revealed that the conjugated neurotrophic factors enhanced early nerve fiber sprouting compared to the corresponding free factors. The most meaningful result was that conjugated-GDNF, accelerated the onset and progression of myelin significantly earlier than the free GDNF and the other free and conjugated factors. This is probably due to the beneficial and long-acting effect that the stabilized conjugated-GDNF had on neurons and Schwann cells. These conclusive results make NVR-Gel enriched with conjugated-GDNF, a desirable scaffold for the reconstruction of severed peripheral nerve.

  3. Curcumin upregulates S100 expression and improves regeneration of the sciatic nerve following its complete amputation in mice

    Directory of Open Access Journals (Sweden)

    Guo-min Liu

    2016-01-01

    Full Text Available The repair of peripheral nerve injury after complete amputation is difficult, and even with anastomosis, the rapid recovery of nerve function remains challenging. Curcumin, extracted from plants of the genus Curcuma, has been shown to have anti-oxidant and anti-inflammatory properties and to improve sciatic nerve crush injury in rats. Here, we determined whether curcumin had neuroprotective effects following complete peripheral nerve amputation injury. BALB/c mice underwent complete sciatic nerve amputation, followed by an immediate epineurium anastomosis. Mice were intragastrically administered curcumin at doses of 40 (high, 20 (moderate, and 10 mg/kg/d (low for 1 week. We found that myelin in the mice of the high- and moderate-dose curcumin groups appeared with regular shape, uniform thickness, clear boundary, and little hyperplasia surrounding the myelin. High and moderate doses of curcumin markedly improved both action potential amplitude of the sciatic nerves and the conduction velocity of the corresponding motor neurons, and upregulated mRNA and protein expression of S100, a marker for Schwann cell proliferation, in L4–6 spinal cord segments. These results suggest that curcumin is effective in promoting the repair of complete sciatic nerve amputation injury and that the underlying mechanism may be associated with upregulation of S100 expression.

  4. Persistent alterations in active and passive electrical membrane properties of regenerated nerve fibers of man and mice

    DEFF Research Database (Denmark)

    Moldovan, Mihai; Alvarez Herrero, Susana; Rosberg, Mette R.

    2016-01-01

    Excitability of regenerated fibers remains impaired due to changes in both passive cable properties and alterations in the voltage-dependent membrane function. These abnormalities were studied by mathematical modeling in human regenerated nerves and experimental studies in mice. In three adult male...... activity protocol triggered partial Wallerian degeneration in regenerated nerves but not in control nerves from age-matched mice. The current data suggest that the nodal voltage-gated ion channel machinery is restored in regenerated axons, although the electrical separation from the internodal compartment...... remains compromised. Due to the persistent increase in number of nodes, the increased activity-dependent Na+ influx could lead to hyperactivity of the Na+/K+ pump resulting in membrane hyperpolarization and neurotoxic energy insufficiency during strenuous activity....

  5. Astrocytes promote myelination in response to electrical impulses.

    Science.gov (United States)

    Ishibashi, Tomoko; Dakin, Kelly A; Stevens, Beth; Lee, Philip R; Kozlov, Serguei V; Stewart, Colin L; Fields, R Douglas

    2006-03-16

    Myelin, the insulating layers of membrane wrapped around axons by oligodendrocytes, is essential for normal impulse conduction. It forms during late stages of fetal development but continues into early adult life. Myelination correlates with cognitive development and can be regulated by impulse activity through unknown molecular mechanisms. Astrocytes do not form myelin, but these nonneuronal cells can promote myelination in ways that are not understood. Here, we identify a link between myelination, astrocytes, and electrical impulse activity in axons that is mediated by the cytokine leukemia inhibitory factor (LIF). These findings show that LIF is released by astrocytes in response to ATP liberated from axons firing action potentials, and LIF promotes myelination by mature oligodendrocytes. This activity-dependent mechanism promoting myelination could regulate myelination according to functional activity or environmental experience and may offer new approaches to treating demyelinating diseases.

  6. Imaging of the facial nerve

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    Veillon, F. [Service de Radiologie I, Hopital de Hautepierre, 67098 Strasbourg Cedex (France)], E-mail: Francis.Veillon@chru-strasbourg.fr; Ramos-Taboada, L.; Abu-Eid, M. [Service de Radiologie I, Hopital de Hautepierre, 67098 Strasbourg Cedex (France); Charpiot, A. [Service d' ORL, Hopital de Hautepierre, 67098 Strasbourg Cedex (France); Riehm, S. [Service de Radiologie I, Hopital de Hautepierre, 67098 Strasbourg Cedex (France)

    2010-05-15

    The facial nerve is responsible for the motor innervation of the face. It has a visceral motor function (lacrimal, submandibular, sublingual glands and secretion of the nose); it conveys a great part of the taste fibers, participates to the general sensory of the auricle (skin of the concha) and the wall of the external auditory meatus. The facial mimic, production of tears, nasal flow and salivation all depend on the facial nerve. In order to image the facial nerve it is mandatory to be knowledgeable about its normal anatomy including the course of its efferent and afferent fibers and about relevant technical considerations regarding CT and MR to be able to achieve high-resolution images of the nerve.

  7. Interaction between the C-terminal region of human myelin basic protein and calmodulin: analysis of complex formation and solution structure

    Directory of Open Access Journals (Sweden)

    Hayashi Nobuhiro

    2008-02-01

    Full Text Available Abstract Background The myelin sheath is a multilamellar membrane structure wrapped around the axon, enabling the saltatory conduction of nerve impulses in vertebrates. Myelin basic protein, one of the most abundant myelin-specific proteins, is an intrinsically disordered protein that has been shown to bind calmodulin. In this study, we focus on a 19-mer synthetic peptide from the predicted calmodulin-binding segment near the C-terminus of human myelin basic protein. Results The interaction of native human myelin basic protein with calmodulin was confirmed by affinity chromatography. The binding of the myelin basic protein peptide to calmodulin was tested with isothermal titration calorimetry (ITC in different temperatures, and Kd was observed to be in the low μM range, as previously observed for full-length myelin basic protein. Surface plasmon resonance showed that the peptide bound to calmodulin, and binding was accompanied by a conformational change; furthermore, gel filtration chromatography indicated a decrease in the hydrodynamic radius of calmodulin in the presence of the peptide. NMR spectroscopy was used to map the binding area to reside mainly within the hydrophobic pocket of the C-terminal lobe of calmodulin. The solution structure obtained by small-angle X-ray scattering indicates binding of the myelin basic protein peptide into the interlobal groove of calmodulin, while calmodulin remains in an extended conformation. Conclusion Taken together, our results give a detailed structural insight into the interaction of calmodulin with a C-terminal segment of a major myelin protein, the myelin basic protein. The used 19-mer peptide interacts mainly with the C-terminal lobe of calmodulin, and a conformational change accompanies binding, suggesting a novel mode of calmodulin-target protein interaction. Calmodulin does not collapse and wrap around the peptide tightly; instead, it remains in an extended conformation in the solution structure

  8. 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.

  9. Age-Dependent Schwann Cell Phenotype Regulation Following Peripheral Nerve Injury.

    Science.gov (United States)

    Chen, Wayne A; Luo, T David; Barnwell, Jonathan C; Smith, Thomas L; Li, Zhongyu

    2017-12-01

    Schwann cells are integral to the regenerative capacity of the peripheral nervous system, which declines after adolescence. The mechanisms underlying this decline are poorly understood. This study sought to compare the protein expression of Notch, c-Jun, and Krox-20 after nerve crush injury in adolescent and young adult rats. We hypothesized that these Schwann cell myelinating regulatory factors are down-regulated after nerve injury in an age-dependent fashion. Adolescent (2 months old) and young adult (12 months old) rats (n = 48) underwent sciatic nerve crush injury. Protein expression of Notch, c-Jun, and Krox-20 was quantified by Western blot analysis at 1, 3, and 7 days post-injury. Functional recovery was assessed in a separate group of animals (n = 8) by gait analysis (sciatic functional index) and electromyography (compound motor action potential) over an 8-week post-injury period. Young adult rats demonstrated a trend of delayed onset of the dedifferentiating regulatory factors, Notch and c-Jun, corresponding to the delayed functional recovery observed in young adult rats compared to adolescent rats. Compound motor action potential area was significantly greater in adolescent rats relative to young adult rats, while amplitude and velocity trended toward statistical significance. The process of Schwann cell dedifferentiation following peripheral nerve injury shows different trends with age. These trends of delayed onset of key regulatory factors responsible for Schwann cell myelination may be one of many possible factors mediating the significant differences in functional recovery between adolescent and young adult rats following peripheral nerve injury.

  10. Assessment of nerve ultrastructure by fibre-optic confocal microscopy.

    Science.gov (United States)

    Cushway, T R; Lanzetta, M; Cox, G; Trickett, R; Owen, E R

    1996-01-01

    Fibre-optic technology combined with confocality produces a microscope capable of optical thin sectioning. In this original study, tibial nerves have been stained in a rat model with a vital dye, 4-(4-diethylaminostyryl)-N-methylpyridinium iodide, and analysed by fibre-optic confocal microscopy to produce detailed images of nerve ultrastructure. Schwann cells, nodes of Ranvier and longitudinal myelinated sheaths enclosing axons were clearly visible. Single axons appeared as brightly staining longitudinal structures. This allowed easy tracing of multiple signal axons within the nerve tissue. An accurate measurement of internodal lengths was easily accomplished. This technique is comparable to current histological techniques, but does not require biopsy, thin sectioning or tissue fixing. This study offers a standard for further in vivo microscopy, including the possibility of monitoring the progression of nerve regeneration following microsurgical neurorraphy.

  11. Acellular Nerve Allografts in Peripheral Nerve Regeneration: A Comparative Study

    Science.gov (United States)

    Moore, Amy M.; MacEwan, Matthew; Santosa, Katherine B.; Chenard, Kristofer E.; Ray, Wilson Z.; Hunter, Daniel A.; Mackinnon, Susan E.; Johnson, Philip J.

    2011-01-01

    Background Processed nerve allografts offer a promising alternative to nerve autografts in the surgical management of peripheral nerve injuries where short deficits exist. Methods Three established models of acellular nerve allograft (cold-preserved, detergent-processed, and AxoGen® -processed nerve allografts) were compared to nerve isografts and silicone nerve guidance conduits in a 14 mm rat sciatic nerve defect. Results All acellular nerve grafts were superior to silicone nerve conduits in support of nerve regeneration. Detergent-processed allografts were similar to isografts at 6 weeks post-operatively, while AxoGen®-processed and cold-preserved allografts supported significantly fewer regenerating nerve fibers. Measurement of muscle force confirmed that detergent-processed allografts promoted isograft-equivalent levels of motor recovery 16 weeks post-operatively. All acellular allografts promoted greater amounts of motor recovery compared to silicone conduits. Conclusions These findings provide evidence that differential processing for removal of cellular constituents in preparing acellular nerve allografts affects recovery in vivo. PMID:21660979

  12. Neurotization of the phrenic nerve with accessory nerve for high cervical spinal cord injury with respiratory distress: an anatomic study.

    Science.gov (United States)

    Wang, Ce; Zhang, Ying; Nicholas, Tsai; Wu, Guoxin; Shi, Sheng; Bo, Yin; Wang, Xinwei; Zhou, Xuhui; Yuan, Wen

    2014-01-01

    High cervical spinal cord injury is associated with high morbidity and mortality. Traditional treatments carry various complications such as infection, pacemaker failure and undesirable movement. Thus, a secure surgical strategy with fewer complications analogous to physiological ventilation is still required. We hope to offer one potential method to decrease the complications and improve survival qualities of patients from the aspect of anatomy. The purpose of the study is to provide anatomic details on the accessory nerve and phrenic nerve for neurotization in patients with high spinal cord injuries. 38 cadavers (76 accessory and 76 phrenic nerves) were dissected in the study. The width, length and thickness of each accessory nerve and phrenic nerve above clavicle were measured. The distances from several landmarks on accessory nerve to the origin and the end of the phrenic nerve above clavicle were measured too. Then, the number of motor nerve fibers on different sections of the nerves was calculated using the technique of immunohistochemistry. The accessory nerves distal to its sternocleidomastoid muscular branches were 1.52 ± 0.32 mm ~1.54 ± 0.29 mm in width, 0.52 ± 0.18 mm ~ 0.56 ± 0.20mm in thickness and 9.52 ± 0.98 cm in length. And the phrenic nerves above clavicle were 1.44 ± 0.23 mm ~ 1.45 ± 0.24 mm in width, 0.47 ± 0.15 mm ~ 0.56 ± 0.25 mm in thickness and 6.48 ± 0.78 cm in length. The distance between the starting point of accessory nerve and phrenic nerve were 3.24 ± 1.17 cm, and the distance between the starting point of accessory nerve and the end of the phrenic nerve above clavicle were 8.72 ± 0.84 cm. The numbers of motor nerve fibers in accessory nerve were 1,038 ± 320~1,102 ± 216, before giving out the sternocleidomastoid muscular branches. The number of motor nerve fibers in the phrenic nerve was 911 ± 321~1,338 ± 467. The accessory nerve and the phrenic were similar in width, thickness and the number of motor nerve fibers. And

  13. 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 reflex bladder contractions to 8.5 ± 1.9 cmH2O. Injection of lidocaine (2%, 1-2 ml) into the sacral spinal cord or transection of the sacral spinal roots and spinal cord further reduced the contraction amplitude to 4.2 ± 1.3 cmH2O. Pudendal nerve stimulation (PNS) at frequencies of 0.5-5 Hz and 40 Hz but not at 10-20 Hz inhibited reflex bladder contractions, whereas tibial nerve stimulation (TNS) failed to inhibit bladder contractions at all tested frequencies (0.5-40 Hz). These results indicate that PNS inhibition of nociceptive afferent C-fiber-mediated spinal reflex bladder contractions can occur at the spinal level in the absence of supraspinal pathways, but TNS inhibition requires supraspinal pathways. In addition, this study shows, for the first time, that after acute spinal cord transection reflex bladder contractions can be triggered by activating nociceptive bladder afferent C-fibers using acetic acid 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.

  14. Electrophysiological Assessment of a Peptide Amphiphile Nanofiber Nerve Graft for Facial Nerve Repair.

    Science.gov (United States)

    Greene, Jacqueline J; McClendon, Mark T; Stephanopoulos, Nicholas; Álvarez, Zaida; Stupp, Samuel I; Richter, Claus-Peter

    2018-04-27

    Facial nerve injury can cause severe long-term physical and psychological morbidity. There are limited repair options for an acutely transected facial nerve not amenable to primary neurorrhaphy. We hypothesize that a peptide amphiphile nanofiber neurograft may provide the nanostructure necessary to guide organized neural regeneration. Five experimental groups were compared, animals with 1) an intact nerve, 2) following resection of a nerve segment, and following resection and immediate repair with either a 3) autograft (using the resected nerve segment), 4) neurograft, or 5) empty conduit. The buccal branch of the rat facial nerve was directly stimulated with charge balanced biphasic electrical current pulses at different current amplitudes while nerve compound action potentials (nCAPs) and electromygraphic (EMG) responses were recorded. After 8 weeks, the proximal buccal branch was surgically re-exposed and electrically evoked nCAPs were recorded for groups 1-5. As expected, the intact nerves required significantly lower current amplitudes to evoke an nCAP than those repaired with the neurograft and autograft nerves. For other electrophysiologic parameters such as latency and maximum nCAP, there was no significant difference between the intact, autograft and neurograft groups. The resected group had variable responses to electrical stimulation, and the empty tube group was electrically silent. Immunohistochemical analysis and TEM confirmed myelinated neural regeneration. This study demonstrates that the neuroregenerative capability of peptide amphiphile nanofiber neurografts is similar to the current clinical gold standard method of repair and holds potential as an off-the-shelf solution for facial reanimation and potentially peripheral nerve repair. This article is protected by copyright. All rights reserved.

  15. Chronic cuffing of cervical vagus nerve inhibits efferent fiber integrity in rat model

    Science.gov (United States)

    Somann, Jesse P.; Albors, Gabriel O.; Neihouser, Kaitlyn V.; Lu, Kun-Han; Liu, Zhongming; Ward, Matthew P.; Durkes, Abigail; Robinson, J. Paul; Powley, Terry L.; Irazoqui, Pedro P.

    2018-06-01

    Objective. Numerous studies of vagal nerve stimulation (VNS) have been published showing it to be a potential treatment for chronic inflammation and other related diseases and disorders. Studies in recent years have shown that electrical stimulation of the vagal efferent fibers can artificially modulate cytokine levels and reduce systematic inflammation. Most VNS research in the treatment of inflammation have been acute studies on rodent subjects. Our study tested VNS on freely moving animals by stimulating and recording from the cervical vagus with nerve cuff electrodes over an extended period of time. Approach. We used methods of electrical stimulation, retrograde tracing (using Fluorogold) and post necropsy histological analysis of nerve tissue, flow cytometry to measure plasma cytokine levels, and MRI scanning of gastric emptying. This novel combination of methods allowed examination of physiological aspects of VNS previously unexplored. Main results. Through our study of 53 rat subjects, we found that chronically cuffing the left cervical vagus nerve suppressed efferent Fluorogold transport in 43 of 44 animals (36 showed complete suppression). Measured cytokine levels and gastric emptying rates concurrently showed nominal differences between chronically cuffed rats and those tested with similar acute methods. Meanwhile, results of electrophysiological and histological tests of the cuffed nerves revealed them to be otherwise healthy, consistent with previous literature. Significance. We hypothesize that due to these unforeseen and unexplored physiological consequences of the chronically cuffed vagus nerve in a rat, that inflammatory modulation and other vagal effects by VNS may become unreliable in chronic studies. Given our findings, we submit that it would benefit the VNS community to re-examine methods used in previous literature to verify the efficacy of the rat model for chronic VNS studies.

  16. Degeneration and regeneration of motor and sensory nerves: a stereological study of crush lesions in rat facial and mental nerves.

    Science.gov (United States)

    Barghash, Z; Larsen, J O; Al-Bishri, A; Kahnberg, K-E

    2013-12-01

    The aim of this study was to evaluate the degeneration and regeneration of a sensory nerve and a motor nerve at the histological level after a crush injury. Twenty-five female Wistar rats had their mental nerve and the buccal branch of their facial nerve compressed unilaterally against a glass rod for 30s. Specimens of the compressed nerves and the corresponding control nerves were dissected at 3, 7, and 19 days after surgery. Nerve cross-sections were stained with osmium tetroxide and toluidine blue and analysed using two-dimensional stereology. We found differences between the two nerves both in the normal anatomy and in the regenerative pattern. The mental nerve had a larger cross-sectional area including all tissue components. The mental nerve had a larger volume fraction of myelinated axons and a correspondingly smaller volume fraction of endoneurium. No differences were observed in the degenerative pattern; however, at day 19 the buccal branch had regenerated to the normal number of axons, whereas the mental nerve had only regained 50% of the normal number of axons. We conclude that the regenerative process is faster and/or more complete in the facial nerve (motor function) than it is in the mental nerve (somatosensory function). Copyright © 2013 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  17. 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.

  18. An Exceptional Case of Intraparotid Plexiform Neurofibroma Originating from Autonomic Fibers of the Auriculotemporal Nerve

    Directory of Open Access Journals (Sweden)

    Sarantis Blioskas

    2017-01-01

    Full Text Available Plexiform neurofibromas are benign tumors that tend to occur in patients suffering from neurofibromatosis type 1 (NF-1. This report addresses a rare case where the tumor affected the parotid gland, deriving almost exclusively from the peripheral portion of the facial nerve. A 6-year-old male was referred to us complaining about a gradually enlarging swelling over the right parotid area. Imaging localized the lesion to the superficial lobe of the parotid gland, suggesting a neurofibroma. Cosmetic disfigurement and a functional deficit led us to perform complete surgical resection. Meticulous surgical dissection as well as auriculotemporal nerve origin made complete extirpation possible with almost zero morbidity and ensured alleviation of both aesthetic impairment and pain. This is the first case of an intraparotid PN in a pediatric NF-1 patient, which originated from branches of the auriculotemporal nerve and particularly from fibers of the autonomic nervous system. Radical surgical excision was decided according to established decision-making algorithms.

  19. 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

  20. Retinal Nerve Fiber Layer Segmentation on FD-OCT Scans of Normal Subjects and Glaucoma Patients.

    Science.gov (United States)

    Mayer, Markus A; Hornegger, Joachim; Mardin, Christian Y; Tornow, Ralf P

    2010-11-08

    Automated measurements of the retinal nerve fiber layer thickness on circular OCT B-Scans provide physicians additional parameters for glaucoma diagnosis. We propose a novel retinal nerve fiber layer segmentation algorithm for frequency domain data that can be applied on scans from both normal healthy subjects, as well as glaucoma patients, using the same set of parameters. In addition, the algorithm remains almost unaffected by image quality. The main part of the segmentation process is based on the minimization of an energy function consisting of gradient and local smoothing terms. A quantitative evaluation comparing the automated segmentation results to manually corrected segmentations from three reviewers is performed. A total of 72 scans from glaucoma patients and 132 scans from normal subjects, all from different persons, composed the database for the evaluation of the segmentation algorithm. A mean absolute error per A-Scan of 2.9 µm was achieved on glaucomatous eyes, and 3.6 µm on healthy eyes. The mean absolute segmentation error over all A-Scans lies below 10 µm on 95.1% of the images. Thus our approach provides a reliable tool for extracting diagnostic relevant parameters from OCT B-Scans for glaucoma diagnosis.

  1. Sodium Channel Nav1.8 Underlies TTX-Resistant Axonal Action Potential Conduction in Somatosensory C-Fibers of Distal Cutaneous Nerves.

    Science.gov (United States)

    Klein, Amanda H; Vyshnevska, Alina; Hartke, Timothy V; De Col, Roberto; Mankowski, Joseph L; Turnquist, Brian; Bosmans, Frank; Reeh, Peter W; Schmelz, Martin; Carr, Richard W; Ringkamp, Matthias

    2017-05-17

    Voltage-gated sodium (Na V ) channels are responsible for the initiation and conduction of action potentials within primary afferents. The nine Na V channel isoforms recognized in mammals are often functionally divided into tetrodotoxin (TTX)-sensitive (TTX-s) channels (Na V 1.1-Na V 1.4, Na V 1.6-Na V 1.7) that are blocked by nanomolar concentrations and TTX-resistant (TTX-r) channels (Na V 1.8 and Na V 1.9) inhibited by millimolar concentrations, with Na V 1.5 having an intermediate toxin sensitivity. For small-diameter primary afferent neurons, it is unclear to what extent different Na V channel isoforms are distributed along the peripheral and central branches of their bifurcated axons. To determine the relative contribution of TTX-s and TTX-r channels to action potential conduction in different axonal compartments, we investigated the effects of TTX on C-fiber-mediated compound action potentials (C-CAPs) of proximal and distal peripheral nerve segments and dorsal roots from mice and pigtail monkeys ( Macaca nemestrina ). In the dorsal roots and proximal peripheral nerves of mice and nonhuman primates, TTX reduced the C-CAP amplitude to 16% of the baseline. In contrast, >30% of the C-CAP was resistant to TTX in distal peripheral branches of monkeys and WT and Na V 1.9 -/- mice. In nerves from Na V 1.8 -/- mice, TTX-r C-CAPs could not be detected. These data indicate that Na V 1.8 is the primary isoform underlying TTX-r conduction in distal axons of somatosensory C-fibers. Furthermore, there is a differential spatial distribution of Na V 1.8 within C-fiber axons, being functionally more prominent in the most distal axons and terminal regions. The enrichment of Na V 1.8 in distal axons may provide a useful target in the treatment of pain of peripheral origin. SIGNIFICANCE STATEMENT It is unclear whether individual sodium channel isoforms exert differential roles in action potential conduction along the axonal membrane of nociceptive, unmyelinated peripheral nerve

  2. Biology of Schwann cells.

    Science.gov (United States)

    Kidd, Grahame J; Ohno, Nobuhiko; Trapp, Bruce D

    2013-01-01

    The fundamental roles of Schwann cells during peripheral nerve formation and regeneration have been recognized for more than 100 years, but the cellular and molecular mechanisms that integrate Schwann cell and axonal functions continue to be elucidated. Derived from the embryonic neural crest, Schwann cells differentiate into myelinating cells or bundle multiple unmyelinated axons into Remak fibers. Axons dictate which differentiation path Schwann cells follow, and recent studies have established that axonal neuregulin1 signaling via ErbB2/B3 receptors on Schwann cells is essential for Schwann cell myelination. Extracellular matrix production and interactions mediated by specific integrin and dystroglycan complexes are also critical requisites for Schwann cell-axon interactions. Myelination entails expansion and specialization of the Schwann cell plasma membrane over millimeter distances. Many of the myelin-specific proteins have been identified, and transgenic manipulation of myelin genes have provided novel insights into myelin protein function, including maintenance of axonal integrity and survival. Cellular events that facilitate myelination, including microtubule-based protein and mRNA targeting, and actin based locomotion, have also begun to be understood. Arguably, the most remarkable facet of Schwann cell biology, however, is their vigorous response to axonal damage. Degradation of myelin, dedifferentiation, division, production of axonotrophic factors, and remyelination all underpin the substantial regenerative capacity of the Schwann cells and peripheral nerves. Many of these properties are not shared by CNS fibers, which are myelinated by oligodendrocytes. Dissecting the molecular mechanisms responsible for the complex biology of Schwann cells continues to have practical benefits in identifying novel therapeutic targets not only for Schwann cell-specific diseases but other disorders in which axons degenerate. Copyright © 2013 Elsevier B.V. All rights

  3. Nonenzymatic glycosylation of bovine myelin basic protein

    International Nuclear Information System (INIS)

    Hitz, J.B.

    1987-01-01

    In the CNS myelin sheath the nonenzymatic glycosylation reaction (at the early stage of the Amadori product) occurs only with the myelin basic protein and not with the other myelin proteins. This was observed in isolated bovine myelin by in vitro incubation with [ 14 C]-galactose and [ 14 C]-glucose. The respective in-vitro incorporation rates for purified bovine myelin basic protein with D-galactose, D-glucose and D-mannose were 7.2, 2.4 and 2.4 mmoles/mole myelin basic protein per day at 37 0 C. A more rapid, HPLC method was devised and characterized to specifically analyze for the Amadori product. The HPLC method was correlated to the [ 14 C]-sugar incorporation method for myelin basic protein under a set of standard reaction conditions using [ 14 C]-glucose and [ 14 C]-mannose with HPLC values at 1/6 and 1/5 of the [ 14 C]-sugar incorporation method. A novel myelin basic protein purification step has been developed that yields a relativity proteolytic free preparation that is easy to work with, being totally soluble at a neutral pH. Nine new spots appear for a trypsinized glycosylated MBP in the paper peptide map of which eight correspond to positions of the [ 3 H]-labeled Amadori product in affinity isolated peptides. These studies provide a general characterization of and a structural basis for investigations on nonenzymatically glycosylated MBP as well as identifying MBP as the only nonenzymatically glycosylated protein in the CNS myelin sheath which may accumulate during aging, diabetes, and demyelinating diseases in general

  4. An Evaluation of Peripapillary Retinal Nerve Fiber Layer Thickness in Children With Epilepsy Receiving Treatment of Valproic Acid.

    Science.gov (United States)

    Dereci, Selim; Koca, Tuğba; Akçam, Mustafa; Türkyilmaz, Kemal

    2015-07-01

    We investigated the peripapillary retinal nerve fiber layer thickness with optical coherence tomography in epileptic children receiving valproic acid monotherapy. The study was conducted on children aged 8-16 years who were undergoing valproic acid monotherapy for epilepsy. The study group comprised a total of 40 children who met the inclusion criteria and 40 healthy age- and sex-matched children as a control group. Children with at least a 1-year history of epilepsy and taking 10-40 mg/kg/day treatment were included in the study. Peripapillary retinal nerve fiber layer thickness measurements were performed using Cirrus HD optical coherence tomography. All children and parents were informed about the study and informed consent was obtained from the parents of all the participants. The study group included 21 girls and 19 boys with a mean age of 10.6 ± 2.3 years. According to the results of optical coherence tomography measurements, the mean peripapillary retinal nerve fiber layer thickness was 91.6 ± 9.7 in the patient group and 95.5 ± 7.4 μm in the control group (P epilepsy who were receiving valproic acid monotherapy compared with healthy children. This situation can lead to undesirable results in terms of eye health. New studies are needed to investigate whether these findings are the result of epilepsy or can be attributed to valproic acid and whether there are adverse effects of valproic acid later in life. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Effect of chronic administration of sildenafil citrate (Viagra) on the histology of the retina and optic nerve of adult male rat.

    Science.gov (United States)

    Eltony, Sohair A; Abdelhameed, Sally Y

    2017-04-01

    Abnormal vision has been reported by 3% of patients treated with sildenafil citrate (Viagra). Although many men use Viagra for an extended period for treatment of erectile dysfunction, the implications of the long term-daily use of it on the retina and optic nerve are unclear. To investigate the effect of chronic daily use of sildenafil citrate in a dose equivalent to men preferred therapeutic dose on the histology of the retina and optic nerve of adult male rat. Eighteen adult male Wistar rats were equally divided into three groups. Group I: control. Group II: treated with sildenafil citrate orally (10mg/kg/day) for 8 weeks. Group III (withdrawal): treated as group II and then left for 4 weeks without treatment. Specimens from the retina and optic nerve were processed for light and electron microscopy. In sildenafil citrate treated group, the retina and optic nerve revealed vacuolations and congested blood capillaries with apoptotic endothelial and pericytic cells, and thickened basal lamina. Caspase-3 (apoptotic marker) and CD31 (endothelial marker) expression increased. Glial cells revealed morphological changes: Müller cells lost their processes, activated microglia, astrocytic clasmatodendrosis, degenerated oligodendrocytes surrounded by disintegrated myelin sheathes of the optic nerve fibers. The retina and optic nerve of the withdrawal group revealed less vacuolations and congestion, and partial recovery of the glial cells. Chronic treatment with sildenafil citrate (Viagra) caused toxic effect on the structure of the retina and optic nerve of the rat. Partial recovery was observed after drug withdrawal. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Loss-of-Function Mutations in LGI4, a Secreted Ligand Involved in Schwann Cell Myelination, Are Responsible for Arthrogryposis Multiplex Congenita.

    Science.gov (United States)

    Xue, Shifeng; Maluenda, Jérôme; Marguet, Florent; Shboul, Mohammad; Quevarec, Loïc; Bonnard, Carine; Ng, Alvin Yu Jin; Tohari, Sumanty; Tan, Thong Teck; Kong, Mung Kei; Monaghan, Kristin G; Cho, Megan T; Siskind, Carly E; Sampson, Jacinda B; Rocha, Carolina Tesi; Alkazaleh, Fawaz; Gonzales, Marie; Rigonnot, Luc; Whalen, Sandra; Gut, Marta; Gut, Ivo; Bucourt, Martine; Venkatesh, Byrappa; Laquerrière, Annie; Reversade, Bruno; Melki, Judith

    2017-04-06

    Arthrogryposis multiplex congenita (AMC) is a developmental condition characterized by multiple joint contractures resulting from reduced or absent fetal movements. Through genetic mapping of disease loci and whole-exome sequencing in four unrelated multiplex families presenting with severe AMC, we identified biallelic loss-of-function mutations in LGI4 (leucine-rich glioma-inactivated 4). LGI4 is a ligand secreted by Schwann cells that regulates peripheral nerve myelination via its cognate receptor ADAM22 expressed by neurons. Immunolabeling experiments and transmission electron microscopy of the sciatic nerve from one of the affected individuals revealed a lack of myelin. Functional tests using affected individual-derived iPSCs showed that these germline mutations caused aberrant splicing of the endogenous LGI4 transcript and in a cell-based assay impaired the secretion of truncated LGI4 protein. This is consistent with previous studies reporting arthrogryposis in Lgi4-deficient mice due to peripheral hypomyelination. This study adds to the recent reports implicating defective axoglial function as a key cause of AMC. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  7. Optic nerve head and intraocular pressure in the guinea pig eye.

    Science.gov (United States)

    Ostrin, Lisa A; Wildsoet, Christine F

    2016-05-01

    The guinea pig is becoming an increasingly popular model for studying human myopia, which carries an increased risk of glaucoma. As a step towards understanding this association, this study sought to characterize the normal, developmental intraocular pressure (IOP) profiles, as well as the anatomy of the optic nerve head (ONH) and adjacent sclera of young guinea pigs. IOP was tracked in pigmented guinea pigs up to 3 months of age. One guinea pig was imaged in vivo with OCT and one with a fundus camera. The eyes of pigmented and albino guinea pigs (ages 2 months) were enucleated and sections from the posterior segment, including the ONH and surrounding sclera, processed for histological analyses - either hematoxylin and eosin (H&E) staining of paraffin embedded, sectioned tissue (n = 1), or cryostat sectioned tissue, processed for immunohistochemistry (n = 3), using primary antibodies against collagen types I-V, elastin, fibronectin and glial fibrillary acidic protein (GFAP). Transmission and scanning electron microscopy (TEM, SEM) studies of ONHs were also undertaken (n = 2 & 5 respectively). Mean IOPs ranged from 17.33 to 22.7 mmHg, increasing slightly across the age range studied, and the IOPs of individual animals also exhibited diurnal variations, peaking in the early morning (mean of 25.8, mmHg, ∼9 am), and decreasing across the day. H&E-stained sections showed retinal ganglion cell axons organized into fascicles in the prelaminar and laminar region of the ONHs, with immunostained sections revealing collagen types I, III, IV and V, as well as elastin, GFAP and fibronectin in the ONHs. SEM revealed a well-defined lamina cribrosa (LC), with radially-oriented collagen beams. TEM revealed collagen fibrils surrounding non-myelinated nerve fiber bundles in the LC region, with myelination and decreased collagen posterior to the LC. The adjacent sclera comprised mainly crimped collagen fibers in a crisscross arrangement. Both the sclera and LC were

  8. 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...

  9. Differential effects of myostatin deficiency on motor and sensory axons.

    Science.gov (United States)

    Jones, Maria R; Villalón, Eric; Northcutt, Adam J; Calcutt, Nigel A; Garcia, Michael L

    2017-12-01

    Deletion of myostatin in mice (MSTN -/- ) alters structural properties of peripheral axons. However, properties like axon diameter and myelin thickness were analyzed in mixed nerves, so it is unclear whether loss of myostatin affects motor, sensory, or both types of axons. Using the MSTN -/- mouse model, we analyzed the effects of increasing the number of muscle fibers on axon diameter, myelin thickness, and internode length in motor and sensory axons. Axon diameter and myelin thickness were increased in motor axons of MSTN -/- mice without affecting internode length or axon number. The number of sensory axons was increased without affecting their structural properties. These results suggest that motor and sensory axons establish structural properties by independent mechanisms. Moreover, in motor axons, instructive cues from the neuromuscular junction may play a role in co-regulating axon diameter and myelin thickness, whereas internode length is established independently. Muscle Nerve 56: E100-E107, 2017. © 2017 Wiley Periodicals, Inc.

  10. Axon-glia interaction and membrane traffic in myelin formation

    Directory of Open Access Journals (Sweden)

    Robin eWhite

    2014-01-01

    Full Text Available In vertebrate nervous systems myelination of neuronal axons has evolved to increase conduction velocity of electrical impulses with minimal space and energy requirements. Myelin is formed by specialised glial cells which ensheath axons with a lipid-rich insulating membrane. Myelination is a multi-step process initiated by axon-glia recognition triggering glial polarisation followed by targeted myelin membrane expansion and compaction. Thereby, a myelin sheath of complex subdomain structure is established. Continuous communication between neurons and glial cells is essential for myelin maintenance and axonal integrity. A diverse group of diseases, from multiple sclerosis to schizophrenia, have been linked to malfunction of myelinating cells reflecting the physiological importance of the axon-glial unit. This review describes the mechanisms of axonal signal integration by oligodendrocytes emphasising the central role of the Src-family kinase Fyn during CNS myelination. Furthermore, we discuss myelin membrane trafficking with particular focus on endocytic recycling and the control of PLP (proteolipid protein transport by SNARE proteins. Finally, PLP mistrafficking is considered in the context of myelin diseases.

  11. MRI assessment of myelination: an age standardization

    Energy Technology Data Exchange (ETDEWEB)

    Staudt, M. (Kinderklinik Dritter Orden, Passau (Germany)); Schropp, C. (Kinderklinik Dritter Orden, Passau (Germany)); Staudt, F. (Kinderklinik Dritter Orden, Passau (Germany)); Obletter, N. (Radiologische Praxis, Klinikum Ingolstadt (Germany)); Bise, K. (Neuropathologisches Inst., Muenchen Univ. (Germany)); Breit, A. (MR Tomographie, Klinikum Passau (Germany)); Weinmann, H.M. (Kinderklinik Schwabing, Muenchen (Germany))

    1994-04-01

    777 cerebral MRI examinations of children aged 3 days to 14 years were staged for myelination to establish an age standardization. Staging was performed using a system proposed in a previous paper, separately ranking 10 different regions of the brain. Interpretation of the results led to the identification of foue clinical diagnoses that are frequently associated with delays in myelination: West syndrome, cerebral palsy, developmental retardation, and congenital anomalies. In addition, it was found that assessment of myelination in children with head injuries was not practical as alterations in MRI signal can simulate earlier stages of myelination. Age limits were therefore calculated from the case material after excluding all children with these conditions. When simplifications of the definition of the stages are applied, these age limits for the various stages of myelination of each of the 10 regions of the brain make the staging system applicable for routine assessment of myelination. (orig.)

  12. Magnetic resonance imaging evaluation of acute crush injury of rabbit sciatic nerve: correlation with histology

    International Nuclear Information System (INIS)

    Li, X.; Shen, J.; Chen, J.; Wang, X.; Liu, Q.; Liang, B.

    2008-01-01

    To investigate the relation between the quantitative assessment of magnetic resonance imaging (MRI) features and the correlation with histology and functional recovery by using the rabbit sciatic nerve crush model. In New Zealand, 32 rabbits were randomly divided into 2 groups (group A and B); all rabbits underwent crushing injury of their left sciatic nerve. In group A (n = 16), the sciatic nerves were crushed by using microvessel clamps with a strength of 3.61 kg. In group B (n = 16), the sciatic nerves were crushed with a strength of 10.50 kg. Right sciatic nerves were served as controls. Serial MRI of both hind limbs in each rabbit was performed before and at the time point of 1, 2, 4, and 8 weeks after crushed injury. The MRI protocol included T1-weighted spin-echo (T1WI), 3 dimension turbo spin-echo T2-weighted (3DT2WI), T2-weighted turbo spin-echo images with spectral presaturation with inversion recovery (T2WI/SPIR), balanced fast-field echo (B-FFE) and short-time inversion recovery (STIR) sequences. The coronal image of the sciatic nerve was obtained. The nerve and muscle signal ratio (SIR) on each sequence was measured. The function recovery was observed and pathological examination was performed at each time point. A signal intensity increase of the distal segment of crushed sciatic nerves was found on 3DT2WI, T2WI/SP1R, B-FFE, and STIR, but not on T,WI images. Of 32 crushed nerves, 30 nerves showed high signal intensity. The correct diagnostic rate was 93.75% with false negative-positive of 6.25%. The SIR of the crushed sciatic nerve at distal portion was higher than those of the control nerves; there was a statistically significant difference (P 0.05). The SIR between group A and group B was not found statistically significantly different (P > 0.05). The SIR of crushed nerves at distal portion increased at one week after the crush injury, subsequently further increased, and reached a maximum at 2 weeks. The pathological examination revealed myelin

  13. Propofol promotes spinal cord injury repair by bone marrow mesenchymal stem cell transplantation

    OpenAIRE

    Zhou, Ya-jing; Liu, Jian-min; Wei, Shu-ming; Zhang, Yun-hao; Qu, Zhen-hua; Chen, Shu-bo

    2015-01-01

    Propofol is a neuroprotective anesthetic. Whether propofol can promote spinal cord injury repair by bone marrow mesenchymal stem cells remains poorly understood. We used rats to investigate spinal cord injury repair using bone marrow mesenchymal stem cell transplantation combined with propofol administration via the tail vein. Rat spinal cord injury was clearly alleviated; a large number of newborn non-myelinated and myelinated nerve fibers appeared in the spinal cord, the numbers of CM-Dil-l...

  14. Hyperglycemia Promotes Schwann Cell De-differentiation and De-myelination via Sorbitol Accumulation and Igf1 Protein Down-regulation*

    Science.gov (United States)

    Hao, Wu; Tashiro, Syoichi; Hasegawa, Tomoka; Sato, Yuiko; Kobayashi, Tami; Tando, Toshimi; Katsuyama, Eri; Fujie, Atsuhiro; Watanabe, Ryuichi; Morita, Mayu; Miyamoto, Kana; Morioka, Hideo; Nakamura, Masaya; Matsumoto, Morio; Amizuka, Norio; Toyama, Yoshiaki; Miyamoto, Takeshi

    2015-01-01

    Diabetes mellitus (DM) is frequently accompanied by complications, such as peripheral nerve neuropathy. Schwann cells play a pivotal role in regulating peripheral nerve function and conduction velocity; however, changes in Schwann cell differentiation status in DM are not fully understood. Here, we report that Schwann cells de-differentiate into immature cells under hyperglycemic conditions as a result of sorbitol accumulation and decreased Igf1 expression in those cells. We found that de-differentiated Schwann cells could be re-differentiated in vitro into mature cells by treatment with an aldose reductase inhibitor, to reduce sorbitol levels, or with vitamin D3, to elevate Igf1 expression. In vivo DM models exhibited significantly reduced nerve function and conduction, Schwann cell de-differentiation, peripheral nerve de-myelination, and all conditions were significantly rescued by aldose reductase inhibitor or vitamin D3 administration. These findings reveal mechanisms underlying pathological changes in Schwann cells seen in DM and suggest ways to treat neurological conditions associated with this condition. PMID:25998127

  15. Sciatic nerve regeneration in rats by a promising electrospun collagen/poly(ε-caprolactone nerve conduit with tailored degradation rate

    Directory of Open Access Journals (Sweden)

    Jiang Xinquan

    2011-07-01

    Full Text Available Abstract Background To cope with the limitations faced by autograft acquisitions particularly for multiple nerve injuries, artificial nerve conduit has been introduced by researchers as a substitute for autologous nerve graft for the easy specification and availability for mass production. In order to best mimic the structures and components of autologous nerve, great efforts have been made to improve the designation of nerve conduits either from materials or fabrication techniques. Electrospinning is an easy and versatile technique that has recently been used to fabricate fibrous tissue-engineered scaffolds which have great similarity to the extracellular matrix on fiber structure. Results In this study we fabricated a collagen/poly(ε-caprolactone (collagen/PCL fibrous scaffold by electrospinning and explored its application as nerve guide substrate or conduit in vitro and in vivo. Material characterizations showed this electrospun composite material which was made of submicron fibers possessed good hydrophilicity and flexibility. In vitro study indicated electrospun collagen/PCL fibrous meshes promoted Schwann cell adhesion, elongation and proliferation. In vivo test showed electrospun collagen/PCL porous nerve conduits successfully supported nerve regeneration through an 8 mm sciatic nerve gap in adult rats, achieving similar electrophysiological and muscle reinnervation results as autografts. Although regenerated nerve fibers were still in a pre-mature stage 4 months postoperatively, the implanted collagen/PCL nerve conduits facilitated more axons regenerating through the conduit lumen and gradually degraded which well matched the nerve regeneration rate. Conclusions All the results demonstrated this collagen/PCL nerve conduit with tailored degradation rate fabricated by electrospinning could be an efficient alternative to autograft for peripheral nerve regeneration research. Due to its advantage of high surface area for cell attachment, it

  16. Altered brain morphometry in carpal tunnel syndrome is associated with median nerve pathology☆☆☆

    Science.gov (United States)

    Maeda, Yumi; Kettner, Norman; Sheehan, James; Kim, Jieun; Cina, Stephen; Malatesta, Cristina; Gerber, Jessica; McManus, Claire; Mezzacappa, Pia; Morse, Leslie R.; Audette, Joseph; Napadow, Vitaly

    2013-01-01

    Objective Carpal tunnel syndrome (CTS) is a common median nerve entrapment neuropathy characterized by pain, paresthesias, diminished peripheral nerve conduction velocity (NCV) and maladaptive functional brain neuroplasticity. We evaluated structural reorganization in brain gray matter (GM) and white matter (WM) and whether such plasticity is linked to altered median nerve function in CTS. Methods We performed NCV testing, T1-weighted structural MRI, and diffusion tensor imaging (DTI) in 28 CTS and 28 age-matched healthy controls (HC). Voxel-based morphometry (VBM) contrasted regional GM volume for CTS versus HC. Significant clusters were correlated with clinical metrics and served as seeds to define associated WM tracts using DTI data and probabilistic tractography. Within these WM tracts, fractional anisotropy (FA), axial (AD) and radial (RD) diffusivity were evaluated for group differences and correlations with clinical metrics. Results For CTS subjects, GM volume was significantly reduced in contralesional S1 (hand-area), pulvinar and frontal pole. GM volume in contralesional S1 correlated with median NCV. NCV was also correlated with RD and was negatively correlated with FA within U-fiber cortico-cortical association tracts identified from the contralesional S1 VBM seed. Conclusions Our study identified clear morphometric changes in the CTS brain. This central morphometric change is likely secondary to peripheral nerve pathology and altered somatosensory afference. Enhanced axonal coherence and myelination within cortico-cortical tracts connecting primary somatosensory and motor areas may accompany peripheral nerve deafferentation. As structural plasticity was correlated with NCV and not symptomatology, the former may be a better determinant of appropriate clinical intervention for CTS, including surgery. PMID:23799199

  17. 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

    and mimicked the S100A4-induced neuroprotection in brain trauma. Here, we investigated a possible function of S100A4 and its mimetics in the pathologies of the peripheral nervous system (PNS). We found that S100A4 was expressed in the injured PNS and that its peptide mimetic (H3) affected the regeneration......, these effects were attributed to the modulatory effect of H3 on initial axonal sprouting. In contrast to the modest effect of H3 on the time course of regeneration, H3 had a long-term neuroprotective effect in the myelin protein P0 null mice, a model of dysmyelinating neuropathy (Charcot-Marie-Tooth type 1...... disease), where the peptide attenuated the deterioration of nerve conduction, demyelination and axonal loss. From these results, S100A4 mimetics emerge as a possible means to enhance axonal sprouting and survival, especially in the context of demyelinating neuropathies with secondary axonal loss...

  18. Localisation of N-acetylaspartate in oligodendrocytes/myelin.

    Science.gov (United States)

    Nordengen, Kaja; Heuser, Christoph; Rinholm, Johanne Egge; Matalon, Reuben; Gundersen, Vidar

    2015-03-01

    The role of N-acetylaspartate in the brain is unclear. Here we used specific antibodies against N-acetylaspartate and immunocytochemistry of carbodiimide-fixed adult rodent brain to show that, besides staining of neuronal cell bodies in the grey matter, N-acetylaspartate labelling was present in oligodendrocytes/myelin in white matter tracts. Immunoelectron microscopy of the rat hippocampus showed that N-acetylaspartate was concentrated in the myelin. Also neuronal cell bodies and axons contained significant amounts of N-acetylaspartate, while synaptic elements and astrocytes were low in N-acetylaspartate. Mitochondria in axons and neuronal cell bodies contained higher levels of N-acetylaspartate compared to the cytosol, compatible with synthesis of N-acetylaspartate in mitochondria. In aspartoacylase knockout mice, in which catabolism of N-acetylaspartate is blocked, the levels of N-acetylaspartate were largely increased in oligodendrocytes/myelin. In these mice, the highest myelin concentration of N-acetylaspartate was found in the cerebellum, a region showing overt dysmyelination. In organotypic cortical slice cultures there was no evidence for N-acetylaspartate-induced myelin toxicity, supporting the notion that myelin damage is induced by the lack of N-acetylaspartate for lipid production. Our findings also implicate that N-acetylaspartate signals on magnetic resonance spectroscopy reflect not only vital neurons but also vital oligodendrocytes/myelin.

  19. The morphological substrate for Renal Denervation: Nerve distribution patterns and parasympathetic nerves. A post-mortem histological study.

    Science.gov (United States)

    van Amsterdam, Wouter A C; Blankestijn, Peter J; Goldschmeding, Roel; Bleys, Ronald L A W

    2016-03-01

    Renal Denervation as a possible treatment for hypertension has been studied extensively, but knowledge on the distribution of nerves surrounding the renal artery is still incomplete. While sympathetic and sensory nerves have been demonstrated, there is no mention of the presence of parasympathetic nerve fibers. To provide a description of the distribution patterns of the renal nerves in man, and, in addition, provide a detailed representation of the relative contribution of the sympathetic, parasympathetic and afferent divisions of the autonomic nervous system. Renal arteries of human cadavers were each divided into four longitudinal segments and immunohistochemically stained with specific markers for afferent, parasympathetic and sympathetic nerves. Nerve fibers were semi-automatically quantified by computerized image analysis, and expressed as cross-sectional area relative to the distance to the lumen. A total of 3372 nerve segments were identified in 8 arteries of 7 cadavers. Sympathetic, parasympathetic and afferent nerves contributed for 73.5% (95% CI: 65.4-81.5%), 17.9% (10.7-25.1%) and 8.7% (5.0-12.3%) of the total cross-sectional nerve area, respectively. Nerves are closer to the lumen in more distal segments and larger bundles that presumably innervate the kidney lie at 1-3.5mm distance from the lumen. The tissue-penetration depth of the ablation required to destroy 50% of the nerve fibers is 2.37 mm in the proximal segment and 1.78 mm in the most distal segments. Sympathetic, parasympathetic and afferent nerves exist in the vicinity of the renal artery. The results warrant further investigation of the role of the parasympathetic nervous system on renal physiology, and may contribute to refinement of the procedure by focusing the ablation on the most distal segment. Copyright © 2015 Elsevier GmbH. All rights reserved.

  20. Biological conduits combining bone marrow mesenchymal stem cells and extracellular matrix to treat long-segment sciatic nerve defects

    Directory of Open Access Journals (Sweden)

    Yang Wang

    2015-01-01

    Full Text Available The transplantation of polylactic glycolic acid conduits combining bone marrow mesenchymal stem cells and extracellular matrix gel for the repair of sciatic nerve injury is effective in some respects, but few data comparing the biomechanical factors related to the sciatic nerve are available. In the present study, rabbit models of 10-mm sciatic nerve defects were prepared. The rabbit models were repaired with autologous nerve, a polylactic glycolic acid conduit + bone marrow mesenchymal stem cells, or a polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel. After 24 weeks, mechanical testing was performed to determine the stress relaxation and creep parameters. Following sciatic nerve injury, the magnitudes of the stress decrease and strain increase at 7,200 seconds were largest in the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel group, followed by the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells group, and then the autologous nerve group. Hematoxylin-eosin staining demonstrated that compared with the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells group and the autologous nerve group, a more complete sciatic nerve regeneration was found, including good myelination, regularly arranged nerve fibers, and a completely degraded and resorbed conduit, in the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel group. These results indicate that bridging 10-mm sciatic nerve defects with a polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel construct increases the stress relaxation under a constant strain, reducing anastomotic tension. Large elongations under a constant physiological load can limit the anastomotic opening and shift, which is beneficial for the regeneration and functional reconstruction of sciatic nerve. Better

  1. Differential distribution of voltage-gated channels in myelinated and unmyelinated baroreceptor afferents.

    Science.gov (United States)

    Schild, John H; Kunze, Diana L

    2012-12-24

    Voltage gated ion channels (VGC) make possible the frequency coding of arterial pressure and the neurotransmission of this information along myelinated and unmyelinated fiber pathways. Although many of the same VGC isoforms are expressed in both fiber types, it is the relative expression of each that defines the unique discharge properties of myelinated A-type and unmyelinated C-type baroreceptors. For example, the fast inward Na⁺ current is a major determinant of the action potential threshold and the regenerative transmembrane current needed to sustain repetitive discharge. In A-type baroreceptors the TTX-sensitive Na(v)1.7 VGC contributes to the whole cell Na⁺ current. Na(v)1.7 is expressed at a lower density in C-type neurons and in conjunction with TTX-insensitive Na(v)1.8 and Na(v)1.9 VGC. As a result, action potentials of A-type neurons have firing thresholds that are 15-20 mV more negative and upstroke velocities that are 5-10 times faster than unmyelinated C-type neurons. A more depolarized threshold in conjunction with a broader complement of non-inactivating K(V) VGC subtypes produces C-type action potentials that are 3-4 times longer in duration than A-type neurons and at markedly lower levels of cell excitability. Unmyelinated baroreceptors also express KCa1.1 which provides approximately 25% of the total outward K⁺ current. KCa1.1 plays a critically important role in shaping the action potential profile of C-type neurons and strongly impacts neuronal excitability. A-type neurons do not functionally express the KCa1.1 channel despite having a whole cell Ca(V) current quite similar to that of C-type neurons. As a result, A-type neurons do not have the frequency-dependent braking forces of KCa1.1. Lack of a KCa current and only a limited complement of non-inactivating K(V) VGC in addition to a hyperpolarization activated HCN1 current that is nearly 10 times larger than in C-type neurons leads to elevated levels of discharge in A-type neurons, a

  2. Genipin-Cross-Linked Chitosan Nerve Conduits Containing TNF-α Inhibitors for Peripheral Nerve Repair.

    Science.gov (United States)

    Zhang, Li; Zhao, Weijia; Niu, Changmei; Zhou, Yujie; Shi, Haiyan; Wang, Yalin; Yang, Yumin; Tang, Xin

    2018-07-01

    Tissue engineered nerve grafts (TENGs) are considered a promising alternative to autologous nerve grafting, which is considered the "gold standard" clinical strategy for peripheral nerve repair. Here, we immobilized tumor necrosis factor-α (TNF-α) inhibitors onto a nerve conduit, which was introduced into a chitosan (CS) matrix scaffold utilizing genipin (GP) as the crosslinking agent, to fabricate CS-GP-TNF-α inhibitor nerve conduits. The in vitro release kinetics of TNF-α inhibitors from the CS-GP-TNF-α inhibitor nerve conduits were investigated using high-performance liquid chromatography. The in vivo continuous release profile of the TNF-α inhibitors released from the CS-GP-TNF-α inhibitor nerve conduits was measured using an enzyme-linked immunosorbent assay over 14 days. We found that the amount of TNF-α inhibitors released decreased with time after the bridging of the sciatic nerve defects in rats. Moreover, 4 and 12 weeks after surgery, histological analyses and functional evaluations were carried out to assess the influence of the TENG on regeneration. Immunochemistry performed 4 weeks after grafting to assess early regeneration outcomes revealed that the TENG strikingly promoted axonal outgrowth. Twelve weeks after grafting, the TENG accelerated myelin sheath formation, as well as functional restoration. In general, the regenerative outcomes following TENG more closely paralleled findings observed with autologous grafting than the use of the CS matrix scaffold. Collectively, our data indicate that the CS-GP-TNF-α inhibitor nerve conduits comprised an elaborate system for sustained release of TNF-α inhibitors in vitro, while studies in vivo demonstrated that the TENG could accelerate regenerating axonal outgrowth and functional restoration. The introduction of CS-GP-TNF-α-inhibitor nerve conduits into a scaffold may contribute to an efficient and adaptive immune microenvironment that can be used to facilitate peripheral nerve repair.

  3. Differential inhibitory effect on human nociceptive skin senses induced by local stimulation of thin cutaneous fibers.

    Science.gov (United States)

    Nilsson, H J; Schouenborg, J

    1999-03-01

    It is known that stimulation of thin cutaneous nerve fibers can induce long lasting analgesia through both supraspinal and segmental mechanisms, the latter often exhibiting restricted receptive fields. On this basis, we recently developed a new method, termed cutaneous field stimulation (CFS), for localized stimulation of A delta and C fibers in the superficial part of the skin. In the present study, we have evaluated the effects of CFS on non-nociceptive and nociceptive skin senses. We compared the effects of CFS with those of conventional transcutaneous electrical nerve stimulation (TENS), known to preferentially activate coarse myelinated fibers. A battery of sensory tests were made on the right volar forearm of 20 healthy subjects. CFS (16 electrodes, 4 Hz per electrode, 1 ms, up to 0.8 mA) and TENS (100 Hz, 0.2 ms, up to 26 mA) applied either on the right volar forearm (homotopically), or on the lower right leg (heterotopically) were used as conditioning stimulation for 25 min. The tactile threshold was not affected by either homo- or heterotopical CFS or TENS. The mean thresholds for detecting warming or cooling of the skin were increased by 0.4-0.9 degrees C after homo- but not heterotopical CFS and TENS. Regarding nociceptive skin senses, homo- but not heterotopical CFS, markedly reduced CO2-laser evoked A delta- and C fiber mediated heat pain to 75 and 48% of control, respectively, and mechanically evoked pain to 73% of control. Fabric evoked prickle, was not affected by CFS. Neither homo- nor heterotopical TENS induced any marked analgesic effects. It is concluded that different qualities of nociception can be differentially controlled by CFS.

  4. High cholesterol level is essential for myelin membrane growth.

    Science.gov (United States)

    Saher, Gesine; Brügger, Britta; Lappe-Siefke, Corinna; Möbius, Wiebke; Tozawa, Ryu-ichi; Wehr, Michael C; Wieland, Felix; Ishibashi, Shun; Nave, Klaus-Armin

    2005-04-01

    Cholesterol in the mammalian brain is a risk factor for certain neurodegenerative diseases, raising the question of its normal function. In the mature brain, the highest cholesterol content is found in myelin. We therefore created mice that lack the ability to synthesize cholesterol in myelin-forming oligodendrocytes. Mutant oligodendrocytes survived, but CNS myelination was severely perturbed, and mutant mice showed ataxia and tremor. CNS myelination continued at a reduced rate for many months, and during this period, the cholesterol-deficient oligodendrocytes actively enriched cholesterol and assembled myelin with >70% of the cholesterol content of wild-type myelin. This shows that cholesterol is an indispensable component of myelin membranes and that cholesterol availability in oligodendrocytes is a rate-limiting factor for brain maturation.

  5. Age-related ultrastructural and monoamine oxidase changes in the rat optic nerve.

    Science.gov (United States)

    Taurone, S; Ripandelli, G; Minni, A; Lattanzi, R; Miglietta, S; Pepe, N; Fumagalli, L; Micera, A; Pastore, F S; Artico, M

    2016-01-01

    The aim of this paper is to study the morphology and the distribution of the monoamine oxidase enzymatic system in the optic nerve of 4 month-old Wistar (young) and 28 month-old Wistar (old) rats. The optic nerve was harvested from 20 young and old rats. The segment of optic nerve was divided longitudinally into two pieces, each 0.1 mm in length. The first piece was used for transmission electron microscopy. The second piece was stained with histochemical reaction for monoamine oxidase. The agerelated changes in the optic nerve of rats include micro-anatomical details, ultrastructure and monoamine oxidase histochemical staining. A strong decrease of the thin nerve fibers and a swelling of the thick ones can be observed in optic nerve fibers of old rats. Increased monoamine oxidase histochemical staining of the optic nerve of aged rats is well demonstrated. The increase of meningeal shealth and the decrease of thin nerve fibers of the optic nerve in old rats are well documented. Morphological, ultrastructural and histochemical changes observed in optic nerve fibers of the old rats show a close relation with aging.

  6. Effects of umbilical cord tissue mesenchymal stem cells (UCX® on rat sciatic nerve regeneration after neurotmesis injuries

    Directory of Open Access Journals (Sweden)

    Gärtner A

    2013-04-01

    Full Text Available Peripheral nerves have the intrinsic capacity of self-regeneration after traumatic injury but the extent of the regeneration is often very poor. Increasing evidence demonstrates that mesenchymal stem/stromal cells (MSCs may play an important role in tissue regeneration through the secretion of soluble trophic factors that enhance and assist in repair by paracrine activation of surrounding cells. In the present study, the therapeutic value of a population of umbilical cord tissue-derived MSCs, obtained by a proprietary method (UCX®, was evaluated on end-to-end rat sciatic nerve repair. Furthermore, in order to promote both, end-to-end nerve fiber contacts and MSC cell-cell interaction, as well as reduce the flush away effect of the cells after administration, a commercially available haemostatic sealant, Floseal®, was used as vehicle. Both, functional and morphologic recoveries were evaluated along the healing period using extensor postural thrust (EPT, withdrawal reflex latency (WRL, ankle kinematics analysis, and either histological analysis or stereology, in the hyper-acute, acute and chronic phases of healing. The histological analysis of the hyper-acute and acute phase studies revealed that in the group treated with UCX ® alone the Wallerian degeneration was improved for the subsequent process of regeneration, the fiber organization was higher, and the extent of fibrosis was lower. The chronic phase experimental groups revealed that treatment with UCX® induced an increased number of regenerated fibers and thickening of the myelin sheet. Kinematics analysis showed that the ankle joint angle determined for untreated animals was significantly different from any of the treated groups at the instant of initial contact (IC. At opposite toe off (OT and heel rise (HR, differences were found between untreated animals and the groups treated with either UCX® alone or UCX® administered with Floseal®. Overall, the UCX® application presented

  7. Propofol promotes spinal cord injury repair by bone marrow mesenchymal stem cell transplantation

    Science.gov (United States)

    Zhou, Ya-jing; Liu, Jian-min; Wei, Shu-ming; Zhang, Yun-hao; Qu, Zhen-hua; Chen, Shu-bo

    2015-01-01

    Propofol is a neuroprotective anesthetic. Whether propofol can promote spinal cord injury repair by bone marrow mesenchymal stem cells remains poorly understood. We used rats to investigate spinal cord injury repair using bone marrow mesenchymal stem cell transplantation combined with propofol administration via the tail vein. Rat spinal cord injury was clearly alleviated; a large number of newborn non-myelinated and myelinated nerve fibers appeared in the spinal cord, the numbers of CM-Dil-labeled bone marrow mesenchymal stem cells and fluorogold-labeled nerve fibers were increased and hindlimb motor function of spinal cord-injured rats was markedly improved. These improvements were more prominent in rats subjected to bone marrow mesenchymal cell transplantation combined with propofol administration than in rats receiving monotherapy. These results indicate that propofol can enhance the therapeutic effects of bone marrow mesenchymal stem cell transplantation on spinal cord injury in rats. PMID:26487860

  8. Age and Glaucoma-Related Characteristics in Retinal Nerve Fiber Layer and Choroid: Localized Morphometrics and Visualization Using Functional Shapes Registration

    Directory of Open Access Journals (Sweden)

    Sieun Lee

    2017-07-01

    Full Text Available Optical coherence tomography provides high-resolution 3D imaging of the posterior segment of the eye. However, quantitative morphological analysis, particularly relevant in retinal degenerative diseases such as glaucoma, has been confined to simple sectorization and averaging with limited spatial sensitivity for detection of clinical markers. In this paper, we present point-wise analysis and visualization of the retinal nerve fiber layer and choroid from cross-sectional data using functional shapes (fshape registration. The fshape framework matches two retinas, or generates a mean of multiple retinas, by jointly optimizing the surface geometry and functional signals mapped on the surface. We generated group-wise mean retinal nerve fiber layer and choroidal surfaces with the respective layer thickness mapping and showed the difference by age (normal, younger vs. older and by disease (age-matched older, normal vs. glaucomatous in the two layers, along with a more conventional sector-based analysis for comparison. The fshape results visualized the detailed spatial patterns of the differences between the age-matched normal and glaucomatous retinal nerve fiber layers, with the glaucomatous layers most significantly thinner in the inferior region close to Bruch's membrane opening. Between the young and older normal cases, choroid was shown to be significantly thinner in the older subjects across all regions, but particularly in the nasal and inferior regions. The results demonstrate a comprehensive and detailed analysis with visualization of morphometric patterns by multiple factors.

  9. Trophic Effects of Dental Pulp Stem Cells on Schwann Cells in Peripheral Nerve Regeneration.

    Science.gov (United States)

    Yamamoto, Tsubasa; Osako, Yohei; Ito, Masataka; Murakami, Masashi; Hayashi, Yuki; Horibe, Hiroshi; Iohara, Koichiro; Takeuchi, Norio; Okui, Nobuyuki; Hirata, Hitoshi; Nakayama, Hidenori; Kurita, Kenichi; Nakashima, Misako

    2016-01-01

    Recently, mesenchymal stem cells have demonstrated a potential for neurotrophy and neurodifferentiation. We have recently isolated mobilized dental pulp stem cells (MDPSCs) using granulocyte-colony stimulating factor (G-CSF) gradient, which has high neurotrophic/angiogenic potential. The aim of this study is to investigate the effects of MDPSC transplantation on peripheral nerve regeneration. Effects of MDPSC transplantation were examined in a rat sciatic nerve defect model and compared with autografts and control conduits containing collagen scaffold. Effects of conditioned medium of MDPSCs were also evaluated in vitro. Transplantation of MDPSCs in the defect demonstrated regeneration of myelinated fibers, whose axons were significantly higher in density compared with those in autografts and control conduits only. Enhanced revascularization was also observed in the MDPSC transplants. The MDPSCs did not directly differentiate into Schwann cell phenotype; localization of these cells near Schwann cells induced several neurotrophic factors. Immunofluorescence labeling demonstrated reduced apoptosis and increased proliferation in resident Schwann cells in the MDPSC transplant compared with control conduits. These trophic effects of MDPSCs on proliferation, migration, and antiapoptosis in Schwann cells were further elucidated in vitro. The results demonstrate that MDPSCs promote axon regeneration through trophic functions, acting on Schwann cells, and promoting angiogenesis.

  10. 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

  11. Reversible acute axonal polyneuropathy associated with Wernicke-Korsakoff syndrome: impaired physiological nerve conduction due to thiamine deficiency?

    Science.gov (United States)

    Ishibashi, S; Yokota, T; Shiojiri, T; Matunaga, T; Tanaka, H; Nishina, K; Hirota, H; Inaba, A; Yamada, M; Kanda, T; Mizusawa, H

    2003-05-01

    Acute axonal polyneuropathy and Wernicke-Korsakoff encephalopathy developed simultaneously in three patients. Nerve conduction studies (NCS) detected markedly decreased compound muscle action potentials (CMAPs) and sensory nerve action potentials (SNAPs) with minimal conduction slowing; sympathetic skin responses (SSRs) were also notably decreased. Sural nerve biopsies showed only mild axonal degeneration with scattered myelin ovoid formation. The symptoms of neuropathy lessened within two weeks after an intravenous thiamine infusion. CMAPs, SNAPs, and SSRs also increased considerably. We suggest that this is a new type of peripheral nerve impairment: physiological conduction failure with minimal conduction delay due to thiamine deficiency.

  12. Immunoglobulin deposits in peripheral nerve endings detected by skin biopsy in patients with IgM M proteins and neuropathy

    DEFF Research Database (Denmark)

    Jønsson, V; Jensen, T S; Friis, M L

    1987-01-01

    biopsies provide a simple effective method of detecting immunoglobulin binding to peripheral nerves in patients suspected of having an autoimmune neuropathy. In contrast to sural nerve biopsy, skin biopsy does not cause sensory loss or pain in a denervated area and can easily be repeated.......Immunofluorescence studies of sural nerve and skin biopsies from three patients with IgM M proteins and clinical neuropathy showed that IgM M protein was bound to the nerve myelin in two patients and by the peri- and endoneurium in one. It is suggested that immunohistochemical studies of skin...

  13. Significant correlations between optic nerve head microcirculation and visual field defects and nerve fiber layer loss in glaucoma patients with myopic glaucomatous disk

    Directory of Open Access Journals (Sweden)

    Yokoyama Y

    2011-12-01

    Full Text Available Yu Yokoyama, Naoko Aizawa, Naoki Chiba, Kazuko Omodaka, Masahiko Nakamura, Takaaki Otomo, Shunji Yokokura, Nobuo Fuse, Toru NakazawaDepartment of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai, JapanBackground: Eyes with glaucoma are characterized by optic neuropathy with visual field defects in the areas corresponding to the optic disk damage. The exact cause for the glaucomatous optic neuropathy has not been determined. Myopia has been shown to be a risk factor for glaucoma. The purpose of this study was to determine whether a significant correlation existed between the microcirculation of the optic disk and the visual field defects and the retinal nerve fiber layer thickness (RNFLT in glaucoma patients with myopic optic disks.Methods: Sixty eyes of 60 patients with myopic disks were studied; 36 eyes with glaucoma (men:women = 19:17 and 24 eyes with no ocular diseases (men:women = 14:10. The mean deviation (MD determined by the Humphrey field analyzer, and the peripapillary RNFLT determined by the Stratus-OCT were compared between the two groups. The ocular circulation was determined by laser speckle flowgraphy (LSFG, and the mean blur rate (MBR was compared between the two groups. The correlations between the RNFLT and MBR of the corresponding areas of the optic disk and between MD and MBR of the optic disk in the glaucoma group were determined by simple regression analyses.Results: The average MBR for the entire optic disk was significantly lower in the glaucoma group than that in the control group. The differences of the MBR for the tissue in the superior, inferior, and temporal quadrants of the optic disk between the two groups were significant. The MBR for the entire optic disk was significantly correlated with the MD (r = 0.58, P = 0.0002 and the average RNFLT (r = 0.53, P = 0.0008. The tissue MBR of the optic disk was significantly correlated with the RNFLT in the superior, inferior, and temporal quadrants

  14. Long-term retinal nerve fiber layer changes following nonarteritic anterior ischemic optic neuropathy

    Directory of Open Access Journals (Sweden)

    Dotan G

    2013-04-01

    Full Text Available Gad Dotan,1 Michaella Goldstein,1 Anat Kesler,1 Barry Skarf21Department of Ophthalmology, Tel Aviv Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; 2Eye Care Services, Henry Ford Hospital, Detroit, MI, USABackground: In cases of nonarteritic anterior ischemic optic neuropathy (NAION, retinal nerve fiber layer (RNFL thickness changes have been described during the first 12 months following the acute event. The purpose of this study was to report on the long-term RNFL changes in these eyes beyond the first year following onset of NAION.Methods: Fourteen eyes of 13 patients with NAION were analyzed in this retrospective observational case series study. Uninvolved eyes served as controls. All patients underwent a complete neuro-ophthalmological examination and repeat measurements of peripapillary RNFL thickness using Stratus optical coherence tomography.Results: On optical coherence tomography scan performed on average 6 months following onset of NAION, the mean global RNFL thickness (59.8 ± 11.8 μm was significantly thinner (P < 0.001 compared with uninvolved eyes (95.1 ± 13.9 μm. In a second optical coherence tomography scan performed on average 13 (range 12–23 months later, the mean global RNFL thickness (58.9 ± 6.5 μm was not significantly different (P = 0.702 from the first scan.Conclusion: There appears to be no further RNFL loss beyond the first 6 months following an acute event of NAION.Keywords: optical coherence tomography, retinal nerve fiber layer, nonartertic anterior ischemic optic neuropathy

  15. 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.

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

    OpenAIRE

    Gencer, Baran; Cosar, Murat; Tufan, Hasan Ali; Kara, Selcuk; Arikan, Sedat; Akman, Tarik; Kiraz, Hasan Ali; Comez, Arzu Taskiran; Hanci, Volkan

    2015-01-01

    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. ...

  17. Transplantation of Human Dental Pulp-Derived Stem Cells or Differentiated Neuronal Cells from Human Dental Pulp-Derived Stem Cells Identically Enhances Regeneration of the Injured Peripheral Nerve.

    Science.gov (United States)

    Ullah, Imran; Park, Ju-Mi; Kang, Young-Hoon; Byun, June-Ho; Kim, Dae-Geon; Kim, Joo-Heon; Kang, Dong-Ho; Rho, Gyu-Jin; Park, Bong-Wook

    2017-09-01

    Human dental mesenchymal stem cells isolated from the dental follicle, pulp, and root apical papilla of extracted wisdom teeth have been known to exhibit successful and potent neurogenic differentiation capacity. In particular, human dental pulp-derived stem cells (hDPSCs) stand out as the most prominent source for in vitro neuronal differentiation. In this study, to evaluate the in vivo peripheral nerve regeneration potential of hDPSCs and differentiated neuronal cells from DPSCs (DF-DPSCs), a total of 1 × 10 6 hDPSCs or DF-hDPSCs labeled with PKH26 tracking dye and supplemented with fibrin glue scaffold and collagen tubulization were transplanted into the sciatic nerve resection (5-mm gap) of rat models. At 12 weeks after cell transplantation, both hDPSC and DF-hDPSC groups showed notably increased behavioral activities and higher muscle contraction forces compared with those in the non-cell transplanted control group. In immunohistochemical analysis of regenerated nerve specimens, specific markers for angiogenesis, axonal fiber, and myelin sheath increased in both the cell transplantation groups. Pretransplanted labeled PKH26 were also distinctly detected in the regenerated nerve tissues, indicating that transplanted cells were well-preserved and differentiated into nerve cells. Furthermore, no difference was observed in the nerve regeneration potential between the hDPSC and DF-hDPSC transplanted groups. These results demonstrate that dental pulp tissue is an excellent stem cell source for nerve regeneration, and in vivo transplantation of the undifferentiated hDPSCs could exhibit sufficient and excellent peripheral nerve regeneration potential.

  18. Electrodiagnosis and nerve conduction studies.

    Science.gov (United States)

    Posuniak, E A

    1984-08-01

    The use of electrodiagnostic techniques in evaluation of complaints in the lower extremities provides an objective method of assessment. A basic understanding of principles of neurophysiology, EMG and NCV methodology, and neuropathology of peripheral nerves greatly enhances physical diagnosis and improves the state of the art in treatment of the lower extremity, especially foot and ankle injuries. Familiarity with the method of reporting electrodiagnostic studies and appreciation of the electromyographer's interpretation of the EMG/NCV studies also reflects an enhanced fund of knowledge, skills, and attitudes as pertains to one's level of professional expertise. Information regarding the etiology of positive sharp waves, fibrillation potentials, fasciculation, and normal motor action potentials and conduction studies serves as a sound basis for the appreciation of the categories of nerve injury. Competence in understanding the degree of axonal or myelin function or dysfunction in a nerve improve one's effectiveness not only in medical/surgical treatment but in prognostication of recovery of function. A review of the entrapment syndromes in the lower extremity with emphasis on tarsal tunnel syndrome summarizes the most common nerve entrapments germane to the practice of podiatry. With regard to tarsal tunnel syndrome, the earliest electrodiagnostic study to suggest compression was reported to be the EMG of the foot and leg muscles, even before prolonged nerve latency was noted.

  19. Therapeutic potential of Mucuna pruriens (Linn.) on ageing induced damage in dorsal nerve of the penis and its implication on erectile function: an experimental study using albino rats.

    Science.gov (United States)

    Seppan, Prakash; Muhammed, Ibrahim; Mohanraj, Karthik Ganesh; Lakshmanan, Ganesh; Premavathy, Dinesh; Muthu, Sakthi Jothi; Wungmarong Shimray, Khayinmi; Sathyanathan, Sathya Bharathy

    2018-02-15

    To study the effect of ethanolic seed extract of Mucuna pruriens on damaged dorsal nerve of the penis (DNP) in aged rat in relation to penile erection. The rats were divided into four groups Young (3 months), Aged (24 - 28 months), Aged + M. pruriens, and Young + M. pruriens (200 mg/kg b.w/60 days) and were subjected to the hypophysial - gonadal axis, nerve conduction velocity (NCV), and penile reflex. DNP sections were stained with nitric oxide synthase (nNOS), nicotinamide adenine dinucleotide phosphate (NaDPH) diaphorase, androgen receptor (AR), and osmium tetroxide. Terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) staining, electron microscopy(EM) and histometric analyses were done. Significant disturbance in hypophysial - gonadal axis was noted in aged rat. With reduced number of myelinated fibers, diameter, vacuolization, indentation of the myelin sheath, and degeneration. nNOS and its cofactor (NaDPH diaphorase) were reduced in aged rat DNP. NCV was slow in aged rats and concomitant poor penile reflex was also noted. AR showed reduced expression in aged rat DNP when compared to young and control groups. TUNEL positive cells were increased in aged rat DNP. These pathological changes were remarkably reduced or recovered in M. pruriens treated aged rats. The results indicate a multi-factorial therapeutic activity in penile innervations towards sustaining the penile erection in the presence of the extract in aged rats and justifying the claim of traditional usage.

  20. Loss of temporal peripapillary retinal nerve fibers in prediabetes or type 2 diabetes without diabetic retinopathy: The Maastricht Study

    NARCIS (Netherlands)

    de Clerck, E.E.B.; Schouten, J.S.A.G.; Berendschot, T.T.J.M.; Beckers, H.J.M.; Schaper, N.C.; Schram, M.T.; Stehouwer, C.D.A.; Webers, C.A.B.

    Purpose: The purpose of this study was to assess thinning of the peripapillary retinal nerve fiber layer (RNFL) in prediabetes or type 2 diabetes without diabetic retinopathy (DM2 w/o DRP) compared with that in individuals with normal glucose metabolism (NGM). Methods: We measured sectoral and mean

  1. 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.

  2. Hyperglycemia Promotes Schwann Cell De-differentiation and De-myelination via Sorbitol Accumulation and Igf1 Protein Down-regulation.

    Science.gov (United States)

    Hao, Wu; Tashiro, Syoichi; Hasegawa, Tomoka; Sato, Yuiko; Kobayashi, Tami; Tando, Toshimi; Katsuyama, Eri; Fujie, Atsuhiro; Watanabe, Ryuichi; Morita, Mayu; Miyamoto, Kana; Morioka, Hideo; Nakamura, Masaya; Matsumoto, Morio; Amizuka, Norio; Toyama, Yoshiaki; Miyamoto, Takeshi

    2015-07-10

    Diabetes mellitus (DM) is frequently accompanied by complications, such as peripheral nerve neuropathy. Schwann cells play a pivotal role in regulating peripheral nerve function and conduction velocity; however, changes in Schwann cell differentiation status in DM are not fully understood. Here, we report that Schwann cells de-differentiate into immature cells under hyperglycemic conditions as a result of sorbitol accumulation and decreased Igf1 expression in those cells. We found that de-differentiated Schwann cells could be re-differentiated in vitro into mature cells by treatment with an aldose reductase inhibitor, to reduce sorbitol levels, or with vitamin D3, to elevate Igf1 expression. In vivo DM models exhibited significantly reduced nerve function and conduction, Schwann cell de-differentiation, peripheral nerve de-myelination, and all conditions were significantly rescued by aldose reductase inhibitor or vitamin D3 administration. These findings reveal mechanisms underlying pathological changes in Schwann cells seen in DM and suggest ways to treat neurological conditions associated with this condition. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Distribution of elements in rat peripheral axons and nerve cell bodies determined by x-ray microprobe analysis

    Energy Technology Data Exchange (ETDEWEB)

    LoPachin, R.M. Jr.; Lowery, J.; Eichberg, J.; Kirkpatrick, J.B.; Cartwright, J. Jr.; Saubermann, A.J.

    1988-09-01

    X-ray microprobe analysis was used to determine concentrations (millimoles of element per kilogram dry weight) of Na, P, Cl, K, and Ca in cellular compartments of frozen, unfixed sections of rat sciatic and tibial nerves and dorsal root ganglion (DRG). Five compartments were examined in peripheral nerve (axoplasm, mitochondria, myelin, extraaxonal space, and Schwann cell cytoplasm), and four were analyzed in DRG nerve cell bodies (cytoplasm, mitochondria, nucleus, and nucleolus). Each morphological compartment exhibited characteristic concentrations of elements. The extraaxonal space contained high concentrations of Na, Cl, and Ca, whereas intraaxonal compartments exhibited lower concentrations of these elements but relatively high K contents. Nerve axoplasm and axonal mitochondria had similar elemental profiles, and both compartments displayed proximodistal gradients of decreasing levels of K, Cl, and, to some extent, Na. Myelin had a selectively high P concentration with low levels of other elements. The elemental concentrations of Schwann cell cytoplasm and DRG were similar, but both were different from that of axoplasm, in that K and Cl were markedly lower whereas P was higher. DRG cell nuclei contained substantially higher K levels than cytoplasm. The subcellular distribution of elements was clearly shown by color-coded images generated by computer-directed digital x-ray imaging. The results of this study demonstrate characteristic elemental distributions for each anatomical compartment, which doubtless reflect nerve cell structure and function.

  4. Effect of Platelet-Rich Fibrin on Peripheral Nerve Regeneration.

    Science.gov (United States)

    Şenses, Fatma; Önder, Mustafa E; Koçyiğit, Ismail D; Kul, Oğuz; Aydin, Gülümser; Inal, Elem; Atil, Fethi; Tekin, Umut

    2016-10-01

    This study aimed to evaluate the effect of platelet-rich fibrin (PRF) on peripheral nerve regeneration on the sciatic nerve of rats by using functional, histopathologic, and electrophysiologic analyses. Thirty female Wistar rats were divided randomly into 3 experimental groups. In group 1 (G1), which was the control group, the sciatic nerve was transected and sutured (n = 10). In group 2 (G2), the sciatic nerve was transected, sutured, and then covered with PRF as a membrane (n = 10). In group 3 (G3), the sciatic nerve was transected, sutured by leaving a 5-mm gap, and then covered by PRF as a nerve guide (n = 10). Functional, histopathologic, and electrophysiologic analyses were performed. The total histopathologic semiquantitative score was significantly higher in G1 compared to G2 and G3 (P < 0.05). Myelin thickness and capillaries were significantly lower in G3 compared to G1 (P < 0.05). There was no statistically significant difference between the groups with regard to the functional and electrophysiologic results. The study results suggest that PRF decreases functional recovery in sciatic nerve injury. Further studies are required to determine the efficacy of PRF on peripheral nerve regeneration.

  5. Metabolic Changes in the Visual Cortex Are Linked to Retinal Nerve Fiber Layer Thinning in Multiple Sclerosis

    Science.gov (United States)

    Schubert, Florian; Bock, Markus; Walaszek, Bernadeta; Waiczies, Helmar; Schwenteck, Thomas; Dörr, Jan; Bellmann-Strobl, Judith; Mohr, Christian; Weinges-Evers, Nicholetta; Ittermann, Bernd; Wuerfel, Jens T.; Paul, Friedemann

    2011-01-01

    Objective To investigate the damage to the retinal nerve fiber layer as part of the anterior visual pathway as well as an impairment of the neuronal and axonal integrity in the visual cortex as part of the posterior visual pathway with complementary neuroimaging techniques, and to correlate our results to patients' clinical symptoms concerning the visual pathway. Design, Subjects and Methods Survey of 86 patients with relapsing-remitting multiple sclerosis that were subjected to retinal nerve fiber layer thickness (RNFLT) measurement by optical coherence tomography, to a routine MRI scan including the calculation of the brain parenchymal fraction (BPF), and to magnetic resonance spectroscopy at 3 tesla, quantifying N-acetyl aspartate (NAA) concentrations in the visual cortex and normal-appearing white matter. Results RNFLT correlated significantly with BPF and visual cortex NAA, but not with normal-appearing white matter NAA. This was connected with the patients' history of a previous optic neuritis. In a combined model, both BPF and visual cortex NAA were independently associated with RNFLT. Conclusions Our data suggest the existence of functional pathway-specific damage patterns exceeding global neurodegeneration. They suggest a strong interrelationship between damage to the anterior and the posterior visual pathway. PMID:21494672

  6. Roles of neural stem cells in the repair of peripheral nerve injury.

    Science.gov (United States)

    Wang, Chong; Lu, Chang-Feng; Peng, Jiang; Hu, Cheng-Dong; Wang, Yu

    2017-12-01

    Currently, researchers are using neural stem cell transplantation to promote regeneration after peripheral nerve injury, as neural stem cells play an important role in peripheral nerve injury repair. This article reviews recent research progress of the role of neural stem cells in the repair of peripheral nerve injury. Neural stem cells can not only differentiate into neurons, astrocytes and oligodendrocytes, but can also differentiate into Schwann-like cells, which promote neurite outgrowth around the injury. Transplanted neural stem cells can differentiate into motor neurons that innervate muscles and promote the recovery of neurological function. To promote the repair of peripheral nerve injury, neural stem cells secrete various neurotrophic factors, including brain-derived neurotrophic factor, fibroblast growth factor, nerve growth factor, insulin-like growth factor and hepatocyte growth factor. In addition, neural stem cells also promote regeneration of the axonal myelin sheath, angiogenesis, and immune regulation. It can be concluded that neural stem cells promote the repair of peripheral nerve injury through a variety of ways.

  7. Experimental ethylene oxide neuropathy. Chronic exposure to 250 ppm in rats

    Energy Technology Data Exchange (ETDEWEB)

    Ohnishi, A.; Yamamoto, T.; Inoue, N.; Tanaka, I.; Koga, M.

    1985-12-01

    In Wistar rats subjected to a six-hour exposure to ethylene oxide (ETO) at the concentration of 250 parts per million once a day, five times a week for 9 months, histopathologic studies of myelinated fibers of the proximal sural, distal sural and peroneal nerves and of the fasciculus gracilis at the fifth thoracic and third cervical segments of the spinal cord were performed to reveal whether ETO of such concentration produces the degeneration of the primary sensory neuron. Throughout the study, no definite abnormality of the gait or posture was observed in both control and test rats. Qualitative histologic studies disclosed preferential distal axonal degeneration of myelinated fibers in both sural nerves and gracile fascicles in test rats, although the extent of the distribution and the severity of the degenerative findings were variable among test rats. Therefore, it was concluded that exposure to 250 ppm ethylene oxide produces central-peripheral distal axonal degeneration of the primary sensory neuron in rats.

  8. Transplantation of olfactory ensheathing cells as adjunct cell therapy for peripheral nerve injury.

    Science.gov (United States)

    Radtke, Christine; Wewetzer, Konstantin; Reimers, Kerstin; Vogt, Peter M

    2011-01-01

    Traumatic events, such as work place trauma or motor vehicle accident violence, result in a significant number of severe peripheral nerve lesions, including nerve crush and nerve disruption defects. Transplantation of myelin-forming cells, such as Schwann cells (SCs) or olfactory ensheathing cells (OECs), may be beneficial to the regenerative process because the applied cells could mediate neurotrophic and neuroprotective effects by secretion of chemokines. Moreover, myelin-forming cells are capable of bridging the repair site by establishing an environment permissive to axonal regeneration. The cell types that are subject to intense investigation include SCs and OECs either derived from the olfactory bulb or the olfactory mucosa, stromal cells from bone marrow (mesenchymal stem cells, MSCs), and adipose tissue-derived cells. OECs reside in the peripheral and central nervous system and have been suggested to display unique regenerative properties. However, so far OECs were mainly used in experimental studies to foster central regeneration and it was not until recently that their regeneration-promoting activity for the peripheral nervous system was recognized. In the present review, we summarize recent experimental evidence regarding the regenerative effects of OECs applied to the peripheral nervous system that may be relevant to design novel autologous cell transplantation therapies. © 2011 Cognizant Comm. Corp.

  9. Novel drug delivering conduit for peripheral nerve regeneration

    Science.gov (United States)

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

    2017-12-01

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

  10. CAPSAICIN-SENSITIVE SENSORY NERVE FIBERS CONTRIBUTE TO THE GENERATION AND MAINTENANCE OF SKELETAL FRACTURE PAIN

    OpenAIRE

    Jimenez-Andrade, Juan Miguel; Bloom, Aaron P.; Mantyh, William G.; Koewler, Nathan J.; Freeman, Katie T.; Delong, David; Ghilardi, Joseph R.; Kuskowski, Michael A.; Mantyh, Patrick W.

    2009-01-01

    Although skeletal pain can have a marked impact on a patient’s functional status and quality of life, relatively little is known about the specific populations of peripheral nerve fibers that drive non-malignant bone pain. In the present report, neonatal male Sprague Dawley rats were treated with capsaicin or vehicle and femoral fracture was produced when the animals were young adults (15–16 weeks old). Capsaicin treatment, but not vehicle, resulted in a significant (>70%) depletion in the de...

  11. 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

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

  12. Cross-population myelination covariance of human cerebral cortex.

    Science.gov (United States)

    Ma, Zhiwei; Zhang, Nanyin

    2017-09-01

    Cross-population covariance of brain morphometric quantities provides a measure of interareal connectivity, as it is believed to be determined by the coordinated neurodevelopment of connected brain regions. Although useful, structural covariance analysis predominantly employed bulky morphological measures with mixed compartments, whereas studies of the structural covariance of any specific subdivisions such as myelin are rare. Characterizing myelination covariance is of interest, as it will reveal connectivity patterns determined by coordinated development of myeloarchitecture between brain regions. Using myelin content MRI maps from the Human Connectome Project, here we showed that the cortical myelination covariance was highly reproducible, and exhibited a brain organization similar to that previously revealed by other connectivity measures. Additionally, the myelination covariance network shared common topological features of human brain networks such as small-worldness. Furthermore, we found that the correlation between myelination covariance and resting-state functional connectivity (RSFC) was uniform within each resting-state network (RSN), but could considerably vary across RSNs. Interestingly, this myelination covariance-RSFC correlation was appreciably stronger in sensory and motor networks than cognitive and polymodal association networks, possibly due to their different circuitry structures. This study has established a new brain connectivity measure specifically related to axons, and this measure can be valuable to investigating coordinated myeloarchitecture development. Hum Brain Mapp 38:4730-4743, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  13. Evaluation of Morphological and Functional Nerve Recovery of Rat Sciatic Nerve with a Hyaff11-Based Nerve Guide

    Directory of Open Access Journals (Sweden)

    K. Jansen

    2006-01-01

    Full Text Available Application of a Hyaff11-based nerve guide was studied in rats. Functional tests were performed to study motor nerve recovery. A withdrawal reflex test was performed to test sensory recovery. Morphology was studied by means of histology on explanted tissue samples. Motor nerve recovery was established within 7 weeks. Hereafter, some behavioral parameters like alternating steps showed an increase in occurence, while others remained stable. Sensory function was observed within the 7 weeks time frame. Nerve tissue had bridged the 10-mm gap within 7 weeks. The average nerve fiber surface area increased significantly in time. In situ degradation of the nerve conduit was fully going on at week 7 and tubes had collapsed by then. At weeks 15 and 21, the knitted tube wall structure was completely surrounded by macrophages and giant cells, and matrix was penetrating the tube wall. We conclude that a Hyaff11-based nerve guide can be used to bridge short peripheral nerve defects in rat. However, adaptations need to be made.

  14. 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

    This paper discusses the potential of fuzzy logic methods within medical imaging. Technical advances have produced imaging techniques that can visualize structures and their functions in the living human body. The interpretation of these images plays a prominent role in diagnostic and therapeutic...... decisions, so physicians must deal with a variety of image processing methods and their applications.This paper describes three different sources of medical imagery that allow the visualization of nerve fibers in the human brain: (1) an algorithm for automatic segmentation of some parts of the thalamus....... Fuzzy logic methods were applied to analyze these pictures from low- to high-level image processing. The solutions presented here are motivated by problems of routine neuroanatomic research demonstrating fuzzy-based methods to be valuable tools in medical image processing....

  15. Localization of lead in rat peripheral nerve by electron microscopy

    International Nuclear Information System (INIS)

    Windebank, A.J.; Dyck, P.J.

    1985-01-01

    Lead intoxication in rats reliably produces segmental demyelination. Following a single intravenous injection of radioactive lead, localization of tracer was observed sequentially by quantitative electron microscopical autoradiography. The animals injected had been on a lead-containing diet for 70 days; as a result, the blood-nerve barrier was broken down and demyelination was proceeding. Six hours after a single dose, the lead was localized to the endoneurial space of the peroneal nerve, and 72 hours later, to the myelin membrane. Lead may exert a direct effect on the membrane and alter its stability both by altering the lipid content of the membrane and by directly interfering with the lamellar structure

  16. MRI shows thickening and altered diffusion in the median and ulnar nerves in multifocal motor neuropathy

    Energy Technology Data Exchange (ETDEWEB)

    Haakma, Wieke [University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Aarhus University, Department of Forensic Medicine and Comparative Medicine Lab, Aarhus (Denmark); Jongbloed, Bas A.; Goedee, H.S.; Berg, Leonard H. van den; Pol, W.L. van der [University Medical Center Utrecht, Brain Centre Rudolf Magnus, Department of Neurology and Neurosurgery, Utrecht (Netherlands); Froeling, Martijn; Bos, Clemens; Hendrikse, Jeroen [University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Leemans, Alexander [University Medical Center Utrecht, Image Sciences Institute, Utrecht (Netherlands)

    2017-05-15

    To study disease mechanisms in multifocal motor neuropathy (MMN) with magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) of the median and ulnar nerves. We enrolled ten MMN patients, ten patients with amyotrophic lateral sclerosis (ALS) and ten healthy controls (HCs). Patients underwent MRI (in a prone position) and nerve conduction studies. DTI and fat-suppressed T2-weighted scans of the forearms were performed on a 3.0T MRI scanner. Fibre tractography of the median and ulnar nerves was performed to extract diffusion parameters: fractional anisotropy (FA), mean (MD), axial (AD) and radial (RD) diffusivity. Cross-sectional areas (CSA) were measured on T2-weighted scans. Forty-five out of 60 arms were included in the analysis. AD was significantly lower in MMN patients (2.20 ± 0.12 x 10{sup -3} mm{sup 2}/s) compared to ALS patients (2.31 ± 0.17 x 10{sup -3} mm{sup 2}/s; p < 0.05) and HCs (2.31± 0.17 x 10{sup -3} mm{sup 2}/s; p < 0.05). Segmental analysis showed significant restriction of AD, RD and MD (p < 0.005) in the proximal third of the nerves. CSA was significantly larger in MMN patients compared to ALS patients and HCs (p < 0.01). Thickening of nerves is compatible with changes in the myelin sheath structure, whereas lowered AD values suggest axonal dysfunction. These findings suggest that myelin and axons are diffusely involved in MMN pathogenesis. (orig.)

  17. Spatiotemporal dynamics of re-innervation and hyperinnervation patterns by uninjured CGRP fibers in the rat foot sole epidermis after nerve injury

    NARCIS (Netherlands)

    L.S. Duraku (Liron); S.M. Hossaini (Mehdi); S. Hoendervangers (Sieske); H.E. Falke; S. Kambiz (Shoista); V. Mudera (Vivek); J.C. Holstege (Jan); E.T. Walbeehm (Erik); T.J.H. Ruigrok (Tom)

    2012-01-01

    textabstractThe 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

  18. Impact of morphometry, myelinization and synaptic current strength on spike conduction in human and cat spiral ganglion neurons.

    Directory of Open Access Journals (Sweden)

    Frank Rattay

    Full Text Available Our knowledge about the neural code in the auditory nerve is based to a large extent on experiments on cats. Several anatomical differences between auditory neurons in human and cat are expected to lead to functional differences in speed and safety of spike conduction.Confocal microscopy was used to systematically evaluate peripheral and central process diameters, commonness of myelination and morphology of spiral ganglion neurons (SGNs along the cochlea of three human and three cats. Based on these morphometric data, model analysis reveales that spike conduction in SGNs is characterized by four phases: a postsynaptic delay, constant velocity in the peripheral process, a presomatic delay and constant velocity in the central process. The majority of SGNs are type I, connecting the inner hair cells with the brainstem. In contrast to those of humans, type I neurons of the cat are entirely myelinated. Biophysical model evaluation showed delayed and weak spikes in the human soma region as a consequence of a lack of myelin. The simulated spike conduction times are in accordance with normal interwave latencies from auditory brainstem response recordings from man and cat. Simulated 400 pA postsynaptic currents from inner hair cell ribbon synapses were 15 times above threshold. They enforced quick and synchronous spiking. Both of these properties were not present in type II cells as they receive fewer and much weaker (∼26 pA synaptic stimuli.Wasting synaptic energy boosts spike initiation, which guarantees the rapid transmission of temporal fine structure of auditory signals. However, a lack of myelin in the soma regions of human type I neurons causes a large delay in spike conduction in comparison with cat neurons. The absent myelin, in combination with a longer peripheral process, causes quantitative differences of temporal parameters in the electrically stimulated human cochlea compared to the cat cochlea.

  19. Impact of Morphometry, Myelinization and Synaptic Current Strength on Spike Conduction in Human and Cat Spiral Ganglion Neurons

    Science.gov (United States)

    Rattay, Frank; Potrusil, Thomas; Wenger, Cornelia; Wise, Andrew K.; Glueckert, Rudolf; Schrott-Fischer, Anneliese

    2013-01-01

    Background Our knowledge about the neural code in the auditory nerve is based to a large extent on experiments on cats. Several anatomical differences between auditory neurons in human and cat are expected to lead to functional differences in speed and safety of spike conduction. Methodology/Principal Findings Confocal microscopy was used to systematically evaluate peripheral and central process diameters, commonness of myelination and morphology of spiral ganglion neurons (SGNs) along the cochlea of three human and three cats. Based on these morphometric data, model analysis reveales that spike conduction in SGNs is characterized by four phases: a postsynaptic delay, constant velocity in the peripheral process, a presomatic delay and constant velocity in the central process. The majority of SGNs are type I, connecting the inner hair cells with the brainstem. In contrast to those of humans, type I neurons of the cat are entirely myelinated. Biophysical model evaluation showed delayed and weak spikes in the human soma region as a consequence of a lack of myelin. The simulated spike conduction times are in accordance with normal interwave latencies from auditory brainstem response recordings from man and cat. Simulated 400 pA postsynaptic currents from inner hair cell ribbon synapses were 15 times above threshold. They enforced quick and synchronous spiking. Both of these properties were not present in type II cells as they receive fewer and much weaker (∼26 pA) synaptic stimuli. Conclusions/Significance Wasting synaptic energy boosts spike initiation, which guarantees the rapid transmission of temporal fine structure of auditory signals. However, a lack of myelin in the soma regions of human type I neurons causes a large delay in spike conduction in comparison with cat neurons. The absent myelin, in combination with a longer peripheral process, causes quantitative differences of temporal parameters in the electrically stimulated human cochlea compared to the cat

  20. Lentiviral-mediated transfer of CDNF promotes nerve regeneration and functional recovery after sciatic nerve injury in adult rats

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Lei; Liu, Yi; Zhao, Hua; Zhang, Wen; Guo, Ying-Jun; Nie, Lin, E-mail: chengleiyx@126.com

    2013-10-18

    Highlights: •CDNF was successfully transfected by a lentiviral vector into the distal sciatic nerve. •CDNF improved S-100, NF200 expression and nerve regeneration after sciatic injury. •CDNF improved the remyelination and thickness of the regenerated sciatic nerve. •CDNF improved gastrocnemius muscle weight and sciatic functional recovery. -- Abstract: Peripheral nerve injury is often followed by incomplete and unsatisfactory functional recovery and may be associated with sensory and motor impairment of the affected limb. Therefore, a novel method is needed to improve the speed of recovery and the final functional outcome after peripheral nerve injuries. This report investigates the effect of lentiviral-mediated transfer of conserved dopamine neurotrophic factor (CDNF) on regeneration of the rat peripheral nerve in a transection model in vivo. We observed notable overexpression of CDNF protein in the distal sciatic nerve after recombinant CDNF lentiviral vector application. We evaluated sciatic nerve regeneration after surgery using light and electron microscopy and the functional recovery using the sciatic functional index and target muscle weight. HE staining revealed better ordered structured in the CDNF-treated group at 8 weeks post-surgery. Quantitative analysis of immunohistochemistry of NF200 and S-100 in the CDNF group revealed significant improvement of axonal and Schwann cell regeneration compared with the control groups at 4 weeks and 8 weeks after injury. The thickness of the myelination around the axons in the CDNF group was significantly higher than in the control groups at 8 weeks post-surgery. The CDNF group displayed higher muscle weights and significantly increased sciatic nerve index values. Our findings suggest that CDNF gene therapy could provide durable and stable CDNF protein concentration and has the potential to enhance peripheral nerve regeneration, morphological and functional recovery following nerve injury, which suggests a

  1. Lentiviral-mediated transfer of CDNF promotes nerve regeneration and functional recovery after sciatic nerve injury in adult rats

    International Nuclear Information System (INIS)

    Cheng, Lei; Liu, Yi; Zhao, Hua; Zhang, Wen; Guo, Ying-Jun; Nie, Lin

    2013-01-01

    Highlights: •CDNF was successfully transfected by a lentiviral vector into the distal sciatic nerve. •CDNF improved S-100, NF200 expression and nerve regeneration after sciatic injury. •CDNF improved the remyelination and thickness of the regenerated sciatic nerve. •CDNF improved gastrocnemius muscle weight and sciatic functional recovery. -- Abstract: Peripheral nerve injury is often followed by incomplete and unsatisfactory functional recovery and may be associated with sensory and motor impairment of the affected limb. Therefore, a novel method is needed to improve the speed of recovery and the final functional outcome after peripheral nerve injuries. This report investigates the effect of lentiviral-mediated transfer of conserved dopamine neurotrophic factor (CDNF) on regeneration of the rat peripheral nerve in a transection model in vivo. We observed notable overexpression of CDNF protein in the distal sciatic nerve after recombinant CDNF lentiviral vector application. We evaluated sciatic nerve regeneration after surgery using light and electron microscopy and the functional recovery using the sciatic functional index and target muscle weight. HE staining revealed better ordered structured in the CDNF-treated group at 8 weeks post-surgery. Quantitative analysis of immunohistochemistry of NF200 and S-100 in the CDNF group revealed significant improvement of axonal and Schwann cell regeneration compared with the control groups at 4 weeks and 8 weeks after injury. The thickness of the myelination around the axons in the CDNF group was significantly higher than in the control groups at 8 weeks post-surgery. The CDNF group displayed higher muscle weights and significantly increased sciatic nerve index values. Our findings suggest that CDNF gene therapy could provide durable and stable CDNF protein concentration and has the potential to enhance peripheral nerve regeneration, morphological and functional recovery following nerve injury, which suggests a

  2. High-frequency electrical stimulation can be a complementary therapy to promote nerve regeneration in diabetic rats.

    Directory of Open Access Journals (Sweden)

    Chia-Hong Kao

    Full Text Available The purpose of this study was to evaluate whether 1 mA of percutaneous electrical stimulation (ES at 0, 2, 20, or 200 Hz augments regeneration between the proximal and distal nerve stumps in streptozotocin diabetic rats. A10-mm gap was made in the diabetic rat sciatic nerve by suturing the stumps into silicone rubber tubes. Normal animals were used as the controls. Starting 1 week after transection, ES was applied between the cathode placed at the distal stump and the anode at the proximal stump every other day for 3 weeks. At 4 weeks after surgery, the normal controls and the groups receiving ES at 20, and 200 Hz had a higher success percentage of regeneration compared to the ES groups at 0 and 2 Hz. In addition, quantitative histology of the successfully regenerated nerves revealed that the groups receiving ES at a higher frequency, especially at 200 Hz, had a more mature structure with more myelinated fibers compared to those in the lower-frequency ES groups. Similarly, electrophysiology in the ES group at 200 Hz showed significantly shorter latency, larger amplitude, larger area of evoked muscle action potentials and faster conduction velocity compared to other groups. Immunohistochemical staining showed that ES at a higher frequency could significantly promote calcitonin gene-related peptide expression in lamina I-II regions in the dorsal horn and recruit a higher number of macrophages in the diabetic distal sciatic nerve. The macrophages were found that they could stimulate the secretion of nerve growth factor, platelet-derived growth factor, and transforming growth factor-β in dissected sciatic nerve segments. The ES at a higher frequency could also increase cutaneous blood flow in the ipsilateral hindpaw to the injury. These results indicated that a high-frequency ES could be necessary to heal severed diabetic peripheral nerve with a long gap to be repaired.

  3. Analysis of Caribbean ciguatoxin-1 effects on frog myelinated axons and the neuromuscular junction.

    Science.gov (United States)

    Mattei, César; Marquais, Michel; Schlumberger, Sébastien; Molgó, Jordi; Vernoux, Jean-Paul; Lewis, Richard J; Benoit, Evelyne

    2010-10-01

    Caribbean ciguatoxin-1 (C-CTX-1) induced, after about 1h exposure, muscle membrane depolarisation and repetitive post-synaptic action potentials (APs) in frog neuromuscular preparations. This depolarising effect was also observed in a Ca(2+)-free medium with a strong enhancement of spontaneous quantal transmitter release, compared with control conditions. The ciguatoxin-induced increase in release could be accelerated when Ca(2+) was present in the extracellular medium. C-CTX-1 also enhanced nerve-evoked quantal acetylcholine (ACh) release. At normal neuromuscular junctions loaded with the fluorescent dye FM1-43, C-CTX-1 induced swelling of nerve terminals, an effect that was reversed by hyperosmotic d-mannitol. In myelinated axons, C-CTX-1 increased nodal membrane excitability, inducing spontaneous and repetitive APs. Also, the toxin enlarged the repolarising phase of APs in control and tetraethylammonium-treated axons. Overall, our data suggest that C-CTX-1 affects nerve excitability and neurotransmitter release at nerve terminals. We conclude that C-CTX-1-induced up-regulation of Na(+) channels and the inhibition of K(+) channels, at low nanomolar concentrations, produce a variety of functional dysfunctions that are in part responsible for the human muscle skeletal symptoms observed in ciguatera. All these dysfunctions seem to result from the subtle balance between ionic currents, intracellular Na(+) and Ca(2+) concentrations, and engaged second messengers. Copyright 2009 Elsevier Ltd. All rights reserved.

  4. 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 ...

  5. Identification of a novel mutation in the PTCH gene in a patient with Gorlin-Goltz syndrome with unusual ocular disorders.

    Science.gov (United States)

    Romano, Mary; Iacovello, Daniela; Cascone, Nikhil C; Contestabile, Maria Teresa

    2011-01-01

    To document the clinical, functional, and in vivo microanatomic characteristics of a patient with Gorlin-Goltz syndrome with a novel nonsense mutation in PTCH (patched). Optical coherence tomography (OCT), fluorescein angiography, electrophysiologic testing, visual field, magnetic resonance imaging, and mutation screening of PTCH gene. Visual acuity was 20/20 in the right eye and 20/25 in the left. Fundus examination revealed myelinated nerve fibers in the left eye and bilateral epiretinal membranes with lamellar macular hole also documented with macular OCT. A reduction of the retinal nerve fiber layers in both eyes was found with fiber nervous OCT. Fluorescein angiography showed bilaterally foveal hyperfluorescence and the visual field revealed inferior hemianopia in the right eye. Pattern visual evoked potentials registered a reduction of amplitude in both eyes and latency was delayed in the left eye. Pattern electroretinogram showed a reduction in P50 and N95 peak time and a delay in P50 peak time in the left eye. Flash electroretinogram was reduced in rod response, maximal response, and oscillatory potentials in both eyes. Cone response was normal and 30-Hz flicker was slightly reduced in both eyes. Mutation screening identified a novel nonsense mutation in PTCH. A novel nonsense mutation in the PTCH gene was found. We report the occurrence of epiretinal membranes and the persistence of myelinated nerve fibers. Electrophysiologic and visual field alterations, supporting a neuroretinal dysfunction, were also documented.

  6. 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.

  7. Vascularized nerve grafts: an experimental study.

    Science.gov (United States)

    Donzelli, Renato; Capone, Crescenzo; Sgulò, Francesco Giovanni; Mariniello, Giuseppe; Maiuri, Francesco

    2016-08-01

    The aim of this study is to define an experimental model in order to promote the functional recovery of the nerves using grafts with vascular support (Vascular Nerve Grafts - VNG). The aim of this study is to define, on an experimental model in normal recipient bed, whether the functional recovery with VNG is superior to that obtained non-vascularized graft (NNG). Twenty male rabbits, which underwent dissection of sciatic nerve, were later treated by reinnervation through an autograft. In 10 animals the reconstruction of sciatic nerve was realized with VNG; in 10 control animals the reconstruction of sciatic nerve was realized with NNG. The VNG group showed a better axonal organization and a significantly higher number of regenerated axons in the early phases (after 30 days) than the NNG group, whereas the difference in the axonal number at day 90 was less significant; besides, the axon diameter and the myelin thickness were not significantly improved by VNG group. Our data suggests that the use of VNG leads to a faster regeneration process and a better functional recovery, although the final results are comparable to those of the NNG. VNG improve the quality of the axonal regeneration (axonal diameter and Schwann cells), although the increase in the axonal number is not significant and does not improve the long-term functional outcome.

  8. 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

  9. Sustained Expression of Negative Regulators of Myelination Protects Schwann Cells from Dysmyelination in a Charcot-Marie-Tooth 1B Mouse Model.

    Science.gov (United States)

    Florio, Francesca; Ferri, Cinzia; Scapin, Cristina; Feltri, M Laura; Wrabetz, Lawrence; D'Antonio, Maurizio

    2018-05-02

    Schwann cell differentiation and myelination in the PNS are the result of fine-tuning of positive and negative transcriptional regulators. As myelination starts, negative regulators are downregulated, whereas positive ones are upregulated. Fully differentiated Schwann cells maintain an extraordinary plasticity and can transdifferentiate into "repair" Schwann cells after nerve injury. Reactivation of negative regulators of myelination is essential to generate repair Schwann cells. Negative regulators have also been implicated in demyelinating neuropathies, although their role in disease remains elusive. Here, we used a mouse model of Charcot-Marie-Tooth neuropathy type 1B (CMT1B), the P0S63del mouse characterized by ER stress and the activation of the unfolded protein response, to show that adult Schwann cells are in a partial differentiation state because they overexpress transcription factors that are normally expressed only before myelination. We provide evidence that two of these factors, Sox2 and Id2, act as negative regulators of myelination in vivo However, their sustained expression in neuropathy is protective because ablation of Sox2 or/and Id2 from S63del mice of both sexes results in worsening of the dysmyelinating phenotype. This is accompanied by increased levels of mutant P0 expression and exacerbation of ER stress, suggesting that limited differentiation may represent a novel adaptive mechanism through which Schwann cells counter the toxic effect of a mutant terminal differentiation protein. SIGNIFICANCE STATEMENT In many neuropathies, Schwann cells express high levels of early differentiation genes, but the significance of these altered expression remained unclear. Because many of these factors may act as negative regulators of myelination, it was suggested that their misexpression could contribute to dysmyelination. Here, we show that the transcription factors Sox2 and Id2 act as negative regulators of myelination in vivo , but that their sustained

  10. Abundant extracellular myelin in the meninges of patients with multiple sclerosis.

    Science.gov (United States)

    Kooi, E-J; van Horssen, J; Witte, M E; Amor, S; Bø, L; Dijkstra, C D; van der Valk, P; Geurts, J J G

    2009-06-01

    In multiple sclerosis (MS) myelin debris has been observed within MS lesions, in cerebrospinal fluid and cervical lymph nodes, but the route of myelin transport out of the brain is unknown. Drainage of interstitial fluid from the brain parenchyma involves the perivascular spaces and leptomeninges, but the presence of myelin debris in these compartments has not been described. To determine whether myelin products are present in the meninges and perivascular spaces of MS patients. Formalin-fixed brain tissue containing meninges from 29 MS patients, 9 non-neurological controls, 6 Alzheimer's disease, 5 stroke, 5 meningitis and 7 leucodystrophy patients was investigated, and immunohistochemically stained for several myelin proteins [proteolipid protein (PLP), myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG) and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase)]. On brain material from MS patients and (non)neurological controls, PLP immunostaining was used to systematically investigate the presence of myelin debris in the meninges, using a semiquantitative scale. Extensive extracellular presence of myelin particles, positive for PLP, MBP, MOG and CNPase in the leptomeninges of MS patients, was observed. Myelin particles were also observed in perivascular spaces of MS patients. Immunohistochemical double-labelling for macrophage and dendritic cell markers and PLP confirmed that the vast majority of myelin particles were located extracellularly. Extracellular myelin particles were virtually absent in meningeal tissue of non-neurological controls, Alzheimer's disease, stroke, meningitis and leucodystrophy cases. In MS leptomeninges and perivascular spaces, abundant extracellular myelin can be found, whereas this is not the case for controls and other neurological disease. This may be relevant for understanding sustained immunogenicity or, alternatively, tolerogenicity in MS.

  11. Confocal mapping of myelin figures with micro-Raman spectroscopy

    Science.gov (United States)

    Huang, Jung-Ren; Cheng, Yu-Che; Huang, Hung Ji; Chiang, Hai-Pang

    2018-01-01

    We employ confocal micro-Raman spectroscopy (CMRS) with submicron spatial resolution to study the myelin structures (cylindrical lamellae) composed of nested surfactant C12E3 or lipid DMPC bilayers. The CMRS mapping indicates that for a straight C12E3 myelin, the surfactant concentration increases with the myelin width and is higher in the center region than in the peripheral region. For a curved C12E3 myelin, the convex side has a higher surfactant concentration than the corresponding concave side. The spectrum of DMPC myelins undergoes a qualitative change as the temperature increases above 60 °C, suggesting that the surfactant molecules may be damaged. Our work demonstrates the utility of CMRS in bio-soft material research.

  12. An electron microscopic study of intraepithelial nerves of oral mucosa of rats during aging

    International Nuclear Information System (INIS)

    Choi, Dai Ho; You, Dong Soo

    1984-01-01

    Observation made in this study bring home salient features that may contribute towards a better understanding of the relationship between the available physiologic data and anatomical characteristics of those nerve fibers that penetrate into the intraepithelial space in the oral cavity. The present investigation characterized the fine structure of nerve fibers in oral mucosae with respect to the manner in which presumed sensory fibers enter into the intraepithelial space by penetration of the basal lamina. The conclusions were made little discernible qualitative difference exists between young and old animals, concerning the fine structural characteristics of nerve fibers and nerve endings and in old animals, significant reductions exist in the number of neural elements in the intraepithelial space.

  13. Cranial nerve contrast using nerve-specific fluorophores improved by paired-agent imaging with indocyanine green as a control agent

    Science.gov (United States)

    Torres, Veronica C.; Vuong, Victoria D.; Wilson, Todd; Wewel, Joshua; Byrne, Richard W.; Tichauer, Kenneth M.

    2017-09-01

    Nerve preservation during surgery is critical because damage can result in significant morbidity. This remains a challenge especially for skull base surgeries where cranial nerves (CNs) are involved because visualization and access are particularly poor in that location. We present a paired-agent imaging method to enhance identification of CNs using nerve-specific fluorophores. Two myelin-targeting imaging agents were evaluated, Oxazine 4 and Rhodamine 800, and coadministered with a control agent, indocyanine green, either intravenously or topically in rats. Fluorescence imaging was performed on excised brains ex vivo, and nerve contrast was evaluated via paired-agent ratiometric data analysis. Although contrast was improved among all experimental groups using paired-agent imaging compared to conventional, solely targeted imaging, Oxazine 4 applied directly exhibited the greatest enhancement, with a minimum 3 times improvement in CNs delineation. This work highlights the importance of accounting for nonspecific signal of targeted agents, and demonstrates that paired-agent imaging is one method capable of doing so. Although staining, rinsing, and imaging protocols need to be optimized, these findings serve as a demonstration for the potential use of paired-agent imaging to improve contrast of CNs, and consequently, surgical outcome.

  14. Scaffoldless tissue-engineered nerve conduit promotes peripheral nerve regeneration and functional recovery after tibial nerve injury in rats

    Institute of Scientific and Technical Information of China (English)

    Aaron M. Adams; Keith W. VanDusen; Tatiana Y. Kostrominova; Jacob P. Mertens; Lisa M. Larkin

    2017-01-01

    Damage to peripheral nerve tissue may cause loss of function in both the nerve and the targeted muscles it innervates. This study compared the repair capability of engineered nerve conduit (ENC), engineered fibroblast conduit (EFC), and autograft in a 10-mm tibial nerve gap. ENCs were fabricated utilizing primary fibroblasts and the nerve cells of rats on embryonic day 15 (E15). EFCs were fabricated utilizing primary fi-broblasts only. Following a 12-week recovery, nerve repair was assessed by measuring contractile properties in the medial gastrocnemius muscle, distal motor nerve conduction velocity in the lateral gastrocnemius, and histology of muscle and nerve. The autografts, ENCs and EFCs reestablished 96%, 87% and 84% of native distal motor nerve conduction velocity in the lateral gastrocnemius, 100%, 44% and 44% of native specific force of medical gastrocnemius, and 63%, 61% and 67% of native medial gastrocnemius mass, re-spectively. Histology of the repaired nerve revealed large axons in the autograft, larger but fewer axons in the ENC repair, and many smaller axons in the EFC repair. Muscle histology revealed similar muscle fiber cross-sectional areas among autograft, ENC and EFC repairs. In conclusion, both ENCs and EFCs promot-ed nerve regeneration in a 10-mm tibial nerve gap repair, suggesting that the E15 rat nerve cells may not be necessary for nerve regeneration, and EFC alone can suffice for peripheral nerve injury repair.

  15. Alteração da camada de fibras nervosas da retina em usuários crônicos de cloroquina Retinal nerve fiber layer alteration in chronic users of chloroquine

    Directory of Open Access Journals (Sweden)

    Daniela de Almeida Lyra Antunes

    2005-04-01

    Full Text Available OBJETIVOS: Avaliar a camada de fibras nervosas da retina (CFN por meio da polarimetria a laser, em pacientes em uso crônico de cloroquina. MÉTODOS: Foram estudados 44 olhos de 22 pacientes em uso de cloroquina por doenças reumatológicas, por pelo menos um ano. Como controle, foram incluídos vinte indivíduos sem uso de cloroquina com idade, gênero e raça similares. Foram excluídos os pacientes que apresentavam história familiar de hipertensão ocular ou glaucoma. Ambos os olhos foram submetidos à análise da camada de fibras nervosas da retina, com o aparelho GDx® Nerve Fiber Analyser, pelo mesmo examinador. RESULTADOS: Nos usuários crônicos de cloroquina, verificou-se alteração em mais de dois parâmetros do GDx em 28 olhos (63,6%. Ocorreu também alteração no gráfico "Deviation from normal" com perda de fibras nervosas em 11 olhos (25%. Quando comparado com o grupo controle, os parâmetros que demonstraram diferença estatisticamente significante foram: Superior Ratio, Inferior Ratio, Superior Nasal, Elipse Modulation, The Number, Superior Average e Superior Integral. Houve também associação estatisticamente significante entre o tempo de uso de cloroquina e perda da CFN. CONCLUSÕES: Comprovou-se a associação entre o uso crônico da cloroquina e a alteração da CFN detectada pelo GDx. Desta forma, esses resultados podem contribuir para o diagnóstico precoce da perda de fibras nervosas na retinopatia por cloroquina.PURPOSES: To evaluate the retina nerve fiber layer by laser polarimetry in patients in chronic use of chloroquine. METHODS: Forty-four eyes of twenty-two patients were studied. These were in use of chloroquine due to rheumatic diseases during at least one year. As a control group, twenty patients without use of chloroquine with similar characteristics (age, gender and race were included. Patients who had a family history of ocular hypertension or glaucoma were not included in this group. Both eyes were

  16. Waveform efficiency analysis of auditory nerve fiber stimulation for cochlear implants

    International Nuclear Information System (INIS)

    Navaii, Mehdi Lotfi; Sadhedi, Hamed; Jalali, Mohsen

    2013-01-01

    Evaluation of the electrical stimulation efficiency of various stimulating waveforms is an important issue for efficient neural stimulator design. Concerning the implantable micro devices design, it is also necessary to consider the feasibility of hardware implementation of the desired waveforms. In this paper, the charge, power and energy efficiency of four waveforms (i.e. square, rising ramp, triangular and rising ramp-decaying exponential) in various durations have been simulated and evaluated based on the computational model of the auditory nerve fibers. Moreover, for a fair comparison of their feasibility, a fully integrated current generator circuit has been developed so that the desired stimulating waveforms can be generated. The simulation results show that stimulation with the square waveforms is a proper choice in short and intermediate durations while the rising ramp-decaying exponential or triangular waveforms can be employed for long durations.

  17. Estrogen replacement avoids the decrease of bladder innervations in ovariectomized adult virgin rats: in vivo stereological study.

    Science.gov (United States)

    de Fraga, Rogerio; Palma, Paulo; Dambros, Miriam; Riccetto, Cassio L Z; Mandarim-de-Lacerda, Carlos; Miyaoka, Ricardo

    2009-05-01

    The authors quantified the nerve fibers in the bladder wall of ovariectomized rats with and without estradiol replacement. This study was conducted on 40 Wistar rats (3 months old). Group 1: remained intact; Group 2: underwent bilateral ovariectomy, and after 30 days was started on subcutaneous sesame oil replacement (0.2 ml per day) for 90 days; Group 3: sham-operated, and after 30 days was started on subcutaneous sesame oil replacement (0.2 ml per day) for 90 days; Group 4: bilateral ovariectomy, and after 30 days was started on subcutaneous injection of 17β-estradiol (10 μg/kg body weight) for 90 days. S-100 was used to stain nerves myelinized fibers on paraffin rat bladder sections. The G-50 grid system was used to quantitatively analyze the fibers. Long-term estrogen deprivation caused significant changes in bladder innervations, which can be characterized by a decreased number of nerve fibers by 65% (p < 0.001).

  18. 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.

  19. Activation of MAPK overrides the termination of myelin growth and replaces Nrg1/ErbB3 signals during Schwann cell development and myelination

    NARCIS (Netherlands)

    M.E. Sheean (Maria); E. McShane (Erik); C. Cheret (Cyril); J. Walcher (Jan); T. Müller (Thomas); A. Wulf-Goldenberg (Annika); S. Hoelper (Soraya); A.N. Garratt (Alistair); M. Krüger (Markus); K. Rajewsky (Klaus); D.N. Meijer (Dies); W. Birchmeier (Walter); G.R. Lewin (Gary); M. Selbach (Matthias); C. Birchmeier (Carmen)

    2014-01-01

    textabstractMyelination depends on the synthesis of large amounts of myelin transcripts and proteins and is controlled by Nrg1/ErbB/Shp2 signaling. We developed a novel pulse labeling strategy based on stable isotope labeling with amino acids in cell culture (SILAC) to measure the dynamics of myelin

  20. Schwann Cell Precursors from Human Pluripotent Stem Cells as a Potential Therapeutic Target for Myelin Repair.

    Science.gov (United States)

    Kim, Han-Seop; Lee, Jungwoon; Lee, Da Yong; Kim, Young-Dae; Kim, Jae Yun; Lim, Hyung Jin; Lim, Sungmin; Cho, Yee Sook

    2017-06-06

    Schwann cells play a crucial role in successful nerve repair and regeneration by supporting both axonal growth and myelination. However, the sources of human Schwann cells are limited both for studies of Schwann cell development and biology and for the development of treatments for Schwann cell-associated diseases. Here, we provide a rapid and scalable method to produce self-renewing Schwann cell precursors (SCPs) from human pluripotent stem cells (hPSCs), using combined sequential treatment with inhibitors of the TGF-β and GSK-3 signaling pathways, and with neuregulin-1 for 18 days under chemically defined conditions. Within 1 week, hPSC-derived SCPs could be differentiated into immature Schwann cells that were functionally confirmed by their secretion of neurotrophic factors and their myelination capacity in vitro and in vivo. We propose that hPSC-derived SCPs are a promising, unlimited source of functional Schwann cells for treating demyelination disorders and injuries to the peripheral nervous system. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  1. 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

  2. Pannexin 1 Modulates Axonal Growth in Mouse Peripheral Nerves

    Directory of Open Access Journals (Sweden)

    Steven M. Horton

    2017-11-01

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

  3. The effects of FK1706 on nerve regeneration and bladder function recovery following an end-to-side neurorrhaphy in rats.

    Science.gov (United States)

    Gao, Wansheng; He, Xiangfei; Li, Yunlong; Wen, Jianguo

    2017-11-07

    Immunophilin ligands are neuroregenerative agents binding to FK506 binding proteins, by which stimulate recovery of neurons in a variety of injury nerves. FK1706 is a novel immunophilin ligand which has neuroprotective and neuroregenerative effects but without immunosuppressive activity. At present, most reports about FK1706 in ameliorating nerve injury and functional recovery are limited to cavernous nerve injury and erectile function recovery. This study aimed to demonstrate the effects of FK1706 on nerve regeneration and bladder function recovery following an end-to-side neurorrhaphy in rat models. The numbers of regenerated myelinated axons of the pelvic parasympathetic nerve (PPN) in the three groups' rats (FK1706 + ETS, ETS and control groups) were evaluated. Their intravesical pressure (IVP), S100β and growth associated protein 43 (GAP43) expressions were also compared. In FK1706 + ETS group, 90% the rats showed that the frequency of FG labeled neurons was larger than the 3.5 cutoff value, 100% the rats showed that the frequency of FG-FB double-labeled neurons was larger than the 5.5 cutoff value. The average maximum of IVP in FK1706 + ETS group reached 76.3% of the value in control group. Their average number of myelinated axons of regenerated PPN reached 80% of the amount in control group. The nerve regeneration-associated markers data indicated that the expression level of S100β and GAP43 in FK1706 + ETS group was approximately 2-fold higher than that of ETS group (P side neurorrhaphy, FK1706 effectively enhanced the nerve regeneration and bladder function recovery.

  4. Chronic inorganic mercury induced peripheral neuropathy

    Energy Technology Data Exchange (ETDEWEB)

    Chu, C.-C.; Huang, C.-C.; Ryu, S.-J. [Chang Gung Memorial Hospital and Chang Gung University, Dept. of Neurology, Tapei (Taiwan, Province of China); Wu, T.-N. [Executive Yuan, Dept. of Health, Surveillance and Quarantine Service, Taipei (Taiwan, Province of China)

    1998-12-01

    We report the clinical features, electrophysiological studies, and morphometric analysis of sural nerve pathology in a patient with polyneuropathy due to inorganic mercury intoxication. He developed slowly progressive generalized paralysis of all limbs after 3 months ingestion of herb drugs which contained mercuric sulfate. Electrophysiologic studies revealed axonal polyneuropathy involving both motor and sensory fibers. Sural nerve biopsy demonstrated axonal degeneration with demyelination and a predominant loss of large myelinated fibers. His muscle strength showed only mild improvement after 2 years` follow-up. We concluded that inorganic mercury exposure may induce severe axonal sensorimotor polyneuropathy in humans and that neurological deficits may persist in severe cases. (au) 21 refs.

  5. Bipolar electrocautery: A rodent model of Sunderland third-degree nerve injury.

    Science.gov (United States)

    Moradzadeh, Arash; Brenner, Michael J; Whitlock, Elizabeth L; Tong, Alice Y; Luciano, Janina P; Hunter, Daniel A; Myckatyn, Terence M; Mackinnon, Susan E

    2010-01-01

    To determine the Sunderland classification of a bipolar electrocautery injury. Twenty-two rats received crush (a reproducible Sunderland second-degree injury) or bipolar electrocautery injury and were evaluated for functional, histomorphometric, and immunohistochemical recovery at 21 or 42 days. Animal experiments were performed between July 3 and December 12, 2007. Axonal regeneration and end plate reinnervation were evaluated in double transgenic cyan fluorescent protein-conjugated Thy1 and green fluorescent protein-conjugated S100 mice. Compared with crush injury, bipolar electrocautery injury caused greater disruption of myelin and neurofilament architecture at the injury site and decreased nerve fiber counts and percentage of neural tissue distal to the injury (P =.007). Complete functional recovery was seen after crush but not bipolar electrocautery injury. Serial live imaging demonstrated axonal regeneration at week 1 after crush and at week 3 after bipolar electrocautery injury. Qualitative assessment of motor end plate reinnervation at 42 days demonstrated complete neuromuscular end plate reinnervation in the crush group and only limited reinnervation in the bipolar electrocautery group. Bipolar electrocautery injury in a rodent model resulted in a Sunderland third-degree injury, characterized by gradual, incomplete recovery without intervention.

  6. 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. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Compound sensory action potential in normal and pathological human nerves

    DEFF Research Database (Denmark)

    Krarup, Christian

    2004-01-01

    The compound sensory nerve action potential (SNAP) is the result of phase summation and cancellation of single fiber potentials (SFAPs) with amplitudes that depend on fiber diameter, and the amplitude and shape of the SNAP is determined by the distribution of fiber diameters. Conduction velocities...... dispersion over increasing conduction distance is greater for the SNAP than CMAP, and demonstration of conduction block is therefore difficult. In addition, the effect of temporal dispersion on amplitude and shape is strongly dependent on the number of conducting fibers and their distribution, and......, with fiber loss or increased conduction velocity variability changes of the SNAP may be smaller than expected from normal nerve. The biophysical characteristics of sensory and motor fibers differ, and this may to some extent determine divergent pathophysiological changes in sensory and motor fibers...

  8. The visceromotor and somatic afferent nerves of the penis.

    Science.gov (United States)

    Diallo, Djibril; Zaitouna, Mazen; Alsaid, Bayan; Quillard, Jeanine; Ba, Nathalie; Allodji, Rodrigue Sètchéou; Benoit, Gérard; Bedretdinova, Dina; Bessede, Thomas

    2015-05-01

    Innervation of the penis supports erectile and sensory functions. This article aims to study the efferent autonomic (visceromotor) and afferent somatic (sensory) nervous systems of the penis and to investigate how these systems relate to vascular pathways. Penises obtained from five adult cadavers were studied via computer-assisted anatomic dissection (CAAD). The number of autonomic and somatic nerve fibers was compared using the Kruskal-Wallis test. Proximally, penile innervation was mainly somatic in the extra-albugineal sector and mainly autonomic in the intracavernosal sector. Distally, both sectors were almost exclusively supplied by somatic nerve fibers, except the intrapenile vascular anastomoses that accompanied both somatic and autonomic (nitrergic) fibers. From this point, the neural immunolabeling within perivascular nerve fibers was mixed (somatic labeling and autonomic labeling). Accessory afferent, extra-albugineal pathways supplied the outer layers of the penis. There is a major change in the functional type of innervation between the proximal and distal parts of the intracavernosal sector of the penis. In addition to the pelvis and the hilum of the penis, the intrapenile neurovascular routes are the third level where the efferent autonomic (visceromotor) and the afferent somatic (sensory) penile nerve fibers are close. Intrapenile neurovascular pathways define a proximal penile segment, which guarantees erectile rigidity, and a sensory distal segment. © 2015 International Society for Sexual Medicine.

  9. Quantification of retinal nerve fiber layer thickness using spectral domain optical coherence tomography in normal Indian population

    Directory of Open Access Journals (Sweden)

    Tarannum Mansoori

    2012-01-01

    Full Text Available The purpose of this study was to measure peripapillary retinal nerve fiber layer thickness (RNFLT using spectral domain optical coherence tomography (SD-OCT in normal Indian eyes, for which, 210 normal volunteers were recruited. One eye of each subject underwent RNFL scanning at 3.4 mm circle diameter around optic nerve using SD OCT. The data were analyzed to determine RNFLT in the sample population and its variation with age and gender. The average peripapillary RNFLT was 114.03 ± 9.59 μm. There was no effect of gender on RNFLT parameters. Age had significant negative correlation with average (P = 0.005, superior (P = 0.04, temporal (P = 0.049, and nasal quadrants (P = 0.01 RNFLT. Inferior quadrant RNFLT also had a negative correlation with age, but it was not statistically significant (P = 0.15.

  10. Whole mount preparation of the adult Drosophila ventral nerve cord for giant fiber dye injection.

    Science.gov (United States)

    Boerner, Jana; Godenschwege, Tanja A

    2011-06-04

    To analyze the axonal and dendritic morphology of neurons, it is essential to obtain accurate labeling of neuronal structures. Preparing well labeled samples with little to no tissue damage enables us to analyze cell morphology and to compare individual samples to each other, hence allowing the identification of mutant anomalies. In the demonstrated dissection method the nervous system remains mostly inside the adult fly. Through a dorsal incision, the abdomen and thorax are opened and most of the internal organs are removed. Only the dorsal side of the ventral nerve cord (VNC) and the cervical connective (CvC) containing the big axons of the giant fibers (GFs) are exposed, while the brain containing the GF cell body and dendrites remains in the intact head. In this preparation most nerves of the VNC should remain attached to their muscles. Following the dissection, the intracellular filling of the giant fiber (GF) with a fluorescent dye is demonstrated. In the CvC the GF axons are located at the dorsal surface and thus can be easily visualized under a microscope with differential interference contrast (DIC) optics. This allows the injection of the GF axons with dye at this site to label the entire GF including the axons and their terminals in the VNC. This method results in reliable and strong staining of the GFs allowing the neurons to be imaged immediately after filling with an epifluorescent microscope. Alternatively, the fluorescent signal can be enhanced using standard immunohistochemistry procedures suitable for high resolution confocal microscopy.

  11. Measurement of wavefront aberrations in cortex and peripheral nerve using a two-photon excitation guidestar

    Science.gov (United States)

    Futia, Gregory L.; Fontaine, Arjun; McCullough, Connor; Ozbay, Baris N.; George, Nickolas M.; Caldwell, John; Restrepo, Diego; Weir, Richard; Gibson, Emily A.

    2018-02-01

    Neural-machine interfaces using optogenetics are of interest due to their minimal invasiveness and potential for parallel read in and read out of activity. One possible biological target for such an interface is the peripheral nerve, where axonlevel imaging or stimulation could greatly improve interfacing with artificial limbs or enable neuron/fascicle level neuromodulation in the vagus nerve. Two-photon imaging has been successful in imaging brain activity using genetically encoded calcium or voltage indicators, but in the peripheral nerve, this is severely limited by scattering and aberrations from myelin. We employ a Shack-Hartman wavefront sensor and two-photon excitation guidestar to quantify optical scattering and aberrations in peripheral nerves and cortex. The sciatic and vagus nerves, and cortex from a ChAT-Cre ChR-eYFP transgenic mouse were excised and imaged directly. In peripheral nerves, defocus was the strongest aberration followed by astigmatism and coma. Peripheral nerve had orders of magnitude higher aberration compared with cortex. These results point to the potential of adaptive optics for increasing the depth of two-photon access into peripheral nerves.

  12. Electrospun micro- and nanofiber tubes for functional nervous regeneration in sciatic nerve transections

    Directory of Open Access Journals (Sweden)

    Amadio Stefano

    2008-04-01

    Full Text Available Abstract Background Although many nerve prostheses have been proposed in recent years, in the case of consistent loss of nervous tissue peripheral nerve injury is still a traumatic pathology that may impair patient's movements by interrupting his motor-sensory pathways. In the last few decades tissue engineering has opened the door to new approaches;: however most of them make use of rigid channel guides that may cause cell loss due to the lack of physiological local stresses exerted over the nervous tissue during patient's movement. Electrospinning technique makes it possible to spin microfiber and nanofiber flexible tubular scaffolds composed of a number of natural and synthetic components, showing high porosity and remarkable surface/volume ratio. Results In this study we used electrospun tubes made of biodegradable polymers (a blend of PLGA/PCL to regenerate a 10-mm nerve gap in a rat sciatic nerve in vivo. Experimental groups comprise lesioned animals (control group and lesioned animals subjected to guide conduits implantated at the severed nerve stumps, where the tubular scaffolds are filled with saline solution. Four months after surgery, sciatic nerves failed to reconnect the two stumps of transected nerves in the control animal group. In most of the treated animals the electrospun tubes induced nervous regeneration and functional reconnection of the two severed sciatic nerve tracts. Myelination and collagen IV deposition have been detected in concurrence with regenerated fibers. No significant inflammatory response has been found. Neural tracers revealed the re-establishment of functional neuronal connections and evoked potential results showed the reinnervation of the target muscles in the majority of the treated animals. Conclusion Corroborating previous works, this study indicates that electrospun tubes, with no additional biological coating or drug loading treatment, are promising scaffolds for functional nervous regeneration. They

  13. Vesicular glutamate release from central axons contributes to myelin damage.

    Science.gov (United States)

    Doyle, Sean; Hansen, Daniel Bloch; Vella, Jasmine; Bond, Peter; Harper, Glenn; Zammit, Christian; Valentino, Mario; Fern, Robert

    2018-03-12

    The axon myelin sheath is prone to injury associated with N-methyl-D-aspartate (NMDA)-type glutamate receptor activation but the source of glutamate in this context is unknown. Myelin damage results in permanent action potential loss and severe functional deficit in the white matter of the CNS, for example in ischemic stroke. Here, we show that in rats and mice, ischemic conditions trigger activation of myelinic NMDA receptors incorporating GluN2C/D subunits following release of axonal vesicular glutamate into the peri-axonal space under the myelin sheath. Glial sources of glutamate such as reverse transport did not contribute significantly to this phenomenon. We demonstrate selective myelin uptake and retention of a GluN2C/D NMDA receptor negative allosteric modulator that shields myelin from ischemic injury. The findings potentially support a rational approach toward a low-impact prophylactic therapy to protect patients at risk of stroke and other forms of excitotoxic injury.

  14. Nerve-Highlighting Fluorescent Contrast Agents for Image-Guided Surgery

    Directory of Open Access Journals (Sweden)

    Summer L. Gibbs-Strauss

    2011-03-01

    Full Text Available Nerve damage is the major morbidity of many surgeries, resulting in chronic pain, loss of function, or both. The sparing of nerves during surgical procedures is a vexing problem because surrounding tissue often obscures them. To date, systemically administered nerve-highlighting contrast agents that can be used for nerve-sparing image-guided surgery have not been reported. In the current study, physicochemical and optical properties of 4,4‘-[(2-methoxy-1,4-phenylenedi-(1E-2,1-ethenediyl]bis-benzenamine (BMB and a newly synthesized, red-shifted derivative 4-[(1E-2-[4-[(1E-2-[4-aminophenyl]ethenyl]-3-methoxyphenyl]ethenyl]-benzonitrile (GE3082 were characterized in vitro and in vivo. Both agents crossed the blood-nerve barrier and blood-brain barrier and rendered myelinated nerves fluorescent after a single systemic injection. Although both BMB and GE3082 also exhibited significant uptake in white adipose tissue, GE3082 underwent a hypsochromic shift in adipose tissue that provided a means to eliminate the unwanted signal using hyperspectral deconvolution. Dose and kinetic studies were performed in mice to determine the optimal dose and drug-imaging interval. The results were confirmed in rat and pig, with the latter used to demonstrate, for the first time, simultaneous fluorescence imaging of blood vessels and nerves during surgery using the FLARE™ (Fluorescence-Assisted Resection and Exploration imaging system. These results lay the foundation for the development of ideal nerve-highlighting fluorophores for image-guided surgery.

  15. Regeneration of Optic Nerve

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    Kwok-Fai So

    2011-05-01

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

  16. Anatomic assessment of sympathetic peri-arterial renal nerves in man.

    Science.gov (United States)

    Sakakura, Kenichi; Ladich, Elena; Cheng, Qi; Otsuka, Fumiyuki; Yahagi, Kazuyuki; Fowler, David R; Kolodgie, Frank D; Virmani, Renu; Joner, Michael

    2014-08-19

    Although renal sympathetic denervation therapy has shown promising results in patients with resistant hypertension, the human anatomy of peri-arterial renal nerves is poorly understood. The aim of our study was to investigate the anatomic distribution of peri-arterial sympathetic nerves around human renal arteries. Bilateral renal arteries were collected from human autopsy subjects, and peri-arterial renal nerve anatomy was examined by using morphometric software. The ratio of afferent to efferent nerve fibers was investigated by dual immunofluorescence staining using antibodies targeted for anti-tyrosine hydroxylase and anti-calcitonin gene-related peptide. A total of 10,329 nerves were identified from 20 (12 hypertensive and 8 nonhypertensive) patients. The mean individual number of nerves in the proximal and middle segments was similar (39.6 ± 16.7 per section and 39.9 ± 1 3.9 per section), whereas the distal segment showed fewer nerves (33.6 ± 13.1 per section) (p = 0.01). Mean subject-specific nerve distance to arterial lumen was greatest in proximal segments (3.40 ± 0.78 mm), followed by middle segments (3.10 ± 0.69 mm), and least in distal segments (2.60 ± 0.77 mm) (p renal sympathetic nerve fibers is lower in distal segments and dorsal locations. There is a clear predominance of efferent nerve fibers, with decreasing prevalence of afferent nerves from proximal to distal peri-arterial and renal parenchyma. Understanding these anatomic patterns is important for refinement of renal denervation procedures. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

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

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    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.

  18. The structural and functional role of myelin fast-migrating cerebrosides

    DEFF Research Database (Denmark)

    Podbielska, Maria; Levery, Steven B; Hogan, Edward L

    2011-01-01

    A family of neutral glycosphingolipids containing a 3-O-acetyl-sphingosine galactosylceramide (3-SAG) has been characterized. Seven new derivatives of galactosylceramide (GalCer), designated as fast-migrating cerebrosides (FMCs) by TLC retention factor, have been identified. The simplest compounds...... myelin lipid biomarkers coappear with GalCer during myelinogenesis and disappear along with GalCer in de- or dys-myelinating disorders. Myelin lipid antigens, including FMCs, are keys to myelin biology, opening the possibility of new and novel immune modulatory tools for treatment of autoimmune diseases...

  19. Nanoparticles carrying neurotrophin-3-modified Schwann cells promote repair of sciatic nerve defects.

    Science.gov (United States)

    Zong, Haibin; Zhao, Hongxing; Zhao, Yilei; Jia, Jingling; Yang, Libin; Ma, Chao; Zhang, Yang; Dong, Yuzhen

    2013-05-15

    Schwann cells and neurotrophin-3 play an important role in neural regeneration, but the secretion of neurotrophin-3 from Schwann cells is limited, and exogenous neurotrophin-3 is inactived easily in vivo. In this study, we have transfected neurotrophin-3 into Schwann cells cultured in vitro using nanoparticle liposomes. Results showed that neurotrophin-3 was successfully transfected into Schwann cells, where it was expressed effectively and steadily. A composite of Schwann cells transfected with neurotrophin-3 and poly(lactic-co-glycolic acid) biodegradable conduits was transplanted into rats to repair 10-mm sciatic nerve defects. Transplantation of the composite scaffold could restore the myoelectricity and wave amplitude of the sciatic nerve by electrophysiological examination, promote nerve axonal and myelin regeneration, and delay apoptosis of spinal motor neurons. Experimental findings indicate that neurotrophin-3 transfected Schwann cells combined with bridge grafting can promote neural regeneration and functional recovery after nerve injury.

  20. COMP-angiopoietin-1 recovers molecular biomarkers of neuropathy and improves vascularisation in sciatic nerve of ob/ob mice.

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    Joanna Kosacka

    Full Text Available BACKGROUND: Leptin-deficient ob/ob mice are a model of type 2 diabetes induced peripheral neuropathy. Ob/ob mice exhibit obesity, insulin resistance, hyperglycaemia, and alterations of peripheral nerve fibres and endoneural microvessels. Here we test the hypothesis that cartilage oligomeric matrix protein (COMP-Ang-1, a soluble and stabile form of Ang-1 which promotes angiogenesis and nerve growth, improves regeneration of nerve fibres and endoneural microvessels in ob/ob mice. METHODS AND FINDINGS: COMP-Ang-1 (100 ng/ml or NaCl were intraperitoneally (i.p. injected into male (N = 184, 3-month old, ob/ob or ob/+ mice for 7 and 21 days. We measured expression of Nf68, GAP43, Cx32, Cx26, Cx43, and TNFα in sciatic nerves using Western blot analysis. To investigate the inflammation in sciatic nerves, numbers of macrophages and T-cells were counted after immunofluorescence staining. In ultrathin section, number of myelinated/non-mylinated nerve fibers, g-ratio, the thickness of Schwann cell basal lamina and microvessel endothelium were investigated. Endoneural microvessels were reconstructed with intracardial FITC injection. Treatment with COMP-Ang-1 over 21 days significantly reduced fasting blood glucose and plasma cholesterol concentrations compared to saline treated ob/ob mice. In addition, COMP-Ang-1 treatment: 1 up-regulated expression of Nf68 and GAP43; 2 improved expression of gap junction proteins including connexin 32 and 26; 3 suppressed the expression of TNFα and Cx43 and 4 led to decreased macrophage and T-cell infiltration in sciatic nerve of ob/ob mice. The significant changes of sciatic nerve ultrastructure were not observed after 21-day long COMP-Ang-1 treatment. COMP-Ang-1 treated ob/ob mice displayed regeneration of small-diameter endoneural microvessels. Effects of COMP-Ang-1 corresponded to increased phosphorylation of Akt and p38 MAPK upon Tie-2 receptor. CONCLUSIONS: COMP-Ang-1 recovers molecular biomarkers of neuropathy

  1. Design of barrier coatings on kink-resistant peripheral nerve conduits

    Directory of Open Access Journals (Sweden)

    Basak Acan Clements

    2016-02-01

    Full Text Available Here, we report on the design of braided peripheral nerve conduits with barrier coatings. Braiding of extruded polymer fibers generates nerve conduits with excellent mechanical properties, high flexibility, and significant kink-resistance. However, braiding also results in variable levels of porosity in the conduit wall, which can lead to the infiltration of fibrous tissue into the interior of the conduit. This problem can be controlled by the application of secondary barrier coatings. Using a critical size defect in a rat sciatic nerve model, the importance of controlling the porosity of the nerve conduit walls was explored. Braided conduits without barrier coatings allowed cellular infiltration that limited nerve recovery. Several types of secondary barrier coatings were tested in animal studies, including (1 electrospinning a layer of polymer fibers onto the surface of the conduit and (2 coating the conduit with a cross-linked hyaluronic acid-based hydrogel. Sixteen weeks after implantation, hyaluronic acid-coated conduits had higher axonal density, displayed higher muscle weight, and better electrophysiological signal recovery than uncoated conduits or conduits having an electrospun layer of polymer fibers. This study indicates that braiding is a promising method of fabrication to improve the mechanical properties of peripheral nerve conduits and demonstrates the need to control the porosity of the conduit wall to optimize functional nerve recovery.

  2. Sulfatide levels correlate with severity of neuropathy in metachromatic leukodystrophy

    DEFF Research Database (Denmark)

    Dali, Christine I; Barton, Norman W; Farah, Mohamed H

    2015-01-01

    OBJECTIVE: Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal storage disorder due to deficient activity of arylsulfatase A (ASA) that causes accumulation of sulfatide and lysosulfatide. The disorder is associated with demyelination and axonal loss in the central and peripheral...... had a sensory-motor demyelinating neuropathy on electrophysiological testing, whereas two patients had normal studies. Sural nerve and CSF (lyso)sulfatide levels strongly correlated with abnormalities in electrophysiological parameters and large myelinated fiber loss in the sural nerve, but there were...

  3. Guinea pigs as an animal model for sciatic nerve injury

    Directory of Open Access Journals (Sweden)

    Malik Abu Rafee

    2017-01-01

    Full Text Available The overwhelming use of rat models in nerve regeneration studies is likely to induce skewness in treatment outcomes. To address the problem, this study was conducted in 8 adult guinea pigs of either sex to investigate the suitability of guinea pig as an alternative model for nerve regeneration studies. A crush injury was inflicted to the sciatic nerve of the left limb, which led to significant decrease in the pain perception and neurorecovery up to the 4th weak. Lengthening of foot print and shortening of toe spread were observed in the paw after nerve injury. A 3.49 ± 0.35 fold increase in expression of neuropilin 1 (NRP1 gene and 2.09 ± 0.51 fold increase in neuropilin 2 (NRP2 gene were recorded 1 week after nerve injury as compared to the normal nerve. Ratios of gastrocnemius muscle weight and volume of the experimental limb to control limb showed more than 50% decrease on the 30th day. Histopathologically, vacuolated appearance of the nerve was observed with presence of degenerated myelin debris in digestion chambers. Gastrocnemius muscle also showed degenerative changes. Scanning electron microscopy revealed loose and rough arrangement of connective tissue fibrils and presence of large spherical globules in crushed sciatic nerve. The findings suggest that guinea pigs could be used as an alternative animal model for nerve regeneration studies and might be preferred over rats due to their cooperative nature while recording different parameters.

  4. [Effect of meliae toosendan fructus on nerves system and its mechanism].

    Science.gov (United States)

    Xiang, Xiao-Xue; Tang, Da-Xuan; Xiong, Jing-Yue; Liang, Ya-Jun; Mu, Dao-Hua; Yang, Xiao-Wei; Hang, Min; Tan, Zheng-Huai

    2013-05-01

    To study the effect of the ethanol extract of stir-bake to yellowish Meliae Toosendan Fructus on nerve system and its mechanism. The effect of the ethanol extract on sensory nerve was carried out through ache models induced by hot board method and radiant heat stimulation method in mice. The thermalgesia liminal value was investigated. The effect of the ethanol extract on the A-delta fiber and C fiber was measured by electrical stimulation procedure. Motor nerve conduction velocity (NCV) was measured by indirect detection method in vivo. The pathology changes of the motor nerve were observed by transmission electron microscope and the silver stain test. The ethanol extract of Meliae Toosendan Fructus could increase the thermalgesia liminal value of mice and reduce the conduction velocity of motor nerves. Meanwhile, pathology results showed the changes of the fiber of motor nerve, including demyelination and the number of Schwann cells dropping. The ethanol extract of stir-bake to yellowish Meliae Toosendan Fructus can reduce the pain sensitivity of mice and slow down NCV, which may be related to decreasing of the number of Schwann cells.

  5. Omental pedicle transposition and suture repair of peripheral nerve ...

    African Journals Online (AJOL)

    Abu wael

    This study aimed to compare the effectiveness of omental pedicle transposition and ... Assessment of the nerve regeneration was based on functional (motor and sensory), ..... peripheral nerve fibers regenerating after crush, multiple crush, and.

  6. Endogenous phosphorylation of basic protein in myelin of varying degrees of compaction

    International Nuclear Information System (INIS)

    Schulz, P.; Moscarello, M.A.; Cruz, T.F.

    1988-01-01

    Fractions containing myelin of varying degrees of compaction were prepared from human white matter. Protein kinase activity in these fractions was measured by using both endogenous and exogenous myelin basic protein (MBP) as substrates. In both cases, less compact myelin fractions possessed higher levels of protein kinase activity than the compact myelin fraction. In addition, the specific activity of phosphorylated basic protein was greater in the loosely compacted fractions than in compact multilamellar myelin. When basic protein in compact myelin or the myelin fractions was phosphorylated by the endogenous kinase, approximately 70% of the [ 32 P]phosphate was incorporated at a single site, identified as Ser-102. The remaining 30% was found in three other minor sites. Electron microscopy of less compact myelin showed it was composed of fewer lamellae which correlated with a relative decrease in the proportion of cationic charge isomers (microheteromers) when MBP was subjected to gel electrophoresis at alkaline pH. The shift in charge microheterogeneity of basic protein to the less cationic isomers in the less compact myelin fractions correlated with an increase in protein kinase activity and a greater specific activity of phosphorylated basic protein

  7. Combining Quantitative Susceptibility Mapping with Automatic Zero Reference (QSM0) and Myelin Water Fraction Imaging to Quantify Iron-Related Myelin Damage in Chronic Active MS Lesions.

    Science.gov (United States)

    Yao, Y; Nguyen, T D; Pandya, S; Zhang, Y; Hurtado Rúa, S; Kovanlikaya, I; Kuceyeski, A; Liu, Z; Wang, Y; Gauthier, S A

    2018-02-01

    A hyperintense rim on susceptibility in chronic MS lesions is consistent with iron deposition, and the purpose of this study was to quantify iron-related myelin damage within these lesions as compared with those without rim. Forty-six patients had 2 longitudinal quantitative susceptibility mapping with automatic zero reference scans with a mean interval of 28.9 ± 11.4 months. Myelin water fraction mapping by using fast acquisition with spiral trajectory and T2 prep was obtained at the second time point to measure myelin damage. Mixed-effects models were used to assess lesion quantitative susceptibility mapping and myelin water fraction values. Quantitative susceptibility mapping scans were on average 6.8 parts per billion higher in 116 rim-positive lesions compared with 441 rim-negative lesions ( P quantitative susceptibility mapping values of both the rim and core regions ( P Quantitative susceptibility mapping scans and myelin water fraction in rim-positive lesions decreased from rim to core, which is consistent with rim iron deposition. Whole lesion myelin water fractions for rim-positive and rim-negative lesions were 0.055 ± 0.07 and 0.066 ± 0.04, respectively. In the mixed-effects model, rim-positive lesions had on average 0.01 lower myelin water fraction compared with rim-negative lesions ( P quantitative susceptibility mapping scan was negatively associated with follow-up myelin water fraction ( P Quantitative susceptibility mapping rim-positive lesions maintained a hyperintense rim, increased in susceptibility, and had more myelin damage compared with rim-negative lesions. Our results are consistent with the identification of chronic active MS lesions and may provide a target for therapeutic interventions to reduce myelin damage. © 2018 by American Journal of Neuroradiology.

  8. Structure-function relationships with spectral-domain optical coherence tomography retinal nerve fiber layer and optic nerve head measurements.

    Science.gov (United States)

    Pollet-Villard, Frédéric; Chiquet, Christophe; Romanet, Jean-Paul; Noel, Christian; Aptel, Florent

    2014-05-02

    To evaluate the regional structure-function relationship between visual field sensitivity and retinal nerve fiber layer (RNFL) thickness and optic nerve head (ONH) measurements using spectral-domain optical coherence tomography (SD-OCT). Prospective cross-sectional study conducted on patients with glaucoma, suspected glaucoma, and healthy subjects. Eyes were tested on Cirrus OCT and standard achromatic perimetry. RNFL thickness of 12 peripapillary 30° sectors, neuroretinal rim thickness extracted from 36 neuroretinal rim scans, and Bruch membrane opening minimum rim width (BMO-MRW)-a recently defined parameter-extracted from 36 neuroretinal rim scans were obtained. Correlations between peripapillary RNFL thickness, neuroretinal rim thickness, all six sectors of BMO-MRW, and visual field sensitivity in the six corresponding areas were evaluated using logarithmic regression analysis. Receiver operating curve areas were calculated for each RNFL, ONH, and macular ganglion cell analysis parameter. We included 142 eyes of 142 subjects. The correlations (r(2)) between RNFL thickness, Cirrus-based neuroretinal rim thickness, BMO-MRW and visual field sensitivity ranged from 0.07 to 0.60, 0.15 to 0.49, and 0.24 to 0.66, respectively. The structure-function correlations were stronger with BMO-MRW than with Cirrus-based neuroretinal rim thickness. The largest areas under the receiver operating curve were seen for rim area (0.926 [95% confidence interval 0.875, 0.977]; P function relationship was significantly stronger with BMO-MRW than other ONH SD-OCT parameters. The best diagnostic capabilities were seen with rim area and average RNFL.

  9. Postirradiation disturbances in peripheral nerve regeneration and role of free radical oxidation products in their occurrence

    International Nuclear Information System (INIS)

    Radlinskaya, V.N.; Zhutaev, I.A.; Bobyrev, V.N.; Voskresenskij, O.N.

    1985-01-01

    Long-term keeping of guinea pigs on antioxidant-free diet was shown to increase the rate of free-radical oxidation processes after local exposure to 20 Gy γ-radiation. Alimentary antioxidant deficiency enhanced new formation and growth of young axons, inhibited myelinization both in the exposed ad contralateral nonirradiated nerves being regenarated after ligating thereof

  10. Dynamics of myelin content decrease in the rat stroke model

    Science.gov (United States)

    Kisel, A.; Khodanovich, M.; Atochin, D.; Mustafina, L.; Yarnykh, V.

    2017-08-01

    The majority of studies were usually focused on neuronal death after brain ischemia; however, stroke affects all cell types including oligodendrocytes that form myelin sheath in the CNS. Our study is focused on the changes of myelin content in the ischemic core and neighbor structures in early terms (1, 3 and 10 days) after stroke. Stroke was modeled with middle cerebral artery occlusion (MCAo) in 15 male rats that were divided into three groups by time points after operation. Brain sections were histologically stained with Luxol Fast Blue (LFB) for myelin quantification. The significant demyelination was found in the ischemic core, corpus callosum, anterior commissure, whereas myelin content was increased in caudoputamen, internal capsule and piriform cortex compared with the contralateral hemisphere. The motor cortex showed a significant increase of myelin content on the 1st day and a significant decrease on the 3rd and 10th days after MCAo. These results suggest that stroke influences myelination not only in the ischemic core but also in distant structures.

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

    Science.gov (United States)

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

    2012-01-01

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

  12. Neuronal Regulation of Schwann Cell Mitochondrial Ca2+ Signaling during Myelination

    OpenAIRE

    Daisuke Ino; Hiroshi Sagara; Junji Suzuki; Kazunori Kanemaru; Yohei Okubo; Masamitsu Iino

    2015-01-01

    Schwann cells (SCs) myelinate peripheral neurons to promote the rapid conduction of action potentials, and the process of myelination is known to be regulated by signals from axons to SCs. Given that SC mitochondria are one of the potential regulators of myelination, we investigated whether SC mitochondria are regulated by axonal signaling. Here, we show a purinergic mechanism that sends information from neurons to SC mitochondria during myelination. Our results show that electrical stimulati...

  13. Regulation of Peripheral Myelination through Transcriptional Buffering of Egr2 by an Antisense Long Non-coding RNA

    Directory of Open Access Journals (Sweden)

    Margot Martinez-Moreno

    2017-08-01

    Full Text Available Precise regulation of Egr2 transcription is fundamentally important to the control of peripheral myelination. Here, we describe a long non-coding RNA antisense to the promoter of Egr2 (Egr2-AS-RNA. During peripheral nerve injury, the expression of Egr2-AS-RNA is increased and correlates with decreased Egr2 transcript and protein levels. Ectopic expression of Egr2-AS-RNA in dorsal root ganglion (DRG cultures inhibits the expression of Egr2 mRNA and induces demyelination. In vivo inhibition of Egr2-AS-RNA using oligonucleotide GapMers released from a biodegradable hydrogel following sciatic nerve injury reverts the EGR2-mediated gene expression profile and significantly delays demyelination. Egr2-AS-RNA gradually recruits H3K27ME3, AGO1, AGO2, and EZH2 on the Egr2 promoter following sciatic nerve injury. Furthermore, expression of Egr2-AS-RNA is regulated through ERK1/2 signaling to YY1, while loss of Ser184 of YY1 regulates binding to Egr2-AS-RNA. In conclusion, we describe functional exploration of an antisense long non-coding RNA in peripheral nervous system (PNS biology.

  14. Electron microscopy of human peripheral nerves of clinical relevance to the practice of nerve blocks. A structural and ultrastructural review based on original experimental and laboratory data.

    Science.gov (United States)

    Reina, M A; Arriazu, R; Collier, C B; Sala-Blanch, X; Izquierdo, L; de Andrés, J

    2013-12-01

    The goal is to describe the ultrastructure of normal human peripheral nerves, and to highlight key aspects that are relevant to the practice of peripheral nerve block anaesthesia. Using samples of sciatic nerve obtained from patients, and dural sac, nerve root cuff and brachial plexus dissected from fresh human cadavers, an analysis of the structure of peripheral nerve axons and distribution of fascicles and topographic composition of the layers that cover the nerve is presented. Myelinated and unmyelinated axons, fascicles, epineurium, perineurium and endoneurium obtained from patients and fresh cadavers were studied by light microscopy using immunohistochemical techniques, and transmission and scanning electron microscopy. Structure of perineurium and intrafascicular capillaries, and its implications in blood-nerve barrier were revised. Each of the anatomical elements is analyzed individually with regard to its relevance to clinical practice to regional anaesthesia. Routine practice of regional anaesthetic techniques and ultrasound identification of nerve structures has led to conceptions, which repercussions may be relevant in future applications of these techniques. In this regard, the ultrastructural and histological perspective accomplished through findings of this study aims at enlightening arising questions within the field of regional anaesthesia. Copyright © 2013 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

  15. Ameliorative effect of Pimpinella anisum oil on immunohistochemical and ultrastuctural changes of cerebellum of albino rats induced by aspartame.

    Science.gov (United States)

    Abdul-Hamid, Manal; Gallaly, Sanaa Rida

    2014-05-01

    The study aims to investigate the protective effect of Pimpinella anisum oil on aspartame (ASP) which resulted in cerebellar changes. The rats were divided into four equal groups: Group 1: (control group): served as control animals. Group 2: control P. anisum oil received .5 mL/kg/d/b wt. once daily. Group 3 (ASP group): received daily 250 mg/kg/b wt. of ASP dissolved in distilled water and given orally to the animals by intra-gastric tube for 2 months. Group 4: received .5 mL/kg/b wt. of prophylactic P. anisum oil once daily, followed by ASP after 2 h for 2 months. The histopathological approach revealed marked changes in the Purkinje cells, myleinated nerve fibers and granular cells of ASP-treated animals. Some of these cells appeared with deeply stained cytoplasm. Ultrastructural examination showed Purkinje cells with dilated rough endoplasmic reticulum and condensed mitochondria. Granular cells appeared with less c nuclei and surrounded by dissolution of most Mossy rosettes structures. Most myelinated nerve fibers showed thickening of myelinated sheath and others showed splitting of their myelin sheath. The histopathological, immunohistochemical and ultrastructural alterations were much less observed in concomitant use of P. anisum oil with ASP. Cerebellar cortex is considered target areas of ASP neurotoxicity, while P. anisum oil, when used in combination with ASP displays a protective action against neurotoxicity.

  16. Microfasciculation: a morphological pattern in leprosy nerve damage.

    Science.gov (United States)

    Antunes, Sérgio L G; Medeiros, Mildred F; Corte-Real, Suzana; Jardim, Márcia R; Nery, José A da Costa; Hacker, Mariana A V B; Valentim, Vânia da Costa; Amadeu, Thaís Porto; Sarno, Euzenir N

    2011-01-01

    To study Microfasciculation, a perineurial response found in neuropathies, emphasizing its frequency, detailed morphological characteristics and biological significance in pure neural leprosy (PNL), post-treatment leprosy neuropathy (PTLN) and non-leprosy neuropathies (NLN). Morphological characteristics of microfascicles were examined via histological staining methods, immunohistochemical expression of neural markers and transmission electronmicroscopy. The detection of microfasciculation in 18 nerve biopsy specimens [12 PNL, six PTLN but not in the NLN group, was associated strongly with perineurial damage and the presence of a multibacillary inflammatory process in the nerves, particularly in the perineurium. Immunoreactivity to anti-S100 protein, anti-neurofilament, anti-nerve growth receptor and anti-myelin basic protein immunoreactivity was found within microfascicles. Ultrastructural examination of three biopsies showed that fibroblast-perineurial cells were devoid of basement membrane despite perineurial-like NGFr immunoreactivity. Morphological evidence demonstrated that multipotent pericytes from inflammation-activated microvessels could be the origin of fibroblast-perineurial cells. A microfasciculation pattern was found in 10% of leprosy-affected nerves. The microfascicles were composed predominantly of unmyelinated fibres and denervated Schwann cells (SCs) surrounded by fibroblast-perineurial cells. This pattern was found more frequently in leprosy nerves with acid-fast bacilli (AFB) and perineurial damage while undergoing an inflammatory process. Further experimental studies are necessary to elucidate microfascicle formation. © 2011 Blackwell Publishing Limited.

  17. 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

  18. Bone marrow mesenchymal stem cells with Nogo-66 receptor gene silencing for repair of spinal cord injury

    Science.gov (United States)

    Li, Zhiyuan; Zhang, Zhanxiu; Zhao, Lili; Li, Hui; Wang, Suxia; Shen, Yong

    2014-01-01

    We hypothesized that RNA interference to silence Nogo-66 receptor gene expression in bone marrow mesenchymal stem cells before transplantation might further improve neurological function in rats with spinal cord transection injury. After 2 weeks, the number of neurons and BrdU-positive cells in the Nogo-66 receptor gene silencing group was higher than in the bone marrow mesenchymal stem cell group, and significantly greater compared with the model group. After 4 weeks, behavioral performance was significantly enhanced in the model group. After 8 weeks, the number of horseradish peroxidase-labeled nerve fibers was higher in the Nogo-66 receptor gene silencing group than in the bone marrow mesenchymal stem cell group, and significantly higher than in the model group. The newly formed nerve fibers and myelinated nerve fibers were detectable in the central transverse plane section in the bone marrow mesenchymal stem cell group and in the Nogo-66 receptor gene silencing group. PMID:25206893

  19. Imaging the Facial Nerve: A Contemporary Review

    International Nuclear Information System (INIS)

    Gupta, S.; Roehm, P.C.; Mends, F.; Hagiwara, M.; Fatterpekar, G.

    2013-01-01

    Imaging plays a critical role in the evaluation of a number of facial nerve disorders. The facial nerve has a complex anatomical course; thus, a thorough understanding of the course of the facial nerve is essential to localize the sites of pathology. Facial nerve dysfunction can occur from a variety of causes, which can often be identified on imaging. Computed tomography and magnetic resonance imaging are helpful for identifying bony facial canal and soft tissue abnormalities, respectively. Ultrasound of the facial nerve has been used to predict functional outcomes in patients with Bell’s palsy. More recently, diffusion tensor tractography has appeared as a new modality which allows three-dimensional display of facial nerve fibers

  20. 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.

  1. Use of α-Lipoic Acid and Benfotiamine for Correction of Disturbance of Gastric Motor-Evacuation Function in Type 1 Diabetic Patients

    Directory of Open Access Journals (Sweden)

    I.O. Kostitska

    2015-09-01

    Full Text Available The therapeutic effectiveness of α-lipoic acid and benfotiamine in treating symptoms of gastroparesis in type 1 diabetic patients was evaluated. Pathogenetic correlations between increased concentration of peripheral myelin protein and a decrease in the gastric motor-evacuation function were determined. The results of a three-month course of pathogenetic therapy demonstrate the effectiveness of combination therapy which is not associated with an improved compensation of carbohydrate and lipid metabolism. It is a result of the direct effect of preparations on the investigated metabolic processes and restoration of myelination of the nerve fibers.

  2. Histopathology of cryoballoon ablation-induced phrenic nerve injury.

    Science.gov (United States)

    Andrade, Jason G; Dubuc, Marc; Ferreira, Jose; Guerra, Peter G; Landry, Evelyn; Coulombe, Nicolas; Rivard, Lena; Macle, Laurent; Thibault, Bernard; Talajic, Mario; Roy, Denis; Khairy, Paul

    2014-02-01

    Hemi-diaphragmatic paralysis is the most common complication associated with cryoballoon ablation for atrial fibrillation, yet the histopathology of phrenic nerve injury has not been well described. A preclinical randomized study was conducted to characterize the histopathology of phrenic nerve injury induced by cryoballoon ablation and assess the potential for electromyographic (EMG) monitoring to limit phrenic nerve damage. Thirty-two dogs underwent cryoballoon ablation of the right superior pulmonary vein with the objective of inducing phrenic nerve injury. Animals were randomized 1:1 to standard monitoring (i.e., interruption of ablation upon reduction in diaphragmatic motion) versus EMG guidance (i.e., cessation of ablation upon a 30% reduction in the diaphragmatic compound motor action potential [CMAP] amplitude). The acute procedural endpoint was achieved in all dogs. Phrenic nerve injury was characterized by Wallerian degeneration, with subperineural injury to large myelinated axons and evidence of axonal regeneration. The degree of phrenic nerve injury paralleled the reduction in CMAP amplitude (P = 0.007). Animals randomized to EMG guidance had a lower incidence of acute hemi-diaphragmatic paralysis (50% vs 100%; P = 0.001), persistent paralysis at 30 days (21% vs 75%; multivariate odds ratio 0.12, 95% confidence interval [0.02, 0.69], P = 0.017), and a lesser severity of histologic injury (P = 0.001). Mature pulmonary vein ablation lesion characteristics, including circumferentiality and transmurality, were similar in both groups. Phrenic nerve injury induced by cryoballoon ablation is axonal in nature and characterized by Wallerian degeneration, with potential for recovery. An EMG-guided approach is superior to standard monitoring in limiting phrenic nerve damage. © 2013 Wiley Periodicals, Inc.

  3. Regulation of Central Nervous System Myelination in Higher Brain Functions

    Directory of Open Access Journals (Sweden)

    Mara Nickel

    2018-01-01

    Full Text Available The hippocampus and the prefrontal cortex are interconnected brain regions, playing central roles in higher brain functions, including learning and memory, planning complex cognitive behavior, and moderating social behavior. The axons in these regions continue to be myelinated into adulthood in humans, which coincides with maturation of personality and decision-making. Myelin consists of dense layers of lipid membranes wrapping around the axons to provide electrical insulation and trophic support and can profoundly affect neural circuit computation. Recent studies have revealed that long-lasting changes of myelination can be induced in these brain regions by experience, such as social isolation, stress, and alcohol abuse, as well as by neurological and psychiatric abnormalities. However, the mechanism and function of these changes remain poorly understood. Myelin regulation represents a new form of neural plasticity. Some progress has been made to provide new mechanistic insights into activity-independent and activity-dependent regulations of myelination in different experimental systems. More extensive investigations are needed in this important but underexplored research field, in order to shed light on how higher brain functions and myelination interplay in the hippocampus and prefrontal cortex.

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

    Science.gov (United States)

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

    2018-04-20

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

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

    Directory of Open Access Journals (Sweden)

    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.

  6. In vitro incorporation of (U-C/sup 14/)-glucose and (1-C/sup 14/)-sodium acetate in peripheral nerves of malnourished young rhesus monkeys

    Energy Technology Data Exchange (ETDEWEB)

    Rana, S V; Mehta, S; Chopra, J S; Nain, C K; Mehta, J; Dhand, U K

    1984-01-01

    The effect of protein calorie malnutrition (PCM) on synthesis of lipids in peripheral nerves was studied by in vitro incorporation of (U-C/sup 14/)-glucose and (1-C/sup 14/)-sodium acetate. Ulnar and tibial nerves obtained from five young rhesus monkeys with PCM, five rehabilitated monkeys, and five control monkeys were incubated for 2 h with the radioactive precursors. Uptake of both radioactive precursors in whole peripheral nerves as well as myelin marker lipids was significantly decreased in animals with PCM. However, uptake returned to normal in rehabilitated monkeys.

  7. Enhanced uptake of multiple sclerosis-derived myelin by THP-1 macrophages and primary human microglia.

    Science.gov (United States)

    Hendrickx, Debbie A E; Schuurman, Karianne G; van Draanen, Michael; Hamann, Jörg; Huitinga, Inge

    2014-03-31

    The pathological hallmark of multiple sclerosis (MS) is myelin phagocytosis. It remains unclear why microglia and macrophages demyelinate axons in MS, but previously found or yet-unknown changes in the myelin of MS patients could contribute to this process. We therefore studied whether myelin from normal-appearing white matter (NAWM) of MS donors is phagocytosed more efficiently than myelin from control donors. Myelin was isolated from 11 MS and 12 control brain donors and labeled with the pH-sensitive fluorescent dye pHrodo to quantify uptake in lysosomes. Phagocytosis by differentiated THP-1 macrophages and by primary human microglia was quantified with flow cytometry. Whereas myelin uptake by THP-1 macrophages reached a plateau after approximately 24 hours, uptake by primary human microglia showed an almost linear increase over a 72-hour period. Data were statistically analyzed with the Mann-Whitney U test. MS-derived myelin was phagocytosed more efficiently by THP-1 macrophages after 6-hour incubation (P = 0.001 for the percentage of myelin-phagocytosing cells and P = 0.0005 for total myelin uptake) and after 24-hour incubation (P = 0.0006 and P = 0.0001, respectively), and by microglia after 24-hour incubation (P = 0.0106 for total myelin uptake). This enhanced uptake was not due to differences in the oxidation status of the myelin. Interestingly, myelin phagocytosis correlated negatively with the age of myelin donors, whereas the age of microglia donors showed a positive trend with myelin phagocytosis. Myelin isolated from normal-appearing white matter of MS donors was phagocytosed more efficiently than was myelin isolated from control brain donors by both THP-1 macrophages and primary human microglia. These data indicate that changes in MS myelin might precede phagocyte activation and subsequent demyelination in MS. Identifying these myelin changes responsible for enhancing phagocytic ability could be an interesting therapeutic target to

  8. Rapid myelin water content mapping on clinical MR systems

    International Nuclear Information System (INIS)

    Tonkova, Vyara; Arhelger, Volker; Schenk, Jochen; Neeb, Heiko; Koblenz Univ.

    2012-01-01

    We present an algorithm for the fast mapping of myelin water content using standard multiecho gradient echo acquisitions of the human brain. The method extents a previously published approach for the simultaneous measurement of brain T 1 , T * 2 and total water content. Employing the multiexponential T * 2 decay signal of myelinated tissue, myelin water content was measured based on the quantification of two water pools ('myelin water' and 'rest') with different relaxation times. As the existing protocol was focussed on the fast mapping of quantitative MR parameters with whole brain coverage in clinically relevant measurement times, the sampling density of the T * 2 curve was compromised to 10 echo times with a T Emax of approx. 40 ms. Therefore, pool amplitudes were determined using a quadratic optimisation approach. The optimisation was constrained by including a priori knowledge about brain water pools. All constraints were optimised in a simulation study to minimise systematic error sources given the incomplete knowledge about the real pool-specific relaxation properties. Based on the simulation results, whole brain in vivo myelin water content maps were acquired in 10 healthy controls and one subject with multiple sclerosis. The in vivo results obtained were consistent with previous reports which demonstrates that a simultaneous whole brain mapping of T 1 , T * 2 , total and myelin water content is feasible on almost any modern MR scanner in less than 10 minutes. (orig.)

  9. Hereditary sensory and autosomal peripheral neuropathy-type IV: case series and review of literature.

    Science.gov (United States)

    Ashwin, D P; Chandan, G D; Jasleen, Handa Kaur; Rajkumar, G C; Rudresh, K B; Prashanth, R

    2015-06-01

    Hereditary sensory and autonomic neuropathy (HSAN) IV is a rare autosomal recessive disorder which is characterized by a decrease in the number of myelinated and non-myelinated nerve fibers of peripheral nerves which causes diminished or absent pain sensation leading to increase in self-mutilative habits. A retrospective study of eight cases ranging from age group of 4 to 17 years for oral and digital signs and symptoms is presented. All the patients showed congenital insensitivity to pain and anhidrosis. Oral self-mutilations, such as autoextraction of teeth and severe bite injuries (with resultant scarring) of the finger tips and oral soft tissues (tongue, lip, and buccal mucosa) were found in most patients. Our study suggests that early diagnosis and specific treatment plan are important for prevention of characteristic of the oral as well as digital trauma associated with this disorder.

  10. Rac1 controls Schwann cell myelination through cAMP and NF2/merlin

    Science.gov (United States)

    Guo, Li; Moon, Chandra; Niehaus, Karen; Zheng, Yi; Ratner, Nancy

    2013-01-01

    During peripheral nervous system development, Schwann cells (SCs) surrounding single large axons differentiate into myelinating SCs. Previous studies implicate RhoGTPases in SC myelination, but the mechanisms involved in RhoGTPase regulation of SC myelination are unknown. Here, we show that SC myelination is arrested in Rac1 conditional knockout (Rac1-CKO) mice. Rac1 knockout abrogated phosphorylation of the effector p21-activated kinase (PAK) and decreased NF2/merlin phosphorylation. Mutation of NF2/merlin rescued the myelin deficit in Rac1-CKO mice in vivo, and the shortened processes in cultured Rac1-CKO SCs in vitro. Mechanistically, cyclic adenosine monophosphate (cAMP) levels and E-cadherin expression were decreased in the absence of Rac1, and both were restored by mutation of NF2/merlin. Reduced cAMP is a cause of the myelin deficiency in Rac1-CKO mice, as elevation of cAMP by rolipram in Rac1-CKO mice in vivo allowed myelin formation. Thus NF2/merlin and cAMP function downstream of Rac1 signaling in SC myelination, and cAMP levels control Rac1-regulated SC myelination. PMID:23197717

  11. Optical Coherence Tomography in Optic Nerve Hypoplasia: Correlation With Optic Disc Diameter, Nerve Fiber Layer Thickness, and Visual Function.

    Science.gov (United States)

    Kelly, John P; Baran, Francine; Phillips, James O; Weiss, Avery H

    2017-12-15

    The correlation between optic disc diameters (DDs) with average retinal nerve fiber layer thickness (RNFLT) and visual function in children with optic nerve hypoplasia (ONH) having nystagmus is unknown. Data were obtained from a retrospective review of 28 children (mean age: 9.4 years; ±5.1). Optic DD was defined as the maximal horizontal opening of Bruch membrane with spectral optical coherence tomography combined with a confocal laser ophthalmoscope. Average RNFLT was obtained from circumpapillary b-scans. RNFLT was also remeasured at eccentricities that were proportionate with DD to rule out potential sampling artifacts. Visual function was assessed by visual acuity at last follow-up and by visual evoked potentials (VEP) in 11 patients. The eye with the larger DD, which had better visual acuity, was analyzed to exclude potential effects of amblyopia. DD was correlated with average RNFLT (r = 0.61), visual acuity (r = 0.32), and VEPs (r = 0.66). The relationship between RNFLT and DD was as follows: average RNFLT (μm) = 0.074 * DD (μm) - 18.8. RNFLT also correlated with the ratio of horizontal optic DD to macula-disc-margin distance (DD:DM; r = 0.59). RNFLT measured at eccentricities proportionate with DD showed progressive decrease in thickness only for DDs <1,100 μm. All patients with DD <1,000 μm had subnormal visual acuity, whereas those with DD <1,200 μm had subnormal VEPs. DD correlates with average RNFLT and with visual function in children with ONH. Using OCT imaging, DD can be obtained in children with nystagmus and provides objective information.

  12. Peripapillary retinal nerve fiber layer and optic nerve head characteristics in eyes with situs inversus of the optic disc.

    Science.gov (United States)

    Kang, Sunah; Jin, Sunyoung; Roh, Kyu Hwa; Hwang, Young Hoon

    2015-01-01

    This study was performed to investigate the peripapillary retinal nerve fiber layer (RNFL) and optic nerve head (ONH) characteristics, as determined using a spectral-domain optical coherence tomography (OCT), in eyes with situs inversus of the optic disc. The peripapillary RNFL and the ONH were assessed in 12 eyes belonging to 6 subjects with situs inversus of the optic disc (situs inversus group) and 24 eyes in 12 age-matched, sex-matched, and refractive error-matched healthy subjects (control group) by using OCT. The average, quadrant, and clock-hour RNFL thicknesses (clock-hour 9 on the scan represented the temporal side of the optic disc in both eyes), the superior/inferior RNFL peak locations, and ONH characteristics such as disc area, rim area, cup-to-disc ratio, vertical cup-to-disc ratio, and cup volume were obtained. The differences in RNFL and ONH characteristics between the 2 groups were analyzed. The situs inversus group had a thicker RNFL in the clock-hour sectors 3 and 4, a thinner RNFL in the clock-hour sectors 7, 8, and 11, and more nasally located superior and inferior RNFL peak locations than the control group (P≤0.001). The situs inversus group had a smaller cup-to-disc area ratio, smaller vertical cup-to-disc ratio, and a lesser cup volume than the control group (Poptic disc showed different peripapillary RNFL and ONH characteristics from those without this abnormality. These findings should be considered when assessing eyes with situs inversus of the optic disc.

  13. Administration of Oxygen Ultra-Fine Bubbles Improves Nerve Dysfunction in a Rat Sciatic Nerve Crush Injury Model

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    Hozo Matsuoka

    2018-05-01

    Full Text Available Ultra-fine bubbles (<200 nm in diameter have several unique properties and have been tested in various medical fields. The purpose of this study was to investigate the effects of oxygen ultra-fine bubbles (OUBs on a sciatic nerve crush injury (SNC model rats. Rats were intraperitoneally injected with 1.5 mL saline, OUBs diluted in saline, or nitrogen ultra-fine bubbles (NUBs diluted in saline three times per week for 4 weeks in four groups: (1 control, (sham operation + saline; (2 SNC, (crush + saline; (3 SNC+OUB, (crush + OUB-saline; (4 SNC+NUB, (crush + NUB-saline. The effects of the OUBs on dorsal root ganglion (DRG neurons and Schwann cells (SCs were examined by serial dilution of OUB medium in vitro. Sciatic functional index, paw withdrawal thresholds, nerve conduction velocity, and myelinated axons were significantly decreased in the SNC group compared to the control group; these parameters were significantly improved in the SNC+OUB group, although NUB treatment did not affect these parameters. In vitro, OUBs significantly promoted neurite outgrowth in DRG neurons by activating AKT signaling and SC proliferation by activating ERK1/2 and JNK/c-JUN signaling. OUBs may improve nerve dysfunction in SNC rats by promoting neurite outgrowth in DRG neurons and SC proliferation.

  14. EFFECT OF INTRAVITREAL RANIBIZUMAB ON GANGLION CELL COMPLEX AND PERIPAPILLARY RETINAL NERVE FIBER LAYER IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION USING SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY.

    Science.gov (United States)

    Zucchiatti, Ilaria; Cicinelli, Maria V; Parodi, Maurizio Battaglia; Pierro, Luisa; Gagliardi, Marco; Accardo, Agostino; Bandello, Francesco

    2017-07-01

    To analyze the changes in ganglion cell complex and peripapillary retinal nerve fiber layer thickness, in central macular thickness and choroidal thickness on spectral domain optical coherence tomography in patients with neovascular age-related macular degeneration treated with intravitreal ranibizumab injections. All consecutive patients with untreated neovascular age-related macular degeneration received loading phase of three monthly intravitreal ranibizumab, followed by retreatments on a pro re nata protocol for 12 months. changes in ganglion cell complex and retinal nerve fiber layer at the end of follow-up. Secondary outcome: changes in best-corrected visual acuity, central macular thickness, and choroidal thickness at the end of follow-up. Choroidal thickness was measured at 500 μm, 1000 μm, and 1,500 μm intervals nasally, temporally, superiorly, and inferiorly to the fovea, respectively, on horizontal and vertical line scans centered on the fovea. Twenty-four eyes were included. Ganglion cell complex and peripapillary retinal nerve fiber layer thickness did not show statistically significant changes through 12 months (55.6 ± 18.5 and 81.9 ± 9.9 μm at baseline, 52.7 ± 19.3 and 84.6 ± 15.5 μm at month 12, P > 0.05). Central macular thickness showed progressive decrease from baseline to month 12, with maximum reduction at month 3 (P macular thickness was significantly reduced at the end of treatment. Further studies, with larger sample, longer follow-up, and greater number of injections, are warranted.

  15. Watery and dark axons in Wallerian degeneration of the opossum's optic nerve: different patterns of cytoskeletal breakdown?

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    MARCELO S. NARCISO

    2001-06-01

    Full Text Available In this paper we report a qualitative morphological analysis of Wallerian degeneration in a marsupial. Right optic nerves of opossums Didelphis marsupialis were crushed with a fine forceps and after 24, 48, 72, 96 and 168 hours the animals were anaesthetized and perfused with fixative. The optic nerves were immersed in fixative and processed for routine transmission electron microscopy. Among the early alterations typical of axonal degeneration, we observed nerve fibers with focal degeneration of the axoplasmic cytoskeleton, watery degeneration and dark degeneration, the latter being prevalent at 168 hours after crush. Our results point to a gradual disintegration of the axoplasmic cytoskeleton, opposed to the previous view of an "all-or-nothing'' process (Griffin et al 1995. We also report that, due to an unknown mechanism, fibers show either a dark or watery pattern of axonal degeneration, as observed in axon profiles. We also observed fibers undergoing early myelin breakdown in the absence of axonal alterations.Neste trabalho, relatamos uma análise morfológica qualitativa da degeneração Walleriana em um marsupial. Os nervos ópticos direito de gambás da espécie Didelphis marsupialis foram esmagados com uma pinça fina. Após 24, 48, 72, 96 e 168 horas, os animais foram anestesiados e perfundidos com fixador. A seguir, os nervos foram imersos em fixador e processados para microscopia eletrônica de rotina. Entre as alterações precoces típicas da degeneração, observamos fibras nervosas com degeneração focal do citoesqueleto axoplasmático, degeneração aquosa e degeneração escura, com o último tipo prevalente às 168 horas após esmagamento. Nossos resultados indicam uma desintegração gradual do citoesqueleto axoplasmático, oposta à prévia visão de um processo "tudo-ou-nada''. Relatamos também que, devido a um mecanismo desconhecido, as fibras mostram ou um padrão aquoso ou um padrão escuro de degeneração axonal

  16. 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

  17. Axo-Glia Interaction Preceding CNS Myelination Is Regulated by Bidirectional Eph-Ephrin Signaling

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    Cecilie Linneberg

    2015-09-01

    Full Text Available In the central nervous system, myelination of axons is required to ensure fast saltatory conduction and for survival of neurons. However, not all axons are myelinated, and the molecular mechanisms involved in guiding the oligodendrocyte processes toward the axons to be myelinated are not well understood. Only a few negative or positive guidance clues that are involved in regulating axo-glia interaction prior to myelination have been identified. One example is laminin, known to be required for early axo-glia interaction, which functions through α6β1 integrin. Here, we identify the Eph-ephrin family of guidance receptors as novel regulators of the initial axo-glia interaction, preceding myelination. We demonstrate that so-called forward and reverse signaling, mediated by members of both Eph and ephrin subfamilies, has distinct and opposing effects on processes extension and myelin sheet formation. EphA forward signaling inhibits oligodendrocyte process extension and myelin sheet formation, and blocking of bidirectional signaling through this receptor enhances myelination. Similarly, EphB forward signaling also reduces myelin membrane formation, but in contrast to EphA forward signaling, this occurs in an integrin-dependent manner, which can be reversed by overexpression of a constitutive active β1-integrin. Furthermore, ephrin-B reverse signaling induced by EphA4 or EphB1 enhances myelin sheet formation. Combined, this suggests that the Eph-ephrin receptors are important mediators of bidirectional signaling between axons and oligodendrocytes. It further implies that balancing Eph-ephrin forward and reverse signaling is important in the selection process of axons to be myelinated.

  18. Biomarkers of neuropathic pain in skin nerve degeneration neuropathy: contact heat-evoked potentials as a physiological signature.

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    Wu, Shao-Wei; Wang, Yi-Chia; Hsieh, Paul-Chen; Tseng, Ming-Tsung; Chiang, Ming-Chang; Chu, Chih-Pang; Feng, Fang-Ping; Lin, Yea-Huey; Hsieh, Sung-Tsang; Chao, Chi-Chao

    2017-03-01

    Contact heat-evoked potentials (CHEPs) have become an established method of assessing small-fiber sensory nerves; however, their potential as a physiological signature of neuropathic pain symptoms has not been fully explored. To investigate the diagnostic efficacy in examining small-fiber sensory nerve degeneration, the relationship with skin innervations, and clinical correlates with sensory symptoms, we recruited 188 patients (115 men) with length-dependent sensory symptoms and reduced intraepidermal nerve fiber (IENF) density at the distal leg to perform CHEP, quantitative sensory testing, and nerve conduction study. Fifty-seven age- and sex-matched controls were enrolled for comparison of CHEP and skin innervation. Among patients with neuropathy, 144 patients had neuropathic pain and 64 cases had evoked pain. Compared with quantitative sensory testing and nerve conduction study parameters, CHEP amplitudes showed the highest sensitivity for diagnosing small-fiber sensory nerve degeneration and exhibited the strongest correlation with IENF density in multiple linear regression. Contact heat-evoked potential amplitudes were strongly correlated with the degree of skin innervation in both patients with neuropathy and controls, and the slope of the regression line between CHEP amplitude and IENF density was higher in patients with neuropathy than in controls. Patients with evoked pain had higher CHEP amplitude than those without evoked pain, independent of IENF density. Receiver operating characteristic analysis showed that CHEP had better performance in diagnosing small-fiber sensory nerve degeneration than thermal thresholds. Furthermore, CHEPs showed superior classification accuracy with respect to evoked pain. In conclusion, CHEP is a sensitive tool to evaluate pathophysiology of small-fiber sensory nerve and serves as a physiological signature of neuropathic pain symptoms.

  19. 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.

  20. The gross anatomy of the renal sympathetic nerves revisited.

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    Mompeo, Blanca; Maranillo, Eva; Garcia-Touchard, Arturo; Larkin, Theresa; Sanudo, Jose

    2016-07-01

    Catheter-based renal denervation techniques focus on reducing blood pressure in resistant hypertension. This procedure requires exact knowledge of the anatomical interrelation between the renal arteries and the targeted renal nervous plexus. The aim of this work was to build on classical anatomical studies and describe the gross anatomy and anatomical relationships of the renal arteries and nerve supply to the kidneys in a sample of human cadavers. Twelve human cadavers (six males and six females), age range 73 to 94 years, were dissected. The nervous fibers and renal arteries were dissected using a surgical microscope. The renal plexus along the hilar renal artery comprised a fiber-ganglionic ring surrounding the proximal third of the renal artery, a neural network along the middle and distal thirds, and smaller accessory ganglia along the course of the nerve fibers. The fibers of the neural network were mainly located on the superior (95.83%) and inferior (91.66%) surfaces of the renal artery and they were sparsely interconnected by diagonal fibers. Polar arteries were present in 33.33% of cases and the renal nerve pattern for these was similar to that of the hilar arteries. Effective renal denervation needs to target the superior and inferior surfaces of the hilar and polar arteries, where the fibers of the neural network are present. Clin. Anat. 29:660-664, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.